Search

Abstract Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has become the leading cause of chronic liver disease. Liver biopsy, as the diagnostic gold standard, is invasive and has sampling bias, making it particularly important to search for sensitive and specific biomarkers for diagnosis. Cytokeratin 18 (CK18) M30 and M65 are products of liver cell apoptosis and necrosis, respectively, and liver-expressed antimicrobial peptide 2 (LEAP-2) is a related indicator of glucose and lipid metabolism. Correlation studies have found that all three indicators positively correlate with the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Through comparison of diagnostic values, it was found that CK18 M65 can better distinguish between healthy individuals and MAFLD; LEAP-2 can effectively distinguish MAFLD from other liver diseases, especially ALD.

Abstract Endoplasmic reticulum (ER)-mitochondria contacts are critical for the regulation of lipid transport, synthesis, and metabolism. However, the molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, we show that Mic19, a key subunit of MICOS (mitochondrial contact site and cristae organizing system) complex, regulates ER-mitochondria contacts by the EMC2-SLC25A46-Mic19 axis. Mic19 liver specific knockout (LKO) leads to the reduction of ER-mitochondrial contacts, mitochondrial lipid metabolism disorder, disorganization of mitochondrial cristae and mitochondrial unfolded protein stress response in mouse hepatocytes, impairing liver mitochondrial fatty acid β-oxidation and lipid metabolism, which may spontaneously trigger nonalcoholic steatohepatitis (NASH) and liver fibrosis in mice. Whereas, the re-expression of Mic19 in Mic19 LKO hepatocytes blocks the development of liver disease in mice. In addition, Mic19 overexpression suppresses MCD-induced fatty liver disease. Thus, our findings uncover the EMC2-SLC25A46-Mic19 axis as a pathway regulating ER-mitochondria contacts, and reveal that impairment of ER-mitochondria contacts may be a mechanism associated with the development of NASH and liver fibrosis.

Metal lattice structural materials are widely used in aerospace, automotive industry, and other fields due to their advantages of lightweight, high specific strength, energy absorption, and porosity. High strength and toughness FeCrNi medium entropy alloy (MEA) was taken as the research object, and selective laser melting (SLM) was used to prepare FeCrNi medium entropy alloy lattice structure materials with four simulated lattice structures: BCC, BCCZ, FCC and FCC. The microstructure, mechanical properties, and deformation behavior of these materials were systematically studied.The results indicate that the FeCrNi medium entropy alloy lattice structure prepared by the skip scanning strategy has high node overlap quality, dense interlaced stacking of molten pools, and uniform and fine grains. When the relative density is similar, the specific strength and specific energy absorption values of BCC, FCC, BCCZ, and FCCZ lattice structures increase sequentially.The specific energy absorption of FeCrNi medium entropy alloy material with FCCZ lattice structure reaches 49.8J·g-1, significantly higher than that of Ti6Al4V and 316L stainless steel lattice materials.The finite element simulation analysis shows that the presence of Z-shaped pillars increases the apparent strength and stiffness of the lattice material, and leads to a transition in deformation behavior from bending dominated to tensile dominated, which is the main reason for the strength improvement of the FCCZ lattice structure.

Background: Observational studies have highlighted the pivotal role of inflammatory cytokines in cirrhosis progression. However, the existence of a causal link between inflammatory cytokines and cirrhosis remains uncertain. In this study, we conducted a bidirectional Mendelian randomization (MR) analysis at a summarized level to illuminate the potential causal relationship between the two variables. Methods: This study utilized genetic variance in cirrhosis and inflammatory cytokines from a genome-wide association study (GWAS) of European descent. The MR-PRESSO outlier test, Cochran’s Q test, and MR-Egger regression were applied to assess outliers, heterogeneity, and pleiotropy. The inverse variance weighted method and multiple sensitivity analyses were used to evaluate causalities. Furthermore, the validation set was used for simultaneous data validation. Results: The inflammatory cytokine monocyte chemoattractant protein 3 (MCP-3) was supposedly associated with a greater risk of cirrhosis. And cirrhosis was significantly correlated with increased levels of hepatocyte growth factor (HGF). Conclusions: This study suggests that MCP-3 might be associated with the etiology of cirrhosis, while several inflammatory cytokines could potentially play a role in its downstream development. Additionally, the progression of cirrhosis was associated with elevated levels of HGF, suggesting a possible role for liver repair functions.

Abstract Background Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. Aims In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. Methods SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. Results In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. Conclusions In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.

Background Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer worldwide. The histopathological features, risk factors, and prognosis of HCC caused by nonalcoholic fatty liver disease (NAFLD) appear to be significantly different from those of HCC caused by other etiologies of liver disease.

