Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease.

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.

Rapid and Sensitive Quantification of Bacterial Viability Using Ratiometric Fluorescence Sensing.

Bacterial viability assessment plays an important role in food-borne pathogen detection and antimicrobial drug development. Here, we first used GelRed as a DNA-binding stain for a bacterial viability assessment. It was found that live bacteria were able to exclude GelRed, which however could easily penetrate dead ones and be absorbed nonspecifically on the bacterial periplasm. Cations were used to reduce the nonspecific adsorption and greatly increase the red fluorescence ratio of dead to live bacteria. Combined with SYTO 9 (a membrane-permeable dye) for double-staining, a ratiometric fluorescent method was established. Using Escherichia coli O157:H7 as a bacteria model, the ratiometric fluorescent method can probe dead bacteria as low as 0.1%. A linear correlation between the ratiometric fluorescence and the theoretical ratio of dead bacteria was acquired, with a correlation coefficient R2 of 0.97. Advantages in sensitivity, accuracy, and safety of the GelRed/SYTO9-based ratiometric fluorescent method against traditional methods were demonstrated. The established method was successfully applied to the assessment of germicidal efficacy of different heat treatments. It was found that even 50 °C treatment could lead to the death of minor bacteria. The as-developed method has many potential applications in microbial researches, and we believe it could be expanded to the viability assessment of mammalian cells.

Unveiling the role of APOM gene in liver cancer: Investigating the impact of hsa-miR-4489/MUC1-mediated ferroptosis on the advancement of hepatocellular carcinoma cells.

Primary liver cancer has consistently exhibited a high prevalence and fatality rate, necessitating the investigation of associated diagnostic markers and inhibition mechanisms to effectively mitigate its impact. The significance of apolipoprotein M (ApoM) in impeding the progression of neoplastic ailments is progressively gaining recognition. However, a comprehensive understanding of its underlying mechanism in liver cancer advancement remains to be elucidated. Recent evidence indicates a potential association between ApoM and polyunsaturated fatty acids (PUFAs), with the peroxidation of phospholipids (PLs) containing PUFAs being recognized as a crucial element in the occurrence of ferroptosis. This prompts us to investigate the impact of the APOM gene on the progression of liver cancer through the ferroptosis pathway and elucidate its underlying mechanisms. The findings of this study indicate that the liver cancer cell model, which was genetically modified to overexpress the APOM gene, demonstrated a heightened ferroptosis effect. Moreover, the observed inhibition of the GSH (Glutathione) - GPX4 (Glutathione Peroxidase 4) regulatory axis suggests that the role of this axis in inhibiting ferroptosis is weakened. Through intersection screening and validation, we found that Mucin 1,cell surface associated (MUC1) can inhibit ferroptosis and is regulated by the APOM gene. Bioinformatics analysis and screening identified miR-4489 as a mediator between the two. Experimental results using the dual luciferase reporter gene confirmed that has-miR-4489 targets MUC1's 3'-UTR and inhibits its expression. In conclusion, this study provides evidence that the APOM gene induces a down-regulation in the expression of the ferroptosis-inhibiting gene MUC1, mediated by miR-4489, thereby impeding the advancement of liver cancer cells through the facilitation of ferroptosis.

Gelatin nanocarriers assembled by a self-immolative cross-linker for targeted cancer therapy.

With a number of outstanding properties, gelatin is an ideal candidate for assembling nanoplatforms in biomedical applications. Generally, gelatin nanocarriers are cross-linked by aldehydes to improve their stability in water solution. However, aldehydes could cause multiple toxicities and their cross-linking products are uncontrollable. Here, we first used a self-immolative cross-linker to assemble gelatin nanocarriers for the controlled release of drugs and targeted cancer therapy. The cross-linker contains a disulphide bridge and two symmetrical succinimidyl-esters, endowing it with multiple functions: 1) to cross-link the gelatin nanocarriers and thus improve their stability in water; 2) to conjugate the drug and tumor-targeting ligands with nanocarriers through covalent linkage; 3) to redox-responsively degrade the nanocarriers through hydrolysis of disulphide bridge; and 4) to produce traceless drug molecules through self-immolative reaction. Good biocompatibility and controllable drug release were demonstrated by in vitro experiments. Both qualitative and quantitative analyses confirmed the intracellular uptake of the nanocarriers by using doxorubicin (DOX) as a drug model and phenylboronic acid (PBA) as the targeting ligand. In vivo results demonstrated high therapeutic efficiency and low toxic side effects of the DOX loaded nanocarriers against artificial liver tumors.

