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Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned. We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate. Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes. No other acyltransferase activity was detected when a variety of substrates, including cholesterol, were used as acyl acceptors. The gene was expressed in all tissues examined: during differentiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activity. The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation

The liquid product obtained from biomass pyrolysis is very valuable that it could be used for extraction of chemicals as well as for liquid fuel. The desire goal is to obtain the most bio-oil with desired higher heating value (HHV), high physicochemical stability. The yields and chemical composition of products from biomass pyrolysis are closely related to the feedstock, pyrolysis parameters and catalysts. Current researches mainly concentrated on the co-pyrolysis of different biomass and introduce of novel catalysts as well as the combined effect of catalysts and pyrolysis parameters. This review starts with the chemical composition of biomass and the fundamental parameters and focuses on the influence of catalysts on bio-oil. What is more, the pyrolysis facilities at commercial scales were also involved. The classic researches and the current literature about the yield and composition of products (mainly liquid products) are summarized.

Decorating single atoms of transition metals on MXenes to enhance the electrocatalytic properties of the resulting composites is a useful strategy for developing efficient electrocatalysts, and the mechanisms behind this enhancement are under intense scrutiny. Herein, we anchored Co single atoms onto several commonly used MXene substrates (V2CTx, Nb2CTx and Ti3C2Tx) and systematically studied the electrocatalytic behavior and the mechanisms of oxygen and hydrogen evolution reactions (OER and HER, respectively) of the resulting composites. Co@V2CTx composite displays an OER overpotential of 242 mV and an HER overpotential of 35 mV at 10 mA cm−2 in 1.0 M KOH electrolyte, which is much lower than for Co@Nb2CTx and Co@Ti3C2Tx, making it comparable to the commercial noble metal Pt/C and RuO2/C electrocatalysts. The experimental and theoretical results point out that the enhanced bifunctional catalytic performance of Co@V2CTx benefits from the stronger hybridization between Co 3d and surface terminated O 2p orbitals which optimized the electronic structure of Co single atoms in the composite. This, in turn, results in lowering the OER and HER energy barriers and acceleration of the catalytic kinetics in case of the Co@V2CTx composite. The advantage of Co@V2CTx was further validated by its high overall water splitting performance (1.60 V to deliver 10 mA cm−2). Our study sheds light on the origins of the catalytic activity of single transition metals atoms on MXene substrates, and provides guidelines for designing efficient bifunctional MXene‐based electrocatalysts. Co single atoms were anchored on three different MXenes substrates, namely Co@V2CTx, Co@Nb2CTx and Co@Ti3C22Tx, which were tested as electrocatalysts of oxygen and hydrogen evolution reactions (OER and HER). Combinations of experimental and theoretical studies point out that the enhanced bifunctional catalytic performance of Co@V2CTx benefits from the higher electron transfer, which results in lowering the energy barriers and accelerating the catalytic kinetics for both OER and HER.

Background:The pathological feature of rheumatoid arthritis (RA) is chronic synovitis leading to joint destruction. Fibroblast - like synoviocytes (FLS) are crucial drivers of chronicity inflammation in RA synovitis. Previous studies showed the aggressive behaviors of RA-FLS are associated with abnormal glucose metabolism. However, whether cholesterol metabolic reprogramming attributes to the cellular activation and pro-inflammatory processes of RA-FLS remains unknow. Niemann-Pick proteins type C2 (NPC2) is a key regulator requiring for cholesterol trafficking from lysosome to other intracellular compartments. Newly evidences reported NPC2 is associated with liver fibrosis and hepatoma. But there is no report on the expression and regulatory role of NPC2 in RA-FLS.Objectives:To investigate the expression and clinical significance of NPC2 in RA synovium and its roles on RA-FLS activity and underlying mechanism.Methods:(1)RA patients were recruited from a real-world prospective cohort who treated according to the “treat-to-target” strategy and completed at least one-year follow up. Clinical data were collected at baseline and visited at 1, 3, 6, 9 and 12 months. Disease activity was assessed by CDAI and the therapeutic target was defined as remission (CDAI≤2.8). Physical function was assessed by HAQ-DI.