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Abstract Objective To investigate the prognostic significance of CXCL8 in cervical cancer and its effect on immune response based on bioinformatics method. Methods This study employs the HPA database to investigate CXCL8 expression in normal human tissues.The TIMER2.0 database is utilized to analyze CXCL8 expression across various types of cancer.Utilizing the TCGA database, we analyze the correlation between CXCL8 and the overall survival (OS) and progression-free interval (PFI) of patients with various tumors using R 4.3.2.Additionally, its association with immune checkpoint-related genes across various types of cancer is examined.We further analyze the association between CXCL8 expression and the expression of LAG3, CTLA4, PDCD1, and CD274 in cervical cancer.The TIMER database is used to study the association between CXCL8 and the extent of Tumor-Infiltrating Immune Cells (TIICs) infiltration.Enrichment analysis of genes related to CXCL8 is conducted using the LinkedOmics database. Result CXCL8 is found in a wide range of normal human tissues.In the majority of tumor tissues, CXCL8 expression is elevated compared to their normal counterparts.There is a significant correlation between CXCL8 expression and the overall survival (OS) and progression-free interval (PFI) of patients with various tumors.CXCL8 expression is associated with the expression of diverse immune checkpoint-related genes and the extent of Tumor-Infiltrating Immune Cells (TIICs) infiltration.Genes related to CXCL8 participate in diverse immune-related processes in cervical cancer. Conclusion CXCL8 plays a role in modulating immune infiltration, thereby influencing the prognosis of patients with various tumors, particularly those with cervical cancer.CXCL8 could potentially act as a biomarker for forecasting the prognosis and immune response of patients with tumors.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases. Methods From January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance. Results The multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452–4.360), elevated serum PT (p 8.0 μmol/L) (p

Abstract Background To retrospectively analyze the risk factors of liver metastases in patients with gastric cancer in a single center, and to establish a Nomogram prediction model to predict the occurrence of liver metastases. Methods A total of 96 patients with gastric cancer who were also diagnosed with liver metastasis (GCLM) and treated in our center from January 1, 2010 to December 31, 2020 were included. The clinical data of 1095 patients with gastric cancer who were diagnosed without liver metastases (GC) in our hospital from January 1, 2014 to December 31, 2017 were retrospectively compared by univariate and multivariate logistic regression. 309 patients diagnosed with gastric cancer in another medical center from January 1, 2014 to December 31, 2018 were introduced as external validation cohorts. Results Based on the training cohort, multivariate analysis revealed that tumor site (OR = 0.55, P = 0.046), N stage (OR = 4.95, P = 0.004), gender (OR = 0.04, P = 0.001), OPNI (OR = 0.95, P = 0.041), CEA (OR = 1.01, P = 0.018), CA724 (OR = 1.01, P = 0.006), CA242 (OR = 1.01, P = 0.006), WBC (OR = 1.13, P = 0.024), Hb (OR = 0.98, P

Abstract Background To explore the role of GAB2 in pan-cancer based on bioinformatics analysis. Methods Based on TCGA and GTEx databases, we used TIMER2.0 online analysis tool and R language to analyze the expression of GAB2 in pan-cancer. We used Kaplan–Meier Plotter to analyze the relationship between GAB2 and OS and RFS in pan-cancer. We utilized the CPTAC database to examine the expression of phosphorylated GAB2 in pan-cancer. We investigated the effects of mutation features on the occurrence and development of human cancers by cBioPortal and COSMIC. Using the database, we conducted an analysis of molecular compounds that have the potential to interact with GAB2 through molecular docking. Moreover, we use the TIMER to explore the relationship between GAB2 and immune cell infiltration, and draw relevant heatmaps by R language. Results GAB2 was abnormally expressed in various tumors and was associated with prognosis. There were differences in the expression of GAB2 phosphorylation in tumor tissues and corresponding normal tissues among different types of tumors. GAB2 interacts with Docetaxel and was associated with immune cell infiltration in various tumors. Conclusion GAB2 participates in regulating immune infiltration and affects the prognosis of patients. GAB2 may serve as a potential tumor marker.

Abstract This study aims to explore the risk factors associated with frozen shoulder (FS) and develop a predictive model for diagnosing FS, in order to facilitate early detection of the condition. A total of 103 patients diagnosed with FS and admitted to the Department of Joint Surgery at Suining Central Hospital between October 2021 and October 2023 were consecutively included in the study. Additionally, 309 individuals without shoulder joint diseases, matched for age and gender, who visited the department during the same time, were included as the control group.The complete recording of clinical data for all patients was followed by the utilization of statistical tests such as the Mann–Whitney U test, sample t test, and chi-square test to compare different groups. Additionally, multivariate binary logistic regression analysis was employed to identify risk factors associated with the occurrence of FS in patients, leading to the establishment of a prediction model and derivation of a simplified equation. The diagnostic effectiveness of individual indicators and prediction models was assessed through the use of receiver operating characteristic (ROC) curve analysis. In the sample of 103 individuals, 35 were identified as male and 68 as female, with an average age range of 40–70 years (mean age: 54.20 ± 6.82 years). The analysis conducted between different groups revealed that individuals with a low body mass index (BMI), in conjunction with other factors such as diabetes, cervical spondylosis, atherosclerosis, and hyperlipidemia, were more susceptible to developing FS. Logistic regression analysis further indicated that low BMI, diabetes, cervical spondylosis, and hyperlipidemia were significant risk factors for the occurrence of FS. These variables were subsequently incorporated into a predictive model, resulting in the creation of a simplified equation.The ROC curve demonstrated that the combined indicators in the predictive model exhibited superior diagnostic efficacy compared to single indicators, as evidenced by an area under the curve of 0.787, sensitivity of 62.1%, and specificity of 82.2%. Low BMI, diabetes, cervical spondylosis, and hyperlipidemia are significant risk factors associated with the occurrence of FS. Moreover, the utilization of a prediction model has demonstrated superior capability in forecasting the likelihood of FS compared to relying solely on individual indicators. This finding holds potential in offering valuable insights for the early diagnosis of FS.

