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Posttransplant antiglomerular basement membrane (anti-GBM) disease occurs in approximately 5% of Alport patients and usually ends in irreversible graft failure. Recent research has focused on characterizing the structure of the anti-GBM alloepitope. Here we present a case of a 22-year-old male with end-stage renal disease secondary to Alport syndrome, with a previously failed renal allograft, who received a second deceased-donor kidney transplant. Six days after transplantation, he developed acute kidney injury. The serum anti-GBM IgG was negative by enzyme immunoassay (EIA). On biopsy, he had crescentic glomerulonephritis with linear GBM fixation of IgG. With further analysis by western blotting, we were able to detect antibodies to an unidentified protein from the basement membrane. This patient was treated with plasmapheresis twice per week and monthly intravenous immunoglobulin (IVIG) for a total of five months. At the end of treatment, these unknown antibodies were no longer detected. His renal function improved, and he has not required dialysis. We conclude that anti-GBM disease in patients with Alport Syndrome may be caused by circulating antibodies to other components of the basement membrane that are undetectable by routine anti-GBM EIA and may respond to treatment with plasmapheresis and IVIG.

Abstract Image hiding is a task that embeds secret images in digital images without being detected. The performance of image hiding has been greatly improved by using the invertible neural network. However, current image hiding methods are less robust in the face of Joint Photographic Experts Group (JPEG) compression. The secret image cannot be extracted from the stego image after JPEG compression of the stego image. Some methods show good robustness for some certain JPEG compression quality factors but poor robustness for other common JPEG compression quality factors. An image‐hiding network (RIHINNet) that is robust to all common JPEG compression quality factors is proposed. First of all, the loss function is redesigned; thus, the secret image is hidden as much as possible in the area that is less likely to be changed after JPEG compression. Second, the classifier is designed, which can help the model to select the extractor according to the range of JPEG compression degree. Finally, the interval robustness of the secret image extraction is improved through the design of a denoising module. Experimental results show that this RIHINNet outperforms other state‐of‐the‐art image‐hiding methods in the face of JPEG compressed noise with random compression quality factors, with more than 10 dB peak signal‐to‐noise ratio improvement in secret image recovery on ImageNet, COCO and DIV2K datasets.

Abstract Glaucoma poses a significant threat to vision, capable of causing irreversible damage and, in severe instances, leading to permanent blindness. Accurate optic cup (OC) and optic disc (OD) segmentation are essential in glaucoma screening. In this study, a novel OC and OD segmentation approach is proposed. Based on U‐Net, it is optimized by introducing cardinality dimensions. Moreover, attention gates are implemented to reinforce salient features while suppressing irrelevant information. Additionally, a convolutional block attention module (CBAM) is integrated into the decoder segment. This fusion hones in on effective information in both channel and spatial dimensions. Meanwhile, an image processing procedure is proposed for image normalization and enhancement. All of these increase the accuracy of the model. This model is evaluated on the ORIGA and REFUGE datasets, demonstrating the model's superiority in OC and OD segmentation compared to the state‐of‐the‐art methods. Additionally, after the proposed image processing, cup‐to‐disc ratio (CDR) prediction on a batch of 155 in‐house fundus images yields an absolute CDR error of 0.099, which is reduced by 0.04 compared to the case where only conventional processing was performed.

Abstract Image hiding is a task that hides secret images into cover images. The purposes of image hiding are to ensure the secret images are invisible to the human and the secret images can be recovered. The current state‐of‐the‐art steganography methods run the risk of secret information leakage. A safe image hiding network (SIHNet) is presented to reduce the leakage of secret information. Based on some phenomena of image hiding methods which use invertible neural network, a reversible secret image processing (SIP) module is proposed to make the secret images suitable for hiding and make the stego images leak less secret information. Besides, a reversible lost information hiding (LIH) module is used to hide the lost information into the cover images, thus the method can recover the secret images better than the method that uses random noise to replace the lost information. Experimental results show that SIHNet outperforms other state‐of‐the‐art methods on the PSNR and SSIM values of the recovered secret images and the stego images. Besides, residual images of other state‐of‐the‐art methods all contain information about secret images while residual images of SIHNet leak almost no secret information. Thus the method can prevent the listener of transmission channel from obtaining the information of the secret image through the residual image, which means SIHNet performs better in security than other state‐of‐the‐art methods.

Abstract The harmonic compensation of SAPF (shunt active power filter) may trigger harmonic oscillation due to the interaction with grid impedance and non‐linear loads, which distorts the power quality. In previous research, the relevant mechanism has been studied. However, the SAPF generally employs complex harmonic detection algorithm, which significantly increases the computational demands. The SAPF in full compensation mode can effectively solve this problem. But the modification of harmonic detection link may change the oscillation mechanism and previous stabilization methods need to be re‐evaluated. Therefore, this paper establishes the small signal model of the SAPF system in full compensation mode and investigates its oscillation mechanism. It is revealed that harmonic compensation and passive resonance collectively induce the harmonic oscillation. Based on the model, the working mechanism and application performance of the main stabilization methods proposed in the past (harmonic virtual admittance and harmonic compensation canceling) are analyzed and compared. However, neither of them can achieve effective stabilization without sacrificing the performance of compensation. Consequently, the harmonic phase compensation method is proposed to achieve the stabilization of the SAPF system in full compensation mode without affecting normal compensation. Finally, simulations and experiments are performed to verify the mechanism analysis and proposed methods.

Abstract Background To use an automated system exploiting the advantages of both a neural network and radiomics for analysis of non‐calcified predominant plaque (NCPP). Methods This study retrospectively included 234 patients. Using the workflow of the previous study, the coronary artery was first segmented, images containing plaques were then extracted, and a classifier was built to identify non‐calcified predominant plaques. Radiomics feature analysis and a visualization tool were used to better distinguish NCPP from other plaques. Results Twenty‐six representative radiomics features were selected. DenseNet achieved an area under the curve of 0.889, which was significantly larger (p = 0.001) than that obtained using a gradient‐boosted decision tree (0.859). The feature variances and energy features in calcified predominant plaque were both different from those in NCPP. Conclusions Our automated system provided high‐accuracy analysis of vulnerable plaques using a deep learning approach and predicted useful features of NCPP using a radiomics‐based approach.

