The association of initial and changes in serum A-FABP level with the development and improvement of pre-sarcopenia.

CONTEXT: Several cross-sectional studies have reported the association between serum adipocyte fatty acid binding protein (A-FABP) level and pre-sarcopenia. However, data on the impacts of serum A-FABP level and its changes over time on the development and improvement of pre-sarcopenia are scarce. METHODS: This longitudinal cohort study included 1496 adults (41.2% men; median age, 58 [53-63] years) in 2013-2014 and was followed up to 2015-2016. Participants underwent serum A-FABP level measurements at baseline and follow-up visit. Visceral fat area (VFA) was measured using magnetic resonance imaging. Skeletal muscle mass (SMM) was estimated by bioelectrical impedance analysis and converted to skeletal muscle index (SMI). Pre-sarcopenia was defined as SMI < 1 standard deviation of the sex-specific mean for the young reference group. RESULTS: During an average follow-up period of 2.1 years, baseline serum A-FABP level was positively associated with the incidence of pre-sarcopenia (standardized by weight: risk ratio [RR] 3.22, 95% confidence interval [CI] 1.96-5.38; standardized by VFA: RR 2.11, 95%CI 1.29-3.51) and negatively associated with the improvement of pre-sarcopenia (standardized by weight: RR 0.66, 95%CI 0.45-0.97; standardized by VFA: RR 0.71, 95%CI 0.54-0.94), regardless of whether SMM was standardized by weight or VFA. Moreover, changes in serum A-FABP level provided additional information on the incidence and improvement of pre-sarcopenia, independent of baseline serum A-FABP level (all P < 0.05). CONCLUSIONS: Baseline serum A-FABP level and its changes were positively associated with the incidence, and negatively associated with the improvement of pre-sarcopenia.

The effects of different lung parts, age, and batches on the lung microbiota of healthy rats.

BACKGROUND: Rat models are valuable tools to study the lung microbiota in diseases. Yet the impacts of different lung parts, young and mature adult stages, and the different batches of the same conditions on the healthy rat lung microbiome have not been investigated. METHODS: The rat lung microbiome was analyzed to clarify the lung part-dependent and age-dependent differences and to evaluate the effects of several 'batch environmental factors' on normal rats, after eliminating potential contamination. RESULTS: The results showed that the contamination could be identified and excluded. The lung microbiome from left and right lung parts was very similar so one representative part could be used in the microbiome study. There were significantly different lung microbial communities between the young and mature adult groups, and also between the different feeding batches groups of the same repetitive feeding conditions, but a common lung microbiota characterized by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria as the most dominant phyla were present in all adult rats. It indicated that the experiment under the same condition of the same rats batch was needed to compare the difference in the lung microbiota and repeated experiments were necessary to confirm the results. CONCLUSION: These data represented that the lung bacterial communities were dynamic and rapidly susceptible to environmental influence, clustered strongly by age or different feeding batches but similar in the different lung tissue parts. This study improved the basic understanding of the potential effects on the lung microbiome of healthy rats.

Structural analysis and blood-enriching effects comparison based on biological potency of Angelica sinensis polysaccharides.

Angelica sinensis is a long-standing medicine used by Chinese medical practitioners and well-known for its blood-tonic and blood-activating effects. Ferulic acid, ligustilide, and eugenol in Angelica sinensis activate the blood circulation; however, the material basis of their blood-tonic effects needs to be further investigated. In this study, five homogeneous Angelica sinensis polysaccharides were isolated, and their sugar content, molecular weight, monosaccharide composition, and infrared characteristics determined. Acetylphenylhydrazine (APH) and cyclophosphamide (CTX) were used as inducers to establish a blood deficiency model in mice, and organ indices, haematological and biochemical parameters were measured in mice. Results of in vivo hematopoietic activity showed that Angelica sinensis polysaccharide (APS) could elevate erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and interleukin-3 (IL-3) serum levels, reduce tumor necrosis factor-α (TNF-α) level in mice, and promote hematopoiesis in the body by regulating cytokine levels. Biological potency test results of the in vitro blood supplementation indicated strongest tonic activity for APS-H2O, and APS-0.4 has the weakest haemopoietic activity. The structures of APS-H2O and APS-0.4 were characterized, and the results showed that APS-H2O is an arabinogalactan glycan with a main chain consisting of α-1,3,5-Ara(f), α-1,5- Ara(f), ß-1,4-Gal(p), and ß-1,4-Gal(p)A, and two branched chains of ß-t-Gal(p) and α-t-Glc(p) connected to each other in a (1→3) linkage to α-1,3,5-Ara(f) on the main chain. APS-0.4 is an acidic polysaccharide with galacturonic acid as the main chain, consisting of α-1,4-GalA, α-1,2-GalA, α-1,4-Gal, and ß-1,4-Rha. In conclusion, APS-H2O can be used as a potential drug for blood replenishment in patients with blood deficiency, providing a basis for APS application in clinical treatment and health foods, as well as research and development of new polysaccharide-based drugs.

