Cigarette smoke extract induces malignant transformation and DNA damage via c-MET phosphorylation in human bronchial epithelial cells.

Cigarette smoke, a complex mixture produced by tobacco combustion, contains a variety of carcinogens and can trigger DNA damage. Overactivation of c-MET, a receptor tyrosine kinase, may cause cancer and cellular DNA damage, but the underlying mechanisms are unknown. In this work, we investigated the mechanisms of cigarette smoke extract (CSE) induced malignant transformation and DNA damage in human bronchial epithelial cells (BEAS-2B). The results demonstrated that CSE treatment led to up-regulated mRNA expression of genes associated with the c-MET signaling pathway, increased expression of the DNA damage sensor protein γ-H2AX, and uncontrolled proliferation in BEAS-2B cells. ATR, ATR, and CHK2, which are involved in DNA damage repair, as well as the phosphorylation of c-MET and a group of kinases (ATM, ATR, CHK1, CHK2) involved in the DNA damage response were all activated by CSE. In addition, CSE activation promotes the phosphorylation modification of ATR, CHK1 proteins associated with DNA damage repair. The addition of PHA665752, a specific inhibitor of c-MET, or knock-down with c-MET both attenuated DNA damage, while overexpression of c-MET exacerbated DNA damage. Thus, c-MET phosphorylation may be involved in CSE-induced DNA damage, providing a potential target for intervention in the prevention and treatment of smoking-induced lung diseases.

The influence factors on pit and fissure sealing behavior of 12-year-old children: a cross-sectional study in Zhejiang, China.

BACKGROUND: In the 21st century, dental caries remains a global burden, particularly severely affecting the growth and quality of life of 12-year-old children. Fortunately, pit and fissure sealing (PFS) procedures can effectively prevent molars from caries. Hence, this study focused on the relationship between PFS and oral epidemiological factors in 12-year-old children. METHODS: A cross-sectional survey was conducted in 12-year-old children from 11 cities in Zhejiang Province. Their dental conditions were collected through questionnaires, as well as basic information such as relevant family information, oral health knowledge and behavior. Then, logistic regression analysis was used to identify the influencing factors associated with PFS. RESULTS: A total of 1204 children were included, with 252 in the PFS group and 952 in the non-PFS group. There were significant differences between the two groups in terms of decayed, missing and filled teeth (DMFT) score, first permanent molar DMFT score, residential area, educational level of parents, tooth-brushing frequency, use of dental floss, oral examination in a medical institution, having taken courses on oral health care, as well as having knowledge that tooth brushing could effectively prevent gingival inflammation, PFS could protect teeth, and oral disease may affect general health. According to further logistic regression analysis, the independent factors influencing PFS included use of dental floss [odds ratios (OR) = 1.672, 95% confidence intervals (CI) = 1.235-2.263, P = 0.001], having taken courses on oral health care (OR = 0.713, 95% CI = 0.515-0.988, P = 0.042), having knowledge that tooth brushing is effective in preventing gingival inflammation (OR = 0.627, 95% CI = 0.389-0.987, P = 0.044) and having knowledge that PFS can protect teeth (OR = 0.589, 95% CI = 0.438-0.791, P < 0.001). CONCLUSION: PFS can reduce the mean DMFT score of 12-year-old children. Independent influencing factors of PFS consist of use of dental floss, having taken courses on oral health care, oral health behavior and knowledge level.

Research Progress on Modification of Aerogels by Chemical Vapor Deposition.

Aerogels are three-dimensional nanomaterials with low thermal conductivity, low density, high specific surface area, and high porosity. They have demonstrated remarkable performance advantages in thermal insulation, catalysis, and adsorption in recent years. However, their inherent brittleness and weak skeletal structure limit their applications. In order to improve the resilience and expand the capabilities of aerogels, it is essential to optimize their intrinsic properties. The chemical vapor deposition (CVD) method offers a number of advantages, including fine control, high selectivity, and the ability to modify the aerogel in both the outer surface and the inner layer. This approach allows for reinforcement of the gel skeleton while achieving functionalization. This paper reviews the research progress of aerogel modification by the CVD method with a focus on hydrophobic modification, structural improvement, antioxidant modification, catalytic modification, etc. In light of the current demand for aerogel applications and the difficulties encountered in modifying aerogels, this review proposes future research directions for aerogel modification by CVD.

