Precisely targeted drug delivery by mesenchymal stem cells-based biomimetic liposomes to cerebral ischemia-reperfusion injured hemisphere.

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.

A comprehensive workflow for optimizing RNA-seq data analysis.

BACKGROUND: Current RNA-seq analysis software for RNA-seq data tends to use similar parameters across different species without considering species-specific differences. However, the suitability and accuracy of these tools may vary when analyzing data from different species, such as humans, animals, plants, fungi, and bacteria. For most laboratory researchers lacking a background in information science, determining how to construct an analysis workflow that meets their specific needs from the array of complex analytical tools available poses a significant challenge. RESULTS: By utilizing RNA-seq data from plants, animals, and fungi, it was observed that different analytical tools demonstrate some variations in performance when applied to different species. A comprehensive experiment was conducted specifically for analyzing plant pathogenic fungal data, focusing on differential gene analysis as the ultimate goal. In this study, 288 pipelines using different tools were applied to analyze five fungal RNA-seq datasets, and the performance of their results was evaluated based on simulation. This led to the establishment of a relatively universal and superior fungal RNA-seq analysis pipeline that can serve as a reference, and certain standards for selecting analysis tools were derived for reference. Additionally, we compared various tools for alternative splicing analysis. The results based on simulated data indicated that rMATS remained the optimal choice, although consideration could be given to supplementing with tools such as SpliceWiz. CONCLUSION: The experimental results demonstrate that, in comparison to the default software parameter configurations, the analysis combination results after tuning can provide more accurate biological insights. It is beneficial to carefully select suitable analysis software based on the data, rather than indiscriminately choosing tools, in order to achieve high-quality analysis results more efficiently.

Graphitized Carbon-Supported Co@Co3O4 for Ozone Decomposition over the Entire Humidity Range.

Ground-level ozone (O3) pollution has emerged as a significant concern due to its detrimental effects on human health and the ecosystem. Catalytic removal of O3 has proven to be the most efficient and cost-effective method. However, its practical application faces substantial challenges, particularly in relation to its effectiveness across the entire humidity range. Herein, we proposed a novel strategy termed "dual active sites" by employing graphitized carbon-loaded core-shell cobalt catalysts (Co@Co3O4-C). Co@Co3O4-C was synthesized via the pyrolysis of a Co-organic ligand as the precursor. By utilizing this approach, we achieved a nearly constant 100% working efficiency of the Co@Co3O4-C catalyst for catalyzing O3 decomposition across the entire humidity range. Physicochemical characterization coupled with density functional theory calculations elucidates that the presence of encapsulated metallic Co nanoparticles enhances the reactivity of the cobalt oxide capping layer. Additionally, the interface carbon atom, strongly influenced by adjacent metallic Co nuclei, functions as a secondary active site for the decomposition of O3 decomposition. The utilization of dual active sites effectively mitigates the competitive adsorption of H2O molecules, thus isolating them for adsorption in the cobalt oxide capping layer. This optimized configuration allows for the decomposition of O3 without interference from moisture. Furthermore, O3 decomposition monolithic catalysts were synthesized using a material extrusion-based three-dimensional (3D) printing technology, which demonstrated a low pressure drop and exceptional mechanical strength. This work provides a "dual active site" strategy for the O3 decomposition reaction, realizing O3 catalytic decomposition over the entire humidity range.

Ectopic adrenocortical adenoma characterized by hypogonadism: a case report and review of the literature.

BACKGROUND: Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas. CASE PRESENTATION: A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis. REVIEW: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization. CONCLUSION: Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.

The relationship between health behaviors and quality of life: the mediating roles of activities of daily living and psychological distress.

