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In this paper, the electrochemical and corrosion behavior of pure titanium (TA1) in simulated Proton Exchange Membrane Water Electrolysis (PEMWE) anodic environment was investigated. In this condition, the corrosion potential of TA1 was −689 mV, with a self-corrosion current density of 232.5 μA cm–2, and a polarization resistance of 125.9 Ω cm2. During potentiostatic polarization at 2 V, the current density was maintained at approximately 6 mA cm–2. However, the passivation process exhibited instability. Furthermore, this process has been shown to significantly facilitate the formation of surface oxides, and the passive film that formed displays the lowest bound water and OH−, and the highest content of O2–, exhibiting the highest average valence. Notably, dynamic potentials caused current transients, among which square wave potential was the most remarkable. The square wave potential shows an O2– content just below that of 2V potential polarization when fluctuating potentials are applied. The interfacial contact resistance (ICR) of 2 V potentiostatic polarization was slightly higher than that of square, sine and triangular waves. Additionally, the high temperature condition of PEMWE will aggravate the corrosion of TA1 by fluoride ions.

ObjectiveThis study aims to examine the mental health of patients with lumbar disc herniation with radiculopathy (LDHR) and to evaluate the effects of percutaneous transforaminal endoscopic discectomy (PTED) on their mental well-being.MethodThis study included 114 LDHR patients who received PTED in the Spinal Orthopedics Department of Zhongshan Hospital of Traditional Chinese Medicine between May 2022 and May 2023. The study population was stratified into two groups according to the presence of preoperative anxiety and depression: Group A comprised patients with such symptoms, and Group B included the remainder. Patients were assessed using the Hospital Anxiety and Depression Scale (HADS), the Visual Analog Scale for Pain (VAS), and the Oswestry Disability Index (ODI) at preoperative and final follow-up visits. Evaluations were performed using the Hospital Anxiety and Depression Scale (HADS), the Visual Analog Scale, and the Oswestry Disability Index (ODI) at the time of preoperation and during the last follow-up.ResultsAmong the 114 LDHR patients who obtained complete follow-up, fifty-four had anxiety/depression symptoms before surgery, which accounted for a incidence of 47%. Both Group A and Group B patients showed significant improvement in all evaluation indicators after PTED, but the overall prognosis of Group A was worse than that of Group B.ConclusionPTED can effectively improve patients’ pain, functional activities and mental health, which has a positive impact on patients’ quality of life, and there is a significant correlation between patients’ preoperative mental health and prognosis.

Chimeric antigen receptor T (CAR-T) cell therapy is a new treatment for cancers, but reports on curing immune-related skin diseases are limited. We report a case of successful CAR-T-cell therapy in a patient with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) who was incidentally cured of chronic generalized plaque psoriasis. The patient, a 65-year-old male who had a known history of psoriasis for 45 years, did not receive immunotherapy for psoriasis during this period. Imaging, molecular biology and immunology diagnostics confirmed DLBCL. After several weeks of standard-dose R-CHOP chemotherapy, the patient achieved partial remission, but according to CT, the patient relapsed, and there was no significant improvement in her psoriasis symptoms. Subsequently, the patient was enrolled in the CD19 CAR-T-cell therapy group. Four weeks after CAR-T-cell infusion, the patient’s abdominal pain disappeared, and there was a significant improvement in overall skin lesions. One year later, follow-up results indicated complete remission of R/R DLBCL (confirmed by PET-CT), with only minimal residual psoriatic skin lesions limited to the patient’s neck. The results of using CAR-T-cell therapy to achieve an incidental cure for psoriasis highlight the potential for exploring cell-based therapies for complex autoinflammatory skin diseases.

ObjectivesTo explore the relationship between glymphatic dysfunction and cognitive impairment in unilateral temporal lobe epilepsy (TLE).MethodsThis study retrospectively included 38 patients with unilateral TLE and 26 age- and gender-matched healthy controls (HCs). The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and cognitive assessment were obtained for each participant. Neuropsychological test batteries included Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination, Arithmetic Test (AT), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Boston Naming Test, Block design, Phonological Fluency Test (PFT), and Semantic Verbal Fluency (SVF).ResultsCompared to HCs, TLE patients had lower scores of MoCA, AT, DSST, DST, Block design, PFT and SVF (all p

BackgroundNovel β-lactam antibiotics as well as other kinds of antibiotics have been used to treat complicated urinary tract infections (cUTIs); however, their efficacy and safety remain controversial.ObjectiveWe conducted a systematic review with meta-analysis to explore the efficacy and safety of novel β-lactam antibiotics versus other antibiotics against cUTIs.MethodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched systematically from inception through 15 March 2024 for clinical trials comparing novel β-lactam antibiotics with other antibiotics for treatment of cUTIs. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of clinical response, microbiologic response, adverse effects (AEs), serious adverse effects (SAEs). The quality of evidence was evaluated with the Cochrane Risk of Bias assessment tool. The review was registered in INPLASY (INPLASY202440054).ResultsTen randomized controlled trials involving 5, 925 patients met our inclusion criteria. Our meta-analysis revealed that there was no significant difference in overall clinical response (RR = 1.02), AEs (RR = 1.07), SAEs (RR = 1.20) between novel β-lactam antibiotics groups and other antibiotics groups. However, a significant difference was found in a subgroup of clinical cure rates at the end of treatment between novel β-lactam antibiotics groups and carbapenems groups, with low heterogeneity (RR = 1.02). A significant difference was observed in microbiologic response (RR = 1.11). Subgroup analysis revealed a significant difference in microbiologic response between novel BBL/BLS groups and carbapenems groups (RR = 1.13, I2 = 21%, P = 0.005). Differences was observed between novel BBL/BLS groups and piperacillin/tazobactam sodium groups (RR = 1.21, I2 = 70%, P = 0.02). Similar results were obtained from subgroup analysis of the difference in microbiologic response between novel β-lactam antibiotics groups and ertapenem groups (RR = 0.92, I2 = 0, P = 0.01).ConclusionNovel β-lactam antibiotics had similar overall clinical cure, AEs, SAE, to other antibiotics in the treatment of cUTIs. However, novel β-lactam antibiotics demonstrated superior clinical cure rates compared to carbapenems in a subgroup analysis, and exhibited better microbiologic response than other antibiotics.

