Associations between 25 hydroxyvitamin D concentration and spontaneous abortion.

BACKGROUND: Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. MATERIALS AND METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. RESULTS: MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90-1.06; MR Egger, OR = 0.94, 95%CI = 0.84-1.05; Weighted median, OR = 0.93, 95%CI = 0.82-1.06; Weighted mode, OR = 0.93, 95%CI = 0.84-1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D's protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). CONCLUSIONS: This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.

A causal relationship between particulate matter 2.5 and obesity and its related indicators: a Mendelian randomization study of European ancestry.

Background: In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM2.5) on obesity, but their relationship remains ambiguous. Methods: Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings. Results: The UVMR analysis demonstrated a significant association between PM2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881-21.968; P FDR = 0.005). Additionally, PM2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244-2.776; P FDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092-5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106-2.841; P FDR = 0.019). Furthermore, PM2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269-3.022; P FDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34-4.649; P FDR = 0.007). Finally, a significant negative association was observed between PM2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025-0.89; P FDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21. Conclusion: Our MR study demonstrates conclusively that higher PM2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.

Occurrence, distribution, and genetic diversity of faba bean viruses in China.

With worldwide cultivation, the faba bean (Vicia faba L.) stands as one of the most vital cool-season legume crops, serving as a major component of food security. China leads global faba bean production in terms of both total planting area and yield, with major production hubs in Yunnan, Sichuan, Jiangsu, and Gansu provinces. The faba bean viruses have caused serious yield losses in these production areas, but previous researches have not comprehensively investigated this issue. In this study, we collected 287 faba bean samples over three consecutive years from eight provinces/municipalities of China. We employed small RNA sequencing, RT-PCR, DNA sequencing, and phylogenetic analysis to detect the presence of viruses and examine their incidence, distribution, and genetic diversity. We identified a total of nine distinct viruses: bean yellow mosaic virus (BYMV, Potyvirus), milk vetch dwarf virus (MDV, Nanovirus), vicia cryptic virus (VCV, Alphapartitivirus), bean common mosaic virus (BCMV, Potyvirus), beet western yellows virus (BWYV, Polerovirus), broad bean wilt virus (BBWV, Fabavirus), soybean mosaic virus (SMV, Potyvirus), pea seed-borne mosaic virus (PSbMV, Potyvirus), and cucumber mosaic virus (CMV, Cucumovirus). BYMV was the predominant virus found during our sampling, followed by MDV and VCV. This study marks the first reported detection of BCMV in Chinese faba bean fields. Except for several isolates from Gansu and Yunnan provinces, our sequence analysis revealed that the majority of BYMV isolates contain highly conserved nucleotide sequences of coat protein (CP). Amino acid sequence alignment indicates that there is a conserved NAG motif at the N-terminal region of BYMV CP, which is considered important for aphid transmission. Our findings not only highlight the presence and diversity of pathogenic viruses in Chinese faba bean production, but also provide target pathogens for future antiviral resource screening and a basis for antiviral breeding.

Maternal diseases and congenital anomalies of the kidney and urinary tract in offspring: a cohort study.

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of prenatally diagnosed developmental malformation. This study aimed to assess the relationship between maternal diseases and CAKUT in offspring. METHODS: This retrospective study enrolled all pregnant women registered from January 2020 to December 2022 at one medical center. Medical information on maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease was collected. Based on the records of ultrasound scanning during the third trimester, the diagnosis was classified as isolated urinary tract dilation (UTD) or kidney anomalies. Multivariate logistic regression was performed to establish models to predict antenatal CAKUT. RESULTS: Among the 19,656 pregnant women, perinatal ultrasound detected suspicious CAKUT in 114 (5.8/1000) fetuses, comprising 89 cases with isolated UTD and 25 cases with kidney anomalies. The risk of antenatal CAKUT was increased in the fetuses of mothers who experienced gestational diabetes, thyroid dysfunction, neuropsychiatric disease, anemia, ovarian and uterine disorders. A prediction model for isolated UTD was developed utilizing four confounding factors, namely gestational diabetes, gestational hypertension, maternal thyroid dysfunction, and hepatic disease. Similarly, a separate prediction model for kidney anomalies was established based on four distinct confounding factors, namely maternal thyroid dysfunction, gestational diabetes, disorders of ovarian/uterine, and kidney disease. CONCLUSIONS: Isolated UTD and kidney anomalies were associated with different maternal diseases. The results may inform the clinical management of pregnancy and highlight potential differences in the genesis of various subtypes of CAKUT.

