Frailty index trajectories in Chinese older adults with diverse levels of social participation: findings from a national population-based longitudinal study.

BACKGROUND: Aging and frailty pose significant challenges globally, placing a substantial burden on healthcare and social services due to their adverse consequences. AIM: The primary objective of this study was to investigate the relationship between social participation and development of frailty transition and trajectory. METHODS: This study utilized data from the CLHLS Cohort, a 10-year follow-up study involving 6713 participants, to investigate the association between social participation and development of frailty. Frailty reflects a comprehensive decline in various body functions. The study employed a group-based trajectory model to analyze the development trajectory of the frailty index and used logistic regression to assess the odds ratio (OR) of frailty risk. RESULTS: We identified two distinct groups of frailty progression trajectories: the "stable development group" and the "rapid growth group." Individuals who engaged in social activities at least once a month, but not daily, exhibited a significant association with an increased risk of transitioning into the "rapid growth group" (OR 1.305, 95% CI 1.032-1.649). Those with social participation less than once a month had an even greater risk (OR 1.872, 95% CI 1.423-2.463). Moreover, low social participation frequency (occasionally/never) has a more pronounced impact on frailty progression in males. CONCLUSION: A higher frequency of social participation is associated with a lower risk of being classified into the "rapid growth group" and a slower rate of frailty index progression. Preventing the progression of frailty can contribute to enhanced support for healthy aging among older adults.

Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin-Nucleoside Conjugates as AntitumorAgents.

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin-nucleoside conjugates 9a-10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon's antitumor activity based on our present study.

Ca mobilization and signaling pathways induced by rRgpB in human gingival fibroblast.

: To assess the () recombinant gingivalis gingipain R2 (rRgpB)-induced Ca mobilization in human gingival fibroblast (HGF) mediated by protease-activated receptor (PAR) and its downstream signal transduction pathways. : Flow cytometry was used to detect the expression of PAR in HGF. The proliferation of HGF was measured by CCK-8. The dynamic changes of intracellular Ca concentration in HGF induced by rRgpB and the blocking effect of PAR-1 antagonist were observed by laser confocal microscopy. Western blot was performed to determine the phosphorylation levels of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein kinase (p38 MAPK) and p65 in HGF. : PAR-1 and PAR-3 were expressed in HGF, and the rRgpB could promote the proliferation of HGF. rRgpB caused a transient increase in [Ca], which could be completely suppressed by vorapaxar, a PAR-1 antagonist. The phosphorylation levels of JNK, ERK1/2 and p65 were significantly up-regulated after the induction of rRgpB for and (all <0.05), which was completely inhibited by vorapaxar. However, the phosphorylation level of p38 MAPK had no significant change after rRgpB stimulation. : rRgpB causes an increase in [Ca] in HGF mediated by PAR-1. JNK, ERK1/2 and nuclear factor-κB may be involved in intracellular signal transduction after PAR-1 activation.

Activation of calcium signaling in human gingival fibroblasts by recombinant Porphyromonas gingivalis RgpB protein.

Arginine-specific cysteine proteinases, such as Arg-gingipain B (RgpB), mediate inflammation by activating protease-activated receptors (PARs). Arg-gingipain B is produced by Porphyromonas gingivalis, and is implicated in the causation of periodontal disease. The purpose of the present study was to observe the influence of recombinant RgpB protein (rRgpB) on PAR activation by monitoring intracellular Ca2+ ion concentration ([Ca2+]i) and inositol-1,4,5-triphosphate (IP3) levels in human gingival fibroblasts (HGFs). Our findings showed that rRgpB could cause a transient increase in [Ca2+]i. This increase in [Ca2+]i was completely suppressed by vorapaxar, a PAR-1 antagonist. Recombinant Arg-gingipain B increased the concentration of IP3, reaching a maximum at 60 s after treatment; this was completely inhibited by vorapaxar. We therefore conclude that rRgpB-induced calcium signaling in HGFs is mainly caused by PAR-1 activation. This suggests that PAR-1 activation plays a significant role in chronic inflammatory periodontal disease induced by P. gingivalis RgpB.

Development and application of a rapid detection system for human papillomavirus and Herpes simplex virus-2 by loop-mediated isothermal amplification assay.

