Extracorporeal Shock Wave and Melatonin Alleviate Joint Capsule Fibrosis after Knee Trauma in Rats by Regulating Autophagy.

BACKGROUND: Joint contracture is a common clinical problem affecting joint function. Capsule fibrosis plays a pivotal role in the progression of Joint contracture. Previous studies have reported that autophagy plays a regulatory role in visceral fibrosis. OBJECTIVE: This study aimed to investigate whether extracorporeal shock wave therapy (ESWT) and melatonin alleviate joint capsule fibrosis in rats with extended knee joint contracture by regulating autophagy. METHODS: A rat knee joint extension contracture model was made. Then, the rats were treated with ESWT, melatonin, ESWT + melatonin, or ESWT + melatonin + mTOR agonist for 4 weeks. The range of motion (ROM) of the knee joints was measured. Joint capsules were collected and observed for pathological changes by H&E and Masson staining. LC3B protein expression was evaluated by immunofluorescence staining. TGF-ß1, MMP-1, Col-Ⅰ, Col-Ⅲ, LC3, ATG7, Beclin1, p-AMPK, p-mTOR and p-ULK1 protein expressions were measured by Western blot assay. RESULTS: The intervention groups had significantly improved ROM of knee joint (P < 0.05), significantly improved pathological changes on HE and Masson staining, significantly decreased protein expressions of TGF-ß1, MMP-1, Col-Ⅰ, Col-Ⅲ and pmTOR (P < 0.05), and significantly increased protein expressions of LC3B, LC3II/LC3I ratio, ATG7, Beclin1, p-AMPK, and p-ULK1 (P < 0.05). Among these groups, the effects demonstrated by the ESWT + melatonin group were the best. With the mTOR agonist supplement, the therapeutic effects of extracorporeal shock waves and melatonin were significantly reduced. CONCLUSION: ESWT plus melatonin alleviated knee joint capsule fibrosis in rats by regulating autophagy.

Zangsiwei prevents particulate matter-induced lung inflammation and fibrosis by inhibiting the TGF-ß/SMAD pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zangsiwei(ZSW) is a traditional Tibetan medicine from China consisting of extracts of Rhododendron anthopogonoides Maxim, Gentiana Tourn, Corydalis hendersonii Hemsl and Berberis kansuensis C.K.Schneid. Traditionally, ZSW has been used by Tibetan physicians to treat chronic respiratory diseases. The role of ZSW in particulate matter-induced lung inflammation and fibrosis remains unclear. AIM OF THE STUDY: Combining non-targeted metabolomics, network pharmacology, and molecular docking to explore the mechanism of ZSW in the treatment of particulate matter-induced lung inflammation and fibrosis, and validated by in vivo and in vitro experiments. MATERIALS AND METHODS: The serum metabolite profile post-ZSW administration was first identified utilizing non-targeted metabolomics. Network pharmacology and molecular docking were employed to predict potential bioactive components and their corresponding targets. The in silico predictions were subsequently validated through in vivo studies in mice exposed to PM2.5 and silica dust, as well as in vitro studies utilizing human lung epithelial cells (A549) and lung fibroblasts (MRC5). RESULTS: Metabolomic analysis identified specific serum metabolites that were associated with ZSW treatment. Network pharmacology and molecular docking identified key targets involved in the Transforming growth factor-ß (TGF-ß)/SMAD pathway, which were subsequently validated through in vivo experiments demonstrating a reduction in lung inflammation and fibrosis in ZSW-treated mice. In vitro studies demonstrated that ZSW exerts protective effects against PM2.5-induced cytotoxicity and modulates fibrotic markers in a dose-dependent manner. This is consistent with the inhibition of the TGF-ß/SMAD pathway. CONCLUSION: Our integrated approach, which combines non-targeted metabolomics, network pharmacology, and molecular docking, followed by rigorous in vivo and in vitro validation, establishes ZSW as a potential therapeutic agent for particulate matter-induced lung inflammation and fibrosis.

Loss of electrical ß-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes.

