Search

Abstract Research on low‐light image enhancement focuses on improving image quality in dim conditions. Recently, deep learning has driven significant advancements, with many studies using neural networks to enhance low‐light images. However, most focus on complex network designs to increase nonlinearity, often neglecting the implicit information from local image transformations. This paper introduces an improved U‐net‐based method for low‐light enhancement, retaining the original encoding network and adding branch links in the decoding network. The method uses attention feature fusion to handle image noise and gradients separately, adjusting brightness through a gradient‐adaptive transform. This approach optimizes performance using loss functions like peak signal‐to‐noise ratio and colour consistency. Unlike previous methods, the approach emphasizes extracting implicit information from image gradients, achieving enhancement that aligns with the original brightness distribution. The result is enhanced images with high detail similarity to the original, achieved through end‐to‐end inference in experiments.

Abstract Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is marked by impaired immune tolerance and heightened activity in both innate and adaptive immune systems. Hallmarks of SLE include elevated type I interferons and autoantibody production, though the exact causes of SLE remain elusive despite advances in research techniques. Crucial to SLE research is understanding its pathogenesis and developing effective diagnostic and therapeutic methods. Recent studies have highlighted a significant link between mitochondrial abnormalities and SLE's development and progression. Mitochondrial dysfunction plays a key role in SLE pathogenesis through various mechanisms such as mitochondrial DNA mutations, oxidative stress, immune metabolic reprogramming, and cellular death. These factors collectively contribute to the loss of self‐tolerance, increased autoantibody production, and impaired clearance of immune complexes, leading to their deposition. This triggers sustained inflammatory responses and damages multiple organs. This review focuses on the diagnostic and therapeutic approaches related to mitochondrial abnormalities in SLE. Targeting mitochondrial pathways presents a promising strategy for treating SLE, potentially improving prognosis and quality of life for those affected. Future research should further investigate the role of mitochondria in the onset and progression of SLE, providing new avenues for understanding and managing this complex disease.

Abstract Sepsis is responsible for approximately 5.3 million deaths globally each year. Here, we constructed hierarchical chitin microspheres loaded with MOF‐919 (Ch/metal–organic frameworks [MOFs]) for the rapid and efficient removal of lipopolysaccharide (LPS) in complex blood environments. Furthermore, abundant active sites on MOF‐919(Sc) also enable a record‐high adsorption capacity of 9.56 mg/g in biomass‐based adsorbents due to the coordination interactions between endotoxin and MOF‐919(Sc). The LPS level of sepsis rabbits was less than 2 EU/mL (clearance rate >95%) after 90‐min hemoperfusion, showing no adverse effect on the rabbit organs. Additionally, compared to the commonly used LPS scrubber Toraymyxin (polymethyl methacrylate), the chitin adsorbent is significantly more cost‐effective and environmentally friendly. The preparation strategy for hierarchical porous microspheres offers notable advantages in designability, recyclability, and renewability, providing a new approach to sepsis treatment and promising prospects for the biomedical application of sustainable biomass materials.

Abstract Objective To explore the clinical characteristics, short‐ and long‐term functional outcomes, and risk factors for antibody‐related autoimmune encephalitis (AE) in patients with disorders of consciousness (DoC). Methods Clinical data were collected from AE patients admitted to Xuanwu Hospital of Capital Medical University from January 2012 to December 2021, and patients were followed up for up to 24 months after immunotherapy. Results A total of 312 patients with AE were included: 197 (63.1%) with anti‐NMDAR encephalitis, 71 (22.8%) with anti‐LGI1 encephalitis, 20 (6.4%) with anti‐GABAbR encephalitis, 10 (3.2%) with anti‐CASPR2 encephalitis, 10 (3.2%) with anti‐GAD65 encephalitis, and 4 (1.3%) with anti‐AMPAR2 encephalitis. Among these patients, 32.4% (101/312) presented with DoC, and the median (interquartile range, IQR) time to DoC was 16 (7.5, 32) days. DoC patients had higher rates of various clinical features of AE (p

Abstract Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain‐associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg−1) in alleviating pain‐associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety‐like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress‐related hormones including corticosterone, corticotropin‐releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety‐reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ‐aminobutyric acid type A receptor β3 (GABAAβ3) subunits in PVNCRH neurons diminished the anxiety‐relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain‐associated anxiety‐like behaviors using a single dose of propofol.

