Synergistic Protecting-Etching Synthesis of Carbon Nanoboxes@Silicon for High-Capacity Lithium-Ion Battery.

Silicon (Si) is considered as the most likely choice for the high-capacity lithium-ion batteries owing to its ultrahigh theoretical capacity (4200 mA h g-1) being over 10 times than that of traditional graphite anode materials (372 mA h g-1). However, its widespread application is limited by problems such as a large volume expansion and low electrical conductivity. Herein, we design a hollow nitrogen-doped carbon-coated silicon (Si@Co-HNC) composite in a water-based system via a synergistic protecting-etching strategy of tannic acid. The prepared Si@Co-HNC composite can effectively mitigate the volume change of silicon and improve the electrical conductivity. Moreover, the abundant voids inside the carbon layer and the porous carbon layer accelerate the transport of electrons and lithium ions, resulting in excellent electrochemical performance. The reversible discharge capacity of 1205 mA h g-1 can be retained after 120 cycles at a current density of 0.5 A g-1. In particular, the discharge capacity can be maintained at 1066 mA h g-1 after 300 cycles at a high current density of 1 A g-1. This study provides a new strategy for the design of Si-based anode materials with excellent electrical conductivity and structural stability.

Therapeutic strategies for aberrant splicing in cancer and genetic disorders.

Accurate pre-mRNA splicing is essential for proper protein translation; however, aberrant splicing is commonly observed in the context of cancer and genetic disorders. Notably, in genetic diseases, these splicing abnormalities often play a pivotal role. Substantial challenges persist in accurately identifying and classifying disease-induced aberrant splicing, as well as in development of targeted therapeutic strategies. In this review, we examine prevalent forms of aberrant splicing and explore potential therapeutic approaches aimed at addressing these splicing-related diseases. This summary contributes to a deeper understanding of the complexities about aberrant splicing and provide a foundation for the development of effective therapeutic interventions in the field of genetic disorders and cancer.

Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin.

Lung cancer's mortality is predominantly linked to post-chemotherapy recurrence, driven by the reactivation of dormant cancer cells. Despite the critical role of these reactivated cells in cancer recurrence and metastasis, the molecular mechanisms governing their therapeutic selection remain poorly understood. In this study, we conducted an integrative analysis by combining PacBio single molecule real-time (SMRT) sequencing with short reads Illumina RNA-seq. Our study revealed that cisplatin-induced dormant and reactivated cancer cells exhibited a noteworthy reduction in gene transcripts and alternative splicing events. Particularly, the differential alternative splicing events were found to be overlapping with the differentially expression genes and enriched in genes related to cell cycle and cell division. Utilizing ENCORI database and correlation analysis, we identified key splicing factors, including SRSF7, SRSF3, PRPF8, and HNRNPC, as well as RNA helicase such as EIF4A3, DDX39A, DDX11, and BRIP1, which were associated with the observed reduction in alternative splicing and subsequent decrease in gene expression. Our study demonstrated that lung cancer cells reduce gene transcripts through diminished alternative splicing events mediated by specific splicing factors and RNA helicase in response to the chemotherapeutic stress. These findings provide insights into the molecular mechanisms underlying the therapeutic selection and reactivation of dormant cancer cells. This discovery opens a potential avenue for the development of therapeutic strategies aimed at preventing cancer recurrence following chemotherapy.

High-Speed and Ultrasensitive Solar-Blind Ultraviolet Photodetectors Based on In Situ Grown ß-Ga2O3 Single-Crystal Films.