Abstract Mitochondria are the key organelles for sensing oxygen, which is consumed by oxidative phosphorylation to generate ATP. Lysosomes contain hydrolytic enzymes that degrade misfolded proteins and damaged organelles to maintain cellular homeostasis. Mitochondria physically and functionally interact with lysosomes to regulate cellular metabolism. However, the mode and biological functions of mitochondria-lysosome communication remain largely unknown. Here, we show that hypoxia remodels normal tubular mitochondria into megamitochondria by inducing broad inter-mitochondria contacts and subsequent fusion. Importantly, under hypoxia, mitochondria-lysosome contacts are promoted, and certain lysosomes are engulfed by megamitochondria, in a process we term megamitochondria engulfing lysosome (MMEL). Both megamitochondria and mature lysosomes are required for MMEL. Moreover, the STX17-SNAP29-VAMP7 complex contributes to mitochondria-lysosome contacts and MMEL under hypoxia. Intriguingly, MMEL mediates a mode of mitochondrial degradation, which we termed mitochondrial self-digestion (MSD). Moreover, MSD increases mitochondrial ROS production. Our results reveal a mode of crosstalk between mitochondria and lysosomes and uncover an additional pathway for mitochondrial degradation.

Abstract Background Non-suicidal self-injury (NSSI) by adolescent patients with depression has become a serious public health problem. This cross-sectional study aims to identify subgroups of adolescents based on NSSI and explore the factors related to these subgroups. Methods The study recruited 326 in- and out-patient adolescents (263 girls and 63 boys) aged 12 to 18 years (mean = 14.7, SD = 1.6) who had self-injured in the past year. Latent class indicators included 12 NSSI variables, as well as suicidal ideation. Logistic regression examined associations between identified classes and related factors. Results In this study, two distinct subgroups were identified: a “high suicidal ideation NSSI group” (n = 129, 39.6%) and a “low suicidal ideation NSSI group” (n = 197, 60.4%). Depression (OR = 1.10; 95% CI, 1.05–1.16), female (OR = 2.01; 95% CI, 1.09–3.69), left-behind experience (OR = 2.08; 95% CI, 1.17–3.71), single-parent family (OR = 1.84; 95% CI, 1.11–3.04) and peer victimization (OR = 1.04; 95% CI, 1.02–1.05) increases the probability of belonging to the “high suicidal ideation NSSI group”. A high level of perceived social support (OR = 0.99; 95% CI, 0.97–0.99) was a protective factor towards NSSI. Conclusions This study identifies two subgroups of NSSI and the factors associated with each subgroup. The early identification of high-risk groups for major NSSI in adolescents diagnosed with depression is possible due to the identification of correlating factors. Different treatment plans can be developed for different subtypes of NSSI to improve the effectiveness of prevention and intervention, promoting the healthy physical and mental development of adolescents with depression.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly defined as non-alcoholic fatty liver disease (NAFLD), is a disorder marked by the excessive deposition of lipids in the liver, giving rise to a spectrum of liver pathologies encompassing steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. Despite the alarming increase in its prevalence, the US Food and Drug Administration has yet to approve effective pharmacological therapeutics for clinical use. MASLD is characterized by the accretion of lipids within the hepatic system, arising from a disarray in lipid provision (whether through the absorption of circulating lipids or de novo lipogenesis) and lipid elimination (via free fatty acid oxidation or the secretion of triglyceride-rich lipoproteins). This disarray leads to the accumulation of lipotoxic substances, cellular pressure, damage, and fibrosis. Indeed, the regulation of the lipid metabolism pathway is intricate and multifaceted, involving a myriad of factors, such as membrane transport proteins, metabolic enzymes, and transcription factors. Here, we will review the existing literature on the key process of lipid metabolism in MASLD to understand the latest progress in this molecular mechanism. Notably, de novo lipogenesis and the roles of its two main transcription factors and other key metabolic enzymes are highlighted. Furthermore, we will delve into the realm of drug research, examining the recent progress made in understanding lipid metabolism in MASLD. Additionally, we will outline prospective avenues for future drug research on MASLD based on our unique perspectives.

The effect of additive noise on the channel state information (CSI) quality is a crucial issue in mobile communication systems. The adaptive subcarrier grouping (ASG) for sample matrix inversion (SMI) based minimum mean square error (MMSE) adaptive array has been previously proposed. However, this method needs to know the signal-to-noise ratio (SNR) in advance to set the threshold, perform grouping, and take the average, causing an insufficient number of signal samples. As a result, the ability to eliminate noise is limited. In this paper, we propose a new method based on data-aided weight calculation and the least mean square (LMS) algorithm without SNR information, which increases the number of samples. The decision results and initial weight are obtained by the SMI method with subcarrier grouping, and then the LMS method with subcarrier grouping is applied to reduce the channel estimation error as well as the amount of computation. Simulation results demonstrate that the proposed scheme is an efficient approach to improve Bit Error Rate (BER) performance under various Rician K factors.

