Imaging characteristics of hip joint microinstability: a case-control study of hip arthroscopy patients.

OBJECTIVES: Hip microinstability is a clinical entity increasingly recognized and treated but challenging to diagnose with a lack of objective criteria. This study assessed the prevalence and diagnostic accuracy of different imaging findings for hip microinstability on radiograph and MR. METHODS: A retrospective case-control study of 224 hips treated with arthroscopic surgery by a single orthopedic surgeon, 112 hips with clinical microinstability and 112 controls without. Pre-operative radiograph and MRI/MRA imaging were evaluated by two musculoskeletal radiologists to assess morphological parameters and imaging signs reportedly associated with hip microinstability. RESULTS: Four imaging features reached significance as predictors of microinstability via three-step logistic regression: labral hyperplasia and decreased lateral center edge angle on MR (OR 2.45 and 0.93, respectively) and the absence of positive ischial spine sign and absence of osteophytes on radiographs (OR 0.47 and 0.28, respectively). Increased acetabular anteversion and absence of cam lesions were more likely in the microinstability group (p = 0.02 and 0.04, respectively), but not independent predictors. Labral tears, chondral loss, abnormal ligamentum teres, anterior capsule thinning, iliocapsularis to rectus femoris ratio, posterior crescent sign, cliff sign, and femoro-epiphyseal acetabular roof (FEAR) index were not associated with microinstabillity. CONCLUSION: Imaging features may be predictive of hip microinstability in some cases. Decreased LCEA, increased acetabular anteversion, and labral hyperplasia were associated with microinstability in this study, while many other published imaging findings were not. Imaging remains complementary, but not definitive, in the diagnosis of hip microinstability.

A Tumor-Homing Nanoframework for Synergistic Microwave Tumor Ablation and Provoking Strong Anticancer Immunity Against Metastasis.

Microwave thermotherapy (MT) is a clinical local tumor ablation modality, but its applications are limited by its therapeutic efficacy and safety. Therefore, developing sensitizers to optimize the outcomes of MT is in demand in clinical practice. Herein, we engineered a special nanoframework (i.e., FdMI) based on a fucoidan-decorated zirconium metal-organic framework incorporating manganese ions and liquid physisorption for microwave tumor ablation. The monodisperse nanoframework exhibited both microwave thermal effects and microwave dynamic effects, which could effectively kill cancer cells by efficient intracellular drug delivery. Through fucoidan-mediated targeting of P-selectin in the tumor microenvironment (TME), the FdMI effectively accumulated in tumor regions, leading to significant eradication of orthotropic triple-negative breast cancer (TNBC) and aggressive Hepa1-6 liver tumors by the synergistic effects of microwave thermotherapy/dynamic therapy (MT/MDT). The eradication of primary tumors could activate systemic immune responses, which effectively inhibited distant TNBC tumors and lung metastasis of Hepa1-6 liver tumors, respectively. This work not only engineered nanoparticle sensitizers for tumor-targeted synergistic MT/MDT but also demonstrated that nanocarrier-based microwave tumor ablation could stimulate antitumor immunity to effectively inhibit distant and metastatic tumors, demonstrating the high potential for effectively managing advanced malignant tumors.

Paeoniflorin regulates microglia-astrocyte crosstalk, inhibits inflammatory response, and alleviates neuropathic pain through HSP90AA1/HMGB1 signaling pathway.

Given the unclear, complex pathogenesis of neuropathic pain and the potential of paeoniflorin in relieving neuropathic pain, this study aimed to further clarify the therapeutic effect of paeoniflorin on neuropathic pain and to preliminarily explore the possible protective mechanisms of paeoniflorin. Chronic constrictive injury-induced Sprague Dawley rats and lipopolysaccharide-induced BV-2 cells were used for in vivo and in vitro experiments, respectively. The exosome uptake assay of mouse astrocytes (PKH-67 fluorescent labeling) and the mechanical nociceptive assay (the von Frey fibrous filaments) were performed. The effects of paeoniflorin and its downstream mechanisms on microglial and astrocyte activation, inflammation-associated proteins and exosome marker were determined. Paeoniflorin alleviated mechanical abnormal pain, decreased levels of ionized calcium binding adapter molecule-1 (Iba-1), glial fibrillary acidic protein, Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1, inflammatory factor) and High Mobility Group Box 1 (HMGB1, inflammation-related protein), and inhibited neuronal apoptosis in chronic constrictive injury rats or lipopolysaccharide-induced BV-2 cells. However, these effects were offset by HSP90AA1 overexpression in lipopolysaccharide-induced BV-2 cells. Exosomes of BV-2 cells could be absorbed by mouse astrocytes. In addition, HSP90AA1 overexpression reversed the effects of paeoniflorin on HMGB1 expression and inflammatory factors and proteins in mouse astrocytes co-cultured with exosome. Collectively, paeoniflorin alleviates neuropathic pain and inhibits inflammatory responses in chronic constrictive injury by modulating microglia-astrocyte crosstalk through HSP90AA1/HMGB1 pathways, which further evidences the potential of paeoniflorin in the treatment of neuropathic pain.

