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Objectives Fluoxetine has been used as the first line for the therapy of depression. However, lack of therapeutic efficacy and time lag still limit the application of fluoxetine. Gap junction dysfunction is a potentially novel pathogenic mechanism for depression. To clarify the mechanism underlying these limitations, we investigated whether gap junction was related to the antidepressant effects of fluoxetine. Methods and key findings After chronic unpredictable stress (CUS), animals showed decreases in gap junction intracellular communication (GJIC). Treatment with fluoxetine 10 mg/kg significantly improved GJIC and anhedonia of rats until six days. These results indicated that fluoxetine improved gap junction indirectly. Furthermore, to test the role of gap junction on antidepressant effects of fluoxetine, we blocked gap junction using carbenoxolone (CBX) infusion in the prefrontal cortex. CBX dampened fluoxetine-induced decrease in immobility time of mice in tail suspension test (TST). Conclusions Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine.

Aim: We aimed to design RGD-anchored liposomes encapsulating an antipyroptosis drug that could efficiently target macrophages and relieve the rate of cytokine release syndrome, providing a new strategy for sepsis treatment, especially sepsis-induced acute renal injury. Background: Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by host response disorders due to infection. Sepsis has a high incidence and remains one of the leading causes of death worldwide. Objective: Macrophage-mediated pyroptosis plays an important role in the occurrence and development of cytokine release syndrome and organ injury caused by sepsis. Curcumin can inhibit inflammasome assembly and slow the progression of pyroptosis by scavenging intracellular reactive oxygen species, but it has poor water solubility and low bioavailability. The emergence of drug-delivery nanosystems has overcome this problem, but there is still a lack of research on how to accurately deliver antipyroptotic drugs to innate immune cells and subsequently hinder pyroptosis. Method: We constructed a curcumin-loaded RGD-modified liposome (RGD-lipo/Cur) and demonstrated that RGD-lipo/Cur could effectively target macrophages. Result: In vitro, RGD-lipo/Cur reduced the upregulation of caspase-1, caspase-3, NLRP3, IL-1β and GSDMD, inhibiting pyroptosis, reducing oxidative stress, and attenuating the proinflammatory cytokine cascade. Conclusion: RGD-lipo/Cur was considered to have great potential for sepsis treatment.

Due to the unavoidable stress concentrations and welding defects, the trapezoidal rib-to-deck welded joints of Orthotropic Steel Bridge Decks (OSBD) are prone to fatigue cracking. It is a new exploration to apply Carbon Fiber Reinforced Polymer (CFRP) sheets to strengthen the complex welded joints to improve the fatigue strength. In this paper, the comparative tests of un-strengthened and CFRP strengthened welded joints were carried out. The hot spot stress distribution under static load and fatigue behavior under cyclic load were studied, considering the influence of the number of CFRP sheet layers. The experimental results indicate that CFRP reinforcement can effectively reduce the stress concentrations at weld toe of the deck, and three-layers reinforcement has a greater effect than one-layer reinforcement. There was no significant difference in failure modes between the un-strengthened and CFRP strengthened welded joints. The fatigue cracks of all joints originated from weld toe of the deck, and then expanded along the width and thickness of the deck which caused the deck to break. CFRP reinforcement can significantly improve the fatigue life of trapezoidal rib-to-deck welded joints under the same nominal stress range and three-layers reinforcement presented a longer fatigue life. The S-N curve [Formula: see text] based on the hot spot stress range at weld toe of the deck was established, which can be applied to the fatigue strength design of un-strengthened and CFRP strengthened rib-to-deck welded joints. The mechanism that CFRP reinforcement can significantly improve the fatigue performance of welded joints can be concluded to less stress concentrations and slower growth rate of the crack.

To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene-specific methylation and recurrent spontaneous abortion (RSA).A total of 50 RSA patients who visited our hospital were recruited in the study group; 50 multiparous women who underwent physical examinations during the same period were enrolled in the control group. The levels of homocysteine, folic acid, and vitamin B12 and their MTHFR gene polymorphism and specific methylation were measured in both groups. The Logistic regression equation was used to analyze the correlation between MTHFR gene-specific methylation and RSA.The methylated allele MM was not found in the control group, and the frequency in the study group was 1.19%. The frequency of the MU genotype in the study group 32.93% was higher than that in the control group 12.45%. The frequency of methylated alleles of CC and CT genotypes carrying MTHFR C677T polymorphism in the study group was higher than that in the control group (P 0.05). There was no significant difference in the TT genotype between the two groups (P 0.05). Multivariate Logistic regression analysis exhibited that patients with methylated alleles of CC genotype had a risk of RSA increased by 1.167 times, and the risk increased by 2.500 times in patients with methylated alleles of CT genotype (P 0.05). 83.33% of RSA patients carrying methylated alleles affected hyperhomocysteinemia. In patients with elevated homocysteine levels, the risk of RSA caused by methylated allele was significantly increased by 7.321 times.MTHFR gene-specific methylation can significantly increase the risk of RSA.