Effect of RNAi mediated silencing of DIB, JHE, and CAM on the diapause termination of Calliptamus italicus (Orthoptera: Acrididae) eggs.

BACKGROUND: Calliptamus italicus L. is a major pest in Xinjiang grassland. The diapause overwintering strategy is one of the important reasons for the large population of this pest. This study investigated the function of the genes associated with the release of diapause (DIB, JHE and CAM) in Calliptamus italicus by RNA interference (RNAi) technology to aid in its biological control. RESULTS: The expression levels of DIB and its downstream-associated genes (EcR and FTZ-F1) in the eggs injected with dsDIB for 12 h decreased by 96.6%, 55.8% and 81.8%, respectively. Diapause began to terminate on day 3, and development was almost complete on day 6. However, the head was significantly smaller. The expression levels of JHE and its downstream-associated genes (JHEH and VgR) at 48 h after dsJHE treatment decreased by 76.5%, 85.6% and 85.9%, respectively. The termination of diapause occured on day 3 of incubation. The development was basically complete on day 6, but the yolk had been incompletely absorbed. The expression of CAM and its downstream-associated genes (CAMK4 and MYL) at 24 h after dsCAM treatment decreased by 42.4%, 95.3% and 82.7%, respectively. Diapause termination was completed on day 4 for incubation, and development was abnormal on day 6. The absorption of yolk was incomplete. CONCLUSION: DIB, JHE and CAM can delay the diapause termination of Calliptamus italicus eggs to different degrees and can be developed as potential target genes for its biological control. © 2024 Society of Chemical Industry.

Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball.

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

Effect of alternating nicotinamide phosphoribosyltransferase expression levels on mitophagy in Alzheimer's disease mouse models.

AD is the abbreviation for Alzheimer's Disease, which is a neurodegenerative disorder that features progressive dysfunction in cognition. Previous research has reported that mitophagy impairment and mitochondrial dysfunction have been crucial factors in the AD's pathogenesis. More recently, literature has emerged which offers findings suggesting that the nicotinamide adenine dinucleotide (short for NAD+) augmentation eliminates the defective mitochondria and restores mitophagy. Meanwhile, as an enzyme which is rate-limiting, the Nicotinamide phosphoribosyltransferase, or NAMPT, is part of the salvage pathway of NAD+ synthesis. Therefore, the aim of the research project has been to produce proof for how the NAMPT-NAD +-silent information-regulated transcription factors1/3 (short for SIRT1/3) axis function in mediating mitophagy in APP/PS1 mice aged six months. The results revealed that the NAMPT-NAD+-SIRT1/3 axis in the APP/PS1 mice's hippocampus was considerably declined. Surprisingly, P7C3 (an NAMPT activator) noticeably promoted the NAD+-SIRT1/3 axis, improved mitochondrial structure and function, enhanced mitophagy activity along with the ability of learning and memory. While FK866 (an NAMPT inhibitor) reversed the decreased NAD+-SIRT1/3 axis, and even exacerbated Aß plaque deposition level in the APP/PS1 mice's hippocampus. The findings observed in this study indicate two main points: avoiding downregulation of the NAMPT activity can prevent AD-related mitophagy impairment; on the other hand, NAMPT characterizes a potential therapeutic intervention regarding AD pathogenesis.

Hydrogen peroxide is required for light-induced stomatal opening across different plant species.

