KinomeMETA: a web platform for kinome-wide polypharmacology profiling with meta-learning.

Kinase-targeted inhibitors hold promise for new therapeutic options, with multi-target inhibitors offering the potential for broader efficacy while minimizing polypharmacology risks. However, comprehensive experimental profiling of kinome-wide activity is expensive, and existing computational approaches often lack scalability or accuracy for understudied kinases. We introduce KinomeMETA, an artificial intelligence (AI)-powered web platform that significantly expands the predictive range with scalability for predicting the polypharmacological effects of small molecules across the kinome. By leveraging a novel meta-learning algorithm, KinomeMETA efficiently utilizes sparse activity data, enabling rapid generalization to new kinase tasks even with limited information. This significantly expands the repertoire of accurately predictable kinases to 661 wild-type and clinically-relevant mutant kinases, far exceeding existing methods. Additionally, KinomeMETA empowers users to customize models with their proprietary data for specific research needs. Case studies demonstrate its ability to discover new active compounds by quickly adapting to small dataset. Overall, KinomeMETA offers enhanced kinome virtual profiling capabilities and is positioned as a powerful tool for developing new kinase inhibitors and advancing kinase research. The KinomeMETA server is freely accessible without registration at https://kinomemeta.alphama.com.cn/.

Ultrastrong Coupling between Polar Distortion and Optical Properties in Ferroelectric MoBr2O2.

Tuning the properties of materials by using external stimuli is crucial for developing versatile smart materials. Strong coupling among the order parameters within a single-phase material constitutes a potent foundation for achieving precise property control. However, cross-coupling is fairly weak in most single materials. Leveraging first-principles calculations, we demonstrate a layered mixed anion compound MoBr2O2 that exhibits electric-field switchable spontaneous polarization and ultrastrong coupling between polar distortion and electronic structures as well as optical properties. It offers feasible avenues of achieving tunable Rashba spin-splitting, electrochromism, thermochromism, photochromism, and nonlinear optics by applying an external electric field to a single domain sample and heating, as well as intense light illumination. Additionally, it exhibits an exceptionally large photostrictive effect. These findings not only showcase the feasibility of achieving multiple order parameter coupling within a single material but also pave the way for comprehensive applications based on property control, such as energy harvesting, information processing, and ultrafast control.

Microplastics alter cadmium accumulation in different soil-plant systems: Revealing the crucial roles of soil bacteria and metabolism.

Cadmium (Cd) and microplastics (MPs) gradually increased to be prevalent contaminants in soil, it is important to understand their combined effects on different soil-plant systems. We studied how different doses of polylactic acid (PLA) and polyethylene (PE) affected Cd accumulation, pakchoi growth, soil chemical and microbial properties, and metabolomics in two soil types. We found that high-dose MPs decreased Cd accumulation in plants in red soil, while all MPs decreased Cd bioaccumulation in fluvo-aquic soil. This difference was primarily attributed to the increase in dissolved organic carbon (DOC) and pH in red soil by high-dose MPs, which inhibited Cd uptake by plant roots. In contrast, MPs reduced soil nitrate nitrogen and available phosphorus, and weakened Cd mobilization in fluvo-aquic soil. In addition, high-dose PLA proved detrimental to plant health, manifesting in shortened shoot and root lengths. Co-exposure of Cd and MPs induced the shifts in bacterial populations and metabolites, with specific taxa and metabolites closely linked to Cd accumulation. Overall, co-exposure of Cd and MPs regulated plant growth and Cd accumulation by driving changes in soil bacterial community and metabolic pathways caused by soil chemical properties. Our findings could provide insights into the Cd migration in different soil-plant systems under MPs exposure. ENVIRONMENTAL IMPLICATION: Microplastics (MPs) and cadmium (Cd) are common pollutants in farmland soil. Co-exposure of MPs and Cd can alter Cd accumulation in plants, and pose a potential threat to human health through the food chain. Here, we investigated the effects of different types and doses of MPs on Cd accumulation, plant growth, soil microorganisms, and metabolic pathways in different soil-plant systems. Our results can contribute to our understanding of the migration and transport of Cd by MPs in different soil-plant systems and provide a reference for the control of combined pollution in the future research.

