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Long non-coding RNAs (lncRNAs), once thought to be mere transcriptional noise, are now revealing a hidden code. Recent advancements like ribosome sequencing have unveiled that many lncRNAs harbor small open reading frames and can potentially encode functional micropeptides. Emerging research suggests these micropeptides, not the lncRNAs themselves, play crucial roles in regulating homeostasis, inflammation, metabolism, and especially in breast cancer progression. This review delves into the rapidly evolving computational tools used to predict and validate lncRNA-encoded micropeptides. We then explore the diverse functions and mechanisms of action of these micropeptides in breast cancer pathogenesis, with a focus on their roles in various species. Ultimately, this review aims to illuminate the functional landscape of lncRNA-encoded micropeptides and their potential as therapeutic targets in cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In basketball training, self-evaluation plays a crucial role in the decision-making and execution of movements of players. The self-evaluation of players is influenced by their perception of own basketball ability and self-confidence state. This study aimed to explore potential discrepancies between self-confidence levels of players and their decision-making performance, while also characterizing different types of players., Method: Data was collected from 20 youth basketball players who participated in a decision-making video task and a self-confidence assessment. Based on data from their self-confidence and decision-making awareness assessment, the K-means cluster analysis was used to categorize the players into different groups. Then, ANOVA and post hoc Scheffe test were conducted to compare these clusters., Results: The cluster analysis identified four distinct profiles of players and the results of the ANOVA and post hoc Scheffe tests revealed significant differences between the four clusters. The "High Self-confidence & Low Decision-making Awareness" players might display an overconfident mindset, while the "High Self-confidence & High Decision-making Awareness" players potentially demonstrated the better performance and maintained a consistent and confident attitude. The "Low Self-confidence & High Decision-making Awareness" players appeared to lack confidence and needed to foster greater faith in their abilities. Finally, the "Low Self-confidence & Low Decision-making Awareness" players required a long-term and comprehensive training program to improve their skills., Discussion: These preliminary findings informed the development of a self-evaluation matrix, designed to help coaches better understand player profiles and design tailored interventions. Moreover, this study contributes on sport calibration and enhances understanding of the behavioral and psychological states of players., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Kong, Lau, Feng and Liu.)

Background: Arrhythmias in patients with cancer are predominantly attributed to heart disease, anti-tumor drugs, and primary cardiac tumors. Arrhythmias directly induced by noncardiac primary tumors are rare. To date, there have been no reported cases of paroxysmal supraventricular tachycardia or sinus bradycardia caused by a posterior mediastinal tumor originating from the lung tissue., Case Description: We present the case of a 65-year-old male diagnosed with a giant posterior mediastinal tumor originating from the lung tissue, A mediastinal lymph node biopsy was performed, and histopathological examination revealed a poorly differentiated adenocarcinoma of pulmonary origin. Based on the PET-CT and cranial enhancend MRI results, the posterior mediastinal tumor has a diameter exceeding 7 cm and has metastasized to the right hilar and mediastinal lymph nodes, with no distant metastasis observed. On the basis of these findings, the patient was diagnosed with stage IIIB mediastinal lung adenocarcinoma (cT4N3M0). The tumor measured 12.8 cm × 8.1 cm and could not be completely resected. Prior to immunochemotherapy, the patient experienced paroxysmal supraventricular tachycardia, followed by sinus bradycardia. After the first cycle of immunochemotherapy, the arrhythmia was corrected, and the body temperature returned to normal. However, the massive tumor led to malnutrition and various complications prior to the second cycle of treatment. Despite undergoing chemotherapy combined with immunotherapy, the patient's condition worsened, ultimately resulting in death. The overall survival period was 3 months., Conclusion: This case report highlights the fact that a giant mediastinal lung adenocarcinoma can induce arrhythmias, which may manifest as supraventricular tachycardia or sinus bradycardia. Additionally, tumor fever also can induce elevated temperatures of 39 °C. Notably, giant posterior mediastinal tumors that are unsuitable for resection have a significantly poorer prognosis., Competing Interests: The authors declare no conflict of interest.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yintao Li reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China. Yintao Li reports financial support was provided by the 10.13039/501100007129Natural Science Foundation of Shandong Province. Yintao Li reports a relationship with the 10.13039/501100007129Natural Science Foundation of Shandong Province that includes: funding grants. Yintao Li reports a relationship with 10.13039/501100001809National Natural Science Foundation of China that includes: non-financial support. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