Autophagy Blockage Enhancing Photothermal and Chemodynamic Synergistic Therapy Based on HCQ/CuS Nanoplatform.

As an intracellular protective mechanism, autophagy has the potential to significantly impair the therapeutic effects of photothermal therapy (PTT) and chemodynamic therapy (CDT), which helps cancer cells survive under harsh conditions, such as high temperature and reactive oxygen species (ROS). In this study, an autophagy blockage enhanced PTT and CDT synergistic therapy nanoplatform is constructed by loading hydroxychloroquine (HCQ) with autophagy inhibitory effect into hollow copper sulfide (HCuS). Specifically, HCuS produces toxic ROS through Fenton-like reaction in the tumor microenvironment (TME). At the same time, PTT-mediated temperature elevation of the tumor region accelerates the Fenton-like reaction and ROS production, enhancing the therapeutic effect of CDT. Furthermore, the internal autophagy inhibitor HCQ significantly blocks the fusion of autophagosomes and lysosomes by deacidifying lysosomes, cutting off the self-protection mechanism of cancer cells, and amplifying the combined treatment of PTT and CDT. Both in vitro and in vivo results demonstrate that the combination of photothermal-enhanced chemodynamic therapy with inhibition of autophagy provides new insights into designing multifunctional therapeutic nanoagents.

Echotexture of recurrent laryngeal nerves: the depiction of recurrent laryngeal nerves at high-frequency ultrasound during radical thyroidectomy.

Introduction: To investigate the ultrasound characteristics of recurrent laryngeal nerves (RLNs) during radical surgery for thyroid cancer and to enhance the understanding of RLN ultrasound features. Methods: From October 2021 to December 2022, a prospective study was conducted involving 24 patients scheduled for bilateral thyroid surgery. Near the conclusion of the surgery, intraoperative ultrasonography of the RLN within the tracheoesophageal groove was performed using a 15-7 MHz transducer. The thickness and width of the RLN were measured during the procedure. Results: The internal architecture of the RLN was observed to consist of multiple hypoechoic, parallel, but discontinuous linear hyperechoic areas separated by bands. In the normal RLN group, the diameter of the RLN was relatively consistent, with thickness ranging from 2.20 to 2.71 mm (mean: 2.48 ± 0.14 mm) and width from 1.25 to 1.70 mm (mean: 1.45 ± 0.11 mm). Both weight and the body mass index (BMI) showed a statistically significant correlation with RLN thickness (Weight: r=0.544, P=0.001; BMI: r=0.605, P=0.001). The BMI also showed a statistically significant correlation with the RLN width (r=0.377, P=0.033). In the RLN invasion group, the width of invaded RLNs ranged from 1.9 to 2.3 mm (mean: 2.10 ± 0.11 mm), while the width of non-invaded RLNs ranged from 2.6 to 3.2 mm (mean: 2.93 ± 0.20 mm). Conclusions: Ultrasound effectively reveals the structural features of the RLN and enhances sonographers' understanding of RLN characteristics.

Prevalence and Spatial Distribution Characteristics of Female Stress Urinary Incontinence in Mainland China.

