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Abstract Background The Aryl Hydrocarbon Receptor (AHR) is a transcription factor that regulates several biological processes. Its potential in anti-tumor immunotherapy is becoming clearer, yet no bibliometric studies on this topic exist. This study aims to understand the current research landscape and identify future directions through a bibliometric analysis of AHR’s anti-tumor immunological effects. Methods We conducted a comprehensive bibliometric analysis of AHR antitumor immunotherapy papers in the Web of Science Core Collection. Various aspects of the publications were analyzed, and research hotspots and future trends were identified using scientific bibliometric tools and statistical methods. Results We collected 592 English papers published between 2010 and 2023, with an almost annual increase. Most publications were from the USA, followed by China, Germany, and Italy. The journal “Frontiers in Immunology” had the most papers, and the most cited paper was Christiane A. Opitz’s “An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor.” The research is centered around AHR gene expression, with a growing focus on intestinal disease and the development of Programmed cell death ligand 1 (PD-L1) drugs. Conclusion This bibliometric study highlights the significance of AHR in immunomodulatory research, outlining the research trends and key contributors. It suggests AHR’s immune effects may mediate the process of colitis cancer transformation, providing valuable insights for future anti-tumor immunotherapy strategies based on AHR.

Abstract Salmonella enterica serovar Gallinarum (S. Gallinarum) is an avian-specific pathogen responsible for fowl typhoid, a severe systemic disease with high mortality in chickens. This disease poses a substantial burden to the poultry industry, particularly in developing countries like China. However, comprehensive genome datasets on S. Gallinarum are lacking. Here, we present the most extensive S. Gallinarum genome dataset, comprising 574 well-collated samples. This dataset consists of 366 genomes sequenced in our laboratory and 208 publicly available genomes, collected from various continents over the past century. Using in silico prediction, we categorized S. Gallinarum into three distinct biovars. Regarding antimicrobial resistance, 238 strains (41.5%) carried antimicrobial resistance genes (ARGs) with a total of 635 records, while 232 strains (40.4%) exhibited multi-drug resistance. Mobile genomic elements (MGEs) serve as critical drivers for ARGs. Our dataset includes 5,636 MGEs records, with most MGEs belonging to prophages and plasmids. This dataset expands our understanding of the genomic characteristics of S. Gallinarum, providing valuable resources for future genomic studies to improve disease management.

Abstract Aim To construct evidence-based sensitive quality indicators for patients’ rapid rehabilitation care after combined pancreaticoduodenectomy (PD) and to provide a reference for clinical nursing professionals to scientifically evaluate the quality of patients’ rehabilitation post-PD. Background Since PD is associated with higher surgical risk and anastomotic complications, it leads to higher complication rates and longer postoperative recovery cycles. This reiterates the need for rapid recovery of patients after PD; however, the evaluation of sensitive nursing care indicators regarding rapid recovery post-PD has not yet been established to date. Methods Based on the Donabedian structure-process-result theory model, we used available literature, semi-structured interviews, the Delphi method, and hierarchical analysis to establish a sensitive indicator system for patients’ rapid rehabilitation after PD and evaluate the importance of such indicators. Results There were two rounds of expert correspondence, and the effective recovery rate of the questionnaires of these rounds was 100%. The expert authority coefficients, as well as the Kendall coordination coefficients of the expert opinions, were 0.859 and 0.872 as well as 0.423 and 0.431, with statistically significant differences (p

Abstract Background Contactin-associated protein-2(CASPR2) antibody-associated autoimmune encephalitis(AE) is rare in children. This study aimed to report the clinical characteristics and long-term outcome of CASPR2 autoimmunity in children to expand the disease spectrum. Methods Children who were hospitalized in our hospital with clinically suspected AE from May 2015 to April 2022 and underwent neuronal surface antibodies detections were retrospectively analyzed. Clinical data of patients with CASPR2 autoimmunity were collected. Results Patients who were positive for NMDAR-IgG, CASPR2-IgG, LGI1-IgG and IgLON5-IgG occupied 95.2%(119/125),3.2%(4/125),0.8%(1/125) and 0.8%(1/125), respectively.The median onset age of the 4 patients with CASPR2-IgG was 5.6 years. The most common symptoms were psychiatric symptoms/abnormal behavior(3/4) and sleep dysfunction(3/4). One patient developed a phenotype of Rasmussen encephalitis(RE). Tumor was absent in our patients. Two patients showed abnormal findings on initial brain magnetic resonance imaging(MRI) scans. All the patients showed favorable response to immunotherapy except the patient with RE experienced recurrent symptoms who finally achieved remission after surgery. All the patients had a favorable long-term outcome at the last follow-up(33-58months). Conclusions CASPR2 autoimmunity may be the second most common anti-neuronal surface antibodies associated neurological disease in children. Psychiatric symptoms/abnormal behavior and sleep disorder were common in children with CASPR2-associated AE. Tumor was rare in those patients. Most pediatric patients had a favorable long-term outcome.

The mechanical properties of 40CrNi2Si2MoV martensitic steel are affected by the large size carbides，the strength and toughness of martensitic steel can be effectively improved by optimizing the composition design and reasonable heat treatment process. The effects of M6C carbide on mechanical properties and microstructure of ultrahigh strength steel were studied at different quenching temperatures （860 ℃-1150 ℃）， and the evolution of M6C particle size， quantity and composition was studied by means of SEM and TEM. The results show that large M6C particles reduce the toughness of ultrahigh strength steel， and the M6C particles in the 880 ℃ quenching sample are large （~400 nm）， which is easy to cause stress concentration around the large M6C carbide ， weaken the binding force between the matrix and M6C carbide， and easy to crack around M6C carbide， resulting in material fracture.With the increase of quenching temperature， the size and quantity of M6C particles in the test steel decrease， and the concentration of Si in M6C particles is increased， and the atoms in M（Fe， Mo， Ni， Co）6C are replaced by Si， which improves the stability of M6C carbide. The size of M6C particle in the 1050 ℃ quenching temperature test steel is 25 nm， and the growth of the original austenite grain （8.5 μm） is inhibited. The strength of the test steel is 2227 MPa and the elongation is 7.0%， achieving a good strength and toughness matching.

