Search

Abstract Background Diabetic ketoacidosis (DKA) is a potentially life-threatening disorder associated with severe alterations in metabolism and acid–base status. Mitochondrial dysfunction is associated with diabetes and its complications. Thiamine and coenzyme Q10 (CoQ10) are important factors in aerobic metabolism. In this study, we measured cellular oxygen consumption rates (OCRs) and the effects of in vitro administration of thiamine and CoQ10 on OCRs in patients with DKA versus healthy controls. Methods Blood samples were collected from a prospective cohort of patients with DKA and from controls. Cellular OCRs were measured in peripheral blood mononuclear cells (PBMC) without treatment and after treatment with thiamine, CoQ10, or both. The mitochondrial profile was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear quantile mixed model was used to compare OCRs and estimate treatment effects. Results A total of 62 patients with DKA and 48 controls were included in the study. The median basal and maximal OCRs were lower in the DKA group than in the control group (basal: 4.7 [IQR: 3.3, 7.9] vs. 7.9 [5.0, 9.5], p = 0.036; maximal: 16.4 [9.5, 28.1] vs. 31.5 [20.6, 46.0] pmol/min/µg protein, p

Abstract Qingdai (QD), derived from various plant sources, is commonly used in traditional Chinese medicine for ulcerative colitis (UC) treatment. However, the clinical efficacy and mechanisms of orally administered QD remain unclear. This study aims to evaluate QD’s efficacy in UC treatment and uncover its active components and mechanisms. A randomized controlled trial compared QD to Adisa, followed by UPLC-Q-TOF/MS and network pharmacology analyses to identify QD’s core components and targets. In vivo experiments on a UC mouse model explored QD’s impact on the AHR-Th17/Treg pathway using PCR, WB, ELISA, and flow cytometry. Results showed QD’s efficacy in UC treatment, with mucosal healing and remission comparable to Adisa. UPLC-Q-TOF/MS identified 16 core components in mouse colon tissue, with network pharmacology revealing 67 targets, potentially involving the IL-17 signaling pathway and Th17 cell differentiation. QD and its components up-regulated AHR, CYP1A1, and Foxp3, while down-regulating RORγt. Additionally, QD modulated pro-inflammatory (IL-6, IL-17 A) and anti-inflammatory (IL-10, TGF-β1) factors, and Treg/Th17 cell ratios in LPMC. Oral QD administration effectively promoted mucosal healing and improved UC symptoms, potentially through AHR-Th17/Treg pathway regulation.

Abstract Background Usher syndrome type 3 (USH3) is an autosomal recessive inherited disorder caused by pathogenic variants in the CLRN1 gene. Object To evaluate the genotype-phenotype correlation of Usher syndrome type 3 (USH3) in a deaf-blind Chinese family of 3 generations with 2 patients. Methods We collected blood samples and clinical data from all of the pedigree family members. Genomic DNA was isolated from peripheral leukocytes using standard method. Targeted next generation sequencing and Sanger sequencing were performed to find the pathogenic variants in this family. Digital PCR and plasmid overexpression assay were used to verify the pathogenicity of variant sites in different transcripts. Results All patients developed bilateral sensorineural hearing loss (SHL), progressive vision loss and nyctalopia. NGS of genes for Usher syndrome, deafness and retinal dystrophy identified a locus mutation in CLRN1 that caused completely different amino acid changes in different transcripts[CLRN1:c.474T > A(P.Cys158Ter) at NM_001256819.2 or c.302T > A(p.Val101Asp) at NM_174878.3], and plasmid overexpression experiments confirmed that the c.474T > A(P.Cys158Ter, NM_001256819.2) was a pathogenic variant which has never been associated with Usher syndrome in China, and the transcript of this mutation was not the version commonly found worldwide. Conclusions The CLRN1c.474T > A(NM_001256819.2) mutation is the causative variant in the Chinese family with USH3. The pathogenicity of different transcripts should be particularly considered in pathogenicity analysis.

Objective: This study aimed to investigate the protective effect and mechanism of yeast extract and curcumin-yeast extract on acute alcoholic liver injury in mice. Methods: The mouse model of acute alcoholic liver injury was established, and the mice were administered with yeast extract and curcumin-yeast extract. Changes in ALT, AST, T-GSH, GSH-Px, and MDA levels were observed in the serum and liver tissue, respectively. Pathological sections of liver tissue were examined to observe the damage. The intestinal flora of mice was analyzed. Results: Compared with the model group, both yeast extract and curcumin-yeast extract reduced the levels of ALT, AST, MDA, TC, and TG, increased the activities of GSH-Px and T-GSH, and alleviated fatty infiltration and inflammatory infiltration of hepatocytes. Curcumin-yeast extract effectively restored the abundance of Acinetobacter, Prevotella, and Ruminococcus, which had been altered by alcohol. The restorative effect was superior to that of the yeast extract group. Conclusion: Yeast extract and curcumin-yeast extract showed significant protective effects against acute alcoholic liver injury in mice. This mechanism may be associated with the regulation of oxidative stress, lipid metabolism, and intestinal flora.

Abstract Background Programmed cell death ligand 1 (PD-L1), as a reliable predictive biomarker, plays an important role in guiding immunotherapy of lung cancer. To investigate the value of CT-based deep learning radiomics signature to predict PD-L1 expression in non-small cell lung cancers(NSCLCs). Methods 259 consecutive patients with pathological confirmed NSCLCs were retrospectively collected and divided into the training cohort and validation cohort according to the chronological order. The univariate and multivariate analyses were used to build the clinical model. Radiomics and deep learning features were extracted from preoperative non-contrast CT images. After feature selection, Radiomics score (Rad-score) and deep learning radiomics score (DLR-score) were calculated through a linear combination of the selected features and their coefficients. Predictive performance for PD-L1 expression was evaluated via the area under the curve (AUC) of receiver operating characteristic, the calibration curves, and the decision curve analysis. Results The clinical model based on Cytokeratin 19 fragment and lobulated shape obtained an AUC of 0.767(95% CI: 0.673–0.860) in the training cohort and 0.604 (95% CI:0.477–0.731) in the validation cohort. 11 radiomics features and 15 deep learning features were selected by LASSO regression. AUCs of the Rad-score were 0.849 (95%CI: 0.783–0.914) and 0.717 (95%CI: 0.607–0.826) in the training cohort and validation cohort, respectively. AUCs of DLR-score were 0.938 (95%CI: 0.899–0.977) and 0.818(95%CI:0.727–0.910) in the training cohort and validation cohort, respectively. AUCs of the DLR-score were significantly higher than those of the Rad-score and the clinical model. Conclusion The CT-based deep learning radiomics signature could achieve clinically acceptable predictive performance for PD-L1 expression, which showed potential to be a surrogate imaging biomarker or a complement of immunohistochemistry assessment.

Abstract H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.

