Chinese Medicine for Treatment of COVID-19: A Review of Potential Pharmacological Components and Mechanisms.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.

Tremor-associated short tandem repeat intermediate and pathogenic expansions in familial essential tremor.

There is an obvious clinical-pathological overlap between essential tremor and some known tremor-associated short tandem repeat expansion disorders. The aim is to analyse whether these short tandem repeat genes, including ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATXN8OS, ATXN10, PPP2R2B, TBP, BEAN1, NOP56, DAB1, ATN1, SADM12 and FMR1, are associated with familial essential tremor patients. Genetic analysis of repeat sizes in tremor-associated short tandem repeat expansions was performed in a large cohort of 515 familial essential tremor probands and 300 controls. The demographic and clinical features among carriers of pathogenic expansions, intermediate repeats and non-carriers were compared. A total of 18 out of 515 (18/515, 3.7%) patients were found to have repeats expansions, including 12 cases (12/515, 2.5%) with intermediate repeat expansions (one ATXN1, eight TBP, two FMR1, one ATN1), and six cases (6/515, 1.2%) with pathogenic expansions (one ATXN1, one ATXN2, one ATXN8OS, one PPP2R2B, one FMR1, one SAMD12). There were no statistically significant differences in intermediate repeats compared to healthy controls. Furthermore, there were no significant differences in demographics and clinical features among individuals with pathogenic expansions, intermediate repeat expansions carriers and non-carriers. Our study indicates that the intermediate repeat expansion in tremor-associated short tandem repeat expansions does not pose an increased risk for essential tremor, and rare pathogenic expansion carriers have been found in the familial essential tremor cohort. The diagnosis of essential tremor based solely on clinical symptoms remains a challenge in distinguishing it from known short tandem repeat expansions diseases with overlapping clinical-pathological features.

Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves' Disease.

Aberrant accumulation of circulating follicular helper T cells (cTfh) has been found in the peripheral blood mononuclear cells (PBMCs) of Graves' disease (GD) patients. However, the underlying mechanism that contributes to the imbalance of cTfh cells remains unknown. Previously, studies described a GD-related circular RNAs (circRNAs)-circZNF644 that might be associated with cTfh cells. This study aimed to investigate the role of circZNF644 on cTfh cells in GD patients. Here, we found that circZNF644 was highly stable expression in the PBMCs of GD patients, which was positively correlated with the serum levels of TSH receptor autoantibodies (TRAb). Knockdown of circZNF644 caused a reduction of the proportion of cTfh cells in vitro. Mechanistically, circZNF644 served as a ceRNA for miR-29a-3p to promote ICOS expression, resulting in increased cTfh cells. In the PBMCs of GD patients, circZNF644 expression was positively correlated with ICOS expression and the percentage of cTfh cells, but negatively related to miR-29a-3p expression. Additionally, a strong relationship between circZNF644 and IL-21 was revealed in GD patients, and silencing of circZNF644 inhibited IL-21 expression. Our study elucidated that elevated expression of circZNF644 is a key feature in the development of GD and may contribute to the pathogenic role of cTfh cells in GD.

Identification of candidate genes associated with primary feathers of tianfu nonghua ducks based on Genome-wide association studies.

The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393-116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552-2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209-142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

The role of the cGAS-STING pathway in metabolic diseases.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a critical innate immune pathway primarily due to its vital DNA sensing mechanism in pathogen defence. Recent research advances have shown that excessive activation or damage to the cGAS-STING pathway can exacerbate chronic inflammatory responses, playing a significant role in metabolic dysfunction and aging, leading to the development of related diseases such as obesity, osteoporosis, and neurodegenerative diseases. This article reviews the structure and biological functions of the cGAS-STING signaling pathway and discusses in detail how this pathway regulates the occurrence and development of metabolic and age-related diseases. Additionally, this article introduces potential small molecule drugs targeting cGAS and STING, aiming to provide new research perspectives for studying the pathogenesis and treatment of metabolic-related diseases.