Diabetes mellitus involves both insufficient insulin secretion and dysregulation of glucagon secretion1. In healthy people, a fall in plasma glucose stimulates glucagon release and thereby increases counter-regulatory hepatic glucose production. This response is absent in many patients with type-1 diabetes (T1D)2, which predisposes to severe hypoglycaemia that may be fatal and accounts for up to 10% of the mortality in patients with T1D3. In rats with chemically induced or autoimmune diabetes, counter-regulatory glucagon secretion can be restored by SSTR antagonists4-7 but both the underlying cellular mechanism and whether it can be extended to humans remain unestablished. Here, we show that glucagon secretion is not stimulated by low glucose in isolated human islets from donors with T1D, a defect recapitulated in non-obese diabetic mice with T1D. This occurs because of hypersecretion of somatostatin, leading to aberrant paracrine inhibition of glucagon secretion. Normally, KATP channel-dependent hyperpolarization of ß-cells at low glucose extends into the δ-cells through gap junctions, culminating in suppression of action potential firing and inhibition of somatostatin secretion. This 'electric brake' is lost following autoimmune destruction of the ß-cells, resulting in impaired counter-regulation. This scenario accounts for the clinical observation that residual ß-cell function correlates with reduced hypoglycaemia risk8.

Perinatal exposure to PBEB aggravates liver injury via macrophage-derived TWEAK in male adult offspring mice under western diet.

Liver injury and inflammation are the most commonly observed adverse outcomes following exposure to penta-brominated flame retardants (penta-BFRs). However, the role of inflammation in the development of liver injury in their alternatives has not yet been explored. Our study aimed to investigate the effects and the underlying mechanism of perinatal exposure to pentabromoethylbenzene (PBEB), a penta-BDE alternative, on liver injury in adult offspring mice under both chow and western diet in later life. Results showed that perinatal exposure to PBEB at 0.2 mg/kg or above led to liver injury in male offspring upon challenge with a western diet, but not in females. Utilizing the Olink immunology panel, our study specifically revealed an upregulation of tumor necrosis factor-related weak inducer of apoptosis (TWEAK) within the livers of male mice. This cytokine was further demonstrated to derive from the secretion by infiltrating macrophages in livers both in vivo and in vitro, which facilitated a shift towards M1 macrophage polarization. TWEAK further activated the hepatic NF-κB and NLRP3 inflammasome pathways, subsequently leading to hepatic pyroptosis in male mice of maternal PBEB exposure. Inhibition of TWEAK signaling mitigated macrophage polarization and inflammasome induction in a co-culture system of macrophages and liver cells. Our findings revealed that perinatal exposure to PBEB precipitated liver injury, partially through an inflammatory pathway mediated by macrophage-derived TWEAK, in male mice offspring under western diet.

Clinical efficacy and safety of the self-developed Zangsiwei Qingfei Mixture combined with conventional treatment in patients with acute exacerbation of chronic obstructive pulmonary disease. / è‡ªä¸»ç ”å‘çš„è—å››å‘³æ¸ è‚ºåˆå‰‚è”åˆå¸¸è§„æ²»ç–—å¯¹æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— æ€¥æ€§åŠ é‡æœŸæ‚£è€ çš„ä¸´åºŠç–—æ•ˆå’Œå®‰å ¨æ€§.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a significant global public health issue. Modern medical treatments have both benefits and limitations, prompting increasing attention from scholars worldwide on traditional ethnic medicine, and the Zangsiwei Qingfei Mixture is a newly developed formula derived from the effective components of classical Tibetan medicine to treat chronic respiratory diseases. This study aims to investigate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture combined with conventional treatment in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: Sixty AECOPD patients admitted to the Second Xiangya Hospital of Central South University from May 2021 to May 2023 were enrolled and randomly divided into 2 groups, with 30 patients in each group. The control group received conventional treatment, including bronchodilators, anti-infection agents, expectorants, and oxygen therapy. The experimental group received the Zangsiwei Qingfei Mixture in addition to conventional treatment. The treatment duration was 7 d for both groups. Baseline data such as gender, age, body mass index (BMI), smoking status, Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, COPD course, and the number of COPD exacerbations in the past year were collected. The primary efficacy indicators were assessed using the modified Medical Research Council (mMRC) dyspnea scale and the modified Borg scale. Secondary indicators included arterial lactic acid (LAC) and serum tumor necrosis factor alpha (TNF-α) levels. Safety indicators included liver and kidney function [alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (SCr), serum uric acid (SUA)], coagulation function [activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), and D-dimer]. The generalized linear mixed model (GLMM) was used to evaluate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture. RESULTS: Before treatment, there were no statistically significant differences in general baseline data, grading of mMRC dyspnea scale, score of modified Borg scale, arterial LAC, ALT, AST, SCr, SUA, APTT, FIB, and D-dimer between the 2 groups (all P>0.05). However, serum TNF-α and PT levels in the experimental group were significantly lower than those in the control group (both P<0.05). GLMM analysis showed that after adjusting for pre- and post-treatment, gender, age, BMI, smoking status, GOLD classification, COPD course, and the number of COPD exacerbations in the past year, the experimental group demonstrated significantly lower grading of mMRC dyspnea scale (coefficient=-0.329, P=0.036), score of modified Borg scale (coefficient=-1.077, P=0.001), serum TNF-α level (coefficient=-14.378, P<0.001), and arterial LAC level (coefficient=-0.409, P=0.012) compared to the control group. The Zangsiwei Qingfei Mixture had no significant effect on liver, kidney, or coagulation function indicators (all P>0.05). CONCLUSIONS: The Zangsiwei Qingfei Mixture combined with conventional treatment can improve clinical symptoms and promote homeostasis in AECOPD patients, demonstrating safety and reliability. Combining modern medicine with traditional ethnic medicine offers a feasible approach to treating chronic respiratory diseases in the future.