ObjectiveLevosimendan and Sacubitril/Valsartan are both potent pharmacotherapeutic agents in the clinical management of heart failure characterized by reduced ejection fraction. However, the limited efficacy of monotherapy and the lack of extensive clinical experience with combination therapy necessitate further investigation. This study aimed to evaluate the therapeutic effects of combining levosimendan with sacubitril/valsartan on chronic heart failure with reduced ejection fraction, specifically through a meta-analysis of studies conducted in China.MethodsCochrane systematic evaluation method was used to complete data retrieval from the following related databases: (1) Wanfang database; (2) CNKI China Academic Journal Network; (3) Wipo Full-text Database of Chinese Sci-tech journals; (4) PubMed; (5) Medline; (6) Chinese Biomedical Literature Database; (7) Web of Science; and (8) Google Scholar database. We searched for studies published up to December 2021. Data were extracted from applicable articles. Meta-analyses were performed to assess the left ventricular ejection fractions (LVEF) level, NT-proBNP level, Clinical efficacy, and the left ventricular end-diastolic dimension (LVEDD) level outcomes, following PRISMA 2020 guidelines.ResultsA total of five randomized controlled trials (RCTs) comprising 398 patients were included, half of the patients for levosimendan combined with Sacubitril/Valsartan and half of the patients for control groups. The effective rate in experimental group was significantly higher than that in control group [Peto-OR = 3.08, 95% CI (1.83, 5.19), P

ObjectiveThis study aimed to use visual mapping and bibliometric analysis to summarize valuable information on the tumor microenvironment (TME)-related research on hepatocellular carcinoma (HCC) in the past 20 years and to identify the research hotspots and trends in this field.MethodsWe screened all of the relevant literature on the TME of HCC in the Web of Science database from 2003 to 2023 and analysed the research hotspots and trends in this field via VOSviewer and CiteSpace.ResultsA total of 2,157 English studies were collected. According to the prediction, the number of papers that were published in the past three years will be approximately 1,394, accounting for 64.63%. China published the most papers (n=1,525) and had the highest total number of citations (n=32,253). Frontiers In Immunology published the most articles on the TME of HCC (n=75), whereas, Hepatology was the journal with the highest total number of citations (n=4,104) and average number of citations (n=91). The four clusters containing keywords such as “cancer-associated fibroblasts”, “hepatic stellate cells”, “immune cells”, “immunotherapy”, “combination therapy”, “landscape”, “immune infiltration”, and “heterogeneity” are currently hot research topics in this field. The keywords “cell death”, “ferroptosis”, “biomarkers”, and “prognostic features” have emerged relatively recently, and these research directions are becoming increasingly popular.ConclusionsWe identified four key areas of focus in the study of the TME in HCC: the main components and roles in the TME, immunotherapy, combination therapy, and the microenvironmental landscape. Moreover, the result of our study indicate that effect of ferroptosis on the TME in HCC may become a future research trend.

BackgroundMedical health workers play an essential role in the healthcare system and face unique workplace stressors. However, the impact of psychological stress on their physical health has received less attention compared to the general population.MethodsWe retrospectively analyzed the Self-rating Depression Scale (SDS) questionnaires and blood testing results from 1963 medical health workers. Multivariate linear regression analysis using a backward stepwise selection strategy to identify physical examination indicators that were significantly affected by depression.ResultsDepression severity, as measured by SDS index score, was positively correlated with the levels of hemoglobin (coefficient 0.0027, p = 0.0412), platelet count (coefficient 0.0005, p = 0.0198), and uric acid (coefficient 0.0004, p = 0.0492), while negatively correlated with red blood cell count (coefficient-0.0895, p = 0.0406). Similar results were observed in the subgroup analysis stratified by age and sex.ConclusionOur study found a significant association between higher levels of depression and specific physiological indicators in healthcare professionals, including elevated hemoglobin, platelet counts, and uric acid levels, as well as decreased red blood cell counts. These changes in blood parameters may reflect underlying physiological stress and inflammation, potentially increasing overall health risks for healthcare workers. Addressing these physiological changes may be crucial for mitigating the health risks associated with depression. To validate our findings and develop targeted interventions, larger multi-center studies are needed to further explore the relationship between depression severity and blood parameters in healthcare professionals.

BackgroundFor patients with metastatic upper tract urothelial carcinoma (UTUC), the preferred first-line treatment is platinum-based chemotherapy. Immunotherapy can be considered a subsequent treatment if the chemotherapy is ineffective or the disease progresses. However, how should treatment be administered if immunotherapy is useless and the patient cannot take chemotherapy? Especially in patients who have metastasized after radical nephroureterectomy (RNU).Case presentationA 68-year-old woman was admitted to the hospital due to left flank pain for two weeks and was diagnosed with metastatic UTUC after RNU. The patient underwent systemic chemotherapy with gemcitabine and cisplatin (GC), as well as reduced-dose GC, but developed myelosuppression. Immunotherapy was ineffective, so Disitamab vedotin (RC48) was chosen.ResultsDisitamab vedotin (RC48) monotherapy was administered for 13 cycles, during which thyroid function remained normal, the patient responded well to the treatment, and the disease was controlled well. In the subsequent two years of follow-up, there was no disease recurrence.ConclusionThe long-term treatment regimen with RC48 is feasible for metastatic UTUC after RNU, and RC48 monotherapy is suitable as first-line therapy for selected patients.

BackgroundThe relationship between dietary selenium intake and sarcopenia remains poorly understood. Therefore, this study investigates the associations between dietary selenium intake and sarcopenia among American adults.MethodsThis cross-sectional study analyzed data from 19,696 participants in the National Health and Nutrition Examination Survey (NHANES) for the periods 1999–2006 and 2011–2018. Appendicular muscle mass, assessed using dual-energy x-ray absorptiometry and adjusted for body mass index, was used as a marker for sarcopenia. Dietary selenium intake was evaluated using the 24-h dietary recall system, and the study accounted for the complex sampling methodology and incorporated dietary sample weights in the analysis.ResultsAmong the 19,696 participants, the prevalence of sarcopenia was found to be 8.46%. When compared to the lowest quintile of dietary selenium intake (Q1, < 80.10 μg/day), the odds ratios for sarcopenia in the second quintile (Q2, 80.10–124.61 μg/day) and the third quintile (Q3, >124.61 μg/day) were 0.80 [95% confidence interval (CI): 0.70–0.92, p = 0.002] and 0.61 (95% CI: 0.51–0.73, p < 0.001), respectively. A negative relationship was observed between dietary selenium intake and sarcopenia (non-linear: p = 0.285). Furthermore, sensitivity analyses revealed a robust association between selenium intake and the prevalence of sarcopenia after further adjusting for blood selenium levels.ConclusionThe results suggest an inverse association between dietary selenium intake and the prevalence of sarcopenia among American adults.

IntroductionGrazer exclosure is widely regarded as an effective measure for restoring degraded grasslands, having positive effects on soil microbial diversity. The Intergovernmental Panel on Climate Change (IPCC) predicts that global surface temperatures will increase by 1.5–4.5°C by the end of the 21st century, which may affect restoration practices for degraded grasslands. This inevitability highlights the urgent need to study the effect of temperature on grassland soil microbial communities, given their critical ecological functions.MethodsHere, we assessed the effects of heavy grazing (control), grazer exclosure, and grazer exclosure plus warming by 1.5°C on soil microbial community diversity and network properties as well as their relationships to soil physicochemical properties.Results and discussionOur results showed that grazer closure increased soil microbial richness relative to heavy grazing controls. Specifically, bacterial richness increased by 7.9%, fungal richness increased by 20.2%, and the number of fungal network nodes and edges increased without altering network complexity and stability. By contrast, grazer exclosure plus warming decreased bacterial richness by 9.2% and network complexity by 12.4% compared to heavy grazing controls, while increasing fungal network complexity by 25.8%. Grazer exclosure without warming increased soil ammonium nitrogen content, while warming increased soil nitrate nitrogen content. Soil pH and organic carbon were not affected by either exclosure strategy, but nitrate nitrogen was the dominant soil factor explaining changes in bacterial communities.ConclusionOur findings show that grazer exclosure increases soil microbial diversity which are effective soil restoration measures for degraded desert steppe, but this effect is weakened under warming conditions. Thus, global climate change should be considered when formulating restoration measures for degraded grasslands.