Objective: The aim of this study is to examine the role of activities of daily living performance (ADLs) and psychological distress in mediating the process by which health behaviors affect QOL. Methods: A non-probabilistic study was conducted among 1,065 older adult people older than 60 years. Participants were assessed using the Barthel Index, Functional Activities Questionnaire (FAQ), Kessler Psychological Distress Scale (K10), Australian Active Survey, and EQ-VAS score. The SPSS22.0 software was used to analyze the differences in QOL scores among older adults with different demographic characteristics. Pearson correlation analysis was used to analyze the correlation between health behaviors, psychological distress, ADLs, and QOL. Amos23.0 software was used to construct structural equation model (SEM) to analyze the path of health behavior affecting QOL and the mediating role of BADLs, IADLs and psychological distress. Results: (1) The direct effect of health behaviors on QOL was not significant in the model; (2) ADLs had multiple mediating effects on the relationship between health behaviors and QOL, and the incidence of ADL limitation was negatively correlated with the reported QOL in the older adult; (3) Psychological distress had a significant mediating effect on the relationship between health behaviors and QOL. Conclusion: The results of this study elucidated the mechanisms of the correlation between health behaviors and QOL, and added to the existing literature. In addition, these mediating factors and indirect pathways have been identified as targets for intervention to improve the QOL of older adult individuals, which is important for achieving healthy aging.

Unveiling Highly Sensitive Active Site in Atomically Dispersed Gold Catalysts for Enhanced Ethanol Dehydrogenation.

Developing a desirable ethanol dehydrogenation process necessitates a highly efficient and selective catalyst with low cost. Herein, we show that the "complex active site" consisting of atomically dispersed Au atoms with the neighboring oxygen vacancies (Vo) and undercoordinated cation on oxide supports can be prepared and display unique catalytic properties for ethanol dehydrogenation. The "complex active site" Au-Vo-Zr3+ on Au1/ZrO2 exhibits the highest H2 production rate, with above 37,964 mol H2 per mol Au per hour (385 g H2 g-1 Au h-1) at 350 oC, which is 3.32, 2.94 and 15 times higher than Au1/CeO2, Au1/TiO2, and Au1/Al2O3, respectively. Combining experimental and theoretical studies, we demonstrate the structural sensitivity of these complex sites by assessing their selectivity and activity in ethanol dehydrogenation. Our study sheds new light on the design and development of cost-effective and highly efficient catalysts for ethanol dehydrogenation. Fundamentally, atomic-level catalyst design by colocalizing catalytically active metal atoms forming a structure-sensitive "complex site", is a crucial way to advance from heterogeneous catalysis to molecular catalysis. Our study advanced the understanding of the structure sensitivity of the active site in atomically dispersed catalysts.

High Expression of KIFC1 in Glioma Correlates with Poor Prognosis.

OBJECTIVE: Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. METHODS: Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. RESULTS: The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. CONCLUSION: Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

Adenosine kinase inhibits ß-cell proliferation by upregulating DNA methyltransferase 3A expression.

AIM: To investigate the effects of adenosine kinase (ADK), a key enzyme in determining intracellular adenosine levels, on ß cells, and their underlying mechanism. METHODS: Genetic animal models and transgenic immortalized cells were applied to study the effect of ADK on islet beta-cell proliferation and function. The beta-cell mass and response to glucose were measured in vivo using mice with beta-cell-specific ADK overexpression, and in vitro using ADK-overexpressed immortalized beta-cell. RESULTS: The expression of ADK in human islets at high abundance, especially in ß cells, was decreased during the process of ß-cell proliferation. Additionally, a transgenic mouse model (ADKtg/tg /Mip-Cre) was generated wherein the mouse Insulin1 gene promoter specifically overexpressed ADK in pancreatic ß cells. The ADKtg/tg /Mip-Cre model exhibited impaired glucose tolerance, decreased fasting plasma insulin, loss of ß-cell mass, and inhibited ß-cell proliferation. Proteomic analysis revealed that ADK overexpression inhibited the expression of several proteins that promote cell proliferation and insulin secretion. Upregulating ADK in the ß-cell line inhibited the expression of ß-cell related regulatory molecules, including FoxO1, Appl1, Pxn, Pdx-1, Creb and Slc16a3. Subsequent in vitro experiments indicated that the inhibition of ß-cell proliferation and the decreased expression of Pdx-1, Creb and Slc16a3 were rescued by DNA methyltransferase 3A (DNMT3A) knockdown in ß cells. CONCLUSION: In this study, we found that the overexpression of ADK decreased the expression of several genes that regulate ß cells, resulting in the inhibition of ß-cell proliferation and dysfunction by upregulating the expression of DNMT3A.

