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Abstract The permanent magnet eddy‐current coupler (PMEC) is a kind of non‐contact, stepless speed regulation device and has been widely used in transmissions. However, the current PMECs are coaxial and cannot achieve transmission and speed regulation in intersecting axes. An intersecting‐axis permanent magnet (PM) eddy current coupler (IPMEC), which consists of a disk‐type PM rotor and a barrel‐type conductive sheet (CS) rotor arranged with intersecting axes, is proposed. It generates eddy currents through the speed difference between the two rotors and uses the non‐contact electromagnetic force between the eddy currents and permanent magnets to transmit torque. During operation, the speed can be adjusted by altering the coupling area or air gap. A theoretical model of the IPMEC based on the equivalent magnetic circuit method is presented and verified by finite element simulation using ANSYS. Then, the effects of the pole number of the PMs, the radius of the CS rotor and the PM rotor on the performance were analysed, and the design method of the IPMEC was proposed. This study can be used to expand the application range of PMECs.

Abstract Hepatic polypeptide nutrient solution (HP) is a mixture of hepatoprotective peptides derived from fresh porcine liver with various effects. However, the role and mechanisms of HP in nonalcoholic fatty liver disease (NAFLD) are still not well understood. We investigated the effects of HP NAFLD rats induced by high‐cholesterol diet (HCD) and its underlying mechanisms. Rats were provided with HCD for 4 weeks and then received HP or metformin after 2 weeks of HCD feeding. The study found that HP reduced cholesterol and triglyceride levels in rats with NAFLD (all p

Background Vascular smooth muscle cell (VSMC) proliferation is involved in many types of arterial diseases, including neointima hyperplasia, in which Ca2+ has been recognized as a key player. However, the physiological role of Ca2+ release via inositol 1,4,5‐trisphosphate receptors (IP3Rs) from endoplasmic reticulum in regulating VSMC proliferation has not been well determined. Methods and Results Both in vitro cell culture models and in vivo mouse models were generated to investigate the role of IP3Rs in regulating VSMC proliferation. Expression of all 3 IP3R subtypes was increased in cultured VSMCs upon platelet‐derived growth factor‐BB and FBS stimulation as well as in the left carotid artery undergoing intimal thickening after vascular occlusion. Genetic ablation of all 3 IP3R subtypes abolished endoplasmic reticulum Ca2+ release in cultured VSMCs, significantly reduced cell proliferation induced by platelet‐derived growth factor‐BB and FBS stimulation, and also decreased cell migration of VSMCs. Furthermore, smooth muscle–specific deletion of all IP3R subtypes in adult mice dramatically attenuated neointima formation induced by left carotid artery ligation, accompanied by significant decreases in cell proliferation and matrix metalloproteinase‐9 expression in injured vessels. Mechanistically, IP3R‐mediated Ca2+ release may activate cAMP response element–binding protein, a key player in controlling VSMC proliferation, via Ca2+/calmodulin‐dependent protein kinase II and Akt. Loss of IP3Rs suppressed cAMP response element–binding protein phosphorylation at Ser133 in both cultured VSMCs and injured vessels, whereas application of Ca2+ permeable ionophore, ionomycin, can reverse cAMP response element–binding protein phosphorylation in IP3R triple knockout VSMCs. Conclusions Our results demonstrated an essential role of IP3R‐mediated Ca2+ release from endoplasmic reticulum in regulating cAMP response element–binding protein activation, VSMC proliferation, and neointima formation in mouse arteries.

Abstract Numerous studies have demonstrated that exposure to cadmium disrupts the diversity and composition of the gut microbiota, resulting in damage to organ tissue. However, there remains a lack of comprehensive understanding regarding the broader ecological reality associated with this phenomenon. In this study, we conducted a thorough evaluation of the effects of different concentrations of Cd (6, 12, 24, and 48 mg/L) over a period of 35 consecutive days on the organ viscera and the gut microbiota of long‐tailed dwarf hamsters, Cricetulus longicaudatus (Rodentia: Cricetidae), using histopathological analysis, 16S rDNA, and metagenome sequencing. Our findings revealed that the results suggest that Cd exposure induced liver, spleen, and kidney damage, potentially leading to increased intestinal permeability and inflammation. These alterations were accompanied by significant perturbations in the gut microbiota composition, particularly affecting potentially pathogenic bacteria such as Prevotella and Treponema within the gut ecosystem. Consequently, host susceptibility to underlying diseases was heightened due to these changes. Notably though, Cd exposure did not significantly impact the overall structure of the gut microbiota itself. Additionally, Cd exposure induced significant changes in the metabolic functions, with the pathways related to disease and environmental information processing notably enhanced, possibly indicating stronger innate defense mechanisms against external injuries among wild mammals exposed to Cd. This study offers a novel approach to comprehensively evaluate the significant impact of Cd pollution on ecosystems by investigating both structural and functional alterations in the digestive system, as well as disruptions in intestinal flora among wild mammals.

Abstract Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota‐derived 3‐hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6‐mediated radiation damage. Irradiated cell‐fecal microbiota co‐culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43‐mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut‐immune axis in radiation pathophysiology, with potential therapeutic applications.

Abstract Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR‐Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC.

Abstract Ingenious design and fabrication of advanced carbon‐based sulfur cathodes are extremely important to the development of high‐energy lithium‐sulfur batteries, which hold promise as the next‐generation power source. Herein, for the first time, we report a novel versatile hyphae‐mediated biological assembly technology to achieve scale production of hyphae carbon fibers (HCFs) derivatives, in which different components including carbon, metal compounds, and semiconductors can be homogeneously assembled with HCFs to form composite networks. The mechanism of biological adsorption assembly is also proposed. As a representative, reduced graphene oxides (rGOs) decorated with hollow carbon spheres (HCSs) successfully co‐assemble with HCFs to form HCSs@rGOs/HCFs hosts for sulfur cathodes. In this unique architecture, not only large accommodation space for sulfur but also restrained volume expansion and fast charge transport paths are realized. Meanwhile, multiscale physical barriers plus chemisorption sites are simultaneously established to anchor soluble lithium polysulfides. Accordingly, the designed HCSs@rGOs/HCFs‐S cathodes deliver a high capacity (1189 mA h g−1 at 0.1 C) and good high‐rate capability (686 mA h g−1 at 5 C). Our work provides a new approach for the preparation of high‐performance carbon‐based electrodes for energy storage devices.