Abstract Introduction Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. Methods We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. Results One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0–3 was 58.4%. Conclusion Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.

Abstract Background A few previous cross-sectional studies investigated correlated factors of suicidal ideation or suicide attempts among suicide prevention hotline callers; however, scarcely any evidence was from a longitudinal study. In addition, it is still unclear whether improvements in some suicide risk factors could reduce the occurrence of subsequent suicidal acts. This longitudinal study focusing on the risk factors for subsequent suicidal acts among adolescent and young adult callers with high suicide risk aims to fill this gap. Methods This study recruited 12–25-year-old high-risk callers to a China nationwide suicide prevention hotline. Potential risk factors, including hopefulness, psychological distress, depression, history of suicide attempts, alcohol or substance misuse, and acute life events, were examined during the index calls, and improvements in hopefulness, psychological distress, and suicide intent were assessed before ending the index calls. The recruited callers were followed up 12 months after their index calls. The primary outcome was the occurrence of suicidal acts (suicide attempts or suicide death) during follow-up. Kaplan–Meier survival curves, log-rank tests, and Cox proportional hazards model were used. Results During the follow-up period, 271 of 1656 high-risk adolescent and young adult callers attempted suicide, and seven callers died by suicide. After adjusting for demographic variables, low hopefulness (Hazard Ratio [HR] = 2.03, 95% Confidence Interval [CI]=[1.47, 2.80]) at the beginning of the index call was associated with a higher risk for subsequent suicidal acts, whereas improvements in psychological distress (HR = 0.61, 95%CI [0.41, 0.89]) and suicidal intent (HR = 0.56, 95%CI [0.38, 0.84]) during the index call reduced the risk of subsequent suicidal acts. In addition, alcohol or substance misuse (Model 2, HR = 1.65, 95%CI [1.11, 2.46]) and suicide attempt history(Model 1: one episode, HR = 1.96, 95%CI=[1.05, 3.66]; two or more episodes, HR = 2.81, 95%CI [1.59, 4.96]. Model 2: one episode, HR = 2.26, 95%CI [1.06, 4.82]; two or more episodes: HR = 3.28, 95%CI [1.63, 6.60]) were risk factors for subsequent suicidal acts. Conclusions While suicide prevention hotline operators deliver brief psychological interventions to high-risk adolescent and young adult callers, priority should be given to callers with low hopefulness and to the alleviation of callers’ high psychological distress and suicide intent.

Abstract Background Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia. Methods This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates. Results The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08–17.83]) or during hospitalization (4.18[1.62–10.78]). Conclusion The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.

Abstract Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Graphical Abstract

BackgroundPralsetinib, a selective oral inhibitor of rearranged during transfection (RET) fusion proteins and oncogenic RET mutants, has shown significant efficacy in treating RET fusion-positive non-small cell lung cancer and thyroid cancer. However, since pralsetinib was approved in the United States in September 2020, there have been limited reports of post-marketing adverse events (AEs). In this study, we aimed to analyze the AE signals with pralsetinib on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice.MethodsAll AE reports were obtained from the FAERS database from the first quarter (Q3) of 2020 to the second quarter (Q2) of 2024. Various signal quantification techniques were used for analysis, including reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker (MGPS)-based empirical Bayesian geometric mean.ResultsOut of 8,341,673 case reports in the FAERS database, 1,064 reports of pralsetinib as the “primary suspected (PS)” AEs were recorded, covering 26 system organ classes and 256 preferred terms. Of the reports, 62.5% were from consumers rather than healthcare professionals. The most common systems were general disorders and administration site conditions (n = 704), investigations (n = 516), and gastrointestinal disorders (n = 405). A total of 95 significant disproportionality preferred terms (PTs) conformed to the four algorithms simultaneously. AEs that ranked the top three at the PT level were hypertension (n = 80), asthenia (n = 79), and anemia (n = 65). Of the 95 PTs with significant disproportionation, unexpected significant AEs such as increased blood calcitonin, increased myocardial necrosis marker, and bacterial cystitis were observed, which were not mentioned in the drug’s instructions. The median onset time of pralsetinib-associated AEs was 41 days [interquartile range (IQR) 14–86 days]. The majority of the AEs occurred in 30 days (42.86%).ConclusionOur pharmacovigilance analysis of real-world data from the FEARS database revealed the safety signals and potential risks of pralsetinib usage. These results can provide valuable evidence for further clinical application of pralsetinib and are important in enhancing clinical medication safety.

The radial load distribution integral given by Harris integral method always plays a significant role in calculating the radial load distribution of radial bearings. The error of Harris integral method for calculating the radial load distribution is found caused by the inaccurate values of the radial load distribution integral given by Harris. The radial load distribution integral is corrected in three loading stages using a discrete method. The corrected radial load distribution integral is capable of calculating the load distribution of a bearing with a small load zone caused by a light external load or a great radial clearance. The corrected radial load distribution integral shows different phases varying with the number of rolling elements participating in the radial load transfer. Some specific numerical examples show the higher accuracy and superiority of the corrected radial load distribution integral.

Abstract Quark-gluon plasma’s (QGP) properties at non-hydrodynamic and non-perturbative regimes remain largely unexplored. Here, we examine the response functions describing how a QGP-like plasma responds to initial energy-momentum disturbance in both static and Bjorken-expanding plasma at non-hydrodynamic gradient using the Boltzmann equation in the relaxation-time approximation (RTA). We show that the resulting response functions are remarkably similar in both static and expanding backgrounds at non-hydrodynamic gradients. While non-hydrodynamic response can not be described by the conventional first-order and second-order theories, its behavior is reasonably captured by the extended version of hydrodynamics proposed by us [1]. The potential sensitivity of the Euclidean correlator to non-hydrodynamic response is also illustrated.