Abstract Cervical cancer remains one of the most lethal gynecological malignancies. However, biomarkers for more precise patient care are an unmet need. Herein, the concentration of 285 plasma cell‐free DNA (cfDNA) samples are analyzed from 84 cervical patients and the clinical significance of cfDNA fragmentomic characteristics across the neoadjuvant chemotherapy (NACT) treatment. Patients with poor NACT response exhibit a significantly greater escalation in cfDNA levels following the initial cycle of treatment, in comparison to patients with a favorable response. Distinctive end motif profiles and promoter coverages of cfDNA in initial plasma are observed between patients with differing NACT responses. Notably, the DNASE1L3 analysis further demonstrates the intrinsic association between cfDNA characteristics and chemotherapy resistance. The cfDNA and motif ratios show a good discriminative capacity for predicting non‐responders from responders (area under the curve (AUC) > 0.8). In addition, transcriptional start sites (TSS) coverages around promoters discern the alteration of biological processes associated with chemotherapy resistance and reflect the potential value in predicting chemotherapy response. These findings in predictive biomarkers may optimize treatment selection, minimize unnecessary treatment, and assist in establishing personalized treatment strategies for cervical cancer patients.

Abstract Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte‐specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2‐ to 4‐cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2‐cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS‐related GTP‐binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.

Abstract Background Oral squamous cell carcinoma (OSCC) is the predominant form of head and neck cancer, often diagnosed at late stages, resulting in a poor prognosis. Recent studies indicate a potential association between OSCC and microbial presence. Microorganisms have been identified in various tumors and lesions, including OSCC and oral potentially malignant disorders (OPMDs). Intralesional microbiota are considered important components of the tumor microenvironment (TME) and may contribute to carcinogenesis. Methods Sources were collected through thorough searches of databases PubMed and Embase. The review focused on microbial characteristics, potential origins, and their impact on cancer progression. Results Bacteria display varying abundance and diversity throughout the stages of OSCC and OPMDs. Intraleisional bacteria may have diverse sources, including not only oral plaque and saliva but also potentially the gut. Intralesional bacteria have both pro‐carcinogenic and anti‐carcinogenic effects, affecting processes like cell proliferation, invasion, and immune response. Conclusions Intralesional microbiota are crucial in OSCC and OPMDs, influencing both disease progression and treatments. Despite their significance, challenges like inconsistent sampling and microbial identification remain. Future research is required to fully understand their role and improve clinical applications.

Abstract Background Various epigenetic regulations systematically govern gene expression in cells involving various biological processes. Dysregulation of the epigenome leads to aberrant transcriptional programs and subsequently results in diseases, such as cancer. Therefore, comprehensive profiling epigenomics is essential for exploring the mechanisms underlying gene expression regulation during development and disease. Methods In this study, we developed single‐cell chromatin proteins and accessibility tagmentation (scCPA‐Tag), a multi‐modal single‐cell epigenetic profile capturing technique based on barcoded Tn5 transposases and a droplet microfluidics platform. scCPA‐Tag enables the simultaneous capture of DNA profiles of histone modification and chromatin accessibility in the same cell. Results By applying scCPA‐Tag to K562 cells and a hepatocellular carcinoma (HCC) sample, we found that the silence of several chromatin‐accessible genes can be attributed to lysine‐27‐trimethylation of the histone H3 tail (H3K27me3) modification. We characterized the epigenetic features of the tumour cells and different immune cell types in the HCC tumour tissue by scCPA‐Tag. Besides, a tumour cell subtype (C2) with more aggressive features was identified and characterized by high chromatin accessibility and a lower abundance of H3K27me3 on tumour‐promoting genes. Conclusions Our multi‐modal scCPA‐Tag provides a comprehensive approach for exploring the epigenetic landscapes of heterogeneous cell types and revealing the mechanisms of gene expression regulation during developmental and pathological processes at the single‐cell level. Highlights scCPA‐Tag offers a highly efficient and high throughput technique to simultaneously profile histone modification and chromatin accessibility within a single cell. scCPA‐Tag enables to uncover multiple epigenetic modification features of cellular compositions within tumor tissues. scCPA‐Tag facilitates the exploration of the epigenetic landscapes of heterogeneous cell types and provides the mechanisms governing gene expression regulation.

Abstract Drug resistance after long‐term use of Tyrosine kinase inhibitors (TKIs) has become an obstacle for prolonging the survival time of patients with clear cell renal cell carcinoma (ccRCC). Here, genome‐wide CRISPR‐based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied. Mechanically, HDAC8 deacetylated ETS1 at the K245 site to promote the interaction between ETS1 and HIF‐2α and enhance the transcriptional activity of the ETS1/HIF‐2α complex. However, the antitumor effect of inhibiting HDAC8 on sensitized TKI is not very satisfactory. Subsequently, inhibition of HDAC8 increased the expression of NEK1, and up‐regulated NEK1 phosphorylated ETS1 at the T241 site to promote the interaction between ETS1 and HIF‐2α by impeded acetylation at ETS1‐K245 site is showed. Moreover, TKI treatment increased the expression of HDAC8 by inhibiting STAT3 phosphorylation in ccRCC cells is also found. These 2 findings highlight a potential mechanism of acquired resistance to TKIs and HDAC8 inhibitors in ccRCC. Finally, HDAC8‐in‐PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC‐targeted therapies.

