Proteo-transcriptomic profiles reveal key regulatory pathways and functions of LDHA in the ovulation of domestic chickens (Gallus gallus).

BACKGROUND: In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear. RESULTS: Critical biochemical events involved in ovulation in domestic chickens (Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle (F1) and postovulatory follicle (POF1) in continuous laying (CL) and intermittent laying (IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes (DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A (LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro. CONCLUSIONS: This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.

Achieving High Ionic Conductivity and Mechanical Strength by a Leather Gel Electrolyte for Flexible Zinc-Ion Batteries.

The continuous advancement in the field of flexible and wearable electronics has led to increased research interest in safe, low-cost, and flexible zinc-ion batteries, particularly with a focus on flexible electrolytes. In this study, we present a leather gel electrolyte (LGE) that offers robust mechanical properties and an excellent electrochemical performance. LGE exhibits an ionic conductivity of 1.36 × 10-2 S cm-1 and achieves a capacity of 303.7 mAh g-1 in flexible zinc-manganese dioxide batteries. Even after 1000 cycles, the capacity retention remains above 90%, demonstrating outstanding performance in protecting the zinc anode. Furthermore, such a flexible battery shows good resistance to damage due to the strong mechanical strength originating from leather. Notably, LGE utilizes green and sustainable leather as a raw material, making it a promising option for sustainable flexible devices.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

High expression of SRSF1 facilitates osteosarcoma progression and unveils its potential mechanisms.

BACKGROUND: SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. METHODS: SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. RESULTS: SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. CONCLUSIONS: Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.

Association between autoimmune liver diseases and chronic hepatitis B: A multivariable Mendelian randomization study in European population.

BACKGROUND: Observational studies have indicated a link between autoimmune liver diseases (AILD) and chronic hepatitis B (CHB) through observational studies. The association between AILD and CHB remains indeterminate. METHODS: A two-sample Mendelian randomization (MR) analysis was conducted to scrutinize the causal nexus between AILD and CHB utilizing summary statistics derived from extensive genome-wide association studies (GWASs) in European populations. The primary statistical methodology employed was the inverse variance-weighted (IVW) method to deduce the causal connection of AILD on CHB. This study incorporated primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) as subtypes of AILD. Additionally, we conducted a multivariable MR (MVMR) analysis to account for the potential confounding effects of smoking, alcohol consumption, body mass index (BMI), and some autoimmune diseases. RESULTS: Our MR investigation encompassed a cohort of 725,816 individuals. The MR analysis revealed that genetically predicted PSC significantly correlated with a reduced risk of CHB (IVW OR = 0.857; 95%CI: 0.770-0.953, P = 0.005). Conversely, the reverse MR analysis suggested that genetic susceptibility to PSC might not modify the risk of CHB (IVW OR = 1.004; 95% CI: 0.958-1.053, P = 0.866). Genetically proxied PBC and AIH exhibited no discernible causal association with CHB in the MR analysis using the IVW method (P = 0.583; P = 0.425). The MVMR analysis still indicated a decreased risk of CHB associated with PSC (OR = 0.853, P = 0.003). CONCLUSION: Our study elucidates a causal relationship between PSC and a diminished risk of CHB.

Discovery of novel cholesteryl ester transfer protein (CETP) inhibitors by a multi-stage virtual screening.

Cholesteryl ester transfer protein (CETP) is a promising therapeutic target for cardiovascular diseases. It effectively lowers the low-density lipoprotein cholesterol levels and increases the high-density lipoprotein cholesterol levels in the human plasma. This study identified novel and highly potent CETP inhibitors using virtual screening techniques. Molecular docking and molecular dynamics (MD) simulations revealed the binding patterns of these inhibitors, with the top 50 compounds selected according to their predicted binding affinity. Protein-ligand interaction analyses were performed, leading to the selection of 26 compounds for further evaluation. A CETP inhibition assay confirmed the inhibitory activities of the selected compounds. The results of the MD simulations revealed the structural stability of the protein-ligand complexes, with the binding site remaining significantly unchanged, indicating that the five compounds (AK-968/40709303, AG-690/11820117, AO-081/41378586, AK-968/12713193, and AN-465/14952302) identified have the potential as active CETP inhibitors and are promising leads for drug development.

The complete degradation of 1,2-dichloroethane in Escherichia coli by metabolic engineering.