This is an article in the field of metallurgical engineering. The preparation of black copper electrolyte by removing copper from secondary refining slag of high copper and high tin anode furnace by hydrogen peroxide oxidation and acid leaching was studied. The process conditions related to the removal efficiency of the copper and arsenic were researched including the hydrogen peroxide dosage, reaction temperature, sulfuric acid concentration and reaction time. Results show that, under the following optimal conditions, including refining slag of 20.0 g, 2.5 mol/L sulfuric acid of 200 mL, solid-liquid ratio of 1/10, temperature of 65 ℃, dosage of hydrogen peroxide of 10.0 mL, stirring speed of 400 r/min and leaching time of 60 min, the leaching ratios of Cu and As can reach 88.98% and 87.33%, respectively, and the leaching ratios of Ni and Sn were only 7.72% and 1.34%, respectively. The concentration of copper ion in the leaching solution was 48.48 g/L, which can be used as the supplement of black copper electrolyte.

Terrestrial sedimentary basins are influenced by rapid changes in the clay content, resulting in significant differences in the lateral sealing capacity (shale gouge ratio, SGR) of different parts of the fault. In the present study, we used a method of setting virtual wells and using seismic inversion data to accurately calculate the SGR of faults in strata composed of interbedded sandstone and mudstone calculate the clay content of the strata and to compensate for the low level of the actual well control. Optimal well spacing was determined based on the variable clay content of the formation. The planar variation of the fault throw was characterized via seismic interpretation. We also examined the lateral sealing of faults. The Putaohua oil layer in the S14 area of the Sanzhao Sag in the Songliao Basin was chosen as an case study. Based on the calculation of fault SGR values and the oil distribution, the evaluation criteria for the fault sealing capacity were determined, and the changes in the lateral sealing capacity of the faults were analyzed. This approach accurately estimates fault SGR values and predicts the effective oil-bearing area within the fault zone. It is also suitable for evaluating the lateral sealing of faults in strata composed of interbedded sandstone and mudstone. Our findings provide an in-depth understanding of the lateral sealing of faults and can aid in further research on petroleum distribution patterns.

Abstract Low birth weight and unhealthy lifestyle are both associated with an increased risk of hypertension. The authors aimed to assess the joint association and interaction of birth weight and lifestyle with incident hypertension. The authors included 205 522 participants free of hypertension at baseline from UK Biobank. A healthy lifestyle score was constructed using information on body mass index, physical activity, diet, smoking status and alcohol intake. Cox proportional hazard models were used to investigate the impact of birth weight, healthy lifestyle score and their joint effect on hypertension. The authors documented 13 548 (6.59%) incident hypertension cases during a median of 8.6 years of follow‐up. The multivariate adjusted hazard ratios and 95% confidence intervals were 1.12 (1.09, 1.15) per kg lower birth weight and 0.76 (0.75, 0.77) per score increment in healthy lifestyle score. Healthy lifestyle reduced the risk of hypertension in any category of different birth weight groups. The preventive effect of healthy lifestyle on hypertension was the most pronounced at lower birth weight with

Abstract A prompt diagnosis of breast cancer in its earliest phases is necessary for effective treatment. While Computer-Aided Diagnosis systems play a crucial role in automated mammography image processing, interpretation, grading, and early detection of breast cancer, existing approaches face limitations in achieving optimal accuracy. This study addresses these limitations by hybridizing the improved quantum-inspired binary Grey Wolf Optimizer with the Support Vector Machines Radial Basis Function Kernel. This hybrid approach aims to enhance the accuracy of breast cancer classification by determining the optimal Support Vector Machine parameters. The motivation for this hybridization lies in the need for improved classification performance compared to existing optimizers such as Particle Swarm Optimization and Genetic Algorithm. Evaluate the efficacy of the proposed IQI-BGWO-SVM approach on the MIAS dataset, considering various metric parameters, including accuracy, sensitivity, and specificity. Furthermore, the application of IQI-BGWO-SVM for feature selection will be explored, and the results will be compared. Experimental findings demonstrate that the suggested IQI-BGWO-SVM technique outperforms state-of-the-art classification methods on the MIAS dataset, with a resulting mean accuracy, sensitivity, and specificity of 99.25%, 98.96%, and 100%, respectively, using a tenfold cross-validation datasets partition.

Abstract The haemagglutinin–neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines.

Abstract Objective The objective of this study was to evaluate the association between hyperthyroidism and the risk of developing erectile dysfunction (ED). Methods A comprehensive search of multiple databases, including PubMed, Embase, Cochrane, and Web of Science, was conducted to identify relevant studies investigating the relationship between hyperthyroidism and ED in men. The quality of the included studies was assessed using the Newcastle‒Ottawa Quality Rating Scale, and a meta-analysis was performed using Stata 16.0 and RevMan 5.3 software. Results A total of four papers encompassing 25,519 study subjects were included in the analysis. Among these, 6,429 individuals had hyperthyroidism, while 19,090 served as controls. The overall prevalence of ED in patients with hyperthyroidism was determined to be 31.1% (95% CI 0.06–0.56). In patients with uncomplicated hyperthyroidism, the incidence of ED was 21.9% (95% CI 0.05–0.38). The combined odds ratio (OR) for the four studies was 1.73 (OR: 1.73; 95% CI [1.46–2.04]; p

Abstract Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

Objectives Osteoporotic vertebral fractures (OVFs) are a critical public health concern requiring urgent attention, and severe OVFs impose substantial health and economic burdens on patients and society. Analysis of the risk factors for severe OVF is imperative to actively prevent the occurrence of this degenerative disorder. This study aimed to investigate the risk factors associated with the severity of OVF, with a specific focus on changes in the paraspinal muscles. Methods A total of 281 patients with a first‐time single‐level acute OVF between January 2016 and January 2023 were enrolled in the study. Clinical and radiological data were collected and analyzed. The cross‐sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles, including the multifidus muscles (MFMs), erector spinae muscles (ESMs), and psoas major muscles (PSMs), were measured by magnetic resonance imaging (MRI) of the L4/5 intervertebral discs. According to the classification system of osteoporotic fractures (OF classification) and recommended treatment plan, OVFs were divided into a low‐grade OF group and a high‐grade OF group. Univariate and multivariate logistic regression analyse s were performed to identify risk factors associated with the severity of OVF. Results Ninety‐eight patients were included in the low‐grade OF group, and 183 patients were included in the high‐grade OF group. Univariate analysis revealed a significantly higher incidence of a high degree of FI of MFMs (OR = 1.71, p = 0.002) and ESMs (OR = 1.56, p = 0.021) in the high‐grade OF group. Further multivariate logistic regression analysis demonstrated that a high degree of FI of the MFMs (OR = 1.71, p = 0.002) is an independent risk factor for the severity of OVF. Conclusion A high degree of FI of the MFMs was identified as an independent risk factor for the severity of OVF. Decreasing the degree of FI in the MFMs might lower the incidence of the severity of OVF, potentially reducing the necessity for surgical intervention in OVF patients.