[Early gait analysis after total knee arthroplasty based on artificial intelligence dynamic image recognition].

OBJECTIVE: To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty (TKA). METHODS: From February 2023 to July 2023, 26 patients with unilateral knee osteoarthritis (KOA) were treated with TKA, including 4 males and 22 females, aged from 57 to 85 years old with an average of (67.58±6.49) years old;body mass index (BMI) ranged from 18.83 to 38.28 kg·m-2 with an average of (26.43±4.15) kg·m-2;14 patients on the left side, 12 patients on the right side;according to Kellgren-Lawrence(K-L) classification, 6 patients with grade Ⅲ and 20 patients with grade IV;the courses of disease ranged from 1 to 14 years with an average of (5.54±3.29) years. Images and videos of standing up and walking, walking side shot, squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation. The human posture estimation framework OpenPose were used to analyze stride frequency, step length, step length, step speed, active knee knee bending angle, stride length, double support phase time, as well as maximum hip flexion angle and maximum knee bending angle on squatting position. Western Ontario and McMaster Universities (WOMAC) arthritis index and Knee Society Score (KSS) were used to evaluate clinical efficacy of knee joint. RESULTS: All patients were followed up for 5 to 7 weeks with an average of (6.00±0.57) weeks. The total score of WOMAC decreased from (64.85±11.54) before operation to (45.81±7.91) at 6 weeks after operation (P<0.001). The total KSS was increased from (101.19±9.58) before operation to (125.50±10.32) at 6 weeks after operation (P<0.001). The gait speed, stride frequency and stride length of the affected side before operation were (0.32±0.10) m·s-1, (96.35±24.18) steps·min-1, (0.72±0.14) m, respectively;and increased to (0.48±0.11) m·s-1, (104.20±22.53) steps·min-1, (0.79±0.10) m at 6 weeks after operation (P<0.05). The lower limb support time and active knee bending angle decreased from (0.31±0.38) s and (125.21±11.64) ° before operation to (0.11±0.04) s and (120.01±13.35) ° at 6 weeks after operation (P<0.05). Eleven patients could able to complete squat before operation, 13 patients could able to complete at 6 weeks after operation, and 9 patients could able to complete both before operation and 6 weeks after operation. In 9 patients, the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation, and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation. CONCLUSION: Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of patients' gait. Knee pain of KOA was relieved and the function was improved, the supporting ability of the affected limb was improved after TKA, and the patient's stride frequency, stride length and stride speed were improved, and the overall movement rhythm of both lower limbs are more coordinated.

Abdominal obesity is associated with increased worsening renal function risk in patients with heart failure with preserved ejection fraction.