In Parkinson's disease (PD), exogenous ghrelin protects dopaminergic neurons through its receptor, growth hormone secretagogue receptor (GHSR). However, in contrast to the strikingly low levels of ghrelin, GHSR is highly expressed in the substantia nigra (SN). What role does GHSR play in dopaminergic neurons is unknown. In this study, using GHSR knockout mice (Ghsr -/- mice) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, we found that GHSR deletion aggravated dopaminergic neurons degeneration, and the expression and activity of GHSR were significantly reduced in PD. Furthermore, we explored the potential mechanism that GHSR deficiency aggregated PD-related neurodegeneration. We showed that DEPTOR, a subunit of mTORC1, was overexpressed in Ghsr -/- mice, positively regulating autophagy and enhancing autophagy initiation. The expression of lysosomal markers was abnormal, implying lysosomal dysfunction. As a result, the damaged mitochondria could not be effectively eliminated, which ultimately exacerbated the injury of nigral dopaminergic neurons. In particular, we demonstrated that DEPTOR could be transcriptionally regulated by KLF4. Specific knockdown of KLF4 in dopaminergic neurons effectively alleviated neurodegeneration in Ghsr -/- mice. In summary, our results suggested that endogenous GHSR deletion-compromised autophagy by impairing lysosomal function, is a key contributor to PD, which provided ideas for therapeutic approaches involving the manipulation of GHSR., Competing Interests: Declaration of competing interest The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The excessive use of nitrofurantoin (NFT) represents a threat to ecosystems and food safety, making it necessary to develop efficient and accurate detection methods. Herein, the Ru/NiFe-LDH-MXene/SPCE electrode was successfully synthesized by one-step electrodeposition and employed to the NFT electrochemical sensing. Combining 2D MXenes with multifunctional 2D layered double hydroxides (LDHs) creates synergistic interactions within the MXene-LDH heterostructures, modifying the electrochemical performance. Furthermore, the incorporation of noble metal nanoparticles and nanoclusters can significantly enhance electrochemical performance by promoting favorable interactions at the metal-carrier interface and optimizing the rearrangement of electronic structure. Based on this, the developed Ru/NiFe-LDH-MXene/SPCE sensor demonstrates remarkable sensitivity (152.44 μA μM -1  cm -2 ) and an ultralow detection limit (2.2 nM). Notably, the sensor was employed for NFT detection in food samples with satisfactory recoveries, making it a promising electrochemical sensor for the detection of NFT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to construct an imaging genomics nomogram based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to predict the status of the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene in patients with brain gliomas. We retrospectively analyzed routine MR and IVIM-DWI data from 85 patients with pathologically confirmed brain gliomas from January 2017 to May 2023. The data were divided into a training set (N=61) and a test set (N=24) in a 7:3 ratio. Regions of interest (ROIs) of brain gliomas, including the solid tumor region (rCET), edema region (rE), and necrotic region (rNec), were delineated using 3D-Slicer software and projected onto the D, D*, and f sequences. A total of 1037 features were extracted from each ROI, resulting in 3111 features per patient. Age was incorporated in the calculation of the Radscore, and a clinical-imaging genomics combined model was constructed, from which a nomogram graph was generated. Separate models were built for the D, D*, and f parameters. The AUC value of the D parameter model was 0.97 (95% CI: 0.93-1.00) in the training set and 0.91 (95% CI: 0.79-1.00) in the validation set, which was significantly higher than that of the D* parameter model (0.90, 0.82) and the f parameter model (0.89, 0.91). The imaging genomics nomogram based on IVIM-DWI can effectively predict the ATRX gene status of patients with brain gliomas, with the D parameter showing the highest efficacy., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Morse code recognition plays a very important role in the application of human-machine interaction. In this paper, based on the carbon nanotube (CNT) and polyurethane sponge (PUS) composite material, a flexible tactile CNT/PUS sensor with great piezoresistive characteristic is developed for detecting Morse code precisely. Thirty-six types of Morse code, including 26 letters (A-Z) and 10 numbers (0-9), are applied to the sensor. Each Morse code was repeated 60 times, and 2160 (36 × 60) groups of voltage time-sequential signals were collected to construct the dataset. Then, smoothing and normalization methods are used to preprocess and optimize the raw data. Based on that, the long short-term memory (LSTM) model with excellent feature extraction and self-adaptive ability is constructed to precisely recognize different types of Morse code detected by the sensor. The recognition accuracies of the 10-number Morse code, the 26-letter Morse code, and the whole 36-type Morse code are 99.17%, 95.37%, and 93.98%, respectively. Meanwhile, the Gated Recurrent Unit (GRU), Support Vector Machine (SVM), Multi-Layer Perceptron (MLP), and Random Forest (RF) models are built to distinguish the 36-type Morse code (letters of A-Z and numbers of 0-9) based on the same dataset and achieve the accuracies of 91.37%, 88.88%, 87.04%, and 90.97%, respectively, which are all lower than the accuracy of 93.98% based on the LSTM model. All the experimental results show that the CNT/PUS sensor can detect the Morse code's tactile feature precisely, and the LSTM model has a very efficient property in recognizing Morse code detected by the CNT/PUS sensor.

Invasive candidiasis (IC) is a notable healthcare-associated fungal infection, characterized by high morbidity, mortality, and substantial treatment costs. Candida albicans emerges as a principal pathogen in this context. Recent academic advancements have shed light on the critical role of exosomes in key biological processes, such as immune responses and antigen presentation. This burgeoning body of research underscores the potential of exosomes in the realm of medical diagnostics and therapeutics, particularly in relation to fungal infections like IC. The exploration of exosomal functions in the pathophysiology of IC not only enhances our understanding of the disease but also opens new avenues for innovative therapeutic interventions. In this investigation, we focus on exosomes (Exos) secreted by macrophages, both uninfected and those infected with C. albicans. Our objective is to extract and analyze these exosomes, delving into the nuances of their protein compositions and subgroups. To achieve this, we employ an innovative technique known as Proximity Barcoding Assay (PBA). This methodology is pivotal in our quest to identify novel biological targets, which could significantly enhance the diagnostic and therapeutic approaches for C. albicans infection. The comparative analysis of exosomal contents from these two distinct cellular states promises to yield insightful data, potentially leading to breakthroughs in understanding and treating this invasive fungal infection. In our study, we analyzed differentially expressed proteins in exosomes from macrophages and C. albicans -infected macrophages, focusing on proteins such as ACE2, CD36, CAV1, LAMP2, CD27, and MPO. We also examined exosome subpopulations, finding a dominant expression of MPO in the most prevalent subgroup, and a distinct expression of CD36 in cluster14. These findings are crucial for understanding the host response to C. albicans and may inform targeted diagnostic and therapeutic approaches. Our study leads us to infer that MPO and CD36 proteins may play roles in the immune escape mechanisms of C. albicans. Additionally, the CD36 exosome subpopulations, identified through our analysis, could serve as potential biomarkers and therapeutic targets for C. albicans infection. This insight opens new avenues for understanding the infection's pathology and developing targeted treatments., (© 2024. The Author(s).)

This paper investigates a tracking control issue for a class of time-varying output constrained nonlinear systems subject to non-affine nonlinear faults and virtual control coefficients. In the controller design process, the nonlinear function is approximated by fuzzy logic systems. Utilizing a feasible function to convert the system, a new transformation strategy is proposed to handle the system with time-varying output constraints or without output constraints. The mean value theorem is applied to split non-affine faults, and the Nussbaum-type function is used to eliminate the effect of the unknown directional affine variable gain of input resulted from non-affine faults. Combined with adaptive fuzzy backstepping technology and the error transformation function, a new control strategy is presented, which not only deals with the time-varying output constraint but also handles non-affine faults, effectively. Finally, all closed-loop system signals are bounded, and the tracking error can converge to a small preset set. Two simulations are performed to confirm the validity of the presented strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 ISA. Published by Elsevier Ltd. All rights reserved.)

Myeloid-derived suppressor cells (MDSCs) increase in number and gain immunosuppressive functions in tumours and many other pathological conditions. MDSCs are characterized by their strong T-cell immunosuppressive capacity. The effects that MDSCs may have on B cells, especially within the tumour microenvironment, are less well understood. Here, we report that either monocytic MDSCs or polymorphonuclear MDSCs can promote increases in interleukin (IL)-10-expressing CD19 hi FcγRIIb hi regulatory B cells in vitro and in vivo. Splenic transitional-1, -2, and -3 cells and marginal zone B cells, but not follicular B cells, differentiate into IL-10-expressing CD19 hi FcγRIIb hi regulatory B cells. The adoptive transfer of CD19 hi FcγRIIb hi regulatory B cells via tail vein injection can promote subcutaneous 3LL tumour growth in mice. The expression of programmed death-ligand 1 on MDSCs was found to be strongly associated with CD19 hi FcγRIIb hi regulatory B cell population expansion. Furthermore, the frequency of circulating CD19 + FcγRII hi regulatory B cells was significantly increased in advanced-stage lung cancer patients. Our results unveil a critical role of MDSCs in regulatory B-cell differentiation and population expansion in lung cancer patients., (© 2024 John Wiley & Sons Ltd.)