Background Endovascular treatment (EVT) has been demonstrated to be effective for patients with tandem occlusion. The efficacy and safety of intravenous thrombolysis before EVT in patients with tandem occlusion remain debatable. Methods and Results We conducted a systematic review and meta‐analysis with PubMed, EMBASE, and the Cochrane Library from inception to September 2023. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days. The secondary outcomes included the successful recanalization rate, symptomatic intracerebral hemorrhage, and mortality at 90 days. In total, 9 studies with 1838 enrolled participants were identified. Our results showed that, compared with treatment with EVT alone, intravenous thrombolysis before EVT was associated with a greater proportion of functional independence at 90 days (odds ratio [OR], 1.39 [95% CI, 1.14–1.69]; P=0.001), a greater rate of successful recanalization (OR, 1.45 [95% CI, 1.11–1.89]; P=0.007) and decreased mortality (OR, 0.68 [95% CI, 0.50–0.93]; P=0.02). Furthermore, there was no significant difference in symptomatic intracerebral hemorrhage between the intravenous thrombolysis plus EVT group and the EVT alone group (OR, 1.16 [95% CI, 0.79–1.70]; P=0.45). Conclusions In patients with acute ischemic stroke and tandem occlusion, intravenous thrombolysis before EVT was associated with a greater rate of favorable functional outcomes and successful recanalization and a lower mortality rate without an increased risk of symptomatic intracerebral hemorrhage compared with patients receiving EVT alone.

Abstract Sodium ion hybrid capacitors (SIHC) are emerging as promising next‐generation energy storage devices with high energy/power density. Presodiation is an essential part of SIHC production due to the lack of sodium sources in the cathode and anode. However, in the current presodiation methods, electrochemical presodiation by galvanostatic current charging and discharging requires a temporary half‐cell or a complex reassembling process, which severely hinders the commercialization of SIHC. Herein, in situ synthesized Na2S infiltrated in activated carbon was used as a sodium salt additive for supplying Na+ in SIHC. Due to a low ratio of Na2S additive attributed to high theoretical specific capacity, the fabricated Na2S/activated carbon composite//HC SIHC can show a higher energy density of 129.71 Wh kg−1 than previously reported SIHC on presodiation of cathode additives. Moreover, the designed SIHC shows an excellent cycling performance of 10,000 cycles, which is attributed to the Na2S additive with the advantages of low decomposition potential and no gas generation. This work provides a novel approach for the fabrication of highly efficient Na2S additive composite cathodes for SIHC.

Abstract Background There is no diagnostic assessment procedure with moderate or strong evidence of use, and evidence for current means of treating prolonged disorders of consciousness (pDOC) is sparse. This may be related to the fact that the mechanisms of pDOC have not been studied deeply enough and are not clear enough. Therefore, the aim of this study was to explore the mechanism of pDOC using functional near‐infrared spectroscopy (fNIRS) to provide a basis for the treatment of pDOC, as well as to explore preclinical markers for determining the arousal of pDOC patients. Methods Five minutes resting‐state data were collected from 10 pDOC patients and 13healthy adults using fNIRS. Based on the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the time series, the resting‐state cortical brain functional connectivity strengths of the two groups were calculated, and the functional connectivity strengths of homologous and heterologous brain networks were compared at the sensorimotor network (SEN), dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), frontoparietal network (FPN), and visual network (VIS) levels. Univariate binary logistic regression analyses were performed on brain networks with statistically significant differences to identify brain networks associated with arousal in pDOC patients. The receiver operating characteristic (ROC) curves were further analyzed to determine the cut‐off value of the relevant brain networks to provide clinical biomarkers for the prediction of arousal in pDOC patients. Results The results showed that the functional connectivity strengths of oxyhemoglobin (HbO)‐based SEN∼SEN, VIS∼VIS, DAN∼DAN, DMN∼DMN, SEN∼VIS, SEN∼FPN, SEN∼DAN, SEN∼DMN, VIS∼FPN, VIS∼DAN, VIS∼DMN, HbR‐based SEN∼SEN, and SEN∼DAN were significantly reduced in the pDOC group and were factors that could reflect the participants' state of consciousness. The cut‐off value of resting‐state functional connectivity strength calculated by ROC curve analysis can be used as a potential preclinical marker for predicting the arousal state of subjects. Conclusion Resting‐state functional connectivity strength of cortical networks is significantly reduced in pDOC patients. The cut‐off values of resting‐state functional connectivity strength are potential preclinical markers for predicting arousal in pDOC patients.

Abstract The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG‐M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG‐M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC‐MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH‐mediated OXPHOS pathway, thereby inducing MG‐M2 polarization, promoting neuronal survival and exerting an anti‐AD role is elucidated.

Abstract Wearing face masks is the best way to stop the spread of respiratory infections. However, if masks are not sterilized, changing them too frequently can actually increase the risk of cross‐contamination. Herein, the construction of an antipathogen photocatalytic mask with carbon vacancy‐modified carbon nitride nanosheets (g‐C3N4‐VC Ns) coated on the non‐woven fabrics of the out layer of the mask, offering effective and long‐term protection against damaging pathogens when exposed to light is reported. The introduced carbon vacancies are found capable of creating energy‐disordered sites and inducing energetic electric force to overcome the Coulomb interactions between electron‐hole pairs, thus promoting the electron‐hole separation to achieve a high generation of reactive oxygen species (ROS). Thanks to its high activity in generating ROS upon exposure to light, the as‐prepared photocatalytic mask shows high pathogen sterilization performance. This, in turn, prolongs the mask's protective lifetime, decreases the need for regular replacement, and decreases medical waste production. The work demonstrated here opens new viewpoints in designing pathogens biocidal protective devices for health protection, offering significant promise in specific environment self‐protection.