Abstract Background The triglyceride and glucose index (TyG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute markers of insulin resistance (IR). In a retrospective cross-sectional study, the authors aimed to compare the efficacy of the two indicators in diagnosing metabolic-associated fatty liver disease (MAFLD) to construct a novel disease diagnosis model. Methods Overall, 229 patients (97 MAFLD and 132 Non-MAFLD at West China Hospital of Sichuan University were included. MAFLD was diagnosed using ultrasonography. Biochemical indexes were collected and analyzed by logistic regression to screen out indicators that were expressed differently in MAFLD patients and healthy controls, which were incorporated into a diagnostic model. Results After adjusting for age, sex, and body mass index (BMI), serum alanine transaminase (ALT), aspartate transaminase (AST), AST/ALT (A/A), fasting plasma glucose (FPG), cystatin C (Cys-C), uric acid (URIC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), non-HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C, TG/HDL-C, TC/HDL-C, TyG, and TyG-BMI were risk factors for MAFLD. The odds ratio of TG/HDL-C and TyG were 5.629 (95%CI: 3.039–10.424) and 182.474 (95%CI: 33.518–993.407), respectively. In identifying MAFLD, TyG, TyG-BMI, TG, and TG/HDL-C were found to be the most vital indexes based on the random forest method, with the area under the curve (AUC) greater than 0.9. In addition, the combination of BMI, ALT, and TyG had a high diagnostic efficiency for MAFLD. Conclusions TyG and TG/HDL-C were potential risk factors for MAFLD, and the former performed better in diagnosing MAFLD. The combination of BMI, ALT, and TyG improved the diagnostic capability for MAFLD.

Abstract Background Methamphetamine (METH) dependence is a complex and dynamic public health problem. Long-term abuse of METH can increase numerous risks of mental and physical problems. Currently, the methods to reduce METH dependence and improve the withdrawal symptoms are limited and ineffective. Resilience is seen as a multidimensional and dynamic capability to recover or bounce back from stressful events and is also generally considered as a protective factor against mental dysfunction. Methods One hundred thirty-four males with METH dependence were consecutively recruited from Huanglong Compulsory Isolated Detoxification Center between 2019 and 2021, of whom 112 were into the group. The Connor-Davidson Resilience Scale (CD-RISC), Self-rating depression scale (SDS), Self-rating anxiety scale (SAS), Barratt Impulsiveness Scale-11(BIS-11), and the Repeatable Battery for the Assessment of Neuropsychological Status (Rbans) were used to evaluate resilience, depression, anxiety, impulsivity, and cognition respectively. Results The results mainly indicated that high resilience group showed lower SDS, SAS and BIS-11 scores than low resilience group (all p

Metallic nanolaminated materials possess excellent mechanical properties due to their unique modulation structures and interfacial properties. However, how microdefects affect their mechanical properties is still uncertain. To evaluate the influences of void location (in the crystalline layer and the Ti/Ni interface), void diameter (d) and thickness of the intermediate layer (h) on overall tensile behaviors, various types of defective Ti/Ni nanolaminates with pre-existing void are established by the molecular dynamics method in this work. The results indicate that the strength and plastic deformation mechanisms are strongly dependent on those determinants. Yield stresses of Ti/Ni nanolaminates decrease distinctly with increasing void diameter, while peak stresses with a void in the crystalline layer decrease with increasing d/h. Different void locations lead eventually to disparate initial plastic deformation carriers around the void, and various evolutions in the microstructure of the defective Ti/Ni nanolaminates. The Ti/Ni interface plays a significant role in the tensile process. The semi-coherent interface impedes new grains and lattice dislocations from passing across the interface, while the incoherent interface facilitates dislocations generating and sliding along the interface, and absorbs the dislocations moving to the interface. The results also indicate that the strain rate significantly affects the evolution of the microstructure and the tensile properties of defective Ti/Ni nanolaminates.

