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Abstract Commutation failure (CF) is one of the most common issues in line‐commuted converter‐based high voltage direct current systems (LCC‐HVDC), leading to critical power system security and stability problems. Accurate and rapid identification of CF is crucial to prevent subsequent CF in HVDC systems. However, the existing CF identification methods are lack of the required accuracy and speed. The relationship between bridge arm current, commutation voltage, and trigger pulse based on the commutation progress mechanism after the AC fault is analysed in this paper. A novel CF identification method is presented, which utilises the CF identification factor, enabling fast and high‐accurate identification without relying on the value of the extinction angle. The proposed method offers a simpler and more efficient implementation in engineering practice. Finally, the effectiveness of the proposed method is verified in both the standard International Council on Large Electric systems HVDC model and the Hardware in Loop test using practical project parameters. The results demonstrate that the proposed method can accurately and fast identify CF.

Background High levels of catecholamines are cardiotoxic and associated with stress‐induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Methods and Results Purpose‐bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine‐stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High‐dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular‐aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800‐fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular‐aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Conclusions Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion‐induced ischemia. However, epinephrine itself has potentially harmful long‐lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Background Septic shock is associated with increases in end‐diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown. Methods and Results Purpose‐bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular‐arterial coupling, and circumferential strain. Early during sepsis, (0–24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes. Conclusions The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.

Abstract Background Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non‐Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown. Methods The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP‐5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes. Results Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non‐Asians: (weighted mean difference [WMD], −0.59, 95% CI, −0.73 to −0.45, p .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, −5.12, 95% CI, −5.84 to −4.41, p

Abstract Cushing's syndrome is a rare cause of myocardial infarction and heart failure. Herein, we report a female patient who presented acute myocardial infarction and heart failure with reduced ejection fraction. The patient was found to have hypercortisolism secondary to adrenocortical adenoma and responded well to therapy. This case underlines the effects of hypercortisolism on the cardiovascular system. The clinical presentation of this patient is unique because non‐atherosclerotic myocardial infarction is rarely reported in Cushing's syndrome patients.

Abstract Background Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5‐year survival rate. Method Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely‐targeted metabolomics by UPLC‐MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. Results A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p

Abstract Revealing the energy transfer (ET) process from excitons to rare earth ions in halide perovskites has great guiding value for designing optoelectronic materials. Here, the multiple ET channels in multi‐exciton emissive Sb3+/Nd3+ co‐doped Cs2ZrCl6 are explored to comprehend the ET processes. Förster–Dexter ET theory reveals that the sensitizer concentration rather than the overlap integral of the spectra plays the leading function in the comparison of the ET efficiency among multiple ET channels from the host self‐trapped excitons (STEs) and dopant triplet STEs to Nd3+ ions. Besides, Sb3+/Nd3+ co‐doped Cs2ZrCl6 enables varied color delivery and has great potential as anti‐counterfeiting material. Under X‐ray irradiation, Sb3+/Nd3+ co‐doped Cs2ZrCl6 presents a high light yield of ≈13300 photons MeV−1 and promising X‐ray imaging ability. This work provides new insight for investigating the ET efficiency among multiple ET processes and presents great potentiality of multi‐exciton emissive perovskites in the fields of anti‐counterfeiting and X‐ray imaging.

There is no targeted therapy for KRAS proto‐oncogene, GTPase (KRAS)‐mutant metastatic colorectal cancer (mCRC) because the underlying mechanism remains obscure. Based on bioinformatic analysis, this study aims to elucidate a potential gene target for which an approved drug is available, and to reveal the function as well as the underlying mechanism of the candidate gene. Here, we identified that ryanodine receptor 2 (RyR2) expression was upregulated in KRAS‐mutant mCRC, and that this promoted cancer cell metastasis. S107, an approved drug to inhibit calcium release from RyR2 in the clinic, inhibited cancer cell metastasis both in vitro and in vivo. High expression of RyR2 predicts poor survival in our patient cohort. CRC patients with serosa invasion and vascular tumor thrombus are characterized by high RyR2 expression. Analysis of expression profiles upon RyR2 knockdown and inhibition, revealed a set of metastasis‐related molecules, and identified BTB domain and CNC homolog 1 (BACH1) as the main transcription factor regulated by RyR2. RyR2 regulates cellular reactive oxygen species (ROS) levels, which activates nuclear factor erythroid 2‐related factor 2 (Nrf2; also known as NFE2L2) and HMOX1 expression, and thus BACH1 accumulation. Collectively, this study provides evidence that the RyR2/ROS/BACH1 axis may be a potential intervention target for CRC metastasis.