(2)Synovial biopsies were conducted on swollen knee joints of RA patients to obtain synovium at baseline. Synovium obtained from patients with osteoarthritis (OA) and orthopaedic arthropathies (Orth.A) were choose as control. The expression of NPC2 in synovial tissues were detected by immunohistochemistry (IHC) staining with semi-quantitative scoring. Cellular localization of synovial NPC2 was determined by multiplex immunofluorescence staining.(3)In vitro model of NPC2 knockdown on primary RA-FLS was developed. Inflammatory cytokines in supernatants were detected by ELISA. For the measurement of cholesterol metabolic reprogramming, downstream genes of NPC2 were analyzed by RNA sequencing and verified by qRT-PCR. Lysosomes in RA-FLS was detected by cellular immunofluorescence staining of LAMP1 and free cholesterol level was detected by Filipin III staining.Results:(1)Positive cytoplasmic expression of NPC2 were found in both lining layer and sublining areas of synovium, and the expression of synovial NPC2 in RA patients (n=23) was significantly higher than that in OA (n=16) and Orth.A patients (n=15, Figure 1A). According to the IHC score of synovial NPC2 at baseline, RA patients were divided into high synovial NPC2 (n=12) and low synovial NPC2 (n=11) groups. RA patients in high synovial NPC2 group had significantly higher disease activity and worse physical function from 6 to 12 months, accompanied with significantly lower remission rates from 3 to 12 months.(2)Multiplex immunofluorescence staining showed that NPC2 was predominantly expressed in FAPα+ FLS in RA synovium (Figure 1B). Western Blot showed higher NPC2 expression was also found in primary RA-FLS than those in Orth.A-FLS. NPC2 knockdown in RA-FLS significantly reduced the levels of TNF-α and IL-1β in the culture supernatant, suggesting NPC2 could promote inflammatory cytokines secretion of RA-FLS.(3)After NPC2 knockdown, RNA sequencing showed abnormalities of cholesterol biosynthesis in RA-FLS. Transcription of endogenous cholesterol biosynthesis (HMGCR, SREBP2, and SQLE), exogenous uptake (LDLR), exocytosis (ABAC1), and esterification (ACAT1) were increased, while its level in cholesterol oxidative (CYP27A1, CYP46A1, CYP39A1) was decreased in RA-FLS. Cholesterol was found to accumulate in the lysosomes of RA-FLS, implying NPC2 mediates cholesterol metabolic reprogramming in RA-FLS.Conclusion:NPC2 could drive proinflammatory properties of RA-FLS through mediating cholesterol metabolic reprogramming, which provides a new strategy of restoring cholesterol metabolic dysregulation by targeting NPC2 for RA treatment.REFERENCES: NIL.Acknowledgements:This work was supported by the National Natural Science Foundation of China (82171780, 81971527 and 82101892), Basic and Applied Basic Research Foundation of Guangdong province (2022A1515010524 and 2020A1515110061).Disclosure of Interests:None declared.

Objective Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. Design Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. Results Age range for CRC screening is defined as 50–75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. Conclusions Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

Background:Rheumatoid arthritis (RA) is characterized with joint damage and physical dysfunction, leading to reducing quality of life. The causes of physical dysfunction in RA are multifactorial, including disease activity, joint pain, and joint deformity. Recent studies have reported that baseline sarcopenia is associated with long-term physical activity restriction in general population. Our previous cross-sectional and one-year follow-up study showed that low muscle mass is common in Chinese patients with RA and is associated with poor physical function. Surprisingly, the muscle mass only increased slightly across 1-year follow-up. There were no other published studies