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We developed pinhole matrix optical solution of fingerprint on display technology for FLI OLED to avoid its low module transmittance. We investigated the influence of pinhole size and touch metal lines on the fingerprint on FLI technology in both regid and foldable display based on a 6.2inch QHD resolution OLED panel. [ABSTRACT FROM AUTHOR]

Background: Previous studies of guselkumab have demonstrated clinical benefits in patients with plaque‐type psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and palmoplantar pustulosis (PPP). Objective: The aim of this exploratory analysis of a double‐blind, multicenter, placebo‐controlled, phase 3 study in Japanese patients with PPP was to evaluate the efficacy of guselkumab in the subset of patients with pustulotic arthro‐osteitis (PAO). Methods: Patients were randomized to receive guselkumab 100 or 200 mg at weeks 0, 4, 12 and every 8 weeks, or placebo with cross‐over to guselkumab 100 or 200 mg at week 16 (placebo group). Efficacy endpoints were changes from baseline in magnetic resonance imaging (MRI) score, EuroQOL‐5 dimensions (EQ‐5D) index score, EQ‐5D pain/discomfort dimension score and C‐reactive protein (CRP, mg/L) level in all PAO patients through week 52. Data from both guselkumab groups were combined and presented as results for a single overall guselkumab group. Results: Among 159 patients with PPP, 66 with PAO were randomized across treatment groups. For patients with MRI data for all regions assessed, the proportion of patients in the guselkumab group with PAO characterized as severe decreased from 23.8% (10/42) at baseline to 5.4% (2/42) at week 52. The mean (SD) change from baseline at week 52 in EQ‐5D index score was 0.20 (0.17) among PPP patients with PAO and 0.15 (0.17) among those without PAO in the guselkumab group. Among all PAO patients, the proportions with an EQ‐5D pain/discomfort dimension score of no or slight pain/discomfort in the guselkumab group increased from baseline to week 52 [33.3% (7/21) vs. 87.5% (35/40)]. The mean (SD) CRP levels decreased in all PAO patients in the guselkumab group at week 52 compared to baseline [−1.71 (8.16) mg/L]. Conclusion: Guselkumab treatment showed beneficial outcomes for PAO signs and symptoms in Japanese patients with PPP. [ABSTRACT FROM AUTHOR]

The Haiyuan fault is a major left‐lateral strike‐slip fault at the boundary between northeast Tibet and the Gobi platform. Combining measurements of offset alluvial terraces with 10Be‐26Al cosmogenic radionuclides dating, we bracket the late Quaternary slip rate along the Hasi Shan fault section (37°00′N, 104°25′E) of the Haiyuan fault. At our reference site, terrace‐riser offsets for five successive terraces range from ~5 to ~200 m, and associated cosmogenic radionuclide ages range from 9 ± 3 to 44 ± 7 kyr. These measurements yield a geological slip rate between 2.7 and 3.0 mm/year. Extending the offset measurements to the entire Hasi Shan front, it yields a slip rate of 3.2 ± 0.2 mm/year over the last ~50 kyr. Our rate is consistent with the lower estimates of other long‐term rates of 4 to 5 mm/year, as well as with geodetic rates of 3 to 5 mm/year, determined in the same area. About 150 km farther west, however, Holocene terraces and moraines offsets have suggested higher slip rate values, between 6 and 15 mm/year. We interpret such discrepancy between rates determined along the western section of the Haiyuan fault and rates determined in the Hasi Shan section as being related to the complex geometry of the Haiyuan fault system along its eastern part, with several active strands moving at the same time and resulting in distributed slip among several sections of the fault system. Key Points: Slip rate along the Hasi Shan section of the Haiyuan fault is determined from numerous offsets and cosmogenic exposure dates over a period of 50,000 yearsThe Hasi Shan fault strand horizontal slip rate is about 3.2 mm/year; this rate is stable over 50,000 years; the uplift rate is about 0.5 mm/yearCombining slip rate for the Hasi Shan strand and all subparallel stands yields a slip rate of 5 to 7 mm/year for the Haiyuan fault system [ABSTRACT FROM AUTHOR]

