CTRP6-mediated cardiac protection in heart failure via the AMPK/SIRT1/PGC-1α signalling pathway.

Heart failure (HF) remains a significant global health concern with limited effective treatments available. C1q/TNF-related protein 6 (CTRP6) is a member of the CTRP family analogous to adiponectin and its role in HF pathogenesis remains unclear. Here, we investigated the impact of CTRP6 on HF progression. To mimic heart failure with reduced ejection fraction (HFrEF), we used isoproterenol injection in mice and administered adenovirus vectors expressing CTRP6 (Ad-CTRP6) via tail vein injection. We assessed cardiac function through echocardiography and histology. CTRP6's effects on hypertrophy, fibrosis, apoptosis, oxidative stress and mitochondrial function were analysed. Downstream pathways (phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) were studied in heart tissues. In vitro, isoproterenol-stimulated H9c2 cardiomyocytes were treated with CTRP6 to examine viability, apoptosis, F-actin and signalling proteins. Compound C was used to assess AMPK involvement. CTRP6 expression was lower in the plasma of HF patients. In an isoproterenol-induced HFrEF mouse model, adenovirus-mediated overexpression of CTRP6 ameliorated cardiac dysfunction and reduced cardiomyocyte apoptosis, oxidative stress, inflammation and myocardial injury markers. Mechanistically, CTRP6 activation of the AMPK/SIRT1/PGC-1α signalling pathway restored mitochondrial homeostasis, evidenced by reduced mitochondrial reactive oxygen species levels, increased ATP content, and enhanced mitochondrial complex I/III activities in cardiac tissues. In vitro studies using isoproterenol-stimulated H9c2 cardiomyocytes corroborated these findings, demonstrating that CTRP6 upregulation attenuated hypertrophy, apoptosis, oxidative stress and mitochondrial dysfunction. Furthermore, these effects were partially reversed by the AMPK inhibitor Compound C, implicating the involvement of the AMPK pathway in CTRP6-mediated cardioprotection. CTRP6 alleviates HF progression through the AMPK/SIRT1/PGC-1α signalling pathway.

An inhalable nanoparticle enabling virulence factor elimination and antibiotics delivery for pneumococcal pneumonia therapy.

Streptococcus pneumoniae (S. pneumoniae) is a major cause of community-acquired pneumonia. Current standard clinical therapies mainly focus on combating S. pneumoniae through antibiotics. However, the limited delivery of antibiotics and the undetoxified hydrogen peroxide (H2O2) virulence factor secreted by S. pneumoniae impede the therapeutic outcomes. Here we report an inhalable catalase (CAT)-tannic acid (TA) nanoassembly for local antibiotic (levofloxacin) delivery and simultaneously neutralizing the secreted H2O2 virulence factors to treat pneumococcal pneumonia. After aerosol inhalation, the inhalable formulation (denoted as CT@LVX) effectively accumulates in lung tissues through TA-mediated mucoadhesion. CAT can reduce alveolar epithelial cells apoptosis by catalyzing the decomposition of accumulated H2O2 in the infected lung tissues. In synergy with antibiotic LVX-mediated S. pneumoniae elimination, CT@LVX significantly decreases lung injury companied with reduced inflammatory, resulting in 100 % survival of mice with pneumonia. In a clinically isolated S. pneumoniae strain-induced pneumonia mouse model, CT@LVX also shows superior outcomes compared to the traditional antibiotic treatment, highlighting its potential clinical application prospects.

Characterisation of an edible active film prepared from bacterial nanocellulose/forsythia essential oil Pickering emulsions with funoran and its application in fresh meat.

