Serine peptidases (SPs) of the chymotrypsin S1A subfamily are an extensive group of enzymes found in all animal organisms, including insects. Here we provide analysis of SPs in the yellow mealworm Tenebrio molitor transcriptomes and genomes datasets and profile their expression pattern at various stages of ontogeny. A total of 269 SPs were identified, including 137 with con-served catalytic triad residues, while others 125 lacking conservation were proposed as non-active serine peptidase homologs (SPHs). Seven deduced sequences exhibit a complex do-main organization with two or three peptidase units (domains), predicted both as active or non-active. The largest group of 84 SP and 102 SPH had no regulatory domains in the propep-tide, and the majority of them were expressed only in the feeding life stages, larvae and adults, presumably playing an important role in digestion. The remaining 53 SP and 23 SPH had differ-ent regulatory domains, showed constitutive or upregulated expression at eggs or/and pupae stages, participating in regulation of various physiological processes. The majority of polypep-tidases was mainly expressed at the pupal and adult stages. The data obtained expand our knowledge on SPs/SPHs and provide a foundation for further research on the functions of this gene family in T. molitor.

Due to bacterial contamination, natural medicinal preservatives may be an alternative to enhance the quality of milk. Besides, thorough biocompatibility testing is deemed essential before integrating natural extracts into food products. To address this matter, our research focused on evaluating the antimicrobial potential of Plectranthus amboinicus, Flueggea leucopyrus, Cymbopogon citratus, and Bacopa monnieri against prevalent foodborne pathogens, including Staphylococcus aureus, Escherichia coli, Salmonella spp, and Pseudomonas aeruginosa and investigating the efficacy of plant extracts as natural preservatives along with biocompatibility and toxicity assessments. The methanolic extracts of plant materials were used for measuring antimicrobial activity using the agar well diffusion method, Minimum Inhibitory Concentration (MIC) and Minimum bactericidal concentration (MBC) assays. The preservative activity was tested by isolating pathogenic organisms in a sterilized milk medium and toxicity and biocompatibility was assessed using zebrafish embryo and brine shrimp lethality assays. At a concentration of 400 mg/ml, all plant extracts demonstrated notable activity against bacterial strains. B. monnieri at 400 mg/ml exhibited particularly significant effects on S. aureus (30.3 mm ± 0.6), surpassing the positive control, gentamicin (28.3 mm ± 0.6), while also displaying pronounced activity against E. coli. F. leucopyrus, at the same concentration, showed antimicrobial activity comparable to the positive control against both S. aureus (28.0 mm ± 1.0) and E. coli (27.0 mm ± 1.0). However, as there’s weak-mild toxicity in these herbs, prior to consumption, careful consideration of their toxicity and biocompatibility is imperative for ensuring their safe use.

Neisseria gonorrhoeae is a bacterium that causes the sexually transmitted infection gonorrhea. This study employed molecular docking simulations to investigate potential interactions between natural molecules and the Fe(3+) ions import ATP-binding protein fbpC in Neisseria gonorrhoeae FA 1090. Among the screened molecules, Hypericin exhibited a remarkable binding energy of approximately -13.2 kcal/mol, indicating a robust and favorable binding affinity with the target protein. This promising outcome suggests that Hypericin could serve as a potential candidate for further exploration as a therapeutic agent against Neisseria gonorrhoeae infections. However, it is imperative to emphasize that these in silico findings necessitate experimental validation through in vitro and in vivo studies to ascertain the actual efficacy and safety of Hypericin as a treatment option.

The low-temperature environment significantly inhibits the growth and metabolism of denitrifying bacteria, leading to an excessive concentration of ammonia nitrogen and total nitrogen in sewage treatment plants during the cold season. In this study, an efficient denitrifying strain of heterotrophic nitrification–aerobic denitrification(HN-AD) bacteria named HS2 was isolated and screened from industrial sewage of a chemical factory in Inner Mongolia at 8°C. The strain was confirmed to be Achromobacter spiritinus, a colorless rod-shaped bacterium. When cultured with sodium succinate as the carbon source, a carbon-to-nitrogen ratio of 20-30, a shaking rate of 150-180 r/min, and the initial pH of 6-10, the Strain HS2 exhibited excellent nitrogen removal at 8°C. Through the results of whole-genome sequencing, gene amplification, and gas product detection, the Strain HS2 was determined to possess key enzyme genes in both nitrification and denitrification pathways, suggesting a HN-AD pathway of NH4+-N→NH2OH→NO2--N→NO→N2O→N2. At 8°C, the Strain HS2 could completely remove ammonia nitrogen from industrial sewage with an initial concentration of 127.23 mg/L. Microbial species diversity analysis of the final sewage confirmed Achromobacter sp. as the dominant genus, this indicated that the low-temperature denitrifying strain HS2 plays an important role in nitrogen removal of actual low-temperature sewage.

This study investigated the presence, distribution, and antimicrobial resistance profiles of extend-ed-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in a dairy herd located in Northern Italy. A questionnaire was administered, and the feces of clinically healthy pre-weaned dairy calves, their mothers, and the cows treated for mastitis, waste milk, water, and environmental samples, were collected and inoculated on Chromagar ESBL™ medium. The questionnaire identi-fied several risk factors including administration of waste milk to male calves, lack of routine cleaning of calf feeding and housing equipment, and blanket dry cow therapy. Escherichia coli was identified by MALDI-TOF MS in the feces of 28 of 37 (75.67%) calves, 2 of 3 (66.67%) treated cows, 8 of 14 (57.15%) environmental samples, and the waste milk. Six of 14 (42.85%) environmental samples were also positive for ESBL Acinetobacter baumannii, while all fecal samples were negative. ESBL production was confirmed for all E. coli isolates based on the double disk susceptibility test (DDST), while none were carbapenemase producers. Upon minimal inhibitory concentration (MIC) analysis, all of them showed multiple resistances and were categorized as multi-drug resistant (MDR). This study confirms the widespread presence of MDR, ESBL-E. coli in dairy calves and highlights their diffusion in the farm environment.

The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD_7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD_7.40 value and the MIC of 46 plant flavonoids reported in literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than about 3.0, but the opposite is true when their LogP values are more than about 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

Salmonella causes various type of disease worldwide with a remarkable pace. Salmonella enteric serotype typhi (S. typhi), a gram-negative bacterium (only cause disease in man) is the mainly causative agent of Typhoid fever. Typhoid fever is most common in poor and unprivileged developing countries of Asia and Africa. One of the major components of virulence factors produced during salmonella infection is Lipid A, which acts as a potent human immuno-modulator bacterial endotoxin. Regulation of Lipid A biosynthetic pathway occurs at second step, catalyzed by LpxC, a Zn2+ dependent metalloamidase. Systematic Screening of a pool of drug datasets like natural products library from Zinc database, Asinex database, Thiophene analogues fruitfully provided us 3 potent lead molecules s1_dl_mseq2, s1_ll_mseq2, and s2_ll_mseq8 which actively binds with LpxC enzyme and could be developed into sound inhibitors of LpxC enzyme after the application of drug development and processing strategies. Wet lab experimentation is required to validate these results for further use.

Diesel contamination of farming soils is of great concern because hydrocarbons are toxic to all forms of life and can potentially enter the food web through crops or plants used for remediation. Data on plant ability to uptake, translocate and accumulate diesel-derived compounds are controversial not only due to the probable diverse attitude of plant species but also because of the lack of a reliable method to distinguish petrogenic from biogenic compounds in plant tissues. The purpose of this study was to set up a GC-MS-based protocol enabling the determination of diesel-derived hydrocarbons in plants grown in contaminated soil for assessing human and ecological risks, predicting phytoremediation effectiveness and biomass disposal. To this aim two plant species Vicia sativa L. and Secale cereale L., belonging to two diverse vascular plant families, were used as plant models. They were grown in soil spiked with increasing concentrations of diesel fuel and the produced biomass was used to set up the hydrocarbon extraction and GC-MSD analysis. The developed protocol was also applied to the analysis of Typha latifolia L. plants, belonging to a different botanical family and grown in a long-time and highly contaminated natural soil. Results showed the possibility of distinguishing diesel-derived compounds from biogenic hydrocarbons in most terrestrial vascular plants, just considering the total diesel compounds in the n-alkanes carbon range C10-C26, where the interference of biogenic compounds is negligible. Diesel hydrocarbons quantification in plant tissues was strongly correlated (0.92<r2<0.99) to the concentration of diesel in spiked soils, suggesting a general ability of the considered plant species to adsorb and translocate relative low amounts of diesel hydrocarbons and the reliability of the developed protocol.

The goal of the current study was to discover a novel potential probiotic strain of Lactobacillus spp. with anti-Escherichia coli activity from locally produced yogurt in Tongi, Gazipur, Bangladesh, compare its antagonistic activity with a commercial probiotic mixture of several strains, and approve a novel method for confirming the viability and relative abundance of the microbial community in a probiotic mixer. We carried out 16S sequencing, 16S metagenomics, Transmission Electron Microscopy (TEM) analysis, and other in vitro laboratory experiments to reach this objective. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus (16S sequence accession number OQ652026). It was gram-positive, anaerobic, lactose fermenting, and round-ended rod that typically measured 0.7 to 1.3 µm by 2.2 to 9 µm. In addition to having seven probiotic characteristics, it also showed an antagonistic impact on six different pathogens, but what's more noteworthy is that E. coli was the pathogen it inhibited most strongly (inhibition zone diameter was 18.88±0.18 mm). The most important and ground-breaking finding of this work was determining the probiotic features of a new probiotic strain, TY-11, whose antibacterial activity was virtually as effective as that of the probiotic combination with three different strains. Furthermore, the results of 16S high throughput sequencing and the conventional plate count method demonstrated a strong correlation (0.999) at the genus level, indicating that the use of both of these approaches in combination may be a practical way to assess the relative abundance of the microbial community and their viability in commercially available probiotic blends.

Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). The co-occurrence of ARMs and CSS in an individual is unexpected since both diseases are very rare. A review of the literature enabled us to identify 12 individuals with both CSS and ARMs. Among these 12 individuals, 9 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are likely a rare consequence of CSS, especially for ARID1A-related CSS.

Citrus species essential oils (EOs) are significant sources of bioactive compounds and demonstrate diverse therapeutic effects. However, limited documentation exists regarding the phytochemicals associated with their biological activities. This study aims to assess the antioxidant activity, plant inhibitory properties, and brine shrimp cytotoxic effects of EOs derived from three Citrus species: C. sinensis, C. limon, and C. hystrix. Utilizing chemometric analysis and gas chromatography-mass spectrometry (GC-MS) fingerprints, the volatile components contributing to antioxidant activity were elucidated. The peels of the Citrus samples were hydro-distillated to obtain EOs, and subsequently subjected to antioxidant, plant inhibitory, and brine shrimp cytotoxic assays. The results indicated that C. limon EO exhibited the highest antioxidant activity, while C. hystrix and C. sinensis EOs demonstrated pronounced inhibitory effects against Aetrmia salina and Lactuca sativa, respectively. GC-MS analysis facilitated the identification of key compounds in each EO. Principal component analysis (PCA) and hierarchy cluster analysis (HCA) effectively categorized Citrus EOs based on their antioxidant properties, highlighting the proximity of C. limon and C. sinensis. Among the identified compounds, D-limonene, α-Terpineol, Caryophyllene, (+)-3-Carene, β-Pinene, (-)-Spathulenol, trans-p-Mentha-1(7),8-dien-2-ol, and trans-Verbenol were the most discriminating compounds affected the antioxidant activity of C.limon and C. sinensis EOs.

Our study explores the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the rpt5a mutant characterized by persistent reddish-brown leaf spots from seedling stage to maturity, leading to extensive leaf necrosis. Through map-based cloning, we localized the responsible locus to a 330Kb region on chromosome 2 and identified LOC_Os02g56000 (named OsRPT5A) as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and generation of knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. Our study also revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by mutations. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in rpt5a mutants, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the rpt5a mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice's pathogen resistance mechanisms. These findings elucidate the genetic basis of the spotted leaf phenotype and emphasize the intricate interplay between plant defense responses and developmental pathways.

This study aimed to identify whether gyrate atrophy of the choroid and retina (GACR) heterozygous individuals have possible clinical manifestations and to explore the potential pathogenic mechanism. In this retrospective study, we surveyed a two-generation pedigree of an individual diagnosed with GACR. Two family members underwent ophthalmological, hematologic, and genetic tests. An arginine-restricted diet with vitamin B6 supplementation was implemented; clinical assessments were repeated every 3 months during follow-up. Relative OAT mRNA expression was determined using real-time quantitative polymerase chain reaction. The 19-year-old compound heterozygous daughter (OAT: c.1186C&gt;T; c.748C&gt;T), had bilateral high myopia, posterior staphyloma, chorioretinal atrophy, macular abnormalities, and elevated hematologic ornithine. The 54-year-old heterozygous mother (OAT: c.1186C&gt;T), presented with bilateral severe myopia, asymmetric posterior staphyloma, retina and choroidal capillary layer atrophy, retinal pigment epithelium abnormalities, and mildly elevated hematologic ornithine. Compared to normal individuals, the daughter and mother had 29% and 46% relative OAT mRNA expression, respectively (P&lt;0.001). We believe that this is the first report of a carrier of one OAT variant allele with mild phenotypes, suggesting that family members should be aware of the possible involvement of autosomal recessive conditions. Additional data suggests nonsense mediated decay-initiated mRNA degradation may cause GACR.

The importance of conflict analysis and safety considerations during work zone intervals at signalized intersections cannot be overstated, as these periods pose unique challenges and safety risks for both motorists and pedestrians. Work zones introduce temporary changes to traffic patterns, lane configurations, and signal timings, which can disrupt the flow of traffic and increase the likelihood of conflicts between vehicles and pedestrians. By conducting comprehensive conflict analysis, it is possible to identify potential conflict points, such as merging areas, pedestrian crossings, and lane transitions, and implement targeted safety measures to mitigate risks. Additionally, considering safety considerations during work zone intervals is paramount to safeguarding the well-being of road users and minimizing the occurrence of conflicts or collisions. Measures such as enhanced signage, temporary traffic control devices, and increased enforcement efforts can help promote compliance with traffic regulations and ensure the safe passage of vehicles and pedestrians through work zones. This study investigates the dynamics of traffic behavior and safety implications within work zones at signalized intersections, aiming to address key challenges and enhance intersection management strategies. Through comprehensive analysis, varying frequencies of Vehicle-to-Vehicle (V2V) conflicts were observed across different movement directions, with significant occurrences identified in specific phases of the traffic signal cycle. Specifically, 69 V2V conflicts in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8 were recorded. Furthermore, the examination of Vehicle-to-Pedestrian (V2P) conflicts underscored the importance of prioritizing pedestrian safety, with notable occurrences observed in phases associated with pedestrian crossing movements. Meanwhile, despite the closure of left-turn movements, instances of red light running persisted, with 69 red light running events in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8.To mitigate these safety concerns during work zone intervals, proactive measures are essential. Strategies include improving communication through clear signage and advanced warning systems, enhancing enforcement efforts with red light cameras and increased police presence, and investing in infrastructure improvements such as temporary pedestrian facilities. Integration of real-time data from sensors, particularly LiDAR technology, offers significant advantages in detecting conflicts and red light runners during work zone intervals. LiDAR's precise, real-time data on vehicle and pedestrian movements, combined with its 360-degree coverage and high spatial resolution, facilitates accurate detection and tracking of potential conflict scenarios, contributing to enhanced intersection safety and traffic management efficiency. This study endeavored to conduct a traffic safety analysis during work zone intervals at a signalized intersection in Baltimore City, known for its high rate of traffic crashes, utilizing LiDAR sensor technology.

Corrugated board is a composite material characterized by strong orthotropy in both the elastic and plastic phases. Additionally, due to its layered structure, which consists of alternately arranged flat and wavy layers of paper, its mechanics becomes complicated. Therefore, a precisely selected set of laboratory tests is needed to correctly identify all the necessary material parameters of cardboard. The work attempts to define a full set of laboratory tests in order to determine material parameters describing the linear-elastic, orthotropic behavior of cardboard and the basic parameters defining popular plasticity criteria, such as the asymmetric orthotropic Hoffman criterion. For this purpose, sensitivity analysis and numerical models of several selected basic laboratory tests were used. Since the aim of the work is to choose appropriate laboratory tests necessary to correctly determine the material parameters of corrugated board (not its individual layers), the numerical models do not contain detailed cardboard geometry, but only its homogenized representation in the form of the flat shell models. All numerical models are based on the nonlinear finite element method and constitutive modelling in the form of UMAT subroutines implemented in the ABAQUS software. Based on the analyses, appropriate measurements and laboratory tests were indicated that are most sensitive to the material parameters sought.

Sorghum grain processing can improve the nutritional content by promoting dietary properties that contribute to food security and economic development. The quality, nutritional content, and processing properties of sorghum bicolor grain can greatly affected by the inbred line races and variance in pericarp colour.The current study assessed the influence of the Husking Fraction Time Units (HFTU) process, which employed set time units per second (S), on the variation in the nutritional profile of fifty-one inbred line sorghum varieties based on distinct pericarp colours. When the assessment of the nutritional profile was involved: dry matter, total protein besides, namely mineral (P, K, S, Ca, Mg, Na, Fe, Zn, and Mn). The variety groups showed a significance value of (P < 0.05), indicating the study hypothesis's truth.The results demonstrated substantial impacts implied by the Husking Fraction Time Unit (HFTU) technique. This occurrence was noted when the dry matter percentage was increased in the husked products, specifically the endosperm (grits) and bran. The protein percentage redistributed by 19.2% compared to the whole grain and bran content. In comparison, the ratio of N/S was 14:1 in the S. bicolor and 12:1 in the kafirin in the bran part. Moreover, a strong correlation was observed among the examined minerals of S.bicolor and kafirin, such as the correlation between Ca: P, K: Na, and Fe: Zn attributed 80 (S) time unit, with correlation coefficients of R = 0.784 and R = 0.586, R= 517, R= 0.884, R= 0.745, and R = 0.893, respectively. At the same time, the 80 (S) time unit showed a significant effect on the colour property profile.The study results could benefit breeders and nutrition specialists in developing genotypes and processing sorghum grains, promoting research, and aiding several industrial sectors owing to the grain's adaptability and nutritional properties.