Abstract The induction of regulated cell death (RCD) through photo/ultrasound sensitization therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors. Aggregation‐induced emission (AIE) therapeutic agents generate reactive oxygen species through photo/ultrasound activation, which can synergize with RCD inducers or directly induce RCD, ultimately resulting in the death of tumor cells. The presented comprehensive review delves into recent advancements in AIE therapeutic agents designed to trigger RCD or synergize with RCD inducers, encompassing apoptosis, necroptosis, pyroptosis, immunogenic cell death, autophagy, ferroptosis, and cuproptosis. Additionally, the intricate regulatory mechanisms through which activatory‐AIE therapeutics influence distinct RCD pathways are examined. A forward‐looking perspective on future developments and pertinent challenges within this exciting realm is presented, anticipating the continued evolution of activatable AIE therapeutics as a transformative approach to enhance tumor therapy.

Abstract Ferroptosis is an iron‐dependent cell death form that initiates lipid peroxidation (LPO) in tumors. In recent years, there has been growing interest on ferroptosis, but how to propel it forward translational medicine remains in mist. Although experimental ferroptosis inducers such as RSL3 and erastin have demonstrated bioactivity in vitro, the poor antitumor outcome in animal model limits their development. In this study, we reveal a novel ferroptosis inducer, oxaliplatin–artesunate (OART), which exhibits substantial bioactivity in vitro and vivo, and we verify its feasibility in cancer immunotherapy. For mechanism, OART induces cytoplasmic and mitochondrial LPO to promote tumor ferroptosis, via inhibiting glutathione‐mediated ferroptosis defense system, enhancing iron‐dependent Fenton reaction, and initiating mitochondrial LPO. The destroyed mitochondrial membrane potential, disturbed mitochondrial fusion and fission, as well as downregulation of dihydroorotate dehydrogenase mutually contribute to mitochondrial LPO. Consequently, OART enhances tumor immunogenicity by releasing damage associated molecular patterns and promoting antigen presenting cells maturation, thereby transforming tumor environment from immunosuppressive to immunosensitive. By establishing in vivo model of tumorigenesis and lung metastasis, we verified that OART improves the systematic immune response. In summary, OART has enormous clinical potential for ferroptosis‐based cancer therapy in translational medicine.

Abstract Background Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era. Methods A total of 5089 newly diagnosed DLBCL patients treated with rituximab‐containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group‐affiliated institutes were identified, of whom 135 diagnosed with PB‐DLBCL were eligible for this analysis. Results PB‐DLBCL accounted for 2.7% of all DLBCLs. With a median follow‐up of 4.2 years, the 5‐year overall survival and progression‐free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5‐year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high‐dose methotrexate (HD‐MTX) than for patients who did not (5‐year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB‐DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD‐MTX did not experience CNS relapse. Conclusion Collectively, our results indicate combined modality therapy including rituximab‐containing immunochemotherapy and consolidative breast RT is a promising approach for PB‐DLBCL, while HD‐MTX is useful for preventing CNS relapse.

Abstract Explaining the spatially variable impacts of flood‐generating mechanisms is a longstanding challenge in hydrology, with increasing and decreasing temporal flood trends often found in close regional proximity. Here, we develop a machine learning‐informed approach to unravel the drivers of seasonal flood magnitude and explain the spatial variability of their effects in a temperate climate. We employ 11 observed meteorological and land cover (LC) time series variables alongside 8 static catchment attributes to model flood magnitude in 1,268 catchments across Great Britain over four decades. We then perform a sensitivity analysis to assess how a 10% increase in precipitation, a 1°C rise in air temperature, or a 10 percentage point increase in urban or forest LC may affect flood magnitude in catchments with varying characteristics. Our simulations show that increasing precipitation and urbanization both tend to amplify flood magnitude significantly more in catchments with high baseflow contribution and low runoff ratio, which tend to have lower values of specific discharge on average. In contrast, rising air temperature (in the absence of changing precipitation) decreases flood magnitudes, with the largest effects in dry catchments with low baseflow index. Afforestation also tends to decrease floods more in catchments with low groundwater contribution, and in dry catchments in the summer. Our approach may be used to further disentangle the joint effects of multiple flood drivers in individual catchments.

Abstract Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APCMin/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic‐based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus–bile acid–intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.

