Regio- and enantioselective nickel-alkyl catalyzed hydroalkylation of alkynes.

The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

Highly efficient removal of aqueous phosphate via iron-manganese fabricated biochar: Performance and mechanism.

Biochar (BC) has emerged as a potential solution to phosphate removal from wastewater primarily resulting from global overuse of fertilizers. Further modification by embedment of iron (Fe)-manganese (Mn) oxides on BC can enhance phosphate removal; however, the modification method serves as a vital factor underlying distinctive removal performances and mechanisms, which have yet been systematically examined. Herein, two Fe-Mn modified BC, Fe/MnBC (comprised of Fe3O4 and MnO2) and Fe-MnBC (comprised of MnFe2O4), were comprehensively investigated for gaining insights into the unsolved perspectives. The results indicated that Fe-MnBC exhibited a markedly greater maximum phosphate adsorption capacity of 135.88 mg g-1 than that of Fe/MnBC with 17.93 mg g-1. The comparative results based on microstructure and spectroscopic analyses suggested that different Fe and Mn oxides were successfully loaded, which played a distinctive role in phosphate removal. Further characterizations unveiled that the key mechanisms for phosphate removal by Fe/MnBC are inner-sphere complexation and precipitation, while electrostatic interaction and outer-sphere complexation are the dominant mechanisms underlying the notable performance of Fe-MnBC. The delicately designed Fe-MnBC with special structure and property also enabled a superior regeneration capacity, which presented a promisingly high phosphate removal efficacy of over 81.34% after five cycles. These results enhance comprehension regarding the impact of biochar modification techniques on phosphate removal, offering positive indications for the remediation of excessive phosphate and other pollutant-containing water through feasible design and green chemicals.

Bone marrow mesenchymal stem cell-derived exosomal miR-221-3p promotes angiogenesis and wound healing in diabetes via the downregulation of forkhead box P1.

AIM: Impaired wound healing in patients with diabetes can develop into nonhealing ulcerations. Because bone marrow mesenchymal stem cells (BMSCs) exosomes can promote wound healing, this study aims to investigate the mechanism of BMSCs-isolated exosomal miR-221-3p in angiogenesis and diabetic wound healing. METHODS: To mimic diabetes in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to high glucose (HG). Exosomes were derived from BMSCs and identified by transmission electron microscopy (TEM), western blot analysis and dynamic light scattering (DLS). The ability to differentiate BMSCs was assessed via Oil red O staining, alkaline phosphatase (ALP) staining and alizarin red staining. The ability to internalise PKH26-labelled exosomes was assessed using confocal microscopy. Migration, cell viability and angiogenesis were tested by scratch, MTT and tube formation assays separately. The miRNA and protein levels were analysed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or western blotting. The relationship among miR-221-3p, FOXP1 and SPRY1 was determined using the dual-luciferase reporter, ChIP and RIP assays. RESULTS: Exosomal miR-221-3p was successfully isolated from BMSCs and delivered into HUVECs. HG was found to suppress the angiogenesis, cell viability and migration of HUVECs and exosomal miR-221-3p separated from BMSCs inhibited the above phenomenon. FOXP1 could transcriptionally upregulate SPRY1, and the silencing of FOXP1 reversed the HG-stimulated angiogenesis inhibition, cell viability and migration in HUVECs via the downregulation of SPRY1. Meanwhile, miR-221-3p directly targeted FOXP1 and the overexpression of FOXP1 reversed the positive effect of exosomal miR-221-3p on HUVEC angiogenesis. CONCLUSION: Exosomal miR-221-3p isolated from BMSCs promoted angiogenesis in diabetic wounds through the mediation of the FOXP1/SPRY1 axis. Furthermore, the findings of this study can provide new insights into probing strategies against diabetes.

PCV2 Induced Endothelial Derived IL-8 Affects MoDCs Maturation Mainly via NF-κB Signaling Pathway.

