Recent knowledge in phages, phage-encoded endolysin, and phage encapsulation against foodborne pathogens.

The use of antibiotics had reached a plateau due to antibiotic resistance, overuse, and residue. Bacteriophages have recently attracted considerable attention as alternative biocontrol agents. Here, we provide an up-to-date overview of phage applications in the food industry. We reviewed recently reported phages against ten typical foodborne pathogens, studies of competitive phage-encoded endolysins, and the primary outcomes of phage encapsulation in food packaging and pathogen detection. Furthermore, we identified existing barriers that still need to be addressed and proposed potential solutions to overcome these obstacles in the future.

Risk Stratification and Efficacy of Spironolactone in Patients with Heart Failure with Preserved Ejection Fraction: Secondary Analysis of the TOPCAT Randomized Clinical Trial.

PURPOSE: We aimed to develop a simple risk score for patients with HFpEF and assessed the efficacy of spironolactone across baseline risk. METHODS: We developed risk stratification scheme for cardiovascular death in placebo arm of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT). We screened candidate risk indicators and determined strong risk predictors using COX regression. The absolute risk reduction (ARR) in cardiovascular death with spironolactone was evaluated across baseline risk groups. COX regressions were performed to assess the hazard ratios (HRs) of spironolactone therapy for cardiovascular death and drug discontinuation in each risk category. RESULTS: A simple risk score scheme was constructed based on five risk indicators weighted by estimates from the model, including age, diastolic blood pressure, renal dysfunction, white blood cell, and left ventricular ejection fraction. The risk score scheme showed good discrimination in placebo cohort (C index=0.70). ARR with spironolactone therapy was observed only in patients at very high risk (7.9%). Spironolactone therapy significantly reduced the risk of cardiovascular death in the very high-risk group (HR: 0.57; 95%CI, 0.39-0.84; P =0.005 and P for interaction 0.03) but showed similar risk of drug discontinuation across risk categories (P for interaction=0.928). CONCLUSION: This simple risk score stratifies patients with HFpEF by their baseline risk of cardiovascular death. Patients at very high risk derive great benefits from spironolactone therapy. This easy-to-use risk score provides a practical tool that can facilitate risk stratification and tailoring therapy for those who benefit most from spironolactone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00094302.

Wheat Flour-Based Edible Films: Effect of Gluten on the Rheological Properties, Structure, and Film Characteristics.

This work investigates the structure, rheological properties, and film performance of wheat flour hydrocolloids and their comparison with that of a wheat starch (WS)-gluten blend system. The incorporation of gluten could decrease inter-chain hydrogen bonding of starch, thereby reducing the viscosity and solid-like behavior of the film-forming solution and improving the frequency-dependence, but reducing the surface smoothness, compactness, water vapor barrier performance, and mechanical properties of the films. However, good compatibility between starch and gluten could improve the density of self-similar structure, the processability of the film-forming solution, and film performance. The films based on wheat flours showed a denser film structure, better mechanical properties, and thermal stability that was no worse than that based on WS-gluten blends. The knowledge gained from this study could provide guidance to the development of other flour-based edible packaging materials, thereby promoting energy conservation and environmental protection.

Interfacial characteristics and in vitro digestion of emulsion coated by single or mixed natural emulsifiers: lecithin and/or rice glutelin hydrolysates.

BACKGROUND: The interfacial characteristics and in vitro digestion of emulsion were related to emulsifier type. The mean droplet diameter, ζ-potential, microstructure, interfacial tension, Quartz crystal microbalance with dissipation (QCM-D) and in vitro gastrointestinal fate of emulsions stabilized by soybean lecithin, hydrolyzed rice glutelin (HRG) and their mixture were researched. RESULTS: The value of interfacial tension was much more dramatically declined for the sample containing 20 g kg-1 of HRG. For QCM-D, a rigid layer was formed for all the samples after rinsing. The layer thickness was 0.87 ± 0.20, 2.11 ± 0.31 and 2.63 ± 0.22 nm, and adsorbed mass was 87.17 ± 10.31, 210.56 ± 20.12 and 263.09 ± 23.23 ng cm-2 , for HRG, lecithin and HRG/lecithin, respectively, indicating both HRG and lecithin were adsorbed at the oil-water interface. Structural rearrangements at the interface occurred for HRG/lecithin. The kinetics and final amount of lipid digestion depended on emulsifier type: lecithin > HRG/lecithin > HRG. These differences in digestion rate were primarily due to differences in the aggregation state of the emulsifiers. CONCLUSION: The incorporation of lecithin into HRG emulsions had better interfacial properties comparing with HRG emulsion and facilitated lipid digestibility. These results provide important information for the rational design of plant-based functional food. © 2021 Society of Chemical Industry.

