Glucagon-like peptide-1 (GLP-1) is an incretin hormone that acts on the pancreas to increase insulin and decrease glucagon secretion. Albuminuria is the pivotal marker for diabetic nephropathy, which is the leading microvascular complication of diabetes mellitus. Most of the previous studies mainly focused on the clinical trials of the therapeutic renal protective effect after administration of GLP-1 receptor agonists (GLP-1 RAs), not prior to administration. Therefore, this study aimed to investigate the association between fasting plasma GLP-1 levels and albuminuria before GLP-1 RA administration. A cross-sectional study was designed to evaluate the association between fasting plasma GLP-1 levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 68 T2DM participants were analyzed from the data at Wonkwang University Hospital in Iksan, Korea. Logistic regression analysis was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of albuminuria between the GLP-1 low group (Group L) and the high group (Group H). The OR (95% CI) for the incidence of albuminuria comparing the Group L with the Group H of fasting plasma GLP-1 levels was 3.410 (1.160-10.023), p = 0.026 after adjustment for age, gender, fasting plasma glucose, HbA1c, C-peptide, the use of ACE inhibitors or ARBs, SGLT-2 inhibitors, and DPP-4 inhibitors. As a continuous variable, the OR (95% CI) for the incidence of albuminuria associated with the reduction of each 1 pmol/L in fasting plasma GLP-1 levels was 1.673 (1.173-1.870), p = 0.018, after full adjustment. This study showed the negative association between fasting plasma GLP-1 levels and the incidence of albuminuria in Korean patients with T2DM, before GLP-1 RA administration. This result suggests that endogenous GLP-1 may play a role in attenuating albuminuria.

The effect of ferromagnetic CaMnO3 (CMO) addition on structural, magnetic, dielectric, and ferroelec-tric properties of BiFeO3 are presented. X ray diffraction and Raman investigation allowed the identifi-cation of single pseudo cubic perovskite structure. The magnetic measurement showed that the pre-pared films exhibit a ferromagnetic behavior at low temperature with both coercive field and remnant magnetization increased with increasing CMO content. However, a deterioration of magnetization was observed at room temperature. Ferroelectric study revealed an antiferroelectric like behavior with a pinched P-E hysteresis loop for 5%CMO doping BFO resulting in low remnant polarization and double hysteresis loops. Whereas, high remnant polarization and coercive field with a likely square hysteresis loop are obtained for 10 % CMO addition. Furthermore, a bipolar resistive switching behavior with a threshold voltage of about 1.8V is observed for high doped film that can be linked to the ferroelectric polarization switching.

The Burkholderia cepacia complex (Bcc) are a group of increasingly multi-drug resistant opportunistic bacteria that can cause severe pulmonary infections. This resistance is driven through a combination of intrinsic factors and the carriage of a broad range of conjugative plasmids harbouring virulence determinants. Therefore, novel treatments are required to not only treat Bcc infection but also to prevent further spread of these virulence determinants. In the search for phages infective for two clinical Bcc isolates, CSP1 phage, a PRD1-like phage was isolated. CSP1 phage was found to require pilus machinery commonly encoded on conjugative plasmids to facilitate infection of multiple Gram-negative bacteria genera including Escherichia and Pseudomonas. Whole genome sequencing and characterisation of one of the clinical Burkholderia isolates revealed it to be Burkholderia contaminans. B. contaminans 5080 was found to contain a genome of over 8 Mbp encoding multiple intrinsic resistance factors, such as efflux pump systems, but more interestingly, carried three novel plasmids encoding multiple putative virulence factors for increased host fitness, including antimicrobial resistance. Even though PRD1-like phages are broad host range, their use in novel antimicrobial treatments shouldn’t be dismissed, as the dissemination potential of conjugative plasmids is extensive. Continued survey of clinical bacterial strains is

In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin's ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.

A half-harmonic oscillator, which gets its name because the coordinate is strictly positive, has been quantized and determined that it was a physically correct quantization. This positive result was found using affine quantization (AQ). The main purpose of this paper is to compare results of this new quantization procedure with those of canonical quantization (CQ). Using Ashtekar-like classical variables and CQ, we quantize the same toy model. While these two quantizations lead to different results, they both would reduce to the same classical Hamiltonian if $\hbar\rightarrow0$. Since these two quantizations have differing results, only one of the quantizations can be physically correct. Two brief sections illustrate how AQ can correctly help quantum gravity and the quantization of most field theory problems.

The measurements of the proton electromagnetic form factors in the time-like region using the initial state radiation technique are reviewed. Recent experimental studies have shown that initial state radiation processes at high luminosity electron-positron colliders can be effectively used to probe the electromagnetic structure of hadrons. The BABAR experiment at the B-factory PEP-II in Stanford and the BESIII experiment at the $\tau$-charm factory BEPC-II in Beijing have measured the time-like form factors of the proton using the initial state radiation process $e^{+}e^{-}\to pbar{p}\gamma$. The two kinematical regions where the photon is emitted from the initial state at small and large polar angles have been investigated. In the first case the photon is in the region not covered by the detector acceptance and is not detected. The Born cross section and the proton effective form factor have been measured over a wide and continuous range of the the momentum transfer squared $q^2$ from threshold up to ~42 (GeV/c)$^2$. The ratio of electric and magnetic form factors of the proton has been also determined. In this report, the theoretical aspect and the experimental studies of the initial state radiation process $e^{+}e^{-}\to p\bar{p}\gamma$ are described. The measurements of the Born cross section and the proton form factors obtained in these analyses near the threshold region and in the relatively large $q^2$ region are examined. The experimental results are compared to the predictions from theory and models. Their impact on our understanding of the nucleon structure is discussed.

There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results from an exaggerated immune response in genetically susceptible individuals. In oncologic pa-tients with sarcoidosis, tumoral antigens and antineoplastic treatment are considered potential triggering factors. The observation of a patient with granulomas in a parotid carcinoma that later developed SS led us to review previous tumors of patients with SS. The aim of the study is to see if granulomas were already present in the tumors that preceded sarcoidosis. We identified 196 sarcoidosis patients, 47 of which had a previous tumor. We were able to review 29 cases 12 of which showed tumor associated granulomas (TAGs)(41.4%). This ratio is much higher than that of the normal population. We analyzed five control patients without sarcoidosis for each tumor. In conclusion, we have observed TAGs in patients who later develop SS. In our series, the ratio of TAGs in patients with SS was significantly greater than in the normal population. To prove our findings, we suggest reviewing the history of patients with SS in search of previous tumors. The histology of such tumors should be reviewed in an attempt to identify granulomas.

Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prion-like domains are critical for virulence and the development of therapeutic targets; however, the prion-like domains in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in the SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike protein, since SARS-CoV-2 was the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of the spike protein is particularly interesting, since although the SARS-CoV-2 and SARS-CoV S proteins share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. Finally, we identified prion-like domains in the α1 helix of the ACE2 receptor that interact with the viral receptor-binding domain of SARS-CoV-2. Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interact with RBD have important functional roles in viral adhesion and entry.

The ongoing pandemic of the 2019 novel coronavirus disease (COVID-19) raises a global health crisis, which has resulted in 75,778 confirmed cases with 2130 deaths in China and beyond. Atypical symptom renders it challenging to earlier recognize the 2019-nCoV carrier with the potential ability of equivalent transmission. Therefore, it is needed to gain full spectrum of COVID-19. Here we report clustered COVID-19 cases of person-to-person transmission. The symptoms of typical pneumonia are shared by the two familial members, namely son (Patient 1) and father (Patient 2). Unexpectedly, an influenza-like illness (ILI) is also caused in Patient 3 having close contact with Patient 1 at personal dinner party. Combined with clinical and epidemiological study, chest computed tomography (CT) and molecular diagnosis demonstrate that all the three cases tested positive for COVID-19 with distinct symptoms by human-to-human transmission. To the best of knowledge, it closes in part (if not all), a missing gap of clinical repertoires of COVID-19 outbreaks and underlines the possibility that neglection of cryptic/asymptomatic/mild cold-like syndromes gives biased screen in the earlier stage of COVID-19 cases.

Viruses are the most abundant biological entities in aquatic ecosystems and harbor an enormous genetic diversity. While their great influence on the marine ecosystems is widely acknowledged, current information about their diversity remains scarce. A viral metagenomic analysis of three water samples was conducted from sites on the South Scotia Ridge (SSR) near the Antarctic Peninsula, during the austral summer 2016. The taxonomic composition and diversity of the viral communities were investigated and a functional assessment of the sequences was determined. Phylotypic analysis showed that most viruses belonging to the order Caudovirales, especially the family Podoviridae (41.92-48.7%), similar to the viromes from the Pacific Ocean. Functional analysis revealed a relatively high frequency of phage-associated and metabolism genes. Phylogenetic analyses of phage TerL and Capsid_NCLDV (nucleocytoplasmic large DNA viruses) marker genes indicated that many sequences associated with Caudovirales and NCLDV were novel and distinct from known phage genomes. High Phaeocystis globosa virus virophage (Pgvv) signatures were found in SSR area and complete and partial Pgvv-like were obtained which may have an influence on host-virus interactions. Our study expands the existing knowledge of viral communities and their diversities from the Antarctic region and provides basic data for further exploring polar microbiomes.