Abstract The increase in anthropogenic carbon dioxide (CO2) emissions has exacerbated the deterioration of the global environment, which should be controlled to achieve carbon neutrality. Central to the core goal of achieving carbon neutrality is the utilization of CO2 under economic and sustainable conditions. Recently, the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO2 into carboxylic acids, which can effectively alleviate CO2 emissions and create high‐value chemicals. The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO2 conversion into carboxylic acids through photo‐, electric‐, and thermal catalysis. Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level, inspiring the preparation of high‐performance catalysts. In addition, theoretical calculations, advanced technologies, and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity. Finally, challenges and prospects are provided for the future development of this field. It is hoped that this review will contribute to a deeper understanding of the conversion of CO2 into carboxylic acids and inspire more innovative breakthroughs.

Abstract Background Trastuzumab is a first‐line targeted therapy for human epidermal growth factor receptor‐2 (HER2)‐positive gastric cancer. However, the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit, and there is currently no effective reversal measure. Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves, while the understanding of the mechanisms of environment‐mediated drug resistance is relatively lacking. This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients. Methods Trastuzumab‐sensitive and trastuzumab‐resistant HER2‐positive tumor tissues and cells were collected for transcriptome sequencing. Bioinformatics were used to analyze cell subtypes, metabolic pathways, and molecular signaling pathways. Changes in microenvironmental indicators (such as macrophage, angiogenesis, and metabolism) were verified by immunofluorescence (IF) and immunohistochemical (IHC) analyses. Finally, a multi‐scale agent‐based model (ABM) was constructed. The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM. Results Based on transcriptome sequencing, molecular biology, and in vivo experiments, we found that the level of glutamine metabolism in trastuzumab‐resistant HER2‐positive cells was increased, and glutaminase 1 (GLS1) was significantly overexpressed. Meanwhile, tumor‐derived GLS1 microvesicles drove M2 macrophage polarization. Furthermore, angiogenesis promoted trastuzumab resistance. IHC showed high glutamine metabolism, M2 macrophage polarization, and angiogenesis in trastuzumab‐resistant HER2‐positive tumor tissues from patients and nude mice. Mechanistically, the cell division cycle 42 (CDC42) promoted GLS1 expression in tumor cells by activating nuclear factor kappa‐B (NF‐κB) p65 and drove GLS1 microvesicle secretion through IQ motif‐containing GTPase‐activating protein 1 (IQGAP1). Based on the ABM and in vivo experiments, we confirmed that the combination of anti‐glutamine metabolism, anti‐angiogenesis, and pro‐M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2‐positive gastric cancer. Conclusions This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism, M2 macrophage polarization, and pro‐angiogenic function of macrophages, leading to acquired trastuzumab resistance in HER2‐positive gastric cancer. A combination of anti‐glutamine metabolism, anti‐angiogenesis, and pro‐M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.

Abstract In this Editorial, the Geo: Geography and Environment Editors reflect on the journal over the past year, highlighting some of the key papers published and ‘Geo Themes’ being developed: ‘Decolonising Climate Geography’; ‘Climate Change, AI and Sustainability’; ‘Geographies of Energy Futures’. The Editors renew the call for submissions on these topics and put out a new call for Special Section proposals on subjects around the environment, climate and sustainability.

Abstract This paper analyses the integration of the Sustainable Development Goals (SDGs) in the revisions of China's primary, secondary and high school curriculum standards. Employing a word frequency analysis of SDGs‐related keywords across ten disciplines, the study reveals an increasing trend in SDGs integration, particularly in Physical Education and Health, and Biology, but notes a lack of growth in the Arts discipline. Key findings include the widespread presence of SDG3 (Good Health and Well‐being) and SDG11 (Sustainable Cities and Communities), with a notable absence of SDG5 (Gender Equality) and SDG12 (Responsible Consumption and Production). This study suggests enhancing SDGs coverage in Arts education, broadening the scope to include underrepresented SDGs and promoting a balanced integration of all SDGs across disciplines. It emphasizes the critical role of Geography Education in addressing global challenges and advocates for interdisciplinary teaching methods. The study highlights the importance of regular assessment in curriculum standards to ensure effective SDGs integration, aiming to align China's educational framework with global developmental objectives for a sustainable future.

Human activity recognition (HAR) has gained popularity in the field of computer vision such as video surveillance, security, and virtual reality. However, traditional methods are limited in terms of computations and holistic learning of human skeletal sequences. In this article, a new time‐series skeleton joint data imaging method is infused into an improved convolutional neural network to handle these problems. First, the raw time‐series data of 33 body nodes are transformed to red–green–blue images by encoding the 3D positional information to one pixel. Second, the LeNet‐5 network is enhanced by expanding the receptive field, introducing coordinate attention and the smooth maximum unit to improve smoothness and feature extraction. Third, the ability of coded images to express human activities is studied in various environments. It is shown in the experimental results that the method achieves an impressive accuracy of 98.02% in recognizing 25 daily human activities, such as running, writing, and walking. In addition, it is shown that the number of floating point operations, parameters, and inference time of the method are 0.08%, 0.47%, and 3.05%, respectively, of the average values for six other networks (including AlexNet, GoogLeNet, and MobileNet). The proposed method is thus a novel, lightweight, and high‐precision solution for HAR.