Abstract The illegal water injection into meat not only breaks the market equity, but also deteriorates the meat quality and produces harmful substances. In this work, we proposed a fiber Bragg grating (FBG) sensor that enabled fast, quantitative, and in-situ detection of the moisture content of water-injected meat. The FBG was written in the erbium-ytterbium (Er/Yb) co-doped fiber, which could perform the self-photothermal effect by injecting the near infrared laser into the fiber. As the heated fiber sensor probe was inserted into the meat sample, the temperature decreased due to the heat dissipation mediated by moisture. The intracore Bragg grating could monitor the temperature loss by recording the Bragg wavelength shift, which reflected the water content quantitatively. The results revealed that the sensor could complete the detection within 15 s. The sensor’s sensitivity to detect changes in the pork water content was theoretically calculated to be 0.090847%. The proposed sensor is expected to provide a novel approach for examination of the meat moisture.

Abstract Dynamic stress is one of the key indicators reflecting the fatigue characteristics of metro bogie frames. Considering the test costs, operation safety, and other factors, it is impossible to record all the dynamic stress data for the whole service period in the tracking test. Therefore, the overall stress spectrum is statistically deduced based on limited dynamic stress data samples, which can not only provide a basis for the fatigue reliability research of the bogie frame, but also save costs. In this paper, the typical fatigue control points in different areas of the frame with large equivalent stress are selected for research. The daily measured stress spectrum samples are obtained through the rainflow counting method, and the statistical stress spectrum is then compiled. Weibull distribution fitting of the stress spectrum is carried out to obtain the scale and shape parameter samples for different fatigue control parts. After sampling of the obtained parameter samples and conducting variance homogeneity tests as well as t-tests, the minimum sample size representing the overall distribution of the interval is obtained. Therefore, the shortest tracking test period reflecting the overall stress distribution of typical fatigue control parts can be obtained.

Abstract To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)–based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE–based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann–Whitney U test and receiver operating characteristic analysis. The Dstar values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = − 4.522, p

Abstract Background Chronic low back pain (LBP) related to flight is a prevalent health issue in military aviation, impacting pilots. The objective of this investigation was to ascertain if the application of core muscle training in conjunction with interferential current (IFC) therapy results in a reduction in pain severity and associated disability, consequently enhancing core muscle functionality in Chinese Air Force high-performance fighter pilots experiencing chronic LBP. Methods Fifty-three fighter pilots with chronic LBP were randomized into 3 groups: a core muscle exercise combined with IFC group (CG, n = 19), a core muscle exercise group (EG, n = 19), and an IFC group (IG, n = 15). The three groups underwent therapeutic intervention 5 times a week for 12 weeks. The primary outcomes were pain intensity, Oswestry Disability Index (ODI) score and SF-12 health-related quality of life (PCS and MCS) score. Secondary outcomes included evaluations of trunk muscle strength, endurance, and range of motion (ROM) during medial/lateral rotation to assess muscle functionality. Measurements were obtained both before and after the implementation of the intervention therapy. Results After 12 weeks of intervention therapy, all the health condition parameters significantly improved among the three groups. However, the CG had a significant improvement in pain intensity compared to the EG (MD = − 0.84 scores; 95% CI = − 1.54 to − 0.15; p = 0.013) and the IG (MD = − 1.22 scores; 95% CI = − 1.96 to − 0.48; p = 0.000). Additionally, the CG led to greater conservation of ODI and improved SF-12 PCS scores than did the IG (p 0.05). Conclusion Among participants with chronic LBP, three intervention therapies appear effective in reducing pain, diminishing disability, and enhancing quality of life. Also, combined therapy significantly improved pain and disability compared to the other two monotherapies; moreover, combined therapy and core muscle exercise provided similar benefits in terms of core muscle function after 12 weeks of intervention therapy.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

BackgroundThe relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis.MethodsThis study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient’s serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (β-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and β-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result’s stability.ResultsIt was observed that APOA1 levels were positively correlated with lumbar BMD (β = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to β-CTX (β = −0.19, 95% CI: −0.29 to −0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses.ConclusionThis study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

BackgroundThe systemic inflammatory response index (SIRI) is a novel composite biomarker of inflammation. However, there is limited information on its use in the context of osteoporotic fractures. Hence, this study aimed to investigate the association between baseline SIRI values and bone turnover markers (BTMs) in Chinese patients diagnosed with osteoporotic fractures (OPFs), to offer a more precise method for assessing bone health and inflammation in clinical settings.MethodsA retrospective cross-sectional study was conducted on 3,558 hospitalized patients with OPFs who required surgery or hospitalization at the First People’s Hospital of Kunshan City from January 2017 to July 2022. Baseline measurements of SIRI, β-CTX (beta-C-terminal telopeptide of type I collagen), and P1NP (procollagen type I N-terminal propeptide) were obtained. The analyses were adjusted for variables, including age, sex, body mass index (BMI), and other initial laboratory and clinical findings. Furthermore, multivariable logistic regression, smooth curve fitting, and threshold analysis were also performed.ResultsThe results revealed a negative correlation between baseline SIRI values and both β-CTX and P1NP levels. After adjusting for covariates in the regression analysis, each unit increase in SIRI was found to be inked to a reduction of 0.04 (β = −0.04; 95% confidence interval [CI], −0.05 to −0.03; with p-value

Globally, anthropogenic disturbance and climate change caused a rapid decline of submerged macrophytes in lake ecosystems. Potamogeton crispus (P. crispus), a species that germinates in winter, explosively expanded throughout many Chinese lakes, yet the underlying mechanism remained unclear. Here, this study examined the long-term changes in the distribution patterns of P. crispus in Lake Gaoyou by combining remote sensing images and hydrometeorological data from 1984 to 2022 and water quality data from 2009 to 2022. It aims to unravel the relationships between the distribution patterns of P. crispus and hydrometeorological and water quality factors. The results showed that the area of P. crispus in Lake Gaoyou showed a slight increase from 1984 to 2009, a marked increase from 2010 to 2019, followed by a decline after 2020. Spatially, P. crispus was primarily distributed in the western and northern parts of Lake Gaoyou, with less distribution in the central and southeastern parts of the lake. Wind speed (WS), temperature (Temp), water level (WL), ammonia nitrogen (NH3-N), and Secchi depth (SD) were identified as the key factors regulating the variation in the P. crispus area in Lake Gaoyou. We found that the P. crispus area showed an increasing trend with increasing Temp, WL, and SD and decreasing WS and NH3-N. The influence of environmental factors on the area of P. crispus in Lake Gaoyou varied among seasons. The results indicated that hydrometeorology (WS, Temp, and WL) may override water quality (NH3-N and SD) in driving the succession of P. crispus distribution. The findings of this study offer valuable insights into the recent widespread expansion of P. crispus in shallow lakes across Eastern China.