Organoids in gastrointestinal diseases: from bench to clinic.

The etiology of gastrointestinal (GI) diseases is intricate and multifactorial, encompassing complex interactions between genetic predisposition and gut microbiota. The cell fate change, immune function regulation, and microenvironment composition in diseased tissues are governed by microorganisms and mutated genes either independently or through synergistic interactions. A comprehensive understanding of GI disease etiology is imperative for developing precise prevention and treatment strategies. However, the existing models used for studying the microenvironment in GI diseases-whether cancer cell lines or mouse models-exhibit significant limitations, which leads to the prosperity of organoids models. This review first describes the development history of organoids models, followed by a detailed demonstration of organoids application from bench to clinic. As for bench utilization, we present a layer-by-layer elucidation of organoid simulation on host-microbial interactions, as well as the application in molecular mechanism analysis. As for clinical adhibition, we provide a generalized interpretation of organoid application in GI disease simulation from inflammatory disorders to malignancy diseases, as well as in GI disease treatment including drug screening, immunotherapy, and microbial-targeting and screening treatment. This review draws a comprehensive and systematical depiction of organoids models, providing a novel insight into the utilization of organoids models from bench to clinic.

Clinical Characteristics of Lung Abscess Caused by Streptococcus Constellatus Infection.

BACKGROUND: This study aimed to understand the clinical characteristics of pulmonary abscess caused by Streptococcus constellatus infection. METHODS: The clinical manifestations, laboratory examination, drug sensitivity, chest CT manifestations, and treatment and prognosis of patients with pulmonary abscess caused by Streptococcus constellatus infection were retrospectively collected and analyzed. RESULTS: A total of 9 cases of pulmonary abscess caused by Streptococcus constellatus infection were confirmed; one case was confirmed by traditional cultures, while metagenomic next-generation sequencing (mNGS) confirmed the other 8 cases. All of the 9 patients had different degrees of cough, sputum, fever, chest pain, and/or dyspnea, and the physical examination showed fast breathing, reduced respiratory sound, or moist rales on the affected side. In laboratory tests, 8 patients had elevated white blood cells and hypoproteinemia upon admission. Blood gas analysis showed an oxygenation index < 300. The antimicrobial susceptibility testing results in 1 patient with culture-confirmed pathogen diagnosis showed that Streptococcus constellatus was susceptible to ampicillin, penicillin G, cefotaxime, ceftriaxone, cefepime, meropenem, chloramphenicol, linezolid, levofloxacin, and vancomycin and resistant to tetracycline and clindamycin. Relevant antibiotic resistance genes were not detected by mNGS in the 8 patients with negative culture and positive mNGS results. A chest CT showed lung consolidation or cavity formation in 9 patients admitted to the hospital, and 5 patients had pleural effusion. 3 cases were admitted to the respiratory intensive care unit (RICU) and 6 cases were admitted to the general ward. There were 3 cases of nasal catheter oxygen inhalation, 1 case of mask oxygen inhalation, and 5 cases of non-invasive ventilator assisted ventilation. All patients received penicillin or respiratory quinolones anti-infection therapy, and 3 cases were treated with a thoracic closed drainage tube. All patients were discharged from the hospital after improvement, and the hospital stay was 15 - 23 days. CONCLUSIONS: Patients with pulmonary abscess caused by Streptococcus constellatus infection have an urgent condition and rapid progression. It is helpful to use mNGS combined with traditional culture as soon as possible to identify the pathogenic bacteria. Penicillin antibiotics should be the first choice for pulmonary abscess caused by a suspected Streptococcus constellatus infection. If a patient´s condition worsens during the treatment, especially for patients who have lesions involving the interlobar fissure or pleura, compressive atelectasis caused by pleural fluid formation or an increase in the amount of pleural effusion needs to be highly suspected.

The cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term.

Background: Cervical ripening is crucial for induction. However, its influencing factors, mechanistic understanding, and effective risk stratification are still challenging. Recent research suggested that microorganisms and their metabolites in vaginal spaces correlate to preterm birth. However, it remains unclear whether the cervicovaginal metabolome is related to the natural physiological process of cervical maturation. Objective: We aimed to analyze the cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term. Study design: Cervicovaginal swabs were collected between 40 and 41 weeks gestation from the following 2 different groups of patients: Ripe group (n = 25) which was favorable for the induction cervix and Unripe group which was unfavorable for the induction cervix (n = 25). Samples were tested using untargeted metabolomics analysis and analyzed by a bioinformatics platform. The correlation analysis between the metabolome and the previously acquired microbiome was also performed. Results: A total of 629 metabolites were identified in cervicovaginal fluid. The cervicovaginal metabolome was significantly different between the women with the ripe cervix and those with the unripe cervix, especially within each stratum of the same CST. Metabolites within the amino acid, carbohydrate, and dipeptide pathways may play a role in this distinction. Thirty-four metabolites were significantly upregulated, and the remaining fourteen were significantly downregulated in the Unripe group with an unripe cervix unfavorable for induction. Statistical modeling identified Arachidonic Acid and Nicotinate associated with the risk of cervical maturation disorder (AUC 0.87) in negative ion mode. A combination of Choline and d-Mannose identified a risk of cervical maturation disorder (AUC 0.80) in positive ion mode, improved by Lactobacillus relative abundance (AUC 0.89). Conclusion: These data suggested that the cervicovaginal space was metabolically active during pregnancy and significantly altered among the women with the mature and immature cervix. Combining the genera-level phylotypes and metabolites could build better cervix maturity prediction models. By using cervicovaginal fluid samples, we demonstrated the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to the remodeling of cervix during term pregnancy.

An internally and externally validated nomogram for predicting cancer-specific survival in octogenarians after radical resection for colorectal cancer.

AIMS: We aimed to develop an elaborative nomogram that predicts cancer-specific survival (CSS) in American and Chinese octogenarians treated with radical resection for CRC. METHODS: The patient data of newly diagnosed patients aged 80 years or older who underwent radical resection for CRC from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and then randomly divided into a training cohort and a validation cohort. The patients collected from our hospital were defined as the external validation cohort. Univariate and multivariate Cox regression was used to select independent predictive factors for the construction of a nomogram to predict 1-, 2- and 3-year CSS. RESULTS: The multivariate Cox regression model identified age, T stage, N stage, perineural invasion, chemotherapy, tumour deposits, carcinoembryonic antigen level, number of lymph node metastases, and number of solid organ metastases as independent predictors of survival. The C-index of the nomogram for 1-, 2- and 3-year CSS was 0.758, 0.762, and 0.727, respectively, demonstrating significant clinical value and substantial reliability compared to the TNM stage. The calibration curve and area under the curve also indicated considerable predictive accuracy. In addition, decision curve analysis demonstrated desirable net benefits in clinical application. CONCLUSION: We constructed a nomogram for predicting the CSS of individual octogenarian patients with CRC who underwent radical resection. The nomogram performed better than the TNM staging system in this particular population and could guide clinicians in clinical follow-up and individual therapeutic plan formulation.

Survey on pattern of myopia in school children in Hangzhou after the COVID-19 pandemic: a school-based vision screening study.