Estimating industrial carbon dioxide emissions at the national scale is crucial for China's carbon peak and carbon neutralization targets, as well as the low-carbon development of the Chinese furniture manufacturing industry. For this purpose, in this study the Intergovernmental Panel on Climate Change Tier-2 methodology was used to evaluate the carbon dioxide emissions of the Chinese furniture manufacturing industry at the national scale. The results show that carbon dioxide emissions increased from 219.50 × 10,000 tons of CO2 equivalent in 2000 to 850.68 × 10,000 tons of CO2 equivalent in 2019. Moreover, carbon dioxide emission intensity decreased from 9.50 tons of CO2 per million dollars to 1.73 tons of CO2 per million dollars in this period. Moreover, electricity and raw coal were observed to have a significant influence on carbon dioxide emissions, followed by diesel oil, gasoline, heat energy, and natural gas. The results reveal that the Chinese furniture manufacturing industry has generally realized low-carbon development over the past two decades. This work proposes several suggestions to reduce carbon dioxide emissions from the Chinese furniture manufacturing industry, including promoting the use of clean electricity, the installation of photovoltaic cells, industrial transformation and upgrading, the optimization of transport modes for product delivery and material supply, and the employment of low-carbon raw materials.

For simulation-based systems, finding a set of test cases with the least cost by exploring multiple goals is a complex task. Domain-specific optimization goals (e.g. maximize output variance) are useful for guiding the rapid selection of test cases via mutation. But evaluating the selected test cases via mutation (that can distinguish the current program from the mutated systems) is a different goal to domain-specific optimizations. While the optimization goals can be used to guide the mutation analysis, that guidance should be viewed as a weak indicator since it can hurt the mutation effectiveness goals by focusing too much on the optimization goals. Based on the above, this paper proposes DoLesS (Domination with Least Squares Approximation) that selects the minimal and effective test cases by averaging over a coarse-grained grid of the information gained from multiple optimizations goals. DoLesS applies an inverted least squares approximation approach to find a minimal set of tests that can distinguish better from worse parts of the optimization goals. When tested on multiple simulation-based systems, DoLesS performs as well or even better as the prior state-of-the-art, while running 80-360 times faster on average (seconds instead of hours)., 17 pages, 5 figures, 7 tables. Accepted by TSE

A synthetic modulation approach has given rise to two topologically distinct thorium-based MOFs, whose polymorphism allows for elucidating how the structure of MOF, in isolation, influences the sensing efficacy of Cr(vi) oxyanions.

The efficient and catalytic biscyclization of dithioallylic alcohols with 1-styrylnaphthols under mild conditions was achieved, thus affording pharmaceutically important cyclopenta[b]dihydronaphthofurans.

Background: Ventricular septal defect (VSD) is one of the most common congenital cardiac defects, However, in some cases VSD sites are difficult to expose due to obstruction from chordal attachments and leaflets of the tricuspid valve (TV)[6](#ref-0006). To systematically review the efficacy and safety of tricuspid valve detachment,( TVD) versus conventional surgical repair ( non-TVD) in the treatment of ventricular septal defect ( VSD) ．This article is aimed to compare the many outcomes from existing studies and provide evidence regarding the necessity of performing TVD. Methods:We searched the following databases: PubMed via NCBI, the Cochrane Central Register of Controlled Trials (no date restriction),Medline via Ovid (from 1966 to May 2020); Embase via Ovid (no date restriction) and China National Knowledge Infrastructure for studies comparing the efficacy of tricuspid valve detachment (TVD) and other surgical techniques in VSD repair. Cardiopulmonary bypass time, Cross-clamp time; postoperative complications including residual defect ,Postoperative atrioventricular block ,Implantation of pacemakers, tricuspid regurgitation ;Length of stay, Length of ICU stay were analyzed． Results: Only 9 studies were included after selection (Table 1), including 7 retrospective cohort studies, 1 respective cohort study and 1 prospective observational stud，a patient pool of 1404 patients with 374 underwent TVD and 1030 underwent non-TVD procedures,met the inclusion criteria．Meta analysis has drawn to the following conclusions. Firstly, TVD prolongs CPB time (MD=7.75, 95% CI=2.60-12.89, p=0.003) and cross-clamp time(MD=7.77, 95% CI=4.76-10.78, pConclusion: VSD closure using TVD technique results in longer CPB and cross-clamp time, and increases risk of TR during follow-up. TVD provides equally viable and safe alternative in treating VSD．

