Does environmental regulation truly enhance corporate green environmental investment? Evidence from the supervision of independent directors in listed companies.

With the increasingly prominent environmental issues in China, the government and citizens alike have intensified their focus on corporate investments in green environmental protection. Nevertheless, as government regulations become more stringent, there is substantial debate over whether environmental regulatory policies can consistently encourage listed companies to increase green environmental investments. Simultaneously, independent board supervision plays a crucial role in promoting the compliance and sustainability of listed companies regarding environmental protection. This paper selected a sample of 246 Chinese listed companies from 2010 to 2019, and used a fixed effects model to examine the impact of environmental regulation on the environmental investment of listed companies in China. Moreover, we used a mediation effect model to analyze the role of independent director supervision in influencing the relationship between environmental regulation and companies' green environmental investment. Additionally, we discuss the heterogeneous impact of environmental regulations on corporate environmental investments. Our findings are as follows: first, during the sample period, the tightening of environmental regulations significantly reduces the growth of environmental investment among the studied firms. As government environmental regulatory policies gradually intensify, the negative impact on environmental investments by listed companies becomes increasingly evident. Second, independent directors help alleviate the adverse impacts of environmental regulations on the environmental investment levels of listed companies. This suggests that the inclusion of independent directors in board governance plays a role in assessing government environmental regulatory policies and overseeing corporate decisions related to environmental investment. Lastly, the heterogeneity analysis indicates that environmental regulation significantly negatively impacts the environmental investment of listed companies in pollution-intensive industries and those located in the western regions. Furthermore, environmental regulatory policies impose greater constraints on the environmental investments of small-sized listed companies compared to their large-sized counterparts.

Syndecan-3 inhibits LPS-induced Inflammation of Bovine Mammary Epithelial Cells through the NF-κB Signal Transduction Pathway.

In mastitis, excessive inflammation caused by lipopolysaccharide (LPS) is an important factor leading to mammary tissue damage. Therefore, exploring the regulatory factors that can inhibit the widespread inflammation caused by LPS is crucial. Syndecan-3 (SDC3) has been found to play an active role in anti-inflammatory infection by inhibiting leukocyte adhesion, reducing the accumulation of inflammatory products, such as reactive oxygen species, and competing with chemokines; however, the role and regulatory mechanism of SDC3 in mastitis remains unknown. Therefore, this study aimed to reveal the effect of SDC3 on LPS-induced inflammation in bovine mammary epithelial cells (BMECs) and explore its possible molecular mechanisms. First, we constructed a BMEC inflammatory model. It was found that cells stimulated with 10 µg/mL LPS for 24 h strongly induced the expression of inflammatory cytokines and had no toxic effect on cells, which was the best condition to simulate the BMECs inflammatory response in vitro. Subsequently, we used overexpression and RNAi interference, Real Time Quantitative PCR (RT-qPCR), and Western blot assays to explore the effects of SDC3 on LPS-induced inflammatory factors and their mechanisms. The results showed that overexpression of SDC3 could inhibit the transcriptional levels of inflammatory cytokines IL-6, IL-1ß, and TNFα induced by LPS and inhibit the activation of the NF-κB inflammatory pathway by inhibiting the expression of NF-κB p50 and p-IκBα and promoting the expression of IκBα. Our results suggest that SDC3 inhibits the LPS-induced inflammatory response of BMECs through the NF-κB pathway, in which NF-κB p50 may be an important target of SDC3. These findings lay the foundation for elucidating the molecular regulatory mechanisms of dairy cow mastitis.

A Lysosome-Targeting hNEU1 Inhibitor Treats Myocardial Infarction: A Potential Therapeutic Breakthrough.

The overexpression of NEU1 has recently been certified as being associated with myocardial infarction. However, the pursuit of an efficacious human NEU1 (hNEU1) inhibitor remains challenging, and viral NEU1 (viNEU1) inhibitor drugs are significantly weaker in terms of hNEU1 inhibition. Recognizing that hNEU1 is located within the lysosome, we designed a series of lysosome-targeting compounds, derived from oseltamivir, aimed at hNEU1 inhibition. Among these compounds, OsMo exhibits the most potent activity. Our findings reveal that OsMo accumulates within lysosomes and releases its pharmacophore via enzymatic catalysis. OsMo enhances hNEU1 inhibition by accumulating pharmacophores at the target site. OsMo exhibits improved regulation of abnormal autophagy during myocardial injury, demonstrating superior efficacy in treating myocardial infarction in vivo. Furthermore, OsMo exhibits acceptable pharmacokinetic parameters. Importantly, the development of molecules with lysosome-targeting abilities represents a promising avenue for addressing myocardial injuries linked to hNEU1 overexpression.