Association between echocardiographic features, troponin levels, and survival time in hospitalized COVID-19 patients with cardiovascular events.

Introduction: This study aims to explore the predictive roles of echocardiographic parameters and biomarkers in determining outcomes among hospitalized COVID-19 patients experiencing cardiovascular events. Methods: A retrospective cohort study was conducted involving 49 COVID-19 patients who encountered cardiovascular events during hospitalization and underwent echocardiography. Our findings revealed notable associations between echocardiographic parameters and survival time. Results: A decrease in left ventricular ejection fraction (LVEF) of 10% was linked to a 20% reduction in survival time (TR: 0.80, 95% CI: 0.67 - 0.96, p = .017). Similarly, an increase in left ventricular (LV) volume by 10 mL was associated with a 9% decrease in survival time (TR: 0.91, 95% CI: 0.84 - 0.98, p = .011). Moreover, an increase in left atrial (LA) volume by 10 mL corresponded to an 8% decrease in survival time (TR: 0.92, 95% CI: 0.86 - 0.99, p = .026). Additionally, each 1 cm increase in right ventricular (RV) diameter was linked to a 22% reduction in survival time (TR: 0.78, 95% CI: 0.61 - 0.99, p = .043). Furthermore, a 10 mL increase in right atrial (RA) volume was associated with a 12% decrease in survival time (TR: 0.88, 95% CI: 0.78 - 0.98, p = .017). Notably, a tenfold rise in troponin levels was linked to a 33% decrease in survival time (TR: 0.67, 95% CI: 0.48 - 0.93, p = .014). Conclusions: Our study emphasizes the significant associations between various echocardiographic parameters and troponin levels with reduced survival time among COVID-19 patients experiencing cardiovascular events. These findings highlight the potential utility of echocardiography and troponin assessment in predicting outcomes and guiding management strategies in this patient population.

Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach.

Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD.

Human brain proteome-wide association study provides insights into the genetic components of protein abundance in obesity.

BACKGROUNDS: Genome-wide association studies have identified multiple genetic variants associated with obesity. However, most obesity-associated loci were waiting to be translated into new biological insights. Given the critical role of brain in obesity development, we sought to explore whether obesity-associated genetic variants could be mapped to brain protein abundances. METHODS: We performed proteome-wide association studies (PWAS) and colocalization analyses to identify genes whose cis-regulated brain protein abundances were associated with obesity-related traits, including body fat percentage, trunk fat percentage, body mass index, visceral adipose tissue, waist circumference, and waist-to-hip ratio. We then assessed the druggability of the identified genes and conducted pathway enrichment analysis to explore their functional relevance. Finally, we evaluated the effects of the significant PWAS genes at the brain transcriptional level. RESULTS: By integrating human brain proteomes from discovery (ROSMAP, N = 376) and validation datasets (BANNER, N = 198) with genome-wide summary statistics of obesity-related phenotypes (N ranged from 325,153 to 806,834), we identified 51 genes whose cis-regulated brain protein abundance was associated with obesity. These 51 genes were enriched in 11 metabolic processes, e.g., small molecule metabolic process and metabolic pathways. Fourteen of the 51 genes had high drug repurposing value. Ten of the 51 genes were also associated with obesity at the transcriptome level, suggesting that genetic variants likely confer risk of obesity by regulating mRNA expression and protein abundance of these genes. CONCLUSIONS: Our study provides new insights into the genetic component of human brain protein abundance in obesity. The identified proteins represent promising therapeutic targets for future drug development.

Explainable machine learning for predicting 30-day readmission in acute heart failure patients.

