The toxic cadmium (Cd) poses a serious threat to plant growth and human health. Populus euphratica CPK21 has previously been shown to attenuate Cd toxicity by reducing Cd accumulation, enhancing antioxidant defense and improving water balance in transgenic Arabidopsis. Here, we confirmed a protein-protein interaction between PeCPK21 and AtNF-YC3 by yeast two-hybrid, HaloTag pull-down and bimolecular fluorescence complementation assays. AtNF-YC3 was induced by Cd and strongly expressed in PeCPK21-overexpressed plants. Overexpression of AtNF-YC3 in Arabidopsis reduced salt inhibition of root length, fresh weight and membrane stability under Cd stress conditions (100 µM, 7 d), suggesting that AtNF-YC3 appears to contribute to the improvement of Cd stress tolerance. AtNF-YC3 improved Cd tolerance by limiting Cd uptake and accumulation, activating antioxidant enzymes, and reducing H2O2 production under Cd stress. We conclude that PeCPK21 interacts with AtNF-YC3 to limit Cd accumulation, enhance the ROS scavenging system, and thereby positively regulate plant adaptation to Cd environments. This study highlights the interaction between PeCPK21 and AtNF-YC3 under Cd stress conditions, which can be utilized to improve Cd tolerance in higher plants.

Patients with Peripheral-artery-disease (PAD) are prone to risks of major-adverse-limb-events (MALE), and major-adverse-cardiovascular-events (MACE). CHA2DS2-VASc is a prognostic score for Atrial fibrillation stroke risk, however, no study exists that evaluated its predictability for MALE and MACE in PAD patients. In this study, patients with PAD were stratified into four risk groups based on CHA2DS2-VASc score. Cox-proportional hazards models,10-fold cross-validation and Receiver operating characteristic (ROC) analyses were utilized to evaluate the predictability of CHA2DS2-VASc for predicting MALE, MACE, and MALE+MACE. Kaplan-Meier analysis estimated the survival-probability of risk-groups. CHA2DS2-VASc was found to be a significant predictor of MACE (hazard ratio (95% confidence interval; P) = 3.47 (0.99 - 12.18; 0.052), 4.12 (1.19 - 14.14; 0.024), and 5.06 (1.48 – 17.28; 0.009), for moderate-, high- and very-high-risk groups, respectively, while for MALE and MALE+MACE significance was achieved only for high-risk group. MACE demonstrated AUC > 0.8, good-discrimination (c-index > 0.8) and good-calibration. However, MALE and MALE+MACE models failed to achieve good performances. Based on all findings, CHA2DS2-VASc could potentially serve as a risk stratification score for predicting MACE in patients with PAD but failed to qualify as a good predictor for MALE.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

In the realm of construction industry, the management of claims constitutes a pervasive and multifaceted issue, with potential repercussions extending to project delays, cost overruns, work suspensions, and, in extreme cases, project termination. This challenge is a significant and unavoidable hurdle due to the unique features of construction projects, which are complex, involve many stakeholders and come with inherent risks. To address this complex issue, it becomes imperative to undertake a comprehensive appraisal of the claims management procedures employed within the industry, culminating in the presentation of findings within a risk-based framework. The overarching objective of this endeavour is threefold: firstly, to discern the pivotal attributes that affect each category of construction claims; secondly, to establish a coherent decision-making paradigm for the effective administration of such claims; and finally, to provide data that can be harnessed to either address concerns related to claims or enhance the effectiveness of the claims administration process. Keeping this in mind, this study serves to evaluate the factors associated with claim management gathered from a wide overview of literature, encompassing a range of construction projects, varying in terms of types, sizes/capacities and contractual arrangements. Hence, it advanced a refined method within the domain of fuzzy group decision-making, denoted as the Modified Fuzzy Group Decision-Making Approach (FGDMA) in addition to extensive statistical analysis using SPSS.V.25 software. They were applied to assess, analyze and prioritize claim about 108 claim management factors based on the responses obtained from the comprehensive questionnaire survey involving 104 industry professionals. This multi-faceted approach, which combines the insights from previous publications, along with the collective experience of the surveyed professionals with the analytical capabilities of the FGDMA- Statically Factor Analysis, reinforces the robustness and practical applicability of proposed methodology within the context of construction claims management.

Regulatory cystathionine β-synthase (CBS) domains are widespread in proteins; however, difficulty in structure determination prevents a comprehensive understanding of the underlying regulation mechanism. Tetrameric microbial inorganic pyrophosphatase containing such domains (CBS-PPase) is allosterically inhibited by AMP and ADP and activated by ATP and cell alarmones diadenosine polyphosphates. Each CBS-PPase subunit contains a pair of CBS domains but binds cooperatively only one molecule of the mono-adenosine derivatives. We used site-directed mutagenesis of Desulfitobacterium hafniense CBS-PPase to identify the key elements determining the direction of the effect (activation or inhibition) and the “half-of-the-sites” ligand binding stoichiometry. Seven amino acid residues were selected in CBS1 domain based on the available X-ray structure of the regulatory domains and substituted by alanine and other residues. The interaction of 11 CBS-PPase variants with the regulating ligands was characterized by activity measurements and isothermal titration calorimetry. Lys100 replacement reversed the effect of ADP from inhibition to activation, whereas Lys95 and Gly118 replacements made ADP activator at low concentrations but inhibitor at high concentrations. Replacements of these residues for alanine increased the stoichiometry of mono-adenosine phosphate binding twofold. These findings identify several key protein residues and suggest “two non-interacting pairs of interacting regulatory sites” concept in CBS-PPase regulation.

In this paper, we define the cohomology of a modified $\lambda$-differential left-symmetric algebra with coefficients in a suitable representation. We also introduce the notion of modified $\lambda$-differential left-symmetric 2-algebra. We classify linear deformations and abelian extensions of modified $\lambda$-differential left-symmetric algebras using the second cohomology group and classify skeletal modified $\lambda$-differential left-symmetric 2-algebra using the third cohomology group as our propose cohomology applications. Moreover, we prove that strict modified $\lambda$-differential left-symmetric 2-algebras are equivalent to crossed modules of modified $\lambda$-differential left-symmetric algebras.

Semenov-Tian-Shansky has introduced the modified classical Yang-Baxter equation, which is called the modified $r$-matrix. Relevant studies have been extensive in recent times. This paper is devoted to study cohomology theory of modified Rota-Baxter pre-Lie algebras and its applications. First we introduce the concept and representations of modified Rota-Baxter pre-Lie algebras. We then develop the cohomology of modified Rota-Baxter pre-Lie algebras with coefficients in a suitable representation. As applications, we consider the infinitesimal deformations, abelian extensions and skeletal modified Rota-Baxter pre-Lie 2-algebra in terms of lower degree cohomology groups.

To investigate the effects of organic fertilizer combined with reduced chemical fertilizer on radish yield, quality, and soil environment in high mountainous areas (elevation: 1800 m), and to mitigate the environmental pollution caused by excessive use of chemical fertilizers. The field trial was conducted to study the effects of different fertilizer treatments. (Control:local fertilizer application rate: 375 kg·hm² reduction in chemical fertilizer + 4500 kg·hm² organic fertilizer; T1:12% reduction in chemical fertilizer + 4500 kg·hm² organic fertilizer; T2:20% reduction in chemical fertilizer + 4500 kg·hm² of organic fertilizer; T3:28% reduction in chemical fertilizer + 4500 kg·hm² organic fertilizer). Four different fertilizer ratios were studied to assess their impacts on radish quality, yield, and soil environment. The findings showed that T2 significantly increased radish yield by 12.92%. Moreover, it led to significant improvements in the content of vitamin C, soluble sugars, soluble solids, soluble proteins, titratable acidity, and glucosinolates, which increased by 10.62%, 2.15%, 50.00%, 26.90%, 43.90%, and 44.57%, respectively. Treatment T2 also significantly increased soil nutrient content, with a 7.69% and 14.29% increase in total nitrogen and total phosphorus content compared to the control (Control) treatment, and a significant reduction of 21.64% in soil bulk density . T2 treatment significantly enhanced soil urease activity, sucrase activity, alkaline phosphatase activity, and catalase activity, showing an improvement of 28.97%, 55.92%, 52.08%, and 17.47% compared to the control, respectively (p<0.05). Moreover, treatment T2 resulted in a relative abundance increase of 12.25% and 10.43% in Proteobacteria and Actinobacteria respectively. Thus, the combined application of T2:20% reduction in chemical fertilizer + 4500 kg·hm² of organic fertilizer improved the quality and yield of radish while optimizing the soil environment. T2 effectively promoted radish growth, enhanced radish yield and quality, and improved the soil environment.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

In this study, we successfully synthesized a novel branched polyamide 6 with ε-caprolactam(CPL) and α-Amino-ε-caprolactam(ACL) through hydrolytic ring-open co-polymerization. The NMR characterization and rheological test result proved the existence of branched chain structure additionally. The branched chain structure caused a remarkable enhancement in the rheological properties. The met index(MFR),zero shear rate viscosity and storage modulus at low frequency region had a remarkable increase.The shear thinning phenomenon became more obvious. The thermal properties test determined by differential scanning calorimetry(DSC) showed that the melting point and crystallinity of co-polymers decreased with the increase of ACL addition.However, the crystal structure of the samples remained unchanged. The appropriate addition amount of ACL can improve the tensile mechanical properties of the co-polymers. When the amount of ACL was 1%, the tensile strength and fracture elongation rate of the co-polymers had the most significant increase.

Thromboembolic conditions, such as stroke and myocardial infarction [MI], are the primary causes of mortality globally. High efficiency was demonstrated by fibrinolytic enzymes isolated from microbial sources in dissolving various blood clots. The study aimed to investigate and produce bacterial fibrinolytic enzymes from various Egyptian soil conditions using recombinant DNA technology. Fifty soil samples were examined to determine the production of fibrinolytic enzymes. The plasmin plate technique assessed the thrombolytic activities of the strong fibrinolytic enzyme-producing bacterial isolates. In addition to determining the molecular mass using a mass spectrometer and the western blot method, the activity and thermostability of the enzymes were characterized. An affinity chromatography approach was used to purify the fibrinolytic enzymes. However, bacterial recombinant DNA technology produced the pure bacterial fibrinolytic enzyme. Several dosage formulations for the formulation of fibrinolytic enzymes were tested. By using affinity chromatography and the SDS-PAGE test, the isolated bacterial fibrinolytic enzyme in this investigation was almost 83% pure. Bacillus cereus ATCC 4342 was identified as the predominant bacterial isolate secreting fibrinolytic enzymes. It was discovered that the fibrinolytic enzyme activity of fifty soil samples ranged from 0.167 U/ml to 1.853 U/ml. The extracellular enzyme extracted from Bacillus cereus culture supernatant demonstrated a relatively stable fibrinolytic activity over 18 hours at a pH range of 7.4–10, as well as stability with maximum productivity at 43℃ for over 60 minutes. In this investigation, the enzyme was referred to as Fibrin-proteinase[ FP]. The fibrin clots were directly thrombolyzed by the FP. The calculated values for the specific activity and molecular mass of the FP were approximately 40.71 units/mg of protein and approximately 30 KDa, respectively. It was observed that the presence of Fe+3 marginally boosted protease activity, but the presence of EDTA decreased it. On the other hand, adding monovalent cations like K+1 and Na+1 significantly increased the fibrinolytic activity of FP. The enzyme exhibited activity throughout the temperature range of 20 to 65℃, peaking at 55℃. The ideal range for the generation of protease was 35–43℃ and 8.0–10. The thermostable fibrinolytic enzyme FP, which was isolated from Bacillus cereus ATCC 4342 in various soil environments in Egypt during the current study, was a promising fibrinolytic enzyme because it demonstrated a more extensive and effective fibrinolytic activity and fewer side effects than the fibrinolytic enzymes that are currently available worldwide. It is advised that further research be done on optimizing the right formulation of bacterial fibrinolytic enzymes in the future to help dissolve different types of blood clots and, as a result, lower the high death rate that exists worldwide.

