Expression of a novel hydrolase MhpC in Brevibacillus parabrevis BCP-09 and its characteristics for degrading synthetic pyrethroids.

Synthetic pyrethroids are widely used insecticides which may cause chronic diseases in non-target organisms upon long-term exposure. Microbial degradation offers a reliable method to remove them from the environment. This study focused on Brevibacillus parabrevis BCP-09 and its enzymes for degrading pyrethroids. The predicted deltamethrin-degrading genes phnA and mhpC were used to construct recombinant plasmids. These plasmids, introduced into Escherichia coli BL21(DE3) cells and induced with L-arabinose. The results indicated that the intracellular crude enzyme efficiently degraded deltamethrin by 98.8 %, ß-cypermethrin by 94.84 %, and cyfluthrin by 73.52 % within 24 h. The hydrolytic enzyme MhpC possesses a catalytic triad Ser/His/Asp and a typical "Gly-X-Ser-X-Gly" conservative sequence of the esterase family. Co-cultivation of induced E. coli PhnA and E. coli MhpC resulted in degradation rates of 41.44 ± 3.55 % and 60.30 ± 4.55 %, respectively, for deltamethrin after 7 d. This study states that the degrading enzymes from B. parabrevis BCP-09 are an effective method for the degradation of pyrethroids, providing available enzyme resources for food safety and environmental protection.

Quantitative proteomic analysis reveals the mechanism and key esterase of ß-cypermethrin degradation in a bacterial strain from fermented food.

Beta-cypermethrin (ß-CY) residues in food are an important threat to human health. Microorganisms can degrade ß-CY residues during fermentation of fruits and vegetables, while the mechanism is not clear. In this study, a comprehensively investigate of the degradation mechanism of ß-CY in a food microorganism was conducted based on proteomics analysis. The ß-CY degradation bacteria Gordonia alkanivorans GH-1 was derived from fermented Pixian Doubanjiang. Its crude enzyme extract could degrade 77.11% of ß-CY at a concentration of 45 mg/L within 24 h. Proteomics analysis revealed that the ester bond of ß-CY is broken under the action of esterase to produce 3-phenoxy benzoic acid, which was further degraded by oxidoreductase and aromatic degrading enzyme. The up-regulation expression of oxidoreductase and esterase was confirmed by transcriptome and quantitative reverse transcription PCR. Meanwhile, the expression of esterase Est280 in Escherichia coli BL21 (DE3) resulted in a 48.43% enhancement in the degradation efficiency of ß-CY, which confirmed that this enzyme was the key enzyme in the process of ß-CY degradation. This study reveals the degradation mechanism of ß-CY by microorganisms during food fermentation, providing a theoretical basis for the application of food microorganisms in ß-CY residues.

Enhancing the Quality of Low-Alcohol Navel Orange Wine through Simultaneous Co-Fermentation Using Saccharomyces cerevisiae SC-125, Angel Yeast SY, and Lactiplantibacillus plantarum BC114.

To date, there has been limited research on the interactive effects of yeast and lactic acid bacteria (LAB) on the sensory qualities of navel orange wine. In this study, using Jintang navel orange juice as the raw material, multi-microbial fermentation was conducted with Saccharomyces cerevisiae SC-125 and Angel yeast SY, as well as Lactiplantibacillus plantarum BC114. Single yeast and co-fermentation with Lactiplantibacillus plantarum were used as the control groups. The research aimed to investigate the physicochemical parameters of navel orange wine during fermentation. Additionally, headspace solid-phase microextraction gas chromatography-mass spectrometry (HP-SPME-GC-MS) was employed to determine and analyze the types and levels of flavor compounds in the navel orange wines produced through the different fermentation methods. The co-fermentation using the three strains significantly enhanced both the quantity and variety of volatile compounds in the navel orange wine, concomitant with heightened total phenol and flavonoid levels. Furthermore, a notable improvement was observed in the free radical scavenging activity. A sensory evaluation was carried out to analyze the differences among the various navel orange wines, shedding light on the impact of different wine yeasts and co-fermentation with LAB on the quality of navel orange wines.

Clinical finite element analysis of mandibular displacement model treated with Twin-block appliance.