Deep-level defects in ß-Ga2O3 that worsen the response speed and dark current (Id) of photodetectors (PDs) have been a long-standing issue for its application. Herein, an in situ grown single-crystal Ga2O3 nanoparticle seed layer (NPSL) was used to shorten the response time and reduce the Id of metal-semiconductor-metal (MSM) PDs. With the NPSL, the Id was reduced by 4 magnitudes from 0.389 µA to 81.03 pA, and the decay time (τd1/τd2) decreased from 258/1690 to 62/142 µs at -5 V. In addition, the PDs with the NPSL also exhibit a high responsivity (43.5 A W-1), high specific detectivity (2.81 × 1014 Jones), and large linear dynamic range (61 dB) under 254 nm illumination. The mechanism behind the performance improvement can be attributed to the suppression of the deep-level defects (i.e., self-trapped holes) and increase of the Schottky barrier. The barrier height extracted is increased by 0.18 eV compared with the case without the NPSL. Our work contributes to understanding the relationship between defects and the performance of PDs based on heteroepitaxial ß-Ga2O3 thin films and provides an important reference for the development of high-speed and ultrasensitive deep ultraviolet PDs.

EphB1 promotes the differentiation and maturation of dendritic cells in non-small cell lung cancer.

EphB1 is implicated in numerous physiological and pathological processes, including nervous system diseases, cardiovascular diseases and cancers. It binds to membrane-bound ligands and drives bidirectional signaling. EphB1, along with its ligand ehrinB, plays a pivotal role in activating immune cells. However, despite its presence in dendritic cells (DCs), EphB1's involvement in the differentiation and maturation of DCs in cancers remains inadequately understood. In this study, we found compromised differentiation and maturation of DCs in EphB1-/- mice bearing lung adenocarcinoma syngeneic tumors. Our in vitro assays revealed that EphB1 phosphorylation induced DC differentiation and maturation. Cox-2, a key enzyme involved in the production of proinflammatory molecules, is implicated in DC differentiation induced by phosphorylated EphB1. Additionally, the study has identified lead compounds that specifically target EphB1 phosphorylation sites. Collectively, this research on EphB1 phosphorylation has provided valuable insights into the regulation of immune cell functionality and holds the potential for the development of innovative therapeutic strategies for a range of diseases.

FVC/DLCO identifies pulmonary hypertension and predicts 5-year all-cause mortality in patients with COPD.

BACKGROUND: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). However, it is unknown whether the ratio of forced vital capacity (FVC) to diffusing lung capacity for carbon monoxide (DLCO) can identify PH in the patients with COPD and predict its prognosis. METHODS: The study population I included 937 COPD patients who were admitted to inpatient treatments from 2010 to 2017, and finally 750 patients were available to follow-up the 5-year all-cause mortality (study population II). Clinical characteristics of the study population were recorded. RESULTS: COPD patients with PH had a higher FVC/DLCO value compared with the patients without PH. The threshold for FVC/DLCO to identify PH in COPD patients was 0.44 l/mmol/min/kPa. Multivariate logistic regression analysis showed that FVC/DLCO was a significant predictor for PH in the patients with COPD. The study population II showed that the 5-year all-cause mortality of COPD patients was significantly higher in combined with PH group than without PH group. Compared with the survivor group, FVC/DLCO value was significantly increased in non-survivor group. The threshold for FVC/DLCO to predict 5-year all-cause mortality was 0.41 l/mmol/min/kPa. Kaplan-Meier survival curves showed that 5-year cumulative survival rate for COPD patients were significantly decreased when the value of FVC/DLCO was ≥ 0.41 l/mmol/min/kPa. Multivariate cox regression analysis showed that FVC/DLCO was an independent prognostic factor for 5-year all-cause mortality in COPD patients. CONCLUSION: FVC/DLCO could identify PH in the patients with COPD and was an independent predictor for 5-year all-cause mortality of COPD.

Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy.

