Network pharmacology and molecular docking analysis on the mechanism of Tripterygium wilfordii Hook in the treatment of Sjögren syndrome.

Tripterygium wilfordii Hook. F (TWH) has significant anti-inflammatory and immunosuppressive effects, and is widely used in the inflammatory response mediated by autoimmune diseases. However, the multi-target mechanism of TWH action in Sjögren syndrome (SS) remains unclear. Therefore, the aim of this study was to explore the molecular mechanism of TWH in the treatment of SS using network pharmacology and molecular docking methods. TWH active components and target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. SS-related targets were obtained from the GeneCards database. After overlap, the therapeutic targets of TWH in the treatment of SS were screened. Protein-protein interaction and core target analysis were performed by STRING network platform and Cytoscape software. In addition, the affinity between TWH and the disease target was confirmed by molecular docking. Finally, the DAVID (visualization and integrated) database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of overlapping targets. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database shows that TWH contains 30 active components for the treatment of SS. Protein-protein interaction and core target analysis suggested that TNF, MMP9, TGFB1, AKT1, and BCL2 were the key targets of TWH in the treatment of SS. In addition, the molecular docking method confirmed that the bioactive molecules of TWH had a high affinity with the target of SS. Enrichment analysis showed that TWH active components were involved in multiple signaling pathways. Pathways in cancer, Lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications is the main pathway. It is associated with a variety of biological processes such as inflammation, apoptosis, immune injury, and cancer. Based on data mining network pharmacology, and molecular docking method validation, TWH is likely to be a promising candidate for the treatment of SS drug, but still need to be further verified experiment.

Chlorination Design for Highly Stable Electrolyte toward High Mass Loading and Long Cycle Life Sodium-Based Dual-Ion Battery.

Sodium-based dual ion batteries (SDIBs) have garnered significant attention as novel energy storage devices offering the advantages of high-voltage and low-cost. Nonetheless, conventional electrolytes exhibit low resistance to oxidation and poor compatibility with electrode materials, resulting in rapid battery failure. In this study, for the first time, a chlorination design of electrolytes for SDIB, is proposed. Using ethyl methyl carbonate (EMC) as a representative, chlorine (Cl)-substituted EMC not only demonstrates increased oxidative stability ascribed to the electron-withdrawing characteristics of chlorine atom, electrolyte compatibility with both the cathode and anode is also greatly improved by forming Cl-containing interface layers. Consequently, a discharge capacity of 104.6 mAh g-1 within a voltage range of 3.0-5.0 V is achieved for Na||graphite SDIB that employs a high graphite cathode mass loading of 5.0 mg cm-2, along with almost no capacity decay after 900 cycles. Notably, the Na||graphite SDIB can be revived for an additional 900 cycles through the replacement of a fresh Na anode. As the mass loading of graphite cathode increased to 10 mg cm-2, Na||graphite SDIB is still capable of sustaining over 700 times with ≈100% capacity retention. These results mark the best outcome among reported SDIBs. This study corroborates the effectiveness of chlorination design in developing high-voltage electrolytes and attaining enduring cycle stability of Na-based energy storage devices.

A GAN-BO-XGBoost model for high-quality patents identification.

The number of patents increases quickly, while more and more low-quality patents are emerging. It's important to identify high-quality patents from massive data quickly and accurately for organizational R&D decision-making and patent layout. However, due to low percentage of high-quality patents, it is challenging to identify them efficiently. In order to solve above problem, we reconstruct the existing index system for identifying high-quality patents by adding 4 features from technological strength of patentees. Furthermore, we propose an improved model by integrating resampling technique and ensemble learning algorithm. First, generative adversarial networks (GAN) are used to expand minority samples. Second, Extreme Gradient Boosting algorithm (XGBoost) with Bayesian optimization (BO) is used to identify high-quality patents. For clarity, this model is called a GAN-BO-XGBoost model. To test the effectiveness of above model, we use patent data in field of lithography technology. Tenfold cross-validation is carried out to evaluate the performance between our proposed model and other models. The results show that GAN-BO-XGBoost model performs better and it's more stable than other models.