Omics analysis of 'Shine Muscat' grape grafted on different rootstocks in response to cadmium stress.

Cadmium (Cd) is detrimental to grape growth, development, and fruit quality. Grafting is considered to be a useful method to improve plant adaptability to Cd stress in grape production. However, little information is available on how Cd stress affects grafted grapes. In this study, the effects of Cd on Shine Muscat grapes (Vitis vinifera L. cv. 'Shine Muscat') were studied under different "Cd treatments" concentrations (0, 0.2, 0.4, 0.8, 1.6, 3.2 mg kg-1) and "rootstock treatments" (SO4, 5BB, and 3309C). The results showed that low levels of Cd had hormesis effect and activated the grape antioxidant system to eliminate the ROS induced by Cd stress. The antioxidant capacity of the SM/3309C rootstock combination was stronger than that of the other two groups under low-concentration Cd stress. Moreover, the rootstock effectively sequestered a substantial amount of Cd, consequently mitigating the upward translocation of Cd to the aboveground portions. Transcriptomic and metabolomic analysis revealed several important pathways enriched in ABC transporters, flavonoid biosynthesis, Plant hormone signal transduction, phenylpropanoid biosynthesis, and glutathione metabolism under Cd stress. WGCNA analysis identified a hub gene, R2R3-MYB15, which could promote the expression of several genes (PAL, 4CL, CYP73A, ST, CHS, and COMT), and alleviate the damage caused by Cd toxicity. These findings might shed light on the mechanism of hormesis triggered by low Cd stress in grapes at the transcriptional and metabolic levels.

Relation of myocardial dysfunction to biomarkers, COVID-19 severity and all-cause mortality.

AIMS: The COVID-19 infection has been described as affecting myocardial injury. However, the relation between left ventricular global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS), disease severity and all-cause mortality in COVID-19 is unclear. METHODS AND RESULTS: The study consisted of 220 patients with COVID-19, including 127 (57.5%) with mild, 43 (19.5%) with moderate and 50 (22.7%) with severe/critical conditions. Myocardial dysfunction was analysed by GLS, GCS and GRS using two-dimensional speckle-tracking echocardiography. Hazard ratios and Kaplan-Meier curves were produced to assess the association between strains and cardiac biomarker indices with a composite outcome of all-cause mortality. With an average follow-up period of 11 days, 19 patients reached the endpoint (death). Significant associations were found for the three strain parameters and the levels of blood urea nitrogen (BUN) (r = 0.206, 0.221 and 0.355, respectively). Cardiac troponin I (cTnI) was closely related to the GLS and GCS (r = 0.240 and 0.324, respectively). In multivariable Cox regression, GCS > -21.6% was associated with all-cause death {hazard ratio, 4.007 [95% confidence interval (CI), 11.347-11.919]}. CONCLUSIONS: GLS, GCS and GRS are significantly related to myocardial dysfunction in patients with COVID-19. Worsening GCS poses an increased risk of death in COVID-19.

Chemical passivation of 2D transition metal dichalcogenides: strategies, mechanisms, and prospects for optoelectronic applications.

The interest in obtaining high-quality monolayer transition metal dichalcogenides (TMDs) for optoelectronic device applications has been growing dramatically. However, the prevalence of defects and unwanted doping in these materials remain challenges, as they both limit optical properties and device performance. Surface chemical treatments of monolayer TMDs have been effective in improving their photoluminescence yield and charge transport properties. In this scenario, a systematic understanding of the underlying mechanism of chemical treatments will lead to a rational design of passivation strategies in future research, ultimately taking a step toward practical optoelectronic applications. We will therefore describe in this mini-review the strategies, progress, mechanisms, and prospects of chemical treatments to passivate and improve the optoelectronic properties of TMDs.

Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and Marvinbryantia and Allobaculum were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.

Hydrangea paniculata coumarins alleviate adriamycin-induced renal lipotoxicity through activating AMPK and inhibiting C/EBPß.