Abstract Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride‐based alloys are still the best for near‐room‐temperature applications. In this work, a ≈38% enhancement of the average ZT (300−473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2−yTe3‐based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6‐based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high‐density dislocations in the same region can effectively scatter the phonons, decoupling the electron‐phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single‐leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate‐matrix interface microstructure in improving the performance of materials for relatively low‐temperature applications.

Abstract Background The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. Methods In this real‐world study, we enrolled 143 COVID‐19‐vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti‐spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4‐BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. Results Patients with liver cancer receiving booster doses had higher levels of anti‐spike RBD IgG against circulating omicron (BA.4‐BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4‐BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti‐spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti‐spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. Conclusion Our study found that there may be differences in vaccine response and protective effect against COVID‐19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID‐19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Abstract Tornadoes, as highly destructive weather events, require accurate detection for effective decision‐making. Traditional radar‐based tornado detection algorithms (TDA) face challenges with limited tornado feature extraction capabilities, leading to high false alarm rates and low detection probabilities. This study introduces the Multi‐Task Identification Network (MTI‐Net), leveraging Doppler radar data to enhance tornado recognition. MTI‐Net integrates tornado detection and estimation tasks to acquire comprehensive spatial and locational information. As part of MTI‐Net, we introduce a novel backbone network of Multi‐Head Convolutional Block (MHCB), which incorporates Spatial and Channel Attention Units (SAU and CAU). SAU optimizes local tornado feature extraction, while CAU reduces false alarms by enhancing dependencies among input variables. Experiments demonstrate the superiority of MTI‐Net over TDA, with a decrease in false alarm rates from 0.94 to 0.46 and an increase in hit rates from 0.23 to 0.81, highlighting the effectiveness of MTI‐Net in handling small‐scale tornado events.

Abstract Machine learning‐based approaches demonstrate a significant potential in radar quantitative precipitation estimation (QPE) applications. In contrast to conventional methods that depend on local raindrop size distributions, deep learning (DL) can establish an effective mapping from three‐dimensional radar observations to ground rain rates. However, the lack of transparency in DL models poses challenges toward understanding the underlying physical mechanisms that drive their outcomes. This study aims to develop a DL‐based QPE system and provide a physical explanation of radar precipitation estimation process. This research is designed by employing a deep neural network consisting of two modules. The first module is a quantitative precipitation estimation network that has the capability to learn precipitation patterns and spatial distribution from multidimensional polarimetric radar observations. The second module introduces a quantitative precipitation estimation shapley additive explanations method to quantify the influence of each radar observable on the model estimate across various precipitation intensities.

Abstract Aims To investigate the effect of Self‐designed Metabolic Equivalent Exercises (SMEE) on cancer‐related fatigue in patients with gastric cancer. Methods 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ‐C30 Quality of Life Scale were used to measure cancer‐caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. Results After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow‐up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ‐C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p

Abstract Polarization surrounding bias correction (BC) in creating climate projections arises from its lack of physicality. Here, we perform and analyze 18 dynamical downscaling simulations (with and without BC) to better understand the physical impacts of BC, applied before downscaling, on regional climate output across the western United States. Without BC, downscaled precipitation is systematically and unrealistically wet biased compared to a hierarchy of observationally based datasets over the 1980–2014 period due to cascading mean‐state Global Climate Model (GCM) biases: (a) overly strong lower‐tropospheric lapse rates (5 K/km), (b) overly cold (2 K) tropospheric temperatures, and (c) anomalous mid‐tropospheric cyclonic vorticity advection. With BC, downscaled precipitation (snow) biases are virtually eliminated (halved). Identified GCM biases are common to the broader Coupled Model Intercomparison Project ensemble. Physical effects of BC on the quality of the regionalized projections, pending an evaluation of BC's distortion of the downscaled climate response, may motivate its broader application by dynamical downscalers.

Abstract Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra‐conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory‐polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4‐ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein‐based conduits. Moreover, the NGC can gradually regulate the intra‐conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

Abstract Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large‐scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi‐omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS‐I), moderate AZS (AZS‐II), and severe AZS (AZS‐III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS‐I) and an AZS group (AZS‐II and AZS‐III). Correlation and cross‐reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium‐Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite‐targeting gene analysis and single‐cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

Abstract Background Peripheral blood immunomarkers are associated with prognosis in patients with solid tumors receiving chemotherapy or immunotherapy. In this study, the associations of circulating neutrophil‐to‐lymphocyte ratio (NLR), monocyte‐to‐lymphocyte ratio (MLR), and platelet‐to‐lymphocyte ratio (PLR), as well as their dynamic changes were investigated in relation to the efficacy of immunotherapy in patients with primary liver cancer. Methods Comparisons were made between NLR, MLR, and PLR among individuals exhibiting disease control (defined as the best response of partial response [PR] or stable disease [SD]) and those with progressive disease (PD). Additionally, disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) were compared between individuals with different NLR, MLR, and PLR levels before initiating palliative immunotherapy. Furthermore, comparisons were made between patients with different alterations in the ratios at the second cycle of immunotherapy compared to baseline. These analyses were performed using univariate and multivariate approaches. A total of 119 Chinese patients with liver cancer who underwent immunotherapy were included in this study, which focused on hepatocellular carcinoma (HCC). Results In cases with HCC (n = 104), the cutoffs of NLR, MLR, and PLR to differentiate treatment responders from nonresponders were 3.38, 0.28, and 227.18, respectively. Patients with the best response of PR or SD had significantly lower NLR and MLR. Patients with NLR

Abstract Introduction Lung adenocarcinoma (LUAD) is the major type of non‐small cell lung cancer with low a survival rate caused by metastasis. SCN4B encoding voltage‐gated sodium channel β subunit is regarded as a metastasis‐suppressor gene. We aim to explore how SCN4B influences the progression and prognosis of LUAD. Methods The gene expression profiles of 585 LUAD samples in TCGA and GSE31210, GSE116959, and GSE72094 datasets from the GEO database were downloaded for analysis. Differentially expressed genes were obtained through the “limma” package. The “clusterProfiler” package was used to conduct GSEA. Survival analysis was conducted via “survival” and “survminer” packages. Transcription factors regulating SCN4B expression were screened by correlation analysis and further predicted by FIMO. Infiltration of immune cells was analyzed by CIBERSORT. ESTIMATE algorithm was used to evaluate the immune‐related scores. Results SCN4B expressed higher in normal samples than in LUAD samples and higher in female samples than male samples. One hundred and twenty‐six pathways were significantly enriched between high and low SCN4B expression groups. Six transcription factors' expressions were positively related to SCN4B expression, and ChIP‐seq data from “Cistrome” verified that TAL1 and ERG might bind to the upstream sequence of SCN4B. SCN4B expression was significantly correlated with activated memory CD4 T cells, resting mast cells, and monocytes. TMB status, three scores based on ESTIMATE algorithm, and expression of three immune checkpoints showed significant differences between SCN4B high‐ and low‐expression groups. SCN4B could be considered as an independent prognostic signature of LUAD patients that higher expression represents a better prognosis. Conclusion SCN4B expresses higher in normal samples, and SCN4B is able to be an independent prognostic signature for LUAD patients. TAL1 and ERG may regulate the expression of SCN4B by binding its upstream sequences. Our research is valuable in improving the effectiveness of treatment in LUAD.