ABSTRACT: H9N2 avian influenza virus is a significant poultry pathogen that provides internal genes for multiple zoonotic subtypes of avian influenza, presenting a severe threat to public health. The isolation rate of H9N2 in poultry has increased annually in recent years. In this study, a recombinant Herpesvirus of Turkeys (HVT) vaccine expressing H9-HA was constructed using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. In the construction of HVT-EGFP-HA recombinant virus, nonhomologous end joining (NHEJ) is a much more efficient strategy compare to Homology-directed recombination (HDR). HVT-HA demonstrated stability and consistent replication with the parent strain. Subcutaneous injection and in-ovo injection of HVT-HA induced different levels of immune response. Compared to in-ovo injection of HVT-HA, subcutaneous injection induced significantly higher neutralizing serum antibodies. This finding is supported by the significantly higher CD4+ T cell response in Peripheral blood mononuclear cell Peripheral blood mononuclear cell (PBMC) in the subcutaneous injection group. However, in-ovo injection of HVT-HA resulted in significantly higher neutralizing antibodies in the Harderian glands. In addition, it significantly inhibited viral shedding after intranasal exposure to H9N2. This phenomenon could be attributed to the mucosal immunity present in the Hadrian gland. Thus, our findings indicate that the in-ovo injection of the HVT-HA recombinant vaccine is a promising method to inhibit the transmission of H9N2 via the upper respiratory tract in chickens.

Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China’s primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.

ABSTRACTCancer-associated fibroblasts (CAFs) exhibit remarkable phenotypic heterogeneity, with specific subsets implicated in immunosuppression in various malignancies. However, whether and how they attenuate anti-tumor immunity in gastric cancer (GC) remains elusive. CPT1C, a unique isoform of carnitine palmitoyltransferase pivotal in regulating fatty acid oxidation, is briefly indicated as a protumoral metabolic mediator in the tumor microenvironment (TME) of GC. In the present study, we initially identified specific subsets of fibroblasts exclusively overexpressing CPT1C, hereby termed them as CPT1C+CAFs. Subsequent findings indicated that CPT1C+CAFs fostered a stroma-enriched and immunosuppressive TME as they correlated with extracellular matrix-related molecular features and enrichment of both immunosuppressive subsets, especially M2-like macrophages, and multiple immune-related pathways. Next, we identified that CPT1C+CAFs promoted the M2-like phenotype of macrophage in vitro. Bioinformatic analyses unveiled the robust IL-6 signaling between CPT1C+CAFs and M2-like phenotype of macrophage and identified CPT1C+CAFs as the primary source of IL-6. Meanwhile, suppressing CPT1C expression in CAFs significantly decreased IL-6 secretion in vitro. Lastly, we demonstrated the association of CPT1C+CAFs with therapeutic resistance. Notably, GC patients with high CPT1C+CAFs infiltration responded poorly to immunotherapy in clinical cohort. Collectively, our data not only present the novel identification of CPT1C+CAFs as immunosuppressive subsets in TME of GC, but also reveal the underlying mechanism that CPT1C+CAFs impair tumor immunity by secreting IL-6 to induce the immunosuppressive M2-like phenotype of macrophage in GC.

ABSTRACTNewcastle disease virus (NDV) typically induces severe illness in poultry and results in significant economic losses for the worldwide poultry sector. NDV, an RNA virus with a single-stranded negative-sense genome, is susceptible to mutation and immune evasion during viral transmission, thus imposing enormous challenges to avian health and poultry production. NDV is composed of six structural proteins and two nonstructural proteins that exert pivotal roles in viral infection and antiviral responses by interacting with host proteins. Nowadays, there is a particular focus on the mechanisms of virus-host protein interactions in NDV research, yet a comprehensive overview of such research is still lacking. Herein, we briefly summarize the mechanisms regarding the effects of virus-host protein interaction on viral infection, pathogenesis, and host immune responses. This review can not only enhance the present comprehension of the mechanism underlying NDV and host interplay, but also furnish a point of reference for the advancement of antiviral measures.

Introduction Perioperative anaphylaxis (POA) can lead to significant complications. Therefore, accurate identification of allergens for POA patients is critical to ensure the safety of future surgical and anaesthetic procedures. Existing perioperative allergen detection methods face challenges in sensitivity and specificity. The passive mast cell activation test (pMAT) has recently emerged as a potential diagnostic tool. Our study aims to evaluate the diagnostic efficacy of pMAT for identifying perioperative allergens, with a focus on non-depolarising neuromuscular blocking agents, the most common culprits of POA.Methods and analysis This prospective diagnostic accuracy study will measure the diagnostic accuracy of pMAT in POA patients. Participants will undergo skin testing (ST), basophil activation testing (BAT) and pMAT. The diagnostic validity of pMAT will be assessed based on the results of ST and BAT. The assessment of diagnostic accuracy will include sensitivity, specificity, likelihood ratios, and false-positive and false-negative rates while measurement of the consistency rate will assess reliability.Ethics and dissemination This study has been approved by the Institutional Review Board of China-Japan Friendship Hospital (2023-KY-247). Results will be disseminated through academic presentations and peer-reviewed journal publications and will provide valuable scientific data and some new insights into the diagnostic accuracy of pMAT.

Summary: Maternal-to-zygotic transition (MZT) is central to early embryogenesis. However, its underlying molecular mechanisms are still not well described. Here, we revealed the expression dynamics of 5,000 proteins across four stages of zebrafish embryos during MZT, representing one of the most systematic surveys of proteome landscape of the zebrafish embryos during MZT. Nearly 700 proteins were differentially expressed and were divided into six clusters according to their expression patterns. The proteome expression profiles accurately reflect the main events that happen during the MZT, i.e., zygotic genome activation (ZGA), clearance of maternal mRNAs, and initiation of cellular differentiation and organogenesis. MZT is modulated by many proteins at multiple levels in a collaborative fashion, i.e., transcription factors, histones, histone-modifying enzymes, RNA helicases, and P-body proteins. Significant discrepancies were discovered between zebrafish proteome and transcriptome profiles during the MZT. The proteome dynamics database will be a valuable resource for bettering our understanding of MZT.