SOAT1 regulates cholesterol metabolism to induce EMT in hepatocellular carcinoma.

Cholesterol metabolism reprogramming is one of the significant characteristics of hepatocellular carcinoma (HCC). Cholesterol increases the risk of epithelial-mesenchymal transition (EMT) in cancer. Sterol O-acyltransferases 1 (SOAT1) maintains the cholesterol homeostasis. However, the exact mechanistic contribution of SOAT1 to EMT in HCC remains unclear. Here we demonstrated that SOAT1 positively related to poor prognosis of HCC, EMT markers and promoted cell migration and invasion in vitro, which was mediated by the increased cholesterol in plasmalemma and cholesterol esters accumulation. Furthermore, we reported that SOAT1 disrupted cholesterol metabolism homeostasis to accelerate tumorigenesis and development in HCC xenograft and NAFLD-HCC. Also, we detected that nootkatone, a sesquiterpene ketone, inhibited EMT by targeting SOAT1 in vitro and in vivo. Collectively, our finding indicated that SOAT1 promotes EMT and contributes to hepatocarcinogenesis by increasing cholesterol esterification, which is suppressed efficiently by nootkatone. This study demonstrated that SOAT1 is a potential biomarker and therapeutic target in NAFLD-HCC and SOAT1-targeting inhibitors are expected to be the potential new therapeutic treatment for HCC.

Analysis of the total serum IgE levels in patients with acute exacerbations chronic obstructive pulmonary disease: A retrospective study.

Currently, few studies have demonstrated the relationship between total serum IgE (T-IgE) and acute exacerbation chronic obstructive pulmonary disease (AECOPD). In this study, T-IgE in AECOPD patients were investigated and jointly analyzed with the clinical characteristics. AECOPD patients hospitalized from July 2018 to July 2019 were included in this study. In this patient cohort, clinical information was investigated. Routine blood tests, C-reactive protein and T-IgE levels of patients were determined along with blood gas analysis. The length of hospital stays, mechanical ventilation during hospitalization, ICU admission, glucocorticoid related clinical information were recorded. A total of 285 AECOPD patients were included in this study, which consisted of a high proportion of males. Of all patients, 49.82% patients exhibited higher T-IgE levels. Based on the reference T-IgE value 60 kU/L, patients were divided into high T-IgE group with T-IgE > 60 kU/L, and low T-IgE group with T-IgE ≤ 60 kU/L. There was no significant difference in the dosage of glucocorticoid between the two groups. Patients in the high T-IgE group had shorter hospital stays and lower probability of mechanical ventilation compared to the low T-IgE group. After adjustment for confounding factors, T-IgE was negatively correlated with the length of hospital stays. AECOPD patients with elevated T-IgE had shorter hospital stays and lower risks of mechanical ventilation and ICU admission. Our results showed that T-IgE might play an important role on evaluating the condition and guiding for treatment decisions in AECOPD patients.

Theabrownin from Fu Brick tea ameliorates high-fat induced insulin resistance, hepatic steatosis, and inflammation in mice by altering the composition and metabolites of gut microbiota.

Fu Brick tea belongs to fermented dark tea, which is one of the six categories of tea. Fu Brick tea has been reported to reduce adiposity and has beneficial effects in the treatment of hypercholesterolemia and cardiovascular disease. Theabrownin (TB) is one of the pigments with the most abundant content in Fu Brick tea. TB has also been reported to have lipid-lowering effects, but its mechanism remains unclear. We found that TB could effectively reduce the insulin resistance and fat deposition induced by a high fat diet (HFD), decrease inflammation in the liver, improve intestinal integrity, and reduce endotoxins in circulation. Further studies showed that TB increased the abundance of Verrucomicrobiota and reduced the abundance of Firmicutes and Desulfobacterota in the intestinal tract of obese mice. The alteration of gut microbiota is closely linked to the metabolic phenotype after TB treatment through correlation analysis. Moreover, TB changed the gut microbial metabolites including L-ornithine, α-ketoglutarate, and glutamine, which have also been found to be upregulated in the liver after TB intervention. In vitro, L-ornithine, α-ketoglutarate, or glutamine significantly reduced lipopolysaccharide (LPS)-induced inflammation in macrophages. Therefore, our results suggest that TB can reduce adiposity, systemic insulin resistance, and liver inflammation induced by a HFD through altering gut microbiota and improving the intestinal tight junction integrity. The metabolites of gut microbiota might also play a role in ameliorating the HFD-induced phenotype by TB.