This study sought to develop an edible active film by integrating Pickering emulsions of forsythia essential oil and bacterial nanofibers at various concentrations into a film-forming matrix composed of funoran (F). The stability of the emulsions was evaluated through examination of the micro-morphology, particle size and distribution, 7-day emulsification index, and embedding rate of the Pickering emulsions. Subsequently, selected Pickering emulsions were incorporated into F to generate the edible active film. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and Raman spectroscopy revealed that the Pickering emulsion was uniformly distributed throughout the F film, interconnected by hydrogen bonds. X-ray Diffraction spectra exhibited changes in peak intensity and shifts in position attributable to the edible active film. Pickering emulsion had a minimal impact on thermal stability. The film's tensile strength significantly increased, while elongation at break decreased. The heightened concentration of hydroxyl groups in the film led to increased thickness, reduced moisture content, and enhanced hygroscopicity. The edible active film exhibited superior antioxidant and antibacterial properties, thereby more efficiently shielding against oxygen and water vapour. In preservation tests involving chicken and lamb, the Pickering emulsion led to elevations in pH, total volatile basic nitrogen, and thiobarbituric acid reactive substance levels in the meat.

Fabrication and characterization of Karaya gum-based films reinforced with bacterial nanocellulose stabilized valerian root extract Pickering emulsion for lamb meat preservation.

A novel biodegradable film was fabricated by incorporating bacterial nanocellulose stabilized valerian root extract (VRE) Pickering emulsion into karaya gum with better antioxidant and antibacterial properties for lamb meat preservation. The valerian root extract Pickering emulsion (VPE) exhibited 98 ± 1.84 % encapsulating efficiency and excellent physical stability with an average particle size of 274.6 nm. The incorporation of VPE-5 into the film matrix increased its elongation at break (EAB), and improved water resistance and barrier properties against oxygen, water vapor, and UV light. Moreover, the antioxidant and anti-bacterial properties against S.aerous and E. coli were also improved based on VPE-5 concentration. The SEM images showed a uniform distribution of VPE-5 while FTIR and XRD revealed its compatibility with karaya gum, which improved its thermal stability. The active films showed a significant preservative effect by reducing the pH, total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), and total viable count (TVC) value of lamb meat and maintained its texture and color during the storage period of 9 days at 4 °C. These results demonstrated the inclusion of VPE-5 into Karaya gum was a promising technique and offers a great potential application as a bioactive material in food packaging.

The Optimal Cut-off Value of Upper Arm Circumference and Calf Circumference for Assessing Sarcopenia Among Chinese Community-Dwelling Older Adults.

Objective: To explore the cut-off values and health evaluations of upper arm circumference (AC) and calf circumference (CC) on sarcopenia in Chinese community-dwelling older people. Methods: In this cross-sectional study, AC, CC, handgrip strength, muscle mass and gait speed were measured in 1537 Chinese community-dwelling older people in Sub-study 1. Correlation analysis, receiver operator characteristic curve (ROC curve) analysis, and consistency analysis were used for determination of AC and CC cut-off values for sarcopenia diagnosis (sarcopenia-AC and CC). Thereafter, 269 participants accepted additional assessments on physical function, body composition and muscle strength in Sub-study 2. T-test or Mann-Whitney U-test was used to explore the differential effects of sarcopenia-AC and CC on health indicators between sarcopenic and non-sarcopenic participants. Results: In Sub-study 1, the Area Under ROC (AUC) of AC and CC for sarcopenia screening were greater than 0.700 (P<0.05). The cut-off values, sensitivity and specificity of AC and CC on sarcopenia in males were 25.9 cm (86.0%, 83.6%) and 33.7 cm (90.7%, 81.4%) whereas in females were 26.5 cm (70.8%, 69.7%) and 33.0 cm (86.5%, 69.4%), respectively. In Sub-study 2, the participants with sarcopenia-AC or sarcopenia-CC showed lower muscle strength and lower fat and muscle mass than the ones without (P<0.05). Additionally, males instead of females with sarcopenia-AC or sarcopenia-CC showed worse performance in time-up and go test and 6-Minute Walk Test (P<0.05). However, the 30-second chair stand test was not different between participants with and without sarcopenia-AC or sarcopenia-CC in both sexes. Conclusion: We found accurate and Chinese population targeted cut-off values of AC and CC on sarcopenia diagnosis (25.9 cm and 33.7 cm in males; 26.5 cm and 33.0 cm in females) and a good evaluation effect of AC and CC on fat and muscle mass, muscle strength and physical functions in males, not females.