Background: Temperature affects influenza transmission; however, currently, limited evidence exists about its effect in China at the national and city levels as well as how temperature can be integrated into influenza interventions. Methods: Meteorological, pollutant, and influenza data from 201 cities in mainland China between 2013 and 2018 were analyzed at both the city and national levels to investigate the relationship between temperature and influenza prevalence. We examined the impact of temperature on the time-varying reproduction number (Rt) using generalized additive quasi-Poisson regression models combined with the distributed lag nonlinear model. Threshold temperatures were determined for seven regions based on the early warning threshold of serious influenza outbreaks, set at Rt = 1.2. A multivariate random-effects meta-analysis was employed to assess region-specific associations. The excess risk (ER) index was defined to investigate the correlation between Rt and temperature, modified based on seasonal and regional characteristics. Results: At the national level and in the central, northern, northwestern, and southern regions, temperature was found to be negatively correlated with relative risk, whereas the shapes of the data curves for the eastern, southwestern, and northeastern regions were not well defined. Low temperatures had an observable effect on influenza prevalence; however, the effects of high temperatures were not obvious. At an Rt of 1.2, the threshold temperatures for reaching a warning for serious influenza outbreaks were − 24.3 °C in the northeastern region, 16.6 °C in the northwestern region, and between 1℃ and 10 °C in other regions. Conclusion: The study findings revealed that temperature had a varying effect on influenza transmission trends (Rt) across different regions in China. By identifying region-specific temperature thresholds at Rt = 1.2, more effective early warning systems for influenza outbreaks could be tailored. These findings emphasize the significance of the region-specific adaptation of influenza prevention and control measures.

Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.

PurposeHow cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents.MethodsSixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score.ResultsALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p

A 42-days study was conducted to evaluate the effects of different dietary types (corn-or wheat-soybean meal-based diet) and phytase (Phy) or a multi-carbohydrase and phytase complex (MCPC) supplementation on growth performance, digestibility of phosphorus (P), intestinal transporter gene expression, plasma indexes, bone parameters, and fecal microbiota in growing pigs. Seventy-two barrows (average initial body weight of 24.70 ± 0.09 kg) with a 2 × 3 factorial arrangement of treatments and main effects of diet type (corn-or wheat-soybean meal-based-diets) and enzyme supplementation (without, with Phy or with MCPC). Each group was designed with 6 replicate pens. The MCPC increased (p

AIM: To observe the effects of N-acetylserotonin (NAS) administration on retinal ischemia-reperfusion (RIR) injury in rats and explore the underlying mechanisms involving the high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor-kappa B (NF-κB) signaling pathway. METHODS: A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye. Eighty male Sprague Dawley were randomly divided into five groups: sham group (n=8), RIR group (n=28), RIR+NAS group (n=28), RIR+FPS-ZM1 group (n=8) and RIR+NAS+ FPS-ZM1 group (n=8). The therapeutic effects of NAS were examined by hematoxylin-eosin (H&E) staining, and retinal ganglion cells (RGCs) counting. The expression of interleukin 1 beta (IL-1β), HMGB1, RAGE, and nod-like receptor 3 (NLRP3) proteins and the phosphorylation of nuclear factor-kappa B (p-NF-κB) were analyzed by immunohistochemistry staining and Western blot analysis. The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats. With NAS therapy, the HMGB1 and RAGE expression decreased significantly, and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression. Additionally, NAS exhibited an anti-inflammatory effect by reducing IL-1β expression. The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression, so as to the IL-1β expression and retinal edema, accompanied by an increase of RGCs in RIR rats. CONCLUSION: NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway, which may be a useful therapeutic target for retinal disease.

Advancing crop yield within limited agricultural land use is crucial to alleviate potential food shortages from the increasing world population. While genetic breeding holds great potential in improving crop yield, real-world practices are often constrained by the limitations of scaling the laboratory findings with respect to coupled environmental feedback and limited tools to project the optimal strategies based on environment and crop traits such as crop density management. Aided by a process- and trait-based vegetation model, we review and theoretically evaluate approaches that aim to improve crop yield through canopy radiative transfer optimization. The evaluated approaches include trait breeding (e.g. leaf color and chlorophyll action spectrum), canopy structure (e.g. canopy density and spacing), and environment manipulation (e.g. supplemental radiation intensity and source). We prototype vegetation modeling applications that can theoretically explore the potentials of a number of approaches at various setups that otherwise require tremendous effort in the real world, and propose to use vegetation modeling to guide more efficient agricultural practices. Future elaborations in vegetation modeling with respect to more physiological representations of vegetation processes, quantification of maintenance costs, and utilization of remote sensing data would further advance the utilization of modeling in agriculture.

Abstract To investigate the biomechanical properties of posterior cruciate ligament avulsion fractures of the tibia fixed using four different methods, including triple tibial channel net suture fixation. In 40 porcine knees, a standardized bony avulsion of the posterior cruciate ligament was generated. Double tibial bone channel suture fixation was performed in group A, double-head hollow compression screw fixation was performed in group B, triple tibial bone channel net suture fixation was performed in group C, and cortical suspension EndoButton fixation was performed in group D. The constructs were cyclically loaded 500 times (10 to 100 N) to measure the initial displacement and stiffness values. Subsequently, loading to failure was performed, and the yield load and peak load were measured. The results were analysed by one-way ANOVA, with significance set at P

