The Micron-Droplet-Confined Continuous-Flow Synthesis of Freestanding High-Entropy-Alloy Nanoparticles by Flame Spray Pyrolysis.

Alloying multiple immiscible elements into a nanoparticle with single-phase solid solution structure (high-entropy-alloy nanoparticles, HEA-NPs) merits great potential. To date, various kinds of synthesis techniques of HEA-NPs are developed; however, a continuous-flow synthesis of freestanding HEA-NPs remains a challenge. Here a micron-droplet-confined strategy by flame spray pyrolysis (FSP) to achieve the continuous-flow synthesis of freestanding HEA-NPs, is proposed. The continuous precursor solution undergoes gas shearing and micro-explosion to form nano droplets which act as the micron-droplet-confined reactors. The ultrafast evolution (<5 ms) from droplets to <10 nm nanoparticles of binary to septenary alloys is achieved through thermodynamic and kinetic control (high temperature and ultrafast colling). Among them, the AuPtPdRuIr HEA-NPs exhibit excellent electrocatalytic performance for alkaline hydrogen evolution reaction with 23 mV overpotential to achieve 10 mA cm-2, which is twofold better than that of the commercial Pt/C. It is anticipated that the continuous-flow synthesis by FSP can introduce a new way for the continuous synthesis of freestanding HEA-NP with a high productivity rate.

Q-space imaging based on Gaussian radial basis function with Laplace regularization.

PURPOSE: To introduce the diffusion signal characteristics presented by spherical harmonics (SH) basis into the q-space imaging method based on Gaussian radial basis function (GRBF) to robustly reconstruct ensemble average diffusion propagator (EAP) in diffusion MRI (dMRI). METHODS: We introduced the Laplacian regularization of the signal into the dMRI imaging method based on GRBF, and derived the relevant indicators of microstructure imaging and the orientation distribution function (ODF) providing fiber bundle direction information based on EAP. In addition, this method is combined with a multi-compartment model to calculate the diameter of fiber bundle axons. The evaluation of the results included qualitative comparisons and quantitative assessments of the signal fitting. RESULTS: The results show that the proposed method achieves the more significant accuracy improvement in reconstructing signal. Meanwhile, ODFs estimated by the proposed method show the sharper profiles and less spurious peaks, even under the sparse and noisy conditions. In the 36 sets of axon diameter estimation experiments, 34 and 30 sets of results showed that the proposed method reduced the mean and SD of axon diameter estimates, respectively. Moreover, compared with the current state-of-the-art method, the mean and SD of axon diameter estimated by the proposed method are mostly lower, with 32 and 29 of 36 groups. CONCLUSION: The proposed method outperforms the GRBF regarding signal fitting and the estimation of the EAP and ODF with multi-shell sparse samples. Moreover, it shows the potential to recover important features of microstructures with less uncertainty by using proposed method together with multi-compartment models.

Highly reusable Bi2O3/electron-Cu-shuttle in-situ immobilized polyacrylonitrile fibrous mat for efficient photocatalytic degradation of methylene blue and rhodamine B dyes.

Organic semiconductor-based photocatalysts have been alluring due to their edge over inorganic photocatalysts. In this study, a reusable copper-bismuth oxide/polyacrylonitrile (Cu-Bi2O3/PAN) fibrous mat was prepared by fast-process flame spray pyrolysis and electrospinning for photocatalytic degradation of methylene blue (MB) and rhodamine B (RhB) dyes. The results confirmed a well-defined morphology of Cu-Bi2O3/PAN fibers and good coordination of flame-made Cu-Bi2O3 particles with the functional groups of PAN. The Cu-Bi2O3/PAN fibrous mat exhibits remarkable photocatalytic performance of 96.2% MB and 98.6% RhB degradation, with a reaction rate as high as about 4.5- and 10.2-times than that of flame-made Cu-Bi2O3 particles and PAN under neutral condition, even after 10 cycles. The Cu-Bi2O3/PAN exhibits complete degradation of MB and RhB in 90 and 150 min under alkaline and slightly acidic conditions, respectively. The synergistic effect of Cu-Bi2O3 and coordination bond between particles and functional groups of PAN promoted carrier migration, suppressed recombination of carriers and provided abundant radicals on the surface of the mat. Superoxide and hydroxyl radicals were the major active species involved in the degradation of RhB and MB, respectively. This work provides an insight into designing the Cu-metal-shuttle based photocatalysts to optimize fibrous mat application in water remediation.

ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1.

Zinc finger CCHC-type containing 4 (ZCCHC4), RNA binding protein, has been reported to mediate rRNA methylation and affect tumor cell proliferation. However, the role of ZCCHC4 in the regulation of osteosarcoma (OS) remains unknown. ZCCHC4 was highly expressed in OS tissues and cell lines. Overexpression or silencing of ZCCHC4 promoted or inhibited cell proliferation, epithelial-mesenchymal transition (EMT), and motility. Additionally, we proved that ZCCHC4 facilitates OS progression through upregulating integrin ß1 (ITGB1). In the animal model, ZCCHC4 knockdown reduced OS tumor growth and metastases in vivo. Our findings showed that ZCCHC4 promoted the progression of OS through upregulating ITGB1 and suggested that inhibition of ZCCHC4 could be a novel therapeutic strategy for OS.

Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis.

BACKGROUND: Metastasis of cancer causes more than 90% of cancer deaths and is severely damaging to human health. In recent years, several studies have linked sarcopenia to shorter survival in patients with metastatic cancer. Several predictive models exist to predict mortality in patients with metastatic cancer, but have reported limited accuracy. METHODS: We systematically searched Medline, EMBASE, and the Cochrane Library for articles published on or before October 14, 2022. Pooled Hazard Ratio (HR) estimates with 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was an increased risk of death or tumor progression in patients with metastatic cancer, which is expressed as progression-free survival (PFS). In addition, we performed subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Sixteen retrospective cohort studies with 1,675 patients were included in the 888 papers screened. The results showed that sarcopenia was associated with lower progression-free survival (HR = 1.56, 95% CI = 1.19-2.03, I2 = 76.3%, P < 0.001). This result was further confirmed by trim-and-fill procedures and leave-one-out sensitivity analysis. CONCLUSIONS: This study suggests that sarcopenia may be a risk factor for reduced progression-free survival in patients with metastatic cancer. Further studies are still needed to explain the reason for this high heterogeneity in outcome. TRIAL REGISTRATION: CRD42022325910.

Highly Stable and Ultrahigh-Rate Li Metal Anode Enabled by Fluorinated Carbon Fibers.

The advanced energy storage of an Li metal substituted for graphite anode can provide a significant enhancement in a battery's energy density. Nevertheless, the practical implementation of metallic Li has seriously been fettered by the notorious Li dendrite growth and the huge volumetric variation of Li metal inducing poor cycling performance and safety concerns. In this regard, constructing a robust SEI layer combined with a 3D host to stabilize the Li metal is strongly in demand. Herein, a highly stable hosted Li with an LiF dominated SEI has successfully been achieved through metal-free fluorinated carbon fibers (FCF) with strong lithiophilicity. The metal-free design is cost-effective and can retain the energy density of the Li metal, minimizing the unnecessary energy sacrifice from the extra high gravimetric density lithiophilic sites. The FCF hosted Li delivers a promoted high Coulombic efficiency, homogeneous Li deposition, and ultrahigh rate stable cycling over 1000 cycles at 20 mA cm-2 with a much lower voltage polarization (≈220 mV). Moreover, half cells coupled with LiNi0.8 Co0.1 Mn0.1 O2 , sulfur or even thick LiCoO2 cathode demonstrate superior rate performances and enhanced cycling stability even under a lean electrolyte. This work proves the feasibility of FCF hosted Li for practical usage and provides a novel approach toward cost-effective and high performance lithium metal batteries.

Long-term follow-up in patients with Brugada Syndrome in South China.