An "off-on-enhanced on" electrochemiluminescence biosensor based on resonance energy transfer and surface plasmon coupled 3D DNA walker for ultra-sensitive detection of microRNA-21.

In this study, a novel electrochemiluminescence (ECL) biosensor was developed to detect microRNA-21 (miRNA-21) with high sensitivity by leveraging the combined mechanisms of resonance energy transfer (RET) and surface plasmon coupling (SPC). Initially, the glassy carbon electrode (GCE) were coated with Cu-Zn-In-S quantum dots (CZIS QDs), known for their defect-related emission suitable for ECL sensing. Subsequently, a hairpin DNA H3 with gold nanoparticles (Au NPs) attached at the end was modified over the surface of the quantum dots. The Au NPs could effectively quench the ECL signals of CZIS QDs via RET. Further, a significant amount of report DNA was generated through the action of a 3D DNA walker. When the report DNA opened H3-Au NPs, the hairpin structure experienced a conformational change to a linear shape, increasing the gap between the CZIS QDs and the Au NPs. Consequently, the localized surface plasmon resonance ECL (LSPR-ECL) effect replaced ECL resonance energy transfer (ECL-RET). Moreover, the report DNA was released following the addition of H4-Au NPs, resulting in the formation of Au dimers and a surface plasma-coupled ECL (SPC-ECL) effect that enhanced the ECL intensity to 6.97-fold. The integration of new ECL-RET and SPC-ECL biosensor accurately quantified miRNA-21 concentrations from 10-8 M to 10-16 M with a limit of detection (LOD) of 0.08 fM, as well as successfully applied to validate human serum samples.

Dual-signal ratiometric electrochemiluminescence biosensor based on Au NPs-induced low-potential emission of PFO Pdots and LSPR-ECL mechanism for ultra-sensitive detection of microRNA-141.

In this study, we have for the first time constructed a ratiometric ECL biosensor for the ultrasensitive detection of microRNAs (miRNAs) using gold nanoparticles (Au NPs) to trigger both the low-potential emission from conjugated polymer poly(9,9-dioctylfluorene-2,7-diyl) dots (PFO Pdots) and the LSPR-ECL effect with sulfur-doped boron nitride quantum dots (S-BN QDs). PFO Pdots were first applied to the Au NPs-modified electrode, followed by covalent binding to capture the hairpin H1. Immediately thereafter, a small amount of miRNA-141 was able to generate a large amount of output DNA (OP) by traversing the target cycle. OP, H3-S-BN QDs, and H4-glucose oxidase (H4-GOD) were then added sequentially to the Au NPs-modified electrode surface, and the hybridization chain reaction (HCR) was initiated. This resulted in the introduction of a large amount of GOD into the system, which catalyzed the in situ formation of the co-reactant hydrogen peroxide (H2O2) from the substrate glucose. Due to the electron transfer effect, the production of H2O2 led to the ECL quenching of PFO Pdots. Meanwhile, H2O2 served as a co-reactant of S-BN QDs, resulting in strong ECL emission of S-BN QDs at the cathode. Furthermore, the cathodic ECL intensity of S-BN QDs was further enhanced by an LSPR-ECL mechanism between Au NPs and S-BN QDs. By measuring the ratio of ECL intensities at two excitation potentials, this approach could provide sensitive and reliable detection of miRNA-141 in the range of 0.1 fM ∼10 nM, with a detection limit of 0.1 fM.

Non-surgical treatment of idiopathic gingival enlargement: A case report.