Abstract Background Hypercalcemia can be a rare contributor to acute pancreatitis (AP) in pregnancy. This is primarily due to primary hyperparathyroidism (PHPT), resulting from parathyroid carcinoma. We exhibited a case report to analyze the diagnosis and treatment during the onset of hypercalcemia-induced AP. Case presentation A 32-year-old primigravida presented with acute pancreatitis near full-term gestation. Following a cesarean delivery, there was a reduction in serum amylase and peripancreatic exudate, but her serum calcium concentrations persistently elevated over 4.0 mmol/L. Interventions to lower the hypercalcemia were only temporarily effective, until a high serum parathyroid hormone (PTH) concentration of 1404 pg/mL was detected. Ultrasound revealed a 31 mm × 24 mm hypoechoic oval nodule in the left lower lobe of the thyroid gland. She underwent a parathyroidectomy, resulting in a dramatic decrease in serum PTH level, from preoperative levels of 2051 pg/mL to 299 pg/mL just 20 minutes after removal. Similarly, her serum calcium declined from 3.82 mmol/L to 1.73 mmol/L within 24 hours postoperatively. The final histopathology suggested parathyroid carcinoma. Conclusion When refractory hypercalcemia is present, serum PTH levels should be measured to determine PHPT. Parathyroidectomy is the optimal strategy for alleviating hypercalcemia and clarifying the underlying pathology.

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent swine pathogen, which has caused adverse impact on the global swine industry for almost 30 years. However, due to the immune suppression caused by the virus and the genetic diversity in PRRSV, no virus-targeting broad neutralizing strategy has been successfully developed yet. Antiviral peptide and nanobody have attracted extensive attention with the ease in production and the efficacy in practice. In this study, four new fusion proteins named nanobody peptide conjugates (NPCs) were developed by combining PRRSV specific non-neutralizing nanobodies with CD163-derived peptides targeting the receptor binding domain (RBD) of PRRSV proteins. Results Four NPCs were successfully constructed using two nanobodies against PRRSV N and nsp9 individually, recombining with two antiviral peptides 4H7 or 8H2 from porcine CD163 respectively. All four NPCs demonstrated specific capability of binding to PRRSV and broad inhibitory effect against various lineages of PRRSV in a dose-dependent manner. NPCs interfere with the binding of the RBD of PRRSV proteins to CD163 in the PRRSV pre-attachment stage by CD163 epitope peptides in the assistance of Nb components. NPCs also suppress viral replication during the stage of post-attachment, and the inhibitory effects depend on the antiviral functions of Nb parts in NPCs, including the interference in long viral RNA synthesis, NF-κB and IFN-β activation. Moreover, an interaction was predicted between aa K31 and T32 sites of neutralizing domain 4H7 of NPC-N/nsp9-4H7 and the motif 171NLRLTG176 of PRRSV GP2a. The motif 28SSS30 of neutralizing domain 8H2 of NPC-N/nsp9-8H2 could also form hydrogens to bind with the motif 152NAFLP156 of PRRSV GP3. The study provides valuable insights into the structural characteristics and potential functional implications of the RBD of PRRSV proteins. Finally, as indicated in a mouse model, NPC intranasally inoculated in vivo for 12–24 h sustains the significant neutralizing activity against PRRSV. These findings inspire the potential of NPC as a preventive measure to reduce the transmission risk in the host population against respiratory infectious agents like PRRSV. Conclusion The aim of the current study was to develop a peptide based bioactive compound to neutralize various PRRSV strains. The new antiviral NPC (nanobody peptide conjugate) consists of a specific nanobody targeting the viral protein and a neutralizing CD163 epitope peptide for virus blocking and provides significant antiviral activity. The study will greatly promote the antiviral drug R&D against PRRSV and enlighten a new strategy against other viral diseases. Graphical abstract image

Abstract Background The prevalence of multiple nosocomial infections (MNIs) is on the rise, however, there remains a limited comprehension regarding the associated risk factors, cumulative risk, probability of occurrence, and impact on length of stay (LOS). Method This multicenter study includes all hospitalized patients from 2020 to July 2023 in two sub-hospitals of a tertiary hospital in Guangming District, Shenzhen. The semi-Markov multi-state model (MSM) was utilized to analyze risk factors and cumulative risk of MNI, predict its occurrence probability, and calculate the extra LOS of nosocomial infection (NI). Results The risk factors for MNI include age, community infection at admission, surgery, and combined use of antibiotics. However, the cumulative risk of MNI is lower than that of single nosocomial infection (SNI). MNI is most likely to occur within 14 days after admission. Additionally, SNI prolongs LOS by an average of 7.48 days (95% Confidence Interval, CI: 6.06–8.68 days), while MNI prolongs LOS by an average of 15.94 days (95% CI: 14.03–18.17 days). Furthermore, the more sites of infection there are, the longer the extra LOS will be. Conclusion The longer LOS and increased treatment difficulty of MNI result in a heavier disease burden for patients, necessitating targeted prevention and control measures.

Objectives The micro‐nano structure of 3D‐printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation provides a new opportunity for the development of bone implants, but it necessitates higher requirements for bone tissue differentiation and the antibacterial properties of bone implants in clinical practice. Methods This study investigated the preparation, antimicrobial properties, and osteogenesis‐promoting ability of the 3D printed porous Ti alloy anodic oxidized Ag‐carrying (Ag@3D‐TiO2) scaffolds. The 3D printed porous Ti alloy (3D‐Ti), anodized 3D printed porous Ti alloy (3D‐TiO2), and Ag@3D‐TiO2 scaffolds were synthesized using electron beam melting. The antimicrobial properties of the scaffolds were examined using antibacterial tests and their cytocompatibility was assessed using a cell proliferation assay and acridine orange/ethidium bromide (AO/EB) staining. In vitro cellular assays were used to investigate the effects of the scaffold microstructural features on cell activity, proliferation, and osteogenesis‐related genes and proteins. In vivo animal experiments were used to evaluate the anti‐inflammatory and osteogenesis‐promoting abilities of the scaffolds. Results The Ag@3D‐TiO2 scaffolds exhibited sustained anti‐microbial activity over time, enhanced cell proliferation, facilitated osteogenic differentiation, and increased extracellular matrix mineralization. In addition, alkaline phosphatase (ALP), collagen type I (COL‐I), and osteocalcin (OCN)‐related genes and proteins were upregulated. In vivo animal implantation experiments, the anti‐inflammatory effect of the Ag@3D‐TiO2 scaffolds were observed using histology, and a large amount of fibrous connective tissue was present around it; the Ag@3D‐TiO2 scaffolds were more bio‐compatible with the surrounding tissues compared with 3D‐Ti and 3D‐TiO2; a large amount of uniformly distributed neoplastic bone tissue existed in their pores, and the chronic systemic toxicity test showed that the 3D‐Ti, 3D‐TiO2, and Ag@3D‐TiO2 scaffolds are biologically safe. Conclusion The goal of this study was to create a scaffold that exhibits antimicrobial properties and can aid bone growth, making it highly suitable for use in bone tissue engineering.