Discovery and Analysis of the Relationship between Organic Components in Exhaled Breath and Bronchiectasis.

BACKGROUND: The prevalence of patients with bronchiectasis (BE) has been rising in recent years, which increases the substantial burden on the family and society. Exploring a convenient, effective, and low-cost screening tool for the diagnosis of BE is urgent. We expect to identify the accuracy of breath biomarkers(BBs) for the diagnosis of BE through breathomics testing and explore the association between BBs and clinical features of BE. Method: Exhaled breath samples were collected and detected by high-pressure photon ionization time-of-flight mass spectrometry(HPPI-TOF MS) in a cross-sectional study. Exhaled breath samples were from 215 patients with BE and 295 control individuals. The potential BBs were selected via the machine learning method. The overall performance was assessed for the BBs-based BE detection model. The significant BBs between different subgroups such as the severity of BE, acute or stable stage, combined with hemoptysis or not, with or without Nontuberculous Mycobacterium (NTM), Pseudomonas aeruginosa (P.a) isolation or not, and the BBs related to the number of involved lung lobes and lung function were discovered and analyzed. Results: The top 10 BBs based machine learning model achieved an area under the curve (AUC) of 0.940, sensitivity of 90.7%, specificity of 85%, and accuracy of 87.4% in BE diagnosis. Except for the top ten BBs, other BBs were found also related to the severity, acute/stable status, hemoptysis or not, NTM infection, P.a isolation, the number of involved lobes, and three lung functional paramters in BE patients. Conclusions: BBs-based BE detection model showed good accuracy for diagnosis. BBs have a close relationship with the clinical features of BE. The breath test method may provide a new strategy for bronchiectasis screening and personalized management. Clinical Trail Number: NCT05293314 .

Highly efficient CuNi-ZrO2 nanocomposites for selective hydrogenation of levulinic acid to γ-valerolactone.

CuNi-ZrO2 nanocomposites were prepared by a simple coprecipitation technique of copper, nickel and zirconium ions with potassium carbonate. The structures of the nanocomposites were characterized by N2 physical adsorption, XRD, H2-TPR and STEM-EDS. The Cu0.05Ni0.45-ZrO2 nanocomposite showed outstanding catalytic performance in hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL), especially NaOH solution (0.5 mol L-1) as a solvent. 100% LA conversion and > 99.9% GVL selectivity are achieved over Cu0.05Ni0.45-ZrO2 catalyst at 200 °C, 3 MPa for 1.5 h. Characterization results suggest that the excellent reactivity of the Cu0.05Ni0.45-ZrO2 may be due to a better reducibility of nickel oxide in the CuONiO-ZrO2, dispersion of Ni in the Cu0.05Ni0.45-ZrO2 compared to nickel oxide in the NiO-ZrO2 and Ni in the Ni0.5-ZrO2 and promotion of OH-. The results demonstrate that the Cu0.05Ni0.45-ZrO2 nanocomposite has potential to realize high efficiency and low-cost synthesis of liquid fuels from biomass.

LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/ß-catenin signaling pathway.

OBJECTIVE: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. METHODS: RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent in situ hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/ß-catenin signaling pathway. RESULTS: Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (p < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (p < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of ß-catenin (p < 0.05), p-GSK-3ß (p < 0.05), Cyclin D1 (p < 0.05), PCNA (p < 0.05), and thus reduced the cell proliferation. CONCLUSION: NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/ß-catenin signaling.

Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts.

The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth's magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth's rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.

Development and validation of a predictive model assessing the risk of sarcopenia in rheumatoid arthritis patients.

Background: Sarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients. Methods: Patients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA). Results: A total of 480 patients with RA were included in the study (90% female, with the largest number in the 45-59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795-0.9498) and 0.907 (95% CI: 0.8552-0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility. Conclusion: This study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients.

Visualization of Solvent Effect and Oxygen Content via a Red Room-Temperature Phosphorescent Material.