Abstract The current instance segmentation method can achieve satisfactory results in common scenarios. However, under the overlap or partial occlusion between targets caused by the complex scenes, accurate segmentation of pigs remains a challenging task. To address the problem, the authors propose an instance segmentation method based on Mask Scoring region‐based convolutional neural networks (R‐CNN) (MS R‐CNN), which creates the adversarial network called MaskDis in the head branch of MS R‐CNN. The MaskDis is trained as a discriminator using a generative adversarial network, and the MS R‐CNN model is used as a generator during model training. The adversarial training enables the generator to learn context information and features at the pixel level, which effectively improves the segmentation quality under pigs’ overlapping or dense occlusions scenes. Experimental conducted on the pig object segmentation dataset show that the proposed approach achieves a precision of 92.03%, a recall of 92.18%, and an F1 score of 0.9210. Compared with the basic MS R‐CNN model, the approach achieved a 2.25% improvement in precision and 1.18% improvement in F1 score. Furthermore, the improved approach outperformed advanced instance segmentation methods such as YOLACT, Swin Transformer, YOLOv5‐seg, and SOLOv2 on COCO evaluation metrics. These experimental results demonstrate the effectiveness of the proposed approach in instance segmentation of pigs in complex scenes, providing technical support for non‐contact pig automatic management.

Abstract Background With the growing challenge of an aging population, addressing the needs of elderly individuals who face living difficulties and lack family support becomes increasingly difficult. Volunteer services are crucial in this context, yet their effectiveness is hindered by unclear service scopes and uncertain volunteer inclinations. Aim To explore the role and specific preference of volunteers with nursing backgrounds in support of older adults living in the urban community. Design, Setting and Participants A descriptive qualitative study was conducted between September and October 2022. Twenty‐three participants (hospital nurses [10], community nurses [4], nursing teachers [4] and nursing students [5]) were selected. Data analysis followed conventional content analysis. Results Nine major themes were identified based on interview data. Four themes described the service scope of nursing volunteers: (1) environment domain, (2) physiological domain, (3) psychosocial domain and (4) health‐related behaviours domain. Another five themes highlighted the service inclination of these volunteers: (1) service frequency, (2) service duration per person/time, (3) service coverage, (4) service place and (5) service object. Conclusion This study clarifies the service focus and scope of necessary support for volunteers, exploring the potential service capabilities of scarce volunteers to the greatest extent. Meanwhile, the results of this study also provide a foundation for stakeholders to fully exploit the synergy. The important findings of this study will help the government and relevant authorities better understand the service attributes of nursing volunteers, allowing them to develop detailed training plans and provide nursing volunteers with targeted support and assistance to meet the health expectations of urban community‐living older adults in need. Patient or Public Contribution Developing research questions, participation and conduct and provision and interpretation of evidence.

Abstract It has been reported that the sea level falls in the tropical Southwest Indian Ocean (SWIO) from the 1960s to the early 2000s. However, a rising trend of 4.05 ± 0.56 cm/decade has occurred during the recent two decades with our analysis showing that manometric sea level contributes 41% to this sea level rise. 30% of this rise is due to steric sea level (SSL) change in the upper 2,000 m with SSL rise in the upper 300 m of secondary importance. Conversely, thermal expansion below the thermocline (300–2,000 m), likely caused by water mass spread from the Southern Ocean, induces major contribution to SSL changes. Compared to existing studies demonstrating the contribution of thermal variations above the thermocline to sea level variability in the tropical SWIO, this study emphasizes the importance of ocean mass and deeper ocean changes in a warming climate.

There is a ubiquitous boundary reflection effect of stress wave propagation in the indoor experimental studies. It is critical to improve the validity of waveform data by optimizing boundary materials to absorb reflection waves. In the present study, a calculation method for the optimal wave impedance of boundary materials was proposed based on the transmission and reflection principle of one-dimensional stress waves at the interface of different media. By using the calculation method, the optimal wave impedance value of the boundary material was obtained. A one-dimensional stress wave propagation test apparatus was developed for exploring the improvement effect of absorbing materials on the boundary reflection effect. One-dimensional stress wave propagation experimental studies in the complete red sandstone samples were carried out by setting various boundary absorbing materials such as pine pad, rubber pad, and steel pad. The results indicated that the experimental test results were consistent with the theoretical calculation results. In the stress wave propagation tests, the optimal wave impedance value of the boundary material was 1.12 × 106 kg/m2·s. When the pine pads were used as boundary absorbing materials, the suppression effect of boundary reflection effects is relatively the best. The present study provides references for analyzing the characteristics and mechanism of stress wave propagation and attenuation.

Abstract Merging activities at freeway merging areas can cause significant recurrent and non‐recurrent bottleneck congestion due to vehicles’ mandatory lateral conflicts. The Connected and Automated Vehicles (CAVs), with their capabilities of real‐time communication and precise trajectory control, hold great potential to prevent or mitigate such critical conflicts at merging areas. However, the performance of CAVs may be impaired by the imbalance of lane flow distribution, and non‐cooperative movements of Human‐driven Vehicles (HDVs) in the mixed traffic environment (i.e. traffic mixed with CAVs and HDVs). In this paper, a novel two‐level hierarchical traffic control framework for multilane merging areas under the mixed traffic environment is developed. Note that this paper assumes that the merging sequence is determined by the high control level and focuses on the low level of the control framework. The low control level not only establishes a trajectory optimization strategy for CAVs with lane‐changing optimization and cooperative merging control, but includes a human‐like merging strategy for HDVs. First, to balance downstream lane flow distribution and provide sufficient merging space for on‐ramp vehicles, a lane‐changing optimization method is proposed to choose a certain number of designated mainline CAVs to perform early lane changes at the upstream mainline. Second, a cooperative merging control method is presented to optimize the longitudinal trajectories of both mainline and on‐ramp CAVs while accounting for the movement of HDVs. Third, Gipps car‐following model and heuristic control are combined to represent the HDVs’ merging maneuvers. The proposed algorithm simulates and performs merging maneuvers at a typical two‐lane freeway merging area and verifies it in various scenarios considering demand level, demand splits and CAV Penetration Rate (PR). The simulation results show that the proposed algorithm can effectively facilitate merging operations, reduce the Total Travel Time (TTT), and increase the Average Travel Speeds (ATS) compared to other merging algorithms. Specifically, compared to the case of using only cooperative merging control method, the proposed algorithm can further reduce TTT by 25.5% and increase ATS by 33.38%. When PR gradually increased, the control performance of the proposed algorithm can be further improved.