The objective of the present paper is to get a better understanding of the electrochemical properties of organoclays, which were prepared via solid-state intercalation of three cationic surfactants, such as dodecyltrimethylammonium, tetradecyltrimethylammonium, and hexadecyltrimethylammonium, as bromide salts, at different loading levels into the interlayers of two natural smectite clays (AH and DI). The electrochemical properties of the prepared organoclays were investigated by cyclic voltammetry. The cyclic voltammetry response of the electrochemical probe, 〖Fe(CN)〗_6^(3-)/〖Fe(CN)〗_6^(4-), shows that the intensities of the anodic and cathodic peaks don’t increase when the working electrode is based on carbon paste modified with the raw clays (AH or DI), whereas the peaks intensities increase significantly when the working electrode consists of carbon paste modified with organoclays. This increase in the intensity of the current indicates an improvement in the surface conductivity of the carbon paste electrode when they are modified with organoclays. When the working Electrode is based on organoclays modified carbon paste, the potential differences (ΔEp) are ranged between 140 and 170 mV, which are lower than those of the unmodified carbon paste electrode (330 mV) and those modified with raw clays (520 mV). This indicates an easy electron transfer process on the surface of the organoclays modified carbon paste electrodes.

Soil extracellular enzyme activity (EEAs) and enzymatic stoichiometry (ES) can provide a crucial indication of changes in soil ecosystem's nutrient availability and the microbial resource limitations. However, the changing characteristics of soil EEAs and ES at different stages of the native succession process and their key drivers are unclear. In order to investigate the soil EEAs, ES and driving factors of soil under vegetation at different succession stages, we adopted the "spatio-temporal substitution" method to collect the surface soil of bryophyte community, herbaceous community, shrub community and tree community in the new volcanic lava platform of Wudalianchi Volcanic Nature Reserve. We measured seven soil EEA, including carbon(C)-acquiring enzyme (β-1,4-glucosidase (BG)), N-acquiring enzymes (β-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase (LAP)) and phosphorus (P)-acquiring enzyme (acid phosphatase (AP)) activities. The length and angle of vectors defined by ratios of enzyme activities (BG/(NAG + LAP) vs. BG/AP) were used to indicate relative microbial investments in C- (length), and N- and P- (angle) acquiring enzymes. Our results showed that the contents of TC, TN, TP, MBC, DOC and NO3-N in shrub community soil were significantly higher than those in bryophyte, herb and tree communities, and increased by 441%, 246%, 137%, 5570%, 12% and 484%, respectively. The highest soil EEA of C-, N- and P-acquiring were found in shrub community, and the soil EEAs/MBC of C-, N- and P-acquiring were the highest in bryophyte community. Enzyme C:N, C:P and N:P ratios increased progressively in the order of bryophyte, herb and shrub community, but the enzyme C:N, C:P and N:P ratios of tree community were both far less than shrub community. Vector lengths increased progressively in the order of bryophyte (1.16), herb (1.27), tree (1.29) and shrub (1.40), and Vector angles decreased progressively in the order of bryophyte (49.15°), herb (45.65°), Tree (45.31°) and shurb (44.54°), suggested that as succession progresses, soil microbial nutrients transforms from P limitation (angle＞45°) to N limitation (angle＜45°). Redundancy analysis showed that TC, TN, EC and C:N were important drivers of variation in soil EEAs and ES in vegetation at different succession stages. Our findings highlight that the primary succession process cause nutrient limitation transformation. Soil ES might be a sensitive indicator mediated by soil microorganisms to the relative resource limitation at different stages of the primary succession process.

(i) Investigations of stellar systems known as wide binaries suggest that Newton’s law of gravitation breaks down at low accelerations. This can be explained by proposing a fifth force with $U(1)$ gauge symmetry, whose corresponding gauge boson is the sought for dark matter candidate. (ii) Relativistic causality (i.e. no faster than light signalling) permits nonlocal correlations stronger than those permitted by quantum mechanics. This can be explained if our universe possesses a second 4D spacetime with a signature opposite to ours. (iii) Such a fifth force, and a second spacetime, arise naturally in a recently proposed theory of unification based on an $E_8\times E_8$ symmetry. Our spacetime arises from breaking of an $SU(2)_R\times U(1)_{YDEM}$ symmetry, and the second spacetime arises from broken electroweak symmetry.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance of inactivated SARS-COV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-COV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprising of UV-inactivated SARS CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (Limit of Detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a twenty amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates.

The long-term use of fertilizers and pesticides in conventional cultivation has resulted in a decrease in soil productivity and vegetable yields in greenhouses. However, only a limited number of studies have explored the impacts of organic cultivation on greenhouse soil. Specifically, there is a scarcity of research examining the alterations in soil aggregate mediated organic carbon and microbial communities, which are known to enhance soil productivity. This study investigated the properties of soil aggregates, including the levels of organic carbon fractions, microbial community, and enzyme activity with the three aggregate classes microaggregates (<0.25 mm), small macroaggregates (2-0.25 mm) and large macroaggregates (>2 mm). These investigations were conducted under three different cultivation methods in a greenhouse: conventional cultivation (CC), integrated cultivation (IC), and organic cultivation (OC) in greenhouse. The results showed that (1) OC and IC promoted the formation of small macro-aggregates and enhanced aggregate stability compared to CC, (2) SOC in the three size fractions of OC increased by 98.99%-92.06% compared to CC; EOC increased by 98.47%-117.59%; POC increased by 138.59%-208.70%; MBC increased by 104.71%-230.61%; DOC increased by 21.93%-40.90%, respectively; (3) Organic cultivation significantly increased enzyme activity in all three particle size aggregates and increased the relative abundance of bacteria in micro-aggregates as well as the relative abundance of fungi in small macro-aggregates. Structural equation model (SEM) analysis revealed that organic farming practices fostered the development of smaller macro-aggregates, elevated microbial and enzyme activities within soil aggregates, and facilitated the conversion of soil nutrients and carbon sequestration. consequently, this led to an increase in soil organic carbon content and improved vegetable yield in greenhouse environments. In conclusion, the soil carbon content and vegetable yield are enhanced through long-term organic cultivation in greenhouses, primarily by increasing the proportion of small macro-aggregates.

The importance of frailty in older people is getting constant recognition as an important aspect both in terms of public health, as well in personal level for the appropriate management of an older person health condition. This is reflected by the continuously increasing number of research studies carried out in several settings across different countries. Sometimes this is very solid, but in other cases there is a considerable gap in terms of accurate and well grounded documentation of frailty status. This is the case in Greece, where we are missing clinically validated tools to approach frailty. We are missing frailty screening tools, such as for instance PRISMA 7, the gold standard tool of Fried criteria is somehow problematic since the question referring to physical activity originates from a questionnaire that has not been translated and validated, while Clinical Frailty Scale has been validated for the translation but not for the capacity to detect frailty. Aim of this study is to validate these tools for their accuracy to detect frailty by using a measurable index of frailty, previously proposed for use in clinical studies: the Short Physical Performance Battery (SPPB). 74 male and female participants have been evaluated for their frailty status using different tools. We observed that PRISMA 7 translation detects frailty only when one question is removed at a cut-off of ≥ 2 and indicated a sensitivity of 88.1%, and specificity of 99.9% with a good correlation with SPPB measurements (r = 0.858; p < 0.001). When CFS was validated using SPPB it demonstrated a very good correlation (r = -0.838; p < 0.001 respectively) as it was the case for the modified Fried Criteria (r = -0.725; p < 0.001). All items demonstrated a good correlation between them. We can here propose that we can accurately assess frailty status in the community setting by using a modified version of Fried criteria, Clinical Frailty Scale translation in Greek and we can screen for frailty by using the Greek translation of PRISMA 7 only after removing the item 6 of the questionnaire.

Scedosporium species are human pathogenic fungi, responsible for chronic, localised, and life-threatening disseminated infections in both immunocompetent and immunocompromised individuals. Diagnosis of Scedosporium infections currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Scedosporium-specific biomarkers. Here we report the development of a rapid (30 min) and sensitive (pmol/L sensitivity) lateral-flow device (LFD) test, incorporating a Scedosporium-specific IgG1 monoclonal antibody (mAb), HG12, which binds to extracellular polysaccharide (EPS) antigens of between ~15 kDa and 250 kDa secreted during hyphal growth of the pathogens. The test is compatible with human serum, and allows the detection of the Scedosporium species most-frequently reported as agents of human disease (Scedosporium apiospermum, Scedosporium aurantiacum, and Scedosporium boydii), with limits of detection (LOD) of the EPS biomarkers in human serum of ~0.81 ng/mL (S. apiospermum), ~0.94 ng/mL (S. aurantiacum), and ~1.95 ng/mL (S. boydii). The Scedosporium-specific LFD (ScedLFD) test therefore provides a potential novel opportunity for the detection of infections caused by different Scedosporium species.

Classroom resource allocation is a challenging problem in educational institutions. The use of cloud computing can aid in the optimization of this process by allowing resource providers to allocate resources to users in a timely and efficient manner. In this paper, we propose a modified Salp Swarm Algorithm (SSA) to optimize the allocation of classroom resources. The proposed approach involves generating a population of salps representing potential solutions to the resource allocation problem and updating the positions of the salps iteratively based on a fitness function and mathematical equations. We conducted simulations of the proposed algorithm on various numbers of tasks and sources to evaluate its performance. The results indicate that the modified SSA algorithm can efficiently allocate classroom resources, achieving lower completion time of tasks (makespan) with lower costs. This paper contributes to the literature by introducing an effective approach to solve the classroom resource allocation problem.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

Bacterial endophytes (120) were isolated from six halophytes (Distichlis spicata, Cynodon dactylon, Eragrostis obtusiflora, Suaeda torreyana, Kochia scoparia, and Baccharis salicifolia). These halophiles were molecularly identified and characterized with or without NaCl conditions. Characterization was based on tests such as indole acetic acid (IAA), exopolysaccharides (EPS), and siderophores (SID) production; solubilization of phosphate (P), potassium (K), zinc (Zn), and manganese (Mn); mineralization of phytate; enzymatic activity (acid and alkaline phosphatase, phytases, xylanases, and chitinases) and mineralization/solubilization mechanisms involved (organic acids and sugars). Eleven halophiles (tolerated NaCl 2.5 M) were identified as Oceanobacillus sp. (1), Bacillus sp. (2), Nesterenkonia sp. (3), Bacillus velezensis (4), Halobacillus sp. (5), Oceanobacillus sp. (6), B. velezensis (7) Halomonas sp. (8), B. pumilus (9), Pseudomonas sp. (10) and Oceanobacillus sp. (11). Biochemical responses of nutrient solubilization and enzymatic activity varied between bacteria and the presence of NaCl. Organic acids were involved in P-mineralization and nutrient solubilization. Tartaric acid was common in the solubilization of P, Zn, and K. Maleic and vanillic acid were only detected in Zn and K solubilization, respectively. Moreover, sugars appeared to be involved in the solubilization of nutrients; fructose was detected in solubilization tests. Therefore, these bacteria should be tested as a consortium to mitigate saline stress in glycophytes under a global climate change scheme that threatens to exacerbate soil salinity.

Pathogenicity of many bacteria including Bacillus cereus and Staphylococcus aureus depends on pore-forming toxins (PFTs), which cause lysis of host cells by forming pores in membranes of eukaryotic cells. Bioinformatic analysis revealed in over 600 PFTs a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus, which we designated as “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them –HlyII and cytotoxin K2 (CytK2), – are synthesized in Bacillus cereus sensu lato; the third – S. aureus α-toxin (Hla) – is the most investigated representative of the family. Protein modeling showed certain amino acids of homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide DSFNTFYGNQLFMK as part of homologous peptide. The HlyII, CytK2 and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of the work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular docking were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating noncompetitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. Simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

Additive manufacturing (AM) techniques are widely investigated for the cost-effective use of titanium (Ti) alloys in various aerospace applications. One of the AM techniques developed for such applications is plasma transferred arc solid free-form fabrication (PTA-SFFF). Materials manufactured through AM techniques often exhibit anisotropies in mechanical properties due to the layer-by-layer material build. In this regard, the present study investigates the isothermal directional fatigue of Ti-TiB metal matrix composite (MMC) manufactured by PTA-SFFF. This investigation includes rotating beam fatigue test, electron microscopy, and fatigue calculations. The fatigue experiments were performed at 350 ºC using specimen with the test axis oriented diagonally (45º) and parallel (90º) to the AM builds directions. The fatigue values from the current experiments along with literature data find that Ti MMC manufactured via PTA-SFFF exhibit fatigue anisotropy reporting highest strength in 90º and lowest in perpendicular (0º) AM build directions. Further, the electron microscopy investigations on 0º, 45º, and 90º AM build specimens reveal frequent TiB clusters in all three AM build directions and suggest that the spread of these TiB clusters play a role in fatigue anisotropy. Moreover, the fatigue calculations were performed using both the Paris’ and recently reported modified Paris’ equations. Comparison of R^2 values for these calculations show that modified Paris’ equation predicts the fatigue life of AM Ti-TiB MMC more accurately than the Paris’ equation.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

This study explores optimizing Synthetic Aperture Radar (SAR) satellite constellation scheduling for multi-imaging missions in densely targeted areas using an in-house developed Modified Dynamic Programming (MDP) algorithm. By employing Mixed-Integer Linear Programming (MILP) to define the mission planning problem, the research aims to maximize observation of high-value targets within restricted planning horizons. Numerical simulations, covering a wide range of target numbers and satellite configurations, reveal the MDP algorithm’s superior mission allocation efficiency, enhanced success rates, and reduced revisit times, compared to the Greedy algorithm. The findings underscore the MDP algorithm’s improved operational efficiency and planning robustness for complex imaging tasks, demonstrating significant advancements over traditional approaches.