1,2-Dichloroethane (1,2-DCA), a widely utilized chemical intermediate and organic solvent in industry, frequently enters the environment due to accidental leaks and mishandling during application processes. Thus, the in-situ remediation of contaminated sites has become increasingly urgent. However, traditional remediation methods are inefficient and costly, while bioremediation presents a green, efficient, and non-secondary polluting alternative. In this study, an engineered strain capable of completely degrading 1,2-DCA was constructed. We introduced six exogenous genes of the 1,2-DCA degradation pathway into E. coli and confirmed their normal transcription and efficient expression in this engineered strain through qRT-PCR and proteomics. The degradation experiments showed that the strain completely degraded 2 mM 1,2-DCA within 12 h. Furthermore, the results of isotope tracing verified that the final degradation product, malic acid, entered the tricarboxylic acid cycle (TCA) of E. coli and was ultimately fully metabolized. Also, morphological changes in the engineered strain and control strain exposed to 1,2-DCA were observed under SEM, and the results revealed that the engineered strain is more tolerant to 1,2-DCA than the control strain. In conclusion, this study paved a new way for humanity to deal with the increasingly complex environmental challenges.

Rehabilitation Applications Based on Behavioral Therapy for People With Knee Osteoarthritis: Systematic Review.

BACKGROUND: The development of digital applications based on behavioral therapies to support patients with knee osteoarthritis (KOA) has attracted increasing attention in the field of rehabilitation. This paper presents a systematic review of research on digital applications based on behavioral therapies for people with KOA. OBJECTIVE: This review aims to describe the characteristics of relevant digital applications, with a special focus on the current state of behavioral therapies, digital interaction technologies, and user participation in design. The secondary aim is to summarize intervention outcomes and user evaluations of digital applications. METHODS: A systematic literature search was conducted using the keywords "Knee Osteoarthritis," "Behavior Therapy," and "Digitization" in the following databases (from January 2013 to July 2023): Web of Science, Embase, Science Direct, Ovid, and PubMed. The Mixed Methods Assessment Tool (MMAT) was used to assess the quality of evidence. Two researchers independently screened and extracted the data. RESULTS: A total of 36 studies met the inclusion criteria and were further analyzed. Behavioral change techniques (BCTs) and cognitive behavioral therapy (CBT) were frequently combined when developing digital applications. The most prevalent areas were goals and planning (n=31) and repetition and substitution (n=27), which were frequently used to develop physical activity (PA) goals and adherence. The most prevalent combination strategy was app/website plus SMS text message/telephone/email (n=12), which has tremendous potential. This area of application design offers notable advantages, primarily manifesting in pain mitigation (n=24), reduction of physical dysfunction (n=21), and augmentation of PA levels (n=12). Additionally, when formulating design strategies, it is imperative to consider the perspectives of stakeholders, especially in response to the identified shortcomings in application design elucidated within the study. CONCLUSIONS: The results demonstrate that "goals and planning" and "repetition and substitution" are frequently used to develop PA goals and PA behavior adherence. The most prevalent combination strategy was app/website plus SMS text message/telephone/email, which has tremendous potential. Moreover, incorporating several stakeholders in the design and development stages might enhance user experience, considering the distinct variations in their requirements. To improve the efficacy and availability of digital applications, we have several proposals. First, comprehensive care for patients should be ensured by integrating multiple behavioral therapies that encompass various aspects of the rehabilitation process, such as rehabilitation exercises and status monitoring. Second, therapists could benefit from more precise recommendations by incorporating additional intelligent algorithms to analyze patient data. Third, the implementation scope should be expanded from the home environment to a broader social community rehabilitation setting.

Microstructure and Mechanical Properties of a New TWIP Steel under Different Heat Treatments.

The effects of solution treatment and annealing temperature on the microstructure and mechanical properties of a new TWIP steel that was alloyed from aluminum (Al), silicon (Si), vanadium (V), and molybdenum (Mo) elements were investigated by a variety of techniques such as microstructural characterization and room tensile testing. The austenite grain size grew slowly with the increase in annealing temperature. The relatively weak effect of the solution treatment and annealing temperature on the austenite grain size was attributed to the precipitation of MC and M2C, which hindered the growth of the austenite grain. The plasticity of the TWIP steel in cold rolling and annealing after solution treatment was obviously higher than that in cold rolling and annealing without solution treatment. This was because the large-size precipitates redissolved in the matrix after solution treatment, which were not retained in the subsequently annealed structure. Through cold rolling and annealing at 800 °C after solution treatment, the prepared steel exhibited excellent strength and plasticity simultaneously, with a yield strength of 877 MPa, a tensile strength of 1457 MPa, and an elongation of 46.1%. The strength improvement of the designed TWIP steel was mainly attributed to the grain refinement and precipitation strengthening.

Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. METHODS: A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. MAIN RESULTS: This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81-2.24, p = 0.25, I2 = 0%). CONCLUSION: Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.

The transcription factor HMGB2 indirectly regulates APRIL expression and Gd-IgA1 production in patients with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Proliferation-inducing ligand (APRIL) was identified as an important cause of glycosylation deficiency of IgA1 (Gd-IgA1), which can 'trigger' IgAN. Our previous study indicated that high migration group protein B2 (HMGB2) in peripheral blood mononuclear cells from patients with IgAN was associated with disease severity, but the underlying mechanism remains unclear. MATERIALS AND METHODS: The location of HMGB2 was identified by immunofluorescence. qRT-PCR and Western blotting were used to measure HMGB2, HMGA1, and APRIL expression. Gd-IgA1 levels were detected by enzyme-linked immunosorbent assay (ELISA). In addition, we used DNA pull-down, protein profiling, and transcription factor prediction software to identify proteins bound to the promoter region of the APRIL gene. RNA interference and coimmunoprecipitation (Co-IP) were used to verify the relationships among HMGB2, high mobility group AT-hook protein 1 (HMGA1), and APRIL. RESULTS: HMGB2 expression was greater in IgAN patients than in HCs and was positively associated with APRIL expression in B cells. DNA pull-down and protein profiling revealed that HMGB2 and HMGA1 bound to the promoter region of the APRIL gene. The expression levels of HMGA1, APRIL, and Gd-IgA1 were downregulated after HMGB2 knockdown. Co-IP indicated that HMGB2 binds to HMGA1. The Gd-IgA1 concentration in the supernatant was reduced after HMGA1 knockdown. HMGA1 binding sites were predicted in the promoter region of the APRIL gene. CONCLUSION: HMGB2 expression is greater in IgAN patients than in healthy controls; it promotes APRIL expression by interacting with HMGA1, thereby inducing Gd-IgA1 overexpression and leading to IgAN.

[Characterization of Microplastic Surface Bacterial Community Structure and Prediction of Ecological Risk in Poyang Lake, China].

In recent years, the environmental pollution of microplastics in Poyang Lake has received increasing attention. Baisha Lake of Poyang Lake was selected as the study area, and samples of water and sediments of Baisha Lake and the microplastics therein were collected, and the polymer types of microplastics were identified as polyethylene (PE), polyester (PET), polypropylene (PP), and polystyrene (PS) using Fourier infrared spectroscopy. We also analyzed the structural composition of bacterial communities in water, in sediments, and on microplastic surfaces using 16S high-throughput sequencing. The species richness and diversity of bacteria on the microplastic surfaces were lower than those in the surrounding water and sediments. The results of NMDS analysis showed that the bacterial community structures on the microplastic surfaces differed greatly from those in the surrounding sediments and water. The bacterial community composition in water and sediment differed from that on the microplastic surfaces, and the dominant bacterial phyla on the microplastic surfaces were Proteobacteria and Bacteroidota, and their relative abundance on the microplastic surfaces was higher than that in sediment. The relative abundance of Proteobacteria was higher than that in water. The relative abundances of Bacteroidota and Actinobacteriota were significantly lower than that of water. Massilia and Pseudomonas were the dominant genera on the microplastic surfaces, and their relative abundances were significantly higher than those in the surrounding water and sediments. BugBase phenotype prediction revealed that the relative abundance of contains mobile elements, biofilm formation, potential pathogenicity, and stress tolerance phenotypes of microplastic bacterial communities were significantly higher than those of the surrounding water and sediments. The results revealed that microplastics may have contributed to the spread of harmful bacteria, including pathogenic bacteria, and increased the potential pathogenicity of bacterial communities. Additionally, microplastic surface bacterial communities had higher phenotypes of mobile gene element content. Revealing the potential harm of microplastic pollution to wetland ecology at the micro level may provide a scientific reference for maintaining the ecological stability of wetlands.

Double-blinded, randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia.