BackgroundLimbic structures have recently garnered increased attention in Parkinson’s disease (PD) research. This study aims to explore changes at the whole-brain level in the structural network, specifically the white matter fibres connecting the thalamus and limbic system, and their correlation with the clinical characteristics of patients with PD.MethodsBetween December 2020 and November 2021, we prospectively enrolled 42 patients with PD and healthy controls at the movement disorder centre. All participants underwent diffusion tensor imaging (DTI), 3D T1-weighted imaging (3D-T1WI), and routine brain magnetic resonance imaging on a 3.0 T MR scanner. We employed the tract-based spatial statistical (TBSS) analytic approach, examined structural network properties, and conducted probabilistic fibre tractography to identify alterations in white matter pathways and the topological organisation associated with PD.ResultsIn patients with PD, significant changes were observed in the fibrous tracts of the prefrontal lobe, corpus callosum, and thalamus. Notably, the fibrous tracts in the prefrontal lobe and corpus callosum showed a moderate negative correlation with the Freezing of Gait Questionnaire (FOG-Q) scores (r = −0.423, p = 0.011). The hippocampus and orbitofrontal gyrus exhibited more fibre bundle parameter changes than other limbic structures. The mean streamline length between the thalamus and the orbitofrontal gyrus demonstrated a moderate negative correlation with Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III (r = −0.435, p = 0.006). Topological parameters, including characteristic path length (Lp), global efficiency (Eg), normalised shortest path length (λ) and nodal local efficiency (Nle), correlated moderately with the MDS-UPDRS, HAMA, MoCA, PDQ-39, and FOG-Q, respectively.ConclusionDTI is a valuable tool for detecting changes in water molecule dispersion and the topological structure of the brain in patients with PD. The thalamus may play a significant role in the gait abnormalities observed in PD.

Plant-associated microbial communities are crucial for plant growth and health. However, assembly mechanisms of microbial communities and microbial interaction patterns remain elusive across vary degrees of pathogen-induced diseases. By using 16S rRNA high-throughput sequencing technology, we investigated the impact of wildfire disease on the microbial composition and interaction network in plant three different compartments. The results showed that pathogen infection significantly affect the phyllosphere and rhizosphere microbial community. We found that the primary sources of microbial communities in healthy and mildly infected plants were from the phyllosphere and hydroponic solution community. Mutual exchanges between phyllosphere and rhizosphere communities were observed, but microbial species migration from the leaf to the root was rarely observed in severely infected plants. Moreover, wildfire disease reduced the diversity and network complexity of plant microbial communities. Interactions among pathogenic bacterial members suggested that Caulobacter and Bosea might be crucial “pathogen antagonists” inhibiting the spread of wildfire disease. Our study provides deep insights into plant pathoecology, which is helpful for the development of novel strategies for phyllosphere disease prediction or prevention.

This study explored the intersection of race, gender, and sexuality as they pertain to experiences of Asian American female sexual minority (AAFSM) students attending Midwestern universities in the United States through an intersectional lens. The study utilized intersectionality as a theoretical framework, a data generation tool, and a methodological approach to guide the study. The results showed that the participants experienced constructed objectifications, which included gendered, racial, and sexual objectification. The findings also revealed that participants’ race, gender, and sexual orientation were contextualized based on the situation. Further, participants devalued their Asianness, womanhood, and LGBTQness owing to the lack of positive representation in the curriculum. The analyzed data can be best categorized as the lack of intersectional representations in curricula, contextualized race, gender, and sexuality, and reported experiences of constructed objectifications. Discussions provided an inclusive campus environment for participants who were AAFSMs. These discussions also provided meaningful suggestions for educators, administrators, policymakers, and stakeholders to foster an equal and equitable educational environment for students with multiple marginalized identities.

IntroductionMesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs.MethodsIn this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16).ResultsThe median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events.DiscussionThese finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

Porcine epidemic diarrhea virus (PEDV) is responsible for causing fatal watery diarrhea in piglets, resulting in significant economic losses within the pig farming industry. Although vaccination is currently employed as a preventive measure, certain vaccines do not provide complete protection against PEDV field strains. Probiotics present a promising alternative due to their ability to regulate intestinal flora, enhance host immunity, and improve resistance against pathogenic microorganisms. We isolated six lactic acid bacteria (LAB) from the fecal microorganisms of Bama pigs, compared to Limosilactobacillus mucosae DSM13345 of the same genus in which Limosilactobacillus mucosae G01 (L. mucosae G01) proved to have a potent anti-PEDV effect. In a comprehensive manner, L. mucosae G01 significantly augmented the phosphorylation of IRF3 in IPEC-J2 cells, resulting in the induction of interferons (IFN α, IFN β, IFN λ1, and IFN λ3) and subsequent upregulation of interferon-stimulated genes (ISGs) (MX1, MX2, OAS1, and ZAP) in a dose-dependent fashion, consequently leading to the mitigation of PEDV replication. These findings underscore the promising prospects of L. mucosae G01 as a naturally derived substitute for combating PEDV and other enteric coronavirus infections.

PurposeOvarian cancer (OC) is a common gynecological malignancy with poor prognosis and substantial tumor heterogeneity. Due to the complex tumor immune microenvironment (TIME) among ovarian cancer, only a few patients have an immune response to immunotherapy. To investigate the differences in immune function and identify potential biomarkers in OC, we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify critical prognostic IRG signatures.MethodsSingle-sample gene set enrichment analysis (ssGSEA) was used to investigate the infiltration of various immune cells in 372 OC patients. Then, COX regression analysis and Lasso regression analysis were used to screen IRGs and construct PRSM. Next, the immunotherapy sensitivity of different risk groups regarding the immune checkpoint expression and tumor mutation burden was evaluated. Finally, a nomogram was created to guide the clinical evaluation of the patient prognosis.ResultsIn this study, 320 immune-related genes (IRGs) were identified, 13 of which were selectively incorporated into a Prognostic Risk Scoring Model (PRSM). This model revealed that the patients in the high-risk group were characterized as having poorer prognosis, lower expression of immune checkpoints, and decreased tumor mutation load levels compared with those in the low-risk group. The nomogram based on the risk score can distinguish the risk subtypes and individual prognosis of patients with OC. Additionally, M1 macrophages may be the critical target for immunotherapy in OC patients.ConclusionWith the in-depth analysis of the immune microenvironment of OC, the PRSM was constructed to predict the OC patient prognosis and identify the subgroup of the patients benefiting from immunotherapy.

BackgroundRobert’s uterus combined with transverse uterine septum is a rare uterine malformation. Only one case has been reported to date, and it is challenging to diagnose and treat.Case presentationHere we report the case of a 19-year-old female had undergone multiple treatments at a previous hospital for primary amenorrhea and periodic lower abdominal pain, with the cause remaining unclear. Ultrasonography and magnetic resonance imaging conducted at our hospital displayed the presence of uterine dysplasia with an incomplete septum. Following a multidisciplinary discussion, a preliminary diagnosis of Robert’s uterus combined with transverse uterine septum was made. Following this, laparoscopic exploration and ultrasound-guided hysteroscopic metroplasty were performed. The patient experienced periodic menstruation postoperatively and did not manifest periodic lower abdominal pain.ConclusionRobert’s uterus combined with transverse uterine septum is a very rare uterine malformation, with hysteroscopic metroplasty being the preferred surgical option. Nevertheless, preoperative diagnosis is extremely difficult, and there are also many difficulties in the surgical process. This case outlines the diagnostic and treatment process of a patient with Robert’s uterus and transverse uterine septum. It is of great significance to fill the gap in clinical diagnosis and treatment of this special uterine malformation.