This study examined the tourism spatial distribution of nine cities in the Fujian province and assessed the impacts of COVID-19. The modified gravity model found that it was widely dispersed, with uneven and relatively independent tourism development in different cities. The social network analysis showed that tourism connections across cities were significantly reduced after the pandemic. The impacts of brand awareness and transport accessibility on spatial networks were positive in pre-pandemic but became negative during the pandemic. In contrast, tourist volume had negative impacts on spatial networks in pre-pandemic but had positive ones during the pandemic. Tourism resources and market performance had significantly positive impacts in the post-pandemic era. These findings provide advice on tourism recovery and destination management in coping with future critical events. It also contributes to the theoretical gravity framework in tourism and the research scope of the social networks analysis at the city level.

Plants significantly shape root-associated microbiota, making rhizosphere microbes useful environmental indicator organisms for safety assessment. Here, we report the pyrosequencing of the bacterial 16S ribosomal RNA in rhizosphere soil samples collected from transgenic cry1Ab/cry1Ac Bt rice Huahui No. 1 (GM crop) and its parental counterpart, Minghui63. We identified a total of 2,579 quantifiable bacterial operational taxonomic units (OTUs). Many treatment-enriched microbial OTUs were identified, including 14 NonGM-enriched OTUs and 10 GM-enriched OTUs. The rhizosphere microbiota communities were influenced more strongly by growth in the field than by rice varieties. Furthermore, Huahui No. 1 transgenic Bt rice had a greater impact on the rhizosphere bacterial communities than Minghui63. Early developmental stages of the transgenic Bt rice had a significant impact on many Bacillaceae communities. While soil chemical properties were not significantly altered by the presence of transgenic Bt rice, we found peak expression level of Bt proteins during the seedling stage, which may be an intriguing factor for bacterial diversity variations. Based on these findings, we conclude that transgenic Bt rice has a significant impact on root-associated bacteria. This information may be leveraged in future environmental safety assessments of transgenic Bt rice varieties.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

Nereis as a mudflat organism has a variety of uses, in the history of China as a Chinese herbal record, because of its body contains rich amino acids, fatty acids and other nutrients, it can be used for therapeutic treatment and treatment can also be used as health care products. acids, fatty acids and other nutrients, it can be used for therapeutic treatment and treatment can also be used as health care products. In modern times, more and more researchers have studied the protease extract of Nereis as a mudflat organism. In modern times, more and more researchers have studied the protease extracted from the body of nereis and found that there are a variety of functional proteins in nereis, including superoxide dismutase, superoxide dismutase, superoxide dismutase and superoxide dismutase. More and more researchers have studied the proteases extracted from the body of nereis and found that there are a variety of functional proteins in nereis, including superoxide dismutase, adenylate cyclase, glycosidase, and plasminase. In this paper, the functional proteases in the extracts of nereis were summarized, and the functions and characteristics of proteases in nereis were discussed from the perspective of molecular structure.

Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N2-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACEi-induced angioedema (ACEi-AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACEi induced-AE is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, the early clinical recognition and the ACEi discontinuation are the treatment of choice for the long term management of ACEi-AE.

If visible matter alone is present in the Universe, General Relativity (GR) and its Newtonian weak field limit cannot explain several pieces of evidence, from the largest to the smallest scales. The most investigated solution is the cosmological model ΛCDM, where GR is valid and two dark components are introduced, dark energy and dark matter, to explain the ∼70% and ∼25% of the mass-energy budget of the Universe, respectively. An alternative approach is provided by modified gravity theories, where a departure of the gravity law from ΛCDM is assumed and no dark components are included. This work presents refracted gravity (RG), a modified theory of gravity formulated in a classical way where the presence of DM is mimicked by a gravitational permittivity ϵ(ρ) monotonically increasing with the local mass density ρ, which causes the field lines to be refracted in small density environments. Specifically, the flatter the system the stronger the refraction effect and, thus, the larger the mass discrepancy if interpreted in Newtonian gravity. RG presented several encouraging results in modelling the dynamics of disk and elliptical galaxies and the temperature profiles of the hot X-ray emitting gas in galaxy clusters and a covariant extension of the theory seems to be promising.

Amylin, also known as islet amyloid polypeptide (IAPP), is a metabolic homeostasis-related hormone that is produced and released by the β cells of the pancreas, the same cells that produce insulin. Insulin-degrading enzyme (IDE) is a protease enzyme that plays an essential role in the breakdown and degradation of various peptides, including insulin and amylin. Direct binding & interaction between amylin and IDE is inextricably linked to the degradation of amylin, and research and development effort in this area is crucial to understand the potential therapeutic implications of disrupting the IDE-amylin interaction in the context of conditions where metabolic homeostasis needs to be regulated, such as diabetes and obesity. Here, this article incorporates currently available experimental complex structure of amylin and IDE, and delves deep into the interstructural biophysics underlying the binding interface of the two interacting partners. With a set of comprehensive structural biophysical analysis, this article identified an intriguing region of high electrostatic potential indicative of strong binding sites between the first N-terminal lysine (Lys1, K1) residue of amylin and Glu341 (E341) of IDE. This unique electrostatic hotspot presented herein paves the way for the rational design of drug-like small molecules that can selectively disrupt this interaction, offering a targeted therapeutic strategy for improved metabolic homeostasis, particularly for patients with diabetes and obesity.

Blocking the interaction of the SARS-CoV-2 spike protein with the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim in this study was to explore the efficacy of TCM treatments for SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. The antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis was found to be effective against SARS-CoV-2 infection through affecting the interaction of viral spike protein with the hACE2 protein. The active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside, respectively, found in S. baicalensis, exhibited strong inhibitory activities, targeting the viral spike protein or hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors of the interaction of the Omicron spike protein and hACE2 receptor from S. baicalensis. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

The architecture, organization and functioning of biocatalytic reaction networks, which are coded in the cell specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. The knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary which is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims at outlining advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.

This article addresses the challenge of simulating rainstorm waterlogging in urban-scale areas where reliable drainage pipe network data is often lacking. Despite existing methods attempting to tackle this issue, there remains a gap in effectiveness. We present a novel approach, the Modified Equivalent Infiltration (MEI) method, building upon the foundation of the Equivalent Infiltration (EI) method. The study focuses on the outer ring area of Shanghai, utilizing data from the "In-Fa" typhoon period for simulation and comparison. Our findings reveal that the MEI method, requiring the same data inputs as the EI method, surpasses its predecessor in both principle and simulation results. Additionally, the MEI method demonstrates robustness in handling rainstorm waterlogging scenarios.

SARS-CoV-2 virulence is known to increase with lowering of environmental temperature and solar ultraviolet radiation; therefore, we have focused our real-world nationwide study concerning with COVID-19 trends and dynamics on the coldest seasons of the year in Italy, the Western country hardest hit at the onset of the pandemic, comparing the autumn-winter of 2020 (before mass vaccination but when the emergency machinery was fully operative in terms of tracing and swabs) with the autumn-winter of 2021 (after mass vaccination), and analyzing the mortality burden by age groups and life stages in the years 2019 (pre-COVID-19), 2020 (before mass vaccination) and 2021 (after mass vaccination). Methods: During the state of national health emergency, the Civil Defense Department released the aggregate data coming from the Higher Institute of Health, the Ministry of Health, the Italian Regions, and the Independent Provinces, to inform the population (58.85 million people) about the pandemic situation, daily. Among these data there were the number of contagions, performed swabs, hospitalizations in Intensive Care Units (ICU), non-ICU patients, and deaths. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the autumn-winter of 2020 with the autumn-winter of 2021. Moreover, we have extracted from the database of the National Institute of Statistics the total number of annual deaths in Italy during the years 2019, 2020 and 2021, comparing them to each other in order to evaluate the mortality burden attributable to COVID-19. Results: From the autumn-winter of 2020 to the autumn-winter of 2021, the contagions increased by ≈285%, however against a ≈290% increase in the performed swabs; therefore, the mean positivity rate passed from 8.74% before mass vaccination to 8.59% after mass vaccination. The unprecedent vaccination campaign allowed a ≈251% abatement in COVID-19 deaths, and a reduction of ≈224% and ≈228% in daily ICU and non-ICU hospitalizations due to COVID-19, respectively. Regarding COVID-19 deaths, in 2020 there was a mortality excess of ≈14.3% quantifiable in 105,900 more deaths compared to 2019, the pre-COVID-19 year; 103,183 out of 105,900 deaths occurred in older adults (≥60 years), which is equivalent to ≈97.4%, while in adults over 50, the segment of population just below older adults, in 2020 there were 2807 more deaths than in 2019. Surprisingly, from the analysis of our data, it is emerged that under the age of 40 in the years 2019, 2020 and 2021 there were 7103, 6808 and 7165 deaths, respectively. This means that in subjects under 40 during 2020 there were 295 fewer deaths than in 2019, while during 2021 there were 357 more deaths than in 2020, equivalent to ≈5.2% more. Conclusions: COVID-19 is a potential life-threatening disease mainly in older adults, as they are the most vulnerable due to inherent immunosenescence and inflammaging. Extensive vaccination in this segment of population with up-to-date vaccines is the means to reduce deaths, hospitalizations, and ICU pressure in the public interest. In the event of future threats, a new mass vaccination campaign must not be implemented without taking into account the individual age; it should primarily be aimed at people over 60 and at patients of any age with immune deficits, and secondly at people over 50. COVID-19 vaccination shows a favorable benefit-risk balance in older adults, while this balance falls under the age of 40; this younger segment of population should be therefore exempt from any mandatory vaccination.

Introduction: The viral respiratory disorder known as severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus. End of May 2021, there have been over 170 million reported cases and more than 3.53 million deaths worldwide. In the field of cardiovascular performance, the shock index (SI) is a simple and widely used formula that measures the physiological response prior to systemic hypotension. It is obtained by dividing the heart rate by the systolic blood pressure. Another parameter, the modified shock index (MSI), is defined as the ratio of heart rate to mean arterial pressure (MAP). Methods: In this retrospective study, we examined the data of COVID-19 patients who were admitted to the ICU between June 1st, 2020, and January 31st, 2021. The patient details were collected from the Medical Records Department (MRD) in a tertiary care center. A case-recorded proforma was used to record the patient information, which was then analyzed using SPSS software. Results: The mean age of the patients was 67 years, consisting of 64 males (68.9%) and 29 females (31.1%). The standard deviation was calculated as 13.557. Among the patients, the minimum age recorded was 28, while the maximum age was 97. Patients with known CAD (Coronary Artery Disease) had a higher mortality rate among comorbidities. The p-value for Shock Index and Mortality Status was 0.205 (with an alpha value greater than 0.05), indicating no significant association. However, the modified shock index (MSI) showed a significant association with mortality status. The Pearson chi-square value for MSI and Mortality Status was 4.19, with a p-value of 0.041 (with an alpha value less than 0.05). These results suggest that there is a higher risk of mortality for patients with a Modified Shock Index of less than 0.7 or greater than 1.3. The MSI Odds ratio was found to be 4.500, indicating that such patients have a 4.5 times higher risk of mortality compared to others. Conclusion: In conclusion, our study found that there is no significant association between the Shock Index (SI) and mortality, as the p-value was greater than 0.05. However, the Modified Shock Index (MSI) showed a significant association with mortality status, with a p-value less than 0.05. This suggests that patients with a Modified Shock Index less than 0.7 or greater than 1.3 are at a higher risk of mortality. It is important to consider these findings when assessing the prognosis and potential interventions for COVID-19 patients.