Abstract Background ASXL2 encodes proteins involved in epigenetic regulation and the assembly of transcription factors at specific genomic loci. Germline de novo truncating variants in ASXL2 have been implicated in Shashi‐Pena syndrome, which results in features of developmental delay (DD), glabellar nevus flammeus, hypotonia, and cardiac disorders. However, the variants are rare, and the clinical spectrum may be incomplete. Methods The clinical data such as brain MRI were collect. The whole exome sequencing was performed for genetic etiology analysis. Results Here, we report a patient with DD, hypotonia, early atrial septal defect, and abnormal white matter signal. She presented with Shashi–Pena syndrome with a truncated variant in ASXL2 (NM_018263.6, c.2142_2152del, p.Ser714Argfs*5). She died of a digestive tract infection when she was 1 year and 6 months old. Conclusions Our study further expanded the spectrum of phenotypes and genetic variations of the syndrome, and we believe that it is necessary to screen the ASXL2 gene in patients with DD and cardiac and bone disorders.

Abstract Introduction Ferroptosis has recently been recognized as a new cause of ischemia reperfusion injury due to blood–brain barrier (BBB) disruption followed by secondary iron‐loaded transferrin (TF) influx. As a novel and independent cell death pathway, ferroptosis was characterized by iron‐dependent lipid peroxidation, decline of GSH, GPX4, and shrinking mitochondria. Cottonseed oil (CSO), a liposoluble solvent, can alleviate ischemia stroke injuries and oxidative stress. However, the effect of CSO on ischemic stroke–induced ferroptosis has not been explored. In this study, we investigated the effect of CSO on ferroptosis caused by cerebral ischemic injury in rats. Methods We conducted the subcutaneous injection of 1.3 mL/kg CSO every other day for 3 weeks on rats with middle cerebral artery occlusion–reperfusion (MCAO‐R) injury. We used Garcia Test, TTC staining, HE, Nissl and NeuN staining, Evans blue test, 68Ga‐citrate PET, Western blot, immunofluorescence staining, Elisa kits, and transmission electron microscopy to detect the infarct volume, neural injuries, and ferroptosis‐related indexes. Results CSO treatment could significantly ameliorate MCAO‐R‐induced neurological dysfunction in a male rat model. Furthermore, it reduced infarct volume and neuronal injuries; protected BBB integrity; reduced the influx of iron ion, TF, and TF receptors; up‐regulated anti‐ferroptosis proteins (GPX4, xCT, HO1, FTH1), while down‐regulating ferroptosis‐related protein ACSL4; increased the activity of GSH and SOD; and decreased MDA and LPO levels. Mitochondrial destruction induced by ischemic stroke was also alleviated by CSO treatment. Conclusion CSO treatment can alleviate ischemic stroke injury via ferroptosis inhibition, which provides a new potential therapeutic mechanism for CSO neuroprotection against ischemic stroke.

Abstract The increasing development of biomedicine and bioelectronics has highlighted the requirement for smart materials that can respond to changes in physical and chemical properties under external environments, such as magnetic fields, electric fields, and temperature. Accordingly, hydrogels have been widely evaluated as promising candidates for smart materials owing to their intriguing structures comprising a cross‐linked network of polymer chains with interstitial spaces filled with solvent water. This feature endows hydrogels with soft and wet characteristics, which not only induce high tissue affinity but also allow the introduction of environmentally responsive nanoparticles to release specific smart properties. Herein, we reviewed novel smart hydrogels that can be applied in biomedicine and bioelectronics, and highlighted and discussed existing challenges in current technologies and research.

Abstract Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy‐M‐Exo) is developed via fusing tumor‐derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T‐cell response. Moreover, the nanovaccine Hy‐M‐Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy‐M‐Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy.