Plasma-derived exosomes contributes to endothelial-to-mesenchymal transition in Moyamoya disease.

Background: Moyamoya disease (MMD) is a cerebrovascular disease with a high disability rate; however, its pathogenesis remains unknown. Endothelial-mesenchymal transition (EndMT) is the pathological basis of many vascular diseases; however, the key role of EndMT in MMD has not yet been reported. Method: We collected vascular tissues from three control samples and six patients with MMD to detect the expression of EndMT-related genes. To elucidate the mechanism of EndMT in MMD, we performed in vitro cell experiments. Plasma-derived exosomes (PDEs) can transmit information between cells and tissues and are of considerable importance in several disease studies. PDEs were used to stimulate EndMT phenotype in cerebrovascular endothelial cells. Results: Multiplex fluorescent immunohistochemistry staining confirmed that CD31, VE-cadherin and E-cadherin down-regulated, whereas α-SMA and vimentin were significantly up-regulated in moyamoya vascular endothelial cells than in control samples. PDEs from MMD patients significantly promoted cell proliferation and migration, resulting in slender cells. PDEs induce EndMT-related phenotype changes in cerebral vascular endothelial cells, including decreased endothelial cell marker expression and increased mesenchymal cell marker expression. We demonstrated that EndMT phenotypic alterations are mediated, in part, by microRNA(miRNAs). Conclusion: This study was the first to propose that EndMT may exist in the vessels of patients with MMD. PDEs induce the EndMT phenotype to promote the development of MMD. This study aimed to provide a new theoretical basis for elucidating the pathogenesis of MMD.

Low triiodothyronine syndrome and depression: a cross-sectional study in the elderly based on comprehensive geriatric assessment.

INTRODUCTION: Thyroid diseases such as low triiodothyronine syndrome (LT3S) are more common in the elderly population. Comprehensive geriatric assessment (CGA) has been proposed as a supplementary tool for evaluating medical, functional, psychological, and frailty status and various geriatric syndromes. This study aimed to evaluate the impact of thyroid diseases on overall health status using a novel CGA strategy. MATERIAL AND METHODS: 477 patients were enrolled between January 2019 and December 2022. A structured CGA was conducted by a multidisciplinary team to identify older high-risk patients. Multivariate regression was performed to assess independent factors associated with thyroid status and CGA. RESULTS: The prevalence of abnormal thyroid hormone levels in the elderly was 34.2%. LT3S and anti-thyroglobulin antibody (anti-TgAb)-positivity or anti-thyroid peroxidase antibody (anti-TPOAb)-positivity were the main manifestations of thyroid diseases in elderly patients. The patients with LT3S had a higher prevalence of diabetes (p = 0.023), were older (p = 0.000), more often female (p = 0.014), with higher C-reactive protein (p = 0.001), and with lower body mass index (BMI) (p = 0.002), albumin (Alb) (p = 0.000), and haemoglobin (Hb) (p = 0.000) than patients with normal thyroid function. The CGA results showed higher rates of malnutrition and depression in patients with LT3S. Further multivariate logistic regression analysis showed that Hb [odds ratio (OR): 0.975; 95% confidence interval (CI): 0.959-0.990; p = 0.002] and LT3S (OR: 2.213; 95% CI: 1.048-4.672; p = 0.037) were independently associated with depression. Female (OR: 0.393; 95% CI: 0.160-0.968; p = 0.042), Alb (OR: 0.892; 95% CI: 0.811-0.981; p = 0.018), Hb (OR, 0.964; 95% CI: 0.939-0.989; p = 0.006), and LT3S (OR: 3.749; 95% CI: 1.474-9.536; p = 0.006) were independently associated with malnutrition. CONCLUSIONS: LT3S was closely related to depression and malnutrition. Physicians should be more concerned about elderly patients with LT3S for their physical and mental status. Regular thyroid function checks might help to detect depression earlier.

Enhancement of the thermal stability of G-quadruplex structures by urea.