Flower color is an important ornamental feature, often modulated by the contents of flavonoid. Chalcone synthase is the first key enzyme in the biosynthesis of flavonoid, but little is known about the role of R. delavayi CHS in flavonoid biosynthesis. In this paper, three CHS genes (RdCHS1-3) were successfully cloned from R. delavayi flowers. According to multiple sequence alignment and phylogenetic analysis, only RdCHS1 contained all the highly conserved and important residues, and classified into the cluster of bona fide CHSs. Thus RdCHS1 was then subjected for further functional analysis. Real-Time PCR analysis revealed that transcripts of RdCHS1 was the highest in leaves and lowest in root, did not match the anthocyanin accumulation patterns during flower development. Biochemical characterization displayed that RdCHS1 could catalyze p-coumaroyl-CoA and malonyl-CoA molecules to produce naringenin chalcone. Physiological function of RdCHS1 was checked in Arabidopsis mutant and tobacco, the results showed RdCHS1 transgenes could recover the color phenotypes of tt4 mutant and made tobacco flower color from pink to dark pink through modulating the expression of endogenous structural and regulatory genes in tobacco. All these results demonstrated that RdCHS1 is a bona fide CHS and contribute to flavonoid biosynthesis in R. delavayi.

Experimental tests and numerical analyses were carried out on short, thin-walled channel columns with modified cross-sectional shape. The columns were loaded with an axial compressive force applied at the center of gravity of the cross section. Tests were carried out on a universal testing machine, while numerical analyses were performed in ANSYS software. The purpose of the tests was to determine the values of critical forces for the compressed columns and to determine the values of maximum forces at which failure of the columns occurs. Critical forces were determined based on the strain-averaged method. Based on the study, it was found that the strength and resistance to loss of stability of columns is primarily affected by their stiffness, and therefore by the shape of the cross-sections. In addition, for short columns, it seems more important to determine the value of maximum forces than the values of critical forces.

The definitive negative results of various direct searches for dark matter particles and non-observation of them has increasingly indicated that we should consider alternate models like the Modification of Newtonian Dynamics (MOND) and Modification of Newtonian Gravity (MONG). It is puzzling how the Oort cloud, despite its great distance from the Sun, is gravitationally bound to the Sun’s gravity. In this work, we suggest that this could be explained by the modifications to Newtonian dynamics (MOND) and to gravity (MONG).

: Protease-producing yeasts were isolated from potato wastes and screened for protease production on skim milk agar plates The best producer of protease isolate was identified as Clavispora lusitaniae. The strain showed better enzyme production using tomato pomace and bread waste mix as a solid fermentation substrate. The optimized conditions improved enzyme activity and showed a maximal production of 33450±503 IU/g compared with the initial activity of 11205,78 ±360 without medium optimization. A threefold increase in protease activity after medium optimization proved the reliability of using the PBD and CCD design. A 19.76-fold purified enzyme and a yield of 32.94% were obtained after purification. The protease showed maximum activity at pH 4 and 60 °C and was resistant to Tween 20, Tween 40, SDS, and β-mercaptoethanol, Ca2+, and Mg2+ stimulated it. The protease activity was strongly inhibited in the presence of urea, and EDTA. The results revealed Clavispora lusitaniae protease's ability to degrade wheat seeds and flour gluten by 98.7% and 97% respectively under pH 4 for 24 hours at 40 °C. According to this study, this enzyme could be a potential candidate for the food industry, particularly for treating wheat seed and flour to reduce the immunogenicity of gluten.

Background and Objectives: This study aimed to evaluate the effects of subtalar joint axis-based balance exercises on the anterior talofibular ligament (ATFL) thickness, ankle strength, and ankle stability after an arthroscopic modified Broström operation (AMBO) for chronic ankle instability (CAI). Materials and Methods: The study included 47 patients diagnosed with CAI who underwent AMBO and were randomly divided into three groups: control (n=11), general balance exercise (n=17), and subtalar joint axis balance exercise (n=19), regardless of the affected area. Participants in the exercise rehabilitation group performed exercises for 60 min twice a week for 6 weeks, starting 6 weeks after AMBO. ATFL thickness, ankle strength, and ankle dynamic stability were measured using musculoskeletal ultrasonography, Biodex, and Y-balance test, respectively, before and after treatment. Results: Compared with the remaining groups, the subtalar joint axis balance exercise group had reduced ATFL thickness (p = 0.000), improved ankle strength for eversion (p = 0.000) and inversion (p = 0.000), and enhanced ankle stability (p = 0.000). Conclusions: The study results suggests that subtalar joint axis-based balance exercises may contribute to the early recovery of the ankle joint after AMBO.

Schiff bases attract research interest due to their applications in chemical synthesis and medicinal chemistry. In recent years, benitrobenrazide and benserazide containing imine moiety, have been synthesized and characterized as promising inhibitors of hexokinase 2 (HK2) an enzyme overexpressed in most cancer cells. Both compounds possess a common structural fragment, a 2,3,4-trihydroxybenzaldehyde moiety connected through hydrazone or hydrazine linker with acylated on N’-nitrogen atom by serine or 4-nitrobenzoic acid fragment. To avoid presence of toxicophoric nitro group in benitrobenrazide molecule we introduced common pharmacophores 4-fluorophenyl or 4-aminophenyl substituents. Modification of benserazide regards an introduction of other endogenous amino acids instead of serine. Herein we report the synthesis of benitrobenrazide and benserazide analogues and preliminary results of inhibitory activity against HK2 evoked by these structural changes. The derivatives contain a fluorine atom or amino group instead of a nitro group in BNB, exhibited the most potent inhibitory effects against HK2 at a concentration of 1 µM, with HK2 inhibition rates of 60% and 54%, respectively.

We show that the entropy or information flow of a gravitational system constrains the dependence of gravitational force on radial distance r which for very large r is equivalent to gravity in two dimensions. This explains the "origin" of dark matter and provides a natural solution to the problem of flat rotation curves of galaxies at very large distances and a larger deflection angle for a gravitational lens.

Generalized distributions have been studied a lot recently because of their flexibility and relia-bility in modeling lifetime data. The two-parameter exponentially-modified logistic distribution is a new flexible modified distribution that was introduced recently. It is regarded as a strong competitor for widely used classical symmetrical and non-symmetrical distributions such as normal, logistic, lognormal, and log-logistic. In this study, the unknown parameters of the dis-tribution are estimated using the maximum likelihood method. The Grey Wolf Optimization al-gorithm, which is a new meta-heuristic algorithm, is applied in order to solve the nonlinear like-lihood equations of the study model. The performance of the Grey Wolf Optimization method is compared to that of the other meta-heuristic algorithms used in this study, which include the Whale Optimization Algorithm, the Sine Cosine Algorithm, and the Particle Swarm Optimiza-tion Algorithm. The efficiencies of maximum likelihood estimates for all algorithms are com-pared via an extensive Monte-Carlo simulation study. The likelihood estimates for the location α and scale β parameters of the exponentially-modified logistic distribution developed with the Grey Wolf Optimization algorithm are the most efficient among others, according to simulation findings. Four real datasets are analyzed to show the flexibility of this distribution.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for survival of cancer patients. Therefore, extension and increasing quality of life of PC patients can be achieved by broadening the Cancer Screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need in standard, sensitive, robust, and commonly available screening and diagnosis tools for identification of early signs of cancer pathologies. In this respect, “Holy Grail” of cancer researchers and bioengineers for decades have been molecular sensing probes that would allow diagnosis, prognosis, and monitoring of cancer diseases by their interaction with cell-secreted and cellassociated PC biomarkers, e.g. PSA and PSMA correspondinly. At present, most PSA tests are performed at centralized laboratories using high throughput Total PSA immune analyzers which are suitable for dedicated laboratories and are not readily available for the broad health screening. Therefore, the current trend in detection of PC is developments of the portable biosensors for mobile laboratories and individual use. Phage display since its conception by George Smith in 1985 has emerged as a premier tool in molecular biology with widespread applications. This review describes how the paradigm of molecular evolution and phage display revolutionized the methods of early diagnosis and monitoring of PC.

In this paper, we examine a modified Friedmann model designed to explain cosmic structures and late-time accelerated expansion of the universe, grounded in the spatial distribution of luminous matter. Through comprehensive simulations of our universe, we observe a notable surge in the formation rate of galaxies at redshift z≈1, characterized by a peak expansion rate in cosmic structures formed at z ≈0.9, reaching its zenith at z ≈2. Subsequently, a transition occurs before the onset of dark matter-induced accelerated expansion. The acceleration of the universe stands as an entrenched and virtually model-independent theoretical tenet, resilient to the ongoing debate surrounding the enigma of dark energy. A distinctive redshift transition zone marks the shift from cosmic deceleration to accelerated expansion. The transition is proportional to matter density and contingent upon the geometry of the universe. The influence of the cosmological constant on the evolution of cosmic structures in the CDM paradigm appears insufficient in curtailing the efficiency of late-time structure formation compared to the observed values in the modified model

This article is devoted to overcoming the contradiction between the problem of maximizing the extraction of wind energy as the goal of optimizing wind turbines, and the use of traditional methods based on criteria for the aerodynamic quality of the blades. A modified technique is considered in which the optimization criterion is the directly extracted flow power. It is based on pulse theory methods that use specific power as an optimization criterion. A comparative analysis of the energy efficiency of different types of turbines is carried out, and the effects of blade inversion are considered. A method for calculating multi-rotor turbines based on the concept of uniform power distribution is presented. The compatibility of proprietary and traditional methods is considered by comparing the results of numerical experiments with calculated and experimental data from sources. Optimization computational algorithms generate data from numerical experiments and determine optimal parameter configurations for the turbines under consideration. It is shown that orthogonal Darrieus turbines in high-speed mode provide energy efficiency comparable to collinear turbines, and multi-rotor turbines with power uniformly distributed over the working section are not inferior in energy efficiency to basic turbines, with linear blade velocities halved.

The current communication presents the application of a consolidated model combination strategy to analyze the medium-term carbon fluxes in two Mediterranean pine wood ecosystems. The modelling strategy is based on the use of a NDVI-driven parametric model, Modified C-Fix, and of a bio-geochemical model, BIOME-BGC, the outputs of which are combined taking into account the actual development phase of each ecosystem. The two pine ecosystems examined correspond to an old-growth forest and to a secondary succession after clearcuts, which differently respond to the same climatic condition during a ten-year period (2013-2022). Increasing dryness, in fact, exerts a fundamental role in controlling the gross primary and net ecosystem production of the mature stand, while the effect of forest regeneration is prevalent for the uprising of the same variables in the other stand. In particular, the simulated net carbon exchange fluctuates around 200 g C m-2 year-1 in the first stand and rises to over 600 g C m-2 year-1 in the second stand; correspondingly, the accumulation of new biomass is nearly undetectable in the former case while becomes notable in the latter. The study therefore supports the potential of the applied strategy for predicting the forest carbon balances consequent on diversified natural and human-induced factors.

The aim of this study was to assess and contrast the effects on the vertical marginal fit of full contour CAD/CAM generated monolithic zirconia crowns pre- and post-cementation of employing chamfer finishing line designs with various occlusal reduction schemes (planar and flat) and cements. Material and Method: Forty sound human maxillary first premolars were selected for this study. Samples will be divided into two main groups of twenty samples in each group according to the occlusal reduction scheme: Group A: chamfer finishing line design with planar occlusal reduction scheme. Group B: chamfer finishing line design with flat occlusal reduction scheme. Each main group will be subsequently separated into two smaller groups based on the kind of cement that was utilized (n=10) Subgroup A1: crowns will be cemented by using resin-modified Glass Ionomer cement (Fuji Plus). Subgroup A2: crowns will be cemented using a Universal adhesive system (Duo Estecem II). Subgroup B1: crowns will be cemented by using Fuji Plus. Subgroup B2: crowns will be cemented using a Duo Estecem II. Result: Marginal gaps were measured at 4 indentations, using a Dino light-stereomicroscope (230X). Paired T-tests and student t-tests analyzed the data. Prior to cementation, subgroup A1 scored the lowest mean of vertical marginal gap values (80.284±23.021), while subgroup B2 scored the highest mean (118.597±9.956); following cementation, subgroup A1 scored the lowest mean of vertical marginal gap values (95.45±17.598), and subgroup B2 scored the highest mean of vertical marginal gap values (134.806 ±8.114). Chamfer finishing line design with a planar occlusal reduction scheme could be a preferable occlusal reduction scheme.

Transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in root and shoot of Populus euphratica (salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba ‘717-1B4’ (P. × canescens) increased salt sensitivity, which was reflected in plant growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich target mRNAs that physically interact with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in transgenic poplar. Particularly, PeGRP2 negatively affected the stability of target mRNAs encoding photosynthetic proteins (PETC and RBCMT), antioxidant enzymes (SOD[Mn], CDSP32 and CYB1-2), ATPases (AHA11, ACA8 and ACA9), and Na+/H+ antiporter (NHA1). This resulted in (i) a greater reduction in Fv/Fm, YII, ETR and Pn, (ii) a less pronounced salt activation of antioxidative enzymes, and (iii) a reduced ability to maintain Na+ homeostasis in transgenic poplars during long-term salt stress, leading to a lowered ability to tolerate salinity stress.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) utilizes Angiotensin Converting Enzyme 2 (ACE2) as its main receptor for cell entry. We have bioengineered a soluble ACE2 protein termed ACE2 618-DDC-ABD that has increased binding to SARS-CoV-2 and prolonged duration of action. Here we investigated the protective effect of this protein when administered intranasally to k18-hACE2 mice infected with the aggressive SARS-CoV-2 delta variant. k18-hACE2 mice were infected with the SARS-CoV-2 delta variant by inoculation of a lethal dose (2x104 PFU) and followed for up to 14 days. ACE2-618-DDC-ABD (10mg/kg) or PBS was administered intranasally six hours prior and 24 and 48 hours post viral inoculation. All animals in the PBS-control group had succumbed to the disease on day 7 post infection (0% survival) whereas, by contrast, there was only one casualty in the group that received ACE2-618-DDC-ABD (90% survival). Mice in the ACE2-618-DDC-ABD group had minimal disease as assessed by a clinical score and stable weight and both brain and lung viral titers were markedly reduced. These findings demonstrate the efficacy of a bioengineered soluble ACE2 decoy with extended duration of action in protecting against the aggressive delta SARS-CoV-2 variant. Together with previous work these findings demonstrate the universal protective potential against current and future emerging SARS-CoV-2 variants.

The impact of long-term soil and crop management practices on soil biological and chemical properties in oilseed brassica-based production systems were deliberated for holistic soil health improvement in the present study. Different tillage, crop residue re-cycling and cropping systems were studied for 5-years in 0-15 and 15-30 cm soil profiles. No-till permanent beds with crop residue (PB+R) noticeably improved soil organic carbon (SOC), microbial biomass carbon (MBC), enzymes [dehydrogenase (DHA) and alkaline phosphatase (AlP)], nitrogen fractions (available, nitrate and total), and available phosphorus and potassium content in both the soil layers compared to conventional tillage without crop residues. Though, the plow soil layer (0-15 cm) showed higher concentration of soil carbon, enzymes, N fractions and available P than in the sub soil (15-30 cm). The dynamic soil biological and chemical properties were also varied with the crop stage, and recorded higher MBC at 30 days, SOC and enzymatic activities at 60 days, and N fractions and available P and K at harvest of mustard crop. Green gram-mustard rotation showed higher values of biological and chemical parameters. Thus, the legume-based mustard crop rotation following no-till permanent beds and residue re-cycling found holistic in improving soil health, and nutrient cycling.

To study the mechanism of light color on a sea urchin (Tripneustes gratilla), blue light (B, λ450nm), yellow light (Y, λ585-590nm), red light (R, λ640nm), green light (G, λ510nm), white light (W, λ400-780nm) and darkness groups (H) were set up in a seawater recirculating aquaculture system. Six different LED light color treatment groups with a photoperiod of 12 L:12 D were tested for 30 d to investigate the effects of different light colors on the feeding, growth and enzyme activities of T. gratilla (142.45±4.36 g). We found that varying LED light colors significantly impacts the feeding, growth, and enzyme activity of T. gratilla. Notably, the sea urchins in group B exhibited better growth with a weight gain rate of 39.26%, while those in group R demonstrated poorer growth with a weight gain rate of only 26%. The feeding differed significantly (P<0.01) between groups B and R, with group B consuming the highest daily intake (6.03±1.69 g) and group R consuming the lowest (4.54±1.26 g). Throughout the three phases, there was no significant change in the viability of the AMS (P>0.05). Conversely, pepsin viability significantly increased (P<0.01) in group B. LPS viability remained consistently at the lowest level, with no notable differences in group W from those observed in group B. In group R, both AMS and pepsin viability remained lower, whereas lipase viability was noticeably higher in each phase compared to group B (P<0.01). Regarding antioxidant enzymes, group R exhibited a trend of initially increasing and then decreasing CAT, SOD, and GSH-PX activities, particularly during the third stage (15-30 d), with a significant decrease observed in antioxidant enzyme activities (P<0.01). The outcomes suggest that blue light positively affects the growth, feeding, digestion, and antioxidant capacity of T. gratilla in comparison to other light environments, whereas the red light has an inhibitory impact.

The increasing enhancement in the modulation accuracy of spatial light modulators has garnered significant attention towards real-time control technology for light fields based on these modulators. It has been empirically demonstrated that this technology possesses a remarkable capability to generate vector beams with arbitrary complex amplitude distributions. Nevertheless, past studies indicate that the generation of only one vector beam at a time has been observed. The simultaneous generation of numerous vector light fields can give rise to several challenges, including compromised picture quality, limited single mode operation, and intricate optical path configurations. In pursuit of this objective, we present a novel methodology that integrates the coding methodology of modified off-axis interferometric holography with the idea of optical superposition. This technique facilitates the concurrent generation of several vector beams. In this study, we present a demonstration of the simultaneous creation of twelve vector beams using a single spatial light modulator (SLM) as a proof of concept. Significantly, this technology has the ability to generate an unlimited quantity of vector light fields concurrently, under the assumption that the resolution of the SLM does not impose any limitations. The findings indicate that the imaging quality achieved by this technology is of a high standard. Furthermore, it is possible to separately control the beam waist radius, topological charge, polarization order, and extra phase of each beam.

‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear encoded mitochondrial peptidase that has been conserved through evolutionary history as has its target enzyme ‘mitochondrial glycerol phosphate dehydrogenase 2’ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear encoded mitochondrial respiratory related protein cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD-/- KO mouse and in this study EchoMRI analysis found that many organs of the Immp2lKD-/- KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p<0.05). Moreover, all of the organs analysed from the Immp2lKD-/- KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD-/- KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lower in the kidney of the Immp2lKD-/- KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to wildtype when glutamate was used as substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2 we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD-/- KO mice over time. Together these findings suggest that the respiratory related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues in the Immp2lKD-/- KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial encoded cytochrome b (Cyb) in Complex III had been altered as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD-/- KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS) which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD-/- KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD-/- KO mouse displayed a ~27% decrease in total respiration comprised of a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration where the latter was consistent with the decreases in substrate specific mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.

In this work, a ferrocene-containing gallic acid derivative modified carbon nanotubes paste electrode (Gal-Fc-CNT) obtained by simple mechanical mixing was studied for fast simultaneous voltammetric detection of doxorubicin (DOX), capecitabine (CPB) and cyclophosphamide (CPP) as cytostatic index by cumulative signal and selective detection of DOX. The electrochemical behaviors of individual and simultaneous DOX, CPB and CPP studied by cyclic voltammetry (CV) on Gal-Fc-CNT electrode at various pHs and potential ranges allowed the development of simple simultaneous detection method as cytostatic index at pH of 12 using square-wave voltammetry technique operated at modulation amplitude of 100 mV, step potential of 4 mV, frequency of 25 Hz and 100 mV·s−1 potential scan rate that allowed better performance than reported electrodes. Faster and selective detection of DOX with the lowest limit of detection of 75 ng⸱L-1 was achieved using square-wave voltammetry technique operated at modulation amplitude of 100 mV, step potential of 4 mV, frequency of 50 Hz and 200 mV·s−1 potential scan rate. The good results obtained for real tap water assessment indicated the utility of Gal-Fc-CNT paste electrode for practical applications (water samples, pharmaceutical formulations).

The adoption of sustainable forest management practices emerged as a contemporary imperative for forest biodiversity preservation, functional integrity, and mitigation of climate change. Within the spectrum of these practices, thinning is recognized as an environmentally sustainable strategy. The primary objective of thinning is the equitable redistribution of aboveground growth, diverting resources from younger trees to promote the accelerated development of more valuable specimens compared to unthinned forests. Thinning, while fostering aboveground changes, induces substantial alterations in soil chemical and biochemical properties. This review addresses the often-debated consequences of thinning on soil characteristics, focusing on the intricate interplay involving different thinning intensities and their impact on soil chemical and biochemical parameters. Specifically, the analysis delves into the modulation of organic carbon levels, microbial biomass, and enzymes crucial to the organic matter cycle. Two key aspects are scrutinized: firstly, the influence of thinning intensity and the temporal dimension post-thinning on soil properties; secondly, the comparative impact of thinning intensity versus the time elapsed from the thinning event on soil properties and associated biological processes. The findings underscore pivotal insights: a) temporal dynamics significantly affect soil organic matter across broadleaved (excluding beech), coniferous, and mixed forests, manifesting as early as 2-7 years post-thinning; b) thinning intensity, up to a threshold of 50%, enhances soil quality by augmenting organic carbon content, bolstering microbial communities, and amplifying associated enzyme activities. This review consolidates valuable information for forest managers, providing guidance to optimize natural processes in tandem with achieving specific management objectives. By illuminating the nuanced interactions between thinning practices and soil dynamics, this knowledge equips stakeholders to make informed decisions in the pursuit of sustainable forest management and ecological resilience.

Fluorescent labels, especially FRET probes, are promising tools for studying a number of bio-chemical processes. In this paper, we promoted 2 important applications of FRET probes (MUTMAC-R6G and FITC-R6G): i) the formation of micelles from surfactants of various natures and polymers (chitosan – fatty acid), as well as ii) monitoring of enzymatic activity with improved parameters (increased analytical signal and improved selectivity due to shift to the long-wavelength region). The formation of micelles is accompanied by the convergence of fluorophores in the hydrophobic micelle core by a distance closer than in the buffer solution, thus r/R0 (where R0 – Foerster radius) is chosen as an analytical signal of micelle formation, including critical micelle concentration (CMC) and critical pre-micelle concentration (CPMC). The CMC values calculated using FRET probes are in a good agreement with literature data. At the same time, the r/R0 function provides valuable information about the nature and mechanism of micelle formation. With the second analytical application of FRET probes, we considered the optimization of techniques for studying enzymatic activity. The enzyme catalyses the reaction with the release of a fluorescent product, the signal from which may not be enough for detection, or it may be quenched, for example, in the reverse micelles (AOT-octane). Here we have proposed a solution – a FRET probe containing a rhodamine 6G (R6G) acceptor, which allows us to monitor the enzymatic reaction selectively (in the red region, 550-600 nm), and obtain a significantly higher fluorescence yield (potentially from 10 to 250 times). Thus, we have demonstrated a high potential for the FRET probes application as indicators of micelle formation as well as for the study of the enzyme catalytic activity. In the future, the method developed has prospects for application in the visualization of the enzyme functioning in cells due to the shift of the fluorescence signal to the long-wavelength region with an increase in the signal selectivity to suppress autofluorescence.

We performed arthroscopically assisted coracoclavicular (CC) stabilization using a suture button device for modified Neer type IIb lateral clavicle fractures accompanied by CC ligament injury. The purpose of the present study was to evaluate the radiological and clinical outcomes of this procedure. Six consecutive patients with modified Neer type IIb fractures were treated with the technique and followed for 12 months. Postoperative ranges of motion (ROMs) and X-rays were evaluated every 3 months. Shoulder functional scores (University of California Los Angeles score, Japanese Orthopedics Association score), visual analog scale (VAS) scores for pain at rest, at night, and during motion, and VAS score for satisfaction were analyzed at 12 months after surgery. For the clinical outcomes, early ROM recovery and excellent outcomes were achieved. For the radiological outcomes, all patients accomplished bone union, slight superior displacement was noted in the CC distance and Dog Bone distance, and bone hole dilation was observed in the superior coracoid and inferior clavicle, but there were no critical complications. The present findings indicate that arthroscopically assisted CC stabilization with a suture button device for unstable lateral clavicle fractures can produce satisfactory radiological and clinical results.