Abstract Over the past few decades, more alcohol‐problem concerns focused on reducing the risk of hangover caused by the alcoholic beverages over‐consumption. Chinese distilled spirits (Baijiu) is one of the most favorite alcoholic beverages. The intention of this study is to explore the associations of main flavor components in Baijiu and hangover symptoms using mice acute alcohol withdrawal model. The behaviors of each mouse were assessed by open‐field tests using separate groups of mice with the treatment of sauce‐aroma Baijiu, light‐aroma Baijiu, strong‐aroma Baijiu, pure alcohol, and distilled water, respectively. The behavioral data including total move distance and immobile time were used as indicators for the evaluation of the liquor intoxicating effects. Alcohol and acetaldehyde concentrations in mice plasma and the neurotransmitter contents of GABA and Glu in mice cerebellum were detected afterward. The results showed that the mice with the treatment of Baijiu samples displayed unusual exciting behaviors including increased alcohol metabolization with alleviating drunken and hangover symptoms, compared with that of pure alcohol control groups after 2–4 h. Moreover, the sauce‐aroma Baijiu treatment group showed lessening intoxicated symptoms than those of light‐aroma Baijiu and strong‐aroma Baijiu. In addition, there were significant differences between Baijiu and pure alcohol treatment groups at the inhibitory neurotransmitter GABAergic levels and its receptor GABA‐AR1 activating levels in the mice neuron cells. Furthermore, the Principal Component Analysis (PCA) analysis inferred that the flavor compounds acetic acid, ethyl acetate, ethyl lactate, and 1‐propanol in the sauce‐aroma Baijiu were played the major roles in the drunk behaviors that caused by the hangover. While, the acetic acid in the sauce‐aroma Baijiu was speculated as a major flavor component to accelerate the alcohol metabolism and retard hangover symptoms.

Abstract Pulmonary adenoid cystic carcinoma (PACC) is an extremely rare neoplasm. Adenoid cystic carcinoma (ACC) usually occurs in the salivary glands of the head and neck. Given its rare occurrence, there are no established guidelines for the treatment of progressive and/or relapsed disease. We herein report a case of a 57‐year‐old female who was incidentally found to have biopsy confirmed PACC following trauma diagnostic workup. She underwent pneumonectomy and adjuvant radiation therapy with an initial good response. On follow‐up a year later, she was noted to have two metastatic liver lesions treated with stereotactic body radiation therapy (SBRT) and lenvatinib. This case report adds to the growing area of research on PACC, especially among patients requiring SBRT for oligometastatic disease.

Abstract Aims/Introduction This study was carried out to assess the association of dehydroepiandrosterone (DHEA) with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus to better predict the progression of diabetic nephropathy. Materials and Methods A total of 1,082 patients with type 2 diabetes mellitus in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital were enrolled in this study, and grouped for comparison. The effect of serum DHEA on DN was evaluated by multivariate logistic regression analysis, and receiver operating characteristic curves were established to explore the optimal concentration of DHEA in patients with DN and non‐DN. Results DHEA was significantly decreased in patients with DN (P