ObjectiveThis study sought to identify circulating proteins causally linked to Inflammatory Bowel Disease (IBD) traits through a Mendelian Randomization (MR) analytical framework.MethodsUsing a large-scale, two-sample MR approach, we estimated the genetic links of numerous plasma proteins with IBD and its subtypes, leveraging information from the Inflammatory Bowel Disease Genetics Consortium. To assess the robustness of MR findings, methods like Bayesian colocalization, and Steiger filtering analysis, evaluation of protein-altering variants. Further insights into IBD’s underlying mechanisms and therapeutic targets were gleaned from single-cell sequencing analyses, protein-protein interaction assessments, pathway enrichment analyses, and evaluation of drug targets.ResultsBy cis-only MR analysis, we identified 83 protein-phenotype associations involving 27 different proteins associated with at least one IBD subtype. Among these proteins, DAG1, IL10, IL12B, IL23R, MST1, STAT3 and TNFRSF6B showed overlapping positive or negative associations in all IBD phenotypes. Extending to cis + trans MR analysis, we further identified 117 protein-feature associations, including 44 unique proteins, most of which were not detected in the cis-only analysis. In addition, by performing co-localization analysis and Steiger filtering analysis on the prioritized associations, we further confirmed the causal relationship between these proteins and the IBD phenotype and verified the exact causal direction from the protein to the IBD-related feature.ConclusionMR analysis facilitated the identification of numerous circulating proteins associated with IBD traits, unveiling protein-mediated mechanisms and promising therapeutic targets.

There is little available attenuation relationship for Arias Intensity (AI) in China. Empirical relationships between AI and peak ground acceleration (PGA) provide another option for predicting AI. We establish empirical relationships for AI and PGA for western China, utilizing 3,169 horizontal and 979 vertical strong motion records with PGA ≥0.01 g from 274 earthquakes (MS 4.0–8.0), originating in eight provinces in southwest (Yunnan, Sichuan) and northwest China (Gansu, Shaanxi, Ningxia, Qinghai, Inner Mongolia, and Xinjiang). The influences of MS epicenter distance, and site conditions indicators VS30, generic site classes (i.e., rock and soil) are explored. The results show that the logarithm of AI increases linearly with the increase of the logarithm of PGA and MS, and decreases with the logarithm of VS30. However, the influence of site conditions on AI-PAG relationships can't be recognized by the simple generic rock and soil site classes. The epicenter distance has little effect on the AI-PAG relationships. Empirical relationships are developed to estimate horizontal or vertical AI as a function of PGA (basic model), PGA and MS (model 2) for southwest, northwest, and western China, using all the records. Empirical relationships for AI as a function of PGA, MS, and VS30 (model 1) are established using the 2,248 horizontal (70.9% of the total) and 670 vertical (68.4% of the total) records with VS30 between 148 and 841m/s. The notable disparity between model 1 of the southwest and northwest regions is chiefly attributed to local site conditions, indicating that the AI-PGA correlation is region-dependent. These findings enable one way of estimating AI for western China and will contribute to a better understanding of AI attenuation.

IntroductionDual specificity protein phosphatase 6 (DUSP6) was recently identified as a key hub gene in a causal VGF gene network that regulates late-onset Alzheimer’s disease (AD). Importantly, decreased DUSP6 levels are correlated with an increased clinical dementia rating (CDR) in human subjects, and DUSP6 levels are additionally decreased in the 5xFAD amyloidopathy mouse model.MethodsTo investigate the role of DUSP6 in AD, we stereotactically injected AAV5-DUSP6 or AAV5-GFP (control) into the dorsal hippocampus (dHc) of both female and male 5xFAD or wild type mice, to induce overexpression of DUSP6 or GFP.ResultsBarnes maze testing indicated that DUSP6 overexpression in the dHc of 5xFAD mice improved memory deficits and was associated with reduced amyloid plaque load, Aß1–40 and Aß1–42 levels, and amyloid precursor protein processing enzyme BACE1, in male but not in female mice. Microglial activation, which was increased in 5xFAD mice, was significantly reduced by dHc DUSP6 overexpression in both males and females, as was the number of “microglial clusters,” which correlated with reduced amyloid plaque size. Transcriptomic profiling of female 5xFAD hippocampus revealed upregulation of inflammatory and extracellular signal-regulated kinase pathways, while dHc DUSP6 overexpression in female 5xFAD mice downregulated a subset of genes in these pathways. Gene ontology analysis of DEGs (p < 0.05) identified a greater number of synaptic pathways that were regulated by DUSP6 overexpression in male compared to female 5xFAD.DiscussionIn summary, DUSP6 overexpression in dHc reduced amyloid deposition and memory deficits in male but not female 5xFAD mice, whereas reduced neuroinflammation and microglial activation were observed in both males and females, suggesting that DUSP6-induced reduction of microglial activation did not contribute to sex-dependent improvement in memory deficits. The sex-dependent regulation of synaptic pathways by DUSP6 overexpression, however, correlated with the improvement of spatial memory deficits in male but not female 5xFAD.

Backgroundβ-blockers have been widely used in patients with extensive cardiovascular disease (CVD) and have provided benefits. However, they are more likely to cause symptomatic bradycardia, hypotension, or glucose metabolism disorders, which may lead to an increased risk of atrial fibrillation (AF), but evidence is lacking.AimsThis study was to analyze the association between the use of β-blockers and the risk of developing AF.MethodsThis nationwide, prospective cohort study utilized data from the 2013–2020 National Health and Nutrition Examination Survey (NHANES). The patients were stratified into a β-blocker treatment group (n = 2585) and a non-β-blocker treatment group (n = 8525). Univariate and multivariate logistic regression analyses were performed to identify the relationship between β-blockades and the risk of AF. Propensity matching analysis was used to balance patient baseline characteristics and to control for confounders.ResultsA total of 11,110 subjects were included in this study (mean [SD] age, 59.89 [15.07] years; 5657 [49.7%] males). A total of 111/2585 subjects developed AF in the β-blocker treatment group, and 75/8525 developed AF in the non-β-blocker treatment group (incidence rate, 4.2% vs. 0.8%). Compared with the non-β-blocker group, the β-blocker group had an increased risk of incident AF (aOR, 2.339; 95% CI, 1.614–3.410). Some sensitivity analyses also revealed consistent findings of increased AF risk associated with β-blocker treatment.ConclusionThe findings from this study suggest that β-blocker treatment is associated with an increased risk of incident AF and may help physicians select a modest medication for patients while also assessing the risk of AF.