Background and objective: Stress urinary incontinence (SUI) in women is a common condition that affects middle-aged and elderly women. Currently, there are still many limitations in the epidemiological research on SUI. This study aims to address the gap in the prevalence of female SUI in mainland China and provide theoretical support for the prevention and treatment of SUI. Methods: A comprehensive literature search was conducted on the prevalence of female SUI in mainland China, systematically searching Chinese and English databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Weipu Database as of April 1, 2024. Detailed criteria for screening and exclusion were established. The prevalence of SUI in the selected studies was synthesized using Stata MP (version 15) software, and a multisubgroup analysis, a sensitivity analysis, and publication bias detection of the prevalence of SUI were also performed using the software. Additionally, ArcGIS software (version 10.8) and Geoda software (version 1.2) were utilized to explore the geographical distribution characteristics of the prevalence of female SUI in mainland China. Key findings and limitations: A total of 688 articles were screened, and finally 85 articles were included. The overall rate of female SUI in mainland China was 24.5% (95% confidence interval: 22.5-26.5%). The heterogeneity of the study is statistically significant (I2 = 99.0%, p < 0.001). Based on significant heterogeneity, a multisubgroup analysis was conducted. The results showed that the prevalence of SUI varies among different publication years, literature quality scores, investigators, study settings, sampling methods, provinces, regions, coastal or inland areas, and rural or urban areas. A spatial econometric analysis indicated that the incidence of SUI in the east-west distribution showed a downward trend, while in the north-south distribution, the incidence rate of SUI showed a trend of first increasing and then decreasing. Additionally, a spatial metrology analysis showed similar trends in the distribution of SUI incidence. Conclusions and clinical implications: The high incidence rate of female SUI in mainland China and the regional differences observed indicate the need for further rigorous epidemiological investigation in the future. Patient summary: Stress urinary incontinence (SUI) is common among middle-aged and elderly women. The high prevalence of SUI in mainland China and the differences across regions emphasize the need for conducting more robust epidemiological studies in the future.

Alterations in liver triglyceride profiles in CCl4-induced liver regeneration.

Lipid metabolism, particularly triglyceride (TG) metabolism, is crucial for liver regeneration. During the early phase of liver regeneration, the liver temporarily accumulates a substantial amount of TG-dominated lipids. However, the specific composition of the TG profile during this phase is not yet fully understood. Here, we showed that the TG molecular composition in the liver was significantly altered during liver regeneration following carbon tetrachloride (CCl4)-induced liver injury. Lipid accumulation in livers was observed as early as 12 hours after CCl4 treatment, with transient regeneration-associated steatosis (TRAS) lasting until 24 hours. Hepatocyte proliferation began only after liver lipid levels returned to baseline at 48 hours. Furthermore, the profile of TG species changed significantly during liver regeneration. During the TRAS period, the accumulated TGs in the liver were mainly long-chain triglycerides, with most of the fatty acids constituting these triglycerides having fewer than 20 carbon atoms. In the proliferation phase, the fatty acid composition of these triglycerides shifted from long-chain to ultra-long-chain fatty acids. Our results suggest a significant TRAS-related change in the TG lipid profile of the liver during liver regeneration.

Female genital prolapse and risk of psychiatric disorders: A two-sample Mendelian randomization analysis.

BACKGROUND: There is a growing body of evidence suggests a strong link between female genital prolapse (FGP) and mental health. However, the causal relationship between FGP and psychological disorders remains unclear. OBJECTIVES: Bidirectional Mendelian Randomization (MR) analysis has been applied to investigate the potential impact of FGP on the risk of seven common psychiatric disorders. METHODS: The two-sample MR analysis was conducted using genetic instruments such as Inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode from the genome-wide association study (GWAS) summary data in European populations. In addition, the Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers (MR-PRESSO) test and leave-one-out analysis were employed to assess the sensitivity and heterogeneity. RESULTS: The MR results revealed that FGP exhibited a potential marginal protective effect on bipolar disorder (BD) (odds ratio(OR) = 0.92, 95%confidence interval (95%CI: 0.85-0.99, P = 0.03) as well as schizophrenia(OR = 0.91, 95%CI:0.85-0.98, P = 0.01). Nevertheless, there was no causal correlation between genetically predicted FGP and obsessive compulsive disorder (OCD) (OR = 0.98, 95%CI:0.80-1.20, P = 0.84),depression (broad) (OR = 1.00, 95%CI:0.99-1.01, P = 0.76), major depression(OR = 0.98, 95%CI:0.94-1.03, P = 0.43), anxiety disorders (OR = 1.00, 95%CI:0.94-1.07,P = 0.97) and post-traumatic stress disorder(PTSD) (OR = 1.18, 95%CI:0.88-1.57,P = 0.27),respectively. In addition, BD was found to have a potential significant influence on FGP in the inverse MR analysis (OR = 0.83, 95%CI:0.72-0.97, P = 0.02). No significant heterogeneity or horizontal pleiotropy detected, and the results were deemed stable based on sensitivity analysis and leave-one-out test . LIMITATIONS: There are shortcomings such as data limitations, population bias, potential pleiotropy, and stratified analysis. CONCLUSIONS: While there is potential causal relationship between FGP and BD or schizophrenia, it does not exhibit any correction with OCD, depression (broad), major depression, anxiety disorders and PTSD among European populations.