The solute urea has been used extensively as a denaturant in protein folding studies; double-stranded nucleic acid structures are also destabilized by urea, but comparatively less than proteins. In previous research, the solute has been shown to strongly destabilize folded G-quadruplex DNA structures. This contribution demonstrates the stabilizing effect of urea on the G-quadruplex formed by the oligodeoxyribonucleotide (ODN), G3T (d[5'-GGGTGGGTGGGTGGG-3']), and related sequences in the presence of sodium or potassium cations. Stabilization is observed up to 7 M urea, which was the highest concentration we investigated. The folded structure of G3T has three G-tetrads and three loops that consist of single thymine residues. ODNs related to G3T, in which the thymine residues in the loop are substituted by adenosine residues, also exhibit enhanced stability in the presence of molar concentrations of urea. The circular dichroism (CD) spectra of these ODNs in the presence of urea are consistent with that of a G-quadruplex. As the urea concentration increases, the spectral intensities of the peaks and troughs change, while their positions change very little. The heat-induced transition from the folded to unfolded state, Tm, was measured by monitoring the change in the UV absorption as a function of temperature. G-quadruplex structures with loops containing single bases exhibited large increases in Tm with increasing urea concentrations. These data imply that the loop region play a significant role in the thermal stability of tetra-helical DNA structures in the presence of the solute urea.

Reversible cross-linking of gelatin by a disulphide-containing bis-succinimide for tunable degradation and release.

Generally, gelatin was irreversibly cross-linked by chemical reagents to improve its water-resistance. However, few chemical reagents meet both the requirements of high cross-inking efficiency and tunable degradation. Here a reversible cross-linker, disulphide-containing bis-succinimide, was synthesized and used to control the cross-linking and degradation of edible gelatin film. Mixture of the gelatin and cross-linker for 120 min generated gelatin films that could preserve their morphology in 37 ℃ warm water for above 40 days. The gelatin film changed its microstructure from net to tightness after the cross-linking, thus facilitating the embedding of the targeted molecule into the gelatin material. The degradation of the cross-linked gelatin film and the release of its inclusion could be controlled by biocompatible glutathione. This work provides a good method for preparing modified gelatin with promising water-resistance, good biocompatibility, and tunable degradation for food/biomedical engineering applications.

High intact fibroblast growth factor 23 levels associated with low hemoglobin levels in patients on chronic hemodialysis.

Introduction: A negative association between C-terminal fibroblast growth factor 23 (cFGF23) and hemoglobin (Hb) levels has been reported in patients with predialysis chronic kidney disease. In dialysis patients, the dominant form of serum FGF23 is intact FGF23 (iFGF23); however, its association with the Hb level remains unclear. Therefore, simultaneously monitoring iFGF23 and cFGF23 levels is crucial. In this study, we investigated the associations between both forms of FGF23 (iFGF23 and cFGF23) and renal anemia in chronic hemodialysis (CHD) patients. Methods: We included 166 CHD patients from two hospitals in this cross-sectional, observational study. The primary predictors were serum iFGF23, cFGF23, and iFGF23/cFGF23 levels. The main outcome was the Hb level. Results: Among the CHD patients included, 60.8% were men with a mean age of 59.4 ± 12.7 years. In the crude analysis, iFGF23 and iFGF23/cFGF23 levels showed a significant negative association (-0.27, p = 0.004 and -0.22, p = 0.034, respectively) with the Hb level. Even after adjusting for multiple variables (a parsimonious model), every increment of natural log transformation by 1 for (ln)iFGF23 and ln(iFGF23/cFGF23) levels showed a negative correlation with the Hb level (estimate: -0.27 [95%CI: -0.44, -0.10, p = 0.001]; -0.19 [95%CI: -0.37, -0.01, p = 0.042], respectively), whereas both were positively associated with erythropoietin-stimulating agent (ESA) hyporesponsiveness (odds ratio [OR]: [95%CI: 2.30, 1.26-4.17], p = 0.006; 1.95 [95%CI: 1.08-3.50], p = 0.025). Moreover, these abovementioned associations were more dominant in patients with diabetes who used angiotensin receptor blockers. Discussion: In conclusion, a negative association between serum iFGF23 or iFGF23/cFGF23 level and the Hb level was observed in our CHD patients. Meanwhile, a higher iFGF23 or iFGF23/cFGF23 level may predispose patients to ESA hyporesponsiveness.