Theoretical Analysis of a Magnetic Shielding System Combining Active and Passive Modes.

Considering the magnetic shielding requirements of both geomagnetic field and 50 Hz power-line frequency in the complex working conditions of the power grid, an electromagnetic shielding system combining active and passive modes is proposed in this article. A three-dimensional Helmholtz coil with a magnetic shielding barrel nested inside is established by the COMSOL simulation tool, and the magnetic shielding efficiency of the system is analyzed. Comparing different materials, the simulation results indicate that permalloy alloy exhibits better shielding performance than pure iron and nickel materials. Additionally, the overall shielding efficiency of the shielding barrel increases linearly with the number of multiple layers. Under the combined active and passive electromagnetic shielding conditions, the system achieves a shielding efficiency of SE = 113.98 dB, demonstrating excellent performance in shielding both AC and DC interference magnetic fields. This study provides theoretical guidance for the construction of magnetic shielding systems in electromagnetic interference environment.

Robust Solid-State Na-CO2 Battery with Na2.7Zr2Si2PO11.7F0.3-PVDF-HFP Composite Solid Electrolyte and Na15Sn4/Na Anode.

Solid-state Na-CO2 batteries are a kind of energy storage devices that can immobilize and convert CO2. They have the advantages of both solid-state batteries and metal-air batteries. High-performance solid electrolyte and electrode materials are important for improving the performance of solid-state Na-CO2 batteries. In this work, we investigate the influence of fluorine doping on the structure and ionic conductivity of Na3Zr2Si2PO12 (NZSP). An ionic conductive solid electrolyte membrane was prepared by compositing the inorganic solid electrolyte Na2.7Zr2Si2PO11.7F0.3 (NZSPF3) with poly(vinylidene fluoride)-co-hexafluoropropylene (PVDF-HFP). It shows an ionic conductivity of up to 2.17 × 10-4 S cm-1 at room temperature, a high sodium ionic transfer number of ∼0.70, a broad electrochemical window of ∼5.18 V, and better mechanical strength. Furthermore, we studied the Na15Sn4/Na composite foil with the ability to inhibit dendrite as the anode for solid-state Na-CO2 batteries. Through density functional theory (DFT) calculations, the Na15Sn4 particle has been verified with a strong sodiophilic property, which reduces the nucleation barrier during the deposition process, leading to a lower overpotential. The symmetric cell assembled with the composite solid-state electrolyte NZSPF3-PVDF-HFP and Na15Sn4/Na composite anode can inhibit the growth of Na dendrites effectively and maintain the stability of the whole cell structure. Solid-state Na-CO2 batteries assembled with Ru-carbon nanotube (Ru-CNTs) as cathode catalysts exhibit a high discharge capacity of 6371.8 mAh g-1 at 200 mA g-1, excellent cycling stability for 1100 h, and good rate performance. This work provides a promising strategy for designing high-performance solid-state Na-CO2 batteries.

Soil microbial subcommunity assembly mechanisms are highly variable and intimately linked to their ecological and functional traits.