BACKGROUND: CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed or refractory pediatric B-lineage acute lymphoblastic leukemia (B-ALL). However, poor results are obtained when the same product is reused in patients who relapse after CAR-T. Therefore, there is a need to explore the safety and efficacy of co-administration of CD19- and CD22-targeted CAR-T as a salvage second CAR-T therapy (CART2) in B-ALL patients who relapse after their first CD19 CAR-T treatment (CART1). METHODS: In this study, we recruited five patients who relapsed after CD19-targeted CAR-T. CD19- and CD22-CAR lentivirus-transfected T cells were cultured separately and mixed before infusion in an approximate ratio of 1:1. The total dose range of CD19 and CD22 CAR-T was 4.3 × 106-1.5 × 107/kg. Throughout the trial, we evaluated the patients' clinical responses, side effects, and the expansion and persistence of CAR-T cells. RESULTS: After CART2, all five patients had minimal residual disease (MRD)-negative complete remission (CR). The 6- and 12-month overall survival (OS) rates were 100%. The median follow-up time was 26.3 months. Three of the five patients bridged to consolidated allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CART2 and remained in MRD-negative CR at the cut-off time. In patient No. 3 (pt03), CAR-T cells were still detected in the peripheral blood (PB) at 347 days post-CART2. Cytokine release syndrome (CRS) only occurred with a grade of ≤ 2, and no patients experienced symptoms of neurologic toxicity during CART2. CONCLUSIONS: Mixed infusion of CD19- and CD22-targeted CAR-T cells is a safe and effective regimen for children with B-ALL who relapse after prior CD19-targeted CAR-T therapy. Salvage CART2 provides an opportunity for bridging to transplantation and long-term survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000032211. Retrospectively registered: April 23, 2020.

Chelation-Assisted formation of carbon nanotubes interconnected Yolk-Shell Silicon/Carbon anodes for High-Performance Lithium-ion batteries.

As a viable replacement to commercial graphite anodes, silicon (Si) anodes have gained much attention from academics because of their considerable theoretical specific capacity and appropriate reaction voltage. Nevertheless, some limitations still exist in developing silicon anodes, including significant volume expansion and poor electrical conductivity. Herein, the carbon nanotubes (CNTs) interconnected yolk-shell silicon/carbon anodes (YS-Si@CoNC) were prepared via the chelation competition induced polymerization (CCIP) approach. The YS-Si@CoNC anode, designed in this study, demonstrates improved performance. At the current density of 0.5 A g-1 and 1 A g-1, a capacity of 1001 mAh g-1 and 956.5 mAh g-1 can be achieved after 150 cycles and after 300 cycles, respectively. In particular, at the current density of 5 A g-1, the reversible specific capacity of 688 mAh g-1 is realized. The exceptional outcomes are mainly attributed to the internal voids that adequately alleviate the volumetric expansion and the CNTs and carbon shells that provide an efficient conducting matrix to fasten the diffusion of electrons and lithium-ions. Our research presents a convenient way of designing Si/C anode materials with a yolk-shell structure to guarantee impressive electrical conductivity and robust structural integrity for high-performance LIBs.

Activation of PPAR-γ prevents TERT-mediated pulmonary vascular remodeling in MCT-induced pulmonary hypertension.

Background: It has been demonstrated that elevated telomerase reverse transcriptase (TERT) expression or activity is implicated in pulmonary hypertension (PH). In addition, activation of peroxisome-proliferator-activated receptor γ (PPAR-γ) has been found to prevent PH progression. However, the molecular mechanism responsible for the protective effect of PPAR-γ activation on TERT expression in the pathogenesis of PH remains unknown. This study was performed to address these issues. Methods: Intraperitoneal injection of monocrotaline (MCT) was used to establish PH. BIBR1532 was applied to inhibit the activity of telomerase. The right ventricular systolic pressure (RVSP) and histological analysis were used to detect the development of PH. The protein levels of p-Akt, t-Akt, c-Myc and TERT were determined by western blotting. Pharmacological inhibition of TERT by BIBR1532 effectively suppressed RVSP, RVHI and the WT% in MCT-induced PH rats. Results: Pharmacological inhibition of Akt/c-Myc pathway by LY294002 diminished TERT upregulation, RVSP, RVHI and WT% in MCT-PH rats. Activation of PPAR-γ by pioglitazone inhibited p-Akt and c-Myc expressions and further downregulated TERT, thus to reduced RVSP, RVHI and WT% in MCT-treated PH rats. Conclusions: In conclusion, TERT upregulation contributes to PH development in MCT-treated rats. Activation of PPAR-γ prevents pulmonary arterial remodeling through Akt/c-Myc/TERT axis suppression.