OBJECTIVE: To evaluate the presence of Brugada electrocardiogram (ECG) pattern, clinical characteristics, treatment, and long-term prognosis of Brugada syndrome in southern Chinese population. METHODS: This prospective study consisted of a consecutive series of patients with diagnostic coved type I Brugada ECG pattern at baseline between January 2007 and February 2020. Histories of symptoms including ventricular tachycardia (VT)/ventricular fibrillation (VF) episode, syncope, and family history of Brugada Syndrome (BrS) or unexplained sudden cardiac death were collected. Electrophysiological study and implantable cardioverter-defibrillator (ICD) were performed. All patients included in this study were followed up in the outpatient department every 6 months after baseline evaluation. Occurrences of syncope, VF, and sudden death were independently analyzed by two cardiologists. RESULTS: 45 (56.3%) patients were diagnosed with BrS. During a mean follow-up of 7.9 ± 3.6 years, six patients had experienced documented VF/sudden cardiac death (SCD) or recurrent syncope. Two patients experienced episodes of syncope more than once. Two patients experienced onset of electrical storm with a total of 11 episodes of VF. There were 50% of these events occurring in fever status. One of patient with BrS died of SCD. CONCLUSION: There was a very low prevalence of Brugada syndrome in southern Chinese population. The risk of arrhythmic events was low in asymptomatic patients. ICD was high effective in preventing SCD without adverse device outcome in long-term follow-up. Fever can lead to predispose to malignant arrhythmia, and aggressive treatment of febrile state in Brugada syndrome was recommended.

Tp-e and (Tp-e)/QT ratio as a non-invasive risk factors for malignant ventricular arrhythmia in patients with idiopathic ventricular premature complexes.

BACKGROUND: To evaluate the role of Tp-e and (Tp-e)/QT ratio in differentiating benign ventricular premature complex (VPC) and malignant polymorphic ventricular tachycardia (PVT). METHODS: From January 2017 to December 2017, patients with documented polymorphic ventricular tachycardia (PVT) or ventricular fibrillation (VF) were consecutive included and classified as PVT/VF group. Sixty age- and sex-matched healthy individuals were recruited as comparative control and subdivided into non-VPC and VPC group. Clinical characteristics and Tp-e and Tp-e/QT ratio between the three groups were compared. RESULTS: Tp-e and (Tp-e)/QT ratio were significantly higher in patients of PVT/VF group compared with the other two groups (P < .001). Episodes of syncope were more frequent in patients with PVT/VF (P < .05). The sensitivity and specificity of a Tp-e interval ≥86 ms for malignant arrhythmias triggered by VPCs were 88% and 66%, respectively, while the sensitivity and specificity of the Tp-e/QT ratio ≥0.24 were 82% and 70%, respectively. Five patients complained recurrence of syncope in the PVT/VF group and 1 patient died with mean follow-up of 18 months. CONCLUSION: Tp-e interval and the Tp-Te/QT ratio is significantly increased in patients with PVT/VF and may be used as a novel non-invasive marker of differentiating malignant and benign VPC.

Mining, heterologous expression, purification, antibactericidal mechanism, and application of bacteriocins: A review.

Bacteriocins are generally considered as low-molecular-weight ribosomal peptides or proteins synthesized by G+ and G- bacteria that inhibit or kill other related or unrelated microorganisms. However, low yield is an important factor restricting the application of bacteriocins. This paper reviews mining methods, heterologous expression in different systems, the purification technologies applied to bacteriocins, and identification methods, as well as the antibacterial mechanism and applications in three different food systems. Bioinformatics improves the efficiency of bacteriocins mining. Bacteriocins can be heterologously expressed in different expression systems (e.g., Escherichia coli, Lactobacillus, and yeast). Ammonium sulfate precipitation, dialysis membrane, pH-mediated cell adsorption/desorption, solvent extraction, macroporous resin column, and chromatography are always used as purification methods for bacteriocins. The bacteriocins are identified through electrophoresis and mass spectrum. Cell envelope (e.g., cell permeabilization and pore formation) and inhibition of gene expression are common antibacterial mechanisms of bacteriocins. Bacteriocins can be added to protect meat products (e.g., beef and sausages), dairy products (e.g., cheese, milk, and yogurt), and vegetables and fruits (e.g., salad, apple juice, and soybean sprouts). The future research directions are also prospected.