Revealing the mechanisms underlying soil microbial community assembly is a fundamental objective in molecular ecology. However, despite increasing body of research on overall microbial community assembly mechanisms, our understanding of subcommunity assembly mechanisms for different prokaryotic and fungal taxa remains limited. Here, soils were collected from more than 100 sites across southwestern China. Based on amplicon high-throughput sequencing and iCAMP analysis, we determined the subcommunity assembly mechanisms for various microbial taxa. The results showed that dispersal limitation and homogenous selection were the primary drivers of soil microbial community assembly in this region. However, the subcommunity assembly mechanisms of different soil microbial taxa were highly variable. For instance, the contribution of homogenous selection to Crenarchaeota subcommunity assembly was 70%, but it was only around 10% for the subcommunity assembly of Actinomycetes, Gemmatimonadetes and Planctomycetes. The assembly of subcommunities including microbial taxa with higher occurrence frequencies, average relative abundance and network degrees, as well as wider niches tended to be more influenced by homogenizing dispersal and drift, but less affected by heterogeneous selection and dispersal limitation. The subcommunity assembly mechanisms also varied substantially among different functional guilds. Notably, the subcommunity assembly of diazotrophs, nitrifiers, saprotrophs and some pathogens were predominantly controlled by homogenous selection, while that of denitrifiers and fungal pathogens were mainly affected by stochastic processes such as drift. These findings provide novel insights into understanding soil microbial diversity maintenance mechanisms, and the analysis pipeline holds significant value for future research.

Generative Listener EEG for Speech Emotion Recognition Using Generative Adversarial Networks with Compressed Sensing.

Currently, emotional features in speech emotion recognition are typically extracted from the speeches, However, recognition accuracy can be influenced by factors such as semantics, language, and cross-speech datasets. Achieving consistent emotional judgment with human listeners is a key challenge for AI to address. Electroencephalography (EEG) signals prove to be an effective means of capturing authentic and meaningful emotional information in humans. This positions EEG as a promising tool for detecting emotional cues conveyed in speech. In this study, we proposed a novel approach named CS-GAN that generates listener EEGs in response to a speaker's speech, specifically aimed at enhancing cross-subject emotion recognition. We utilized generative adversarial networks (GANs) to establish a mapping relationship between speech and EEGs to generate stimulus-induced EEGs. Furthermore, we integrated compressive sensing theory (CS) into the GAN-based EEG generation method, thereby enhancing the fidelity and diversity of the generated EEGs. The generated EEGs were then processed using a CNN-LSTM model to identify the emotional categories conveyed in the speech. By averaging these EEGs, we obtained the event-related potentials (ERPs) to improve the cross-subject capability of the method. The experimental results demonstrate that the generated EEGs by this method outperform real listener EEGs by 9.31% in cross-subject emotion recognition tasks. Furthermore, the ERPs show an improvement of 43.59%, providing evidence for the effectiveness of this method in cross-subject emotion recognition.

A Co-Sputtering Process Optimization for the Preparation of FeGaB Alloy Magnetostrictive Thin Films.

A co-sputtering process for the deposition of Fe0.8Ga0.2B alloy magnetostrictive thin films is studied in this paper. The soft magnetic performance of Fe0.8Ga0.2B thin films is modulated by the direct-current (DC) sputtering power of an FeGa target and the radio-frequency (RF) sputtering power of a B target. Characterization results show that the prepared Fe0.8Ga0.2B films are amorphous with uniform thickness and low coercivity. With increasing FeGa DC sputtering power, coercivity raises, resulting from the enhancement of magnetism and grain growth. On the other hand, when the RF sputtering power of the B target increases, the coercivity decreases first and then increases because of the conversion of the films from a crystalline to an amorphous state. The lowest coercivity of 7.51 Oe is finally obtained with the sputtering power of 20 W for the FeGa target and 60 W for the B target. Potentially, this optimization provides a simple way for improving the magnetoelectric coefficient of magnetoelectric composite materials and the sensitivity of magnetoelectric sensors.

Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study.

BACKGROUND: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments. METHODS: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1-18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended. FINDINGS: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6-10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37-41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89-100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4-20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66-91), duration of remission was 80% (68-92), and disease-free survival was 80% (68-92) with transplantation censoring; overall survival was 96% (91-100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7-14) after CD19-directed and 12 days (10-15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia. INTERPRETATION: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition. FUNDING: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Multi-supervised bidirectional fusion network for road-surface condition recognition.

