Restriction on molecular fluxionality by substitution: A case study for the 1,10-dicyanobullvalene.

We show herein that 1,10-dicyano substitution restricts the paragon fluxionality of bullvalene to just 14 isomers which isomerize along a single cycle. The restricted fluxionality of 1,10-dicyanobullvalene (DCB) is investigated by means of: (i) Bonding analyses of the isomer structures using the adaptive natural density partitioning (AdNDP). (ii) Quantum dynamical simulations of the isomerizations along the cyclic intrinsic reaction coordinate of the potential energy surface (PES). The PES possesses 14 equivalent potential wells supporting 14 isomers which are separated by 14 equivalent potential barriers supporting 14 transition states. Accordingly, at low temperatures, DCB appears as a hindered molecular rotor, without any delocalization of the wavefunction in the 14 potential wells, without any nuclear spin isomers, and with completely negligible tunneling. These results are compared and found to differ from those for molecular boron rotors. (iii) Born-Oppenheimer molecular dynamics (BOMD) simulations of thermally activated isomerizations. (iv) Calculations of the rate constants in the frame of transition state theory (TST) with reasonable agreement achieved with the BOMD results. (v) Simulations of the equilibration dynamics using rate equations for the isomerizations with TST rate coefficients. Accordingly, in the long-time limit, isomerizations of the 14 isomers, each with Cs symmetry, approach the "14 Cs → C7v" thermally averaged structure. This is a superposition of the 14 equally populated isomer structures with an overall C7v symmetry. By extrapolation, the results for DCB yield working hypotheses for so far un-explored properties e.g. for the equilibration dynamics of C10H10.

Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

Causal analysis of body composition measurements in osteoarthritis knee: a two-sample mendelian randomization study.

BACKGROUND: To analyse the causal associations of different physical measures with osteoarthritis knee (KOA). METHODS: Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist-hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources. RESULTS: Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35-1.51)), BMI (1.40(1.10-1.78)), body fat percentage (1.56(1.44-1.68)), waist circumference (1.40(1.10-1.78)), hip circumference (1.37(1.30-1.44)), WHR (0.86(0.71-1.04)) and BMR (1.36(1.27-1.46) were consistent with the ones by Mendelian randomization analyses. CONCLUSIONS: Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA.

Gut microbiome causal impacts on the prognosis of breast cancer: a Mendelian randomization study.

BACKGROUND: Growing evidence has shown that gut microbiome composition is associated with breast cancer (BC), but the causality remains unknown. We aimed to investigate the link between BC prognosis and the gut microbiome at various oestrogen receptor (ER) statuses. METHODS: We performed a genome-wide association study (GWAS) to analyse the gut microbiome of BC patients, the dataset for which was collected by the Breast Cancer Association Consortium (BCAC). The analysis was executed mainly via inverse variance weighting (IVW); the Mendelian randomization (MR) results were verified by heterogeneity tests, sensitivity analysis, and pleiotropy analysis. RESULTS: Our findings identified nine causal relationships between the gut microbiome and total BC cases, with ten and nine causal relationships between the gut microbiome and ER-negative (ER-) and ER-positive (ER+) BC, respectively. The family Ruminococcaceae and genus Parabacteroides were most apparent among the three categories. Moreover, the genus Desulfovibrio was expressed in ER- BC and total BC, whereas the genera Sellimonas, Adlercreutzia and Rikenellaceae appeared in the relationship between ER + BC and total BC. CONCLUSION: Our MR inquiry confirmed that the gut microbiota is causally related to BC. This further explains the link between specific bacteria for prognosis of BC at different ER statuses. Considering that potential weak instrument bias impacts the findings and that the results are limited to European females due to data constraints, further validation is crucial.

Multi-resource collaborative scheduling problem of automated terminal considering the AGV charging effect under COVID-19.