Effect of Dispersant on Disperse Dyeing in Silicone Waterless Dyeing System.

Traditional water-based dyeing of polyester textiles usually generates burdensome processes and a great deal of wastewater, which can no longer meet the green and sustainable developments in the textile dyeing industry. In the silicone waterless dyeing system, polyester textiles can be dyed with disperse dye without water. However, the dyeing performance of polyester textiles is influenced by the dispersant. In this study, the relationship between the properties of dispersants and disperse dyeing performance was studied. When the amount of dispersant NNO (2-Naphthalenesulfonic acid) was 1.2%, the exhaustion of disperse red 177 and the final K/S value of the dyed fabric improved to 94.18% and 14.73, respectively. However, the exhaustion of disperse red 177 was reduced from 90.73% to 82.61%, and the final K/S value of the dyed fabric was decreased from 14.77 to 14.01 when the dosage of MF (Naphthalenesulfonic acid) was 1.2%. Compared with different dyeing systems, the final uptake of disperse red 177 was 93.81% and 94.18% in traditional water-based and silicone waterless dyeing systems and the K/S value of the dyed fabric was almost the same. The washing and rubbing fastness (wet and dry) of the dyed fabric were found to be at a level of 4 or 4-5, and the light fastness of the dyed fabric was 3-4. If only the dispersant was added in the silicone waterless dyeing system, there was no leveling problems on dyed samples. Moreover, the maximum absorption wavelength of disperse red 177 was not changed after adding the dispersant. With an increasing amount of dispersant NNO, the solubility of the dye in the silicone solvent decreased, but it increased with an increasing amount of dispersant MF. In the relationship between dye exhaustion and dye solubility in a silicone waterless dyeing system, the exhaustion of dye was linearly and inversely proportional to the dye solubility. A dispersant with better hydrophilicity can decrease the solubility of the dye in dyeing media, and the dyeing performance of dye is better. Compared with previous studies, the exhaustion of dye was consistent with the ClogP value (hydrophobic constant) of the dyeing accelerant. Therefore, a dispersant with high hydrophilicity can reduce the solubility of dye and improve the exhaustion of disperse dye in a silicone waterless dyeing system. Moreover, the color fastness of the dyed fabric did not change before and after adding the dispersant.

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial.

PURPOSE: We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS: This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS: Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19-/CD22+, one CD19-/CD22-, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients (P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION: CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse.[Media: see text].

Cell-cell contact-driven EphB1 cis- and trans- signalings regulate cancer stem cells enrichment after chemotherapy.

Reactivation of chemotherapy-induced dormant cancer cells is the main cause of relapse and metastasis. The molecular mechanisms underlying remain to be elucidated. In this study, we introduced a cellular model that mimics the process of cisplatin responsiveness in NSCLC patients. We found that during the process of dormancy and reactivation induced by cisplatin, NSCLC cells underwent sequential EMT-MET with enrichment of cancer stem cells. The ATAC-seq combined with motif analysis revealed that OCT4-SOX2-TCF-NANOG motifs were associated with the enrichment of cancer stem cells induced by chemotherapy. Gene expression profiling suggested a dynamic regulatory mechanism during the process of enrichment of cancer stem cells, where Nanog showed upregulation in the dormant state and SOX2 showed upregulation in the reactivated state. Further, we showed that EphB1 and p-EphB1 showed dynamic expression in the process of cancer cell dormancy and reactivation, where the expression profiles of EphB1 and p-EphB1 showed negatively correlated. In the dormant EMT cells which showed disrupted cell-cell contacts, ligand-independent EphB1 promoted entry of lung cancer cells into dormancy through activating p-p38 and downregulating E-cadherin. On the contrary, in the state of MET, in which cell-cell adhesion was recovered, interactions of EphB1 and ligand EphrinB2 in trans promoted the stemness of cancer cells through upregulating Nanog and Sox2. In conclusion, lung cancer stem cells were enriched during the process of cellular response to chemotherapy. EphB1 cis- and trans- signalings function in the dormant and reactivated state of lung cancer cells respectively. It may provide a therapeutic strategy that target the evolution process of cancer cells induced by chemotherapy.