Stomatal movement is vital for plants to exchange gases and adaption to terrestrial habitats, which is regulated by environmental and phytohormonal signals. Here, we demonstrate that hydrogen peroxide (H2O2) is required for light-induced stomatal opening. H2O2 accumulates specifically in guard cells even when plants are under unstressed conditions. Reducing H2O2 content through chemical treatments or genetic manipulations results in impaired stomatal opening in response to light. This phenomenon is observed across different plant species, including lycopodium, fern, and monocotyledonous wheat. Additionally, we show that H2O2 induces the nuclear localization of KIN10 protein, the catalytic subunit of plant energy sensor SnRK1. The nuclear-localized KIN10 interacts with and phosphorylates the bZIP transcription factor bZIP30, leading to the formation of a heterodimer between bZIP30 and BRASSINAZOLE-RESISTANT1 (BZR1), the master regulator of brassinosteroid signaling. This heterodimer complex activates the expression of amylase, which enables guard cell starch degradation and promotes stomatal opening. Overall, these findings suggest that H2O2 plays a critical role in light-induced stomatal opening across different plant species.

Thrombopoietin receptor agonists regulate myeloid-derived suppressor cell-mediated immunomodulatory effects in ITP.

TPO receptor agonists (TPO-RAs) are a class of clinical second-line regimens for the treatment of primary immune thrombocytopenia (ITP). It can promote megakaryocyte maturation and increase platelet production, but its effect on immunosuppressive cells in patients with ITP has not been explored. Sixty-two ITP patients and 34 healthy controls (HCs) were included in this study. The proportion and functions of myeloid-derived immunosuppressive cells (MDSCs) in ITP patients and HCs were investigated. We found that the proportion and function of MDSCs in ITP patients treated with TPO-RAs were significantly higher than those treated with glucocorticoids (GCs), which was correlated with the clinical efficacy. The proportion and function of cytotoxic Th1 cells and CD8+T cells decreased, while the proportion and immunosuppressive function of Treg cells increased in ITP patients treated with TPO-RAs. We further proved, through MDSC depletion tests, that the inhibitory effect of MDSCs on Th1 cells and the promotion of Treg cells in the original immune micro-environment of GCs-treated ITP patients were impaired; however, these MDSCs' functions were improved in TPO-RAs-treated patients. Finally, we found that the KLF9 gene in MDSCs cells of ITP patients treated with TPO-RAs was down-regulated, which contribute to the higher mRNA expression of GADD34 gene and improved function of MDSCs. These results demonstrate a novel mechanism of TPO-RAs for the treatment of ITP through the assessment of MDSCs and their subsequent impact on T cells, which provides a new basis for TPO-RAs as first-line treatment approach to the treatment of ITP.

A DNA-Modularized STING Agonist with Macrophage-Selectivity and Programmability for Enhanced Anti-Tumor Immunotherapy.

The activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) and its adaptor, stimulator of interferon genes (STING), is known to reprogram the immunosuppressive tumor microenvironment for promoting antitumor immunity. To enhance the efficiency of cGAS-STING pathway activation, macrophage-selective uptake, and programmable cytosolic release are crucial for the delivery of STING agonists. However, existing polymer- or lipid-based delivery systems encounter difficulty in integrating multiple functions meanwhile maintaining precise control and simple procedures. Herein, inspired by cGAS being a natural DNA sensor, a modularized DNA nanodevice agonist (DNDA) is designed that enable macrophage-selective uptake and programmable activation of the cGAS-STING pathway through precise self-assembly. The resulting DNA nanodevice acts as both a nanocarrier and agonist. Upon local administration, it demonstrates the ability of macrophage-selective uptake, endosomal escape, and cytosolic release of the cGAS-recognizing DNA segment, leading to robust activation of the cGAS-STING pathway and enhanced antitumor efficacy. Moreover, DNDA elicits a synergistic therapeutic effect when combined with immune checkpoint blockade. The study broadens the application of DNA nanotechnology as an immune stimulator for cGAS-STING activation.

Simulation analysis of the evolution law of creep rupture crack extension in X-fractured rock body.