The microalgae Phaeodactylum tricornutum (PT) is distinguished by its rich nutrient profile, characterized by well-documented neuroprotective activities, including fucoxanthin (FX), a major carotenoid, and polyunsaturated omega-3 fatty acids (n-3 PUFA). The current study aims to evaluate the protective effects of a standardized extract of PT (Mi136) containing 2% FX on cognitive function, oxidative stress, and inflammation parameters in a mouse model of accelerated aging. Seventy-two (72) male mice were randomly assigned to the blank control group (BC), negative control group (NC), and four similar microalgae extract of PT groups (branded as BrainPhytTM) with different human equivalent doses. From day 01 to day 51, mice in the BC group were injected with a 0.9% normal saline solution, while mice in all other groups were subcutaneously injected with D-galactose (D-Gal) at a dose of 150 mg/kg once per day, five days per week. Results indicated that, for the three higher microalgae extract of PT dose groups, spatial cognitive function, swim latency, and step-through latency impairments induced by chronic D-Gal intoxication were significantly and fully inhibited, with mean values similar to those in the BC group during each day of testing. Similar benefits were observed in biochemical analysis, specifically regarding brain and plasma levels of lipid peroxidation, TNF-α, and IL-6 markers. These data underscore the positive effects of a standardized extract of PT containing 2% FX on cognitive function parameters such as spatial working memory, long-term memory, and short-term memory through the regulation of oxidative stress and inflammation pathways.

Small-scale fisheries are significant sources of nutrition and livelihood globally. However, increasing anthropogenic activities in coastal areas of developing countries have threatened the sustainability of artisanal fisheries and species. Fisheries of Sardinella maderensis (Lowe, 1838), to which Nigeria contributes 9% of the global stock and is a significant livelihood source in the coastal communities of Ibeju-Lekki, Lagos, face sustainability threats. This research investigated the effects of anthropogenic activities on S. maderensis fishery in the coastal areas of Ibeju-Lekki, Lagos, Nigeria. The study adopted a mixed-method approach involving qualitative and quantitative research methods. These include species identification, water quality analysis, land use change analysis, field surveys, focus group discussions and interviews. Results show genetic analysis of the fish samples from six stations revealed that the species had a mean of 98% similarity to Sardinella maderensis in NCBI. Multiple linear regression indicates that anthropogenic variables explained approximately 4.62% of the variance in the fish catch (p &lt; .001, R2 = .05). Water samples showed heavy metal levels were above international limits, high total petroleum hydrocarbon (TPH) pollution in all stations (27.56 mg/L- 3985.40 mg/L). Physiochemical analysis of water samples indicated TDS higher than acceptable limits (Mean = 24971.1 mg/L) and inadequate chlorophyll-a level (Mean = 0.01 µg/L). Hence, urgent strategies are required to mitigate anthropogenic threats through inclusive coastal management policies supporting resilient artisanal fisheries and marine spatial planning.

Understanding the genotype x environment (GE) interaction for traget trait is valuable for growers, agronomists, breeders and the seed industry. The objective of this study was to see and explore the genotype x environment interaction for grain yield of wheat to better guide genotype selection and breeding. The genotype main effect and GE interaction effect (GGE) biplots resolved the following three genotypes: 85 (ETW17-377), 82 (ETW17-374) and 13 (ETW17-281) for being the best yielding and stable. The Kulumsa site planted on 4^th of July 2017 (environment 7=E7) and the DebreZeit site on 20^th of July 2017 (E3) were the most effective environments in distinguishing the test genotypes and are thus suitable environments for future evaluation and selection with specific adaptation. Melkasa site planted on 4^th July (E9) was a representative environment where genotypes can be evaluated for wide adpaptation. The genetic covariate biplot indicated that thousand kernel weight (TKW) and plant height (PH) had significant positive associations with grain yield implying the possible concurrent indirect selection of both traits for exploiting GE interaction for grain yield of wheat.

Solventogenic Clostridium species are important for establishing sustainable industrial bioproduction of fuels and important chemicals. The inherent versatility of these species in substrate utilization and the range of solvents produced during acetone butanol-ethanol (ABE) fermentation make solventogenic Clostridium an attractive choice for biotechnological applications such as production of fuels and chemicals. The functional qualities of these microbes have thus been identified to be due to complex regulatory networks that play essential roles in modulating the metabolism of this group of bacteria. Genomes of solventogenic Clostridium species have relatively greater prevalence of genes that are intricately controlled by various regulatory molecules than most other species. Consequently, the use of genetic or metabolic engineering strategies that do not consider the underlying regulatory mechanisms will not be effective. Several regulatory factors involved in substrate uptake/utilization, sporulation, solvent production, and stress responses (Carbon Catabolite Protein A, Spo0A, AbrB, Rex, CsrA) have been identified and characterized. In this review, the focus is on newly identified regulatory factors in solventogenic Clostridium species, the interaction of these factors with previously identified molecules, and potential implications on substrate utilization, solvent production, and resistance/tolerance to lignocellulose-derived microbial inhibitory compounds.

Cinnamomum tamala leaf (CTL), also known as tejpat and Indian bay leaf, is used all over the world for seasoning, flavouring, and medicinal purposes. Numerous researchers are interested in exploring the nutritional and medicinal benefits of CTL due to their potential as nutraceuticals. These characteristics could be explained by the presence of several essential bioactive substances and lipid derivatives. There are no reports available on this species about its metabolites profile. In this work, rapid screen and identify chemical compounds in supercritical (SC)-CO2 extracts of CTL by use of UPLC-Q-TOF-MSE with multivariate statistical analysis approach was established in both negative and positive mode. As a results, a total of 166 compounds, including 66 monocarboxylic fatty acids, 52 dicarboxylic fatty acids, 27 fatty acid amides, and 21 others were tentatively identified based on accurate mass, and the mass spectrometric fragmentation pattern, out of which 142 compounds are common and found in all five CTL extracts. They displayed robust [M+H]+ and/or [M-H]- ions in both low- and high-energy collision-induced dissociations (CIDs). Based on chemical profiling and chemometric analysis, CTL4 (300bar/55°C) extract was found significantly more potent in other CTL’s extracts. A new mono- and di-carboxylic fatty acids, fatty acid amides and other essential bioactive compounds were separated within 20 min runtime and identified in CTL for the first time. The combination of UPLC-Q-TOF-MSE and chemometric analysis is a powerful method to rapidly screen the metabolites profile for the quality control of C. tamala leaf.

Helicobacter Pylori (H. Pylori) is a common pathogen with high prevalence of infection in human populations. Diagnosis of H. Pylori infection is critical for its treatment, eradication, and prognosis. Biosensors have been demonstrated to be powerful for rapid onsite detection of pathogens, particularly for point-of-care test (POCT) scenarios. In this work, we propose a novel optical biosensor, based on nanomaterial porous silicon (PSi) and photonic surface state Tamm Plasmon Polariton (TPP), for detection of cytotoxin-associated antigen A (CagA) antigen of H. Pylori bacterium. We fabricated the PSi TPP biosensor, analysed its optical characteristics and demonstrated through experiments towards sensing of CagA antigen, that TPP biosensor has sensitivity of 100 pm/(ng/ml), limit of detection of 0.01 ng/ml, and specificity in terms of positive-to-negative ratio of more than six. From these performance factors, it can be concluded that TPP biosensor can serve as an effective tool for diagnosis of H. Pylori infection, either in analytical labs or in POCT applications.

To date, various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an E. coli cell-free expression method to screen better chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the amount variables between samples without protein purification. We applied it to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin, and determined the rank orders of antibacterial activities on different S. aureus strains in our experimental conditions.

Information geometry (IG) is a fascinating combination of differential geometry and statistics where a Riemannian manifold's structure is applied to a statistical model. It may find numerous fascinating uses in the domains of theoretical neurology, machine learning, complexity, and (quantum) information theory, among others. (IG) aims to provide a differential-geometric perspective on statistical geodesic models' structure. In this case, IG, KD, and J-divergence (JD) are used to define the manifold of the Generalised Brownian Motion (GBM). Consequently, the geodesic equations (GEs) are devised, and GB information matrix exponential (IME) is presented. Moreover, for first time ever, the necessary and sufficient mathematical requirement that characterizes the developability of Generalized Brownian Motion(GBM) manifold is devised. Also, a novel sufficient and necessary conditions which characterizes the regions where the surface describing GBM is minimal is determined. Also, it is shown that GBM has a non-zero 0-Gaussian and Ricci curvatures. Consequently, this advances the establishment of a unified GBM- Relativistic Info-Geometric based analysis.

Recently, Shehata et al. [37] introduced the r+1Rs(B;C; z) matrix function and established some properties. The aim of this study established to devote and derive certain basic properties including analytic properties, recurrence matrix relations, dierential properties, new integral representations, k- Beta transform, Laplace transform, fractional k-Fourier transform, fractional integral properties, the k-Riemann{Liouville and k-Weyl fractional integral and derivative operators an extended version of r+1Rs;k matrix function. We establish its relationships with other well known special matrix functions which have some particular cases in the context of three parametric Mittag-Leer matrix function, k- Konhauser and k-Laguerre matrix polynomials. Finally, some special cases of the established formulas are also discussed.