Semiconductor materials have been shown to have better photocatalytic behavior and can be utilized for the photodegradation of organic pollutants. In this work, three-dimensional flower-like SnS₂ were synthesized by a facile hydrothermal method. Core-shell structured SiO₂@α-Fe₂O₃ nanocomposites were then deposited on the top of the SnS₂ flowers. The as-synthesized nanocomposites were characterized by X-ray diffraction (XRD), Raman spectroscopy, field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET) and photoluminescence spectroscopy (PL). The photocatalytic behavior of the SnS₂-SiO₂@α-Fe₂O₃ nanocomposites was observed by observing the degradation of methylene blue (MB). The results show an effective enhancement of photocatalytic activity for the degradation of MB especially for the 15 wt. % SiO₂@α-Fe₂O₃ nanocomposites on SnS₂ flowers.

Background: Benveniste’s biology experiments suggested the existence of molecular-like effects without molecules (“memory of water”). In this article, it is proposed that these disputed experiments could have been the consequence of a previously unnoticed and non-conventional experimenter effect. Methods: A probabilistic modelling is built in order to describe an elementary laboratory experiment. A biological system is modelled with two possible states (“resting” and “activated”) and exposed to two experimental conditions labelled “control” and “test”, but both biologically inactive. The modelling takes into account not only the biological system, but also the experimenters. In addition, an outsider standpoint is adopted to describe the experimental situation. Results: A classical approach suggests that, after experiment completion, the “control” and “test” labels of biologically-inactive conditions should be both associated with “resting” state (i.e. no significant relationship between labels and system states). However, if the fluctuations of the biological system are also considered, a quantum-like relationship emerges and connects labels and system states (analogous to a biological “effect” without molecules). Conclusions: No hypotheses about water properties or other exotic explanations are needed to describe Benveniste’s experiments, including their unusual features. This modelling could be extended to other experimental situations in biology, medicine and psychology.

GCTs are developmental tumors and likely to reflect ontogenetic and teratogenetic determinants. The objective was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were used. According to Teilum's holistic concept malignant and benign teratomas were registered. We used a case control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher’s exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7-2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2-88.6). We additionally found 17 isolated cases of eGCT with a wide range of syndromes, however not significantly associated following Bonferroni correction. All these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies.

Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently reg-ulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic al-terations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was up-regulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced anti-gen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.

Abstract Epithelial ovarian carcinoma (EOC) is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. EOC is poorly responsive to immune check-point inhibitors due to immunologic features including limited tumor mutational burden (TMB), poor infiltration by immune cells and active immunosuppression. Thus, novel strategies are needed to overcome the frequent lack of preexisting immunity in patients with EOC. We developed and tested an autologous dendritic cell (DC)-based vaccine (DCVAC) which has recently been shown to be safe and to significantly improve progression-free survival (PFS) in two independent randomized phase II clinical trials enrolling patients with EOC (SOV01, NCT02107937; SOV02, NCT02107950). In addition, our exploratory data analyses suggest that the clinical benefits of DCVAC were more pronounced in patients with EOC with lower than-median TMB and scant CD8+ T cells infiltration. Thus, DC-based vaccine stands out as a promising clinical tool to jumpstart anticancer immunity in patients with immunologically „cold“ EOC. Our findings underscore the need for personalized immunotherapy and clinical relevance of potential tumor-related biomarkers within immunotherapy field. Additional clinical trials are needed to address these strategies as well as the potential value of TMB and immune infiltrate at baseline as biomarkers to guide the clinical management of EOC.

Glioblastoma (GB), even though not frequent, is an extremely aggressive brain tumor, with a strong impact on patient outcomes, in terms of both length and quality of life. The protocol estab-lished by Stupp and coworkers in 2005, based on radiotherapy and temozolomide chemotherapy, after maximum safe surgical resection, remains the gold standard for GB treatment. However, it is evident nowadays that the extreme GB intratumoral and intertumoral heterogeneity, invasive-ness and recurrence are not compatible with a routinary and unfortunately uneffective treatment. In this review article, we summarize the principal challenging issues in finding new valuable therapies for GB and focus on the impact that extracellular vesicle (EV) research and exploitation can have in the field. EVs are natural particles delimited by a lipidic bilayer and full of functional cellular content, released and uptaken by cells as key means of cell communications. Moreover, being stable in body fluids, well-immunotolerated, able to cross physiological, inter-species, and inter-kingdom barriers, and to target specific cells, releasing inherent or externally loaded functionally active molecules, EVs can be potentially ideal allies in fighting GB and assuring to GB patients a better prognosis. Here we report the main results obtained until now, focusing on both EV sources and molecular cargo used in the different functional studies, mainly in vivo. Finally, we perform a SWOT analysis reporting both the main advantages and the pitfalls of developing EV-based GB therapeutic strategies to highlight the main directions to explore for realizing the promise of EV exploitation for GB treatment.

CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin super family, is a multifunctional molecule with various binding partners. CD147 binds to monocarboxylate transporters (MCTs) and supports their expression on plasma membranes. MCTs play an important role in glycolysis, the enzymatic conversion of glucose to pyruvate and adenosine triphosphate (ATP). Pyruvate is further converted to lactic acid which is exported from the cytoplasm by MTC-1 and MCT-4 to maintain intracellular pH and a stable metabolic state. Under physiological conditions, cellular energy production is induced by mitochondrial oxidative phosphorylation. Glycolysis usually occurs under anaerobic conditions, whereas cancer cells depend on glycolysis under aerobic conditions. T cells also require glycolysis for differentiation, proliferation, and activation. Human malignant melanoma cells expressed higher levels of MCT-1 and MCT-4, co-localized with CD147 on the plasma membrane and showed an increased glycolysis rate compared to normal human melanocytes. Silencing of CD147 by siRNA abrogated the membrane expression of MCT-1 and MCT-4 and disrupted glycolysis, inhibiting cancer cell activity. The differentiation of CD4+ T cells into Th17 cells is a pivotal process in the development of various immune disorders, including psoriasis. Studies using CD147-deficient mice demonstrated the involvement of CD147 in psoriasis. MCT-1 was absent on CD4+ T cells in CD147-deficient mice. Naïve CD4+ T-cells from CD147-deficient mice show low potential for differentiation into Th17 cells. Imiquimod-induced skin inflammation was significantly milder in CD147-deficient mice than in wild-type mice. These findings indicate that CD147/Basigin is involved in the development of malignant tumors and T cell mediated immunological disorders via regulation of glycolysis.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

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.

MicroRNA (miRNA) is small non-coding RNAs that play vital roles in post-transcriptional gene regulation by inhibiting mRNA translation or promoting mRNA degradation. Dysregulation of miRNA has been implicated in numerous human diseases, including cancers. The family members of miR-34 (miR-34s), composed of miR-34a, miR-34b, and miR-34c, have emerged as the most extensively studied tumor-suppressive miRNAs. In this comprehensive review, we aim to provide an overview of the major signaling pathways and gene networks regulated by the miR-34s in various cancers and highlight the critical tumor suppressor role of miR-34s. Furthermore, we will discuss the potential of using miR-34 mimics as a novel therapeutic approach against cancer, while also addressing the challenges associated with their development and delivery. It is anticipated that gaining a deeper understanding of the functions and mechanisms of miR-34s in cancer will greatly contribute to the development of effective miR-34-based cancer therapeutics.

Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has con-tinued to increase by about 1% each year in both men and women. Although the 5‐year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strate-gies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct type of programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression.

Neuroendocrine tumors (NETs) of duodenal origin are an unusual subset among all NETs, comprising only about 3% of this neoplasm class. In general, NETs are characterized by overexpression of somatostatin receptors and carry an excellent prognosis with early diagnosis and intervention. Chromogranin A (CgA), a protein originating in secretory vesicles of neurons and endocrine cells, has gained wide usage in NET diagnosis and surveillance. Lanreotide is a synthetic octapeptide somatostatin analog with potent anti-proliferative action which has been approved by the FDA (U.S.) and EMA (E.U.) for NET treatment. It is known for its inhibitory effects on growth hormone, serotonin, CgA, and other markers. Here we describe a 56yr-old female with functional NET of duodenal origin, where serum CgA was successfully reduced from 3636 to <100 ng/mL after multidose lanreotide within five months. Of note, no metastatic spread was identified on positron emission tomography/computed tomography with 64Cu-labeled somatostatin analog tracer. Surgical resection of distal antrum, pylorus, and proximal duodenum followed without complication. Histology revealed several foci of well-differentiated tumor cells with characteristic neuroendocrine features and clear surgical margins; low proliferation index (2%) was noted on Ki-67 staining. While select laboratory and imaging modalities are available for diagnosis and monitoring of duodenal NET, this is the first reported therapeutic use of lanreotide in this NET setting. The observed serum CgA attenuation, even before surgery, supports its effectiveness in management of primary nonmetastatic duodenal NET.

Cancer diseases lead to the second-highest death rate all over the world. The dynamics of invasion of cancer cells into the human body tissues and metastasis are the main causes of death in patients with cancer. This study deals with theoretical investigation of the dynamics of invasion of cancer cells for tumour growths in human body tissues using discretized Cahn-Hilliard, concentration and reaction-diffusion equations which were solved by Finite Difference Method with the aid of MATLAB computer software. A Crank-Nicolson numerical scheme was developed for the discretized model equations. The numerical result obtained was used to describe the dynamics of cancer invasion of tissues with respect to cancer cells density on tumour growth, turbulence and mobility and equilibrium between charge and discharge of cancer cells. The results of the study provide new insights into combating cancer disease by providing mitigating and intervention measures to this major health problem.