BACKGROUND: Idiopathic gingival enlargement is associated with plaque, but other contributing factors are unclear. The prognosis of idiopathic gingival enlargement is closely related to the patient's oral hygiene habits and regular follow-up. CASE PRESENTATION: This article reports a case of a 32-year-old male patient with idiopathic gingival enlargement. The patient presented to the department of stomatology with a 2-month history of gingival swelling and pain on the right upper posterior teeth. During the treatment, oral hygiene instruction, supragingival cleaning, subgingival scaling, and root planning were carried out, and part of the hyperplastic gingiva was taken and sent for pathology. Pathological examination showed gingival enlargement with chronic suppurative inflammation. At 4-month follow-up, the patient's periodontal condition remained basically stable, and the gingival enlargement did not recur. CONCLUSION: The treatment of this case resulted in significant reduction of gingival swelling and patient's pain reduction through non-surgical treatment and good plaque control, indicating that patients with idiopathic gingival enlargement can also achieve ideal results through non-surgical treatment. Through oral hygiene instruction, the patient mastered the method of self-plaque control, which is conducive to the long-term stabilization of the periodontal situation.

Rational design to improve the catalytic efficiency and stability of arginine deiminase.

Arginine deiminase (ADI) has garnered significant interest because of its ability to objectively eradicate cancer cells and produce L-citrulline. To meet the production demands, this study focused on enhancing the enzyme activity and thermal stability of ADI. In this study, 24 ADI mutants were obtained through computer aid site-specific mutation in the ADI of Enterobacter faecalis. Notably, the specific enzyme activities of F44W, N163P, E220I, E220L, N318E, A336G, T340I, and N382F increased, reaching 1.33-2.53 times that of the original enzyme. This study confirmed that site-specific mutations are critical for optimizing enzyme function. Additionally, the F44W, N163P, E220I, T340I, and A336G mutants demonstrated good thermal stability. The optimal pH for mutant F44W increased to 8, whereas mutants E220I, I244V, A336G, T340I, and N328F maintained an optimal pH of 7.5. Conversely, the M109L, N163P, E220L, I244L, and N318E mutants shad an optimal pH of 7. This study revealed that mutant enzymes with increased activity were more likely to contain mutation sites situated near the four loops associated with catalytic residues, whereas mutations at the dimer junction sites had a higher tendency to enhance enzyme stability. These findings contribute to the development of ADI industrial applications and its modifications.

The correlation between subendocardial viability ratio and the degree of coronary artery stenosis in patients with coronary heart disease and its predictive value for the incidence of short-term cardiovascular events.

OBJECTIVES: This study aimed to analyze the ability of subendocardial viability ratio (SEVR) to predict the degree of coronary artery stenosis and the relationship between SEVR and the incidence of short-term cardiovascular endpoint events. METHOD: The indexes of 243 patients with chest pain were collected.. Binary logistic regression analyses were performed using the dichotomous outcome of high and non-high SYNTAX scores. Receiver operating characteristic curves were employed to comparatively analyze the diagnostic efficiencies of the indices and models. A survival analysis combined with the Cox regression analysis was performed using the Kaplan-Meier method to understand the relationship between the SEVR and the incidence of cardiovascular events within 1 year in patients with coronary heart disease (CHD). RESULTS: SEVR was significantly lower ( P  < 0.05) in the high-stenosis group than control and low-stenosis groups. The diagnostic efficacy of SEVR [area under the curve (AUC) = 0.861] was better than those of age (AUC = 0.745), ABI (AUC = 0.739), and AIx@HR75 (AUC = 0.659). The cutoff SEVR was 1.105. In patients with confirmed CHD who had been discharged from the hospital for 1 year, only SEVR affected survival outcomes (hazard ratio = 0.010; 95% confidence interval: 0.001-0.418; P  = 0.016). CONCLUSION: A significant decrease in SEVR predicted severe coronary artery stenosis, with a cutoff value of 1.105 and an accuracy of 0.861. In patients with CHD, the lower the SEVR, the higher was the rate of cardiovascular events at 1 year after hospital discharge.