A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2-AS1 or SMAD3 and miR-143-3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis. RESULTS: ACTA2-AS1 was significantly increased in CC tissues and cells and miR-143-3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells. CONCLUSIONS: In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC.

Clinical observation of percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fracture.

OBJECTIVE: To investigate the clinical efficacy of percutaneous vertebroplasty (PVP) on osteoporotic vertebral compression fracture and relevant issues. METHODS: The data of 80 patients with osteoporotic vertebral compression fracture admitted to Orthopaedics Department, Huanggang Central Hospital from September 2013 to September 2015 was selected for analysis. The data selection was done from December 2018 to February 2019 Under local anaesthesia and C-arm X-ray fluoroscopy, percutaneous kyphoplasty was performed by puncturing into unilateral (or bilateral) pedicle(s) percutaneously and fixing with bone cement. The degree of lower back pain and the recovery of vertebral height in patients were observed and recorded before surgery, 24 hours and 3 months after surgery. RESULTS: All of the 80 patients had a successful surgery. After 24 hours of surgery, 47 (58.75%) patients had no lower back pain, 33 (41.25%) had mild dull pain locally; 74 (92.50%) patients were able to have out-of-bed activity on Day1 after surgery, and 6 (7.50%) patients were able to have out-of-bed activity on Day 3 after surgery. The visual analogue scale (VAS) score and percentage of injured vertebra height to original vertebra height 24 hours and 3 months after surgery were significantly better than those before surgery (P<0.01). The VAS score 3 months after surgery was significantly superior to the VAS score 24 hours after surgery (P<0.01). Compared with 24 hours after surgery, the injured vertebra height was lost 3 months after surgery, but it was not statistically significant (P>0.05). There were no complications, such as infection, haematoma, spinal nerve injury and bone cement toxicosis. CONCLUSIONS: In the treatment of thoracolumbar osteoporotic vertebral compression fracture, PVP can effectively relieve pain, restore vertebral height partially and the efficacy is satisfactory.

Long non-coding RNA expressed in macrophage co-varies with the inflammatory phenotype during macrophage development and polarization.

Advances in microarray, RNA-seq and omics techniques, thousands of long non-coding RNAs (lncRNAs) with unknown functions have been discovered. LncRNAs have presented a diverse perspective on gene regulation in diverse biological processes, especially in human immune response. Macrophages participate in the whole phase of immune inflammatory response. They are able to shape their phenotype and arouse extensive functional activation after receiving physiological and pathological stimuli. Emerging studies indicated that lncRNAs participated in the gene regulatory network during complex biological processes of macrophage, including macrophage-induced inflammatory responses. Here, we reviewed the existing knowledges of lncRNAs in the processes of macrophage development and polarization, and their roles in several different inflammatory diseases. Specifically, we focused on how lncRNAs function in macrophage, which might help to discover some potential therapeutic targets and diagnostic biomarkers.

[The significance of monitoring procalcitonin when applying antibiotics to trichlorethylene dermatitis].

OBJECTIVE: To investigate the significance of monitoring procalcitonin (PCT) when applying antibiotics to trichlorethylene (TCE)-induced dermatitis. METHODS: One hundred and two patients who were hospitalized and recovered from TCE-induced dermatitis in our hospital from 2006 to 2013 were enrolled as subjects. Based on whether the PCT level was monitored or not, we divided patients into regular group and PCT group. For the regular group, we applied antibiotic treatment and determined the course of treatment based on clinical symptoms, laboratory test results, medical imaging results, and bacterial culture. For the PCT group, in addition to the above treatments, antibiotic treatment was applied when the PCT level was not lower than 0.25 ng/ml and stopped when the PCT level was lower than 0.25 ng/ml. The distribution of bacterial infection sites, type of bacteria, type of antibiotics, average period of hospitalization, and course of antibiotic treatment were compared between the two groups. RESULTS: There were no significant differences in the distribution of bacterial infection sites, type of bacteria, type of antibiotics, and average period of hospitalization between the two groups (P > 0.05). The course of antibiotic treatment for the PCT group was significantly shorter than that for the regular group (25.37 ± 11.66 vs 20.58 ± 7.53 d, P < 0.05). CONCLUSION: Under similar conditions of bacterial infection, antibiotic treatment of TCE-induced dermatitis based on the serum PCT level can significantly shorten the course of treatment and avoid the abuse of antibiotics.