Objective: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases worldwide, and studies have found significant differences in the composition and ratio of intestinal flora between patients with T2DM and normal glucose tolerance, and fecal microbiota transplantation (FMT) may modulate the composition of the intestinal microbiota thereby alleviating the hyperglycemic state. We conducted a meta-analysis and systematic review of existing randomized controlled trials (RCTs) to assess the efficacy of FMT in T2DM., Methods: We conducted a computer search of PubMed, Embase, The Cochrane Library, and Web of Science to screen randomized controlled trials studies on FMT treatment for T2DM and extracted data from studies that met inclusion criteria. RevMan 5.4 software and Stata 11 software was used for meta-analysis. The indexes of Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were mainly evaluated after FMT treatment of T2DM patients, and the changes of intestinal flora were evaluated., Results: Four RCTs met the inclusion criteria and were included in the meta-analysis. Results of the meta-analysis showed that compared with the non-FMT group, FMT combined treatment could significantly reduce the PBG level in patients with type 2 diabetes (MD = -0.51, 95% CI: -1.42-0.40, P = 0.27). Compared with single FMT treatment, FMT combined treatment could reduce TG levels in patients with type 2 diabetes (MD = -0.60, 95% CI: -1.12~-0.07, P = 0.03). The levels of TG (MD = -0.26, 95% CI: -0.51~-0.02, P = 0.03), HOMA-IR (MD = -2.73, 95% CI: -4.71~0.75, P = 0.007) and HDL (MD = -0.06,95% CI: -0.10~-0.02, P = 0.003) were significantly decreased after treatment in the single FMT group. The level of TC (MD = -0.65, 95% CI: -1.00~-0.31, P = 0.0002) was significantly decreased after FMT combined treatment. Compared with before treatment, ALT (MD = -2.52, 95% CI: -3.86~-1.17, P = 0.0002) and DBP (MD = -2, 95% CI: -3.32~0.68, P = 0.003) levels decreased after treatment in the single FMT group and the FMT combined group. FPG (MD = -0.94, 95% CI: -1.86~-0.02, P = 0.04), TG (MD = -0.73, 95% CI: -1.42~-0.04, P = 0.04) and TC (MD = -0.94, 95% CI: -1.45~-0.43, P = 0.0003) were significantly decreased after combined drug and diet therapy. Secondly, FMT can promote the colonization and growth of donor-related flora in patients with type 2 diabetes., Conclusion: In patients with type 2 diabetes mellitus, FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP, especially in the combined treatment regimen. In addition, FMT can reshape the intestinal flora and establish the balance of dominant flora., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice., Methods: The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3., Results: GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3., Conclusions: Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.

This study aims to explore the specific mechanism by which miR-155 regulates SHP2 expression in mouse ischemia-reperfusion (I/R) induced necroptosis. Various methods including cardiac ultrasound, TTC staining, Masson staining, TUNEL staining, and Western blotting were used to examine changes in the morphology and function of the rat left ventricle, myocardial fibrosis, as well as the expression of proteins related to tissue and cardiomyocyte necroptosis pathways. In vivo results showed that knockdown (KD) of miR-155 significantly improved cardiac ultrasound parameters (EF, FS, LVAW;d, and LVAW;s), reduced the myocardial infarction area, myocardial fibrosis, and cell apoptosis in I/R mice, upregulated cardiac SHP2 protein expression, and other proteins including p-ERK1/2, NLRP3, GSDMD, caspase-3, caspase-4, and caspase-11 were also significantly decreased. In vitro experiments showed that compared with the SHP2 WT miR-155 KD group, SHP2 protein expression was significantly increased in the SHP2 WT miR-155 KD group, while the expression of other proteins was significantly reduced, consistent with in vivo results. MiR-155 can regulate ERK1/2 and NLRP3 through SHP2. After adding the ERK1/2 inhibitor U0126 to cardiomyocytes from SHP2 KO mice, it was found that the expression of proteins other than SHP2 significantly decreased compared to SHP2 KO cells without the inhibitor. In summary, low expression of miR-155 promoted the expression of SHP2 and improved mouse I/R-induced necroptosis by inhibiting the activation of the ERK1/2 pathway.

Objective: Leukocyte Ig-like receptor A3 (LILRA3) is a soluble receptor belongs to the immunoglobulin superfamily. Our previous studies demonstrated that LILRA3 is a common genetic risk for multiple autoimmune diseases, including RA. Functional LILRA3 conferred increased risk of joint destruction in patients with early RA. We undertook this study to further investigate the pathological role of LILRA3 in joint inflammation of RA., Methods: Soluble LILRA3 was measured by ELISA. LILRA3 plasmids were transfected into human fibroblast-like synoviocytes (FLSs) using electroporation. Activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was determined by western blots. Cytokine transcripts were quantified by real-time PCR. Migratory and invasive capacities of FLSs were evaluated using transwell migration and Matrigel invasion assays. FLS apoptosis was analysed using flow cytometry. Colocalization of LILRA3, LILRB1 and HLA-G in RA-FLSs was visualized by immunofluorescence staining., Results: Soluble LILRA3 was specifically expressed in synovial fluid and serum LILRA3 was significantly increased and positively correlated with disease activity/severity in RA patients. LILRA3 induced an increased expression of IL-6, IL-8 and MMP3 in RA-FLSs. In vitro LILRA3 stimulation or overexpression promoted RA-FLS migration and invasion, and enhanced phosphorylation of ERK/JNK. Inhibition of ERK/JNK resulted in suppression of IL-6/IL-8 expression in LILRA3-stimulated RA-FLSs. LILRA3 was co-localized with its homologue LILRB1 and shared ligand HLA-G in RA-FLSs., Conclusion: The present study provides the first evidence that soluble LILRA3 is a novel proinflammatory mediator involved in synovial inflammation by promoting RA-FLS activation, migration and invasion, probably through the ERK/JNK signalling pathways., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Flexible pressure sensors play a crucial role in detecting human motion and facilitating human-computer interaction. In this paper, a type of flexible pressure sensor unit with high sensitivity (2.242 kPa -1 ), fast response time (80 ms), and remarkable stability (1000 cycles) is proposed and fabricated by the multi-walled carbon nanotube (MWCNT)/cotton fabric (CF) material based on a dip-coating method. Six flexible pressure sensor units are integrated into a flexible wristband and made into a wearable and portable wrist sensor with favorable stability. Then, seven wrist gestures (Gesture Group #1), five letter gestures (Gesture Group #2), and eight sign language gestures (Gesture Group #3) are performed by wearing the wrist sensor, and the corresponding time sequence signals of the three gesture groups (#1, #2, and #3) from the wrist sensor are collected, respectively. To efficiently recognize different gestures from the three groups detected by the wrist sensor, a fusion network model combined with a convolutional neural network (CNN) and the bidirectional long short-term memory (BiLSTM) neural network, named CNN-BiLSTM, which has strong robustness and generalization ability, is constructed. The three types of Gesture Groups were recognized based on the CNN-BiLSTM model with accuracies of 99.40%, 95.00%, and 98.44%. Twenty gestures (merged by Group #1, #2, and #3) were recognized with an accuracy of 96.88% to validate the applicability of the wrist sensor based on this model for gesture recognition. The experimental results denote that the CNN-BiLSTM model has very efficient performance in recognizing different gestures collected from the flexible wrist sensor.