Abstract Background Although the constitutively activated Wnt/β‐catenin signaling pathway plays vital roles in gastric cancer (GC) progression, few Wnt inhibitors are approved for clinical use. Additionally, the clinical significance of long non‐coding RNAs (lncRNAs) in GC intraperitoneal dissemination (IPD) remains elusive. Here, we investigated the function and therapeutic potential of Wnt‐transactivated lncRNA, colon cancer‐associated transcript 5 (CCAT5), in GC metastasis. Methods LncRNA‐sequencing assay was performed to document abundance changes of lncRNAs induced by Wnt family member 3A (Wnt3a) and degradation‐resistant β‐catenin (S33Y mutated) in ascites‐derived GC cells with low Wnt activity. Luciferase reporter, Chromatin immunoprecipitation (ChIP)‐re‐ChIP assays were performed to determine how CCAT5 was transcribed. The clinical significance of CCAT5 was examined in 2 cohorts of GC patients. The biological function of CCAT5 was investigated through gain‐ and loss‐of‐function studies. The molecular mechanism was explored through RNA‐sequencing, mass spectrometry, and CRISPR/Cas9‐knocknout system. The therapeutic potential of CCAT5 was examined through RNAi‐based cell xenograft model and patient‐derived xenograft (PDX) model of IPD. Results We identified a novel Wnt‐regulated lncRNA, CCAT5, which was transactivated by the β‐catenin/transcription factor 3 (TCF3) complex. CCAT5 was significantly upregulated in GC and predicted poor prognosis. Functional studies confirmed the promotive role of CCAT5 in GC growth and metastasis. Mechanistically, CCAT5 bound to the C‐end domain of signal transducer and activator of transcription 3 (STAT3) and blocks Src homology 2 domain‐containing protein tyrosine phosphatase 1 (SHP‐1)‐mediated STAT3Y705 dephosphorylation, leading to STAT3 nuclear entry and transactivation, thus accelerating GC progression. Furthermore, we demonstrated that both Wnt3a and β‐catenin acted as activator of STAT3 signaling pathway, and the interplay between CCAT5 and STAT3 was functionally essential for Wnt‐drived STAT3 signaling and tumor evolution. Finally, we revealed in vivo si‐CCAT5 selectively attenuated growth and metastasis of Wnthigh GC, but not Wntlow GC. The combination of si‐CCAT5 and oxaliplatin displayed obvious synergistic therapeutic effects on Wnthigh PDX mice. Conclusions We identified a novel Wnt‐transactivated lncRNA, CCAT5. Our study revealed a mechanism of STAT3 signaling regulation via canonical Wnt signaling and the functional significance of CCAT5 as critical mediator. We provided conceptual advance that lncRNAs serve as therapeutic targets reversing GC progression.

AbstractContext Da-Cheng-Qi Decoction (DCQD) has a significant effect on Severe Acute Pancreatitis-Associated Acute Lung Injury (SAP-ALI).Objective To explore the mechanism of DCQD in the treatment of SAP-ALI based on intestinal barrier function and intestinal lymphatic pathway.Materials and methods Forty-five Sprague-Dawley rats were divided into three groups: sham operation, model, and DCQD. The SAP model was induced by a retrograde infusion of 5.0% sodium taurocholate solution (1 mg/kg) at a constant rate of 12 mL/h using an infusion pump into the bile-pancreatic duct. Sham operation and model group were given 0.9% normal saline, while DCQD group was given DCQD (5.99 g/kg/d) by gavage 1 h before operation and 1, 11 and 23 h after operation. The levels of HMGB1, RAGE, TNF-α, IL-6, ICAM-1, d-LA, DAO in blood and MPO in lung were detected using ELISA. The expression of HMGB1, RAGE, NF-κB p65 in mesenteric lymph nodes and lung were determined.Results Compared with SAP group, DCQD significantly reduced the histopathological scoring of pancreatic tissue (SAP, 2.80 ± 0.42; DCQD, 2.58 ± 0.52), intestine (SAP, 3.30 ± 0.68; DCQD, 2.50 ± 0.80) and lung (SAP, 3.30 ± 0.68; DCQD, 2.42 ± 0.52). DCQD reduced serum HMGB1 level (SAP, 134.09 ± 19.79; DCQD, 88.05 ± 9.19), RAGE level (SAP, 5.05 ± 1.44; DCQD, 2.13 ± 0.54). WB and RT-PCR showed HMGB1-RAGE pathway was inhibited by DCQD (p

Newcastle disease virus (NDV) poses a significant threat to the poultry industry, with the emergence of genotype VII NDV leading to extensive outbreaks and economic losses. Vaccination is the primary means of controlling NDV, but the presence of maternal antibodies (MDAs) can interfere with the immunological effect of live virus vaccines. Thus, we constructed a chimeric NDV live virus vaccine, LX-OAI4S, by replacing the extracellular regions of the F and HN genes of the NDV LX strain with the corresponding regions of the A-VII vaccine strain. The chimeric vaccine LX-OAI4S demonstrated high genetic stability, good safety, and strong reproductive capacity in chicken embryos. The LX-OAI4S vaccine induced rapid antibody production in specific pathogen-free (SPF) and commercial chickens via the intranasal and intraocular (IN/IO) routes, with hemagglutination inhibition (HI) antibody titers reaching 4.71 ± 1.03 log2 at 7 days post-vaccination (dpv), significantly higher than those of the two classical vaccine strains La Sota and VG/GA. The LX-OAI4S vaccine group provided effective protection against the challenge of genotype VII NDV virulent strain JS2/06 and inhibited viral shedding. When administered via spray, the LX-OAI4S vaccine elicited high systemic immunity against NDV in both SPF and commercial chickens, effectively protecting against clinical disease and reducing viral shedding. The chickens were exposed to high-dose vaccine for spray vaccination, and no adverse reactions were observed after vaccination. Despite the presence of anti-NDV MDAs in chickens, the NDV-specific antibody titers were significantly greater in the vaccinated groups than in the unvaccinated group. The vaccine exhibited high immunogenicity and the potential to overcome maternal antibody interference. The LX-OAI4S vaccine is a promising candidate for an ND vaccine. Its administration via spray can effectively prevent the occurrence of ND, making it a valuable tool for the poultry industry.

Newcastle disease virus (NDV), known as avian paramyxovirus-1, poses a significant threat to poultry production worldwide. Vaccination currently stands as the most effective strategy for Newcastle disease control. However, the mesogenic vaccine strain Mukteswar has been observed to evolve into a velogenic variant JS/7/05/Ch during poultry immunization. Here, we aimed to explore the mechanisms underlying virulence enhancement of the two viruses. Pathogenically, JS/7/05/Ch mediated stronger virulence and pathogenicity in vivo compared to Mukteswar. Comparative transcriptome analysis revealed 834 differentially expressed genes (DEGs), comprising 339 up-regulated and 495 down-regulated genes, in the spleen, and 716 DEGs, with 313 up-regulated and 403 down-regulated genes, in the thymus. Gene Ontology (GO) analysis indicated that these candidate targets primarily participated in cell and biological development, extracellular part and membrane composition, as well as receptor and binding activity. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis unveiled a substantial portion of candidate genes predominantly involved in cellular processes, environmental information processing, metabolism, and organismal systems. Additionally, five DEGs (TRAT1, JUP, LPAR4, CYB561A3, and CXCR5) were randomly identified through RNA-seq analysis and subsequently confirmed via quantitative real-time polymerase chain reaction (qRT-PCR). The findings revealed a marked up-regulation in the expression levels of these DEGs induced by JS/7/05/Ch compared to Mukteswar, with CYB561A3 and CXCR5 exhibiting significant increases. The findings corroborated the sequencing accuracy, offering promising research directions. Taken together, we comprehensively evaluated transcriptomic alterations in chicken immune organs infected by NDV strains of diverse virulence. This study establishes a basis and direction for NDV virulence research.

Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT.