Dexmedetomidine ameliorates diabetic intestinal injury by promoting the polarization of M2 macrophages through the MMP23B pathway.

BACKGROUND: Diabetes is often associated with gastrointestinal dysfunctions, which can lead to hypoglycemia. Dexmedetomidine (DEX) is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal function. AIM: To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction. METHODS: Sedation/anesthesia scores and vital signs of streptozotocin (STZ)-induced diabetic mice under DEX sedation were observed. Diabetic mice were divided into saline and DEX groups. After injecting sedatives intraperitoneally, tight junctions (TJs) and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier function. The role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial deletion. In vitro, high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ inter-vention. Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions. RESULTS: MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice, with the DEX group displaying decreased MMP23B levels. Diabetes-mediated TJ dis-ruption, increased intestinal mucosal permeability, and systemic inflammation in wild-type mice might be reversed by DEX. In Caco-2 cells, MMP23B was associated with increased reactive oxygen species accumulation, mitochondrial membrane potential depolarization, and TJ disruption. CONCLUSION: DEX reduces MMP23B, which may potentially contribute to STZ-induced intestinal barrier dysfunction, affecting TJ modification through mitochondrial dysfunction.

Identification of amino acids metabolomic profiling in human plasma distinguishes lupus nephritis from systemic lupus erythematosus.

Lupus nephritis (LN) is an immunoinflammatory glomerulonephritis associated with renal involvement in systemic lupus erythematosus (SLE). Given the close relationship between plasma amino acids (AAs) and renal function, this study aimed to elucidate the plasma AA profiles in LN patients and identify key AAs and diagnostic patterns that distinguish LN patients from those with SLE and healthy controls. Participants were categorized into three groups: normal controls (NC), SLE, and LN. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to quantify AA levels in human plasma. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to identify key AAs. The diagnostic capacity of the models was assessed using receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) values. Significant alterations in plasma AA profiles were observed in LN patients compared to the SLE and NC groups. The OPLS-DA model effectively separated LN patients from the SLE and NC groups. A joint model using histidine (His), lysine (Lys), and tryptophan (Trp) demonstrated exceptional diagnostic performance, achieving an AUC of 1.0 with 100% sensitivity, specificity, and accuracy in predicting LN. Another joint model comprising arginine (Arg), valine (Val), and Trp also exhibited robust predictive performance, with an AUC of 0.998, sensitivity of 93.80%, specificity of 100%, and accuracy of 95.78% in distinguishing between SLE and LN. The joint forecasting models showed excellent predictive capabilities in identifying LN and categorizing lupus disease status. This approach provides a novel perspective for the early identification, prevention, treatment, and management of LN based on variations in plasma AA levels.

ChangPu YuJin Tang improves Tourette disorder symptoms by modulating amino acid neurotransmitters in IDPN model rats.

INTRODUCTION: Changpu Yujin Tang(CPYJT), a Chinese herbal compound, is an effective therapeutic strategy for pediatric patients with Tourette disorder (TD). Therefore, this work aims to investigate the therapeutic mechanisms of CPYJT. METHODS: Behavioral and cellular ultrastructural evaluation of the therapeutic effects of CPYJT in TD model rats. Colorimetric methods, reverse transcription­quantitative PCR, and Western Blot were used to measure the altered levels of GLU, GABA, and the levels of VGLUT1, GLUD1, GABRA3, and GAD65 in the cortex, striatum, and thalamus of the TD model rats after 7, 14, 21, and 28 days of CPYJT administration. RESULTS: CPYJT significantly reduced stereotypic behavior and motor behavior scores in TD model rats. CPYJT ameliorates myelin structural damage in TD model rat neuronal cells. CPYJT decreased GLU content, elevated GABA content, decreased GLUD1 and VGLUT1 levels, and elevated GAD65 and GABRA3 levels in TD model rats' cortex, striatum, and thalamus. CPYJT has different regulatory time points in the cortex, striatum, and thalamus for critical factors of amino acid-based neurotransmission. CONCLUSION: CPYJT protects behavioral and structural damage of neuronal cells in multiple brain regions in TD model rats.