AimsThis study aims to investigate the effects of coronary collateral circulation (CCC) on the prognosis of chronic total occlusion (CTO) patients with or without metabolic syndrome (MetS).MethodsThe study included 342 CTO patients who underwent successful percutaneous coronary intervention at the People's Hospital of Liaoning Province between 1 February 2021 and 30 September 2023. The Rentrop score was used to assess the status of CCC. The outcome was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of all-cause mortality, cardiac death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR), and non-fatal stroke. Univariate and multivariate logistic analyses were used to investigate the association of CCC, MetS, and MACCEs with odds ratios (ORs) and 95% confidence intervals (CIs). The effect of CCC was further investigated in different MetS, diabetes mellitus (DM), and Syntax score groups.ResultsMACCEs were more common in patients with poor CCC compared to those with good CCC (38.74% vs. 16.56%). Statistical differences were found in MACCEs (OR = 3.33, 95% CI: 1.93–5.72), MI (OR = 3.11, 95% CI: 1.73–5.58), TVR (OR = 3.06, 95% CI: 1.70–5.53), and stent thrombosis (OR = 6.14, 95% CI: 2.76–13.65) between the good and poor CCC groups. Poor CCC patients with MetS had a higher incidence of MACCEs (OR = 4.21, 95% CI: 2.05–8.65), non-fatal MI (OR = 4.44, 95% CI: 2.01–9.83), TVR (OR = 3.28, 95% CI: 1.51–7.11), and stent thrombosis (OR = 10.80, 95% CI: 3.11–37.54). Similar findings were also observed in CTO patients with DM and a Syntax score ≥23.ConclusionPoor CCC could increase the risk of MACCEs in CTO patients, particularly those with MetS, DM, and a Syntax score ≥23. Further prospective, multicenter studies are needed to validate our findings and to explore potential therapeutic interventions.

To address the efficiency bottleneck encountered in reactor design calculations for the newly developed lead-based reactor neutronics analysis code system MOSASAUR, we recently developed acceleration functions based on various coarse-mesh finite difference (CMFD) methods and spatial domain decomposition parallel algorithm. However, the applicability of these improvements to different lead-based reactors remains to be analyzed. This work collected and established core models for various types of lead-based reactor. Based on different SN nodal transport solvers, we analyzed the acceleration performance of different CMFD methods, different CPU cores, and the combination of CMFD and parallel calculation. The results indicated that the impact of different CMFD acceleration or parallel acceleration on the calculation accuracy was negligible; the rCMFD method had good stability and convergence rate, achieving speedup of several to dozens; parallel efficiency was related to the number of meshes, and for large reactor cores, superlinear speedup was achieved with 200 CPU cores; rCMFD and parallel computing could achieve combined speedup, with 200 cores achieving speedup of hundreds to thousands, typically completing a reactor core transport calculation in 1 min.

Introductionβ-nicotinamide mononucleotide (β-NMN) is an essential precursor of nicotinamide adenine dinucleotide (NAD+) and plays a key role in supplying NAD+ and maintaining its levels. Existing methods for NMN production have some limitations, including low substrate availability, complex synthetic routes, and low synthetic efficiency, which result in low titers and high costs.MethodsWe constructed high-titer, genetically engineered strains that produce NMN through a new pathway. Bacillus subtilis WB600 was used as a safe chassis strain. Multiple strains overexpressing NadE, PncB, and PnuC in various combinations were constructed, and NMN titers of different strains were compared via shake-flask culture.ResultsThe results revealed that the strain B. subtilis PncB1-PnuC exhibited the highest total and extracellular NMN titers. Subsequently, the engineered strains were cultured in a 5-L fermenter using batch and fed-batch fermentation. B. subtilis PncB1-PnuC achieved an NMN titer of 3,398 mg/L via fed-batch fermentation and glucose supplementation, which was 30.72% higher than that achieved via batch fermentation.DiscussionThis study provides a safe and economical approach for producing NMN on an industrial scale.

ObjectiveAlthough extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia.MethodsTo address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV.ResultsOur findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure.ConclusionOur research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

ObjectiveThis study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS.MethodsA retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration.ResultsThe C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration.ConclusionThe TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response.

Objective: Titanium implants are widely used in surgeries for their biocompatibility and mechanical properties. However, excessive titanium particle release can cause implant failure. This study explores Atomic Layer Deposition (ALD) to coat commercially pure titanium (Cp-Ti) with TiO2, aiming to improve its frictional and corrosion resistance while reducing particle release. By comparing TiO2 films with varying ALD cycle numbers, we assess surface properties, particle release, friction, and corrosion performance, providing insights into mitigating particle release from implants.Methods: Cp-Ti surfaces were prepared and coated with TiO2 films of 100, 300, and 500 ALD cycles. Surface characterization involved SEM, EDX, and XRD. Friction was tested using SEM, nanoindentation, and ICP-MS. Corrosion resistance was evaluated through immersion tests and electrochemical analysis. Cytotoxicity was assessed using BMSCs.Results: Surface characterization revealed smoother surfaces with increased ALD cycles, confirming successful TiO2 deposition. Friction testing showed reduced friction coefficients with higher ALD cycles, supported by nanoindentation results. Corrosion resistance improved with increasing ALD cycles, as evidenced by electrochemical tests and reduced titanium release. Cytotoxicity studies showed no significant cytotoxic effects.Conclusion: ALD-coated TiO2 films significantly enhance frictional and corrosion resistance of titanium implants while reducing particle release. The study underscores the importance of ALD cycle numbers in optimizing film performance, offering insights for designing implants with improved properties.

Interactions between macrophages and adipocytes in adipose tissue are critical for the regulation of energy metabolism and obesity. Macrophage polarization induced by cold or other stimulations can drive metabolic reprogramming of adipocytes, browning, and thermogenesis. Accordingly, investigating the roles of macrophages and adipocytes in the maintenance of energy homeostasis is critical for the development of novel therapeutic approaches specifically targeting macrophages in metabolic disorders such as obesity. Current review outlines macrophage polarization not only regulates the release of central nervous system and inflammatory factors, but controls mitochondrial function, and other factor that induce metabolic reprogramming of adipocytes and maintain energy homeostasis. We also emphasized on how the adipocytes conversely motivate the polarization of macrophage. Exploring the interactions between adipocytes and macrophages may provide new therapeutic strategies for the management of obesity-related metabolic diseases.

Most host-microbiota interactions occur within the intestinal barrier, which is essential for separating the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. Gut inflammation allows pathogenic bacteria to enter the blood stream, forming immune complexes which may deposit on organs. Despite increased circulating immune complexes (CICs) in patients with inflammatory bowel disease (IBD) and discussions among IBD experts regarding their potential pathogenic role in extra-intestinal manifestations, this phenomenon is overlooked because definitive evidence demonstrating CIC-induced extra-intestinal manifestations in IBD animal models is lacking. However, clinical observations of elevated CICs in newly diagnosed, untreated patients with IBD have reignited research into their potential pathogenic implications. Musculoskeletal symptoms are the most prevalent extra-intestinal IBD manifestations. CICs are pivotal in various arthritis forms, including reactive, rheumatoid, and Lyme arthritis and systemic lupus erythematosus. Research indicates that intestinal barrier restoration during the pre-phase of arthritis could inhibit arthritis development. In the absence of animal models supporting extra-intestinal IBD manifestations, this paper aims to comprehensively explore the relationship between CICs and arthritis onset via a multifaceted analysis to offer a fresh perspective for further investigation and provide novel insights into the interplay between CICs and arthritis development in IBD.