Human papillomavirus (HPV) infection is an important factor that causes cervical cancer and non-melanoma skin cancer (NMSC), while HSV-2 plays an important role when HR-HPV triggers the cancer. Thus, a quick and convenient assay in the detection of HPV and HSV-2in the screening of HPV and HSV-2 infection is required. Two respective HPV and HSV-2 detection methods were established based on loop-mediated isothermal amplification (LAMP) assay. Specific outer primers, inner primers, and loop primers were designed according to the conserved domains of HPV and HSV-2 genomes, respectively, while degenerate primers were used for HPV assay. After optimizing the reaction conditions, the results were observed by LAMP Tubidimeter real-time LA-320. Standard plasmids HPV-L-P and HSV-2-L-P were cloned and used in sensitivity tests of HPV LAMP and HSV-2 LAMP, respectively. Fifty samples of actinic keratosis (AK), 20 samples of squamous cell carcinoma (SCC), 50 samples of basal cell carcinoma (BCC) and 20 samples of seborrheic keratosis (SK) were detected by HPV assay. Seventy three clinical samples of vaginitis, chronic cervicitis, cervical intraepithelial neoplasias and cervical cancer level positive were detected with HPV and HSV-2 assays. The reaction conditions of two assays were the same with a reaction temperature of 63 °C and a reaction time of 45 min. The sensitivity of HPV LAMP assay was 10 copies/µL, while that of the HSV-2 LAMP assay was 100 copies/µL. No cross-reactivity was observed. The HPV positive rates of AK, SCC, BCC and SK samples were 80% (40/50), 75% (15/20), 44% (22/50) and 21% (15/72), respectively. As an economic and quick diagnostic tool, LAMP assay is conducive to the extensive screening of HPV and HSV-2 and has huge potential to be promoted in resource-limited hospitals.

Long-term impact of PM2.5 exposure on frailty, chronic diseases, and multimorbidity among middle-aged and older adults: insights from a national population-based longitudinal study.

Particulate Matter 2.5 (PM2.5) is a significant risk factor for frailty and chronic diseases. Studies on the associations between PM2.5 and frailty, chronic diseases, and multimorbidity are scarce, especially from large cohort studies. We aimed to explore the potential association between PM2.5 exposure and the risk of frailty, chronic diseases, and multimorbidity. We collected data from a national cohort (CHARLS) with a follow-up period of 11-18 years, totaling 13,366 participants. We obtained PM2.5 concentration data from the Atmospheric Composition Analysis Group at Dalhousie University. PM2.5 exposure is based on the average annual concentration in the prefecture-level city where residents live. We define frailty as the comprehensive manifestation of declining various body functions, characterized by a frailty index of 0.25 or greater, and multimorbidity as the presence of at least two or more chronic conditions. Cox proportional hazards regression was used to estimate the hazard ratio (HR) with its 95% confidence interval (95%CI). A 10-µg/m3 increase for PM2.5 was significantly associated with an increased risk of frailty (HR = 1.289, 95%CI = 1.257-1.322, P < 0.001). A 10-µg/m3 increase for PM2.5 was significantly associated with the elevated risk for most chronic diseases. Compared to those with no morbidity or only single morbidity, a 10-µg/m3 increase for PM2.5 was significantly associated with the elevated risk for multimorbidity (HR = 1.220, 95%CI = 1.181-1.260, P < 0.001). Ambient PM2.5 exposure is a significant risk factor for frailty, chronic diseases, and multimorbidity, and some measures need to be taken to reduce PM2.5 concentration and prevent frailty and chronic diseases.

The association between declining lung function and stroke risk: insights from an observational study and Mendelian randomization.

Background: Stroke, prevalent globally, particularly impacts low- and middle-income countries. Decreased lung function is one of the risk factors for stroke, and there is a lack of sufficient research on the association between the two, especially based on evidence from representative large samples. We aimed to explore the association between lung function and stroke incidence. Methods: We collected data from 13,371 participants from the 2007-2012 U.S. national cross-sectional study and 11,192 participants from the Chinese national cohort study during the 2011-2018 follow-up period. Multivariate logistic regression and Cox proportional hazards regression were used to assess cross-sectional and longitudinal associations of peak expiratory flow with stroke risks. Additionally, we used publicly available GWAS data from a European population to conduct Mendelian randomization analysis, further exploring the potential causal relationship. Results: The results of the cross-sectional study suggest that a decline in peak expiratory flow may be associated with an increased risk of stroke. The cohort study revealed that, compared to the first tertile group, the risk of stroke incidence in the second and third tertile groups of PEF decreased by 19% (hazard ratio (HR) = 0.810, 95%CI = 0.684-0.960) and 21.4% (HR = 0.786, 95%CI = 0.647-0.956), respectively. Mendelian randomization analysis clarified that higher PEF levels are significantly associated with a reduced risk of stroke (OR = 0.852, 95%CI = 0.727-0.997). Conclusion: Decreased lung function is a risk factor for stroke. As a simple and accurate indicator of lung function, PEF can be used to monitor lung function in community populations and patients for primary stroke prevention.