ETHNOPHARMACOLOGICAL RELEVANCE: Throughout Chinese history, Hydrangea paniculata Siebold has been utilized as a traditional medicinal herb to treat a variety of ailments associated to inflammation. In a number of immune-mediated kidney disorders, total coumarins extracted from Hydrangea paniculata (HP) have demonstrated a renal protective effect. AIM OF THE STUDY: To investigate renal beneficial effect of HP on experimental Adriamycin nephropathy (AN), and further clarify whether reversing lipid metabolism abnormalities by HP contributes to its renoprotective effect and find out the underlying critical pathways. MATERIALS AND METHODS: After establishment of rat AN model, HP was orally administrated for 6 weeks. Biochemical indicators related to kidney injury were determined. mRNAs sequencing using kidney tissues were performed to clarify the underlying mechanism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, western blot, molecular docking, and drug affinity responsive target stability (DARTS) assay was carried out to further explore and confirm pivotal molecular pathways and possible target by which HP and 7-hydroxylcoumarin (7-HC) played their renal protection effect via modulating lipid metabolism. RESULTS: HP could significantly improve renal function, and restore renal tubular abnormal lipid metabolism and interstitial fibrosis in AN. In vitro study demonstrated that HP and its main metabolite 7-HC could reduce ADR-induced intracellular lipid deposition and fibrosis characteristics in renal tubular cells. Mechanically, HP and 7-HC can activate AMP-activated protein kinase (AMPK) via direct interaction, which contributes to its lipid metabolism modulation effect. Moreover, HP and 7-HC can inhibit fibrosis by inhibiting CCAAT/enhancer binding protein beta (C/EBPß) expression in renal tubular cells. Normalization of lipid metabolism by HP and 7-HC further provided protection of mitochondrial structure integrity and inhibited the nuclear factor kappa-B (NF-κB) pathway. Long-term toxicity using beagle dogs proved the safety of HP after one-month administration. CONCLUSION: Coumarin derivates from HP alleviate adriamycin-induced lipotoxicity and fibrosis in kidney through activating AMPK and inhibiting C/EBPß.

Thermosensitive methyl-cellulose-based injectable hydrogel carrying oxaliplatin for the treatment of peritoneal metastasis in colorectal cancer.

Advanced colorectal cancer (CRC) with peritoneal metastasis (PM) is a highly aggressive malignancy with poor prognosis. Systematic chemotherapy and local treatments are the primary therapeutic approaches. However, systemic chemotherapy is limited by low accumulation of drugs at the tumor site and systemic toxicity. Local treatments include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, CRS faces challenges related to incomplete tumor resection, while HIPEC is restricted by the uneven distribution of drugs and potential complications. Herein, a thermosensitive methyl-cellulose-based injectable hydrogel carrying oxaliplatin (OXA) was synthesized to improve this situation. Specifically, methyl cellulose (MC) coagulated into a hydrogel, and OXA was loaded into the MC hydrogel to construct the OXA-MC hydrogel. We explored the OXA-MC hydrogel for the treatment of PM in CRC. The results demonstrated that the OXA-MC hydrogel had favorable biocompatibility and thermo-sensitivity and could act as a local slow-release drug carrier. Moreover, in a CT-26 tumor-bearing model, it showed a remarkable anti-tumor effect by inhibiting proliferation and promoting apoptosis. Additionally, transcriptome analysis indicated that the OXA-MC hydrogel might be involved in the regulation of the PI3K-AKT signaling pathway. In summary, we successfully prepared the OXA-MC hydrogel and provided a valid approach in the treatment of PM in CRC, which lays a foundation for other PM treatments.

Biochar derivation at low temperature: A novel strategy for harmful resource usage of antibiotic mycelial dreg.

Antibiotic mycelial dreg (AMD) has been categorized as hazardous waste due to the high residual hazardous contaminants. Inappropriate management and disposal of AMD can cause potential environmental and ecological risks. In this study, the potential of pleuromutilin mycelial dreg (PMD) as a novel feedstock for preparing tetracycline hydrochloride (TC) adsorbent was explored to achieve safe management of PMD. The results suggested that residual hazardous contaminants were completely eliminated after pyrolysis. With the increase of pyrolysis temperature, the yields, H/C, O/C, (O + N)/C, and pore size in PMD-derived biochars (PMD-BCs) decreased, while BET surface area and pore volume increased, resulting in the higher stability of the PMD-BCs prepared from higher temperatures. The TC adsorption of the PMD-BCs increased from 27.3 to 46.9 mg/g with the increase of the pyrolysis temperature. Surprisingly, pH value had a strong impact on the TC adsorption, the adsorption capacity of BC-450 increased from 6.5 to 71.1 mg/g when the solution pH value increased from 2 to 10. Lewis acid-base interaction, pore filling, π-π interaction, hydrophobic interaction, and charge-assisted hydrogen bond (CAHB) are considered to drive the adsorption. This work provides a novel pathway for the concurrent detoxification and reutilization of AMD.