Designing definite transition metal heterointerfaces is considered an effective strategy for the construction of efficient and robust oxygen evolution reaction (OER) electrocatalysts, but rather challenging. Herein, amorphous NiFe hydr(oxy)oxide nanosheet arrays (A-NiFe HNSAs) are grown in situ on the surface of a self-supporting Ni metal-organic frameworks (SNMs) electrode via a combination strategy of ion exchange and hydrolytic co-deposition for efficient and stable large-current-density water oxidation. The existence of the abundant metal-oxygen bonds on the heterointerfaces can not only be of great significance to alter the electronic structure and accelerate the reaction kinetics, but also enable the redistribution of Ni/Fe charge density to effectively control the adsorption behavior of important intermediates with a close to the optimal d-band center, dramatically narrowing the energy barriers of the OER rate-limiting steps. By optimizing the electrode structure, the A-NiFe HNSAs/SNMs-NF exhibits outstanding OER performance with small overpotentials of 223 and 251 mV at 100 and 500 mA cm -2 , a low Tafel slope of 36.3 mV dec -1 , and excellent durability during 120 h at 10 mA cm -2 . This work significantly provides an avenue to understand and realize rationally designed heterointerface structures toward effective oxygen evolution in water-splitting applications., (© 2023 Wiley-VCH GmbH.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction: Many causes lead to sympathetic-vagus imbalance, which promotes the development of hypertension and accelerates the process of target organ damage. Many studies have shown that exercise training and heart rate variability (HRV) biofeedback can improve diseases caused by autonomic nerve dysfunction, such as hypertension. Based on these theories and the Yin-Yang balance theory of traditional Chinese medicine and Cannon's homeostasis theory, we have developed an assessment system of autonomic nerve regulation system and a harmony instrument. In this study, we aimed to find a new way to control blood pressure of hypertensive patients via cardiopulmonary resonance indices-based respiratory feedback training., Methods and Analysis: This is a prospective, randomised, parallel-controlled clinical trial, which aims to evaluate the effectiveness and safety of biofeedback therapy and exercise rehabilitation combined intervention in hypertension management. 176 healthy individuals will be recruited to get their autonomic nerve function parameters as normal control, while 352 hypertensive patients will be enrolled and randomly divided into a conventional treatment group and an experiment group in a ratio of 1:1. All patients will continue to receive standard hypertension blood pressure treatment, except that patients in the experiment group will have to complete additional daily respiratory training for 6 months. The primary outcome is the difference of clinical systolic blood pressure (SBP) between the two groups after 6 months of intervention. The secondary outcomes include the changes in the mean SBP and diastolic blood pressure (DBP) by 24-hour blood pressure monitoring, home SBP, clinical and home DBP, clinical and home heart rate, the standard-reaching rate of clinic and home SBP and the incidence of composite endpoint events at 6 months., Ethics and Dissemination: This study has been approved by the clinical research ethics committee of China-Japan Friendship Hospital (No. 2018-132 K98-2), the results of this study will be disseminated via peer-reviewed publications or conference presentations., Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800019457, registered on 12 August 2018., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To determine differences in kinesiophobia levels among COPD patients at different time points 6 months after discharge；To identify potential subgroups of COPD patients who perceived different levels of kinesiophobia over time；and to evaluate differences in identified subgroups based on demographic and disease-related characteristics DESIGN: An observational longitudinal study., Methods: OPD patients hospitalized in respiratory department of a grade A hospital in Huzhou city from October 2021 to May 2022 were selected as the research objects. TSK scale was used to evaluate the level of kinesiophobia at discharge (T1), 1 month after discharge (T2), 4 months after discharge (T3) and 6 months after discharge (T4). The kinesiophobia level scores at different time points were compared using latent class growth modelling. ANOVA and Fisher's exact tests were used to test differences in demographic characteristics，and univariate analysis and multinomial logistic regression analysis were used to explore the influencing factors., Results: During the first 6 months after discharge, kinesiophobia levels decreased significantly in the entire sample of COPD patients. The best-fitting group-based trajectory model described three distinctive trajectories: Low kinesiophobia group (31.4% of sample); Medium kinesiophobia group (43.4% of sample)；and High kinesiophobia group (25.2% of sample). Logistic regression results showed that sex, age, course of disease, pulmonary function, education level, BMI, the level of pain, MCFS and mMRC were influencing factors of kinesiophobia trajectory in COPD patients (p < 0.05)., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: The differentiation status of gastric cancer is related to clinical stage, treatment and prognosis. It is expected to establish a radiomic model based on the combination of gastric cancer and spleen to predict the differentiation degree of gastric cancer. Thus, we aim to determine whether radiomic spleen features can be used to distinguish advanced gastric cancer with varying states of differentiation., Materials and Methods: January 2019 to January 2021, we retrospectively analyzed 147 patients with advanced gastric cancer confirmed by pathology. The clinical data were reviewed and analyzed. Three radiomics predictive models were built from radiomics features based on gastric cancer (GC), spleen (SP) and combination of two organ position (GC+SP) images. Then, three Radscores (GC, SP and GC+SP) were obtained. A nomogram was developed to predict differentiation statue by incorporating GC+SP Radscore and clinical risk factors. The area under the curve (AUC) of operating characteristics (ROC) and calibration curves were assessed to evaluate the differential performance of radiomic models based on gastric cancer and spleen for advanced gastric cancer with different states of differentiation (poorly differentiated group and non- poorly differentiated group)., Results: There were 147 patients evaluated (mean age, 60 years ± 11SD, 111 men). Univariate and multivariate logistic analysis identified three clinical features (age, cTNM stage and CT attenuation of spleen arterial phase) were independent risk factors for the degree of differentiation of GC ( p =0.004,0.000,0.020, respectively). The clinical radiomics (namely, GC+SP+Clin) model showed powerful prognostic ability in the training and test cohorts with AUCs of 0.97 and 0.91, respectively. The established model has the best clinical benefit in diagnosing GC differentiation., Conclusion: By combining radiomic features (GC and spleen) with clinical risk factors, we develop a radiomic nomogram to predict differentiation status in patients with AGC, which can be used to guide treatment decisions., Competing Interests: Author XC is employed by the Beijing Deepwise & League of PHD Technology Company, and author CH is employed by the Beijing Deepwise & League of PHD Technology Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lyu, Liang, Huang, Chen, Cheng, Zhu, Liu, Yue and Gao.)