Basel III modified the requirements for approving new regulatory capital norms to improve capital quality. Because bank liquidity problems were a defining feature of the crisis, Basel III established new requirement ratios while also tightened capital requirements. The Liquidity Coverage Ratio (LCR) was developed to safeguard banks' short-term liquidity, whereas the Net Stable Funding Ratio (NSFR) is being proposed to strengthen banks' medium- and long-term liquidity shock resilience. As a necessary consequence, Islamic financial institutions (IFIs) must issue instruments that satisfy both Basel III and Shari’ah requirements. This study aims to identify the regulatory requirements for Basel III and the Islamic Financial Services Board (IFSB)'s new capital and liquidity rules, as well as the implications for Islamic banks (IB). This study employs a mixed research methodologies approach which includes document analysis of primary and secondary sources, as well as the relevant regulations published by BCBS and IFSB. This study relies on the identification of Standards for each criterion before conducting a systematic review of the 23 publications that meet the study's requirements published between 2013 and 2022. There is a scarcity of Shari’ah-compliant research on capital buffers, tier 1 capital, and common equity tier 1 capital, according to certain findings. Furthermore, the empirical literature suggests that Basel III has a significant impact on the financial risk of the IB sector in the samples collected. However, there is still a significant gap in studies investigating the influence of Basel III/IFSB capital and liquidity regulations on Islamic bank risk, or more precisely, supportive data from empirical investigations. The wealth of research will provide new insights to standard-setters (BCBS and IFSB), regulators, researchers, and academicians.

Air pollution was considered one of the main causes linked to increased morbidity and mortality around the world. This study aimed to estimate the effect of air pollutants on daily death in Baotou city of Inner Mongolia. Daily deaths data were provided by Baotou Centers for Disease Control and Prevention for the years 2015-2019 (Baotou CDC). The air pollutants, PM

Pericardial fistula is a rare complication. Generally, the diagnosis can be confirmed by imaging examination, but our patient was an exception. We present a 71-year-old female patient that complained of remnant gastric cancer for five months and dyspnea for seven days; the dyspnea became aggravated during the last two days. After admission, emergency thoracic computed tomography and echocardiography showed pericardial effusion, and pericardiocentesis was performed. After conventional treatment, the pericardial effusion was unchanged and no cancer cells were found in the pericardial drainage. However, the color changed from turbid to golden yellow and, finally, to green. After 20 days of repeated laboratory, imaging, and gastrointestinal contrast examinations, no cause was found. Moreover, a clinical diagnosis could not be obtained following numerous comprehensive clinical analyses. Given the color change of the pericardial drainage, we strongly suspected pericardial fistula, but the imaging examinations were negative. Finally, a methylene blue test confirmed the existence of a pericardial fistula. When the color of the pericardial effusion changes, the existence of a pericardial fistula must be considered in advance, and other methods should be evaluated if imaging cannot assist in the diagnosis.

Retinopathy of prematurity (ROP) is characterized by pathologic angiogenesis in retina, and it remains a leading cause of blindness in children. Although enhanced extracellular adenosine is markedly increased in response to retinal hypoxia, adenosine acting at the A