Rapid developments in automatic driving technology have given rise to new experiences for passengers. Safety is a main priority in automatic driving. A strong familiarity with road-surface conditions during the day and night is essential to ensuring driving safety. Existing models used for recognizing road-surface conditions lack the required robustness and generalization abilities. Most studies only validated the performance of these models on daylight images. To address this problem, we propose a novel multi-supervised bidirectional fusion network (MBFN) model to detect weather-induced road-surface conditions on the path of automatic vehicles at both daytime and nighttime. We employed ConvNeXt to extract the basic features, which were further processed using a new bidirectional fusion module to create a fused feature. Then, the basic and fused features were concatenated to generate a refined feature with greater discriminative and generalization abilities. Finally, we designed a multi-supervised loss function to train the MBFN model based on the extracted features. Experiments were conducted using two public datasets. The results clearly demonstrated that the MBFN model could classify diverse road-surface conditions, such as dry, wet, and snowy conditions, with a satisfactory accuracy and outperform state-of-the-art baseline models. Notably, the proposed model has multiple variants that could also achieve competitive performances under different road conditions. The code for the MBFN model is shared at https://zenodo.org/badge/latestdoi/607014079.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) alleviate paclitaxel-induced spermatogenesis defects and maintain male fertility.

Chemotherapeutic drugs can cause reproductive damage by affecting sperm quality and other aspects of male fertility. Stem cells are thought to alleviate the damage caused by chemotherapy drugs and to play roles in reproductive protection and treatment. This study aimed to explore the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on alleviating paclitaxel (PTX)-induced spermatogenesis and male fertility defects. An in vivo PTX-induced mice model was constructed to evaluate the reproductive toxicity and protective roles of hUC-MSCs in male fertility improvement. A 14 day PTX treatment regimen significantly attenuated mice spermatogenesis and sperm quality, including affecting spermatogenesis, reducing sperm counts, and decreasing sperm motility. hUC-MSCs treatment could significantly improve sperm functional indicators. Mating experiments with normal female mice and examination of embryo development at 7.5 days post-coitum (dpc) showed that hUC-MSCs restored male mouse fertility that was reduced by PTX. In IVF experiments, PTX impaired sperm fertility and blastocyst development, but hUC-MSCs treatment rescued these indicators. hUC-MSCs' protective role was also displayed through the increased expression of the fertility-related proteins HSPA2 and HSPA4L in testes with decreased expression in the PTX-treated group. These changes might be related to the PTX-induced decreases in expression of the germ cell proliferation protein PCNA and the meiosis proteins SYCP3, MLH1, and STRA8, which were restored after hUC-MSCs treatment. In the PTX-treated group, the expression of testicular antioxidant proteins SIRT1, NRF2, CAT, SOD1, and PRDX6 was significantly decreased, but hUC-MSCs could maintain these expressions and reverse PTX-related increases in BAX/BCL2 ratios. hUC-MSCs may be a promising agent with antioxidant and anti-apoptosis characteristics that can maintain sperm quality following chemotherapy treatment.

Engineering Strategy for Enhancing the Co Loading of Co-N4-C Single-Atomic Catalysts Based on the ZIF-67@Yeast Construction.

The Co-N4-C single-atom catalysts (SACs) have attracted great research interest in the energy storage and conversion fields owing to 100% atom utilization. However, enhancing the Co loading for higher electrocatalytic performance is still challenging. In this context, we propose an engineering strategy to fabricate the high Co atomic loading Co-N4-C SACs based on the zeolitic imidazolate framework-67 (ZIF-67)@yeast construction. The rich amino groups provide the possibility for Co2+ ion anchorage and ZIF-67@yeast construction via the biomineralization of yeast cells. The functional design induces the formation of Co-N4-C sites and regulates the porosity for exposure of such Co-N4-C sites. As a result, the Co-N4-C sites were anchored on spherical micrometer flower carbonaceous materials through our novel strategy. The as-obtained optimal sample exhibited a Co atomic loading of 12.18 wt % and a specific surface area of 403.26 m2 g-1. High Co atomic loading and large specific surface area delivered excellent electrocatalytic kinetics as well as a high discharge voltage of 1.08 V at 10 mA cm-2 for more than 100 h in Zn-air batteries. This work represents a promising strategy for fabricating high-loading SACs with high activity and good durability.

