Multimorbidity patterns and the risk of falls among older adults: a community-based study in China.

BACKGROUND: Due to the high prevalence of multimorbidity and realistic health service demands for fall prevention, there is growing interest in the association between multimorbidity and falls. Our study aimed to identify multimorbidity patterns among Chinese older adults and explore the association between multimorbidity patterns and falls. METHODS: Data from 4,579 Chinese community-dwelling older adults was included in this analysis. Information regarding falls and 10 chronic conditions was collected. An exploratory factor analysis was performed to determine multimorbidity patterns. Regression models were fitted to explore the associations of individual chronic disease or multimorbidity patterns with falls. RESULTS: Among 4,579 participants, 368 (8.0%) were defined as fallers, including 92 (2.0%) frequent fallers, and multimorbidity affected 2,503 (54.7%) participants. Older adults with multimorbidity were more likely to be fallers [odds ratio (OR) = 1.3, P = 0.02] and frequent fallers (OR = 1.7, P = 0.04). Three multimorbidity patterns were identified (i.e., cardiovascular-metabolic diseases, psycho-cognitive diseases and organic diseases), and the associations between psycho-cognitive diseases/organic diseases and prevalent falls or frequent falls were found to be significant. CONCLUSIONS: The psycho-cognitive disease pattern and organic disease pattern are significantly associated with falls. Therefore, more attention should be paid to patients with psycho-cognitive diseases and timely, targeted diagnostic and treatment services should be provided in fall prevention.

Impact of different anastomosis methods on post-recurrence after intestinal resection for Crohn's disease: A meta-analysis.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, often requiring intestinal resection as a common treatment. However, recurrence after surgery is common. The anastomotic configuration after bowel resection appears to be associated with the recurrence of CD. Previous studies have suggested that the Kono-S anastomosis may help to reduce the recurrence rate. However, the results remain controversial. Therefore, evidence-based evidence is needed to prove the advantages of Kono-S anastomosis. AIM: To measure the influence of anastomosis techniques on the long-term relapse rate of CD by conducting a meta-analysis. METHODS: PubMed, Scopus, and Cochrane Library were searched until October 8, 2023. Patients who underwent intestinal resection due to CD were included. The intervention measures included Kono-S anastomosis, whereas the control group received traditional anastomosis such as end-to-end, end-to-side, and side-to-side anastomosis. Only randomized clinical trials and observational studies were included. The primary outcome measures were hospital stay post-surgery, overall postoperative complication incidence, the proportion of Clavien-Dindo grade IIIa or higher, overall postoperative recurrence rate, and Rutgeerts score. RESULTS: From 2011 to 2023, six articles met the inclusion and exclusion criteria. The results indicated that Kono-S anastomosis can reduce the hospital stay post-surgery of patients with CD [MD = -0.26, 95%CI: -0.42 to -0.10, P = 0.002] than other traditional anastomosis methods. Compared to other traditional anastomosis methods, Kono-S anastomosis can significantly reduce the total recurrence rate [MD = 0.40, 95%CI: 0.17 to 0.98, P = 0.05] and postoperative Rutgeerts score [MD = -0.81, 95%CI: -0.96 to -0.66, P < 0.001] in patients with CD. However, there is no significant disparity in the overall occurrence of postoperative complications and the proportion of Clavien-Dindo ≥ IIIa. CONCLUSION: Kono-S anastomosis has the potential to expedite the recuperation of CD and diminish relapse hazards; however, additional larger trials are necessary to authenticate its effectiveness.

Genome-wide association study and genomic selection of spike-related traits in bread wheat.

KEY MESSAGE: Identification of 337 stable MTAs for wheat spike-related traits improved model accuracy, and favorable alleles of MTA259 and MTA64 increased grain weight and yield per plant. Wheat (Triticum aestivum L.) is one of the three primary global, staple crops. Improving spike-related traits in wheat is crucial for optimizing spike and plant morphology, ultimately leading to increased grain yield. Here, we performed a genome-wide association study using a dataset of 24,889 high-quality unique single-nucleotide polymorphisms (SNPs) and phenotypic data from 314 wheat accessions across eight diverse environments. In total, 337 stable and significant marker-trait associations (MTAs) related to spike-related traits were identified. MTA259 and MTA64 were consistently detected in seven and six environments, respectively. The presence of favorable alleles associated with MTA259 and MTA64 significantly reduced wheat spike exsertion length and spike length, while enhancing thousand kernel weight and yield per plant. Combined gene expression and network analyses identified TraesCS6D03G0692300 and TraesCS6D03G0692700 as candidate genes for MTA259 and TraesCS2D03G0111700 and TraesCS2D03G0112500 for MTA64. The identified MTAs significantly improved the prediction accuracy of each model compared with using all the SNPs, and the random forest model was optimal for genome selection. Additionally, the eight stable and major MTAs, including MTA259, MTA64, MTA66, MTA94, MTA110, MTA165, MTA180, and MTA164, were converted into cost-effective and efficient detection markers. This study provided valuable genetic resources and reliable molecular markers for wheat breeding programs.