The development of pure organic room-temperature phosphorescent (RTP) materials greatly facilitates the integrated application of luminescent materials. Herein, a type of photoactivated red RTP material was constructed by simply doping 4-(benzo[c][1,2,5]thiadiazol-5-ylthio)benzonitrile (p-NNS) into a poly(methyl methacrylate) (PMMA) matrix. The obtained film realized a controllable photoactivation process by regulation of diverse solvent levels, demonstrating potential advantages in optical anti-counterfeiting applications. Furthermore, luminescent properties of the doped film were utilized to detect oxygen content from 2.00% to 4.90%, which revealed the exact consumption of ambient oxygen under UV light. Every CIE point of the luminescence corresponds to a certain oxygen content, illustrating the visualization of oxygen content. The remarkable regulation of solvent effect and oxygen content in this work will provide competitive material for further optical applications.

Setup errors analysis in iterative kV CBCT: A clinical study of cervical cancer treated with Volumetric Modulated Arc Therapy.

OBJECTIVE: This study aims to analyze setup errors in pelvic Volumetric Modulated Arc Therapy (VMAT) for patients with non-surgical primary cervical cancer, utilizing the onboard iterative kV cone beam CT (iCBCT) imaging system on the Varian Halcyon 2.0 ring gantry structure accelerator to enhance radiotherapy precision. METHOD: We selected 132 cervical cancer patients who underwent VMAT with daily iCBCT imaging guidance. Before each treatment session, a registration method based on the bony structure was employed to acquire iCBCT images with the corresponding planning CT images. Following verification and adjustment of image registration results along the three axes (but not rotational), setup errors in the lateral (X-axis), longitudinal (Y-axis), and vertical (Z-axis) directions were recorded for each patient. Subsequently, we analyzed 3642 iCBCT image setup errors. RESULTS: The mean setup errors for the X, Y, and Z axes were 4.50 ± 3.79 mm, 6.08 ± 6.30 mm, and 1.48 ± 2.23 mm, respectively. Before correction with iCBCT, setup margins based on the Van Herk formula for the X, Y, and Z axes were 6.28, 12.52, and 3.26 mm, respectively. In individuals aged 60 years and older, setup errors in the X and Y axes were significantly larger than those in the younger group (p < 0.05). Additionally, there is no significant linear correlation between setup errors and treatment fraction numbers. CONCLUSION: Data analysis underscores the importance of precise Y-axis setup for cervical cancer patients undergoing VMAT. Radiotherapy centers without daily iCBCT should appropriately extend the planning target volume (PTV) along the Y-axis for cervical cancer patients receiving pelvic VMAT. Elderly patients exhibit significantly larger setup errors compared to younger counterparts. In conclusion, iCBCT-guided radiotherapy is recommended for cervical cancer patients undergoing VMAT to improve setup precision.

Interfacial Cooperative Assembly of Surfactants and Opposite Wettability Nanoparticles Stabilizes Water-in-Oil Emulsions at High Temperature.

Pickering emulsions have promising applications in the development of unconventional oil and gas resources. However, the high-temperature environment of the reservoir is not conducive to the stabilization of Pickering emulsions. In addition, the preparation of Pickering emulsions under low-energy emulsification and low-concentration emulsifier conditions is a difficult challenge. Here, we report a high-temperature resistant water-in-paraffin oil Pickering emulsion, which is synergistically stabilized by polyglycerol ester (PGE) and nanoparticles with opposite wettability (lipophilic silica and hydrophilic alumina). This emulsion can be prepared under mild stirring (500 rpm) conditions and can be stable at 140 °C for at least 30 days. The synergistic effects of surfactant, silicon nanoparticles (MSNPs) with different wettability, and alumina nanoparticles (AONPs) on the stability of both emulsions and water-oil interfacial membranes were investigated through bottle experiments, cryogenic scanning electron microscopy (cryo-SEM), optical microscopy, fluorescence microscopy, etc. The results showed that both hydrophobic MSNPs and hydrophilic AONPs are adsorbed together at the water-oil interface to stabilize the W/O emulsion, which can be prepared by 500 rpm stirring. The stability of emulsions strongly depends on the wettability of MSNPs, and the MSNP with moderate hydrophobicity (for example, aqueous phase contact angle of 136°) makes the emulsion exhibit the highest stability against aggregation and settling at elevated temperatures. The emulsion stabilization mechanism was revealed in terms of the adsorption capacity of the surfactant by MSNPs, the adsorption morphology and desorption energy of nanoparticles at the water-oil interface adsorption layer, and emulsion rheology. These findings demonstrate a novel and simple strategy to prepare Pickering W/O emulsions with high-temperature stability at low shear strength.