Diagnostic Accuracy of Serum Amyloid A in Acute Appendicitis: A Systematic Review and Meta-Analysis.

Background: Serum amyloid A has been widely reported as a useful biochemical marker in the diagnoses of acute appendicitis. The aim of this study was to appraise the diagnostic accuracy of serum amyloid A in the diagnosis of acute appendicitis. Methods: A systematic search of several databases was conducted. The search time was from the beginning of the databases creation to March 1, 2021, and the languages were restricted to English and Chinese. Clinical studies using serum amyloid A for the diagnosis of acute appendicitis were included. The overall sensitivity and specificity were calculated by using a bivariable mixed effects model. Heterogeneity was tested using I2 statistics. This study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42021241343). Results: Five studies comprising 668 participants were eligible for inclusion. The overall sensitivity and specificity of serum amyloid A in diagnosing acute appendicitis were 0.87 (95% confidence interval [CI], 0.79-0.92) and 0.74 (95% CI, 0.59-0.85), respectively. The positive and negative likelihood were 3.3 (95% CI, 2.1-5.4) and 0.18 (95% CI, 0.11-0.28), respectively. The area under the summary receiver operating characteristic curves was 0.89 (95% CI, 0.86-0.91). The heterogeneity was significant (I2 = 82%; 95% CI [63%-100%]). Conclusions: Serum amyloid A has good diagnostic accuracy for acute appendicitis. It is expected that serum amyloid A could be helpful in the early clinical diagnosis of acute appendicitis.

Dissecting of the Deterioration in Eating Quality for Erect Panicle (Ep) Type High Yield Japonica Super Rice in Northest China.

Ep type is an important morphological improvement (following dwarf breeding and ideal plant type) that has contributed to breeding super-high yielding, and shows a pleiotropic effect in increasing grain yield and also nitrogen-use efficiency (NUE) in rice. Nevertheless, it remains unclear whether Ep has adverse effects on eating quality and how it affects nitrogen uptake and assimilation. In this study, we developed a pair of near-isogenic lines (NILs) for panicle type (NIL-Ep, NIL-non Ep) in the Liaogeng 5 (LG5) and Akihikari (AKI) backgrounds. Rice plants of the NIL-Ep had higher grain numbers per panicle in the middle to bottom spike positions than plants of the NIL-non Ep. The increased grain number is not only is the key factor leading to increased yield but also is the reason for reduced the eating quality. The content of prolamin and glutelin was significantly higher in NIL-Ep, which resulted in higher hardness and worse viscosity of rice after cooking. In addition, the activity of several essential enzymes catalyzing nitrogen metabolism was higher in the NIL-Ep line grains than in the NIL-non Ep, especially from the mid to late grain filling stage. Based on these results, we conclude that Ep positively regulates grain protein accumulation, primarily through enhancing the activity of enzymes involved in nitrogen assimilation and redistribution during the mid to late grain-filling stage, resulting in excessive accumulation of grain protein and decreased eating quality.

Prognostic role of tripartite motif containing 24 in various human solid malignant neoplasms: An updated meta-analysis and systematic review.

BACKGROUND: Currently, clinical studies of tripartite motif containing 24 (TRIM24) on human solid malignant neoplasms were developing, but the prognosis value of TRIM24 continues to be controversial. The aim of our study is to explore the prognostic effect of TRIM24 in various human solid malignant neoplasms. METHODS: We performed a comprehensive research for eligible studies which evaluated the prognostic roles of TRIM24 in cancer patients based on PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The hazard ratios (HRs) with 95% confidence intervals (CIs) for various malignances were extracted from eligible studies. RESULTS: A total of 13 studies with 1909 patients were enrolled in this analysis. Combined analyses showed that high expression of TRIM24 significantly predicted poorer overall survival both in univariate analysis (HR = 1.61, 95% CI 1.21-2.15, P = .001) and multivariate analysis (HR = 2.19, 95% CI 1.10-4.38, P = .026). In stratified analyses, high TRIM24 expression level predicted even worse overall survival in hormone-related cancers (HR = 1.92, 95% CI 1.28-2.86, P = .001). Although, expression of TRIM24 failed to show a significant relation with progression-free survival/disease-free survival/recurrence-free survival (HR = 1.42, 95% CI 0.93-2.16, P = .106), high expression predicted significant worse progression-free survival/disease-free survival/recurrence-free survival in hormone-related cancer (HR = 1.71, 95% CI 1.12-2.59, P = .013). CONCLUSION: TRIM24 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients especially for patients with hormone-related malignancies.