Abstract Hepatocellular carcinoma (HCC) is the most widespread histological form of primary liver cancer, and it faces great diagnostic and therapeutic difficulties owing to its tumor diversity. Herein, we aim to establish a unique prognostic molecular subtype (MST) and based on this to find potential therapeutic targets to develop new immunotherapeutic strategies. Using calcium channel molecules expression-based consensus clustering, we screened 371 HCC patients from The Cancer Genome Atlas to screen for possible MSTs. We distinguished core differential gene modules between varying MSTs, and Tumor Immune Dysfunction and Exclusion scores were employed for the reliable assessment of HCC patient immunotherapeutic response rate. Immunohistochemistry and Immunofluorescence staining were used for validation of predicted immunotherapy outcomes and underlying biological mechanisms, respectively. We identified two MSTs with different clinical characteristics and prognoses. Based on the significant differences between the two MSTs, we further identified Follistatin-like 3 (FSTL3) as a potential indicator of immunotherapy resistance and validated this result in our own cohort. Finally, we found that FSTL3 is predominantly expressed in HCC stromal components and that it is a factor in enhancing fibroblast-M2 macrophage signaling crosstalk, the function of which is relevant to the pathogenesis of HCC. The presence of two MSTs associated with the calcium channel phenotype in HCC patients may provide promising directions for overcoming immunotherapy resistance in HCC, and the promotion of FSTL3 expressed in stromal components for HCC hyperfibrosis may be responsible for the poor response rate to immunotherapy in Cluster 2 (C2) patients.

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.

Abstract Vegetation Optical Depth (VOD) has emerged as a valuable metric to quantify water stress on vegetation's carbon uptake from a remote sensing perspective. However, existing spaceborne microwave remote sensing platforms face limitations in capturing the diurnal VOD variations and global products lack site‐level validation against plant physiology. To address these challenges, we leveraged the Global Navigation Satellite System (GNSS) L‐band microwave signal, measuring its attenuation by the canopy of a temperate broadleaf forest using a pair of GNSS receivers. This approach allowed us to collect continuous VOD observations at a sub‐hourly scale. We found a significant seasonal‐scale correlation between VOD and leaf water potential. The VOD diurnal amplitude is affected by soil moisture, plant transpiration and leaf surface water. Additionally, VOD can help independently estimate plant transpiration. Our findings pave the way for a deeper understanding of response of the vegetation to water stress at finer temporal scales.

Background: Clinically, Jian Pi Yang Zheng Xiao Zheng (JPYZXZ) has been used for many years to treat gastric cancer (GC); however, the underlying mechanism and targets are still undetermined. Methods: The active JPYZXZ components were assessed by Liquid chromatography combined with quadrupole-orbitrap high-resolution mass spectrometry (LC-Q-orbitrap-HRMS). These findings were combined with the TCM Systematic Pharmacology Database and Analysis Platform (TCMSP) database to perform network pharmacological analysis. Using second-generation sequencing on nude mouse samples and single-cell sequencing on human GC tissue, we investigated the potential targets and mechanisms of action of JPYZXZ. A multi-center clinical trial (www.chictr.org.cn ChiCTR1900028147) validated our findings. Results: A total of 869 compounds were detected using LC-Q-orbitrap-HRMS analysis of JPYZXZ granules in order to examine the underlying mechanism of JPYZXZ in the treatment of GC. The network pharmacology analysis indicated that the potential mechanism of JPYZXZ in treating GC is associated with multiple molecular mechanisms and signaling pathways. The overlap between target genes was identified by second-generation sequencing and gene expression patterns obtained from single-cell transcriptome sequencing. We identified many crucial genes, including DZIP1, FSTL3, USP51, LHFPL6, and NREP. Subsequent investigations have consistently demonstrated that the upregulation of these genes is strongly associated with the development of an immunosuppressive microenvironment. JPYZXZ has been shown in clinical trials to reduce the number of immunosuppressive cell types in patients' peripheral blood, lower the levels of inflammatory factors, extend survival, and modify the immunosuppressive microenvironment. Conclusions: This investigation elucidated the positive impact of multi-component, multi-target, and multi-approach JPYZXZ intervention for GC treatment.

Background: Gastric cancer (GC) is among the prevalent gastrointestinal malignancies and is the leading reason for cancer-related mortality. There is an urgent need for novel anti-cancer drugs that are highly active against GC. Parthenolide extracted from the traditional medicines houpo and xinyi is a potential small molecular agent against GC. Methods: GC cell proliferation was assessed in vitro and in vivo using Cell Counting Kit-8 (CCK-8), the colony formation assay, and a xenograft tumor model. Cell death, the cytoskeleton, and mitochondrial membrane potential were examined using TUNEL, phalloidin, and JC-1 staining, respectively. Reactive oxygen and nitrogen species (ROS and RNS, respectively) were investigated using DCFH-DA and DAF-FM DA probes. Cell metabolites were discovered using metabonomics. The degree of DNA damage in GC cells was described using the comet assay and γ-H2AX immunofluorescence staining. Subsequently, protein levels were determined using western blotting. Furthermore, DNA agarose gel electrophoresis was performed to clarify whether parthenolide bound directly to DNA. Results: The potent anti-cancer mechanisms of parthenolide were attributed to its ability to interfere with microtubule assembly, trigger an oxidative stress response, damage DNA by directly binding to DNA or generating excessive free radicals, and ultimately activate the mitochondrial pathway, leading to GC cell death. This investigation determined that parthenolide exhibited a suppressive effect on GC cells in vitro and in vivo. Conclusion: Parthenolide is a potential GC therapeutic agent.

Abstract Osteoporosis (OP) is often associated with other complications, such as impaired glucose homeostasis. Vitamin D deficiency is common and has been linked to bone metabolism and the regulation of blood sugar levels. The aim of this study was to evaluate the independent relationship between serum 25-hydroxyvitamin D (25[OH]D) and fasting blood glucose levels (FBG) in a group of patients diagnosed with OP. This is a retrospective cross-sectional study from a prospectively collected database at our tertiary referral center. Consecutive 2084 OP patients who were hospitalization were finally analyzed in this study. FBG is the dependent variable, serum 25(OH)D level of OP patients is exposure variable of this study. There was a linear significantly negative association between serum 25(OH)D and FBG (β, − 0.02; 95% CI − 0.03 to − 0.01; P = 0.0011) in the fully adjusted models. Specifically, when serum 25(OH)D level was less than 23.39 ng/mL, FBG decreased by 0.04 mmol/L for every 1 ng/mL increase of serum 25(OH)D level. When serum 25(OH)D was greater than 23.39 ng/ mL, the negative association was insignificant (P = 0.9616). If the association is confirmed, the clinical management of blood glucose in OP patients with serum 25(OH)D deficiency has instructive implications.