Chronic inflammation may have a detrimental impact on human health as it tends to result in cancer. In addition, it is often linked to different steps that participate in tumorigenesis, including cellular transformation, survival, promotion, invasion, proliferation, angiogenesis, and metastasis. Hence, inflammation predisposes cancer development and plays a vital role in promoting all tumorigenesis stages. Inflammation is caused by many factors, such as bacterial and viral infections, tobacco smoking, autoimmune diseases, obesity, asbestos exposure, and many others, increasing cancer risk. Moreover, cancer can be enhanced by mutations that proceed to cancer progression. Consequently, it leads to immunosuppression and provides a favorable background for tumor development. Although many studies address the question of relationships between inflammation and cancer development, little attention is paid to the link between inflammation and blood cancer. Therefore, the current study reviews the role of inflammation in cancer development, particularly in blood cancer. A meta-analysis research approach meets the research objective and answers the research question. The review results indicate that chronic inflammation directly relates to the development of many cancer types, blood cancer in particular.

(1) Background: The present study was carried out to provide new information about the relation between angiogenesis, tumor stage Oral squamous cell carcinoma (OSCC); (2) Materials and methods: Thirty formalin-fixed paraffin embedded blocks were used, 10 of them were previously diagnosed as well differentiated OSCC, 10 moderate differentiated OSCC and 10 poorly differentiated OSCC. To determine the expression of CD31 and D2-40 proteins, streptavidin-biotin immunoperoxidase staining technique was used. The areas with the most vascular density (hot spots) were determined. The stained vessels were counted independently in intratumoral and peritumoral stroma in five areas of hot spot at ×400 magnification; (3) Results: Immunohistochemical staining using CD 31 protein showed that CD31-positive vessels in the peritumoral and intratumoral stroma subjacent to the malignant invading nests which was recorded highest values in poor differentiated OSSC followed by moderate differentiated OSSC then well differentiated OSSC. D2-40 expression was positive in lymphatic vessel in the peritumoral and intratumoral stroma subjacent to the malignant invading nests. Poorly differentiated OSSC tissue sections recorded the highest vessels count followed by moderate differentiated OSSC then well differentiated OSSC. There was statistically significant difference found between the three studied groups regarding CD31 and D2-40 levels. Also there was statistically significant positive correlation found between CD31 level and D2-40 level and vice versa; (4) Conclusion: CD31 and D2-40 are related to stage of OSCC and are consistent with angiogenesis in tumor progression.

Neuroendocrine tumors develop from systemic endocrine and nerve cells, and their occurrence has increased recently. Since these tumors are heterogeneous, pathological classification has been based on the affected organ. In 2019, the World Health Organization introduced a change that is expected to influence neuroendocrine tumor research, as gastroenteropancreatic neuroendocrine tumors are now included within a unified classification. In this retrospective study, we aimed to investigate the characteristics (e.g., lymph node metastases, all other metastases) of gastroenteropancreatic neuroendocrine tumors using this new classification in 50 cases. Tumor size, depth, MIB-1 index, lymphatic invasion, venous invasion, and neuroendocrine tumor grade were significantly correlated with lymph node metastasis and all other metastases. Venous invasion was more strongly correlated with lymph node metastasis and all other types of metastasis than with lymphatic invasion. Identification rates for lymphatic invasion were considered lower because of structural problems such as lymphatic vessels being much thinner than veins. However, venous invasion was considered effective in compensating for the low rate of identification in cases of lymphatic invasion. In future research, a unified classification and standardized framework for assessment will be important when analyzing the characteristics of neuroendocrine tumors, and large-scale studies are required.

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.

Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage. Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy. Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in-depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.

Although pancreatic neuroendocrine neoplasms (PNENs) are relatively rare tumors, their number is increasing with advances in diagnostic imaging modalities. Even small lesions that are difficult to detect using computed tomography or magnetic resonance imaging can be detected with endoscopic ultrasound (EUS). Contrast-enhanced EUS is useful, and not only diagnosis but also malignancy detection have become possible by evaluating the vascularity of tumors. Pathological diagnosis using EUS with fine-needle aspiration (EUS-FNA) is useful when diagnostic imaging is difficult. EUS-FNA can also evaluate the grade of malignancy. Pooling the data of the studies which compared the PNENs grading between EUS-FNA samples and surgical specimen, the concordance rate was 77.5% (κ-statistic: 0.65, 95% confidence interval = 0.59 - 0.71, P< 0.01). EUS is a particularly important modality for the treatment of PNENs.

Glioma tumors are one of the most devastating cancer types. Of the different glioma tumors, glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advantages in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OV) in cancer treatment is one of those immune-therapeutic alternatives. OV have a double oncolytic action by both, directly destroying the cancer cells, sparing the patient’s life, and stimulating a tumor specific immune response to revert the ability of tumors to escape the control of the immune system. OV are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility to use some viruses to specifically infect tumors eluding undesired toxic effects in the patient. Here we have revisited the literature in order to describe the main OV proposed so far as therapeutic alternatives to destroy glioma cells in vitro and trigger tumor destruction in vivo. Some clinical trials are exploring the use of this therapy as an alternative were other approaches provide limited hope.

The use of circulating cell-free (cf) DNA to monitor cancer progression and response to therapy has significant potential but there is only limited data on whether this technique can detect the presence of low frequency subclones that may ultimately confer therapy resistance. In this study, we sought to evaluate whether whole-exome sequencing of cfDNA can accurately profile the mutation landscape of metastatic melanoma. We used whole-exome sequencing (WES) to identify variants in matched tumor-derived genomic (g) DNA and plasma-derived cfDNA isolated from a cohort of 10 metastatic cutaneous melanoma patients. WES parameters such as sequencing coverage and total sequencing reads were comparable between gDNA and cfDNA. There was significant concordance between gDNA and cfDNA based on the total number of variants identified and the degree of overlap in variants which was independent of the site of tumor biopsy. The mutant allele frequency of common single nucleotide variants was lower in cfDNA reflecting lower read depth and dilution of circulating tumor DNA in the circulation by other cfDNA species. In addition to known melanoma driver mutations, several other melanoma-associated mutations were found to be concordant between matched gDNA and cfDNA. This study highlights that WES of cfDNA can capture clinically-relevant mutations present in melanoma metastases, but does not appear to provide any additional unique information on tumor heterogeneity. Targeted deep sequencing may be required to detect low frequency genomic aberrations known for predicting therapy resistance.

Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen the immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors such as cGAS/STING in combination with immunotherapies. In this review, we present a case for targeting nucleic acid sensing pathways within the tumor vasculature to invigorate tumor immune responses. We introduce two specific nucleic acid sensors, the DNA sensor TREX1 and the RNA sensor RIG-I and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment.

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

Caribbean sponges of the genus Smenospongia are a prolific source of chlorinated secondary metabolites. The use of molecular networking as a powerful dereplication tool revealed the presence in the metabolome of S. aurea of two new members of the smenamide family, namely smenamide F (1) and G (2). The structure of smenamide F (1) and G (2) was determined by spectroscopic analysis (NMR, MS, ECD). The relative and the absolute configuration at C-13, C-15, and C-16 was determined on the basis of the conformational rigidity of a 1,3-disubstituted alkyl chain system (i.e. the C-12/C-18 segment of compound 1). Smenamide F (1) and G (2) were shown to exert a selective moderate antiproliferative activity against cancer cell lines MCF-7 and MDA-MB-231, while being inactive against MG-63.

Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.

The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

The ubiquitin proteasome system (UPS) utilizes an orchestrated enzymatic cascade of E1, E2, and E3 ligases to add single or multiple ubiquitin-like molecules as post-translational modification (PTM) to proteins. Ubiquitination can alter protein functions and/ or marks ubiquitinated proteins for proteasomal degradation but deubiquitinases (DUBs) can reverse protein ubiquitination. While the importance of DUBs as regulatory factors in the UPS is undisputed, many questions remain on DUB selectivity for protein targeting, their mechanism of action, and the impact of DUBs on the regulation of diverse biological processes. Furthermore, little is known about the expression and role of DUBs in tumors of the human central nervous system (CNS). In this comprehensive review, we have used publicly available transcriptional datasets to determine the gene expression profiles of 99 deubiquitinases (DUBs) from five major DUB families in seven primary pediatric and adult CNS tumor entities. Our analysis identified selected DUBs as potential new functional players and biomarkers with prognostic value in specific subtypes of primary CNS tumors. Collectively, our analysis highlights an emerging role for DUBs in regulating CNS tumor cell biology and offers a rationale for future therapeutic targeting of DUBs in CNS tumors.

This review systematically examines the multifaceted relationship between the tumor microenvironment, stromal interactions, and colorectal cancer (CRC) progression and metastasis. The analysis begins by assessing the gut microbiome's influence on CRC development, emphasizing its association with gut-associated lymphoid tissue (GALT). The role of the Wnt signaling pathway in CRC tumor stroma is scrutinized, elucidating its impact on disease progression. Tumor budding, its effect on tumor stroma, and implications for patient prognosis are investigated. The review also identifies conserved oncogenic signatures (COS) within CRC stroma and explores their potential as therapeutic targets. Lastly, the seed and soil hypothesis is employed to contextualize metastasis, accentuating the significance of both tumor cells and the surrounding stroma in metastatic propensity. In summary, this review highlights the intricate interdependence between CRC cells and their microenvironment, providing valuable insights into prospective therapeutic approaches targeting tumor-stroma interactions.

Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation, and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, H2O2 or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed.

Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. This paper provides deep insight into immune related adverse events (irAEs) posing a major challenge and drawback to ICIT, and presents right management strategies for very complex complications. Moreover, for the first time in literature, a non-linear mathematical model is introduced to measure the ICIT success rate and to decide about the optimum ICIT duration. Furthermore, a strategy is presented to overcome or to delay the progression after initial good response in a subset of patients.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

In this study, we investigate the behavior of randomly moving particles with a defined average energy, focusing on their biased motion around a specific point. These particles' velocity magnitudes follow a Maxwell distribution with a specific scale parameter. Our analysis derives the stochastic rotation rules for these particles and introduces the Ito equation conditions for biased stochastic rotation at a given curl value. We also consider the special relativistic-like effects in this context. The findings are validated through a representative example.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

The study of mechanical properties of rock mass can be effectively carried out through rock-like material model test. The similarity of mechanical properties between rock-like material and protolith is dependent on the appropriate selection of composition and content of rock-like materials. In this research, X-Ray diffraction test was conducted to analyze the composition of deep rock, which confirmed silica, quartz, and dolomite as the primary components of deep sandstone. An orthogonal design test was used to execute the ratio test of rock-like material. River sand was used as an aggregate, cement as a binder, gypsum powder as a regulator, and polystyrene foam (EPS) as rock damage simulation material. The influencing factors considered in the orthogonal mechanical tests were the proportion of aggregate and binder, ratio of binder and regulator, quantity of damage simulation material, and size of damage simulation material. Three levels were set for each factor, and mechanical parameters such as compressive strength, tensile strength, elastic modulus, axial strain, and Poisson's ratio were tested for each group of samples. The changes of those parameters with the levels of the above four factors were studied. The study revealed that adjusting the size of polystyrene foam (EPS) can adjust the values of elastic modulus, tensile strength, and Poisson's ratio of rock-like material. Similarly, changing the ratio of binder and regulator can adjust the values of axial strain and compressive strength of rock-like material. The rock-like material developed in the study can simulate the mechanical properties of different rock masses such as granite, sandstone, shale, and limestone.

Existence of carcinogenic nitrite in food has attracted much attention, however, it is still a challenge to develop nitrite sensor with higher sensitivity and selectivity to enlarge its applications in daily life. Herein, one-dimensional honeycomb-like carbon nanofibers (HCNFs) were synthesized with an electrospun technology, and its specific structure enables the controlling growth and highly dispersed bismuth nanoparticles (Bi NPs) on its surface, which endows the obtained Bi/HCNFs with excellent electrocatalytic activity toward nitrite oxidation. By modifying Bi/HCNFs on screen-printed electrode, the constructed Bi/HCNFs electrode (Bi/HCNFs-SPE) can be used for nitrite detection in one drop of solution, and exhibits higher sensitivity (1269.9 μA mM-1 cm-2) in a wide range of 0.1~800 μM with lower detection limit (19 nM). Impressively, the Bi/HCNFs-SPE has been successfully used for nitrite detection in food and environment samples, the satisfactory property and recovery indicates its feasibility in further practical applications.

In January 2019, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on risks related to the presence of hazardous chemicals in infant diapers. ANSES found that health reference values were largely exceeded for polycyclic aromatic hydrocarbons (PAHs), dioxins (PCCD/Fs) and dioxin-like polychlorobiphenyls (DL-PCBs). The levels of formaldehyde and of some fragrances were also considered potentially unsafe. Therefore, ANSES concluded that actions have to be taken to restrict levels of these contaminants in diapers. Under the exposure scenario deemed the most reliable by ANSES, estimates of cancer risks of the most potent PAHs detected in diapers exceeded 10-3 and hazard quotients for neurobehavioral effects attained values up to 66. Regarding dioxins and DL-PCBs, ANSES derived a hazard quotient of 12 for the risk of decreased sperm count at adult age. The aim of this critical review was to examine whether the exposure and risk assessment conducted by ANSES contained potential flaws that could explain such a high exceedance of health reference values. The review will also put into perspective the exposure from diapers with that from breast milk whose benefits for child’s health are undisputable despite contamination by PAHs, dioxins and DL-PCBS.

A typical white-light light-emitting diode (LED) can achieve a sunlight-like spectral profile in the visible spectrum by means of using an optical filter, with an inverted transmission profile to the white LED, fabricated using a deposition coating process. The unfiltered white LED generates white light by mixing light emitted by a blue LED (450 nm) with emission from the yellow phosphorescence excited by the blue light and differs significantly from the characteristics of the full-spectrum natural light. In this study, the spectral characteristics of the filtered LED light can be improved to reach a general color rendering index value (Ra) of 95.6 at the D65.

In the last decade, the objectives outlined by the needs of personal robotics have led to the rise of new biologically-inspired techniques for arm motion planning. This paper presents a literature review of the most recent research on the generation of human-like arm movements in humanoid and manipulation robotic systems. Search methods and inclusion criteria are described. The studies are analysed taking into consideration the sources of publication, the experimental settings, the type of movements, the technical approach, and the human motor principles that have been used to inspire and assess human-likeness. Results show that there is a strong focus on the generation of single-arm reaching movements and biomimetic-based methods. However, there has been poor attention to manipulation, obstacle-avoidance mechanisms, and dual-arm motion generation. For these reasons, human-like arm motion generation may not fully respect human behavioural and neurological key features and may result restricted to specific tasks of human-robot interaction. Limitations and challenges are discussed to provide meaningful directions for future investigations.

Trophoblasts are the first cell-type to be specified during embryogenesis, and they are essential for placental morphogenesis and function. Trophoblast stem (TS) cells are the progenitor cells for all trophoblast lineages; control of TS cell differentiation into distinct trophoblast subtypes is not well understood. Mice lacking the transcription factor OVO-like 2 (OVOL2) fail to produce a functioning placenta, and die around embryonic day 10.5, suggesting that OVOL2 may be critical for trophoblast development. Therefore, our objective was to determine the role of OVOL2 in mouse TS cell fate. We found that OVOL2 was highly expressed in mouse placenta and differentiating TS cells. Placentas and TS cells lacking OVOL2 showed poor trophoblast differentiation potential, including increased expression of stem-state associated genes (Eomes, Esrrb, Id2) and decreased levels of differentiation-associated transcripts (Gcm1, Tpbpa, Prl3b1, Syna). Ectopic OVOL2 expression in TS cells elicited precocious differentiation. OVOL2 bound proximate to the gene encoding inhibitor of differentiation 2 (ID2), a dominant negative helix-loop-helix protein, and directly repressed its activity. Overexpression of ID2 was sufficient to reinforce the TS cell stem state. Our findings reveal a critical role of OVOL2 as a regulator of TS cell differentiation and placental development, in-part by coordinating repression of ID2.

Physical measurements might display range values extending towards infinite. The occurrence of infinity in physical equations, such as the black hole singularities, is a troublesome issue that causes many theories to break down when assessing extreme events. Different methods, such as re-normalization, have been proposed to avoid detrimental infinity. Here a novel technique is proposed, based on physical geometrical considerations and the Alexander Horned sphere, that permits to undermine infinity in physical equations. In this unconventional approach, a continuous monodimensional line becomes an assembly of countless bidimensional lines that superimpose in quantifiable knots and bifurcations.

Introduction. The “memory of water” experiments suggested the existence of molecular-like effects without molecules. Although no convincing evidence of modifications of water – specific of biologically-active molecules – has been reported, consistent changes of biological systems were nevertheless recorded. We propose an alternate explanation based on classical conditioning of the experimenter.Methods. Using a probabilistic modelling, we describe not only the biological system, but also the experimenter engaged in an elementary dose-response experiment. We assume that during conventional experiments involving genuine biologically-active molecules, the experimenter is involuntarily conditioned to expect a pattern, namely a relationship between the descriptions (or “labels”) of experimental conditions and the corresponding biological system states.Results. The modelling predicts that the conditioned observer could continue to record the learned pattern even in the absence of the initial cause, namely biologically-active molecules. The phenomenon is self-sustained since the observation of the expected pattern reinforces the initial conditioning. A necessary requirement is the use of a system submitted to random fluctuations with autocorrelated successive states (no forced return to the initial position). The relationship observed by the conditioned observer is however not causal and has a quantum-like structure. The modelling predicts also that blind experiments with an “outside” supervisor lead to a loss of correlations (i.e. system states randomly associated to “labels”). Conclusion. This psychophysical modelling allows explaining the results of “memory of water” experiments without referring to water or another local cause. It could be extended to other scientific fields in biology, medicine and psychology when an experimenter effect is suspected.

In this work, a mixture of Elzaki transform and projected differential transform method is applied to solve a nonlinear wave-like equations with variable coefficients. Nonlinear terms can be easily manipulated by using the projected differential transformation method. The method gives the results show that the proposed method is very efficient, simple and can be applied to other applications.