Speciation analysis and formation mechanism of iron-phosphorus compounds during chemical phosphorus removal process.

Iron (Fe) salt was applied extensively to remove phosphorus (P) in wastewater treatment plants (WWTPs). Exploring the formation mechanism of iron-phosphorus compounds (FePs) during the chemical P removal (CPR) process is beneficial to P recovery. In this study, the performance of P removal, FePs speciation analysis and the kinetics of P removal under different conditions (pH, Fe/P molar ratio (Fe/Pmol), type of Fe salt, dissolved organic matters) were comprehensively investigated. More than 95% of P was removed under the optimal conditions with pH = 4.7, Fe/Pmol = 2, FeCl3 or polymeric ferric sulfate (PFS) as the coagulant. The FePs formation mechanism was considerably influenced by reaction conditions. Iron-phosphate compounds were the dominant FePs species (>76%) at pH < 6.2, while more iron oxides were formed at pH ≥ 6.2 with decreased P removal efficiency. When the initial Fe/Pmol was 2, iron-phosphate compound was the only product that was formed by the reaction between PO43- and Fe(III) or Fe(II) ions directly. More iron oxides were generated when the initial Fe/Pmol was 1 or 3. At Fe/Pmol = 1, the Fe(III) was hydrolyzed to form iron oxides and trapped PO43-, while at Fe/Pmol = 3, iron-phosphate compounds were produced firstly and the remaining Fe(III) was hydrolyzed to form iron oxides. The pseudo-second-order kinetic model simulated the chemical P removal process well. The reaction rate of P with Fe(II) was slower than that with Fe(III), but complete removal was still achieved when the reaction time was more than 30 min. Poly-Fe salt exhibited a fast P removal rate, while the removal efficiency depended on its iron content. Organic matters in wastewater with large molecular weight and multiple functional groups (such as humic acids) inhibited P removal rate but hardly affect the removal amount. This study provides an insight into CPR by Fe salts and is beneficial for P recovery in WWTPs.

Deep Learning-Based Road Traffic Noise Annoyance Assessment.

With the development of urban road traffic, road noise pollution is becoming a public concern. Controlling and reducing the harm caused by traffic noise pollution have been the hot spots of traffic noise management research. The subjective annoyance level of traffic noise has become one of the most important measurements for evaluating road traffic pollution. There are subjective experimental methods and objective prediction methods to assess the annoyance level of traffic noise: the subjective experimental method usually uses social surveys or listening experiments in laboratories to directly assess the subjective annoyance level, which is highly reliable, but often requires a lot of time and effort. The objective method extracts acoustic features and predicts the annoyance level through model mapping. Combining the above two methods, this paper proposes a deep learning model-based objective annoyance evaluation method, which directly constructs the mapping between the noise and annoyance level based on the listening experimental results and realizes the rapid evaluation of the noise annoyance level. The experimental results show that this method has reduced the mean absolute error by 30% more than the regression algorithm and neural network, while its performance is insufficient in the annoyance interval where samples are lacking. To solve this problem, the algorithm adopts transfer learning to further improve the robustness with a 30% mean absolute error reduction and a 5% improvement in the correlation coefficient between the true results and predicted results. Although the model trained on college students' data has some limitations, it is still a useful attempt to apply deep learning to noise assessment.

Manipulation of sterol homeostasis for the production of 24-epi-ergosterol in industrial yeast.

