Modified magnesium oxide/silver nanoparticles reinforced poly (butylene succinate-co-terephthalate) composite biofilms for food packaging application.

MgO/Ag nanoparticles (NPs) were surface-modified with titanate coupling agent titaniumtriisostearoylisopropoxide (NDZ-130). A new antibacterial biofilm for food packaging was synthesized by combining the modified MgO/Ag NPs with poly (butylene succinate-co-terephthalate) (PBST). The modification improved the compatibility between the MgO/Ag NPs and the PBST matrix. The effects of the modified MgO/Ag NPs on biofilm mechanical, barrier, thermal, antibacterial and food preservation properties were evaluated. Compared with the PBST/MgO/Ag composite film, the modified PBST/MgO/Ag composite film showed an increase in tensile strength (TS) of 8.71% and elongation at break (EB) of 16.66%, additionally decreasing water vapor permeability (WVP) by 42.86%. The composite film also exhibited over 95% inhibition of Staphylococcus aureus and Escherichia coli. The modified PBST/MgO/Ag composite film avoided microbial contamination and preserved cherry tomatoes while maintaining moisture and firmness for six days. All results indicated that the prepared biofilms have a high potential for use as food packaging films.

Exposure to PM2.5, seminal plasma metabolome, and semen quality among Chinese adult men: Association and potential mediation analyses.

Exposure to ambient fine particulate matter (PM2.5) has been linked to a decline in semen quality, but the underlying mechanisms for this association remain unclear. We aimed to examine whether specific metabolites act as mediators in the association between PM2.5 exposure and changes in semen quality. We conducted untargeted metabolomics analysis using LC-MS/MS platforms to identified seminal plasma metabolites associated with various semen quality parameters among 200 Chinese adult men. Additionally, we performed mediation analyses to examine the effects of the seminal plasma metabolites on the association between PM2.5 exposure and semen quality. We identified 140 differential metabolites between the normal and abnormal semen groups, involving two metabolic pathways: Alanine, aspartate and glutamate metabolism, and Aminoacyl-tRNA biosynthesis. We additionally identified 7 specific seminal plasma metabolites that were associated with discrepant metabolic networks related to semen quality. The mediation analysis revealed that D-Aspartate might play a mediating role in the adverse effects of ambient PM2.5 exposure on both total and progressive motility during spermatogenesis period (70-90 days before ejaculation), with a proportion of mediation up to 16% and 17%, respectively. Exposure to PM2.5 was associated with alterations in D-Aspartate levels, which might partially mediate the association between PM2.5 and reduced sperm motility.

Comprehensive Characterization of HATs and HDACs in Human Cancers Reveals Their Role in Immune Checkpoint Blockade.

Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types. In particular, HDAC10 and HDAC6 show significant downregulation in most cancers. Principal components analysis (PCA) of pan-cancer reveals significant difference of HDACs and HATs between normal tissues and normal tissue adjacent to the tumor. The abnormal expression of HDACs and HATs was partially due to CNV and DNA methylation in multiple types of cancer. Prognostic significance (AUC reached 0.736) of HDACs and HATs demonstrates a five-gene signature including KAT2A, HAT1, KAT5, CREBBP and SIRT1 in KIRC. Analysis of NCI-60 drug database reveals the cytotoxic effect of several drugs are associated with dysregulated expression of HDACs and HATs. Analysis of immune infiltration and immunotherapy reveals that KAT2B and HDAC9 are associated with immune infiltration and immunotherapy. Our analysis provided comprehensive understanding of the regulation and implication of HDACs and HATs in pan-cancer. These findings provide novel evidence for biological investigating potential individual HDACs and HATs in the development and therapy of cancer in the future.

Machine learning-assisted photoluminescent sensor array based on gold nanoclusters for the discrimination of antibiotics with test paper.