Single-Cell RNA Sequencing and Spatial Transcriptomics Reveal Pathogenesis of Meningeal Lymphatic Dysfunction after Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke with high mortality and disability rate. Meningeal lymphatic vessels (mLVs) are a newly discovered intracranial fluid transport system and are proven to drain extravasated erythrocytes from cerebrospinal fluid into deep cervical lymph nodes after SAH. However, many studies have reported that the structure and function of mLVs are injured in several central nervous system diseases. Whether SAH can cause mLVs injury and the underlying mechanism remain unclear. Herein, single-cell RNA sequencing and spatial transcriptomics are applied, along with in vivo/vitro experiments, to investigate the alteration of the cellular, molecular, and spatial pattern of mLVs after SAH. First, it is demonstrated that SAH induces mLVs impairment. Then, through bioinformatic analysis of sequencing data, it is discovered that thrombospondin 1 (THBS1) and S100A6 are strongly associated with SAH outcome. Furthermore, the THBS1-CD47 ligand-receptor pair is found to function as a key role in meningeal lymphatic endothelial cell apoptosis via regulating STAT3/Bcl-2 signaling. The results illustrate a landscape of injured mLVs after SAH for the first time and provide a potential therapeutic strategy for SAH based on mLVs protection by disrupting THBS1 and CD47 interaction.

Melatonin improves the ability of spermatozoa to bind with oocytes in the mouse.

CONTEXT AND AIMS: Melatonin is a powerful antioxidant regulating various biological functions, including alleviating male reproductive damage under pathological conditions. Here, we aim to analyse the effect of melatonin on normal male reproduction in mice. METHODS: Male mice received an intraperitoneal injection of melatonin (10mg/kg body weight) for 35 consecutive days. The testis and epididymis morphology, and epididymal sperm parameters were examined. PCNA, HSPA2, SYCP3, ZO-1 and CYP11A1 expressions in epididymis or testis were detected by immunohistochemistry or Western blotting. Male fertility was determined by in vivo and in vitro fertilisation (IVF) experiments. The differentially expressed sperm proteins were identified by proteomics. KEY RESULTS: No visible structural changes and oxidative damage in the testis and epididymis, and no significant side effects on testis weight, testosterone levels, sperm motility, and sperm morphology were observed in the melatonin-treatment group compared with the control group. Spermatogenesis-related molecules of PCNA, SYCP3, ZO-1, and CYP11A1 showed no significant differences in melatonin-treated testis. However, PCNA and HSPA2 increased their expressions in the epididymal initial segments in the melatonin-treatment group. Normal sperm fertilisation, two-cell and blastocyst development were observed in the melatonin-treated group, but melatonin significantly enhanced the sperm binding ability characterised as more sperm binding to one oocyte (control 7.2±1.3 versus melatonin 11.8±1.5). Sperm proteomics demonstrated that melatonin treatment enhanced the biological process of cell adhesion in sperm. CONCLUSIONS AND IMPLICATIONS: This study suggests that melatonin can promote sperm maturation and sperm function, providing important information for further research on the physiological function and protective effect of melatonin in male reproduction.

Solvation Structure Modulation of High-Voltage Electrolyte for High-Performance K-Based Dual-Graphite Battery.