with longer prospective follow-up about the dynamic change of muscle mass in RA patients.Objectives:To investigate the trajectory of muscle mass over 5-year follow-up and its impact on longitudinal changes of physical function in RA patients.Methods:Our real-world prospective RA cohort recruited patients from September, 2015 which conducted at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, China. Those who finished at-least 5 years followed up were eligible in this study. Clinical data, including RA disease activity (DAS28-ESR, DAS28-ESR, SDAI and CDAI) and physical function indicator (HAQ-DI), were collected at baseline and visits at 3, 6, 12, 24, 36, 48 and 60 months. Physical dysfunction was indicated as HAQ-DI > 0.Body composition was assessed by bioelectric impedance analysis annually, including percentage of body fat mass (PBF) and appendicular skeletal muscle mass index (ASMI). Myopenia was defined by ASMI≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women, while overfat was defined by the PBF ≥ 25% in men and ≥ 35% in women, respectively.The transitions of muscle and fat status across 5-year follow-up were displayed alluvial plot and transition probabilities were estimated through continuous-time multistage Markov modelling. Generalized estimating equation (GEE) analysis was performed to evaluate the longitudinal relations between time-varying ASMI/PBF and HAQ-DI.Results:①A total of 288 RA patients were enrolled. RA patients had a mean age of 49.4±11.2 years, and 245 (85.1%) were females. The median RA disease duration was 52 (IQR 24-108) months. ②There were 229 (79.5%) RA patients with active disease (CDAI > 2.8) at baseline. Under treat-to-target strategy, RA disease activity improved significantly with CDAI remission rates 37.3% at 3 months, 40.7% at 6 months, and remained 37.0%-39.4% in the subsequent 5-year follow-up (Figure 1A). Meanwhile, the physical function improved significantly with the rate of physical dysfunction decreased from 62.3% at baseline to 42.7% at 3 months, 41.8% at 6 months, and remained 38.8%-43.9% in the subsequent follow-up (Figure 1B). ③At baseline, there were 38.2% patients with myopenia. Surprisingly, there were no significant change of ASMI, PBF, BMI or the rate of myopenia over time (Figure 1C-F). ④In the longitudinal analysis using GEE, ASMI was negatively associated with HAQ-DI over time [model 1: OR = 0.931, 95% CI (0.887-0.978), P = 0.004]. After adjusting for gender, age, active smoking, disease duration, RF status, ACPA status, comorbidities, and previous treatments, ASMI was still negatively associated with HAQ-DI [model 2: OR = 0.928, 95% CI (0.885-0.972), P = 0.002] and remained significant for further adjusting for time-varying CDAI [model 3: OR = 0.959, 95% CI (0.926-0.993), P = 0.017, Table 1].Conclusion:Our study first illustrates muscle mass remains stable over 5-year follow-up in RA patients, though disease activity and physical function have been significantly improved. Low muscle mass is associated with worse physical function over time in RA. The results imply the importance to improve muscle mass in RA.Figure 1Longitudinal changes of the remission rate of RA disease activity, HAQ-DI and body compositionBMI, body mass index; PBF, percentage of body fat mass; ASMI, appendicular skeletal muscle mass indexREFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

A photoinduced method for converting large quantities of silver nanospheres into triangular nanoprisms is reported. The photo-process has been characterized by time-dependent ultraviolet-visible spectroscopy and transmission electron microscopy, allowing for the observation of several key intermediates in and characteristics of the conversion process. This light-driven process results in a colloid with distinctive optical properties that directly relate to the nanoprism shape of the particles. Theoretical calculations coupled with experimental observations allow for the assignment of the nanoprism plasmon bands and for the first identification of two distinct quadrupole plasmon resonances for a nanoparticle. Unlike the spherical particles they are derived from that Rayleigh light-scatter in the blue, these nanoprisms exhibit scattering in the red, which could be useful in developing multicolor diagnostic labels on the basis not only of nanoparticle composition and size but also of shape.