Serum uric acid level is associated with glomerular ischemic lesions in patients with primary membranous nephropathy: an analytical, cross-sectional study.

To investigate the relationship between serum uric acid level and glomerular ischemic lesions (GIL) in patients with primary membranous nephropathy (PMN) and identify relevant risk factors. A total of 201 patients with PMN but normal renal function confirmed by renal biopsy executed in the Liaocheng People's Hospital, China, during January 2020-January 2023 were analyzed retrospectively. The enrolled patients were divided into a hyperuricemia group and a normal serum uric acid group (control group) according to their serum uric acid levels. Then, the participants were further divided into a non-GIL group or a GIL group based on the patient's renal biopsy results. The two groups' clinical and pathological data and meaningful indicators for differences were analyzed by binary logistic regression analysis. Additionally, the serum uric acid level prediction value on GIL was investigated using receiver operating characteristic (ROC) curves. Compared with the control group, the hyperuricemia group exhibited high serum uric acid, the prevalence of GIL, serum albumin, the prevalence of hypertension, and low-density lipoprotein cholesterol (LDL) levels (P < 0.05). Compared with the non-GIL group, the GIL group exhibited were older, had enhanced serum uric acid, serum albumin, and an increased prevalence of tubular atrophy/interstitial fibrosis (TA/IF), arteriolosclerosis, and low eGFR levels (P < 0.05). The binary logistic regression analysis revealed that the serum uric acid and the TA/IF are independent risk factors of GIL (P < 0.05). The AUC of ROC of GIL of PMN patients, predicted based on the serum uric acid concentration, was 0.736 (P < 0.05), wherein the threshold = 426.5 µmol/L and the Youden's index = 0.41. Serum uric acid concentration and the TA/IF are independent risk factors of GIL in patients with PMN, and the former exhibits prediction value on GIL in patients with PMN.

Evidence for chromium crosses blood brain barrier from the hypothalamus in chromium mice model.

It has been shown that exposure to hexavalent Chromium, Cr (Ⅵ), via nasal cavity can have neurotoxicological effects and induces behavioral impairment due to the fact that blood brain barrier (BBB) does not cover olfactory bulb. But whether Cr (Ⅵ) can cross the BBB and have a toxicological effects in central nervous system (CNS) remains unclear. Therefore, we investigated the effects of Cr (Ⅵ) on mice treated with different concentrations and exposure time (14 days and 28 days) of Cr (Ⅵ) via intraperitoneal injection. Results revealed that Cr accumulated in hypothalamus (HY) in a timely dependent manner. Much more severer neuropathologies was observed in the group of mice exposed to Cr (Ⅵ) for 28 days than that for 14 days. Gliosis, neuronal morphological abnormalities, synaptic degeneration, BBB disruption and neuronal number loss were observed in HY. In terms of mechanism, the Nrf2 related antioxidant stress signaling dysfunction and activated NF-κB related inflammatory pathway were observed in HY of Cr (Ⅵ) intoxication mice. And these neuropathologies and signaling defects appeared in a timely dependent manner. Taking together, we proved that Cr (Ⅵ) can enter HY due to weaker BBB in HY and HY is the most vulnerable CNS region to Cr (Ⅵ) exposure. The concentration of Cr in HY increased along with time. The accumulated Cr in HY can cause BBB disruption, neuronal morphological abnormalities, synaptic degeneration and gliosis through Nrf2 and NF-κB signaling pathway. This finding improves our understanding of the neurological dysfunctions observed in individuals who have occupational exposure to Cr (Ⅵ), and provided potential therapeutic targets to treat neurotoxicological pathologies induced by Cr (Ⅵ).

Universal Strategy for Metal-Organic Framework Growth: From Cascading-Functional Films to MOF-on-MOFs.