Behavioral Factors Mediating the Impact of Educational Attainment on Incident Heart Failure　- A Mediation Analysis.

BACKGROUND: To examine the association of low educational attainment with incident heart failure (HF) and explore potential behavioral mediators of the causal pathway.Methods and Results:A total of 12,109 participants in the Atherosclerosis Risk in Communities Study (ARIC) were included. Educational attainment was measured at baseline, and the risk of HF across educational attainment groups was assessed by Cox proportional hazards models. Using mediation analysis, we evaluated the mediating role of behavioral factors in the causal pathway between educational attainment and HF. During a median follow-up of 25.1 years, 2,407 cases (19.9%) of HF occurred. Educational attainment showed an inverse association with HF risk (hazard ratio (HR), 1.41; 95% confidence interval (CI), 1,26-1.57 for low educational attainment; HR, 1.13; 95% CI, 1.02-1.25 for medium educational attainment). In the mediation analysis, the association between educational attainment and HF was partially mediated by income, waist-to-hip ratio, current smoking, body mass index, current drinking, sports and physical activity, which explained 24.3%, 20.2%, 13.8%, 10.1%, 7.7%, 7.3% and 4.5%, respectively, of the relationship. In total, all mediators contributed 56.3% of the total effect. CONCLUSIONS: Low educational attainment was associated with increased risk for HF. Income, obesity and current smoking mediated a great proportion of the total effect of educational attainment on HF. Our results provide underlying insights for the development of targeted public health interventions to reduce educational disparities on HF incidence.

Correlation between C9ORF72 mutation and neurodegenerative diseases: A comprehensive review of the literature.

Chromosome 9 open reading frame 72 (C9ORF72) encodes a 54-kDa protein with unknown function that is expressed at high levels in the central nervous system. The C9ORF72 hexanucleotide amplification is one of the most recently discovered repetitive amplification diseases related to neurodegeneration. Its association with amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) spectrum diseases has been fully established, although a causative role for C9ORF72 in Alzheimer's disease (AD) and Parkinson's disease (PD) remains to be established. Therefore, in this article, we will review the evidence for C9ORF72 as a causative factor in neurodegenerative diseases, the underlying mechanisms, and the potential for targeting C9ORF72 as a strategy to alleviate neurodegenerative disease progression.

Impact of RAAS Blockers on Contrast-Induced Nephropathy in Patients With Renal Insufficiency: A Meta-Analysis.

The effect of renin-angiotensin-aldosterone system (RAAS) blockers [angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers] on Contrast-induced nephropathy (CIN) is unclear in patients with renal insufficiency. Thus, we conduct a meta-analysis to evaluate the association between the administration of RAAS blockers and CIN in patients with renal insufficiency. We searched PubMed, EMBASE, and Cochrane Library for relevant studies published before September 2019. The primary outcome was the incidence of CIN, and the secondary outcome was the changes in serum creatinine (SCr) from baseline to postprocedure (ΔSCr). Pooled odds ratio (OR) or weighted mean difference (WMD) with their 95% confidence interval (CIs) for the CIN incidence, ΔSCr were used to calculate original data. A total of 8 studies were included in the meta-analysis. Compared with controls, ACEI/angiotensin receptor blocker increased the risk of CIN (OR = 1.61, 95% CI 1.14-2.28, I = 30%; P = 0.007), whereas this association was not significant in Chinese patients (OR = 1.07, 95% CI 0.65-1.77, I = 19%, P = 0.79). The total weighted mean differences of the ΔSCr were 0.06 mg/dL (95% CI: 0.01-0.11, I = 82%; P = 0.03). Administration of RAAS blockers in patients with renal insufficiency was associated with a significantly higher incidence of CIN, whereas it did not show a significant effect on Chinese patients.