Due to the advantages of dual-ion batteries (DIBs) and abundant resources, potassium-based dual-carbon batteries (K-DCBs) have wide application prospects. However, conventional carbonate ester-based electrolyte systems have obvious drawbacks such as poor oxidation resistance and difficulty in sustaining the anion intercalation process at high voltages, which seriously affect the capacity and cycle performance of K-DCBs. Therefore, a rational design of more efficient novel electrolyte systems is urgently required to realize high-performance K-DCBs. Herein, a solvation structure modulation strategy for the K-DCB electrolyte systems is reported. Consequently, substantial K+ ion storage improvement at the graphite anode and enhanced bis(fluorosulfonyl)imide anion (FSI- ) intercalation capacity at the graphite cathode are successfully realized simultaneously. As a proof-of-concept, the assembled K-DCB exhibited a discharge capacity of 103.4 mAh g-1 , and after 400 cycles, ≈90% capacity retention is observed. Moreover, the energy density of the K-DCB full cell reached 157.6 Wh kg-1 , which is the best performance in reported K-DCBs till date. This study demonstrates the effectiveness of solvation modulation in improving the performance of K-DCBs.

Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia.

BACKGROUND: Donor-derived CD7-directed chimeric antigen receptor (CAR) T cells showed feasibility and early efficacy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL), in a previous phase I trial report, at a median follow-up of 6.3 months. Here we report long-term safety and activity of the therapy after a 2-year follow-up. METHODS: Participants received CD7-directed CAR T cells derived from prior stem cell transplantation (SCT) donors or from HLA-matched new donors after lymphodepletion. The target dose was 1 × 106 (± 30%) CAR T cells per kg of patient weight. The primary endpoint was safety with efficacy secondary. This report focuses on the long-term follow-up and discusses them in the context of previously reported early outcomes. RESULTS: Twenty participants were enrolled and received infusion with CD7 CAR T cells. After a median follow-up time of 27.0 (range, 24.0-29.3) months, the overall response rate and complete response rate were 95% (19/20 patients) and 85% (17/20 patients), respectively, and 35% (7/20) of patients proceeded to SCT. Six patients experienced disease relapse with a median time-to-relapse of 6 (range, 4.0-10.9) months, and 4 of these 6 patients were found to have lost CD7 expression on tumor cells. Progression-free survival (PFS) and overall survival (OS) rates 24 months after treatment were respectively 36.8% (95% CI, 13.8-59.8%) and 42.3% (95% CI, 18.8-65.8%), with median PFS and OS of respectively 11.0 (95% CI, 6.7-12.5) months and 18.3 (95% CI, 12.5-20.8) months. Previously reported short-term adverse events (< 30 days after treatment) included grade 3-4 cytokine release syndrome (CRS; 10%) and grade 1-2 graft-versus-host disease (GVHD; 60%). Serious adverse events reported > 30 days after treatment included five infections and one grade 4 intestinal GVHD. Despite good CD7 CAR T-cell persistence, non-CAR T and natural killer cells were predominantly CD7-negative and eventually returned to normal levels in about half of the participants. CONCLUSIONS: In this 2-year follow-up analysis, donor-derived CD7 CAR T-cell treatment demonstrated durable efficacy in a subset of patients with r/r T-ALL. Disease relapse was the main cause of treatment failure, and severe infection was a noteworthy late-onset adverse event. TRIAL REGISTRATION: ChiCTR2000034762.

Thermogenic adipocyte-derived zinc promotes sympathetic innervation in male mice.

Sympathetic neurons activate thermogenic adipocytes through release of catecholamine; however, the regulation of sympathetic innervation by thermogenic adipocytes is unclear. Here, we identify primary zinc ion (Zn) as a thermogenic adipocyte-secreted factor that promotes sympathetic innervation and thermogenesis in brown adipose tissue and subcutaneous white adipose tissue in male mice. Depleting thermogenic adipocytes or antagonizing ß3-adrenergic receptor on adipocytes impairs sympathetic innervation. In obesity, inflammation-induced upregulation of Zn chaperone protein metallothionein-2 decreases Zn secretion from thermogenic adipocytes and leads to decreased energy expenditure. Furthermore, Zn supplementation ameliorates obesity by promoting sympathetic neuron-induced thermogenesis, while sympathetic denervation abrogates this antiobesity effect. Thus, we have identified a positive feedback mechanism for the reciprocal regulation of thermogenic adipocytes and sympathetic neurons. This mechanism is important for adaptive thermogenesis and could serve as a potential target for the treatment of obesity.