BiPLS-RF: A hybrid wavelength selection strategy for laser induced fluorescence spectroscopy of power transformer oil.

In this paper, a method for indirect diagnosis of transformer faults based on the fluorescence spectrum and characteristic wavelength screening of transformer oil has been proposed. Specifically, a hybrid strategy (BiPLS-RF) for establishing the fluorescence spectrum feature screening of transformer oil using backward interval partial least squares (BiPLS) and random forest (RF) has been proposed. Aiming at the problem of transformer fault diagnosis, the laser induced fluorescence (LIF) spectroscopy of transformer oil in different states was first collected, and it is found that the fluorescence spectrum intensity of normal transformer oil was stronger than that of faulty transformer oil. Then the characteristic bands of the original fluorescence spectra were screened by BiPLS. It is found that when the original fluorescence spectra were divided into 15 sub-intervals, the minimum root mean squares error of cross-validation can be obtained by selecting 3 sub-intervals (including 411 wavelengths). On this basis, RF was employed to further screen the characteristic wavelengths and realized the identification of the fluorescence spectrum. It is found that in the RF model composed of 54 trees, the selected 196 characteristic wavelengths of the fluorescence spectrum can minimize the analysis error (0.56%). In addition, the selected characteristic wavelength information was fed into other common classifiers to construct a fluorescence spectrum identification model, which further proved the effectiveness of BiPLS-RF for wavelength selection for LIF spectroscopy of power transformer oil. The results show that it is feasible to use BiPLS-RF to screen the characteristic wavelength of LIF spectroscopy and apply it to transformer fault diagnosis, which provides a new solution for transformer fault diagnosis.

Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study.

BACKGROUND: Emerging evidences have demonstrated that gut microbiota composition is associated with pulmonary arterial hypertension (PAH). However, the underlying causality between intestinal dysbiosis and PAH remains unresolved. METHOD: An analysis using the two-sample Mendelian randomization (MR) approach was conducted to examine the potential causal relationship between gut microbiota and PAH. To assess exposure data, genetic variants associated with 196 bacterial traits were extracted from the MiBioGen consortium, which included a sample size of 18,340 individuals. As for the outcomes, summary statistics for PAH were obtained from the NHGRI-EBI GWAS Catalog, which conducted a meta-analysis of four independent studies comprising a total of 11,744 samples. Causal effects were estimated employing various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weight mode and simple mode, with sensitivity analyses also being implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. RESULTS: Following false discovery rate (FDR) correction, the genetically predicted genus Eubacterium fissicatena group (odds ratio (OR) 1.471, 95% confidence interval (CI) 1.178-1.837, q = 0.076) exhibited a causal association with PAH. In addition, the genus LachnospiraceaeUCG004 (OR 1.511, 95% CI 1.048-2.177) and genus RuminococcaceaeUCG002 (OR 1.407, 95% CI 1.040-1.905) showed a suggestive increased risk of PAH, while genus Eubacterium eligens group (OR 0.563, 95% CI 0.344-0.922), genus Phascolarctobacterium (OR 0.692, 95% CI 0.487-0.982), genus Erysipelatoclostridium (OR 0.757, 95% CI 0.579-0.989) and genus T-yzzerella3 (OR 0.768, 95% CI 0.624-0.945) were found to have nominal protective effect against PAH. CONCLUSION: The findings from our MR study have revealed a potential causal relationship between gut microbiota and PAH. Specifically, we have identified four types of gut microbiota that exhibit a protective effect on PAH, as well as three types that have a detrimental impact on PAH, thereby offering valuable insights for future mechanistic and clinical investigations in the field of PAH.

Re-analysis of single-cell transcriptomics reveals a critical role of macrophage-like smooth muscle cells in advanced atherosclerotic plaque.

