Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure: A multicenter study.

BACKGROUND: Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model. AIM: To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model. METHODS: This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score. RESULTS: A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score. CONCLUSION: This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.

Reproducibility study of intravoxel incoherent motion and apparent diffusion coefficient parameters in normal pancreas.

BACKGROUND: The consistency of pancreatic apparent diffusion coefficient (ADC) values and intravoxel incoherent motion (IVIM) parameter values across different magnetic resonance imaging (MRI) devices significantly impacts the patient's diagnosis and treatment. AIM: To explore consistency in image quality, ADC values, and IVIM parameter values among different MRI devices in pancreatic examinations. METHODS: This retrospective study was approved by the local ethics committee, and informed consent was obtained from all participants. In total, 22 healthy volunteers (10 males and 12 females) aged 24-61 years (mean, 28.9 ± 2.3 years) underwent pancreatic diffusion-weighted imaging using 3.0T MRI equipment from three vendors. Two independent observers subjectively scored image quality and measured the pancreas's overall ADC values and signal-to-noise ratios (SNRs). Subsequently, regions of interest (ROIs) were delineated for the IVIM parameters (true diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction) using post-processing software. These ROIs were on the head, body, and tail of the pancrease. The subjective image ratings were assessed using the kappa consistency test. Intraclass correlation coefficients (ICCs) and mixed linear models were used to evaluate each device's quantitative parameter values. Finally, a pairwise analysis of IVIM parameter values across each device was performed using Bland-Altman plots. RESULTS: The Kappa value for the subjective ratings of the different observers was 0.776 (P < 0.05). The ICC values for inter-observer and intra-observer agreements for the quantitative parameters were 0.803 [95% confidence interval (CI): 0.684-0.880] and 0.883 (95%CI: 0.760-0.945), respectively (P < 0.05). The ICCs for the SNR between different devices was comparable (P > 0.05), and the ICCs for the ADC values from different devices were 0.870, 0.707, and 0.808, respectively (P < 0.05). Notably, only a few statistically significant inter-device agreements were observed for different IVIM parameters, and among those, the ICC values were generally low. The mixed linear model results indicated differences (P < 0.05) in the f-value for the pancreas head, D-value for the pancreas body, and D-value for the pancreas tail obtained using different MRI machines. The Bland-Altman plots showed significant variability at some data points. CONCLUSION: ADC values are consistent among different devices, but the IVIM parameters' repeatability is moderate. Therefore, the variability in the IVIM parameter values may be associated with using different MRI machines. Thus, caution should be exercised when using IVIM parameter values to assess the pancreas.

Corrigendum: Characterizing the neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

[This corrects the article DOI: 10.3389/fcell.2021.793073.].

TaMYB-CC5 gene specifically expressed in root improve tolerance of phosphorus deficiency and drought stress in wheat.

Phosphate deficiency and drought are significant environmental constraints that impact both the productivity and quality of wheat. The interaction between phosphorus and water facilitates their mutual absorption processes in plants. Under conditions of both phosphorus deficiency and drought stress, we observed a significant upregulation in the expression of wheat MYB-CC transcription factors through the transcriptome analysis. 52 TaMYB-CC genes in wheat were identified and analyzed their evolutionary relationships, structures, and expression patterns. The TaMYB-CC5 gene exhibited specific expression in roots and demonstrated significant upregulation under phosphorus deficiency and drought stress compared to other TaMYB-CC genes. The overexpression of TaMYB-CC5A in Arabidopsis resulted in a significant increase of root length under stress conditions, thereby enhancing tolerance to phosphate starvation and drought stress. The wheat lines with silenced TaMYB-CC5 genes exhibited reduced root length under stress conditions and increased sensitivity to phosphate deficiency and drought stress. In addition, silencing the TaMYB-CC5 genes resulted in altered phosphorus content in leaves but did not lead to a reduction in phosphorus content in roots. Enrichment analysis the co-expression genes of TaMYB-CC5 transcription factors, we found the zinc-induced facilitator-like (ZIFL) genes were prominent associated with TaMYB-CC5 gene. The TaZIFL1, TaZIFL2, and TaZIFL5 genes were verified specifically expressed in roots and regulated by TaMYB-CC5 transcript factor. Our study reveals the pivotal role of the TaMYB-CC5 gene in regulating TaZIFL genes, which is crucial for maintaining normal root growth under phosphorus deficiency and drought stress, thereby enhanced resistance to these abiotic stresses in wheat.