Improving the predictive accuracy of efficacy evaluation using tumor orthotopic transplant and resection model.

Preclinical efficacy evaluation and tumor drug sensitivity analysis are two main applications of efficacy evaluation. Preclinical efficacy evaluation is to predict whether candidate drugs or therapies may improve patient outcomes in clinical trials. Tumor drug sensitivity analysis is an approach for the personalized evaluation and optimization of approved anti-cancer drugs and treatment regimens. Overall survival (OS) is the gold standard to evaluate the outcome of drugs or therapies in both clinical trials and clinical treatment. Many efficacy evaluation models, such as cell model, tumor cell-line transplant model, patient-derived tumor xenograft model, tumor organoid model, have been developed to assess the inhibitory effect of tested drugs or therapies on tumor growth. In fact, many treatments may also lead to malignant progression of tumors, such as chemotherapy, which can lead to metastasis. Therefore, tumor growth inhibition does not necessarily predict OS benefit. Whether it can prevent or inhibit tumor recurrence and metastasis is the key to whether drugs and therapies can improve patient outcomes. In this perspective, we summarize the current understanding of the pathological progression of tumor recurrence and metastasis, point out the shortcomings of existing tumor transplant models for simulating the clinical scenario of malignant progression of tumors, and propose five improved indicators for comprehensive efficacy evaluation to predict OS benefit using tumor orthotopic transplant and resection model. Improvement in the accuracy of efficacy evaluation will accelerate the development process of anti-cancer drugs or therapies, optimize treatment regimens to improve OS benefit, and reduce drug development and cancer treatment costs.

11ß-Hydroxysteroid dehydrogenase type 1 amplifies inflammation in LPS-induced THP-1 cells.

Objectives: The role of glucocorticoids as anti-inflammatory and immune-stimulatory drugs has been widely reported. However, the role of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which catalyzes the conversion of inactive cortisone into active cortisol, in inflammation remains unclear. This study aimed to examine the mechanism of actions of 11ß-HSD1 in lipopolysaccharide (LPS)-induced THP-1 cells. Materials and Methods: The gene expression of 11ß-HSD1 and pro-inflammatory cytokines was detected via RT-PCR. The protein expression of IL-1ß in cell supernatants was detected via ELISA. Oxidative stress and mitochondrial membrane potential were assessed using a reactive oxygen species (ROS) kit and a mitochondrial membrane potential (MMP) kit, respectively. The expression of Nuclear Factor- Kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) was detected via western blotting. Results: Elevated levels of 11ß-HSD1 contributed to the expression of inflammatory cytokines, whereas BVT.2733, a selective 11ß-HSD1 inhibitor, ameliorated inflammatory responses, ROS, and mitochondrial damage in LPS-stimulated THP-1 cells. Furthermore, cortisone and cortisol, which are the substrate and product of 11ß-HSD1, respectively, showed biphasic responses and induced the expression of pro-inflammatory cytokines at a low concentration in both LPS-stimulated or untreated THP-1 cells. The enhanced inflammation was attenuated by co-treatment with BVT.2733 and the glucocorticoid receptor (GR) antagonist RU486, but not in those treated with the mineralocorticoid receptor (MR) antagonist spironolactone. Overall, the results indicate that 11ß-HSD1 amplifies inflammatory responses by activating the NF-κB and MAPK signaling pathways. Conclusion: Inhibition of 11ß-HSD1 may serve as a potential therapeutic target against the excessive activation of inflammation.

Colorimetric Chemosensor Based on Fe3O4 Magnetic Molecularly Imprinted Nanoparticles for Highly Selective and Sensitive Detection of Norfloxacin in Milk.