BACKGROUND: Worsening renal function (WRF) is a frequent comorbidity of heart failure with preserved ejection fraction (HFpEF). However, its relationship with abdominal obesity in terms of HFpEF remains unclear. This study aimed to evaluate the value of waist circumference (WC) and body mass index (BMI) in predicting WRF and examine the correlation between abdominal obesity and the risk of WRF in the HFpEF population. METHODS: Data were obtained from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Abdominal obesity was defined as WC ≥ 102 cm for men and ≥ 88 cm for women. WRF was defined as doubling of serum creatinine concentration from baseline. Restricted cubic splines and receiver operating characteristic curves were used to evaluate the value of WC and BMI in predicting WRF. Cumulative incidence curves and cox proportional-hazards models were used to compare patients with and without abdominal obesity. RESULTS: We included 2,806 patients with HFpEF in our study (abdominal obesity, n: 2,065). Although baseline creatinine concentrations did not differ, patients with abdominal obesity had higher concentrations during a median follow-up time of 40.9 months. Unlike BMI, WC exhibited a steady linear association with WRF and was a superior WRF predictor. Patients with abdominal obesity exhibited a higher risk of WRF after multivariable adjustment (hazard ratio: 1.632; 95% confidence interval: 1.015-2.621; P: 0.043). CONCLUSIONS: Abdominal obesity is associated with an increased risk of WRF in the HFpEF population. TRIAL REGISTRATION: URL: https://beta. CLINICALTRIALS: gov . Unique identifier: NCT00094302.

Impact of imaging features on selecting limited lymph node resection for cT1N0M0 lung cancer.

Background: Controversy still exists in the medical community regarding the performance of limited mediastinal lymphadenectomy (LML) in early-stage lung cancer. The objective of this study was to identify predictors of mediastinal lymph node (mLN) status and analyze its role in guiding surgical strategy. Methods: A retrospective cohort study was conducted on 2,834 surgical patients with peripheral cT1N0M0 non-small cell lung cancer between 2016 and 2018. Logistic regression was employed to identify predictors of N2 metastasis. Prognosis was compared between groups and independent prognostic factors were identified using Kaplan-Meier and multivariate Cox analysis. Results: There were 2,126 patients with systematic mLN dissection and 708 with LML. The multivariate analysis showed that N2 metastasis were associated with tumor size and consolidation tumor ratio (CTR). Patients in group A, with CTR >0.5 and tumor size ≤1 cm or CTR ≤0.5, had a significantly lower rate of N2 metastasis compared to those in group B, with CTR >0.5 and tumor size >1 cm (14.2% vs. 0.2%, P<0.001). Additionally, LML demonstrated comparable recurrence-free survival (RFS) and overall survival (OS) in group A, but a worse prognosis in group B compared to systematic lymph node dissection (SND). Furthermore, multivariate Cox regression analysis indicated that SND (vs. LML) was a favorable prognostic predictor for patients in group B [RFS: hazard ratio (HR) =0.71, P=0.005; OS: HR =0.66, P=0.01]. But univariate analysis in group A showed no significant difference in prognosis between SND and LML (RFS: P=0.24; OS: P=0.10). Conclusions: The combination of CTR and tumor size can predict mLN metastasis and procedure-specific outcome (SND vs. LML). This information may assist surgeons in identifying suitable candidates for LML.

Designing Polychromatic Er3+/Yb3+-Codoped Bi2WO6 Upconverting Nanoparticles with Enhanced Visible-Light-Triggered Photocatalytic Properties toward Tetracycline Degradation.

To address the unsatisfactory photodegradation capacities of photocatalysts, Er3+/Yb3+-codoped Bi2WO6 (Bi2WO6:Er3+/xYb3+) nanoparticles (NPs) with polychromatic upconversion (UC) emission and boosted visible-light-triggered photocatalytic abilities were designed. First-principles density functional theory was employed to study the impact of Er3+ and Yb3+ codoping on the electronic structure of Bi2WO6. Upon 980 nm excitation, the resultant NPs emitted polychromatic UC emissions caused by energy back transfer from Er3+ to Yb3+. Moreover, the involved UC emission mechanism was clarified through examining the pump power related to UC emission spectra. By investigating the visible-light-induced tetracycline (TC) decomposition, the photocatalytic activities of developed NPs were explored, where Bi2WO6:Er3+/0.07Yb3+ NP can degrade 81.76% of TC within 30 min, with a k value of 0.0552 min-1. Both the theoretical calculation and trapping results reveal that the •O2-, h+, and •OH were formed during the pollutant removal process. Additionally, the toxic TC can be photodegraded to nontoxic products via the synthesized photocatalysts, leading to wastewater purification. These achievements manifest that Bi2WO6:Er3+/xYb3+ NPs are promising visible-light-triggered photocatalysts to degrade pollutants, and our findings also propose a facile approach to regulate the photocatalytic activities of photocatalysts via utilizing doping and UC emission strategies.