Aims To observe changes in atrial natriuretic peptide levels after treatment with sodium-glucose co-transporter-2 inhibitors in patients with newly diagnosed type 2 diabetes. Methods A total of 28 patients with newly diagnosed Type 2 diabetes and HbA1c levels of 58 -91 mmol/mol (7.5-10.5%) were randomly selected to receive sodium-glucose co-transporter-2 inhibitor treatment ( n = 18) or placebo ( n = 10) for 24 weeks. We analysed atrial natriuretic peptide concentrations, using an enzyme-linked immunosorbent assay. In addition, sodium and HbA1c levels were measured at baseline, 12 weeks and 24 weeks and blood lipid levels and insulin sensitivities at baseline and 24 weeks. Results Compared with patients treated with placebo, patients who received sodium-glucose co-transporter-2 inhibitor treatment exhibited lower atrial natriuretic peptide levels (36.74 vs 56.90 pg/ml in the placebo group; P < 0.05) and higher sodium levels (144.3 vs 141.4 mmol/l in the placebo group; P < 0.01) at 24 weeks, after adjusting for baseline values. HbA1c levels were lower after sodium-glucose co-transporter-2 inhibitor treatment compared with placebo (51 vs 60 mmol/mol; P < 0.01). No correlation was found between atrial natriuretic peptide and HbA1c levels. Homeostatic model assessment of β-cell function values and lipid profiles were generally similar after 24 weeks of treatment with placebo or sodium-glucose co-transporter-2 inhibitor. Conclusions This study shows the ability of sodium-glucose co-transporter-2 inhibitors to lower atrial natriuretic peptide levels and improve glycaemic control, which may benefit the cardiovascular system. [ABSTRACT FROM AUTHOR]

Aims 14,15-Epoxyeicosatrienoic acid (14,15-EET) is abundantly expressed in brain and exerts protective effects against ischaemia. 14,15-EET is hydrolysed by soluble epoxide hydrolase (sEH). sEH−/− mice show a higher level of 14,15-EET in the brain. Astrocytes play a pivotal role in neuronal survival under ischaemic conditions. However, it is unclear whether the neuroprotective effect of 14,15-EET is associated with astrocytes. Methods A mouse model of focal cerebral ischaemia was induced by middle cerebral artery occlusion. Oxygen-glucose deprivation/reoxygenation (OGD/R) was performed on cultured murine astrocytes, neurons and a human cell line. Cell viabilities were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The mRNA expressions were quantified by real-time PCR. Brain derived neurotrophic factor (BDNF) concentration was measured by ELISA. Protein expressions were quantified by Western blotting. BDNF and peroxisome proliferators-activated receptor gamma (PPAR-γ) expressions were analysed by confocal microscopy. Results Decreased infarct volumes, elevated BDNF expression and increased numbers of BDNF/GFAP Glial Fibrillary Acidic Protein double-positive cells were observed in the ischaemic penumbra of sEH−/− mice. The decreased infarct volumes of sEH−/− mice were diminished by intracerebroventricular injection of a blocker of BDNF receptor. 14,15-EET increases BDNF expression and cell viability of murine astrocytes and U251 cells by BDNF-TrkB Tyrosine receptor kinase-B-extracellular signal-regulated kinase 1/2 signalling during OGD/R. 14,15-EET protects neurons from OGD/R by stimulating the production of astrocyte-derived BDNF. 14,15-EET stimulates the production of astrocyte-derived BDNF through PPAR-γ/p-cAMP-response element binding protein signal pathways. Conclusions Our study demonstrates the importance of 14,15-EET-mediated production of astrocyte-derived BDNF for enhancing viability of astrocytes and protecting neurons from the ischaemic injury and provides insights into the mechanism by which 14,15-EET is involved in neuroprotection. [ABSTRACT FROM AUTHOR]