This study aims to investigate the regulatory effect of Xuesaitong (XST) and miR-3158-3p on angiogenesis. All mice were randomly assigned into Sham group, Model group, XST group, XST + miR-3158-3P-overexpression (miRNA-OE) group. XST was found to increase the left ventricular anterior wall thickness at end diastole and end systole (LVAWd and LVAWs), left ventricular internal dimension at end diastole and end systole (LVIDd and LVIDs), fractional shortening (FS), and ejection fraction (EF) and decrease the proportion of fibrotic areas in mice. In contrast to those in Sham group, the protein expressions of Nur77, p-PI3K, HIF-1α, VEGFs, COX-2 in the heart tissues of mice in Model group were elevated and further increased after XST treatment in comparison with those in Model group. Nur77-/- mice were utilized. It was found that XST enhanced cell viability through a methyl thiazolyl tetrazolium assay and facilitated angiogenesis in each group, as assessed by a catheter formation assay. Specifically, XST was shown to promote the formation of blood vessels. Moreover, the protein expression levels of Associated proteins in the heart tissues of Nur77-/- mice were dramatically reduced in mice in Model and XST group compared with those in WT mice. Additionally, the above-mentioned protein expressions in the heart tissues of Nur77-/- mice did not change significantly in mice in Model + miRNA-OE + XST group compared with those in WT mice, suggesting that miR-3158-3p can specifically inhibit the expression of Nur77. In conclusion, XST inhibits miR-3158-3p targeting Nur77 to facilitate myocardial angiogenesis in mice with myocardial infarction.

In order to explore the computerized tomography (CT) based on three-dimensional reconstruction of coronary artery model, the functional evaluation was made after percutaneous coronary intervention (PCI). In this study, 90 patients with coronary heart disease who received elective PCI were selected. The blood flow reserve fraction (FFR) and SYNTAX score were calculated by three-dimensional reconstruction of CT images, followed up for 2-4 years. According to the SYNTAX score, 0-22 points were defined as the low group (28 cases), 23-32 points as the medium group (33 cases), and 33 points as the high group (29 cases). In this paper, the accuracy, sensitivity, and specificity of CT images of three-dimensional reconstructed coronary artery model are 91%, 73%, and 62%, respectively. The follow-up results showed that the incidence of major adverse cerebrovascular events in the high group was significantly higher than that in the low group and the middle group, and the difference was statistically significant ( P < 0.05). Pearson correlation analysis showed that SYNTAX score was related to serum total cholesterol ( r  = 0.234, P =0.003), triglyceride ( r  = 0.237, P =0.014), low-density lipoprotein cholesterol ( r  = 0.285, P =0.004), and ApoB/ApoA1 ( R  = 0.004). In this study, FFR is calculated by CT images based on three-dimensional reconstruction of coronary artery model, which can provide support for the diagnosis and treatment of coronary heart disease. SYNTAX score can be used as a risk predictor for PCI patients with coronary heart disease., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Dongliang Fu et al.)

Introduction: Bovine ephemeral fever virus (BEFV), belonging to the genus Ephemerovirus under the family Rhabdoviridae , is the etiological cause for the bovine ephemeral fever (BEF) in cattle and water buffalo., Methods: In this study, we report recent BEF outbreaks in Southwest China and sequence the complete genome sequence of one BEFV isolate BEFV/CQ1/2022., Results and Discussion: Comparative genomic analyses between BEFV/CQ1/2022 and isolates available in GenBank revealed remarkable inter-isolate divergence. Meanwhile, the sequence divergence was related to the evolutionary relationships and geographical distribution of the isolates. Phylogenetic analysis indicated that the global BEFV isolates can be divided into 4 distinct lineages. The East Asia lineage was the most diverse and could be subdivided into 4 sublineages. Notably, BEFV/CQ1/2022 and other 10 recent isolates from Mainland China were found to be clustered in sublineage 2. Additionally, recombination analysis provided evidence of BEFV recombination among East Asian isolates for the first time. Taken together, a novel sublineage of the East Asian BEFV emerged in Southwest China, and large divergence and potential recombination among BEFV strains were investigated in this study, which may improve understanding of BEFV epidemiology and evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Liu, Li, Yang, Tang, Dan, Xie, Fang, Li, Ye and Peng.)

The aim of this study was to elucidate the effects of dietary pterostilbene supplementation on physicochemical changes and gel properties of myofibrillar protein (MP) in chicken when subjected to short-term frozen storage. The results showed that pterostilbene supplementation diminished the oxidation of MP compared to the control, as the carbonyl content was significantly reduced and the loss of sulfhydryl and free amino groups was slowed. Meanwhile, the surface hydrophobicity and insolubility of MP were significantly reduced. FT-IR and endogenous fluorescence spectroscopy analysis indicated that dietary pterostilbene inhibited the unfolding of protein structure and the transition of α-helix to β-sheet structure. The integrity of the protein structure contributed to the gel quality. The strength, whiteness and water-holding capacity (WHC) of MP gels were improved in the pterostilbene treatment group. In terms of microstructure, pterostilbene facilitated the formation of dense and homogeneous gel network structure. In summary, these findings suggest that pterostilbene could be used as a dietary supplement to maintain the structural stability of MP in postmortem chicken breast muscle, allowing for excellent gel functional properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To investigate spiritual care perceptions, spiritual well-being, and empathy, examine the correlations among spiritual care perceptions, spiritual well-being, and empathy, and explore the mediating role of spiritual well-being between other two variables of Chinese nursing students., Methods: A cross-sectional design was implemented, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist was used to ensure quality reporting of the study. A cluster sample of 2,718 nursing students was selected from 7 universities and colleges in China. The demographic characteristics questionnaire, the Chinese Version of the Spiritual Care-Giving Scale (C-SCGS), the Spiritual Health Scale Short Form (SHS-SF), and the Jefferson Scale of Physician Empathy-Nursing Student (JSPE-NS) were used. Descriptive statistics, correlation, and process plug-in mediation effect analyses were used to analyze the data., Results: The total score of spiritual care perceptions, spiritual well-being, and empathy were 173.83 ± 25.62, 98.74 ± 12.87, and 105.04 ± 21.34, respectively. Spiritual care perceptions were positively correlated with spiritual well-being ( r = 0.617, p < 0.01) and empathy ( r = 0.528, p < 0.01). And spiritual well-being played a partial mediating role between the other two variables (accounting for 28.1%)., Significance of Results: Spiritual care perceptions, spiritual well-being, and empathy were quite moderate, which need in improving. It is suggested that nursing educators pay attention to the spiritual care education of nursing students, perfect the spiritual care education system, and take targeted measures according to nursing students' individual personality traits and differences, improve their spiritual well-being and empathy in multiple ways, so as to improve their spiritual care perceptions and competence.