Abstract Polysulfides aqueous redox flow batteries (PS‐ARFBs) with large theoretical capacity and low cost are one of the most promising solutions for large‐scale energy storage technology. However, sluggish electrochemical redox kinetics and nonnegligible crossover of aqueous polysulfides restrict the battery performances. Herein, it is found that the Co, Zn dual‐doped N‐C complex have enhanced electrochemical adsorption behaviors for Na2S2. It exhibits significantly electrochemical redox activity compared to the bare glassy carbon electrode. And the redox reversibility is also improved from ΔV = 210 mV on Zn‐doped N‐C complex to ΔV = 164 mV on Co, Zn‐doped N‐C complex. Furthermore, membrane‐electrode assembly (MEA) based on Co, Zn‐doped N‐C complex is firstly proposed to enhance the redox performances and relieve the crossover in PS‐ARFBs. Thus, an impressively high and reversible capacity of 157.5 Ah L−1 for Na2S2 with a high capacity utilization of 97.9% could be achieved. Moreover, a full cell PS‐ARFB with Na2S2 anolyte and Na4[Fe(CN)6] catholyte exhibits high energy efficiency ≈88.4% at 10 mA cm−2. A very low capacity decay rate of 0.0025% per cycle is also achieved at 60 mA cm−2 over 200 cycles.

Abstract Background The mortality of castration‐resistant prostate cancer (CRPC) is high due to lack of an effective treatment. Chimeric antigen receptor (CAR)‐based therapy is a promising immunotherapeutic strategy. Here, we aimed to design a novel CAR‐natural killer (NK) cells with a clinically significant tumoricidal effect on CRPC. Methods We constructed novel CAR‐NK92MI cells with a CD244‐based recombinant lentiviral vector. Different intracellular segments (CD244, NKG2D, or CD3ζ) were screened to identify the best candidate according to cell lysis assay and CD107a expression levels. To enhance the affinity of the CAR to the tumor antigen, we compared an antibody specific for prostate‐specific membrane antigen (anti‐PSMA) with PSMA‐targeted polypeptide (p‐PSMA), which was screened by phage display combinatorial library. Then, CAR‐NK92MI cells with both a high affinity for PSMA and a strong tumoricidal capacity were generated. In addition, we verified their tumor‐killing effect in vitro and in vivo. The release of cytokine by NK92MI cells was compared with that by CAR‐NK92MI cells through flow cytometry and enzyme‐linked immunosorbent assay. Moreover, ferroptosis‐related cell death was explored as a possible underlying mechanism. Results Three different CAR intracellular regions CAR1 (CD244), CAR2 (CD244, NKG2D) and CAR3 (CD244, NKG2D, and CD3ζ) were constructed. CAR2 was chosen to confer a stronger tumoricidal ability on CAR‐NK92MI cells. Compared with anti‐PSMA, p‐PSMA exhibited enhanced affinity for the tumor antigen. Thus, p‐PSMA‐CAR‐NK92MI cells, which expressed CAR with a polypeptide‐based antigen‐binding region, an intracellular CD244 and a NKG2D costimulatory domain, were generated. They could selectively and successfully kill PSMA+ target cells and exhibited specific lysis rate of 73.19% for PSMA‐positive C4‐2 cells and 33.04% for PSMA‐negative PC3 cells. Additionally, p‐PSMA‐CAR‐NK92MI cells had significantly higher concentrations of IFN‐γ, TNF‐α and granzyme B than NK92MI cells. In a CRPC cancer xenograft model, p‐PSMA‐CAR‐NK92MI cells significantly inhibited tumor growth and exerted a more consistent killing effect than NK92MI cells. Moreover, ferroptosis is a potential mechanism through which CAR‐NK92MI cells attack cancer cells, and is triggered by IFN‐γ. Conclusions p‐PSMA‐CAR‐NK92MI cells can effectively kill CRPCPSMA+ cells in vitro and in vivo. This strategy may provide additional treatment options for patients with CRPC.

Abstract Contaminants within cell culture media often co‐isolate with eukaryotic extracellular vesicles (EVs) thus affecting their biological properties. It has yet to be investigated if this is also true for bacterial EVs (BEVs), especially for organisms grown in complex culture media containing animal‐derived products. To address this question, we isolated BEVs from the fastidious bacterium Helicobacter pylori grown in either standard Brain Heart Infusion (BHI) medium or BHI depleted of animal‐derived products (D‐BHI). We show that BEVs prepared from bacteria grown in D‐BHI medium have similar morphologies, size ranges and yields to those prepared from standard medium. Similarly, no differences were found in the ability of H. pylori BEVs to induce IL‐8 responses in epithelial cells. However, H. pylori BEVs prepared from D‐BHI medium were of higher purity than those prepared from standard medium. Importantly, proteomic analyses detected 3.4‐fold more H. pylori proteins and 10‐fold fewer bovine‐derived proteins in BEV samples prepared from D‐BHI rather than the standard method. Fifty‐seven H. pylori proteins were uniquely detected in BEV samples prepared from D‐BHI. In conclusion, we have described an improved method for BEV isolation. Furthermore, we demonstrate how animal‐derived products in bacteriological culture media may adversely affect proteomic analyses of BEVs.