A quick, easy, cheap, effective, rugged and safe pre-treatment method (QuEChERS) was established to evaluate the risk of tetracycline residues in the muscle of Channa argus. The Box-Behnken design (BBD) response surface optimization method was used to optimize the extraction and purification conditions. The samples were extracted with 10 mL acetonitrile (containing 1% formic acid) and 2 mL 0.1 mol/L Na2EDTA-Mcllvaine buffer solution, and the extracts were purified by 150 mg primary secondary amine（PSA）and 200 mg C18, and detected with Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The result showed that the calibration curve was linear in the range of 0.50~100 ng/mL, with high correlation coefficients (r≥0.999). The limits of detection (LOD) and quantification (LOQ) were 0.25～0.75 μg/kg and 0.84～2.00 μg/kg, respectively. The average recoveries of tetracycline, oxytetracycline, chlortetracycline and doxycycline at three different spiked levels in the muscle of Channa argus were 89.5%～118%, with relative standard deviations (RSDs) of 1.11%～8.88%. This method is simple, sensitive and accurate, and can be used for the rapid quantitative determination of tetracyclines in Channa argus.

Abstract Background The association between lipid metabolism disorder and carcinogenesis is well-established, but there is limited research on the connection between lipid metabolism-related genes (LRGs) and lung adenocarcinoma (LUAD). The objective of our research was to identify LRGs as the potential biomarkers for prognosis and assess their impact on immune cell infiltration in LUAD. Methods We identified novel prognostic LRGs for LUAD patients via the bioinformatics analysis. CYP27A1 expression level was systematically evaluated via various databases, such as TCGA, UALCAN, and TIMER. Subsequently, LinkedOmics was utilized to perform the CYP27A1 co-expression network and GSEA. ssGSEA was conducted to assess the association between infiltration of immune cells and CYP27A1 expression. CYP27A1’s expression level was validated by qRT-PCR analysis. Results CYP27A1 expression was decreased in LUAD. Reduced CYP27A1 expression was linked to unfavorable prognosis in LUAD. Univariate and multivariate analyses indicated that CYP27A1 was an independent prognostic biomarker for LUAD patients. GSEA results revealed a positive correlation between CYP27A1 expression and immune-related pathways. Furthermore, CYP27A1 expression was positively correlated with the infiltration levels of most immune cells. Conclusion CYP27A1 is a potential biomarker for LUAD patients, and our findings provided a novel perspective to develop the prognostic marker for LUAD patients.

Abstract Purpose This study aimed to evaluate the efficacy of arthroscopic sciatic neurolysis for treating deep gluteal syndrome (DGS) and to analyse the application value of high-frequency ultrasound during perioperative period. Methods Between June 2020 and February 2022, 30 patients with DGS who underwent failed conservative treatment were retrospectively analysed. Lateral arthroscopic exploration of the deep gluteal space and sciatic neurolysis were performed. In addition to pelvic X-ray, lumbar disc and hip magnetic resonance imaging (MRI), ultrasonography of the sciatic nerve was also performed in all patients. The visual analogue scale pain score (VAS), modified Harris hip score (mHHS) and Benson symptom-rating scale were used to evaluate the clinical efficacy. The correlation between preoperative sciatic nerve ultrasound and arthroscopic findings was analysed. Results The median follow-up for these patients was 13 months (range,12–21 months). Preoperative ultrasonography showed precise morphological changes in 26 sciatic nerves of patients. The VAS score decreased from 5.0 (4.0, 6.0) preoperatively to 0.5 (0, 1.0) postoperatively (p

Background: Evidence is inefficient about how meteorological factors influence the trends of influenza transmission in different regions of China. Methods: We estimated the time-varying reproduction number (Rt) of influenza and explored the impact of temperature and relative humidity on Rt using generalized additive quasi-Poisson regression models combined with the distribution lag non-linear model (DLNM). The effect of temperature and humidity interaction on Rt of influenza was explored. The multiple random-meta analysis was used to evaluate region-specific association. The excess risk (ER) index was defined to investigate the correlation between Rt and each meteorological factor with the modification of seasonal and regional characteristics. Results: Low temperature and low relative humidity contributed to influenza epidemics on the national level, while shapes of merged cumulative effect plots were different across regions. Compared to that of median temperature, the merged RR (95%CI) of low temperature in northern and southern regions were 1.40(1.24,1.45) and 1.20 (1.14,1.27), respectively, while those of high temperature were 1.10(1.03,1.17) and 1.00 (0.95,1.04), respectively. There were negative interactions between temperature and relative humidity on national (SI = 0.59, 95%CI: 0.57–0.61), southern (SI = 0.49, 95%CI: 0.17–0.80), and northern regions (SI = 0.59, 95%CI: 0.56,0.62). In general, with the increase of the change of the two meteorological factors, the ER of Rt also gradually increased. Conclusions: Temperature and relative humidity have an effect on the influenza epidemics in China, and there is an interaction between the two meteorological factors, but the effect of each factor is heterogeneous among regions. Meteorological factors may be considered to predict the trend of influenza epidemic.

Molybdenum (Mo) is a rare and important element extensively utilised in aerospace, radar communications, optoelectronic devices, and the military. This study proposes an environmentally friendly physical method based on photon–phonon resonance absorption for the separation of Mo from sodium molybdate (Na2MoO4). We examined the vibrational spectrum of Na2MoO4 using the CASTEP code, employing first-principles density functional theory. Through dynamic process analysis, we analysed the vibrational modes and assigned peaks corresponding to experimental infrared (IR) and Raman data. We focused on the vibrational modes associated with Mo and identified that the highest-intensity IR-active peak at 858 cm−1 corresponded to Mo–O bond asymmetric stretching. Therefore, we propose the use of a high-power terahertz laser at ~25 THz to facilitate the separation of Mo from Na2MoO4. Experimental investigations are expected in the future.