Abstract To eliminate unnecessary background information, such as soft tissues in original CT images and the adverse impact of the similarity of adjacent spines on lumbar image segmentation and surgical path planning, a two‐stage approach for localising lumbar segments is proposed. First, based on the multi‐scale feature fusion technology, a non‐linear regression method is used to achieve accurate localisation of the overall spatial region of the lumbar spine, effectively eliminating useless background information, such as soft tissues. In the second stage, we directly realised the precise positioning of each segment in the lumbar spine space region based on the non‐linear regression method, thus effectively eliminating the interference caused by the adjacent spine. The 3D Intersection over Union (3D_IOU) is used as the main evaluation indicator for the positioning accuracy. On an open dataset, 3D_IOU values of 0.8339 ± 0.0990 and 0.8559 ± 0.0332 in the first and second stages, respectively is achieved. In addition, the average time required for the proposed method in the two stages is 0.3274 and 0.2105 s respectively. Therefore, the proposed method performs very well in terms of both precision and speed and can effectively improve the accuracy of lumbar image segmentation and the effect of surgical path planning.

To overcome the dependency of strategies utilizing cell‐free DNA (cfDNA) on tissue sampling, the emergence of sequencing panels for non‐invasive mutation screening was promoted. However, cfDNA sequencing with panels still suffers from either inaccuracy or omission, and novel approaches for accurately screening tumor mutations solely based on plasma without gene panel restriction are urgently needed. We performed unique molecular identifier (UMI) target sequencing on plasma samples and peripheral blood mononuclear cells (PBMCs) from 85 hepatocellular carcinoma (HCC) patients receiving surgical resection, which were divided into an exploration dataset (20 patients) or an evaluation dataset (65 patients). Plasma mutations were identified in pre‐operative plasma, and the mutation variant frequency change (MVFC) between post‐ and pre‐operative plasma was then calculated. In the exploration dataset, we observed that plasma mutations with MVFC

Abstract Background Preclinical studies and clinical trials have demonstrated that tumor‐intrinsic activation of the cell cycle program impedes anticancer immunotherapy. Identification of cell cycle‐related biomarkers may provide novel therapeutic targets to augment the efficacy of immunotherapy in hepatocellular carcinoma (HCC). Method and Results Based on the genes related to cell cycle program, two clusters (Cluster 1 and Cluster 2) were detected in HCC patients via non‐negative matrix factorization algorithm. Multivariable‐adjusted Cox regression analysis indicated that the cell cycle gene‐based classification was a significant prognostic factor for predicting the clinical outcome of HCC patients. Cluster 1 showed shorter overall survival time and progression‐free interval time was associated with activated cell cycle program, higher infiltration of myeloid‐derived suppressor cells (MDSCs) and less sensitivity to immunotherapy. A three‐gene prognostic model, including BIRC5, C8G, and SPP1, was constructed to characterize the cell cycle‐based classification of HCC, which had strong robustness and a stable predictive performance. Notably, Birc5 was positively correlated with CD11b expression (a MDSC marker) in HCC tissue. Concordant high expression of Birc5 and intratumor infiltration level of MDSCs were correlated with worse prognosis of HCC patients. In vitro, hepatocellular Birc5 overexpression promoted immunosuppressive CD11b+CD33+HLA‐DR−MDSC expansion from human peripheral blood mononuclear cells. Genetically modified animal model of liver cancer revealed that Birc5 depletion upregulated the genes related to lymphocyte‐mediated immunity, natural killer cell‐mediated immunity, interferon‐gamma production, T‐cell activation, and T‐cell‐mediated cytotoxicity. These results suggest an immunosuppressive function of Birc5 in HCC. Conclusion Birc5 was a potential biomarker and inducer of intratumor infiltration of MDSCs, which led to T cell exclusion or dysfunction in tumor immune microenvironment, consequently resulting in reduced response to ICIs in HCC.

Abstract In the process of coping with energy and environmental protection issues, technologies such as energy materials, energy devices, and energy systems have made great progress. With excellent performance, film capacitors play an increasingly important role in energy‐related fields. With the increase of application scenarios and the continuous development of film material technology, it is urgent to establish a better theoretical connection from films to capacitors. First, the main components of the capacitor including the film and the positional relationships among them are given. Then, from the two perspectives of indirect calculation according to the volume and the direct calculation according to the winding process, the equation between the dielectric constant of films and the corresponding capacitance of capacitors is established. Further, the measurement data and error analysis results of the built test platform prove the accuracy and great potential of the proposed calculation methods. In addition, error sources, including film thickness uniformity, are listed. Finally, the challenges faced by the proposed calculation methods and the paths that can be referenced for future research are summarised and discussed.