Abstract Mitochondrial dysfunction is becoming one of the main pathology factors involved in the etiology of neurological disorders. Recently, mutations of the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and 10 (CHCHD10) which encode two homologous proteins that belong to the mitochondrial CHCH domain protein family, are linked to Parkinson’s disease and amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), respectively. However, the physiological and pathological roles of these twin proteins have not been well elaborated. Here, we show that, in physiological conditions, CHCHD2 and CHCHD10 interact with OMA1 and suppress its enzyme activity, which not only restrains the initiation of the mitochondrial integrated response stress (mtISR), but also suppresses the processing of OPA1 for mitochondrial fusion. Further, during mitochondria stress-induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment, CHCHD2 and CHCHD10 translocate to the cytosol and interacte with eIF2a, which attenuates mtISR overactivation by suppressing eIF2a phosphorylation and its downstream response. As such, knockdown of CHCHD2 and CHCHD10 triggers mitochondrial ISR, and such cellular response is enhanced by CCCP treatment. Therefore, our findings demonstrate the first “mtISR suppressor” localized in mitochondria for regulating stress responses in mammalian cells, which has a profound pathological impact on the CHCH2/CHCH10-linked neurodegenerative disorder.

BackgroundTo provide reliable evidence to exercise rehabilitation therapists and clinicians, we compared and analyzed the effects of different exercise modalities on cardiopulmonary function in hemodialysis patients using Bayesian network meta-analysis.MethodsPubMed, OVID, Web of Science, Cochrane Library, Embase, Scopus, CINAHL, SPORT Discus, SinoMed, CNKI, Wanfang, and VIP were searched from inception to July 20, 2022. We included randomized controlled trials comparing 12 exercise modalities to improve cardiorespiratory fitness in hemodialysis patients. All statistical analysis was performed using STATA and R.ResultA total of 82 randomized controlled trials involving 4146 maintenance hemodialysis patients were included in this study. The pair-wise meta-analysis showed that all exercise modalities had a positive effect on all indicators of cardiorespiratory capacity. The network meta-analysis demonstrated that Blood flow restriction training (BFRT), Cycle exercise (CE), Inspiratory muscle training (IMT), Combined aerobic and resistance training (CT), and Aerobic training (AT) were significantly better than usual care for 6-min walkability; Medium intensity continuous training (MICT), CT, CE, and AT were considerably better than usual care for VO2Peak; body and mind training (MBT) and CT significantly improved SBP compared to usual care; and only MBT was significantly better than usual care for DBP. Both the two-dimensional plot and the radar plot demonstrated that CT had the best combined-effect on each index of cardiorespiratory fitness. Subgroup and sensitivity analyses demonstrated the robustness of the results. The evidence was mainly “low” to “very low” for this network meta-analysis.ConclusionThere is no one exercise that can achieve the best effect on all of the outcomes. The benefits of MBT in decreasing arterial blood pressure are unsurpassed by other exercise methods. The intervention effect of the CT is better and more stable. Electrical muscle stimulation training (MEST) can be employed in individuals who do not wish to exercise actively but may cause an increase in blood pressure. On the basis of the characteristics of different exercise types, guidelines developers, clinicians, and patients may employ them appropriately.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Objective: Inflammation and oxidative stress play critical roles in sepsis-induced acute lung injury (ALI). Sprout4 (Spry4) is involved in regulating inflammation and tissue injury; however, its role and mechanism in sepsis-induced ALI remain elusive. Methods: Macrophage-specific Spry4 knockout (Spry4MKO), transgenic (Spry4MTG) mice and matched control littermates were generated and exposed to cecum ligation and puncture (CLP) surgery to establish bacterial sepsis-induced ALI. Bone marrow-derived macrophages (BMDMs) from Spry4MKO or Spry4MTG mice were isolated and subjected to lipopolysaccharide (LPS) stimulation to further validate the role of Spry4 in vitro. To verify the necessity of AMP-activated protein kinase (AMPK), Spry4 and AMPK double knockout mice and compound C were used in vivo and in vitro. BMDMs were treated with STO-609 to inhibit calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2). Results: We found that macrophage Spry4 was increased in CLP mice and positively correlated with sepsis-induced ALI. Macrophage Spry4 deficiency prevented, while macrophage Spry4 overexpression exacerbated sepsis-induced inflammation, oxidative stress and ALI in mice and BMDMs. Mechanistic studies revealed that macrophage Spry4 deficiency alleviated sepsis-induced ALI through activating CaMKK2/AMPK pathway. Conclusion: Our study identify macrophage Spry4 as a promising predictive and therapeutic target of sepsis-induced ALI.

