Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3-/- mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

[4 + 2] Cyclization or Lossen Rearrangement: Rhodium-Catalyzed Divergent Synthesis of Carboline Derivatives with Anticancer Activity.

An unusual rhodium-catalyzed C-H activation/Lossen rearrangement/oxa-Michael addition tandem cyclization has been achieved along with a tunable well-known C-H activation/[4 + 2] annulation, leading to regio-, chemo-, and diastereoselective access to diverse pentacyclic α-carbolines and ß-carboline-1-one derivatives in moderate to good yields with significant anticancer activity.

The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis.

Background: Immunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients. Methods: Fifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment. Results: Compared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients. Conclusion: Exogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.

Impairment of Left Ventricular Function in the Depressed Chinese Miniature Swine Model by Cardiovascular Magnetic Resonance Feature-Tracking: A Preliminary Study.

PURPOSE: Individuals with depression have an increased risk of cardiovascular disease, and more often have a poor prognosis with cardiovascular disease. This study aimed to investigate the impact of depression on Left Ventricular (LV) alterations using Cardiovascular Magnetic Resonance Featuretracking (CMR-FT). METHODS: Seven anesthetized, healthy Chinese miniature swine were included in the study. Basic data, including CMR scans at baseline and after 14 days of depression modeling, were collected. Behavioral tests, including the Open-field Test (OFT), Sucrose Preference Test (SPT), and measurements of the time taken to consume a specific amount of food and sugar, were conducted to assess the success of the depression models. CMR cine images were acquired and CVI software was employed to analyze Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS), and Global Radial Strain (GRS). Late Gadolinium Enhancement (LGE) imaging was used to detect myocardial infarction and/or scar. RESULTS: The outcomes demonstrated successful depression modeling, indicated by reduced scores in the OFT and SPT, as well as an extended time to intake food and sugar compared to baseline. However, no significant differences were observed in LV End-diastolic Volume (LVEDV), LV Endsystolic Volume (LVESV), LV Ejection Fraction (LVEF), LV End-diastolic Myocardial Mass (LVMASSED), and Cardiac Output (CO) before and after modeling. Regarding LV global strain parameters, there was a downward trend in GRS (25.35% ± 6.9% vs. 22.86% ± 6.4%, P=0.021), GCS (-16.71% ± 4.2% vs. -14.78% ± 2.3%, P=0.043), and GLS (-17.66% ± 2.9% vs. -14.53% ± 2.5%, P=0.056), respectively, after modeling. GRS and GCS were significantly reduced after modeling compared to baseline. CONCLUSION: The study suggests that depression may contribute to early LV systolic dysfunction, particularly affecting LV GCS and GRS.

Green synthesis for diverse bioactive benzo-fused spiroindolines through DBU-catalysed post-Ugi double cyclization.

A metal-free protocol utilizing DBU catalysis for post-Ugi amide-ester exchange and Conia-ene double cyclization has been successfully developed, allowing the synthesis of diverse highly functionalized benzo-fused spiroindolines with anti-cancer activities under mild conditions. Remarkably, this methodology demonstrates promising prospects for green chemistry, as it allows for the preparation of the spiroindolines in water. Control experiments indicate that a crucial role of the cyclic imide, specifically ring rigidification, facilitates the subsequent Conia-ene cyclization.

Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders.

Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.

Keplerate-Type Polyoxometalates-Based Triboelectric Nanogenerator for Higher Performance via the Morphology Modulation of Blackberry Structure.

The triboelectric material is the key factor affecting the performance of triboelectric nanogenerators (TENGs). Inorganic materials have higher heat resistance and stability than widely used organic materials. However, the weaker triboelectric property limits the application of TENGs. Modulating surface roughness by changing particle shape and size is a simple way to increase performance for TENGs. Polyoxometalates (POMs) have unrivalled structural diversity and can self-assemble to form different nanostructures. In this study, we propose [{(NH4)42[Mo72VIMo60VO372(CH3COO)30(H2O)7.ca.300H2O.ca.CH3COONH4)]}-Mo132] and [{Na8K14(VO)2[{(MoVI)(Mo5VIO21)(H2O)3]}10{(MoVI)Mo5VIO21(H2O)3(SO4)}2{VIVO(H2O)20}{VIVO}10({KSO4}5)2]·150H2O)}-Mo72V30] with blackberry structure which are cured and prepared into film by spin-coating technique, are used as triboelectric positive materials for the first time in the field of TENGs. Keplerate-type polyoxometalates can form blackberry structures with higher dispersibility and flexibility, which can be used to control surface roughness by regulating the size of particles. The discovery proves that the particle size influences the surface roughness, which adjusts the output of TENGs. According to our findings, Mo132-h-TENG generates an output voltage of 29.3 V, an output charge of 8 nC 2-3 folds higher than Mo132-TENG, and a maximum power density of 6.25 mW·m-2 at 300 MΩ. Our research provides that altering the dimensional size can be an available way to raise the output of TENGs.