Methyl 7,7′-dimethoxy-5′-(morpholinomethyl)-[4,4′-bibenzo[d][1,3] dioxole]-5-carboxylate methanesulfonate (IMM) is an innovative drug for the treatment of nonalcoholic fatty liver disease (NAFLD) owing to its high efficacy and low toxicity. In this study, five minor impurities (I, II, III, IV, and V) were identified and analyzed using spectroscopic evidence, chemical synthetic methods, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The impurities included hydrolysates and oxidation by-products extracted from both the drug in its final formulation and during synthesis. Toxicity prediction revealed potential carcinogenicity of impurity V containing an N-oxygen fragment. A reliable and selective HPLC method for the quantitative analysis of impurities I–IV and a sensitive HPLC-MS/MS method for potential genotoxic impurity V were developed and optimized. The methods were validated based on the International Council for Harmonization guidelines. Satisfactory linearity was obtained for the analytes over the range of 0.1–2.0 μg/mL for impurities I–IV and 0.3–30.0 ng/mL for impurity V, and in all cases, the fitting correlation coefficients exceeded 0.999. The obtained limits of detection values were 0.05 ng/mL and 0.005 μg/mL for impurity V and impurities I–IV, respectively. The precision and repeatability of the methods were less than 1.08% and 8.72% for each impurity. The recovery percentages of all impurities were in the range of 91.18%–111.27%, with the relative standard deviation of less than 3.69%. The greenness assessment of the HPLC method and the HPLC-MS/MS method were evaluated by using AGREE software with a score value of 0.72 and 0.68, respectively. The recommended procedures that were accurate, specific, and ecofriendly were applied to the existing active pharmaceutical ingredients of IMM, and they generated satisfactory results.

Abstract DNA nanomachines with artificial intelligence have attracted great interest, which may open a new era of precision medicine. However, their in vivo behavior, including early diagnosis and therapeutic effect are limited by their targeting efficiency. Here, a tetrahedral DNA framework (TDF)‐based nanodevice for in vivo near‐infrared (NIR) diagnosis of early‐stage AKI is developed. This nanodevice comprises three functional modules: a size‐tunable TDF nanostructure as kidney‐targeting vehicle, a binding module for the biomarker kidney injury molecule‐1 (Kim‐1), and a NIR signaling module. The cooperation of these modules allows the nanodevice to be selectively accumulated in injured kidney tissues with high Kim‐1 level, generating strong NIR fluorescence; whereas the nanodevice with the proper size can be rapidly cleared in healthy kidneys to minimize the background. By using this nanodevice, the early diagnosis of AKI onset is demonstrated at least 6 h ahead of Kim‐1 urinalysis, or 12 h ahead of blood detection. It is envisioned that this TDF‐based nanodevice may have implications for the early diagnosis of AKI and other kidney diseases.

Abstract The mechanism of obesity‐related metabolic dysfunction involves the development of systemic inflammation, largely mediated by macrophages. Switching of M1‐like adipose tissue macrophages (ATMs) to M2‐like ATMs, a population of macrophages associated with weight loss and insulin sensitivity, is considered a viable therapeutic strategy for obesity‐related metabolic syndrome. However, mechanisms for reestablishing the polarization of ATMs remain elusive. This study demonstrates that CD146+ ATMs accumulate in adipose tissue during diet‐induced obesity and are associated with increased body weight, systemic inflammation, and obesity‐induced insulin resistance. Inactivating the macrophage CD146 gene or antibody targeting of CD146 alleviates obesity‐related chronic inflammation and metabolic dysfunction. Macrophage CD146 interacts with Glycoprotein 130 (Gp130), the common subunit of the receptor signaling complex for the interleukin‐6 family of cytokines. CD146/Gp130 interaction promotes pro‐inflammatory polarization of ATMs by activating JNK signaling and inhibiting the activation of STAT3, a transcription factor for M2‐like polarization. Disruption of their interaction by anti‐CD146 antibody or interleukin‐6 steers ATMs toward anti‐inflammatory polarization, thus attenuating obesity‐induced chronic inflammation and metabolic dysfunction in mice. The results suggest that macrophage CD146 is an important determinant of pro‐inflammatory polarization and plays a pivotal role in obesity‐induced metabolic dysfunction. CD146 could constitute a novel therapeutic target for obesity complications.

Abstract Obesity and its related complications pose an increasing threat to human health; however, targetable obesity‐related membrane receptors are not yet elucidated. Here, the membrane receptor CD146 is demonstrated to play an essential role in obesity. In particular, CD146 acts as a new adipose receptor for angiopoietin‐like protein 2 (ANGPTL2), which is thought to act on endothelial cells to activate adipose inflammation. ANGPTL2 binds to CD146 to activate cAMP response element‐binding protein (CREB), which then upregulates CD146 during adipogenesis and adipose inflammation. CD146 is present in preadipocytes and mature adipocytes, where it is mediated by its ligands ANGPTL2 and galectin‐1. In preadipocytes, CD146 ablation suppresses adipogenesis, whereas the loss of CD146 in mature adipocytes suppresses lipid accumulation and enhances energy expenditure. Moreover, anti‐CD146 antibodies inhibit obesity by disrupting the interactions between CD146 and its ligands. Together, these findings demonstrate that ANGPTL2 directly affects adipocytes via CD146 to promote obesity, suggesting that CD146 can be a potential target for treating obesity.