Tripedal DNA Walker as a Signal Amplifier Combined with a Potential-Resolved Multicolor Electrochemiluminescence Strategy for Ultrasensitive Detection of Prostate Cancer Staging Indicators.

A multicolor electrochemiluminescence (ECL) biosensor based on a closed bipolar electrode (BPE) array was proposed for the rapid and intuitive analysis of three prostate cancer staging indicators. First, [Irpic-OMe], [Ir(ppy)2(acac)], and [Ru(bpy)3]2+ were applied as blue, green, and red ECL emitters, respectively, whose mixed ECL emission colors covered the whole visible region by varying the applied voltages. Afterward, we designed a simple Mg2+-dependent DNAzyme (MNAzyme)-driven tripedal DNA walker (TD walker) to release three output DNAs. Immediately after, three output DNAs were added to the cathodic reservoirs of the BPE for incubation. After that, we found that the emission colors from the anode of the BPE changed as a driving voltage of 8.0 V was applied, mainly due to changes in the interfacial potential and faradaic currents at the two poles of the BPE. Via optimization of the experimental parameters, cutoff values of such three indicators at different clinical stages could be identified instantly with the naked eye, and standard precision swatches with multiple indicators could be prepared. Finally, in order to precisely determine the prostate cancer stage, the multicolor ECL device was used for clinical analysis, and the resulting images were then compared with standard swatches, laying the way for accurate prostate cancer therapy.

Feasibility and preliminary effects of a mindfulness-based physical exercise (MBPE) program for community-dwelling older people with sarcopenia: A protocol for a parallel, two-armed pilot randomised controlled trial.

INTRODUCTION: Physical exercise (PE) is essential for alleviating the symptoms of sarcopenia. Low motivation is a major barrier to PE. Mindfulness-based intervention (MBI) has the potential to improve motivation. However, few studies have used a mindfulness-based PE (MBPE) intervention among older people with sarcopenia. OBJECTIVES: To assess the feasibility, acceptability and preliminary effects of the MBPE program among community-dwelling older people with sarcopenia. METHODS AND ANALYSIS: A two-arm pilot randomised controlled trial will be conducted to assess the feasibility, acceptability and preliminary effects of an MBPE program among community-dwelling older people with sarcopenia. A total of 60 participants will be randomised into the intervention group, receiving the MBPE intervention twice a week over 12 weeks, or the control group, receiving health education with the same duration, number of sessions and frequency as the intervention group. Each session of the MBPE program will last about 60 min, including 5-10- min introduction, 20-min MBI, 30-min PE and 5-10-min sharing and discussion. The primary outcomes will be the feasibility (i.e., the time spent recruiting participants, the eligibility rate and the recruitment rate) and acceptability (i.e., the attendance rate, completion rate and attrition rate) of the MBPE program. The secondary outcomes will be the preliminary effects of the MBPE program on symptoms of sarcopenia, motivation for PE, psychological well-being, mindfulness level, physical activity level and quality of life. Individual interviews will be conducted to identify the strengths, limitations and therapeutic components of the intervention. The quantitative data will be analysed by generalised estimating equations. The qualitative data will be analysed by Braun and Clarke's thematic approach. CONCLUSION: The findings of this study will be able to provide evidence for the health professionals in adopting MBPE as a supportive intervention for the older adults with sarcopenia and the groundworks for the researchers in developing non-pharmacological intervention for older adults. The positive effects could facilitate healthy ageing and relief the burden of the medical system, especially in the countries facing the ageing population. TRIAL REGISTRATION NUMBER: NCT05982067; ClinicalTrials.gov.

Dual "on-off" signal conversion strategy based on surface plasmon coupling and resonance energy transfer for visual electrochemiluminescence ratiometric analysis of MiRNA-141.