Individual suicide risk factors with resting-state brain functional connectivity patterns in bipolar disorder patients based on latent Dirichlet allocation model.

BACKGROUND: The widespread problem of suicide and its severe burden in bipolar disorder (BD) necessitate the development of objective risk markers, aiming to enhance individual suicide risk prediction in BD. METHODS: This study recruited 123 BD patients (61 patients with prior suicide attempted history (PSAs), 62 without (NSAs)) and 68 healthy controls (HEs). The Latent Dirichlet Allocation (LDA) model was used to decompose the resting state functional connectivity (RSFC) into multiple hyper/hypo-RSFC patterns. Thereafter, according to the quantitative results of individual heterogeneity over latent factor dimensions, the correlations were analyzed to test prediction ability. RESULTS: Model constructed without introducing suicide-related labels yielded three latent factors with dissociable hyper/hypo-RSFC patterns. In the subsequent analysis, significant differences in the factor distributions of PSAs and NSAs showed biases on the default-mode network (DMN) hyper-RSFC factor (factor 3) and the salience network (SN) and central executive network (CEN) hyper-RSFC factor (factor 1), indicating predictive value. Correlation analysis of the individuals' expressions with their Nurses' Global Assessment of Suicide Risk (NGASR) revealed factor 3 positively correlated (r = 0.4180, p < 0.0001) and factor 1 negatively correlated (r = - 0.2492, p = 0.0055) with suicide risk. Therefore, it could be speculated that patterns more associated with suicide reflected hyper-connectivity in DMN and hypo-connectivity in SN, CEN. CONCLUSIONS: This study provided individual suicide-associated risk factors that could reflect the abnormal RSFC patterns, and explored the suicide related brain mechanisms, which is expected to provide supports for clinical decision-making and timely screening and intervention for individuals at high risks of suicide.

An all-in-one microfluidic SlipChip for power-free and rapid biosensing of pathogenic bacteria.

Point-of-care testing of pathogens is becoming more and more important for the prevention and control of food poisoning. Herein, a power-free colorimetric biosensor was presented for rapid detection of Salmonella using a microfluidic SlipChip for fluidic control and Au@PtPd nanocatalysts for signal amplification. All the procedures, including solution mixing, immune reaction, magnetic separation, residual washing, mimicking catalysis and colorimetric detection, were integrated on this SlipChip. First, the mixture of the bacterial sample, immune magnetic nanobeads (IMBs) and immune Au@PtPd nanocatalysts (INCs), washing buffer and H2O2-TMB chromogenic substrate were preloaded into the sample, washing and catalysis chambers, respectively. After the top layer of this SlipChip was slid to connect the sample chamber with the separation chamber, the mixture was moved back and forth through the asymmetrical split-and-recombine micromixer by using a disposable syringe to form the IMB-Salmonella-INC sandwich conjugates. Then, the conjugates were captured in the separation chamber using a magnetic field, and the top layer was slid to connect the washing chamber with the separation chamber for washing away excessive INCs. Finally, the top layer was slid to connect the catalysis chamber with the separation chamber, and the colorless substrate was catalyzed by the INCs with peroxidase-mimic activity to generate color change, followed by using a smartphone app to collect and analyze the image to determine the bacterial concentration. This all-in-one microfluidic biosensor enabled simple detection of Salmonella as low as 101.2 CFU mL-1 within 30 min and was featured with low cost, straightforward operation, and compact design.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Structure and Function of Somatostatin and its Receptors in Endocrinology.