Creep is the macroscopic manifestation of the process of generation, expansion, and penetration of microscopic cracks in a rock body. In this study, the GDEM continuous-discontinuous numerical simulation software was used to model a rock body containing X-fractured for the purposes of exploring creep crack expansion and rupture in the rock body, analyzing the effects of various factors on X-fractured the rock body under the rule of change of the creep curve, and assessing the influences of the intersection angle of the fracture and other factors on the non-parallel fractured rock body on the creep rupture process. The results show that an X-fractured rock body exhibits a mixed tensile-shear damage mode, with tensile damage being the main type of damage. In the isotropic creep stage of a rock body with X-fractured , the steady-state creep rate initially increases and then decreases as the sub- fracture length increases, with the change of the fracture angle of the creep rate of the w-type; the sub-fracture length of h is 14 mm, the rock body is the first to enter into the accelerated creep stage, for the different fracture intersection angle of the rock body For the rock mass with different fracture angles, the time sequence of entering the accelerated creep stage is consistent with the creep rate; when the fracture intersection angle is 45°, and the sub-fracture length is 12 mm, the rock mass has the largest degree of fragmentation, which has a significant impact on the creep damage; after using a single variable processing, it is found that the fracture intersection angle, the sub-fracture length and other factors compared to the fracture intersection angle has a greater impact on the creep damage of the X-fractured rock body. This paper can provide theoretical basis and reference for the study of rock engineering creep damage law and mechanical properties of X-fractured rock body.

Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro.

SARS-CoV-2 papain-like protease (PLpro) could facilitate viral replication and host immune evasion by respectively hydrolyzing viral polyprotein and host ubiquitin conjugates, thereby rendering itself as an important antiviral target. Yet few noncovalent PLpro inhibitors of SARS-CoV-2 have been reported with improved directed towards pathogenic deubiquitinating activities inhibition. Herein, we report that coronavirus PLpro proteases have distinctive substrate bias and are conserved to deubiquitylate K63-linked polyubiquitination, thereby attenuating host type I interferon response. We identify a noncovalent compound specifically optimized towards halting the K63-deubiquitinase activity of SARS-CoV-2 PLpro, but not other coronavirus (CoV) counterparts or host deubiquitinase. Contrasting with GRL-0617, a SARS-CoV-1 PLpro inhibitor, SIMM-036 is 50-fold and 7-fold (half maximal inhibitory concentration (IC50)) more potent to inhibit viral replication during SARS-CoV-2 infection and restore the host interferon-ß (IFN-ß) response in human angiotensin-converting enzyme 2 (hACE2)-HeLa cells, respectively. Structure-activity relationship (SAR) analysis further reveals the importance of BL2 groove of PLpro, which could determine the selectivity of K63-deubiquitinase activity of the enzyme.

Enhancing pathogen description and antibiotic regimen selection in community-acquired pneumonia through RT-qPCR assays.

Background: Adults with community-acquired pneumonia (CAP) in China suffer high morbidity. CAP is caused by a multitude of pathogens; however, pathogen-directed clinical symptoms are often lacking. Therefore, patients lacking an accurate microbiological diagnosis are administered with empirical antimicrobials. Methods: We collected bronchoalveolar lavage fluid, as well as clinical and laboratory data from 650 adult patients with CAP admitted to three hospitals in Hubei, Sichuan, and Zhejiang provinces in China. Specimens were cultured and tested using real-time reverse transcription qPCR (RT-qPCR) assays for the presence of 42 respiratory bacteria and viruses. CAP was investigated with respect to regions, genders, and age and patterns of infections or co-infections. Employing clinical guidelines adapted for diagnosis, we assessed retrospectively the appropriate pathogen-directed therapy and compared it with the initial empirical therapies. Results: Our study identified that 21.38% (139/650) of the patients were classified as having Severe CAP (S-CAP), with a higher prevalence among males, older adults, and during the warm season. Bacterial pathogens were detected in 35.53% (231/650) of cases. K. pneumoniae, H. influenzae, and S. aureus were the most prevalent bacteria across different demographics and regions. Viral pathogens were found in 48.76% (317/650) of patients Epstein-Barr, Human rhinovirus, and Cytomegalovirus were the most common viruses. Co-infections were present in 24.31% (158/650) of cases, with viral-bacterial co-infections being the most frequent. The RT-qPCR demonstrated significantly higher detection rates for key pathogens compared to standard culture methods. It showed potential in optimizing antimicrobial prescriptions by allowing for de-escalation in 18.30% (95/518) of patients, among which reducing the number of excessive antibiotics mainly comprised decreasing the use of 2nd or 3rd generation cephalosporins (5.79%, 30/518) and ß-lactamase inhibitor combinations. Conclusion: The study highlights the significant burden of S-CAP, particularly among specific demographics and seasons. The prevalence of bacterial and viral pathogens, along with the high rate of co-infections, emphasizes the need for comprehensive diagnostic approaches. The RT-qPCR assays emerge as a superior diagnostic tool, offering enhanced pathogen detection capabilities and facilitating more precise antimicrobial therapy. This could lead to improved patient outcomes and contribute to the rational use of antimicrobials, addressing the growing concern of antibiotic resistance.