Abstract Objectives High‐grade gliomas (HGGs) are highly malignant, aggressive, and have a high incidence and mortality rate. The aim of this study was to investigate survival outcomes and prognostic factors in patients with HGGs. Methods In this retrospective study, a total of 159 patients with histologically confirmed HGGs were included. The recruitment period was from January 2011 to December 2019. We evaluated patient demographic data, tumor characteristics, treatment methods, immunocytochemistry results, overall survival (OS) time, and progression‐free survival (PFS) time using Kaplan–<>Meier survival analysis with log‐rank testing. Additionally, we employed Cox regression analysis to identify independent factors associated with survival outcomes. Results Kaplan–Meier survival analysis revealed that the 1‐, 2‐, and 5‐years OS rates were 81.8%, 50.3%, and 12.6%, respectively. Similarly, the 1‐, 2‐, and 5‐years PFS rates were 50.9%, 22.4%, and 3.1%, respectively. The median OS duration was 35.0 months. The univariate analysis indicated that postoperative pathological classification, grade, and age were significantly associated with patient outcomes (p

Abstract Neurological diseases are expected to become the leading cause of death in the next decade. Although little is known about it, the interaction between oxidative stress and inflammation is harmful to the nervous system. To find an advanced tool for neural genetics, mouse haploid neural stem cells (haNSCs) from the somite of chimeric mouse embryos at E8.5 is established. The haNSCs present a haploid neural progenitor identity for long‐term culture, promising to robustly differentiate into neural subtypes and being able to form cerebral organoids efficiently. Thereafter, haNSC mutants via a high‐throughput approach and screened targets of oxidative stress is generated using the specific mutant library. Deletion of Nfkbia (the top hit among the insertion mutants) reduces damage from reactive oxygen species (ROS) in NSCs exposed to H2O2. Transcriptome analysis revealed that Atp2b4 is upregulated significantly in Nfkbia‐null NSCs and is probably responsible for the observed resistance. Additionally, overexpression of Atp2b4 itself can increase the survival of NSCs in the presence of H2O2, suggesting that Atp2b4 is closely involved in this resistance. Herein, a powerful haploid system is presented to study functional genetics in neural lineages, shedding light on the screening of critical genes and drugs for neurological diseases.

Abstract Practical aqueous zinc‐ion batteries require low‐cost thin zinc anodes with long‐term reversible stripping/depositing. However, thin zinc anodes encounter more severe issues than thick zinc, such as dendrites and uneven stripping, resulting in subpar performance and limited lifetimes. Here, this work proposes a three‐in‐one zinc anode obtained by a large‐scale two‐step method to address the above issues. In a three‐in‐one zinc anode, the copper foil as an inactive current collector solves the gradual reduction of the active area when only the pure zinc as an active current collector. This work develops an automatic electroplating device that can continuously deposit a zinc layer on a conducting foil to meet the demand for zinc‐coated copper foils. The sodium carboxymethylcellulose (CMC)‐zinc fluoride (ZnF2) protective layer prevents direct contact between zinc and separator, and provides a uniform and sufficient supply of zinc ions. The CMC‐ZnF2‐coated copper foil performs up to 3000 reversible zinc deposition/stripping cycles with a cumulative capacity of 6 Ah cm−2 and an average Coulombic efficiency of 99.94%. The Zn||ZnVO cell using the three‐in‐one anode achieved a high capacity retention of over 70% after 15 000 cycles. The proposed three‐in‐one anode and the automatic electroplating device will facilitate industrialization of practical thin zinc anodes.

Image preprocessing models are usually employed as the preceding operations of high‐level vision tasks to improve the performance. The adversarial attack technology makes both these models face severe challenges. Prior research is focused solely on attacking single object detection models, without considering the impact of the preprocessing models (multifocus image fusion) on adversarial perturbations within the object detection system. Multifocus image fusion models work in conjunction with the object detection models to enhance the quality of the images and improve the capability of object detection system. Herein, the problem of attacking object detection system that utilizes multifocus image fusion as its preprocessing models is addressed. To retain the attack capabilities of adversarial samples against as many perturbations as possible, new attack method called adaptive retention attack (ARA) is proposed. Additionally, adversarial perturbations concentration mechanism and image selection mechanism, which, respectively, enhance the transferability and attack capability of ARA‐generated adversarial samples. Extensive experiments have demonstrated the feasibility of the ARA. The results confirm that the ARA method can successfully bypass multifocus image fusion models to attack the object detection model.

Abstract Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4‐nitroquinoline 1‐oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single‐cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor‐promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor‐promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment‐associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.

Abstract Currently, the typical combination therapy of programmed death ligand‐1 (PD‐L1) antibodies with radiotherapy (RT) still exhibits impaired immunogenic antitumor response in clinical due to lessened DNA damage and acquired immune tolerance via the upregulation of some other immune checkpoint inhibitors. Apart from this, such combination therapy may raise the occurrence rate of radiation‐induced lung fibrosis (RIPF) due to enhanced systemic inflammation, leading to the ultimate death of cancer patients (average survival time of about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD‐L1 and transforming growth factor‐β (TGF‐β) dual‐downregulation method. Following this, IR‐TAM is prepared by conjugating mitochondria‐targeted heptamethine cyanine dye IR‐68 with oxidative phosphorylation (OXPHOS) inhibitor Tamoxifen (TAM), which then self‐assembled with albumin (Alb) to form IR‐TAM@Alb nanoparticles. By doing this, tumor‐targeting IR‐TAM@Alb nanoparticle effectively reversed tumor hypoxia and depressed PD‐L1 and TGF‐β expression to sensitize RT. Meanwhile, due to the capacity of heptamethine cyanine dye in targeting RIPF and the function of TAM in depressing TGF‐β, IR‐TAM@Alb also ameliorated fibrosis development induced by RT.