Transfer learning enhanced graph neural network for aldehyde oxidase metabolism prediction and its experimental application.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from 13C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Differentiation between depression and bipolar disorder in child and adolescents by voice features.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are serious chronic disabling mental and emotional disorders, with symptoms that often manifest atypically in children and adolescents, making diagnosis difficult without objective physiological indicators. Therefore, we aimed to objectively identify MDD and BD in children and adolescents by exploring their voiceprint features. METHODS: This study included a total of 150 participants, with 50 MDD patients, 50 BD patients, and 50 healthy controls aged between 6 and 16 years. After collecting voiceprint data, chi-square test was used to screen and extract voiceprint features specific to emotional disorders in children and adolescents. Then, selected characteristic voiceprint features were used to establish training and testing datasets with the ratio of 7:3. The performances of various machine learning and deep learning algorithms were compared using the training dataset, and the optimal algorithm was selected to classify the testing dataset and calculate the sensitivity, specificity, accuracy, and ROC curve. RESULTS: The three groups showed differences in clustering centers for various voice features such as root mean square energy, power spectral slope, low-frequency percentile energy level, high-frequency spectral slope, spectral harmonic gain, and audio signal energy level. The model of linear SVM showed the best performance in the training dataset, achieving a total accuracy of 95.6% in classifying the three groups in the testing dataset, with sensitivity of 93.3% for MDD, 100% for BD, specificity of 93.3%, AUC of 1 for BD, and AUC of 0.967 for MDD. CONCLUSION: By exploring the characteristics of voice features in children and adolescents, machine learning can effectively differentiate between MDD and BD in a population, and voice features hold promise as an objective physiological indicator for the auxiliary diagnosis of mood disorder in clinical practice.

Reprimo (RPRM) mediates neuronal ferroptosis via CREB-Nrf2/SCD1 pathways in radiation-induced brain injury.

Neuronal ferroptosis has been found to contribute to degenerative brain disorders and traumatic and hemorrhagic brain injury, but whether radiation-induced brain injury (RIBI), a critical deleterious effect of cranial radiation therapy for primary and metastatic brain tumors, involves neuronal ferroptosis remains unclear. We have recently discovered that deletion of reprimo (RPRM), a tumor suppressor gene, ameliorates RIBI, in which its protective effect on neurons is one of the underlying mechanisms. In this study, we found that whole brain irradiation (WBI) induced ferroptosis in mouse brain, manifesting as alterations in mitochondrial morphology, iron accumulation, lipid peroxidation and a dramatic reduction in glutathione peroxidase 4 (GPX4) level. Moreover, the hippocampal ferroptosis induced by ionizing irradiation (IR) mainly happened in neurons. Intriguingly, RPRM deletion protected the brain and primary neurons against IR-induced ferroptosis. Mechanistically, RPRM deletion prevented iron accumulation by reversing the significant increase in the expression of iron storage protein ferritin heavy chain (Fth), ferritin light chain (Ftl) and iron importer transferrin receptor 1 (Tfr1), as well as enhancing the expression of iron exporter ferroportin (Fpn) after IR. RPRM deletion also inhibited lipid peroxidation by abolishing the reduction of GPX4 and stearoyl coenzyme A desaturase-1 (SCD1) induced by IR. Importantly, RPRM deletion restored or even increased the expression of nuclear factor, erythroid 2 like 2 (Nrf2) in irradiated neurons. On top of that, compromised cyclic AMP response element (CRE)-binding protein (CREB) signaling was found to be responsible for the down-regulation of Nrf2 and SCD1 after irradiation, specifically, RPRM bound to CREB and promoted its degradation after IR, leading to a reduction of CREB protein level, which in turn down-regulated Nrf2 and SCD1. Thus, RPRM deletion recovered Nrf2 and SCD1 through its impact on CREB. Taken together, neuronal ferroptosis is involved in RIBI, RPRM deletion prevents IR-induced neuronal ferroptosis through restoring CREB-Nrf2/SCD1 pathways.