Background:Rheumatoid arthritis (RA) is a female predominant autoimmune disease. The peak incidence coincides with menopause years in female RA. However, the exact interval between the age of RA onset and menopause was unclear in RA. Early menopause (EM, menopause age ≤ 45 years) was associated with almost 2.4-fold risk of subsequent development of RA. Since symptoms of somatoform autonomic dysfunction arose from menopause transition, post-menopause especially EM might exert a negative impact on disease characteristics especially patient-reported outcomes (PROs) of RA. However, published data were controversial.Objectives:This study aims to illustrate the distribution of time interval between age of RA onset and menopause and assess the differences of disease characteristics especially PROs between RA patients with natural EM and usual menopause (UM, menopause age > 45 years).Methods:This cross-sectional study included post-menopausal RA patients from an observational RA cohort which conducted at the Department of Rheumatology and Immunology, Sun Yat-Sen memorial Hospital, Guangdong, China between January, 2015 and October, 2023. RA patients were divided into EM and UM groups. PROs were assessed, including patient global assessment of disease activity (PtGA), pain visual analogue scale (VAS) and Stanford health assessment questionnaire disability index (HAQ-DI). PROs-associated indicators included 28-joint tender joint count (TJC28) and provider global assessment of disease activity (PrGA). The interval time (years) from RA onset to menopause was calculated by age of menopause minus age of RA onset. Patients with first arthritis symptom occurred at 1 year after natural menopause were categorized into patients with RA onset after menopause, otherwise, those were categorized into patients with RA onset before menopause.Results:① Among 557 post-menopausal patients enrolled, their peak RA-onset age was 51-55 years, while the peak menopause age was 46-50 years. Their mean age of menopause was 49.0 ± 4.2 years, while the peak age of menopause was 46-50 years. Both the age of RA onset and menopause showed unimodal distribution. The incidence peak of RA was 5 years after menopause (Figure 1A and B). ②There were 98 (17.6%) EM patients. Compared with UM patients, RA patients with EM had worse PROs and PROs-associated indicators, higher C reactive protein and CDAI (all P < 0.05, Table 1), but not radiographic indicators (all P > 0.05). ③ Among patients with RA onset after menopause, EM patients (18.0%) were characterized with higher TJC28, PrGA, PtGA, HAQ-DI and higher CDAI than those with UM (all P < 0.05), but not inflammatory and radiographic indicators (all P > 0.05). ④Among patients with RA onset before menopause, there were no differences of PROs and PROs-associated indicators, functional or radiographic indicators between patients with EM and UM.Conclusion:Our results supported that the peak years of RA onset in women coincided with the menopausal transition, which was demonstrated after 5 years of natural menopause. RA patients with EM especially in those with postmenopausal-onset RA had worse PROs, but neither inflammation nor radiographic damage. Therefore, improvement of self-management and psychosocial supports based on the well-control of RA disease activity would be more important and beneficial for EM patients with RA.Figure 1.The distribution of RA onset age and menopause age in post-menopausal RA patients. (A) The distribution of RA onset age and menopause age in post-menopausal women with RA; (B) The distribution of time interval between the age of RA onset and menopauseREFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Cardiovascular disease (CVD) is the major cause of mortality among patients with rheumatoid arthritis (RA). Several studies have shown associations between elevated remnant cholesterol (RC) levels and increased risk of CVD in various general populations. However, no study reported the relationship between RC levels and the risk of incident CVD in RA patients.Objectives:To examine if the fasting levels of serum RC were prospectively associated with incident CVD risk in RA patients free of CVD at baseline.Methods:A prospective RA cardiovascular cohort was developed through the inclusion of consecutively enrolled RA patients free of CVD at baseline between January 1, 2001 and June 30, 2022 at the Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Guangdong, China. Fasting serum levels of triglycerides, total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured, while RC and Non-HDL-C levels were calculated. The primary exposure was RC levels. The primary outcome of this study was a composite of incident CVD, consisting of coronary heart disease, heart failure, stroke, peripheral artery disease and CVD-death. A LASSO Cox model was used to select covariates. The Fine-Gray competing risk model was used to estimate hazard ratios (HRs).Results:A total of 1,018 RA patients free of pre-existing CVD at baseline were enrolled. RA patients had a mean age of 53.9 years, and 802 (78.8%) were females. The median RA disease duration was 25 months. The median RC levels in RA patients were 0.50 (0.34, 0.69) mmol/L. RC was significantly positively correlated with disease characteristics indicators in RA patients, including RA disease duration, ESR, CRP, CDAI, HAQ-DI, and mTSS (P < 0.05 for all). By contrast, TG, TC, HDL-C, and LDL-C were statistically significantly negatively correlated with disease activity indicators, including ESR, CRP, CDAI, and HAQ-DI (P < 0.05 for all, Figure 1). After a median follow-up of 5.54 years, 131 patients developed CVD with an incidence rate of 21.6 per 1,000 person-years. Continuous and quartile-categorized RC levels were associated with incident CVD before and after multivariate adjustment and Bonferroni correction (all P < 0.001). There were no robust associations of other lipids with incident CVD. The fully adjusted HRs for RC were 2.30 (95% CI 1.58-3.35) per 1 mmol/L increase, and 2.40 (1.36-4.25) and 2.81 (1.60-4.94) for patients in the 3rd and 4th versus the 1st quartile, respectively (Figure 2).Conclusion:Circulating RC levels are positively associated with incident CVD among RA patients independent of known risk factors, implying its clinically preferable use for improving the stratification of CVD risk in RA patients.Figure 1.Correlation between baseline lipid fractions and disease characteristics among RA patients in the RA CVD cohortSpearman’s rank correlation coefficients were estimated. * P < 0.05; ** P < 0.01.Figure 2.Hazard ratios for incident CVD by quartiles of baseline fasting lipid fractions in RA patients in the RA CVD cohort.* HRs were estimated from the Fine-Gray proportional subdistribution hazards model to account for the competing risk of CVD. Model 1 adjusted for age, gender (male or female), hypertension (yes or no), type 2 diabetes mellitus (yes or no), chronic kidney disease (yes or no), C-reactive protein, clinical disease activity index, modified total Sharp score, and the use of previous medications (including glucocorticoid [yes or no], conventional synthetic disease modifying anti-rheumatic drugs [yes or no], antihypertensives [yes or no]). Model 2 additionally controlled for enrollment year interval (2001~2005, 2006~2010; 2011~2015, 2016~2020, and 2021~2022). The lowest quartile group was the reference.# Bonferroni corrected statistical significance (P < 0.0083) for multiple testing correction.REFERENCES:NIL.Acknowledgements:We thank all subjects and medical staff who generously contributed to this study.Disclosure of Interests:None declared.