Abstract The Pampean flat slab in central Chile and Argentina is characterized by the inland migration and subsequent cessation of arc volcanism since the mid‐Miocene. Slab flattening also affects the distribution and number of intermediate‐depth earthquakes and the evolution of the overlying continental thermal structure. In this study, we combine thermal‐mechanical models with petrological models to examine temporal changes in pressure, temperature, and composition during flat‐slab subduction and estimate water carrying capacity, predicted melt distributions and predicted changes in melt composition. Model results indicate that the present‐day flattened Nazca plate carries water to ∼700 km inland from the trench and could cause flux melting if the material above the slab remains fertile. Observed slab seismicity matches areas where hydrated materials have ∼>3 wt% H2O in the oceanic crust and mantle lithosphere. Seismicity increases as slab water carrying capacity decreases (slab dehydration). As P‐T conditions and compositions of the rock trapped above the slab change during slab flattening, flux melting switches from a peridotite‐dominated early phase to a combined mid‐ocean ridge basalt/eclogite and peridotite melting at ∼8 Ma. The results provide broad consistency with known earthquake distributions, seismic velocities, and observed temporal and spatial changes in volcanic patterns above the Pampean flat slab and point toward the role of melt depletion in the decrease and ultimate cessation of arc volcanism in this region.

Phthalates (PAEs) and polycyclic aromatic hydrocarbons (PAHs) are frequently detected in females of reproductive age. Many studies have found that environmental PAE and PAH levels are independent risk factors for gestational hypertension. However, exposure to both components is a more realistic scenario. To better assess the health effects of PAEs and PAHs in pregnant women, we explored the associations of exposure to both individual and combined PAEs and PAHs with gestational hypertension. This nested case–control study was a component of a prospective cohort study conducted in Beijing, China. We included 206 women with gestational hypertension and 214 pregnant controls. We used gas chromatography/tandem mass spectrometry (GC–MS/MS) to detect 8 PAEs and 13 PAHs in > 80 % of all collected hair samples. Multiple linear regression models were employed to test the individual associations between each component and gestational hypertension. A quantile-based g-computation (qgcomp) model and a weighted quantile sum (WQS) regression model were used to estimate whether exposure to both PAEs and PAHs increased the risk of gestational hypertension. The individual exposure analyses revealed that diethyl phthalate (DEP), diisobutyl phthalate (DIBP) (both PAEs), benzo(k)fluoranthene (BKF), anthracene, (ANT), and benzo(a)pyrene (BAP) (all PAHs) were positively associated with increased risk of gestational hypertension. In mixed-effect analyses, the qgcomp model indicated that co-exposure to PAEs and PAHs increased the risk of gestational hypertension (odds ratio = 2.01; 95 % confidence interval: 1.02, 3.94); this finding was verified by the WQS regression model. Our findings support earlier evidence that both PAEs and PAHs increase the risk of gestational hypertension, both individually and in combination. This suggests that reductions in exposure to endocrine system-disrupting chemicals such as PAEs and PAHs might reduce the risk of gestational hypertension.

Abstract The haemagglutinin-neuraminidase (HN) protein plays a crucial role in the infectivity and virulence of Newcastle disease virus (NDV). In a previous study, the mutant HN protein was identified as a crucial virulence factor for the velogenic variant NDV strain JS/7/05/Ch, which evolved from the prototypic vaccine strain Mukteswar. Furthermore, macrophages are the main susceptible target cells of NDV. However, the possible involvement of cellular molecules in viral infectivity remains unclear. Herein, we elucidate the crucial role of vimentin, an intermediate filament protein, in regulating NDV infectivity through targeting of the HN protein. Using LC‒MS/MS mass spectrometry and coimmunoprecipitation assays, we identified vimentin as a host protein that differentially interacted with prototypic and mutant HN proteins. Further analysis revealed that the variant NDV strain induced more significant rearrangement of vimentin fibres compared to the prototypic NDV strain and showed an interdependence between vimentin rearrangement and virus replication. Notably, these mutual influences were pronounced in HD11 chicken macrophages. Moreover, vimentin was required for multiple infection processes of the variant NDV strain in HD11 cells, including viral internalization, fusion, and release, while it was not necessary for those of the prototypic NDV strain. Collectively, these findings underscore the pivotal role of vimentin in NDV infection through targeting of the HN protein, providing novel targets for antiviral treatment strategies for NDV.

As damming material, fine-grained tailings present challenges such as low dam strength and poor stability. To address these issues, this study employs geotextile tube technology to mix water with fine-grained tailings, forming a tailing slurry with a concentration of 60%, which is filled into a geotextile bag to form a geotextile tube, so as to improve the stability of fine-grained tailings. The shear strength characteristics of each interface under different consolidation times and different filling degrees were studied via an indoor shear experiment, including the shear strength of tailing particles, that between tailings and geotextiles, and that within geotextile tubes themselves. The results show that the shear strength of each interface conforms to the Mohr–Coulomb strength criterion, and that the interface cohesion is greatly affected by the consolidation time, while the interface friction angle is mainly affected by the filling degree. Moreover, the shear strength comparison, based on the comprehensive friction angle concept, indicates a substantial increase in shear strength at the interfaces between geotextile tubes compared to both that of the tailings themselves and the interface between tailings and geotextiles, highlighting the reinforcing effect of the geotextile tube filling technology on tailings’ shear strength.

Pancreatic cancer (PC) is an aggressive malignant tumor with low rate of surgical resection and poor prognosis. Transforming growth factor-β (TGF-β) is a cytokine that has both protumor and antitumor activities, depending on tumor microenvironment. The interaction between TGF-β signaling and the tumor microenvironment in PC is complex. Here, we reviewed the role of TGF-β in the tumor microenvironment of PC, highlighting producers of TGF-β and TGF-β responders in the tumor microenvironment of PC.

Newcastle disease virus (NDV) has been extensively studied as a promising oncolytic virus for killing tumor cells in vitro and in vivo in clinical trials. However, the viral components that regulate the oncolytic activity of NDV remain incompletely understood. In this study, we systematically compared the replication ability of different NDV genotypes in various tumor cells and identified NP protein determines the oncolytic activity of NDV. On the one hand, NDV strains with phenylalanine (F) at the 450th amino acid position of the NP protein (450th-F-NP) exhibit a loss of oncolytic activity. This phenotype is predominantly associated with genotype VII NDVs. In contrast, the NP protein with a leucine amino acid at this site in other genotypes (450th-L-NP) can facilitate the loading of viral mRNA onto ribosomes more effectively than 450th-F-NP. On the other hand, the NP protein from NDV strains that exhibit strong oncogenicity interacts with eIF4A1 within its 366-489 amino acid region, leading to the inhibition of cellular mRNA translation with a complex 5' UTR structure. Our study provide mechanistic insights into how highly oncolytic NDV strains selectively promote the translation of viral mRNA and will also facilitate the screening of oncolytic strains for oncolytic therapy.

Introduction Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA.Methods and analysis In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms.Ethics and dissemination This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations.Trial registration number NCT03717896; clinicaltrials.gov.

Abstract Objective We aimed to evaluate the genotype–phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA). Methods We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard methods. Targeted next‐generation sequencing and Sanger sequencing were performed to find the pathogenic mutation in this family. Minigene assays were used to verify whether the novel intronic mutation SLC26A4c.765+4A>G influenced mRNA splicing. Results Hearing loss in the patients with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.765+4A>G and c.919‐2A>G were detected in SLC26A4. In vitro minigene analysis confirmed that c.765+4A>G variant could cause aberrant splicing, resulting in skipping over exon 6. Conclusions The SLC26A4c.765+4A>G mutation is the causative variant in the Chinese family with EVA. Particular attention should be paid to intronic variants.