INTRODUCTION: The mechanical distribution of the mandible is an important factor that affects functional orthosis during Twin-block (TB) appliance correction. Changes in the mandible before and after TB appliance correction are also key factors in maintaining the therapeutic effect. Finite element analysis, a powerful numerical, analytical tool, is widely used to predict the stress and strain distribution of the craniofacial bone that orthodontics generates. METHODS: The sample was a 14-year-old male patient with Class II malocclusion during growth. A cone-beam computed tomography scan was undertaken at pretreatment and posttreatment. In the Finite element analysis of the pretreatment model, the remote displacement model of the mandible was established with the sella point as the center. A mandibular model under TB appliance loading was established. Its mandibular displacement and von Mises stress were compared before and after loading. Three-dimensional registration was conducted on the pretreatment and posttreatment models to measure the sagittal displacement of the centrosome. RESULTS: The force on the mandible occurred mainly in the condyle neck and medial mandible after the TB appliance moved the mandible. After displacement, the posterior upper margin of the condyle was farther away from the articular fossa. Three-dimensional registration results showed that new bone had formed behind and above the condyle after TB appliance treatment. CONCLUSION: The TB appliance provides additional advantages in treating skeletal Class II malocclusions by helping to reduce the burden on the temporomandibular joint and promoting the adaptive reconstruction of the mandible.

Synthesis of Liquid Gallium@Reduced Graphene Oxide Core-Shell Nanoparticles with Enhanced Photoacoustic and Photothermal Performance.

This report presents nanoparticles composed of a liquid gallium core with a reduced graphene oxide (RGO) shell (Ga@RGO) of tunable thickness. The particles are produced by a simple, one-pot nanoprobe sonication method. The high near-infrared absorption of RGO results in a photothermal energy conversion of light to heat of 42.4%. This efficient photothermal conversion, combined with the large intrinsic thermal expansion coefficient of liquid gallium, allows the particles to be used for photoacoustic imaging, that is, conversion of light into vibrations that are useful for imaging. The Ga@RGO results in fivefold and twofold enhancement in photoacoustic signals compared with bare gallium nanoparticles and gold nanorods (a commonly used photoacoustic contrast agent), respectively. A theoretical model further reveals the intrinsic factors that affect the photothermal and photoacoustic performance of Ga@RGO. These core-shell Ga@RGO nanoparticles not only can serve as photoacoustic imaging contrast agents but also pave a new way to rationally design liquid metal-based nanomaterials with specific multi-functionality for biomedical applications.

Viral and bacterial community responses to stimulated Fe(III)-bioreduction during simulated subsurface bioremediation.

The delivery of fermentable substrate(s) to subsurface environments stimulates Fe(III)-bioreduction and achieves detoxification of organic/inorganic contaminants. Although, much research has been conducted on the microbiology of such engineered systems at lab and field scales, little attention has been given to the phage-host interactions and virus community dynamics in these environments. The objective was to determine the responses of soil bacterial communities and viral assemblages to stimulated anaerobic Fe(III)-bioreduction following electron donor (e.g. acetate) addition. Microbial communities, including viral assemblages, were investigated after 60 days of Fe(III)-bioreduction in laboratory-scale columns continuously fed with acetate-amended artificial groundwater. Viral abundances were greatest in the influent section and decreased along the flow path. Acetate availability was important in influencing bacterial diversity, microbial interactions and viral abundance and community composition. The impact of acetate addition was most evident in the influent section of the columns. The increased relative abundance of Fe(III)-reducing bacteria coincided with an increase in viral abundance in areas of the columns exhibiting the most Fe(III) reduction. The genetic composition of viruses in these column sections also differed from the control column and distal sections of acetate-treated columns suggesting viral communities responded to biostimulated Fe(III)-bioreduction.

Spray drying OZ439 nanoparticles to form stable, water-dispersible powders for oral malaria therapy.