Brassinolide (BL) is the most biologically active compound among natural brassinosteroids. However, the agricultural applications are limited by the extremely low natural abundance and the scarcity of synthetic precursors. Here, we employ synthetic biology to construct a yeast cell factory for scalable production of 24-epi-ergosterol, an un-natural sterol, proposed as a precursor for BL semi-synthesis. First, we construct an artificial pathway by introducing a Δ24(28) sterol reductase from plants (DWF1), followed by enzyme directed evolution, to enable de novo biosynthesis of 24-epi-ergosterol in yeast. Subsequently, we manipulate the sterol homeostasis (overexpression of ARE2, YEH1, and YEH2 with intact ARE1), maintaining a balance between sterol acylation and sterol ester hydrolysis, for the production of 24-epi-ergosterol, whose titer reaches to 2.76 g L-1 using fed-batch fermentation. The sterol homeostasis engineering strategy can be applicable for bulk production of other economically important phytosterols.

Understanding roles of humic substance and protein on iron phosphate transformation during anaerobic fermentation of waste activated sludge.

Effects of fulvic acid (FA) and bovine serum albumin (BSA) on the transformation of ferric phosphate (FePO4) during anaerobic fermentation of waste activated sludge were investigated. Both FA and BSA promoted phosphorus (P) release from FePO4. A higher P release efficiency was achieved with FA addition compared with BSA at the same dose although BSA promoted iron (Fe) reduction more effectively. Both FA and BSA contributed to the enrichment of vivianite but hindered P re-precipitation with other ions, and FA affected more significantly. Microbial analysis revealed that FA contributed to the enrichment of iron-reducing bacteria (IRB) transporting electrons indirectly and increased the bioavailable Fe(III) via siderophores; BSA provided more electron donors, thereby enriched IRB transferring electrons directly to Fe(III). This study provides an in-depth understanding of Fe and P transformations in sludge bearing iron-phosphorus compounds and it is of practical value for P recovery as vivianite.

MicroRNA­223 attenuates LPS­induced inflammation in an acute lung injury model via the NLRP3 inflammasome and TLR4/NF­κB signaling pathway via RHOB.

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome are common and complex inflammatory lung diseases. MicroRNAs (miRs) have emerged as novel gene regulatory molecules, serving a crucial role in a variety of complex diseases, including ALI. In the present study, the anti­inflammatory action of miR­223 on inflammation in ALI was demonstrated and the possible mechanism was further examined. In lipopolysaccharide­induced ALI, the expression of miR­223 was reduced compared with that in the control normal group. An in vitro model was used to analyze the effect of miR­223 downregulation on an ALI model, which increased inflammation, and induced the activation of the NACHT, LRR and PYD domains­containing protein 3 (NLRP3) inflammasome and Toll­like receptor 4 (TLR4)/nuclear factor (NF)­κB signaling pathway via rho­related GTP­binding protein RhoB (RHOB). In addition, the overexpression of miR­223 reduced inflammation and suppressed the NLRP3 inflammasome and TLR4/NF­κB signaling pathway via RHOB in the in vitro model. Furthermore, TLR4 inhibitor or NLRP3 inhibitor reduced the pro­inflammatory effect of miR­223 downregulation in ALI. In conclusion, the results of the present study indicated that miR­223 functioned as a biological indicator by regulating inflammation in ALI, and may represent a novel potential therapeutic target and prognostic marker of ALI.

Predicting the target genes of miRNAs in preterm via targetscore algorithm.

Compared with normal neonates, preterm infants have an immature immune system which causes them to have a higher morbidity rate and even death. In order to reduce the mortality of newborns, we need to find the target genes which affect the preterm and understand their mechanism. It has been verified that microRNA (miRNA)-200 and miRNA-182 are closely related to the incidence of preterm. Therefore, it is significant to predict the target genes which are regulated by them for further understanding the mechanism of preterm. We chose the targetscore method for calculating the variational Bayesian-Gaussian mixture model (VB-GMM) as the target genes prediction method. It is designed for condition-specific target predictions and not limited to predict conserved genes, so the results are more accurate than previous sequence-based target prediction algorithms. In this study, our major contribution is to predict the target mRNAs of the chosen miRNAs with the gene expression profiles and a new method, which can effectively improve the accuracy of the prediction.

Spatial Distribution Characteristics and Pollution Evaluation of Soil Iron in the Middle Hanjiang River.