Antibiotic residues accumulation in the environment endangers ecosystems and human health. There is an urgent need for a facile and efficient strategy to detect antibiotics. Here, we report a photoluminescent sensor array based on protein-stabilized gold nanoclusters (AuNCs) for the detection of two families of antibiotics, tetracyclines and quinolones. The nanoclusters were synthesized with bovine serum albumin (BSA) and ovalbumin (OVA), respectively. They had different interactions with seven kinds of antibiotics and exhibited diverse photoluminescence (PL) responses, which were analyzed by linear discriminant analysis and ExtraTrees algorithms. The sensor array performed well in both classification and quantification of seven antibiotics. And the quantitative results of all antibiotics obtained R2 of no less than 0.99 at 0-100 µM when using suitable regression models. Additionally, the sensor array was able to distinguish antibiotic mixtures and multiple interfering substances, and it also kept 100% classification accuracy in river water samples. Moreover, test paper assisted by a smartphone was applied for quick detection of antibiotics, with good performance in both HEPES buffer and river water. These studies reveal great potential for the point-of-use analysis of antibiotics in environmental monitoring.

Sustainable biomass-based composite biofilm: Sodium alginate, TEMPO-oxidized chitin nanocrystals, and MXene nanosheets for fire-resistant materials and next-generation sensors.

Efficient utilization of natural biomass for the development of fireproof materials and next-generation sensors faces various challenges in the field of fire safety and prevention. In this study, renewable sodium alginate (SA), TEMPO-oxidized chitin nanocrystals (TOChNs), and MXene nanosheets were employed to fabricate a sustainable, flexible, and flame-retardant composite biofilm, donated as STM, utilizing a simple and environmentally friendly evaporation-induced self-assembly technique. The incorporation of SA, TOChNs, and MXene in a weight ratio of 50/10/40 led to improved mechanical properties of the resulting STM-40 films, as evidenced by increased tensile strength and Young's modulus values of approximately 36 MPa and 4 GPa, respectively. Notably, these values were approximately 3 and 11 times higher than those observed for the pure SA film. Moreover, the STM-40 films demonstrated highly sensitive fire alarm capabilities, exhibiting a superior flame alarm response time of 0.6 s and a continuous alarm time of approximately 492 s when exposed to flames. The STM exhibited exceptional flame retardancy due to the synergistic carbonization between MXene and SA/TOChNs, resulting in a limiting oxygen index of 45.0 %. Furthermore, its maximum heat release rate decreased by over 90.1 % during the test. This study presents a novel approach for designing and developing fire-retardant fire alarm sensors by utilizing natural biomass.

Dynamic surfaces of latex films and their antifouling applications.

Latex polymer particles have been widely used in industry and everyday life. For decades the fabrication of "smart" latex film from latex particles has been a great challenge due to the difficulty in the synthesis of the functional latex particles by traditional emulsion polymerization using small molecular surfactants. In this manuscript, a simple and environmentally-friendly approach to the fabrication of "smart" latex films with dynamic surfaces is reported. Latex particles with poly(n-butyl methacrylate) (PnBMA) in the cores and zwitterionic poly-3-[dimethyl-[2-(2-methylprop-2-enoyloxy) ethyl]azaniumyl]propane-1-sulfonate (PDMAPS) in the shells are synthesized by reversible addition-fragmentation chain transfer (RAFT) mediated surfactant-free emulsion polymerization. The kinetics for the emulsion polymerization is studied, and the latex particles are analyzed by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and dynamic light scattering (DLS). Latex films are prepared by casting aqueous solutions of the latex particles at temperatures above the glass transition temperature (Tg) of PnBMA. On the dried latex film, the hydrophobic PnBMA blocks occupy the top surface; after water treatment, the hydrophilic PDMAPS blocks migrate to the surface. A change in the surface hydrophilicity results in a change in the water contact angle of the latex film. A mechanism for the formation of the dynamic surface structure is proposed in this research. Antifouling applications of the latex films are investigated. Experimental results indicate that the water-treated latex film is able to efficiently inhibit protein adsorption and resist bacterial adhesion.