IntroductionAttentional control is crucial in the development and maintenance of anxiety disorders. Understanding the underlying mechanisms of attentional control can help to shed light on the neuropathological processes in anxiety disorders (ANX). Quantitative electroencephalography (QEEG) offers a cost-effective, noninvasive method for examining the neuropathological mechanisms of mental disorders.MethodsIn this study, 67 patients with ANX and 45 healthy controls (HC) were recruited. EEG recordings were obtained for 5 minutes in an eyes-closed condition. QEEG was employed to evaluate the mechanisms of attentional control in ANX.ResultsNeurophysiological measures indicated that anxiety patients exhibited a more frontal topographic pattern of theta/beta ratio (TBR) compared to HC. Additionally, a significant decrease in temporal beta power was observed in the ANX group. Correlation analysis revealed that decreased beta power and increased TBR were significant association between attentional control deficits in ANX.DiscussionThese findings provide electrophysiological evidence of impaired attentional control processing in anxiety patients, characterized by decreased temporal beta power and increased frontal TBR. Temporal beta power and frontal TBR may serve as promising biomarkers for attentional control in ANX.

BackgroundIt is challenging to predict the occurrence of non-suicidal self-injury (NSSI) among adolescents over short periods. Moreover, the predictive value of indices for NSSI remains elusive. Thus, this study aimed to identify predictors of NSSI within 6 months among adolescents after psychiatric hospitalization by establishing a risk assessment model.MethodsA total of 632 high-risk participants were included in this study. The distribution characteristics of adolescent NSSI were initially assessed through a cross-sectional survey, following which risk factors were identified using logistic regression analysis. The risk score method was then used to construct a 6-month risk assessment model for NSSI. Lastly, the predictive effect of the model was evaluated by indicators such as the area under the receiver operating characteristic (ROC) curve and the positive predictive value.ResultsAfter 6 months, 412 cases of NSSI were identified. According to the logistic regression model, the frequency of relapses, medication status, and NSSI history were identified as influencing factors. Higher scores on the Impulsive Behavior Scale and Pittsburgh Sleep Quality Index were associated with a higher risk of NSSI. Conversely, higher scores on the Pain and Belief Perception Scale were correlated with a lower risk of NSSI. Moreover, the area under the ROC curve for the predictive model was 0.9989, with a 95% confidence interval of (0.9979, 0.9999), highlighting its high predictive ability and accuracy. The predictive model was validated using 78 patients, yielding an area under the ROC curve of 0.9703 and a 95% confidence interval of (0.9167, 0.9999), demonstrating outstanding predictability.ConclusionThese results collectively showed that the predictive model could accurately predict adolescent NSSI. Thus, the model’s primary variables may be applied to predict the risk of NSSI in the clinical setting.

BackgroundChina experienced a surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants after adjusting its zero-coronavirus disease 2019 (COVID-19) policy. Although infections with Omicron variants are generally less severe than infections with previous SARS-CoV-2 variants, the clinical characteristics, persistent symptoms, and antibody responses in solid carcinoma patients (SCPs) with COVID-19 during the Omicron wave are unclear.MethodsWe conducted a cross-sectional study in April 2023, recruiting healthy controls (HCs) from the community and SCPs from Zhejiang Provincial People’s Hospital. Serum samples were collected, and a questionnaire was used to assess SARS-CoV-2 infection status, including demographic characteristics, clinical manifestations, and “long COVID” symptoms. Humoral immune responses were analyzed by enzyme-linked immunosorbent assays (ELISAs) targeting immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD; Omicron BA.4/5) protein and cell culture-based neutralization assays against Omicron variants (BA.4/5, BF.7, XBB.1.5, and EG.5).ResultsIn total, 298 SCPs and 258 HCs were enrolled. Self-reported COVID-19 case rates were significantly lower in SCPs than in HCs (78.5% vs. 93.8%, P

Abstract Infected wounds can result in complex clinical complications and delayed healing, presenting a significant global public health challenge. This study explored the effects of topical application of two probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis BB‐12, on the microenvironment of infected wounds and their impact on wound healing. LGG and BB‐12 were applied separately and topically on the Staphylococcus aureus (S. aureus)‐infected skin wounds of the rat model on a daily basis. Both probiotics significantly accelerated wound healing, demonstrated by enhanced granulation tissue formation and increased collagen deposition, with BB‐12 showing superior efficacy. LGG and BB‐12 both effectively inhibited neutrophil infiltration and decreased the expression of pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). Notably, BB‐12 markedly reduced IL‐6 levels, while LGG significantly lowered TNF‐α, transforming growth factor‐β (TGF‐β) and vascular endothelial growth factor (VEGF). Additionally, both probiotics promoted macrophage polarization towards the anti‐inflammatory M2 phenotype. Microbiota analysis revealed that LGG and BB‐12 significantly decreased the abundance of pathogenic bacteria (e.g. Staphylococcus and Proteus) and increased the proportion of beneficial bacteria (e.g. Corynebacterium). Particularly, BB‐12 was more effective in reducing Staphylococcus abundance, whereas LGG excelled in promoting Corynebacterium growth. These findings suggest the ability of LGG and BB‐12 to modulate the wound microenvironment, enhance wound healing and provide valuable insights for the management of infected wounds.

Abstract Gut microbiota is an intricate microbial community containing bacteria, fungi, viruses, archaea, and protozoa, and each of them contributes to diverse aspects of host health. Nevertheless, the influence of interaction among gut microbiota on host health remains uncovered. Here, we showed that the interaction between intestinal fungi and bacteria shaped lung inflammation during infection. Specifically, antifungal drug‐induced dysbiosis of gut mycobiota enhanced lung inflammation during infection. Dysbiosis of gut mycobiota led to gut Escherichia coli (E. coli) overgrowth and translocation to the lung during infection, which induced lung accumulation of the CD45+F4/80+Ly6G−Ly6C−CD11b+CD11c+ macrophages. Clearance of macrophages or deletion of TLR4 (Toll‐like receptor 4, recognition of LPS) rather than Dectin‐1 (recognition of beta‐1,3/1,6 glucans on fungi) blocked the antifungal drug‐induced aggravation of lung inflammation during infection. These findings suggest that the interaction between intestinal mycobiota and commensal bacteria affects host health through the gut–lung axis, offering a potential therapeutic target for ameliorating lung inflammation during infection.