Background. Atrial fibrillation (AF) is the most common serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in general population. Hypertension is the most prevalent and potentially modifiable risk factor for AF. This study is aimed at evaluating the effect of angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) on AF recurrence among patients with hypertension and AF. Methods. The PubMed, EMBASE, Medline, and Cochrane Collaboration of Controlled Clinical Trials registry databases were searched from their inception to September 2020. Results. A total of 7 randomized controlled trials (RCTs) enrolling 1495 patients were included in our study. This finding showed that ARB had a statistically significant superiority in preventing AF recurrence (OR: 0.43, 95% CI: 0.30-0.72, P=0.0006) and persistent AF (OR: 0.41, 95% CI: 0.24-0.71, P=0.001) compared to CCB. Subgroup analysis showed that there was a significant difference in telmisartan subgroup (OR: 0.54, 95% CI: 0.23-1.29, P=0.17) and nontelmisartan subgroup (OR: 0.42, 95% CI: 0.23-0.77, P=0.005). Subgroup analysis indicated that nifedipine subgroup did not show a statistically significant difference on AF recurrence between ARB and CCB (OR: 0.88, 95% CI: 0.46-1.68, P=0.69), but amlodipine subgroup showed that ARB had a significant superiority in prevention of AF recurrence (OR: 0.39, 95% CI: 0.27-0.56, P

The eastern Tianshan metallogenic belt is an important molybdenum resource base in Xinjiang and is characterized by large-scale porphyry Mo deposits formed during the Triassic. The Tieling Cu-Mo porphyry deposit, which is situated in the western part of the eastern Tianshan metallogenic belt, was recently recognized as being related to Carboniferous granite porphyry. Three stages of hydrothermal mineralization were identified, including quartz+K-feldspar+pyrite±molybdenite±magnetite (stage I), quartz+molybdenite+pyrite+chalcopyrite (stage II), and quartz+pyrite±molybdenite±epidote (stage III). Fluid inclusion petrography and microthermometry analyses indicate the presence of gas-liquid inclusions with a H2O-NaCl composition. The ore-forming fluids have a characteristic temperature ranging from 157 to 262°C under stage II and 135 to 173°C under stage III, which correspond to salinities of 7.2-17.2 wt% NaCl equiv. and 5.9 to 9.6 wt% NaCl equiv., respectively. The hydrogen and oxygen isotope data indicate that the ore-forming fluids of the Tieling deposit were originally derived from magmatic hydrothermal fluids and then mixed with meteoric water. The sulfur isotope compositions indicate that the ore-forming materials were mainly derived from the Late Carboniferous felsic magma. Furthermore, zircon U-Pb analysis of ore-bearing granite porphyry yields a concordant age of 298.4±0.7 Ma, indicating that the Tieling Cu-Mo deposit formed during the Late Carboniferous and differed from that processed under pre-Early Carboniferous and Triassic mineralization in the eastern Tianshan metallogenic belt. These results also indicate that the Tieling porphyry deposit was formed in the transition condition between subduction-related accretion and postcollisional orogeny, and it should be given more attention in prospect evaluations.

Abstract The design of multistrain systems has markedly expanded the prospects of using long biosynthetic pathways to produce natural compounds. However, the cooperative use of artificially engineered microbes to synthesize xenobiotic chemicals from renewable carbohydrates is still in its infancy. Here, a microbial system is developed for the production of high‐added‐value N‐heterocycles directly from glucose. Based on a retrosynthetic analysis, eleven genes are selected, systematically modulated, and overexpressed in three Escherichia coli strains to construct an artificial pathway to produce 5‐methyl‐2‐pyrazinecarboxylic acid, a key intermediate in the production of the important pharmaceuticals Glipizide and Acipimox. Via one‐pot tandem collaborations, the designed microbes remarkably realize high‐level production of 5‐methyl‐2‐pyrazinecarboxylic acid (6.2 ± 0.1 g L−1) and its precursor 2,5‐dimethylpyrazine (7.9 ± 0.7 g L−1). This study is the first application of cooperative microbes for the total biosynthesis of functionalized N‐heterocycles and provides new insight into integrating bioretrosynthetic principles with synthetic biology to perform complex syntheses.