We aimed to develop a machine-learning based predictive model to identify 30-day readmission risk in Acute heart failure (AHF) patients. In this study 2232 patients hospitalized with AHF were included. The variance inflation factor value and 5-fold cross-validation were used to select vital clinical variables. Five machine learning algorithms with good performance were applied to develop models, and the discrimination ability was comprehensively evaluated by sensitivity, specificity, and area under the ROC curve (AUC). Prediction results were illustrated by SHapley Additive exPlanations (SHAP) values. Finally, the XGBoost model performs optimally: the greatest AUC of 0.763 (0.703-0.824), highest sensitivity of 0.660, and high accuracy of 0.709. This study developed an optimal XGBoost model to predict the risk of 30-day unplanned readmission for AHF patients, which showed more significant performance compared with traditional logistic regression (LR) model.

Relationship between Indel Variants within the JAK2 Gene and Growth Traits in Goats.

Janus kinase 2 (JAK2) plays a critical role in myoblast proliferation and fat deposition in animals. Our previous RNA-Seq analyses identified a close association between the JAK2 gene and muscle development. To date, research delving into the relationship between the JAK2 gene and growth traits has been sparse. In this study, we sought to investigate the relationship between novel mutations within the JAK2 gene and goat growth traits. Herein, two novel InDel (Insertion/Deletion) polymorphisms within the JAK2 gene were detected in 548 goats, and only two genotypes were designated as ID (Insertion/Deletion) and DD (Deletion/Deletion). The results indicate that the two InDels, the del19008 locus in intron 2 and del72416 InDel in intron 6, showed significant associations with growth traits (p < 0.05). Compared to Nubian and Jianzhou Daer goats, the del72416 locus displayed a more pronounced effect in the Fuqing breed group. In the Nubian breed (NB) group, both InDels showed a marked influence on body height (BH). There were strong linkages observed for these two InDels between the Fuqing (FQ) and Jianzhou (JZ) populations. The DD-ID diplotype was associated with inferior growth traits in chest width (ChW) and cannon circumference (CaC) in the FQ goats compared to the other diplotypes. In the NB population, the DD-DD diplotype exhibited a marked negative impact on BH and HuWI (hucklebone width index), in contrast to the other diplotypes. In summary, our findings suggest that the two InDel polymorphisms within the JAK2 gene could serve as valuable molecular markers for enhancing goat growth traits in breeding programs.

The Influence of Climate Change on the Distribution of Hibiscus mutabilis in China: MaxEnt Model-Based Prediction.

Our study utilized 374 geographical distribution records of H. mutabilis and 19 bioclimatic factors, employing the MaxEnt model and the Geographic Information System (ArcGIS). The key environmental variables influencing the suitable distribution areas of H. mutabilis were analyzed through the comprehensive contribution rate, permutation importance, and Pearson correlation coefficient. Based on this analysis, the contemporary and future suitable distribution areas and their extents were predicted. The results indicate that the key limiting factor affecting the suitable distribution areas of H. mutabilis is the precipitation of the driest month (bio14), with secondary factors being annual precipitation (bio12), annual mean temperature (bio1), and annual temperature range (bio7). Under contemporary climate conditions, the total suitable area for H. mutabilis is approximately 2,076,600 km2, primarily concentrated in the tropical and subtropical regions of southeastern China. Under low-to-medium-emission scenarios (SSP1-2.6, SSP2-4.5), the total suitable area of H. mutabilis shows a trend of first decreasing and then increasing compared to the current scenario. In contrast, under high-emission scenarios (SSP5-8.5), it exhibits a trend of first increasing and then decreasing. The spatial pattern changes indicate that the retention rate of suitable areas for H. mutabilis ranges from 95.28% to 99.28%, with the distribution centers primarily located in Hunan and Guizhou provinces, showing an overall migration trend towards the west and north. These findings suggest that H. mutabilis possesses a certain level of adaptability to climate change. However, it is crucial to consider regional drought and sudden drought events in practical cultivation and introduction processes. The results of our study provide a scientific basis for the rational cultivation management, conservation, and utilization of germplasm resources of H. mutabilis.

Nonlinear and abnormal relationship between turbidity and suspended solids concentration in mountainous rivers: A case study of the Lai Chi Wo river in Hong Kong, China.

