Comparison of long-term radial artery occlusion via distal vs. conventional transradial access (CONDITION): a randomized controlled trial.

BACKGROUND: The distal transradial access (dTRA) has become an attractive and alternative access to the conventional transradial access (TRA) for cardiovascular interventional diagnosis and/or treatment. There was a lack of randomized clinical trials to evaluate the effect of the dTRA on the long-term radial artery occlusion (RAO). METHODS: This was a prospective, randomized controlled study. The primary endpoint was the incidence of long-term RAO at 3 months after discharge. The secondary endpoints included the successful puncture rate, puncture time, and other access-related complications. RESULTS: The incidence of long-term RAO was 0.8% (3/361) for dTRA and 3.3% (12/365) for TRA (risk ratio = 0.25, 95% confidence interval = 0.07-0.88, P = 0.02). The incidence of RAO at 24 h was significantly lower in the dTRA group than in the TRA group (2.5% vs. 6.7%, P < 0.01). The puncture success rate (96.0% vs. 98.5%, P = 0.03) and single puncture attempt (70.9% vs. 83.9%, P < 0.01) were significantly lower in the dTRA group than in the TRA group. However, the number of puncture attempts and puncture time were higher in the dTRA group. The dTRA group had a lower incidence of bleeding than the TRA group (1.5% vs. 6.0%, P < 0.01). There was no difference in the success rate of the procedure, total fluoroscopy time, or incidence of other access-related complications between the two groups. In the per-protocol analysis, the incidence of mEASY type ≥ II haematoma was significantly lower in the dTRA group, which was consistent with that in the as-treated analysis. CONCLUSIONS: The dTRA significantly reduced the incidence of long-term RAO, bleeding or haematoma. TRIAL REGISTRATION: ClinicalTrials.gov identifer: NCT05253820.

Incidence of Distal Radial Artery Occlusion and its Influencing Factors After Cardiovascular Intervention Via the Distal Transradial Access.

INTRODUCTION: One of the important advantages of the distal transradial access (dTRA) is the significant reduction in the incidence of radial artery occlusion (RAO). There are few reports on the influencing factors for distal radial artery occlusion (dRAO) after cardiovascular interventions via the dTRA. METHODS: This retrospective analysis included the clinical data of patients who underwent a cardiovascular intervention via the dTRA. The dRAO was evaluated by ultrasound within 24 hours after the procedure. Multivariate logistic analysis was used to explore the influencing factors for dRAO. RESULTS: The incidence of dRAO was 3.5% (28/805) at 24 hours follow-up after the procedure. In the comparison between the 2 groups, the preoperative distal radial artery (DRA) internal diameter in the dRAO group was significantly smaller than that in the non-dRAO group (p=0.001). The prevalence of DRA inner diameter/sheath outer diameter <1 was significantly higher in the dRAO group than in the non-dRAO group (p=0.013). The number of puncture attempts was significantly greater in the dRAO group than in the non-dRAO group (p=0.007). Multivariate logistic analysis showed that DRA inner diameter/sheath outer diameter <1 was an independent risk factor for dRAO (OR=4.827, 95% CI=1.087-21.441, p=0.039). CONCLUSIONS: The incidence of dRAO 24 hours after cardiovascular intervention via the dTRA was 3.5%, and a DRA inner diameter/sheath outer diameter <1 was an independent risk factor for dRAO. Preoperative ultrasound assessment of vessel inner diameter and selection of a sheath with a smaller outer diameter may reduce the risk of dRAO. CLINICAL IMPACT: The incidence of distal radial artery occlusion after cardiovascular intervention was 3.5%. The distal radial artery inner diameter/sheath outer diameter <1 was an independent risk factor for distal radial artery occlusion. Preoperative ultrasound assessment of vessel inner diameter and selection of a sheath with a smaller outer diameter may reduce the risk of distal radial artery occlusion. The number of puncture attempts and compression time were not related to distal radial artery occlusion.

Endophytic fungus Pseudodidymocyrtis lobariellae KL27 promotes taxol biosynthesis and accumulation in Taxus chinensis.

BACKGROUND: Taxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants. RESULTS: Here, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs. CONCLUSIONS: Our results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.

Identification of DNA methylation-regulated differentially expressed genes in RA by integrated analysis of DNA methylation and RNA-Seq data.