Background: Laryngopharyngeal reflux disease (LPRD) is an extraesophageal syndromic manifestation of gastroesophageal reflux disease (GERD). Despite the increasing incidence of and concern about LPRD, treatment with proton pump inhibitors (PPIs) is unsatisfactory. Here, LPRD was treated with Tonghua Liyan (THLY) granules in combination with PPIs to evaluate treatment efficacy and possible adverse reactions.Methods: Seventy-six LPRD patients with stagnation of phlegm and qi syndrome (SPQS) were randomly divided into an experimental group and a control group. The experimental group received THLY granules combined with rabeprazole capsules. The control group received THLY granule placebo combined with rabeprazole capsules. A parallel, randomized, double-blind, placebo-controlled clinical trial was conducted with these two groups. The treatment cycle was 8 weeks. The reflux symptom index (RSI), clinical symptom score, salivary pepsin content, reflux finding score (RFS) and gastroesophageal reflux disease questionnaire (GerdQ) were used to evaluate clinical efficacy. The final efficacy rate was evaluated according to the RSI and clinical symptom score.Results: Compared with those at baseline, all the indicators in the experimental group and control group significantly improved (p < 0.01). In terms of the RSI, clinical symptom score, and RFS, the experimental group had a higher degree of improvement (p < 0.05), and the overall efficacy rate was higher (p < 0.05). In terms of the salivary pepsin concentration and GerdQ, there was no significant difference between the test group and the control group (p > 0.05). Both groups of safety indicators showed no abnormalities and did not cause any allergic reactions in the body.Conclusion: Compared with PPIs alone, THLY granules combined with PPIs are more effective in the treatment of LPRD patients with SPQS in terms of symptoms and signs. This combination treatment, because of its higher clinical efficacy and lack of obvious adverse reactions, is worthy of clinical promotion and further in-depth study.Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR2100046614

IntroductionPericonceptional use of multivitamins containing folic acid prevents external major birth defects, especially neural tube defects. We aimed to explore the effects of maternal folic acid supplementation alone on perinatal mortality with or without external major birth defects plus neural tube defects.MethodsFrom the China-US Collaborative Project for Neural Tube Defects Prevention, we identified 222, 303 singleton pregnancies with detailed information on periconceptional folic acid use, defined as folic acid supplementary before the last menstrual date until to the end of the first trimester. Perinatal mortality included stillbirths after 20 weeks’ gestation and early neonatal deaths within 7 days of delivery.ResultsAmong the fetuses or infants of women who did not take folic acid, the rate of perinatal mortality was 2.99% and 1.62% at least 20 weeks’ gestation in the northern and southern regions. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.85% and 1.39% in the northern and southern region. The estimated relative risk for perinatal mortality [adjusted risk ratio (RR), 0.72; 95% confidence interval (CI), 0.61- 0.85], stillbirth (adjusted RR, 0.78; 95% CI, 0.64-0.96), early neonatal mortality (adjusted RR, 0.61; 95% CI, 0.45-0.82), and neonatal death (adjusted RR, 0.64; 95% CI, 0.49-0.83) in northern China was significantly decreased in association with periconceptional folic acid supplementation. Compared with northern, there was a lesser effect in southern China.ConclusionPericonceptional intake of 400μg folic acid daily reduces the overall risk perinatal mortality, as well as the risk from external major birth defects and neural tube defects, especially in northern China.

ABSTRACTClade 2.3.4.4 H5N6 avian influenza virus (AIV) has been predominant in poultry in China, and the circulating haemagglutinin (HA) gene has changed from clade 2.3.4.4h to clade 2.3.4.4b in recent years. In 2021, we isolated four H5N6 viruses from ducks during the routine surveillance of AIV in China. The whole-genome sequencing results demonstrated that the four isolates all belonged to the currently prevalent clade 2.3.4.4b but had different internal gene constellations, which could be divided into G1 and G2 genotypes. Specifically, G1 possessed H9-like PB2 and PB1 genes on the H5-like genetic backbone while G2 owned an H3-like PB1 gene and the H5-like remaining internal genes. By determining the characteristics of H5N6 viruses, including growth performance on different cells, plaque-formation ability, virus attachment ability, and pathogenicity and transmission in different animal models, we found that G1 strains were more conducive to replication in mammalian cells (MDCK and A549) and BALB/c mice than G2 strains. However, G2 strains were more advantageously replicated in avian cells (CEF and DF-1) and slightly more transmissible in waterfowls (mallards) than G1 strains. This study enriched the epidemiological data of H5 subtype AIV to further understand its dynamic evolution, and laid the foundation for further research on the mechanism of low pathogenic AIV internal genes in generating novel H5 subtype reassortants.

H9N2 avian influenza viruses (AIVs) pose an increasing threat to the poultry industry worldwide and have pandemic potential. Vaccination has been principal prevention strategy to control H9N2 in China since 1998, but vaccine effectiveness is persistently challenged by the emergence of the genetic and/or antigenic variants. Here, we analysed the genetic and antigenic characteristics of H9N2 viruses in China, including 70 HA sequences of H9N2 isolates from poultry, 7358 from online databases during 2010–2020, and 15 from the early reference strains. Bayesian analyses based on hemagglutinin (HA) gene revealed that a new designated clade16 emerged in April 2012, and was prevalent and co-circulated with clade 15 since 2013 in China. Clade 16 viruses exhibited decreased cross-reactivity with those from clade 15. Antigenic Cartography analyses showed represent strains were classified into three antigenic groups named as Group1, Group2 and Group3, and most of the strains in Group 3 (15/17, 88.2%) were from Clade 16 while most of the strains in Group2 (26/29, 89.7%) were from Clade 15. The mean distance between Group 3 and Group 2 was 4.079 (95%CI 3.605–4.554), revealing that major switches to antigenic properties were observed over the emergence of clade 16. Genetic analysis indicated that 11 coevolving amino acid substitutions primarily at antigenic sites were associated with the antigenic differences between clade 15 and clade 16. These data highlight complexities of the genetic evolution and provide a framework for the genetic basis and antigenic characterization of emerging clade 16 of H9N2 subtype avian influenza virus.

Abstract Background Surgical site infection (SSI) is the most common complications in spinal surgery. In SSI, non-superficial surgical site infections are more likely to result in poor clinical outcomes. It has been reported that there are multiple factors contributing to postoperative non-superficial SSI, but still remains controversial. Therefore, the aim of this meta-analysis is to investigate the potential risk factors for non-superficial SSI following spinal surgery. Methods A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until September 2022. According to the inclusion and exclusion criteria, two evaluators independently conducted literature screening, data extraction and quality evaluation of the obtained literature. The Newcastle–Ottawa Scale (NOS) score was used for quality evaluation, and meta-analysis was performed by STATA 14.0 software. Results A total of 3660 relevant articles were initially identified and 11 articles were finally included in this study for data extraction and meta-analysis. The results of meta-analysis showed that the diabetes mellitus, obesity, using steroids, drainage time and operative time were related to the non-superficial SSI. The OR values (95%CI) of these five factors were 1.527 (1.196, 1.949); 1.314 (1.128, 1.532); 1.687(1.317, 2.162); 1.531(1.313, 1.786) and 4.255(2.612, 6.932) respectively. Conclusions Diabetes mellitus, obesity, using steroids, drainage time and operative time are the current risk factors for non-superficial SSI following spinal surgery. In this study, operative time is the most important risk factor resulting in postoperative SSI.