Enhanced dielectric constant and breakdown strength of sandwiched polymer nanocomposite film for excellent energy storage.

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

Linking performance to dynamic migration of biofilm ecosystem reveals the role of voltage in the start-up of hybrid microbial electrolysis cell-anaerobic digestion.

Applied voltage is a crucial parameter in hybrid microbial electrolysis cells-anaerobic digestion (MEC-AD) systems for enhancing methane production from waste activated sludge (WAS). This study explored the impact of applied voltage on the initial biofilm formation on electrodes during the MEC-AD startup using raw WAS (Rr) and heat-pretreated WAS (Rh). The findings indicated that the maximum methane productivity for Rr and Rh were 3.4 ± 0.5 and 3.4 ± 0.2 mL/gVSS/d, respectively, increasing 1.5 times and 2.6 times over the productivity at 0 V. The biomass on electrode biofilms for Rr and Rh at 0.8 V increased by 70 % and 100 % compared to 0 V. The core functional microorganisms in the cathode biofilm were Methanobacterium and Syntrophomonas, and Geobacter in the anode biofilm, enhancing methane production through syntrophism and direct interspecies electron transfer, respectively. These results offer academic insights into optimizing AD functional electrode biofilms by applying voltage.

Deep learning models for separate segmentations of intracerebral and intraventricular hemorrhage on head CT and segmentation quality assessment.

BACKGROUND: The volume measurement of intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) provides critical information for precise treatment of patients with spontaneous ICH but remains a big challenge, especially for IVH segmentation. However, the previously proposed ICH and IVH segmentation tools lack external validation and segmentation quality assessment. PURPOSE: This study aimed to develop a robust deep learning model for the segmentation of ICH and IVH with external validation, and to provide quality assessment for IVH segmentation. METHODS: In this study, a Residual Encoding Unet (REUnet) for the segmentation of ICH and IVH was developed using a dataset composed of 977 CT images (all contained ICH, and 338 contained IVH; a five-fold cross-validation procedure was adopted for training and internal validation), and externally tested using an independent dataset consisting of 375 CT images (all contained ICH, and 105 contained IVH). The performance of REUnet was compared with six other advanced deep learning models. Subsequently, three approaches, including Prototype Segmentation (ProtoSeg), Test Time Dropout (TTD), and Test Time Augmentation (TTA), were employed to derive segmentation quality scores in the absence of ground truth to provide a way to assess the segmentation quality in real practice. RESULTS: For ICH segmentation, the median (lower-quantile-upper quantile) of Dice scores obtained from REUnet were 0.932 (0.898-0.953) for internal validation and 0.888 (0.859-0.916) for external test, both of which were better than those of other models while comparable to that of nnUnet3D in external test. For IVH segmentation, the Dice scores obtained from REUnet were 0.826 (0.757-0.868) for internal validation and 0.777 (0.693-0.827) for external tests, which were better than those of all other models. The concordance correlation coefficients between the volumes estimated from the REUnet-generated segmentations and those from the manual segmentations for both ICH and IVH ranged from 0.944 to 0.987. For IVH segmentation quality assessment, the segmentation quality score derived from ProtoSeg was correlated with the Dice Score (Spearman r = 0.752 for the external test) and performed better than those from TTD (Spearman r = 0.718) and TTA (Spearman r = 0.260) in the external test. By setting a threshold to the segmentation quality score, we were able to identify low-quality IVH segmentation results by ProtoSeg. CONCLUSIONS: The proposed REUnet offers a promising tool for accurate and automated segmentation of ICH and IVH, and for effective IVH segmentation quality assessment, and thus exhibits the potential to facilitate therapeutic decision-making for patients with spontaneous ICH in clinical practice.