Porcine circovirus type 2 (PCV2) infection can cause immunosuppressive diseases in pigs. Vascular endothelial cells (VECs), as the target cells for PCV2, play an important role in the immune response and inflammatory regulation. Endothelial IL-8, which is produced by porcine hip artery endothelial cells (PIECs) infected with PCV2, can inhibit the maturation of monocyte-derived dendritic cells (MoDCs). Here, we established a co-culture system of MoDCs and different groups of PIECs to further investigate the PCV2-induced endothelial IL-8 signaling pathway that drives the inhibition of MoDC maturation. The differentially expressed genes related to MoDC maturation were mainly enriched in the NF-κB and JAK2-STAT3 signaling pathways. Both the NF-κB related factor RELA and JAK2-STAT3 signaling pathway related factors (IL2RA, JAK, STAT2, STAT5, IL23A, IL7, etc.) decreased significantly in the IL-8 up-regulated group, and increased significantly in the down-regulated group. The expression of NF-κB p65 in the IL-8 up-regulated group was reduced significantly, and the expression of IκBα was increased significantly. Nuclear translocation of NF-κB p65 was inhibited, while the nuclear translocation of p-STAT3 was increased in MoDCs in the PCV2-induced endothelial IL-8 group. The results of treatment with NF-κB signaling pathway inhibitors showed that the maturation of MoDCs was inhibited and the expression of IL-12 and GM-CSF at mRNA level were lower. Inhibition of the JAK2-STAT3 signaling pathway had no significant effect on maturation, and the expression of IL-12 and GM-CSF at mRNA level produced no significant change. In summary, the NF-κB signaling pathway is the main signaling pathway of MoDC maturation, and is inhibited by the PCV2-induced up-regulation of endothelial-derived IL-8.

The significance of m6A RNA methylation regulators in diagnosis and subtype classification of HBV-related hepatocellular carcinoma.

In recent years, abnormal m6A alteration in hepatocellular carcinoma (HCC) has been a focus on investigating the biological implications. In this study, our objective is to determine whether m6A modification contributes to the progression of HBV-related HCC. To achieve this, we employed a random forest model to screen top 8 characteristic m6A regulators from 19 candidate genes. Subsequently, we developed a nomogram model that utilizes these 8 characteristic m6A regulators to predict the prevalence of HBV-related HCC. According to decision curve analysis, patients may benefit from the nomogram model. The clinical impact curves exhibited a robust predictive capability of the nomogram models. Additionally, consensus molecular subtyping was employed to identify m6A modification patterns and m6A-related gene signature. The quantification of immune cell subsets was accomplished through the implementation of ssGSEA algorithms. PCA algorithms were developed to compute the m6A score for individual tumors. Two distinct m6A modification patterns, namely cluster A and cluster B, exhibited significant correlations with distinct immune infiltration patterns and biological pathways. Notably, patients belonging to cluster B demonstrated higher m6A scores compared to those in cluster A, as determined by the m6A score metric. Furthermore, the expression of IGFBP3 proteins was validated through immunofluorescence, revealing their pronounced lower expression in tumor tissues. In summary, our study underscores the importance of m6A modification in the advancement of HBV-related HCC. This research has the potential to yield novel prognostic biomarkers and therapeutic targets for the identification of HBV-related HCC.

Identifying CTH and MAP1LC3B as ferroptosis biomarkers for prognostic indication in gastric cancer decoding.

Gastric cancer (GC), known for its high incidence and poor prognosis, urgently necessitates the identification of reliable prognostic biomarkers to enhance patient outcomes. We scrutinized data from 375 GC patients alongside 32 non-cancer controls, sourced from the TCGA database. A univariate Cox Proportional Hazards Model (COX) regression was employed to evaluate expressions of ferroptosis-related genes. This was followed by the application of Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate COX regression for the development of prognostic models. The composition of immune cell subtypes was quantified utilizing CIBERSORT, with their distribution in GC versus control samples being comparatively analyzed. Furthermore, the correlation between the expressions of Cystathionine Gamma-Lyase (CTH) and Microtubule Associated Protein 1 Light Chain 3 Beta (MAP1LC3B) and the abundance of immune cell subtypes was explored. Our bioinformatics findings underwent validation through immunohistochemical analysis. Our prognostic models integrated CTH and MAP1LC3B. Survival analysis indicated that patients categorized as high-risk, as defined by the model, exhibited significantly lower survival rates compared to their low-risk counterparts. Notably, CTH expression inversely correlated with monocyte levels, while MAP1LC3B expression showed an inverse relationship with the abundance of M2 macrophages. Immunohistochemical validation corroborated lower expressions of CTH and MAP1LC3B in GC tissues relative to control samples, in concordance with our bioinformatics predictions. Our study suggests that the dysregulation of CTH, MAP1LC3B, and the accompanying monocyte-macrophage dynamics could be pivotal in the prognosis of GC. These elements present potential targets for prognostic assessment and therapeutic intervention.