Weakened Crystalline SnNb2 O6 for Enhanced Performance in Photocatalytic H2 Production and CO2 Reduction.

Low crystalline photocatalysts with unsaturated active sites, such as oxygen vacancy (Ov ), is reported to exhibit enhanced adsorption and activation of oxygen-containing small molecules, such as H2 O and CO2 , thus boosting the activity in photocatalytic H2 evolution and CO2 reduction. However, numerous low-crystalline photocatalysts show unsatisfactory stability due to the easily repaired surface Ov . Herein, three SnNb2 O6 with different crystallinity were prepared by hydrothermal approach with similar precursors. Compared with bulk SnNb2 O6 and ultra-thin layered SnNb2 O6 , low-crystalline SnNb2 O6 (SNA) exhibits optimal visible-light-driven evolution rates of H2 (86.04 µmol g-1 h-1 ) and CO from CO2 (71.97 µmol g-1 h-1 ), which is mainly ascribed to the fast separation of the photogenerated carriers and enhanced photoreduction power caused by the surface Ov . More importantly, the sharp decrease of photocatalytic activity of SNA after seven cycles is well restored by the hydrothermal treatment of recycled SNA, ascribed to the reactivated surface Ov with the recovered low-crystalline structure. These works thus offer a promising strategy for developing low-crystalline and amorphous photocatalysts with high activity and stability.

Numerical Investigation of GaN HEMT Terahertz Detection Model Considering Multiple Scattering Mechanisms.

GaN high-electron-mobility transistor (HEMT) terahertz (THz) detectors have been widely studied and applied in the past few decades. However, there are few reports about the influence of GaN/AlGaN heterostructure material properties on the detection model at present. In this paper, a response voltage model for a GaN HEMT THz detector that considers the carrier scattering in a GaN/AlGaN heterostructure is proposed. The phonon scattering, dislocation scattering, and interface roughness scattering mechanisms are taken into account in the classic THz response voltage model; furthermore, the influence of various material parameters on the response voltage is studied. In a low-temperature region, acoustic scattering plays an important role, and the response voltage drops with an increase in temperature. In a high temperature range, optical phonon scattering is the main scattering mechanism, and the detector operates in a non-resonant detection mode. With an increase in carrier surface density, the response voltage decreases and then increases due to piezoelectric scattering and optical phonon scattering. For dislocation and interface roughness scattering, the response voltage is inversely proportional to the dislocation density and root mean square roughness (RMS) but is positively related to lateral correlation length. Finally, a comparison between our model and the reported models shows that our proposed model is more accurate.

Facile and Universal Defect Engineering Toward Highly Stable Carbon-Based Polymer Brushes with High Grafting Density.

Carbon-based polymer brushes (CBPBs) are an important class of functional polymer materials, which synergistically combine the advantageous properties of both carbons and polymers. However, the conventional fabrication procedures of CBPBs involve tedious multistep modification, including preoxidation of carbon substrates, introduction of initiating groups, and subsequent graft polymerization. In this study, a simple yet versatile defect-engineering strategy is proposed for the efficient synthesis of high-grafting-density CBPBs with highly stable CC linkages via free radical polymerization. This strategy involves the introduction and removal of nitrogen heteroatoms in the carbon skeletons via a simple temperature-Fmed heat treatment, leading to the formation of numerous carbon defects (e.g., pentagons, heptagons, and octagons) with reactive C=C bonds in the carbon substrates. The as-proposed methodology enables the facile fabrication of CBPBs with various carbon substrates and polymers. More importantly, the highly grafted polymer chains in the resulting CBPBs are tethered with the carbon skeletons by robust CC bonds, which can endure strong acid and alkali environments. These interesting findings will shed new light on the well-orchestrated design of CBPBs and broaden their applications in various areas with fascinating performances.