Background:The use of tofacitinib, a Janus kinase inhibitor (JAKi) targeting JAK1 and JAK3, was associated with increased cardiovascular risks in the Oral Rheumatoid Arthritis Trial surveillance but not in several observational studies or meta-analysis research. Thus, it was still unclear if all JAKi lead to high cardiovascular risks. A different method to investigate the effect of JAKi on cardiovascular disease (CVD) is needed as it could provide additional and robust evidence.Objectives:Two-sample drug target cis-MR analysis was used to test if JAKi targets proxied with cis-expression quantitative trait loci (eQTLs) was causally associated with CVD, including stroke and coronary artery disease (CAD).Methods:Instrument variables proxy JAKi targets exposure was identified from cis-expression quantitative trait loci (cis-eQTLs) within or near JAK1, JAK2, JAK3, and TYK2 inferred from the 31,684 blood samples-based gene expression data in the eQTLGen Consortium. Genome-wide association studies for stroke and CAD from 461,880 and 463,010 UK Biobank participants were used. SMR and IVW were the primary two-sample MR methods for causal association testing. The robustness and sensitivity of primary analysis findings were assessed using MR-Egger, weighted median, weighted mode, and robust adjusted profile score models.Results:A total of 8, 38, 6 and 53 SNPs within or near JAK1, JAK2, JAK3, and TYK2 were selected for stroke and 8, 31, 6, and 32 SNPs for CAD, respectively. A high expression level of JAK2 inhibitor target was associated with a decreased stroke risk in SMR (OR = 0.997, 95% CI 0.994-0.999, P = 0.041) and IVW (OR = 0.997, 95% CI 0.996-0.998, P < 0.001). Similar results were confirmed in the analyses with the other MR methods. A high expression level of JAK2 inhibitor target was significantly associated with a low CAD risk (OR = 0.998, 95% CI 0.998-0.999, P = 0.001) in the IVW but not SMR analysis. There was no association of the targets of JAK1, JAK3, or TYK2 inhibitors with stroke or CAD risk (Figure 1). The significant associations derived from IVW were not driven by individual SNPs. There was no significant horizontal pleiotropy for the association (Table 1).Conclusion:This study demonstrated a genetic causal association between JAK2 expression levels inhibition and the increased risk of stroke and probably CAD, supporting the need to issue a warning about the increased risk of cardiovascular events associated with JAKi particularly when using JAK2 inhibitor-related medications in clinical practice.Funding:This work was supported by the National Natural Science Foundation of China (82171780, 81971527 and 82101892), Guangzhou Municipal Science and Technology Project (202102010188 and 2023A03J0709), Basic and Applied Basic Research Foundation of Guangdong province (2022A1515010524, 2020A1515110061 and 2019A1515011928), and the Fundamental Research Funds for the Central Universities, Sun Yat-Sen University (22qntd3303).REFERENCES: NIL.Figure 1.Forest plot of MR estimates of genetic risk of JAK expression levels in blood on stroke and CADTable 1. Information about sensitivity analysis of Mendelian randomizationAcknowledgements:We thank all subjects and medical staff who generously contributed to this study.Disclosure of Interests:None declared.