Background. Metagenomic next-generation sequencing (mNGS) is a new technology that allows for unbiased detection of pathogens. However, there are few reports on mNGS of lung biopsy tissues for pulmonary infection diagnosis. In addition, radial endobronchial ultrasound (R-EBUS) is widely used to detect peripheral pulmonary lesions (PPLs), but it is rarely used in the diagnosis of peripheral lung infection. Objective. The present study aims to evaluate the combined application of R-EBUS-guided transbronchial lung biopsy (TBLB) and mNGS for the diagnosis of peripheral pulmonary infectious lesions. Methods. From July 2018 to April 2019, 121 patients from Tianjin Medical University General Hospital diagnosed with PPLs and lung infection were enrolled in this prospective randomized study . Once the lesion was located, either TBLB or R-EBUS-guided-TBLB was performed in randomly selected patients, and mNGS was applied for pathogen detection in lung biopsy tissues. The results of mNGS were compared between the TBLB group and R-EBUS-guided TBLB group. In addition, the clinical characteristics and EBUS images from 61 patients receiving bronchoscopy for peripheral lung infectious detection were analyzed and compared with the results of mNGS. Results. The positivity rate of mNGS in R-EBUS-guided TBLB was (78.7%, 48/61) that was significantly higher than (60.0%, 36/60) in the TBLB group. Difference in the position of R-EBUS probe and image characteristics of peripheral lung infectious lesions affected the positivity rate of mNGS. Tissue collected by R-EBUS within the lesion produced higher positivity rate than samples collected adjacent to the lesion (P=0.030, odds ratio 17.742; 95% confidence interval, from 1.325 to 237.645). Anechoic areas and luminant areas of ultrasonic image characteristics were correlated with lower positivity rate of mNGS (respectively, P=0.019, odds ratio 17.878; 95% confidence interval, from 1.595 to 200.399; P=0.042, odds ratio 16.745; 95% confidence interval, from 1.106 to 253.479). Conclusions. R-EBUS-guided TBLB is a safe and effective technique in the diagnosis of peripheral lung infectious lesions. R-EBUS significantly facilitates the accurate insertion of bronchoscope into the lesions, which improves positivity rate of mNGS analysis in pathogen detection. The R-EBUS probe position within lesion produced a higher positivity rate of mNGS analysis. Nevertheless, the presence of anechoic and luminant areas on ultrasonic image was correlated with poor mNGS positivity rate.

Abstract Breast tumor initiating cells (BTICs) with ALDH+CD24−CD44+ phenotype are the most tumorigenic and invasive cell population in breast cancer. However, the molecular mechanisms are still unclear. Here, it is found that a negative immune regulator interleukin‐1 receptor type 2 (IL1R2) is upregulated in breast cancer (BC) tissues and especially in BTICs. BC patients with high IL1R2 expression have a poorer overall survival and relapse‐free survival. High IL1R2 promotes BTIC self‐renewal and BC cell proliferation and invasion. Mechanistically, IL1R2 is activated by IL1β, as demonstrated by the fact that IL1β induces the release of IL1R2 intracellular domain (icd‐IL1R2) and icd‐IL1R2 then interacts with the deubiquitinase USP15 at the UBL2 domain and promotes its activity, which finally induces BMI1 deubiquitination at lysine 81 and stabilizes BMI1 protein. In addition, IL1R2 neutralizing antibody can suppress the protein expression of both IL1R2 and BMI1, and significantly abrogates the promoting effect of IL1R2 on BTIC self‐renewal and BC cell growth both in vitro and in vivo. The current results indicate that blocking IL1R2 with neutralizing antibody provides a therapeutic approach to inhibit BC progression by targeting BTICs.