Abstract Livestock grazing can strongly determine how grasslands function and their role in the carbon cycle. However, how ecosystem carbon exchange responds to grazing and the underlying mechanisms remain unclear. We measured ecosystem carbon fluxes to explore the changes in carbon exchange and their driving mechanisms under different grazing intensities (CK, control; HG, heavy grazing; LG, light grazing; MG, moderate grazing) based on a 16‐year long‐term grazing experimental platform in a desert steppe. We found that grazing intensity influenced aboveground biomass during the peak growing season, primarily by decreasing shrubs and semi‐shrubs and perennial forbs. Furthermore, grazing decreased net ecosystem carbon exchange by decreasing aboveground biomass, especially the functional group of shrubs and semi‐shrubs. At the same time, we found that belowground biomass and soil ammonium nitrogen were the driving factors of soil respiration in grazed systems. Our study indicates that shrubs and semi‐shrubs are important factors in regulating ecosystem carbon exchange under grazing disturbance in the desert steppe, whereas belowground biomass and soil available nitrogen are important factors regulating soil respiration under grazing disturbance in the desert steppe; this results provide deeper insights for understanding how grazing moderates the relationships between soil nutrients, plant biomass, and ecosystem CO2 exchange, which provide a theoretical basis for further grazing management.

Abstract Cuproptosis is an emerging cell death pathway that depends on the intracellular Cu ions. Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and trigger cuproptosis. However, ES can be rapidly removed and metabolized during intravenous administration, leading to a short half‐life and limited tumor accumulation, which hampers its clinical application. Here, the study develops a reactive oxygen species (ROS)‐responsive polymer (PCP) based on cinnamaldehyde (CA) and polyethylene glycol (PEG) to encapsulate ES‐Cu compound (EC), forming ECPCP. ECPCP significantly prolongs the systemic circulation of EC and enhances its tumor accumulation. After cellular internalization, the PCP coating stimulatingly dissociates exposing to the high‐level ROS, and releases ES and Cu, thereby triggering cell death via cuproptosis. Meanwhile, Cu2+‐stimulated Fenton‐like reaction together with CA‐stimulated ROS production simultaneously breaks the redox homeostasis, which compensates for the insufficient oxidative stress treated with ES alone, in turn inducing immunogenic cell death of tumor cells, achieving simultaneous cuproptosis and immunotherapy. Furthermore, the excessive ROS accelerates the stimuli‐dissociation of ECPCP, forming a positive feedback therapy loop against tumor self‐alleviation. Therefore, ECPCP as a nanoplatform for cuproptosis and immunotherapy improves the dual antitumor mechanism of ES and provides a potential optimization for ES clinical application.

Abstract Background Ovarian cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian cancer is still unknown. Aims The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian cancer. Materials and Methods We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co‐immunoprecipitation and western blotting. Results TRIM8 was overexpressed in ovarian cancer. TRIM8 promoted the proliferation and migration of ovarian cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian cancer progression induced by TRIM8 overexpression. Discussion TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian cancer. Conclusion TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian cancer cells to iron death, and promoted the proliferation and migration of ovarian cancer.

Abstract Generative Adversarial Networks (GANs) emerged thanks to the development of deep neural networks. Forgery images generated by various variants of GANs are widely spread on the Internet, which may be damage personal credibility and cause huge property losses. Thus, numerous methods are proposed to detect forgery images, but most of them are designed to detect forgery faces. Therefore, a method to detect forgery images of various scenes is proposed. In this work, central difference convolution and vanilla convolution (CDC‐Mix) are mixed after considering the depth and width features of neural networks and analyzing the influence of attention on network performance. Based on CDC‐Mix, a separable convolution (SeparableCDC‐Mix) is proposed. The proposed method consists of three parts: (1) CDC‐Mix and SeparableCDC‐Mix are used to extract the gradient information and texture features; (2) CDCM is used to extract the multi‐scale information of the image; (3) multi‐scale fusion module (MS‐Fusion) is used to fuse the multi‐scale information from different locations of the network. A large number of experiments have been carried out on several datasets generated by GAN, and the experimental results show that the proposed method has a great improvement compared with the existing advanced methods.

Abstract Shunt active power filter (SAPF) has emerged as a promising solution for mitigating harmonic distortions. Due to the interaction between the current inner‐loop of SAPF, source impedance and non‐linear loads, harmonic oscillation issue arises and adversely affects the stability of the system, thus in turn exacerbating the harmonic distortion. However, previous studies paid less attention to the value of phase adjustment in improving the dynamic behaviour of the loop and thus stabilizing harmonic oscillation. Taking the dynamic characteristics between source impedance and non‐linear load into consideration, this paper models and analyzes the SAPF system with source current direct control to reveal the law of full harmonic compensation oscillation. Based on the analysis, an enhanced phase adjustment strategy using load current feedforward is proposed and designed to stabilize harmonic oscillation, while maintaining a favourable trade‐off between stability and harmonic compensation performance. The small‐signal model validated for stability analysis and the effectiveness of proposed stabilization strategy are verified by simulation and experiment.

Abstract The emergence and rapid spread of antimicrobial resistance is of global public health concern. The gut microbiota harboring diverse commensal and opportunistic bacteria that can acquire resistance via horizontal and vertical gene transfers is considered an important reservoir and sink of antibiotic resistance genes (ARGs). In this review, we describe the reservoirs of gut ARGs and their dynamics in both animals and humans, use the One Health perspective to track the transmission of ARG‐containing bacteria between humans, animals, and the environment, and assess the impact of antimicrobial resistance on human health and socioeconomic development. The gut resistome can evolve in an environment subject to various selective pressures, including antibiotic administration and environmental and lifestyle factors (e.g., diet, age, gender, and living conditions), and interventions through probiotics. Strategies to reduce the abundance of clinically relevant antibiotic‐resistant bacteria and their resistance determinants in various environmental niches are needed to ensure the mitigation of acquired antibiotic resistance. With the help of effective measures taken at the national, local, personal, and intestinal management, it will also result in preventing or minimizing the spread of infectious diseases. This review aims to improve our understanding of the correlations between intestinal microbiota and antimicrobial resistance and provide a basis for the development of management strategies to mitigate the antimicrobial resistance crisis.

