The association between O2-pulse slope ratio and functional severity of coronary stenosis: A combined cardiopulmonary exercise testing and quantitative flow ratio study.

Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.

Discovery of a potent inhibitor, D-132, targeting AsfvPolX, via protein-DNA complex-guided pharmacophore screening and in vitro molecular characterizations.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections. In this study, a comprehensive approach involving pharmacophore-based inhibitor screening, coupled with biochemical and biophysical analyses, were implemented to identify, characterize, and validate potential inhibitors targeting AsfvPolX. The constructed pharmacophore model, Phar-PolX-S, demonstrated efficacy in identifying a potent inhibitor, D-132 (IC50 = 2.8 ± 0.2 µM), disrupting the formation of the AsfvPolX-DNA complex. Notably, D-132 exhibited strong binding to AsfvPolX (KD = 6.9 ± 2.2 µM) through a slow-on-fast-off binding mechanism. Employing molecular modeling, it was elucidated that D-132 predominantly binds in-between the palm and finger domains of AsfvPolX, with crucial residues (R42, N48, Q98, E100, F102, and F116) identified as hotspots for structure-based inhibitor optimization. Distinctively characterized by a 1,2,5,6-tetrathiocane with modifications at the 3 and 8 positions involving ethanesulfonates, D-132 holds considerable promise as a lead compound for the development of innovative agents to combat ASFV infections.

On rheological properties of disc-shaped cellulose nanocrystals.

The rheological properties of a substance depend greatly on its morphology, and rod-shaped cellulose nanocrystals (RCNCs) and cellulose nanofibrils (CNFs) have been extensively studied for their rheological properties. Nevertheless, the rheological properties of disc-shaped cellulose nanocrystals (DCNCs) with crystalline allomorph II derived from mercerized cellulose remain unknown yet. This work investigated the DCNCs' rheological properties in depth using steady-shear and oscillation measurements. At the same concentration, DCNC's suspension viscosity is lower than that of RCNC; RCNC has an instinct viscosity of 258.2, while DCNC has 187.9. Comparing RCNC suspensions with cellulose nanorods, DCNC has a lower aspect ratio and exhibits a distinct steady shear behavior. Under polarized film, DCNC suspension cannot self-assemble into chiral or liquid crystal phases, and with increasing concentrations, the system transitions from an isotropic phase to a gel phase. Oscillation sweeps demonstrate that the gel transition occurs at 7 %-8 %. Based on thixotropic recovery sweep outcomes, the high-stress oscillations enhance the network structure of DCNC suspensions, which is significantly different from that of RCNC suspensions. Results demonstrate the unique properties of DCNC, highlighting its application as a rheological modifier.

Tracing the transfer characteristics of antibiotic resistance genes from swine manure to biogas residue and then to soil.

Based on laboratory simulation experiments and metagenomic analysis, this study tracked the transmission of antibiotic resistance genes (ARGs) from swine manure (SM) to biogas residue and then to soil (biogas residue as organic fertilizer (OF) application). ARGs were abundant in SM and they were assigned to 11 categories of antibiotics. Among the 383 ARG subtypes in SM, 43 % ARG subtypes were absent after anaerobic digestion (AD), which avoided the transfer of these ARGs from SM to soil. Furthermore, 9 % of the ARG subtypes in SM were introduced into soil after amendment with OF. Moreover, 43 % of the ARG subtypes in SM were present in OF and soil, and their abundances increased slightly in the soil amended with OF. The bacterial community in the soil treated with OF was restored to its original state within 60 to 90 days, probably because the abundances of ARGs were elevated but not significantly in the soil. Network analysis identified 31 potential co-host bacteria of ARGs based on the relationships between the bacteria community members, where they mainly belonged to Firmicutes, followed by Bacteroidetes, Actinobacteria, and Proteobacteria. This study provides a basis for objectively evaluating pollution by ARGs in livestock manure for agricultural use.

Effects of hydrolysis conditions on the morphology of cellulose II nanocrystals (CNC-II) derived from mercerized microcrystalline cellulose.