Long-term use of norfloxacin (NOR) will cause NOR residues in foods and harm human bodies. The determination of NOR residues is important for guaranteeing food safety. In this study, a simple, selective, and label-free colorimetric chemosensor for in situ NOR detection was developed based on Fe3O4 magnetic molecularly imprinted nanoparticles (Fe3O4 MMIP NPs). The Fe3O4 MMIP NPs showed good peroxidase-like catalytic activity to 3,3',5,5'-tetramethylbenzidine (TMB) and selective adsorption ability to NOR. The colorimetric chemosensor was constructed based on the Fe3O4 MMIP NPs-H2O2-TMB reaction system. The absorbance differences were proportional to the concentrations of NOR in the range of 10-300 ng/mL with a limit of detection at 9 ng/mL. The colorimetric chemosensor was successfully applied to detect NOR residue in milk. The recovery range was 78.2-95.81%, with a relative standard deviation of 2.1-9.88%. Together, the proposed colorimetric chemosensor provides a reliable strategy for the detection of NOR residues in foods.

Establishment of a primary renal lymphoma model and its clinical relevance.

Extranodal dissemination is an important feature of aggressive B-cell lymphoma. Owing to the lack of available animal models, the study on extranodal dissemination of lymphoma is greatly limited. Here, we identified a novel cell line, named MA-K, which originated from the Eµ-Myc;Cdkn2a-/- cell line, named MA-LN in this study. Compared to MA-LN, MA-K tended to disseminate in the kidney rather than the lymph nodes in the lymphoma transplantation model, resembling human primary renal lymphoma. The transcriptome analysis revealed that MA-K had undergone transcriptional evolution during the culture. The specialized transcriptional pattern analysis we proposed in this study identified that the FOXO1-BTG1-MYD88 pattern was formed in MA-K. Further analysis found that the translation pathway was the most enriched pathway in specially expressed genes (SEGs) in MA-K. Among the SEGs, three upregulated genes, RPLP2, RPS16, and MRPS16, and five downregulated genes, SSPN, CD52, ANKRD37, CCDC82, and VPREB3, in MA-K were identified as promising biomarkers to predict the clinical outcomes of human DLBCL. Moreover, the joint expression of the five-gene signature could effectively predict clinical outcomes of human DLBCL in three groups. These findings suggested that the MA-K cell line had strong clinical relevance with human aggressive B-cell lymphoma. Moreover, the MA-K primary renal lymphoma model, as a novel syngenetic mouse model, will be greatly useful for both basic research on lymphoma dissemination and preclinical efficacy evaluation of chemotherapy and immunotherapy.

Knockdown of 11ß-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway.

Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis, which is associated with high morbidity and mortality. 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), encoded by Hsd11b1, is a reductase that can convert inactive cortisone into metabolically active cortisol, but the role of 11ß-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood. The current study aimed to investigate the effects of 11ß-HSD1 on a lipopolysaccharide (LPS)-induced mouse model, in which LPS (10 mg/kg) was administered to wild-type C57BL/6J mice and 11ß-HSD1 global knockout mice. We asscessed cardiac function by echocardiography, performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes, and determined the levels of reactive oxygen species and biomarkers of oxidative stress. We also employed polymerase chain reaction analysis, Western blotting, and immunofluorescent staining to determine the expression of related genes and proteins. To investigate the role of 11ß-HSD1 in sepsis-induced myocardial dysfunction, we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes. We found that knockdown of 11ß-HSD1 alleviated LPS-induced myocardial mitochondrial injury, oxidative stress, and inflammation, along with an improved myocardial function; furthermore, the depletion of 11ß-HSD1 promoted the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), and silent information regulator 1 (SIRT1) protein levels both in vivo and in vitro. Therefore, the suppression of 11ß-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.

Risk factors for cardiovascular adverse events from immune checkpoint inhibitors.

Immune-related adverse events (irAEs), including skin injury, liver and kidney injury, colitis, as well as cardiovascular adverse events, are a series of complications arising during the treatment of immune checkpoint inhibitors (ICIs). Cardiovascular events are the most urgent and the most critical, as they can end life in a short period of time. With the widespread use of ICIs, the number of immune-related cardiovascular adverse events (irACEs) induced by ICIs has increased. More attention has been paid to irACEs, especially regarding cardiotoxicity, the pathogenic mechanism, diagnosis and treatment. This review aims to assess the risk factors for irACEs, to raise awareness and help with the risk assessment of irACEs at an early stage.