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, imposing a regime of predation risk. Consequently, prey experience both consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories of prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a great invasive threat to global horticulture. While earlier research has primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated reduced development time in the presence of isolated H. patellifera or H. patellifera odor, yet evidenced significantly increased fecundity. Conversely, males displayed no significant change in development time. Additionally, neither female nor male body weight at death was significantly influenced by predation risk from isolated predators or predator odor. These results indicated adaptive developmental strategies of B. dorsalis when faced with risks from predators and highlight the important role of predator odor, which has the potential to lay the groundwork for improving biological control efforts and innovative approaches within pest control.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigates B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq Tannic acid / 100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq Chlorogenic acid / 100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods; our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and Berberine - Berberine sulfate hydrate (BS) - investigated on Daphnia sp reported significant BS toxicity after 24 h; BVE revealed considerable toxicity after 48 hours and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated on different tumor cell lines after 24 and 48 hours of treatments. The MTS assay evidenced a dose- and time-dependent antiproliferative activity, higher on BS than BVE. The strongest diminution of tumor cell viability was recorded on breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 &lt; 100 µg/mL). However, no cytotoxicity was reported on normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE's concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

There are laws and rights aimed at people with disabilities, especially those with Mild Intellectual Disability (LDD), who actively participate in society but face barriers in learning and participating in various activities. In Colombia, where 1.3 million people with disabilities are registered, 16.8% correspond to the category of DIL, some of whom are part of the economically active population. Despite this, significant employment gaps persist.In order to address this gap, this research focuses on the analysis of the specific problems related to the labor inclusion of people with IDL in logistics environments, particularly in cold rooms. The aim is to prevent occupational hazards through the application of Industry 4.0 technologies.Through the collaboration of the Analytics and Design Research Seedbed, with entrepreneurs and experts in the field, significant challenges in labor inclusion in low-temperature environments were identified. The agile Scrum methodology was used to develop a prototype of an application that addresses these issues. This prototype meets the functional and non-functional requirements necessary to ensure the protection and prevention of risks for workers with DIL who perform functions in refrigerated rooms.This prototype manages to provide an inclusive alternative for people with disability Intellectual Light, challenging business cultural paradigms, by integrating mobile devices with Industry 4.0 technologies, encouraging greater interaction between machines and human beings, thus prioritizing the health and safety of employees in their daily activities.

Transitions from seed to seedling represent a critical developmental step in the life cycle of higher plants, dramatically affecting plant ontogenesis and stress tolerance. The release from dormancy to acquiring the germination ability is defined by a balance of phytohormones, with a substantial contribution of abscisic acid (ABA), which inhibits germination. We studied the embryonic axes of Pisum sativum L. before and after radicle protrusion. Our previous work compared RNA sequencing-based transcriptomics in the embryonic axes isolated before and after radicle protrusion. The current study aims to analyze ABA-dependent gene regulation during the transition of embryonic axes from germination to post-germination stage. First, we determined the levels of abscisates (ABA, phaseic acid, dihydrophaseic acid, and neo-phaseic acid) using the ultra-high-performance liquid chromatography-tandem mass spectrometry. Second, we made a detailed annotation of ABA-associated genes using RNA sequencing-based transcriptome profiling. Finally, we analyzed the DNA methylation pattern in the promoters of the PsABI3, PsABI4, and PsABI5 genes. We showed that changes in the abscisate profile are characterized by the accumulation of ABA catabolites, and the ABA-related gene profile is accompanied by the upregulation of genes controlling the seedling development and the downregulation of genes controlling the water deprivation. The expression of ABI3, ABI4 and ABI5, which encode the crucial transcription factors during late maturation, was downregulated by more than 20-fold, and their promoters exhibited a high level of methylation already at the late germination stage. Thus, although ABA remains important, other regulators seems to be involved in the transition from seed to seedling.

In the face of climate change, bringing more useful alleles and genes from wild relatives of wheat is crucial to develop climate-resilience varieties. We used two populations of backcrossed recombinant inbred lines (BIL1 and BIL2), developed using two intra-specifically diverse Aegilops tauschii accessions from lineage 1 and lineage 2, respectively, and backcrossing to common wheat cultivar ‘Norin 61’. The study aimed to identify quantitative trait loci (QTL) associated with heat stress (HS) tolerance. The two BILs were evaluated under heat stress environments in Sudan for phenology, plant height (PH), grain yield (GY), biomass (BIO), harvest index (HI), and thousand kernel weight (TKW). Grain yield was significantly correlated with BIO and TKW under HS; therefore, stress tolerance index (STI) was calculated for these traits as well as for GY. A total of 16 heat tolerant lines were identified based on GY and STI-GY. The QTL analysis performed using inclusive composite interval mapping identified a total of 40 QTLs in BIL1 and 153 QTLs in BIL2 across all environments. We detected 39 QTLs associated with GY-STI, BIO-STI, and TKW-STI in both populations (14 in BIL1 and 25 in BIL2). The QTL associated with STI were detected on chromosomes 1A, 3A, 5A, 2B, 4B, and all the D-subgenomes. We found that QTL detected only under HS for GY on chromosome 5A, TKW on 3B and 5B, PH on 3B and 4B, and grain filling duration on 2B. The higher number of QTLs identified in BIL2 for heat stress tolerance suggests the importance of assessing the effects of intraspecific variation of Ae. tauschii in wheat breeding as it could modulate the heat stress responses/adaptation. Our study provides useful genetic resources for uncovering heat-tolerant QTLs for wheat improvement for heat stress environments.

Abstract: Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the devel-opment of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granu-lomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a retrospective study at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. Clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n=8) and biliary atresia (n=4). The predominant type of infection for which they received CZA was intra-abdominal infections caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, 2 patients died, with one case directly linked to the infection’s fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA’s potential as a primary treatment option against OXA-48-producing infections.

The study assessed the trapping efficacy of locally-modified 1) Gravid Aedes Trap(GAT) lined with insecticide-treated net (ITN) as a killing agent, 2) Autocidal Gravid Ovitrap(AGO) with sticky board in the semi-field system (SFS) and field setting. Fully-balanced Latin square experiments were conducted to compare GAT lined with ITN vs AGO, both with either yeast or grass infusion. Biogents-Sentinel (BGS) with BG-Lure and no CO2 was used as standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs 49%,OR=2.22,[95%CI:1.89-2.60],p

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.

A reduction of melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding molecular processes of melatonin-related signaling is critical for intervention of AD progression. Recently, we synthesized and tested a series of melatonin derivates with donepezil fragments in silico and in vitro. In this study, one of the most potent compounds, 3c, was studied in an in vivo rat model of pinealectomy (pin) and subsequent icvAβ1-42 infusion. Melatonin was used as a referent drug. The treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) exerted a beneficial effect on memory decline and concomitant rise of Aβ1-42 and pTAU in the hippocampus in the pin + icvAβ1-42 rats. Melatonin supplementation facilitated the non-amyloidogenic signaling via a non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c derivate up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our findings strongly support the hypothesis that melatonin-related derivates may become a promising drug candidate in AD therapy.

To delve into the structure-function relationship of transmembrane proteins (TMPs), robust protocols are needed to produce them in a pure, stable, and functional state. Among all hosts that express heterologous TMPs, E. coli has the lowest cost and fastest turnover. However, many of the expressed in E. coli TMPs are misfolded. Several strategies have been developed to either direct the foreign TMPs to E. coli’s membrane or retain them in a cytosolic soluble form to overcome this deficiency. Here, we summarize protein engineering methods to produce chimera constructs of the desired TMPs fused to either signal peptide or precursor maltose binding protein (pMBP) to direct the entire construct to the periplasm, therefore depositing the fused TMP in the plasma membrane. We further describe strategies to produce TMPs in soluble form by utilizing N-terminally fused MBP without signal peptide. Depending on its N- or C-terminus location, a fusion to apolipoprotein A-I can either direct the TMP to the membrane or shield the hydrophobic regions of the TMP, maintaining the soluble form. Strategies to produce G-protein coupled receptors, TMPs of Mycobacterium tuberculosis, HIV-1 Vpu, and other TMPs are discussed. This knowledge could increase the scope of TMPs’ expression in E. coli.

The spatial and temporal variability in dietary preferences of juvenile three-spined stickleback Gasterosteus aculeatus, was studied across typical coastal habitats of Keret Archipelago, Kandalaksha Bay, the White Sea. Sampling of fish using beach seine was implemented in late July-early August and in late August, and zooplankton samples were collected to make a quantitative evaluation of abundance of potential prey items. Similarity Percentage (SIMPER) analysis implemented over the data obtained from stomach content analysis revealed five planktonic taxa mostly contributing to the diet of juvenile sticklebacks, of which copepod Temora longicornis was the most important prey item at marine sites, while Acartia longiremis prevailed in diet of fishes in marine lagoon. Calculation of selectivity index demonstrated that some taxa (e.g., A. longiremis) were always avoided by juvenile fishes, others (e.g. Microsetella norvegica) were firstly avoided and then selected in late August. Calculation of selectivity index was implemented per sample and per individual fish indicated that taxa like T. longicornis and were selected during the whole period of study, fishes demonstrated pronounced individual variation in prey selectivity. In general, data on selectivity indicated that despite juvenile sticklebacks feed on mostly available prey items, they can demonstrate taxonomic and size-specific prey selectivity.

Kininogens are multidomain glycoproteins found in the blood of most vertebrates. They are important in the blood coagulation cascade pathways - in intrinsic pathway activation leading to thrombin generation partially independently from tissue factor dependent extrinsic pathway, connecting blood coagulation with the kallikrein-kinin system. Nothing is known about the shape on atomic level therefore the endeavor to obtain the good-quality spatial structure of kininogens is important for a better understanding of their role in disease and treatment. Application of cryo-EM is important for solving the spatial structure of kininogens, drawing new frontiers in understanding the function and opening new pathways for drug development.