The properties of cellulose nanocrystals with allomorph II (CNC-II) vary with the sources and the treatments received. In this work, the influences of hydrolysis time, temperature, and the applied acid concentration on the crystal size of CNC-II were investigated by the surface response experimental design. The results showed that temperature was the most significant factor affecting the crystal size of CNC-II during hydrolysis from mercerized cellulose. Then the morphology and colloidal properties of CNC-II were revealed by dynamic laser scattering (DLS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), etc. XRD results indicated that CNC-II had slightly lower crystallinity (80.89 % vs 82.7 %) and larger crystallite size (5.21 vs. 5.13 nm) than CNC-I. TEM and AFM results showed that the morphology of CNC-II were disc-like and rod-like particles, with an average diameter of 14.6 ± 4.7 nm (TEM) and a thickness of 4- 8 nm (AFM). TG and XPS revealed the reduced thermal stability was due to the introduced sulfate groups in CNC-II during hydrolysis. This investigation has addressed the features of CNC-II derived from mercerized cellulose, and it would be promising in fabricating advanced materials.

METTL16-mediated N6-methyladenosine modification of Soga1 enables proper chromosome segregation and chromosomal stability in colorectal cancer.

N6-methyladenosine (m6A) is the most prevalent internal modification in mammalian messenger RNAs and is associated with numerous biological processes. However, its role in chromosomal instability remains to be established. Here, we report that an RNA m6A methyltransferase, METTL16, plays an indispensable role in the progression of chromosome segregation and is required to preserve chromosome stability in colorectal cancer (CRC) cells. Depletion or inhibition of the methyltransferase activity of METTL16 results in abnormal kinetochore-microtubule attachment during mitosis, leading to delayed mitosis, lagging chromosomes, chromosome mis-segregation and chromosomal instability. Mechanistically, METTL16 exerts its oncogenic effects by enhancing the expression of suppressor of glucose by autophagy 1 (Soga1) in an m6A-dependent manner. CDK1 phosphorylates Soga1, thereby triggering its direct interaction with the polo box domain of PLK1. This interaction facilitates PLK1 activation and promotes mitotic progression. Therefore, targeting the METTL16-Soga1 pathway may provide a potential treatment strategy against CRC because of its essential role in maintaining chromosomal stability.

Relationship between air pollutants and spontaneous abortion in a coal resource valley city: a retrospective cohort study.

OBJECTIVE: Pollutants in the atmosphere have been linked to poor pregnancy outcomes in women. However, such investigations are scarce in metropolitan northern China. The major exposure window of air pollution affecting pregnant women is also unknown. METHODS: For the analysis, this retrospective cohort study enrolled 6960 pregnant women recorded at Tongchuan People's Hospital from January 2018 to December 2019. Pollutant concentration values from the nearest monitoring station to the pregnant women were used to estimate exposure doses for each exposure window. Logistic regression models were created to investigate the connection between pollutants and spontaneous abortion while controlling for confounding factors. RESULTS: PM2.5 was a risk factor for spontaneous abortion in T3 (30-60 days before the first day of the last menstrual period [LMP]), (OR: 1.305, 95% CI: 1.143-1.490) and T4 (60-90 days before the first day of the LMP),(OR: 1.450, 95% CI: 1.239-1.696) after controlling for covariates. In the same window, PM10 was a risk factor (OR: 1.308, 95% CI: 1.140-1.500), (OR: 1.386, 95% CI: 1.184-1.621). In T2 (30 days before the first day of the LMP), T3, and T4, SO2 was a risk factor for spontaneous abortion (OR: 1.185, 95% CI: 1.025-1.371), (OR: 1.219, 95% CI: 1.071-1.396), (OR: 1.202, 95% CI: 1.040-1.389). In T3 and T4, NO2 was a risk factor (OR: 1.171, 95% CI: 1.019- 1.346), (OR: 1.443, 95% CI: 1.259-1.655). In T1 (from the first day of the LMP to the date of abortion), O3 was found to be a risk factor (OR: 1.366, 95% CI: 1.226-1.521). CONCLUSION: Exposure to high levels of air pollutants before and during pregnancy may be a risk factor for spontaneous abortion in pregnant women. This study further illustrates the importance of reducing air pollution emissions.

Controlling the nanocellulose morphology by preparation conditions.