Online advance respiration prediction model for percutaneous puncture robotics.

PURPOSE: Surgical robots have significant research value and clinical significance in the field of percutaneous punctures. There have been numerous studies on ultrasound-guided percutaneous surgical robots; however, addressing the respiratory compensation problem of deep punctures remains a significant obstacle. Herein we propose a robotic system for percutaneous puncture with respiratory compensation. METHODS: We proposed an online advance respiratory prediction model based on Bidirectional Gate Recurrent Unit (Bi-GRU) for the respiratory prediction requirements of surgical robot systems. By analyzing the main factors governing the accuracy of the respiratory motion prediction models, various parameters of the online advance prediction model were optimized. Subsequently, we integrated and developed ultrasound-guided percutaneous puncture robot software and a hardware platform to implement respiratory compensation, thus verifying the effectiveness and reliability of various key technologies in the system. RESULTS: The proposed respiratory prediction model has a significantly reduced update time, with an average root mean square error (RMSE) of less than 0.4 mm. This represents a reduction of ~ 20% compared to the online training long short-term memory(LSTM). By conducting puncture experiments based on a respiratory phantom, the average puncture error was 2.71 ± 0.65 mm and the average single-round puncture time was 65.00 ± 6.67 s. CONCLUSION: Herein we proposed and optimized an online training respiratory prediction network model based on Bi-GRU. The stability and reliability of this system are verified by conducting puncture experiments on a respiratory phantom.

Huaier improves the efficacy of anti-PD-L1 Ab in the treatment of hepatocellular carcinoma by regulating tumor immune microenvironment.

BACKGROUND: Combination therapy is an effective method for augmenting the efficacy of immune checkpoint inhibitors (ICIs). Huaier is a commonly used Chinese patent medicine with substantial antitumor effects. The combination of Huaier and ICIs may increase the efficacy of ICIs against hepatocellular carcinoma (HCC). METHODS: The major components of Huaier were detected by high-performance liquid chromatography-mass spectrometry. The optimal antitumor dose of Huaier was investigated in H22-bearing mice. Next, Huaier was combined with anti-CD8α antibody (Ab) or anti-PD-L1 Ab to observe the antitumor effect. The safety of these combination drugs was evaluated through blood biochemical tests and hematoxylin and eosin staining of histological sections. RT-qPCR, immunohistochemistry, flow cytometry, and transcriptome sequencing were performed to investigate the potential action mechanism of anti-PD-L1 Ab combined with Huaier against HCC. RESULTS: HPLC-MS/MS identified 333 components of Huaier, including carboxylic acids and derivatives, thienothiophenes, phenols, flavonoids and so on. Huaier exhibited significant antitumor effects, with the strongest effect noted at a dose of 4 g/kg. Huaier boosted CD8+ T cells infiltration into the tumor. Next, CD8+ T cells were depleted by with anti-CD8α Ab, and the antitumor effect of Huaier was suppressed. Flow cytometry results revealed that CD8+ T cells were reduced in the Huaier+anti-CD8α Ab group, with the antitumor effect of this group being inhibited. This indicated that CD8+ T cells were key players in the antitumor activity of Huaier. Meanwhile, Huaier inhibited microvessel density (MVD), downregulated vascular endothelial growth factor A (VEGFA), and upregulated PD-L1 in tumor tissues. Finally, Huaier combined with anti-PD-L1 Ab exhibited a greater antitumor effect in the H22-bearing mice. And the results of liver and kidney function tests and histological section analysis unveiled that the safety of these drugs was excellent. According to the transcriptome sequencing results, Huaier combined with anti-PD-L1 Ab possibly exerted anti-HCC effects through immunomodulation, immune response, and so on. CONCLUSIONS: Huaier exhibited a significant antitumor effect. It promoted CD8+ T cells infiltration, upregulated PD-L1 expression, downregulated VEGFA expression, and inhibited MVD, thereby playing a significant antitumor immunoregulatory effect. The combination of Huaier and anti-PD-L1 Ab has significant antitumor effects, and this regimen has good safety. Therefore, Huaier combined with anti-PD-L1 Ab is a promising therapeutic approach against HCC.