Enhancing pea protein isolate functionality: A comparative study of high-pressure homogenization, ultrasonic treatment, and combined processing techniques.

Pea protein has attracted widespread attention due to its high nutritional value, low allergenicity, non-GMO status, and broad availability. However, compared to animal proteins, pea protein has inferior functional properties, which limits its application in the food industry. This study used pea protein isolate (PPI) as the main raw material and investigated the effects of high-pressure homogenization (HPH), ultrasonic treatment (US), and the combination of the two in different orders on the structure and function of PPI. The results showed that HPH or US promoted the transformation of PPI insoluble suspension into a uniform protein dispersion, significantly reducing particle size, unfolding the spatial structure, exposing more amino acid residues. These structural changes resulted in a substantial increase in the solubility, foaming capacity and emulsifying activity of PPI. Moreover, the combined treatments further impacted the properties of PPI, largely depending on the order of the processing steps; the combination of HPH-US exhibited the best functional characteristics.

A novel contact optimization algorithm for endomicroscopic surface scanning.

PURPOSE: Probe-based confocal laser endomicroscopy (pCLE) offers real-time, cell-level imaging and holds promise for early cancer diagnosis. However, a large area surface scanning for image acquisition is needed to overcome the limitation of field-of-view. Obtaining high-quality images during scanning requires maintaining a stable contact distance between the tissue and probe. This work presents a novel contact optimization algorithm to acquire high-quality pCLE images. METHODS: The contact optimization algorithm, based on swarm intelligence of whale optimization algorithm, is designed to optimize the probe position, according to the quality of the image acquired by probe. An accurate image quality assessment of total co-occurrence entropy is introduced to evaluate the pCLE image quality. The algorithm aims to maintain a consistent probe-tissue contact, resulting in high-quality images acquisition. RESULTS: Scanning experiments on sponge, ex vivo swine skin tissue and stomach tissue demonstrate the effectiveness of the contact optimization algorithm. Scanning results of the sponge with three different trajectories (spiral trajectory, circle trajectory, and raster trajectory) reveal high-quality mosaics with clear details in every part of the image and no blurred sections. CONCLUSION: The contact optimization algorithm successfully identifies the optimal distance between probe and tissue, improving the quality of pCLE images. Experimental results confirm the high potential of this method in endomicroscopic surface scanning.

Development of pea protein nanoparticle/hydrolyzed rice glutelin fibril emulsion gels for encapsulation of curcumin.

The potential of using emulsion gels stabilized by binary plant protein nanoparticle mixtures for the encapsulation and delivery of lipophilic nutraceuticals was evaluated. The particle characteristics, physical stability, water diffusivity, microrheology, large amplitude oscillating shear (LAOS) properties, and in vitro digestion of emulsion gels prepared by different ratios of hydrolyzed rice glutelin fibrils (HRGFs) and pea protein nanoparticle (PNP) were characterized. The emulsion gel with P/H = 2:1 (0.84 µm) exhibited the best storage stability and freeze-thaw stability, as seen by the smaller oil droplet size (1.02 and 1.42 µm, respectively). Low-field pulsed NMR indicated that the majority of water in samples was highly mobile. All the samples were predominantly elastic-like materials. The P/H 2:1 emulsion gel had the lowest FI value (6.21 × 10-4 Hz), the highest MVI value (5.57 s/nm2), G'/ G″ values and enclosed area, showing that it had denser 3D network structures, higher stiffness values, and a high sensitivity to changes in strain. Additionally, P/H 2:1 emulsion gel had a relatively high lipid digestibility (96.1 %), curcumin bioaccessibility (58.9 %), and curcumin stability (94.2 %). This study showed that emulsion gels stabilized by binary protein nanoparticle mixtures (PNP/HRGF) have potential as edible delivery systems for lipophilic nutraceuticals.

Tailoring hydroxypropyl starch films with curdlan for enhanced properties for edible packaging.