OBJECTIVE: To identify novel DNA methylation-regulated differentially expressed genes (MeDEGs) in RA by integrated analysis of DNA methylation and RNA-Seq data. METHODS: The transcription and DNA methylation profiles of 9 RA and 15 OA synovial tissue were generated by RNA-Seq and Illumina 850K DNA methylation BeadChip. Gene set enrichment analysis (GSEA) and Weighted gene co-expression network analysis (WGCNA) were used to analyze methylation-regulated expressed genes by R software. The differentially expressed genes (DEGs), differentially methylated probes (DMPs), differentially methylated genes (DMGs) were analyzed by DESeq and ChAMP R package. The functional correlation of MeDEGs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction (PPI) network of MeDEGs was constructed by STRING and Reactome FI Cytoscape Plugin. Correlation analysis between methylation level and mRNA expression was conducted with R software. RESULTS: A total of 17,736 genes, 25,578 methylated genes and 755,852 methylation probes were detected. A total of 16,421 methylation-regulated expressed genes were obtained. The GSEA showed that these genes are associated with activation of immune response, adaptive immune response, Inflammatory response in C5 (ontology gene sets). For KEGG analysis, these genes are associated with rheumatoid arthritis, NF-kappa B signaling pathway, T cell receptor signaling pathway. The WGCNA showed that the turquoise module exhibited the strongest correlation with RA (R = 0.78, P = 1.27 × 10- 05), 660 genes were screened in the turquoise module. A total of 707 MeDEGs were obtained. GO analysis showed that MeDEGs were enriched in signal transduction, cell adhesion for BP, enriched in plasma membrane, integral component of membrane for CC, and enriched in identical protein binding, calcium ion binding for MF. The KEGG pathway analysis showed that the MeDEGs were enriched in calcium signaling pathway, T cell receptor signaling pathway, NF-kappa B signaling pathway, Rheumatoid arthritis. The PPI network containing 706 nodes and 882 edges, and the enrichment p value < 1.0 × 10- 16. With Cytoscape, based on the range of more than 10 genes, a total of 8 modules were screened out. Spearman correlation analysis showed RGS1(cg10718027), RGS1(cg02586212), RGS1(cg10861751) were significantly correlated with RA. CONCLUSIONS: RGS1 can be used as novel methylated biomarkers for RA.

Loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome.

BACKGROUND: Periprocedural myocardial infarction is a common complication following percutaneous coronary intervention. The present study was conducted with an aim to compare the safety and efficacy of loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome undergoing elective percutaneous coronary intervention. METHODS: A total of 114 patients with acute coronary syndrome undergoing elective percutaneous coronary intervention were assigned to clopidogrel group (n = 57, the loading and maintenance doses were 300 and 75 mg qd for clopidogrel, and 300 and 100 mg qd for aspirin), or ticagrelor group (n = 57, the loading and maintenance doses were 180 and 90 mg bid for ticagrelor, and 300 and 100 mg qd for aspirin). Cardiac biomarkers were measured before, 8 hours, and 24 hours after percutaneous coronary intervention. The percutaneous coronary intervention-related periprocedural myocardial infarction was defined according to the fourth universal definition of myocardial infarction (2018). RESULTS: The overall incidence of percutaneous coronary intervention-related periprocedural myocardial infarction was 21.1%. The ticagrelor group showed a significantly lower incidence of periprocedural myocardial infarction (12.3% vs 29.8%, p = 0.022) and numerically lower bleeding events (3.5% vs 8.8%, p = 0.242) as compared with clopidogrel group. No patient had major adverse cardiovascular events during the 1-month follow-up. The levels of high-sensitivity C-reactive protein did not differ significantly between the two groups (p > 0.05), indicating that the benefits of ticagrelor were not from its anti-inflammatory effects. Multivariable analysis showed that the use of ticagrelor (odds ratio: 0.50; 95% confidence interval: 0.29-0.87; p = 0.014) and number of stents (odds ratio: 2.75; 95% confidence interval: 1.25-6.06; p = 0.012) were independent predictors of periprocedural myocardial infarction. CONCLUSION: Pretreatment with a loading dose of ticagrelor seems to be superior in reducing the incidence of percutaneous coronary intervention-related periprocedural myocardial infarction in Asian patients with acute coronary syndrome as compared with clopidogrel.