An electrochemiluminescence (ECL) biosensor with a pair of new ECL emitters and a novel sensing mechanism was designed for the high-sensitivity detection of microRNA-141 (miRNA-141). Sulfur-doped boron nitrogen quantum dots (S-BN QDs) were initially employed to modify the cathode of the bipolar electrode (BPE), while the anode reservoir was [Ir(dfppy)2(bpy)]PF6/TPrA system. The next step involved attaching H1-bound ultra-small WO3-x nanodots (WO3-x NDs) to the S-BN QDs-modified BPE cathode via DNA hybridization. A strong surface plasmon coupling (SPC) effect was observed between S-BN QDs and WO3-x NDs, which allowed for the enhancement of the red and visible ECL emission from S-BN QDs. After target-induced cyclic amplification to produce abundant Zn2+ and Au NPs-DNA3-Au NPs (Au NPs-S3-Au NPs), Zn2+ could cleave DNA at a nucleotide sequence-specific recognition site to release the WO3-x NDs, resulting in the first diminution of cathode ECL signal and the first enhancement of anode ECL signal. Moreover, the ECL signal at cathode decreased for the second time and the emission of [Ir(dfppy)2(bpy)]PF6 was continuously enhanced after the introduction of Au nanoparticles-S3-Au nanoparticles on the cathode surface. Our sensing mode with a dual "on-off" signal conversion strategy shows a good detection capability for miRNAs ranging from 10-17 to 10-10 M, with a limit of detection (LOD) as low as 10-17 M, which has great application potential in biomedical research and clinical diagnosis.

Metabolic Engineering of Escherichia coli for High-Titer Biosynthesis of 3'-Sialyllactose.

3'-Sialyllactose (3'-SL) is among the foremost and simplest sialylated breast milk oligosaccharides. In this study, an engineered Escherichia coli for high-titer 3'-SL biosynthesis was developed by introducing a multilevel metabolic engineering strategy, including (1) the introduction of precursor CMP-Neu5Ac synthesis pathway and high-performance α2,3-sialyltransferase (α2,3-SiaT) genes into strain BZ to achieve de novo synthesis of 3'-SL; (2) optimizing the expression of glmS-glmM-glmU involved in the UDP-GlcNAc and CMP-Neu5Ac synthesis pathways, and constructing a glutamine cycle system, balancing the precursor pools; (3) analysis of critical intermediates and inactivation of competitive pathway genes to redirect carbon flux to 3'-SL biosynthesis; and (4) enhanced catalytic performance of rate-limiting enzyme α2,3-SiaT by RBS screening, protein tag cloning. The final strain BZAPKA14 yielded 9.04 g/L 3'-SL in a shake flask. In a 3 L bioreactor, fed-batch fermentation generated 44.2 g/L 3'-SL, with an overall yield and lactose conversion of 0.53 g/(L h) and 0.55 mol 3'-SL/mol, respectively.

Neurotoxicity of Benzotriazole Ultraviolet Stabilizers in Teleost Fishes: A Review.

Plastic additives that maintain integrity have been extensively studied for potential toxicity to fish; however, chemicals that protect polymers from (artificial) UV degradation are less studied. Benzotriazole UV stabilizers (BUVSs) are the most widely used UV stabilizers in plastics and are often used in sunscreens, cosmetics, paint, and food packaging. BUVSs can negatively affect aquatic wildlife when released into the environment via plastic degradation. In this review, we summarize the distribution of BUVSs globally and discuss neurotoxicological endpoints measured in fish to understand how these plastic additives can affect the neurological health of teleost fishes. BUVSs have been detected in aquatic environments at concentrations ranging from 0.05 up to 99,200 ng/L. Studies show that BUVSs affect behavioral responses and acetylcholinesterase activity, indicators of neurotoxicity. Our computational analysis using transcriptome data suggests certain pathways associated with neurodegeneration are responsive to exposure to BUVSs, like "Complement Activation in Alzheimer's Disease". Based on our review, we identify some research needs for future investigations: (1) molecular studies in the central nervous system to define precise mechanisms of neurotoxicity; (2) a wider range of tests for assessing aberrant behaviors given that BUVSs can affect the activity of larval zebrafish; and (3) histopathology of the nervous system to accompany biochemical analyses. These data are expected to enhance understanding of the neurotoxicity potential of benzotriazoles and other plastic additives.