Background: Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus (T2DM), can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian decoction (GQD). This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD. Methods: We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM. During the 12-week intervention, anthropometric measurements and diabetic traits were recorded every 4 weeks. Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing, liquid chromatography-mass spectrometry, and Bio-Plex panels. Results: Anti-diabetic effects were observed in the GQD group in the human trial. Specifically, glycated hemoglobin, fasting plasma glucose, and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group. Additionally, Faecalibacterium was significantly enriched in the GQD group, and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group. Moreover, Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin, fasting plasma glucose, and pro-inflammatory cytokines. Finally, the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzii (DSMZ 17677) in T2DM mouse model. Conclusions: GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state. Trial registration: Registry No. ChiCTR-IOR-15006626.

Quantification of NOx sources contribution to ambient nitrate aerosol, uncertainty analysis and sensitivity analysis in a megacity.

Dual isotopes of nitrogen and oxygen of NO3- are crucial tools for quantifying the formation pathways and precursor NOx sources contributing to atmospheric nitrate. However, further research is needed to reduce the uncertainty associated with NOx proportional contributions. The acquisition of nitrogen isotopic composition from NOx emission sources lacks regulation, and its impact on the accuracy of contribution results remains unexplored. This study identifies key influencing factors of source isotopic composition through statistical methods, based on a detailed summary of δ15N-NOx values from various sources. NOx emission sources are classified considering these factors, and representative means, standard deviations, and 95 % confidence intervals are determined using the bootstrap method. During the sampling period in Tianjin in 2022, the proportional nitrate formation pathways varied between sites. For suburban and coastal sites, the ranking was [Formula: see text] (NO2 + OH radical) > [Formula: see text] (N2O5 + H2O) > [Formula: see text] (NO3 + DMS/HC), while the rural site exhibited similar fractional contributions from all three formation pathways. Fossil fuel NOx sources consistently contributed more than non-fossil NOx sources in each season among three sites. The uncertainties in proportional contributions varied among different sources, with coal combustion and biogenic soil emission showing lower uncertainties, suggesting more stable proportional contributions than other sources. The sensitivity analysis clearly identifies that the isotopic composition of 15N-enriched and 15N-reduced sources significantly influences source contribution results, emphasizing the importance of accurately characterizing the localized and time-efficient nitrogen isotopic composition of NOx emission sources. In conclusion, this research sheds light on the importance of addressing uncertainties in NOx proportional contributions and emphasizes the need for further exploration of nitrogen isotopic composition from NOx emission sources for accurate atmospheric nitrate studies.

Flow field-flow fractionation coupled with multidetector: A robust approach for the separation and characterization of resistant starch.

The unique properties of resistant starch (RS) have made it applicable in the formulation of a broad range of functional foods. The physicochemical properties of RS play a crucial role in its applications. Recently, flow field-flow fractionation (FlFFF) has attracted increasing interest in the separation and characterization of different categories of RS. In this review, an overview of the theory behind FlFFF is introduced, and the controllable factors, including FlFFF channel design, sample separation conditions, and the choice of detector, are discussed in detail. Furthermore, the applications of FlFFF for the separation and characterization of RS at both the granule and molecule levels are critically reviewed. The aim of this review is to equip readers with a fundamental understanding of the theoretical principle of FlFFF and to highlight the potential for expanding the application of RS through the valuable insights gained from FlFFF coupled with multidetector analysis.

Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC.

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.

Does Inter-Residue Hydrogen Bonding in ß-(1→4)-Linked Disaccharides Influence Linkage Conformation in Aqueous Solution?

Two disaccharides, methyl ß-d-galactopyranosyl-(1→4)-α-d-glucopyranoside (1) and methyl ß-d-galactopyranosyl-(1→4)-3-deoxy-α-d-ribo-hexopyranoside (3), were prepared with selective 13C-enrichment to allow measurement of six trans-O-glycosidic J-couplings (2JCOC, 3JCOCH, and 3JCOCC) in each compound. Density functional theory (DFT) was used to parameterize Karplus-like equations that relate these J-couplings to either ϕ or ψ. MA'AT analysis was applied to both linkages to determine mean values of ϕ and ψ in each disaccharide and their associated circular standard deviations (CSDs). Results show that deoxygenation at C3 of 1 has little effect on both the mean values and librational motions of the linkage torsion angles. This finding implies that, if inter-residue hydrogen bonding between O3H and O5' of 1 is present in aqueous solution and persistent, it plays little if any role in dictating preferred linkage conformation. Hydrogen bonding may lower the energy of the preferred linkage geometry but does not determine it to any appreciable extent. Aqueous 1-µs MD simulation supports this conclusion and also indicates greater conformational flexibility in deoxydisaccharide 3 in terms of sampling several, conformationally distinct, higher-energy conformers in solution. The populations of these latter conformers are low (3-14%) and could not be validated by MA'AT analysis. If the MD model is correct, however, C3 deoxygenation does enable conformational sampling over a wider range of ϕ/ψ values, but linkage conformation in the predominant conformer is essentially identical in both 1 and 3.