Aims: Smooth muscle cell (SMC) remodeling poses a critical feature in the development and progression of atherosclerosis. Although fate mapping and in silicon approaches have expanded SMC phenotypes in atherosclerosis, it still remains elusive about the contributions of individual SMC phenotypes and molecular dynamics to advanced atherosclerotic plaque. Methods: Using single-cell transcriptome, we investigated cellular compositions of human carotid plaque laden with atherosclerotic core, followed by in vivo experiments utilizing SMC-lineage tracing technology, bulk RNA sequencing (RNA-seq) and both in vivo and in vitro validation of the underlying molecular mechanism. Results: 5 functionally distinct SMC subtypes were uncovered based on transcriptional features (described as contractile, fibroblast-like, osteogenic, synthetic and macrophage-like) within the niche. A proinflammatory, macrophage-like SMC subtype displaying an intermediary phenotype between SMC and macrophage, exhibits prominent potential in destabilizing plaque. At the molecular level, we explored cluster-specific master regulons by algorithm, and identified interferon regulatory factor-8 (IRF8) as a potential stimulator of SMC-to-macrophage transdifferentiation via activating nuclear factor-κB (NF-κB) signaling. Conclusions: Our study illustrates a comprehensive cell atlas and molecular landscape of advanced atherosclerotic lesion, which might renovate current understanding of SMC biology in atherosclerosis.

Low shear stress exacerbates atherosclerosis by inducing the generation of neutrophil extracellular traps via Piezo1-mediated mechanosensation.

BACKGROUND AND AIMS: Atherosclerosis is a chronic lipid-driven inflammatory disease largely influenced by hemodynamics. Neutrophil extracellular trap (NET)-mediated inflammation plays an important role in atherosclerosis. However, little is known about the relationship between low shear stress (LSS) and NET generation, as well as the underlying mechanism. METHODS: We induced LSS by partial ligation of the left carotid artery in high-fat diet-fed male ApoE-/- mice. To further validate the direct relationship between LSS and NET formation invitro, differentiated human promyelocytic leukemia HL-60 cells and bone marrow-derived neutrophils were suspended in fluid flow under normal or low shear stress using a parallel-plate flow chamber system. RESULTS: Four weeks after surgery, ligated carotid arteries had more lipid deposition, larger plaque area, and increased NET formation than unligated arteries. Inhibition of NETosis could significantly reduce plaque formation in ApoE-/- mice. Invitro, LSS could promote NET generation directly through downregulation of Piezo1, a mechanosensitive ion channel. Downregulation of Piezol could activate neutrophils and promote NETosis in static conditions. Conversely, Yoda1-evoked activation of Piezo1 attenuated LSS-induced NETosis. Mechanistically, downregulation of Piezo1 resulted in decreased Ca2+ influx and increased histone deacetylase 2 (HDAC2), which increased reactive oxygen species levels and led to NETosis. LSS-induced NET generation also promoted apoptosis and adherence of endothelial cells. CONCLUSION: LSS directly promotes NETosis through the Piezo1-HDAC2 axis in atherosclerosis progression. This study uncovers the essential role of Piezo1-mediated mechanical signaling in NET generation and plaque formation, which provides a promising therapeutic strategy for atherosclerosis.

TiN as Radical Scavenger in Fe─N─C Aerogel Oxygen Reduction Catalyst for Durable Fuel Cell.

Fe─N─C is the most promising alternative to platinum-based catalysts to lower the cost of proton-exchange-membrane fuel cell (PEMFC). However, the deficient durability of Fe─N─C has hindered their application. Herein, a TiN-doped Fe─N─C (Fe─N─C/TiN) is elaborately synthesized via the sol-gel method for the oxygen-reduction reaction (ORR) in PEMFC. The interpenetrating network composed by Fe─N─C and TiN can simultaneously eliminate the free radical intermediates while maintaining the high ORR activity. As a result, the H2O2 yields of Fe─N─C/TiN are suppressed below 4%, ≈4 times lower than the Fe─N─C, and the half-wave potential only lost 15 mV after 30 kilo-cycle accelerated durability test (ADT). In a H2─O2 fuel cell assembled with Fe─N─C/TiN, it presents 980 mA cm-2 current density at 0.6 V, 880 mW cm-2 peak power density, and only 17 mV voltage loss at 0.80 A cm-2 after 10 kilo-cycle ADT. The experiment and calculation results prove that the TiN has a strong adsorption interaction for the free radical intermediates (such as *OH, *OOH, etc.), and the radicals are scavenged subsequently. The rational integration of Fe single-atom, TiN radical scavenger, and highly porous network adequately utilize the intrinsic advantages of composite structure, enabling a durable and active Pt-metal-free catalyst for PEMFC.