Correlation between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction in non-obese adults: a cross-sectional study.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with a greater risk of developing cardiovascular disease and have adverse impacts on the cardiac structure and function. Little is known about the effect of non-obese NAFLD upon cardiac function. We aimed to compare the echocardiographic parameters of left ventricle (LV) between non-obese NAFLD group and control group, and explore the correlation of non-obese NAFLD with LV diastolic dysfunction. METHODS AND RESULTS: In this cross-sectional study, 316 non-obese inpatients were enrolled, including 72 participants with NAFLD (non-obese NAFLD group) and 244 participants without NAFLD (control group). LV structural and functional indices of two groups were comparatively analyzed. LV diastolic disfunction was diagnosed and graded using the ratio of the peak velocity of the early filling (E) wave to the atrial contraction (A) wave and E value. Compared with control group, the non-obese NAFLD group had the lower E/A〔(0.80 ± 0.22) vs (0.88 ± 0.35), t = 2.528, p = 0.012〕and the smaller LV end-diastolic diameter〔(4.51 ± 0.42)cm vs (4.64 ± 0.43)cm, t = 2.182, p = 0.030〕. And the non-obese NAFLD group had a higher prevalence of E/A < 1 than control group (83.3% vs 68.9%, X2 = 5.802, p = 0.016) while two groups had similar proportions of LV diastolic dysfunction (58.3% vs 53.7%, X2 = 0.484, p = 0.487). Multivariate logistic regression analysis showed that non-obese NAFLD was associated with an increase in E/A < 1 (OR = 6.562, 95%CI 2.014, 21.373, p = 0.002). CONCLUSIONS: Non-obese NAFLD was associated with decrease of E/A, while more research will be necessary to evaluate risk of non-obese NAFLD for LV diastolic dysfunction in future.

[Risk Factors of Clopidogrel Resistance in the Elderly Patients with Atherosclerotic Cardiovascular Disease].

Objective To explore the risk factors of clopidogrel resistance (CR) in the elderly patients with atherosclerotic cardiovascular disease and to provide evidence for the antiplatelet therapy. Methods A total of 223 elderly patients (≥80 years old) with atherosclerotic cardiovascular disease treated in the Department of Geriatrics in the Peking University People's Hospital from January 18,2013 to November 30,2019 and meeting the inclusion criteria were enrolled in this study.The clinical data and laboratory test results were collected,including clinical disease,drug use,physical examination,complete blood cell analysis,biochemical indicators,and thromboelastogram (TEG).The rate of platelet inhibition induced by adenosine diphosphate was calculated according to the TEG.We assigned the patients into a CR group (n=84) and a control group (n=139) to analyze the incidence and influence factors of CR in the elderly patients with atherosclerotic cardiovascular disease. Results The incidence of CR was 37.7% in the elderly patients with atherosclerotic cardiovascular disease.The CR group had lower hemoglobin (t=3.533,P=0.001) and higher hypertension prevalence rate (χ2=6.581,P=0.006),proportion of multiple drugs (χ2=3.332,P=0.048),body mass index (BMI) (t=-2.181,P=0.030),total cholesterol (t=-2.264,P=0.025),triglycerides (Z=-2.937,P=0.003),low-density lipoprotein cholesterol (LDL-C) (t=-2.347,P=0.020),and proportion of women (χ2=5.562,P=0.014) than the control group.The results of multivariate Logistic regression showed that hemoglobin (OR=0.962,P<0.001),BMI (OR=1.154,P=0.003),and LDL-C (OR=1.688,P=0.018) were the factors influencing CR in the elderly patients with atherosclerotic cardiovascular disease. Conclusion Hemoglobin,BMI,and LDL-C may be independent factors associated with the occurrence of CR in the elderly patients with atherosclerotic cardiovascular disease.

A 9-year analysis of medical malpractice litigations in coronary artery bypass grafting in China.