Facile preparation of maghemite based on iron sludge for arsenic removal from water.

In this study, we demonstrated the effective acquisition of magnetic iron oxide (MIO) for As(V) adsorption by high-temperature pyrolysis of waste iron sludge from the water treatment plant under a confined environment without adding extra chemical reagents. The operating temperature and time in the pyrolysis process were optimized to improve the yield of MIO and its As(V) adsorption capacity. MIO500-2(500 °C, 2 h) had both relatively high yield and arsenic adsorption efficiency, which was characterized by XRD and XPS as mainly γ-Fe2O3 with small particle size (100-900 nm), significant mesopore (12.43 nm), high specific surface area (65.25 m2/g), and effective saturation magnetization intensity (14.45 emu/g). The maximum adsorption capacity was 14.2 ± 0.4 mg/g, and the removal rate could still reach about 80 % after five times of adsorbent regeneration. Considering this facile preparation route and its high yield, large-scale production of MIO from waste iron sludge is feasible, which is expected to provide a low-cost and efficient adsorbent for the treatment of arsenic-containing water in less economically developed areas.

Early-stage economic and environmental impact assessment for optimized bioprocess development: Monoterpenoid indole alkaloids.

Microbial refactoring offers sustainable production of plant-sourced pharmaceuticals associated with high production costs, ecological harms, and supply chain dependencies. Here, microbial tabersonine production in Saccharomyces cerevisiae is modeled during early-stage development (TRL: 3-5), guiding decisions for process-scale economic and environmental optimization. The base-case 0.7 mg/L titer indicated a minimum selling price (MSP) of $3,910,000/kg and global warming potential (GWP) of 2,540 kgCO2eq/g. The industrial process at 1 g/L resulted in an MSP of 4,262 $/kg and a GWP of 6.36 kgCO2eq/g. Location analysis indicated a sustainability trade-off between France, USA, Poland, and China, with the written order of declining MSP and increasing GWP. Continuous processing promised reducing the MSP by 18-27 %, and the GWP by 17-31 %. In-situ product extraction during fermentation was estimated to lower the MSP by 41-61 %, and the GWP by 30-75 %. In addition to showcasing a combined TEA-LCA on biopharmaceuticals, the early-stage assessment approach guides bioprocess optimization.

Green synthesis and anti-tumor efficacy via inducing pyroptosis of novel 1H-benzo[e]indole-2(3H)-one spirocyclic derivatives.

Pyroptosis induction is anticipated to be a new approach to developing anti-tumor medications. A novel class of spirocyclic compounds was designed by hybridization of 1H-Benzo[e]indole-2(3H)-one with 1,4-dihydroquinoline and synthesized through a new green "one-pot" synthesis method using 10 wt% SDS/H2O as a solvent to screen novel tumor cell pyroptosis inducers. The anti-tumor activity of all compounds in vitro was determined by the MTT method, and a fraction of the compounds showed good cell growth inhibitory activity. The quantitative structure-activity relationship models of the compounds were established by artificial intelligence random forest algorithm (R2 = 0.9656 and 0.9747). The ideal compound A9 could, in a concentration-dependent manner, prevent ovarian cancer cells from forming colonies, migrating, and invading. Furthermore, A9 could significantly induce pyroptosis and upregulate the expression of pyroptosis-related proteins GSDME-N, in addition to inducing apoptosis and mediating the expression of apoptosis-related proteins in ovarian cancer cells. A9 (5 mg/kg) significantly reduced tumor volume and weight of ovarian cancer in vivo, decreased caspase-3 expression in tumor tissue, and induced the production of GSDME-N. This study provides a green and efficient atom-economic synthesis method for 1H-Benzo[e]indole-2(3H)-one spirocyclic derivatives and a promising pyroptosis inducer with anti-tumor activity.

High glucose exposure of preimplantation embryos causes glucose intolerance and insulin resistance in F1 and F2 male offspring.