Since the COVID-19 ravaged the global terminals, the Automated Container Terminal (ACT) has become one of important approach to promote the stronger quick response capacity to deal with the uncertainty that COVID-19 brought to the terminal. This research takes Automated Guided Vehicle (AGV) and their effects into account the multi-resource collaborative scheduling model to tradeoff ACT operational efficiency and energy savings. Firstly, the dual-cycle strategy of QC and the pooling strategy of AGV are given, which coordinates the scheduling of Quay Cranes (QCs), Yard Cranes (YCs) and other equipment. Furthermore, a multi-resource collaborative scheduling optimization model is proposed which roots from the principle of the Blocking-type Hybrid Flow Shop Problem (B-HFSP) with the objectives of minimizing the makespan of QC and the transportation energy consumption. And simultaneously, a mixed algorithm SA-GA is designed for solving this mixed integer programming model by an optimizing effect of Simulated Annealing on Genetic algorithms. Numerical experiments show that the model in this research is effective. The convergence of SA-GA is effective for small-scale cases and superior for large-scale cases. Considering both goals of high efficiency and energy saving, the Pareto solution set and collaborative scheduling solution take a priority to ensure that the bottlenecked QC runs efficiently. Here and now the average idle rate of QC is about [14%, 35%] lower than that of other equipment. The collaborative scheduling model constructed above not only has reference value for other multi-device and multi-stage scheduling problem, but also enhance the integrated decision-making ability of the ACT in the post-epidemic era.

Stochastic averaging for a type of fractional differential equations with multiplicative fractional Brownian motion.

This paper focuses on the averaging principle of Caputo fractional stochastic differential equations (SDEs) with multiplicative fractional Brownian motion (fBm), where Hurst parameter 1/2

Genetic characteristics and forensic features of Xibe ethnic group revealed via extended set of Y-STRs.

BACKGROUND: Xibe is the fifth largest minority population of Liaoning province. Predominately they live in Liaoning province (69.52%), followed by Xinjiang (18.06%), Heilongjiang (3.99%), Jilin (1.63%) and Inner Mongolia provinces (1.57%). AIM: To provide an updated and precise population database on an extended set of Y STRs not available before and explore the forensic characteristics of 26 Y chromosomal STRs. SUBJECTS & METHODS: In this study, we genotyped 406 unrelated Xibe male individuals from Liaoning province using Goldeneye® 26Y System kit and calculated the forensic parameters of these 26 Y STRs loci. RESULTS: All haplotypes generated for 406 Xibe samples using Goldeneye® 26Y kit were unique with a discrimination capacity (DC) of 1. On restricting the haplotypes to the Y-filer® set of 17 Y-STRs, we observed 392 haplotypes. Among them 93.53% (380) were unique with a DC of 0.9655 and haplotype diversity (HD) of 0.9998, showing high discrimination power of the extended set of markers in this population. Allelic frequencies ranged from 0.0024 to 0.7684 across 26 Y STRs loci. DYS385 showed the highest gene diversity (0.9691) among all markers. CONCLUSION: According to pairwise RST genetic distances among Xibe populations from China, the Liaoning Xibe population showed the closest genetic distance (0.0035) followed by Xinjiang Xibe population (0.0218). Multidimensional scaling (MDS) analysis among Xibe and 29 other Chinese populations showed that local populations such as Manchu from Liaoning and Han from Beijing had a close affinity while Tibetans from Aba, China, were most distant from Xibe populations. Moreover, 12 individuals showed a null allele at DYS448 in Xibe population samples. We submitted Y-STRs data in the Y-Chromosome Haplotype Reference Database (YHRD) for future forensic and other usage.

A quantitative exploration of symptoms in COVID-19 patients: an observational cohort study.

Background: As the spreading of the COVID-19 around the global, we investigated the characteristics and changes of symptoms in COVID-19 patients. Methods: This was an ambispective observational cohort study, and 133 confirmed COVID-19 patients were included and all symptoms over the course were analyzed qualitatively. The symptoms, their changes over the course in the cohort and in the different clinical types, etc. were illustrated. Differences in different periods and severities were analyzed through Chi square test, association with severity was analyzed through LASSO binomial logistic regression analysis. Inter-correlation and classification of symptoms were completed. Major symptoms were screened and their changes were illustrated. Results: A total of 43 symptoms with frequencies as 6067 in this cohort. Differences of symptoms in different stages and clinical types were significant. Expectoration, shortness of breath, dyspnea, diarrhea, poor appetite were positively but vomiting, waist discomfort, pharyngeal discomfort, acid reflux were negatively correlated with the combined-severe and critical type; dyspnea was correlated with the critical type. The 17 major symptoms were identified. The average daily frequency of symptoms per case was decreased continuously before the transition into the severe type and increased immediately one day before the transition and then decreased. It was decreased continuously before the transition date of the critical type and increased from the transition into the critical type to the next day and decreased thereafter. Dyspnea (P<0.001), shortness of breath (P<0.01) and chest distress (P<0.05) were correlated with death and their corresponding coefficient was 0.393, 0.258, 0.214, respectively. Conclusion: The symptoms of COVID-19 patients mainly related to upper respiratory tract infection, cardiopulmonary function, and digestive system. The mild type and the early stage in other types mainly related to upper respiratory tract infection. The cardiopulmonary function and digestive system associated symptoms were found in all other types and stages. Dyspnea was correlated with critical type, and dyspnea, shortness of breath and chest distress were correlated with death. Respiratory dysfunction (or incompleteness) associated symptoms were the characteristic symptoms. The changes of symptoms did not synchronously with the changes of severity before the transition into the severe or critical type.