BACKGROUND: Myopia is a major health issue around the world. Myopia in children has increased significantly during the COVID-19 pandemic in China, but reports are scarce on the prevalence of myopia following the pandemic. This study collected vision screening data of school children in China for five consecutive years to observe the changes in myopia after the pandemic and compare the observed prevalence of myopia before and after the pandemic. METHODS: A school-based vision screening study used stratified samplings to collect the vision screening data in school children aged 6-13 from 45 primary schools in Hangzhou. Vision screening data including uncorrected visual acuity(UCVA) and spherical equivalent refraction(SER). Calculating the mean of SER and the prevalence of myopia and hyperopia from 2019 to 2023. RESULTS: A total of 79,068 screening results (158,136 eyes) were included in the analysis. A substantial myopic shift (approximately -0.30 diopters [D] on average) was found in 2020 and 2021 compared with 2019 in all age groups and a substantial myopic shift (approximately 0.4 D on average) was found in 2022 compared with 2021. A slight myopic shift (approximately -0.14 D on average) was found in 2023 compared with 2022. The prevalence of myopia in all age groups was the highest for five years in 2020 or 2021, which was 31.3% for 6-year-olds, 43.0% for 7-year-olds, and 53.7% for 8-year-olds. A positive change in the prevalence rate of myopia was found at 6 years old (0.59%, 0.12%, 0.36%, 0.25%, p < 0.001). The change in prevalence rate in myopia was shifted slightly in children aged 10-13 years. Children aged 8 to 13 years had a slight increase in myopia prevalence from 2022 to 2023. The prevalence of hyperopia was low and stable in all grade groups, ranging from 0.7% to 2.2% over five years. CONCLUSION: Myopia in children has increased rapidly during the COVID-19 pandemic. After the pandemic, the prevalence of myopia in children gradually decreased temporarily and then rebounded. Myopic shift was more apparent in younger children. Myopic shift in children may be related to the reduction of outdoor time, less light, and near work habits, and further research is needed.

A Se Nanoparticle/MgFe-LDH Composite Nanosheet as a Multifunctional Platform for Osteosarcoma Eradication, Antibacterial and Bone Reconstruction.

Despite advances in treating osteosarcoma, postoperative tumor recurrence, periprosthetic infection, and critical bone defects remain critical concerns. Herein, the growth of selenium nanoparticles (SeNPs) onto MgFe-LDH nanosheets (LDH) is reported to develop a multifunctional nanocomposite (LDH/Se) and further modification of the nanocomposite on a bioactive glass scaffold (BGS) to obtain a versatile platform (BGS@LDH/Se) for comprehensive postoperative osteosarcoma management. The uniform dispersion of negatively charged SeNPs on the LDH surface restrains toxicity-inducing aggregation and inactivation, thus enhancing superoxide dismutase (SOD) activation and superoxide anion radical (·O2 -)-H2O2 conversion. Meanwhile, Fe3+ within the LDH nanosheets can be reduced to Fe2+ by depleting glutathione (GSH) in the tumor microenvironments (TME), which can catalyze H2O2 into highly toxic reactive oxygen species. More importantly, incorporating SeNPs significantly promotes the anti-bacterial and osteogenic properties of BGS@LDH/Se. Thus, the developed BGS@LDH/Se platform can simultaneously inhibit tumor recurrence and periprosthetic infection as well as promote bone regeneration, thus holding great potential for postoperative "one-stop-shop" management of patients who need osteosarcoma resection and scaffold implantation.

Pharmacological activities of Zanthoxylum L. plants and its exploitation and utilization.

The study aims to provide an up-to-date review at the advancements of the investigations on the ethnopharmacology, phytochemistry, pharmacological effect and exploitation and utilizations of Zanthoxylum L. Besides, the possible tendency and perspective for future research of this plant are discussed, as well. This article uses "Zanthoxylum L." "Zanthorylum bungeanum" as the keywords and collects relevant information on Zanthoxylum L. plants through electronic searches (Elsevier, PubMed, ACS, Web of Science, Science Direct, CNKI, Google Scholar), relevant books, and classic literature about Chinese herb. The plants of this genus are rich in volatile oils, alkaloids, amides, lignans, coumarins and organic acids, and has a wide range of pharmacological activities, including but not limited to anti-inflammatory, analgesic, anti-tumor, hypoglycemic, hypolipidemic, antioxidant and anti-infectious. This article reviewed both Chinese and international research progress on the active ingredients and pharmacological activities of Zanthoxylum L. as well as the applications of this genus in the fields of food, medicinal and daily chemicals, and clarified the material basis of its pharmacological activities. Based on traditional usage, phytochemicals, and pharmacological properties, of Zanthoxylum L. species, which indicate that they possess diverse bioactive metabolites with interesting bioactivities. Zanthoxylum L. is a potential medicinal and edible plant with diverse pharmacological effects. Due to its various advantages, it may have vast application potential in the food and medicinal industries and daily chemicals. Nonetheless, the currently available data has several gaps in understanding the herbal utilization of Zanthoxylum L. Thus, further research into their toxicity, mechanisms of actions of the isolated bioactive metabolites, as well as scientific connotations between the traditional medicinal uses and pharmacological properties is required to unravel their efficacy in therapeutic potential for safe clinical application.