[Research progress on in vitro and in vivo behaviors of poorly soluble Chinese materia medica nanosuspension].

Nanosuspension (also called nanocrystal suspension or nanocrystal) could significantly enhance the saturated solubility and dissolution of insoluble drugs, and improve their bioavailability by reducing particle size and increasing the specific surface, which could then solve the delivery problems of the poorly soluble active ingredients and effective parts of Chinese materia medica (CMM). Based on the brief summaries of nanosuspension preparation methods, this paper would mainly review the in vitro and in vivo behaviors of poorly soluble CMM nanosuspension, discuss and analyze its problems, so as to provide reference and thinking for the further study of nanosuspension drug delivery system of poorly soluble CMM and promote the development and perfection of nanosuspension technology in CMM.

Low-dose adjunctive cilostazol in patients with complex lesions undergoing percutaneous coronary intervention.

Patients with complex coronary lesions undergoing percutaneous coronary intervention (PCI) have more major adverse cardiac events (MACE) than do those with simpler cases. Therefore, intensive antiplatelet therapy might be needed in these patients. A total of 127 patients with complex lesions undergoing PCI in the Second Hospital of Tianjin Medical University from October 2012 to April 2014 were randomized to receive either dual (aspirin plus clopidogrel, DAPT, n = 66), or triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol; TAPT, n = 61). Patients in the TAPT group received low-dose cilostazol (100 mg loading, followed with 50 mg twice per day) for 3-6 months. The primary endpoint was composite MACE. The complex coronary target lesions were defined as at least one of the following: left main disease; severe 3-vessel disease; chronic total occlusion lesions; true bifurcation lesion; ostial lesions; severe calcified lesions; and highly thrombotic lesions. The two groups had similar baseline clinical and angiographic characteristics. One-year clinical outcomes showed that the TAPT group had significantly lower incidences of myocardial infarction (1.6% vs 13.6%, P = 0.018) and MACE (1.6% vs 16.7%, P = 0.004) than DAPT group. The DAPT group had two cases of stent thrombosis, while the TAPT group did not. Furthermore, adjunctive low-dose cilostazol didn't significantly increase the incidence of bleeding events (26.2% vs 19.7%, P = 0.381) regardless of major (4.9% vs 4.5%, P = 0.921) or minor (21.3% vs 15.2%, P = 0.368) bleeding events. In conclusion, low-dose adjunctive cilostazol seems superior to dual antiplatelet therapy in reducing recurrent ischemic events in patients with complex coronary lesions and the two test groups have a similar incidence of bleeding events.

[Whole-genome sequencing and analysis of a adrostenedione yielding strains Mycobacterium neoaurum MN4].

Objective: Mycobaterium neoaurum MN4 is a substrate-resistant mutant strain with high-yield androstenedione. In order to further study MN4 strain substrate-resistant mechanism and androstenedione biosynthetic pathway, it is necessary to decipher the MN4 strain genome. Methods: The genome was sequenced using highthroughput sequencing technology, and analyzed using relevant software for genome assembly, gene prediction and functional annotation, COG cluster analysis and secondary metabolite biosynthesis gene clusters prediction. Results: The whole genome is assembled into 33 contigs, and the genome size is 5.39 Mb, GC content of 66.9% with encoding 4920 protein genes. The genome sequence was deposited in the GenBank database under the accession number JXYZ00000000. Conclusion: This study is the first report of androstenedione producing strain Mycobacterium neoaurum MN4 genome sequence, and provides a theoretical basis for further heterologous expression of secondary metabolites on Mycobacterium neoaurum MN4.

Comparison of long-term prognoses of percutaneous coronary intervention via distal transradial and conventional transradial access for acute coronary syndrome.