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague–Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

Both fibrosis and cirrhosis of the liver are the end results of most kinds of chronic liver damage and present a common but difficult clinical challenge throughout the world. The inhibition of the fibrogenic, proliferative, and migratory effects of hepatic stellate cells (HSCs) has become an experimental therapy for preventing and even reversing hepatic fibrosis. Furthermore, a complete understanding of the function of non-coding RNA-mediated epigenetic mechanisms in HSC activation may improve our perception of liver fibrosis pathogenesis. This review focuses on an evolving view of molecular mechanisms in which HSC activation by miR-29a signaling may moderate their profibrogenic phenotype, thus supporting the use of miR-29a agonists as a potential therapy for treating liver fibrosis in the future.

It is introduced and studied para-Ricci-like solitons with potential Reeb vector field on almost paracontact almost paracomplex Riemannian manifolds. The special cases of para-Einstein-like, para-Sasaki-like and having a torse-forming Reeb vector field have been considered. It is proved a necessary and sufficient condition the manifold to admit a para-Ricci-like soliton which is the structure to be para-Einstein-like. Explicit examples are provided in support of the proven statements.

Despite significant advances in tumor biology and clinical therapeutics, metastasis remains the primary cause of cancer-related deaths. While RNA-seq technology has been used extensively to study metastatic cancer characteristics, challenges persist in acquiring adequate transcriptomic data. To overcome this challenge, we propose MetGen, a generative contrastive learning based on deep learning model. MetGen generates synthetic metastatic cancer expression profiles using primary cancer and normal tissue expression data. Our results demonstrate that MetGen generates comparable samples to actual metastatic cancer samples, and we discuss the learning mechanism of MetGen. Additionally, we demonstrate MetGen's interpretability using metastatic prostate cancer and metastatic breast cancer. MetGen has learned highly relevant signatures in cancer, tissue, and tumor microenvironment, such as immune response and the metastasis process, which potentially fosters a more comprehensive understanding of metastatic cancer biology. The development of MetGen represents a significant step toward the study of metastatic cancer biology by providing a generative model that identifies candidate therapeutic targets for the treatment of metastatic cancer.

MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)- associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs) including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines.

52 years have passed since President Nixon launched the "War on Cancer". The goals outlined by the President were not achieved because cancer treatment applied such as chemotherapy, radiotherapy, and targeted therapy have not fully met expectations. We suggest a new chemotherapeutic strategy: disrupting the communication between cancer cells and their microenvironment by chemical means. Immunological synapses that form between cancer cells and immune or other stromal cells provide an attractive target for this approach. Synapses form ligand-receptor clusters within interface of the interacting cells. Despite their differences, synapses share common properties: intercellular protein clusters; the proximity of these proteins; and their cooperative interaction making a synapse an unified functional unit. Synapses provide the limited space for the focused intercellular exchange of signaling molecules and particles. Therefore, destruction of synapses is expected to cause collapse of various tumor types. Additionally, the clustered arrangement of synapse components offers opportunities to increase treatment safety by reducing the concentration of cell impermeable agents used, to enhance its specificity applying cross-linking reagents, thus restricting modifications of surface-exposed molecules. By attaching a cleavable cell permeable toxic agent to a crosslinker should further enhance a killing potential in treating cancer. The proposed approach promises to be simple, universal, and less expensive than existing cancer therapy methods.

Background: Peripheral Ossifying Fibroma (POF) is a benign gingival tumor generally presenting as a slow-growing mass, usually not ulcerated, and without bleeding. Histopathological exam shows fibrous connective tissue with spots or extensive areas of intralesional calcifications, which can also be detectable on radiograms. Methods and case presentation: We present the case of a 4-year-old male with a retro-incisive swelling of the hard palate, associated with speaking and feeding difficulties. On CT scans, a small intralesional calcification was detected. After conscious sedation, the patient was subjected to diode laser excision (910 nm, 2W, CW, 300 m fiber) with-out post-operative complications. A review was conducted by searching the words “peripheral ossifying fibroma” AND “children” OR “infant” and including manuscripts of the last 15 years. Results: POF is an uncommon lesion of the oral mucosa and may sporadically affect the palatal mucosa in children. Considering its epidemiology and conventional clinical presentation as epu-lis, the pre-operative diagnosis may be relatively difficult. Risk factors could be represented by plaque, calculus, or trauma, all supporting a possible reactive pathogenesis, but a certain etiology is still missing. The main problem of POF is the recurrence rate, which is particularly high (8-20%), thus suggesting that a deep excision is recommended with full extension to the hard tis-sue of bone and to the adjacent periodontal ligament. Diode laser surgery may be recommended for such treatments, especially in pediatric patients, associated with intraoperative conscious se-dation. Data emerging from the relevant literature on POF management in children have been collected and discussed. Conclusions: The authors suggest the use of diode laser for the complete excision of POF, especially in less-compliant patients as children, with a low grade of comorbidi-ties and good outcomes, giving the surgeon a viable alternative to conventional surgery.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

Tumor infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, and total TILs (CD4+, CD8+, Treg, B cells) within chemotherapy-treated tumors compared to chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic response with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherpy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.

Lung cancer accounts for the majority of cancer cases. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment, or TMJ, or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body's response to inflammation and infection. Cytokines are important for immunity in lung cancer. It promotes tumor growth (oncogenic cytokines) or inhibits tumor growth (anti-tumor cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system stop the growth or kill cancer cells. Interleukins and interferons are two types of cytokines used to treat cancer. This article begins by addressing the role of the tumor microenvironment (TMJ) and its components in lung cancer. This review also highlights the functions of various cytokines such as IL, TGF and TNF.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic col-orectal cancer (CRC) without severe symptoms remains controversial. We retrospectively ana-lyzed the role of PTR in overall survival (OS) in different subgroups. Among 331 patients diag-nosed with synchronous metastatic CRC between 2010 and 2020, 223 were analyzed. The PTR group (n = 42) showed better performance (p = 0.038); higher frequencies of right-sided origin (p = 0.014), T4 stage (p = 0.005), M1a stage (p = 0.015), and <2 organ metastases (p = 0.002); and re-ceived fewer targeted agents (p < 0.001) than the chemotherapy group (n = 181). The PTR group showed longer OS (20.5 versus 14.0 months, p = 0.016), but PTR was marginally related to OS in multivariate analysis (p = 0.060). Male sex (p = 0.022), good performance status (p = 0.07), left-sided tumor (p = 0.069), low serum carcinoembryonic antigen level (p = 0.092), T3 stage (p = 0.029), M1a stage (p = 0.025), <2 organ metastases (p = 0.017), and administration of targeted agents, especially bevacizumab (p = 0.024), were related to survival benefit after PTR. Upfront PTR should be considered when selecting patients with favorable prognoses for bevacizumab administration.

Brain metastasis (BrM), involving the spread of cells from a primary tumor through the blood circulation system to the brain microvasculature, eventually progresses despite multiple treatments and remains a substantial contributor to major mortality in patients with advanced- stage cancer. Molecular signatures and immune cellular components of the tumor microenvironment (TME) are emerging as essential regulators involved in establishing an organ-specific metastasis (colonization) and therapeutic response. A comprehensive understanding of detailed characterization and the immune landscape in context of process of BrM formation will greatly expand the horizon of treatments available to target these deadly diseases. In this review, we provide a comprehensive picture of the complex interactions between tumor cells and immune cellular components participated in the BrM process. Based on this knowledge, we will discuss opportunities and challenges for therapeutic strategies against BrM.

MicroRNAs (miRNAs) are single-stranded, noncoding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and dog diseases. Most cancers tested, to date, have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we have comprehensively summarized the importance of miRNA in human and dog cancer research. We have discussed the current state of development and potential for miRNA as both a diagnostic marker and a therapeutic target.

Liquid biopsy has been developed to diagnose and monitor cancer. Despite the recent advances in investigating early cancer detection and diagnosis strategies, there is still a lack of improvements in capturing (CTCs). To archive this, we developed an efficient CTC detection system by integrating gold nanoparticles and a microfluidic platform, which can achieve CTC capture within 120 min. The microdevice was functionalized by immobilizing antibodies specific to the target cells. The method was tested with spiked tumor cells in whole human blood with three pancreatic cancer cell lines and compared with purified cancer cells suspended in a phosphate buffer solution. Our results captured pancreatic cancer cells spiked in blood samples with efficiency (90±3.2)% and were used to isolate CTCs from patients with metastatic pancreatic cancer. This methodology will enable the production of functionalized, patterned surfaces that interact with tumor cells, enhancing the selective capture of CTCs from biological assays.

The tumor microenvironment (TME) plays a critical role in cancer progression and treatment outcomes. Despite advances in cancer research, many therapeutic strategies have failed to provide the desired clinical outcomes. In this integrated review, aimed to explore the role of TME in cancer biology and develop novel therapeutic strategies that target not only cancer cells but also the surrounding microenvironment. Study conducted a comprehensive literature search using PubMed, Embase, and Web of Science databases for articles published between 2016 and 2022. Inclusion of articles that discussed the impact of TME on cancer development and progression, as well as articles that proposed novel therapeutic strategies targeting the TME. The analysis of the literature revealed that the TME plays a crucial role in cancer development and progression by promoting cancer cell survival, angiogenesis, invasion, and metastasis, and by interfering with the efficacy of cancer therapies. The TME is composed of a complex network of non-cancerous cells, extracellular matrix components, and signaling molecules that interact with cancer cells. Several novel therapeutic strategies have been proposed based on the modulation of TME components. One of the most promising approaches is the use of immunotherapy, which aims to enhance the immune system's ability to recognize and attack cancer cells. Immunotherapy drugs such as checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, and immune-stimulatory monoclonal antibodies have been approved for the treatment of different cancer types. These approaches have shown promising results in preclinical studies and clinical trials. The TME plays a critical role in cancer development and progression, and targeting its components represents a promising avenue for cancer therapy. Novel therapeutic strategies such as immunotherapy, extracellular matrix-targeting drugs, and nanoparticle-based therapies have shown promising results in preclinical studies and clinical trials. However, further research is needed to identify the most effective strategies and to overcome the challenges associated with TME targeting.