Debates on climate change challenges around the world are moving in favour of nature-based solutions (NBS) as potential mitigation and adaptation options. Mangroves and associated blue carbon ecosystems are nature-based solutions against sea level rise and other coastal hazards. As such, protecting the existing mangrove forests and restoration of the degraded areas is integral in this aspect. However, conventional mangrove restoration approaches in high-energy areas result in poor performance due to the removal of seedlings by waves. Here, we assessed the efficacy of using modified Riley Encasement Methods in the restoration of eroding intertidal areas of Gazi Bay, Kenya. Vegetation and soil baseline data were collected in 49 square plots of 100m2; established along belt transects perpendicular to the waterline. The following mangrove vegetation data was collected; species composition, tree height (m), and stem diameter (cm); from which the importance value index (IV), basal area and standing density (stems/ha) were derived. Sediment cores were made in the center of each square plot for carbon and grain size analysis. Mangrove (Rhizophora mucronata) planting adopted a randomized complete block design (RCBD) in which the planting area was divided into three blocks (A, B, C). Within each block, treatments (bamboo and different-sized PVC pipes) were randomly assigned locations. Results show that seedlings grown within PVC encasements had high survival and growth rates, surpassing bamboo and control groups. This implies that PVC pipes offer better protection from external factors. These findings are critical in highlighting potential enhancements for the effectiveness of PVC pipes in mangrove restoration. They also reinforce on the need to consider the incorporation of PVC encasements as an alternative mangrove restoration technique in high-energy locations.

Wolfenden and his coworkers observed the astronomical numbers for the catalytic proficiency of some enzymes. We connected that pinnacle of biological evolution to the universal thermodynamic evolution. We added or multiplied a random noise with chosen rate constants to explore the correlation between dissipation and enzyme efficiency for ten enzymes: beta-galactosidase, glucose isomerase, β-lactamases from three bacterial strains, ketosteroid isomerase, triosephosphate isomerase, and carbonic anhydrase I, II, and T200H. The turnover number kcat and catalytic efficiency kcat/KM are proportional to the overall entropy production – the main parameter from irreversible thermodynamics. For most enzymes with the Michaelis-Menten type cycle kinetics, the best increase in the forward kcat/KM follows after increasing the equilibrium constant of substrate-enzyme association. The Discussion section emphasizes the role of biological evolution in harvesting order (high enzyme efficiency) from disorder (high noise and dissipation). It also connects the applications of the maximum partial entropy production theorem in optimizing enzyme kinetics (D. Juretić "Bioenergetics - A Bridge across Life and Universe") with the present total entropy production role analysis. De novo enzyme design and various attempts to speed up the rate-limiting catalytic steps may profit from our theoretical insights.

Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicated its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 38-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. Not only does the heightened specificity of E380Q/S387L improve the hydrolytic activity against pro-immunogenic peptides, but also holds this version of the enzyme as a promising candidate as an oral therapy enzyme for celiac disease.

This paper presents a Modified Gate Diffusion Input (MGDI) design with four inputs for Quantum-dot Cellular Automata (QCA) technology. QCA is a promising nanotechnology that offers benefits such as low power consumption, and high density, making it a potential alternative to CMOS technology. The proposed planar cell design has advantages over previous designs, including a 19% reduction in the number of cells, a 29% reduction in total energy consumption, and a 44% reduction in average energy loss at the same occupancy level. The proposed block is capable of implementing 21 basic combinational functions and various sequential functions. The simulation of functions in 18nm technology and energy consumption calculation indicates that the resulting circuits have improvements of 41%, 27%, 27%, and 20% compared to multiplexers, comparators, four-bit parity circuits, and single-bit memory, respectively. Additionally, the number of cells in the proposed circuits has improved by 10%, 7%, 22%, and 19%, respectively.

A unique method for synthesizing a surface modifier for metallic hydrogen permeable mem-branes based on non-classic bimetallic pentagonally structured Pd-Pt nanoparticles has been de-veloped. It was found that nanoparticles had unique hollow structure. This significantly reduces the cost of their production due to economical use of metal. According to the results of electro-chemical studies, synthesized bimetallic Pd-Pt/Pd-Ag modifier showed excellent catalytic activi-ty (up to 60.72 mA cm–2), long-term stability and resistance to COads poisoning in alkaline oxida-tion reaction of methanol. The membrane with pentagonally structured Pd-Pt/Pd-Ag modifier showed the highest hydrogen permeation flux density up to 27.3 mmol s–1 m–2. Obtained hy-drogen flux density were 2 times higher than that for membranes with classic Pdblack/Pd-Ag modifier and an order of magnitude higher than that for unmodified membrane. Since the rate of transcrystalline hydrogen transfer through a membrane increased, while the speed of transfer through defects remained unchanged, a one and a half times rise in selectivity of the developed Pd-Pt/Pd-Ag membranes was recorded and it amounted to 3514. Achieved results are due to both the synergistic effect of the combination of Pd and Pt metals in the modifier composition and the large number of available catalytically active centers, which are present as a result of non-classic morphology with high-index facets. The specific faceting, defect structure and unusual properties provide great opportunities for the application of nanoparticles in the areas of membrane reac-tors, electrocatalysis, petrochemical and hydrogen industries.

The basis of modern teeth whitening systems is the use of a whitening gel, usually containing hydrogen peroxide or carbamide peroxide. The purpose of our study was to evaluate the effect of chemical and modified office teeth whitening systems on the mineral metabolism of oral fluid and to determine a safer method. The study covered 81 patients aged 22 to 35 years of both sexes with teeth color A2 and darker on the Vita Classic scale. Determination of the concentration of calcium and phosphates in the oral fluid was carried out on a spectrophotometer using ready-made Human kits. Chemical tooth whitening was performed using a gel based on 40% hydrogen peroxide. After the procedure, remineralization therapy with enamel-sealing liquid was performed for 14 days. The obtained results indicate that the most pronounced changes in the content of calcium (+74.4%, p <0.001) and рhosphates (phosphorus) (-23.07%, p <0.001) were observed when using a chemical bleaching system. After the teeth whitening procedure using a modified technique, less pronounced changes in the concentrations of calcium (+29.07, p <0.001) and phosphorus (-14%, p <0.001) were observed. The use of remineralizing agents led to a faster recovery of the initial levels of calcium and phosphates in the oral fluid. Both bleaching systems caused similar changes in the chemical composition of the oral fluid.

Protein–nanoparticle hybridization can ideally lead to novel biological entities characterized by emerging properties, which can sensibly differ from those of the parent components. Herein, the effect of ionic strength on the biological functions of recombinant, His-tagged spermine oxidase (i.e., SMOX) was studied for the first time. Moreover, SMOX was integrated to colloidal surface active maghemite nanoparticles (SAMNs) by direct self-assembly, leading to a biologically active nano-enzyme (i.e., SAMN@SMOX). The hybrid was subjected to an in-depth chemical-physical characterization highlighting that protein structure was perfectly preserved. The catalytic activity of the nanostructured hybrid (SAMN@SMOX) was assessed by extracting kinetics parameters using spermine as substrate and compared to the soluble enzyme as a function of ionic strength. Results revealed that the catalytic function was dominated by electrostatic interactions and that they were drastically modified upon hybridization with colloidal ɣ-Fe2O3. Noteworthy, the affinity of SMOX toward spermine was significantly higher for the nanohybrid at low salinity. The present study supports the vision of using protein–nanoparticle conjugation as a mean for modulating biological functions.

In light of the hazardous effects of global warming brought on by climate change, bioethanol production is one of the key alternatives in which the world has expressed a great deal of interest. Two factors—indigenous production and price—are crucial for bioethanol to be appealing in Africa and, for that matter, Ghana. The objective of this research is to produce bioethanol from cheap lignocellulosic materials using onsite enzymes produced from cassava peels degrading fungi. Due to Ghana's prominent position as one of the leading cassava producers in the world, the study focused on utilizing cassava peels, which are underutilized in the country. The research was conducted in multiple stages. In the first stage, the peels were prepared by washing, drying, and manually crushing them using mortar and pestle. The second stage involved analyzing the chemical composition of the peels, including starch and insoluble fibre, which were determined as Acid Detergent Fiber (ADF), Neutral Detergent Fiber (NDF), and Acid Detergent Lignin (ADL). The results showed significant levels of cellulose (39.78%) and starch (31.21%), indicating that cassava peels are valuable raw materials for bioethanol production. The content of hemicellulose (21.11%) and lignin (3.84%) were also determined. In the third stage, using a Petri dish, three fungi (ICPF1, ICPF2, and ICPF3) were isolated from two different cassava peels. ICPF1 was only identified from fresh cassava peels (FCP), while all three fungi were identified from decayed cassava peels (DCP). Morphologically, these fungi were identified as Aspergillus niger, Aspergillus flavus, and Rhizopus stolonifer. The fourth stage focused on optimizing the enzyme activity of the three isolates for potential applications, with A. niger demonstrating the highest enzyme activity with a diameter of zone of clearance of 16 mm. Stage five involved optimizing the production of the onsite enzyme in a 50ml flask using A. niger, basal salt medium (BSM), and cassava peels as a substrate. The DNSA method was used to measure the absorbance of maltose and glucose at 540 nm for various substrate concentrations (1%, 3%, 5%, 8%, and 10%) at specific intervals of 2, 4, 6, 8, and 10 days with a spore concentration of 2.1 x 105 cells/ml. The maltose and glucose concentrations were calculated as 7.138mg/ml and 6.398 mg/ml, respectively, and the corresponding enzyme activity was determined as 4.759U/ml and 4.265U/ml. The optimal conditions of Day 4 and a substrate concentration of 10%, along with a fixed temperature of 30°C and a pH of 5.5, were used to prepare the onsite enzymes in a 500 ml flask for the fermentation process. The onsite enzymes were used for saccharification and Saccharomyces cerevisiae for fermentation under simultaneous saccharification and fermentation (SSF) process. A mixture of 20 ml of onsite enzymes and 1.5 g of S. cerevisiae were added to substrate concentrations of 5%, 10%, and 20%, and the ethanol concentration was analyzed daily for 7 days using Gas Chromatography (GC). The highest ethanol concentration (1.316%) was observed on Day 5 with a substrate concentration of 20%, while the lowest concentration (0.123%) was recorded on Day 1 with a substrate concentration of 5%.

CD44 is a type I transmembrane glycoprotein, and possesses various isoforms which are largely classified into CD44 standard and CD44 variant (CD44v) isoforms. Some variant-encoded regions play critical roles in tumor progression. However, the function of CD44 variant 4 (CD44v4)-encoded region has not been fully understood. Using peptide immunization, we developed an anti-CD44v4 mAb, C₄₄Mab-108, which is useful for flow cytometry, western blotting, and immunohistochemistry. In this study, we determined the critical epitope of C₄₄Mab-108 by enzyme-linked immunosorbent assay (ELISA). We used the alanine (or glycine)-substituted peptides of the CD44v4-encoded region (amino acids 271-290 of human CD44v3-10), and found that C₄₄Mab-108 did not recognize the alanine-substituted peptides of D280A and W281A. Furthermore, these peptides could not inhibit the recognition of C₄₄Mab-108 in flow cytometry and immunohistochemistry. The results indicate that the critical binding epitope of C₄₄Mab-108 includes Asp280 and Trp281 of CD44v3-10.

Natural montane peatlands generally are not a significant source of nitrous oxide (N₂O) due to environment limitation including phosphorus (P) scarcity and temperature lowness. Phosphorus enrichment and warming caused by global change are altering this limitation, likely to increase the source function of N₂O. However, the combined effects of P addition and warming on N₂O fluxes and biotic/abiotic factor in peatlands are still uncertain. To address this, we investigated the long-term (12 yrs) effects of P addition (5 and 10 kg ha^-1 yr^-1) and its interaction with warming on N₂O fluxes in a peatland. The results showed that although long-term P addition did not significantly affect the source/sink function of N₂O in the peatland, it stimulated enzyme activities, promoted peat decomposition. However, warming amplified the effect of P addition to increase N₂O emissions by stimulating enzyme activities and changing soil stoichiometry, even turned the peatland into a significant source of N₂O with an emission of approximate 100 g m^-2 during the growing season. Our study suggests that P enrichment under the current background of global warming will enhance the possibility of strong N₂O emissions in montane peatlands, which may increase the risk to further aggravate global warming.