BACKGROUND: The coronary artery bypass grafting (CABG) is one of the high-risk litigated medical specialties. Further elucidating the causes behind these malpractice claims can help physicians avoid patient injury. This study analyzed CABG litigations occurred in different level hospitals to outline the basic characteristics, as well as present a analysis on the medical malpractice that result in lawsuits. METHODS: This study utilized the "China Judgments Online" database to compile litigations from 2012 to 2021 across China. 109 cases related to the CABG were included in the study, and were analyzed for demographic, patient outcomes and verdict characteristics in different levels of hospitals. RESULTS: The median age of plaintiff patient was 62 years, the median length of stay was 25 days, and the median responsibility ratio of the litigation cases was 30%. The average proportion of responsibility of national, provincial and municipal hospitals were 29.6%, 28.4% and 39.5% respectively, and the median days after surgery to death of that were 15, 9 and 5 separately. The top 5 postoperative complications in dispute cases were: low cardiac output syndrome, postoperative hemorrhage, non-surgical site infections, surgical site infections and arrhythmia. CONCLUSIONS: The diagnosis and treatment capabilities of coronary artery bypass grafting in different levels of hospitals in China were inconsistent, and the treatment capabilities in prefecture-level hospitals were lower than that in national hospitals. The procedural error, failure to properly monitor the patient and diagnostic errors were common in CABG litigations. Postoperative complications related to surgical injuries and insufficient basic postoperative management lead to a higher responsibility proportion.

Bridge-DNA synthesis triggered by an allosteric aptamer for the colorimetric detection of pathogenic bacteria.

Rapid and sensitive quantification of pathogenic bacteria is highly desired for environmental health supervision and food safety control. Yet, the amplification and detection of bacteria with a concentration lower than 102 cfu mL-1 remains a great challenge. Here, we combined an allosteric aptamer (AAP) with a gold nanoparticle (AuNP) for assembling a bridge-DNA synthesis system (named as AuNP-BDS) to amplify the bacterial signals. The AAP and its paired primer (PP) were covalently linked to two different AuNPs, respectively: one named as AAP-AuNP and the other PP-AuNP. Upon recognition of the antigen from the pathogenic bacteria, AAP alters its conformation to initiate DNA synthesis on the AuNP surface. The DNA products from AAP-AuNP and PP-AuNP form bridges to each other through base pairing, resulting in the aggregation and colorimetric response of the AuNPs. By using E. coli O157:H7 as an example, the AuNP-BDS could quantify pathogenic bacteria in water with a concentration as low as 10 cfu mL-1 within 60 min and without any enrichment. The colorimetric response values of AuNP-BDS were found to be linearly related to the bacterial concentrations in the range of 10 to 103 cfu mL-1. Good practicability of the AuNP-BDS in quantifying E. coli O157:H7 from tap water, juices, and milks was demonstrated. The AuNP-BDS could be exploited to facilitate the rapid and sensitive quantification of pathogenic bacteria for food safety control.

The impact of industrial agglomeration on urban green land use efficiency in the Yangtze River Economic Belt.

At present, the insufficient supply of land resources has seriously hindered the sustainable development of regional economy. Improving the urban green land use efficiency (UGLUE) has become a key issue on the road to sustainable development. As an important feature of economic development, industrial agglomeration has an impact on the UGLUE that cannot be ignored. This paper uses the Global Malmquist-Luenberger Index (GMLI) to measure UGLUE of 107 cities in the Yangtze River Economic Belt (YREB) from 2007 to 2016, and uses a dynamic panel model (DPM) to empirically analyze the effects of industrial specialization agglomeration and diversification agglomeration on UGLUE. On this basis, the heterogeneous impact of industrial agglomeration in different regions on UGLUE is further discussed. The results illustrate that: (1) The UGLUE shows a general downward trend. (2) Different modes of industrial agglomeration have different impacts on UGLUE. The impact of industrial specialization agglomeration on UGLUE was inverted U-shaped. Industrial diversification agglomeration has a positive effect on UGLUE. (3) The impact of industrial agglomeration in different regions on UGLUE is heterogeneous. The relationship between the industrial agglomeration and UGLUE in the YREB revealed in this paper will provide a reference for promoting UGLUE.

Phase angle is a useful bioelectrical marker for skeletal muscle quantity and quality in hospitalized elderly patients.