Spermine oxidase regulates liver inflammation and fibrosis through ß-catenin pathway.

BACKGROUND: Spermine oxidase (SMOX), an inducible enzyme involved in the catabolic pathway of polyamine, was found to be upregulated in hepatocellular carcinoma and might be an important oncogene of it in our previous studies. This study attempted to further investigate its relationship with liver inflammation and fibrosis both in vitro and in vivo. METHODS: The effect of SMOX inhibition on LPS-induced inflammatory response in mouse liver cell line AML12 was validated by using small interfering RNA or SMOX inhibitor MDL72527. Western blotting and immunofluorescence were utilized to verify whether LPS could induce ß-catenin to transfer into the nucleus and whether it could be reversed by interfering with the expression of SMOX or using SMOX inhibitor. Then, the SMOX inhibitor MDL72527 and SMOX knockout mice were used to verify the hypothesis above in vivo. RESULTS: The expression of SMOX could be induced by LPS in AML12 cells. The inhibition of SMOX could inhibit LPS-induced inflammatory response in AML12 cells. LPS could induce ß-catenin transfer from cytoplasm to nucleus, while SMOX downregulation or inhibition could partially reverse this process. In vivo intervention with SMOX inhibitor MDL72527 or SMOX knockout mice could significantly improve the damage of liver function, reduce intrahepatic inflammation, inhibit the nuclear transfer of ß-catenin in liver tissue, and alleviate carbon tetrachloride-induced liver fibrosis in mice. CONCLUSION: SMOX can promote the inflammatory response and fibrosis of hepatocytes. It provides a new therapeutic strategy for hepatitis and liver fibrosis, inhibiting early liver cancer.

Evaluation of visual and optical quality following phacoemulsification cataract surgery with diffractive multifocal intraocular lens implantation: An observational study.

The assessment of patient satisfaction following cataract surgery is heavily reliant on the evaluation of visual quality, specifically after the placement of diffractive multifocal intraocular lenses (MIOLs) under varying pupil conditions. The objective of this study was to examine the visual and optical clarity following cataract phacoemulsification and the use of Tecnis ZMB00 MIOL for implantation. The study involved 116 individuals (135 eyes) who received cataract phacoemulsification and underwent Tecnis ZMB00 MIOL implantation. Assessments were conducted 1 week and 3 months after the surgery. These assessments involved measuring uncorrected and corrected visual acuity for distant, intermediate, and near vision. Additionally, scatter light values and wavefront aberrations were measured under different aperture settings of 3 and 5 mm. There was no noticeable disparity in visual acuity between 1 week and 3 months after the surgery. After 3 months of surgery, there was a considerable decrease in scatter light values and spherical aberrations compared to the values observed 1 week after surgery, under the setting of a 5 mm aperture. Moreover, the modulation transfer function values showed a significant rise after 3 months following the surgery, particularly under the 5 mm aperture condition. The most substantial increase was observed at the intermediate spatial frequency of 20 cycles per degree (cpd), in comparison to the values obtained 1 week after the operation. The combination of cataract phacoemulsification and Tecnis ZMB00 MIOL implantation yielded favorable visual acuity at various distances for patients. Furthermore, enhancements in the measurements of scattered light, higher-order aberrations, and modulation transfer function values were noted 3 months after the surgical procedure, specifically under the condition of a 5 mm pupil. These findings suggest an increase in visual clarity and night vision to a certain degree.

A comparison of Bayesian and score methods for interval estimates of positive/negative likelihood ratios in support of diagnostic device performance evaluation.

BACKGROUND: Positive and negative likelihood ratios (PLR and NLR) are important metrics of accuracy for diagnostic devices with a binary output. However, the properties of Bayesian and frequentist interval estimators of PLR/NLR have not been extensively studied and compared. In this study, we explore the potential use of the Bayesian method for interval estimation of PLR/NLR, and, more broadly, for interval estimation of the ratio of two independent proportions. METHODS: We develop a Bayesian-based approach for interval estimation of PLR/NLR for use as a part of a diagnostic device performance evaluation. Our approach is applicable to a broader setting for interval estimation of any ratio of two independent proportions. We compare score and Bayesian interval estimators for the ratio of two proportions in terms of the coverage probability (CP) and expected interval width (EW) via extensive experiments and applications to two case studies. A supplementary experiment was also conducted to assess the performance of the proposed exact Bayesian method under different priors. RESULTS: Our experimental results show that the overall mean CP for Bayesian interval estimation is consistent with that for the score method (0.950 vs. 0.952), and the overall mean EW for Bayesian is shorter than that for score method (15.929 vs. 19.724). Application to two case studies showed that the intervals estimated using the Bayesian and frequentist approaches are very similar. DISCUSSION: Our numerical results indicate that the proposed Bayesian approach has a comparable CP performance with the score method while yielding higher precision (i.e. a shorter EW).