Causal associations of fatigue and functional outcome after ischemic stroke: a mediation Mendelian randomization study.

Background and objectives: Fatigue has been associated with adverse effects on recovery from ischemic stroke based on previous observational research. The purpose of our study was to explore the potential causal association of fatigue with poor functional outcome after ischemic stroke by employing Mendelian randomization (MR). Methods: A set of instrumental variables, comprising 36 single-nucleotide polymorphisms (SNPs) that are only related to fatigue, were derived from a genome-wide association study (GWAS) that included 449,019 general individuals. The functional outcomes after ischemic stroke were derived from a GWAS (Genetics of Ischemic Stroke Functional Outcome Network) involving 6,021 survivors. Two-sample MR methods were used to assess the causal effect, including inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. In bidirectional MR analysis, the reverse causal association was analyzed using the Wald ratio method. The mediation effects of lipid metabolites were analyzed using two-step MR analysis. Results: Genetic liability to fatigue was causally associated with the poor functional outcome (modified Rankin Scale ≥3 at 3 months) after ischemic stroke (OR = 4.20, 95%CI [1.11-15.99], p < 0.05). However, genetic predicted poor functional outcome after ischemic stroke was not associated with fatigue (OR = 1.00, 95%CI [0.99-1.02], p > 0.05). The results of the two-step MR showed that cholesteryl esters to total lipids ratio in large very low-density lipoprotein (VLDL) (ME = -0.13, p < 0.05); concentration of very large VLDL particles (ME = -0.13, p < 0.05); free cholesterol in large VLDL (ME = -0.13, p < 0.05); free cholesterol to total lipids ratio in very large VLDL (ME = -0.22, p < 0.05); phospholipids in large VLDL (ME = -0.15, p < 0.05); phospholipids in very large VLDL (ME = -0.13, p < 0.05); phospholipids to total lipids ratio in large high-density lipoprotein (HDL) (ME = -0.17, p < 0.05); total lipids in very large VLDL (ME = -0.14, p < 0.05); triglycerides in small VLDL (ME = -0.11, p < 0.05); and triglycerides to total lipids ratio in large HDL (ME = -0.10, p < 0.05) assumed a pivotal role in mediating the association between fatigue and poor functional outcome after ischemic stroke. Conclusion: Our study provides evidence supporting the causal association between fatigue and the poor functional outcome after ischemic stroke, which emphasizes the importance of implementing interventions aimed at addressing fatigue. This could offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context. One potential mechanism by which fatigue affects functional outcomes after ischemic stroke is through the action of lipid metabolites.

Therapeutic inhibition of the JAK-STAT pathway in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses a group of non-specific chronic intestinal inflammatory conditions of unclear etiology. The current treatment and long-term management primarily involve biologics. Nevertheless, some patients experience treatment failure or intolerance to biologics [1], making these patients a primary focus of IBD research. The Janus kinase (JAK)-Signal Transducers and Activator of Transcription (STAT) signal transduction pathway is crucial to the regulation of immune and inflammatory responses [2], and plays an important role in the pathogenesis of IBD. JAK inhibitors alleviate IBD by suppressing the transmission of JAK-STAT signaling pathway. As the first small-molecule oral inhibitor for IBD, JAK inhibitors greatly improved the treatment of IBD and have demonstrated significant efficacy, with tofacitinib and upadacitinib being approved for the treatment of ulcerative colitis (UC) [3]. JAK inhibitors can effectively alleviate intestinal inflammation in IBD patients who have failed to receive biologics, which may bring new treatment opportunities for refractory IBD patients. This review aims to elucidate the crucial roles of JAK-STAT signal transduction pathway in IBD pathogenesis, examine its role in various cell types within IBD, and explore the research progress of JAK inhibitors as therapeutic agents, paving the road for new IBD treatment strategies.