Death receptor 5 (DR5) can inhibit malignant proliferation via tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptosis in many cancers. Here we examined the expression and sublocalization of DR5 in gastric cancer, as well as its effects on clinical prognosis and cellular processes. Our analysis included a cohort of 240 gastric cancer patients. Bioinformatic analysis showed a significant correlation between DR5 and DNA replication, tumor mutation burden (TMB), and tumor stemness. Unlike death receptor 4 (DR4TRAIL‐R1), DR5 was expressed in the cytoplasm and nucleus, and was found to be positively correlated with lymphovascular invasion, lymph node metastasis, and TNM stage. Patients with positive DR5 had worse overall survival (OS) (P = 0.006). The multivariate Cox model showed that DR5 is an independent poor prognostic factor (hazard ratio = 1.693). Furthermore, knockdown of DR5 inhibited aggressive behaviors, including proliferation and metastasis in gastric cancer cells, and inhibited lung metastasis in vivo. In summary, nuclear localization of DR5 expression is a poor prognosis factor in gastric cancer and promotes growth, invasion, and metastasis of tumor cells in vitro and in vivo.

Abstract Given the escalating prevalence of electromagnetic pollution, there is an urgent need for the development of high‐performance electromagnetic interference (EMI) shielding materials. Herein, wood‐based electromagnetic shielding materials have gained significant popularity due to their exceptional performance as building materials. In this study, a novel wood‐based composite with electromagnetic shielding properties is developed. Through the in situ growth of zeolitic imidazolate framework‐8 (ZIF‐8) crystals on wood fibers, coupled with uniform integration of carbon nanotubes (CNTs), a multifunctional composite named ZIF‐8/Poplar‐CNT composite is synthesized via a one‐step thermoforming process. The incorporation of CNTs endows the composites with excellent EMI shielding effectiveness (EMI SE). Among these elements, despite ZIF‐8 crystals not possessing intrinsic electromagnetic shielding functionality, their distinctive dodecahedral structure proves adept at scattering and reflecting electromagnetic waves within the composites, further improving the electromagnetic shielding effect. Hence, the ZIF‐8/Poplar‐CNT composite (56.95 dB) has ≈10 dB higher EMI SE compared to that of the composites without ZIF‐8 crystals. Meanwhile, ZIF‐8 crystals endow the materials with excellent tensile strength (54.84 MPa, enhanced by 4 times). Moreover, the introduction of Zn2+ provides superior antibacterial properties. The potential applications of ZIF‐8/Poplar‐CNT composites extend to diverse areas such as building decoration, electronic products, and medical equipment.

Abstract Objectives The relationship between COVID‐19‐related telehealth calls could be used to predict emergency department visits and hospital surges 3 days later potentially facilitating staffing adjustments in advance of patient arrivals. The purpose of this research was to study the temporal association between frequencies of on demand telehealth calls and emergency department surges during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic. Methods This cohort study examined patients who self‐initiated synchronous audio‐video on‐demand telehealth calls between January 1, 2020 and June 30, 2022, and compared these to emergency department arrivals. The exposure in question was a synchronous audio‐video on‐demand telehealth visit. Our main outcome measured was frequency of emergency department visits. After autocorrelation, a multivariate linear regression model was utilized to determine temporal relationships between the two variables. Results This cohort study examined 42,429 synchronous audio‐video on‐demand telehealth calls, of which 43.6% were COVID‐19 related, and 540,686 emergency department visits, of which 3.9% were diagnosed with COVID‐19. COVID‐19‐related telehealth calls 3 days prior were predictive of emergency department encounters (r2 = 0.85, p

Abstract The Lachnospiraceae family holds promise as a source of next‐generation probiotics, yet a comprehensive delineation of its diversity is lacking, hampering the identification of suitable strains for future applications. To address this knowledge gap, we conducted an in‐depth genomic and functional analysis of 1868 high‐quality genomes, combining data from public databases with our new isolates. This data set represented 387 colonization‐selective species‐level clusters, of which eight genera represented multilineage clusters. Pan‐genome analysis, single‐nucleotide polymorphism (SNP) identification, and probiotic functional predictions revealed that species taxonomy, habitats, and geography together shape the functional diversity of Lachnospiraceae. Moreover, analyses of associations with atherosclerotic cardiovascular disease (ACVD) and inflammatory bowel disease (IBD) indicated that several strains of potentially novel Lachnospiraceae species possess the capacity to reduce the abundance of opportunistic pathogens, thereby imparting potential health benefits. Our findings shed light on the untapped potential of novel species enabling knowledge‐based selection of strains for the development of next‐generation probiotics holding promise for improving human health and disease management.

Abstract Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl‐CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle‐type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6‐HMGCS1‐YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non‐alcoholic fatty liver diseases‐ associated HCC.

Abstract Background The association of systolic blood pressure (SBP) and ischemic stroke outcome has recently been proved to be varied at different time points within 72 h after acute ischemic stroke onset; however, the specific status of how SBP affects prognosis at different time points within 72 h after endovascular treatment (EVT) among patients with large vessel occlusion (LVO) remains unclear. Methods Consecutive LVO patients treated with EVT were enrolled in our study. BP data were collected at eight time points (1, 2, 4, 8, 16, 24, 48, and 72 h post‐EVT). Outcome measure of interest was functional dependence, which was defined as mRS >2 at 90 days. Results A total of 406 LVO patients treated with EVT from 2016 to 2022 were included. At 16 h after EVT, the relationship between SBP and functional dependence showed a nonlinear association. At other time points after EVT, SBP had linear relationships with functional dependence. Furthermore, higher SBP, as either a linear or quadratic term, had an adverse effect on functional outcome. In addition, three SBP trajectories were observed, and the high‐to‐low group was independently associated with functional dependence. Conclusion Taken together, higher SBP within the first 72 h after EVT has a time‐dependent association with adverse clinical outcomes. Optimal blood pressure management during the first 72 h after EVT may be important to improve clinical outcome.