Integrating artificial intelligence in osteosarcoma prognosis: the prognostic significance of SERPINE2 and CPT1B biomarkers.

The principal aim of this investigation is to identify pivotal biomarkers linked to the prognosis of osteosarcoma (OS) through the application of artificial intelligence (AI), with an ultimate goal to enhance prognostic prediction. Expression profiles from 88 OS cases and 396 normal samples were procured from accessible public databases. Prognostic models were established using univariate COX regression analysis and an array of AI methodologies including the XGB method, RF method, GLM method, SVM method, and LASSO regression analysis. Multivariate COX regression analysis was also employed. Immune cell variations in OS were examined using the CIBERSORT software, and a differential analysis was conducted. Routine blood data from 20,679 normal samples and 437 OS cases were analyzed to validate lymphocyte disparity. Histological assessments of the study's postulates were performed through immunohistochemistry and hematoxylin and eosin (HE) staining. AI facilitated the identification of differentially expressed genes, which were utilized to construct a prognostic model. This model discerned that the survival rate in the high-risk category was significantly inferior compared to the low-risk cohort (p < 0.05). SERPINE2 was found to be positively associated with memory B cells, while CPT1B correlated positively with CD8 T cells. Immunohistochemical assessments indicated that SERPINE2 was more prominently expressed in OS tissues relative to adjacent non-tumorous tissues. Conversely, CPT1B expression was elevated in the adjacent non-tumorous tissues compared to OS tissues. Lymphocyte counts from routine blood evaluations exhibited marked differences between normal and OS groups (p < 0.001). The study highlights SERPINE2 and CPT1B as crucial biomarkers for OS prognosis and suggests that dysregulation of lymphocytes plays a significant role in OS pathogenesis. Both SERPINE2 and CPT1B have potential utility as prognostic biomarkers for OS.

Cholinergic Anti-inflammatory Pathway Attenuates Acute Liver Failure Through Inhibiting MAdCAM1/α4ß7-mediated Gut-derived Proinflammatory Lymphocytes Accumulation.

BACKGROUND & AIMS: The function of cholinergic anti-inflammatory pathway (CAP) in acute liver failure (ALF) with inflammatory storm remains indefinite. The liver-gut axis has been proved to be crucial for liver homeostasis. Investigation about CAP regulation on liver-gut axis would enrich our understanding over cholinergic anti-inflammatory mechanism. METHODS: Co-injection of lipopolysaccharide and D-galactosamine was used to establish the model of ALF. PNU-282987 was used to activate the CAP. Histological staining, real-time polymerase chain reaction, Western blotting, RNA sequencing, and flow cytometry were conducted. Liver biopsy specimens and patients' serum from patients with liver failure were also analyzed. RESULTS: We confirmed that activating the CAP alleviated hepatocyte destruction, accompanied by a significant decrease in hepatocyte apoptosis, pro-inflammatory cytokines, and NLRP3 inflammasome activation. Moreover, hepatic MAdCAM1 and serum MAdCAM1 levels were induced in ALF, and MAdCAM1 levels were positively correlated with the extent of liver damage and the expression of pro-inflammatory markers. Furthermore, activating the CAP mainly downregulated ectopic expression of MAdCAM1 on endothelial cells, and inhibition of NF-κB p65 nuclear translocation was partly attributed to the decreased MAdCAM1. Notably, in ALF, the aberrant hepatic expression of MAdCAM1 subsequently recruited gut-derived α4ß7+ CD4+T cells to the liver, which exhibited an augmented IFN-γ-secreting and IL-17-producing phenotype. Finally, we revealed that the levels of serum and hepatic MAdCAM1 were elevated in patients with liver failure and closely correlated with clinical course. Increasing hepatic infiltration of ß7+ cells were also confirmed in patients. CONCLUSIONS: Activating the CAP attenuated liver injury by inhibiting MAdCAM1/α4ß7 -mediated gut-derived proinflammatory lymphocytes infiltration, which provides a potential therapeutic target for ALF.

The effects of water, substrate, and intermediate adsorption on the photocatalytic decomposition of air pollutants over nano-TiO2 photocatalysts.