Suspended solids concentration (SSC) in a river is closely relevant to river water turbidity. Investigation of their relationship in this study is accompanied by observed turbidity and SSC values, which were obtained from the testing results of water samples and monitored conditions in streamflow. The water samples were collected from two observation stations with a broad range of sediment concentrations in the Lai Chi Wo catchment in Hong Kong, China. We classified the target rainfall events into single-peak event type and dual-peak event type for a distinguished discussion of the relationship between SSC and turbidity in this study. At a finer classification, each event is separated into defined processes for the analysis, where two main processes refer to the periods that SSC rises from a normal state to a peak state first and the followed periods that SSC recesses to ordinary status gradually. It is advised by the analysis results that the estimation of SSC through turbidity values should be based on the same rainfall types for the upstream station. However, the results show that the classification of rainfall types does not need to take downstream areas into consideration. Furthermore, current research implies that the individual established connections between SSC and turbidity value at different stages (particularly referring to the rising period and recessing period) could be applied to estimate SSC at the same station via continuous turbidity values for both this and other ungauged stations with similar topographical features in the future. Meanwhile, this research approach provides new insight exploring various behaviors of sediments at different stages during an integral rainfall event. A comparison of distinguished performances of sediment during corresponding stages in a rainfall event makes contributions to diverse relationship between SSC and turbidity in the mountainous river.

Creating and characteristics of a novel biomacromolecules complex of pea protein isolated-tannic acid-magnesium ion.

Pea protein isolate (PPI) was used as a carrier matrix to load tannic acid (TA) due to its multiple cavity structures and reaction sites, after that, magnesium ion (M) was further added to form more stable carrier structures. PPI was covalently bound with TA to form TA-PPI complexes in alkaline conditions, then M induced the aggregation of TA-PPI to produce M-TA-PPI complexes. TA mainly interacted with free amino groups and sulfhydryl groups of PPI, thereby decreasing their content in complexes. TA further decreased the α-helix content and increased the ß-sheet and ß-turn content in TA-PPI complexes correspondingly, nevertheless the M would decline these changes in M-TA-PPI complexes. As a result of binding, TA and M jointly increased the average molecular size of complexes. The higher TA addition amount (10-20 mg/g PPI) was conducive to the stronger intramolecular interactions (more hydrophobic interactions and disulfide bonds), gel structure (higher hardness value) and storage modulus in M-TA-PPI gels. Compared with TA-PPI complexes, M-TA-PPI complexes showed higher stability in gastric digestion and higher TA releasement and antioxidant capacity of its digesta in intestinal digestion. This kind of metal-phenolics-protein complexes may have potentials to be a stable and efficient carrier for loading gastric sensitive polyphenols.

Regulatory mechanisms and potential therapeutic targets in precancerous lesions of gastric cancer: A comprehensive review.

Precancerous lesions of gastric cancer (PLGC) represent a critical pathological stage in the transformation from normal gastric mucosa to gastric cancer (GC). The global incidence of PLGC has been rising over the past few decades, with a trend towards younger onset ages. Increasing evidence suggests that early prevention and treatment of PLGC can effectively reverse the malignant development of gastric mucosal epithelial cells. However, there is currently a lack of effective therapeutic drugs and methods. Recent years have witnessed substantial advancements in PLGC research, with the elucidation of novel regulatory mechanisms offering promising avenues for clinical intervention and drug development. This review aims to delineate potential targets for early prevention and diagnosis of GC while exploring innovative approaches to PLGC management. This article focuses on elucidating the regulatory mechanisms of the inflammatory microenvironment, bile acids (BA), glycolysis, autophagy, apoptosis, ferroptosis, and cellular senescence. We pay particular attention to potential therapeutic targets for PLGC, with the goal of providing insights and theoretical basis for clinical research on PLGC.

Role of ADP ribosylation factor guanylate kinase 1 in the malignant biological behavior of gastric cancer.