BACKGROUND: OZ439 is a new chemical entity which is active against drug-resistant malaria and shows potential as a single-dose cure. However, development of an oral formulation with desired exposure has proved problematic, as OZ439 is poorly soluble (BCS Class II drug). In order to be feasible for low and middle income countries (LMICs), any process to create or formulate such a therapeutic must be inexpensive at scale, and the resulting formulation must survive without refrigeration even in hot, humid climates. We here demonstrate the scalability and stability of a nanoparticle (NP) formulation of OZ439. Previously, we applied a combination of hydrophobic ion pairing and Flash NanoPrecipitation (FNP) to formulate OZ439 NPs 150 nm in diameter using the inexpensive stabilizer hydroxypropyl methylcellulose acetate succinate (HPMCAS). Lyophilization was used to process the NPs into a dry form, and the powder's in vitro solubilization was over tenfold higher than unprocessed OZ439. METHODS: In this study, we optimize our previous formulation using a large-scale multi-inlet vortex mixer (MIVM). Spray drying is a more scalable and less expensive operation than lyophilization and is, therefore, optimized to produce dry powders. The spray dried powders are then subjected to a series of accelerated aging stability trials at high temperature and humidity conditions. RESULTS: The spray dried OZ439 powder's dissolution kinetics are superior to those of lyophilized NPs. The powder's OZ439 solubilization profile remains constant after 1 month in uncapped vials in an oven at 50 °C and 75% RH, and for 6 months in capped vials at 40 °C and 75% RH. In fasted-state intestinal fluid, spray dried NPs achieved 80-85% OZ439 dissolution, to a concentration of 430 µg/mL, within 3 h. In fed-state intestinal fluid, 95-100% OZ439 dissolution is achieved within 1 h, to a concentration of 535 µg/mL. X-ray powder diffraction and differential scanning calorimetry profiles similarly remain constant over these periods. CONCLUSIONS: The combined nanofabrication and drying process described herein, which utilizes two continuous unit operations that can be operated at scale, is an important step toward an industrially-relevant method of formulating the antimalarial OZ439 into a single-dose oral form with good stability against humidity and temperature.

Solid-State Behavior and Solubilization of Flash Nanoprecipitated Clofazimine Particles during the Dispersion and Digestion of Milk-Based Formulations.

Clofazimine, a drug previously used to treat leprosy, has recently been identified as a potential new drug for the treatment for cryptosporidiosis: a diarrheal disease that contributes to 500 000 infant deaths a year in developing countries. Rapid dissolution and local availability of the drug in the small intestine is considered key to the treatment of the infection. However, the commercially available clofazimine formulation (Lamprene) is not well-suited to pediatric use, and therefore reformulation of clofazimine is desirable. Development of clofazimine nanoparticles through the process of flash nanoprecipitation (FNP) has been previously shown to provide fast and improved drug dissolution rates compared to clofazimine crystals and Lamprene. In this study, we investigate the effects of milk-based formulations (as possible pediatric-friendly vehicles) on the in vitro solubilization of clofazimine formulated as either lecithin- or zein/casein-stabilized nanoparticles. Milk and infant formula were used as the lipid vehicles, and time-resolved synchrotron X-ray scattering was used to monitor the presence of crystalline clofazimine in suspension during in vitro lipolysis under intestinal conditions. The study confirmed faster dissolution of clofazimine from all the FNP formulations after the digestion of infant formula was initiated, and a reduced quantity of fat was required to achieve similar levels of drug solubilization compared to the reference drug material and the commercial formulation. These attributes highlight not only the potential benefits of the FNP approach to prepare drug particles but also the fact that enhanced dissolution rates can be complemented by considering the amount of co-administered fat in lipid-based formulations to drive the solubilization of poorly soluble drugs.

Amorphous nanoparticles by self-assembly: processing for controlled release of hydrophobic molecules.