BACKGROUND: Distal transradial access (dTRA) has recently emerged as a new vascular access alternative for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). However, published data on long-term mortality and major adverse cardiac events after PCI via dTRA are inconclusive. The aim of this study was to compare the long-term prognoses of PCI via dTRA and conventional transradial access (cTRA) for acute coronary syndrome (ACS) after 1-3 years of follow-up. METHODS: Patients who were diagnosed with ACS and underwent PCI between January 1, 2020 and December 31, 2021, were retrospectively enrolled. The patients were divided into two groups at a 1:1 ratio, subjected to propensity score matching (PSM), and then followed for 1-3 years after PCI. Cox proportional hazards regression was used to evaluate the relationship between the two access sites and clinical outcomes. RESULTS: Among the 550 patients in the dTRA and cTRA groups, 11 (4.0%) and 19 (6.9%) died during the observation period, respectively. dTRA and cTRA had similar risks of all-cause mortality [hazard ratio (HR) = 0.688; 95% CI = 0.323-1.463; P = 0.331] and major adverse cardiac events (MACEs, HR = 0.806, 95% CI = 0.515-1.263; P = 0.347) after PCI. The risk of cardiovascular mortality (HR = 0.330, 95% CI = 0.107-1.105; P = 0.053), TLR-MACEs (HR = 0.587, 95% CI = 0.339-1.109; P = 0.058), and unplanned revascularization (HR = 0.860, 95% CI = 0.483-1.529; P = 0.606) were not significantly different between the two groups. CONCLUSIONS: PCI via dTRA has the same long-term prognoses as PCI via cTRA in ACS patients, and the compression time and bleeding rate are lower than those in patients undergoing PCI via cTRA.

Modulating the pH profile of vanillin dehydrogenase enzyme from extremophile Bacillus ligniniphilus L1 through computational guided site-directed mutagenesis.

Vanillin dehydrogenase (VDH) has recently come forward as an important enzyme for the commercial production of vanillic acid from vanillin in a one-step enzymatic process. However, VDH with high alkaline tolerance and efficiency is desirable to meet the biorefinery requirements. In this study, computationally guided site-directed mutagenesis was performed by increasing the positive and negative charges on the surface and near the active site of the VDH from the alkaliphilic marine bacterium Bacillus ligniniphilus L1, respectively. In total, 20 residues including 15 from surface amino acids and 5 near active sites were selected based on computational analysis and were subjected to site-directed mutations. The optimum pH of the two screened mutants including I132R, and T235E from surface residue and near active site mutant was shifted to 9, and 8.6, with a 2.82- and 2.95-fold increase in their activity compared to wild enzyme at pH 9, respectively. A double mutant containing both these mutations i.e., I132R/T235E was produced which showed a shift in optimum pH of VDH from 7.4 to 9, with an increase of 74.91 % in enzyme activity. Therefore, the double mutant of VDH from the L1 strain (I132R/T235E) produced in this study represents a potential candidate for industrial applications.

Analysis of the diameter of the distal radial artery at anatomic snuffbox by ultrasonography in patients scheduled for coronary intervention.

BACKGROUND: Assessing the size of the distal radial artery (DRA) in anatomic snuffbox (AS) before coronary intervention is extremely important in the selection of suitable patients, improving the success rate of puncture and reducing the complications. OBJECTIVE: To evaluate the diameter of the DRA in AS and its influencing factors in Chinese patients scheduled for coronary intervention. METHODS: Ultrasound was used to detect the inner diameter of vessels. A total of 1182 patients were involved in the study. RESULTS: In all patients, the mean inner diameters of the DRA, conventional radial artery (CRA) and ulnar artery (UA) were 2.00 ± 0.43 mm, 2.38 ± 0.51 mm and 1.99 ± 0.47 mm, respectively. The proportion of DRA diameter ⩾2.0 mm was 53% (in all patients), 64% (in males), 36% (in females), respectively. The DRA/CRA ratios were 0.85 ± 0.13 in all patients, 0.86 ± 0.13 in males and 0.84 ± 0.13 in females. The diameter of the DRA was strongly positively correlated with the diameter of the CRA (r = 0.750, p < 0.05), and weakly correlated with the body mass index (r = 0.303, p < 0.05) and the diameter of the UA (r = 0.304, p < 0.05). Multivariate regression analysis showed that female sex, age ⩾60 years, body mass index <24 kg/m2, previous CRA/DRA access and history of coronary artery disease were independent predictors of the DRA diameter <2.0 mm. CONCLUSION: Measurement of the diameter of the DRA by ultrasonography may offer important information prior to coronary catheterization.

Identification of clinical characteristics biomarkers for rheumatoid arthritis through targeted DNA methylation sequencing.

OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. METHODS: The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient. RESULTS: The study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64-0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63-0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61-0.96, a balanced accuracy range of 0.46-0.94, and an AUC range of 0.46-0.94. CONCLUSIONS: This study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.

Zishen yutai pill as an adjuvant therapy in threatened Miscarriage:A meta-analysis of 23 randomized controlled trials.

Objective: The purpose of this study was to evaluate the efficacy and safety of Zishen Yutai Pill combined with western medicine for the treatment of women with threatened miscarriage during the first trimester of pregnancy. Methods: Randomized controlled trials published before the end of Apr 1, 2023 on Zishen Yutai Pill and threatened miscarriage were systematically retrieved from China National Knowledge Infrastructure, Wanfang, Sinomed, VIP, PubMed, EMBASE, Web of Science and the Cochrane Library. The international clinical trial registration platform and the Chinese clinical trial registration platform of clinical trials was searched from their inception until Apr 1, 2023. Meta analysis of random effect model was used to combine the research data. Chi-squared test and I2 statistics were used for heterogeneity test. Results: Twenty-three trials (enrolling 2411 participants) were included in the review. Zishen Yutai pill combined with western medicine therapy showed significant improvement on human chorionic gonadotropin [MD 19.33 IU/ml, 95% CI (15.84, 22.81)], the total effective rate [RR 1.19, 95% CI (1.15-1.23)], progesterone [MD 7.14 ng/ml, 95% CI (6.14, 8.13)], estradiol [MD 33.69 pg/ml, 95% CI (27.42, 39.96)], duration of abdominal pain [MD -2.36 d, 95% CI (- 3.54, - 1.18)], duration of vaginal bleeding [MD -1.94 d, 95% CI (- 2.93, - 0.94)], and fibrinogen [MD -0.34 g/L, 95% CI (- 0.57, - 0.11)]. There was no significant difference in hematocrit [MD 0.68%, 95% CI (- 0.08, 1.44)] between the experimental and the control group. Zishen Yutai Pill may improve the clinical symptoms in women with threatened miscarriage, such as human chorionic gonadotropin the total effective rate, progesterone, estradiol, duration of abdominal pain, duration of vaginal bleeding, and fibrinogen. Especially for progesterone, the effect of treatment ≦2 weeks is significantly better than treatment of >2 weeks. For estradiol, the effect of treatment >2 weeks is significantly better than treatment of ≦ 2 weeks. Conclusion: Zishen Yutai Pill, as a complementary therapy, significantly improved human chorionic gonadotropin, the total effective rate, progesterone, estradiol, abdominal pain, vaginal bleeding, and fibrinogen in patients with threatened miscarriage in first-trimester pregnancy. However, the systematic review has some limitations, such as degraded information quality, no blinding of patients or doctors, etc. Due to the small sample size and low quality of research, it needs to be further confirmed by large sample and high-quality randomized controlled trials, such as blinding of patients, doctors and outcome assessment should be complemented, clinical follow-up, live birth rate, fetal growth should be supplemented. Systematic review registration: INPLASY202320039.

Can China's vehicular emissions regulation reduce air pollution?-a quasi-natural experiment based on the latest National Vehicular Emissions Standard (stage-VI).

The existing evidence on the environmental effects of vehicular emissions regulation almost comes from developed countries, but the effectiveness of this policy tool in developing countries, especially in China, remains unclear. This study, for the first time, examined the mitigating effects of China's vehicular emissions regulation on air pollution at the prefecture level cities, by using the latest implementation of China's National Vehicular Emissions Standard VI (CHINA-VI) as a quasi-natural experimental process of policy shocks. To this end, monthly data from 2018 to 2020 was applied to construct a difference-in-differences (DID) model. The results showed that pilot cities' air quality index (AQI) significantly decreased by 4.74 compared to non-pilot cities after the implementation of CHINA-VI. Also, the concentration of PM2.5, PM10, and O3 has decreased by 3.6 µg∕m3, 6.4 µg∕m3, and 3.0 µg∕m3, respectively, which means the new China's vehicular emissions regulation has comprehensively improved air quality. The findings are still valid after a series of robustness tests using different estimation methods such as PSM-DID and IV-2SLS. In addition, we also found heterogeneity in the environmental performance of CHINA-VI across cities. Specifically, cities with lower levels of green finance development and public environmental concern showed a greater emissions reduction effect, but smart cities showed a greater emissions reduction effect than non-smart cities.