Neutrophil extracellular traps: Potential targets for the treatment of rheumatoid arthritis with traditional Chinese medicine and natural products.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Abnormal formation of neutrophil extracellular traps (NETs) at the synovial membrane leads to the release of many inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Elastase, histone H3, and myeloperoxidase, which are carried by NETs, damage the soft tissues of the joints and aggravate the progression of RA. The balance of NET formation coordinates the pro-inflammatory and anti-inflammatory effects and plays a key role in the development of RA. Therefore, when NETs are used as effector targets, highly targeted drugs with fewer side effects can be developed to treat RA without damaging the host immune system. Currently, an increasing number of studies have shown that traditional Chinese medicines and natural products can regulate the formation of NETs through multiple pathways to counteract RA, which shows great potential for the treatment of RA and has a promising future for clinical application. In this article, we review the latest biological progress in understanding NET formation, the mechanism of NETs in RA, and the potential targets or pathways related to the modulation of NET formation by Chinese medicines and natural products. This review provides a relevant basis for the use of Chinese medicines and natural products as natural adjuvants in the treatment of RA.

Research review on land development rights and its implications for China's national territory spatial planning.

Based on the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases, this article analyzes the deductive context, cooperation network, and research hotspots of land development rights (LDR) research in the Chinese and international literature by using CiteSpace software, and it also explores the implications of this research for the theory and practice of national territory spatial planning (NTSP) in China. The results show that (1) the literature on LDR in Chinese and international journal articles initially appeared in 1995 and 1973, respectively, researches in China experienced three stages: embryonic fluctuating development, rapid growth and stable development, and wave development, while international researches experienced two stages: embryonic fluctuating and a gradually increasing development. (2) Among these scholars and research institutions, there is no obvious difference between Chinese and international scholars, while the Renmin University of China and the State University System of Florida are the research institutions with the largest number of Chinese and international journal articles, respectively. (3) In terms of publishing journals, international journals mainly focus on land policy, cities, and resource fields, while Chinese journals mainly focus on the agricultural economy, civil and commercial law, economic systems, and macroeconomic management fields. (4) The direction and scale of thematic research vary greatly, with Chinese research mainly conducted from the perspectives of rights attribution and benefits distribution, while international research mainly focuses on the operation of the right-to-development system and its impact on the environment. In the future, studies focus on China's need to strengthen the research and institutional practice of LDR at the legal level, value level, and extension level following national conditions, formulate a land value-added benefit distribution system with efficiency and fairness, and strengthen the practice of LDR in China's NTSP based on the differences between urban and rural development.

Identification and characterization of new B cell epitopes on the nucleocapsid protein of porcine epidemic diarrhea virus using monoclonal antibodies.

Porcine epidemic diarrhea virus (PEDV) is the pathogen of Porcine epidemic diarrhea (PED) and can mainly cause acute diarrhea, vomiting, dehydration and high mortality in neonatal piglets. The nucleocapsid (N) protein of PEDV is a highly conserved structural protein. In this study, 6-8-week-old BALB/c mice were immunized with purified PEDV, and three monoclonal antibodies (mAbs) against the PEDV N protein were generated, named 3C6,4F8,4C9. Among them, three new B cell epitopes, 235IGENPDKL242, 12KRVPLSLY19, 372DAFKTGNA380 were firstly identified in the viral N-protein. Among them, 4F8 and 4C9 had IgG1 isotype with Kappa light chain, while 3C6 had IgG2a isotype with Kappa light chain. Three monoclonal antibodies (mAbs) demonstrated specific reactivity with PEDV as evidenced by Western blot and indirect immunofluorescence assay. By studying the interaction between the mAbs and the N protein, we can gain insights into the protein's conformation and functional regions. This information will help develop fast and accurate PEDV diagnostic methods.

POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo. Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p, and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p, miR-29a-3p, PIK3R1, and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1, PIK3R1, and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS: The POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.

Identification of factors affecting fattening efficiency of commercial pig herds and analysis of their impact at different performance levels.