Objective Anterolateral coronal fractures are so rare that the mechanism of injury, the type of combined fracture and ligament injury, and the optimal treatment are unknown. To study the outcome of surgical treatments for anterolateral (AL) fracture of the ulna coronoid process (Adams Type IV) and summarize the characteristics of this type of fracture and to guide clinical applications. Methods From February 2015 to April 2021, 32 patients were included in the study. All patients had standard radiography with anteroposterior and lateral views, computed tomography, and intraoperative fluoroscopy. All patients were treated surgically. Surgery‐related information, including surgical approach, operation duration, blood loss, and repairing the lateral collateral ligament and the medial collateral ligament integrity, were recorded. The patient's clinical details, such as the final range of motion (ROM), the Broberg–Morrey scores and the visual analogue scale (VAS) at the last follow‐up, were described. The chi‐square test or Fisher's exact test was used for statistical analysis. Results We divided patients into two groups according to the anterolateral coronoid fracture morphology. In the intact group, 20 patients with an intact anterolateral coronoid fracture fragment. In the comminuted group, 12 patients with comminuted anterolateral coronoid fracture fragments extended the less sigmoid notch of the ulna. There was no difference in age, sex, total incision length, follow‐up duration, and recovery with rehabilitation among the two groups (all Ps >0.05). The other follow‐up outcomes, such as elbow ROM (Flexion, Extension, Posterior rotation, Anterior rotation), VAS score, or Broberg–Morrey scores, were not different between the two groups (all Ps >0.05). Both groups achieved relatively satisfactory clinical outcomes, and the Broberg–Morrey score and index excellence rate reached 84.38%. There is a statistical difference in the history of elbow dislocation (P = 0.017), radial head fracture type (P = 0.041), operation duration (P = 0.014) and blood loss at operation (P = 0.029) between the two groups. Cannulated screws, anchors, and sutures were used as point fixation in the coronoid process of the ulna. There was a statistical difference between the two groups in the choice of internal fixation (P = 0.020). Conclusions For anterolateral ulnar coronoid fractures with different degrees of comminution, effective and reliable surgical treatment can achieve better results and fewer complications.

Objective Calcar comminution has been considered to be the main cause of the failure of internal fixation and fracture nonunion in proximal humerus surgery. Anatomical reduction and increasing the strength of internal fixation is the key to success. The purpose of this study was to investigate the short‐term clinical effect of dual plate fixation in the treatment of proximal humeral fractures with calcar comminution. Methods The data of 37 patients with proximal humeral fractures with calcar comminution, treated in our departments from July 2018 to April 2020, were retrospectively analyzed. These patients were treated with anterior plate and lateral PHILOS plate, and followed up for more than 12 months, including 25 cases in Tianjin Hospital and 12 cases in Shanghai General Hospital. The patients included 12 males and 25 females, their age was 54.89 ± 13.59 years (range from 32–79 years), and 21 patients had dominant hand injury. According to the Neer classification, there were 11 two‐part fractures, 22 three‐part fractures, and four four‐part fractures. The range of motion of the shoulder joint, visual analog scale (VAS), American Shoulder and Elbow Surgeons Shoulder Score (ASES), Constant–Murley shoulder score, neck‐shaft angle, anterior–posterior angle, and other complication scores were recorded at the last follow‐up. Results All 37 patients were followed up after operation, and the follow‐up time was 21.81 ± 7.35 months (range from 12–36 months). The fractures of all 37 patients had healed at the last follow‐up visit. The neck‐shaft angle measured immediately after operation was 132.59° ± 8.34°, and the neck‐shaft angle measured at the last follow‐up visit was 132.38 ± 8.53°. The anterior–posterior angle measured immediately after surgery was 3.45° ± 0.81°, and the anterior–posterior angle at the last follow‐up visit was 3.66° ± 0.77°. The range of motion of the shoulder joint was as follows: the shoulder joint could be forward elevated by 158.11° ± 13.09° (range: 140°–180°), rotated externally by 38.38° ± 7.55° (range: 20°–45°), and internally rotated to T4‐L4 level. The VAS score was 0.46 ± 0.87 (range: 0–3), the ASES was 86.58 ± 8.79 (range: 56.7–100), and the Constant–Murley score was 88.76 ± 8.25 (range: 60–100). Thirty‐three cases were excellent, and four cases were good. No obvious complications occurred. Conclusion The combination of anterior plate and lateral PHILOS plate in the treatment of proximal humeral fractures with calcar comminution can achieve stable fixation, and the postoperative clinical and imaging outcome was satisfactory. Firstly, the anterior plate can provide temporary stability when the Kirschner wires are removed, which can provide space for lateral plate placement during fracture reduction and fixation. Secondly, additional support by the anterior plate can provide higher stability in complex fractures with calcar comminution.

Abstract Garlic (Allium sativum L.), the underground bulb of the Allium plant in the family Liliaceae, is a common and popular spice that has historically been used to prevent and treat many different diseases such as pain, deafness, diarrhea, tumors, and other healthy problems. Garlic essential oil contains a variety of organosulfur compounds, such as the most representative diallyl disulfides (DADS) and diallyl trisulfides (DATS), which have attracted great interest in medicine, food, and agriculture because of their rich biological activities. This paper reviews the research progress on the composition and bioactivities of garlic essential oil mixtures and the bioactivity of some typical monomeric sulfides in garlic essential oil. The active mechanisms of representative sulfides in garlic essential oil were analyzed, and the applications of garlic essential oil in functional food, food additives, and clinical treatment were discussed. Combined with the current research status, the limitations and development direction of garlic essential oil in the study of molecular mechanism were discussed, which is of great significance to the development of garlic essential oil as a natural and safe alternative medicine for treatment.

Abstract To acquire an accurate location on the occasions, such as in an indoor, tunnel, and valley, where satellite navigation signals fail. The paper designs a pedestrian navigation system by using the zero velocity update procedure technology (ZUPT) and Kalman filter to reduce the location error. The measurement noise characteristic (mean and variance) of the micro electro mechanical systems gyros is unknown and time variant, but in traditional studies, it is usually thought and calculated as a constant. So the optimality of the error estimation of the Kalman filter cannot be reached. To address this question, this paper proposes the improved Sage–Husa Adaptive Kalman Filter (SHAKF) based on the index fading memory factor to realise the state estimation of the Kalman filter and navigation error correction. The advantage of improved SHAKF is it can accurately estimate the state vector when the measurement noise is unknown and time variant. To verify the validity of novel navigation methods, walking experiments under outdoor environments and indoor environments are carried out. The results of actual walking experiments demonstrate that the proposed method can effectively reduce the pedestrian location error compared with the traditional ZUPT method. The mean location error is reduced by more than 10%, and the variance of the location error is reduced by more than 5%.