ObjectiveDespite advancements in understanding panic disorder (PD), its etiology and pathogenesis remain elusive, particularly concerning the influence of psychosocial factors. This study aims to explore the mediating roles of neuroticism and anxiety sensitivity (AS) in the relationship between childhood trauma and PD severity.MethodsWe conducted a cross-sectional analysis involving 84 individuals diagnosed with PD and 112 age- and gender-matched healthy controls (HC). Childhood trauma was assessed using the validated Childhood Trauma Questionnaire (CTQ), while anxiety sensitivity levels were measured using the Anxiety Sensitivity Index-3 (ASI-3). Neuroticism was evaluated using the Chinese Big Five Personality Inventory (CBF-PI-B). The severity of PD was determined using the Panic Disorder Severity Scale (PDSS). Statistical analysis encompassed both correlation and mediation techniques to thoroughly examine the relationships among childhood trauma, neuroticism, AS, and PD severity.ResultsIndividuals with PD exhibited significantly higher CTQ, ASI-3, and neuroticism scores compared to HC (all P

BackgroundRecent studies have yielded conflicting results regarding the relationship between smoking history and the effectiveness of immune checkpoint inhibitors (ICIs) for advanced lung cancer. While some studies have suggested that smoking may enhance the response to immunotherapy in patients with lung cancer, other findings indicate the contrary. Therefore, we conducted a systematic review and meta-analysis to thoroughly examine this association.MethodsWe searched the PubMed, Embase, and Scopus databases for clinical trials comparing immunotherapy with conventional chemotherapy as the primary treatment for advanced lung cancer. A random effects model was used to synthesize hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also conducted predefined subgroup analyses to investigate the efficacy disparities between never-smokers and smokers who were administered immunotherapy alone or in combination with chemotherapy, as well as the differences between former and current smokers under similar treatment modalities.ResultsOur analysis included data from 17 Phase III clinical trials involving 10,283 patients. The findings indicate that immunotherapy benefits both smokers and never-smokers with lung cancer or non-small cell lung cancer, yielding pooled HRs for OS of 0.74 (95% CI: 0.59–0.92) and 0.73 (95% CI: 0.67–0.80), respectively. A significant interaction effect was not observed (HR: 0.98, 95% CI: 0.77–1.24, pinteraction = 0.14), and the tumor type, immunotherapy combination, and type of immunotherapy did not differ among the groups in the subgroup analyses. Similarly, both former and current smokers experienced a significant survival benefit from immunotherapy, with pooled HRs for OS of 0.79 (95% CI: 0.68–0.91) and 0.71 (95% CI: 0.59–0.87), respectively. However, a significant interaction effect was also not observed (HR: 0.91, 95% CI: 0.74–1.11, pinteraction = 0.14).ConclusionOur findings suggest that smoking status does not affect the effectiveness of immunotherapy for lung cancer treatment. However, additional high-quality clinical trials are needed to confirm this conclusion.Systematic review registrationhttps://inplasy.com/register/, identifier INPLASY2023110058.

This work aimed to investigate the corrosion behavior of Si-18at%Y alloys in air oxidation and water-oxygen corrosion environments. The objective was to understand how different times, temperatures, and the presence or absence of water vapor affected the distribution and transformation of the alloy’s phases. The results revealed that extended duration facilitates growth of yttrium silicate, while higher temperature promotes stable phase transformation. The distribution and type of yttrium silicate are influenced by the presence of SiO2. At lower temperatures, water vapor facilitated the formation of SiO2, whereas at higher temperatures, it depleted SiO2 and inhibited the generation of yttrium silicate.

Abstract Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations. One promising area of research involves self-assembled protein nanoparticles (SAPNs), which have shown potential for enhancing antigen-presenting cell uptake, B-cell activation, and lymph node trafficking. Numerous nanovaccines have been utilized in veterinary medicine, including natural self-assembled protein nanoparticles, rationally designed self-assembled protein nanoparticles, animal virus-derived nanoparticles, bacteriophage-derived nanoparticles, and plant-derived nanoparticles, which will be discussed in this review. SAPN vaccines can produce robust cellular and humoral immune responses and have been shown to protect against various animal infectious diseases. This article attempts to summarize these diverse nanovaccine types and their recent research progress in the field of veterinary medicine. Furthermore, this paper highlights their disadvantages and methods for improving their immunogenicity.

Converting common biomass materials to high-performance biomedical products could not only reduce the environmental pressure associated with the large-scale use of synthetic materials, but also increase the economic value. Chitosan as a very promising candidate has drawn considerable attention owing to its abundant sources and remarkable bioactivities. However, pure chitosan materials usually exhibit insufficient mechanical properties and excessive swelling ratio, which seriously affected their in vivo stability and integrity when applied as tissue engineering scaffolds. Thus, simultaneously improving the mechanical strength and biological compatibility of pure chitosan (CS) scaffolds becomes very important. Here, inspired by the fiber-reinforced construction of natural extracellular matrix and the porous structure of cancellous bone, we built silk microfibers/chitosan composite scaffolds via ice-templating technique. This biomimetic strategy achieved 500% of mechanical improvement to pure chitosan, and meanwhile still maintaining high porosity (> 87%). In addition, the increased roughness of chitosan pore walls by embedded silk microfibers significantly promoted cell adhesion and proliferation. More importantly, after subcutaneous implantation in mice for four weeks, the composite scaffold showed greater structural integrity, as well as better collagenation, angiogenesis, and osteogenesis abilities, suggesting its great potential in biomedicine.

Abstract Background Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. Results Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. Conclusions Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.

Abstract Pasteurella multocida is an important zoonotic respiratory pathogen capable of infecting a diverse range of hosts, including humans, farm animals, and wild animals. However, the precise mechanisms by which P. multocida compromises the pulmonary integrity of mammals and subsequently induces systemic infection remain largely unexplored. In this study, based on mouse and rabbit models, we found that P. multocida causes not only lung damage but also bacteremia due to the loss of lung integrity. Furthermore, we demonstrated that bacteremia is an important aspect of P. multocida pathogenesis, as evidenced by the observed multiorgan damage and systemic inflammation, and ultimately found that this systemic infection leads to a cytokine storm that can be mitigated by IL-6-neutralizing antibodies. As a result, we divided the pathogenesis of P. multocida into two phases: the pulmonary infection phase and the systemic infection phase. Based on unbiased RNA-seq data, we discovered that P. multocida-induced apoptosis leads to the loss of pulmonary epithelial integrity. These findings have been validated in both TC-1 murine lung epithelial cells and the lungs of model mice. Conversely, the administration of Ac-DEVD-CHO, an apoptosis inhibitor, effectively restored pulmonary epithelial integrity, significantly mitigated lung damage, inhibited bacteremia, attenuated the cytokine storm, and reduced mortality in mouse models. At the molecular level, we demonstrated that the FAK-AKT-FOXO1 axis is involved in P. multocida-induced lung epithelial cell apoptosis in both cells and animals. Thus, our research provides crucial information with regard to the pathogenesis of P. multocida as well as potential treatment options for this and other respiratory bacterial diseases.