Brain tumors are abnormal cells growth in the brain tissues that can be cancerous, or not. In any case, they could be a very aggressive disease that should be detected as early as possible. Usually, magnetic resonance imaging (MRI) is the main tool commonly adopted by neurologists and radiologists to identify and classify any possible anomalies present in the brain anatomy. In the present work, an automatic unsupervised method called Z2-$\gamma$, based on the use of adaptive finite-elements and suitable pre-processing and post-processing techniques, is introduced. In particular, the proposed methodology is able to automatically classify whether a given MR image represents a healthy or a diseased brain and in this latter case, is able to locate the tumor area.

Extensive growth in the volume of irregular brain cells is known as brain tumor. Human brain is surrounded by stiff skull. There are various issues that occur due to the growth of any tumor inside this restricted space. The malignant and benign are two main categories of the brain tumor. The skull is pressurized to enlarge from inside in case of growth of any benign or malignant tumor. This tumor leads to harm in brain and it may be dangerous to life also. The brain tumor is divided into two kinds - primary or secondary. The brain tumor detection techniques have various phases. In this paper, comparative study of CNN with GLCM approach and superpixel based spectral clustering is done tumor. This work takes into account metrics like accuracy, sensitivity and specificity for drawing the comparison between both the techniques.

Segmentation of brain tumor images is a major research topic in medical imaging to have a refined detection and understanding of abnormal masses in the brain. This paper proposes a new segmentation method, consisting of three main steps, to detect brain lesions using magnetic resonance imaging (MRI). In the first step, the parts of the image delineating the skull bone are removed to exclude insignificant data. In the second step, which is the main contribution of this study, the particle swarm optimization (PSO) technique is applied to detect the block that contains the brain lesions. The fitness function, used to determine the best block among all candidate blocks, is based on a two-way fixed-effects analysis of variance (ANOVA). In the last step of the algorithm, the K-means segmentation method is used in the lesion block to classify it as tumor or not. A thorough evaluation of the proposed algorithm is performed using the MRI database provided by the Kouba imaging center in Algiers, Algeria. Estimates of the selected fitness function are first compared to those based on the sum-of-absolute-differences (SAD) dissimilarity criterion and demonstrate the efficiency and robustness of the ANOVA. The performance of the optimized brain tumor segmentation algorithm is then compared to the results of several state-of-the-art techniques, including fuzzy C-means, K-means, Otsu thresholding, local thresholding, and watershed segmentation. The results obtained using Dice coefficient, Jaccard distance, correlation coefficient, and root mean square error (RMSE) measurements demonstrate the superiority of the proposed optimized segmentation algorithm over equivalent techniques.

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method that enables the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.

Liquid biopsy via isolation of circulating tumour cells (CTCs) represents a promising diagnostic tool capable of supplementing state-of-the-art for prostate cancer (PC) prognosis. Unfortunately, most of CTC technologies, such as AdnaTest or Cellsearch, critically rely on the Epithelial-Cell-Adhesion-Molecule (EpCAM) marker, limiting the possibility of detecting stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this tontext, dielectrophoresis (DEP) is an epCAM independent, label-free, enrichment system, separating rare cells simply on the basis of their specific electrical properties. As compared to other technollgies, DEP represents a superior technique in terms of running costs, cells yield and specificity, but due to its higher complexity, requires still further technical as well as clinical development. Interestingly, DEP can be improved by the use of microfluid, nanostructured materials and fluoroimaging in order to increase its potential applications. In the context of PC, the utility of DEP can be translated in its capacity to detect CTC in the bloodstream in their epithelial, mesenchymal, or epithelial-mesenchymal phenotypes, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and early diagnosis.

Metastasis is the leading cause of cancer death and can be realized through the phenomenon of tumor cell fusion. The fusion of tumor cells with other tumor or normal cells leads to the appearance of tumor hybrid cells (THCs) exhibiting novel properties such as increased proliferation and migration, drug resistance, decreased apoptosis rate and avoiding immune surveillance. Experimental studies showed the association of THCs with a high frequency of cancer metastasis; however, the underlying mechanisms remain unclear. Many other questions also remain to be answered: the role of genetic alterations in tumor cell fusion, the molecular landscape of cells after fusion, the lifetime and fate of different THCs, and the specific markers of THCs, and their correlation with various cancers and clinicopathological parameters. In this review, we discuss the factors and potential mechanisms involved in the occurrence of THCs, the types of THCs, and their role in cancer drug resistance and metastasis, as well as potential therapeutic approaches for the prevention and targeting of tumor cell fusion. In conclusion, we emphasize the current knowledge gaps in the biology of THCs that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.

: Increased glucose and choline uptake are hallmarks of cancer. We investigated if the uptake and conversion of [2H9]choline alone and together with that of [6,6’ 2H2]glucose can be assessed in subcutaneous tumors by deuterium metabolic imaging (DMI) after bolus administration of these compounds. Therefore tumors with human renal carcinoma cells were grown subcutaneously in mice up to ~0.5 cm3. Mice were anesthetized with isoflurane and IV infused in the MR magnet for ~20 sec with ~0.2 ml solutions containing either [2H9]choline (0.05g/kg) alone or together with [6,6’ 2H2]glucose (1.3g/kg). 2H MR was performed on a 11.7T MR system with a home-built 2H/1H coil using a 900 excitation pulse and 400ms repetition time. 3D DMI was recorded at high resolution (2x2x2mm) in 37 min or at low resolution (3.7x3.7x3.7mm) in 2:24 min. Absolute tissue concentrations were calculate assuming initial [HOD]=13.7mM. Within 5 minutes after [2H9]choline infusion its signal appeared in tumor spectra representing concentration increasing up to 0.3–1.2 mM and then slowly decreased or remained constant over 100 minutes. In plasma [2H9]choline disappeared within 15 minutes post-infusion implying that its tumor signal arises from tissue and not blood. After infusing a mixture of [2H9]choline and [6,6’ 2H2]glucose their signals were observed separately in tumor 2H spectra. Over time the [2H9]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6’ 2H2]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of all 2H compounds were reconstructed from high resolution DMIs. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.

Breast cancer, although the most frequently diagnosed malignant tumour in humans, has a less clear aetiology compared to other frequent cancer types. Mouse-mammary tumour virus (MMTV) is involved in breast cancer in mice and dogs and might play a role in the aetiology of some breast cancers in humans, since it has been identified in 20-40% of breast cancer samples in Western Europe, USA, Australia and some other parts of the world population. The purpose of our study was to identify MMTV DNA sequences in breast tissue samples from breast cancer patients operated in our regional centre from Romania. We have selected 75 patients with non-metastatic breast cancer treated with curative intent and searched with PCR the MMTV-like DNA sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. Since none of the examined samples was positive for MMTV-like target sequences on PCR we could not prove that MMTV plays a role in the aetiology of breast cancer in our patient group. This finding is similar to publications of other geographically related research groups and might be due to the fact that only the Mus musculus domesticus mouse species was proven to carry infectious MMTV, but not the Mus musculus musculus species, which is specific to South-Eastern Europe (including Romania) and some parts of Asia.

Tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment. The latter feature is achieved by soothing immune effector cells, mainly cytotoxic T lymphocytes, B and NK cells, and/or through expansion of regulatory cell populations, including regulatory T and B cells, tumor-associated macrophages and myeloid-derived suppressor cells. In this context, immune checkpoints (IC) are key players in the control of T cell activation and anti-cancer activities, leading to the inhibition of tumor cell lysis and of pro-inflammatory cytokine production. Thus, these pathways represent promising targets for the development of effective and innovative therapies both in adults and childhood. Here we address the role of different cell populations homing the TME and of well-known and recently characterized IC in the context of pediatric solid tumors. We also discuss preclinical and clinical data available using IC inhibitors alone, in combination each other or administered with standard therapies.

Proper and timely segregation of cellular genome is an important and a prime requirement of all cell division programmes. Mis-segregation of chromosomes and resulting aneuploidy leads to several clinical consequences. Over the years, shugoshin emerges as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or altered level of shugoshin is reported in several human malignancies, as a result, shugoshin now emerges as an important tumour associated gene and a possible target for cancer therapy. Apart from the role in cancer, recent studies also showed the involvement of shugoshin in several other clinical disorders. Through this review, we tried to highlight the clinical relevance of shugoshin.

In the last few decades, the dynamics of tumor cells and their growths are presented via clinical, experimental, and theoretical approaches, which leads to the development of the new idea of multiple cancer therapies to control and reduce the death rate for earlier detection. In this paper, we discussed the dynamics of tumor cell growth and its treatment process. We analyzed some simple mathematical models and generalized the study to understand the growth of tumor cells. The main proposed model is a system of ordinary differential equations which combines interactions among natural killer cells, dendritic cells and cytotoxic CD8+ T cells. The model is solved numerically to explain how the tumor cells spread and become more dangerous as well as the treatment process of cancer. It is also studied that how the cell behaves in the presence of different therapy and drugs. The optimal control of chemotherapy has been discussed. It has also been explained how much the model is effective in reducing tumor cells over time. Finally, a couple of spatially distributed models are discussed for tumor cell growth.

