Search

Abstract Connected and autonomous driving technologies offer a novel solution for intersection control optimization. Connected and autonomous vehicles (CAVs) can access signal plans and optimize trajectories to minimize delays and reduce fuel consumption. However, optimizing trajectories for individual vehicles significantly increases complexity, especially for joint optimization of traffic signals and vehicle trajectories. Given the current technical, regulatory, and policy constraints, a superior intersection management approach is necessary before fully automated driving is achieved. This paper introduces an adaptive coupling control (ACC) method based on vehicle platooning to optimize signal timings and vehicle trajectories in mixed traffic. Initially, vehicle platoon segmentation is conducted, led by CAVs. The study then proposes a single‐layer coupled optimization model based on vehicle platoons, simplifying the joint optimization model. To address logistic constraint difficulties, a linearization of the coupled model (LCM) method is developed. Numerical experiments demonstrate that the ACC method significantly reduces vehicle delay and fuel consumption. At high CAV penetration rates (0.8 < R

Abstract Aims A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well‐known HR‐lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. Methods and results This multicentre, single‐arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment‐emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor–neprilysin inhibitor (ARNI) or beta‐blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P

Abstract Carbon reduction is an important issue of global concern today, and with the construction industry accounting for a significant portion of global carbon emissions, carbon reduction research for the civil engineering industry is becoming increasingly important. The current research on carbon emission of buildings mainly focus on energy consumption, choice of building materials, and energy‐saving technologies. While different construction programs can affect the construction sequence and have a significant impact on carbon emissions, especially for ultra‐high‐rise steel structures. In this paper, carbon emission is introduced as the optimization objective, and a nodal optimization procedure based on carbon emission is given to explore the optimization scheme of ultra‐high‐rise steel structure construction based on carbon emission. Calculations using the carbon emission factor method were carried out to analyze the differences in carbon emissions between different construction schemes and to explore the impact of the method of carbon emission optimization. Results show that the combined lifting scheme can save 463.4 kg carbon emissions and reduce the number of lifts by 780 times.

Abstract With the advancement of coal resources mining to the deep part, the control of the surrounding rock of the roadway has become one of the main problems in the field of mining. At the present stage, the bolt support technology of the roadway in China still faces problems such as unclear support mechanism and poor support effect. Based on the mechanism of bolt support, through theoretical analysis and experimental research, this study proposes the differentiated support technology for roadways based on the mechanical response of the plastic zone and applies this method in the Gada Coal Mine. The results of the study showed that the plastic zones with different shapes have different mechanical responses. compared with other plastic zone shapes, the control method of the roadway with a butterfly‐shaped plastic zone is more complex. Consequently, the support design of a bolt should not only consider the scope of the plastic zone of support construction but also grasp the development law of the plastic zone. Effective support measures should be taken as early as possible for roadways with butterfly‐shaped plastic zones to prevent aggressive development of the butterfly‐shaped plastic zone. Field tests show that this support method realizes the ideal supporting effect in practical applications.

Abstract INTRODUCTION Patients with Alzheimer's disease present with difficulty in lexical retrieval and reversal of the concreteness effect in nouns. Little is known about the phenomena before the onset of symptoms. We anticipate early linguistic signs in the speech of people who suffer from amnestic mild cognitive impairment (MCI). Here, we report the results of a corpus‐linguistic approach to the early detection of cognitive impairment. METHODS One hundred forty‐eight English‐speaking Singaporeans provided natural speech data, on topics of their choice; 74 were diagnosed with single‐domain MCI (38 amnestic, 36 non‐amnestic), 74 cognitively healthy. The recordings yield 267,310 words, which are tagged for parts of speech. We calculate the per‐minute word counts and concreteness scores of all tagged words, nouns, and verbs in the dataset. RESULTS Compared to controls, subjects with amnestic MCI produce fewer but more abstract nouns. Verbs are not affected. DISCUSSION Slower retrieval of nouns and the reversal of the concreteness effect in nouns are manifested in natural speech and can be detected early through corpus‐based analysis. Highlights Reversal of the concreteness effect is manifested in patients with Alzheimer's disease (AD) and semantic dementia. The paper reports a corpus‐based analysis of natural speech by people with amnestic and non‐amnestic mild cognitive impairment (MCI) and cognitively healthy controls. People with amnestic MCI produce fewer and more abstract nouns than people with non‐amnestic MCI and healthy controls. Verbs appear to be unaffected. The imageability problem can be detected in natural everyday speech by people with amnestic MCI, which carries a higher risk of conversion to AD.

Pepper (Capsicum annuum L.) is an economically important crop containing capsaicinoids in the seed and placenta, which has various culinary, medical, and industrial applications. Late embryogenesis abundant (LEA) proteins are a large group of hydrophilic proteins participating in the plant stress response and seed development. However, to date there have been no genome‐wide analyses of the LEA gene family in pepper. In the present study, 82 LEA genes were identified in the C. annuum genome and classified into nine subfamilies. Most CaLEA genes contain few introns (≤ 2) and are unevenly distributed across 10 chromosomes. Eight pairs of tandem duplication genes and two pairs of segmental duplication genes were identified in the LEA gene family; these duplicated genes were highly conserved and may have performed similar functions during evolution. Expression profile analysis indicated that CaLEA genes exhibited different tissue expression patterns, especially during embryonic development and stress response, particularly in cold stress. Three out of five CaLEA genes showed induced expression upon cold treatment. In summary, we have comprehensively reviewed the LEA gene family in pepper, offering a new perspective on the evolution of this family.

ABSTRACT Introduction and aims Sarcopenia is a complication of diabetes mellitus, which can increase hospitalization and lead to poor outcomes. The present study investigated the relationship between the serum musclin concentration and the sarcopenia morbidity in Chinese middle–elderly patients with type 2 diabetes mellitus. Methods We recruited 220 patients with type 2 diabetes mellitus, all of whom completed gait speed, handgrip strength tests, and whole‐body dual‐energy x‐ray measurements to calculate the appendicular skeletal muscle mass index (ASMI). The patients were divided into sarcopenia (n = 110) and non‐sarcopenia groups (n = 110). The serum musclin concentration was measured using an enzyme‐linked immunosorbent assay. Results The serum musclin concentration was significantly lower in the sarcopenia group (712.82 pg/mL) than in the non‐sarcopenia group (922.53 pg/mL). The serum musclin concentration positively correlated with the whole‐body skeletal mass (r = 0.230; P = 0.001). Sarcopenia morbidity declined as the quartile of serum musclin concentration increased (P = 0.001), and a negative correlation was observed between the serum musclin concentration and the prevalence of sarcopenia (odds ratio = 0.998, P = 0.001). The correlation remained when quartiles were considered. Conclusions The serum musclin concentration is an independent protective factor for sarcopenia in Chinese middle‐elderly patients with type 2 diabetes mellitus.

Abstract Objective This study aimed to identify the molecular defects and clinical manifestations in a Chinese family with brachydactyly (BD) type A1 (BDA1) and multiple‐synostoses syndrome 2 (SYNS2). Methods A Chinese family with BDA1 and SYNS2 was enrolled in this study. Whole‐exome sequencing was used to analyze the gene variants in the proband. The sequences of the candidate pathogenic variant in GDF5 was validated via Sanger sequencing. I‐TASSER and PyMOL were used to analyze the functional domains of the corresponding mutant proteins. Results The family was found to have an autosomal‐dominantly inherited combination of BDA1 and SYNS2 caused by the S475N variant in the GDF5 gene. The variant was located within the functional region, and the mutated residue was found to be highly conserved among species. Via bioinformatic analyses, we predicted this variant to be deleterious, which perturb the protein function. The substitution of the negatively charged amino acid S475 with the neutral N475 was predicted to disrupt the formation of salt bridges with Y487 and impair the structure, stability, and function of the protein, consequently, the abnormalities in cartilage and bone development ensue. Conclusions A single genetic variant (S475N) which disrupt the formation of salt bridges with Y487, in the interface of the antagonist‐ and receptor‐binding sites of GDF5 concurrently causes two pathological mechanisms. This is the first report of this variant, identified in a Chinese family with BDA1 and SYNS2.

Abstract Peripheral T‐cell lymphoma (PTCL) is a highly heterogeneous group of mature T‐cell malignancies. The efficacy of current first‐line treatment is dismal, and novel agents are urgently needed to improve patient outcomes. A close association between the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway and tumor promotion exists, revealing prospective therapeutic targets. This study, investigates the role of the cGAS‐STING pathway and its underlying mechanisms in PTCL progression. Single‐cell RNA sequencing showes that the cGAS‐STING pathway is highly expressed and closely associated with PTCL proliferation. cGAS inhibition suppresses tumor growth and impaires DNA damage repair. Moreover, Cdc2‐like kinase 1 (CLK1) is critical for residual tumor cell survival after treatment with cGAS inhibitors, and CLK1 suppression enhances sensitivity to cGAS inhibitors. Single‐cell dynamic transcriptomic analysis indicates reduced proliferation‐associated nascent RNAs as the underlying mechanism. In first‐line therapy, chemotherapy‐triggered DNA damage activates the cGAS‐STING pathway, and cGAS inhibitors can synergize with chemotherapeutic agents to kill tumors. The cGAS‐STING pathway is oncogenic in PTCL, whereas targeting cGAS suppresses tumor growth, and CLK1 may be a sensitivity indicator for cGAS inhibitors. These findings provide a theoretical foundation for optimizing therapeutic strategies for PTCL, especially in patients with relapsed/refractory disease.

Abstract Background Histiocytic necrotizing lymphadenitis (HNL) is a self‐limited inflammatory disease of unknown pathogenesis. A very small fraction of patients with HNL could develop hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder. These patients are diagnosed as HNL with HLH (HNL‐HLH). HNL‐HLH in the pediatric population has been systemically studied, however, the clinical, laboratory, and radiological features and outcomes of adult patients with HNL‐HLH remain to be explored. We aimed to explore the clinical, laboratory, and radiological features and outcomes of adult patients with HNL‐HLH. Methods We collected the clinical data of patients with HNL‐HLH admitted to the First Affiliated Hospital of Nanjing Medical University from October 2010 to June 2015. All the patients underwent lymph node biopsy and have a pathological diagnosis of HNL. The age, gender, clinical presentation, lymph node signs, laboratory findings and imaging data, and pathological findings of the patients were collected. Results In this study, we reported five adult patients with HNL‐HLH. All five patients showed enlarged lymph nodes and prolonged fever. Laboratory findings were consistent with the diagnosis of HLH. 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) showed enlarged lymph nodes with increased FDG uptake and splenic hypermetabolism could be present. All the patients responded well to corticosteroids and had a good prognosis. Two of the five patients were diagnosed with systemic lupus erythematosus during the follow‐up. Conclusions Our study demonstrated that adult patients with HNL‐HLH showed distinct clinical, laboratory, and radiological features. And the prognosis is good and patients could be managed with steroids and supportive care.

Abstract The location and origin of Neoproterozoic‐Cambrian sutures provide keys to understand the formation and evolution of the supercontinent Gondwana. The Larsemann Hills is located near a major Neoproterozoic‐Cambrian suture zone in the Prydz Belt, but has not been examined locally by comprehensive geophysical studies. In this study, we analyzed data collected from a one‐dimensional (1D) joint seismic‐MT array deployed during the 36th Chinese National Antarctic Research Expedition. We found that a sharp Moho discontinuity offset of 6–8 km shows up in the stacked image of teleseismic P‐wave receiver function analysis; coinciding with the abrupt Moho offset, a near‐vertical channel with (a) low resistivity extending to the uppermost mantle depths, and (b) high crustal Poisson's ratio in the crust is identified. These findings provide evidence for the determination of the location and collisional nature of the Prydz belt or a portion of it.

Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.

Abstract Aim To examine how the effects of hardiness, self‐efficacy and positive academic emotion related to the SRL ability of undergraduate nursing students. Design A cross‐sectional survey was designed. Methods A total of 395 Chinese undergraduate nursing students from two undergraduate colleges filled out the questionnaires from May to June 2019. The relationships between hardiness, self‐efficacy, positive academic emotion and SRL ability were analysed by structural equation modelling. Results The response rate was 94.05%. SRL ability was significantly positive correlated with hardiness, self‐efficacy and positive academic emotion in undergraduate nursing students. Self‐efficacy (β = 0.417, p

Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is the most common histological subtype of non‐Hodgkin lymphoma worldwide. The emergence of multiple primary malignancies (MPMs) has been described as a new prognostic factor in many types of tumors. Methods To investigate the morbidity, incidence, and survival of MPM in DLBCL, we retrospectively reviewed the characteristics of 788 patients with DLBCL. Results Forty‐two patients were diagnosed with MPM, and 22 of them were diagnosed with subsequent primary malignancies (SPM) by pathologic biopsy. The incidence of SPM was associated with older age. Germinal center B‐cell‐like (GCB) subtype and earlier Ann Arbor stage DLBCL patients were more prone to SPM. MPM, age, lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group performance status (ECOG PS), Hans classification, and international prognostic index (IPI) score were prognostic risk factors for overall survival (OS). Conclusion These data provide a comprehensive view of MPM in DLBCL. MPM was an independent prognostic factor of DLBCL in univariate analysis.

Abstract Exosomes, membrane‐enclosed vesicles, are secreted by all types of cells. Exosomes can transport various molecules, including proteins, lipids, functional mRNAs, and microRNAs, and can be circulated to various recipient cells, leading to the production of local paracrine or distal systemic effects. Numerous studies have proved that exosomes can pass through the blood—brain barrier, thus, enabling the transfer of peripheral substances into the central nervous system (CNS). Consequently, exosomes may be a vital factor in the exchange of information between the periphery and CNS. This review will discuss the structure, biogenesis, and functional characterization of exosomes and summarize the role of peripheral exosomes deriving from tissues like the lung, gut, skeletal muscle, and various stem cell types in communicating with the CNS and influencing the brain's function. Then, we further discuss the potential therapeutic effects of exosomes in brain diseases and the clinical opportunities and challenges. Gaining a clearer insight into the communication between the CNS and the external areas of the body will help us to ascertain the role of the peripheral elements in the maintenance of brain health and illness and will facilitate the design of minimally invasive techniques for diagnosing and treating brain diseases.

Abstract Bone defects are encountered substantially in clinical practice, and bionic scaffolds represent a promising solution for repairing bone defects. However, it is difficult to fabricate scaffolds with bionic structures and reconstruct the microenvironment to fulfill the satisfying repair effects. In this review article, we first discuss various strategies for the design and construction of bionic scaffolds to promote bone defect repair, especially including the structural construction of the scaffold and the integration of bioactive substances together with the application of external stimuli. We then discuss the roles of artificial intelligence and medical imaging in aiding clinical treatment. Finally, we point out the challenges and future outlooks in developing multifunctional bone repair scaffolds, aiming to provide insights for improving bone regeneration efficacy and accelerating clinical translation.

Abstract Chronic lymphocytic leukemia (CLL) is a hematological malignancy with high metabolic heterogeneity. N6‐methyladenosine (m6A) modification plays an important role in metabolism through regulating circular RNAs (circRNAs). However, the underlying mechanism is not yet fully understood in CLL. Herein, an m6A scoring system and an m6A‐related circRNA prognostic signature are established, and circTET2 as a potential prognostic biomarker for CLL is identified. The level of m6A modification is found to affect the transport of circTET2 out of the nucleus. By interacting with the RNA‐binding protein (RBP) heterogeneous nuclear ribonucleoprotein C (HNRNPC), circTET2 regulates the stability of CPT1A and participates in the lipid metabolism and proliferation of CLL cells through mTORC1 signaling pathway. The mTOR inhibitor dactolisib and FAO inhibitor perhexiline exert a synergistic effect on CLL cells. In addition, the biogenesis of circTET2 can be affected by the splicing process and the RBPs RBMX and YTHDC1. CP028, a splicing inhibitor, modulates the expression of circTET2 and shows pronounced inhibitory effects. In summary, circTET2 plays an important role in the modulation of lipid metabolism and cell proliferation in CLL. This study demonstrates the clinical value of circTET2 as a prognostic indicator as well as provides novel insights in targeting treatment for CLL.

Abstract We examined the Indian Ocean Dipole (IOD)'s predictive ability for El Niño‐Southern Oscillation (ENSO). Our findings indicate that positive IODs have a stronger impact on the subsequent year's ENSO compared to negative IODs. To explain this asymmetry, we proposed the “IOD‐Atlantic‐Pacific” pathway, which involves the Atlantic in boreal winter as an intermediary. The pathway comprises two stages: (a) The asymmetric “IOD‐Atlantic” connection, where positive IODs in autumn trigger winter Atlantic Niño while negative IODs cannot trigger Atlantic Niña. This asymmetry is due to the modulation of the climatological mean state on the IOD‐induced atmospheric anomalies. (b) The “Atlantic‐ENSO” connection, which is symmetric, where winter Atlantic Niño (Niña) promotes the development of La Niña (El Niño), functioning independently of ENSO's self‐oscillation behavior. The Atlantic intermediary mechanism explains the asymmetric connection between IOD and the subsequent year's ENSO and provides the IOD with independent predictive power for ENSO beyond its self‐oscillation.

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0–1 versus 2–3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow‐up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high‐UA‐level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197–1.804]) and medium‐UA‐level group (adjusted HR, 1.478 [95% CI, 1.012–2.160]), compared with the low‐UA‐level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence‐based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.

Abstract Sarcopenia is a progressive skeletal muscle disorder involving the loss of muscle mass and function, associated with an increased risk of disability and frailty. Though its prevalence in dementia has been studied, its occurrence in mild cognitive impairment (MCI) has not been well established. As MCI is often a prelude to dementia, our study aims to investigate the prevalence of MCI among individuals with sarcopenia and to also ascertain whether sarcopenia is independently associated with MCI. The Cochrane Library, PubMed, Ovid, Embase and Web of Science were systematically searched for articles on MCI and/or sarcopenia published from inception to 1 February 2022. We reviewed the available literature on the number of individuals with MCI and/or sarcopenia and calculated odds ratios (ORs) of sarcopenia in MCI and MCI in sarcopenia, respectively. Statistical analyses were performed using the meta package in Stata, Version 12.0. A total of 13 studies and 27 428 patients were included in our analysis. The pooled prevalence of MCI in participants with sarcopenia was 20.5% (95% confidence interval [CI]: 0.140–0.269) in a total sample of 2923 cases with a high level of heterogeneity (P

Abstract This study aims to investigate the underlying mechanisms driving changes in the contemporaneous relationship between El Niño–Southern Oscillation (ENSO) and tropical South Atlantic (TSA) sea surface temperatures (SST) during boreal summer over the past century. Our findings indicate that the negative TSA–ENSO relationship is primarily attributed to persistent ENSO years rather than ENSO transition or development years. This is because of the distinct anomalies observed in both spring ENSO and the tropical North Atlantic (TNA) during ENSO persistent years, whose impacts on summer TSA are of the same sign. Thus, their combined effects lead to a strong TSA anomaly that is opposite to that of ENSO. On a decadal timescale, the frequency of persistent ENSO occurrence can explain the fluctuation of the ENSO–TSA relationship over the past century. These findings enhance our comprehension of the relationship between summer ENSO and the tropical Atlantic SST.

Abstract Acute liver failure (ALF) is a life‐threatening condition. Cell‐based and cell‐free‐based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)‐based bioartificial liver (hUCMSC‐BAL), which is a simple and efficient strategy for ALF. D‐galactosamine‐based pig and mouse ALF models were used to explore the effectiveness of hUCMSC‐BAL and hUCMSC‐sEV therapies. Furthermore, high‐throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR‐139‐5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC‐BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC‐sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC‐sEV miRNA transcriptome analysis showed that miR‐139‐5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR‐139‐5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC‐BAL can inhibit cytokine storms and cell apoptosis through the sEV miR‐139‐5p/PDE4D axis. Therefore, we propose hUCMSC‐BAL as a therapeutic strategy for patients with early ALF.

Ibrutinib exerts promising anticancer effects in chronic lymphocytic leukaemia (CLL). However, acquired resistance occurs during treatment, necessitating the exploration of underlying mechanisms. Although three‐dimensional genome organization has been identified as a major player in the development and progression of cancer, including drug resistance, little is known regarding its role in CLL. Therefore, we investigated the molecular mechanisms underlying ibrutinib resistance through multi‐omics analysis, including high‐throughput chromosome conformation capture (Hi‐C) technology. We demonstrated that the therapeutic response to ibrutinib is associated with the expression of p21‐activated kinase 1 (PAK1). PAK1, which was up‐regulated in CLL and associated with patients' survival, was involved in cell proliferation, glycolysis and oxidative phosphorylation. Furthermore, the PAK1 inhibitor IPA‐3 exerted an anti‐tumour effect and its combination with ibrutinib exhibited a synergistic effect in ibrutinib‐sensitive and ‐resistant cells. These findings suggest the oncogenic role of PAK1 in CLL progression and drug resistance, highlighting PAK1 as a potential diagnostic marker and therapeutic target in CLL including ibrutinib‐resistant CLL.

Introduction The use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) has been suggested to lower the risk of distal embolization and improve first pass revascularization rates in patients with acute ischemic stroke. However, a recent large randomized controlled trial suggests there is no significant difference in initial and final revascularization scores among EVT performed with a BGC versus without. We assessed the influence of BGC use during EVT on first pass (FP) and revascularization (RV) success in a historical database from a multi‐hospital health system. Methods Patients with anterior circulation large vessel occlusion undergoing EVT with stent‐retriever or aspiration between 2012 and 2018 at three Kaiser Permanente Southern California (KPSC) region hospitals were identified from the database. BGC use was determined through manual chart review. A chi‐squared test compared the relationship of BGC use with the primary outcomes. The primary outcomes were FP and RV success using a dichotomized TICI score of 2b or greater. Results 218 patients were included in the study. BGC was used in 35/218 (16%) of patients. There was no significant difference in age (p = 0.65), gender (p = 0.92), presenting NIHSS (p = 0.45), hypertension (p = 0.66), diabetes (p = 0.85), atrial fibrillation (p = 0.36), serum glucose (p = 0.43), or pre‐EVT TPA administration (p = 0.36). Among EVT with BGC, FP success was 13/35 (37%) and EVT without BGC had a FP success of 76/183 (42%); p = 0.71. Successful final RV with BGC occurred in 30/35 (86%) while EVT without BGC had a successful final RV of 162/183 (89%); p = 0.78. Because BGC use occurred only with stent‐retriever treatment, subgroup analysis was performed comparing the BGC group (N = 35) with the non‐BGC stent‐retriever (N = 88) and aspiration thrombectomy (N = 95) groups. There was no significant difference in FP (p = 0.88) or RV success (p = 0.42) between the BGC (37% FP and 86% RV), non‐BGC stent‐retriever (42% FP and 92% RV), and aspiration thrombectomy groups (41% FP and 86% RV). Conclusions Among our population, BGC use was not associated with higher first pass or final revascularization success.

Abstract Using 51 models of the AMIP and historical experiments of CMIP6, we investigate the inter‐model diversity of atmospheric and coupled models in the strength of the Indian Summer Monsoon Rainfall (ISMR)–El Niño‐Southern Oscillation (ENSO) relationship. In atmospheric models, the Walker Circulation (WC) intensity associated with the western Pacific convective activity is most responsible for the inter‐model diversity. Models with strong WC have a strong ISMR–ENSO relationship via enhancing ENSO‐induced anomalies of the WC and monsoon circulation. The secondary source is the monsoon circulation differences associated with meridional rainfall contrast over the Indian monsoon region. In coupled models, the primary (secondary) source is the ENSO amplitude (WC intensity). In observation, the decadal variation of WC can also explain the changes in the ISMR–ENSO relationship. This study provides a basis for improving the model performance and advances our understanding of the observed ISMR–ENSO relationship changes.

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient’s bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians’ understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients.

Human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising candidates for stem cell therapy in clinical trials. Applications of hBMSCs in clinical therapy are limited by cellular senescence due to long-term ex vivo expansion. Metformin, an oral hypoglycemic drug for type 2 diabetes, has been shown to have antiaging effects. However, the mechanisms of metformin in antiaging treatment remain controversial. Here, we used D-galactose (D-gal) to establish an appropriate model of senescent hBMSCs to explore the antiaging effects of metformin. Following metformin treatment with a low concentration range, senescence phenotypes induced by D-gal significantly changed, including generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and cell cycle arrest. In contrast, no apparent change was found in unsenescent hBMSCs. Furthermore, the results show that activation of 5′AMP-activated protein kinase (AMPK) by metformin enhances cell autophagy in senescent hBMSCs. These findings suggest that metformin exerts antiaging function within the low concentration range by enhancing autophagy and exhibits potential benefits for clinical stem cell therapy by ameliorating the ex vivo replicative senescence of hBMSCs.

Purpose. This study investigated the correlation between corneal biomechanical parameters and the speed of myopia progression. Methods. This is a retrospective, multicenter study. Both Chinese and Caucasian children were involved. The follow-up time was at least 12 months. Ocular biometry data including the central corneal thickness (CCT), axial length (AL), corneal keratometry (K), anterior chamber depth (ACD), white-to-white (WTW) distance, and pupil size (PS) were measured. The age of onset, speed of progression of spherical equivalent (SE), and speed of AL elongation were calculated. Data were analyzed using the R programming language. Results. This study comprised 306 eyes of 153 myopic children. 122 children were Chinese, and 31 children were Caucasian. The myopia progression was faster in Chinese children than that in the Caucasian group in both SE progression speed and AL elongation speed. The CCT was negatively correlated with the SE speed of progression (correlation coefficient, R = −0.65, and p=7.25×10−38) and AL speed (R = −0.47 and p=1.62×10−18). CCT was positively correlated with the age of onset (R = 0.35 and p=4.53×10−10). No significant correlation (R > 0.3 and p

Abstract Droughts cause extreme anomalies in tropical forest growth, but the direction and magnitude of tropical forests in response to droughts are still widely debated. Here, we used four satellite‐based canopy growth proxies (CGPs), including three optical and one passive microwave, and in situ fluxes observations from eddy covariance (EC) measurements for a retrospective investigation of the impacts of historical droughts on tropical forest growth from a statistical point of view. Results indicate two opposite directions in drought‐related canopy dynamics across pantropical forests. The canopy of tropical forests with higher CGPs is more vulnerable to drought stress and recovers faster in the post‐drought recovery period. In contrast, the canopy of tropical forests with lower CGPs increases during the drought period and declines in the subsequent recovery period, which is beyond general expectation. In situ measurements from eddy‐covariance flux towers showed that forests with higher gross primary production and latent heat flux decreased photosynthesis and evapotranspiration during the drought period but increased photosynthesis and evapotranspiration faster during the post‐drought recovery period, supporting the findings from satellite observations. Our statistical analysis against climatic factors predicts that higher‐CGPs tress with probably taller and bigger canopies are more responsive to shortage of water availability caused by drought; while lower‐CGPs tress with shorter and smaller canopies are more responsive to sunlight availability and tend to increase their canopy leaves and enhance photosynthesis in sunnier days during the drought period. Our results highlight the differences in tropical forests in responding to drought stress, which are worth incorporated in Earth system models for time‐series evaluations.

Abstract Reducing energy consumption, regardless of fuel or electricity, of ground vehicles is a paramount pursuit in academia and industry. Current research concentrates exclusively on the improvement of the vehicle, but accepts the road conditions as external influences. The innovation of this article is to consider the road conditions, particularly the grade angle, as design variables. It is assumed that the stochastic speed trajectories of all vehicles on the road can be modelled by a Markov chain. The expected value of the average energy consumptions of all vehicles running on the road is defined as the objective function. The optimisation problem is solved by dynamic programming with Markov model. Evaluations have been made on both simulated and measured speed trajectories. For the simulated speed trajectories, the optimal road grade profile designed by the method saves up to 22% energy compared with a flat road. For the measured speed trajectories, the optimal road grade profile saves up to 2.7% transportation energy compared with the actual road profile. Application of this method on building road could lead to considerable energy saving.

Abstract Semantic segmentation is crucial to the autonomous driving, as an accurate recognition and location of the surrounding scenes can be provided for the street scenes understanding task. Many existing segmentation networks usually fuse high‐level and low‐level features to boost segmentation performance. However, the simple fusion may impose a limited performance improvement because of the gap between high‐level and low‐level features. To alleviate this limitation, we respectively propose spatial aggregation and channel fusion to bridge the gap. Our implementation, inspired by the attention mechanism, consists of two steps: (1) Spatial aggregation relies on the proposed pyramid spatial context aggregation module to capture spatial similarities to enhance the spatial representation of high‐level features, which is more effective for the latter fusion. (2) Channel fusion relies on the proposed attention‐based channel fusion module to weight channel maps on different levels to enhance the fusion. In addition, the complete network with U‐shape structure is constructed. A series of ablation experiments are conducted to demonstrate the effectiveness of our designs, and the network achieves mIoU score of 81.4% on Cityscapes test dataset and 84.6% on PASCALVOC 2012 test dataset.

Using magnetically powered microagents as precise delivery carriers is a promising technology for targeted therapy. It is a significant challenge to converge microagents to the desired position without sufficient support of real‐time imaging feedback. Herein, a new drive solution is proposed, which generates a rotating gradient‐based magnetic field by sequentially energizing each coil of the electromagnetic coil system. With this method, a high magnetic field gradient concentrated onto a specific target site is generated, which will attract microagent swarms to automatically converge to the target site from different directions. Based on the established model of rotating gradient magnetic field actuation, the relationship between the current inputs of coils and the location of the aggregation center is characterized, so that the target site can be adjusted in the entire workspace by changing the coil current inputs. The method drives microagents to rotate while moving forward, thereby reducing the viscous resistance and friction on microagents. It does not rely on specific trajectory planning and real‐time visual guidance to navigate microagents, and can drive magnetic microagents with different characteristics such as size, shape, and materials. This research provides a basis for using microagent delivery in clinical applications and precision‐targeted therapy.

Objectives Measure and systematically evaluate the distribution of microhardness in the human skeleton. Methods Three fresh corpses were obtained, aged 62 (male), 45 (female), and 58 years (male). Soft tissues were removed, and all axial and unilateral appendicular bones were freshly harvested. All three skeletons were examined by X‐ray and computed tomography (CT) to exclude skeletal pathology. Only bones from donors with no known skeletal pathology were included in the study. Axial and unilateral appendicular skeleton bones from each of the three donors were obtained, except for ear ossicles, hyoid bone, tailbone, and 14 phalanges of the foot, for which samples were difficult to obtain. Precision bone specimens with a thickness of 3 mm, which were cut with a Buehler IsoMet 11‐1280‐250 low‐speed diamond saw (Buehler, USA), were obtained from all important anatomic sites in a direction perpendicular to the mechanical axis of each bone. Micro‐indentation (the Vickers hardness test) was performed on the surface of each specimen using a microhardness tester with a diamond indenter. Hardness value (HV) was computed for each indentation. Each bone specimen was divided into several regions of interest. Indentations were carefully made and computed. Then we analyzed the data to identify hardness distribution rules at different anatomic sites. Results In total, 5360 indentations were made in 1072 regions of interest in each donor. Hardness of the axial and appendicular bones were all inhomogeneous depending on the anatomic sites, but the distribution of microhardness followed certain rules. The mean hardness value ranged from 24.46 HV (HV = hardness value, kgf/mm2) for the sacrum to 53.20 HV for the shaft of the tibia. The diaphysis was harder than the metaphysis, and the proximal and distal epiphysis had lower values (8.85%– 40.39%) than the diaphysis. Among the long bone diaphyses, the tibia cortical bone (51.20 HV) was the hardest, harder than the humerus (47.25 HV), the ulna (43.26 HV), the radius (42.54 HV), and the femur (47.53 HV). However, in some anatomic sites such as the lumbar vertebra (cortical bone 32.86 HV, cancellous bone 31.25 HV), the cortical shells were sometimes not harder than the internal cancellous bones. The lumbar vertebra (32.86 HV) was harder than the cervical vertebra (28.51 HV) and the thoracic vertebra (29.01 HV). Conclusions The distribution of microhardness in the human skeleton follows certain rules. These distribution rules could be used to predict the mechanical properties of bone and progress in this field could provide data for the basis of a new three‐dimensional printing technique, which may lead to new perspectives for custom‐made implants.

Abstract Circadian rhythms play a crucial role in the health and survival of organisms. However, little is known concerning how intrinsic and extrinsic factors affect animal daily rhythms in the field, especially in nocturnal animals. Here, we investigated the first emergence, mid‐emergence, and return times of Vespertilio sinensis, and also integrated environmental conditions (temperature, humidity, and light intensity) and biotic factors (reproductive status and predation risk) to determine causes of variation in the activity rhythms of the bats. We found that variation in the first emergence time, the mid‐emergence time, and the final return time were distinct. The results demonstrated that the emergence and return times of bats were affected by light intensity, reproductive status, and predation risk in a relatively complex pattern. Light intensity had the greatest contribution to activity rhythms. Moreover, we first investigated the effects of actual predators on the activity rhythms of bats; the results showed that the mid‐emergence time of bats was earlier as predators were hunting, but the final return time was later when predators were present. Finally, our results also highlighted the importance of higher energy demands during the lactation in bats to variation in activity rhythms. These results improve our understanding of the patterns and causes of variation in activity rhythms in bats and other nocturnal animals.

Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma. Histone deacetylase inhibitors (HDACis) have been widely applied in multiple tumours, but the expected efficacy was not observed in DLBCL. Therefore, this study is aimed to explore superior HDACis and optimise a relative combinational therapeutic strategy. Methods The antitumour effects of the drug were evaluated by Cell Counting Kit‐8 (CCK‐8) assay and apoptosis analysis. Single‐cell RNA sequencing (scRNA‐Seq) was used to analyse the intratumoural heterogeneity of DLBCL cells. Whole‐exome sequencing and RNA sequencing were performed to analyse the genetic and transcriptional features. Western blotting, qRT–PCR, protein array, immunohistochemistry, and chromatin immunoprecipitation assays were applied to explore the involved pathways. The antitumour effects of the compounds were assessed using subcutaneous xenograft tumour models. Results LAQ824 was screened and confirmed to kill DLBCL cells effectively. Using scRNA‐Seq, we characterised the heterogeneity of DLBCL cells under different drug pressures, and c‐Fos was identified as a critical factor in the survival of residual tumour cells. Moreover, we demonstrated that combinatorial treatment with LAQ824 and a c‐Fos inhibitor more potently inhibited tumour cells both in vitro and in vivo. Conclusion Altogether, we found an HDACi, LAQ824, with high efficacy in DLBCL and provided a promising HDACi‐based combination therapy strategy.

Abstract Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair.

Background Lp(a) (lipoprotein[a]) plays an important role in predicting cardiovascular events in patients with coronary artery disease through its proatherogenic and prothrombotic effects. We hypothesized that prolonged dual antiplatelet therapy (DAPT) might be beneficial for patients undergoing percutaneous coronary intervention who had elevated Lp(a) levels. This study aimed to evaluate the effect of Lp(a) on the efficacy and safety of prolonged DAPT versus shortened DAPT in stable patients with coronary artery disease who were treated with a drug‐eluting stent. Methods and Results We selected 3201 stable patients with CAD from the prospective Fuwai Percutaneous Coronary Intervention Registry, of which 2124 patients had Lp(a) ≤30 mg/dL, and 1077 patients had Lp(a) >30 mg/dL. Patients were divided into 4 groups according to Lp(a) levels and the duration of DAPT therapy (≤1 year versus >1 year). The primary end point was major adverse cardiovascular and cerebrovascular event, defined as a composite of all‐cause death, myocardial infarction, or stroke. The median follow‐up time was 2.5 years. Among patients with elevated Lp(a) levels, DAPT >1 year presented lower risk of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis compared with DAPT ≤1 year. In contrast, in patients with normal Lp(a) levels, the risks of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis were not significantly different between the DAPT >1 year and DAPT ≤1 year groups. Prolonged DAPT had 2.4‐times higher risk of clinically relevant bleeding than shortened DAPT in patients with normal Lp(a) levels, although without statistical difference. Conclusions In stable patients with coronary artery disease, who underwent percutaneous coronary intervention with a drug‐eluting stent, prolonged DAPT was associated with reduced risk of cardiovascular events among those with elevated Lp(a) levels, whereas it did not show statistically significant evidence of benefit for reducing ischemic events and tended to increase clinically relevant bleeding among those with normal Lp(a) levels.

Abstract In this study, we tested soil water reflectometers represented by the CS65x series soil water reflectometers. The objectives were to (a) quantify the sensing volume of the CS65x sensors, (b) evaluate common univariate and multivariate calibration models, and (c) assess the implications of using uncalibrated sensors. The support volume was determined by analyzing the response of the bulk dielectric permittivity to a changing amount of surrounding media in the radial and axial directions of the sensor. Calibration models were tested using a dataset of ∼300 soil samples spanning nine soil textural classes. A time series of rootzone soil water storage recorded in two contrasting soils and two intensive (n ∼300) spatial surveys of near‐surface soil moisture were used to quantify the implications of using uncalibrated sensors. The electromagnetic signal of CS655 was concentrated within a ∼3.5‐cm radius around the center of the sensor rods. Univariate and multivariate calibration equations reduced the mean absolute error (MAE) in soil moisture observations by ∼40% compared with factory default equations. Uncalibrated sensors did not change the pattern of soil moisture temporal dynamics but resulted in a strong bias in soil water storage in a silty clay loam soil and altered the soil moisture spatial patterns obtained in moderate to wet field conditions in a silty clay soil. The CS655 sensor with the Kargas and Soulis calibration equation (MAE = 0.026 cm3 cm−3) appears to be an acceptable candidate for deployment in soil moisture monitoring networks seeking to avoid site‐specific sensor calibrations.

Objective To evaluate the clinical efficacy of micro‐locking plate through vertical or parallel technique for treatment of Dubberley B‐type capitellar fractures. Methods A retrospective analysis was performed in 24 patients (17 males and seven females, with an average age of 44.9 years, range from 19 to 75 years) with capitellar fractures that were treated with micro‐locking plate using vertical or parallel technique between January 2016 to January 2019. The inclusion criteria include closed capitellar fracture, normal anterior elbow joint movement before injury, and recent capitellar fracture with injury within past 3 weeks. Fractures classified according to Dubberley included four cases of type IB, eight cases of type IIB, and 12 cases of type IIIB. Radiographic evaluation was performed. Surgery time, blood loss, range of motion of the elbow, forearm rotation, and complications were recorded. Elbow joint function was evaluated by Mayo Elbow Performance Score (MEPS). Results The mean follow‐up period was 19.6 months (range, 12–36 months). The average clinical healing time for fractures was 11.2 ± 3.2 weeks (range, 8–20 weeks). Fracture united in all patients. Two patients showed slight delayed union, but union was achieved eventually. The mean time from injury to surgery was 6.3 ± 3.1 days (range, 2–15 days). The average surgical time was 68.1 ± 11.5 min (range, 50–90 min), and the mean blood loss was 75.2 ± 26.5 mL (range, 40–120 mL). The mean range of flexion was 122.5° ± 10.5°(range, 95°–140°). The mean range of extension was 8.5° ± 5.8°(range, 0°–20°). The mean range of pronation was 79.7° ± 8.0°(range, 65°–90°). The mean range of supination was 80.5° ± 7.1°(range, 60°–90°). The mean MEPS at final follow‐up was 89.8 ± 9.0 (range, 60–100). Based on the MEPS, 18 (75%) patients had excellent, five (20.8%) patients had good, and one (4.2%) patient had fair. None of the 24 patients suffered vascular or nerve injury. One patient showed superficial infection, which was treated with surgical dressing. Conclusions The vertical or parallel technique of the micro‐locking plate is an excellent method for treating Dubberley B‐type capitellar fractures.

Chondroitin polymerizing factor (CHPF) plays an important role in the development of certain malignant tumors. However, the role of CHPF in breast carcinoma (BRCA) and its underlying mechanism are still not fully elucidated. Expression profiles for CHPF in BRCA tissues were retrieved from The Cancer Genome Atlas database and used for prognostic analysis. Cell viability, invasion and migration were measured in vitro using MCF7 and MDA‐MB‐231 cell lines upon knockdown or over‐expression of CHPF. Bioinformatic analysis showed that CHPF was substantially upregulated in BRCA tissues, and a quantitative reverse transcriptase‐PCR was performed to confirm its upregulation in BRCA cells. High expression of CHPF was observed to be significantly associated with pathologic stage, metastasis and worse prognosis. We also observed that depletion of CHPF significantly inhibited cell proliferative, invasive and migratory abilities, whereas overexpression of CHPF exerted the opposite effects. Furthermore, analysis of the GEPIA database revealed that CHPF expression is positively correlated with the epithelial–mesenchymal transition‐related markers vimentin, Snail, Slug and motion‐related protein matrix metallopeptidase 2; these findings were confirmed via western blotting. Our data suggest that CHPF may contribute to BRCA progression by modulating epithelial–mesenchymal transition‐related markers and matrix metallopeptidase 2 expression.

Abstract We described protein A immunoadsorption combination with immunosuppressive treatment improved rapidly a patient with Neuropsychiatric systemic lupus erythematosus.

Background Transient receptor potential canonical (TRPC) channels play a role in angiogenesis. However, the involvement of TRPC1 in myocardial infarction (MI) remains unclear. The present study was aimed at investigating whether TRPC1 can improve the recovery of cardiac function via prompting angiogenesis following MI. Methods and Results In vitro, coronary artery endothelial cells from floxed TRPC1 mice and endothelial cell‐specific TRPC1 channel knockout mice were cultured to access EC angiogenesis. Both EC tube formation and migration were significantly suppressed in mouse coronary artery endothelial cells from endothelial cell‐specific TRPC1 channel knockout mice. In vivo, coronary artery endothelial cells from floxed TRPC1 and endothelial cell‐specific TRPC1 channel knockout mice were subjected to MI, then echocardiography, triphenyltetrazolium chloride staining and immunofluorescence were performed to assess cardiac repair on day 28. Endothelial cell‐specific TRPC1 channel knockout mice had higher ejection fraction change, larger myocardial infarct size, and reduced capillary density in the infarct area compared with coronary artery endothelial cells from floxed TRPC1 mice. Furthermore, we found underlying regulation by HIF‐1α (hypoxic inducible factor‐1α) and MEK‐ERK (mitogen‐activated protein kinase/extracellular signal‐regulated kinase) that could be the mechanism for the angiogenetic action of TRPC1. Significantly, treatment with dimethyloxaloylglycine, an activator of HIF‐1α, induced cardiac improvement via the HIF‐1α‐TRPC1‐MEK/ERK pathway in MI mice. Conclusions Our study demonstrated TRPC1 improves cardiac function after MI by increasing angiogenesis via the upstream regulator HIF‐1α and downstream MEK/ERK, and dimethyloxaloylglycine treatment has protective effect on MI through the HIF‐1α‐TRPC1‐MEK/ERK pathway.