One-year monitoring of grass-type architectural waterscapes with long-term operation: Water quality and microorganism.

Grass-type architectural waterscapes (GAWs) utilize submerged plants to enhance self-purification ability and maintain a clear-water state. However, knowledge about their long-term water quality and microbial community dynamics remains limited. This study monitored the water quality, microbial community composition, and networks in two GAWs. GAW1 consisted solely Hydrilla verticillata with a water depth of 0.70 m, while GAW2 primarily contained Vallisneria natans, Microsorum pteropus, and Aquarius grisebachii with a water depth of 0.30 m. Results show that both water depth and submerged plant species play crucial roles in GAW establishment. The water depth of 0.7 m enabled Hydrilla verticillata to thrive underwater despite temperature variations, which demonstrated excellent nutrient uptake capacity. Thus, GAW1 exhibited superior self-purification ability, consistently meeting Class III standard for surface water in China. In contrast, GAW2 had a shallow water depth and contained ornamental plants, only meeting Class V standard. Furthermore, microbial communities were shaped by water quality, with distinct enriched genera serving as potential "microbial indicators". Enrichment of the hgcI clade and Sporichthyaceae_unclassified indicated superior water quality in GAW1, while prevalence of Comamonadaceae_unclassified, Flavobacterium, Rhodoluna, and Pseudarcicella suggested poor water quality in GAW2. Additionally, highly complex and connected microbial networks suggested elevated pollutant levels in GAWs. This study emphasized the significance of submerged plant species and water depth in GAWs construction and highlighted microbial communities and networks as potential indicators of water quality.

Natural variation in the Tn1a promoter regulates tillering in rice.

Rice tillering is an important agronomic trait that influences plant architecture and ultimately affects yield. This can be genetically improved by mining favourable variations in genes associated with tillering. Based on a previous study on dynamic tiller number, we cloned the gene Tiller number 1a (Tn1a), which encodes a membrane-localised protein containing the C2 domain that negatively regulates tillering in rice. A 272 bp insertion/deletion at 387 bp upstream of the start codon in the Tn1a promoter confers a differential transcriptional response and results in a change in tiller number. Moreover, the TCP family transcription factors Tb2 and TCP21 repress the Tn1a promoter activity by binding to the TCP recognition site within the 272 bp indel. In addition, we identified that Tn1a may affect the intracellular K+ content by interacting with a cation-chloride cotransporter (OsCCC1), thereby affecting the expression of downstream tillering-related genes. The Tn1a+272 bp allele, associated with high tillering, might have been preferably preserved in rice varieties in potassium-poor regions during domestication. The discovery of Tn1a is of great significance for further elucidating the genetic basis of tillering characteristics in rice and provides a new and favourable allele for promoting the geographic adaptation of rice to soil potassium.

No causal relationship between serum vitamin D levels and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

Background: Numerous observational studies have presented an association between Vitamin D (VD) and Alcoholic Liver Disease (ALD). However, sufficient evidence from Randomized Controlled Trials (RCTs) substantiating this correlation is scarce, thus leaving the causality of this relationship ambiguous. To overcome the shortcomings of traditional observational studies, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal relationship between VD and ALD. Methods: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 64,979), and retrieved ALD statistics from GWASs, inclusive of 1,416 cases and 217,376 healthy controls, while excluding chronic liver diseases such as nonalcoholic fatty liver disease, toxic liver disease, and viral hepatitis. Subsequent, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic and MR-Egger regression intercept analyses were used to assess pleiotropy. Sensitivity analyses using the MR Egger, weighted median, simple mode, and weighted mode methods were also performed. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed. Results: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results. Conclusion: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.

Revealing the Thermodynamic Mechanism of Phase Transition Induced by Activation Polarization in Lithium-Ion Batteries.