Multiprotein bridging factor 2 (MBF2) was first isolated from the posterior silk gland of Bombyx mori. However, its function in B. mori is still unknown. Herein, MBF2 transcripts were detected mainly in the posterior silk gland and Malpighian tubules of B. mori larvae via a quantitative PCR analysis. An analysis of temporal expression patterns showed that the expression pattern of MBF2 was the opposite of that of the fibroin heavy chain (fibH) gene, as its expression was high during the fourth-instar moulting stage, decreased gradually during the fifth-instar feeding stage and disappeared at the end of the fifth-instar phase. Furthermore, bimolecular fluorescent complementation and Far-Western blot assays showed that MBF2 interacted with the basic helix-loop-helix transcription factor Bmdimmed. Dual luciferase reporter assays showed that MBF2 down-regulated the promoter activity of fibH and inhibited the effect of Bmdimmed (Bmdimm) on fibH expression. MBF2 expression was induced in silk glands after treatment with 20-hydroxyecdysone in vivo and in vitro. These findings suggest that MBF2 is a transcriptional repressor that is involved in controlling the regulation of the fibH gene in the posterior silk gland by interacting with Bmdimm. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effect of bake-hardening (BH) treatment on C-Mn-Si Transformation Induced Plasticity (TRIP) and Dual Phase (DP) steels' microstructure and mechanical properties. It mentions that the study uses X-ray diffraction, three-dimensional atom probe tomography (APT), and transmission electron microscopy (TEM) to characterize the steels. Moreover, the study shows that the steels have a high BH response.

Crystallization, surface morphology, and electrical behavior of BiFeO3 thin films are improved by SrRuO3 (SRO) buffer layer with optimized grain size. Large-grained SRO buffer layer promotes the growth of dense multiferroic BiFeO3 (BFO) thin films and reduces structural defects. Phase identification by using X-ray diffraction and surface morphology studies by using scanning electron microscopy show that the large-grained SRO buffer layer formed by sputtering thicker SRO films promotes the formation of the perovskite phase as well as the crystallinity. These BFO films have also shown reduced leakage current, as suggested by the weaker frequency dependence of the ferroelectric hysteresis loops as compared with the BFO films deposited on smaller-grained SRO buffer layer. Investigation into the dielectric properties and fatigue endurance reveals that the structural defects of the BFO thin film have also been reduced by employing the larger-grained SRO buffer layer. [ABSTRACT FROM AUTHOR]

The WebQuest as an instructional tool has recently been widely adopted in K-16 education. However, its underlying principles and functionality are not well understood, which has resulted in an inconsistency in practice. This study identifies the underlying constructs of WebQuests as perceived by teachers and variables affecting their perceptions on WebQuests. A survey was conducted on teachers ( n = 226) recruited from one large research university in the USA and a professional listserv. The findings reveal three constructs perceived by teachers as critical to WebQuests: constructivist problem solving, social interaction and scaffolded learning. Results also show that variables like purpose of WebQuest use, years of teaching, years of WebQuest use and gender predict, at various degrees, teachers’ perceptions on WebQuests. Discussions are made on how the constructs identified can be used to improve online teaching and learning. Suggestions for future study are included by examining the influences of social, psychological and affective factors on learners’ learning in WebQuests. [ABSTRACT FROM AUTHOR]

Background cis-AB enzymes are rare glycosyltransferases that synthesize both blood group A and B antigens. We have identified a large cohort of Korean cis-AB blood donors and studied the N-acetylgalactosaminyltransferase (glycosyltransferase A, GTA) and galactosyltransferase (glycosyltransferase B, GTB) activity of their cis-AB serum enzymes. Materials and methods The cis-AB01 allele was identified by PCR–RFLP (polymerase chain reaction–restriction fragment length polymorphism) in 60 donors collected at the Gwangju-Chonnam Red Cross Blood Center. Enzyme assays of this cis-AB enzyme were performed on available serum samples from 16 donors with the cis-AB01/ O genotype and three with the cis-AB01/ A genotype. Results In cis-AB donors with an O allele, both the GTA and GTB activity of the cis-AB enzyme were markedly reduced compared to normal A and B controls (29% and 27%, respectively). This is consistent with the behaviour predicted from kinetic studies of a recombinant model of the corresponding AAAB enzyme. Conclusion Although variable, cis-AB enzymes feature reduced GTA and GTB activities. Cis-AB enzymes feature variable but reduced GTA and GTB activities with relatively weaker GTB activity, consistent with the weak agglutination present on forward typing with anti-B. [ABSTRACT FROM AUTHOR]