Boosting the Performance of Low-Platinum Fuel Cells via a Hierarchical and Interconnected Porous Carbon Support.

The design of a low-platinum (Pt) proton-exchange-membrane fuel cell (PEMFC) can reduce its high cost. However, the development of a low-Pt PEMFC is severely hindered by the high oxygen transfer resistance in the catalyst layer. Herein, a carbon with interconnected and hierarchical pores is synthesized as a support for the low-Pt catalyst to lower the oxygen transfer resistance. A H2-air fuel cell assembled by Pt/hierarchical porous carbon shows 1610 mW/cm2 peak power density, 2230 mA/cm2 current density at 0.60 V, and only 18.4 S/m local oxygen transfer resistance with 0.10 mgPt/cm2 Pt loading at the cathode, which far exceeds those of various carbon black supports and commercially used Pt/C catalysts. Both the experimental and simulation results have shown the advancement of hierarchical pores toward the high efficiency of oxygen transportation.

Efficacy of mesenchymal stromal cells in the treatment of unexplained recurrent spontaneous abortion in mice: An analytical and systematic review of meta-analyses.

OBJECTIVES: Unexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to evaluate the preclinical evidence for the mesenchymal stromal cell (MSC) treatment for URSA. METHODS: A meticulous literature search was independently performed by two authors across the Cochrane Library, EMBASE, and PubMed databases from inception to April 9, 2023. Each study incorporated was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. The amalgamated standardized mean difference (SMD) accompanied by 95% confidence interval (CI) were deduced through a fixed-effects or random-effects model analysis. RESULTS: A total of ten studies incorporating 140 mice were subjected to data analysis. The MSC treatment yielded a significant reduction in the abortion rate within the URSA model (OR = 0.23, 95%CI [0.17, 0.3], P<0.00001). Moreover, it elicited a positive modulatory impact on the expression profiles of several inflammatory cytokines in the decidual tissue of URSA murine models, inclusive of IL4 (SMD 1.63, 95% CI [0.39, 2.86], P = 0.01), IL10 (SMD 1.60, 95% CI [0.58, 2.61], P = 0.002), IFN-γ (SMD -1.66, 95%CI [-2.79, -0.52], P = 0.004), and TNF-α (SMD -1.98, 95% CI [-2.93, -1.04], P< 0.0001). Subgroup analyses underscored that the administration mode of intraperitoneal and uterine horn injections, and sources of bone MSCs and adipose-derived MSCs contributed positively to the expression of IL4, IL10, and decreased the expression of IFN-γ in decidual tissue of URSA (P<0.05). Conversely, the tail vein injections subgroup was observed with no statistical significance (P>0.05). CONCLUSIONS: The findings underscore the considerable potential of MSCs in URSA therapy. Nonetheless, the demand for enhanced transparency in research design and direct comparisons between various MSC sources and administration routes in URSA is paramount to engendering robust evidence that could pave the way for successful clinical translation.

Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Effect of body mass index on clinical outcomes after robotic cardiac surgery: is there an obesity paradox?