Soil iron has an important impact on the ecological environment and on crop growth. This study selected a typical small watershed basin in the middle reaches of the Han River (Yujiehe) at Ankang City and used geostatistical methods and kriging interpolation to analyze the spatial distribution and structure of soil iron content for different land uses and at different depths, using the single-factor pollution evaluation to evaluate the pollution degree of soil iron. The results showed that soil iron in the Yujie River basin decreased with increasing soil depth, with contents of 8.80 mg/kg, 5.52 mg/kg, and 4.92 mg/kg at depths A1 (0-20 cm), A2 (20-40 cm), and A3 (40-60 cm). According to the classification index of effective trace elements in soil, the average contents of soil iron at these three depths were between 4.5 and 10 mg/kg, which are all considered moderate values. The coefficients of variation of soil iron at the three soil depths were 59%, 75%, and 83%, all of which showed moderate spatial variability, and the coefficient of variation increased gradually with soil depth. With semi-variance calculated at the three soil depths, soil iron optimal theoretical models were all exponential models with nugget coefficients of 9.52%, 47.76%, and 33.93%, indicating that spatial correlation was very strong in the A1 layer and moderate in the A2 and A3 layers. The spatial distribution of soil iron showed some variation in the study area, and the soil content was higher in the midwestern part in the A1 and A2 layers; however, in the A3 layer, the higher content was in the center and lower content was in the southern region. Correlations were significant between soil iron content on the one hand and land-use type and topographic factors on the other. The pollution indices of soil iron at the three soil depths under different land uses were all greater than 1.0, with the A1 layer in farmland being the worst, at 3.34. In the study area, using the background value of soil iron as an evaluation standard, the soil iron content of more than 65% of the Yujiehe region exceeded this standard.

Runoff change and sediment source during rainstorms in an ecologically constructed watershed on the Loess Plateau, China.

The sediment-reducing effect of check dams and the safety issues following dam breaks are long-standing concerns. This study analyzed the runoff change and sediment source during rainstorms in a small watershed using a multivariate mixed model and a comparative analysis of watersheds. The problem of sediment loss from dammed farmland following check dam break during rainstorms was evaluated. The results showed that the flood peak lag time (PLT) was significantly influenced by pre-soil moisture in cases of small amounts of rainfall but not during rainstorms. Ecological construction significantly reduced the linear correlation between rainfall and runoff modulus (RM). The reduction in sediment delivery modulus (SDM) due to the check dam was more significant than that in RM. The reduction in RM and SDM under rainstorm conditions were 16%-74% and 53%-93%, respectively. The contributions of inter-gully and gully lands to the sediment deposited in dammed farmland during a large rainstorm on July 26, 2017 were 38.07% and 61.93%, respectively. Soil erosion remained significant during large rainstorms. The increase in vegetation coverage on the hill slope increased the amount of sediment from gully lands. Check dam breaches have accounted for a loss of only 1.2% of the total area of the dammed farmland, and thus have not caused a large loss of sediment. However, breaches in them clearly increased the coefficient of variation of RM and SDM. Therefore, check dams have a critical effect on controlling sediment delivery at the watershed scale. Dam breaks do not result in a large percentage of sediment loss in the dammed farmland.

Identification of key genes in endometrioid endometrial adenocarcinoma via TCGA database.

BACKGROUND: Understanding the molecular mechanisms is important in development and therapy of endometrioid endometrial adenocarcinoma. OBJECTIVE: To identify key genes in endometrioid endometrial adenocarcinoma. METHODS: The data of mRNA, miRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA) database and differential analysis was performed. Then, bioinformatic analysis was used to explore the regulatory mechanisms of miRNA and DNA methylation on gene expression. The regulatory network between differentially expressed miRNAs and target genes was established. Finally, the quantitative RT-PCR was applied to validate the bioinformatics results. RESULTS: We obtained biological omics data of 381 patients with endometrioid endometrial adenocarcinoma from TCGA data portal. After data processing, up to 2068 DEGs and 69 differentially expressed miRNAs were identified. Prediction and correlation analysis revealed that 175 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. After the integrated analysis of differentially methylated CpG islands and DEGs, 16 related genes were obtained. The quantitative RT-PCR results were roughly consistent with the bioinformatics analysis. CONCLUSIONS: The altered DEGs (ZEB1, ZEB2, TIMP2, TCF4, CYP1B1, PITX1, PITX2, ZNF154 and TSPYL5) may be involved in tumor differentiation of endometrioid endometrial adenocarcinoma and could be used as potential therapeutic targets for the disease.