Somatostatin analogs, such as octreotide (OCT), lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors (NETs). Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins (GPCRs) that play a role in metabolism, growth, and pathological conditions such as hormone disorders, neurological diseases, and cancers. Cryogenic electron microscopy (cryo-EM) combined with the protein structure prediction platform AlphaFold has been used to determine the three-dimensional structures of many proteins. Recently, several groups published a series of papers illustrating the three-dimensional structure of SSTR2, including that of the inactive/activated SSTR2-G protein complex bound to different ligands. The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies.

Physicochemical stability of corn protein hydrolysate/tannic acid complex-based ß-carotene nanoemulsion delivery system.

Moderate non-covalent interaction of protein and polyphenols can improve the emulsifying property of protein itself. The corn protein hydrolysate (CPH) and tannic acid (TA) complex was successfully used to construct nanoemulsion for algal oil delivery. There has been no study on the feasibility of this nanoemulsion delivery system for other food functional components, for example, ß-carotene (ß-CE). CPH/TA complex-based nanoemulsion system for ß-CE delivery was studied, focusing on the effect of ß-CE content on the physicochemical stability of the nanoemulsions. The nanoemulsion delivery systems (dia. 150 nm) with low viscosity and good liquidity were easily fabricated by two-step emulsification. The nanoemulsions with high ß-CE content (>71.5 µg/mL) significantly increased (p < .05) the emulsion droplet size. However, there was no significant (p > .05) effect of ß-CE content on polydispersity index (PDI) and zeta potential of the nanoemulsions. The storage (30 days) experiment results demonstrated that the droplet size of the nanoemulsions with varying ß-CE content increased slightly during storage. However, the PDI values showed a slightly decreasing trend. Zeta potentials of the nanoemulsions showed no noticeable change during storage. Moreover, after storage of 30 days, the retention ratios of ß-CE were found to be up to 90%, which suggests an excellent protective effect for ß-CE by the nanoemulsion systems. The CPH/TA complex stabilized nanoemulsions could aggregate in gastric condition, but the ß-CE content did not have obvious effect on the digestive stability of the nanoemulsions. The CPH/TA complex could be employed as an emulsifier to construct a physicochemical stable nanoemulsion delivery system for lipophilic active components.

Evaluation of the FPMC respiratory panel for detection of respiratory tract pathogens in nasopharyngeal swab and sputum specimens.

OBJECTIVES: The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. METHODS: Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. RESULTS: The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. CONCLUSIONS: The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

γ-Tocotrienol enhances autophagy of gastric cancer cells by the regulation of GSK3ß/ß-Catenin pathway.

γ-Tocotrienol (γ-T3) is a major subtype of vitamin E, mainly extracted from palm trees, barley, walnuts, and other plants. γ-T3 has effects on anti-inflammation, anti-oxidation, and potential chemoprevention against malignancies. It is still uncompleted to understand the effect of γ-T3 on the inhibitory mechanism of cancer. This study aimed to investigate whether γ-T3 enhanced autophagy in gastric cancer and the underlying molecular mechanism. The results showed that γ-T3 (0-90 µmol/L) inhibited the proliferation of gastric cancer MKN45 cells and AGS cells, and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Autophagy was increased in MKN45 cells treated with γ-T3 (0-45 µmol/L), especially at a dose of 30 µmol/L for 24 h. These effects were reversed by 3-methyladenine pretreatment. Furthermore, γ-T3 (30 µmol/L) also significantly downregulated the expression of pGSK-3ß (ser9) and ß-catenin protein in MKN45 cells, and γ-T3 (20 mg/kg b.w.) effectively decreased the growth of MKN45 cell xenografts in BABL/c mice. GSK-3ß inhibitor-CHIR-99021 reversed the negative regulation of GSK-3ß/ß-Catenin signaling and autophagy. Our findings indicated that γ-T3 enhances autophagy in gastric cancer cells mediated by GSK-3ß/ß-Catenin signaling, which provides new insights into the role of γ-T3 enhancing autophagy in gastric cancer.