Abstract Drought stress has been a key environmental factor affecting plant growth and development. The plant genome is capable of producing long noncoding RNAs (lncRNAs). To better understand white mulberry (Morus alba L.) drought response mechanism, we conducted a comparative transcriptome study comparing two treatments: drought‐stressed (EG) and well‐watered (CK) plants. A total of 674 differentially expressed lncRNAs (DElncRNAs) were identified. In addition, 782 differentially expressed messenger RNAs (DEmRNAs) were identified. We conducted Gene Ontology (GO) and KEGG enrichment analyses focusing on the differential lncRNAs cis‐target genes. The target genes of the DElncRNAs were most significantly involved in the biosynthesis of secondary metabolites. Gene regulatory networks of the target genes involving DElncRNAs–mRNAs–DEmRNAs and DElncRNA–miRNA–DEmRNA were constructed. In the DElncRNAs–DEmRNAs network, 30 DEmRNAs involved in the biosynthesis of secondary metabolites are collocated with 46 DElncRNAs. The interaction between DElncRNAs and candidate genes was identified using LncTar. In summary, quantitative real‐time polymerase chain reaction (qRT‐PCR) validated nine candidate genes and seven target lncRNAs including those identified by LncTar. We predicted that the DElncRNAs–DEmRNAs might recruit microRNAs (miRNAs) to interact with gene regulatory networks under the drought stress response in mulberry. The findings will contribute to our understanding of the regulatory functions of lncRNAs under drought stress and will shed new light on the mulberry–drought stress interactions.

Abstract Classic biphasic pulmonary blastoma (CBPB), a distinct type of lung cancer, is a dual‐phasic tumor characterized by the co‐existence of low‐grade fetal adenocarcinoma and primitive mesenchymal stroma. Accounting for less than 0.1% of surgically removed lung cancers, CBPB commonly presents in individuals during their fourth to fifth decades of life, with smoking as a significant risk factor. The optimal management strategy entails surgical resection, supplemented by chemotherapy to improve prognosis. The frontline chemotherapeutic agents typically include platinum agents and etoposide, with preoperative neoadjuvant chemotherapy potentially enabling operability for initially inoperable cases. In recent years, targeted therapies, such as antiangiogenic agents, have emerged as promising new treatment strategies for CBPB. For patients exhibiting brain metastases or deemed inoperable, radiation therapy proves to be a crucial therapeutic component. CBPB prognosis is adversely affected by factors such as early metastasis, tumor size exceeding 5 cm, and tumor recurrence. In this regard, serological markers have been identified as valuable prognostic indicators. To exemplify, we recount the case of a 44‐year‐old female patient with CBPB, wherein serum lactate dehydrogenase levels showed significant diagnostic value. This report further incorporates a comprehensive review of CBPB literature from the past 22 years.

Abstract The use of radiolabeled cells for positron emission tomography (PET) imaging tracking has been a promising approach for monitoring cell‐based therapies. However, the presence of free radionuclides released from dead cells during tracking can interfere with the signal from living cells, leading to inaccurate results. In this study, the effectiveness of the iron chelators deferoxamine (DFO) and deferiprone in removing free radionuclides 89Zr and 68Ga, respectively, was demonstrated in vivo utilizing PET imaging. The use of DFO during PET imaging tracking of 89Zr‐labeled mesenchymal stem cells (MSCs) significantly reduced uptake in bone while preserving uptake in major organs, resulting in more accurate and reliable tracking. Furthermore, the clearance of free 89Zr in vivo resulted in a significant reduction in radiation dose from 89Zr‐labeled MSCs. Additionally, the avoidance of free radionuclide accumulation in bone allowed for more precise observation of the homing process and persistence during bone marrow transplantation. The efficacy and safety of this solution suggest this finding has potential for widespread use in imaging tracking studies involving various cells. Moreover, since this method employed iron chelator drugs in clinical use, which makes it is a good prospect for clinical translation.

Abstract Pitolisant, a novel histamine H3‐receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real‐world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant‐associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant‐associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life‐threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.

Abstract Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan–Meier method to find survival differences. All tumors in this study were negative for Epstein–Barr virus‐encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death‐ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence‐to‐death survival: 23 months versus 6 months); HAS patients who received anti‐HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti‐HER2 therapy, immunotherapy, and anti‐angiogenesis therapy.

Abstract The development of castration‐resistant prostate cancer (CRPC) is a significant factor that reduces life expectancy among patients with prostate cancer. Previously, it is reported that CDK4/6 inhibitors can overcome the resistance of CRPC to BET inhibitors by destabilizing BRD4, suggesting that the combination of CDK4/6 inhibitors and BET inhibitors is a promising approach for treating CRPC. In this study, candidates that affect the combined antitumor effect of CDK4/6 inhibitors and BET inhibitors on CRPC is aimed to examine. The data demonstrates that CBX3 is abnormally upregulated in CDK4/6 inhibitors‐resistant cells. CBX3 is almost positively correlated with the cell cycle in multiple malignancies and is downregulated by BET inhibitors. Mechanistically, it is showed that CBX3 is transcriptionally upregulated by BRD4 in CRPC cells. Moreover, it is demonstrated that CBX3 modulated the sensitivity of CRPC to CDK4/6 inhibitors by binding with RB1 to release E2F1. Furthermore, it is revealed that PLK1 phosphorylated CBX3 to enhance the interaction between RB1 and CBX3, and desensitize CRPC cells to CDK4/6 inhibitors. Given that BRD4 regulates CBX3 expression and PLK1 affects the binding between RB1 and CBX3, it is proposed that a dual BRD4/PLK1 inhibitor can increase the sensitivity of CRPC cells to CDK4/6 inhibitors partially through CBX3.