Features of α-HBDH in COVID-19 patients: A cohort study.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has spread all over the world and brought extremely huge losses. At present, there is a lack of study to systematically analyze the features of hydroxybutyrate dehydrogenase (α-HBDH) in COVID-19 patients. METHODS: Electronic medical records including demographics, clinical manifestation, α-HBDH results and outcomes of all included patients were extracted. RESULTS: α-HBDH in COVID-19 group was higher than that in excluded group (p < 0.001), and there was no significant difference in α-HBDH before and after the exclusion of 5 patients with comorbidity in heart or kidney (p = 0.671). In COVID-19 group, the α-HBDH value in ≥61 years old group, severe group, and critical group, death group all increased at first and then decreased, while no obvious changes were observed in other groups. And there were significant differences of the α-HBDH value among different age groups (p < 0.001), clinical type groups (p < 0.001), and outcome groups (p < 0.001). The optimal scale regression model showed that α-HBDH value (p < 0.001) and age (p < 0.001) were related to clinical type. CONCLUSIONS: α-HBDH was increased in COVID-19 patients, obviously in ≥61 years old, death and critical group, indicating that patients in these three groups suffer from more serious heart and kidney and other tissues and organs damage, higher α-HBDH value, and risk of death. The difference between death and survival group in early stage might provide a approach to judge the prognosis. The accuracy of the model to distinguish severe/critical type and other types was 85.84%, suggesting that α-HBDH could judge the clinical type accurately.

Anticardiolipin antibody and anti-ß2 glycoprotein I antibody are potential risk markers of ischaemic stroke in Chinese adults.

OBJECTIVES: aCL and anti-ß2 glycoprotein I antibody (aß2GPI) are autoantibodies associated with thromboembolic diseases. Here we investigated whether they are correlated with ischaemic cardiovascular disease in a Chinese population. METHODS: Serum total aCL and aß2GPI isotypes (IgA, IgG or IgM, separately) were measured in 11 015 Chinese adults. Differences of antibody level between disease and non-disease groups were examined by t-test. The correlation between antibody and ischaemic cardiovascular disease was determined by logistic regression analysis. Performance of risk prediction models employed aCL or aß2GPI isotypes was evaluated by C statistic, net reclassification improvement index and integrated discrimination improvement. RESULTS: Total aCL and aß2GPI isotypes maintained low levels and increased with increasing age except total aCL and aß2GPI IgG in participants older than 70 years. When distinguishing ischaemic cardiovascular disease by coronary heart disease (CHD) and ischaemic stroke, the stroke group had higher levels of aCL and aß2GPI isotypes than the non-stroke group, while the CHD group only had a slightly higher aß2GPI IgG than non-CHD groups. aCL and aß2GPI were positively correlated with stroke but not with CHD, and improved the performance of conventional risk factors for stroke risk prediction, with C statistic from 0.769 (95% CI 0.744, 0.793) to 0.777 (95% CI 0.754, 0.800) (aß2GPI IgG, P = 0.0091), and 0.778 (95% CI 0.754, 0.801) (aß2GPI IgA, P = 0.0793). Stroke risk could be better reclassified by aCL and aß2GPI, in association with both net reclassification improvement and integrated discrimination improvement statistics (P < 0.05). CONCLUSION: aCL and aß2GPI are associated with ischaemic stroke and have added value for stroke risk prediction.

Transduction with Lentiviral Vectors Altered the Expression Profile of Host MicroRNAs.