Foundation models play an increasingly pivotal role in the field of deep neural networks. Given that deep neural networks are widely used in real-world systems and are generally susceptible to adversarial attacks, securing foundation models becomes a key research issue. However, research on adversarial attacks against the Segment Anything Model (SAM), a visual foundation model, is still in its infancy. In this paper, we propose the prompt batch attack (PBA), which can effectively attack SAM, making it unable to capture valid objects or even generate fake shards. Extensive experiments were conducted to compare the adversarial attack performance among optimizing without prompts, optimizing all prompts, and optimizing batches of prompts as in PBA. Numerical results on multiple datasets show that the cross-prompt attack success rate (ASR∗) of the PBA method is 17.83% higher on average, and the attack success rate (ASR) is 20.84% higher. It is proven that PBA possesses the best attack capability as well as the highest cross-prompt transferability. Additionally, we introduce a metric to evaluate the cross-prompt transferability of adversarial attacks, effectively fostering research on cross-prompt attacks. Our work unveils the pivotal role of the batched prompts technique in cross-prompt adversarial attacks, marking an early and intriguing exploration into this area against SAM.

The diagenetic facies of tight oil reservoirs reflect the diagenetic characteristics and micro-pore structure of reservoirs, determining the formation and distribution of sweet spot zones. By establishing the correlation between diagenetic facies and logging curves, we can effectively identify the vertical variation of diagenetic facies types and predict the spatial variation of reservoir quality. However, it is still challenging work to establish the correlation between logging and diagenetic facies, and there are some problems such as low accuracy, high time consumption and high cost. To this end, we propose a lithofacies identification method for tight oil reservoirs based on hybrid intelligence using the Fuyu oil layer of the Sanzhao depression in Songliao Basin as the target area. Firstly, the geological characteristics of the selected area were analyzed, the definition and classification scheme of diagenetic facies and the dominant diagenetic facies were discussed, and the logging response characteristics of various diagenetic facies were summarized. Secondly, based on the standardization of logging curves, the logging image data set of various diagenetic facies was built, and the imbalanced data set processing was performed. Thirdly, by integrating CNN (Convolutional Neural Networks) and ViT (Visual Transformer), the C-ViTM hybrid intelligent model was constructed to identify the diagenetic facies of tight oil reservoirs. Finally, the effectiveness of the method is demonstrated through experiments with different thicknesses, accuracy and single-well identification. The experimental results show that the C-ViTM method has the best identification effect at the sample thickness of 0.5 m, with Precision of above 86%, Recall of above 90% and F1 score of above 89%. The calculation result of the Jaccard index in the identification of a single well was 0.79, and the diagenetic facies of tight reservoirs can be identified efficiently and accurately. At the same time, it also provides a new idea for the identification of the diagenetic facies of old oilfields with only logging image data sets.

PurposeThis study aimed to develop and validate a cine cardiovascular magnetic resonance (CMR)-based radiomics nomogram model for predicting microvascular obstruction (MVO) following reperfusion in patients with ST-segment elevation myocardial infarction (STEMI).MethodsIn total, 167 consecutive STEMI patients were retrospectively enrolled. The patients were randomly divided into training and validation cohorts with a ratio of 7:3. All patients were diagnosed with myocardial infarction with or without MVO based on late gadolinium enhancement imaging. Radiomics features were extracted from the cine CMR end-diastolic volume phase of the entire left ventricular myocardium (3D volume). The least absolute shrinkage and selection operator (LASSO) regression was employed to select the features that were most relevant to the MVO; these features were then used to calculate the radiomics score (Rad-score). A combined model was developed based on independent risk factors screened using multivariate regression analysis and visualized using a nomogram. Performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA).ResultsThe univariate analysis of clinical features demonstrated that only cardiac troponin I (cTNI) was significantly associated with MVO. LASSO regression revealed that 12 radiomics features were strongly associated with MVO. Multivariate regression analysis indicated that cTNI and Rad-score were independent risk factors for MVO. The nomogram based on these two features achieved an area under the curve of 0.86 and 0.78 in the training and validation cohorts, respectively. Calibration curves and DCA indicated the clinical feasibility and utility of the nomogram.ConclusionsA CMR-based radiomics nomogram offers an effective means of predicting MVO without contrast agents and radiation, which could facilitate risk stratification of patients with STEMI after PCI for reperfusion.

IntroductionLymphovascular space invasion (LVSI) is associated with lymph node metastasis and poor prognosis in cervical cancer. In this study, we investigated the potential of radiomics, derived from magnetic resonance (MR) images using habitat analysis, as a non-invasive surrogate biomarker for predicting LVSI in cervical cancer.MethodsThis retrospective study included 300 patients with cervical cancer who underwent surgical treatment at two centres (centre 1 = 198 and centre 2 = 102). Using the k-means clustering method, contrast-enhanced T1-weighted imaging (CE-T1WI) images were segmented based on voxel and entropy values, creating sub-regions within the volume ofinterest. Radiomics features were extracted from these sub-regions. Pearson correlation coefficient and least absolute shrinkage and selection operator LASSO) regression methods were used to select features associated with LVSI in cervical cancer. Support vector machine (SVM) model was developed based on the radiomics features extracted from each sub-region in the training cohort.ResultsThe voxels and entropy values of the CE-T1WI images were clustered into three sub-regions. In the training cohort, the AUCs of the SVM models based on radiomics features derived from the whole tumour, habitat 1, habitat 2, and habitat 3 models were 0.805 (95% confidence interval [CI]: 0.745–0.864), 0.873(95% CI: 0.824–0.922), 0.869 (95% CI: 0.821–0.917), and 0.870 (95% CI: 0.821–0.920), respectively. Compared with whole tumour model, the predictive performances of habitat 3 model was the highest in the external test cohort (0.780 [95% CI: 0.692–0.869]).ConclusionsThe radiomics model based on the tumour sub-regional habitat demonstrated superior predictive performance for an LVSI in cervical cancer than that of radiomics model derived from the whole tumour.