VALD-2 mitigates cisplatin-induced acute kidney injury: Mechanistic insights into oxidative stress modulation and inflammation suppression.

This study explores the compelling antitumor properties of VALD-2, a synthetic Schiff base ligand known for its low toxicity. The focus is on investigating VALD-2's protective role against cisplatin-induced acute kidney injury (AKI) in mice, with a specific emphasis on mitigating oxidative stress and inflammation. The study involves daily intraperitoneal injections of amifostine or VALD-2 over 7 days to establish an AKI model. Subsequently, mice were assigned to normal control, cisplatin group, cisplatin + amifostine group, and cisplatin + VALD-2 10 mg/kg group, cisplatin + VALD-2 20 mg/kg, and cisplatin + VALD-2 40 mg/kg. Kidney injury is assessed through serum blood urea nitrogen (BUN) and creatinine (Cr) activity assays. Levels of inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), in kidney tissue of mice were assessed through enzyme-linked immunosorbent assay (ELISA). The protective effect of VALD-2 is further examined through HE staining to observe pathological changes in kidney injury. The ultrastructural changes of renal cells and tubular epithelial cells were observed by electron microscopy under experimental conditions, indicating the effect of VALD-2 on reversing cisplatin-induced renal injury. The study delves into VALD-2's protective mechanisms against cisplatin-induced kidney injury by using western blot analysis to assess the expression levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in kidney tissues. VALD-2 demonstrates significant improvement in cisplatin-induced AKI, as evidenced by increased BUN and Cr levels. It effectively protects kidney tissue from oxidative damage, enhancing SOD and GSH-Px activities while reducing MDA levels. The study also reveals a decrease in TNF-α and IL-6 levels, supported by ELISA results, and histological findings confirm anti-nephrotoxic effects. Western blot analysis shows an upregulation of antioxidant enzymes (SOD, GSH-Px) and a reduction in MDA production. VALD-2 emerges as a promising mitigator of cisplatin-induced AKI, showcasing its ability to enhance oxidative stress-related protein expression. The findings suggest VALD-2 as a potential therapeutic agent for protecting against cisplatin-induced kidney injury.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

The Role of Serine Protease 8 in Mediating Gefitinib Resistance in Non-small Cell Lung Cancer.

OBJECTIVE: This investigation aims to explore the expression levels of serine protease 8 (PRSS8) in gefitinib-resistant Non-Small Cell Lung Cancer (NSCLC) cell lines (PC9/GR) and elucidate its mechanism of action. METHODOLOGY: We measured PRSS8 expression in gefitinib-resistant (PC9/GR) and sensitive (PC9) NSCLC cell lines using Western blot analysis. PRSS8-specific small interfering RNA (PRSS8-siRNA), a recombinant plasmid, and a corresponding blank control were transfected into PC9/GR cells. Subsequently, Western blot analyses were conducted to assess the expression levels of PRSS8, phosphorylated AKT (p-AKT), AKT, phosphorylated mTOR (p-mTOR), mTOR, and various apoptosis-related proteins within each group. Additionally, a cell proliferation assay utilizing Cell Counting Kit-8 (CCK8) was performed on each group treated with gefitinib. RESULT: PRSS8 expression was markedly higher in PC9/GR cells compared to PC9 cells (p < 0.05). The group treated with PRSS8-siRNA exhibited significantly reduced protein expression levels of PRSS8, p-AKT, p-mTOR, ß-catenin, and BCL-2 compared to the control siRNA (Con-siRNA) group, whereas expressions of Caspase9 and Bax were significantly increased. In the untransfected PC9/GR cells, protein expressions of PRSS8, p-AKT, pmTOR, and BCL-2 were significantly elevated when compared with the plasmid-transfected group, which also showed a significant reduction in Bax expression. The proliferative activity of the PRSS8-siRNA group postgefitinib treatment was significantly diminished at 24, 48, and 72 hours in comparison to the Con-siRNA group. CONCLUSION: The findings indicate that PRSS8 contributes to the acquisition of resistance to gefitinib in NSCLC, potentially through regulation of the AKT/mTOR signaling pathway.