BACKGROUND: To investigate the effect of body mass index (BMI) on clinical outcomes after robotic cardiac surgery, and to explore the postoperative obesity paradox. METHODS: The data of 146 patients who underwent robotic cardiac surgery under cardiopulmonary bypass (CPB) from July 2016 to June 2022 in Daping Hospital of Army Medical University were retrospectively analyzed, and their demographic data and related clinical data were statistically analyzed. The mean age was (42.88 ± 13.01) years, 55 (37.67%) were male and 91 (62.33%) were female. Patients were divided into 3 groups according to preoperative BMI: lean group (BMI < 18.5 kg/m2; n = 17; 11.64%), normal group (BMI 18.5 kg/m2 to 23.9 kg/m2; n = 81; 55.48%), and overweight and obese group (BMI ≥ 24 kg/m2; n = 48; 32.88%). Multivariate analysis was performed to compare clinical outcomes across BMI groups. RESULTS: Preoperative data in different BMI groups showed that there were statistically significant differences in age, height, weight, body surface area (BSA), diabetes, left atrial anteroposterior diameter (LAD), triglyceride (TG), and high-density lipoprotein (HDL) (all P < 0.05). Postoperative clinical outcomes showed that there was no statistical difference between the lean group and the normal group; the intensive care unit stay and postoperative hospital stay in the overweight and obese group were significantly higher than those in the normal group (P < 0.05), and the risk of postoperative cardiac surgery-related acute kidney injury (CSA-AKI) was significantly increased (P = 0.021); further Multiple Binary Logistic Regression Analysis suggested that preoperative TG (OR = 1.772, 95% CI 1.068-2.942, P = 0.027) and operation time ≥ 300 min (OR = 3.823, 95% CI 1.098-13.308, P = 0.035) were independent risk factors for postoperative CSA-AKI. CONCLUSIONS: Overweight and obese patients had significantly prolonged intensive care unit stay and postoperative hospital stay after robotic cardiac surgery, and significantly increased incidence of postoperative CSA-AKI, which did not support the obesity paradox; preoperative TG and operation time ≥ 300 min were independent risk factors for postoperative CSA-AKI.

Assembling nanocelluloses into fibrous materials and their emerging applications.

Nanocelluloses, derived from various plants or specific bacteria, represent the renewable and sophisticated nano building blocks for emerging functional materials. Especially, the assembly of nanocelluloses as fibrous materials can mimic the structural organization of their natural counterparts to integrate various functions, thus holding great promise for potential applications in various fields, such as electrical device, fire retardance, sensing, medical antibiosis, and drug release. Due to the advantages of nanocelluloses, a variety of fibrous materials have been fabricated with the assistance of advanced techniques, and their applications have attracted great interest in the past decade. This review begins with an overview of nanocellulose properties followed by the historical development of assembling processes. There will be a focus on assembling techniques, including traditional methods (wet spinning, dry spinning, and electrostatic spinning) and advanced methods (self-assembly, microfluidic, and 3D printing). In particular, the design rules and various influencing factors of assembling processes related to the structure and function of fibrous materials are introduced and discussed in detail. Then, the emerging applications of these nanocellulose-based fibrous materials are highlighted. Finally, some perspectives, key opportunities, and critical challenges on future research trends within this field are proposed.

Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.

Ischemia/reperfusion injury of the kidney is associated with high morbidity and mortality, and treatment of this injury remains a challenge. G protein-coupled receptor kinase 4 (GRK4) plays a vital role in essential hypertension and myocardial infarction, but its function in kidney ischemia/reperfusion injury remains undetermined. Among the GRK subtypes (GRK2-6) expressed in kidneys, the increase in GRK4 expression was much more apparent than that of the other four GRKs 24 hours after injury and was found to accumulate in the nuclei of injured mouse and human renal tubule cells. Gain- and loss-of-function experiments revealed that GRK4 overexpression exacerbated acute kidney ischemia/reperfusion injury, whereas kidney tubule-specific knockout of GRK4 decreased injury-induced kidney dysfunction. Necroptosis was the major type of tubule cell death mediated by GRK4, because GRK4 significantly increased receptor interacting kinase (RIPK)1 expression and phosphorylation, subsequently leading to RIPK3 and mixed lineage kinase domain-like protein (MLKL) phosphorylation after kidney ischemia/reperfusion injury, but was reversed by necrostatin-1 pretreatment (an RIPK1 inhibitor). Using co-immunoprecipitation, mass spectrometry, and siRNA screening studies, we identified signal transducer and activator of transcription (STAT)1 as a GRK4 binding protein, which co-localized with GRK4 in the nuclei of renal tubule cells. Additionally, GRK4 phosphorylated STAT1 at serine 727, whose inactive mutation effectively reversed GRK4-mediated RIPK1 activation and tubule cell death. Kidney-targeted GRK4 silencing with nanoparticle delivery considerably ameliorated kidney ischemia/reperfusion injury. Thus, our findings reveal that GRK4 triggers necroptosis and aggravates kidney ischemia/reperfusion injury, and its downregulation may provide a promising therapeutic strategy for kidney protection.