Abstract Background The sedative dexmedetomidine has been shown to reduce mortality in adult patients with severe sepsis, but it is not known whether children benefit. This study explored the effects of dexmedetomidine on the outcomes of children with severe sepsis with mechanical ventilation. Methods In this retrospective cohort study, children with severe sepsis requiring mechanical ventilation from 2016 to 2020 were categorized as dexmedetomidine and non-dexmedetomidine group. The propensity score matching was performed to match cases in both groups. The primary outcome was 28-day mortality, and the secondary outcomes were acute kidney injury, ventilator-free days, lengths of PICU and hospital stays. The Kaplan-Meier method and was the log-rank test used to estimate the 28-day mortality rate and assess between-group differences. Results In total, 250 patients were eligible patients: 138 in the dexmedetomidine group and 112 in the non-dexmedetomidine group. After 1:1 propensity score matching, 61 children in each group. dexmedetomidine group showed more lower 28-day mortality (9.84% vs. 26.23%, P = 0.008). During the 7-day observation period after PICU admission, the dexmedetomidine group showed significantly lower neurological and renal sub-scores at day 7 and serum creatinine level at day 3 and day 7. There were no statistical differences in the incidence of acute kidney injury, ventilator-free days, lengths of PICU and hospital stays between the two groups. Conclusions dexmedetomidine treatment in children with severe sepsis is associated with better outcomes and should therefore be considered for the sedation strategy.

Abstract Background Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps. Methods A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry. Results Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L− T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII‑immunized mice. Conclusions PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities. Graphical Abstract

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Abstract Two‐dimensional transition metal dichalcogenides (TMDs) are needed in high‐performance piezoresistive sensors due to their strong strain‐induced bandgap modification and thereby large gauge factors. However, integrating a conventional high‐temperature chemical vapor deposition (CVD)‐grown TMD with a flexible substrate necessitates a transfer process that inevitably degrades the sensing properties of the TMDs and increases the overall fabrication complexity. We present a high‐performance piezoresistive strain sensor that employs large‐area PdSe2 films grown directly on polyimide (PI) substrates via plasma‐assisted selenization of a sputtered Pd film. The reliable strain transfer from the substrate to the PdSe2 film ensures an outstanding strain‐sensing capability of the sensor. Specifically, the sensors have a gauge factor of up to −315 ± 2.1, a response time under 25 ms, a detection limit of 8 × 10−6, and an exceptional stability of over 104 loading–unloading cycles. By attaching the sensors to the skin surface, we demonstrate their application for measuring physiological parameters in health care monitoring, including motion, voice, and arterial pulse vibration. Furthermore, using the PdSe2 film sensor combined with deep learning technology, we achieved intelligent recognition of artery temperature from arterial pulse signals with only a 2% difference between predicted and actual temperatures. The excellent sensing performance, together with the advantages of low‐temperature fabrication and simple device structure, make the PdSe2 film sensor promising for wearable electronics and health care sensing systems.

Cryptotanshinone (CPT), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza, exhibits promising antidepressant properties. Employing a rat model subjected to Chronic Unpredictable Mild Stress (CUMS), behavioral analyses (open field experiment, elevated cross maze experiment, sugar water preference experiment, forced swimming experiment) and inflammatory factor assessments were conducted to assess the efficacy of CPT in alleviating depressive symptoms and inflammatory responses induced by CUMS. Moreover, 16 S rDNA analysis revealed alterations in the gut microbiota of rats exposed to both CUMS and CPT administration. Notably, CPT administration was found to mitigate harmful bacterial shifts associated with depression. Preliminary exploration of the molecular mechanism underlying CPT’s antidepressant effects via transcriptomics analysis and molecular docking indicated that CPT might exert its influence by regulating the PI3K-AKT pathway. This study sheds light on the potential therapeutic role of CPT in managing depressive disorders, offering a comprehensive understanding of its impact on behavior, inflammation, gut microbiota, and molecular pathways.

Abstract Objective To detect the expression of Growth factor binding protein 2 associated binding protein 2 (Gab2) and CT10 regulator of kinase II (CrkII) in ovarian cancer and analyze their clinical significance. To explore the effects of Gab2 and CrkII on the biological behavior of ovarian cancer cells. To analyze the possible molecular mechanism of Gab2 in the development of ovarian cancer. Methods Immunohistochemistry was used to detect the expression of Gab2 and CrkII in ovarian cancer. Chi square test was used to analyze the correlation between Gab2, CrkII and clinical parameters. Using Cox regression model to evaluate the risk factors affecting the prognosis. To analyze the correlation between Gab2, CrkII and survival rate by Kaplan–Meier. Cell experiments were preformed to explore the effects of Gab2 and CrkII on the biological behavior of cells. The interaction between Gab2 and CrkII was explored by immunoprecipitation. Results Immunohistochemistry revealed that high expression of Gab2 and CrkII in ovarian cancer. Patients with high expression of Gab2 or CrkII had higher International Federation of Gynecology and Obstetrics (FIGO) stage, grade and platinum-resistance recurrence. Multivariate analysis showed that Gab2 and CrkII were independent prognostic factors. Kaplan–Meier curve showed that the higher Gab2 and CrkII were, the poor prognosis the patients had. We observed that the overexpression of Gab2 and CrkII promoted the proliferation, metastasis and reduced chemosensitivity of cells. Conversely, the knockdown of Gab2 and CrkII resulted in the opposite results. In CrkII-knockdown cells, we found that Gab2 mediates biological behavior through CrkII. Conclusions The expression of Gab2 and CrkII increase in ovarian cancer. The higher expression of Gab2 and CrkII predict the poor prognosis of patients. Gab2 and CrkII promote the proliferation and migration and reduce the chemosensitivity of cells. Gab2 regulates the biological behaviors of ovarian cancer cells through CrkII.