Transformation of metal-organic framework (MOF) particles into thin films is urgently needed for the persistent development of well-applicable devices, and recently emerging functional-integrated hybrid frameworks. Although some flexible polymers and exclusive modification approaches have been proposed, the additive-free and widely applicable strategy has not been reported, hampering the deep investigation of the structure-performance relationship. A universal strategy for the in situ growth of large-area and continuous MOF films with controllable microstructures is introduced, through the modification of multi-scale and multi-structure substrates with poly(4-vinylpyridine) as the anchor to capture metal ions via Coulomb attraction. Based on the clarified structure-adsorption-separation mechanisms, the customized devices fabricated by in situ growth can achieve highly selective adsorption and excellently synergetic separation of various industrially relevant isomers. In addition, this strategy is also feasible for the construction of MOF-on-MOFs with varied lattice parameters. This strategy is easy to implement and will be widely applicable to the surface growth of diverse MOFs on desired substrates, and provides a new concept for developing hybrid MOFs integrating with customized functionalities.

α-synuclein-lack expression rescues methamphetamine-induced mossy fiber degeneration in dorsal hippocampal CA3.

Methamphetamine (METH) - induced cognitive impairments may be related to synaptic degeneration at mossy fiber terminals, critical for spatial memory formation in hippocampal circuits. We have previously found METH-induced neurodegeneration in the striatum by increasing the α-synuclein (α-SYN) level. However, whether and how the METH-induced mossy fiber degeneration is also blamed for the abnormal accumulation of α-SYN remains to be elucidated. Chronic METH exposure decreased mossy fiber density but upregulatedα-SYN and phosphorylated TAU (TAU-pSer396) in hippocampal CA3, associated with glial cell overactivation, axonal neuropathies, and memory impairment. Notably, the knockout of the α-SYN gene significantly alleviated the METH-induced mossy fiber degeneration and memory impairment. Meanwhile, the TAU-pSer396 accumulation and glial activation were ameliorated by α-SYN knockout. Our findings suggest an essential role of α-SYN in mediating METH-induced mossy fiber degeneration, providing promising therapeutic and prophylactic targets for METH-related neurodegenerative diseases.

The optimal dose of indacaterol for treatment of chronic obstructive pulmonary disease: a systematic review and Bayesian network meta-analysis.

Background: The optimal dose of indacaterol for treatment of chronic obstructive pulmonary disease (COPD) was in debate. We did this network meta-analysis to assess the efficacy and safety of three dosages (75, 150, and 300 µg) of indacaterol in patients with moderate-to-severe COPD. Methods: We searched studies from inception until January 20, 2023 on PubMed, Embase, Cochrane Library, and Web of Science database. All studies comparing different doses of indacaterol for COPD were included in this network meta-analysis. Outcomes were forced expiratory volume in 1 second (FEV1), exacerbation rate, St. George respiratory questionnaire (SGRQ), transitional dyspnea index (TDI), and adverse events. Weighted mean difference (WMD) and odds ratio (OR) with 95% credible interval (CrI) was calculated by R software with gemtc package. Results: Finally, a total of 10 studies (4,991 patients) were finally included in this network meta-analysis. Indacaterol 75 µg (WMD: 0.07; 95% CrI: 0.05-0.08), indacaterol 150 µg (WMD: 0.13; 95% CrI: 0.12-0.14), and indacaterol 300 µg (WMD: 0.22; 95% CrI: 0.22-0.23) were all more effective than the placebo, and the difference was statistically significant. Indacaterol 75 µg (OR: 0.80; 95% CrI: 0.53-1.21), indacaterol 150 µg (OR: 0.59; 95% CrI: 0.45-0.78), indacaterol 300 µg (OR: 0.35; 95% CrI: 0.26-0.46) were more effective than the placebo in terms of exacerbation rate, and the difference was statistically significant. The surface under the cumulative ranking (SUCRA) showed that indacaterol 300 µg ranked first, indacaterol 150 µg ranked second, indacaterol 75 µg ranked third, and placebo ranked the last for FEV1, SGRQ, TDI, exacerbation rate. There was no significant difference among the adverse events (P>0.05). Conclusions: Considering the network meta-analysis and rankings, 300 µg indacaterol is superior to the other two dosages in treating patients with moderate-to-severe COPD. However, the quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of different doses of indacaterol used to treat COPD. Higher-quality randomized controlled trials (RCTs) are required for further research in the future.