Aim: This study aims to investigate the influence of ASAP1 (ADP ribosylation factor guanylate kinase 1) on the malignant behavior of gastric cancer (GC) cells and to elucidate the potential molecular mechanisms involved in cancer development and progression. Methods: We assessed the impact of ASAP1 overexpression and knockdown on GC cell malignancy using CCK8, colony formation, flow cytometry (Annexin V/propidium iodide), Transwell migration, invasion, and scratch assays. Western blot analysis was used to assess the effects of ASAP1 on angiogenesis, matrix metalloproteinases (MMPs), apoptotic proteins, epithelial-mesenchymal transition (EMT)-related proteins, as well as AKT and p-AKT. The influence of ASAP1 knockdown was also evaluated in nude mice bearing BGC823 cell-derived tumors. Results: Our findings revealed that ASAP1 was significantly overexpressed in GC cells, enhancing their proliferation, invasion, and migration, while reducing apoptosis. Conversely, ASAP1 knockdown reversed these effects, markedly increasing the expression of cleaved-caspase 3 (Casp3), PARP, and the epithelial marker E-cadherin, and significantly decreasing MMP2, MMP9, VEGFA, and mesenchymal markers such as N-cadherin and vimentin. Additionally, it reduced AKT, and p-AKT levels (P < 0.01). Tumor growth in nude mice was suppressed following ASAP1 knockdown. Conclusion: The overexpression of ASAP1 significantly promotes malignant behaviors in GC cells, whereas its knockdown diminishes these effects. This modulation is potentially through the downregulation of VEGFA, leading to reduced angiogenesis, Cleaved-Casp3 and Cleaved-PARP overexpression, and a decrease in MMPs, EMT, AKT, and p-AKT activity.

Circulating/cerebrospinal T lymphocytes as indicators of clinical prognosis in intracerebral hemorrhage: A prospective study.

Secondary injury of cerebral hemorrhage is induced by systemic inflammatory cascades, which are related to perihematomal brain edema, cellular apoptosis, and the disruption of the blood-brain barrier. This study was to specifically elaborate the relationship of circulating/cerebrospinal T lymphocytes and Glasgow Coma Scale (GCS) score at 6 months after intracerebral hemorrhage (ICH). The enrolled patients were divided into 2 groups based on GCS score: the favorable prognosis group (GCS > 12) and unfavorable prognosis group (GCS ≤ 12). T lymphocyte subpopulations were analyzed by flow cytometry. A total of 30 samples of peripheral blood and 17 samples of cerebrospinal fluid were collected and analyzed, including 19 cases and 12 cases in the favorable prognosis group (GCS > 12) respectively. Both CD3+ and CD3+CD4+ T lymphocyte counts on Day 1 after ICH were lower in the peripheral blood of patients with unfavorable prognosis (GCS ≤ 12) (P = .025 and .022, respectively). There were correlation trends between the GCS scores and CD3+ T lymphocyte count (P = .0144), and CD3+CD4+ T lymphocyte count (P = .0135). In cerebrospinal fluid, there was a close correlation between the GCS scores and CD3+CD4+ percentage, CD4+/CD8+ ratio, CD3+ and CD3+CD4+ T lymphocyte counts. The area under the curve of CD4+/CD8+ T lymphocyte ratio was the largest among them (P = .000 and area under the curve = 0.917), with a significantly high specificity and sensitivity (0.917 and 1.000). Based on cerebrospinal fluid samples, the CD4+/CD8+ T lymphocyte ratio on Day 1 after ICH may be a more significant indicator to predict the short-term prognosis at 6 months after ICH.

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50 × 109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. FINDINGS: Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. INTERPRETATION: Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. FUNDING: HUTCHMED and Science and Technology Commission of Shanghai Municipality.

Tailoring Oxygen-Depleted and Unitary Ti3C2T x Surface Terminals by Molten Salt Electrochemical Etching Enables Dendrite-Free Stable Zn Metal Anode.