Jia-Li Zhang,1,2,&ast; An-Xin Wang,1,2,&ast; Yang Yang,2,3 Qin Xu,1,2 Xiao-Ling Liao,1,2 Wei-Guo Ma,4 Ning Zhang,2,3 Chun-Xue Wang,2,3,5 Yong-Jun Wang1,2 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Neuropsychiatry and Behavioral Neurology and Clinical Psychology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Zhang; Chun-Xue Wang, Beijing Tiantan Hospital, 119 South 4th Ring West Road, Beijing, 100070, People’s Republic of China, Emails 827582777@qq.com; snowsen@126.comBackground: Although sleep disorders significantly increase the risk of cognitive impairment, literature is relatively scarce regarding the impact of sleep status on cognitive function in patients with acute ischemic stroke (AIS). We seek to study the association between pre-stroke subjective sleep status and cognitive function at 3 months after stroke.Patients and methods: Data were analyzed for 1,759 AIS patients from the Impairment of Cognition and Sleep after Acute Ischemic Stroke or Transient Ischemic Attack in Chinese Patients Study (ICONS). Pre-stroke subjective sleep status was assessed by the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Greater sleep fragmentation was defined as waking up in the middle of the night or early morning ≥ 3 times a week. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) at 3 months after stroke. Primary endpoint was the incidence of post-stroke cognitive impairment (PSCI) at 3 months after stroke. The association between subjective sleep status and PSCI was evaluated using multivariable logistic regression.Results: PSCI occurred in 52.1% at 3 months after stroke. Patients with very bad sleep quality before stroke were at increased risk of PSCI (OR, 2.11; 95% CI, 1.11– 4.03; P=0.03). Subgroup analysis found that the association between very bad sleep quality and PSCI was more evident among patients with high school education or above (OR, 5.73; 95% CI, 1.92– 17.10; P for interaction=0.02). In addition, patients with greater sleep fragmentation before stroke were also at higher risk of PSCI (OR, 1.55; 95% CI, 1.20– 2.01; P< 0.01). Similarly, subgroup analysis showed that the risk of PSCI was more pronounced among patients without employment (OR, 2.45; 95% CI, 1.59– 3.77; P for interaction=0.01).Conclusion: Very bad sleep quality and greater sleep fragmentation before stroke were identified as independent risk factors for PSCI at 3 months after stroke.Keywords: subjective sleep status, cognitive impairment, ischemic stroke

The epidermal growth factor receptor (EGFR) is a pleiotropic glycoprotein which plays a role in regulating cell proliferation, migration and differentiation. However, the genetic diversity of EGFR in crustaceans as well as its function, such as whether it is involved in immune regulation, remains obscure. In this study, two EGFR genes, including EGFR1 and EGFR2, and three transcripts were identified and characterized in Scylla Paramamosain for the first time. To our knowledge, this is the first time that more than one EGFR gene was identified in a single species. The complete open reading frames (ORFs) of SpEGFR1, SpEGFR2a and SpEGFR2b were 4377 bp, 4404 bp and 4341 bp encoding deduced proteins of 1458 amino acids (aa), 1467 aa and 1446 aa, respectively. All EGFR had a signal peptide region and two Recep_L_domain region, followed by a transmembrane region and a conserved tyrosine kinase domain (TyrKc), and phylogenetic analysis demonstrated three SpEGFRs clustered together with invertebrate EGFR branch. Tissue specific expression analysis depicted that all SpEGFRs presented similar transcription patterns. The expression levels of SpEGFR1 and SpEGFR2s in hepatopancreas and gills were significantly altered after the stimulation of bacterial and viral pathogens including Staphylococcus aureus, Vibrio alginolyticus, White spot syndromre virus and Polycytidylinic acid. The in vivo RNA interference assays demonstrated that expression levels of SpIKK, two members of NF-κB (SpRelish and SpDorsal) and six antimicrobial peptide (AMP) genes (SpCrustin and SpALF1-5) were significantly reduced when SpEGFR1 or SpEGFR2 was silenced, respectively. The transcription patterns of SpIKK, SpRelish, SpDorsal and AMPs exhibited similar down- or up-regulation trend when the primary cultured hemocytes were treated with EGFR antagonist or agonist for 24 h. These results suggested that SpEGFR might play an important role in innate immune responses to bacterial and viral infections by regulating the NF-κB pathway. It also provided a better understanding of the origin or evolution of EGFR in crustaceans and even invertebrates.

Tumor heterogeneity in breast cancer hinders proper diagnosis and treatment, and the identification of molecular subtypes may help enhance the understanding of its heterogeneity. Therefore, we proposed a novel integrated multi-omics approach for breast cancer typing, which led to the identification of a hybrid subtype (Mix_Sub subtype) with a poor survival prognosis. This subtype is characterized by lower levels of the inflammatory response, lower tumor malignancy, lower immune cell infiltration, and higher T-cell dysfunction. Moreover, we found that cell-cell communication mediated by NCAM1-FGFR1 ligand-receptor interaction and cellular functional states, such as cell cycle, DNA damage, and DNA repair, were significantly altered and upregulated in patients with this subtype, and that such patients displayed greater sensitivity to targeted therapies. Subsequently, using differential genes among subtypes as biomarkers, we constructed prognostic risk models and subtype classifiers for the Mix_Sub subtype and validated their generalization ability in external datasets obtained from the GEO database, indicating their potential therapeutic and prognostic significance. These biomarkers also showed significant spatially variable expression in malignant tumor cells. Collectively, the identification of the Mix_Sub breast cancer subtype and its biomarkers, based on the driving relationship between omics, has deepened our understanding of breast cancer heterogeneity and facilitated the development of breast cancer precision therapy.