Natural deep eutectic solvents-based green extraction of vanillin: optimization, purification, and bioactivity assessment.

The sustainable extraction of natural compounds has recently attracted significant attention. The extraction of high-quality natural vanillin in active form is crucial for its efficient use in various industries, but conventional solvents are not suitable for this purpose. The flammability, volatility, and toxicity of organic solvents can harm extraction personnel, and their waste liquid can cause environmental pollution. Natural deep eutectic solvents (NADES) are cost-effective, environmentally friendly, biodegradable, and non-toxic organic alternative to conventional solvents. In this study, 20 different NADES were tested for the sustainable extraction of natural vanillin. Among these, a DES system composed of choline chloride: 1,4-butanediol: lactic acid exhibited the highest extraction rate (15.9 mg/g). Employing response surface methodology (RSM), optimal extraction conditions were determined, yielding a vanillin content 18.5 mg/g with water content of 33.9%, extraction temperature of 64.6°C, extraction time of 32.3 min, and a solid-liquid ratio of 44.9 mg/mL. Subsequently, the optimized NADES system was then assessed for reusability in extracting vanillin from vanilla pods and kraft lignin over three cycles, retaining 43% of its extraction efficiency and demonstrating potential for waste reduction. Purification of vanillin was achieved through chromatography using a non-polar resin SP700, with ethanol as a desorption eluent and a feed solution pH of 4.0, resulting in the highest vanillin purity. HPLC and GC-MS analyses confirmed purity, while antioxidant activity assays (DPPH and ABTS) showcased significant antioxidant activity of the purified vanillin. Moreover, vanillin exhibited notable antimicrobial activity against a panel of food-borne bacteria. This study introduces an environmentally friendly approach to vanillin extraction highlights using NADES, emphasizing the potential for producing high-quality bioactive vanillin with reduced environmental impact. The applicability of NADES systems extends beyond vanillin, offering a versatile method for extracting diverse natural compounds.

Insights on the binding mechanism between specified aldehydes and flaxseed protein using multispectral image and molecular docking.

The binding and release behavior of flaxseed proteins to aldehydes is significant for the sensory properties of flaxseed foods. The key aldehydes of flaxseed were selected by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and odor activity value (OAV) method, and the interaction between flaxseed protein and flaxseed protein was investigated by multispectral, molecular docking, molecular dynamics simulation, and particle size techniques. The results showed that 2,4-decadienal presented a higher binding capability and a higher Stern-Volmer constant with flaxseed protein than pentanal, benzaldehyde, and decanal. Thermodynamic analysis revealed that hydrogen bonding and hydrophobic interactions were the main forces. Aldehydes contributed to a certain reduction in radius of gyration (Rg) value and α-helix content of flaxseed protein. In addition, the results of particle size showed that aldehydes caused the proteins to aggregate toward larger particles. This study could provide new insights into the interactions between flaxseed food and flavor.

Characterization and 3D printing of a biodegradable polylactic acid/thermoplastic polyurethane blend with laccase-modified lignin as a nucleating agent.

Polylactic acid (PLA) has been used in fused deposition method (FDM) based 3D printing for many years. Alkali lignin is an undervalued industrial by-product that could upgrade PLA's poor mechanical properties. This work presents a biotechnological approach consisting of a partial degradation of alkali lignin using Bacillus ligniniphilus laccase (Lacc) L1 for its use as a nucleating agent in a polylactic acid/thermoplastic polyurethane (PLA/TPU) blend. Results showed that adding enzymatically modified lignin (EL) increased the elasticity modulus to a maximum of 2.5-fold than the control and conferred a maximum biodegradability rate of 15 % after 6 months under the soil burial method. Furthermore, the printing quality rendered satisfactory smooth surfaces, geometries and a tunable addition of a woody color. These findings open a new door for using laccase as a tool to upgrade lignin's properties and its use as a scaffold in manufacturing more environmentally sustainable filaments with improved mechanical properties for 3D printing.

Case report: Whole exome sequencing and genome-wide methylation profiling of Czech dysplasia in a Chinese pedigree.