Characterization of a wheat stable QTL for spike length and its genetic effects on yield-related traits.

Spike length (SL) is one of the most important agronomic traits affecting yield potential and stability in wheat. In this study, a major stable quantitative trait locus (QTL) for SL, i.e., qSl-2B, was detected in multiple environments in a recombinant inbred line (RIL) mapping population, KJ-RILs, derived from a cross between Kenong 9204 (KN9204) and Jing 411 (J411). The qSl-2B QTL was mapped to the 60.06-73.06 Mb region on chromosome 2B and could be identified in multiple mapping populations. An InDel molecular marker in the target region was developed based on a sequence analysis of the two parents. To further clarify the breeding use potential of qSl-2B, we analyzed its genetic effects and breeding selection effect using both the KJ-RIL population and a natural mapping population, which consisted of 316 breeding varieties/advanced lines. The results showed that the qSl-2B alleles from KN9204 showed inconsistent genetic effects on SL in the two mapping populations. Moreover, in the KJ-RILs population, the additive effects analysis of qSl-2B showed that additive effect was higher when both qSl-2D and qSl-5A harbor negative alleles under LN and HN. In China, a moderate selection utilization rate for qSl-2B was found in the Huanghuai winter wheat area and the selective utilization rate for qSl-2B continues to increase. The above findings provided a foundation for the genetic improvement of wheat SL in the future via molecular breeding strategies.

Association of the TRIM family protein with survival outcomes and clinicopathological features in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: The tripartite motif (TRIM) proteins have been reported to play crucial roles in various malignancies. However, the clinical significance of TRIM proteins in colorectal cancer (CRC) remains controversial. This study aimed to evaluate the association between TRIM proteins and the clinicopathological features and survival outcomes in patients with CRC. METHODS: We performed a meta-analysis to investigate whether TRIM is a prognostic factor in CRC. PubMed, Embase, Web of Science, CNKI and Weipu databases were searched to identify eligible studies that evaluated the association between TRIM proteins and overall survival (OS), as well as the clinicopathological features of patients with CRC. Hazard ratios (HR) or odds ratios (OR) with 95% confidence interval (CI) were derived and pooled using a fixed-effects model. RESULTS: From inception to March 2023, we extracted study characteristics and prognostic data for each identified study. Twelve studies enrolling 1608 patients were eligible for inclusion. Data on OS and recurrence-free survival (RFS) were available for 12 and 2 studies, respectively. The pooled analysis results showed a significant correlation between the elevated TRIM proteins and shorter OS (HR = 2.42, 95% CI: 1.96-2.99) and worse RFS (HR = 2.51, 95% CI: 1.78-3.54) in patients with CRC. The combined ORs indicated that TRIM protein over-expression was significantly associated with advanced TNM stage (OR = 2.26, 95% CI: 1.25-4.10), deep tumor invasion (OR = 2.01, 95% CI: 1.04-3.88), lymph node metastasis (OR = 2.99, 95% CI: 2.19-4.09) and perineural invasion (OR = 1.95, 95% CI: 1.18-3.23). CONCLUSIONS: Our findings suggest that TRIM proteins can predict tumor progression and poor prognosis in CRC. Therefore, TRIM proteins may be promising therapeutic targets for patients with CRC.

Engineering Escherichia coli for Highly Efficient Biosynthesis of Lacto-N-difucohexaose II through De Novo GDP-l-fucose Pathway.