Purpose: Long non-coding RNA (lncRNA) XIST has been shown to be involved in the immune escape of breast cancer, but it is unclear whether it is involved in the immune escape of lung cancer, so it will be discussed in this study., Methods: XIST and miR-34a-5p expression in lung cancer tissues and cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The targeting relationship between miR-34a-5p and XIST/programmed cell death receptor ligand 1 (PDL1) was predicted by bioinformatics website and verified by dual-luciferase report experiment. After co-transfection with XIST specific short hairpin RNA (sh-XIST) and miR-34a-5p inhibitors, the changes in PDL1 expression, and cell biological behavior were detected by qRT-PCR, cell counting kit 8, flow cytometry, and Transwell experiments. Similarly, after co-transfection of PDL1 specific small interfering RNA (siPDL1) and miR-34a-5p inhibitors, the changes in cell biological behavior were detected again. After CD8+ T cells were co-cultured with lung cancer cells transfected with sh-XIST and miR-34a-5p inhibitors, the expression of cytokines and immunosuppressive molecules was detected by western blot and enzyme-linked immunosorbent assay (ELISA)., Results: XIST was up-regulated in lung cancer tissues, while miR-34a-5p was the opposite. XIST up-regulated the expression of PDL1 by targeting miR-34a-5p, thereby affecting the viability, apoptosis, migration, and invasion of lung cancer cells. In the co-culture system, XIST targeted miR-34a-5p to inhibit cytokines secretion and promote the expression of immunosuppressive molecules., Conclusions: XIST/miR-34a-5p/PDL1 axis was involved in the malignant biological behavior of lung cancer cells and the immune function of CD8 + T cells.

Objective: To systematically evaluate the efficacy and safety of Huangqin Tang (HQT) combined with mesalazine for the treatment of ulcerative colitis (UC)., Methods: The China Knowledge Network, Wanfang Data, VIP, PubMed, SinoMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) of UC with HQT in Chinese and English. The search time was from the establishment of the database to October 2021. The included literature was evaluated for data extraction and risk of bias, efficacy and safety were evaluated using the RevMan5.3 software, and the quality of evidence was evaluated using GRADE., Results: Six studies with a total of 565 subjects were included, and a meta-analysis showed that HQT combined with mesalazine for UC significantly improved the cure rate (RR = 1.56, 95% CI [1.23, 1.98), P =0.0003) and overall efficacy rate (RR = 1.24, 95% CI [1.14, 1.35], P =0.00001), which significantly reduced the clinical symptom scores; however, all had high heterogeneity. HQT combined with mesalazine modulated the patients' serum IL-6, IL-10, IgA, and IgG levels. HQT combined with mesalazine for UC tended to reduce adverse effects; however, the difference was not statistically significant. All GRADE ratings of the quality of evidence were of low quality., Conclusions: HQT combined with mesalazine in the treatment of UC significantly improved the cure rate and overall treatment efficiency and regulated the expression levels of serum IL-6, IL-10, IgA, and IgG., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Chengyu Pan et al.)

Regulatory B cells have important roles in inflammation and autoimmune diseases. A newly discovered subpopulation of B cells with a CD19 hi FcγRIIb hi phenotype inhibits the proliferation of CD4 + T cells by secreting interleukin (IL)-10. The expansion of CD19 hi FcγRIIb hi B cells in mouse spleen can be induced by lipopolysaccharide (LPS) or CpG oligodeoxynucleotide stimulation. However, the mechanism of CD19 hi FcγRIIb hi B cell expansion and its role in inflammatory diseases are unclear. Here, we report that, under inflammatory conditions, the proliferation and immunosuppressive function of CD19 hi FcγRIIb hi B cells were decreased in high mobility group box1 (HMGB1) C106A mutant mice, compared with wild-type mice. The HMGB1 (C106A) mutation in B cells reduced STAT3 phosphorylation, restricting the expansion and suppressive function of CD19 hi FcγRIIb hi B cells. Compared with CD19 hi FcγRIIb hi B cells from wild-type mice, CD19 hi FcγRIIb hi B cells from Hmgb1 (C106A) mice significantly reduced the survival of mice with sepsis. Recombinant HMGB1 promoted the expansion of IL-10-producing CD19 hi FcγRIIb hi B cells among LPS-activated B cells in vitro . Furthermore, the percentage of CD19 hi FcγRIIb hi regulatory B cells in the peripheral blood was increased in patients with sepsis, compared with healthy controls. These findings implicate the role of HMGB1 in the expansion and immunosuppressive function of CD19 hi FcγRIIb hi B cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhou, Yin, Yin, Ding, Ma and Qian.)

Cardiomyocyte apoptosis is a fundamental pathogenic factor leading to myocardial ischemia/reperfusion (MI/R) injury. The long non-coding RNA (IncRNA) TUG1 regulates apoptosis in various cell types. We report here that TUG1 expression is induced in mouse heart following MI/R injury as well as in cardiomyocytes subjected to simulated ischemia/reperfusion (SI/R) in vitro. Clinically, TUG1 expression is also elevated in plasma from patients with acute myocardial infarction (AMI), which implies its potential application as a disease biomarker. Functionally, TUG1 overexpression promotes, and its knockdown reduces SI/R-induced lactate dehydrogenase (LDH) release and caspase-3 activity in cardiomyocytes in vitro, illustrating that TUG1 exacerbates SI/R-induced apoptosis. Furthermore, in vivo, TUG1 aggravates MI/R injury in a mouse model, and subsequent observations show concurrent increased apoptosis of cardiomyocytes. Hence, this study unveils a clinical relevance and functional role of TUG1 in MI/R injury, and also implicates that targeting TUG1 may have therapeutic effects in treating MI/R injury.

Background and Aim: Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency., Methods: A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI., Results: No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P>.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P<.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P<.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P>.05), although fewer severe hemorrhagic events occurred in the bivalirudin group., Conclusion: Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.