Abstract Background With the advancement of whole‐genome sequencing (WGS) technology, massively parallel sequencing (MPS) remains the mainstream due to its accuracy, low cost, and high throughput. The development of the analytical pipeline corresponding to MPS has always been of great importance. Increasingly large population genomics studies, as a specific type of big data research, pose new challenges for analysis solutions. Results Here, we introduce ZBOLT, a comprehensive analysis system that incorporates both software and hardware advancements, making it an appropriate choice for large‐scale population genomic studies that require extensive data processing. In this study, we first evaluate ZBOLT's calling accuracy using the Genome in a Bottle (GIAB) benchmark dataset. Then we apply ZBOLT to a large‐scale population genomics study with 5,616 high sequencing depth samples totaling 1.16Pbp (base pair). As the results show, ZBOLT demonstrates exceptional efficiency and low energy consumption, processing 100Tbp per day and using 1kWh per 100Gbp sequenced sample. Conclusion This research serves as a valuable reference for analyzing sequencing data from large population cohorts and underscores the significant potential of ZBOLT in large‐scale population genomics studies.

Abstract The extensive and improper use of antibiotics has led to a dramatic increase in the frequency of antibiotic resistance among human pathogens, complicating infectious disease treatments. In this work, a method for rapid antimicrobial susceptibility testing (AST) is presented using microstructured silicon diffraction gratings integrated into prototype devices, which enhance bacteria‐surface interactions and promote bacterial colonization. The silicon microstructures act also as optical sensors for monitoring bacterial growth upon exposure to antibiotics in a real‐time and label‐free manner via intensity‐based phase‐shift reflectometric interference spectroscopic measurements (iPRISM). Rapid AST using clinical isolates of Escherichia coli (E. coli) from urine is established and the assay is applied directly on unprocessed urine samples from urinary tract infection patients. When coupled with a machine learning algorithm trained on clinical samples, the iPRISM AST is able to predict the resistance or susceptibility of a new clinical sample with an Area Under the Receiver Operating Characteristic curve (AUC) of ∼ 0.85 in 1 h, and AUC > 0.9 in 90 min, when compared to state‐of‐the‐art automated AST methods used in the clinic while being an order of magnitude faster.

Abstract Prokaryotic genomes are generally organized in haploid. In synthetic biological research, efficient chassis cells must be constructed to produce bio‐based products. Here, the essential division of the ftsZ gene to create functional polyploid E. coli is regulated. The artificial polyploid E. coli containing 2–4 chromosomes is confirmed through PCR amplification, terminator localization, and flow cytometry. The polyploid E. coli exhibits a larger cell size, and its low pH tolerance and acetate resistance are stronger than those of haploid E. coli. Transcriptome analysis shows that the genes of the cell's main functional pathways are significantly upregulated in the polyploid E. coli. These advantages of the polyploid E. coli results in the highest reported L‐threonine yield (160.3 g L−1) in fed‐batch fermentation to date. In summary, an easy and convenient method for constructing polyploid E. coli and demonstrated its application in L‐threonine production is developed. This work provides a new approach for creating an excellent host strain for biochemical production and studying the evolution of prokaryotes and their chromosome functions.

The purpose of the infrared and visible image fusion is to generate a fused image with rich information. Although most fusion methods can achieve good performance, there are still shortcomings in extracting feature information from source images, which make it difficult to balance the thermal radiation region information and texture detail information in the fused image. To address the above issues, an expectation maximization (EM) learning framework based on adversarial generative networks (GAN) for infrared and visible image fusion is proposed. The EM algorithm (EMA) can obtain maximum likelihood estimation for problems with potential variables, which is helpful in solving the problem of lack of labels in infrared and visible image fusion. The axial‐corner attention mechanism is designed to capture long‐range semantic information and texture information of the visible image. The multifrequency attention mechanism digs the relationships between features at different scales to highlight target information of infrared images in the fused result. Meanwhile, two discriminators are used to balance two different features, and a new loss function is designed to maximize the likelihood estimate of the data with soft class label assignments, which is obtained from the expectation network. Extensive experiments demonstrate the superiority of EMA‐GAN over the state‐of‐the‐art.

Abstract Predicting future land system changes driven by anthropogenic and climactic impacts can help to explore adaptation and mitigation pathways for regional and global sustainable development. Here, we project land cover changes in China from 2030 to 2100 at a resolution of 1 km × 1 km under eight scenarios based on the Scenario Model Intercomparison Project (ScenraioMIP), which are extracted from Land Use Harmonization version 2 (LUH2). We use a rule‐based method to classify and map 9 land cover dynamic trajectories at patch scale to present land system changes. At the provincial scale we used hierarchical clustering to identify archetypes of land cover change, which can predict ecological risks for future management in western provinces. Our results reveal that anthropogenic mitigation policies under high mitigation pressure do not result in positive impacts on the land system, but rising temperatures will provide a great opportunity for ecological restoration in some regions.

Abstract The skin is the largest organ in the human body. Various skin environments on its surface constitutes a complex ecosystem. One of the characteristics of the skin micro‐ecosystem is low biomass, which greatly limits a comprehensive identification of the microbial species through sequencing. In this study, deep‐shotgun sequencing (average 21.5 Gigabyte (Gb)) from 450 facial samples and publicly available skin metagenomic datasets of 2069 samples to assemble a Unified Human Skin Genome (UHSG) catalog is integrated. The UHSG encompasses 813 prokaryotic species derived from 5779 metagenome‐assembled genomes, among which 470 are novel species covering 20 phyla with 1385 novel assembled genomes. Based on the UHSG, the core functions of the skin microbiome are described and the differences in amino acid metabolism, carbohydrate metabolism, and drug resistance functions among different phyla are identified. Furthermore, analysis of secondary metabolites of the near‐complete genomes further find 1220 putative novel secondary metabolites, several of which are found in previously unknown genomes. Single nucleotide variant (SNV) reveals a possible skin protection mechanism: the negative selection process of the skin environment to conditional pathogens. UHSG offers a convenient reference database that will facilitate a more in‐depth understanding of the role of skin microorganisms in the skin.