The photocatalytic performance of nano-TiO2 photocatalysts in air pollutant degradation greatly depends on the adsorption of water, substrates, and intermediates. Especially under excessive humidity, substrate concentration, and intermediate concentration, the competitive adsorption of water, substrates, and intermediates can seriously inhibit the photocatalytic performance. In the past few years, extensive studies have been performed to investigate the influence of humidity, substrate concentration, and intermediates on the photocatalytic performance of TiO2, and significant advances have been made in the area. However, to the best of our knowledge, there is no review focusing on the effects of water, substrate, and intermediate adsorption to date. A comprehensive understanding of their mechanisms is key to overcoming the limited application of nano-TiO2 photocatalysts in the photocatalytic decomposition of air pollutants. In this review, the progress in experimental and theoretical fields, including a recent combination of photocatalytic experiments and adsorption and photocatalytic simulations by density functional theory (DFT), to explore the impact of adsorption of various reaction components on nano-TiO2 photocatalysts is comprehensively summarized. Additionally, the mechanism and broad perspective of the impact of their adsorption on the photocatalytic activity of TiO2 in air treatment are also critically discussed. Finally, several solutions are proposed to resolve the current problems related to environmental factors. In general, this review contributes a comprehensive perspective of water, substrate, and intermediate adsorption toward boosting the photocatalytic application of TiO2 nanomaterials.

Inhibitory effect of cyclodextrin on Maillard reaction and its mechanism.

Maillard reaction in pharmaceutical preparations refers to a complex chemical reaction existing between reducing excipients and amino-containing drugs in preparations, which can cause a series of quality problems in preparations. Maillard reaction belongs to chemical incompatibility in preparations, and measures should be taken to reduce or avoid it. In this study, the effect of cyclodextrins (commonly used pharmaceutical excipients) on the Maillard reaction and its mechanism in the lysine hydrochloride-lactose solid preparation model were explored for the first time. Our research results show that the embedding of lysine in cyclodextrin can inhibit the Maillard reaction of lysine to some extent, and the embedding of lysine in cyclodextrin with different structures has differences in the inhibitory effects on Maillard reaction.Among the five cyclodextrins we studied, α-CD and HP-ß-CD embedded lysine can reduce Maillard reaction to a greater extent. We suspect that this may be related to the stability of the embedded substance, which needs further study and verification. And our research shows that the inclusion complex between lysine and cyclodextrin may be the result of hydrogen bond, electrostatic attraction, hydrophobic interaction and van der Waals force. Cyclodextrin is expected to solve the problem of Maillard reaction in pharmaceutical industry to some extent.

Nickel-Catalyzed Asymmetric Decarboxyarylation with NHP Esters of α-Amino Acid to Chiral Benzylamines.

A nickel-catalyzed asymmetric decarboxyarylation of NHP esters via reductive cross-coupling has been established. Utilizing the NHP of amino acid esters as radical precursors furnishes a new protocol in which structurally diverse chiral benzylamines could be accessible. This method has demonstrated excellent catalytic efficiency, high enantioselective control, mild conditions, and good functional group tolerance, thus enabling the late-stage modification of bioactive molecules and pharmaceuticals.

Bacterial Changes in Boiled Crayfish between Different Storage Periods and Characterizations of the Specific Spoilage Bacteria.

This study investigated changes in the microbial compositions of crayfish tails during storage at 4 °C (for 0-12 days) as measured using high-throughput sequencing (HTS). The specific spoilage organisms (SSOs) in the crayfish tails were isolated using culture-dependent cultivation methods, and they were identified by 16S rRNA and characterized for their enzymatic spoilage potentials (e.g., protease, lipase, phospholipase, and amylase). The spoilage abilities of the selected strains in the crayfish tails were assessed by inoculating them into real food. Moreover, the microbial growth and the volatile basic nitrogen (TVB-N) changes were monitored during the storage period. The results from the HTS showed that the dominant genus of shrimp tails evolved from Streptococcus (D0) to Pseudomonas (D4) and, finally, to Paenisporosarcina (D12) during storage. Seven bacterial species (Acinetobacter lwoffii, Aeromonas veronii, Kurthia gibsonii, Pseudomonas sp., Exiguobacterium aurantiacum, Lelliottia amnigena, and Citrobacter freundii) were screened from the spoiled shrimp tails by the culture-dependent method, among which Aeromonas veronii had the strongest spoilage ability.

Prognostic and immunological significance of an M1 macrophage-related gene signature in osteosarcoma.