Development and Validation of Estimation Equations for Appendicular Skeletal Muscle Mass in Chinese Community-Dwelling Older Adults.

Purpose: This study aimed to establish equations for estimating muscle mass through anthropometric parameters or together with physical function parameters in the community-dwelling older adults, providing a simple way of muscle mass assessment. Methods: In this cross-sectional descriptive study, a total of 1537 older adults were recruited from the community and accepted the measurements of height, weight, upper arm and calf circumferences, grip strength, and walking speed. Body composition including appendicular skeletal muscle mass (ASM) was measured using bioelectrical impedance analysis (BIA). Participants were randomly divided into the development or validation group. Stepwise multiple linear regression was applied to develop equations in the development group. Thereafter, Pearson correlation coefficients, Bland-Altman plots, paired t-test, intraclass correlation coefficient (ICC) and paired-samples t-tests were used to assess the validity of the equations. Results: All parameters were significantly correlated with ASM (r = 0.195~0.795, P < 0.001) except for the age in the validation group (P = 0.746). The most optimal anthropometric equation was: [adjusted R2 = 0.911, standard error of the estimate (SEE) = 1.311, P < 0.001]. Comparatively speaking, this equation showed high correlation coefficient (r = 0.951, P < 0.001) and ICC (ICC = 0.950, P < 0.001). No significant differences were found between BIA-measured ASM and the estimated ASM. The Bland-Altman plot showed that the mean difference between the estimated ASM and BIA-measured ASM was 0 kg and the limits of agreement of ASM was -2.70~2.60 kg. Furthermore, inclusion of physical function did not significantly improve the adjusted R2 and SEE. Conclusion: The anthropometric equation offers a practical alternative simple and dependable method for estimating ASM in community-dwelling older adults.

Semi-rationally designed site-saturation mutation of Helicobacter pylori α-1,2-fucosyltransferase for improved catalytic activity and thermostability.

Helicobacter pylori HpfutC, a glycosyltransferase (GT) 11 family glycoprotein, has great potential for industrial 2'-fucosyllactose (2'-FL) production. However, its limited catalytic activity, low expression, and poor thermostability hinder practical applications. Herein, a semi-rationally designed site-saturation mutation was applied to engineer the catalytic activity and thermostability of HpfutC. The 6 single point mutants (K102T, R105C, D115S, Y251F, A255G and K282E) and 6 combined mutants (V1, V2, V3, V4, V5, and V6) with enhanced enzyme activity were obtained by mutant library screening and ordered recombination mutation. The optimal mutant V6, with an optimum temperature of 40 °C, was not a metal-dependent enzyme, yet the reaction was facilitated by Mn2+. Compared to wild-type HpfutC, mutant V6 exhibited a 2.3-fold increase in specific activity and a 2.18-fold increase in half-life at 40 °C, respectively. Kinetic parameters indicated that the Km values of mutant V6 were 34.5 % (lactose) and 25.0 % (GDP-L-fucose) lower than those of the wild enzyme, whereas the kcat/Km values were 1.20 and 1.25-fold higher than those of the wild enzyme. Further, 3D-structure analysis revealed that the highly rigid structure, formation of new hydrogen bonds, increased hydrophobic residues and redistribution of electrostatic charges on the surface may be responsible for the elevated enzyme activity and thermostability. The strategy adopted in this study is of great significance to the solution of the technical bottleneck of HpfutC and the industrial application of 2'-FL.

Association between body mass index and cognitive impairment in Chinese older adults.

Background: The association between body mass index (BMI) and the risk of cognitive impairment remains uncertain. Relatively few studies have analyzed the dose-response relationship between BMI and cognitive impairment. This article utilized nationally representative longitudinal data to assess the association between BMI and cognitive impairment in Chinese older adults. Objective: The present study aimed to analyze the association between BMI and cognitive impairment in Chinese older people, including an investigation of gender differences and the dose-response relationship. Methods: Data were obtained from the China Health and Retirement Longitudinal Study database in 2015 and 2018. The present study used logistic regression to analyze the relationship between baseline BMI and cognitive impairment, and adopted a restricted cubic spline model to plot dose-response curves for baseline BMI and prevalence of risk of cognitive impairment. Results: The mean BMI of the survey population was 23.48 ± 3.66 kg/m2, and the detection rate of cognitive impairment was 34.2%. Compared to the normal weight group (18.5 ≤ BMI < 23.9 kg/m2), the odds ratio (OR) for cognitive impairment was 1.473 (95% CI: 1.189-1.823) in the underweight group (BMI < 18.5 kg/m2), whereas the corresponding OR was 0.874 (95% CI: 0.776-0.985) for the overweight or obese group (BMI ≥ 24.0 kg/m2) after adjusting for confounders. Gender subgroup analysis showed that overweight or obese older women were less likely to develop cognitive impairment (OR = 0.843; 95% CI: 0.720-0.987). The results of the restricted cubic spline analysis revealed a curvilinear L-shaped relationship between BMI and the risk of cognitive impairment (P non-linearity <0.05). In particular, the risk of cognitive impairment was higher at a lower baseline BMI. In contrast, BMI in the range of 23.2-27.8 kg/m2 was associated with a decreased risk of cognitive impairment. Conclusion: BMI is a dose-dependent related factor for cognitive impairment in Chinese older adults. Being underweight is a risk factor for the development of cognitive impairment, while being overweight or obese is less likely to have cognitive impairment, particularly in female older people. Keeping BMI ranging from 23.2-27.8 kg/m2 in older adults can help maintain cognitive function.

Development and validation of risk prediction model for premenstrual syndrome in nurses: results from the nurses-based the TARGET cohort study.

Objective: Premenstrual syndrome (PMS) stands as a significant concern within the realm gynecological disorders, profoundly impacting women of childbearing age in China. However, the elusive nature of its risk factors necessitates investigation. This study, therefore, is dedicated to unraveling the intricacies of PMS by focusing on nurses, a cohort with unique occupational stressors, to develop and validate a predictive model for assessing the risk of PMS. Methods: This investigation employed a multi-center cross-sectional analysis drawing upon data from the TARGET Nurses' health cohort. Utilizing online survey versions of the Premenstrual Syndrome Scale (PMSS), a comprehensive dataset encompassing physiological, social, psychological, occupational, and behavioral variables was collected from 18,645 participants. A stepwise multivariate logistic regression analysis was conducted to identify independent risk factors for PMS. Furthermore, a refined variable selection process was executed, combining the Least Absolute Shrinkage and Selection Operator (LASSO) method with 10-fold cross-validation. The visualization of the risk prediction model was achieved through a nomogram, and its performance was evaluated using the C index, receiver operating characteristic (ROC) curves, and the calibration curves. Results: Among the diverse variables explored, this study identified several noteworthy predictors of PMS in nurses, including tea or coffee consumption, sleep quality, menstrual cycle regularity, intermenstrual bleeding episodes, dysmenorrhea severity, experiences of workplace bullying, trait coping style, anxiety, depression and perceived stress levels. The prediction model exhibited robust discriminatory power, with an area under the curve of 0.765 for the training set and 0.769 for the test set. Furthermore, the calibration curve underscored the model's high degree of alignment with observed outcomes. Conclusion: The developed model showcases exceptional accuracy in identifying nurses at risk of PMS. This early alert system holds potential to significantly enhance nurses' well-being and underscore the importance of professional support.

A possible genetic association between obesity and colon cancer in females.

Object: There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms. Methods: GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions. Results: Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p. Conclusion: Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.