Hydroxypropyl starch-based composite system has high potential for many applications such as food packaging and biomedical fields. Here, how the incorporation of curdlan, a thermo-irreversible heating-set gel, tailors the processability, structure, and film performance of hydroxypropyl starch, a cooling-set gel, has been systematically investigated, aiming to achieve enhanced material properties favorable for edible packaging applications. Curdlan incorporation increased the shear-thinning behavior and viscosity of hydroxypropyl starch solution, which was also strongly affected by temperature. The miscibility and comparability between the two polymers with distinct gelation behaviors is a practical and interesting scientific topic. Scanning electron microscopy, dynamic mechanical analysis, and thermogravimetric analysis all indicated good compatibility between hydroxypropyl starch and curdlan. There was no observable phase boundary between the two materials, and all composite films showed only a single relaxation peak and only one polymer thermal decomposition peak. This resulted in improved structural density and overall performance. Compared with pure HPS film, the 7:3 HPS/CD film showed increases in tensile strength by 66.12 % and thermal decomposition temperature by 3 °C, and a reduction in water solubility by 11.72 %. This knowledge gained here may facilitate the development of edible films based on hydroxypropyl starch with satisfying film performance and processability.

The gut microbe-derived metabolite trimethylamine-N-oxide induces aortic valve fibrosis via PERK/ATF-4 and IRE-1α/XBP-1s signaling in vitro and in vivo.

BACKGROUND AND AIMS: The gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) has been implicated in the development of cardiovascular fibrosis. Endoplasmic reticulum (ER) stress occurs after the dysfunction of ER and its structure. The three signals PERK/ATF-4, IRE-1α/XBP-1s and ATF6 are activated upon ER stress. Recent reports have suggested that the activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling contributes to cardiovascular fibrosis. However, whether TMAO mediates aortic valve fibrosis by activating PERK/ATF-4 and IRE-1α/XBP-1s signaling remains unclear. METHODS: Human aortic valve interstitial cells (AVICs) were isolated from aortic valve leaflets. PERK IRE-1α, ATF-4, XBP-1s and CHOP expression, and production of collagen Ⅰ and TGF-ß1 were analyzed following treatment with TMAO. The role of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in TMAO-induced fibrotic formation was determined using inhibitors and small interfering RNA. RESULTS: Diseased valves produced greater levels of ATF-4, XBP-1, collagen Ⅰ and TGF-ß1. Interestingly, diseased cells exhibited augmented PERK/ATF-4 and IRE-1α/XBP-1s activation after TMAO stimulation. Inhibition and silencing of PERK/ATF-4 and IRE-1α/XBP-1s each resulted in enhanced suppression of TMAO-induced fibrogenic activity in diseased cells. Mice treated with dietary choline supplementation had substantially increased TMAO levels and aortic valve fibrosis, which were reduced by 3,3-dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) treatment. Moreover, a high-choline and high-fat diet remodeled the gut microbiota in mice. CONCLUSIONS: TMAO promoted aortic valve fibrosis through activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in vitro and in vivo. Modulation of diet, gut microbiota, TMAO, PERK/ATF-4 and IRE1-α/XBP-1s may be a promising approach to prevent aortic valve fibrosis.

Serum Klotho Modifies the Associations of 25-Hydroxy Vitamin D With All-Cause and Cardiovascular Mortality.

BACKGROUND: The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults. METHODS: A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality. RESULTS: We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P = .028). With klotho > 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho < 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D < 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI, .97-.99; HR, 0.98; 95% CI, .98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75). CONCLUSIONS: Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency.

New Insights into Rate Control: Time in Target Range of Resting Heart Rate and Major Adverse Outcomes in Atrial Fibrillation.

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.

Cardiovascular effects of weight loss in old adults with overweight/obesity according to change in skeletal muscle mass.