For gravitational wave (GW) detected neutron star mergers, one of the leading candidates for electromagnetic (EM) counterparts is the afterglow from an ultra-relativistic jet. Where this afterglow is observed, it will likely be viewed off-axis, such as the afterglow following GW170817/GRB 170817A. The temporal behaviour of an off-axis observed GRB afterglow can be used to reveal the lateral jet structure, and statistical model fits can put constraints on the various model free-parameters. Amongst these parameters is the inclination of the system to the line of sight. Along with the GW detection, the afterglow modelling provides the best constraint on the inclination to the line-of-sight and can improve the estimates of cosmological parameters e.g. the Hubble constant, from GW-EM events. However, modelling of the afterglow depends on the assumed jet structure and, often overlooked, the effects of lateral spreading. Here we show how the inclusion of lateral spreading in the afterglow models can affect the estimated inclination of GW-EM events.

Negative corona discharges occur widely in high voltage transmission lines and charged aircraft, which can cause strong electromagnetic interference. Negative corona discharge is typically performed simultaneously at multiple discharge points. In this study, the current and its EM radiation characteristics of single-needle and multi-needle negative corona discharge in different conditions were tested. The current and electromagnetic radiation characteristics of the two discharge structures were compared. The dipole radiation model was established to analyze the EM radiation characteristics of the negative corona discharge.The results show that, It is only when the voltage reaches a certain threshold that the current and electromagnetic radiation fields of the multi-needle discharge structure will be superimposed and their amplitudes will increase significantly. The frequency of electromagnetic radiation signal does not change with the number of needles, cathode geometry and applied voltage, but only depends on ambient pressure. It provides a basis for detecting corona discharge sources under different conditions.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

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.

Bamboo is considered a sustainable construction material due to its ability to grow quickly and its mechanical properties that are comparable to timber. Contributing to the current effort to establish the structural bamboo standards in the National Structural Code of the Philippines (NSCP), this study establishes the characteristic compressive strength of four bamboo species: Bambusa vulgaris (36 samples), Dendrocalamus asper (36 samples), Bambusa blumeana (94 samples), and Guadua angustifolia Kunth (30 samples). The samples were subjected to compressive loading following ISO 22157-1 (2017). The characteristic compressive strength values obtained, according to ISO 12122-1 (2014), were 40.35 MPa for B. vulgaris, 40.21 MPa for D. asper, 46.63 MPa for B. blumeana, and 36.99 MPa for G. angustifolia Kunth. Simple linear analysis, One-way ANOVA, and Welch’s t-Test were used to analyze the correlation models and establish a comparative analysis of the effect of nodes, and geometric and physical properties on the compressive strength of bamboos. Comparing the characteristic compressive strength obtained from this study to the strength of unseasoned structural timber of Philippine woods, all bamboo species showed higher strength values, and thus have great potential as an alternative construction material to timber.

Pseudomonas aeruginosa is an opportunistic pathogen that poses a significant threat to individuals with chronic respiratory ailments, such as cystic fibrosis (CF). The pathogen is highly prevalent in CF individuals and is responsible for chronic infection, resulting in severe tissue damage and poor patient outcome. However, early detection and immediate treatment are critical to prevent bacterial persistence and establishment of chronic infection. Presently, antibiotics including aminoglycosides, beta-lactams, polymyxins, and fluoroquinolones along with anti-inflammatory medications are being used to treat P. aeruginosa infections in CF patients. However, prolonged antibiotic administration has led to the emergence of widespread multidrug resistance in P. aeruginosa (CF isolates), contributing to antimicrobial resistance (AMR) and failure of antimicrobial therapies. Thus, exploring viable alternatives such as antivirulence therapeutics can be vital towards managing pseudomonal infections in CF patients and mitigating the risk of AMR. In this direction, antivirulence strategies achieving targeted inhibition of bacterial virulence pathways/factors, including quorum sensing, efflux pumps, lectins, and iron chelators, have been widely explored against CF isolates of P. aeruginosa. Simultaneously, there have been discussions about the sufficiency of in vitro findings and their successful translation in pulmonary infection models (in vivo) for the clinical implementation of antivirulence therapies hence, this review article presents a bird’s eye view on the pulmonary infections involving P. aeruginosa in CF patients by laying emphasis on factors contributing to bacterial colonization, persistence, and disease progression along with the current line of therapeutics against P. aeruginosa in CF while underscoring the limitation of antimicrobial approaches. We further collate scientific literature and comprehensively discuss the various antivirulence strategies that have been successfully tested against P. aeruginosa isolates from CF patients. This could pave the way towards a paradigm shift towards clinical therapy of pseudomonal infections in CF and can potentially override conventional antimicrobial treatments.

The infections caused by various bacterial pathogens both in clinical and community settings represent a significant threat to public healthcare worldwide. The growing resistance to antimicrobial drugs acquired by bacterial species causing healthcare-associated infections has already become a life-threatening danger noticed by the World Health Organization. Several groups or lineages of bacterial isolates usually called ‘the clones of high risk’ often drive the spread of resistance within particular species. Thus, it is vitally important to reveal and track the spread of such clones and the mechanisms by which they acquire antibiotic resistance and enhance their survival skills. Currently, the analysis of whole genome sequences for bacterial isolates of interest is increasingly used for these purposes, including epidemiological surveillance and developing of spread prevention measures. However, the availability and uniformity of the data derived from the genomic sequences often represents a bottleneck for such investigations. In this dataset, we present the results of a comprehensive genomic epidemiology analysis of 17,546 genomes of a dangerous bacterial pathogen Acinetobacter baumannii. Important typing information including multilocus sequence typing (MLST)-based sequence types (STs), intrinsic blaOXA-51-like gene variants, capsular (KL) and oligosaccharide (OCL) types, CRISPR-Cas systems, and cgMLST profiles are presented, as well as the assignment of particular isolates to nine known international clones of high risk. The presence of antimicrobial resistance genes within the genomes is also reported. These data will be useful for researchers in the field of A. baumannii genomic epidemiology, resistance analysis and prevention measure development.

The microbiome, once considered peripheral, is emerging as a relevant player in the intricate web of factors contributing to cancer development and progression. These often overlooked microorganisms, in the context of urological malignancies, have been investigated primarily focusing on the gut microbiome, while exploration of urogenital microorganisms remains limited. In light of this, our systematic review delves into the complex role of these understudied actors in various neoplastic conditions, including prostate, bladder, kidney, penile, and testicular cancers. Our analysis found a total of 37 studies, with prostate cancer-12, bladder cancer-20, kidney cancer-4, penile/testicular cancer-1, which reveals distinct associations specific to each condition, hinting at potential therapeutic avenues and future biomarker discoveries. It becomes evident that further research is imperative to unravel the complexities of this domain and provide a more comprehensive understanding.

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (&gt;200 CGG repeats) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. Individuals with FXS experience a wide range of challenges related to social interaction (SI). Animal models, such as Drosophila melanogaster model for FXS where the only ortholog of human FMR1 (dFMR1) is mutated, have played a crucial role in understanding of FXS. The aim of this study was to investigate SI in the dFMR1B55 mutants using the novel Drosophila Shallow Chamber and a Python data processing pipeline based on social network analysis (SNA). In comparison with wild-type flies (w1118), SNA analysis in dFMR1B55 mutants revealed hypoactivity, fewer connections in their networks, a lower ability to efficiently transmit information, fewer alternative pathways for information transmission, a higher variability in the number of interactions they achieved, and tended to stay near the boundaries of the testing chamber. These observed alterations indicate the presence of characteristic strain-dependent social networks in dFMR1B55 flies, commonly referred to as the group phenotype. Finally, a combination of novel research tools is a valuable method for SI research in fruit flies.

Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in Botrytis cinerea, identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylal-lyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associ-ated with B. cinerea's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop pro-tection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into B. cinerea's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interven-tions against B. cinerea. This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.

The continuous flowing spacetime forms a spacetime group G, one of its fundamental groups is the Poincare group PO(1,3), and the matter and interaction fields are representations of its intrinsic spacetime group. As a kind of quantized space-time unit, space-time group elements generate both space-time manifolds and matter. Matter and fields are aggregates of the quantum space-time within them and determine their type: the Lorentz group SO(1,3) represents a rotating spacetime corresponding to visible matter and the translation group P^1,3 represents a translational spacetime corresponding to dark matter and dark energy. The aggregation mode of space-time degrees of freedom in matter reveals that charge conjugation symmetry is the inverse symmetry of internal time of charged particles, and the external parity breaking of neutrinos is also due to their internal spatial aggregation mode.

BACKGROUND: Is pharmacovigilance at a moment of prominence for science and in relation to government responsibilities towards their nations, as the new coronavirus pandemic has surprised everyone in a negative and lethal way. OBJECTIVE: Evaluate pharmacovigilance as a resource for controlling and understanding the adverse effects caused by vaccines in use. DESIGN AND SETTING: Narrative review developed by a research group at Faculty of Medicine of the University of Porto. METHODS: This is a narrative review of the literature available in electronic media, government bulletins and similar bodies. The search was carried out using the descriptors: "Pharmacovigilance AND COVID-19 in Brazil", "Vaccine Development AND COVID-19 in Brazil", "Vaccination Hesitancy AND COVID-19 in Brazil", "Pharmacovigilance AND COVID-19", "Vaccine Development AND COVID-19", "Vaccination Hesitancy AND COVID-19", Pharmacovigilance AND COVID-19, Vaccine Development AND COVID-19, Vaccination Hesitancy AND COVID-19, "Public Health Surveillance AND COVID-19". In the period from May 2021 to June 2022. RESULTS: From the database search, 3 journal articles, 4 government bulletins and 535 scientific articles were identified. Of the total of 542 bibliographic materials, 36 were selected according to the selection criteria and objectives of the study. CONCLUSIONS: The vaccines in use have proven efficacy, despite adverse reactions that cannot be attributed solely and exclusively to their use, since the medical history of each patient should be considered in the investigation of each case, especially when there is death. The Brazilian data for adverse events, although the country is continental in its size, are acceptable given the number of deaths recorded.