Epigallocatechin-3-gallate mitigates cadmium-induced intestinal damage through modulation of the microbiota-tryptophan-aryl hydrocarbon receptor pathway.

Early studies have shown that the gut microbiota is a critical target during cadmium exposure. The prebiotic activity of epigallocatechin-3-gallate (EGCG) plays an essential role in treating intestinal inflammation and damage. However, the exact intestinal barrier protection mechanism of EGCG against cadmium exposure remains unclear. In this experiment, four-week-old mice were exposed to cadmium (5 mg kg-1) for four weeks. Through 16 S rDNA analysis, we found that cadmium disrupted the gut microbiota and inhibited the indole metabolism pathway of tryptophan (TRP), which serves as the principal microbial production route for endogenous ligands to activate the aryl hydrocarbon receptor (AhR). Additionally, cadmium downregulated the intestinal AhR signaling pathway and harmed the intestinal barrier function. Treatment with EGCG (20 mg kg-1) and the AhR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) (1 µg/d) significantly activated the AhR pathway and alleviated intestinal barrier injury. Notably, EGCG partially restored the gut microbiota and upregulated the TRP-indole metabolism pathway to increase the level of indole-related AhR agonists. Our findings demonstrate that cadmium dysregulates common gut microbiota to disrupt TRP metabolism, impairing the AhR signaling pathway and intestinal barrier. EGCG reduces cadmium-induced intestinal functional impairment by intervening in the intestinal microbiota to metabolize AhR agonists. This study offers insights into the toxic mechanisms of environmental cadmium and a potential mechanism to protect the intestinal barrier with EGCG.

Boosting the sonodynamic performance of CoBiMn-layered double hydroxide nanoparticles via tumor microenvironment regulation for ultrasound imaging-guided sonodynamic therapy.

Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e-/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.

The Associations and Causal Relationships of Ovarian Cancer - Construction of a Prediction Model.

Purpose: To explore the risk and protective factors for developing ovarian cancer and construct a risk prediction model. Methods: Information related to patients diagnosed with ovarian cancer on the electronic medical record data platform of three tertiary hospitals in Guangdong Province from May 2018 to September 2023 was collected as the case group. Patients with non-ovarian cancer who attended the clinic during the same period were included in the control group. Logistic regression analysis was used to screen the independent variables and explore the factors associated with the development of ovarian cancer. An ovarian cancer risk prediction model was constructed using a decision tree C4.5 algorithm. The ROC and calibration curves were plotted, and the model was validated. Results: Logistic regression analysis identified independent risk and protective factors for ovarian cancer. The sample size was divided into training and test sets in a ratio of 7:3 for model construction and validation. The AUC of the training and test sets of the decision tree model were 0.961 (95% CI:0.944-0.978) and 0.902 (95% CI:0.840-0.964), respectively, and the optimal cut-off values and their coordinates were 0.532 (0.091, 0.957), and 0.474 (0.159, 0.842) respectively. The accuracies of the training and test sets were 93.3% and 84.2%, respectively, and their sensitivities were 95.7% and 84.2%, respectively. Conclusion: The constructed ovarian cancer risk prediction model has good predictive ability, which is conducive to improving the efficiency of early warning of ovarian cancer in high-risk groups.

Unveiling the role of mtDNA in Liver-Kidney Crosstalk: Insights from trichloroethylene hypersensitivity syndrome.