Nanocellulose (NC) is the desired building block for novel biomaterials. The morphology of NC is one of the core parameters impacting the functionality and property of engineered functional materials. This work aims to reveal the relationship between the product morphology and sulfuric acid hydrolysis conditions (including acid concentration, temperature and time), and to realize morphological regulation of obtained NC. Three representative products were obtained from microcrystalline cellulose via sulfuric acid hydrolysis, which are cellulose nanocrystals with broad size distribution (W-CNC, 383.9 ± 131.7 nm in length, 6 ± 2.1 nm in height) obtained by 61 % H2SO4, 55 °C and 90 min, cellulose nanospheres (CNS, 61.3 ± 15.9 nm in diameter) obtained by 64 % H2SO4, 35 °C and 75 min, and CNC with narrow size distribution (N-CNC, 276.1 ± 28.7 nm in length, 4.1 ± 0.6 nm in height), obtained by 64 % H2SO4, 45 °C and 45 min. The results showed that the crystallographic form of W-CNC and N-CNC are cellulose I, while cellulose I and II coexist in CNS. Only W-CNC and N-CNC can form chiral nematic structures through evaporation-induced self-assembly strategy and reflected light with specific wavelengths. In addition, the formation mechanism of CNS with cellulose I/II was proposed, which provided a better understanding of NC morphology regulation.

Prognostic role of tissue plasminogen activator in coronary artery disease with or without aortic valve sclerosis.

AIMS: We sought to investigate the relationship between circulating tissue plasminogen activator (t-PA) level and long-term outcomes in stable coronary artery disease patients with or without aortic valve sclerosis (AVSc). METHODS AND RESULTS: Serum levels of t-PA were determined in 347 consecutive stable angina patients with (n = 183) or without (n = 164) AVSc. Outcomes were prospectively recorded as planned clinic evaluations every 6 months up to 7 years. The primary endpoint was a composite of cardiovascular death and rehospitalization due to heart failure. The secondary endpoint included all-cause mortality, cardiovascular death, and rehospitalization due to heart failure. Serum t-PA was significantly higher in AVSc than in non-AVSc patients (2131.22 pg/mL vs. 1495.85 pg/mL, P < 0.001). For patients with AVSc, those with t-PA level above the median (>1840.68 pg/mL) were more likely to meet the primary and secondary endpoints (all P < 0.001). After adjusting for potential confounding factors, serum t-PA level remained significantly predictive for each endpoint in the Cox proportional hazard models. The prognostic value of t-PA was good, with an AUC-ROC of 0.753 (P < 0.001). The combination of t-PA with traditional risk factors improved the risk reclassification of AVSc patients, with a net reclassification index of 0.857 and an integrated discrimination improvement of 0.217 (all P < 0.001). However, for patients without AVSc, both primary and secondary endpoints were similar, irrespective of t-PA levels. CONCLUSIONS: Elevated circulating t-PA confers an increased risk for poor long-term clinical outcomes in stable coronary artery disease patients with AVSc.

The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair.

The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20-H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner. In parallel, RPA recruits RNF20 to chromosomal breaks upon DNA damage. Disruption of the RPA-RNF20 interaction or depletion of RNF20 increases mitotic lagging chromosomes and chromosome bridges and impairs BRCA1 and RAD51 loading and homologous recombination repair, leading to elevated chromosome breaks, genome instability, and sensitivities to DNA-damaging agents. Mechanistically, the RPA-RNF20 pathway promotes local H2Bub, H3K4 dimethylation, and subsequent SNF2H recruitment, ensuring proper Aurora B kinase activation at centromeres and efficient loading of repair proteins at DNA breaks. Thus, the RPA-RNF20-SNF2H cascade plays a broad role in preserving genome stability by coupling H2Bub to chromosome segregation and DNA repair.

Inositol possesses antifibrotic activity and mitigates pulmonary fibrosis.