To analyze whether phase angle (PhA) can be a useful bioelectrical marker for skeletal muscle quantity and quality in hospitalized elderly patients. Two hundred hospitalized elderly patients were included in this retrospective observational study. PhA was obtained by Bioelectrical Impedance Analysis, skeletal muscle area index (SMI) and skeletal muscle density (SMD) were measured at the third lumbar vertebra level in computed tomography images using SliceOmatic software. PhA was positively associated with SMD and SMI, with correlation coefficients of 0.629 and 0.674, respectively. Multiple logistic regression analysis showed that 1° reduction of PhA was significantly associated with low SMI [odds ratio (OR) = 4.331 (1.681-11.161)] and low SMD [OR = 6.418 (2.963-13.899)]. Receiver operating characteristic curve analysis showed that the area under the curve (AUC) for PhA to identify patients with low SMI was 0.772 for male and 0.784 for female; the AUC for PhA to identify low SMD patients was 0.829 for male and 0.812 for female; the AUC for PhA to identify low SMD combined with low SMD patients was 0.801 for male and 0.773 for female. The results of this study showed that PhA was highly related to SMI, which can indicate the quantity of skeletal muscle in the entire body, and was highly related to SMD, which can be used to assess skeletal muscle quality. Therefore, PhA may be a useful bioelectrical marker for skeletal muscle quantity and quality.

The role of branched chain amino acids metabolic disorders in tumorigenesis and progression.

Branched-chain amino acids (BCAAs) are essential amino acids in human bodies. They have complex metabolic pathways and various metabolites. Both BCAAs and its metabolites are involved in various processes such as protein anabolism and catabolism, energy supply, signaling transduction and so on. Previous studies have observed the widely alternations of BCAAs and its related proteins in multiple tumor phenotypes, which suggests that BCAAs metabolic disorders may have emerged as a powerful factor for tumor metabolism reprogramming. BCAAs metabolism has a pivotal role in tumorigenesis and progression, including cell growth, proliferation, migration, invasion, and so on. In this review, we try to shed light on the crucial role of BCAAs metabolic disorders in different tumor types by focusing on the impacts of metabolic disorders of BCAAs and discussing the notable proteins involved in cancer metabolic reprogramming of BCAAs, such as BCAT1/2, BCKDH-BCKDK-PPM1K complex, transporters of BCAAs and its metabolites, transcription factors and so on, and present several possible diagnose approaches and therapies to BCAAs-related cancers.

Transcriptomic and Phenomic Investigations Reveal Elements in Biofilm Repression and Formation in the Cyanobacterium Synechococcus elongatus PCC 7942.

Biofilm formation by photosynthetic organisms is a complex behavior that serves multiple functions in the environment. Biofilm formation in the unicellular cyanobacterium Synechococcus elongatus PCC 7942 is regulated in part by a set of small secreted proteins that promotes biofilm formation and a self-suppression mechanism that prevents their expression. Little is known about the regulatory and structural components of the biofilms in PCC 7942, or response to the suppressor signal(s). We performed transcriptomics (RNA-Seq) and phenomics (RB-TnSeq) screens that identified four genes involved in biofilm formation and regulation, more than 25 additional candidates that may impact biofilm formation, and revealed the transcriptomic adaptation to the biofilm state. In so doing, we compared the effectiveness of these two approaches for gene discovery.

Effect of colchicine on inflammatory markers in patients with coronary artery disease: A meta-analysis of clinical trials.

Whether colchicine reduces the levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) remains uncertain. Therefore, this systematic review and meta-analysis were conducted to evaluate the overall effect of colchicine treatment on hs-CRP and IL-6 levels in patients with coronary artery disease (CAD). PubMed/Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published before October 2021. Clinical trials in patients with CAD with reports of hs-CRP and IL-6 level changes before and after colchicine intervention were included. In total, 11 trials on hs-CRP and two trials on IL-6 were included in this meta-analysis. Compared with that in the control group, colchicine treatment was significantly associated with decreased hs-CRP levels (weighted mean differences [WMDs], -0.81 mg/L; 95% confidence interval [CI], -1.34 to -0.28 mg/L; P = 0.003) in patients with CAD. Besides, the levels of IL-6 were significantly reduced in colchicine users compared to that of placebo (WMD, -1.28 pg/mL; 95% CI, -2.35 to -0.21 pg/mL; P = 0.02). In a subgroup analysis, colchicine led to a significant reduction in hs-CRP levels in studies with duration of intervention >7 days (WMD, -0.65 mg/L; 95% CI, -1.08 to -0.21 mg/L; P = 0.004) and studies with baseline hs-CRP levels ≥3.0 mg/L (WMD, -0.99 mg/L; 95% CI, -1.92 to -0.06 mg/L; P = 0.04). Colchicine intervention was associated with a reduction in hs-CRP and IL-6 levels in patients with CAD. Future investigations are required to verify the effect of colchicine on inflammatory markers and clarify the potential mechanisms of the cross talk between colchicine, inflammation, and cardiovascular outcomes.