[Diagnostic efficacy of serum 14-3-3ß protein combined with fractional exhaled nitric oxide and conventional ventilatory lung function parameters for bronchial asthma in children]. / è¡€æ¸ 14-3-3ß蛋白联合呼出气一氧化氮及常规通气肺功能参数对儿童支气管哮喘的诊断效能.

OBJECTIVES: To explore the diagnostic efficacy of serum 14-3-3ß protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children. METHODS: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3ß protein concentrations between the two groups, analyzed the correlation of serum 14-3-3ß protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3ß protein, FeNO, and conventional ventilatory lung function parameters for asthma in children. RESULTS: The concentration of serum 14-3-3ß protein was higher in the asthma group than in the control group (P<0.001). Serum 14-3-3ß protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters (P<0.05). Cross-validation of combined indices showed that the combination of 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy (P<0.001). The model had the best extrapolation. CONCLUSIONS: The combination of serum 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729.

Prevalence and related factors of nephrolithiasis among medical staff in Qingdao, China: a retrospective cross-sectional study.

BACKGROUND: Certain occupations may predispose individuals to urolithiasis, a multi-factorial disease. The study aimed to evaluate the prevalence and related factors of nephrolithiasis in medical staff in Qingdao, China. METHODS: Physical examination results of 5115 in-service medical staff aged 22-60 years old were retrospectively analyzed. Multivariable logistic regression analysis and stratified analyses by age and gender were applied to explore the related factors of nephrolithiasis in these medical staff. RESULTS: The overall nephrolithiasis prevalence in medical staff in Qingdao, China was 4.65%. Doctors were more prone to nephrolithiasis than nurses (5.63% vs. 3.96%, P = 0.013) and the peak prevalence (6.69%) was observed in medical staff working in the emergency department (ED). Male gender (OR = 1.615, 95% CI = 1.123-2.323, P = 0.010), overweight or obesity (OR = 1.674, 95% CI = 1.266-2.214, P < 0.001), work seniority ≥ 10 years (OR = 2.489, 95%CI = 1.675-3.699, P < 0.001) and working in the ED (OR = 1.815, 95% CI = 1.202-2.742, P = 0.005) were independent predictors for nephrolithiasis in medical staff based on the results of multivariate logistic regression analysis. The associations between overweight or obesity and nephrolithiasis risk as well as between work seniority ≥ 10 years and nephrolithiasis risk in medical staff were independent of age or gender in stratified analysis. CONCLUSIONS: Nephrolithiasis prevalence in medical staff in Qingdao, China seemed not to be higher than that in the general population. Medical staff with work seniority ≥ 10 years and working in the ED should pay abundant attention to take measures to modify their nephrolithiasis risk.

High-quality reference genome of cowpea beetle Callosobruchus maculatus.

Callosobruchus maculatus is one of the most competitive stored grain pests, which causes a great loss to agricultural economy. However, due to an inadequacy of high-quality reference genome, the molecular mechanisms for olfactory and hypoxic adaptations to stored environments are unknown and require to be revealed urgently, which will contribute to the detection and prevention of the invasive pests C. maculatus. Here, we presented a high-quality chromosome-level genome of C. maculatus based on Illumina, Nanopore and Hi-C sequencing data. The total size was 1.2 Gb, and 65.17% (797.47 Mb) of it was identified to be repeat sequences. Among assembled chromosomes, chromosome 10 was considered the X chromosome according to the evidence of reads coverage and homologous genes among species. The current version of high-quality genome provides preferable data resources for the adaptive evolution research of C. maculatus.

The LIDPAD Mouse Model Captures the Multisystem Interactions and Extrahepatic Complications in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.

Targeting HTR2B suppresses non-functioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.