Objectives: To assess the efficacy and safety of jakinibs for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response or intolerance to conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs)., Methods: A systematic search was conducted in PubMed, Embase, and the Cochrane Library. Randomized placebo-controlled trials (RCTs) of jakinibs in RA patients were eligible. The effective outcome was RA improvement to reach an American College of Rheumatology 20%/50%/70% (ACR20/50/70) response rate at weeks 12 and 24 after treatment. The safety outcomes included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to adverse events, infections, and serious infections., Results: Twenty-eight randomized, double-blind, controlled trials including 14,500 patients were included. At both weeks 12 and 24, the pooled analysis suggested effective treatment with jakinibs, represented as an increased clinical response of ACR20, ACR50, and ACR70. Subgroup analysis based on different types of jakinibs demonstrated that only peficitinib treatment had no impact on the clinical response of ACR50 or ACR70 at week 12. Jakinibs were associated with an increased incidence of infections at week 12 and TEAEs and infections at week 24. No increase in the risk of SAEs, discontinuations due to adverse events, or serious infections was observed in comparisons between treatment with jakinibs and treatment with placebo in these patients., Conclusions: Jakinibs are efficacious and well tolerated in RA patients up to 24 weeks, although they are associated with an increased risk of infectious complications. Key Points • ACR20/50/70 in patients treated with jakinibs was significantly higher than those in patients treated with placebo. • No difference in ACR50/70 was observed in patients with RA treated with peficitinib and placebo. • Jakinibs are beneficial and well tolerated in RA treatment., (© 2021. International League of Associations for Rheumatology (ILAR).)

Purpose: To investigate the protective effect and mechanism of allicin on myocardial ischemia-reperfusion (MI/R) injury., Methods: We investigated the mechanisms by which allicin attenuated the MI/R injury by focusing on phosphoinositide 3-kinase, G protein coupled receptor kinases 2, phospholipase Cγ and cardiomyocyte apoptosis. Sixty male mice were randomly assigned into three groups: repeated MI/R (model), sham-operated (control), and MI/R+ allicin group (allicin). Ultrasound examination was used to examine the cardiac function. Masson staining was used to evaluate the myocardial infarct area. TUNEL assay was performed to examine the anti-apoptotic effect of allicin. Differentially expressed genes (DEGs) and pathways were analyzed by mRNA microarray analysis. Immunofluorescence staining and western blot were carried out to detect the effect of allicin on the PI3K. A pan-PLC activator, m-3M3FBS, was applied to investigate whether allicin induced cardiomyocyte apoptosis was via the GRK2/PLC/IP3R signaling pathway., Results: Masson staining and the TUNEL assay revealed that allicin reduced infarct size and played an anti-apoptotic role in M/IR. Ultrasound examination revealed that allicin improved cardiac function after M/IR injury. Gene ontology analysis indicated that the calcium signaling pathway and PI3KCA(PI3K) were selected. Immunofluorescence staining and western blot exposed that PI3K was activated by allicin during MI/R injury. Fura-2AM staining revealed that the PI3K -mediated GRK2/PLC-γ/IP3R pathway may be involved in the protective effect of allicin on MI/R injury., Conclusions: Allicin has a protective effect on MI/R injury. This effect might be associated with the inhibition of Ca 2+ overload-induced apoptosis and the inhibition of the PI3K -mediated GRK2/PLC-γ/IP3R signaling pathway.

Background: Myocardial ischemia-reperfusion (IR) injury is a damage due to an initial reduction in blood flow to the heart, preventing it from receiving enough oxygen, and subsequent restoration of blood flow through the opening of an occluded coronary artery producing paradoxical harmful effects. The finding of new therapies to prevent IR is of utmost importance. Allicin is a compound isolated from garlic having the ability to prevent and cure different diseases, and a protective effect on the myocardium was also demonstrated. Therefore, the aim of this study was to evaluate the in vitro protective effect of Allicin against myocardial IR injury on cardiomyocytes., Methods: We established an in vitro hypoxia-reoxygenation (HR) model of primary porcine cardiomyocytes to simulate myocardial IR injury. Primary porcine cardiomyocytes were extracted from Mini-musk swines (1 day old). After a period of adaptation of at least 2-3 days, cardiomyocytes in good condition were selected and randomly divided into control group (normal oxygen for 5 h), HR group (2 h of hypoxia/3 h of reoxygenation), and HR + Allicin group (hypoxia/reoxygenation + Allicin treatment)., Results: After the induction of hypoxia/reoxygenation, Allicin treatment enhanced the cell viability. Moreover, Allicin treatment resulted in a reduction of apoptosis from 13.5 ± 1.2% to 6.11 ± 0.15% compared with the HR group (p < 0.05), and the apoptosis related proteins were regulated as well, with a decreased expression of Bax, cleaved caspase-3 and cytosolic cytochrome C and an increase in Bcl-2 expression in the HR + Allicin group (all p < 0.01). Pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha were down-regulated by the treatment with Allicin (both p < 0.01). In addition, it significantly decreased intracellular reactive oxygen species generation (p < 0.01) and reduced the loss of mitochondrial membrane potential (p < 0.01). Furthermore, the expression of PPARγ coactivator-1α and endothelial nitric oxide synthase was up-regulated (both p < 0.01), while the expression of Endothelin-1, hypoxia inducing factor-1α and transforming growth factor beta was down-regulated (all p < 0.01) by Allicin treatment., Conclusions: These results suggested that Allicin protected the cardiomyocytes against HR damage by reducing apoptosis, inflammation and mitochondrial injury, thus providing a basis for its potential use in the treatment of myocardial IR.

Background: Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by neutrophilia and NLRP3 inflammasome and macrophage activation. We investigated the role of neutrophil extracellular traps (NETs) in the pathogenesis of AOSD, and explored the effect of NETs on activating NLRP3 inflammasome and proinflammatory macrophages., Methods: The sera of 73 AOSD patients and 40 healthy controls were used to detect the level of cell-free DNA and NET-DNA complexes. NET formation ex vivo was analyzed using immunofluorescence and flow plates. The activation of NLRP3 inflammasome in THP-1 cells and proinflammatory macrophages stimulated with DNA purified from NETs was measured using RT-PCR, ELISA, Western blotting and flow cytometry., Results: The levels of cell-free DNA and NET-DNA complexes were significantly increased in the circulation of patients with AOSD compared with healthy controls, and freshly isolated neutrophils from patients with AOSD were predisposed to high levels of spontaneous NET release. Interestingly, enhanced NET release was abrogated with NADPH oxidase inhibitors and a mitochondrial scavenger. Furthermore, DNA purified from AOSD NETs activated NLRP3 inflammasomes. NET DNA from AOSD also exerted a potent capacity to accelerate the activation of CD68 + CD86 + macrophages and increased the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Finally, the copy number of mitochondrial DNA (mtDNA) in NETs and plasma was significantly increased in AOSD patients, suggesting that mtDNA may be involved in the activation of NLRP3 and inflammatory macrophages., Conclusions: These findings implicate accelerated NET formation in AOSD pathogenesis through activation of NLRP3 and proinflammatory macrophages, and identify a novel link between neutrophils and macrophages by NET formation in AOSD.