BACKGROUND: Although studies suggest that maternal high glucose (HG) increases offspring susceptibility to type 2 diabetes mellitus (T2DM), the underlying mechanisms are largely unclear. We studied whether glucose levels in oviducts are elevated when pregestational diabetic females get pregnant and whether the oviductal HG (OVHG) would act directly on embryos to increase offspring's T2DM susceptibility. METHODS: We established an in vivo model of OVHG by injecting female mice with streptozotocin (STZ) during the preimplantation period and an in vitro model of embryo culture with HG (ECHG) by culturing preimplantation embryos with HG, before examining glucose tolerance and insulin resistance (IR) in F1 and F2 offspring. FINDINGS: Injection of female mice with STZ induced a lasting significant glucose elevation in blood and oviduct fluid during the preimplantation period. The glucose tolerance test showed that both the STZ-induced OVHG and the ECHG caused glucose intolerance in F1 male and F1-sired F2 male offspring but had no effect on female offspring. Insulin tolerance test and the analysis for IR-related gene expression and glycogen contents in liver and muscle revealed significant IR in these male offspring. INTERPRETATION: This study provided evidence that HG can act directly on preimplantation embryos to increase offspring's T2DM susceptibility suggesting that the preimplantation period is a critical stage for transmission of mother's diabetes to offspring. FUND: This study was supported by grants from the China National Natural Science Foundation (Nos. 31772599, 32072738, 31702114, and 31902160), and the Natural Science Foundation of Shandong Province (Nos. ZR2022MC036, ZR2017BC025 and ZR2020QC102).

Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice.

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury. However, the precise mechanism of action remains unclear. In this study, we induced moderate traumatic brain injury in mice by intraperitoneal injection of erythropoietin for 3 consecutive days. RNA sequencing detected a total of 4065 differentially expressed RNAs, including 1059 mRNAs, 92 microRNAs, 799 long non-coding RNAs, and 2115 circular RNAs. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway, Wnt pathway, and MAPK pathway. Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs. Because the axon guidance pathway was repeatedly enriched, the expression of Wnt5a and Ephb6, key factors in the axonal guidance pathway, was assessed. Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury, and these effects were reversed by treatment with erythropoietin. These findings suggest that erythropoietin can promote recovery of nerve function after traumatic brain injury through the axon guidance pathway.

Electrochemical denitrification by a recyclable cobalt oxide cathode: Rapid recovery and selective catalysis.

Cathodic aging and fouling have presented significant challenges in the realm of electrochemical denitrification for engineering applications. This study focused on the development of an economical and recyclable nanoporous Co3O4/Co cathode through anodization for nitrate reduction. What distinguished our cathode was its exceptional sustainability. Cobalt from the inactive catalyst could be reclaimed onto the substrate, enabling the regeneration of a new Co3O4 layer. This innovative approach resulted in an exceptionally low Co catalyst consumption, a mere 1.936 g/1 kg N, making it the most cost-effective choice among all Co-based cathodes. The Co3O4 catalyst exhibited a truncated octahedron structure, primarily composed of surface Co2+ ions. Density functional theory calculations confirmed that the bonding between the O atom in NO3- ions and the Co atom in Co3O4 was thermodynamically favorable, with a free energy of - 0.89 eV. Co2+ ions acted as "electron porters" facilitating electron transfer through a redox circle Co2+-Co3+-Co2+. However, the presence of two energy barriers (*NH2NO to *N2 and *N2 to N2) with respective heights of 0.83 eV and 1.17 eV resulted in a N2 selectivity of 9.84% and an NH3 selectivity of 90.02%. In actual wastewater treatment, approximately 78% of TN and 93% of NO3- were successfully removed after 3 h, consistent with the prediction kinetic model. This anodization-based strategy offers a significant advantage in terms of long-term cost and presents a new paradigm for electrode sustainability.