Enhancing the phase transition reversibility of electrode materials is an effective strategy to alleviate capacity degradation in the cycling of lithium-ion batteries (LIBs). However, a comprehensive understanding of phase transitions under microscopic electrode dynamics is still lacking. In this paper, the activation polarization is quantified as the potential difference between the applied potential (Uabs) and the zero-charge potential (ZCP) of electrode materials. The polarization potential difference facilitates the phase transition by driving Li-ion adsorption and supplying an electron-rich environment. A novel thermodynamic phase diagram is constructed to characterize the phase transition of the example MoS2 under various Li-ion concentrations and operating voltages using the grand canonic fixed-potential method (FPM). At thermodynamic quasi-equilibrium, the ZCP is close to the Uabs, and thus is used to form the discharge curve in the phase diagram. The voltage plateau is observed within the phase transition region in the simulation, which will disappear as the phase transition reversibility is impaired. The obtained discharge curve and phase transition concentration both closely match the experimental results. Overall, the study provides a theoretical understanding of how polarization affects phase evolution in electrode dynamics, which may provide a guideline to improve battery safety and cycle life.

Preliminary study of extracorporeal shock wave alleviating joint capsule fibrosis caused by internal bleeding of knee joint in rats.

PURPOSE: Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats. METHODS: Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group's knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, ß-catenin protein expression in joint capsule using Western blotting. RESULTS: Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, ß-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased. CONCLUSIONS: Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.

MrgX2-targeted ligand screening from Artemisia capillaris Thunb. extract and receptor-ligand interaction analysis based on MrgX2-HALO-tag/CMC.

Artemisia capillaris Thunb. (A. capillaris) is a well-known traditional Chinese herbal medicine with a wide range of pharmacological effects, such as soothing the liver and gallbladder, heat clearance, and detoxifying. Hence, its extract is commonly added to various traditional Chinese medicine formulas. Traditional Chinese medicine injection (TCMI) is a mature pharmaceutical dosage form developed using TCM theory combined with modern science and technology. Notably, allergic reactions, especially pseudo­allergic reactions (PARs), greatly limited the use of these injections. Therefore, screening pseudo­allergic components in A. capillaris extract is clinically significant. In the present study, we proposed a two-dimensional screening and identification system based on mas-related G protein-coupled receptor X2-HALO-tag/cell membrane chromatography (MrgX2-HALO-tag/CMC) high performance liquid chromatography mass spectrometry (HPLC-MS); seven potential active components were screened from 75 % ethanol extract of A. capillaris: NCA, CA, CCA, 1,3-diCQA, ICA-B, ICA-A, and ICA-C. The receptor-ligand interactions between these seven compounds and MrgX2 protein were analyzed using frontal analysis and molecular docking technology. Furthermore, a mast cell degranulation-related assay was used to assess the pseudo­allergic activity of these compounds. The screened compounds can serve as ligands of MrgX2, and this study provides a research basis for pseudo­allergic reactions caused by TCMIs containing A. capillaris.

Genetic causality and metabolite pathway identifying the relationship of blood metabolites and psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease that causes significant disability. However, little is known about the underlying metabolic mechanisms of psoriasis. Our study aims to investigate the causality of 975 blood metabolites with the risk of psoriasis. MATERIALS AND METHODS: We mainly applied genetic analysis to explore the possible associations between 975 blood metabolites and psoriasis. The inverse variance weighted (IVW) method was used as the primary analysis to assess the possible association of blood metabolites with psoriasis. Moreover, generalized summary-data-based Mendelian randomization (GSMR) was used as a supplementary analysis. In addition, linkage disequilibrium score regression (LDSC) was used to investigate their genetic correction further. Metabolic pathway analysis of the most suggested metabolites was also performed using MetaboAnalyst 5.0. RESULTS: In our primary analysis, 17 metabolites, including unsaturated fatty acids, phospholipids, and triglycerides traits, were selected as potential factors in psoriasis, with odd ratios (OR) ranging from 0.986 to 1.01. The GSMR method confirmed the above results (ß = 0.001, p < 0.05). LDSC analysis mainly suggested the genetic correlation of psoriasis with genetic correlations (rg) from 0.088 to 0.155. Based on the selected metabolites, metabolic pathway analysis suggested seven metabolic pathways including ketone body that may be prominent pathways for metabolites in psoriasis. CONCLUSION: Our study supports the causal role of unsaturated fatty acid properties and lipid traits with psoriasis. These properties may be regulated by the ketone body metabolic pathway.