Uveal melanoma (UM) is the most common intraocular tumor in adults. Recurrent mutations in BRCA1‐associated protein 1 (BAP1) and splicing factor 3B subunit 1 (SF3B1) display a mutually exclusive pattern in UM, but the underlying mechanism is unknown. We show that combined BAP1 deficiency and SF3B1 hotspot mutation lead to senescence and growth arrest in human UM cells. Although p53 protein expression is induced, deletion of TP53 (encoding p53) only modestly rescues the observed senescent phenotype. UM cells with BAP1 loss or SF3B1 mutation are more sensitive to chemotherapeutic drugs compared with their isogenic parental cells. Transcriptome analysis shows that DNA‐repair genes are downregulated upon co‐occurrence of BAP1 deletion and SF3B1 mutation, thus leading to impaired DNA damage response and the induction of senescence. The co‐occurrence of these two mutations reduces invasion of UM cells in zebrafish xenograft models and suppresses growth of melanoma xenografts in nude mice. Our findings provide a mechanistic explanation for the mutual exclusivity of BAP1 and SF3B1 mutations in human UM.

Abstract Developing smart iontronic materials is highly desired for eradicating the widely occurring potential short‐circuit hazard and subsequent safety problems caused by high ambient humidity. In this work, a humidity‐responsive ionogel (HRIG) based on a poly(benzyl methacrylate) matrix swollen by hydrophobic ionic liquid and hygroscopic lithium salt is reported. The HRIG exhibits an anomalous decrease in ionic conductivity upon hydration by increased humidity, totally differing from traditional ionic conductors, which are usually more conductive due to the plasticizing effect of water molecules. This unique ionogel shows a dramatic decrease in ionic conductivity (as much as 102) when exposed to humidity. The conductive pathway within the HRIG would be shut down spontaneously above a critical relative humidity due to water‐induced phase separation. Moreover, this transition can be perfectly reversed when the ambient humidity drops. A humidity‐responsive smart supercapacitor that can be switched on and off by capturing humidity changes is designed for demonstration. It is believed that such unusual HRIG material will provide new insights into the development and applications of smart iontronics.

Abstract The purpose of 3D human pose estimation is to estimate the 3D coordinates of key points of the human body directly from images. Although multi‐view based methods have better performance and higher precision of coordinate estimation than a single‐view based, they need to know the camera parameters. In order to effectively avoid the restriction of this constraint and improve the generalizability of the model, a dual‐view single‐person 3D pose estimation method without camera parameters is proposed. This method first uses the 2D pose estimation network HR‐net to estimate the 2D joint point coordinates from two images with different views, and then inputs them into the 3D regression network to generate the final 3D joint point coordinates. In order to make the 3D regression network fully learn the spatial structure relationship of the human body and the transformation projection relationship between different views, a self‐supervised training method is designed based on a 3D human pose orthogonal projection model to generate the virtual views. In the pose estimation experiments on the Human3.6 dataset, this method achieves a significantly improved estimation error of 34.5 mm. Furthermore, an action recognition based on the human poses extracted by the proposed method is conducted, and an accuracy of 83.19% is obtained.

Abstract The sluggish ion‐transport in electrodes and low utilization of active materials are critical limitations of organic cathodes, which lead to the slow reaction dynamics and low specific capacity. In this study, the hierarchical tube is constructed by iron‐hexaazatrinaphthalene tricarboxylic acid coordination polymer (Fe‐HATNTA), using HATNTA as the self‐engaged template to coordinate with Fe2+ ions. This Fe‐HATNTA tube with hierarchical porous structure ensures the sufficient contact between electrolyte and active materials, shortens the diffusion distance, and provides more favorable transport pathways for ions. When employed as the cathode for rechargeable Li‐ion batteries, Fe‐HATNTA delivers a high specific capacity (244 mAh g−1 at 50 mA g−1, 91% of theoretical capacity), excellent rate capability (128 mAh g−1 at 9 A g−1), and a long‐term cycle life (73.9% retention over 3000 cycles at 5 A g−1). Moreover, the Li+ ions storage and conduction mechanisms are further disclosed by the ex situ and in situ characterizations, kinetic analyses, and theoretical calculations. This work is expected to boost further enthusiasm for developing the hierarchical structured metal‐organic coordination polymers with superb ionic storage and transport as high‐performance organic cathodes.