Development and validation of machine learning-augmented algorithm for insulin sensitivity assessment in the community and primary care settings: a population-based study in China.

Objective: Insulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the "common soil" of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings. Methods: We analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models. Results: The LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc. Conclusion: The ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.

Nanoscale-controlled organicinorganic hybrid spheres for comprehensive enrichment of ultratrace chlorobenzenes in marine and fresh water.

The size of the adsorbent has the potential to influence extraction performance, but the size effect at the nanoscale is still poorly understood. In this study, organic-inorganic hybrid nanospheres (OIHNs) with controllable nanoscale sizes of 30, 50, and 100 nm were successfully prepared. These materials were further fabricated as solid phase microextraction (SPME) coatings with similar thicknesses, and coupled with gas chromatography-mass spectrometry (GC-MS) to investigate their extraction performance. The results showed that the extraction capacities of OIHNs for chlorobenzenes (CBs) and polycyclic aromatic hydrocarbons (PAHs) were much better than those of their corresponding derived carbon materials, despite the smaller specific surface areas and lower porosities of them. In addition, the enrichment performance increased significantly with decreasing particle size, and the OIHN-30 coating demonstrated the best performance, with enrichment factors ranging from 1098 to 6853 for CBs. Finally, a highly sensitive and practical analytical method was established with a wide linear range of 0.5-5000 ng·L-1, and the limits of quantification (LOQs) were 0.43-1.7 ng·L-1. The determinations of ultratrace CBs in five marine water samples and five fresh water samples were realized successfully. This study is expected to contribute to a deep understanding of the environmental effects of nanoparticles and the design of high-performance adsorbents.

Nitrogen-rich covalent organic framework as a practical coating for effective determinations of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are high-profile organic pollutants to be poisonous, carcinogenic, and mutagenic, and widely distributed at trace levels in the environment. In order to effectively enrich PAHs, two stable covalent organic frameworks (COFs, TAPT-OMe-PDA and TPB-DMTP) were prepared by combining 2,4,6-tri(4-aminophenyl)-1,3,5-triazine (TAPT) and 1,3,5-tri(4-aminophenyl) benzene (TAPB) with 2,5-dimethoxy-phenyl-1,4-diformaldehyde (OMe-PDA), respectively. Even though the surface area of TAPT-OMe-PDA was much lower than that of TPB-DMTP, it still demonstrated much better extraction efficiencies towards PAHs as the solid phase microextraction (SPME) coating. Therefore, the TAPT-OMe-PDA coated fiber was coupled with gas chromatography-mass spectrometry (GC-MS) to establish a practical and sensitive method, after the extraction parameters (extraction time, extraction temperature, desorption temperature, desorption time, salt concentration and pH) were optimized. This developed analytical method showed wide linear ranges, low limits of detection, good repeatability and reproducibility. Finally, five PAHs in three water samples were detected and quantified precisely (2.72-38.7 ng·L-1) with satisfactory recoveries (88.3%-118%).

Gut microbiota alteration and its association with immune function in post-COVID-19 patients.

To reveal the variation of gut microbiota and its association with immune function in cured patients with coronavirus 2019 (COVID-19) disease, gut microbiota of patients discharged from hospital for 20 ~ 23 months and healthy volunteers was analyzed by high throughput 16S rRNA sequencing. The diversity and abundance were compared, and the correlation with immunity factors was investigated, and changes in the content of 6 genera microorganisms with proportion higher than 0.1% were revealed in patients with COVID-19 disease: reduced content of Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group and increased content of Hungatella. NK cells were negatively correlated to Subdoligranulum, while CD8 cells were positively correlated to Subdoligranulum but negative to Hungatella. IL-8 concentration was negatively correlated to Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group but positively to Hungatella, while IL-1ß concentration was negatively correlated to Haemophilus and Eubacterium ventriosum group but positively to Hungatella. The variation of probiotics and potential pathogenic bacteria implies a higher risk in diseases and inflammation, and the modulation of the gut microbiota may help the healing of COVID-19 patients.