BACKGROUND: Myo-inositol (or inositol) and its derivatives not only function as important metabolites for multiple cellular processes but also act as co-factors and second messengers in signaling pathways. Although inositol supplementation has been widely studied in various clinical trials, little is known about its effect on idiopathic pulmonary fibrosis (IPF). Recent studies have demonstrated that IPF lung fibroblasts display arginine dependency due to loss of argininosuccinate synthase 1 (ASS1). However, the metabolic mechanisms underlying ASS1 deficiency and its functional consequence in fibrogenic processes are yet to be elucidated. METHODS: Metabolites extracted from primary lung fibroblasts with different ASS1 status were subjected to untargeted metabolomics analysis. An association of ASS1 deficiency with inositol and its signaling in lung fibroblasts was assessed using molecular biology assays. The therapeutic potential of inositol supplementation in fibroblast phenotypes and lung fibrosis was evaluated in cell-based studies and a bleomycin animal model, respectively. RESULTS: Our metabolomics studies showed that ASS1-deficient lung fibroblasts derived from IPF patients had significantly altered inositol phosphate metabolism. We observed that decreased inositol-4-monophosphate abundance and increased inositol abundance were associated with ASS1 expression in fibroblasts. Furthermore, genetic knockdown of ASS1 expression in primary normal lung fibroblasts led to the activation of inositol-mediated signalosomes, including EGFR and PKC signaling. Treatment with inositol significantly downregulated ASS1 deficiency-mediated signaling pathways and reduced cell invasiveness in IPF lung fibroblasts. Notably, inositol supplementation also mitigated bleomycin-induced fibrotic lesions and collagen deposition in mice. CONCLUSION: These findings taken together demonstrate a novel function of inositol in fibrometabolism and pulmonary fibrosis. Our study provides new evidence for the antifibrotic activity of this metabolite and suggests that inositol supplementation may be a promising therapeutic strategy for IPF.

Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases.

Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics.

Effect of graphene and graphene oxide on antibiotic resistance genes during copper-contained swine manure anaerobic digestion.

Copper is an important selectors for antibiotic resistance genes (ARGs) transfer because of metal-antibiotic cross-resistance and/or coresistance. Due to carbon-based materials' good adsorption capacity for heavy metals, graphene and graphene oxide have great potential to reduce ARGs abundance in the environment with copper pollution. To figure out the mechanics, this study investigated the effects of graphene and graphene oxide on the succession of ARGs, mobile genetic elements (MGEs), heavy metal resistance genes (HMRGs), and bacterial communities during copper-contained swine manure anaerobic digestion. Results showed that graphene and graphene oxide could reduce ARGs abundance in varying degrees with the anaerobic reactors that contained a higher concentration of copper. Nevertheless, graphene decreased the abundance of ARGs more effectively than graphene oxide. Phylum-level bacteria such as Firmicutes, Bacteroidetes, Spirochaetes, and Verrucomicrobiaat were significantly positively correlated with most ARGs. Network and redundancy analyses demonstrated that alterations in the bacterial community are one of the main factors leading to the changes in ARGs. Firmicutes, Bacteroidetes, and Spirochaetes were enriched lower in graphene reactor than graphene oxide in anaerobic digestion products, which may be the main reason that graphene is superior to graphene oxide in reduced ARGs abundance. Additionally, ARGs were close to HMRGs than MGEs in the treatments with graphene, the opposite in graphene oxide reactors. Therefore, we speculate that the reduction of HMRGs in graphene may contribute to the result that graphene is superior to graphene oxide in reduced ARGs abundance in anaerobic digestion.

MTAP deficiency contributes to immune landscape remodelling and tumour evasion.

Methylthioadenosine phosphorylase (MTAP) deficiency occurs in various malignancies and is associated with poor survival in cancer patients. However, the mechanisms underlying tumour progression due to MTAP loss are yet to be elucidated. Utilizing integrated analyses of the transcriptome, proteome and secretome, we demonstrated that MTAP deficiency alters tumour-intrinsic, immune-related pathways and reprograms cytokine profiles towards a tumour-favourable environment. Additionally, MTAP-knockout cells exhibited a marked increase in the immune checkpoint protein PD-L1. Upon co-culturing primary T cells with cancer cells, MTAP loss-mediated PD-L1 upregulation inhibited T cell-mediated killing activity and induced several T cell exhaustion markers. In two xenograft tumour models, we showed a modest increase in average volume of tumours derived from MTAP-deficient cells than that of MTAP-proficient tumours. Surprisingly, a remarkable increase in tumour size was observed in humanized mice bearing MTAP-deficient tumours, as compared to their MTAP-expressing counterparts. Following immunophenotypic characterization of tumour-infiltrating leukocytes by mass cytometry analysis, MTAP-deficient tumours were found to display decreased immune infiltrates with lower proportions of both T lymphocytes and natural killer cells and higher proportions of immunosuppressive cells as compared to MTAP-expressing tumour xenografts. Taken together, our results suggest that MTAP deficiency restructures the tumour immune microenvironment, promoting tumour progression and immune evasion.

Oxygen pulse variation in symptomatic patients with suspected coronary artery disease: a diagnostic analysis.

Background: Cardiopulmonary exercise testing (CPET) has been found high sensitivity and specificity in cardiac ischemia. However, the role of CPET in coronary artery disease (CAD) is unclear. This study was to explore the diagnostic value of CPET indicators in CAD. Methods: A total of 138 symptomatic patients with suspected CAD who underwent a CPET were included in this cross-sectional study. CPET indicators of all individuals were collected. ΔVO2/HR(Peak-AT) defined as the difference between the value of the oxygen consumption/heart rate (VO2/HR) at anaerobic threshold and peak exercise. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score of all the CAD patients was calculated based on the complexity of the coronary lesions. The diagnostic performance of the CPET indicators was assessed by the area under the curve (AUC), sensitivity, and specificity. Results: No significant differences in the CPET indicators were observed among the patients with or without CAD. The high SNYTAX score (≥22) group showed a significant reduction in the ΔVO2/HR(Peak-AT) compared to the low SNYTX score (<22) group (P=0.004). The AUC of the ΔVO2/HR(Peak-AT) was 0.804 (P=0.005), with the sensitivity of 95.7% and the specificity of 62.5%. The other CPET indicators did not differ significantly between the 2 groups. Oxygen pulse variation after the anaerobic threshold (AT) is superior to other CPET-derived variables in detecting intermediate to severe stenosis of the coronary artery in CAD patients. Conclusions: The ΔVO2/HR(Peak-AT) is a quantitative indicator of the variation of the oxygen pulse response after the AT during incremental exercise. However, due to sample limitations, our results need to be interpreted with caution.

Clinical Characteristics and Treatment of Adult Idiopathic Carpal Tunnel Syndrome Accompanied with Trigger Digit.

Purpose: To investigate the clinical characteristics and treatment of adult idiopathic carpal tunnel syndrome (CTS) accompanied with trigger digit. Materials and Methods: A retrospective analysis was performed on a total of 74 patients with adult idiopathic CTS accompanied with trigger digit admitted to and treated at the Hand Surgery Department of Ningbo No. 6 Hospital from January 1, 2017 to December 31, 2019. Data on patients' gender, age, occupation, course of the disease, menstruation, surgeries, examination-related information, complications, treatment methods, and prognoses during follow-up were recorded and subsequently used to analyze the pathogeneses, clinical characteristics, and treatment. Results: A total of 74 patients (72 females and 2 males) were included. Among female patients, 51 were postmenopausal and 18 were non-postmenopausal. There were 101 fingers with trigger digit, including 14 patients with trigger digit in both hands, and 115 wrists affected by the CTS. The average course of CTS was 34.5 ± 49.3 months, and that of trigger digit was 10.5 ± 22.4 months. Seventy had both trigger digit and CTS in one hand, while among patients with both hands involved, only 4 had trigger digit or CTS in one hand. Eighty-nine fingers underwent A1 pulley release, and 104 hands underwent carpal tunnel surgery, with steroids being injected under the adventitia of the median nerve during the surgery. All patients who underwent surgeries had I/A-healed incisions, and 14 of them had obvious synovial hyperplasia observed in the carpal tunnel and flexor tendon sheath during surgeries. Follow-up visits, which lasted 3 to 35 months, had an average duration of 1.34 years and included 72 patients. In 63 patients (63/72), the syndrome of tenosynovitis and numbness disappeared and normal hand functions were restored; in 6 patients, the numbness in hands greatly improved and normal hand functions were almost completely restored, while no improvement in numbness of hands and limited hand functions were still observed in 3 patients. Conclusion: CTS accompanied with trigger digit was more common in postmenopausal females, and the course of CTS was longer than that of trigger digit. CTS and trigger digit were more likely to simultaneously occur in the same hand, while some patients might not have obvious synovial hyperplasia in the carpal tunnel. Surgeries were effective in severe cases.

Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention.

Background Insulin receptor substrate-1 (IRS-1) rs956115 is associated with vascular risk in patients with coronary artery disease and concomitant diabetes. CYP2C19*2 (rs4244285) modulates clopidogrel response and predicts the outcome of coronary artery disease. This study was designed to explore the association between IRS-1, CYP2C19*2 genotypes, platelet reactivity, and 1-year outcome in patients with coronary artery disease undergoing percutaneous coronary intervention. Methods and Results Genotyping was performed using an improved multiplex ligation detection reaction technique. Platelet aggregation was assessed by light transmission aggregometry. Major adverse cardiovascular events were defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke. A total of 2213 consecutive patients were screened and 1614 were recruited. At 1 month, patients with IRS-1 CG genotype had significantly lower levels of ADP-induced platelet aggregation compared with patients with CC homozygotes. Patients with IRS-1 CG or GG genotype had a 2.09-fold higher risk of major adverse cardiovascular events compared with those with CC homozygotes (95% CI, 1.04-4.19; P=0.0376). By comparison, patients with CYP2C19*2 GA or AA genotype had higher ADP-induced platelet aggregation compared with patients with GG homozygotes. Although there was no significant difference in risk of major adverse cardiovascular events between patients with GA/AA and GG genotypes, patients with GA genotype had a 2.19-fold higher risk than those with GG homozygotes (95% CI, 1.13-4.24; P=0.0200). No interaction between IRS-1 and CYP2C19*2 genotypes was observed. Conclusions In patients following percutaneous coronary intervention, IRS-1 GG/CG and CYP2C19*2 GA genotypes were associated with 2.09- and 2.19-fold increased cardiovascular risk, respectively, at 1-year follow-up. The association between IRS-1 genotypes and major adverse cardiovascular events appeared to be independent of known clinical predictors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01968499.

Effects of Traditional Chinese Medicine and its Active Ingredients on Drug-Resistant Bacteria.

The increasing and widespread application of antibacterial drugs makes antibiotic resistance a prominent and growing concern in clinical practice. The emergence of multidrug-resistant bacteria presents a global threat. However, the development and use of novel antibacterial agents involves time-consuming and costly challenges that may lead to yet further drug resistance. More recently, researchers have turned to traditional Chinese medicine to stem the rise of antibiotic resistance in pathogens. Many studies have shown traditional Chinese medicines to have significant bacteriostatic and bactericidal effects, with the advantage of low drug resistance. Some of which when combined with antibiotics, have also demonstrated antibacterial activity by synergistic effect. Traditional Chinese medicine has a variety of active components, including flavonoids, alkaloids, phenols, and quinones, which can inhibit the growth of drug-resistant bacteria and be used in combination with a variety of antibiotics to treat various drug-resistant bacterial infections. We reviewed the interaction between the active ingredients of traditional Chinese medicines and antibiotic-resistant bacteria. At present, flavonoids and alkaloids are the active ingredients that have been most widely studied, with significant synergistic activity demonstrated when used in combination with antibiotics against drug-resistant bacteria. The reviewed studies show that traditional Chinese medicine and its active ingredients have antimicrobial activity on antibiotic-resistant bacteria, which may enhance the susceptibility of antibiotic-resistant bacteria, potentially reduce the required dosage of antibacterial agents and the rate of drug resistance. Our results provide direction for finding and developing alternative methods to counteract drug-resistant bacteria, offering a new therapeutic strategy for tackling antibiotic resistance.

Flow field characterization between vertical plate electrodes in a bench-scale cell of electrochemical water softening.

To analyze the effect of flow characteristics on electrochemical water softening, characteristics of flow fields in the vicinity of vertical plate electrodes in a bench-scale electrolysis cell for electrochemical water softening were visualized using particle image velocimetry technology, and the hardness drop values under different process conditions were measured. Properly increasing the current density or reducing the electrode spacing can increase the average flow velocity in the electrode gap. Excessive current density will cause bubble accumulation, form a bubble vortex, interfere with the orderly flow of surrounding liquid and reduce mass transfer efficiency. When the electrode spacing is 120 mm, the highest water softening efficiency measured at the current density of 60 A/m2 is 16.56%. When the current density is 50 A/m2, the highest average speed measured at the electrode spacing of 60 mm is 0.00169 m/s, but the highest water softening efficiency measured at the electrode spacing of 90 mm is 23.3%.The circulation efficiency in the electrode gap of a semi-closed structure is lower than that of a free convection structure. The behavior of bubbles is the key to flow and mass transfer. It is important to consider its influence on bubble behavior when optimizing electrochemical parameters.