RNA interference (RNAi) is widely used in gene knockdown analysis and as a tool to screen host genes involved in viral infection. Owing to the limitations of transducing cells with synthetic small interfering RNAs (siRNAs), lentiviral short hairpin RNA (shRNA) vectors are more widely used. However, we found that stable transduction with lentiviral shRNA vectors inhibited hepatitis C virus (HCV) propagation in human hepatoma cells. We found by microRNA (miRNA) microarray analysis that this inhibition was induced by the alteration of host miRNA expression. In addition to one miRNA (miR-196b-5p) previously reported to be involved in HCV infection, other miRNAs (miR-216a-5p, -216b-5p, 217, and -30b-5p) were found to influence HCV infection in this study. Further studies suggested that this effect was independent of the transcription of shRNAs. The lentiviral vector itself and the integration site of the lentiviral vector might determine the change in miRNA expression. Moreover, the upregulation of JUN contributed to the dysregulation of miR-216a-5p, -216b-5p, and -217 in stably transduced cells. Although the changes in miRNA expression were beneficial for inhibiting HCV infection in our study, this off-target effect should be considered when transduction with lentiviral vectors is performed for other purposes, especially in therapy.IMPORTANCE We found that stable transduction with lentiviral shRNA was able to nonspecifically inhibit HCV infection by the dysregulation of host miRNAs. Previous studies showed that the overexpression of shRNAs oversaturated the host miRNA pathways to inhibit HCV infection. In contrast, the miRNA machinery was not affected in our study. Knockout studies suggested that the nonspecific effect was independent of the transcription of shRNAs. The lentiviral vector itself and the integration sites in the host genome determined the changes in miRNAs. Stable transduction with lentiviral vectors was able to increase the expression of JUN, which in turn upregulated miR-216a-5p, miR-216b-5p, and miR-217. miR-216a-5p and miR-216b-5p might inhibit HCV by suppressing the host autophagic machinery. Our study suggested a novel nonspecific effect of lentiviral vectors, and this side effect should be considered when transduction with lentiviral vectors is performed for other purposes, especially in therapy.

Enterovirus 71 protease 2Apro and 3Cpro differentially inhibit the cellular endoplasmic reticulum-associated degradation (ERAD) pathway via distinct mechanisms, and enterovirus 71 hijacks ERAD component p97 to promote its replication.

Endoplasmic reticulum-associated degradation (ERAD) is an important function for cellular homeostasis. The mechanism of how picornavirus infection interferes with ERAD remains unclear. In this study, we demonstrated that enterovirus 71 (EV71) infection significantly inhibits cellular ERAD by targeting multiple key ERAD molecules with its proteases 2Apro and 3Cpro using different mechanisms. Ubc6e was identified as the key E2 ubiquitin-conjugating enzyme in EV71 disturbed ERAD. EV71 3Cpro cleaves Ubc6e at Q219G, Q260S, and Q273G. EV71 2Apro mainly inhibits the de novo synthesis of key ERAD molecules Herp and VIMP at the protein translational level. Herp differentially participates in the degradation of different glycosylated ERAD substrates α-1 antitrypsin Null Hong Kong (NHK) and the C-terminus of sonic hedgehog (SHH-C) via unknown mechanisms. p97 was identified as a host factor in EV71 replication; it redistributed and co-exists with the viral protein and other known replication-related molecules in EV71-induced replication organelles. Electron microscopy and multiple-color confocal assays also showed that EV71-induced membranous vesicles were closely associated with the endoplasmic reticulum (ER), and the ER membrane molecule RTN3 was redistributed to the viral replication complex during EV71 infection. Therefore, we propose that EV71 rearranges ER membranes and hijacks p97 from cellular ERAD to benefit its replication. These findings add to our understanding of how viruses disturb ERAD and provide potential anti-viral targets for EV71 infection.

[Analysis of genetic polymorphisms of 21 autosomal short tandem repeat loci among Han Chinese from Quanzhou].

OBJECTIVE: To analyze genetic polymorphisms of 21 autosomal short tandem repeat (STR) loci from Quanzhou Han Chinese groups using a GlobalFiler kit, and to assess its value for forensic practice. METHODS: For 402 unrelated Han individuals, allelic frequencies of 21 autosomal STR loci were determined by using the GlobalFiler kit. Genetic parameters of the 21 STR loci were calculated. RESULTS: No deviation from Hardy-Weinberg equilibrium was observed for the 21 loci. Most of the loci were highly polymorphic. Observed heterozygosity has ranged from 0.637 to 0.945, power of discrimination has ranged from 0.801 to 0.991, polymorphism information content has ranged from 0.570 to 0.940, power of exclusion was between 0.337 to 0.888, and match probability was between 0.009 to 0.199. CONCLUSION: GlobalFiler kit has a high value for personal identification and paternity testing for Han Chinese from Quanzhou.