BACKGROUND: Patients with overweight/obesity and type 2 diabetes are encouraged to lose weight, but not all losing weight gain better cardiovascular health, especially old adults. The change in skeletal muscle mass (SMM) could be the key that explains the heterogenous cardiovascular effects of weight loss. This study aims to assess whether the cardiovascular effects of weight loss vary for those gaining skeletal muscle along with weight loss. METHODS: The old adults with overweight/obesity and type 2 diabetes in the Look AHEAD study having muscle measurement from dual-energy X-ray absorptiometry were included. Based on the weight change (WC) and SMM change (SMMC) between baseline and the 4-year follow-up, participants were allocated into three groups-weight gain (WG) group, weight loss with muscle loss (WL-ML) group and weight loss with muscle gain (WL-MG) group. Cox proportional hazards regression was performed to evaluate the cardiovascular risk of those gaining or losing SMM with weight loss compared with those gaining weight. Among the participants with weight loss, the ratio of SMMC/WC was calculated, and the association of SMMC/WC with primary cardiovascular outcome was assessed. RESULTS: A total of 491 participants were included in the study with an average age of 64.56 ± 3.81 years old. A total of 47.0% were male and 49.9% were from the intensive lifestyle intervention arm. Based on their WC and SMMC, 43 were assigned to the WG group, 373 to the WL-ML group and 75 to the WL-MG group. Over a follow-up of almost 10 years, 97 participants encountered the primary endpoint. The WG group had the highest incidence of 25.59%, the WL-MG group had the lowest incidence of 9.33% and the WL-ML group had 21.18% (P = 0.040). In the fourth adjusted Cox model, the WL-MG group achieved significantly decreased odds of the primary endpoint compared with the WG group (hazard ratio [HR] 0.33, 95% confidence interval [CI] [0.12, 0.87], P = 0.026), whilst the WL-ML group did not (HR 0.91, 95% CI [0.47, 1.78], P = 0.670). Among the participants with weight loss, when SMMC/WC reached around 50%, this HR soared to approximately two-fold. CONCLUSIONS: The participants gaining SMM along with weight loss achieved the lowest odds of adverse cardiovascular events, whilst those who lost SMM along with weight loss had comparable cardiovascular risk with those gaining weight. The more muscle lost during weight loss, the greater the harm. The cardiovascular effects of weight loss were modulated by whether the participants gained SMM meanwhile losing weight.

Flexible endoscopic instrument for diagnosis and treatment of early gastric cancer.

Gastric cancer is a common cancer endangering human life and health worldwide. Early detection and diagnosis of gastric cancer that is normally performed by flexible endoscope can significantly improve the survival rate of patients. However, current endoscopic instruments have some problems, such as limitation of degrees of freedom (DOFs) and lack of surgical triangulation. Meanwhile, the lack of an intraoperative technique for the real-time evaluation of early gastric cancer is also a serious problem. To solve these problems, we have developed a dual-bending flexible endoscopic instrument for the diagnosis and treatment of early gastric cancer. This instrument has a compact structure with a maximum outer diameter of 3 mm and an insertion length of 1220 mm. It has 5 DOFs with a dual-bending function, which can form a surgical operation triangulation to easily perform the endoscopic procedure. Apart from the surgical forceps, the end of the instrument can be equipped with different endoscopic devices to meet the needs of diagnosis and treatment, such as endomicroscopic probes, electrosurgical knives, and laser ablation optical fibers. It is verified that the instrument can carry these devices to complete corresponding tasks, demonstrating the great potential of this instrument in clinical applications.

Hydrogen-Rich Water Treatment of Fresh-Cut Kiwifruit with Slightly Acidic Electrolytic Water: Influence on Antioxidant Metabolism and Cell Wall Stability.

The synergistic impact of hydrogen-rich water (HRW, 394 ppb) and slightly acidic electrolyzed water (SAEW, pH of 6.25 ± 0.19) on the antioxidant metabolism of fresh-cut kiwifruit during storage was investigated (temperature: (3 ± 1) °C, humidity: 80%-85%). Compared with control group, H+S treatment increased the contents of active oxygen-scavenging enzymes (SOD, CAT, POD, and APX) and inhibited the increase of O2•- and H2O2 contents during the storage of fresh-cut kiwifruit. Meanwhile, H+S treatment could reduce the activities of the cell wall-degrading enzymes PG, PME, PL, Cx, and ß-Gal, inhibit the formation of soluble pectin, delay the degradation rate of propectin, cellulose, and pseudocellulose, and maintain higher fruit hardness and chewability. The results showed that H+S treatment could enhance free radical scavenging ability and reduce the cell wall metabolism of fresh-cut kiwifruit, maintaining the good texture found in fresh-cut fruit.

Diversity of the protease-producing bacteria and their extracellular protease in the coastal mudflat of Jiaozhou Bay, China: in response to clam naturally growing and aquaculture.