The Gut Microbial Lipid Metabolite 14(15)-EpETE Inhibits Substance P Release by Targeting GCG/PKA Signaling to Relieve Cisplatin-Induced Nausea and Vomiting in Rats.

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect related to activation of substance P (SP). SP activation can result from dysregulation of the gut-brain axis, and also from activation of protein kinase A signaling (PKA) signaling. In this study, we connected these factors in an attempt to unveil the mechanisms underlying CINV and develop new therapeutic strategies. Female rats were injected with cisplatin (Cis) to induce pica. Fecal samples were collected before/after injection, and subjected to lipid metabolomics analysis. In another portion of pica rats, the PKA inhibitor KT5720 was applied to investigate the involvement of PKA signaling in CINV, while fecal microbiota transplantation (FMT) was implemented to verify the therapeutic effect of the lipid metabolite 14(15)-EpETE. Pica symptoms were recorded, followed by ileal histological examination. The targeting relationship between 14(15)-EpETE and glucagon was determined by bioinformatics. SP and glucagon/PKA signaling in rat ileum, serum, and/or brain substantia nigra were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and/or western blot. The results showed a significantly lower level of 14(15)-EpETE in rat feces after Cis injection. KT5720 treatment alleviated Cis-induced pica symptoms, ileal injury, SP content increase in the ileum, serum, and brain substantia nigra, and ileal PKA activation in rats. The ileal level of glucagon was elevated by Cis in rats. FMT exerted an effect similar to that of KT5720 treatment, relieving the Cis-induced changes, including ileal glucagon/PKA activation in rats. Our findings demonstrate that FMT restores 14(15)-EpETE production, which inhibits SP release by targeting GCG/PKA signaling, ultimately mitigating CINV.

A bibliometric analysis on laparoscopic pelvic floor surgery from 1996-2022.

INTRODUCTION: Pelvic organ prolapse is a common condition in middle-aged and older women. Laparoscopic pelvic floor surgery is frequently researched as a treatment for this issue. However, the effectiveness of this procedure has only been the subject of a few studies. METHODS: To quantitatively evaluate and display the relevant literature from the Web of Science database, we set the publication period of the literature from 1996 to 2022 and used VOSviewer and CiteSpace for visual analysis. RESULTS: Laparoscopic pelvic floor surgery research has increased year-on-year, with 1003 publications identified from 63 countries and published in 210 journals. In the global ranking of studies, the United States was the leader (n = 306; 30.5 %), with the most published authors being Campagna, Giuseppe (n = 17) and Scambia, Giovanni (n = 17). The International urogynecology journal included the most significant articles (n = 173; 17.2 %). Keyword analysis suggests that complications, rectal prolapse, native tissue repair, and warranty may have become hotspots in recent years. CONCLUSIONS: This bibliometric study shows that the depth and breadth of research on pelvic floor laparoscopic surgery have expanded rapidly over the last twenty-five years and that laparoscopic surgery has been recognized by different scholars or countries as an essential modality for the treatment of pelvic floor organ prolapse.

Carbon footprint analysis of wastewater treatment processes coupled with sludge in situ reduction.

The goal of this study was to assess the impacts or benefits of sludge in situ reduction (SIR) within wastewater treatment processes with relation to global warming potential in wastewater treatment plants, with a comprehensive consideration of wastewater and sludge treatment. The anaerobic side-stream reactor (ASSR) and the sludge process reduction activated sludge (SPRAS), two typical SIR technologies, were used to compare the carbon footprint analysis results with the conventional anaerobic - anoxic - oxic (AAO) process. Compared to the AAO, the ASSR with a typical sludge reduction efficiency (SRE) of 30 % increased greenhouse gas (GHG) emissions by 1.1 - 1.7 %, while the SPRAS with a SRE of 74 % reduced GHG emissions by 12.3 - 17.6 %. Electricity consumption (0.025 - 0.027 kg CO2-eq/m3), CO2 emissions (0.016 - 0.059 kg CO2-eq/m3), and N2O emissions (0.009 - 0.023 kg CO2-eq/m3) for the removal of secondary substrates released from sludge decay in the SIR processes were the major contributor to the increased GHG emissions from the wastewater treatment system. By lowering sludge production and the organic matter content in the sludge, the SIR processes significantly decreased the carbon footprints associated with sludge treatment and disposal. The threshold SREs of the ASSR for GHG reduction were 27.7 % and 34.6 % for the advanced dewatering - sanitary landfill and conventional dewatering - drying-incinerating routes, respectively. Overall, the SPRAS process could be considered as a cost-effective and sustainable low-carbon SIR technology for wastewater treatment.

Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

Novel role for Ddx39 in differentiation and telomere length regulation of embryonic stem cells.

Erk signaling is indispensable for the self-renewal and differentiation of mouse embryonic stem cells (ESCs), as well as telomere homeostasis. But how Erk regulates these biological processes remains unclear. We identified 132 Erk2 interacting proteins by co-immunoprecipitation and mass spectrometric analysis, and focused on Ddx39 as a potential Erk2 substrate. We demonstrated that Erk2 phosphorylates Ddx39 on Y132 and Y138. Ddx39 knockout (KO) ESCs are defective in differentiation, due to reduced H3K27ac level upon differentiation. Phosphorylation of Ddx39 promotes the recruitment of Hat1 to acetylate H3K27 and activate differentiation genes. In addition, Ddx39 KO leads to telomere elongation in ESCs. Ddx39 is recruited to telomeres by the telomere-binding protein Trf1, consequently disrupting the DNA loop formed by Trf1 and suppressing the alternative lengthening of telomeres (ALT). Phosphorylation of Ddx39 weakens its interaction with Trf1, releasing it from telomeres. Thus, ALT activity is enhanced, and telomeres are elongated. Altogether, our studies reveal an essential role of Ddx39 in the differentiation and telomere homeostasis of ESCs.

Enhancing Localized Electron Density over Pd1.4Cu Decorated Oxygen Defective TiO2-x Nanoarray for Electrocatalytic Nitrite Reduction to Ammonia.

Electrocatalytic nitrite (NO2 -) reduction to ammonia (NH3) is a promising method for reducing pollution and aiding industrial production. However, progress is limited by the lack of efficient selective catalysts and ambiguous catalytic mechanisms. This study explores the loading of PdCu alloy onto oxygen defective TiO2-x, resulting in a significant increase in NH3 yield (from 70.6 to 366.4 µmol cm-2 h-1 at -0.6 V vs reversible hydrogen electrode) by modulating localized electron density. In situ and operando studies illustrate that the reduction of NO2 - to NH3 involves gradual deoxygenation and hydrogenation. The process also demonstrated excellent selectivity and stability, with long-term durability in cycling and 50 h stability tests. Density functional theory (DFT) calculations elucidate that the introduction of PdCu alloys further amplified electron density at oxygen vacancies (Ovs). Additionally, the Ti─O bond is strengthened as the d-band center of the Ti 3d rising after PdCu loading, facilitating the adsorption and activation of *NO2. Moreover, the presence of Ovs and PdCu alloy lowers the energy barriers for deoxygenation and hydrogenation, leading to high yield and selectivity of NH3. This insight of controlling localized electron density offers valuable insights for advancing sustainable NH3 synthesis methods.

A preliminary study of contrast-enhanced ultrasound guided capsule-preserving hydrodilatation in shoulder adhesive capsulitis.