More than 40% of newly developed drug molecules are highly hydrophobic and, thus, suffer from low bioavailability. Kinetically trapping the drug as a nanoparticle in an amorphous state enhances solubility. However, enhanced solubility can be compromised by subsequent recrystallization from the amorphous state during drying processes. We combine Flash NanoPrecipitation (FNP) to generate nanoparticles with spray-drying to produce stable solid powders. We demonstrate that the continuous nanofabrication platform for nanoparticle synthesis and recovery does not compromise the dissolution kinetics of the drug. Lumefantrine, an anti-malaria drug, is highly hydrophobic with low bioavailability. Increasing the bioavailability of lumefantrine has the potential to reduce the dose and number of required administrations per treatment, thus reducing cost and increasing patient compliance. The low melting temperature of lumefantrine (Tm = 130 °C) makes the drying of amorphous nanoparticles at elevated temperatures potentially problematic. Via FNP, we produced 200-400 nm nanoparticles using hydroxypropyl methylcellulose acetate succinate (HPMCAS), lecithin phospholipid, and zein protein stabilizers. Zein nanoparticles were spray-dried at 100 °C and 120 °C to study the effect of the drying temperature. For zein powders, at two hours the dissolution kinetics under fasted conditions reached 85% release for the 100 °C sample, but only 60% release for the 120 °C sample. Powder X-ray diffraction, differential scanning calorimetry, and solid state nuclear magnetic resonance indicate that the lumefantrine in the nanoparticle core is amorphous for samples spray-dried at 100 °C. Dissolution under fed state conditions showed similar release kinetics for both temperatures, with 90-95% release at two hours. Zein and HPMCAS nanoparticles spray-dried at 100 °C showed release profiles in fasted and fed state media that are identical to those of lyophilized samples, i.e. those dried at cryogenic conditions where no transformation to the crystalline state can occur. Thus, spray drying 30 °C below the melting transition of lumefantrine is sufficient to maintain the amorphous state. These inexpensive formulations have potential to be developed into future therapies for malaria, and the results also highlight the potential of combining FNP and spray-drying as a versatile platform to assemble and rapidly recover amorphous nanoparticles in a solid dosage form.

Gemini Cationic Amphiphiles Control Biofilm Formation by Bacterial Vaginosis Pathogens.

Antibiotic resistance and recurrence of bacterial vaginosis (BV), a polymicrobial infection, justify the need for novel antimicrobials to counteract microbial resistance to conventional antibiotics. Previously, two series of cationic amphiphiles (CAms) which self-assemble into supramolecular nanostructures with membrane-lytic properties were designed with hydrophilic head groups and nonpolar domains. The combination of CAms and commonly prescribed antibiotics is suggested as a promising strategy for targeting microorganisms that are resistant to conventional antibiotics. Activities of the CAms against Gardnerella vaginalis ATCC 14018, a representative BV pathogen, ranged from 1.1 to 24.4 µM. Interestingly, the tested healthy Lactobacillus species, especially Lactobacillus plantarum ATCC 39268, were significantly more tolerant of CAms than the selected pathogens. In addition, CAms prevented biofilm formation at concentrations which did not influence the normal growth ability of G. vaginalis ATCC 14018. Furthermore, the biofilm minimum bactericidal concentration (MBC-Bs) of CAms against G. vaginalis ATCC 14018 ranged from 58.8 to 425.6 µM, while much higher concentrations (≥850 µM) were required to produce ≥3-log reductions in the number of biofilm-associated lactobacilli. The conventional antibiotic metronidazole synergized strongly with all tested CAms against planktonic cells and biofilms of G. vaginalis ATCC 14018. The synergism between CAms and the tested conventional antibiotic may be considered a new, effective, and beneficial method of controlling biofilm-associated bacterial vaginosis.

Design and Solidification of Fast-Releasing Clofazimine Nanoparticles for Treatment of Cryptosporidiosis.

Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable. In this work, clofazimine nanoparticles were prepared with three surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, using the flash nanoprecipitation (FNP) process. Drug encapsulation efficiencies of over 92% were achieved. Lyophilization and spray-drying were applied and optimized to produce redispersible nanoparticle powders. The release kinetics of these clofazimine nanoparticle powders in biorelevant media were measured and compared with those of crystalline clofazimine and the currently marketed formulation Lamprene. Remarkably improved dissolution rates and clofazimine supersaturation levels up to 90 times equilibrium solubility were observed with all clofazimine nanoparticles tested. Differential scanning calorimetry indicated a reduction of crystallinity of clofazimine in nanoparticles. These results strongly suggest that the new clofazimine nanoparticles prepared with affordable materials in this low-cost nanoparticle formulation process can be used as viable cryptosporidiosis therapeutics.

Biodegradable Kojic Acid-Based Polymers: Controlled Delivery of Bioactives for Melanogenesis Inhibition.