Immobilized beta2-adrenergic receptor: A powerful chromatographic platform for drug discovery and evaluation of drug-like property for natural products.

Drug discovery based on natural products like medicinal herbs remains challenging due to the technique limitations for rapidly screening and validating leads. To address the challenges, we employ the immobilized ß2- adrenergic recepotor (ß2-AR), an identified target of asthma, as the stationary phase in chromatographic column to screen compounds extracted from Stemonae Radix, Playtycodonis Radix, and Glycyrrhizae Radix et Rhizoma. To analyze binding properties of the extracted compounds to the immobilized receptors, we measured their retention behavior in the receptor chromatography and compared with six clinical asthma drugs. We identified tuberostemonine, platycodin D, and glycyrrhizic acid as the potential leads against asthma by our ß2-AR chromatography coupled with mass spectrum (MS). The association constants of the three compounds to ß2-AR were 2.85 × 10-5, 2.55 × 10-4, and 4.07 × 10-6 M with the dissociation rate constants of 6.91 ± 0.35, 11.88 ± 0.60, and 9.49 ± 0.64 min-1, respectively. Tuberostemonine, a pentacyclic Stemona alkaloids, presented the most optimum values of binding efficiency index (BEI) and surface efficiency index (SEI) as close to the diagonal of SEI-BEI optimization plane when it is compared with platycodin D, glycyrrhizic and the six clinical drugs. Our results suggest that tuberostemonine is a promising natural product to be developed for treating asthma because it exhibits better drug-like binding properties to ß2-AR than the clinical drugs. As such, we demonstrate a chromatographic strategy to identify bioactive natural products based on the ß2-AR immobilization, which can be widely adopted to screen natural products from mixture of herbal extracts.

Ambipolar Photoresponsivity in an Ultrasensitive Photodetector Based on a WSe2/InSe Heterostructure by a Photogating Effect.

Ambipolar photoresponsivity mainly originates from intrinsic or interfacial defects. However, these defects are difficult to control and will prolong the response speed of the photodetector. Here, we demonstrate tunable ambipolar photoresponsivity in a photodetector built from vertical p-WSe2/n-InSe heterostructures with photogating effect, exhibiting ultrahigh photoresponsivity from -1.76 × 104 to 5.48 × 104 A/W. Moreover, the photodetector possesses broadband photodetection (365-965 nm), an ultrahigh specific detectivity (D*) of 5.8 × 1013 Jones, an external quantum efficiency of 1.86 × 107%, and a rapid response time of 20.8 ms. The WSe2/InSe vertical architecture has promising potential in developing high-performance nano-optoelectronics.