Background: Capsule-preserving hydrodilatation is a common treatment for adhesive capsulitis (AC), and ultrasound (US) has recently become the most popular adjuvant tool for image-guided glenohumeral joint injection. However, traditional US is hardly adequate to assess extracapsular fluid leakage, which may decide the treatment outcomes. In this study, we explored the value of contrast-enhanced ultrasound (CEUS) guided capsule-preserving hydrodilatation with steroids and ultrasonic contrast agents for treatment of AC. Methods: A total of 40 consecutive patients with AC were prospectively enrolled and received CEUS-guided capsule-preserving hydrodilatation. The number of injection attempts, injection volume, and fluid leakage were recorded, and the correlations with clinical features were analyzed by Pearson or Spearman correlation coefficients. Outcome measures including visual analog scale (VAS) score, passive range of motion (ROM), and shoulder pain and disability index (SPADI) score were evaluated at baseline and 4 weeks after treatment. Comparisons between patients with good and poor clinical outcomes were performed with independent t-test, Mann-Whitney U test, and chi-square test. Logistic regression was used to identify predictors of good clinical outcomes. A P value <0.05 defined significance. Results: Access to the glenohumeral joint was successful in 87.5% patients on the first attempt. The infused fluid volume was 21.0±3.40 mL. Longer symptom duration (r=-0.676, P<0.001), greater SPADI (r=-0.148, P=0.007), and decreased ROM in abduction (r=0.38, P=0.016) were associated with a decreased volume of infused fluid. CEUS detected massive fluid leakage in 5 (12.5%) patients, with 4 capsule ruptures confirmed by magnetic resonance imaging (MRI). Longer symptom duration (r=0.485, P=0.001), decreased ROM in the direction of abduction (r=-0.33, P=0.037), and external rotation (r=-0.34, P=0.032) were correlated with an increased incidence of massive fluid leakage. Moreover, patients with good outcomes had significantly shorter symptom duration (5.7±2.09 vs. 11.2±3.89 months, P=0.002) and greater initial VAS score (6.9±1.04 vs. 6.3±0.50, P=0.022) than those with poor outcomes. Absence of massive fluid leakage was an independent predictor of clinical good outcomes at 4 weeks after treatment [odd ratio (OR) =0.05, 95% confidential interval (CI): 0.003-0.882, P=0.041]. Conclusions: CEUS-guided capsule-preserving hydrodilatation allows real-time visualization of capsule dilatation, accurate detection of extracapsular fluid leakage, and identification of risks for capsule rupture. It provides an effective treatment for AC, and is useful to predict patients' clinical outcomes.

Socioeconomic Status Plays a Moderating Role in the Association Between Multimorbidity and Health-Related Quality of Life Among Cancer Patients.

This study aimed to explore the moderating role of socioeconomic status (SES) in the association between multimorbidity and health-related quality of life (HRQOL) among cancer patients in Anhui China. A total of 560 cancer patients were recruited for the cross-section study. Socio-demographic and clinical characteristics were analyzed using descriptive statistics. Tobit regression analysis was employed to investigate the relationship between multimorbidity and HRQOL as well as to assess the moderating effect of SES. The research findings indicated that 76.61% of cancer patients experienced multimorbidity, with psychological multimorbidity being the most prevalent (45.54%), followed by physical-psychological multimorbidity (20.89%). Moreover, physical-psychological multimorbidity had the most substantial adverse effect on HRQOL (P < .001). The presence of multimorbidity was correlated with a significant decline in HRQOL, with a 17.5% (P < .001) decrease in HRQOL for each additional multimorbidity. Additionally, SES played a significant role in moderating the impact of multimorbidity on HRQOL in cancer patients. (Marginal effect = -0.022, P < .01). The high SES group exhibited a higher overall HRQOL than the low SES group (Marginal effect = 0.068, P < .001). And with the increase of multimorbidity, HRQOL in the higher SES showed a more pronounced downward trend, compared with the lower SES (ß = -.270 vs ß = -.201, P < .001). Our findings underscore the importance of preventing and managing multimorbidity in cancer patients, particularly those with low SES. Furthermore, it is essential to consider the impact of the rapid decline in HRQOL as the number of multimorbidity increases in individuals with higher SES. It is imperative to explore interdisciplinary and continuous collaborative management models.

Promotion and Mechanism of Acupotomy on Chondrocyte Autophagy in Knee Osteoarthritis Rabbits.

OBJECTIVE: To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration. METHODS: The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group. After a 3-week treatment course, the knee joint activity was determined by the modified Lequesne MG index. Hematoxylin-eosin staining staining was used to examine the morphological changes of chondrocytes. Autophagy of chondrocytes was observed by transmission electron microscopy. The surface morphology of cartilage tissue was observed by scanning electron microscope. The mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51 (AMPK/mTOR/ULK1) signal pathway key proteins, autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (LC3) in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. RESULTS: The modified Lequesne MG score of acupotomy group was significantly lower than that of model group (P<0.05). Pathological results showed that chondrocyte autophagy decreased and cartilage surface was rough in the model group, which recovered after acupotomy treatment. The mRNA expressions of AMPK, ULK1, Beclin-1 and the protein levels of p-AMPK, p-ULK1, Beclin-1, and LC3 II/LC3 I were decreased in the model group, while the mRNA and protein expressions of mTOR were increased (P<0.01). However, acupotomy treatment reversed these abnormal changes (P<0.05). CONCLUSIONS: Acupotomy could effectively up-regulate the expressions of AMPK, ULK1 and Beclin1, reduce the expression of mTOR, promote autophagy, and alleviate joint degeneration. Acupotomy is a promising complementary and alternative therapy for KOA.