Transient bio-inspired gliders with embodied humidity responsive actuators for environmental sensing.

Collecting temporal and spatial high-resolution environmental data can guide studies in environmental sciences to gain insights in ecological processes. The utilization of automated robotic systems to collect these types of data can maximize accuracy, resilience, and deployment rate. Furthermore, it reduces the risk to researchers deploying sensors in inaccessible environments and can significantly increase the cost-effectiveness of such studies. The introduction of transient robotic systems featuring embodied environmental sensors pushes towards building a digital ecology, while introducing only minimal disturbance to the environment. Transient robots made from fully biodegradable and non-fossil based materials, do not develop into hazardous e-waste at the end of their lifetime and can thus enable a broader adoption for environmental sensing in the real world. In this work, our approach towards the design of transient robots includes the integration of humidity-responsive materials in a glider, which is inspired by the Alsomitra macrocarpa seed. The design space of these gliders is explored and their behavior studied numerically, which allows us to make predictions on their flight characteristics. Results are validated against experiments, which show two different gliding behaviors, that can help improve the spread of the sensors. By tailoring the Cellulose-Gelatin composition of the humidity actuator, self-folding systems for selective rainwater exposure can be designed. The pH sensing layer, protected by the actuator, provides visual feedback on the pH of the rainwater. The presented methods can guide further concepts developing transient aerial robotic systems for sustainable, environmental monitoring.

Association of circulating vaspin levels and patients with metabolic-associated fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: The incidence rate of metabolic-associated fatty liver disease (MAFLD) is increasing annually; however, there are still no effective methods for establishing an early diagnosis and conducting real-time tracing. Vaspin can affect the metabolic processes in the body, and it is closely associated with many metabolic diseases. Many previous studies have speculated on the association between vaspin and MAFLD, but the results of these studies have not been conclusive. This meta-analysis examined the differences in circulating vaspin levels between patients with MAFLD and healthy individuals. METHODS: Six databases and other sources were searched with free terms and Medical Subject Headings terms, and a total of 13 articles were included (900 cases and 669 controls). RevMan 5.3 and Stata 16 were used for analysis. The standardised mean difference (SMD) and 95% confidence interval (CI) were used to assess the overall outcomes. Cohen's kappa coefficient was applied to examine the differences between the two authors in the selection of studies and in the evaluation of the quality of evidence for the studies. RESULTS: The results demonstrated that there was no significant difference in the circulating vaspin levels between the MAFLD group and healthy group (SMD = 0.46, 95% CI: [- 0.12, 1.04]). The subgroup analysis suggested that area and body mass index (BMI) may be the sources of heterogeneity, and the results of univariate meta-regression analysis were consistent with those of the subgroup analysis (P = 0.005 and P < 0.001, respectively). Furthermore, BMI may better explain the source of heterogeneity (P = 0.032) in the multivariate meta-regression analysis. CONCLUSION: In summary, no significant correlation was observed between the circulating vaspin levels and MAFLD. BMI may be an important factor affecting this correlation, which may provide a reference for further studies on mechanism and diagnosis of MAFLD.

G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation.