Two-dimensional Ti3C2Tx MXene materials, with metal-like conductivities and versatile terminals, have been considered to be promising surface modification materials for Zn-metal-based aqueous batteries (ZABs). However, the oxygen-rich and hybridized terminations caused by conventional methods limit their advantages in inhibiting zinc dendrite growth and reducing corrosion-related side reactions. Herein, -O-depleted, -Cl-terminated Ti3C2Tx was precisely fabricated by the molten salt electrochemical etching of Ti3AlC2, and controlled in-situ terminal replacement from -Cl to unitary -S or -Se was achieved. The as-prepared -O-depleted and unitary-terminal Ti3C2Tx as Zn anode coatings provided excellent hydrophobicity and enriched zinc-ionophilic sites, facilitating Zn2+ horizontal transport for homogeneous deposition and effectively suppressing water-induced side reactions. The as-assembled Ti3C2Sx@Zn symmetric cell achieved a cycle life of up to 4200 h at a current density and areal capacity of 2 mA cm-2 and 1 mAh cm-2, respectively, with an impressive cumulative capacity of up to 7.25 Ah cm-2 at 5 mA cm-2 // 2 mAh cm-2. These findings provide an effective electrochemical strategy for tailoring -O-depleted and unitary Ti3C2Tx surface terminals and advancing the understanding of the role of specific Ti3C2Tx surface chemistry in regulating the plating/stripping behaviors of metal ions.

Temporal Transcriptome Dynamics of Longissimus dorsi Reveals the Mechanism of the Differences in Muscle Development and IMF Deposition between Fuqing Goats and Nubian Goats.

In this study, we measured the growth performance and intramuscular fat (IMF) content of the Longissimus dorsi (LD) of Fuqing goats (FQs) and Nubian goats (NBYs), which exhibit extreme phenotypic differences in terms of their production and meat quality traits. RNA-Seq analysis was performed, and transcriptome data were obtained from the LD tissue of 3-month fetuses (E3), 0-month lambs (0M), 3-month lambs (3M), and 12-month lambs (12M) to reveal the differences in the molecular mechanisms regulating the muscle development and IMF deposition between FQs and NBYs. The results showed that a higher body weight and average daily gain were observed in the NBYs at three developmental stages after birth, whereas a higher IMF content was registered in the FQs at 12M. Additionally, transcriptome profiles during the embryonic period and after birth were completely different for both FQs and NBYs. Moreover, DEGs (KIF23, CCDC69, CCNA2, MKI67, KIF11, RACGAP1, NUSAP1, SKP2, ZBTB18, NES, LOC102180034, CAPN6, TUBA1A, LOC102178700, and PEG10) significantly enriched in the cell cycle (ko04110) at E3 (FQs vs. NBYs), and DEGs (MRPS7, RPS8, RPL6, RPL4, RPS11, RPS10, RPL5, RPS6, RPL8, RPS13, RPS24, RPS15, RPL23) significantly enriched in ribosomes (ko03010) at 0M (FQs vs. NBYs) related to myogenic differentiation and fusion were identified. Meanwhile, the differences in glucose and lipid metabolism began at the E3 timepoint and continued to strengthen as growth proceeded in FQs vs. NBYs. DEGs (CD36, ADIROQR2, ACACA, ACACB, CPT1A, IGF1R, IRS2, LDH-A, PKM, HK2, PFKP, PCK1, GPI, FASN, FADS1, ELOVL6, HADHB, ACOK1, ACAA2, and ACSL4) at 3M (FQs vs. NBYs) and 12M (FQs vs. NBYs) significantly enriched in the AMPK signaling pathway (ko04152), insulin resistance (ko04931), the insulin signaling pathway (ko04910), fatty acid metabolism (ko01212), and glycolysis/gluconeogenesis (ko00010) related to IMF deposition were identified. Further, the results from this study provide the basis for future studies on the mechanisms regulating muscle development and IMF deposition in different breeds of goats, and the candidate genes identified could be used in the selection process.