Sequence and directivity in cardiac muscle injury of COVID-19 patients: an observational study.

Objective: To compare cardiac function indicators between mild and moderate to severe COVID-19 patients and to try to identify the sequence and directivity in cardiac muscle injury of COVID-19 patients. Methods: From December 2022 to January 2023, all patients with laboratory-confirmed SARS-CoV-2 infection in Shanghai General Hospital Jiading Branch were enrolled. The clinical classification was stratified into mild, moderate, or severe groups. We collected the clinical and laboratory information, transthoracic echocardiographic and speckle-tracking echocardiographic parameters of patients and compared the differences among different groups. Results: The values of echocardiographic parameters in mild group were lower than that in moderate or severe group (P < 0.05) except LVEF. The values of LVEF of mild and moderate group were higher than severe group (P < 0.05). There were no significant differences between moderate and severe group. Positive correlations were observed between left ventricular global longitudinal strain (LVGLS) and myoglobin (r = 0.72), E/e' and age (r = 0.79), E/e' and BNP (r = 0.67). The multivariate analysis shows that SpO2 (OR = 0.360, P = 0.02), LVGLS (OR = 3.196, P = 0.003) and E/e' (OR = 1.307, P = 0.036) were the independent risk factors for mild cases progressing to moderate or severe. According to the receiver operating characteristic (ROC) curves, when all the COVID-19 patients was taken as the sample size, the area under the curve (AUC) of the LVGLS was the highest (AUC = 0.861). The AUC of the LVGLS was higher than LVGCS (AUC = 0.565, P < 0.001). Conclusion: When mild COVID-19 progresses to moderate or severe, both systolic and diastolic functions of the heart are impaired. LVGLS was the independent risk factor for mild cases progressing to moderate or severe cases. Longitudinal changes may manifest earlier than circumferential changes as myocardial disease progresses in COVID-19.

Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota.

Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.

Gender and age disparities in small-to-medium arterial stiffness among the Chinese population.

BACKGROUND AND AIMS: Arterial pressure-volume index (API) is a non-invasive tool for assessing small-to-medium-sized arterial stiffness. This study aimed to investigate the potential age- and sex-related differences in the API and explore the practical implications of such differences. METHODS AND RESULTS: The study analysed 7620 subjects for whom API measurements were available. Linear regression and restrictive cubic spline models were used to investigate the associations between potential risk conditions and the API. Additionally, this study employed a backward stepwise regression method to identify the independent factors associated with a high API. Middle-aged to older women had higher API values and a higher prevalence of high API than men in the same age group. However, the opposite was observed among younger individuals, with women having lower API values than men. This study also identified a J-shaped relationship between API and age, where API values began to increase at a certain age and rapidly increased after that. In women, the API started to increase at 31 years of age and rapidly increased after 54 years of age. In men, the API started to increase at 38 years of age, followed by a rapid increase after 53 years of age. CONCLUSION: This study's observation of a significant age-sex interaction in small-to-medium-sized arterial stiffening offers a valuable explanation for cardiovascular disease risk and provides important parameters for using API measurements to evaluate such risk.

Antibiotics and antibiotic resistance gene dynamics in the composting of antibiotic fermentation waste - A review.

Fate of antibiotics and antibiotic resistance genes (ARGs) during composting of antibiotic fermentation waste (AFW) is a major concern. This review article focuses on recent literature published on this subject. The key findings are that antibiotics can be removed effectively during AFW composting, with higher temperatures, appropriate bulking agents, and suitable pretreatments improving their degradation. ARGs dynamics during composting are related to bacteria and mobile genetic elements (MGEs). Higher temperatures, suitable bulking agents and an appropriate C/N ratio (30:1) lead to more efficient removal of ARGs/MGEs by shaping the bacterial composition. Keeping materials dry (moisture less than 30%) and maintaining pH stable around 7.5 after composting could inhibit the rebound of ARGs. Overall, safer utilization of AFW can be realized by optimizing composting conditions. However, further removal of antibiotics and ARGs at low levels, degradation mechanism of antibiotics, and spread mechanism of ARGs during AFW composting require further investigation.