Polygonum perfoliatum L. ethanol extract ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum perfoliatum L. (PP) is classified as a heat-clearing and detoxifying agent in traditional Chinese medicine, and is believed to possess therapeutic properties for treating eczema, furuncles, and venomous snake bites. Previous studies have demonstrated that PP extract exhibits multiple bioactivities, including antibacterial, anti-inflammatory, antitumor, antioxidation, and antiviral properties. However, no existing studies have evaluated the effects of PP on animal models of atopic dermatitis (AD)-like skin symptoms, which are closely associated with traditional ethnic usage. AIM OF THE STUDY: In present study, therefore, we aimed to explore the potential anti-atopic effect of Polygonum perfoliatum L. ethanol extract (PPE) in 2,4-Dinitrochlorobenzene (DNCB)-induced dermatitis-like skin lesions. MATERIALS AND METHODS: For reaching this aim, DNCB-induced mice with AD-like skin inflammation were subjected to topical administration of PPE gels for a period of 21 days, and subsequently, the biological impacts of PPE were evaluated. RESULTS: PPE gels effectively mitigated AD-like skin symptoms induced by DNCB in mice, as demonstrated by a marked reduction in epidermal thickness and dermatitis severity. Moreover, PPE significantly decreased the production of various cytokines, including TNF-α, IL-6, IL-1ß, IL-4, IL-5, IL-13 and IgE, in addition to suppressed the production of key inflammation-related enzymes (iNOS and COX-2) and decreased the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in AD-like skin samples. Furthermore, PPE treatment inhibited the abnormally elevated CD4+/CD8+ ratio in DNCB-induced AD mice. The results of the skin irritation test revealed that PPE exhibited no adverse toxicity in mice at dose of 10 mg/day. CONCLUSIONS: PPE exhibits potential as a safe therapeutic agent for atopic dermatitis by efficiently mitigating DNCB-induced atopic symptoms and diminishing inflammation, and does not carry the risk of over-immunosuppression or treatment-associated adverse effects.

Bioactive metabolites reveal the therapeutic consistency of epimedii folium from multi-plant sources for the treatment of kidney-yang deficiency.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedii Folium (Yin-yang-huo in Chinese), a traditional and commonly used herbal medicine (HM), is a representative of multi-plant sources. To date, little is known about the reasons for similar therapeutic effects of this HM from multi-plant sources. AIM OF THE STUDY: To investigate the underlying reasons for the similar pharmacological effects of Epimedii Folium from two botanical sources (Epimedium koreanum Nakai and Epimedium wushanense T. S. Ying). MATERIALS AND METHODS: Firstly, the phytochemicals of the extracts of E. koreanum and E. wushanense were systematically analyzed. Meanwhile, their pharmacological effects on kidney-yang deficiency (KYD) syndrome were evaluated in rats induced by hydrocortisone. Subsequently, we proposed a combined effect index (CEI) to assess the effects of two plants on the secretion of testosterone by combing the system exposure of twelve active components in vivo with their regulation activities of testosterone production in vitro. Moreover, the label-free proteomics and Western blot analysis were conducted to evaluate the possible mechanism of Epimedii Folium from two botanical sources. RESULTS: E. koreanum and E. wushanense exhibited similar pharmacological effects on KYD syndrome with promoting the mating behaviors and testosterone levels of rats, although there is a certain difference in the main components between two plants. The CEI analysis showed that there was no difference (P > 0.05) in the sum of CEIs of two Epimedium, indicating that their similar therapeutic effects are attributed to bioactive metabolites in vivo. Furthermore, Epimedii Folium can regulate testosterone production in rat Leydig cell via reversing expressions of key steroidogenic enzymes, such as steroidogenic acute regulatory protein (StAR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD). CONCLUSION: Our results supply critical evidence for the similar pharmacological effects of two Epimedium species, acting by consistent bioactive components directly exposing in vivo, not chemical compositions presenting in herbs. It provides a reasonable scientific basis for understanding of the HMs originated from multi-plant sources for the same clinical application.