NR5A1 and NR5A2 regulate follicle development in chicken (Gallus gallus) by altering proliferation, apoptosis, and steroid hormone synthesis of granulosa cells.

Chicken ovarian follicle development is regulated by complex and dynamic gene expression. Nuclear receptor 5A1 and 5A2 (NR5A1 and NR5A2, respectively) are key genes that regulate steroid hormone production and gonadal development in mammals; however, studies on follicular development in the chicken ovary are scarce. In this study, we investigated the functions of NR5A1 and NR5A2 on follicle development in chickens. The results showed that the expression of NR5A1 and NR5A2 was significantly higher in small yellow follicles and F5. Furthermore, the expression of NR5A1 and NR5A2 was significantly higher in follicular tissues of peak-laying hens (30 wk) than in follicular tissues of late-laying hens (60 wk), with high expression abundance in granulosa cells (GC). The overexpression of NR5A1 and NR5A2 significantly promoted proliferation and inhibited apoptosis of cultured GC; upregulated STAR, CYP11A1, and CYP19A1 expression and estradiol (E2) and progesterone (P4) synthesis in GC from preovulatory follicles (po-GC); and increased STAR, CYP11A1, and CYP19A1 promoter activities. In addition, follicle-stimulating hormone treatment significantly upregulated NR5A1 and NR5A2 expression in po-GC and significantly promoted FSHR, CYP11A1, and HSD3B1 expression in GC from pre-hierarchical follicles and po-GC. The core promoter region of NR5A1 was identified at the -1,095- to -483-bp and -2,054- to -1,536-bp regions from the translation start site (+1), and the core promoter region of NR5A2 was at -998 to -489 bp. Two single nucleotide polymorphisms (SNP) were identified in the core promoter region of the NR5A1 gene, which differed between high- and low-yielding chicken groups. Our study suggested that NR5A1 and NR5A2 promoted chicken follicle development by promoting GC proliferation and E2 and P4 hormone synthesis and inhibiting apoptosis. Moreover, we identified the promoter core region or functional site that regulates NR5A1 and NR5A2 expression.

Clustering by chemicals: A novel examination of chemical pollutants and social vulnerability in children and adolescents.

BACKGROUND: Inhaled air pollutants are environmental determinants of health with negative impacts on human health. Air pollution has been linked to the incidence and progression of disease, with its effects unequally distributed across the population. Children compared to adults are a highly vulnerable group and suffer disproportionately from systemic environmental inequities exacerbated by social determinants. OBJECTIVE: To explore air pollution cluster patterns among 6- to 19-year-olds from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) and examine chemical cluster associations with social vulnerability. METHODS: NHANES data was extracted for 697 children and adolescents. Social vulnerability characteristics from questionnaires were assembled to construct a modified social vulnerability index (SVI). Thirty-four air pollutant exposure chemicals were measured in urine and available from the laboratory sub-sample A data. K-means clustering classified the sample into three groups: low, medium, and high chemical exposure groups. Logistic regression was used to examine associations between high chemical group membership and SVI after adjusting for age, biological sex, and BMI. Complex survey analysis was conducted using SAS v9.4 to reflect population effects. RESULTS: Air pollution clusters revealed significant differences in mean concentrations between groups for 31 analytes with minimal distinction in mixture profiles. SVI scores differed significantly between the three groups (P = .002), and with each point increase in their SVI, the odds of a child being assigned to the highest-chemical exposure group increased by 11.55% (95% CI: 1.02-1.31), after adjustment. CONCLUSION: Unsupervised clustering of environmental sub-sample specimens from NHANES provides an innovative, multi-pollutant model that can be used to explore exposure patterns in this population. Utilizing the modified SVI allows for the identification of children that may be highly susceptible to air pollution. It is imperative to interpret the research findings in light of historical structural and discriminatory inequalities to develop beneficial and sustainable solutions.