The glycogen synthase gene (GYS1), which encodes the rate-limiting enzyme for glycogen synthesis of skeletal muscle, is a promising candidate gene for traits related to skeletal muscle in pigs. In this study, a G/A single nucleotide polymorphism inGYS1intron 7 detected as aFokI PCR-restriction fragment length polymorphism (PCR-RFLP) showed allele frequency differences among five Chinese indigenous pig breeds and three western commercial pig breeds. Linkage analysis assigned the geneGYS1to marker intervalSW1302– SW1473on SSC6 in a three-generation Meishan X Large White reference family. The results of association analysis and interval mapping suggested that theFokI PCR-RFLP polymorphism might be linked with the quantitative trait loci affecting carcass traits detected on SSC6 in the F2 intercross pedigree. The reverse transcriptase-polymerase chain reaction revealed that the porcineGYS1gene was expressed in spleen, lung, liver, kidney, small intestine, skeletal muscle, heart and stomach, with the highest expression in skeletal muscle. [ABSTRACT FROM AUTHOR]

LIM domain proteins are important regulators of the growth, determination and differentiation of cells. Four-and-a-half LIM-only protein 3 (FHL3) is a type of LIM-only protein that contains four tandemly repeated LIM motifs with an N-terminal single zinc finger (half LIM motif). In this study, we have determined the complete coding sequence of pig FHL3 which encodes a 280 amino acid protein. The coding region of the pig FHL3 gene is organized in five exons and spans an approximately 2.1-kb genomic region. Comparative sequencing of six pig breeds revealed three single nucleotide polymorphisms (SNPs) within exon 2 of which an A→G substitution at position 313 changes a codon for arginine into a codon for glycine. The substitution was situated within a PstI recognition site and developed as a PCR-RFLP marker for further use in population variation investigations and association analysis. The A/G polymorphism was segregating only in Landrace pigs. Association studies of the FHL3 polymorphism with carcass traits provided preliminary evidence that the PstI PCR-restriction fragment length polymorphism (RFLP) genotype may be associated with variation in several carcass traits of interest for pig breeding. Further investigations in more Landrace pigs are needed to confirm this. [ABSTRACT FROM AUTHOR]

Abstract Background. Primary and acquired resistance to the antimicrobial agents is a primary reason for the failure of Helicobacter pylori eradication therapies. We assessed the primary antibiotic resistance rates of H. pylori to three different antibiotics and its relationship due to the annual antibiotic consumption in Japan during the period prior to approval of anti-H. pylori therapy in Japan. Materials and Methods. Antibiotic susceptibility was tested using the agar dilution method for clarithromycin, amoxicillin and metronidazole. Isolates were considered resistant when the MIC value was > 8 mg/l for metronidazole, > 1 mg/l for clarithromycin and < 0.5 mg/l for amoxicillin. Results. Helicobacter pylori isolates were obtained from 593 Japanese patients from 1995 to 2000. Primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin was found in 11%, 9% and 0.3% strains, respectively. The proportion with clarithromycin resistance significantly increased from 7% in 1997–98 to 15.2% in 1999–2000 (p = .003). During the same period the metronidazole resistance rate also increased from 6.6% in 1997–98 to 12% in 1999–2000 (p = .02). The prevalence of clarithromycin and metronidazole was related to the annual consumption of these antimicrobial agents. Conclusion. Resistance rates for both clarithromycin and metronidazole appear to reflect the annual consumption of these agents. The high rate of clarithromycin resistance in Japan suggests that the effectiveness of clarithromycin-based therapies may be compromised in the near future. [ABSTRACT FROM AUTHOR]

We have established previously that human thyroid epithelial cells (TEC) from patients with autoimmune thyroiditis are able to synthesize cytokines, such as interleukin-1(IL-1) and interleukin-6(IL-6). This paper examines TEC in sections from autoimmune thyroiditis for the in vivo production of tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) using the combined techniques of in situ hybridization and immunohistochemistry. Thyroid tissue from patients with Graves' disease, Hashimoto's disease and non-toxic goitre was examined and both mRNA and the protein of TNF-α were detected in TEC on frozen sections. Representative figures of only Graves' samples are illustrated in this paper. In contrast, using the same methods, IFN-γ was detected only in the infiltrating cells and not in TEC of thyroid tissue from the patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Job Satisfaction in Nursing: A Concept Analysis Study."