Background: Czech dysplasia is a rare skeletal disorder with symptomatology including platyspondyly, brachydactyly of the third and fourth toes, and early-onset progressive pseudorheumatoid arthritis. The disorder segregates in an autosomal dominant fashion. A specific missense mutation (R275C, c.823C > T) in exon 13 of the COL2A1 gene has been identified in German and Japanese families. Case summary: We present the case of a Chinese woman diagnosed with Czech dysplasia (proband) who carried a variant in the COL2A1 gene. Whole-exome sequencing (WES) identified the COL2A1 missense mutation (R275C, c.823C > T) in close relatives of the proband who also exhibited the same disorder. Conclusion: This study is a thorough clinical and physiological description of Czech dysplasia in a Chinese patient.

Circulating DNA methylation level of CXCR5 correlates with inflammation in patients with rheumatoid arthritis.

OBJECTIVES: To assess the differences in circulating DNA methylation levels of CXCR5 between rheumatoid arthritis (RA) and osteoarthritis (OA) and healthy controls (HC), and the correlation of methylation changes with clinical characteristics of RA patients. METHODS: Peripheral blood samples were collected from 239 RA patients, 30 patients with OA, and 29 HC. Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis. RESULTS: The methylation level of cg04537602 was significantly higher in the peripheral blood of RA patients compared with OA patients (p = 1.3 × 10-3 ) and in the HC group (p = 5.5 × 10- 4 ). The sensitivity was enhanced when CXCR5 methylation level combined with rheumatoid factor and anti-cyclic citrullinated peptide with area under curve (AUC) of 0.982 (95% confidence interval 0.970-0.995). The methylation level of cg04537602 in RA was positively correlated with C-reactive protein (CRP) (r = .16, p = .01), and in RA patients aged 60 years and above, cg04537602 methylation levels were positively correlated with CRP (r = .31, p = 4.7 × 10- 4 ), tender joint count (r = .21, p = .02), visual analog scales score (r = .21, p = .02), Disease Activity Score in 28 joints (DAS28) using the CRP level DAS28-CRP (r = .27, p = 2.1 × 10- 3 ), and DAS28-ESR (r = .22, p = .01). We also observed significant differences of DNA methylation haplotypes in RA patients compared with OA patients and HC, which was consistent with single-loci-based CpG methylation measurement. CONCLUSION: The methylation level of CXCR5 was significantly higher in RA patients than in OA and HC, and correlated with the level of inflammation in RA patients, our study establishes a link between CXCR5 DNA methylation and clinical features that may help in the diagnosis and disease management of RA patients.

Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis.

Objective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA). Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy controls. We performed differential analysis of all genes and HLA genes. We performed a protein-protein interaction network analysis and identified hub genes based on STRING and cytoscape. Consistent clustering was performed with subgrouping of the disease. SsGSEA were used to calculate immune cell infiltration. Spearman's correlation analysis was employed to identify correlations. Enrichment scores of the GO and KEGG were calculated with the ssGSEA algorithm. The WGCNA and the DGIdb database were used to mine hub genes' interactions with drugs. Results: There were 26 differentially expressed Anoikis-related genes (FDR = 0.05, log2FC = 1) and HLA genes exhibited differential expression (P < 0.05) between the disease and control groups. Protein-protein interaction was observed among differentially expressed genes, and the correlation between PIM2 and RAC2 was found to be the highest; There were significant differences in the degree of immune cell infiltration between most of the immune cell types in the disease group and normal controls (P < 0.05). Anoikis-related genes were highly correlated with HLA genes. Based on the expression of Anoikis-related genes, RA patients were divided into two disease subtypes (cluster1 and cluster2). There were 59 differentially expressed Anoikis-related genes found, which exhibited significant differences in functional enrichment, immune cell infiltration degree, and HLA gene expression (P < 0.05). Cluster2 had significantly higher levels in all aspects than cluster1 did. The co-expression network analysis showed that cluster1 had 51 hub differentially expressed genes and cluster2 had 72 hub differentially expressed genes. Among them, three hub genes of cluster1 were interconnected with 187 drugs, and five hub genes of cluster2 were interconnected with 57 drugs. Conclusion: Our study identified a link between Anoikis-related genes and RA, and two distinct subtypes of RA were determined based on Anoikis-related gene expression. Notably, cluster2 may represent a more severe state of RA.