Knowledge of viral shedding remains limited. Repeated measurement data have been rarely used to explore the influencing factors. In this study, a joint model was developed to explore and validate the factors influencing the duration of viral shedding based on longitudinal data and survival data. We divided 361 patients infected with Delta variant hospitalized in Nanjing Second Hospital into two groups (≤ 21 days group and > 21 days group) according to the duration of viral shedding, and compared their baseline characteristics. Correlation analysis was performed to identify the factors influencing the duration of viral shedding. Further, a joint model was established based on longitudinal data and survival data, and the Markov chain Monte Carlo algorithm was used to explain the influencing factors. In correlation analysis, patients having received vaccination had a higher antibody level at admission than unvaccinated patients, and with the increase of antibody level, the duration of viral shedding shortened. The linear mixed-effects model showed the longitudinal variation of logSARS-COV-2 IgM sample/cutoff (S/CO) values, with a parameter estimate of 0.193 and a standard error of 0.017. Considering gender as an influencing factor, the parameter estimate of the Cox model and their standard error were 0.205 and 0.1093 (P = 0.608), the corresponding OR value was 1.228. The joint model output showed that SARS-COV-2 IgM (S/CO) level was strongly associated with the risk of a composite event at the 95% confidence level, and a doubling of SARS-COV-2 IgM (S/CO) level was associated with a 1.38-fold (95% CI: [1.16, 1.72]) increase in the risk of viral non-shedding. A higher antibody level in vaccinated patients, as well as the presence of IgM antibodies in serum, can accelerate shedding of the mutant virus. This study provides some evidence support for vaccine prevention and control of COVID-19 variants.

Abstract Background Chest computerized tomography (CT) scan is an important strategy that quantifies the severity of COVID-19 pneumonia. To what extent inactivated COVID-19 vaccines could impact the COVID-19 pneumonia on chest CT is not clear. Methods This study recruited 357 SARS-COV-2 B.1.617.2 (Delta) variant-infected patients admitted to the Second Hospital of Nanjing from July to August 2021. An artificial intelligence-assisted CT imaging system was used to quantify the severity of COVID-19 pneumonia. We compared the volume of infection (VOI), percentage of infection (POI) and chest CT scores among patients with different vaccination statuses. Results Of the 357 Delta variant-infected patients included for analysis, 105 were unvaccinated, 72 were partially vaccinated and 180 were fully vaccinated. Fully vaccination had the least lung injuries when quantified by VOI (median VOI of 222.4 cm3, 126.6 cm3 and 39.9 cm3 in unvaccinated, partially vaccinated and fully vaccinated, respectively; p

Brucella virulence relies on its successful intracellular life cycle. Modulating host cell death is a strategy for Brucella to survive and replicate intracellularly. Ferroptosis is a novel regulated cell death characterized by iron-triggered excessive lipid peroxidation, which has been proven to be associated with pathogenic bacteria infection. Thus, we attempted to explore if smooth-type Brucella infection triggers host cell ferroptosis and what role it plays in Brucella infection. We assessed the effects of Brucella infection on the lactate dehydrogenase release and lipid peroxidation levels of RAW264.7 macrophages; subsequently, we determined the effect of Brucella infection on the expressions of ferroptosis defense pathways. Furthermore, we determined the role of host cell ferroptosis in the intracellular replication and egress of Brucella. The results demonstrated that Brucella M5 could induce ferroptosis of macrophages by inhibiting the GPX4-GSH axis at the late stage of infection but mitigated ferroptosis by up-regulating the GCH1-BH4 axis at the early infection stage. Moreover, elevating host cell ferroptosis decreased Brucella intracellular survival and suppressing host cell ferroptosis increased Brucella intracellular replication and egress. Collectively, Brucella may manipulate host cell ferroptosis to facilitate its intracellular replication and egress, extending our knowledge about the underlying mechanism of how Brucella completes its intracellular life cycle.

ABSTRACT Brucella is a facultative intracellular pathogen that preferentially colonizes reproductive organs and utilizes erythritol as a preferred carbon source for its survival and proliferation. In this study, we identified a virulence-related DeoR-family transcriptional regulator (VdtR) and an erythronate metabolic pathway responsible for four-carbon acid sugar metabolism of D-erythronate and L-threonate in Brucella. We found that VdtR plays an important role in Brucella intracellular survival and trafficking to the endoplasmic reticulum in RAW 264.7 macrophages and in virulence in a mouse model. More importantly, we found that VdtR negatively regulates the erythronate metabolic pathway to promote extracellular proliferation of Brucella, depending on utilization of D-erythronate, an oxidative product of erythritol in the host. In a pregnant mouse model, the erythronate metabolic pathway was shown to cooperate with erythritol metabolism and play a crucial role in Brucella proliferation in the placenta, inducing placentitis and finally resulting in abortion or stillbirth. Our results demonstrate that, in addition to erythritol, erythronate is a preferred carbon source for Brucella utilization to promote its extracellular proliferation. This discovery updates the information on the preferential colonization of reproductive organs by Brucella and provides a novel insight into the Brucella-associated induction of abortion in pregnant animals. IMPORTANCE Brucella is an intracellular parasitic bacterium causing zoonosis, which is distributed worldwide and mainly characterized by reproductive disorders. Erythritol is found in allantoic fluid, chorion, and placenta of aborted animals, preferentially utilized by Brucella to cause infertility and abortion. However, the erythritol metabolism-defected mutant was unable to function as a vaccine strain due to its residual virulence. Here, we found that erythronate, an oxidative product of erythritol in the host, was also preferentially utilized by Brucella relying on the function of a deoxyribonucleoside regulator-family transcriptional regulator VdtR. Erythronate utilization activates VdtR regulation of the erythronate metabolic pathway to promote Brucella extracellular proliferation, inducing placentitis/abortion in mice. Double mutations on Brucella erythritol and D-erythronate metabolisms significantly reduced bacterial virulence. This study revealed a novel mechanism of Brucella infection-induced abortion, thus providing a new clue for the study of safer Brucella attenuated vaccines.