In Situ Integration of a Flame Retardant Quasisolid Gel Polymer Electrolyte with a Si-Based Anode for High-Energy Li-Ion Batteries.

Silicon (Si) stands out as a promising high-capacity anode material for high-energy Li-ion batteries. However, a drastic volume change of Si during cycling leads to the electrode structure collapse and interfacial stability degradation. Herein, a multifunctional quasisolid gel polymer electrolyte (QSGPE) is designed, which is synthesized through the in situ polymerization of methylene bis(acrylamide) with silica-nanoresin composed of nanosilica and a trifunctional cross-linker in cells, leading to the creation of a "breathing" three-dimensional elastic Li-ion conducting framework that seamlessly integrates an electrode, a binder, and an electrolyte. The silicon particles within the anode are encapsulated by buffering the QSGPE after cross-linking polymerization, which synergistically interacts with the existing PAA binder to reinforce the electrode structure and stabilize the interface. In addition, the formation of the LiF- and Li3N-rich SEI layer further improves the interfacial property. The QSGPE demonstrates a wide electrochemical window until 5.5 V, good flame retardancy, high ionic conductivity (1.13 × 10-3 S cm-1), and a Li+ transference number of 0.649. The advanced QSGPE and cell design endow both nano- and submicrosized silicon (smSi) anodes with high initial Coulombic efficiencies over 88.0% and impressive cycling stability up to 600 cycles at 1 A g-1. Furthermore, the NCM811//Si cell achieves capacity retention of ca. 82% after 100 cycles at 0.5 A g-1. This work provides an effective strategy for extending the cycling life of the Si anode and constructing an integrated cell structure by in situ polymerization of the quasisolid gel polymer electrolyte.

A potential antiviral role for CCR5+CD8+ T cells in children with hepatitis B.

While dysfunctional exhausted CD8+ T cells hamper viral control when children acquire hepatitis B virus (HBV) infection, it's crucial to recognize that CD8+ T cells have diverse phenotypes and functions. This study explored a subset of CD8+ T cells expressing C-C chemokine receptor type 5 (CCR5) in children with HBV infection. Thirty-six patients in the immune tolerant group, 33 patients in the immune active group, 55 patients in the combined response group, and 22 healthy control children were enrolled. The frequency, functional molecules, and effector functions of the CCR5+CD8+ T cell population in different groups were evaluated. The frequency of CCR5+CD8+ T cells correlated positively with the frequency of CCR5+CD4+ T cells and patient age, and it correlated negatively with alanine aminotransferase, aspartate transaminase, HBV DNA, hepatitis B surface antigen, and lactic dehydrogenase levels. CCR5+CD8+ T cells had higher levels of inhibitory and activated receptors and produced higher levels of IFN-γ, IL-2, and TNF-α than CCR5-CD8+ T cells. CCR5+CD8+ T cells were partially exhausted but possessed a stronger antiviral activity than CCR5-CD8+ T cells. The identification of this subset increases our understanding of CD8+ T cell functions and serves as a potential immunotherapeutic target for children with HBV infection.

SP2509 functions as a novel ferroptosis inhibitor by reducing intracellular iron level in vascular smooth muscle cells.

Previous studies have shown that ferroptosis of vascular smooth muscle cells (VSMCs) is involved in the development of aortic dissection (AD) and that histone methylation regulates this process. SP2509 acts as a specific inhibitor of lysine-specific demethylase 1 (LSD1), which governs a variety of biological processes. However, the effect of SP2509 on VSMC ferroptosis and AD remains to be elucidated. This aim of this study was to investigate the role and underlying mechanism of SP2509-mediated histone methylation on VSMC ferroptosis. Here, a mouse model of AD was established, and significantly reduced levels of H3K4me1 and H3K4me2 (target of SP2509) were found in the aortas of AD mice. In VSMCs, SP2509 treatment led to a dose-dependent increase in H3K4me2 levels. Furthermore, we found that SP2509 provided equivalent protection to ferrostatin-1 against VSMC ferroptosis, as evidenced by increased cell viability, decreased cell death and lipid peroxidation. RNA-sequencing analysis and subsequent experiments revealed that SP2509 counteracted cystine deficiency-induced response to inflammation and oxidative stress. More importantly, we demonstrated that SP2509 inhibited the expression of TFR and ferritin to reduce intracellular iron levels, thereby effectively blocking the process of ferroptosis. Therefore, our findings indicate that SP2509 protects VSMCs from multiple stimulus-induced ferroptosis by reducing intracellular iron levels, thereby preventing lipid peroxidation and cell death. These findings suggest that SP2509 may be a promising drug to alleviate AD by reducing iron deposition and VSMC ferroptosis.