Complementary and Alternative Medicine for the Treatment of Abnormal Endometrial Conditions in Women with PCOS: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Endometrial lesions in patients with polycystic ovary syndrome (PCOS) exhibit complex pathological features, and these patients are at risk of both short-term and long-term complications. Complementary and alternative medicine (CAM), which is gradually becoming more accepted and is believed to be clinically effective, claims to be promising for treating PCOS, and thus its effect on the abnormal endometrium of PCOS patients should be assessed. The present meta-analysis sought to evaluate the efficacy and safety of CAM in treating endometrial lesions in patients with PCOS. METHODS: Randomized trials on CAM were identified in four Chinese and seven English-language databases from their establishment to January 2020. The present study included patients diagnosed with PCOS and abnormal endometrial conditions who underwent CAM therapy independently or in combination with traditional western medicine. Data were extracted, and the Cochrane "risk of bias" tool was used to assess methodological quality. Effects were expressed as the relative risk (RR) or mean difference (MD/SMD) with 95% confidence interval (CI) as calculated with Rev Man 5.3. RESULTS: A total of 13 randomized controlled trials were included, involving 1,297 PCOS patients treated for endometrial abnormalities. Methodological quality was generally unclear or had a low risk of bias. The trials tested four different types of CAM therapies (i.e., traditional Chinese medicine treatment, acupuncture treatment, traditional Chinese medicine in combination with western medicine treatment, and acupuncture in combination with western medicine treatment). CAM treatment could significantly reduce the endometrial thickness in PCOS patients compared to western medicine alone (SMD -0.88, 95% CI [-0.12, -0.57]; I 2 = 64%). Compared with clomiphene treatment for the induction of ovulation, CAM treatment showed a clear improvement in endometrial thickness during ovulation (SMD 2.03, 95% CI [1.64, 2.02]; I 2 = 48%). Moreover, CAM was more effective than western medicine alone in reducing the endometrial spiral artery pulsatility index. No significant difference was seen between CAM and traditional treatment when these were used to improve traditional Chinese medicine syndrome scores. Acupuncture alone or traditional Chinese medicines (taken orally) in combination with western medicine significantly increased the pregnancy rate of PCOS patients (RR 1.59, 95% CI [1.30, 1.93]; I 2 = 51%, P < 0.00001), and CAM was more effective than western medicine alone for improving hormone levels. No serious adverse events were reported in 11 of the 13 trials. CONCLUSIONS: CAM may effectively ameliorate the endometrial condition of PCOS patients, and it can regulate the level of hormone secretion to increase the ovulation rate and the pregnancy rate.

ERK/Drp1-dependent mitochondrial fission contributes to HMGB1-induced autophagy in pulmonary arterial hypertension.

OBJECTIVES: High-mobility group box-1 (HMGB1) and aberrant mitochondrial fission mediated by excessive activation of GTPase dynamin-related protein 1 (Drp1) have been found to be elevated in patients with pulmonary arterial hypertension (PAH) and critically implicated in PAH pathogenesis. However, it remains unknown whether Drp1-mediated mitochondrial fission and which downstream targets of mitochondrial fission mediate HMGB1-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation and migration leading to vascular remodelling in PAH. This study aims to address these issues. METHODS: Primary cultured PASMCs were obtained from male Sprague-Dawley (SD) rats. We detected RNA levels by qRT-PCR, protein levels by Western blotting, cell proliferation by Cell Counting Kit-8 (CCK-8) and EdU incorporation assays, migration by wound healing and transwell assays. SD rats were injected with monocrotaline (MCT) to establish PAH. Hemodynamic parameters were measured by closed-chest right heart catheterization. RESULTS: HMGB1 increased Drp1 phosphorylation and Drp1-dependent mitochondrial fragmentation through extracellular signal-regulated kinases 1/2 (ERK1/2) signalling activation, and subsequently triggered autophagy activation, which further led to bone morphogenetic protein receptor 2 (BMPR2) lysosomal degradation and inhibitor of DNA binding 1 (Id1) downregulation, and eventually promoted PASMCs proliferation/migration. Inhibition of ERK1/2 cascade, knockdown of Drp1 or suppression of autophagy restored HMGB1-induced reductions of BMPR2 and Id1, and diminished HMGB1-induced PASMCs proliferation/migration. In addition, pharmacological inhibition of HMGB1 by glycyrrhizin, suppression of mitochondrial fission by Mdivi-1 or blockage of autophagy by chloroquine prevented PAH development in MCT-induced rats PAH model. CONCLUSIONS: HMGB1 promotes PASMCs proliferation/migration and pulmonary vascular remodelling by activating ERK1/2/Drp1/Autophagy/BMPR2/Id1 axis, suggesting that this cascade might be a potential novel target for management of PAH.