ObjectiveThis study aims to identify risk factors for vascular complications during non-emergency endovascular treatment in patients with internal carotid artery occlusion (ICAO) and to propose potential interventions.MethodA retrospective analysis of 92 patients with ICAO who received non-emergency endovascular treatment in our center from 1 January 2018 to 31 June 2023, was conducted. The correlation between intraoperative vascular complications and potential risk factors was studied, and interaction analysis was performed.ResultsOur findings revealed that the use of non-neurology guide wires to open vessels (adjusted OR: 4.1, 95%CI: 1.3–12.8; p = 0.014) and glycosylated hemoglobin (HbA1c) ≥ 6.5 mmol/L (adjusted OR: 3.2, 95%CI: 1.2–8.9; p = 0.023) was significantly associated with vascular complications in non-emergency endovascular treatment of ICAO patients. The restricted cubic spline (RCS) showed that the higher the HbA1c level, the higher the risk of vascular complications.ConclusionThe use of non-neurology guide wires for vessel opening during non-emergency endovascular treatment in patients with ICAO increases the risk of vascular complications. Preoperative assessment and management of HbA1c levels can reduce the incidence of intraoperative vascular complications.

BackgroundGastroschisis has increased in recent years, however, complicated gastroschisis is associated with higher mortality, as well as higher health care costs and disease burdens from short- and long-term complications.Case introductionA woman aged 25 years old at 37 + 1 weeks gestation (gravida 2; para 0) was admitted to the hospital because of foetal gastroschisis. Targeted quaternary ultrasound performed at our hospital showed that 34 mm of the abdominal wall was interrupted continuously, an intestinal echo with a range of approximately 88 × 50 mm was seen bulging outwards the local area close to the intestinal wall showed a 34 × 23 m anecho, and the foetus was measuring 2 weeks smaller than expected. After MDT including the maternal-foetal medicine, ultrasound, paediatric surgery, neonatal intensive care unit (NICU), and anaesthesiology departments, caesarean section was performed at 37 + 2 weeks. A baby boy was delivered, the small intestine, large intestine and stomach were seen outside of the abdomen, the abdominal cavity was excluded from the defect on the right side of the umbilical cord, the mesentery was shortened, and the intestinal tube had obvious oedema After paediatric surgical discussion, silo bag placement and delayed closure was performed, the placement process was smooth. One week following silo placement, the abdominal contents had been fully reduced below the fascia following daily partial reductions of the viscera,and the second stage of the operation was performed under general anaesthesia. The newborn was successfully discharged from the hospital 20 days after the operation and was followed up, with good growth, normal milk intake and smooth bowel movements.ConclusionsThe diagnosis and treatment of complicated gastroschisis needs to be carried out under multidisciplinary team treatment. Delivery by cesarean section after 37 weeks is feasible.Immediate postpartum surgery is possible, and the choice of surgical modality is determined by the child's condition, emphasizing that it should be performed without adequate sedation under anaesthesia. A standardized postoperative care pathway appropriate to risk should be developed to optimize nutritional support and antibiotic use, and standardized enteral feeding practices should be sought with long-term follow-up.

The Lower Jurassic Reservoir (LJR) in the Lenghu area on the northern margin of the Qaidam Basin (NMoQB) has become the most promising target for hydrocarbon exploration. The reservoir has experienced complex diagenesis; however, the porosity evolution and the influence of different diagenesis events on reservoir densification remains unclear. In this study, various analytical methods was first used to clarify the diagenetic stage and sequence, establish a porosity evolution model, quantitatively analyze the time and influence of different diagenesis events on reservoir densification, and illustrate the densification mechanism of tight sandstone reservoir in the Lenghu area. The results showed that the dominant rock types in the LJR were feldspathic litharenite, followed by litharenite, lithic arkose, and a small amount of subarkose and sublitharenite. The reservoir is a typical tight sandstone reservoir (TSR), with average porosity and permeability of 5.5% and 0.08 mD, respectively. The pore types were primarily secondary pores, followed by residual intergranular pores and occasional fractures. Diagenesis of LJR has entered the meso-diagenetic stage A, with minor progression into meso-diagenetic stage B. Quantitative calculation showed that the initial porosity of LJR is 32.2%. In eo-diagenetic stage A, compaction is the main factor for porosity reduction. In eo-diagenetic stage B, the porosity loss rates caused by compaction and cementation were 81.5% and 11.8%, respectively. In this stage, the LJR in the Lenghu area has almost been densified, mainly affected by compaction, calcite cementation and clay minerals cementation. Additionally, cementation is an important factor causing reservoir heterogeneity and is dominated by calcite and clay mineral cementation. After entering the meso-diagenetic stage A, dissolution is the main diagenesis event, which can increase porosity by 6.0%. This stage is the critical period for forming high-quality reservoir of LJR in the Lenghu area, mainly in the 4,400 m depth. In meso-diagenetic stage B, the influence of dissolution gradually decreased. Simultaneously, in this stage, the cementation of iron-bearing calcite further strengthened the densification of the LJR in the Lenghu area.

As one of the forth-generation nuclear energy system reactor types, lead fast reactor has good safety and economical properties due to the stable chemical properties of the coolant and the proliferation characteristics of the fuel, and modular nuclear power faster reactor designed for nuclear plant can further improve the economics of the reactor. In this article, the conceptual design of the lead-based modular power reactors with different power levels loaded with uranium alloy fuel is found to be found that when reactor core size increased to a certain level, the proliferation performance is too high due to the increase of the reactor core size under a specific core life such as 2000EFPD, so at the end of core life, the reactor core still has a large remaining reactivity. The proliferation advantage of the core cannot be fully released during the current core life time. Based on this phenomenon, in this article, we optimized the conceptual design of lead-based modular nuclear power reactor core loaded with uranium alloy fuel, and proposed to choose the appropriate rod to diameter ratio and effective density of fuel based on the power level and life time of the core. By adjusting the amount of uranium and 235U per unit volume, the proliferation performance of the core can be changed to match the power level and life time of the core. So the reactivity of core during the life period does not change, which not only reduce the difficulty of the reactivity control, but also make full use of the proliferation performance of the core. And at the same time, the reasonable rod to diameter ratio can provide safety and design margin for the analysis of thermal and hydraulic safety, and effectively improve the economy and safety of the core.

IntroductionForage culture is a common way to restore degraded grasslands and soil functions, in which the reconstruction of the soil microbial community and its relationship with extracellular enzyme activity (EEAs) can characterize the recovery effects of degraded grasslands. However, the impacts of forage culture on the interaction between soil microbes and EEAs and whether the recovery effect of soil functions depends on the varying degradation statuses remain unclear.MethodsWe conducted a plantation of a dominant grass, Leymus chinensis, in the soil collected from severe, moderate, light, and non-degradation statuses in the Songnen grassland in northeastern China. We measured soil microbial diversity and soil EEAs, and predicted microbial functional groups using FUNGuild.ResultsThe results showed that L. chinensis culture promoted soil bacterial alpha diversity and soil EEAs only in the moderate degradation status, indicating a dramatic dependence of the recovery effects of the grass culture on degradation status of the grassland. After planting L. chinensis for 10 weeks, a decreasing trend in the chemoheterotrophy and nitrate-reduction microbial functional groups was found. In contrast, the abundance of the nitrogen (N)-fixing microbial functional group tended to increase. The positive correlation between soil EEAs and the nitrate-reduction and N-fixing microbial functional groups was enhanced by planting L. chinensis, indicating that grass culture could promote soil N cycle functions.ConclusionWe illuminate that grass culture may promote the restoration of soil functions, especially soil N cycling in degraded grasslands, and the recovery effect may depend on the grassland degradation status. We emphasized that selection of the plant species for restoration of grasslands needs to consider the restoration effects of microbial functional groups and soil functions.

IntroductionInfectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples.MethodsIn this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform–based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios.ResultsCombined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii.DiscussionRapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

BackgroundCurrently, the prevalence of allergic rhinitis (AR) remains high and there is a great need to develop better and safer ways to alleviate AR symptoms. The Lactobacillus plantarum GUANKE probiotic was reported as an immunomodulator through maintaining Th1/Th2 balance. This study aimed to determine the efficacy of GUANKE in AR subjects.MethodsAdults aged from 18 to 60 years old and previously suffered from AR were recruited and received GUANKE probiotics treatment for 4 weeks. The questionnaires of Total nasal symptom scores (TNSS), total non-nasal symptom score (TNNSS), and rhinitis control assessment test (RCAT) were used to assess the effectiveness before and after treatment. The serum allergen-specific IgE and cytokines were also determined at baseline and after 4 weeks of probiotics administration.ResultsThe results showed that TNSS and TNNSS were significantly reduced and the RCAT score was significantly increased compared to baseline. The sub-symptom score of rhinorrhea, itching, sneezing, and tearing in each questionnaire also showed significant changes, and the serum IgE level was markedly decreased. We further measured inflammatory-related proteins in serum and found that a total of 20 proteins (6 upregulated and 14 downregulated) were significantly changed compared to baseline, including IL-4, IL-7, IL-20, IL-33, CXCL1, CXCL5, CXCL6, CXCL11, CCL4, CCL23, TGF-alpha, LAP-TGF-beta-1, MMP-1, MMP-10, AXIN1, NT-3, OSM, SCF, CD6, and NRTN. Enrichment analysis showed that these significantly altered proteins were mainly enriched in cytokine and chemokine-related signaling pathways.ConclusionTaken together, this study demonstrated the Lactobacillus plantarum GUANKE can serve as an effective immunobiotic for the treatment of AR, which is realized through maintaining the Th1/Th2 balance by modulating the functions of various cytokines and chemokines.

IntroductionHu sheep, known for its high quality and productivity, lack fundamental scientific research in China.MethodsThis study focused on the effects of 24 h postmortem aging on the meat physiological and transcriptomic alteration in Hu sheep.ResultsThe results showed that the 24 h aging process exerts a substantial influence on the mutton color, texture, and water content as compared to untreated group. Transcriptomic analysis identified 1,668 differentially expressed genes. Functional enrichment analysis highlighted the importance of glycolysis metabolism, protein processing in endoplasmic reticulum, and the FcγR-mediated phagocytosis pathway in mediating meat quality modification following postmortem aging. Furthermore, protein-protein interaction analysis uncovered complex regulatory networks involving glycolysis, the MAPK signaling pathway, protein metabolism, and the immune response.DiscussionCollectively, these findings offer valuable insights into the molecular mechanisms underlying meat quality changes during postmortem aging in Hu sheep, emphasizing the potential for improving quality control strategies in mutton production.

BackgroundPreclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC).MethodsPatients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190.ResultsThis study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths.ConclusionIn patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities.

This study employs the power spectrum inversion method to generate the phase screens of atmospheric turbulence over the sea, the theoretical model of the vortex beam array emitted by a focusing system through anisotropic non-Kolmogorov maritime atmospheric turbulence was built. The propagation characteristics of the vortex beam array were investigated theoretically and compared to those of the Gaussian beam array. The results show that the vortex beam array is less affected by turbulence and exhibits stronger resistance to the turbulence. On this basis, using the evaluation parameters including the relative beam width and the beam wander, the influences of various parameters of the vortex beam array and atmospheric turbulence, such as topological charge, beamlet width, number of beamlets, anisotropy factor, and power law, on its propagation characteristics through anisotropic non-Kolmogorov maritime atmospheric turbulence were studied extensively. The results can provide a useful reference for the applications of the vortex beam array in optical communication through the maritime atmosphere.

PurposeTo investigate changes in foveal avascular area (FAZ) and retinal vein diameter in patients with retinal vein occlusion (RVO) after intravitreal ranibizumab, and to analyze the correlation between ranibizumab therapy and visual gain.MethodsThis retrospective study enrolled 95 eyes of 95 patients who had accepted three consecutive monthly ranibizumab injections, including 50 branch RVOs (BRVOs) and 45 central RVOs (CRVOs). BRVOs were divided into ischemia group (n = 32) and non-ischemia group (n = 18), and CRVOs also had ischemia group (n = 28) and non-ischemia group (n = 17). Comprehensive ophthalmic examinations were performed before the first injection and after 6, 12, and 24 months. The FAZ was manually circumscribed on early-phase images of fundus fluorescein angiography. Retinal vein diameters were measured on fundus photographs.ResultsAfter three injections, the FAZ area was significantly enlarged firstly and then reduced in all ischemic RVOs and the non-ischemic BRVOs (p

IntroductionDryland ecosystems face serious threats from climate change. Establishing the spatial pattern of ecosystem multifunctionality, maximum height and the correlation of biodiversity patterns with climate change is important for understanding changes in complex ecosystem processes. However, the understanding of their relationships across large spatial areas remains limited in drylands.MethodsAccordingly, this study examined the spatial patterns of ecosystem multifunctionality, maximum height and considered a set of potential environmental drivers by investigating natural shrub communities in Northwest China.ResultsWe found that the ecosystem multifunctionality (EMF) and maximum height of shrub communities were both affected by longitude, which was positively correlated with the precipitation gradient. Specifically, the EMF was driven by high precipitation seasonality, and the maximum height was driven by high precipitation stability during the growing season. Among the multiple biodiversity predictors, species beta diversity (SD-beta) is the most common in determining EMF, although this relationship is weak.DiscussionUnlike tree life form, we did not observe biodiversity-maximum height relationships in shrub communities. Based on these results, we suggest that more attention should be paid to the climatical fluctuations mediated biodiversity mechanisms, which are tightly correlated with ecosystem’s service capacity and resistance capacity under a rapid climate change scenario in the future.

Kidney formation and nephrogenesis are controlled by precise spatiotemporal gene expression programs, which are coordinately regulated by cell-cycle, cell type-specific transcription factors and epigenetic/chromatin regulators. However, the roles of epigenetic/chromatin regulators in kidney development and disease remain poorly understood. In this study, we investigated the impact of deleting the chromatin remodeling factor Smarca4 (Brg1), a human Wilms tumor-associated gene, in Wnt4-expressing cells. Smarca4 deficiency led to severe tubular defects and a shortened medulla. Through unbiased single-cell RNA sequencing analyses, we identified multiple types of Wnt4Cre-labeled interstitial cells, along with nephron-related cells. Smarca4 deficiency increased interstitial cells but markedly reduced tubular cells, resulting in cells with mixed identity and elevated expression of cell-cycle regulators and genes associated with extracellular matrix and epithelial-to-mesenchymal transition/fibrosis. We found that Smarca4 loss induced a significant upregulation of the oncogene Pttg1 and hyperproliferation of Wnt4Cre-labeled cells. These changes in the cellular state could hinder the cellular transition into characteristic tubular structures, eventually leading to fibrosis. In conclusion, our findings shed light on novel cell types and genes associated with Wnt4Cre-labeled cells and highlight the critical role of Smarca4 in regulating tubular cell differentiation and the expression of the cancer-causing gene Pttg1 in the kidney. These findings may provide valuable insights into potential therapeutic strategies for renal cell carcinoma resulting from SMARCA4 deficiency.