Activation of the angiotensin II type 2 receptor (AT2R) induces diuresis and natriuresis. Increased expression or/and activity of G-protein-coupled receptor kinase 4 (GRK4) or genetic variants (e.g., GRK4γ142V) cause sodium retention and hypertension. Whether GRK4 plays a role in the regulation of AT2R in the kidney remains unknown. In the present study, we found that spontaneously hypertensive rats (SHRs) had increased AT2R phosphorylation and impaired AT2R-mediated diuretic and natriuretic effects, as compared with normotensive Wistar-Kyoto (WKY) rats. The regulation by GRK4 of renal AT2R phosphorylation and function was studied in human (h) GRK4γ transgenic mice. hGRK4γ142V transgenic mice had increased renal AT2R phosphorylation and impaired AT2R-mediated natriuresis, relative to hGRK4γ wild-type (WT) littermates. These were confirmed in vitro; AT2R phosphorylation was increased and AT2R-mediated inhibition of Na+-K+-ATPase activity was decreased in hGRK4γ142V, relative to hGRK4γ WT-transfected renal proximal tubule (RPT) cells. There was a direct physical interaction between renal GRK4 and AT2R that was increased in SHRs, relative to WKY rats. Ultrasound-targeted microbubble destruction of renal GRK4 decreased the renal AT2R phosphorylation and restored the impaired AT2R-mediated diuresis and natriuresis in SHRs. In vitro studies showed that GRK4 siRNA reduced AT2R phosphorylation and reversed the impaired AT2R-mediated inhibition of Na+-K+-ATPase activity in SHR RPT cells. Our present study shows that GRK4, at least in part, impairs renal AT2R-mediated diuresis and natriuresis by increasing its phosphorylation; inhibition of GRK4 expression and/or activity may be a potential strategy to improve the renal function of AT2R.

Early results of totally endoscopic robotic aortic valve replacement: analysis of 4 cases.

OBJECTIVE: To evaluate the role of totally endoscopic robotic aortic valve replacement in cardiac surgery. METHODS: Four cases of totally robotic aortic valve replacement (AVR) were conducted from December 2016 to July 2018. All operations were completed with the Da Vinci robot Si™ system (intuitive Surgical, Inc. Sunnyvale, C.A, USA). Patients were male, with a mean age of 42.8 ± 6.2 years (range 32-49). RESULTS: AVR was completed with the Da Vinci Si™ system (intuitive Surgical, Inc. Sunnyvale, CA, USA). There was no mortality and no procedure-related morbidity. The mean cardiopulmonary bypass and mean cross-clamp time was 252 ± 13.6 min and 178.8 ± 17.1 min, respectively. The mean ICU time was 78.8 ± 27.1 h, and the mean hospital stay was 15 ± 3.5 d. During a mean follow-up of 3 years and 6 months, the patients returned to normal function, and no heart murmur was found. Compared with the operation, the body image score of the four patients increased after the operation, and the hospital anxiety and depression scale scores decreased, indicating that the patient's condition had been alleviated to a certain extent. CONCLUSION: Totally endoscopic robotic AVR is a feasible and viable choice for patients but requires further improvement for broader use.

Perfluoroalkyl-Promoted Synthesis of Perfluoroalkylated Pyrrolidine-Fused Coumarins with Methyl ß-Perfluoroalkylpropionates.

Employing the methyl ß-perfluoroalkylpropionate as the Michael acceptor, an efficient approach for the synthesis of perfluoroalkylated pyrrolidine-fused coumarins has been achieved. A tandem reaction involving [3 + 2] cycloaddition and intramolecular transesterification was proposed for the mechanism. The enhanced electrophilicity resulting from the strong electron-withdrawing ability of the perfluoroalkyl group was crucial for this tandem reaction.

A Polymeric Bilayer Multi-Legged Soft Millirobot with Dual Actuation and Humidity Sensing.

There are numerous works that report wirelessly controlling the locomotion of soft robots through a single actuation method of light or magnetism. However, coupling multiple driving modes to improve the mobility of robots is still in its infancy. Here, we present a soft multi-legged millirobot that can move, climb a slope, swim and detect a signal by near-infrared irradiation (NIR) light or magnetic field dual actuation. Due to the design of the feet structure, our soft millirobot incorporates the advantages of a single actuation mode of light or magnetism. Furthermore, it can execute a compulsory exercise to sense a signal and analyze the ambience fluctuation in a narrow place. This work provides a novel alternative for soft robots to achieve multimode actuation and signal sensing.