Abstract Torn and bent slabs are usually associated with flat‐slab subduction where the descending plate develops a horizontal geometry beneath the overlying continent. How such slab dynamics modify the surrounding mantle flow and the overriding plate remains enigmatic. Here, we conduct three‐dimensional subduction numerical experiments to investigate the flat slab to steep‐angle slab transition region and examine the impact of slab geometry changes on mantle flows. The results show that the along‐strike change due to flattening a segment of slab induces oblique flow toward the mantle corner at the transition region where flat slab bends to steep‐subducting slab. Slab tears can occur due to the buoyancy contrast between an oceanic ridge and the surrounding dense oceanic crust and/or presence of weak zones. A vertical tear at the side edge of a flat slab causes toroidal flow around the steep‐angle slab where sub‐slab mantle floods rapidly through the tear. Flow through the tear spreads to all directions including upwelling toward the continental base that may trigger slab and partial melting and thus affect arc magmatism. A horizontal tear that occurs ahead of the flat portion where slab resumes its steep‐angle results in enhanced plate‐motion parallel flow. Notably, the tear‐induced flow behaves as a rapid injection through the slab breach with the peak velocity up to an order of magnitude higher than plate motion, lasting for 1–2 million years after initially tearing. This rapid pulse flow might be recorded in surface tectonics as distinct transient events of topography or metamorphism.

BackgroundAdherent–invasive E. coli (AIEC) LF82 is capable of adhering to and invading intestinal epithelial cells, as well as replicating within macrophages without inducing host cell death.MethodsWe compared the transcriptomics of LF82 at pH=7.5 and pH=5.8 by RNA-sequencing, and qRT-PCR verified differentially expressed genes (DEGs). The deletion mutants of DEGs in the treatment group (pH=5.8) compared to the control group (pH=7.5) were constructed by λ recombinant. The replication differences between the mutants and WT infected Raw 264.7 at 24 h.p.i were analyzed by combining LB solid plate count and confocal observation. NH4Cl and chloroquine diphosphate (CQ) were used for acid neutralization to study the effect of pH on the replication of LF82 in macrophages. Na2NO3 was added to RPMI 1640 to study the effect of nitrate on the replication of LF82 in macrophages. 0.3% solid LB was used for flagellar motility assay and Hela was used to study flagellar gene deletion mutants and WT adhesion and invasion ability.ResultsIn this study, we found that infection with LF82 results in acidification of macrophages. Subsequent experiments demonstrated that an intracellular acidic environment is necessary for LF82 replication. Transcriptome and phenotypic analysis showed that high expression of acid shock genes and acid fitness genes promotes LF82 replication in macrophages. Further, we found that the replication of LF82 in macrophages was increased under nitrate treatment, and nitrogen metabolism genes of LF82 were upregulated in acid treatment. The replication in macrophages of ΔnarK, ΔnarXL, ΔnarP, and Δhmp were decreased. In addition, we found that the expression of flagellar genes was downregulated in acidic pH and after LF82 invading macrophages. Motility assay shows that the movement of LF82 on an acidic semisolid agar plate was limited. Further results showed that ΔfliC and ΔfliD decreased in motility, adhesion ability, and invasion of host cells, but no significant effect on replication in macrophages was observed.ConclusionIn this study, we simulated the acidic environment in macrophages, combined with transcriptome technology, and explained from the genetic level that LF82 promotes replication by activating its acid shock and fitness system, enhancing nitrate utilization, and inhibiting flagellar function.

Study Design: A retrospective study. Purpose: To firstly introduce a new surgical technique named as selective fenestration and axial decompression (SFAD) to improve the surgical treatment effects of lumbar degenerative diseases. Overview of literature: Posterior lumbar laminectomy and interbody fusion (LIF) is a standard surgical method for the treatment of lumbar degenerative diseases. However, its application has some limitations, and the incidence of spinal cord nerve injury is relatively high. Methods: This retrospective clinical study was conducted from January 2018 to February2020. A total of 101 eligible patients including 62 men and 39 women with lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS) underwent LIF or SFAD were enrolled in this study. The average postoperative follow-up period of the LIF and SFAD groups were 20.1 ± 3.7 months and 19.7 ± 4.1 months, respectively. The clinical effects, imaging manifestation, and postoperative complications in LIF and SFAD groups were analyzed. Results: The operative time, blood loss and hospital stay in SFAD group were significantly lower than those in LIF group (P 0.05). Similarly, improvements of cobb angle of operated segment, intervertebral space height (ISH), intervertebral space foramen (IFH) and lumbar lordosis (LL) showed no statistical difference between the two groups (P > 0.05). Finally, the prevalence of complication rates in LIF group were significantly higher than the SFAD group during the follow-up period (P

Abstract. Background:. Electroacupuncture (EA) has been shown to attenuate airway inflammation in asthmatic mice; however, the underlying mechanism is not fully understood. Studies have shown that EA can significantly increase the inhibitory neurotransmitter γ-aminobutyric acid (GABA) content in mice, and can also increase the expression level of GABA type A receptor (GABAAR). Furthermore, activating GABAAR may relieve inflammation in asthma by suppressing toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway. Therefore, this study aimed to investigate the role of GABAergic system and TLR4/MyD88/NF-κB signaling pathway in asthmatic mice treated with EA. Methods:. A mouse model of asthma was established, and a series of methods including Western blot and histological staining assessment were employed to detect the level of GABA, and expressions of GABAAR and TLR4/MyD88/NF-κB in lung tissue. In addition, GABAAR antagonist was used to further validate the role and mechanism of GABAergic system in mediating the therapeutic effect of EA in asthma. Results:. The mouse model of asthma was established successfully, and EA was verified to alleviate airway inflammation in asthmatic mice. The release of GABA and the expression of GABAAR were significantly increased in asthmatic mice treated with EA compared with untreated asthmatic mice (P

Abstract Background Acute myeloid leukemia (AML) is a common and lethal hematological malignant hyperplastic disease originating from hematopoietic stem cells. The purpose of this study is to obtain the key differentially expressed gene (DEG) related to the survival of AML by The Cancer Genome Atlas (TCGA) database and to verify these genes by a clinical follow-up investigation, in order to identify valuable predictive and prognostic biomarkers for early diagnosis of AML and predict the survival rates. Methods The RNA sequencing (RNA-Seq) data and clinical information of TCGA-LAML were downloaded from the TCGA database. After that we (1) screened the survival-related DEGs by Cox regression analysis, (2) selected the cytogenetics risk-related DEGs by DESeq2 R package, and (3) filtrated the genes in the top10 pathways of up-regulated and down-regulated of Normalization Enrichment Score (NES) by Gene Set Enrichment Analysis (GSEA). Finally, we focused the intersectional genes of above three parts as the key gene of the present study. The following Multivariate.

Sunburn is an acute phototoxic reaction caused by excessive exposure of skin to solar ultravilet (UV) or artificial UV light sources. Studies show that sunburn is common in the general population, so that associated financial burden cannot be ignored. Meanwhile, sunburn at any age increases the risk of melanoma. Only by clarifying the influencing factors of sunburn can precise preventive measures be formulated. Although many studies have been conducted on the influencing factors of sunburn worldwide, there are great heterogeneity in reported influencing factors. In this paper, by means of systematic review, factors affecting sunburn were sorted out and summarized from four aspects, including demographic and socioeconomic characteristics, photosensitive phenotypes, UV-related environmental factors, and sun protection knowledge, attitude & behavior. Combined with population characteristics and data availability in China, our review provided reference for subsequent research and development of precise prevention and control strategies.