The inherited ‘EIA’ process at Brexit is based on a ‘Project’ period from Inception tothe start of construction works. The ‘Incompleteness’ of the process covers andidentifies stages that will impact on the environmental cycle: construction period,operational life, de-commissioning and a return to acceptable environmental footprint.A master environment structure-plan framework is required to commence with theupgrading of the complete ‘EIA’ process, embracing separate limbs for the UK’spriority environmental targets for climate change, and other major adverse effectswhich result in serious ‘harm’ to the UK environment. The identification of the processfor ‘incompleteness’ requires effective sustainability, and inclusion of effectivemanagement tools, for the essential ‘monitoring/control/recording’ proceduresthroughout the project life and the natural environmental cycle. This will allow theopportunity for a new approach to a structured ‘Suite of EIAR Directives’, to enable a‘EIAR’ regime that ‘will remain fit and proper for UK purpose’.

In recent decades, there have been numerous endeavors to develop a novel category of survival distributions possessing enhanced flexibility through the extension of existing distributions. This article constructs and validates the statistical properties of a novel survival distribution in order to obtain an alternative distribution that is suitable for analyzing survival data by presenting the novel mixture of the Fréchet distribution along with statistical properties such as the probability density function (PDF), cumulative distribution function (CDF), rth ordinary moment, skewness, kurtosis, moment-generating function, mean, variance, mode, survival function, hazard function, and asymptotic behavior, as well as constructing the estimators of the unknown parameter by employing the expectation-maximization (EM) algorithm, and simulated annealing. Additionally, the performance of the proposed estimators was compared with bias, mean squared errors (MSE), and simulated variances, and given an illustrative example of the proposed distribution to the survival data set in order to show that the proposed distribution is appropriate for the right-skewed data. This will be extremely advantageous in survival analysis.

In the era of big data with increasingly complex data structures and ever-larger data scales, matrix-type data are becoming highly valued and their applications in the fields of medicine, industry, education, geography, and astronomy are growing in extent. In recent years, significant progress has been made in the practical use of matrix variable t-distribution finite mixture models for handling data in order to address the issues of multi-subgroup structures and long data tails. In this paper, the expectation-maximization (EM) algorithm with penalized maximum likelihood is proposed to resolve the problem of the unbounded nature of the likelihood function applied to the model by considering the degeneracy of the variance-covariance matrix of this model. Our data were analyzed through simulations and real data, and the results demonstrate that our model is effective in both preventing the likelihood function from being unbounded and in ensuring the accuracy of the estimated parameters of the EM algorithm.

The AREB/ABF (ABA response element binding) proteins in plants are vital for plant stress responses, but the understanding of AREB/ABFs in orchid species, an important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genome and classified into three groups (groups I, II, and III) via a phylogenetic analysis, which was further supported by the analysis of their conserved motifs and gene structures. The cis-elements analysis showed that hormone response elements followed by light and stress responses were widely rich in AREB/ABFs. A prediction analysis of orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory elements (CREs) analysis of their promoter regions and revealed that several transcriptional factor (TF) gene family were abundant as the potential regulators for orchid AREB/ABFs. Expression profile analysis based on public transcriptomic data showed that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as the homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that Arabidopsis transgenic overexpressing DcaABI5 could rescue the ABA insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, broken chromosomes may not be restored correctly, allowing breaks to persist or rearrange chromosomes. These abnormalities are potentially catastrophic events that can originate from viral infections. I used bioinformatic analyses of publicly available breast cancer patient data to show that the distribution of chromosome breaks in hereditary breast cancers differs markedly from sporadic breast cancers. Then I tested hereditary breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had decisive matches to Epstein-Barr virus (EBV / HHV4) tumor variants HKHD40 and HKNPC60. Many breakpoints were near EBV genome anchor sites, human EBV tumor-like sequences, EBV-associated epigenetic marks, and some fragile sites. On chromosomes 2 and 12, sequences near EBV genome anchor sites accounted for 90% and 88% of breakpoints (p<0.0001), respectively. On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences in 19 hereditary breast cancers. In contrast, 19 sporadic breast cancers only had 12 interchromosomal breakpoint regions on chromosome 4 near EBV-like sequences. On various other chromosomes, five EBV genome anchor sites were near hereditary breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Independent evidence further implicating EBV in hereditary breast cancer breakpoints is that 25 breast cancer break positions are within 1.25% of breakpoints in model EBV cancers. In addition to BRCA1 or BRCA2 mutations, all the hereditary breast cancers had mutated genes essential for immune responses. This compromise facilitates reactivation of herpes viruses which produce nucleases capable of breaking chromosomes. EBV also causes other deleterious effects: anchored EBV episomes can interfere with normal replication and obstruct DNA break repairs; even very early infection causes massive transcription changes. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.

Urological cancers include a spectrum of malignancies affecting organs of the reproductive and/or urinary systems, such as prostate, kidney, bladder, and testis. Despite improved primary prevention, detection and treatment, urological cancers are still characterized by an increasing incidence and mortality worldwide and although advances have been made toward understanding the molecular basis of these diseases, a complete insight of the pathogenic mechanisms is still a research challenge for defining safer pharmacological therapies and prognostic factors, especially for the metastatic stage of these neoplasms for which no effective therapies exist. Glyoxalases are enzymes that catalyzes the glutathione-dependent metabolism of cytotoxic methylglyoxal (MG), thus protecting against cellular damage and apoptosis. They are generally overexpressed in numerous cancers as a survival strategy by providing a safeguard through enhancement of MG detoxification. Increasing evidence suggest that glyoxalases, especially Glo1, would act as oncogenes in urological malignancies and be central to their initiation, growth and progression. In this review, we highlight the critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and provide an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers. We also discuss the promise and challenges for Glo1 inhibitors as future anti-PCa therapeutics and the potential of glyoxalases as biomarkers for PCa diagnosis.

Gastroesophageal (GE) junction adenocarcinoma is an aggressive malignancy of growing incidence and is associated with public health issues such as obesity and GERD. Management has evolved over the last 2 decades to incorporate a multidisciplinary approach including endoscopic intervention, and neoadjuvant chemotherapy/ chemoradiation and minimally invasive or more limited surgical approaches. Surgical approaches include esophagectomy, total gastrectomy, and more recently proximal gastrectomy. This review analyzes the evidence for and applicability of these varied approaches in management as well areas of continued controversy and investigation.

Blood cancers, including leukemia, lymphoma, and myeloma, pose significant diagnostic challenges due to their diverse and complex nature. Detecting these cancers early and accurately is crucial for timely intervention and improved patient outcomes. This review explores current and emerging detection methods for human blood cancers, focusing on their principles, advantages, limitations, and potential clinical applications.

Epidemiological studies on micronutrient consumption have reported protective associations in the incidence and/or progression of various cancer types. Supplementation with some of these micronutrients has been analyzed, showing chemoprotection, low toxicity, antiproliferation, and the ability to modify epigenetic signatures in various cancer models. The following review inves-tigates the reported effects of micronutrient intake or supplementation in breast cancer progres-sion. A PubMed search was conducted with the keywords “micronutrients breast cancer progres-sion,” and the results were analyzed. The selected micronutrients were: Vitamins (A, C, D, and E), Folic Acid, metals (Cu, Fe, Se, and Zn), fatty acids, polyphenols, and iodine. The majority of in vitro models showed antiproliferative, cell cycle arrest, and antimetastatic effects for almost all the micronutrients analyzed, but these effects do not reflect animal or human studies. Only one clinical trial with Vitamin D and one pilot study with molecular iodine showed favorable overall survival and disease-free interval.

My innovative entropy measure, Ismail entropy, namely, (IE) is an ultimate generalization to numerous generalized entropies within the literature. The fractal dimension of IE is identified in this paper. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

: Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasize, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8,332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8,332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neo-plasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched Pubmed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors, and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further pre-clinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

Cancer risk is known to increase tremendously when the immune system is suppressed, e.g., as observed in young organ-transplant recipients and AIDS patients. Based on such data, it may be hypothesized that the main reason for the development of clinical cancer is the weakening or suppression of the immune system, and that uncontrolled multiplication of cancer cells occurs when some aspects of the immune system fall below certain critical levels. Therefore, cancer may be prevented and treated by boosting these critical aspects of the immune system so that they are maintained above the critical levels. If multiple immune system boosting interventions are utilized, more aspects of the immune system would be boosted, increasing the likelihood of enhancing the critical aspects of the immune system and generating a cancer preventive and/or therapeutic effect. Clinical trials are needed to validate this approach for cancer prevention and treatment. If validated, the proposed approach could result in a major reduction of the death and suffering caused by cancer in the world.

Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The prevalence of this disease is associated with various factors, including age, heredity, and race. Recent research in prostate cancer genetics has identified several genetic variants that may be associated with an increased risk of developing the disease. However, despite the significance of these findings, genetic markers for prostate cancer are not currently utilized in clinical practice as reliable indicators of the disease. In addition to genetics, epigenetic alterations also play a crucial role in prostate cancer development. Aberrant DNA methylation, changes in chromatin structure, and microRNA (miRNA) expression are major epigenetic events that influence oncogenesis. Existing markers for prostate cancer, such as prostate-specific antigen (PSA), have limitations in terms of sensitivity and specificity. The cost of testing, follow-up procedures, and treatment for false-positive results and overdiagnosis contributes to the overall healthcare expenditure. Improving the effectiveness of prostate cancer diagnosis and prognosis requires either narrowing the risk group by identifying new genetic factors or enhancing the sensitivity and specificity of existing markers. Immunological biomarkers (both circulating and intra-tumoral), including markers of immune response and immune dysfunction, represent a potentially useful area of research for enhancing the diagnosis and prognosis of prostate cancer. Our review emphasizes the need for developing novel immunological biomarkers to improve the diagnosis, prognosis, and management of prostate cancer. We highlight the most recent achievements in the identification of biomarkers provided by circulating monocytes and tumor-associated macrophages (TAMs). We highlight that monocytes-derived and TAMs-derived biomarkers can enable to establish the missing links between genetic predisposition, hormonal metabolism and immune responses in prostate cancer.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

In the era of nanotechnology, researchers are implementing point to care service to cancer patients to detect malignancy beforehand and to reduce the mortality rate of cancers. Cancer is known to be the most fatal disease among all other diseases and the survivability from cancer is quite impossible if the stage of the cancer is an advanced level. Though the early detection of cancer can increase the chances of survival with a double fold. Biosensor is a part of nanotechnology which is capable to provide point to care service in the field of medicine. With the rising number of cancer occurrences being identified around the world and the increasing number of deaths because of the identification of advanced cancer, biosensors can play a significant part in the early detection of cancer. New molecular methods, including as genomic and proteomic approaches, are increasingly being used to study patient molecular profiles. When such diagnosis method is paired with bioinformatics tools, they generate new data that can be used to discover new disease biomarkers. Finding precise and sensitive indicators that are corelated to a specific disease, as with many other diseases, can be challenging. Furthermore, the concentration of biomarkers in biological fluids varies according to illness states and phases. Peptides, proteins, up or down regulated expression of gene markers, and gene alternation are all examples of molecular markers that are commonly used to diagnose cancer. In this article, we have highlighted six different deadliest cancers such as Ovarian, Breast, Prostrate, Lung, Colorectal and Liver cancer. The article contains distinct types of biomarkers which are normally found in these kinds of cancer and generally used as a potential diagnostic target in the medicine field. The article mainly summarized the application of different types of biosensors devices in the detection of the mostly found biomarkers in the above cancer types.

Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.

Objective: To provide mechanistic evidence for the epidemiological link between long-term use of alcohol containing mouthwashes and oral cancer.Methods: Human epithelial keratinocytes were exposed for 30 seconds to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay.Results: A marked cytotoxic effect was observed for ethanol concentrations of 20% and above. Conclusions: The cytotoxicity of ethanol can explain the epidemiological association between mouthwash use and oral cancer. Recent findings indicate that the risk of developing cancer in a tissue is strongly determined by the number of stem cell divisions accumulated by the tissue during a person's lifetime; cell division is a major source of mutations and other cancer-promoting errors. Since cell death activates the division of stem cells, the cytotoxicity of ethanol on the cells lining the oral mucosa will promote the division of the stem cells located in deeper layers to produce new cells to regenerate the damaged epithelium. If we regularly use mouthwashes containing cytotoxic concentrations of ethanol, we will force the stem cells of the oral cavity to divide more often than usual and our risk of developing oral cancer will probably increase.Clinical significance: Many mouthwashes contain percentages of ethanol above 20%. Because ethanol is not crucial to prevent and reduce gingivitis and plaque, members of the dental team should consider the potential risk of oral cancer associated with frequent use of alcohol containing mouthwashes when advising their patients.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

The cancer stem cell hypothesis suggests that neoplastic cells with stem characteristics hierarchically regulate tumor generation and its high cellular heterogeneity. These cells have been detected in all cancer types, and specific signaling pathways give the regulation of self-renewal and differentiation. In prostate cancer, androgen receptor signaling has been extensively studied, and in non-stem cells, it promotes cell proliferation and tumor progression, but in the cancer stem cell population, it negatively regulates processes such as self-renewal. However, in other types of cancer, such as breast and glioblastoma, the androgen receptor seems to favor the maintenance of cancer stem cells, suggesting that androgen signaling has different effects depending on the tumor context. This review discusses the role of androgen receptor in maintaining cancer stem cells by regulating proliferation, self-renewal, and differentiation, as well as the possible signaling pathways involved in these processes.

The COVID-19 pandemic has led to numerous delays in cancer-related care and cancer-specific screening, but the extent is not fully understood. For those that experience a delay or disruption in care, health related self-management is required to re-engage in care pathways and the role of health literacy in this pathway has not been explored. The purpose of this analysis is to (1) report the frequency of self-reported delays in cancer treatment and preventative screening services at an academic, NCI-designated center during the COVID-19 pandemic and (2) investigate cancer-related care and screening delays among those with adequate and limited health literacy. A cross-sectional survey was administered from an NCI-designated Cancer Center with a rural catchment area during November 2020 through March 2021. Nearly 19 percent of participants were categorized as having limited health literacy. Twenty percent of those with a cancer diagnosis reported a delay in cancer-related care; and 23-30% of the sample reported a delay in cancer screening. In general, the proportions of delays among those with adequate and limited health literacy were similar with the exception of colorectal cacner screening. There was also a notable difference in the ability to re-engage in cervical cancer screening among those with adequate and limited health literacy. Thus, there is a role for those engaged in cancer-related education and outreach to offer additional navigation resources for those at risk to cancer-related care and screening disruptions. Future study is warranted to investigate the role of health literacy on cancer care engagement.

Despite the recognized benefits of fecal occult blood test (FOBT) and mammography screenings, participation in breast (BC) and colorectal cancer (CRC) screening programs is still suboptimal. This study investigates municipal characteristics associated with their BC/CRC screening uptake profiles among women aged 55–69 years. Using data from 308 municipalities of Flanders from 2014 to 2017, a profile for each municipality based on its BC/CRC screening uptake compared with the median screening uptake was created. Logistic regression with generalized estimating equations was used to assess the associations between municipal characteristics and BC/CRC screening uptake profiles. The overall median uptake of cancer screening was higher for CRC (57.4%) than for BC (54.6%). The following municipal characteristics were associated with worse performance in terms of only CRC, only BC, or both CRC and BC screening uptake, respectively: foreign nationality, self-employment rate, (early) retirement rate, diabetes, disabilities; (early) retirement rate; age group 65–69, foreign nationality, self-employment rate, (early) retirement rate, wage-earners, diabetes. The following municipal characteristics were associated with better performance in terms of only CRC, only BC, or both CRC and BC screening uptake respectively: residential stability, having a partner, having children, jobseeker rate, GP visits, preventive dental visits; having children, GP visits; age group 55–59, residential stability, having a partner, having children, jobseeker rate, higher education, GP visits, preventive dental visits. This study’s results regarding the interrelation between the BC and CRC screening could be used to tailor interventions to improve the participation of the target population in both programs.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy was still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group-1 carcinogenic agents in humans by IARC. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was on average 8.7% of all cancer deaths registered yearly. Approximately 60% of deaths occurred in men and almost the whole burden was due to four infectious agents (Helicobacter pylori, HCV, HPV, and HBV). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, chromosome fragments may not be restored correctly. Resulting chromosome rearrangements can become critical breast cancer drivers. Because I had data from thousands of cancer structural alterations that matched viral infections, I wondered whether infections contribute to chromosome breaks and rearrangements in hereditary breast cancers. There are currently no interventions to prevent chromosome breaks because they are thought to be unavoidable. However, if chromosome breaks come from infections, they can be treated or prevented. I used bioinformatic analyses to test publicly available breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had the strongest matches to Epstein-Barr virus (EBV) tumor variants HKHD40 and HKNPC60. Many breakpoints were near sites that anchor EBV genomes, human EBV tumor-like sequences, EBV-associated epigenetic marks, and fragile sites. On chromosome 2, sequences near EBV genome anchor sites accounted for 90% of breakpoints (p<0.0001). On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences. Five EBV genome anchor sites were near breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Breakpoint flanking regions resembled known EBV-cancers. Twenty-five breakpoints in breast cancers were within 1.25% of EBV cancer breakpoints. In addition to BRCA1 or BRCA2 mutations, all the breast cancers had mutated genes essential for immune responses. Because of this immune compromise, herpes viruses can activate and produce nucleases that break chromosomes. Alternatively, anchored viral episomes can obstruct break repairs, whatever the cause. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

Dyadic data which is also called co-occurrence data (COD) contains co-occurrences of objects. Searching for statistical models to represent dyadic data is necessary. Fortunately, finite mixture model is a solid statistical model to learn and make inference on dyadic data because mixture model is built smoothly and reliably by expectation maximization (EM) algorithm which is suitable to inherent spareness of dyadic data. This research summarizes mixture models for dyadic data. When each co-occurrence in dyadic data is associated with a value, there are many unaccomplished values because a lot of co-occurrences are inexistent. In this research, these unaccomplished values are estimated as mean (expectation) of random variable given partial probabilistic distributions inside dyadic mixture model.