Circ_0006949 as a potential non-invasive diagnosis biomarker promotes the proliferation of NSCLC cells via miR-4673/GLUL axis.

The 5-year survival for non-small cell lung cancer (NSCLC) remains <20 %, primarily due to the early symptoms of lung cancer are inconspicuous. Prompt identification and medical intervention could serve as effective strategies for mitigating the death rate. We therefore set out to identify biomarkers to help diagnose NSCLC. CircRNA microarray and qRT-PCR reveal that sputum circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC, which can enhance the proliferation and clone formation, regulate the cell cycle, and accelerate the migration and invasion of NSCLC cells. Circ_0006949 and miR-4673 are predominantly co-localized in the cytoplasm of NSCLC cell lines and tissues; it upregulates GLUL by adsorption of miR-4673 through competing endogenous RNAs mechanism. The circ_0006949/miR-4673/GLUL axis exerts pro-cancer effects in vitro and in vivo. Circ_0006949 can boost GLUL catalytic activity, and they are highly expressed in NSCLC tissues and correlate with poor prognosis. In summary, circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC. This novel sputum circRNA is statistically more predictive than conventional serum markers for NSCLC diagnosis. Non-invasive detection of patients with early-stage NSCLC using sputum has shown good potential for routine diagnosis and possible screening.

Stage-specificity of STING activation in intrahepatic cholangiocarcinoma determines the efficacy of its agonism.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with an extremely poor prognosis, and new treatment options are needed. Recently, immunotherapy has emerged as an efficient treatment against malignant tumors, but less effective in iCCA. Activation of stimulator of interferon genes (STING) signaling could reignite immunologically inert tumors, but the expression and role of STING in iCCA remains to be determined. Here, we show STING is expressed in iCCA, and patients with high expression of STING in early-stage iCCA have a longer overall survival than those have low expression. Increased immune cell infiltration in early-stage iCCA corresponds to elevated STING expression. In mice iCCA models, treatment with the STING agonist MSA-2 show stage-specific inhibitory effects on tumors, with beneficial effects in early-stage tumors but not with advanced-stage cancer. This discrepancy was associated with greater programmed cell death ligand 1 (PD-L1) expression in advanced-stage tumors. Combination therapy targeting PD-L1 and MSA-2 strikingly reduced tumor burden in such tumors compared to either monotherapy. Cumulatively, these data demonstrate that STING agonism monotherapy improves the immune landscape of the tumor microenvironment in early-stage iCCA, while combination therapy ameliorates advanced-stage iCCA.

Dietary honokiol supplementation improves antioxidant capacity, enhances intestinal health, and modulates cecal microbial composition and function of broiler chickens.