ABSTRACT: Objectives: Citrobacter freundii is one of the important pathogens that can cause nosocomial infections. The advent of carbapenem-resistant C. freundii complicates clinical treatment. Here, we reported the genome sequence of a carbapenem-resistant C. freundii strain carrying a novel IncC-IncFIB-IncX3 plasmid in China. Methods: The genome sequence of C. freundii CRNMS1 was obtained using the Illumina NovaSeq 6000 platform and the long-read Nanopore sequencer. Multilocus sequence typing was identified using MLST (v.2.23.0). The identification of antimicrobial resistance genes (ARGs) and plasmid replicons was performed using the resfinder and plasmidfinder of ABRicate (v.1.0.1). Circular comparisons of plasmids were performed using the BLAST Ring Image Generator (BRIG). Results: CRNMS1 belongs to ST116 in the C. freundii MLST scheme. Thirteen ARGs were predicted in all, including blaNDM-5, which was located in a plasmid. The plasmid pblaNDM5-S1, which carried the blaNDM-5 gene, was discovered to be a novel plasmid including three plasmid replicons (IncC, IncFIB, and IncX3) as well as seven ARGs (sul1, sul2, floR, dfrA17, aadA5, qnrA1, and blaNDM-5). A total of 38 blaNDM-5-bearing C. freundii strains can be retrieved from the NCBI database. Phylogenetic analysis revealed a worldwide distribution of C. freundii strains carrying the blaNDM-5 gene, with China having the highest prevalence (39%, 15/38). However, they were distantly related to CRNMS1 with SNP differences >2545. Conclusion: In summary, we reported a novel IncC-IncFIB-IncX3 plasmid carrying blaNDM-5 in a carbapenem-resistant C. freundii strain in China. The development of such hybrid plasmids facilitates the transmission of ARGs.

Abstract Pasteurella multocida is an opportunistic zoonotic pathogen that primarily causes fatal respiratory diseases, such as pneumonia and respiratory syndromes. However, the precise mechanistic understanding of how P. multocida disrupts the epithelial barrier in mammalian lung remains largely unknown. In this study, using unbiased RNA-seq analysis, we found that the evolutionarily conserved Hippo-Yap pathway was dysregulated after P. multocida infection. Given the complexity of P. multocida infection associated with lung injury and systemic inflammatory processes, we employed a combination of cell culture models, mouse models, and rabbit models to investigate the dynamics of the Hippo-Yap pathway during P. multocida infection. Our findings reveal that P. multocida infection activates the Hippo-Yap pathway both in vitro and in vivo, by upregulating the upstream factors p-Mst1/2, p-Lats1, and p-Yap, and downregulating the downstream effectors Birc5, Cyr61, and Slug. Conversely, pharmacological inhibition of the Hippo pathway by XMU-MP-1 significantly rescued pulmonary epithelial cell apoptosis in vitro and reduced lung injury, systemic inflammation, and mouse mortality in vivo. Mechanistic studies revealed that P. multocida induced up-regulation of Rassf1 expression, and Rassf1 enhanced Hippo-Yap pathway through phosphorylation. Accordingly, in vitro knockdown of Rassf1 significantly enhanced Yap activity and expression of Yap downstream factors and reduced apoptosis during P. multocida infection. P. multocida-infected rabbit samples also showed overexpression of Rassf1, p-Lats1, and p-Yap, suggesting that P. multocida activates the Rassf1-Hippo-Yap pathway. These results elucidate the pathogenic role of the Rassf1-Hippo-Yap pathway in P. multocida infection and suggest that this pathway has the potential to be a drug target for the treatment of pasteurellosis.

Abstract Pasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At present, there is still no effective commercial vaccine against PmA infection. In this study, a mutant strain (PmCQ2Δ4555–4580) with brand-new phenotypes was obtained after serially passaging at 42 °C. Whole genome resequencing and PCR analysis showed that PmCQ2Δ4555–4580 missed six genes, including PmCQ2_004555, PmCQ2_004560, PmCQ2_004565, PmCQ2_004570, PmCQ2_004575, and PmCQ2_004580. Importantly, the virulence of PmCQ2Δ4555–4580 was reduced by approximately 2.8 × 109 times in mice. Notably, live PmCQ2Δ4555–4580 could provide 100%, 100% and 40% protection against PmA, PmB and PmF, respectively; and inactivated PmCQ2Δ4555–4580 could provide 100% and 87.5% protection against PmA and PmB. Interestingly, immune protection-related proteins were significantly upregulated in PmCQ2Δ4555–4580 based on RNA-seq and bioinformatics analysis. Meaningfully, by in vitro expression, purification and in vivo immunization, 12 proteins had different degrees of immune protective effects. Among them, PmCQ2_008205, PmCQ2_010435, PmCQ2_008190, and PmCQ2_004170 had the best protective effect, the protection rates against PmA were 50%, 40%, 30%, and 30%, respectively, and the protective rates against PmB were 62.5%, 42.9%, 37.5%, and 28.6%, respectively. Collectively, PmCQ2Δ4555–4580 is a potential vaccine candidate for the prevention of Pasteurellosis involving in high expression of immune protective related proteins.

Objectives: Since its discovery, blaNDM-5 has spread widely amongst Escherichia coli strains in clinical patients, causing carbapenem resistance. Here we report the complete genome sequence of an NDM-5-producing E. coli strain isolated from the faecal sample of a healthy individual in Hangzhou, China. Methods: The whole-genome sequence of E. coli CREC8 was obtained utilising both the Nanopore sequencer and the Illumina NovaSeq 6000 platform. Antimicrobial resistance genes, multilocus sequence typing, and plasmid replicons were identified using the BacWGSTdb server. The phylogenetic relationship between CREC8 and other E. coli strains was investigated using the core genome multilocus sequence typing (cgMLST) strategy. Results: The complete genome sequence of E. coli CREC8 consists of one chromosome and 7 plasmids. CREC8 belongs to ST167 according to the MLST scheme. Seven ARGs were identified, including carbapenem resistance gene blaNDM-5 which was located in an IncFIA/IncFII type plasmid. A total of 164 E. coli ST167 strains related to 25 countries across four continents can be retrieved from the NCBI database, 95 of them carrying the blaNDM gene with blaNDM-5 the most (N = 79). Phylogenetic analysis revealed a worldwide distribution of E. coli ST167 strains, with China having the highest prevalence (37%, 61/165). Conclusion: In summary, we reported a blaNDM-5-carrying E. coli ST167 strain isolated from a healthy individual in China. Such strains are more commonly isolated from hospitalised patients but are rarely isolated from healthy individuals. This indicates a further epidemic of carbapenem-resistant E. coli strains in the healthy population which needs our attention.