GP205, a new hepatitis C virus NS3/4A protease inhibitor, displays higher metabolic stability in vitro and drug exposure in vivo.

NS3/4A serine protease is a prime target for direct-acting antiviral therapies against hepatitis C virus (HCV) infection. Several NS3/4A inhibitors have been widely used in clinic, while new inhibitors with better characteristics are still urgently needed. GP205 is a new macrocyclic inhibitor of NS3/4A with low nanomolar activities against HCV replicons of genotypes 1b, 2a, 4a, and 5a, with EC50 values ranging from 1.5 to 12.8 nmol/L. In resistance selection study in vitro, we found resistance-associated substitutions on D168: The activity of GP205 was significantly attenuated against 1b replicon with D168V or D168A mutation, similar as simeprevir. No cross resistance of GP205 with NS5B or NS5A inhibitor was observed. Combination of GP205 with sofosbuvir or daclatasvir displayed additive or synergistic efficacy. The pharmacokinetic profile of GP205 was characterized in rats and dogs after oral administration, which revealed good drug exposure both in plasma and in liver and long plasma half-life. The in vitro stability test showed ideal microsomal and hepatic cells stability of GP205. The preclinical profiles of GP205 support further research on this NS3/4A inhibitor to expand the existing HCV infection therapies.

Characterization of the Salmonella enterica Serotype Isangi Isolated from Patients for the First Time in China.

No studies have reported the isolation of serotype Salmonella Isangi from cases of salmonellosis in mainland China. We investigated an outbreak of foodborne disease with salmonella and collected the samples from the patients and surplus foods. Salmonella strains were isolated and the serotype was identified according to the Kauffmann-White scheme. The relatedness of the isolates was determined using pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). Antimicrobial susceptibility was conducted by the broth microdilution method. There were 74 diners in the case, 33 of which got ill, with an attack rate of 44.6% (33/74). A total of 24 samples were collected from the outbreak cases, six Salmonella Isangi strains were isolated and susceptible to all tested drugs. PFGE and WGS analysis suggested that the pathogen dissemination through a single or limited vector(s), the steamed fish and mixed food (fry spicy chicken, braised pork ribs, and goose leg), may be the source of infection or be cross-contaminated. We first report the characteristics of an outbreak and molecular strain relatedness of Salmonella Isangi in mainland China.

[Analysis of genetic polymorphisms of 15 STR loci among ethnic Hans from Xiamen].

OBJECTIVE: To assess the value of 15 short tandem repeat (STR) loci selected by an AmpFLSTR IdentifilerTM system for personal identification and paternity testing among ethnic Hans from Xiamen, Fujian. METHODS: For 400 unrelated individuals, allelic frequencies for the 15 STR loci from the AmpFLSTR IdentifilerTM kit were determined. Population genetics parameters for forensic usage were calculated. RESULTS: No deviation of the observed allele frequency from Hardy-Weinberg equilibrium expectations was found by Chi-square test (P>0.05). All of the 15 loci were highly polymorphic. Observed heterozygosity has varied between 0.580 and 0.868. Matching probability was between 0.036 and 0.148. Power of discrimination was between 0.798 and 0.967. Polymorphic information content was between 0.560 and 0.850. And power of exclusion was between 0.268 and 0.730. CONCLUSION: All of the 15 loci selected by the AmpFLSTR IdentifilerTM system are highly polymorphic among ethnic Hans from Xiamen. By determining the alleles and allelic frequencies, data for genetic polymorphisms usable for paternity testing and personal identification for local population were obtained.

[Research progress in signal bias of G protein-coupled receptor and its mechanism].