As the rapid development of communication industry, especially the 5G communication and IOT, there will be plenty of electromagnetic (EM) waves in the free space, which carry lots of energies. However, some of these energies are wasted in free space. To reuse these wasted energies, significantly growing interests are towards to the energy harvesting antennas. This paper is aimed to investigate a wearable antenna which can transfer RF energy from ambient sources to direct current by a soft and portable textile antenna. Among the numerous signals in mobile network, the GSM 1800, 3G, WiFi and 4G/5G will be chosen due to the city signal intensity distribution. Hence, a corresponding triple bands antenna has been designed to cover those frequency bands. The CST STUDIO SUITE is used in whole process of antenna design and simulation. The proposed antenna is a hooked dipole antenna with tuning bar (HATB) whose ends have small folded part in each side for better bandwidth performance. The presented antenna provides a wide operating band from 1.8 GHz to 2.5 GHz below -10 dB in return loss. And methods to overcome interference between antennas is found. Furthermore, using the corresponding rectifier to achieve the RF/DC conversion. The overall efficiency of whole rectifier is about 56.8 %, and output power level of the antenna system is 45.92nW. The experimental results could indicate that my textile hooked antenna harvester is a good choice for the charging system of personal wearable attachment, which could achieve low power absorbing for long distance anytime and anywhere.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in regulation of both apoptosis and mitosis. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rate in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer.

Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.

Tobacco use, most people would say. Smoking tobacco increases the risk of developing many types of cancer and is responsible for approximately one-third of all cancer deaths. The association between tobacco use and lung cancer is well known; lung cancer occurs about 20 times more often in heavy smokers than in nonsmokers [1]. However, many lung cancers are diagnosed in never smokers [2], and most smokers do not develop lung cancer [3,4].

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.

Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year [the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting]. Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecologic malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.

Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

(1) Background: The interplay between coronavirus disease 2019 (COVID-19) and laryngeal cancer represents a substantial challenge for both patients and healthcare. To garner information on recent mortality data for laryngeal cancer, including during the COVID-19 pandemic, we analyzed real-world data from the US Centers for Disease Control and Prevention (CDC). (2) Methods: We searched the CDC WONDER on-line database 2018-2022 using with the ICD-10 code for laryngeal cancer (C32; malignant neoplasm of larynx). We also performed a sub-analysis between genders, and across ten-year age groups. Data were analyzed with one-way analysis of variance (ANOVA) and Tukey post-hoc test. (3) Results: The trend of age-adjusted mortality ×100,000 did not change significantly between 2018-2022 (p=0.553). Males had higher age-adjusted mortality rates (M/F ratios between 4.6 and 5.0), but no significant variation was found in both genders (males: p=0.676; females: p=0.596). Although the mortality rate remained unchanged in people aged 35-84 years, the variation reached statistical significance in those aged 85 or older (p=0.004), displaying significant increase in 2021 compared to 2018 (p=0.006) and 2019 (p=0.039). (4) Conclusions: The impact of the COVID-19 pandemic on mortality for laryngeal cancer seemed to be relatively modest in the general US population. Nevertheless, closer attention must be paid to older people, in whom the unfavorable consequences of misdiagnosis or mistreating can be exacerbated.

Metformin, a widely used anti-diabetic drug, has garnered attention for its potential in cancer management, particularly in breast and colorectal cancer. It is established that metformin reduces mitochondrial respiration, but its specific molecular targets within mitochondria vary. Proposed mechanisms include inhibiting mitochondrial respiratory chain Complex I and/or Complex IV, and mitochondrial glycerophosphate dehydrogenase, among others. These actions lead to cellular energy deficits, redox state changes, and several molecular changes that reduce hyperglycemia in type 2 diabetic patients. Clinical evidence supports metformin’s role in cancer prevention in type 2 diabetes mellitus patients. Moreover, in these patients with breast and colorectal cancer, metformin consumption leads to an improvement of survival outcomes and prognosis. The synergistic effects of metformin with chemotherapy and immunotherapy highlights its potential as an adjunctive therapy for breast and colorectal cancer. However, nuanced findings underscore the need for further research and stratification by molecular subtype, particularly for breast cancer. This comprehensive review integrates metformin-related findings from epidemiological, clinical, and preclinical studies in breast and colorectal cancer. Here, we discuss current research addressed to define metformin's bioavailability and efficacy, exploring novel metformin-based compounds and drug delivery systems, including derivatives targeting mitochondria, combination therapies, and novel nanoformulations, showing enhanced anticancer effects.

In recent years, cancer therapy has witnessed significant advancements, with a focus on personalized and targeted treatment strategies. One promising approach involves the use of stimuli-responsive biomaterials for site-specific drug release. Among these biomaterials, pH, and redox-triggered polymer-nano composites have gained immense attention due to their ability to respond to the specific tumor microenvironment, enhancing therapeutic efficacy while reducing off-target effects. Cancer cells often exhibit anomalous biochemical properties, attributed to lower cytosolic pH (acidic) and elevated redox potential through the epitomized upregulation of undesired genes. Such biological process substantially imbalance the level ions (protons) and biological thiols glutathione (GHS) in the cytoplasm as well as in the subcellular organelles. Superfluous accumulation of ions and redox imbalance is associated with proliferation, invasion, and growth of tumor. Because of high surface area, deep tissue penetration capability, higher hydrophilicity, hydrophobic interior for drug/gene efficient loading, biocompatibility and site-specific targeting efficiency, functionalized polymer nanocomposites are superior to conventional small molecular materials. Paradoxically conventional methods of drug delivery aided therapeutics accompanied with inherent drug/genes are encapsulated in biocompatible carrier or suitable transfecting agents generally suffered with low bioavailability, uncontrolled drug release, low cellular penetration, cellular internalization, toxicity, and poor drug loading efficiency. To overcome these issues, recently various multifunctional nanomaterials were developed, based on synergistic stimuli responsive aided drug release in a specified cellular or subcellular system. High therapeutic efficacy, of nanoparticles (NPs) mainly associated with surface functionalization through biocompatible polymeric materials, site-specific targeting units accompanied with stimuli responsive components. Followed by therapeutically important drug or genetic materials were loaded into NPs either in covalent or non-covalent approach. Intriguingly, combined pH and redox dual stimuli based functional materials specially based on polymeric nanocomposites for cancer therapeutics scarcely reported. This article provides the recent progress in pH and redox-responsive polymer-nano composites for site-specific drug delivery in cancer therapy. It explores design principles, fabrication methods, mechanism of action, and prospects of these dual-stimuli responsive biomaterials.

Breast cancer is the most prevalent malignancy among women globally. Early diagnosis and treatment improvements are leading to a growing population of survivors. This has increased the risk of developing contralateral breast cancer (CBC), a distinct occurrence in the opposite breast of a previously diagnosed patient. The treatment options for breast cancer are often mas-tectomy or lumpectomy. Patients with lumpectomy frequently undergo a contralateral reduc-tion procedure to achieve more symmetry after the primary breast cancer surgery. The reduc-tion specimen is usually routinely examined by pathology to check for malignancies. The exci-sion in pieces and the absence of specific markers or ink make an examination of tumor size and margin status more challenging, impacting treatment decisions. A new protocol introduced in July 2022 seeks to improve diagnostic precision and treatment planning by excision in toto, marking, and inking excised reduction tissue to examine and treat potential CBC more effectively.

Prostate cancer is a highly heterogeneous disease, and mortality is mainly due to metastases, but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor. We demonstrate that genes related to oxidative phosphorylation are upregulated in LNM and in African-American patients relative to White patients. We further show that mutations in TP53, FLT4, EYA1, NCOR2, CSMD3, and PCDH15 are enriched in prostate cancer metastases. These findings were validated in a meta-analysis of 3,929 primary tumors and 2,721 metastases and reveal a pattern of molecular alterations underlying the pathology of metastatic prostate cancer. We show that LNM contain multiple subclones that are already present in primary tumor foci. We observed enrichment of mutations in several genes including understudied genes such as EYA1, CSMD3, FLT4, NCOR2, and PCDH15 and find that mutations in EYA1 and CSMD3 are associated with poor outcome in prostate cancer.

Cancer is a catchall term that refers to a collection of more than one chronic disease that can adversely affect the body, including the organs of the body. These diseases can be grouped together under the umbrella term "cancer." Cancer is a catch-all term that is used to refer to a number of different diseases. During the process of looking for new chemical entities, it was found that certain compounds with a basic nucleus of benzoic acid (BA) exhibit a remarkable anticancer potential. This was discovered while the researchers were looking for new chemical entities. In the sixteenth century, the aromatic chemical known as BA, which is also known as an aromatic carboxylic acid, was discovered. BA is also referred to as an aromatic carboxylic acid. When it comes to the chemical synthesis of a wide range of different active molecules, the utilization of a sizeable quantity of BA as a raw material is absolutely necessary. In addition to being present in a variety of other naturally occurring compounds, the BA moiety is the component that is responsible for the activity of the naturally occurring compounds vanillin, gallic acid, and syringic acid. In the synthesis of a wide variety of synthetic bioactive molecules, the BA scaffold is utilized as a building block. The drugs furosemide, bumetanide, benzocaine, tetracaine, and bexarotene are all examples of molecules that fall into this category. The scope of this review article allows for the discussion of a number of noteworthy and recent achievements of BA derivatives in terms of their effectiveness against cancer.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, 68Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of 68Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: 68Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those 2/17 had NePC. Semiquantitative analysis with standardized uptake values (SUV) (e.g. SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. 68Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastic lesion with identifiable 68Ga-DOTATATE uptake. Marked 68Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. 3 patients had mild 68Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after 68Ga-DOTATATE imaging. Conclusions: 68Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with 68Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.