An abstract of the article "A primary study on transvaginal real-time three-dimensional hysterosalpingo-contrast sonography in the assessment of tube patency" by X. Zhang and colleagues is presented.

An abstract of the article "Is the 3D/4D transperineal ultrasound useful in the diagnosis of different types of cystocele" by X. Zhang and colleagues.

An abstract of the research paper "The use of contrast enhanced ultrasound in evaluation the effect of chemotherapy in cervical carcinoma," by X. Zhang and colleagues is presented.

An abstract of the research paper "Transvaginal three-dimensional hysterosalpingo-contrast sonography with Sonovue versus X-ray hysterosalpingography in the evaluation of tubal patency," by X. Zhang and colleagues is presented.

An abstract of the research paper "The Value of Contrast-Enhanced Ultrasound for Differential Diagnosis of Subserous Myoma and Ovarian Fibroma," by X. Zhang and colleagues is presented.

An abstract of the research paper "Comparison of color Doppler ultrasound and pathology in endometrial cancer and endometrial hyperplasia," by D. Zhang and colleagues is presented.

An abstract of the article "Primary study of Doppler ultrasound in screening the congenital cardiac defects between 11+0 and 14+6 weeks' gestation," by M. Qian, Y. Meng, L. Zhai, R. Zheng, and L. Zhang is presented.

An abstract of the article "Effects of the breast ultrasound types for detection of mammary lesion in females," by D. Zhang and colleagues is presented.

An abstract of the conference paper "Prenatal screen the abnormal flexed direction of knee joints using the parallel moving examination," by M. Qian and colleagues is presented.

Background and Aims: The pathological characteristics of lymphocyte infiltration in the hepatic portal tracts of patients with primary biliary cholangitis (PBC) remain unclear. Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues associated with the exacerbation of autoimmune reactions. Here, we evaluate the role of TLSs in PBC and investigate their potential therapeutic value., Methods: We recruited 75 patients with PBC and 53 control patients with liver biopsies who were followed more than 2 years. TLSs and their maturity were identified by the amount and spatial distribution of immune cells. Bulk RNA sequencing of liver was performed in PBC patients with different TLS maturity. The sphingosine-1-phosphate receptor (S1PRs) modulator FTY720 was administered to dnTGFβRII mice to assess the role of TLSs on cholangitis., Results: TLSs presented in 61.3% (46/75) of liver tissues from patients with PBC, including 26 patients with mature TLS (mTLS) and 20 patients with immature TLS (imTLS). The proportion of mTLS was higher in PBC compared with chronic hepatitis B and autoimmune hepatitis. PBC patients with mTLS exhibited the highest serum levels of biochemical indicators, immune globulin and proportions of liver cirrhosis. Gene sets for lymphocyte migration and chemokine signalling pathways were enriched in patients with PBC presenting with TLS. FTY720 inhibited TLS formation and relieved cholangitis and fibrosis in dnTGFβRII mice., Conclusion: TLSs are characteristics of lymphocyte accumulation in the portal tracts of PBC, of which the maturity of TLSs correlates with the inflammation and fibrosis of PBC. Targeting TLSs formation is a potential treatment of PBC., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Previous studies indicated that metabolic heterogeneity of obesity would affect the risk of cardiovascular disease (CVD). However, the alterations in CVD risk associated with transitions between various metabolic health statuses influenced by obesity status remain unclear., Methods: We utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal cohort study involving Chinese residents aged 45 years and older. Baseline data were collected in 2011-2012, with follow-up surveys conducted up to 2020. Participants in the study were categorized into four body mass index-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHOO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUOO). Transitions in these phenotypes over 4 years were analysed. Cox regression models were used to assess the associations of these phenotypes and their transitions with CVD incidence., Results: Among 7721 participants, 1353 (17.5%) developed CVD during the follow-up period. Both overweight/obese and metabolically unhealthy statuses were associated with increased CVD risk. The highest risk was observed in the MUOO group (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.50-2.09, p < 0.0001), followed by the MUNW (HR 1.35, 95% CI: 1.13-1.66, p < 0.001) and MHOO (HR: 1.29, 95% CI: 1.08-1.56, p = 0.002) groups compared to the MHNW group. The deteriorations of obesity and metabolic health status elevated the incidence of CVD, whereas improvements in these statuses reduced the risk of CVD. Additionally, alterations in metabolic health status conferred greater benefits in overweight/obese individuals compared to those with normal weight., Conclusion: The study highlights the importance of maintaining and promoting metabolic health, particularly in overweight/obese individuals, to reduce CVD risk. Metabolic health status plays a more crucial role than obesity status in predicting CVD incidence., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background and Aims: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure., Methods: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes., Results: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 μg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01)., Conclusions: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