Abstract Aims Recovery of blood flow is a therapeutic approach for myocardial infarction but paradoxically induces injury to the myocardium. Exosomes (exos) are pivotal mediators for intercellular communication that can be released by different cells and are involved in cardiovascular diseases. This study aimed to explore the possible effects and mechanisms of miR‐155‐5p loaded by serum‐derived exos in myocardial infarction reperfusion injury (MIRI). Methods and results Exos were isolated from mouse serum after induction of ischaemia reperfusion (I/R) and injected into I/R‐treated mice to assess cardiac function, infarction size, and cardiomyocyte apoptosis. Primary cardiomyocytes were transfected with miR‐155‐5p inhibitor before treatment with oxygen–glucose deprivation and re‐oxygenation (OGD/R) and exos derived from the serum of I/R‐treated mice (I/R‐Exos), in which Bcl‐2, Bax, and cleaved‐caspase‐3 levels were detected. The interactions among miR‐155‐5p, NEDD4, and CypD were evaluated. miR‐155‐5p level was evidently increased in I/R‐Exos than in exos from the serum of sham‐operated mice (P

Abstract Background Inhibition of CDK7, a potent transcription regulator, may bring new hope for treating pancreatic ductal adenocarcinoma (PDAC), which is featured by large genetic heterogeneity and abundant KRAS mutations. This investigation aimed at exploring the discrepant efficacies of THZ1, a small‐molecule covalent CDK7 inhibitor, on PDACs with different KRAS mutations and the underlying mechanisms. Methods Associations of CDK7 expression with survival by KRAS mutations were first assessed. Effects of THZ1 on PDAC by different KRAS mutations were then investigated in vitro and in vivo. Moreover, the effects of THZ1 on gene transcription and phosphorylation of RNA polymerase II (RNAPOLII) in different KRAS mutant PDACs were assessed, and the effect of THZ1 on super‐enhancer activity was evaluated using chromatin immunoprecipitation sequencing. Lastly, the effects of THZ1 on the binding of H3K27ac to PIK3CA and on the PI3K/AKT/mTOR signalling were analysed. Results High CDK7 expression was significantly linked to worse survival within PDAC patients carrying KRAS‐G12V mutation but not in those with KRAS‐G12D mutation. The apoptosis‐inducing effect of THZ1 was markedly stronger in KRAS‐G12V PDAC than KRAS‐G12D cancer. THZ1 significantly inhibited the growth of xenograft tumour with KRAS‐G12V mutation, and the inhibition was markedly stronger than for KRAS‐G12D tumour. In mini‐cell‐derived xenograft (CDX) models, THZ1 significantly suppressed KRAS‐G12V PDAC but not KRAS‐G12D cancer. THZ1 significantly suppressed the phosphorylation of RNAPOLII, and this effect was stronger in KRAS‐G12V PDAC (especially at ser5). KRAS‐G12V PDAC had more H3K27ac‐binding super‐enhancers, and the inhibition of THZ1 on super‐enhancer activity was also stronger in KRAS‐G12V PDAC. Furthermore, THZ1 significantly weakened the binding of H3K27ac to PIK3CA in KRAS‐G12V PDAC. THZ1 significantly suppressed the PI3K/AKT/mTOR pathway and its downstream markers, and this effect was stronger in KRAS‐G12V cells. Conclusions In this hypothesis‐generating study, THZ1 might selectively inhibit certain PDACs with KRAS‐G12V mutation more potently compared with some other PDACs with KRAS‐G12D mutation, which might be associated with its effect on super‐enhancer activity and the PI3K/AKT/mTOR signalling. Our findings might offer novel key clues for the precise management of PDAC and important evidence for future targeted trial design. Highlights THZ1 had a stronger effect on PDAC‐bearing KRAS‐G12V mutation than G12D mutation. Suppressive effect of THZ1 on phosphorylation of RNAPOLII was stronger in KRAS‐G12V than KRAS‐G12D PDAC. Inhibition of THZ1 on super‐enhancer activity and H3K27ac binding to PIK3CA was stronger in KRAS‐G12V PDAC. Suppressive effect of THZ1 on PI3K/AKT/mTOR pathway was stronger in KRAS‐G12V PDAC.

Abstract Two major trans‐basin mooring arrays, the Rapid Climate Change‐Meridional Overturning Circulation and Heatflux Array (RAPID) at 26.5°N since 2004 and the Overturning in the Subpolar North Atlantic Program (OSNAP) situated at 53°–60°N since 2014, have been continuously monitoring the Atlantic Meridional Overturning Circulation (AMOC). This study explores the connectivity of AMOC across these two mooring lines from a novel adiabatic perspective utilizing a model‐based data set. The findings unveil significant in‐phase connections facilitated by the adiabatic basinwide redistribution of water between the two lines on a monthly timescale. This adiabatic mode is a possible cause for the observed subpolar AMOC seasonality by OSNAP. Furthermore, the Labrador Sea was identified as a hotspot for adiabatic forcing of the overturning circulations, primarily attributed to its dynamic isopycnal movements.

Abstract Background The molecular mechanism of the significant role of long noncoding RNAs (lncRNAs) in the progression and metastasis of gastric cancer (GC) remains largely elusive. Our objective is to detect overexpressed lncRNA in GC and investigate its role in promoting epithelial‐mesenchymal transition and tumour microenvironment remodel. Methods LncRNA differential expression profile in GC was analysed using RNA microarrays. The level of LINC00501 was evaluated in both GC patient tissues and GC cell lines by quantitative reverse transcription PCR and large‐scale (n = 304) tissue microarray. To explore the biological role and regulatory driver of LINC00501 in GC, various experimental techniques including Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) assay, dual luciferase assays were performed. Results Clinically, it was observed that LINC00501 level was abnormal overexpression in GC tissue and was associated with GC progression and distant metastasis. Gain and loss molecular biological experiments suggested that LINC00501, promoted EMT process and angiogenesis of GC. Mechanically, the enrichment of H3K27 acetylation in LINC00501 promoter region contributed to the increase of LINC00501 in GC. LINC00501 transactivated transcription of SLUG, by recruiting hnRNPR to its promoter. The growth of GC was inhibited both in vitro and in vivo by suppressing the level of LINC00501 using pharmacological intervention from the histone acetyltransferase (HAT) inhibitor ‐C646. Conclusions This study suggests that LINC00501 promotes GC progression via hnRNPR/SLUG pathway, which indicates a promising biomarker and target for GC.

Abstract DNase‐catalyzed hydrolysis of extracellular DNA (eDNA) has been widely employed to eradicate intractable biofilms. Although aggregation‐induced emission (AIE) has become the ideal tool for killing planktonic bacteria, AIE luminogens (AIEgens) often lack DNase‐mimetic activity, so as to suffer from poor anti‐biofilm capacity. Here, an “AIEzyme”, a kind of AIE nanomaterial with enzyme‐like activity, is designed and synthesized, where the AIEgens are used as the ligands of Zr‐based coordination polymer nanoparticles. Not only does AIEzyme have enduring DNase‐mimetic activity with low activation energy, but also structural rigidity‐stabilized fluorescence. Due to the long‐acting hydrolysis for eDNA in biofilm, AIEzyme can efficiently disorganize the established biofilms with good penetrability and realize the healing of superbug‐infected wounds under only one dose of AIEzyme. This work provides a strategy to endow ordinary AIEgens with DNase‐like and anti‐biofilm activities. Moreover, AIEzymes can be observed by virtue of their own AIE character, facilitating the study on self‐positioning and residual amount of AIEzymes in wounds. The concept “AIEzyme” would hopefully stimulate the tremendous expansion for the tool kits and the application of AIEgens and artificial enzymes.

Abstract Proton exchange membrane fuel cells (PEMFCs) have garnered significant attention due to their high efficiency and low emissions. However, PEMFC always suffers mass transfer and water management in performance improvement. Herein, an integrated gas diffusion layer (GDL) with wavy channel and micro‐tunneled rib is designed and prepared to achieve faster and gentler mass transfer and excellent water management capability by laser engraving. Outstandingly, the new integrated GDL can use the back pressure of air as low as 0 and 50 kPa to respectively achieve 80% and 90% of fuel cell performance realized under pure oxygen. Such high performance is mainly due to the turbulent flow caused by wavy channel and express removing pathway of liquid water provided by micro‐tunneled rib. Moreover, the new integrated GDL also shows wide humidity tolerance from 40% to 100% and a very high specific volume power density of 16,300 W L−1 due to the thin thickness of new integrated GDL. This new integrated GDL is expected to be widely used in PEMFC and other energy conversion devices.

Abstract Background Cancer is mostly a disease of aging, and older patients with cancer are generally frailer. This study aimed to describe the characteristics and in‐hospital outcomes and explore factors associated with duration, cost, and mortality during first hospitalization, in older patients with cancer admitted to a top‐ranked hospital in China. Methods Data on patients with solid cancer ≥65 years consecutively hospitalized in 2016–2020 were retrieved from the electronic medical records of Ruijin Hospital in Shanghai, China. Baseline characteristics, duration, cost, and mortality during hospitalization were described. Factors associated with duration, cost, and mortality during first hospitalization were explored using multivariable‐adjusted logistic regression. Results 20,650 eligible patients with male proportion of 59% and median age of 70 years were analyzed. 45% of the patients underwent resection in our hospital. Upon first admission, 49% of patients had hypertension, 19% diabetes, 22% weight loss, and 28% risks of malnutrition. The median duration and cost of first hospitalization were 9 days and 32,000 RMB, respectively. 118 (0.6%) and 228 (1.1%) deaths occurred during first and any hospitalization, respectively. For first hospitalization, longer duration and higher cost were positively associated with older ages, male gender, emergency admission, certain tumor locations and histology, histories of diabetes, cirrhosis, and anticoagulant intake, higher body mass index, weight loss, reduced food intake, risk of falling, and worse self‐care ability; in‐hospital mortality was positively associated with age ≥85 years, emergency admission, certain cancer types, histories of hypertension and psychotropic intake, reduced food intake, and worse self‐care ability. Conclusions This study identified certain baseline patient and tumor characteristics, medical and medication histories, changes of weight and food intake, diet, and self‐care ability which were independently associated with in‐hospital outcomes among older patients with cancer admitted to our hospital and which should be paid special attention to. While the factors might not be easily modifiable, our study can help identify patients at higher risks of inferior in‐hospital outcomes.

Abstract Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%–50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time‐dependent receiver operating characteristic (ROC), Kaplan–Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein–protein interaction). A unique six‐gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision‐making for individual care.

Abstract Electron‐correlated materials have been drawing ever‐increasing attention due to their fascinating physical behaviors and extensive application scenarios. In this review, a new method for material research and design (R&D), named structural‐functional unit ordering (SFU ordering), which is presented, overcomes the shortcomings—for example, the limitation of finite chemical elements and long R&D circle‐of conventional strategy and thus provides guidance for the design of these high‐performance functional materials on demand. Meanwhile, with the development of material characterization technologies, SFUs of different scales and types can be directly observed, which, moreover, regulate the corresponding orderings. The review, starts with an introduction of the profile for SFU ordering and the synergistic effect between SFUs. Then, studies on several new high‐performance electronic‐correlated materials, for example, a ferromagnetic semiconductor with local spin, ferromagnetic metals with spin topologies, ferroelectric thin films with polar topologies, piezoelectric thin films with nanopillars enclosed by charged boundaries, thermoelectric materials with local ferromagnetic nanoparticles and topotactic phase transformation with conducting nanofilaments are stated in detail one by one. The vital aspect is the breaking of local symmetry, the construction, the structure, of SFUs and their orderings existing or theoretically existing, together with the enhanced/new performance. All in all, the main comments of the review tend to the remaining challenges, promising design approaches for the SFUs, and their orderings for high‐performance functional materials.

Abstract Background SIRT6, an important NAD+‐dependent protein, protects endothelial cells from inflammatory and oxidative stress injuries. However, the role of SIRT6 in cardiac microvascular endothelial cells (CMECs) under ischemia‒reperfusion injury (IRI) remains unclear. Methods The HUVECs model of oxygen–glucose deprivation/reperfusion (OGD/R) was established to simulate the endothelial IRI in vitro. Endoplasmic reticulum oxidase 1 alpha (Ero1α) mRNA and protein levels in SIRT6‐overexpressing or SIRT6‐knockdown cells were measured by qPCR and Western blotting. The levels of H2O2 and mitochondrial reactive oxygen species (ROS) were detected to evaluate the status of oxidative stress. The effects of SIRT6 deficiency and Ero1α knockdown on cellular endoplasmic reticulum stress (ERS), inflammation, apoptosis and barrier function were detected by a series of molecular biological experiments and functional experiments in vitro. Chromatin immunoprecipitation, Western blotting, qPCR, and site‐specific mutation experiments were used to examine the underlying molecular mechanisms. Furthermore, endothelial cell‐specific Sirt6 knockout (ecSirt6−/−) mice were subjected to cardiac ischemia‒reperfusion surgery to investigate the effects of SIRT6 in CMECs in vivo. Results The expression of Ero1α was significantly upregulated in SIRT6‐knockdown endothelial cells, and high Ero1α expression correlated with the accumulation of H2O2 and mitochondrial ROS. In addition, SIRT6 deficiency increased ERS, inflammation, apoptosis and endothelial permeability, and these effects could be significantly attenuated by Ero1α knockdown. The deacetylase catalytic activity of SIRT6 was important in regulating Ero1α expression and these biological processes. Mechanistically, SIRT6 inhibited the enrichment of HIF1α and p300 at the Ero1α promoter through deacetylating H3K9, thereby antagonizing HIF1α/p300‐mediated Ero1α expression. Compared with SIRT6‐wild‐type (SIRT6‐WT) cells, cells expressing the SIRT6‐H133Y‐mutant and SIRT6‐R65A‐mutant exhibited increased Ero1α expression. Furthermore, ecSirt6−/− mice subjected to ischemia‒reperfusion surgery exhibited increased Ero1α expression and ERS in CMECs and worsened injuries to microvascular barrier function and cardiac function. Conclusions Our results revealed an epigenetic mechanism associated with SIRT6 and Ero1α expression and highlighted the therapeutic potential of targeting the SIRT6‐HIF1α/p300‐Ero1α axis.

Abstract Intracellular zinc ion (Zn2+) accumulation disrupts the Zn2+ homeostasis, providing an ion‐overloading anticancer strategy with great potential. The self‐adaptation of tumor cells to ion concentration, however, puts forward higher requirements for the design of ion‐overloading strategy. Herein, “block and attack” antitumor strategy was applied through a composite nanomaterials (UHSsPZH NPs). The strategy demonstrated powerful ion interference ability through both “blocking” the efflux of excess Zn2+ via gene silencing and “attacking” tumor cells via target delivery of ZnO2. After cellular internalization, ZnO2 was degraded to Zn2+ and hydrogen peroxide (H2O2), and the gene expression of zinc transporter 1 (ZnT1) was silenced by targeting of released siRNA, which together caused intracellular Zn2+‐overload. Disorder of Zn2+ further interfered with intracellular Ca2+ homeostasis, inhibited the electron transport chain and promoted the production of endogenous reactive oxygen species (ROS), which assisted the “attack” to tumor cells together with the exogenous ROS generated by UHSsPZH NPs under 980 nm laser irradiation. In summary, this work supplies a “block and attack” strategy for the application of ion homeostasis interference in tumor therapy.

Abstract The molecular mechanisms underlying uric acid (UA)‐induced mitochondrial dysfunction and apoptosis have not yet been elucidated. Herein, we investigated underlying mechanisms of UA in the development of mitochondrial dysfunction and apoptosis. We analyzed blood samples of individuals with normal UA levels and patients with hyperuricemia. Results showed that patients with hyperuricemia had significantly elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which may indicate liver or mitochondrial damage in patients with hyperuricemia. Subsequently, lipidomic analysis of mouse liver tissue mitochondria and human liver L02 cell mitochondria was performed. Compared with control group levels, high UA increased mitochondrial phosphatidylserine (PS) and decreased mitochondrial phosphatidylethanolamine (PE) levels, whereas the expression of mitochondrial phosphatidylserine decarboxylase (PISD) that mediates PS and PE conversion was downregulated. High UA levels also inhibited signal transducer and activator of transcription 3 （STAT3） phosphorylation as well as mitochondrial respiration, while inducing apoptosis both in vivo and in vitro. Treatment with allopurinol, overexpression of PISD, and lyso‐PE (LPE) administration significantly attenuated the three above‐described effects in vitro. In conclusion, UA may induce mitochondrial dysfunction and apoptosis through mitochondrial PISD downregulation. This study provides a new perspective on liver damage caused by hyperuricemia.

Abstract Unsupervised clustering is an essential step in identifying cell types from single‐cell RNA sequencing (scRNA‐seq) data. However, a common issue with unsupervised clustering models is that the optimization direction of the objective function and the final generated clustering labels in the absence of supervised information may be inconsistent or even arbitrary. To address this challenge, a dynamic ensemble pruning framework (DEPF) is proposed to identify and interpret single‐cell molecular heterogeneity. In particular, a silhouette coefficient‐based indicator is developed to determine the optimization direction of the bi‐objective function. In addition, a hierarchical autoencoder is employed to project the high‐dimensional data onto multiple low‐dimensional latent space sets, and then a clustering ensemble is produced in the latent space by the basic clustering algorithm. Following that, a bi‐objective fruit fly optimization algorithm is designed to prune dynamically the low‐quality basic clustering in the ensemble. Multiple experiments are conducted on 28 real scRNA‐seq datasets and one large real scRNA‐seq dataset from diverse platforms and species to validate the effectiveness of the DEPF. In addition, biological interpretability and transcriptional and post‐transcriptional regulatory are conducted to explore biological patterns from the cell types identified, which could provide novel insights into characterizing the mechanisms.

The metaverse, where the virtual and real world are fused, is currently under rapid development. Immersive and vivid experience in the metaverse requires human–machine interaction devices that, unlike those currently available, are simultaneously imperceptible, convenient to use, inexpensive, and safe. Herein, an optical‐nanofiber‐based gesture‐recognition wristband that can accurately recognize gestures and be used to interact with a robotic hand is proposed and realized. Requiring only three optical‐nanofiber‐based pressure sensors, the wristband is simple in structure, convenient to use, and remarkably imperceptible to the user. With the assistance of a machine‐learning algorithm, a maximum recognition accuracy of 94% is achieved for testers with different physiques. A robotic hand can be remotely controlled by the wristband through gestures. The wristband has broad application prospects and is a promising solution for advanced human–machine‐interaction devices. An interactive preprint version of the article can be found here: https://doi.org/10.22541/au.167022827.77928491/v1.

Abstract Patient enrollment, data sharing, and data privacy are enormous medical challenges for clinical trial studies. In recent years, blockchain technology has drawn the attention of various researchers and institutes. As a new and innovative distributed ledger technology, blockchain can be critical to addressing these challenges, thus making clinical research transparent and building public trust fairly and openly. However, the existing literature lacks a comprehensive survey on the adoption of blockchain in clinical trials. To fill the research void, this paper presents a punctilious taxonomy of blockchain technology in clinical trials according to the literature. This taxonomy comprises decentralized scenarios, decentralized practices, blockchain types, deployment methods, and consensus algorithms. The results show that blockchain technology can cover all aspects of the clinical trial study in a decentralized, secure, transparent manner. Besides, some open research challenges of blockchain are categorized into three groups: technical challenges, security challenges, and organizational challenges. Moreover, some recent blockchain projects, micro applications in clinical trials, and several research areas or technologies for future research and development are discussed.