Common treatment methods for malignant tumors include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, etc., among which chemotherapy plays an important role. However, chemotherapy brings corresponding side effects while killing tumor cells, and nausea and vomiting are the most common adverse reactions induced by chemotherapy. It not only affects the patient’s appetite, resulting in malnutrition and electrolyte disturbances, but also reduces the patient’s compliance with treatment, which further aggravates the disease. Thus, it is important to quickly prevent and cure nausea and vomiting induced by chemotherapy (CINV). In addition, with the continuous development of medicine, more and more antiemetic drugs have been developed. At present, the most common antiemetic agents for chemotherapy-induced nausea and vomiting are NK-1R antagonists, 5-HT3R antagonists, and dexamethasone. Surprisingly, olanzapine, often used as a psychotropic drug, has been found to be an effective antiemetic and is similar to other regimens on the safety of medicine. However, although there are numerous studies on the antiemetic effects of olanzapine, its comprehensive application remains unclear. Therefore, this review will elaborate the antiemetic effect of olanzapine in terms of the antiemetic mechanism and the safety, economic cost, dose, administration time, and drug delivery aspects.

Background: Diabetes is a common chronic disease which has caused a great burden on families and society. The treatment of diabetes has always been a hotspot. This study aimed to explore the effect and mechanism of miR-30d-5pon inflammation of high glucose-impaired human keloid fibroblasts (HKF). Methods: Differently-expressed miRNAs were predicted by bioinformatics methods. Exosomes were observed by transmission electron microscope. Exosome particle sizes were measured by NanoSight. Western Blot was used to detect the expression of CD81, CD63, CD9, and Calnexin. QRT-PCR was used to detect the expression of miR-30d-5p, IL-1β, TNF-α, VEGF, FGF21, NRF2, and HO-1. The levels of IL-1β, TNF-α, IL-6, IL-10, and TGF-β were determined by ELISA. Cell apoptosis and CD86, CD206 positive cells were detected by flow cytometry. Results: Tori formula could promote the secretion of endothelial progenitor cell (EPCs) exosomes. EPCs exosomes and miR-30d-5p could stimulate the proliferation of HKF impaired by high glucose and the expression of IL-10 and TGF-β. MiR-30d-5p inhibited the proliferation of M1 macrophages and the expression of IL-1β and TNF-α. It could also promote the proliferation of M2 macrophages and the expression of CCL17 and CCL22. Moreover, miR-30d-5p stimulated the expression of VEGF, FGF21, NRF2, and HO-1, as well as suppressed the expression of IL-1β, TNF-α, and IL-6. MiR-30d-5p also restrained the apoptosis of impaired HKF. Conclusion: This study confirmed that miR-30d-5p could promote the M1/M2 polarization and inhibit the inflammatory response of impaired HKF, which provided a certain idea and direction for treating diabetes.

Nitrilases are promising biocatalysts to produce high-value-added carboxylic acids through hydrolysis of nitriles. However, since the enzymes always show low activity and sometimes with poor reaction specificity toward 2-chloronicotinonitrile (2-CN), very few robust nitrilases have been reported for efficient production of 2-chloronicotinic acid (2-CA) from 2-CN. Herein, a nitrilase from Paraburkholderia graminis (PgNIT) was engineered to improve its catalytic properties. We identified the beneficial residues via computational analysis and constructed the mutant library. The positive mutants were obtained and the activity of the "best" mutant F164G/I130L/N167Y/A55S/Q260C/T133I/R199Q toward 2-CN was increased from 0.14 × 10

This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = -0.87, 95% confidence interval [CI]: -1.07 to -0.67, P .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P .00001), and reducing hospital stays (mean difference = -15.29, 95% CI: -16.05 to -14.54, P .00001), but the differences in dressing change times (SMD = -1.27, 95% CI: -2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = -0.16, 95% CI: -13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.

Nanozyme with intrinsic enzyme-like activity has emerged as favorite artificial catalyst during recent years. However, current nanozymes are mainly limited to inorganic-derived nanomaterials, while biomolecule-sourced nanozyme (bionanozyme) are rarely reported. Herein, inspired by the basic structure of natural hydrolase family, we constructed 3 oligopeptide-based bionanozymes with intrinsic hydrolase-like activity by implementing zinc induced self-assembly of histidine-rich heptapeptides. Under mild condition, divalent zinc (Zn