The interaction between poisonous weeds and neighboring plants is complex. Poisonous weeds frequently have a competitive advantage in the interaction between poisonous weeds and neighboring plants. Arbuscular mycorrhizal fungi (AMF) and plant pathogenic fungi (PPF) are closely related to the interspecific relationships of plants. However, the role of AMF and PPF between poisonous weeds and neighboring grasses remains unclear. Here, we designed a pot experiment to determine the interspecific relationship between Leymus chinensis and Stellera chamaejasme and the regulation of AMF and PPF. The results showed that interactive effects between L. chinensis and S. chamaejasme significantly inhibited the aboveground growth of both but promoted the underground growth of L. chinensis. As the proportions of S. chamaejasme increased, the total nitrogen content and pH in the rhizosphere soil of L. chinensis were reduced, the soil pH of S. chamaejasme was reduced, and the relative abundance of AMF in the rhizosphere soil of L. chinensis significantly increased and that of S. chamaejasme decreased considerably. The relative abundances of PPF in the rhizosphere soil of both in the mono-cultures were significantly higher than those in the mixed cultures. Structural equation modeling indicated that soil abiotic (pH and N availability) and biotic (AMF and PPF) factors are major drivers explaining the interactive effects between L. chinensis and S. chamaejasme. We provided new evidence for the interspecific interactions between poisonous weeds and neighboring grasses and revealed the regulatory role of AMF and PPF in the interactive effects of both plants. This study will provide a scientific basis for the prevention and control of poisonous weeds and the vegetation restoration of degraded grasslands in the future.

Introduction: To explore the influence of seismic disturbance and saturation on the mechanical properties of phosphate rock, the paper divided phosphorus rock into natural group, water-saturated Group and “earthquake and water-saturated” group.Methods: Fatigue loading and conventional triaxial compression tests were carried out to study the physical characteristics, degeneration characteristics, strength characteristics and failure characteristics of the samples.Results: The conclusions are as follows: The average wave velocity of samples of water-saturated group and “earthquake and saturation” group is 29.7% and 52.9% lower than that in natural group, respectively, and the average peak strength under various confining pressure conditions is 32.2% and 48.3% lower than that in natural group, respectively, indicating that both seismic stress loading and saturation have deterioration effects on the samples.Discussion: Compared with natural group and watersaturated group, after simulated seismic stress loading, the stress-strain curve of “earthquake and water-saturated” group shakes obviously after the peak, and the steps appear frequently, showing obvious plastic characteristics. Due to the different deterioration degree of the samples, the samples of the natural group were in the overall state of compression during the triaxial test, while the samples of the water-saturated group were compressed before failure and expanded after failure. The sample of earthquake and water-saturated group is in the whole state of expansion. The failure characteristics of natural samples and water-saturated samples are shear or shear failure. The shear plane starts from the edge of sample end face and presents typical diagonal shear failure. The failure characteristics of “earthquake and water-saturated” group samples are heavy shear and through failure. There are several fracture zones extending inward from the end of the sample, resulting in obvious transverse expansion.

PurposeThe aim of this study was to investigate the predictive role of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the prognostic risk stratification of patients with invasive breast cancer (IBC). To achieve this, we developed a clinicopathologic-radiomic-based model (C-R model) and established a nomogram that could be utilized in clinical practice.MethodsWe retrospectively enrolled a total of 91 patients who underwent preoperative 18F-FDG PET/CT and randomly divided them into training (n=63) and testing cohorts (n=28). Radiomic signatures (RSs) were identified using the least absolute shrinkage and selection operator (LASSO) regression algorithm and used to compute the radiomic score (Rad-score). Patients were assigned to high- and low-risk groups based on the optimal cut-off value of the receiver operating characteristic (ROC) curve analysis for both Rad-score and clinicopathological risk factors. Univariate and multivariate Cox regression analyses were performed to determine the association between these variables and progression-free survival (PFS) or overall survival (OS). We then plotted a nomogram integrating all these factors to validate the predictive performance of survival status.ResultsThe Rad-score, age, clinical M stage, and minimum standardized uptake value (SUVmin) were identified as independent prognostic factors for predicting PFS, while only Rad-score, age, and clinical M stage were found to be prognostic factors for OS in the training cohort. In the testing cohort, the C-R model showed superior performance compared to single clinical or radiomic models. The concordance index (C-index) values for the C-R model, clinical model, and radiomic model were 0.816, 0.772, and 0.647 for predicting PFS, and 0.882, 0.824, and 0.754 for OS, respectively. Furthermore, decision curve analysis (DCA) and calibration curves demonstrated that the C-R model had a good ability for both clinical net benefit and application.ConclusionThe combination of clinicopathological risks and baseline PET/CT-derived Rad-score could be used to evaluate the prognosis in patients with IBC. The predictive nomogram based on the C-R model further enhanced individualized estimation and allowed for more accurate prediction of patient outcomes.

Heart diseases have a high incidence and mortality rate, and seriously affect people’s quality of life. Mitochondria provide energy for the heart to function properly. The process of various heart diseases is closely related to mitochondrial dysfunction. Panax ginseng (P. ginseng), as a traditional Chinese medicine, is widely used to treat various cardiovascular diseases. Many studies have confirmed that P. ginseng and ginsenosides can regulate and improve mitochondrial dysfunction. Therefore, the role of mitochondria in various heart diseases and the protective effect of P. ginseng on heart diseases by regulating mitochondrial function were reviewed in this paper, aiming to gain new understanding of the mechanisms, and promote the clinical application of P. ginseng.

Regulatory T cells (Tregs) are an important component of the tumor microenvironment; however, the interaction between Tregs and gastric cancer cells is not completely understood. Recent studies have shown that Tregs participate in cancer cell stemness maintenance. In this study, we performed single-cell RNA sequencing of gastric cancer and adjacent tissues and found that Tregs with high TNF expression were recruited to gastric cancer tissues and were significantly correlated with patient survival. TNF+ Tregs significantly contribute to tumor growth and progression. Our studies have further demonstrated that TNF+ Tregs promote the stemness of gastric cancer cells through the IL13/STAT3 pathway. Therefore, blocking the interaction between TNF+ Tregs and gastric cancer cells may be a new approach in the treatment of gastric cancer.

Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world's swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan dose-dependently inhibited a PEDV infection at 24 h post-infection (EC50 value = 0.67 μM). We found that Fan mainly affected the PEDV replication phase but also inhibited PEDV at the attachment and internalization stages of the viral life cycle. Mechanistically, Fan blocked the autophagic flux in PEDV-infected cells by regulating the expression of autophagy-related proteins and changing PEDV virus particles. In summary, Fan inhibits PEDV infection by blocking the autophagic flux in cells. Our findings will help develop new strategies to prevent and treat PEDV infection.