Continuous cropping system altered soil microbial communities and nutrient cycles.

Understanding the response of microbial communities and their potential functions is essential for sustainability of agroecosystems under long-term continuous cropping. However, limited research has focused on investigating the interaction between soil physicochemical factors and microbial community dynamics in agroecosystems under long-term continuous cropping. This study probed into the physicochemical properties, metabolites, and microbial diversity of tobacco rhizosphere soils cropped continuously for 0, 5, and 20 years. The relative abundance of bacterial genera associated with nutrient cycling (e.g., Sphingomonas) increased while potential plant pathogenic fungi and beneficial microorganisms showed synergistic increases with the duration of continuous cropping. Variations in soil pH, alkeline nitrogen (AN) content, and soil organic carbon (SOC) content drove the shifts in soil microbial composition. Metabolites such as palmitic acid, 3-hydroxypropionic acid, stearic acid, and hippuric acid may play a key role in soil acidification. Those results enhance our ability to predict shifts in soil microbial community structure associated with anthropogenic continuous cropping, which can have long-term implications for crop production.

Sialic acids as attachment factors in mosquitoes mediating Japanese encephalitis virus infection.

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.

'Only to reconcile with it'. The coping experience amongst middle-aged and older cancer survivors: A qualitative study.

BACKGROUND: Cancer threat is relevant to age, and the threat of a foreshortened life coupled with a lengthy treatment process negatively affects middle-aged and older adults. Understanding the coping throughout the cancer experience in middle-aged and older cancer survivors will help develop supportive care to promote their physiological and psychological coping effects. OBJECTIVES: To explore the cancer coping experiences of middle-aged adults aged 40-59 and older adults over 60. DESIGN: A descriptive phenomenological study was employed. METHODS: Face-to-face, in-depth, semistructured interviews were conducted with 22 oncology patients in a tertiary university hospital aged 40 or above from August to October 2023. The interview data were analyzed using thematic analysis procedures. RESULTS: Five themes and 13 subthemes were formed through analysis: acceptance of cancer (considering cancer as chronic, believing in fate and attributing cancer to karma); having different information needs (desired to be truthfully informed, information-seeking behaviour, information avoidance behaviour); getting families involved (developing dependent behaviours, feeling emotional support, family members suffering worse); striving to maintain positive psychological state (positive thinking, seeking peer support) and negative experience (undesirable, low self-esteem). CONCLUSION: Our study reveals that cancer survivors' attitudes towards having cancer have changed from a death sentence to a more positive perception of a chronic disease. Supportive programmes for developing coping strategies should consider the cultural traditions and religious beliefs, different information needs, involvement of family and promoting a positive psychological state while avoiding negative factors. PATIENT OR PUBLIC CONTRIBUTION: Participants with experience of coping with cancer were involved in the semistructured interview.

Triglyceride-Glucose Index is an Independent Risk Factor for Hepatocellular Carcinoma Development in Patients with HBV-Related Liver Cirrhosis.

Aim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC. Results: The median follow-up time was 37 months (range: 6-123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P<0.01), DC (P<0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P<0.01), and HBV DNA positivity (P<0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, <0.01, 0.05, and <0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P<0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively. Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.

GSDME-mediated keratinocyte pyroptosis participates in the pathogenesis of psoriasis by promoting skin inflammation.