MFS Transporter Bdorwp Does Not Affect Antennal Electrophysiology but Regulates Reproductive Behaviors in Bactrocera dorsalis.

Developing behavioral modifying chemicals through molecular targets is a promising way to improve semiochemical-based technology for pest management. Identifying molecular targets that affect insect behavior largely relies on functional genetic techniques such as deletions, insertions, and substitutions. Selectable markers have thus been developed to increase the efficiency of screening for successful editing events. However, the effect of selectable markers on relevant phenotypic traits needs to be considered. In this study, we cloned the wp gene ofBactrocera dorsalis. Knocking out Bdorwp causes white pupae phenotypes. Reproductive behaviors in both males and females were strongly regulated by Bdorwp. Remarkably, Bdorwp did not affect the antennal electrophysiology response to 63 chemical components with various structures. It is recommended to indirectly apply Bdorwp as a selectable marker in functional gene research on behavioral modifying chemicals. Moreover, Bdorwp could also be a potential molecular target for developing new insecticides for tephritid species control.

Fatal motorcycle straddle injury consolidated with traumatic testicular dislocation: A case report.

Straddle injuries are those to the perineum region brought on by straddling or riding over something, such as a horse, vehicle, or other object. The motorcycle fuel tank or handlebars are primarily responsible for the typical injury to the perineum area in motorcycle accidents. Motorcycle straddle injury usually manifest as abrasions to the scrotum or penis, and severe cases can cause pelvic fractures or even testicular dislocation. Because these injuries are usually closed with unclear internal damage, diagnosis presents a significant challenge and can easily lead to misdiagnosis. However, pelvic fractures and the bleeding and nerve damage associated with perineal injury are often fatal, and testicular dislocation can also have serious consequences for patients. Therefore, a clear diagnosis and timely treatment are crucial for patients with this type of injury. This article reports the case of a motorcycle rider who died 4 h after a traffic accident with only minor surface injury visible, showing only bruising in the waist and scrotum. A forensic examination revealed multiple fractures throughout the patient's body, with a slightly more severe pelvic fracture and testicular dislocation on the left side in the left inguinal area. This article analyzes the cause of death and related issues in this case, aiming to provide assistance to clinical physicians and forensic practitioners and to emphasize the importance of handling straddle injury in treatment and related investigations to avoid serious consequences.

Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies. / è ºè‹·å¯¹è‚¿ç˜¤èŽ·å¾—æ€§å ç–«çš„æŠ‘åˆ¶ä½œç”¨åŠå¹²é¢„ç­–ç•¥.

Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.

Molecular mechanism of the effect of Gegen Qinlian decoction on COVID-19 comorbid with diabetes mellitus based on network pharmacology and molecular docking: A review.

To explore the potential mechanism of Gegen Qinlian decoction (GGQL) in the treatment of COVID-19 comorbid with diabetes mellitus (DM) through network pharmacology and molecular docking, and to provide theoretical guidance for clinical transformation research. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen the active compounds and targets of GGQL, the targets of COVID-19 comorbid with DM were searched based on Genecards database. Protein-protein interaction network was constructed using String data platform for the intersection of compounds and disease targets, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the intersection targets was performed using DAVID database. Cytoscape software was used to construct the "compound target-pathway (C-T-P)" of GGQL in the treatment of COVID-19 comorbid with DM, the molecular docking platform was used to complete the simulated docking of key compounds and targets. We obtained 141 compounds from GGQL, revealed 127 bioactive compounds and 283 potential targets of GGQL. Quercetin, kaempferol and formononetin in GGQL play a role by modulating the targets (including AR, GSK3B, DPP4, F2, and NOS3). GGQL might affect diverse signaling pathways related to the pathogenesis of coronavirus disease - COVID-19, AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, human cytomegalovirus infection and Th17 cell differentiation. Meanwhile, molecular docking showed that the selected GGQL core active components had strong binding activity with the key targets. This study revealed that GGQL play a role in the treatment of COVID-19 comorbid with DM through multi-component, multi-target and multi-pathway mode of action, which provided good theoretical basis for further verification research.