Abstract Cervical cancer is one of the most common gynecologic cancers around the world. Long noncoding RNAs (lncRNAs) are considered to be important regulators of some biological processes. Recently, it has been reported that linc‐UFC1 is a putative oncogene in some cancers. However, the functional roles of linc‐UFC1 have not been investigated in cervical cancer. Here, it was demonstrated that linc‐UFC1 expression was significantly increased in cervical cancer tissues, and its overexpression was associated with the poor survival of patients with cervical cancer. Loss‐of‐function assays indicated that linc‐UFC1 exerted as an oncogene because it promoted the growth and metastasis of cervical cancer cells in vitro and in vivo. Mechanistic investigations revealed that linc‐UFC1 upregulated FOXP3 expression through competitively binding miR‐34a. Finally, luciferase reporter and chromatin immunoprecipitation (ChIP) assays provided evidence that E2F1 could directly bind to the linc‐UFC1 promoter region and enhance its transcription. Taken together, our findings indicate that the linc‐UFC1 expression signature may serve as a novel biomarker for the diagnosis and prognosis of cervical cancer, and it is also highlighted that the E2F1‐linc‐UFC1/miR‐34a/FOXP3 axis may be a potentially therapeutic target of cervical cancer.

Acute aortic dissection is a life-threatening clinical emergency, which mostly occurs in aged patients and presents with sharp chest pain. In this paper, we reported a case of acute aortic dissection, which induced septic shock in a young woman, without typical chest pain. The septic shock was possibly due to the bacterial translocation caused by aortic dissection-induced intestinal ischemia and intestinal epithelial barrier dysfunction. Our case appeared as the first case report of aortic dissection presenting as septic shock. This case is rare but can serve as a reminder that aortic dissection may be accompanied by septic shock, and this could result in a grave outcome.

Neural plasticity is associated with memory formation. The coordinated refinement and interaction between cortical glutamatergic and GABAergic neurons remain elusive in associative memory, which we examine in a mouse model of associative learning. In the mice that show odorant-induced whisker motion after pairing whisker and odor stimulations, the barrel cortical glutamatergic and GABAergic neurons are recruited to encode the newly learnt odor signal alongside the innate whisker signal. These glutamatergic neurons are functionally upregulated, and GABAergic neurons are refined in a homeostatic manner. The mutual innervations between these glutamatergic and GABAergic neurons are upregulated. The analyses by high throughput sequencing show that certain microRNAs related to regulating synapses and neurons are involved in this cross-modal reflex. Thus, the coactivation of the sensory cortices through epigenetic processes recruits their glutamatergic and GABAergic neurons to be the associative memory cells as well as drive their coordinated refinements toward the optimal state for the storage of the associated signals.

Pericytes are a population of cells that participate in normal vessel architecture and regulate permeability. Apelin, as the endogenous ligand of G protein-coupled receptor APJ, participates in a number of physiological and pathological processes. To date, the effect of apelin on pericyte is not clear. Our study aimed to investigate the potential protection mechanisms of apelin, with regard to primary rat retinal pericytes under hypoxia. Immunofluorescence staining revealed that pericytes colocalized with APJ in the fibrovascular membranes dissected from proliferative diabetic retinopathy patients. In the in vitro studies, we first demonstrated that the expression of apelin/APJ was upregulated in pericytes under hypoxia, and apelin increased pericytes proliferation and migration. Moreover, knockdown of apelin in pericyte was achieved via lentivirus-mediated RNA interference. After the inhibition of apelin, pericytes proliferation was inhibited significantly in hypoxia culture condition. Furthermore, exogenous recombinant apelin effectively prevented hypoxia-induced apoptosis through downregulating active-caspase 3 expression and increasing the ratio of B cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) in pericytes. These results suggest that apelin suppressed hypoxia-induced pericytes injury, which indicated that apelin could be a potential therapeutic target for retinal angiogenic diseases.

This paper investigates a problem of how to regulate a firm which has private information about the market capacity, leading to adverse selection, and which can increase the market demand by exerting costly effort, resulting in moral hazard. In such a setting, the regulator offers a regulatory policy to the firm with the objective of maximizing a weighted sum of the consumer surplus and the firm’s profit (i.e., the social total surplus). We firstly find that the regulator will set the firm’s effort level as zero under observable effort regardless of the market capacity being full or private information; that is, the effort has no impact on the optimal regulatory policy. Interestingly, we also show that, it is necessary for regulator to consider the difference between the effort’s impact on the demand and the price’s impact on the demand, which may generate different distortion effects about the regulatory policy.