T/myeloid mixed phenotype acute leukaemia (MPAL) is a rare aggressive acute leukaemia with poorly understood pathogenesis. Herein, we report two cases of T/myeloid MPAL harbouring BCL11B-associated structural variants that activate TLX3 (TLX3::BCL11B-TLX3-activation) by genome sequencing and transcriptomic analyses. Both patients were young males with extramedullary involvement. Cooperative gene alterations characteristic of T/myeloid MPAL and T-lymphoblastic leukaemia (T-ALL) were detected. Both patients achieved initial remission following lineage-matched ALL-based therapy with one patient requiring a lineage-switched myeloid-based therapy. Our study is the first to demonstrate the clinicopathological and genomic features of TLX3::BCL11B-TLX3-activated T/myeloid MPAL and provide insights into leukaemogenesis., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Aims: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk., Materials and Methods: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death., Results: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity., Conclusions: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: This study aimed to evaluate the safety and efficacy of the fixed-ratio combination (FRC) and free combination of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with type 2 diabetes mellitus (T2DM)., Methods: PubMed, Web of Science, Embase, The Cochrane Library, and four Chinese databases were searched for relevant studies from inception to April 13, 2023. Phase III clinical trials involving FRC or free combination in patients with uncontrolled T2DM were included. A network meta-analysis (NMA) was used to evaluate the effects of FRC and free combination. The Cochrane Collaboration's tool was used to evaluate the risk-of-bias. The primary outcomes were changes in hemoglobin A1c (HbA1c), body weight, and incident hypoglycemia. Secondary outcomes included changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). This study was registered with PROSPERO (CRD42023409585)., Results: Forty-two trials with 23,619 patients were included in the NMA, and treatments were categorized as FRC, free combination and NOINSGLP (neither FRC nor free combination). The forest plots revealed comparable HbA1c control (mean difference (MD) = 0.07%, 95% confidence interval (CI): -0.17 to -0.30) between free combination and FRC. However, there were significant differences in the body weight (MD = -2.06 kg; 95% CI: -3.34 to -0.77), SBP (MD = -1.22 mmHg; 95% CI: -2.41 to -0.04), and DBP (MD = -1.09 mmHg; 95% CI: -1.94 to -0.24) between the two groups., Conclusions: In patients with uncontrolled T2DM, the safety and efficacy of FRC and free combination therapy were comparable. The use of FRC is justifiable in patients requiring free combination., (© 2024 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Recursive partitioning of healthy consortia led to the development of the Clonal Hematopoiesis Risk Score (CHRS) for clonal haematopoiesis (CH); however, in the practical setting, most cases of CH are diagnosed after patients present with cytopenias or related symptoms. To address this real-world population, we characterize the clinical trajectories of 94 patients with CH and distinguish CH harbouring canonical DNMT3A/TET2/ASXL1 mutations alone ('sole DTA') versus all other groups ('non-sole DTA'). TET2, rather than DNMT3A, was the most prevalent mutation in the real-world setting. Sole DTA patients did not progress to myeloid neoplasm (MN) in the absence of acquisition of other mutations. Contrastingly, 14 (20.1%) of 67 non-sole DTA patients progressed to MN. CHRS assessment showed a higher frequency of high-risk CH in non-sole DTA (vs. sole DTA) patients and in progressors (vs. non-progressors). RUNX1 mutation conferred the strongest risk for progression to MN (odds ratio [OR] 10.27, 95% CI 2.00-52.69, p = 0.0053). The mean variant allele frequency across all genes was higher in progressors than in non-progressors (36.9% ± 4.62% vs. 24.1% ± 1.67%, p = 0.0064). This analysis in the post-CHRS era underscores the natural history of CH, providing insight into patterns of progression to MN., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Flubendazole, an FDA-approved anthelmintic, has been predicted to show strong VEGFR2 inhibitory activity in silico screening combined with in vitro experimental validation, and it has shown anti-cancer effects on some human cancer cell lines, but little is known about the anti-angiogenesis effects and anti-prostate cancer effects. In this study, we analyzed the binding modes and kinetic analysis of flubendazole with VEGFR2 and first demonstrated that flubendazole suppressed VEGF-stimulated cell proliferation, wound-healing migration, cell invasion and tube formation of HUVEC cells, and decreased the phosphorylation of extracellular signal-regulated kinase and serine/threonine kinase Akt, which are the downstream proteins of VEGFR2 that are important for cell growth. What's more, our results showed that flubendazole decreased PC-3 cell viability and proliferation ability, and suppressed PC-3 cell wound healing migration and invasion across a Matrigel-coated Transwell membrane in a concentration-dependent manner. The antiproliferative effects of flubendazole were due to induction of G2-M phase cell cycle arrest in PC-3 cells with decreasing expression of the Cyclin D1 and induction of cell apoptosis with the number of apoptotic cells increased after flubendazole treatment. These results indicated that flubendazole could exert anti-angiogenic and anticancer effects by inhibiting cell cycle and inducing cell apoptosis., (© 2024 John Wiley & Sons Ltd.)