G protein-coupled receptors (GPCRs) mediate signal transduction via G protein or ß-arrestin. Several biased ligands and receptors that preferentially signal through either G protein- or ß-arrestin-mediated pathways have been identified. These discoveries have redefined the classical GPCR signaling paradigm. Distinct ligand-receptor binding sites might be one of the main reasons for biased signal transduction. It is posited that multiple active conformations of receptors lead to distinct kinase phosphorylation patterns on C terminus of receptors. Phosphorylation patterns decide which signal pathway will be transduced. The biased signal pathway transduction has been found in more than 40 GPCRs till now. A few of them have been found involved in fine-regulation of physiological processes. However, most others still need further investigation. The biased ligands may be developed as tools for understanding the basic physiology of GPCR, and, potentially and most importantly, as fine-tuned therapeutics that maximize beneficial effects and minimize adverse or unwanted effects. These studies will provide new insights into new drug discovery.

The association between lipid biomarkers and osteoarthritis based on the National Health and Nutrition Examination Survey and Mendelian randomization study.

To explore the association between lipid markers and osteoarthritis (OA). First, the National Health and Nutrition Examination Survey (NHANES) database was used to screen participants with lipid markers, OA and relevant covariates, and logistic regression was used to analyze the association between lipid markers and OA; Then, under the theoretical framework of Mendelian randomization (MR), two-sample MR was performed using GWAS data of lipid markers and OA to explore the causal association between the two, which was analyzed by inverse variance weighting (IVW) method. Heterogeneity test, sensitivity analysis and pleiotropy analysis were also performed. The NHANES database screened a total of 3706 participants, of whom 836 had OA and 2870 did not have OA. When lipid markers were used as continuous variables, multivariate logistic results showed an association between HDL, LDL and OA (HDL, OR (95%):1.01 (1.00, 1.01); LDL, OR (95%):1.00 (0.99, 1.00)). When lipid markers were used as categorical variables, multivariate logistic results showed the fourth quartile result of 0.713 (0.513, 0.992) for LDL relative to the first quartile. In MR study, the results of the IVW method for TG, TL, HDL and LDL showed OR (95% CI) of 1.06 (0.97-1.16), 0.95 (0.85-1.06), 0.94 (0.86-1.02) and 0.89 (0.80-0.998) with P-values of 0.21, 0.37. 013, 0.046. The heterogeneity tests and multiplicity analyses showed P-values greater than 0.05, and sensitivity analyses showed no abnormal single nucleotide polymorphisms. Through NHANES database and MR analyses, LDL was found to be a protective factor for OA, while HDL still needs further study. Our results provide new biomarkers for preventive and therapeutic strategies for OA.

The burden of low back pain in adolescents and young adults.

BACKGROUND: Low back pain is highly prevalent and the main cause of years lived with disability, but data on the burden and trends of low back pain (LBP) in adolescents and young adults (AYAs) are sparse. OBJECTIVE: To assess trends in the burden of LBP among AYAs aged 15-39 years at the global, regional and national levels from 1990 to 2019. METHODS: Data from the Global Burden of Disease (GBD) 2019 were used to analyze incidence, prevalence and Disability-adjusted life year (DALY) due to LBP at global, regional, and national levels. Joinpoint regression analysis calculated the average annual percentage changes (AAPC). Then analyse the association between incidence, prevalence and DALYs and socioeconomic development using the GBD Socio-demographic Index (SDI). Finally, projections were made until 2030 and calculated in Nordpred. RESULTS: The incidence, prevalence and DALYs rates (95%UI) were 2252.78 (1809.47-2784.79), 5473.43 (4488.62-6528.15) and 627.66 (419.71-866.97) in 2019, respectively. From 1990 to 2019, the incidence, prevalence, and DALYs rates AAPC (95%CI) were -0.49 (-0.56 to -0.42), -0.58 (-0.65 to -0.51) and -0.57 (-0.64 to -0.5), respectively. Incidence, prevalence, and DALYs rates in South Asia, East Asia, High-income North America, Western Europe, and Australasia decreased with SDI. Incidence, prevalence, and DALYs rates in Central Asia, Central Europe, and Eastern Europe decreased and then increased with SDI. At the national level, the incidence, prevalence, and DALYs rates are high in the United States and low in India and China. From the 2020 to 2030, most regions is predicted to decline. CONCLUSION: LBP in AYAs is a major global public problem with a high burden. There are large differences in incidence, prevalence and DALYs across SDIs, regions and countries. there is still a need to focus on LBP in AYAs and tailor interventions to reduce the future burden of this condition.

Association between added sugars and frailty in U.S. adults: a cross-sectional study from the National Health and Nutrition Examination Survey 2007-2018.

Objective: There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study. Methods: This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status. Results: This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty. Conclusion: Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations.