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Objective Osteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in‐depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single‐cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease. Methods Single cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP‐counter, and ssGSEA algorithms. Real‐time fluorescence quantitative PCR (RT‐qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults. Results In OP samples, the proportions of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT‐qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65–0.90), immature B cells (0.76–0.92), and endothelial cells (0.79–0.87), while showing negative correlations with myeloid‐derived suppressor cells (negative 0.54–0.73), T follicular helper cells (negative 0.71–0.86), and natural killer T cells (negative 0.75–0.85). Conclusion Neutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.

Abstract Aims The endoscopic treatment of esophagogastric varices is challenging, and the nationwide application of endoscopic therapies for various types of esophagogastric varices and different clinical scenarios remains unclear. This study investigated the use of endoscopic therapy for portal hypertension in China. Methods This study used a questionnaire survey initiated by the Liver Health Consortium in China to investigate the use of endoscopic therapies for portal hypertension. Questionnaires were released online from January 30, 2023 to February 28, 2023 and filled out by chief physicians or senior instructors responsible for endoscopic therapies in participating hospitals across 31 provinces (autonomous regions and municipalities) in China. Comparisons of guideline adherence between primary and referral medical centers were performed using the chi‐square test or Fisher's exact test. Results In total, 836 hospitals participated in the survey. For primary and secondary prophylaxis of esophagogastric variceal bleeding (EGVB), adherence to the national guidelines was 72.5% (606/836) and 39.2% (328/836), respectively. Significant differences were observed in the rate of adherence between the primary and referral centers for primary (79.9% [111/139] vs. 71.0% [495/697], p = 0.033) and secondary prophylaxis (27.3% [38/139] vs. 41.6% [290/697], p = 0.002). Of the hospitals, 78.2% (654/836) preferred endoscopic therapies for acute EGVB, and the timing of endoscopy was usually within 12 h (48.5%, 317/654) and 12–24 h (36.9%, 241/654) after bleeding. Endoscopic therapy was more likely to be the first choice of treatment for acute EGVB in referral centers than in primary centers (82.6% [576/697] vs. 56.1% [78/139], p

Abstract To address the unique challenges of diabetic wound healing, wound dressings, particularly multifunctional hydrogels have garnered considerable interest. For the first time, a novel environmentally friendly soy protein‐based hydrogel is developed to accelerate the healing of diabetic chronic wounds. Specifically, this hydrogel framework is in direct formation through the dynamic Schiff base between oxidized guar gum and epigallocatechin‐3‐gallate (EGCG)‐modified soy protein isolate. Meantime, the addition of Ag+ enhances the cross‐linking of the hydrogel network by forming metal‐ligand bonds with the catechol groups in EGCG. Interestingly, the stretchability (up to 380%), swelling, and rheology properties of the hydrogel can be controlled by fine‐tuning the density of metal‐ligand bonds, endowing them with a high potential for precise matching. Additionally, various dynamic bonds endow hydrogel with excellent self‐healing ability, adhesiveness, and injectability. This hydrogel also exhibits good antibacterial properties, biocompatibility, and cell migration capabilities. Both in vivo and in vitro experiments demonstrated the outstanding anti‐inflammatory capacity of the hydrogel and its ability to modulate macrophage polarization. Consequently, the hydrogel has proven effective in promoting wound healing in a diabetic full‐thickness wound model through enhanced angiogenesis and collagen deposition. This eco‐friendly plant protein hydrogel offers a sustainable solution for wound care and environmental protection.

Abstract Repair and preservation of the injured meniscus has become paramount in clinical practice. However, the complexities of various clinic stitching techniques for meniscus repair pose challenges for grassroots doctors. Hence, there is a compelling interest in innovative therapeutic strategies such as bioadhesives. An ideal bioadhesive must cure quickly in aqueous and blood environments, bind strongly, endure arthroscopic washing pressures, and degrade appropriately for tissue regeneration. Here, we present a tetra‐poly (ethylene glycol) (PEG)‐based hydrogel bioadhesive, boasting high biocompatibility, ultrafast gelation, facile injectable operation, and favorable mechanical strength. In view of the synergistic effects of chemical anchor and physical chain entanglement to tightly bind the meniscus, a seamless interface was formed between the surrounding meniscal tissues and hydrogels, enabling the longitudinal tear of the meniscus fused in situ to withstand large tensile force with the adhesive strength of 541.5 ± 31.4 kPa and arthroscopic washout resistance of 29.4 kPa. Superior to existing commercial adhesives, ours allows sutureless application and arthroscopic assistance, without requiring specialized clinical skills. This research is expected to significantly impact our understanding of meniscal healing and ultimately promote a simpler process for achieving functional and structural recovery in torn menisci.

Abstract Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)‐ or natural aging‐induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY‐abundant culture medium of osteocytes (OCY‐CM) from osteoarthritic mice possess pro‐inflammatory, pro‐osteoclastic, and pro‐neurite outgrowth effects, while OCY‐CM from the intermittent fasting‐treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM‐induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

Abstract Dual‐polarization programmable metasurfaces can flexibly manipulate electromagnetic (EM) waves while providing approximately twice the information capacity. Therefore, they hold significant applications in next‐generation communication systems. However, there are three challenges associated with the existing dual‐polarization programmable metasurfaces. This article aims to propose a novel design to address them. First, the design overcomes the challenge of element‐ and polarization‐independent controls, enabling more powerful manipulations of EM waves. Second, by using more energy‐efficient tunable components and reducing their number, the design can be nearly passive (maximum power consumption of 27.7 mW), leading to a significant decrease in the cost and power consumption of the system (at least two orders of magnitude lower than the power consumption of conventional programmable metasurfaces). Third, the design can operate in a broad bandwidth, which is attractive for practical engineering applications. Both the element and array of the metasurface are meticulously designed, and their performance has been carefully studied. The experiments demonstrate that 2D wide‐angle beam scanning can be realized. Moreover, secure communication based on directional information modulation can be implemented by exploiting the metasurface and an efficient discrete optimization algorithm, showing its programmable, multiplexing, broadband, green, and secure features.

Abstract Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1‐DXd) is elucidated. DAC treatment significantly enhanced anti‐tumor efficacy of I1‐DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1‐DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

Abstract The left atrial appendage (LAA) occluder is an important medical device for closing the LAA and preventing stroke. The device‐related thrombus (DRT) prevents the implantation of the occluder in exerting the desired therapeutic effect, which is primarily caused by the delayed endothelialization of the occluder. Functional coatings are an effective strategy for accelerating the endothelialization of occluders. However, the occluder surface area is particularly large and structurally complex, and the device is subjected to a large shear friction in the sheath during implantation, which poses a significant challenge to the coating. Herein, a hydrogel coating by the in situ UV‐triggered polymerization of double‐network polyelectrolytes is reported. The findings reveal that the double network and electrostatic interactions between the networks resulted in excellent mechanical properties of the hydrogel coating. The sulfonate and Arg‐Gly‐Asp (RGD) groups in the coating promoted hemocompatibility and endothelial growth of the occluder, respectively. The coating significantly accelerated the endothelialization of the LAA occluder in a canine model is further demonstrated. This study has potential clinical benefits in reducing both the incidence of DRT and the postoperative anticoagulant course for LAA closure.

Abstract In this study, a series of high liposoluble near‐infrared emissive aggregation‐induced emission luminogens with triphenylamine derivatives as donor units and 1‐indanone as electron acceptor units are developed. Specifically, MTTOI has promising lipid droplets targeting ability and viscosity‐response characteristics, and it can monitor the viscosity fluctuations in living cells in real time. It is found that MTTOI is able to fulfill the activation of the apoptosis‐related signaling pathways under white light, and it can also activate the ferroptosis to synergize apoptosis resulting in tumor elimination. Interestingly, the occurrence of ferroptosis is positively related to the enhancement of immunogenic cell‐death effect, thus boosting the tumor infiltration of CD8+ T cells and reducing the proportion of regulatory T cells by cooperating with dendritic cells, which can not only carry out primary antitumor treatment, but also prevent tumor metastasis through strong immunological memory effect. Moreover, in vivo experimental results confirm that MTTOI successfully effectuates fatty liver tissue imaging. MTTOI fluorescence signals can be captured at the tumor site after 3 days of administration due to its high fat‐solubility and ease of fusion with tumors. This classic example could promote the further development of phototherapeutic agents in preclinical research and clinical applications.

Abstract Inflammation‐responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)‐responsive injectable hydrogel is constructed by integrating an MMP‐cleavable peptide (pp) into a covalent tetra‐armed poly‐(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro‐regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG‐pp‐PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG‐pp‐PS to transform macrophages into the anti‐inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell‐free strategy on simultaneous immunoregulation and osteoinduction in bone engineering.

Soft grippers are ideal for grasping delicate, deformable objects with complex geometries. Universal soft grippers have proven effective for grasping common objects, however complex objects or environments require bespoke gripper designs. Multi‐material printing presents a vast design‐space which, when coupled with an expressive computational design algorithm, can produce numerous, novel, high‐performance soft grippers. Finding high‐performing designs in challenging design spaces requires tools that combine rapid iteration, simulation accuracy, and fine‐grained optimization across a range of gripper designs to maximize performance, no current tools meet all these criteria. Herein, a diversity‐based soft gripper design framework combining generative design and topology optimization (TO) are presented. Compositional pattern‐producing networks (CPPNs) seed a diverse set of initial material distributions for the fine‐grained TO. Focusing on vacuum‐driven multi‐material soft grippers, several grasping modes (e.g. pinching, scooping) emerging without explicit prompting are demonstrated. Extensive automated experimentation with printed multi‐material grippers confirms optimized candidates exceed the grasp strength of comparable commercial designs. Grip strength, durability, and robustness is evaluated across 15,170 grasps. The combination of fine‐grained generative design, diversity‐based design processes, high‐fidelity simulation, and automated experimental evaluation represents a new paradigm for bespoke soft gripper design which is generalizable across numerous design domains, tasks, and environments.

Abstract Purpose The purpose of our study was to investigate the clinical significance and prognostic role of the systemic immune‐inflammation index (SII) in patients who underwent surgical resection for nonfunctioning pancreatic neuroendocrine tumors (pNETs). Methods We conducted a retrospective analysis of 364 patients with nonfunctioning pNETs. The association between the SII level and clinical parameters was investigated. The receiver operating characteristic (ROC) curve was used to calculate the optimal SII value. Cox proportional hazard analysis was performed to evaluate the prognostic factors. Results Our study included 364 patients with nonfunctioning pNETs who underwent surgery. The median age was 51.0 (43.0, 59.3), and 164 (45.1%) were male. The optimal threshold of SII determined by ROC analysis was 523.95. Higher SII levels were significantly associated with older age (p = 0.001), sex (p = 0.011), tumor size (p = 0.032), and tumor grade (p = 0.002). Recurrence was observed in 70 (19.2%) patients following a median follow‐up of 98 months. Univariate analysis showed that higher SII (p 4 cm (p = 0.015), and G2/G3 grade (p = 0.002) were significantly associated with disease‐free survival (DFS). Multivariate analysis revealed that higher SII (HR: 7.35; 95% CI: 3.44, 15.70; p

Abstract In the prevailing form of the generalized Ohm's law (GOL), −me/e(J/en)⋅∇(J/en) is often neglected. Because of the resemblance to the magnetic tension, we refer to this term as the current tension electric field (ECT). Our theoretical analysis reveals that ECT with a characteristic length of mi/me1/6λe dominates the electron inertia terms in the electron diffusion region (EDR) and is comparable to the electron pressure term in low‐βe conditions. Using particle‐in‐cell simulations, we demonstrate that ECT can contribute significantly to the reconnection electric field and energy dissipation at the boundaries of the inner EDR and in the outer EDR. Positive and negative J ⋅ ECT can be used to identify inner and outer electron diffusion regions, respectively.

Abstract Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as a prime target in the discovery of novel therapeutics. Our review delves into the complexities of epigenetic regulation, exploring its profound effects on tumor initiation, metastatic behavior, metabolic pathways, and the tumor microenvironment. We place a particular emphasis on the dysregulation at each level of epigenetic modulation, including but not limited to, the aberrations in enzymes responsible for DNA methylation and histone modification, subunit loss or fusions in chromatin remodeling complexes, and the disturbances in higher‐order chromatin structure. Finally, we also evaluate therapeutic approaches that leverage the growing understanding of chromatin dysregulation, offering new avenues for cancer treatment.

Abstract Conventional deadbeat predictive current control (DBPCC) based on space vector modulation (SVM) shows quick dynamic responses and a good steady‐state performance in induction motor (IM) drives. However, the motor parameters change during operation due to temperature and saturation changes, leading to inaccurate reference voltage vectors and a degraded performance. Furthermore, conventional DBPCC uses a fixed vector sequence of 0127 over the entire speed range, which results in large current harmonics at high modulation indices. To address the above issues, this paper proposes a robust deadbeat predictive current control (RDBPCC) for IM drives. Based on an ultra‐local model, the proposed method updates the input voltage gain and unknown system components online according to the voltage and current of the previous two control cycles. Because the final control expression contains only the measured stator current and voltage values, the model shows a strong robustness. The steady‐state performance is significantly improved by selecting the optimal vector sequence according to the modulation index based on the principle of current harmonic minimization. The experimental results confirm that, compared with conventional vector control and conventional DBPCC, the proposed method achieves a strong parameter robustness and reduces the current total harmonic distortion (THD) by more than 10% and 20% at high‐modulation indices.

Abstract Objectives Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision. Methods From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm2/m2 (men) and 38.5 cm2/m2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI 2% and sarcopenia. Results Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan–Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence‐free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well‐differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia. Conclusions Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management.

Abstract Background The relationship between glucose fluctuation and the risk of cardiovascular disease (CVD) in patients with diabetes remains elusive. Glycated hemoglobin (HbA1c) variability is a key parameter of glucose fluctuation. Methods PubMed, Cochrane Library, Web of Science, and Embase were searched up to 1 July 2022. Studies reporting associations of HbA1c variability (HbA1c‐SD), coefficient of variation of HbA1c (HbA1c‐CV), and HbA1c variability score [HVS] with the risk of CVD among patients with diabetes were included. We used three different insights (a high‐low value meta‐analysis, a study‐specific meta‐analysis, and a non‐linear dose–response meta‐analysis) to explore the relationship between HbA1c variability and CVD risk. A subgroup analysis was also performed to screen the potential confounding factors. Results A total of 14 studies with 254 017 patients with diabetes were eligible. The highest HbA1c variability was significantly associated with increased risks of CVD (HbA1c‐SD, risk ratio [RR] 1.45; HbA1c‐CV, RR 1.74; HVS, RR 2.46; all p 1 (all p

Abstract Lipid‐based nanostructures have garnered considerable interests over the last two decades, and have achieved tremendous clinical success including the first clinical approval of a liposome (Doxil) for cancer therapy in 1995 and the recent COVID‐19 mRNA lipid nanoparticle vaccines. Compared to liposomes which have a lipid bilayer surrounding an aqueous core, lipid nanoparticles with a particle structure have several attractive advantages for encapsulating poorly water‐soluble drugs such as better stability due to the particle structure, high drug encapsulation efficiency because of a pre‐ or co‐drug‐loading strategy. While many studies have reported the synthesis of lipid nanoparticles for hydrophobic drug encapsulation, the precise control of drug loading and encapsulation efficiency remains a significant challenge. This work reports a new concentration‐controlled nanoprecipitation platform technology for fabricating lipid nanoparticles with tunable drug loading up to 70 wt%. This method is applicable for encapsulating a wide range of drugs from very hydrophobic to slightly hydrophilic. Using this facile method, nanoparticles with tunable drug loading exhibited excellent properties such as small particle size, narrow size distribution, good particle stability, showing great promise for future drug delivery applications.

Background Cardiac hypertrophy (CH) is a well‐established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain‐containing 7B) is a member of the ovarian tumor‐related protease (OTU) family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH. Methods and Results OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine‐stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery‐induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation‐induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation–mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel‐like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site‐linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway. Conclusions These results demonstrate that the OTUD7B‐KLF4 axis is a novel molecular target for CH treatment.

Abstract Colorless‐to‐black switching has attracted widespread attention for smart windows and multifunctional displays because they are more useful to control solar energy. However, it still remains a challenge owing to the tremendous difficulties in the design of completely reverse absorptions in transmissive and colored states. Herein, we report on an electrochemical device that can switch between colorless and black by using the electrochemical process of hybrid organic–inorganic perovskite MAPbBr3, which shows a high integrated contrast ratio of up to 73% from 400 to 800 nm. The perovskite solution can be used as the active layer to assemble the device, showing superior transmittance over the entire visible region in neutral states. By applying an appropriate voltage, the device undergoes reversible switching between colorless and black, which is attributed to the formation of lead and Br2 in the redox reaction induced by the electron transfer process in MAPbBr3. In addition, the contrast ratio can be modulated over the entire visible region by changing the concentration and the applied voltage. These results contribute toward gaining an insightful understanding of the electrochemical process of perovskites and greatly promoting the development of switchable devices.

Abstract Background Regulatory T cells (Tregs) have an important role in accelerating the immunosuppression of tumor. Tregs regulation is a hopeful strategy to improve the dismal prognosis of Esophageal cancer (EC), while its mechanisms have not yet been fully clarified. Methods To characterize the role of Tregs in EC, we comprehensively explored its prognostic value, clinical pathology partnership, related biological functions and potential mechanisms at transcriptome level. Through the integrated analysis of GEO and TCGA datasets, we comprehensively evaluated the Tregs infiltration patterns in EC patients. The correlation between Tregs infiltration and genomic characteristics, as well as biological functions were analyzed by a variety of computational algorithms. Results We observed that Tregs were significantly upregulated in EC and involved in various immune processes. According to TCGA and GEO transcriptional classification schemes, Tregs specific genes were observed to be highly expressed in tumor samples, as well as were closely associated with poor prognosis and worse clinical outcomes. In addition, EC patients can be stratified into high‐risk and low‐risk immune subgroups according to Tregs/macrophages infiltration level, and the results showed significant differences in tumor development, biological processes and probe gene expression pattern. The multi‐variate analysis revealed that the interaction between STAT3 and Foxp3 was a potential prognostic signature of Tregs in EC, especially the modulation effect of STAT3 on Foxp3 expression, which has not been well studied in EC. We also identified that STAT3 and Foxp3 expression presented a high accuracy in predicting Tregs infiltration level in EC patients (AUC: 0.817; 95% CI: 0.756–0.878). Conclusions Our results revealed that Tregs have the potential to predict prognosis and tumor deterioration in EC patients. A comprehensive landscape of Tregs regulation mechanisms will help us interpret the immunosuppression of tumor microenvironment (TME) and novel strategies for EC immunotherapy.

Abstract Background In this study we explored whether one pleural catheter plus single chest tube drainage could achieve a noninferior drainage effect when compared with the traditional two chest tubes in uniportal video‐assisted thoracoscopic surgery (VATS) for an upper pulmonary lobectomy. Methods Patients that underwent an upper pulmonary lobectomy from January to November 2020 were enrolled in this single‐center, randomized, open‐label, noninferiority trial. Prior to closure, patients were randomized to an intervention group who received an improved drainage strategy involving one pleural catheter with one chest tube (24 Fr), while traditional double chest tube drainage was applied for the control group. Results A total of 390 patients entered the study, although 190 were excluded for changing nonuniportal surgical approaches or opting for nonlobectomy resections. Finally, 200 patients were randomized (100 in the intervention group and 100 in the control group). The baseline demographic and clinical characteristics were comparable between the groups. The incidence of pneumothorax in the intervention and control groups was similar on postoperative Day 1 (noninferiority, 10% vs. 13%, p = 0.658). In addition, there were no significant differences in secondary outcomes such as incidence of pneumothorax by Day 30, postoperative chest tube/pleural catheter removal time, amount of drainage on Day 1, total amount of drainage after operation, or postoperative hospitalization. A significantly lower pain score was observed in the intervention group (3.33 ± 0.68 vs. 3.68 ± 0.94, p = 0.003). Conclusions The new strategy is noninferior to double chest tube drainage after an upper pulmonary lobectomy offers superior pain control, and is recommended for an upper lobectomy by uniportal VATS.

Telomerase activation is required for malignant transformation. Recent advances in high‐throughput technologies have enabled the generation of complex datasets, thus providing alternative approaches to exploring telomerase biology more comprehensively, which has proven to be challenging due to the need for laborious assays required to test for telomerase activity. To solve these issues, several groups have analyzed TCGA pan‐cancer tumor datasets by investigating telomerase reverse transcriptase (TERT), the catalytic subunit for telomerase activity, or its surrogates. However, telomerase is a multiunit complex containing not only TERT, but also numerus cofactors required for telomerase function. Here we determined genomic and molecular alterations of 10 well‐characterized telomerase components in the TCGA and CCLE datasets. We calculated a telomerase score (TS) based on their expression profiles and clustered tumors into low, high, and intermediate subtypes. To validate the in silico analysis result, we used immunoblotting and telomerase assays. High TS subtypes were significantly associated with stemness, proliferation, epithelial to mesenchymal transition, hyperactivation of oncogenic signaling pathways, shorter patient survival, and infiltration of dysfunctional T‐cells or poor response to immunotherapy. Copy number alterations in 10 telomerase components were widespread and associated with the level of their expression. Surprisingly, primary tumors and cancer cell lines frequently displayed a homozygous deletion of the TCAB1 gene, encoding a telomerase protein essential for telomerase trafficking, assembling, and function, as previously reported. However, tumors or cells carrying a TCAB1 deletion still exhibited telomerase activity comparable to or even higher than their wildtype counterparts. Collectively, applying telomerase component‐based TS in complex datasets provided a robust tool for telomerase analyses. Our findings also reveal a tight connection between telomerase and other oncogenic signaling pathways; TCAB1 may acts as a dispensable telomerase component. Moreover, TS may serve as a useful biomarker to predict patient outcomes and response to immunotherapy.

Abstract Deadbeat predictive current control (DPCC) has been widely studied in induction motor drives due to its simple concept, quick response and excellent steady‐state performance. However, conventional DPCC uses a lot of motor parameters to predict current and voltage. Therefore, the performance of DPCC is affected by the accuracy of motor parameters in the controller. The performance of DPCC will severely deteriorate when the motor parameters used in the controller deviate greatly from their actual values. To improve the parameter robustness of DPCC, this paper proposes a robust DPCC (RDPCC), which utilizes the error between the measured currents and predicted currents to compensate for the influence of machine parameter mismatches. The proposed method is compared with the conventional DPCC, and the experimental results confirm its strong robustness against motor parameter mismatch.

Abstract Renal cell carcinoma (RCC) seriously threatens people's lives and health. The identification of some precise biomarkers during the process of RCC progression and the pathophysiologic procedure is critical for improving the diagnosis and management of RCC. Evidence suggests that ferroptosis may play a pivotal role in eradicating clear cell RCC (ccRCC, KIRC) tumor cells. We screened out the target prognostic ferroptosis‐associated genes and examined the functions of farnesyl‐diphosphate farnesyltransferase (FDFT1) in 786‐O cells by plasmid transfection. In our study, we identified FDFT1 as a potential marker correlating with ferroptosis in KIRC. Upregulated FDFT1 inhibited cell proliferation, migration, and invasion, and the underlying antitumor effects may occur via the AKT signaling pathway. Our study provides helpful evidence to study the complex physiopathology of KIRC.

Abstract Background The impact of cardiac troponin on the short‐term and long‐term prognosis of patients with sepsis remains uncertain. Therefore, we conducted a meta‐analysis to investigate the role of cardiac troponin as a potential indicator for sepsis mortality. Methods We performed a comprehensive search for articles published before November 2022 using Google Scholar, PubMed, and Web of Science. Inclusion criteria for the studies were: (1) investigation of cardiac troponin, and (2) investigation of sepsis. Exclusion criteria included: (1) inability to obtain or calculate hazard ratio (HR) and 95% confidence interval (CI) for the relationship between cardiac troponin level and sepsis mortality, and (2) reviews, meta‐analyses, and case reports. Analysis of HRs and 95% CIs for the association between cardiac troponin level and sepsis mortality was conducted using STATA 12.0 software. Results Our study included 24 prospective studies (comprising 20,457 sepsis patients) and 4 retrospective studies (comprising 1416 sepsis patients). Meta‐analysis demonstrated that elevated cardiac troponin levels were significantly associated with increased sepsis mortality using a random effects model (HR = 1.57, 95% CI 1.41−1.75). Moreover, elevated cardiac troponin levels were also significantly associated with increased hospital mortality of sepsis (HR = 1.35, 95% CI 1.19−1.53) and long‐term mortality of sepsis (HR = 1.96, 95% CI 1.51−2.55) using the random effects model. Conclusions Overall, our finding revealed that elevated cardiac troponin for sepsis patients was a predictor of hospital and long‐term mortality. Clinicians may treat septic patients with elevated cardiac troponin more cautious to avoid extra death. Moreover, large clinical studies are warranted to validate this association.

Abstract Background To explore and compare the clinical effects of high‐resolution non‐invasive prenatal screening (NIPS‐Plus) for common/uncommon chromosomal aneuploidy and microdeletion/microduplication syndromes (MMS). Methods The current prospective study included a total of 25,380 pregnant women who performed NIPS‐Plus, and amniocentesis was performed on women with MMS with the screening results to diagnose patients with suspected MMS. Results There were 415 samples with positive results for NIPS‐Plus, included 275 with aneuploidy and 140 with MMS. After diagnosis by amniocentesis, 188 cases were confirmed as true positive, included46 cases of T21, 9 cases of T18, 1 case of T13, 34 cases of SCA, 41 cases of other chromosomal euploidy and 57 cases of MMS. In addition, no false negative cases were found, MMS was classified with 5 Mb with the cutoff value, and the PPV of different fragment size was counted, respectively. Conclusion We found that the corresponding PPV was 44.66% with the fragment of copy number variation (CNV) being less than or equal to 5 Mb, and when it was greater than 5 Mb, the PPV was 29.73%, which suggested that NIPS‐Plus was more suitable for screening the PPV of small fragment abnormalities. NIPS‐Plus has a good application effect in routine aneuploidy screening and had the best detection effect for T21; moreover, it performed well in screening of MMS and had better detection effect on MMS with CNV fragment length less than 5 Mb. Based on the current results, we suggested that NIPS‐Plus should be used as a comprehensive elementary prenatal screening method for all pregnant women, but for MMS caused by abnormal large fragment CNV, the detection method and efficiency still need to be improved.

Abstract Background Concealed accessory pathway (AP) may cause atrial ventricular reentrant tachycardia impacting the health of patients. However, it is asymptomatic and undetectable during sinus rhythm. Methods To detect concealed AP with electrocardiography (ECG) images, we collected normal sinus rhythmic ECG images of concealed AP patients and healthy subjects. All ECG images were randomly allocated to the training and testing datasets, and were used to train and test six popular convolutional neural networks from ImageNet pre‐training and random initialization, respectively. Results We screened 152 ECG recordings in concealed AP group and 600 ECG recordings in control group. There were no statistically significant differences in ECG characteristics between control group and concealed AP group in terms of PR interval and QRS interval. However, the QT interval and QTc were slightly higher in control group than in concealed AP group. In the testing set, ResNet26, SE‐ResNet50, MobileNetV3_large_100, and DenseNet169 achieved a sensitivity rate more than 87.0% with a specificity rate above 98.0%. And models trained from random initialization showed similar performance and convergence with models trained from ImageNet pre‐training. Conclusion Our study suggests that deep learning could be an effective way to predict concealed AP with normal sinus rhythmic ECG images. And our results might encourage people to rethink the possibility of training from random initialization on ECG image tasks.

Abstract Room‐temperature phosphorescence (RTP) of purely organic materials is easily quenched with unexpected purposes because the excited triplet state is extremely susceptible to external stimuli. How to stabilize the RTP property of purely organic luminogens is still challenging and considered as the bottleneck in the further advancement of the bottom‐up approach. Here, we describe a gated strategy that can effectively harness RTP by employing complexation/dissociation with proton. Due to the order‐disorder transition orientation of intermolecular packing, the RTP of organic molecules 2,4,6‐tris(4′‐bromo‐[1,1′‐biphenyl]‐4‐yl)‐1,3,5‐triazine (Br‐TRZ) will easily vanish upon mechanical force. Impressively, by enhancing its intramolecular charge transfer effect, the protonated Br‐TRZ stubbornly possesses an obvious RTP under external grinding, whatever in the ordered or disordered intermolecular arrangement state. Consequently, the “Lock” gate of RTP was achieved in the protonated Br‐TRZ molecule. Combined with theoretical calculation analysis, the enhanced charge transfer effect can narrow the singlet−triplet energy gap significantly, and stabilize the RTP property of triazine derivative sequentially. Furthermore, the locked RTP can be tuned via proton and counterions repeatedly and show excellent reversibility. This gated RTP concept provides an effective strategy for stabilizing the RTP emission of purely organic systems.

Abstract Dust deposition is one of the most predominant processes occurring on Mars. Until now, just a few in situ observations have been conducted to investigate the Martian dust. The Multispectral Camera (MSCam) onboard the Zhurong rover with its calibration target can be used to monitor dust deposition, providing a new ground observation. In this work, we focused on the observations of the MSCam calibration target to retrieve atmospheric optical depth and dust deposition rate over the first 300 sols. The derived atmospheric optical depths are around 0.44, suggesting relatively low airborne dust. The estimated dust deposition rate reveals a distinctive deposition process compared with that of other rovers or landers. Notably, no evident dust is presented during the initial 110 sols, after which dust starts to accumulate. Combining in situ meteorological measurements and numerical modeling, wind speed could be a critical factor to control the dust deposition rate.

Abstract Catalytically inactive CRISPR‐Cas13 (dCas13)‐based base editors can achieve the conversion of adenine‐to‐inosine (A‐to‐I) or cytidine‐to‐uridine (C‐to‐U) at the RNA level, however, the large size of dCas13 protein limits its in vivo applications. Here, a compact and efficient RNA base editor (ceRBE) is reported with high in vivo editing efficiency. The larger dCas13 protein is replaced with a 199‐amino acid EcCas6e protein, derived from the Class 1 CRISPR family involved in pre‐crRNA processing, and conducted optimization for toxicity and editing efficiency. The ceRBE efficiently achieves both A‐to‐I and C‐to‐U base editing with low transcriptome off‐target in HEK293T cells. The efficient repair of the DMD Q1392X mutation (68.3±10.1%) is also demonstrated in a humanized mouse model of Duchenne muscular dystrophy (DMD) after AAV delivery, achieving restoration of expression for gene products. The study supports that the compact and efficient ceRBE has great potential for treating genetic diseases.

Abstract In practical application, the motor speed may need to be greater than the rated speed, so field‐weakening control is required. However, the conventional flux‐weakening control requires much tuning work, because multiple PI controllers are used. In order to make the tuning work easier, this paper combines flux‐weakening control with deadbeat predictive current control (DPCC) to eliminate two PI controllers in current loop. In addition, this paper also proposes a speed adaptive flux‐weakening controller, which can further simplify the tuning work. The effectiveness of this method has been confirmed on a 2.2 kW surface permanent magnet synchronous motor (SPMSM) experimental platform.

Abstract Increasing drug loading remains a critical challenge in the development and translation of nanomedicine. High drug‐loading nanoparticles have demonstrated unique advantages such as less carrier material used, better‐controlled drug release, and improved efficacy and safety. Herein, we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading (up to 66.5 wt%) based on phase separation‐induced nanoprecipitation. Upon addition of salt, phase separation occurs in a miscible solvent‐water solution delaying the precipitation time of drugs and polymers to different extents, facilitating their co‐precipitation thus the formation of high drug‐loading nanoparticles with high encapsulation efficiency (>90%) and excellent stability (>1 month). This technology is versatile and easy to be adapted to various hydrophobic drugs, different polymers, and solvents. This salt‐induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading, and opens great potentials for future nanomedicines.

Abstract Double‐network (DN) hydrogels consisting of noncovalent interacting networks are highly desired due to their well‐controlled compositions and environmental friendliness, but the low water resistance always impairs their mechanical strength. Here, an anti‐swelling hydrogel possessing the core/shell architecture through rational regulation of multiple weak noncovalent interactions is prepared. A composite hydrogel consists of chitosan (CS) and poly(N‐acryloyl 2‐glycine) (PACG), readily forming the shell‐structured DN hydrogel after soaking in a FeCl3 solution because of in situ formation of chain entanglements, hydrogen bonds, and ionic coordination. The produced DN hydrogels exhibit excellent anti‐swelling behaviors and mechanical durability for over half a year, even in some strict situations. Taking the merits of noncovalent bonds in adjustability and reversibility, the swelling property of these hydrogels can be easily customized through control of the ion species and concentrations. A dynamically reversible transition from super‐swelling to anti‐swelling is realized by breaking up and rebuilding the metal‐coordination complexes. This facile but efficient strategy of turning the noncovalent interactions and consequently the mechanics and anti‐swelling properties is imperative to achieve the rational design of high‐performance hydrogels with specific usage requirements and expand their applicability to a higher stage.

Abstract The outliers in traffic flow represent the anomalies or emergencies in the road. The detection and research of outliers will help to reveal the mechanism of such events. Aiming at the problem of outlier detection in urban traffic flow, this paper innovatively proposes a highly efficient traffic outlier detection framework based on the study of road traffic flow patterns. The main research works are as follows: (1) data pre‐processing, the road traffic flow matrix of the roads is calculated based on the collected GPS data, the non‐negative matrix factorisation algorithm is chosen to reduce the dimension of the matrix. (2) Road traffic flow pattern extraction, the fuzzy C‐means clustering algorithm with the Optimal k‐cluster centre (K‐FCM) is adopted to cluster the roads with the same road traffic flow pattern. (3) Outlier detection model training and evaluation, kernel density estimation is introduced to fit the probability density of roads traffic flow matrices which are used to train the back propagation neural network based on particle swarm optimisation to obtain the outlier detection and evaluation model, and a threshold is introduced to optimise the precision and recall of the model. The experimental results show that: the average precision and recall of the proposed method in this paper are 95.38% and 96.23%, respectively, and the average detection time is 28.4 seconds. The method has high accuracy, high efficiency and good practical significance.

Abstract Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has wrought havoc on the world economy and people's daily lives. The inability to comprehensively control COVID‐19 is due to the difficulty of early and timely diagnosis, the lack of effective therapeutic drugs, and the limited effectiveness of vaccines. The body contains billions of extracellular vesicles (EVs), which have shown remarkable potential in disease diagnosis, drug development, and vaccine carriers. Recently, increasing evidence has indicated that EVs may participate or assist the body in defence, antagonism, recovery and acquired immunity against SARS‐CoV‐2. On the one hand, intercepting and decrypting the general intelligence carried in circulating EVs from COVID‐19 patients will provide an important hint for diagnosis and treatment; on the other hand, engineered EVs modified by gene editing in the laboratory will amplify the effectiveness of inhibiting infection, replication and destruction of ever‐mutating SARS‐CoV‐2, facilitating tissue repair and making a better vaccine. To comprehensively understand the interaction between EVs and SARS‐CoV‐2, providing new insights to overcome some difficulties in the diagnosis, prevention and treatment of COVID‐19, we conducted a rounded review in this area. We also explain numerous critical challenges that these tactics face before they enter the clinic, and this work will provide previous ‘meet change with constancy’ lessons for responding to future similar public health disasters. Extracellular vesicles (EVs) provide a ‘meet changes with constancy’ strategy to combat SARS‐CoV‐2 that spans defence, antagonism, recovery, and acquired immunity. Targets for COVID‐19 diagnosis, therapy, and prevention of progression may be found by capture of the message decoding in circulating EVs. Engineered and biomimetic EVs can boost effects of the natural EVs, especially anti‐SARS‐CoV‐2, targeted repair of damaged tissue, and improvement of vaccine efficacy.

Abstract The effectiveness of existing tissue‐engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel‐based TEC holds considerable promise in circumventing these problems. Herein, a non‐toxic, biodegradable, and mechanically optimized double‐network (DN) hydrogel consisting of polyethylene glycol (PEG) and kartogenin (KGN)‐conjugated chitosan (CHI) is constructed using a simple soaking strategy. This PEG‐CHI‐KGN DN hydrogel possesses favorable architectures, suitable mechanics, remarkable cellular affinity, and sustained KGN release, which can facilitate the cartilage‐specific genes expression and extracellular matrix secretion of peripheral blood‐derived mesenchymal stem cells (PB‐MSCs). Notably, after tracing the transplanted cells by detecting the rabbit sex‐determining region Y‐linked gene sequence, the allogeneic PB‐MSCs are found to survive for even 3 months in the regenerated cartilage. Here, the long‐term release of KGN is able to efficiently and persistently activate multiple genes and signaling pathways to promote the chondrogenesis, chondrocyte differentiation, and survival of PB‐MSCs. Thus, the regenerated tissues exhibit well‐matched histomorphology and biomechanical performance such as native cartilage. Consequently, it is believed this innovative work can expand the choice for developing the next generation of orthopedic implants in the loadbearing region of a living body.

Abstract Unsupervised clustering is a kind of popular solution for unsupervised person re‐identification (re‐ID). However, due to the influence of cross‐view differences, the results of clustering labels are not accurate. To solve this problem, an unsupervised re ID method based on cross‐view distributed alignment (CV‐DA) to reduce the influence of unsupervised cross‐view is proposed. Specifically, based on a popular unsupervised clustering method, density clustering DBSCAN is used to obtain pseudo labels. By calculating the similarity scores of images in the target domain and the source domain, the similarity distribution of different camera views is obtained and is aligned with the distribution with the consistency constraint of pseudo labels. The cross‐view distribution alignment constraint is used to guide the clustering process to obtain a more reliable pseudo label. The comprehensive comparative experiments are done in two public datasets, i.e. Market‐1501 and DukeMTMC‐reID. The comparative results show that the proposed method outperforms several state‐of‐the‐art approaches with mAP reaching 52.6% and rank1 71.1%. In order to prove the effectiveness of the proposed CV‐DA, the proposed constraint is added into two advanced re‐ID methods. The experimental results demonstrate that the mAP and rank increase by ∽0.5–2% after using the cross‐view distribution alignment constraint comparing with that of the associated original methods without using CV‐DA.

Abstract Both Alzheimer's disease (AD) and osteoporosis (OP) are common age‐associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCYYoung‐EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCYYoung‐EVs are diminished in aged osteocyte‐derived EVs (OCYAged‐EVs). Based on the self‐constructed OCY‐EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY‐EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a‐shRNA adenovirus inhibits OCYYoung‐EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCYYoung‐EVs, compared to OCYAged‐EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY‐EV as a regulator of brain health, suggesting a novel mechanism in bone‐brain communication.

Abstract Photothermal therapy based on conjugated polymers represents a promising antibacterial strategy but still possesses notable limitations. Herein, degradable pseudo conjugated polymers (PCPs) containing photothermal molecular backbones and reactive oxygen species (ROS)‐sensitive thioketal bonds are designed. Triphenylphosphine (PPh3) is introduced into PCPs to generate phosphonium‐based PCPs (pPCPs), which further assembled with hyaluronic acid into pPCP nanoparticles (pPCP‐NPs). pPCP‐NPs with quaternary phosphonium cations selectively anchor on and destroy bacterial cell membranes through electrostatic action. Under 1064 nm laser irradiation, pPCP‐NPs (pPCP‐NPs/+L) produce near‐infrared‐II (NIR‐II) photothermal antibacterial effect, thereby killing bacteria in a sustained manner. pPCP‐NPs are readily degraded upon ROS abundant at infection sites, therefore exhibiting enough biosafety. pPCP‐NPs/+L display an almost 100% bacterial inhibition rate in vitro and resultin a nearly complete recovery of bacteria‐induced mouse wounds. A further metabolomics analysis denotes that pPCP‐NPs/+L work in a concerted way to induce bacterial DNA damage, inhibit bacterial carbon/nitrogen utilization and amino acid/nucleotide synthesis. Taken together, degradable pPCP‐NPs with both NIR‐II photothermal effect and cationic phosphonium structural bacteriostasis provide a new avenue for antibiotics‐alternative anti‐infection therapy.

Liver cancer stem cells (L‐CSCs) are considered to be an important therapeutic target for hepatocellular carcinoma (HCC). This study provides a new in vitro long‐term culture model for a specific subpopulation of L‐CSCs enriched by cell surface markers. We combined CD13, CD133 and EpCAM to selectively enrich L‐CSCs, which we then cultured in modified chemically defined medium. The enriched L‐CSCs exhibited enhanced proliferation, self‐renewal and long‐term clonal maintenance ability as compared with non‐CSCs. Compared with wild‐type hepatocellular carcinoma, the expression of stemness surface markers, oncogenes, drug resistance and tumorigenicity in enriched L‐CSCs was significantly increased. In summary, the subpopulation of L‐CSCs still maintains cancer stem cell‐related phenotypes after 14 days of culture.

Abstract A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY.

Objective: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. Methods: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan–Meier survival curve analysis. Results: After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors’ clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P