Propellant materials are occasionally experiencing severe dynamic loading during transporting and service process, thus their mechanical characteristics and potential mechanisms under transient loading are needed thoroughly understanding for its integrity designing and reliable service. The paper focuses on the mechanical behaviors of propellant CMDB, along with its potential mechanism and constitutive characterizations. Mechanical behaviors are firstly studied experimentally under strain rates from 0.0001 s−1 to 3800 s−1 using Instron mechanical device and Hopkinson bar apparatus. Strain-controlled experiments are also performed for specific focus on severe multiple loadings. It is found that CMDB presents high rate-dependence, and shares parallel mechanical behaviors under wide strain rates. So does the strain hardening ratio. The microstructural observation on crack maps demonstrates that the crack is rate-dependent too, which presents the increasing dimension and decreasing quantity with increasing strain rate. The mechanisms are accordingly proposed based on microstructures, which can explain reasonably the rate dependences. Finally, a constitutive equation is succinctly deduced to well capture the mechanic characteristics at large deformation under wide strain rate range, and the involved less parameters own the overwhelming merit in engineering simulation and applications.

IntroductionThere is few effective biomarkers for diagnosing nonalcoholic fatty liver disease (NAFLD) in clinical practice. This study was aimed to investigate the predictive ability of novel inflammatory biomarkers, including the monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR), for NAFLD.MethodsA total of 4465 outpatients diagnosed with NAFLD and 3683 healthy controls were enrolled between May 2016 and November 2021 from the West China Hospital of Sichuan University, and anthropometric and laboratory examination data were collected. The two-sample Mann-Whitney U test and binary logistic regression analysis were used to evaluate the correlations between four inflammatory biomarkers and NAFLD. The areas under the curves (AUCs) of receiver operating characteristic were used to evaluate their predictive ability for NAFLD.ResultsThe MHR, NLR and LMR were higher in patients with NAFLD than in healthy controls (P

ObjectiveMetabolic associated fatty liver disease (MAFLD) affects nearly a quarter of the world’s population. Our study aimed to characterize the gut microbiome and overall changes in the fecal and serum metabolomes in MAFLD patients.MethodsThirty-two patients diagnosed with MAFLD and 30 healthy individuals (control group, CG) were included in this study, the basic clinical characteristics and laboratory test results including routine biochemistry, etc. were recorded for all, and their serum and fecal samples were collected. A portion of the fecal samples was subjected to 16S rDNA sequencing, and the other portion of the fecal samples and serum samples were subjected to non-targeted metabolomic detection based on liquid chromatography-mass spectrometry (LC–MS). Statistical analysis of clinical data was performed using SPSS software package version 25.0 (SPSS Inc., Chicago, IL, United States). The analysis of 16S rDNA sequencing results was mainly performed by R software (V. 2.15.3), and the metabolomics data analysis was mainly performed by CD 3.1 software. Two-tailed p value

To identify differentially expressed and clinically significant mRNAs and construct a potential prediction model for metabolic steatohepatitis (MASH).

In the high mobility environment, the channel state information (CSI) in the last part of the packet is different from the beginning part’s actual channel. This phenomenon degrades channel estimation accuracy, and hence it is necessary to be compensated to realize reliable communications. Decision feedback channel estimation (DFCE) has been widely considered as the channel tracking approach. It still causes estimation errors due to the decision-making process in the presence of time and frequency selective fading environments. To address these issues, this paper newly proposes a generalized regression neural network (GRNN) based channel tracking scheme incorporated with frequency-domain CSI smoothing. The latter part is the key to improve the dependability of the training data sets. Computer simulation results confirm that the proposed scheme can achieve superior BER performance and the lower root mean square error (RMSE) value of estimated CSI better than the conventional ones.

Hopkinson bar loading technique needs theoretical instruction for desired stress waves, to achieve controllable deformation under constant high strain rate loading, for it is the indispensable access while investigating material's rate-dependence and deformation mechanism under transient loading. In this work, theoretical and experimental studies are focused on the involved issues. Firstly, the theoretical deduction based on stress wave theory is performed for constant true strain rate loading, and the equation is formulated of an ideal incident strain wave for different materials. The formulated waves are further clarified by case studies of specimens with various mechanical behaviors, and they are found to present concave characteristics under large deformation. Secondly, an efficient methodology is proposed for single stress wave loading, and the target requirement is deduced theoretically. It is easily achieved experimentally by performing specific strain-controlled experiments: prior to and beyond peak stress of epoxy. Finally, some methods are proposed for achieving the formulated stress waves, and experimental verifications are also conducted on various materials.