Kojic acid (KA) is a naturally occurring fungal metabolite that is utilized as a skin-lightener and antibrowning agent owing to its potent tyrosinase inhibition activity. While efficacious, KA's inclination to undergo pH-mediated, thermal-, and photodegradation reduces its efficacy, necessitating stabilizing vehicles. To minimize degradation, poly(carbonate-esters) and polyesters comprised of KA and natural diacids were prepared via solution polymerization methods. In vitro hydrolytic degradation analyses revealed KA release was drastically influenced by polymer backbone composition (e.g., poly(carbonate-ester) vs polyester), linker molecule (aliphatic vs heteroatom-containing), and release conditions (physiological vs skin). Tyrosinase inhibition assays demonstrated that aliphatic KA dienols, the major degradation product under skin conditions, were more potent then KA itself. All dienols were found to be less toxic than KA at all tested concentrations. Additionally, the most lipophilic dienols were statistically more effective than KA at inhibiting melanin biosynthesis in cells. These KA-based polymer systems deliver KA analogues with improved efficacy and cytocompatible profiles, making them ideal candidates for sustained topical treatments in both medical and personal care products.

Self-assembled cationic amphiphiles as antimicrobial peptides mimics: Role of hydrophobicity, linkage type, and assembly state.

Inspired by high promise using naturally occurring antimicrobial peptides (AMPs) to treat infections caused by antimicrobial-resistant bacteria, cationic amphiphiles (CAms) were strategically designed as synthetic mimics to overcome associated limitations, including high manufacture cost and low metabolic stability. CAms with facially amphiphilic conformation were expected to demonstrate membrane-lytic properties and thus reduce tendency of resistance development. By systematically tuning the hydrophobicity, CAms with optimized compositions exhibited potent broad-spectrum antimicrobial activity (with minimum inhibitory concentrations in low µg/mL range) as well as negligible hemolytic activity. Electron microscope images revealed the morphological and ultrastructure changes of bacterial membranes induced by CAm treatment and validated their membrane-disrupting mechanism. Additionally, an all-atom molecular dynamics simulation was employed to understand the CAm-membrane interaction on molecular level. This study shows that these CAms can serve as viable scaffolds for designing next generation of AMP mimics as antimicrobial alternatives to combat drug-resistant pathogens.

Amphiphilic Macromolecule Self-Assembled Monolayers Suppress Smooth Muscle Cell Proliferation.

A significant limitation of cardiovascular stents is restenosis, where excessive smooth muscle cell (SMC) proliferation following stent implantation causes blood vessel reocclusion. While drug-eluting stents minimize SMC proliferation through releasing cytotoxic or immunosuppressive drugs from polymer carriers, significant issues remain with delayed healing, inflammation, and hypersensitivity reactions associated with drug and polymer coatings. Amphiphilic macromolecules (AMs) comprising a sugar-based hydrophobic domain and a hydrophilic poly(ethylene glycol) tail are noncytotoxic and recently demonstrated a concentration-dependent ability to suppress SMC proliferation. In this study, we designed a series of AMs and studied their coating properties (chemical composition, thickness, grafting density, and coating uniformity) to determine the effect of headgroup chemistry on bioactive AM grafting and release properties from stainless steel substrates. One carboxyl-terminated AM (1cM) and two phosphonate- (Me-1pM and Pr-1pM) terminated AMs, with varying linker lengths preceding the hydrophobic domain, were grafted to stainless steel substrates using the tethering by aggregation and growth (T-BAG) approach. The AMs formed headgroup-dependent, yet uniform, biocompatible adlayers. Pr-1pM and 1cM demonstrated higher grafting density and an extended release from the substrate over 21 days compared to Me-1pM, which exhibited lower grafting density and complete release within 7 days. Coinciding with their release profiles, Me-1pM and 1cM coatings initially suppressed SMC proliferation in vitro, but their efficacy decreased within 7 and 14 days, respectively, while Pr-1pM coatings suppressed SMC proliferation over 21 days. Thus, AMs with phosphonate headgroups and propyl linkers are capable of sustained release from the substrate and have the ability to suppress SMC proliferation during the restenosis that occurs in the 3-4 weeks after stent implantation, demonstrating the potential for AM coatings to provide sustained delivery via desorption from coated coronary stents and other metal-based implants.