Senescent cells (SnCs) are implicated in aging and various age-related pathologies. Targeting SnCs can treat age-related diseases and extend health span. However, precisely tracking and visualizing of SnCs is still challenging, especially in in vivo environments. Here, we developed a near-infrared (NIR) fluorescent probe (XZ1208) that targets β-galactosidase (β-Gal), a well-accepted biomarker for cellular senescence. XZ1208 can be cleaved rapidly by β-Gal and produces a strong fluorescence signal in SnCs. We demonstrated the high specificity and sensitivity of XZ1208 in labeling SnCs in naturally aged, total body irradiated (TBI), and progeroid mouse models. XZ1208 achieved a long-term duration of over 6 days in labeling senescence without causing significant toxicities and accurately detected the senolytic effects of ABT263 on eliminating SnCs. Furthermore, XZ1208 was applied to monitor SnCs accumulated in fibrotic diseases and skin wound healing models. Overall, we developed a tissue-infiltrating NIR probe and demonstrated its excellent performance in labeling SnCs in aging and senescence-associated disease models, indicating great potential for application in aging studies and diagnosis of senescence-associated diseases., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Microglial hyperactivation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome contributes to the pathogenesis of Parkinson's disease (PD). Recently, neuronally expressed NLRP3 was demonstrated to be a Parkin polyubiquitination substrate and a driver of neurodegeneration in PD. However, the role of Parkin in NLRP3 inflammasome activation in microglia remains unclear. Thus, we aimed to investigate whether Parkin regulates NLRP3 in microglia. We investigated the role of Parkin in NLRP3 inflammasome activation through the overexpression of Parkin in BV2 microglial cells and knockout of Parkin in primary microglia after lipopolysaccharide (LPS) treatment. Immunoprecipitation experiments were conducted to quantify the ubiquitination levels of NLRP3 under various conditions and to assess the interaction between Parkin and NLRP3. In vivo experiments were conducted by administering intraperitoneal injections of LPS in wild-type and Parkin knockout mice. The Rotarod test, pole test, and open field test were performed to evaluate motor functions. Immunofluorescence was performed for pathological detection of key proteins. Overexpression of Parkin mediated NLRP3 degradation via K48-linked polyubiquitination in microglia. The loss of Parkin activity in LPS-induced mice resulted in excessive microglial NLRP3 inflammasome assembly, facilitating motor impairment, and dopaminergic neuron loss in the substantia nigra. Accelerating Parkin-induced NLRP3 degradation by administration of a heat shock protein (HSP90) inhibitor reduced the inflammatory response. Parkin regulates microglial NLRP3 inflammasome activation through polyubiquitination and alleviates neurodegeneration in PD. These results suggest that targeting Parkin-mediated microglial NLRP3 inflammasome activity could be a potential therapeutic strategy for PD., (© 2023 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background Vascular calcification (VC), associated with enhanced cardiovascular morbidity and mortality, is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells. Inflammation promotes VC initiation and progression. Interleukin (IL)-29, a newly discovered member of type III interferon, has recently been implicated in the pathogenesis of autoimmune diseases. Here we evaluated the role of IL-29 in the VC process and underlying inflammatory mechanisms. Methods and Results The mRNA expression of IL-29 was significantly increased and positively associated with an increase in BMP2 (bone morphogenetic protein 2) mRNA level in calcified carotid arteries from patients with coronary artery disease or chronic kidney disease. IL-29 and BMP2 proteins are colocalized in human calcified arteries. IL-29 binding to its specific receptor IL-28Rα (IL-28 receptor α) (IL-29/IL-28Rα) inhibited the proliferation of rat vascular smooth muscle cells without altering cell apoptosis or migration. IL-29 promoted the calcification of rat vascular smooth muscle cells and their osteogenic transdifferentiation in vitro as well as the rat aortic ring calcification ex vivo, induced by the calcification medium or osteogenic medium. The procalcification effect of IL-29 was reduced by pharmacological inhibition of IL-29/IL-28Rα binding as well as suppression of janus kinase 2/signal transducer and activator of transcription pathway activation, accompanied by decreased BMP2 expression in the cultured rat vascular smooth muscle cells. Conclusions These results suggest an important role of IL-29 in VC development, at least partly, via activating the janus kinase 2/signal transducer and activator of transcription 3 signaling. Inhibition of IL-29 or its specific receptor, IL-28Rα, may provide a novel strategy to reduce VC in patients with vascular diseases.