As the most abundant infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are pivotal in tumor development and treatment. The present investigation endeavors to explore the potential of M1 macrophage-related genes (MRGs) as biomarkers for assessing risk in individuals with osteosarcoma. RNA-sequence data and clinical data were derived from TCGA and GEO databases. The CIBERSORT method was utilized to discern subtypes of tumor-infiltrating immune cells. Identification of MRGs was achieved through Pearson correlation analysis. A prognostic risk model for MRGs was developed using Cox and LASSO regression analyses. A tripartite gene signature comprising CD37, GABRD, and ARHGAP25 was an independent prognostic indicator and was employed to develop a risk score model. The internal and external validation cohort confirmed the results. The area under the ROC curve (AUC) was determined for survival periods of 1 year, three years, and five years, yielding values of 0.746, 0.839, and 0.850, respectively. The C-index of the risk score was found to be superior to clinicopathological factors. GO/KEGG enrichment showed that the differences between high- and low-risk groups were predominantly associated with immune response pathways. Immune-related analysis related to proportions of immune cells, immune function, and expression levels of immune checkpoint genes all showed differences between the high- and low-risk groups. The qRT-PCR and Western blotting results indicate that CD37 expression was markedly higher in MG63 and U2OS cell lines when compared to normal osteoblast hFOB1.19. In U2OS cell line, GABRD expression levels were significantly upregulated. ARHGAP25 expression levels were elevated in both 143B and U2OS cell lines. In summary, utilizing a macrophage genes signature demonstrates efficacy in predicting both the prognosis and therapy response of OS. Additionally, immune analysis confirms a correlation between the risk score and the tumor microenvironment. Our findings, therefore, provide a cogent account for the disparate prognoses observed among patients and furnish a justification for further inquiry into biomarkers and anti-tumor treatment strategies.

The combined effects of ultrasound and plasma-activated water on microbial inactivation and quality attributes of crayfish during refrigerated storage.

In this study, a decontamination technology combining ultrasound (US) and plasma-activated water (PAW) was developed to better preserve crayfish. First, the decontamination efficacy of US, PAW and their combinations (UP) on crayfish was quantified after 0, 20, 40, or 60 min of treatments. The total viable count (TVC) was reduced by 0.27-0.77 Log CFU/g after individual US or PAW treatments, while a TVC reduction of 1.17 Log CFU/g was achieved after 40 min of UP treatment. Besides, the changes in psychrotrophic bacteria, lactic acid bacteria, yeasts and molds followed a similar trend to TVC. UP treatments normally resulted in more significant reductions in the natural microbiota of crayfish than US or PAW treatments. Furthermore, the microbial quality, physicochemical properties and sensory properties of crayfish after different treatments were assessed during storage at 4 °C for 12 days. According to TVC and total volatile basic nitrogen (TVB-N) values, the control group became unacceptable from 4 days, US or PAW groups became unacceptable from 6 days, while UP group extended the storage time to 8-10 days. During storage, thiobarbituric acid reactive substances (TBARS) values of all the groups were maintained below 0.5 mg/kg, among which the control group exhibited the highest value (0.39 mg/kg). Moreover, UP treatment effectively retarded the deterioration in color and texture properties of crayfish. Fourier transform infrared (FTIR) spectroscopy analysis indicated that UP treatment decreased the α-helix contents and increased the ß-sheet contents of crayfish proteins, while the structural changes were not evident at the end of storage. Low-field nuclear magnetic resonance (LF-NMR) analysis revealed that UP treatment reduced the water migration and enhanced the stability of bond water in crayfish. In addition, E-nose analysis revealed the protection of UP treatment on the sensory properties of crayfish during storage. This study demonstrated that the combinations of US and PAW treatments effectively accelerated the decontamination of crayfish and contributed to better storage quality.

Visible-light-driven peroxymonosulfate activation by robust TiO2-base nanoparticles for efficient removal of sulfamethoxazole.