Objective To prepare rabbit-antimouse testis expressed 33 (Tex33) polyclonal antibody and detect the expression of Tex33 during mouse spermatogenesis. Methods Tex33 open reading frame was amplified by PCR from mouse testis cDNA. The PCR product was finally sub-cloned into pET-30a vector. The prokaryotic expression plasmid pET-30a-Tex33 was constructed and then transformed into E. coli BL21. Tex33 prokaryotic protein was induced by IPTG and then purified by Ni-NTA affinity chromatography. Tex33 polyclonal antibody was obtained from adult male New Zealand white rabbits immunized with purified Tex33 protein. ELISA, Western blotting and immunofluorescence assays were used to determine the potency and specificity. Results pET-30a-Tex33 recombinant vector was successfully constructed. After induced by IPTG, the recombinant Tex33 protein could be expressed effectively. The titer of polyclonal antibody was 1:1 000 000. Western blotting showed that the antibody could recognize Tex33 protein in mouse testis. Immunofluorescence assay revealed that Tex33 gene was expressed in spermatids and sperms of adult mouse testis. And Tex33 was located on the acrosome and flagellum of spermatozoa. Conclusion We have prepared rabbit-antimouse Tex33 polyclonal antibody with high specificity and found that Tex33 gene was expressed in mouse testis.

Background: Although several meta-analyses have demonstrated the utility of intravascular ultrasound (IVUS) in guiding drug-eluting stent (DES) implantation compared to angiography-guidance, there has been a dearth of evidence in the left main coronary artery (LMCA) lesion subset., Methods: We performed a meta-analysis to compare clinical outcomes of IVUS versus conventional angiography guidance during implantation of DES for patients with LMCA disease. Pubmed, Cochrane Library, Embase were searched., Results: A total of 1002 publications were reviewed; and finally, seven clinical studies - one prospective randomized controlled trial and six observational studies with 4592 patients (1907 IVUS-guided and 2685 angiography-guided) - were included in the meta-analysis. IVUS guidance was associated with a significant reduction in major adverse cardiac events (relative ratio [RR] 95% CI 0.61; 95% confidence interval [CI] 0.53 to 0.70; P < 0.001), all-cause death (RR 0.55; 95% CI 0.42 to 0.71; P < 0.001), cardiac death (RR 0.45; 95% CI 0.32 to 0.62; P < 0.001), myocardial infarction (RR 0.66; 95% CI 0.55 to 0.80; P < 0.001), and stent thrombosis (RR 0.48; 95% CI 0.27 to 0.84; P = 0.01) compared with angiographic guidance. However, there was no significant difference regarding target lesion revascularization (RR 0.60; 95% CI 0.31 to 1.18; P = 0.099) and target vessel revascularization (RR 0.64; 95% CI 0.26 to 1.56; P = 0. 322)., Conclusions: Compared to angiographic guidance, IVUS-guided DES implantation was associated with better clinical outcomes for patients with LMCA lesions, especially hard endpoints of death, myocardial infarction, and stent thrombosis.

Background: Interleukin (IL)-37 has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of adult-onset Still's disease (AOSD) has not been investigated. In this study, we examined serum IL-37 levels and their clinical association with AOSD, and we explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from patients with AOSD., Methods: Blood samples were collected from 62 patients with AOSD and 50 healthy control subjects (HC). The serum IL-37 levels were determined using an enzyme-linked immunosorbent assay (ELISA). The correlations of serum IL-37 levels with disease activity, laboratory values, and inflammatory cytokines in AOSD were analyzed by Spearman's correlation test. The correlations between serum IL-37 levels and clinical manifestations were analyzed by Mann-Whitney U test. PBMCs from ten patients with AOSD were stimulated with recombinant human IL-37 protein, and expression levels of tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-1β, and IL-18 were determined by qRT-PCR and ELISA., Results: A significantly higher IL-37 protein level was observed in patients with AOSD than in HC. Serum IL-37 levels correlated with systemic score, laboratory values, IL-1β, IL-18, and IL-10 in patients with AOSD. The expression levels of IL-37 were closely related to the patients with AOSD who also had fever, skin rash, lymphadenopathy, splenomegaly, myalgia, and arthralgia. Moreover, the production of proinflammatory cytokines such as IL-6, IL-1β, TNF-α, and IL-18 in PBMCs from patients with AOSD was obviously attenuated after recombinant human IL-37 stimulation., Conclusions: Increased expression of IL-37 and its positive correlation with disease activity suggest its involvement in AOSD pathogenesis. More importantly, IL-37 inhibits the expression of proinflammatory cytokines in PBMCs from patients with AOSD, indicating the potential anti-inflammatory role of IL-37 in AOSD. Thus, IL-37 may be a novel disease activity biomarker and research target in AOSD.

Parkinson's disease (PD) is an aging-associated neurodegenerative disease with a characteristic feature of α-synuclein accumulation. Point mutations (A53T, A30P) that increase the aggregation propensity of α-synuclein result in familial early onset PD. The abnormal metabolism of α-synuclein results in aberrant level changes of α-synuclein in PD. In pathological conditions, α-synuclein is degraded mainly by the autophagy-lysosome pathway. Triptolide (T10) is a monomeric compound isolated from a traditional Chinese herb. Our group demonstrated for the first time that T10 possesses potent neuroprotective properties both in vitro and in vivo PD models. In the present study, we reported T10 as a potent autophagy inducer in neuronal cells, which helped to promote the clearance of various forms of α-synuclein in neuronal cells. We transfected neuronal cells with A53T mutant (A53T) or wild-type (WT) α-synuclein plasmids and found T10 attenuated the cytotoxicity induced by pathogenic A53T α-synuclein overexpression. We observed that T10 significantly reduced both A53T and WT α-synuclein level in neuronal cell line, as well as in primary cultured cortical neurons. Excluding the changes of syntheses, secretion, and aggregation of α-synuclein, we further added autophagy inhibitor or proteasome inhibitor with T10, and we noticed that T10 promoted the clearance of α-synuclein mainly by the autophagic pathway. Lastly, we observed increased autophagy marker LC3-II expression and autophagosomes by GFP-LC3-II accumulation and ultrastructural characterization. However, the lysosome activity and cell viability were not modulated by T10. Our study revealed that T10 could induce autophagy and promote the clearance of both WT and A53T α-synuclein in neurons. These results provide evidence of T10 as a promising mean to treat PD and other neurodegenerative diseases by reducing pathogenic proteins in neurons.