Though individual categorization or decision processes have been studied separately in many previous investigations, few studies have investigated how they interact by using a two-stage task of first categorizing and then deciding. To address this issue, we investigated a categorization-decision task in two experiments. In both, participants were shown six faces varying in width, first asked to categorize the faces, and then decide a course of action for each face. Each experiment was designed to include three groups, and for each group, we manipulated the probabilistic contingencies between stimulus, category assignments, and decision consequences. For each group, each participant received three different sequences of category response, category feedback, decision response, and decision feedback. We found that participants were only partially responsive in the appropriate directions to the contingencies assigned to each group. Comparisons of results from different sequences provided evidence for empirical interference effects of categorization on decisions. The empirical interference effect is defined as the difference between the probability of taking a hostile action in decision-alone conditions and the total probability of taking a hostile action in categorization-decision conditions. To test competing accounts for multiple empirical results, including two-stage choice probabilities and empirical interference effects, we compared a quantum cognition model versus a two-stage exemplar categorization model at both aggregate and individual levels. Using a Bayesian information criterion, we found that the quantum model provided an overall better model fit than the exemplar model. Although both models predicted empirical interference effects, the exemplar model was able to generate probabilistic deviation by incorporating category information of the first stage into the feature representation of the subsequent decision stage, while the quantum model produced interference effect by superposition, measurement, and quantum entanglement., (© 2023 The Authors. Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).)