Honokiol is a multifunctional polyphenol present in Magnolia officinalis. The effects of honokiol as a supplement in broiler chicken diets, and the underlying mechanisms, remain unclear. Therefore, the aim of the present study was to investigate the effects of honokiol on the growth performance, antioxidant capacity, and intestinal histomorphology of broiler chickens and to explore the underlying mechanisms. In total, 240 one-day-old broilers were randomly allocated to 5 dietary treatments, with 6 replicate pens and 8 birds per pen. Birds were fed a basal diet supplemented with 0 (blank control, BC), 100, 200, or 400 mg/kg honokiol (H100, H200, and H400), or 200 mg/kg bacitracin zinc (PC) for 42 d. The results showed that H200 and H400 increased body weight gain (BWG) and decreased feed conversion ratio (FCR) during the starter period (P < 0.05). H100 and H200 increased total superoxide dismutase (T-SOD) activity in the serum and decreased malondialdehyde (MDA) amount in the jejunum on d 42 (P < 0.05). Moreover, H100 increased villus height-to-crypt depth ratio in both the jejunum and ileum on d 21 (P < 0.05). PCR analysis showed that honokiol upregulated intestinal expression of glutathione peroxidase (GSH-Px) and downregulated intestinal expression of inducible nitric oxide synthase (iNOS) on d 42 (P < 0.05). The Shannon index, which represents the microbial alpha diversity, was reduced for the PC, H200, and H400 groups. Notably, honokiol treatment altered the cecal microbial community structure and promoted the enrichment of several bacteria, including Firmicutes and Lactobacillus. Higher production of short-chain fatty acids was observed in the cecal digesta of H100 birds, accompanied by an enriched glycolysis/gluconeogenesis pathway, according to the functional prediction of the cecal microbiota. This study provides evidence that honokiol improves growth performance, antioxidant capacity, and intestinal health of broiler chickens, possibly by manipulating the composition and function of the microbial community.

Venetoclax acts as an immunometabolic modulator to potentiate adoptive NK cell immunotherapy against leukemia.

Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.

Enhancing proton transport in polyvinylidenedifluoride membranes and reducing biofouling for improved hydrogen production in microbial electrolysis cells.

Hydrophilic porous membranes, exemplified by polyvinylidene fluoride (PVDF) membranes, have demonstrated significant potential for replacing ion exchange membranes in microbial electrolysis cells (MECs). Membrane fouling remains a major challenge in MECs, impeding proton transport and consequently limiting hydrogen production. This study aims to investigate a synergistic antifouling strategy for PVDF membrane through the incorporation of a coating composed of polydopamine (PDA), polyethyleneimine (PEI), and silver nanoparticles (AgNPs). The PDA-PEI-Ag@PVDF membrane not only effectively mitigates fouling through steric and electrostatic repulsion forces, but also amplifies ion transport by facilitating water diffusion and electromigration. The PDA-PEI-Ag@PVDF membrane exhibited a reduced membrane resistance of 1.01 mΩ m2 and PDA-PEI-Ag modifying PVDF membrane was found to be effective in enhancing the proton transportation of PVDF membrane. Therefore, the enhanced hydrogen production rate of 2.65 ± 0.02 m3/m3/d was achieved in PDA-PEI-Ag@PVDF-MECs.

Epidemiological Features of Hepatitis C in China From 2015 to 2021: Insights From National Surveillance Data.

The COVID-19 pandemic overwhelmed national health care systems, not least in the context of hepatitis elimination. This study investigates the effects of the pandemic response on the incidence rate, mortality rate, and case fatality rate (CFR) for hepatitis C virus (HCV) cases in China. We extracted the number of hepatitis C cases and HCV-related deaths by month and year for 2015 to 2021 in China and applied two proportional tests to analyze changes in the average yearly incidence rates, mortality rates, and CFRs for 2015 to 2020. We used the autoregressive integrated moving average model to predict these three rates for 2020 based on 2015 to 2019 HCV data. The incidence of hepatitis C decreased by 7.11% and 1.42% (P < .001) in 2020 and 2021, respectively, compared with 2015 to 2019, while it increased by 6.13% (P < .001) in 2021 relative to 2020. The monthly observed incidence in 2020 was significantly lower (-26.07%) than predicted. Meanwhile, no differences in mortality rate or CFR were observed between 2021, 2020, and 2015 to 2019. Our findings suggest that nonpharmaceutical interventions and behavioral changes to mitigate COVID-19 could have reduced hepatitis C incidence and accelerated China's implementation of a plan to eliminate HCV infection.