Pasteurella multocida (P. multocida) can cause infection in various animals, especially livestock and poultry, which can lead to substantial losses to the breeding industry. However, the pathogenesis of avian P. multocida remains largely unknown. In this study, the mechanisms of avian P. multocida pathogenesis were explored. Chicken macrophage HD11 cells were infected with the avian strain PmQ and the bovine strain PmCQ2. PmQ induced higher cytotoxicity and apoptosis and exerted a stronger anti-phagocytotic effect on HD11 cells than PmCQ2. RNA sequencing analysis revealed that focal adhesion (FA)-related genes were significantly downregulated in PmQ-infected HD11 cells compared with that of PmCQ2. Subsequently, phalloidin staining of the F-actin assembly revealed that PmQ more significantly inhibited the formation of FAs in HD11 than PmCQ2. Western blot analysis revealed that the levels of Zyxin and phosphorylated focal adhesion kinase (FAK) were significantly decreased in PmQ-infected cells, confirming that PmQ inhibited FAs. Consequently, PmQ inhibited the FA downstream factor Akt, which decreased NF-κB and FoxO1 phosphorylation, as evidenced by the decreased expression of downstream anti-apoptotic genes (GADD45B, BCL2L1, BCL2A1, and BIRC2) and increased expression of downstream pro-apoptotic genes (BCL6, PKL2, PKL3, and KLF2). Conversely, pharmaceutically inhibiting FA formation using latrunculin A better enhanced PmCQ2-induced than PmQ-induced apoptosis in HD11 cells. Similarly, the knockdown of Zyxin or FoxO1 by siRNA both boosted the PmCQ2-induced apoptosis rates equal to those of PmQ. These results demonstrated that PmQ inhibited Zyxin-dependent FA formation and disrupted the FAK-AKT-FoxO1/NF-κB pathway to induce apoptosis in chicken macrophages. This study thus offers insights into the pathogenesis of avian P. multocida, which could facilitate the development of new strategies against P. multocida infection.

The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, P < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, P = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, P < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ T cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.

ABSTRACTObjective To establish an efficient nomogram model to predict short-term survival in ICU patients with aplastic anemia (AA).Methods The data of AA patients in the MIMIC-IV database were obtained and randomly assigned to the training set and testing set in a ratio of 7:3. Independent prognosis factors were identified through univariate and multivariate Cox regression analyses. The variance inflation factor was calculated to detect the correlation between variables. A nomogram model was built based on independent prognostic factors and risk scores for factors were generated. Model performance was tested using C-index, receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and Kaplan-Meier curve.Results A total of 1,963 AA patients were included. A nomogram model with 7 variables was built, including SAPS II, chronic pulmonary obstructive disease, body temperature, red cell distribution width, saturation of peripheral oxygen, age and mechanical ventilation. The C-indexes in the training set and testing set were 0.642 and 0.643 respectively, indicating certain accuracy of the model. ROC curve showed favorable classification performance of nomogram. The calibration curve reflected that its probabilistic prediction was reliable. DCA revealed good clinical practicability of the model. Moreover, the Kaplan-Meier curve showed that receiving mechanical ventilation could improve the survival status of AA patients in the short term but did not in the later period.Conclusion The nomogram model of the short-term survival rate of AA patients was built based on clinical characteristics, and early mechanical ventilation could help improve the short-term survival rate of patients.

ABSTRACTThis study aimed to elucidate the seroprevalence of antibodies to tetanus and pertussis among Chinese health care workers. Blood specimens from health care workers were collected during the 2021 annual medical examination at the First People’s Hospital of Wuhu. Commercial ELISA kits were employed to quantify serum IgG antibodies against tetanus toxin (anti-TT IgG) and both IgG and IgA antibodies against pertussis toxin (anti-PT IgG, anti-PT IgA). A concentration of anti-TT IgG exceeding 0.1 IU/ml was deemed seroprotective against tetanus, while concentrations of anti-PT IgG ≥ 50 IU/ml or anti-PT IgA ≥ 15 IU/ml were indicative of a prior pertussis infection. The overall seroprotective rate for anti-TT IgG stood at 10.43% (92/882), with the highest seroprotective rate (13.91%) in the 20–29 age group, followed by the 30–39 age group (10.57%), 40–49 age group (5.80%), and 50–59 age group (5.63%). Eighteen (2.04%) of the studied subjects were positive to anti-PT IgG, and the positive rate in 20–39 age group and 40–59 age group was 1.19% (8/673) and 4.78% (10/209), respectively. Thirty (3.40%) subjects displayed anti-PT IgG levels ≥100 IU/ml and/or anti-PT IgA ≥ 15 IU/ml, suggesting a recent pertussis infection within the preceding year. Over half (503/882, 57.03%) had undetectable anti-PT IgG antibodies. The majority of health care workers in China appear susceptible to tetanus and pertussis, and a significant subset has experienced pertussis infection. The implementation of booster vaccinations against these diseases for Chinese health care workers is recommended.

AbstractBackground At present, there are no available genetic data on the AGCU EX22 Kit from the Wuhu Han population.Aim This study investigates the applicability of the AGCU EX22 kit, designed for the Chinese population for forensic analysis and population genetics of the Wuhu Han population.Subjects and methods Bloodstains from 1565 unrelated healthy individuals in Wuhu city, Anhui Province, were collected for analysis. The AGCU EX22 kit was used for amplification, and capillary electrophoresis was used to separate the amplification products. Allele frequencies and forensic parameters were determined. The Wuhu Han population was compared to 10 reference populations through genetic distance, a phylogenetic neighbor-joining tree and principal component analysis.Results In total, 281 alleles and 1187 genotypes were observed. No significant deviations from Hardy-Weinberg equilibrium at any locus were found after Bonferroni’s correction. The 21 autosomal short tandem repeat (STR) genetic markers exhibited high informativeness and polymorphism. The cumulative power of discrimination and power of exclusion were 0.999999999999999999999999913380 and 0.999999996752339, respectively. Population comparisons revealed a genetic affinity between Wuhu Han and southern Han populations, except for the Guangdong Han population, which aligned with the traditional geographical division in China.Conclusion The AGCU EX22 Kit, containing 21 STR loci, is suitable for forensic application and population genetics studies in the Wuhu Han population.

BackgroundKDM6A is a demethylase encoded by a gene with female-biased expression due to escape from X inactivation. Its main role is to facilitate gene expression through removal of the repressive H3K27me3 mark, with evidence of some additional histone demethylase-independent functions. KDM6A mutations have been implicated in congenital disorders such as Kabuki Syndrome, as well as in sex differences in cancer.MethodsKdm6a was knocked out using CRISPR/Cas9 gene editing in F1 male and female mouse embryonic stem cells (ES) derived from reciprocal crosses between C57BL6 x Mus castaneus. Diploid and allelic RNA-seq analyses were done to compare gene expression between wild-type and Kdm6a knockout (KO) clones. The effects of Kdm6a KO on sex-biased gene expression were investigated by comparing gene expression between male and female ES cells. Changes in H3K27me3 enrichment and chromatin accessibility at promoter regions of genes with expression changes were characterized by ChIP-seq and ATAC-seq followed by diploid and allelic analyses.ResultsWe report that Kdm6a KO in male and female embryonic stem (ES) cells derived from F1 hybrid mice cause extensive gene dysregulation, disruption of sex biases, and specific parental allele effects. Among the dysregulated genes are candidate genes that may explain abnormal developmental features of Kabuki syndrome caused by KDM6A mutations in human. Strikingly, Kdm6a knockouts result in a decrease in sex-biased expression and in preferential downregulation of the maternal alleles of a number of genes. Most promoters of dysregulated genes show concordant epigenetic changes including gain of H3K27me3 and loss of chromatin accessibility, but there was less concordance when considering allelic changes.ConclusionsOur study reveals new sex-related roles of KDM6A in the regulation of developmental genes, the maintenance of sex-biased gene expression, and the differential expression of parental alleles.

Abstract By employing metal oxides as oxygen carriers, chemical looping demonstrates its effectiveness in transferring oxygen between reduction and oxidation environments to partially oxidize fuels into syngas and convert CO2 into CO. Generally, NiFe2O4 oxygen carriers have demonstrated remarkable efficiency in chemical looping CO2 conversion. Nevertheless, the intricate process of atomic migration and evolution within the internal structure of bimetallic oxygen carriers during continuous high‐temperature redox cycling remains unclear. Consequently, the lack of a fundamental understanding of the complex ionic migration and oxygen transfer associated with energy conversion processes hampers the design of high‐performance oxygen carriers. Thus, in this study, we employed in situ characterization techniques and theoretical calculations to investigate the ion migration behavior and structural evolution in the bulk of NiFe2O4 oxygen carriers during H2 reduction and CO2/lab air oxidation cycles. We discovered that during the H2 reduction step, lattice oxygen rapidly migrates to vacancy layers to replenish consumed active oxygen species, while Ni leaches from the material and migrates to the surface. During the CO2 splitting step, Ni migrates toward the core of the bimetallic oxygen carrier, forming Fe–Ni alloys. During the air oxidation step, Fe–Ni migrates outward, creating a hollow structure owing to the Kirkendall effect triggered by the swift transfer of lattice oxygen. The metal atom migration paths depend on the oxygen transfer rates. These discoveries highlight the significance of regulating the release–recovery rate of lattice oxygen to uphold the structures and reactivity of oxygen carriers. This work offers a comprehensive understanding of the oxidation/reduction‐driven atomic interdiffusion behavior of bimetallic oxygen carriers.

BackgroundAcute pancreatitis is an inflammatory disease that can lead to persistent organ failure (POF), which is associated with increased morbidity and mortality. Early prediction of POF in AP can significantly improve patient outcomes.ObjectiveTo develop and validate a nomogram that combines pain score with laboratory indicators for predicting POF in patients with AP.MethodsA retrospective cohort study was conducted, including patients diagnosed with AP. Pain score and laboratory indicators were collected within the first 24 h of admission. A nomogram was developed using logistic regression models and validated in a separate cohort.ResultsThere were 807 patients in the training cohort and 375 patients in the internal validation cohort.Multivariate logistic regression demonstrated that pain score, serum creatinine, hematocrit, serum calcium, and serum albumin were independent risk factors for the incidence of POF in patients with AP. The area under the curve of the nomogram constructed from the above factors were 0.924, respectively. The model demonstrated good calibration and discrimination in both the development and validation cohorts.ConclusionThe nomogram had a good performance in predicting POF in patients with AP and can be used to guide clinical decision-making.

Fuel cell vehicles have been paid more and more attention, while the low temperature cold start capability has become the main reason that hinders their large-scale commercialization, especially for the fuel cell bus. Generally, liquid heating (positive temperature coefficient thermistor (PTC) as the heat source) and fuel cell self-starting heating are the common cold start methods. However, these methods can bring about low start speed and high energy consumption. Therefore, a new cold start method combined with liquid heating and fuel cell self-starting is proposed to solve the problems. Besides, phase change material (PCM) is introduced to reduce energy consumption further. The PCM can absorb the waste heat of the fuel cell stack. Then the heat can be used for stack cold start by circulating liquid. In this study, a fuel cell bus cold start system simulating model is built. Based on this model, the fuel cell temperature and energy consumption during the cold start are analyzed. The results show that the method combined with liquid heating and fuel cell self-starting is superior to the liquid heating method. The cold start time and PTC consumption of the PTC-PCM-self-starting heating mode are 19.0 % and 19.2 % less than that of PTC-PCM heating mode. As for the combined heating method, dropping the self-starting temperature can not only increase the cold start speed but also reduce the proportion of electric heating. For every 1 °C decrease, the start-up time is shortened by 1 % on average, and the waste heat utilization rate is increased by 0.5 %. Although increasing the self-starting current can increase energy consumption, it will save more cold start time and reduce the proportion of electric heating. For every 1 A increase, the start-up time is shortened by 0.3 % on average, and the waste heat utilization rate is increased by 0.1 %. The PTC-PCM-self-starting heating method provides a way for fuel cell stack to start quickly and energy-efficiently in low temperature environment.

ABSTRACT Eggs, an important part of a healthy daily diet, can protect chicken embryo development due to the shell barrier and various antibacterial components within the egg white. Our previous study demonstrated that Salmonella Pullorum, highly adapted to chickens, can survive in the egg white and, therefore, be passed to newly hatched chicks. However, the survival strategy of Salmonella Pullorum in antibacterial conditions remains unknown. The overall transcripts in the egg white showed a large-scale shift compared to LB broth. The expression of common response genes and pathways, such as those involved in iron uptake, biotin biosynthesis, and virulence, was significantly changed, consistent with the other transovarial transmission serovar Enteritidis. Notably, membrane stress response, amino acid metabolism, and carbohydrate metabolism were specifically affected. Additional upregulated functionally relevant genes (JI728_13095, JI728_13100, JI728_17960, JI728_10085, JI728_15605, and nhaA) as mutants confirmed the susceptible phenotype. Furthermore, fim deletion resulted in an increased survival capacity in the egg white, consistent with the downregulated expression. The second-round RNA-Seq analysis of the Δfim mutant in the egg white revealed significantly upregulated genes compared with the wild type in the egg white responsible for energy metabolism located on the hyc and hyp operons regulated by FhlA, indicating the Δfim mutant cannot receive enough oxygen and switched to fermentative growth due to its inability to attach to the albumen surface. Together, this study provides a first estimate of the global transcriptional response of Salmonella Pullorum under antibacterial egg white and highlights the new potential role of fim deletion in optimizing energy metabolism pathways that may assist vertical transmission.IMPORTANCEPullorum disease, causing serious embryo death and chick mortality, results in substantial economic losses worldwide due to transovarial transmission. Egg-borne outbreaks are frequently reported in many countries. The present study has filled the knowledge gap regarding how the specific chicken-adapted pathogen Salmonella Pullorum behaves within the challenging environment of egg white. The deletion of the fim fimbrial system can increase survival in the albumen, possibly by reprogramming metabolism-related gene products, which reveals a new adaptive strategy of pathogens. Moreover, the comparison, including previous research on Salmonella Enteritidis, capable of vertical transmission, aims to provide diversified data sets in the field and further help to implement reasonable and effective measures to improve both food safety and animal health.

Abstract Aim To retrieve, analyse and summarize the relevant evidence on the prevention and management of bladder dysfunction in patients with cervical ancer after radical hysterectomy. Design Overview of systematic reviews. Methods 11 databases were searched for relevant studies from top to bottom according to the ‘6S’ model of evidence‐based resources. Two independent reviewers selected the articles, extracted the data and appraised the quality of the included reviews based on different types of evaluation tools. Results A total of 13 studies were identified, including four clinical consultants, four guidelines, four systematic reviews and one randomized controlled trial. 29 best evidence were summarized from five aspects, including definition, risk factors, assessment, prevention and management.

The scale and cluster development of offshore wind power faces the constraints of high construction cost, limited submarine corridor resources, etc. Under the background of offshore wind power parity development, it is urgent to consider the actual constraints of the project and the impact of project income on the owner, and the construction of offshore public station and the optimal selection of transmission method have become an important measure to reduce the cost and increase the efficiency of offshore wind power. A life-cycle cost model for offshore wind farm cluster grid-connection system planning is constructed to consider the project income, and the offshore public station location and capacity, transmission method, and high-voltage cable selection and path are optimized, which are solved by an improved single parent genetic algorithm and a topology repair strategy based on graph theory. The results show that the proposed planning scheme can effectively improve the life-cycle project income of the grid-connection system and provide technical support for the grid-connection planning of large-scale offshore wind farm clusters.

BackgroundDiffuse uterine leiomyomatosis (DUL) is a seldom-seen condition, with only a handful of cases of magnetic resonance imaging (MRI) findings documented. In clinical settings, it is often mistaken for multiple uterine leiomyomas due to a lack of adequate recognition of DUL.ObjectiveThis study shows two instances of DUL, underscoring their MRI findings to improve preoperative diagnostic precision.ConclusionFor patients exhibiting multiple uterine leiomyomas with masses present in the parametrial and abdominal cavities, consideration should be given to diagnosing DUL with DPL. The discoveries outlined in this paper furnish insights that can assist in directing treatment choices.

Abstract Background Patients with DNA mismatch repair‐proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti‐PD‐1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. Methods In this pilot study, we administered six preoperative doses of each 2‐week cycle of the anti‐PD‐1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5‐FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. Results By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow‐up was 24.7 months (IQR: 21.1–26.1). All patients underwent R0 surgical resection without treatment‐related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence‐free. Treatment‐related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10−8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non‐pCR tumors (p = 0.038 and p = 0.015, respectively). Conclusions Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non‐pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD‐1 blockade‐enhanced targeted chemotherapy require further investigation.

BackgroundThe prevalence of pulmonary tuberculosis (PTB) as an infectious disease continues to contribute significantly to global mortality. According to recent studies, the gut microbiota of PTB patients and healthy controls (HCs) show significant disparities. However, the causal relationship between them has yet to be elucidated.MethodsWe conducted a study using Mendelian Randomization (MR) to explore the potential causal link between gut microbiota and pulmonary tuberculosis (PTB). The summary statistics of the gut microbiota were acquired from the MiBioGen consortium, while data on PTB were sourced from pheweb.jp. A range of statistical methodologies were employed to evaluate causality, encompassing inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted model, and simple model. We utilized instrumental variables (IVs) that have a direct causal relationship with PTB to annotate SNPs, aiming to discover the genes harboring these genetic variants and uncover potential associations between host genes and the microbiome in patients with PTB.ResultsAmong the 196 bacterial traits in the gut microbiome, we have identified a total of three microbiomes that exhibit a significant association with PTB. The occurrence of Dorea (P = 0.0458, FDR-adjusted P = 0.0458) and Parasutterella (P = 0.0056, FDR-adjusted P = 0.0168) was linked to an elevated risk of PTB, while the presence of Lachnoclostridium (P = 0.0347, FDR-adjusted P = 0.0520) demonstrated a protective effect against PTB. Our reverse Two-Sample Mendelian Randomization (TSMR) analysis did not yield any evidence supporting the hypothesis of reverse causality from PTB to alterations in the intestinal flora.ConclusionWe have established a connection between the gut microbiota and PTB through gene prediction analysis, supporting the use of gut microecological therapy in managing PTB and paving the way for further understanding of how gut microbiota contributes to PTB’s development.

Pseudolaric acid B (PAB), an acid isolated from the roots of Pseudolarix kaempferi gorden, has shown antitumour effects through multiple mechanisms of action. The objective of this study was to investigate the anticancer effect of PAB on non-small cell lung cancer (NSCLC) and its underlying mechanism. In our experiments, we observed that PAB decreased cell viability, inhibited colony formation, induced cell cycle arrest, impeded scratch healing, and increased apoptosis in H1975 and H1650 cells. Additionally, PAB treatment enhanced the fluorescence intensity of MDC staining in NSCLC cells, upregulated the protein expression of microtubule-associated protein light chain 3 II (LC3 II), and downregulated the expression of sequestosome 1 (SQSTM1/P62). Combined treatment with PAB and chloroquine (CQ) increased the protein expression levels of LC3 II and P62 while decreasing the apoptosis of H1975 and H1650 cells. Moreover, treatment with PAB led to significant mTOR inhibition and AMPK activation. PAB combined with compound C (CC) inhibited autophagy and apoptosis. Furthermore, PAB treatment increased intracellular reactive oxygen species (ROS) levels in NSCLC cells, which correlated with the modulation of the AMPK/mTOR signalling pathway and was associated with autophagy and apoptosis. Finally, we validated the antitumour growth activity and mechanism of PAB in vivo using athymic nude mice bearing H1975 tumour cells. In conclusion, our findings suggest that PAB can induce apoptosis and autophagic cell death in NSCLC through the ROS-triggered AMPK/mTOR signalling pathway, making it a promising candidate for future NSCLC treatment.

To evaluate a novel technique for six-point scleral fixation of a three-looped haptics posterior chamber intraocular lens (PCIOL) by a single suture. Nine eyes of nine patients were studied from September 2021 to March 2023. All patients had undergone vitrectomy. Only a single 9-0 polypropylene suture was used for scleral fixation. The three looped haptics were fixed at 12, 4, and 8 o'clock with six-point scleral fixation. The entire procedure took about 30 min. Among the nine patients, eight (88.8%) eyes had a significant improvement in best-corrected visual acuity, whereas one (11.2%) eye showed no change. No intraoperative or postoperative complications were observed. By ultrasonic biomicroscopy examination, intraocular lenses were well positioned and stable with no tilt in the horizontal and vertical axis. The method of six-point scleral fixation of a three-looped haptics PCIOL by a single suture is safe and effective.