Outdoor physical activities can promote public health and they are largely influenced by the built environment in different urban settings. Understanding the association between outdoor physical activities and the built environment is important for promoting a high quality of life. Existing studies typically focus on one type of outdoor activity using interview-based small samples and are often lack of systematic understanding of the activities' intensity and frequency. In this study, we intend to gain deeper insight into how the built environment influences physical activities using the data extracted from individual's wearables and other open data sources for integrated analysis. Multi-linear regression with logarithm transformation is applied to perform the analysis using the data from Changsha, China. We found that built environment impacts on outdoor physical activities in Changsha are not always consistent with similar studies' results in other cities. The most effective measures to promote outdoor physical activities are the provision of good arterial and secondary road networks, community parks, among others in Changsha. The results shed light on future urban planning practices in terms of promoting public health.

Abstract Background Nonalcoholic steatohepatitis (NASH) progresses from simple nonalcoholic fatty liver (NAFL) and has a poor prognosis. Abnormal lipid metabolism is closely related to the occurrence and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to study the relationships between serum lipid metabolites and NASH, and to improve the early diagnosis of NASH. Methods This study included 86 NAFLD patients (23 NASH and 63 NAFL), and 81 unaffected individuals as controls from West China Hospital between October 2018 and May 2019. With lipid metabolites as the focus of the study, the differences in lipid metabolites were compared between the control group, NAFL patients, and NASH patients. Logistic regression analysis was used to examine the risk factors of NASH. Finally, receiver operating characteristic curve (ROC curve) was used to analyze the efficacy of the metabolites in NASH prediction. Results The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipoprotein A (LPA) increased with the severity of NAFLD. In NAFLD patients, LPA (OR:1.61; 95%CI: 1.03–2.52) was a potential risk factor for NASH, and ROC analysis showed that the combination of LPA, ALT, and AST had a greater predictive efficiency for NASH. Conclusions Abnormal apolipoprotein/lipoprotein is closely related to lipid metabolism disorder in patients with NAFLD. In NAFL, the combination of LPA, ALT, and AST contributes to predicting the occurrence of NASH. LPA may be a potential biomarker and therapeutic target for diagnosing and treating NASH.

Emerging data suggests that 4-methylguaiacol is not only an aroma compound but also a bioactive component of Baijiu (Chinese liquor). To verify the anti-inflammatory potential of 4-methylguaiacol, the influence of 4-methylguaiacol on the secretion of inflammatory cytokines was monitored by ELISA in LPS-induced THP-1 cell model, the regulation of 4-methylguaiacol on the NF-κB, AP-1, and Nrf2 signaling pathways was detected by real-time PCR and western blot as well. Based on the results of ELISA, 4-methylguaiacol significantly inhibited the overproduction of TNF-α, IL-1β, IL-6, IL-8, NO, and PGE2 caused by LPS. Further real-time PCR and western blot analyses revealed that 4-methylguaiacol was able to attenuate LPS-induced inflammatory response and inhibit the expression level of inflammatory cytokines and inflammasome by inducing Nrf2 signaling pathway and inactivating the NF-κB and AP-1 signaling pathways. In light of these findings, 4-methylguaiacol was an effective anti-inflammatory component natural in Baijiu.

The carbon emissions of sectors and households enabled by primary inputs have practical significance in reality. Considering the mutual effect between the industrial sector and the household, this paper firstly constructed an environmentally extended semi-closed Ghosh input–output model with an endogenized household sector to analyze the relationship between carbon emissions and the Chinese economy from the supply-side perspective. The structural decomposition analysis and the hypothetical extraction method were remodified to identify the supply-side driving effects of the changes in carbon emissions and investigate the net carbon linkage. The results show that the electricity, gas, and water supply sector was the key sector with the highest carbon emission intensity enabled by primary inputs. The household sector had an above 93% indirect effect of the enabled intensity, with its enabled intensity dropping significantly by more than 55% from 2007 to 2017. The operating surplus and mixed income caused 3214.67 Gt (34.17%) of the enabled emissions in 2017. The supply-side economic activity, measured by the value added per capita, was the main factor of the carbon emission growth, mainly attributed to the development of the manufacturing sector and the electricity, gas, and water supply sector. The emission intensity and allocation structure both brought a decrease in carbon emissions. The electricity, gas, and water supply sector and the manufacturing sector were the major sources of the supply-induced cross-sectoral input emissions, while the commercial and service sector and the household sector were the top source of supply-induced cross-sectoral output emissions. This paper sheds light on the policies of the carbon emission abatement and the adjustment of the allocation structure from the perspective of supply.