Outcome Analysis of Transition From Peritoneal Dialysis to Hemodialysis: A Population-Based Study.

If a technical failure occurs during peritoneal dialysis (PD), the patients undergoing PD may be transitioned to hemodialysis (HD). However, the clinical outcomes of patients who have undergone such a transition are under studied. This study assessed whether patients undergoing HD who have transitioned from PD have the same clinical outcomes as HD-only patients. This research was a retrospective cohort study by searching a National Health Insurance research database for data on patients in Taiwan who had undergone HD between January 2006 and December 2013. The patients were divided into two groups, namely a case group in which the patients were transitioned from PD to HD and a HD-only control group, through propensity score matching at a ratio of 1:4 (n = 1,100 vs. 4,400, respectively). We used the Cox regression model to estimate the hazard ratios (HRs) for all-cause death, all-cause hospitalization, infection-related admission, and major adverse cardiac events (MACE). Those selected patients will be followed until death or the end of the study period (December, 2017), whichever occurs first. Over a mean follow-up of 3.2 years, 1,695 patients (30.8%) died, 3,825 (69.5%) required hospitalization, and 1,142 (20.8%) experienced MACE. Patients transitioning from PD had a higher risk of all-cause death (HR: 1.36; 95% CI: 1.21-1.53) than HD-only patients. However, no significant difference was noted in terms of MACE (HR: 0.91; 95% CI: 0.73-1.12), all-cause hospitalization (HR: 1.07; 95% CI: 0.96-1.18), or infection-related admission (HR: 0.97, 95% CI: 0.80-1.18) between groups. Because of the violation of the proportional hazard assumption, the piecewise-HRs showed that the risk of mortality in the case group was significant within 5 months of the transition (HR: 2.61; 95% CI: 2.04-3.35) not in other partitions of the time axis. In conclusion, patients undergoing HD who transitioned from PD had a higher risk of death than the HD-only patients, especially in the first 5 months after transition (a 161% higher risk). Therefore, more caution and monitoring may be required for patients undergoing HD who transitioned from PD.

Comparative Genomics of Synechococcus elongatus Explains the Phenotypic Diversity of the Strains.

Strains of the freshwater cyanobacterium Synechococcus elongatus were first isolated approximately 60 years ago, and PCC 7942 is well established as a model for photosynthesis, circadian biology, and biotechnology research. The recent isolation of UTEX 3055 and subsequent discoveries in biofilm and phototaxis phenotypes suggest that lab strains of S. elongatus are highly domesticated. We performed a comprehensive genome comparison among the available genomes of S. elongatus and sequenced two additional laboratory strains to trace the loss of native phenotypes from the standard lab strains and determine the genetic basis of useful phenotypes. The genome comparison analysis provides a pangenome description of S. elongatus, as well as correction of extensive errors in the published sequence for the type strain PCC 6301. The comparison of gene sets and single nucleotide polymorphisms (SNPs) among strains clarifies strain isolation histories and, together with large-scale genome differences, supports a hypothesis of laboratory domestication. Prophage genes in laboratory strains, but not UTEX 3055, affect pigmentation, while unique genes in UTEX 3055 are necessary for phototaxis. The genomic differences identified in this study include previously reported SNPs that are, in reality, sequencing errors, as well as SNPs and genome differences that have phenotypic consequences. One SNP in the circadian response regulator rpaA that has caused confusion is clarified here as belonging to an aberrant clone of PCC 7942, used for the published genome sequence, that has confounded the interpretation of circadian fitness research. IMPORTANCE Synechococcus elongatus is a versatile and robust model cyanobacterium for photosynthetic metabolism and circadian biology research, with utility as a biological production platform. We compared the genomes of closely related S. elongatus strains to create a pangenome annotation to aid gene discovery for novel phenotypes. The comparative genomic analysis revealed the need for a new sequence of the species type strain PCC 6301 and includes two new sequences for S. elongatus strains PCC 6311 and PCC 7943. The genomic comparison revealed a pattern of early laboratory domestication of strains, clarifies the relationship between the strains PCC 6301 and UTEX 2973, and showed that differences in large prophage regions, operons, and even single nucleotides have effects on phenotypes as wide-ranging as pigmentation, phototaxis, and circadian gene expression.