Abstract The promise of speech disorders as biomarkers in clinical examination has been identified in a broad spectrum of neurodegenerative diseases. However, to the best of our knowledge, a validated acoustic marker with established discriminative and evaluative properties has not yet been developed for oral tongue cancers. Here we cross‐sectionally collected a screening dataset that included acoustic parameters extracted from 3 sustained vowels /ɑ/, /i/, /u/ and binary perceptual outcomes from 12 consonant‐vowel syllables. We used a support vector machine with linear kernel function within this dataset to identify the formant centralization ratio (FCR) as a dominant predictor of different perceptual outcomes across gender and syllable. The Acoustic analysis, Perceptual evaluation and Quality of Life assessment (APeQoL) was used to validate the FCR in 33 patients with primary resectable oral tongue cancers. Measurements were taken before (pre‐op) and four to six weeks after (post‐op) surgery. The speech handicap index (SHI), a speech‐specific questionnaire, was also administrated at these time points. Pre‐op correlation analysis within the APeQoL revealed overall consistency and a strong correlation between FCR and SHI scores. FCRs also increased significantly with increasing T classification pre‐operatively, especially for women. Longitudinally, the main effects of T classification, the extent of resection, and their interaction effects with time (pre‐op vs. post‐op) on FCRs were all significant. For pre‐operative FCR, after merging the two datasets, a cut‐off value of 0.970 produced an AUC of 0.861 (95% confidence interval: 0.785–0.938) for T3‐4 patients. In sum, this study determined that FCR is an acoustic marker with the potential to detect disease and related speech function in oral tongue cancers. These are preliminary findings that need to be replicated in longitudinal studies and/or larger cohorts.

Abstract This paper presents new alternative derivations of the well‐known constrained Cramér–Rao bound for estimating parameters that satisfy a set of deterministic and differentiable equality constraints. Specifically, for unbiased parameter estimation, the equality constraints are treated as pseudo‐measurements corrupted by independent zero‐mean Gaussian noise with infinitely small covariance. In this way, the desired constrained Cramér–Rao bound can be established via utilising the property that the Fisher information matrices for independent measurements are additive. This paper also provides a new simple way for deriving the constrained Cramér–Rao bound when the parameter estimate has a specified bias through exploring that the estimation error lies in the null space of the gradient matrix of the constraints and invoking the Cauchy–Schwarz inequality.

Abstract Background The chimeric antigen receptor NK‐92 (CAR NK‐92) cell targeting the prostate‐specific membrane antigen (PSMA) has shown antitumour effects in castration‐resistant prostate cancer (CRPC). However, the expression changes of programmed death ligand 1 (PD‐L1) and its mechanisms on CAR NK‐92 and CRPC cells and the effect of the anti‐PD‐L1 monoclonal antibody (mAb) on PD‐L1 expressed on CAR NK‐92 cells remain unknown. Methods Human dendritic cells and CD8+ T cells were acquired from blood samples of healthy donors and cocultured with C4‐2 cells. Changes in PD‐L1 expression were detected by flow cytometry. Differential gene expressions were investigated by RNA sequence analysis, while the regulation of PD‐L1 molecular signaling was explored using western blotting. In vitro cytotoxicity was evaluated using the Cell Counting Kit‐8 assay and the bioluminescent intensity (BLI) of green fluorescent protein‐labelled C4‐2 cells. CRPC growth in vivo was monitored using callipers and BLI in male NOD/SCID mice subcutaneously injected with C4‐2 cells and treated intravenously with anti‐PD‐L1/PD‐1 mAb, CAR NK‐92 or cocultured CD8+ T cells. Results Significantly upregulated expression of PD‐L1k was observed in cocultured C4‐2 and CAR NK‐92 cells. In addition, upregulation of PD‐L1 expression was dependent on interferon‐γ in C4‐2 cells, while it was dependent on direct cell‐to‐cell interaction via the NK group 2 member D/ phosphatidylinositol 3‐kinase/AKT pathway in CAR NK‐92 cells. The anti‐PD‐L1 mAb directly acted on PD‐L1 expressed on CAR NK‐92 cells and augmented the cytotoxicity of CAR NK‐92 cells against C4‐2 and CRPC cells from one patient in vitro. Anti‐PD‐L1 mAb significantly enhanced the antitumour effect of CAR NK‐92 cells against CRPC cells in vivo when compared to treatment with CAR NK‐92 cells or combined with anti‐PD‐1 mAb in the absence or presence of cocultured CD8+ T cells. Conclusion Combined treatment with CAR NK‐92 and anti‐PD‐L1 mAb improved the antitumour efficacy against CRPC, which is of extraordinary translational value in the clinical treatment of CRPC.