Adopting banana peel as raw material, the adsorption properties of banana peel hydrothermal carbon modified with KOH solution for lead ions in aqueous solution were studied. The surface structure and functional groups of the modified hydrothermal carbon were analyzed by XRD and SEM. The results showed that the banana peel hydrothermal carbon prepared from 0.5 mol/L KOH solution had large pores, and its adsorption capacity reached 42.92 mg/g at a pH value of 6; When the concentration of KOH solution is 0.5 mol/L, the solid liquid ratio is 2 g/L, the adsorption capacity reaches 21.39 mg/g, and the adsorption rate reaches 82.74%; When the concentration of lead solution increased to 100 mg/L, the adsorption capacity of modified hydrothermal carbon for lead ions decreased to 78.26%; The equilibrium adsorption time of lead ion in solution on phosphoric acid modified hydrothermal carbon from banana peel was 250 minutes, and the adsorption process met the quasi second order kinetic model and Freundlich isotherm equation, with an equilibrium adsorption rate of 88.62%. The adsorption of lead ions in solution by KOH modified hydrothermal carbon is mainly chemical physical adsorption.

A new model of gravity is presented here similar to the earlier work of Verlinde on Emergent Gravity but without the use of Verlinde's main assumption on the nature of gravity as an entropic force using the First Law of Thermodynamics. Instead, the model will be shown to be consistent with the Second Law of Thermodynamics as used in Black Hole Physics. Moreover, it does not use the Equipartition Theorem such that there is no need to define a thermal bath enclosed within a holographic screen. The theory uses $E=NE_{p}$, for the total energy of a massive object where $E_{p}$ is the Planck Energy while $N$ is the number of Planck Energy to represent the maximum possible density of information that can reside in matter. The theory uses also the Holographic Principle as the basis for an information-theoretic approach to the nature of gravity. It is shown here that gravity emerges whenever there is an updating of the information within a given volume of space by the presence of matter.

Introduction: Antitumor host immune response is an important factor, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) in breast cancer as an immunological biomarker has been significantly explored over the past years. The number of patients treated with neoadjuvant chemotherapy (NAC) increased and identification of a biomarker to predict the probability of pCR (pathological complete response) is a high priority. Materials and methods: We evaluated 334 cases of BC treated with NAC followed by surgical resection from 2020-2022 in Ist Clinic of Oncological Surgery, Oncological Institute "Prof Dr I Chiricuta" Cluj Napoca. Of the above, 122 cases were available for histological evaluation both in pre-NAC biopsy and post-NAC resection tissue. Evaluation of biopsy fragments and resection parts using hematoxylin eosin (H&E). The TIL evaluation took place according to the recommendations of the International TIL Working Group (ITILWG). Results: There was a strong association between elevated levels of pre-NAC TIL. At the same time, there is a statistically significant correlation between stromal TIL and tumor grade, the number of lymph node metastases, the molecular subtype, and the number of mitoses (p <0.005). Intratumoral TIL showed a significant correlation with tumor size, distant metastasis, molecular subtype, number of mitosis, stage and lymph node metastasis (p<0.005). We also demonstrated that high pre-NAC TILs represent a strong predictive marker for pCR. Conclusion: This study reveals the role of TIL as a predictive biomarker in breast cancer not only for the well-established TNBC (triple negative breast cancer) and HER2+ (Her2 overexpressed) subtypes but also in Luminal A and B molecular subtypes. In this scenario, the evaluation of TILs as novel predictive and therapy-predicting factors should become a routinely performed analysis that could guide clinicians into the choice of the most appropriate therapy.

The study aimed to manage and to analyse the results of the laboratory tests, routinallypractice for hepatitis C diagnosis, using blood tests. Statistical analysis of this study results, was performed using the laboratory informatic system. The results of the study are substantial and intricate reffering to comparision between two methods concretlly ELISA method (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods and their results. Good to know our opinion that RT-PCR technique, it is considered proper for the diagnosis of HCV ( Hepatitis C virus).

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble Amyloid-beta Oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzheimer's disease, generate aberrant Ca2+ signals in primary hippocampal neurons, increase their oxidative tone and disrupt structural plasticity. Here, we explored the effects of sub-lethal AβOs concentrations on activity-generated nuclear Ca2+ signals and on the Ca2+-dependent expression of neuroprotective genes. To induce neuronal activity, neuron-enriched primary hippocampal cultures were treated with the GABAA receptor blocker gabazine (GBZ), and nuclear Ca2+ signals were measured in AβOs-treated or control neurons transfected with a genetically encoded nuclear Ca2+ sensor. Incubation (6 h) with AβOs significantly reduced the nuclear Ca2+ signals and the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) induced by GBZ. Likewise, incubation (6 h) with AβOs significantly reduced the GBZ-induced increases in the mRNA levels of Neuronal Per Arnt Sim domain protein 4 (Npas4), Brain-derived Neurotrophic Factor (Bdnf), Ryanodine Receptor type-2 (RyR2), and the antioxidant enzyme NADPH-Quinone-Oxidoreductase (Nqo1). Based on these findings we propose that AβOs, by inhibiting the generation of activity induced nuclear Ca2+ signals, disrupt key neuroprotective gene expression pathways required for hippocampal-dependent learning and memory processes.

Hemolysin II (HlyII) – one of the pathogenic factors of Bacillus cereus, a pore-forming β-barrel toxin – possesses a C-terminal extension of 94 amino acid residues, designated as the C-terminal domain of HlyII (HlyIICTD), which plays an important role in the functioning of the toxin. Our previous work described a monoclonal antibody (HlyIIC-20), capable of strain-specific inhibi-tion of hemolysis caused by HlyII, and demonstrated the dependence of the efficiency of hemol-ysis on the presence of proline at position 324 in HlyII outside the conformational antigenic de-terminant. In this work, we studied 16 mutant forms of HlyIICTD. Each of the mutations, ob-tained by multiple site-directed mutagenesis leading to the replacement of amino acid residues lying on the surface of the 3D structure of HlyIICTD, led to a decrease in the interaction of HlyIIC-20 with the mutant form of the protein. Changes in epitope structure confirm the high conformational mobility of HlyIICTD required for the functioning of HlyII. Comparison of the effect of the introduced mutations on the effectiveness of interaction between HlyIICTD and HlyIIC-20 and a control antibody recognizing a non-overlapping epitope enabled identifying the amino acid residues N339, K340 included in the conformational antigenic determinant rec-ognized by HlyIIC-20.

Optimum postharvest storage conditions increase the shelf life and postharvest quality of horticultural crops. The effects of forced-air precooling (FAP) and modified atmosphere packaging (MAP) on shelf life, physicochemical quality, and health-promoting properties of bell pepper (Capsicum annuum L. cv. Nagano) harvested at 90% and 50% coloring stages in May and July respectively, stored at 11℃, 95% relative humidity were assessed. Fruits were treated with FAP + 30 μm polyethylene liner (FOLO), FAP (FOLX), 30 μm polyethylene liner (FXLO), and control (FXLX). The quality attributes, viz. weight loss, firmness, color, SSC, soluble sugars, TPC, TFC, DPPH, and ABTS were evaluated. FOLO maintained sensory quality (weight loss, firmness, and color), physicochemical (soluble solids content and soluble sugars), and health-promoting properties compared to other treatments during storage. The investigated parameters differed significantly (p < 0.05) among treatments except soluble sugars. The 50% coloring fruits had a huge variation between treatments than 90% coloring. The results revealed more TPC and antioxidant capacity in 50% than in 90% coloring fruits. The study highlights the need to consider the ideal fruit coloring stage at harvest under the effect of FAP and MAP treatments in preserving bell pepper's postharvest quality and shelf life.

Constructed wetlands (CWs) is a kind of green environmental protection technology, which is widely used in sewage treatment. The traditional CWs is faced with the problem of low treatment effect of high concentration sewage. In recent years, biochar, as a new type of adsorption material, has been used in CWs because of its advantages of large specific surface area, strong adsorption capacity and wide material sources. This paper systematically summarized the characteristics of biochar and the preparation of biochar by studying the changes of microorganisms added to CWs, and compared the effects of different treatment methods coupled with biochar on the treatment performance of CWs, the effects of biochar coupled with CWs on enzyme activity, functional genes, metabolites and microbial communities were investigated. This review summarizes how different preparation methods affect the properties of biochar and how these biochar cause changes in the microorganisms added to CWs.

In the context of post-harvest pest management in agricultural products, the adoption of modified atmospheres presents an eco-friendly alternative to conventional pesticides. This study focuses on nitrogen gas as a potential agent for insect control in stored commodities, utilizing computational simulations to investigate its penetration and distribution within two common storage configurations: chamber-contained pallets and silos. By employing the convection-diffusion equation, the simulations reveal insights into nitrogen distribution dynamics and duration required for oxygen reduction. The results highlight the influence of boundary conditions, commodity porosity, and convection effects on nitrogen dispersion. In chamber scenarios, boundary condition type significantly affects oxygen reduction time, while in silos, convection and diffusion interact to establish a consistent diffusion layer thickness. This research enhances the understanding of modified atmosphere techniques and their potential for sustainable pest management. It provides practitioners with valuable quantitative insights, paving the way for optimized modified atmosphere strategies in real-world agricultural contexts.

COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.

Excess weight, which is seen as the background cause of most diseases, is gradually becoming the most important problem in the world. The cafeteria diet is robust diet that mimics the western diet and provides rapid weight gain associated with the obesity, diabetes, and cancer. The relationship between obesity and cancer is well known. For this reason, it is of great importance to reveal the first molecular and metabolic alterations that occur before entering the obesity process with any factor to understand the pathology of many diseases and to treat them in the early period. The beneficial effects of probiotics are attributed to their metabolite content with antioxidant properties or the postbiotic metabolites produced by them. In this study, the effects of different dietary practices on the hepatic antioxidant system of rats in developmental period were investigated by real-time PCR, enzyme activity measurements, and quantitative measurements of metabolites. After all, it was observed that CAF caused serious impairments by affecting the hepatic antioxidant system at gene and protein levels, and these impairments were relatively reversed with SCD Probiotics supplementation. In addition, regardless of the CAF diet, the regulatory effect of SCD Probiotics supplementation on the hepatic antioxidant system is remarkable.

The subtropical forest soil plays a pivotal role in terrestrial carbon (C) cycling. Although global warming is expected to influence subtropical soil C cycling, a consensus on its impact on soil C dynamics remains elusive. Given the significant response of soil microbial respiration to temperature in subtropical soils, understanding its behavior under varying temperature regimes is critical for predicting soil organic C (SOC) responses to climate warming. We conducted a short-term laboratory soil warming incubation experiment, sampling both warmed and un-warmed soils from a subtropical plantation in southeastern China, incubating them at 20 °C, 30 °C, and 40 °C. Our aim was to study the SOC mineralization response to increasing temperatures. Our findings revealed that the temperature sensitivity (Q10) of SOC mineralization to short-term experimental warming varied between the warmed soil and the un-warmed soil. The Q10 of the un-warmed soil escalated with the temperature treatment (20-30 ℃: 1.31, 30-40℃: 1.63). Conversely, the Q10 of the warmed soil decreased (20-30 ℃:1.57, 30-40 ℃:1.41). Increasing temperature treatments enhanced hydrolytic enzyme activity but decreased soil substrate availability in both un-warmed and warmed soil. The Q10 of un-warmed soil was positively correlated with the response ratio of DOC. Additionally, soil microbial biomass exhibited a significant decline, leading to a reduced total amount of PLFAs and a decreased abundance of bacteria, fungi, and Gram-negative bacteria (GN). The changes in temperature also considerably altered the composition of the warmed soil microbial community. A drop in the microbial quotient coupled with a rise in the metabolic quotient indicated that warming amplified microbial respiration over microbial growth. The differential Q10 of SOC mineralization, in response to temperature across varying soil, can largely be attributed to shifts in soil nutrients, C-degrading enzyme activities, and microbial communities (the ratio of fungal to bacterial PLFAs).