Linear-inverse associations of serum Klotho protein with prevalence of frailty among adults in the United States.

AIMS: To investigate the potential linear relationship between serum concentrations of klotho and frailty. METHODS: A retrospective analysis was conducted on the data of 9,597 middle-aged and older adults (aged 40-79 years) from the five cycles of the National Health and Nutrition Examination Survey (NHANES). Frailty was assessed using the Frailty Index, calculated as a percentage of accumulated deficits across 53 health items. Restricted cubic spline curves, subgroup analyses and logistic regression models were employed to evaluate the specific linear trend connection between circulating klotho protein concentration and frailty. RESULTS: When taking Klotho into account as a continuous component in Models 1 and 2, there was a substantial association between the increasing Klotho level and the reduced risk of frailty. Model 3 revealed a strong negative correlation between the Klotho and Frailty, suggesting that high levels of Klotho protein decreases the frailty prevalence [Odd ratio (OR): 0.25; 95% confidence interval (CI): 0.15-0.43]. Furthermore, according to the quartile analyses, after fully adjusting for the covariates, it was observed that, comparing to the lowest quartile of Klotho, the highest quartile of Klotho demonstrated lowest risk of frailty (OR 0.69; 95% CI 0.58-0.81, Ptrend < 0.001). The restricted cubic spline curves showed a linear relationship and an inverse association between frailty and the Klotho levels (Plinearity < 0.001; Pnon-linearity = 0.736). CONCLUSION: Klotho is inversely and linearly associated with physical frailty in the general population (aged 40-79 years), specifically in the population with an age < 65 and body mass index (BMI) ≥ 25 kg/m2. More necessary prospective studies should be done to further investigate the mechanisms underlying frailty and aging and to elucidate individual frailty causes.

Service demand analysis and optimization strategy construction of emergency observation patients based on the Kano model.

Background: Emergency observation unit in China are characterized by a high number of patients, complexity of diseases, and instability of patient conditions, leading to low patient satisfaction. The Kano model is an effective method widely used to identify customer demands and improve service quality to enhance customer satisfaction. However, its application in emergency observation unit has been studied less. This study aims to design a questionnaire based on the Kano model and identify the demands of emergency observation patients to determine priorities for improvements in the emergency observation unit and improve patient satisfaction. Methods: A cross-sectional study was conducted in Guizhou Provincial People's Hospital from March 21st, 2023, to May 20th, 2023. A convenient sampling method was used to recruit 100 patients from the emergency observation unit, who completed a questionnaire designed based on the Kano model to assess their demands for care service. Data were analyzed using IBM SPSS Statistics 28.0 software. The element selection line and sensitivity analysis were used to determine factors for patient service demand improvement. Results: A total of 13 patient service demands for improvement were screened out from 19 service demands, including 1 item of must-be quality (M), 11 item of one-dimensional quality (O), and 1 item of attractive quality (A), These attributes showed significant differences in patients' sociodemographic characteristics. Conclusion: The Kano model is a valuable tool for identifying the characteristics of patients' service demands, and the element screening method can be employed to establish the hierarchy of these demands. These results offer crucial direction for creating forthcoming nursing management initiatives in emergency observation unit.

Relationship between hyperuricemia and the risk of cardiovascular events and chronic kidney disease in both the general population and hypertensive patients: A systematic review and meta-analysis.