Improving fattening efficiency is an important goal of breeding commercial pigs, especially for the large-scale pig farms. Fattening efficiency index (FEI) can be used to evaluate the fattening efficiency. The aim of this study was to identify the factors affecting the fattening efficiency of commercial pigs in large-scale pig farms and further study the impact of these factors on the production performance of commercial pig batches at different production levels. The data of 9,570 batches was mainly consisted of four parts (farm facilities, general information of piglets, production performance of nursery pigs and finishing pigs). A total of 28 variables were evaluated by the multi-variable linear regression models. The differences in production factors significantly correlated with FEI at piglets-finishing stage were compared among high-performing (HP), moderate-performing (MP), and low-performing (LP) batches of commercial pigs during the nursery and finishing stage. Among the 28 variables, 18 were significantly correlated with fattening efficiency (P < 0.05), including 11 continuous variables and seven discrete variables. The significant differences among the 11 consecutive variables in the HP, MP, and LP batches of commercial pigs mostly persisted from the piglets-nursery stage to the growing-finishing stage, ultimately affecting the FEI at piglets-finishing stage. For the seven significant discrete variables, the HP batches had a lower proportions in owned source of piglets, number of the purchasing piglets in spring and winter, number of batches in the East and North regions and five-way crossbred pigs, while a higher proportions in the use of closed circuit television video (CCTV) and wastes treatment system. The fattening efficiency of commercial pigs in large-scale pig farms was comprehensively affected by farm facilities, piglets, and production performance at nursery and finishing stage. The low fattening efficiency may have started at the end of nursery stage.

CFTR Inhibitors Display Antiviral Activity against Herpes Simplex Virus.

The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl- channel, is closely associated with multiple pathogen infections, such as SARS-CoV-2. However, whether the function of the CFTR is involved in herpes simplex virus (HSV) infection has not been reported. To evaluate the association of CFTR activity with HSV infection, the antiviral effect of CFTR inhibitors in epithelial cells and HSV-infected mice was tested in this study. The data showed that treatment with CFTR inhibitors in different concentrations, Glyh-101 (5-20 µM), CFTRi-172 (5-20 µM) and IOWH-032 (5-20 µM), or the gene silence of the CFTR could suppress herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) replication in human HaCaT keratinocytes cells, and that a CFTR inhibitor, Glyh-101 (10-20 µM), protected mice from HSV-1 and HSV-2 infection. Intracellular Cl- concentration ([Cl-]i) was decreased after HSV infection via the activation of adenylyl cyclase (AC)-cAMP signaling pathways. CFTR inhibitors (20 µM) increased the reduced [Cl-]i caused by HSV infection in host epithelial cells. Additionally, CFTR inhibitors reduced the activity and phosphorylation of SGK1 in infected cells and tissues (from the eye and vagina). Our study found that CFTR inhibitors can effectively suppress HSV-1 and HSV-2 infection, revealing a previously unknown role of CFTR inhibitors in HSV infection and suggesting new perspectives on the mechanisms governing HSV infection in host epithelial cells, as well as leading to potential novel treatments.

Bovine colostrum prevents formula-induced gut microbiota dysbiosis in preterm pigs.

BACKGROUND: Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM. METHODS: Colonic GM (profiled by 16S ribosomal RNA gene amplicon sequencing) was compared in preterm pigs fed colostrum for 4 days, either before, after, or together with formula feeding for 4 days. Correlations between GM and gut parameters were assessed on day 5 or 9. RESULTS: Both exclusive and partial colostrum feeding induced higher GM diversity, lower Enterococcus abundance, and improved intestinal maturation parameters (villus structure, digestive enzyme activities, permeability), relative to exclusive formula feeding (all p < 0.05). Across feeding regimens, Enterococcus abundance was inversely correlated with intestinal maturation parameters. Conversely, there was no correlation between GM changes and early NEC lesions. CONCLUSION: Bovine colostrum inhibits formula-induced Enterococcus overgrowth and gut dysfunctions just after preterm birth but these effects are not causally linked. Optimising diet-related host responses, not GM, may be critical to prevent NEC in preterm newborn pigs and infants. IMPACT: Supplement of bovine colostrum to formula feeding modified the gut microbiota by increasing species diversity and reducing Enterococcus abundance, while concurrently improving intestinal functions in preterm pigs. Diet-related changes to the gut microbiota were not clearly associated with development of necrotizing enterocolitis (NEC) in preterm pigs, suggesting that diet-related gut microbiota effects are not critical for diet-related NEC protection. The study highlights the potential to use bovine colostrum as a supplement to formula feeding for preterm infants lacking human milk.