This research paper is about to obtain new soliton solutions to the M-fractional (1+1)-dimensional nonlinear Westervelt model by utilizing $\exp_a$ function and modified simplest equation techniques. The gained solutions involving dark, bright, periodic, dark-bright and other solitons. These results have many applications in wave propagation of sound waves, high amplitude in medical imaging and therapy. Achieved results are verified by Mathematica tool and the effect of M-fractional derivative on the solutions is explained through 2-Dimensional, 3-Dimensional and contour plots. At the end, these techniques are simple, fruitful and effective to deal with nonlinear FPDEs.

Cystic Fibrosis is a chronic disease affecting multiple systems including the GI tract. Clinical manifestation in patients can start as early as infancy and vary across different age groups. With the advent of new highly effective modulators, the life expectancy of PwCF has improved significantly. Various GI aspects of CF care such as nutrition are linked to the overall improvement in morbidity, lung function, and quality of life of PwCF. The variable clinical presentations and management of GI diseases in pediatrics and adults CF should be recognized. Therefore, it is necessary to ensure efficient transfer of information between pediatric and adult providers for proper continuity of management and coordination of care at the time of transition. The transition of care is a challenging process for both patients and providers and currently, there are no specific tools for GI providers to help ensure smooth transition. In this review, we aim to highlight the crucial features of GI care at the time of transition and provide a checklist that can assist in ensuring an effective transition and ease the challenges associated with it.

Biochars are often proposed as a strategy for long-term carbon sequestration. Nevertheless, application of pyrolysed feedstock, particularly along with exogenous organic matter, may affect carbon dynamics in soil through introduction of labile carbon pools and stimulation of extracellular enzymes activity. The main aim of this research was to evaluate the influence of biochars and unprocessed organic amendments addition in two agricultural soils on the dissolved organic carbon (DOC) content and activity of three enzymes involved in carbon turnover. In the incubation experiment, activity of dehydrogenase, β-glucosidase, cellulase and DOC content were measured on day 30, 60, 90, 180 and 360. Addition of biochars stimulated the activity of dehydrogenase and β-glucosidase, while cellulase was suppressed. Fresh biomass amendment enhanced activity of the enzymes through priming effect. DOC content tended to be the highest in treatments with high enzyme activity, suggesting that DOC introduced with amendments acted as a source of energy for microbes. Our findings support the hypothesis that biochar properties and presence of exogenous organic matter affect microbial response in soil, what might be crucial for carbon sequestration potential of biochar. However, long-term studies are recommended to fully understand the mechanisms that determine response of soil biota to biochar addition.

The term new genomic techniques (NGTs), is an umbrella term to describe a variety of techniques that can alter the genetic material of an organism and that have emerged or have been developed since 2001, when the existing genetically modified organism (GMO) legislation was adopted. The analytical framework to detect GMOs in Europe is a established single harmonized procedure which is mandatory for authorization of GM food and feed, thus generating reliable, transparent and effective labelling scheme for GMO products. However, NGT products challenge the implementation and enforcement of the current regulatory system in the EU, relating in particular to the detection of NGT products that contain no foreign genetic material. Consequently, current detection methods will fail to meet minimum performance requirements. Although existing detection methods may be able to detect and quantify even small alterations in the genome, this does not necessarily confirm the distinction between products resulting from NGTs subject to the GMO legislation and other products. Therefore, this study provides a stepwise approach for the in silico prediction of PCR systems specificity by testing a bioinformatics pipeline for amplicon and primer set searches in current genomic databases. We have tested our methodology in two mutant genotypes produced by CRISPR/Cas9 in Arabidopsis thaliana. Overall, our results demonstrated that the single PCR system developed for the identification of a nucleotide insertion in the grf1-3 genotype has sufficient hits in the databases that would not allow discrimination of this mutanted event. Differently, the second mutated genotype grf8-61 which contains a -3bp deletion, found no matches in the sequence variant database. Our approach is the first step in decision making on PCR system and modification of them for empirical testings.

No-till and cereal-legume intercropping have been recognized as favorable cropping practices to increase crop yields while maintaining soil quality in arid and semiarid environment, but the bio-logical mechanisms are poorly understood. The present study was to determine the response of soil properties, enzyme activities, and microbial community diversity and composition in mono- and inter-cropping under conventional and no-tillage conditions. We initiated a field experiment in Wuwei, a typical arid area of China, in 2014. Soil was sampled in August 2022 and, yields, soil properties, enzyme activities, and the microbial community diversity and composition were de-termined in the maize and pea strips in inter- and mono-cropping systems. Results revealed that the maize and pea strips in the no-till intercropping significantly increased yields, total and or-ganic carbon stocks, decreased NO3--N, and obtained the highest total and organic P in the soil. The α- and β-diversity of archaea and eukaryotes were significantly affected by planting patterns, while α- and β-diversity of the bacterial community were significantly affected by tillage practices. Both no-tillage and intercropped maize significantly increased the abundance of archaea phylum Thaumarchaeota and bacterial phylum Nitrospirae, benefiting nitrogen fixation of intercropped pea from the atmosphere under the no-tillage cereal/legume intercropping. No-till intercropping was conducive to the accumulation of organic carbon, while decreasing the abundance of Prote-obacteria, Acidobacteria, and Verrucomicrobia. Limited soil enzyme activities (ACP, ALP, DP, NAG, BG, AG, CB) led to decreases in organic carbon turnover and utilization. Intercropping al-tered soil microbial community diversity and composition due to changes in soil properties and enzyme activities. These findings suggest that no-tilled cereal-legume intercropping is a sustaina-ble cropping practice for improving soil properties and enhancing microbial (archaea, bacterial, Eukaryota) diversity, but the long-term persistence is not conducive to rapid turnover of soil nu-trients due to limited enzyme activities.

In this paper, new types of M-fractional wave solutions of mathematical physics model named as truncated M-fractional (1+1)-dimensional non-linear simplified Modified Camassa-Holm model are achieved by applying the modified simplest equation (MSE), Sardar sub-equation and generalized Kudryashov techniques. The gained solutions containing dark, bright, periodic and mixed wave solitons. Effect of fractional order derivative is also discussed. Achieved wave solitons are verified by Mathematica tool. Few of the gained wave solitons are also described through 2-dimensional, 3-dimensional and contour graphs through Mathematica tool. The gained solutions are helpful for the further development of concerned model. Finally, these techniques are simple, fruitful and effective to deal with non-linear FPDEs.

Macrolide antibiotics, effective antimicrobial agents, are intensively used in human and veterinary medicine as well as in agriculture and therefore are found all over the world as environmental pollutants, harming sensitive eco-community organisms and provoking the selection of resistant forms. A novel azithromycin derivative was synthesized and as a rationally designed hapten conjugate ensured group immunorecognition of 6 major macrolide representatives (105-41%), erythromycin, erythromycin ethylsuccinate, clarithromycin, roxithromycin, azithromycin and dirithromycin in competitive immunoassay based on anti-clarithromycin antibodies. The heterologous hapten-based ELISA format simultaneously contributed to a 5-fold increase in sensitivity (ERY IC50 = 0.04 ng/mL). However, for the detection of trace macrolides in environmental samples, an underexploited in immunoassay field strategy was proposed in the present study to significantly improve the detectability of analytes. Unlike most approaches, it does not require special enhancers/amplifiers or additional concentration/extraction procedures, but only involves a larger volume of test samples. Gradual volume increase of samples (from 0.025 to 10 mL) analyzed in direct competitive ELISA, immunobeads, and immunofiltration assay formats based on the same reagents resulted in a significant improvement (more than 50-fold) in assay sensitivity and detection limit up to 5 and 1 pg/mL, respectively. The suitability of the test for detecting macrolide contamination of natural water was confirmed by recovery of macrolides from spiked blank samples (71.7-141.3%). A series of natural water samples from Lake Onega and its influents near Petrozavodsk were analyzed during a 2022-2023 using both the developed immunoassay and HPLC-MS/MS and revealed no macrolide antibiotic contamination.

In this letter, we construct an effective field theory of gravity at large distances. We obtain to the leading order for large distances: a cosmological constant term and a logarithmic term in addition to the usual General Relativistic terms. The novel logarithmic term has important implications in explaining phenomena such as flat galactic rotation curves and stronger gravitational lensing than predicted that are generally attributed to the presence of dark matter.

The feasibility of using zeolites, synthesized from components found in municipal solid waste fly ash (MSW-FA), as sorbents for the recovery of nutrients (nitrate and phosphate) and heavy metals is critically assessed in this review. The inherent drawbacks of utilising a highly contaminated, variable, and relatively Al- and Si-dilute source such as MSW-FA to synthesize zeolites are discussed, and different methods to extract and decontaminate zeolite precursor materials from MSW-FA are considered. Ways to synthesize tailored zeolites and how their properties as well as the operational conditions impact the adsorption of cations such as ammonium and heavy metals are summarized. The use of surface-modified zeolites to adsorb nitrate and phosphate is also reviewed. And subsequently, approaches to utilise directly or recover for reuse the adsorbed compounds are considered, discussing potential challenges and mitigating measures related to leaching of unwanted compounds from the zeolites. Moreover, the possibility to regenerate the adsorption capacity of the zeolites for multiple adsorption cycles is considered. In the final chapter of the review a more general discussion of the main challenges and existing research gaps is provided, giving directions for recommended studies.

In this paper, the new optical wave solutions of truncated M-fractional perturbed Kundu-Eckhaus model with full non-linearity are obtained by utilizing the expa function technique and modified extended tanh expansion function technique. The solutions are in the form of dark soliton, bright soliton, singular solitons and other form of solutions. The gained solutions are helpful for the further development of concerned model. The obtained results have also been presented graphically in both two-dimensional and three-dimensional formats to discuss the dynamical features as well as the parametric dependence of the constructed solutions. The study offers a highly spectacular and acceptable techniques to combine various intriguing wave demonstrations for more sophisticated models of the modern day.

This study will lead to the development of a numerical data set that will assist in the design of Savonius wind turbines. A major objective of this study is to develop a better design for Savonius turbine blades in order to increase their torque coefficients, rotational speeds, and pressure coefficients. As part of the experimental design methodology, a full dataset was generated by simulating three-dimensional scale models utilizing computational fluid dynamics (CFD) simulations that were validated by wind tunnel data. This process is multi-objective optimization for optimizing turbine performance. The twist angle, aspect ratio, and overlap ratio are all important factors in determining the optimal torque and power coefficients. The group method of data handling (GMDH) algorithm was utilized to model objective functions based on input-output data. The Pareto fronts were plotted using polynomial models obtained from the evolutionary Pareto-based optimization approach (modified NSGA-II), and the optimal commercial points were determined using TOPSIS. A comparison of three- and two-objective optimization data revealed that two-objective optimization data lie within the boundaries of a three-objective optimization problem. The torque coefficient, rotational speed, and power coefficient are all improved by 13.74%, 0.071%, and 5.32%, respectively, using multi-objective optimization. As a result of the multi-objective optimization of the turbine, some significant characteristics of objective functions were discovered.

Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attrac-tion in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogues; molecules similar to natural sub-strates of numerous fungal enzymes and Quorum Sensing signaling molecules of fungi and yeast; etc. Most part of the review is devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the cur-rent scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.

Genetic engineering technology offers opportunities to improve many important agronomic traits in crops, including insect-resistance. However, genetically modified (GM) exogenous proteins in edible tissues of transgenic crops has become an issue of intense public concern. To advance the application of GM techniques in maize, a Cre/loxP-based strategy was developed for manipulating the transgenes in green tissues while locking it in non-green tissues. In the strategy, the site-specific excision can be used to switch on or off the expression of transgenes at specific tissues. In this work, two basic transgenic maize named KEY carrying the Cre gene and LOCK containing the Vip3A gene with a blocked element, were obtained based on their separate fusion gene cassettes. The expression level and concentration of Vip3A were observed with high specific accumulation in green tissues (leaf and stem), and only a small amount in root and kernel tissues in the KEY × LOCK hybrids. The insect-resistance of transgenic maize against two common lepidopteran pests, Ostrinia furnacalis and Spodoptera frugiperda, was assessed in the laboratory and field. The results indicated that the hybrids possessed high resistance levels against the two pests, with mortality rates above 73.6% and damage scales below 2.4 compared with the control group. Our results suggested that the Cre/loxP-mediated genetic engineering approach has a competitive advantage in GM maize. Overall, findings from this study are significant for providing a feasible strategy for transgenes avoiding expression in edible parts and exploring novel techniques toward the biosafety of GM plants.