The booming mudflat aquaculture poses an accumulation of organic matter and a certain environmental threat. Protease-producing bacteria are key players in regulating the nitrogen content in ecosystems. However, knowledge of the diversity of protease-producing bacteria in coastal mudflats is limited. This study investigated the bacterial diversity in the coastal mudflat, especially protease-producing bacteria and their extracellular proteases, by using culture-independent methods and culture-dependent methods. The clam aquaculture area exhibited a higher concentration of carbon, nitrogen, and phosphorus when compared with the non-clam area, and a lower richness and diversity of bacterial community when compared with the clam naturally growing area. The major classes in the coastal mud samples were Bacteroidia, Gammaproteobacteria, and Alphaproteobacteria. The Bacillus-like bacterial community was the dominant cultivated protease-producing group, accounting for 52.94% in the non-clam area, 30.77% in the clam naturally growing area, and 50% in the clam aquaculture area, respectively. Additionally, serine protease and metalloprotease were the principal extracellular protease of the isolated coastal bacteria. These findings shed light on the understanding of the microbes involved in organic nitrogen degradation in coastal mudflats and lays a foundation for the development of novel protease-producing bacterial agents for coastal mudflat purification.

Effect of intensive lifestyle intervention on the association between weight variability and major adverse cardiovascular events in overweight or obese adults with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Weight variability is associated with cardiovascular outcomes in diabetic patients. However, whether the guideline-recommended intensive lifestyle intervention (ILI) will affect this association in overweight or obese adults with diabetes is not well established. MATERIALS AND METHODS: In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, the associations of 4 year weight variability measured by variability independent of the mean (VIM) with major adverse cardiovascular event (MACE) and secondary outcomes in ILI and diabetes support & education (DSE) arm were evaluated. RESULTS: During a median follow-up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23-fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51-3.30). Compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were associated with higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20-2.95), all-cause mortality (HR 3.19; 95% CI 1.75-5.82), and myocardial infarction (HR 1.95; 95% CI 1.12-3.37) in the DSE arm. CONCLUSIONS: Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm. Therefore, a guideline-recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without worrying about the effect of weight fluctuations.

Effect of blood pressure index on clinical outcomes in patients with heart failure and chronic kidney disease.

AIMS: This study aimed to assess the effect of blood pressure (BP) index, in terms of level and variability, on the progression of cardiovascular and renal diseases in patients with both heart failure (HF) and chronic kidney disease (CKD). METHODS AND RESULTS: The study involved patients with HF and CKD from the database of the Chronic Renal Insufficiency Cohort (CRIC) study. The study endpoint includes the following: (i) primary endpoint, including cardiovascular disease (CVD) events, renal events, and all-cause death; (ii) CVD events; (iii) renal events; and (iv) all-cause death. Among 3939 participants in the CRIC study, a total of 382 patients were included. The duration of the follow-up was 6.3 ± 2.7 years, the age was 60.2 ± 8.9 years, and 57.6% were male. BP index included 20 indicators in relation to BP level and variability, 4 of which were analysed including baseline systolic BP (SBP), standard deviation of SBP, coefficient of variation of diastolic BP (DBP CV), and average real variability of pulse pressure. In the Cox regression analysis after adjustment, baseline SBP was significant for the risk of primary endpoint [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.03-1.44, P = 0.02] and renal events (HR 1.54, 95% CI 1.22-1.95, P < 0.001), and DBP CV was significant for the risk of primary endpoint (HR 1.03, 95% CI 1.01-1.06, P = 0.02) and CVD events (HR 1.04, 95% CI 1.02-1.07, P < 0.01). The result of the forest plot depicted that baseline SBP had a linear association with the risk of CVD and renal events (P = 0.04 and 0.001, respectively) and DBP CV with CVD events (P = 0.02). As the restricted cubic spline models displayed, DBP CV featured a J- or L-curved association with the primary endpoint, renal events, and all-cause death (P for nonlinearity = 0.01, <0.001, and 0.01, respectively). CONCLUSIONS: The baseline SBP and DBP CV may remain significant for clinical outcomes in patients with both HF and CKD. The increase in baseline SBP is associated with a higher risk of primary endpoint, CVD events, and renal events, and the increase in DBP CV with a higher risk of CVD events. Concerning nonlinear association, DBP CV features a J- or L-curved relationship with the primary endpoint, renal events, and all-cause death, with a higher risk at both low and high values. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov; unique identifier: NCT00304148.