As an important tool to control CO2 emission, carbon emission trading (CET) has been highlighted in prior studies for its positive effects on firms. However, we are concerned about the role of the CET in corporate financing. Through a quasi-natural experiment from China’s CET pilot, regarded as the start-up stage of China’s emission trading system, we investigate the manufacturing corporate financing (i.e., debt and commercial credit financing). The results show that the firms in China’s CET market have less debt financing. Additionally, in the heterogeneity analysis, we found that (1) the CET is negatively related to corporate financing when their financing constraints are weak, whereas it only reduces long-term debt for the firms with strong financing constraints. (2) The impact of the CET on corporate financing is not significant for the firms located in first-tier cities in China, but in other cities, the CET negatively influences firms’ long-term debt and contributes to commercial credit financing. (3) The CET only plays a negative role in long-term debt and a positive role in commercial credit financing for firms in high energy-consuming industries. This study enlightens the government to improve the emission trading system and increase financing support to manufacturing firms in the CET market.

As a critical node of the global transportation network, ports have great potential in promoting transportation emission reduction. Promoting the low-carbon transition of ports by using clean energy is effective. Using hydrogen energy in automated container terminals (ACTs) has become popular in port emission-reduction research. The research object is the main port equipment—the automated rail-mounted container gantry crane (ARMG). This research designs a staged investment decision-making scheme for ARMGs’ hydrogen energy transition. The Internet of Things (IoT) architecture in ACTs collects ARMG equipment operation and carbon emission data. It provides a basis for data acquisition in ARMGs’ hydrogen energy transition. Furthermore, ports can adopt big data technology to analyze the correlation between equipment operation and carbon emissions. Finally, the digital twin platform will visualize the ARMG equipment operation and carbon emission behavior to remote operators. These advanced technologies can achieve status monitoring and simulation prediction, which will support ARMGs’ hydrogen energy transition. However, the ARMGs’ hydrogen energy transition has a long cycle, large investment, and strong variability. Ports should make staged investment decisions based on the digital twin platform’s status monitoring and simulation prediction analysis results. Therefore, this research establishes an optimization model for ARMGs’ low-carbon transition investment decision based on the real options method, and analyzes the staged investment scale and timing of ARMGs’ hydrogen energy transition. The results provide a popularized decision-making scheme for the low-carbon transition of ports’ equipment, which could facilitate the low-carbon transition of ports’ equipment.

Multiple myeloma (MM) is a neoplastic disorder characterized by clonal proliferation of malignant plasma cells derived from B cells in bone marrow. Pediatric MM is rare with only approximately 0.3% of cases diagnosed before the age of 30. In this report, we present a 14 years old boy diagnosed as MM with multiple pathologic vertebral fractures. To our knowledge, our patient is the youngest Chinese case in the literature to present with MM. He was treated with bortezomib, dexamethasone, and cyclophosphamide followed by autologous hematopoietic stem cell transplantation with good clinical response. We hope to aid in the understanding of the pathophysiology and management of this condition.

AimsMetabolic associated fatty liver disease (MAFLD) is the most common cause of chronic liver disease and is a major health and economic burden in society. New drugs are urgently needed to treat MAFLD. This systematic review and meta-analysis was conducted to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with MAFLD.MethodWe searched PubMed, Embase, Cochrane Library database, and Web of Science since 1977. We selected all randomized controlled trials which met the inclusion and exclusion criteria and evaluated the quality of evidence. A random-effects meta-analysis was performed to assess all the primary and second outcomes.ResultsEight randomized controlled trials, including 396 patients, of which 265 patients had type 2 diabetes mellitus, met the inclusion criteria. Compared with the placebo or active agents group, the GLP-RA group showed a significant reduction in the liver fat content [weight mean difference (WMD) -3.17%, 95%CI -5.30 to -1.03, P < 0.0001], body weight (WMD -4.58 kg, 95%CI -8.07 to -1.10, P = 0.010), waist circumference (WMD -3.74 cm, 95%CI -6.73 to -0.74, P = 0.010), alanine aminotransferase (WMD -10.73 U/L, 95%CI -20.94 to -0.52, P = 0.04), γ- glutamyl transferase (WMD -12.25 U/L,95% -18.85 to -5.66, P = 0.0003, with I²=23%), fasting blood glucose (MD, -0.36 mmol/L; 95%CI, -0.69 to -0.03, P = 0.030), and hemoglobin A1c (WMD -0.36%, 95%CI -0.52 to -0.19, P < 0.0001). The reported adverse events were gastrointestinal complications with no serious adverse events, and most symptoms were relieved within 1–2 weeks after dose titration.ConclusionGLP-RAs may improve liver injury and metabolic disorder in patients with MAFLD, regardless of the presence of type 2 diabetes mellitus. The benefits of GLP-RAs treatment outweigh the adverse effects of drugs in patients with MAFLD.