In specific pathological conditions, addressing liver injury may yield favorable effects on renal function through the phenomenon of liver-kidney crosstalk. Mitochondrial DNA (mtDNA) possesses the capability to trigger downstream pathways of inflammatory cytokines, ultimately leading to immune-mediated organ damage. Consequently, understanding the intricate molecular mechanisms governing mtDNA involvement in diseases characterized by liver-kidney crosstalk is of paramount significance. This study seeks to elucidate the role of mtDNA in conditions marked by liver-kidney crosstalk. In previous clinical cases, it has been observed that patients with Trichloroethylene Hypersensitivity Syndrome (TCE-HS) who experience severe liver injury often also exhibit renal injury. In this study, patients diagnosed with trichloroethylene hypersensitivity syndrome were recruited from Shenzhen Occupational Disease Control Center. And Balb/c mice were treated with trichloroethylene. The correlation between liver and kidney injuries in patients with TCE-HS was assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Alterations in mtDNA levels were examined in mouse hepatocytes, red blood cells (RBCs), and renal tubular epithelial cells utilizing immunofluorescence and PCR techniques. TCE-sensitized mice exhibited a significant increase in reactive oxygen species (ROS) and the opening of the mitochondrial permeability transition pore in hepatocytes, resulting in the release of mtDNA. Furthermore, heightened levels of mtDNA and Toll-like Receptor 9 (TLR9) expression were observed in RBCs. Additional experiments demonstrated elevated expression of TLR9 and its downstream mediator MyD88 in renal tubule epithelial cells of TCE-sensitized mice. In vitro investigations confirmed that mtDNA activates the TLR9 pathway in TCMK-1 cells. Collectively, these results suggest that mtDNA released from mitochondrial damage in hepatocytes is carried by RBCs to renal tubular epithelial cells and mediates inflammatory injury in renal tubular epithelial cells through activation of the TLR9 receptor.

Balancing the equation: assessing the impact of management practices on staff and faculty wellbeing in Chinese higher education institutions.

Introduction: The intersection of work-family dynamics and job contentment has become a pivotal area of investigation within the higher education landscape, drawing scholarly attention, especially in the Chinese context. This study delves into the intricate relationship between work-family culture and job satisfaction, with a particular spotlight on the mediating influence of perceptions of organizational fairness. The impetus behind this emphasis lies in the burgeoning acknowledgment of organizational justice as a pivotal force shaping employee attitudes and conduct within academic establishments. Method: This research was conducted using two distinct groups. The first group consisted of 1,075 faculty members at Chinese universities, while the second group comprised 972 administrative and technical employees at these institutions. Results: The mediational analyses provided in this study offer an enhanced comprehension of the intricate relationships under discussion. Significantly, the findings reveal that Work-Family Culture plays a crucial predictive role in influencing perceptions of Organizational Justice among both faculty and administrative staff. More importantly, the study uncovers that Work-Family Culture indirectly affects Job Satisfaction through its impact on Organizational Justice. Discussion: This insight underscores the importance of harmonious work-family interactions as a determinant of job-related attitudes and satisfaction levels.

PAD4 Inhibitor-Functionalized Layered Double Hydroxide Nanosheets for Synergistic Sonodynamic Therapy/Immunotherapy Of Tumor Metastasis.

Sonodynamic therapy (SDT) is demonstrated to trigger the systemic immune response of the organism and facilitate the treatment of metastatic tumors. However, SDT-mediated neutrophil extracellular traps (NETs) formation can promote tumor cell spread, thus weakening the therapeutic effectiveness of metastatic tumors. Herein, the amorphous CoW-layered double hydroxide (a-CoW-LDH) nanosheets are functionalized with a peptidyl arginine deiminase 4 (PAD4) inhibitor, i.e., YW3-56, to construct a multifunctional nanoagent (a-LDH@356) for synergistic SDT/immunotherapy. Specifically, a-CoW-LDH nanosheets can act as a sonosensitizer to generate abundant reactive oxygen species (ROS) under US irradiation. After loading with YW3-56, a-LDH@356 plus US irradiation not only effectively induces ROS generation and immunogenic cell death, but also inhibits the elevation of citrullinated histone H3 (H3cit) and the release of NETs, enabling a synergistic enhancement of anti-tumor metastasis effect. Using 4T1 tumor model, it is demonstrated that combining a-CoW-LDH with YW3-56 stimulates an anti-tumor response by upregulating the proportion of immune-activated cells and inducing polarization of M1 macrophages, and inhibits immune escape by downregulating the expression of PD-1 on immune cells under US irradiation, which not only arrests primary tumor progression with a tumor inhibition rate of 69.5% but also prevents tumor metastasis with the least number of lung metastatic nodules.