Unveiling the Impact of Thiophanate-Methyl on Arthrospira platensis: Growth, Photosynthetic Pigments, Biomolecules, and Detoxification Enzyme Activities.

BACKGROUND: The intensive and injudicious use of pesticides in agriculture has emerged as a major concern due to its detrimental impact on aquatic ecosystems. However, the specific impact of broad-spectrum fungicides, such as Thiophanate-methyl (TM), on cyanobacteria remains a subject of ongoing research and debate. METHODS: In order to fill this knowledge gap, The present study aimed to comprehensively investigate the toxicological effects of TM (10-30 µg/L) on the growth, photosynthetic pigments, oxidative stress, and biochemical composition of the non-nitrogen-fixing cyanobacterium Arthrospira platensis. RESULTS: Our findings unequivocally demonstrated that TM exposure significantly inhibited the growth of A. platensis. Moreover, the decrease in chlorophyll content indicated a pronounced negative impact on the photosynthetic system of A. platensis caused by TM exposure. Notably, TM induced oxidative stress in A. platensis, as substantiated by a significant increase in lipid peroxidation (MDA) within the culture. Furthermore, the intracellular generation of hydrogen peroxide (H2O2) exhibited a positive correlation with higher TM dosages, while the levels of vital antioxidant enzymes, such as catalase (CAT) and ascorbate peroxidase (APX), exhibited a discernible decrease. This suggests that TM compromises the antioxidant defense mechanisms of A. platensis. Additionally, TM was found to enhance the activity of a plethora of enzymes involved in the detoxification of pesticides, including peroxidase (POD) and glutathione-S-transferase (GST), thereby indicating a robust detoxification response by A. platensis. Interestingly, exposure to TM resulted in a general suppression of biocomponent production, such as total proteins and total carbohydrates, which exhibited a diminishing trend with increasing TM concentration. Conversely, the lipid content witnessed a significant increase, possibly as an adaptive response to TM-induced stress. CONCLUSIONS: These findings contribute to a deeper understanding of the ecological implications of pesticide usage and emphasize the urgent need for the adoption of sustainable and environmentally-friendly agricultural practices to safeguard aquatic ecosystems.

Double Aneuploidy of Down Syndrome (Trisomy 21) and Jacobs Syndrome (Trisomy XYY) with Complete Tracheal Rings Deformity: Case Report and Literature Review.

Down syndrome (DS, trisomy 21) with an extra copy of chromosome 21 is one of the most common aneuploidies in humans. Jacobs syndrome or XYY syndrome (trisomy XYY) with an extra copy of sex chromosome Y is a rare sex chromosome trisomy in males. Double aneuploidy (DA) with an extra copy of chromosome 21 and sex chromosome Y is an extremely rare occurrence. Most trisomy 21 results from nondisjunction during maternal oocyte meiosis-I, whereas trisomy XYY is results from nondisjunction during paternal spermatocyte meiosis-I. We present a case of natural conception premature newborn of 30.4 weeks gestational age who had a DS facial phenotype with extensive syndactyly on both hands and feet. Other multisystem congenital anomalies were discovered, including mal-aligned perimembranous ventricular septal defect, bicuspid aortic valve, Dandy-Walker malformation's tetra-ventriculomegaly, and a rare complete tracheal rings deformity (CTRD) with trachea stenosis. Prenatal amniocentesis and postnatal chromosomal karyotyping analysis detected 48, XYY, + 21 nontranslocation trisomy 21, and free-lying Y chromosome without translocation. The existence of DA is rarely reported in literature reviews. In this review, we will discuss the characteristics of DS and Jacobs syndrome as well as the associated multiorgan malformation including the rare lethal CTRD.