Background: Cerebral ischemia–reperfusion (I/R) injury can lead to severe dysfunction, and its treatment is difficult. It is reported that nucleotide-binding domain and leucine-rich repeat family protein 3 (NLRP3) inflammasome-mediated cell pyroptosis is an important part of cerebral I/R injury and the activation of autophagy can inhibit pyroptosis in some tissue injury. Our previous study found that the protective effects of bone marrow mesenchymal stem cells (BMSCs) in cerebral I/R injury may be associated with the regulation of autophagy. Recent studies have demonstrated that exosomes secreted from BMSCs (BMSC-Exos) may play an essential role in the effective biological performance of BMSCs and the protective mechanism of BMSC-Exos is associated with the activation of autophagy and the remission of inflammation, but it has not been reported in studies of cerebral I/R injury. We aimed to investigate the effects of BMSC-Exos on cerebral I/R injury and determine if the mechanism is associated with the regulation of pyroptosis and autophagic flux.Method: PC12 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cerebral I/R in vitro and were cocultured with BMSC-Exos. Cell viability was determined with CCK-8 and lactate dehydrogenase (LDH) detection kits. Scanning electron microscopy (SEM), Hoechst 33342/propidium iodide (PI) double staining, 2′,7′-dichlorodihydrofluorescein diacetate assay, immunofluorescence, Western blot, and Enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. Furthermore, transmission electron microscopy (TEM), GFP-RFP-LC3 adenovirus transfection, and Western blot were used to detect autophagic flux and its influence on pyroptosis. Finally, coimmunoprecipitation was used to detect the binding interaction between NLRP3 and LC3.Results: BMSC-Exos increased cell viability in OGD/R. The inhibitory effect of BMSC-Exos on pyroptosis was comparable to the NLRP3 inhibitor MCC950 and was reversed by NLRP3 overexpression. Furthermore, BMSC-Exos promoted autophagic flux through the AMP-activated kinase (AMPK)/mammalian target of the rapamycin pathway, whereas chloroquine, AMPK silencing, and compound C blocked the inhibitory effect on pyroptosis.Conclusions: BMSC-Exos can protect PC12 cells against OGD/R injury via attenuation of NLRP3 inflammasome-mediated pyroptosis by promoting AMPK-dependent autophagic flux.

Background: There is an increasing trend for researchers to combine mirror therapy with another rehabilitation therapy when treating the upper extremity of patients with stroke.Objective: To evaluate the synergistic effect of combined mirror therapy (MT) on the upper extremity in patients with stroke and to judge efficacies of four combined mirror therapy subgroups [EMGBF group: electromyographic biofeedback (EMGBF) + MT; MG group: mesh glove (MG) + MT; AT group: acupuncture (AT) + MT; ES group: EMG-triggered electrical stimulation (ES) + MT].Methods: CNKI, Wan Fang, VIP, Web of Science, ScienceDirect, PubMed, OVID LWW, and Cochrane were used. We searched these databases for randomized controlled trials published from January 2013 to August 2019, which presented results of combining mirror therapy with other rehabilitation therapies. Quality assessments were performed using the Cochrane Handbook criteria in order to accurately review interventions. The primary outcomes were measured by the Fugl–Meyer Assessment—upper extremity (FMA-UE).Results: Ten trials, with a total of 444 patients whose upper limb functions were damaged after stroke, were included in the meta-analysis. Compared with the control group, a remarkable effect of combined mirror therapy [all: weight mean difference in random effects model (WMD): 8.07, 95% confidence interval (CI) 5.87, 10.26] on functional recovery of the upper limb was detected. However, a high value of heterogeneity (χ2 = 20.09, df = 9; I2 = 55%) was found. The subgroup analysis (EMGBF group: WMD = 8.95, 95% CI 6.33, 11.58; ES group: WMD = 10.14, 95% CI: 5.67, 15.01) showed moderate improvement in functional recovery of the upper extremity in patients with stroke when mirror therapy was combined with conventional therapy. Furthermore, no difference in efficacy on upper extremity in patients with stroke was observed between the EMGBF group and the ES group.Conclusion: Despite the heterogeneity, the results indicate that combining mirror therapy with another rehabilitation therapy on the upper extremity in patients with stroke is better than single rehabilitation therapy. However, more randomized controlled clinical trials and larger sample sizes are required for an in-depth meta-analysis.

Due to excellent performance properties such as strong activity and high selectivity, single-atom catalysts have been widely used in various catalytic reactions. Exploring the application of single-atom catalysts and elucidating their reaction mechanism has become a hot area of research. This article first introduces the structure and characteristics of single-atom catalysts, and then reviews recent preparation methods, characterization techniques, and applications of single-atom catalysts, including their application potential in electrochemistry and photocatalytic reactions. Finally, application prospects and future development directions of single-atom catalysts are outlined.