The lymphocyte function–associated antigen-1 (LFA-1) (also CD11a/CD18 and αLβ2), is just one of many integrins in the human body, but its significance derives from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1. A more detailed examination of LFA’s role within B-cell chronic lymphocytic leukemia is made. Finally, we discuss the role of LFA-1-harboring exosomes in tumor growth and metastasis.

MicroRNAs (miRNAs) are a kind of conserved small non-coding RNAs that participate in regulating gene expression by targeting multiple molecules. Early studies have shown that the expression of miRNAs changes significantly in different tumor tissues and cancer cell lines. It is well acknowledged that such variation is involved in almost all biological processes, including cell proliferation, mobility, survival and differentiation. Increasing experimental data indicate that miRNA dysregulation is a biomarker of several pathological conditions including cancer, and that miRNA can exert a causal role, as oncogenes or tumor suppressor genes, in different steps of the tumorigenic process. Anticancer therapies based on miRNAs are currently being developed with a goal to improve outcomes of cancer treatment. In our present study, we review the function of miRNAs in tumorigenesis and development, and discuss the latest clinical applications and strategies of therapy targeting miRNAs in cancer.

Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.

A generalization of $\eta$-Ricci solitons is considered involving an additional metric and functions as soliton coefficients. The soliton potential is torse-forming and orthogonal to the contact distribution of the almost contact B-metric manifold. Then such a manifold can also be considered as an almost Einstein-like manifold, a generalization of an $\eta$-Einstein manifold with respect to both B-metrics and functions as coefficients. Necessary and sufficient conditions are found for a number of properties of the curvature tensor and its Ricci tensor of the studied manifolds. Finally, an explicit example of an arbitrary dimension is given and some of the results are illustrated.

The precise molecular basis of anti-tumor immunity is not yet fully understood, although commensal Bifidobacterium (c-BIF) is expected to be one of the key players in cancer control via antigenic mimicry. We investigated the sequence similarity between c-BIF and cytotoxic T lymphocyte (CTL) epitope peptides against human tumor-associated antigens to better understand the molecular basis of antigenic mimicry. We used two different similarity analyses for this purpose, a linear sequence analysis and a similarity analysis of T cell receptor (TCR)-mediated recognition of CTL epitope peptides on antigen-presenting cells. The linear sequence analysis revealed 3,900 positive numbers of similarity sites between them with 126 mean per peptide and 107 median per peptide, while the TCR-mediated recognition analysis revealed 5,018 positive numbers with a mean of 162 and median of 132 per peptide. These results demonstrated the existence of durable and abundant sequence similarities between c-BIF and CTL epitope peptides, suggesting that the former play a pivotal in inducing cellular and humoral immunity against the latter in the absence of cancer cells via antigenic mimicry.

An emerging picture in cancer biology is that, paradoxically, chemotherapy can actively induce changes that favor cancer progression. These pro-cancer changes can be either inside (intrinsic) or outside (extrinsic) the cancer cells. In this review, we will discuss the extrinsic pro-cancer effect of chemotherapy; that is, the effect of chemotherapy on the non-cancer host cells to promote cancer progression. We will focus on metastasis, and will first discuss recent data from mouse models of breast cancer. Intriguingly, despite reducing the size of primary tumors, chemotherapy changes the tumor microenvironment, resulting in an increased escape of cancer cells into the blood stream. Furthermore, chemotherapry changes the tissue microenvironment at the distant sites, making it more hospitable to cancer cells upon their arrival. We will then discuss the idea and evidence that these devastating pro-metastatic effects of chemotherapy can be explained in the context of stress response. At the end, we will discuss the potential relevance of these mouse data to human breast cancer and their implication on chemotherapy in the clinic.

Exosomes are nano-sized extracellular vesicles released by cells that contain nucleic acids, proteins, lipids, and other bioactive compounds that play a role in the body's physiological and pathological processes. Exosomes have significant and distinct benefits over synthetic carriers such as liposomes and nanoparticles in the realm of illness diagnostics and therapy due to their endogeneity and heterogeneity. Exosomes are classified as either natural or designed, depending on whether they have been deliberately altered. Natural exosomes are further classified as either animal-derived or plant-derived exosomes. Plant-derived exosome-like nanoparticles (PDENs) are comprised of numerous kinds of bioactive biomolecules. As an alternative cell-free therapeutic strategy, they have the ability to transfer nano-bioactive chemicals to the human body, resulting in diverse anti-inflammatory, antioxidant, and anti-tumour effects. This review focuses on the beneficial effects of plant-derived exosomes against a range of inflammatory conditions, including as periodontitis, inflammatory bowel disease (IBD), autoimmune skin disorders, and inflammation of the liver, lungs, and intestines. Inflammatory disorders are a major issue because of their widespread influence on both personal health and public healthcare systems. Since these illnesses are persistent, the affected people's quality of life is negatively impacted and long-term morbidity is exacerbated. The complicated interaction of genetic, environmental, and immunological variables in the development of various disorders makes effective prevention and therapy more challenging. Plant exosomes present a promising avenue for developing novel therapeutic strategies against inflammatory diseases, offering unique advantages over other alternatives. In order to exploit this efficient carrier, future research will concentrate on creating a PELNV delivery system with high stability, transdermal volume, and ease of administration. Plant exosomes have the potential to become reliable therapeutic agents for a range of common disorders if they are targeted and generated with interdisciplinary expertise.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the chemical components on eggshell deserve further exploration. In two representative Coleopterans, a Coccinellid Henosepilachna vigintioctopunctata and a Chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and declined CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two Coleopteran species. Moreover, our findings propose the deposition of a CLS on the chorions.

In this study, we once again use a set of Fibonacci-like sequences to examine the symmetries within the genetic code. This time, our focus is on the physiological state of the amino acids, considering them as charged, in contrast to our previous work where they were seen as neutral. In a pH environment around 7.4, there are four charged amino acids. We utilize the properties of our sequences to accurately describe the symmetries in the genetic code table. These include Rumer’s symmetry, the third-base symmetry and the "ideal" symmetry, along with the "supersymmetry" classification schemes. We also explore the special chemical structure of the amino acid proline, presenting two perspectives—shCherbak’s view and the Downes-Richardson view, which perspectives are included in the description of the above-mentioned symmetries. Our investigation employs also elementary modular arithmetic to precisely describe the chemical structure of proline, connecting the two views seamlessly. Finally, our Fibonacci-like sequences prove instrumental in quickly establishing the multiplet structure of non-standard versions of the genetic code. We illustrate this with an example, showcasing the efficiency of our method in unraveling the complex relationships within the genetic code.

Human sepsis is one of the leading cause of death worldwide and is known to be a harmful damaging host inflammatory condition, primarily caused by endotoxin released by gram-negative bacteria. Despite antibiotics administration being widely used to treat disease, effective targeted therapeutic strategies for the sepsis are still lacking. Here, we demonstrate that CM1, a derivative of natural polyphenol chrysin, exerts anti-inflammatory activity by inducing the ubiquitin-editing protein TNFAIP3 and NAD-dependent deacetylase sirtuin 1 (SIRT1). We found that CM1 attenuated Toll-like receptor 4 (TLR4)-induced the generation of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signaling pathway. In addition, the treatment of macrophages with CM1 induced the expression of TNFAIP3 and SIRT1 in TLR4-stimulated primary macrophages, however the anti-inflammatory properties of CM1 was disappeared by siRNA silencing of TNFAPI3 or by the genetic and pharmacologic inhibition of SIRT1. Importantly, intravenously administration of CM1 resulted in the decreased susceptibility to endotoxin-induced sepsis, leading to inhibition of the generation of proinflammatory cytokines and neutrophils infiltration into lung than control mice. Collectively, these findings suggest that CM1 has the potential to be a treatment candidate for diverse inflammatory diseases including sepsis.

The 2-Acetyl-1-pyrroline (2-AP) is the most important volatile in determining the aroma of fragrant rice, however, the transcriptional regulation mechanism of 2-AP biosynthesis in fragrant rice is still unclear. In this study, the Osp5cs1 knockout mutant lines and OsP5CS1 over-expression lines were constructed by genetic transformation of indica rice cultivar i.e., ‘Zhonghua11’, which was knocked out OsBADH2 to produce fragrance in aromatic rice. The OsP5CS1 gene was also identified as a key gene in the 2-AP biosynthesis pathway of aromatic rice. The OsP5CS1 promoter was used as bait, and the transcription factor OsbZIP60-like was screened by yeast one-hybrid assays. The transcription factor OsbZIP60-like specifically bound to the OsP5CS1 gene. The dual luciferase reporting system found that OsbZIP60-like transcription factor promoted the transcriptional activation of OsP5CS1. Compared with the wild type, the OsP5CS1 gene expression was significantly down-regulated in Osbzip60-like mutant, and resulted in substantial reduction in 2-AP biosynthesis. Moreover, the OsP5CS1 gene expression was significantly up-regulated in OsbZIP60-like over-expressed plants, and the 2-AP concentrations were also increased whereas the Osbzip60-like mutants were found to be sensitive to Zn deficiency. Overall, the OsbZIP60-like transcription factor promoted the 2-AP accumulation. This study provides a theoretical basis for the transcriptional regulation mechanism of 2-AP biosynthesis and explores the function of OsbZIP transcription factor in fragrant rice.