BACKGROUND: To explore the relationships between hyperuricemia and the risk of cardiovascular diseases (CVD) and chronic kidney disease (CKD) in both the general population and hypertensive patients through meta-analysis. METHODS AND RESULTS: We systematically searched PubMed, Embase, and Cochrane Library databases from January 2012. The eligibility criteria were predefined, and quality was assessed using the Newcastle-Ottawa Scale (NOS). Stata 15.1 was used for meta-analysis, heterogeneity and sensitivity analysis. Subgroup analysis was used to explore heterogeneity, funnel plots and Egger tests were used to assesse publication bias and applicability. A total of 10,662 studies were retrieved, 45 of which were included in this meta-analysis utilizing a random effects model. Hyperuricemia was significantly associated with an increased risk of new-onset hypertension (RR = 1.36, 95% CI 1.16-1.59; I2 = 98.8%), total CVD (RR = 1.53, 95% CI 1.23-1.89; I2 = 93.7%), stroke (RR = 1.97, 95% CI 1.71-2.26, I2 = 0.0%), coronary heart disease (CHD) (RR = 1.56, 95% CI 1.06-2.30, I2 = 93.3%), and CKD (RR = 1.71, 95% CI 1.56-1.87; I2 = 87.3%). However, subgroup analysis showed no significant associations between hyperuricemia and hypertension in non-Asian populations (RR = 0.88, 95% CI 0.59-1.33), or between hyperuricemia and CVD with a follow-up duration <5 years (RR = 1.26, 95% CI 0.97-1.63). Among hypertensive patients, hyperuricemia was significantly associated with total CVD (RR = 2.32, 95% CI 1.31-4.12, I2 = 90.2%), but not with stroke (RR = 1.48, 95% CI 0.86-2.55; I2 = 90.7%) or CHD (RR = 1.51, 95% CI 0.98-2.33; I2 = 71.7%). CONCLUSION: Hyperuricemia was significantly associated with an increased risk of new-onset hypertension, total CVD, stroke, CHD, and CKD in the general population. Among hypertensive patients, hyperuricemia was associated with an increased risk of CVD but not stroke or CHD alone. REGISTRATION NUMBER: CRD42022370692.

Impact of VO 2peak on the Clinical Outcomes of Older Patients With Coronary Heart Disease in China.

PURPOSE: The aim of this study was to explore the role of cardiopulmonary exercise test parameters, especially peak oxygen uptake (VO 2peak ), in predicting the incidence of adverse cardiovascular events in older Chinese patients with coronary heart disease (CHD). METHODS: Older patients with CHD who underwent cycle ergometer cardiopulmonary exercise test at the Cardiac Rehabilitation Clinic of Chinese PLA General Hospital from July 1, 2015 to January 31, 2020 were enrolled. The follow-up intervals were 6 mo. Cox regression was used to analyze the relationship between VO 2peak and adverse cardiovascular events. Restricted cubic splines and subgroup analyses were used to observe the relationship between VO 2peak and the hazard ratio (HR) of the primary end point event (PEE), which included a composite of all-cause death, nonfatal recurrent myocardial infarction, unscheduled revascularization, and stroke. The composite end point event was the PEE combined with cardiac rehospitalization. RESULTS: A total of 1223 participants (mean age 68 ± 5 yr) were included. Median follow-up was 68 mo. Mean VO 2peak was 16.5 ± 4.0 mL/kg/min, and VO 2peak was an independent predictor of the PEE (HR = 0.929; 95% CI, 0.891-0.970; P = .001). This association was further validated by restricted cubic spline and subgroup analyses. Peak oxygen uptake was also an independent risk factor for the composite end point event (HR = 0.968; 95% CI, 0.941-0.996; P = .025). CONCLUSION: In conclusion, VO 2peak is an independent risk factor for adverse cardiovascular events in older Chinese patients with CHD, and more optimal therapy should be recommended to patients with lower VO 2peak .

Microbial Fermentation as an Efficient Method for Eliminating Pyrethroid Pesticide Residues in Food: A Case Study on Cyfluthrin and Aneurinibacillus aneurinilyticus D-21.

The microbial fermentation of food has emerged as an efficient means to eliminate pesticide residues in agricultural products; however, the specific degradation characteristics and mechanisms remain unclear. In this study, a Gram-positive bacterium, Aneurinibacillus aneurinilyticus D-21, isolated from fermented Pixian Douban samples exhibited the capability to degrade 45 mg/L of cyfluthrin with an efficiency of 90.37%. Product analysis unveiled a novel cyfluthrin degradation pathway, involving the removal of the cyanide group and ammoniation of the ester bond into an amide. Whole genome analysis discovered the enzymes linked to cyfluthrin degradation, including nitrilase, esterase, carbon-nitrogen ligases, and enzymes associated with aromatic degradation. Additionally, metabolome analysis identified 140 benzenoids distributed across various aromatic metabolic pathways, further substantiating D-21's catabolic capability toward aromatics. This study underscores the exceptional pyrethroid degradation prowess of A. aneurinilyticus D-21, positioning it as a promising candidate for the biotreatment of pesticide residues in food systems.