In this study, a novel bimetallic Co-Mo-TiO2 nanomaterial was fabricated through a simple two-step method, and applied as photocatalyst to activate peroxymonosulfate (PMS) with high efficiency for sulfamethoxazole (SMX) removal under visible light. Nearly 100% of SMX was degraded within 30 min in Vis/Co-Mo-TiO2/PMS system, and its kinetic reaction rate constant (0.099 min-1) was 24.8 times higher compare with the Vis/TiO2/PMS system (0.014 min-1). Moreover, the quenching experiments and the electronic spin resonance analysis results confirmed that both 1O2 and SO4•- were the dominant active species in the optimal system, and the redox cycles of Co3+/Co2+ and Mo6+/Mo4+ promoted the generation of the radicals during the PMS activation process. Additionally, the Vis/Co-Mo-TiO2/PMS system exhibited a wide working pH range, superior catalytic performance toward different pollutants and excellent stability with 92.8% SMX removal capacity retention after three consecutive cycles. The result of density functional theory (DFT) suggested that Co-Mo-TiO2 exhibited a high affinity for PMS adsorption, as indicated by the length O-O bond from PMS and the Eads of the catalysts. Finally, the possible degradation pathway of SMX in optimal system was proposed through intermediate identification and DFT calculation, and a toxicity assessment of the by-products was also conducted.

Mechanism of Particle-Mediated Inhibition of Demetalation for Single-Atom Catalytic Sites in Acidic Electrochemical Environments.

Demetalation, caused by the electrochemical dissolution of metal atoms, poses a significant challenge to the practical application of single-atom catalytic sites (SACSs) in proton exchange membrane-based energy technologies. One promising approach to inhibit SACS demetalation is the use of metallic particles to interact with SACSs. However, the mechanism underlying this stabilization remains unclear. In this study, we propose and validate a unified mechanism by which metal particles can inhibit the demetalation of Fe SACSs. Metal particles act as electron donors, decreasing the Fe oxidation state by increasing the electron density at the FeN4 position, thereby strengthening the Fe-N bond, and inhibiting electrochemical Fe dissolution. Different types, forms, and contents of metal particles increase the Fe-N bond strength to varying extents. A linear correlation between the Fe oxidation state, Fe-N bond strength, and electrochemical Fe dissolution amount supports this mechanism. Our screening of a particle-assisted Fe SACS led to a 78% reduction in Fe dissolution, enabling continuous operation for up to 430 h in a fuel cell. These findings contribute to the development of stable SACSs for energy applications.

Porcine Circovirus 2 Increases the Frequency of Transforming Growth Factor-ß via the C35, S36 and V39 Amino Acids of the ORF4.

Porcine circovirus 2 (PCV2) is one of the most important endemic swine pathogens, inducing immunosuppression in pigs and predisposing them to secondary bacterial or viral infections. Our previous studies show that PCV2 infection stimulated pig intestinal epithelial cells (IPEC-J2) to produce the secretory transforming growth factor-ß (TGF-ß), which, in turn, caused CD4+ T cells to differentiate into regulatory T cells (Tregs). This may be one of the key mechanisms by which PCV2 induces immunosuppression. Here, we attempt to identify the viral proteins that affect the TGF-ß secretion, as well as the key amino acids that are primarily responsible for this occurrence. The three amino acids C35, S36 and V39 of the ORF4 protein are the key sites at which PCV2 induces a large amount of TGF-ß production in IPEC-J2 and influences the frequency of Tregs. This may elucidate the regulatory effect of PCV2 on the Tregs differentiation from the perspective of virus structure and intestinal epithelial cell interaction, laying a theoretical foundation for improving the molecular mechanism of PCV2-induced intestinal mucosal immunosuppression in piglets.

Clinical isolates of hepatitis B virus genotype C have higher in vitro transmission efficiency than genotype B isolates.

Serum samples were collected from 54 hepatitis B e antigen (HBeAg)-positive Chinese patients infected with hepatitis B virus (HBV) subgenotype B2 or C2. They were compared for transmission efficiency using same volume of samples or infectivity using same genome copy number. Adding polyethylene glycol (PEG) during inoculation did not increase infectivity of fresh samples but markedly increased infectivity following prolonged sample storage. Differentiated HepaRG cells infected without PEG produced more hepatitis B surface antigen (HBsAg) and higher HBsAg/HBeAg ratio than sodium taurocholate cotransporting polypeptide (NTCP)-reconstituted HepG2 cells infected with PEG. They better supported replication of core promoter mutant in contrast to wild-type (WT) virus by HepG2/NTCP cells. Overall, subgenotype C2 samples had higher viral load than B2 samples, and in general produced more HBeAg, HBsAg, and replicative DNA following same-volume inoculation. Precore mutant was more prevalent in subgenotype B2 and had reduced transmission efficiency. When same genome copy number of viral particles was inoculated, viral signals were not necessarily higher for three WT C2 isolates than four WT B2 isolates. Using viral particles generated from cloned HBV genome, three WT C2 isolates showed slightly reduced infectivity than three B2 isolates. In conclusion, subgenotype C2 serum samples had higher transmission efficiency than B2 isolates in association with higher viral load and lower prevalence of precore mutant, but not necessarily higher infectivity. PEG-independent infection by HBV viremic serum samples is probably attributed to a labile host factor.

Low-molecular-weight heparin therapy reduces 28-day mortality in patients with sepsis-3 by improving inflammation and coagulopathy.

Background and aim: Sepsis is a syndromic response to infection and is associated with high mortality, thus imposing a significant global burden of disease. Although low-molecular-weight heparin (LMWH) has been recommended to prevent venous thromboembolism, its anticoagulant and anti-inflammatory effects in sepsis remain controversial. Owing to the modification of the Sepsis-3 definition and diagnostic criteria, further evaluation of the efficacy and benefit population of LMWH is required. Methods: We performed a retrospective cohort study to assess whether LMWH improved the inflammation, coagulopathy, and clinical outcomes against Sepsis-3 and to identify the target patients. All patients diagnosed with sepsis at the First Affiliated Hospital of Xi'an Jiaotong University (the largest general hospital in northwest China) from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria. Results: After 1:1 propensity score matching, 88 pairs of patients were categorized into the treatment and control groups based on subcutaneous LMWH administration. Compared with the control group, a significantly lower 28-day mortality was observed in the LMWH group (26.1 vs. 42.0%, p = 0.026) with a comparable incidence of major bleeding events (6.8 vs. 8.0%, p = 0.773). Cox regression analysis showed that LMWH administration was the independent protective factor for septic patients (aHR, 0.48; 95% CI, 0.29-0.81; p = 0.006). Correspondingly, the LMWH treatment group showed a significant improvement in inflammation and coagulopathy. Further subgroup analysis showed that LMWH therapy was associated with favorable outcomes in patients younger than 60 years and diagnosed with sepsis-induced coagulopathy (SIC), ISTH overt DIC, non-septic shock, or non-diabetics and in patients included in the moderate-risk group (APACHE II score 20-35 or SOFA score 8-12). Conclusion: Our study results showed that LMWH improves 28-day mortality by improving inflammatory response and coagulopathy in patients meeting Sepsis-3 criteria. The SIC and ISTH overt DIC scoring systems can better identify septic patients who are likely to benefit more from LMWH administration.

Fracture Types Influence the Likelihood of Lower Urinary Tract Injuries in Patients with Pelvic Fractures.

BACKGROUND: The combination of pelvic fractures with lower urinary tract injuries (LUTIs) is a severe traumatic injury. This study was performed to determine the relationship between LUTIs and pelvic fracture types. METHODS: Patients who sustained pelvic fractures combined with LUTIs between 1 January 2018 and 1 January 2022 in our institution were retrospectively analyzed. The patients' demographics, mechanism of injury, presence of open pelvic fractures, types of pelvic fractures, patterns of LUTIs, and early complications were analyzed. The association between pelvic fracture types and the identified LUTIs was statistically analyzed. RESULTS: This study involved 54 patients diagnosed with pelvic fractures combined with LUTIs. The overall incidence of pelvic fractures combined with LUTIs was 7.7% (n = 54/698). All patients had unstable pelvic fractures. The male:female ratio was approximately 2.4:1.0. The incidence of LUTIs was higher in men than women with pelvic fractures (9.1% vs. 4.4%). Bladder injuries occurred at roughly equal rates in men and women (4.5% vs. 4.4%, p = 0.966), but urethral injuries were more frequent in men (6.1% vs. 0.5%, p = 0.001). The most common pelvic injury pattern was a type C fracture according to the Tile classification and a vertical-shear-type fracture according to the Young-Burgess classification. The Young-Burgess fracture classification was related to the severity of bladder injury in men (p = 0.037). There was no significant difference in bladder injury according to the two classifications among women (p = 0.524 vs. p = 1.000) or among the entire cohort (p = 0.454 vs. p = 0.342). CONCLUSIONS: Men and women are equally likely to sustain a bladder injury, but a urethral injury with pelvic fracture is more frequent in men. LUTIs tend to be accompanied by unstable pelvic fractures. It is imperative to be vigilant for potential bladder injury when men sustain vertical-shear-type pelvic fractures.