OBJECTIVE: Psoriasis is a common, chronic inflammatory disease with unclear etiology. Keratinocytes in psoriasis are susceptible to exogenous triggers that induce inflammatory cell death. This study investigated whether GSDME-mediated pyroptosis in keratinocytes contributes to the pathogenesis of psoriasis. METHODS: Skin samples from patients with psoriasis and healthy controls were collected to evaluate the expression of GSDME, cleaved-caspase-3, and inflammatory factors. We then analyzed the data series, GSE41662, to further compare the expression of GSDME between lesional and non-lesional skin samples in those with psoriasis. In vivo, caspase-3 inhibitor and GSDME deficiency mice (Gsdme-/-) were applied to block caspase-3/GSDME activation in the imiquimod-induced psoriasis model. Skin inflammation, disease severity, and pyroptosis-related proteins were analyzed. In vitro, tumor necrosis factor-α (TNF-α)-induced caspase-3/GSDME-mediated pyroptosis in the HACAT cell line was explored. RESULTS: Our analysis of the GSE41662 data series found that GSDME were upregulated in psoriasis lesions, compared to normal skin. High levels of inflammatory cytokines such as IL-1ß, IL-6, and TNF-α were also found in psoriasis lesions. In mice of Gsdme-/- and caspase-3 inhibitor groups, the severity of skin inflammation was attenuated, and GSDME and C-caspase-3 levels decreased after imiquimod treatment. Similarly, IL-1ß, IL-6, and TNF-α were decreased in Gsdme-/- and caspase-3 inhibitor groups. In vitro, TNF-α induced HACAT cell pyroptosis through caspase-3/GSDME pathway activation, which was suppressed by blocking caspase-3 or silencing GSDME. CONCLUSION: Our study provides a novel explanation that TNF-α/caspase-3/GSDME-mediated keratinocyte pyroptosis is highly responsible for the initiation and acceleration of skin inflammation and progression of psoriasis.

Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain.

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.

Hovenia dulcis: a Chinese medicine that plays an essential role in alcohol-associated liver disease.

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment.

Myocardial deformation characteristics assessed by cardiovascular magnetic resonance feature tracking in a healthy Chinese population.

Purpose: To explore global/regional myocardial deformation across various layers, vascular distributions, specific levels and distinct walls in healthy individuals using cardiovascular magnetic resonance feature tracking (CMR-FT). Methods: We selected a cohort of 55 healthy participants and CMR cine images were used to obtain the left ventricular (LV) peak longitudinal, circumferential, radial strains (LS, CS, RS). The characteristics of normal LV strain in various layers (endocardium, myocardium, epicardium), territories [left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA)], levels (basal, middle, apical) and walls (anterior, septum, inferior, lateral) were compared. Results: The absolute values of the LV global LS and CS gradually decreased from endocardium to epicardium. The absolute LV global RS (65.7 ± 47.7%) was maximum relative to LS (-22.0 ± 10.8%) and CS (-22.8 ± 7.7%). The absolute values of the LCX territorial strain were the largest compared with the LAD and RCA territorial strains. Regional RS, endo-CS and endo-LS gradually increased from the basal to the apical level. The LV lateral walls had the highest strain values (CS, LS, and RS). Conclusions: Variations in normal LV strain values across various layers, territories, levels, and walls were observed, suggesting the necessity for careful clinical interpretation of these strain values. These findings also partially revealed the complexity of normal cardiac mechanics.

Data-mining framework for in-depth quantitative study of influences on low-wind-velocity area from morphological parameters of cuboid-form buildings.

Wind environment is important in architectural sustainable design, as existing studies show that it can be considerably influenced by building morphologies. This study aimed to develop a data-mining framework to quantitatively evaluate and compare influences on Low-Wind-Velocity Area (LWVA) of common cuboid-form buildings with typical morphological parameters. The data-mining framework was originally developed by integrating multiple computational methods for rapid in-depth iterative analyses, including the generation of building models using parametric modelling, the big data generation based on hybrid model, and the statistical metric analysis method. The hybrid model was created by combining the CFD model and machine learning model. The accuracy and efficiency of the framework were fully demonstrated through the comprehensive validation and analyses of different models. The data of more than fifty thousand building cases with different morphological parameters and relevant wind conditions were generated and analyzed. Influences on LWVA of morphological parameters of cuboid-form building was comprehensively evaluated, including the visualization of multiple parameters, calculation and comparison of several correlation coefficients. It suggested that the reduction of height and width on the windward side would significantly decrease the LWVA and promote the outdoor ventilation. The change of depth would have relatively limited influence on the LWVA. Multivariate regression model-fit and variance analyses were further implemented, and it was found that there was a relatively significant linear correlation between the LWVA and morphological parameters. The equation of multivariate regression model was provided for extra rapid prediction. The study outcome could contribute to efficient evaluation of LWVA and provide useful information for sustainable design.

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.