Abstract Electrocatalytic water splitting using renewable energy is widely considered as a clean and sustainable way to produce hydrogen as an ideal energy fuel for the future. Electrocatalysts are indispensable elements for large‐scale water electrolysis, which can efficiently accelerate electrochemical reactions occurring at both ends. Benefitting from high specific surface area, well‐defined void space, and tunable chemical compositions, hollow nanostructures can be applied as promising candidates of direct electrocatalysts or supports for loading internal or external electrocatalysts. Herein, some recent progress in the structural design of micro‐/nanostructured hollow materials as advanced electrocatalysts for water splitting is summarized. First, the design principles and corresponding strategies toward highly effective hollow electrocatalysts for oxygen/hydrogen evolution reactions are highlighted. Afterward, an overview of current reports about hollow electrocatalysts with diverse architectural designs and functionalities is given, including direct hollow electrocatalysts with single‐shelled, multi‐shelled, or open features and heterostructured electrocatalysts based on hollow hosts. Finally, some future research directions of hollow electrocatalysts for water splitting are discussed based on personal perspectives.

Abstract Bioenergy will play an intimate and critical role in energy supply and carbon mitigation in the future. In recent years, “customizing the development of bioenergy to local conditions” and “prioritizing distributed utilization” have been the two key principles that have been released by the Chinese government to promote the national‐ and provincial‐level development of bioenergy. While many recognize the importance of bioenergy in achieving low‐carbon transition, little is known about the high‐resolution distribution of usable biomass feedstock and technical bioenergy potential in China, which brings about uncertainties and additional challenges for creating localized utilization plans. We propose a new assessment framework that integrates crop growth models, a land suitability assessment, and the geographic information systems to address these knowledge gaps. Distributions of 11 types of usable biomass feedstock and three kinds of technical bioenergy potential are mapped out through specific transformation technologies at 1 km resolution. At the national level, the final technical biogas potential is 1.91 EJ. The technical bioethanol potential (0.04–0.96 EJ) from the energy crop can supply 0.13–3.12 times the bioethanol demand for the consumption of E10 gasoline in 2015. The technical heat potential (1.06 EJ) can meet 20% of the demand for heating in all provinces (5.38 EJ). Most of the 2020 bioenergy goals can be achieved, excluding that for bioethanol, which will need to require more cellulosic ethanol from residues. At the provincial level, Henan and Inner Mongolia have the potential to develop clean heating alternatives via the substitution of agroforestry residues for coal. The results can provide a systematic analysis of the distribution of biomass feedstocks and technical bioenergy potential in China. With economic factors taken into consideration in further research, it can also support national and provincial governments in making bioenergy development plans in an effective and timely manner.

Abstract Marked by large interannual variability, East Asian summer monsoon (EASM) rainfall has profound socio‐economic impacts through its dominant influence on floods and droughts. Improving predictions of the interannual variations of EASM rainfall has important implications for over 20% of the world's population. While coupled modeling systems have demonstrated some prediction skill related to the El Niño Southern Oscillation with remote influence on EASM rainfall, the impact of soil moisture has heretofore not been systematically investigated. Using a weakly coupled data assimilation (WCDA) system to constrain the soil moisture and soil temperature in a coupled climate model with a global land data assimilation product, this study demonstrates significant improvements in simulating the interannual variations of EASM rainfall, capturing the notable shift to a “wetter‐South‐drier‐North” rainfall pattern in China in the early 1990s. Hindcast simulations initialized with the well‐balanced states from a coupled simulation with WCDA also show significant multi‐year rainfall prediction skill over East China and Tibetan Plateau. Improvements in predicting the EASM rainfall are attributed to the strong land‐atmosphere coupling in large areas over China, which allows improved predictions of soil moisture to influence precipitation through soil moisture‐precipitation feedback, and the effects of land anomalies on the EASM circulation. This study highlights the significant contribution of land to the interannual predictability of EASM rainfall, with a great potential to advance skillful interannual predictions of benefit to the large populations influenced by the annual whiplash of the summer monsoon rain.