Signaling modules that integrate the diverse extra- and intracellular inputs to control cell proliferation are essential during both development and adult stages to guarantee organism homeostasis. Mobs are small adaptor proteins that participate in several of these signalling pathways. Here we review recent advances unraveling Mob4 cellular functions, a highly conserved non-catalytic protein, that plays a diversity of roles in cell proliferation, sperm cell differentiation and simultaneously is involved in synapse formation and neural development. In addition, the gene is often overexpressed in a wide range of tumors and is linked to poor clinical outcomes. Nevertheless, Mob4 molecular functions remain poorly defined, although it integrates the core structure of STRIPAK, a kinase/phosphatase protein complex, that can act upstream of the Hippo pathway. In this review we focus on the recent findings of Mob4 functions, that have begun to clarify its critical role on cell proliferation and development of tissues and individuals.

During shearer operation, piston rod is susceptible to wear from invasion of pollutants, and then ruins sealing ring in hydraulic cylinder. This work attempts to conduct a systematical investigation of Cu-DLC (Cu-doped Diamond-like Carbon) film to improve the seal performance. Failure process of hydraulic cylinder was analyzed, and relevant parameters were determined. Several Cu-DLC films were deposited on the substrate of piston rod in a multi-ion beam assisted system, and their structures and combined tribological performances were investigated. As a result, dust particles attached to the piston rod may enter the cylinder, and damage the sealing ring under the radial force. Cu grains prefer to orientate (111) crystal plane with increase of Cu content, and may induce drop of hardness and internal stress for the film. Friction coefficient of the film ranges from 0.04 to 0.15, and rise of IG/ID ratio from 1.4 to 2.3 in Raman data indicates that bond transition from sp3-C to sp2-C may lower the friction coefficient. Modification mechanism of Cu-DLC film for the seal performance may come from synergistic effects of (i) contact force and friction heat induce the film graphitization, (ii) Cu doping improves toughness of the film and acts as a solid lubricant, and (iii) transfer layer plays a role of self-lubrication.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among different pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TB), and Xiangcun black (XB) piglets (20 piglets per breed) were selected at 21 and 24 days of age (three days of post-weaning) to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF system-related components in different tissues. The plasma IGFBP-3 level in TB piglets was higher (P > 0.05) than in the XB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (P < 0.05) in the kidney but was higher (P < 0.05) in the spleen of XB and TB piglets. At 24 days of age, the IGF-1 expression was higher (P < 0.05) in the kidney of TB piglets than in the XB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XB and TB piglets were lower (P < 0.05) compared with the DR piglets. Weaning down-regulated (P < 0.05) the IGF-1 expression in the jejunum, spleen, and liver of piglets, while up-regulated (P < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman’s correlation analysis showed a negative correlation (P < 0.05) between plasma IGFBP-2 and IGFBP-5 and the organ index of piglets. Collectively, there were significant differences in IGF system components among different pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

In this study, considering the peroxidase-like activity of the SiO₂@AuNPs nanocomposite, their biochemical properties including, pH stability, cycling stability, shelf stability, and kinetic parameters were investigated. The results revealed that the as-mentioned SiO₂@AuNPs nanocomposite reveal its maximal activity at pH=4.0 along with saving 83.3% of its maximal activity at pH=5.0. Besides, the reusability and shelf-storage studies exhibited that the SiO₂@AuNPs nanocomposite retained 90% and 100% of its initial activity after 5 operational cycles and 30 days of storage, in order. The kinetic parameters of the as-prepared nanozymes were calculated using Menten kinetic model, revealing a V_max of 1.35 µM min^-1 and a K_m as low as 0.06 mM for the SiO₂@AuNPs nanocomposite. Based on the results of this work, the as-prepared SiO₂@AuNPs nanocomposite with intrinsic peroxidase-like activity shows high substrate affinity and catalytic efficiency along with excellent cycling- and shelf-stability, making them suitable for application in peroxidase-mediated reactions instead of the native enzyme.

Brassica napus is an important vegetable and oil crop worldwide. The research is meaningful for yield and plant architecture in B. napus. In this study, one natural mutant (MT) line with determinate and capitulum-like inflorescence was chosen for further study. The paraffin sectioning detected that the inflorescence apex began to split and developed into one terminal flower, starting from five-leaf stage. Genetic analysis indicated that the segregation patterns of inflorescences in the F2 populations supported a digenic inheritance model, which was further approved by BSA-Seq technique. The BSA-Seq method detected two QTL region on C02 (14.27-18.41 Mb) and C06 (32.98-33.68 Mb) for the genetic control of determinate inflorescences in MT plants. In addition, the expression profile in MT compared with WT was analysized, and a total of 133 candidate genes for regulating the flower development (75 genes, 56.4%), shoot meristem development (29 genes, 21.8%) and inflorescence meristem development (13 genes, 9.8%) were identified. Then one joint analysis combing BSA-Seq and RNA-Seq identified two candidate gene of BncTFL1 and BncAP1 for regulating the MT phenotype. Besides, the potential utilization of the MT plants was also discussed.

In order to reduce the environmental damage caused by coal waste landfills, it is necessary to look for rational ways of their management. One of the methods of their development may be the creation of soil-like substrates. The aim of the study was to assess the properties of soil-like substrates from coal mining waste with a varied share of sewage sludge and waste mineral wool. The evaluation of the properties of the substrates was carried out in a pot experiment. The properties of the substrates and their yield potential were determined. Coal mining waste as a substrate, compared to anthropogenic soil, was characterized by: significantly higher sorption capacity, content of alkaline cations and pH, significantly higher content of organic carbon, nitrogen and assimilable forms of K and Mg, and lower content of assimilable P. The substrates enriched with sewage sludge showed: significant increase in the content of organic carbon, nitrogen and assimilable forms of P and Mg, optimization of sorption properties. Extending the composition of substrates with mineral wool resulted in further improvement of their properties. Yields of plants grown on coal mining waste were significantly lower than on anthropogenic soil. Substrates with sewage sludge and mineral wool had a significantly higher yield potential.

The Sry-related HMG-box (Sox) family is a group of transcriptional regulators that play a critical role in many important developmental processes in both vertebrates and invertebrates. In aquatic animals, the function of Sox genes on sexual development has been gained particular attentions. The present study reported the molecular characterization of a Sox member (PtSoxE) in the swimming crab, Portunus trituberculatus, and tissue distribution analysis showed it was male-specific. Since the most highly expression of PtSoxE was found in the androgenic gland (AG), its relation to the insulin-like androgenic gland hormone (IAG) was further investigated. The PtSoxE siRNA caused a significant decrease in IAG expression in both AG and testis, whereas PtSoxE expression could be induced by treating with AG homogenate and rIAG. The result suggested a transcriptional interaction between PtSoxE and IAG. In addition, PtSoxE expression showed a closely positive correlation with several reported spermatogenesis-related genes, suggesting its involvement in testicular development of P. trituberculatus.

In this contribution, unmodified silver nanoparticles were synthesized and characterized for their size and morphological properties. Thereafter, their peroxidase-like activity as the common catalytic property of silver nanoparticles was investigated by catalyzing the oxidation of 3,3’,5,5’-tetramethyl-benzidine (TMB) as peroxidase substrate, exhibiting, a specific activity as high as 5.4 µM min^-1 for the as-prepared unmodified silver nanoparticles. The stability of the catalytic activity of the as-prepared nanozymes was also checked upon their storage at ambient temperature within 7 days at different storage conditions. The results revealed that the peroxidase-like activity of unmodified silver nanoparticles was approximately retained at about 75%, and 63% after 7 days exposing daylight and air oxygen, in order. The shelf-life (storage stability) of the as-prepared nanozymes was also investigated at usual storage conditions (i.e., 4 ℃ under dark), revealed that the nanozymes saved their activity about 96% of their initial activity after 10 days of storage at 4 ℃ under dark conditions.

Introduction: Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficit and anxiety-like behavior. In this study, minocycline was compared to memantine, the NMDA receptor antagonist, for its effects on LPS-induced locomotor deficit and anxiety-like behavior in rats. Methodology: Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to LPS (5 mg/kg, i.p.) injection. The locomotor activity and anxiety-like behavior were assessed using the open field test (OFT). The phosphorylated tau protein level was measured using ELISA while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and western blot, respectively. Results: In the mPFC, minocycline treatment reduced the locomotor deficit and anxiety-like behavior, reduced phosphorylated tau protein level, and upregulated BDNF/CREB protein expression comparable to memantine, with the higher dose of minocycline having better benefits. Conclusion: Minocycline treatment attenuated LPS-induced locomotor deficit and anxiety-like behavior in rats, possibly via a decrease in phosphorylated tau protein levels and an increase in the expression of the BDNF/CREB proteins.

The effect of the negative effective mass emerging in the gravitating core-spring-shell system is considered. The effect appears when the entire system is exerted to the external harmonic force and the frequency of external force approaches to the critical frequency from above. The critical frequency depends on the density of the self-gravitating system only. The scaling law predicting the value of for condensed phases is derived. The generalization of the effect for the Coulomb-like forces is reported