Lacto-N-difucohexaose II (LNDFH II) is a typical fucosylated human milk oligosaccharide and can be enzymatically produced from lacto-N-tetraose (LNT) by a specific α1,3/4-fucosyltransferase from Helicobacter pylori DMS 6709, referred to as FucT14. Previously, we constructed an engineered Escherichia coli BL21(DE3) with a single plasmid for highly efficient biosynthesis of LNT. In this study, two additional plasmids harboring the de novo GDP-L-fucose pathway module and FucT14, respectively, were further introduced to construct the strain for successful biosynthesis of LNDFH II. FucT14 was actively expressed, and the engineered strain produced LNDFH II as the major product, lacto-N-fucopentaose (LNFP) V as the minor product, and a trace amount of LNFP II and 3-fucosyllactose as very minor products. Additional expression of the α1,3-fucosyltransferase FutM1 from a Bacteroidaceae bacterium from the gut metagenome could obviously enhance the LNDFH II biosynthesis. After optimization of induction conditions, the maximum titer reached 3.011 g/L by shake-flask cultivation. During the fed-batch cultivation, LNDFH II was highly efficiently produced with the highest titer of 18.062 g/L and the productivity yield of 0.301 g/L·h.

Efficient Biosynthesis of Lacto-N-Biose I, a Building Block of Type I Human Milk Oligosaccharides, by a Metabolically Engineered Escherichia coli.

Lacto-N-biose I (LNB), termed a Type 1 disaccharide, is an important building block of human milk oligosaccharides. It shows promising prebiotic activity by stimulating the proliferation of many gut-associated bifidobacteria and thus displays good potential in infant foods or supplements. Enzymatic and microbial approaches to LNB synthesis have been studied, almost all of which involve glycosylation of LNB phosphorylase as the final step. Herein, we report a new and easier microbial LNB synthesis strategy through the route "lactose → lacto-N-triose II (LNTri II) → lacto-N-tetraose (LNT) → LNB". A previously constructed LNT-producing Escherichia coli BL21(DE3) strain was engineered for LNB biosynthesis by introducing Bifidobacterium bifidum LnbB. LNB was efficiently produced, accompanied by lactose regeneration. Genomic integration of key pathway genes related to LNTri II and LNT synthesis was performed to enhance LNB titers. The final engineered strain produced 3.54 and 26.88 g/L LNB by shake-flask and fed-batch cultivation, respectively.

Fine mapping of a major QTL, qKl-1BL controlling kernel length in common wheat.

KEY MESSAGE: A major stable QTL, qKl-1BL, for kernel length of wheat was narrowed down to a 2.04-Mb interval on chromosome 1BL; the candidate genes were predicated and the genetic effects on yield-related traits were characterized. As a key factor influencing kernel weight, wheat kernel shape is closely related to yield formation, and in turn affects both wheat processing quality and market value. Fine mapping of the major quantitative trait loci (QTL) for kernel shape could provide genetic resources and a theoretical basis for the genetic improvement of wheat yield-related traits. In this study, a major QTL for kernel length (KL) on 1BL, named qKl-1BL, was identified from the recombinant inbred lines (RIL) in multiple environments based on the genetic map and physical map, with 4.76-21.15% of the phenotypic variation explained. To fine map qKl-1BL, the map-based cloning strategy was used. By using developed InDel markers, the near-isogenic line (NIL) pairs and eight key recombinants were identified from a segregating population containing 3621 individuals derived from residual heterozygous lines (RHLs) self-crossing. In combination with phenotype identification, qKl-1BL was finely positioned into a 2.04-Mb interval, KN1B:698.15-700.19 Mb, with eight differentially expressed genes enriched at the key period of kernel elongation. Based on transcriptome analysis and functional annotation information, two candidate genes for qKl-1BL controlling kernel elongation were identified. Additionally, genetic effect analysis showed that the superior allele of qKl-1BL from Jing411 could increase KL, thousand kernel weight (TKW), and yield per plant (YPP) significantly, as well as kernel bulk density and stability time. Taken together, this study identified a QTL interval for controlling kernel length with two possible candidate genes, which provides an important basis for qKl-1BL cloning, functional analysis, and application in molecular breeding programs.

Quantitative trait loci detection for three tiller-related traits and the effects on wheat (Triticum aestivum L.) yields.

KEY MESSAGE: A total of 38 putative additive QTLs and 55 pairwise putative epistatic QTLs for tiller-related traits were reported, and the candidate genes underlying qMtn-KJ-5D, a novel major and stable QTL for maximum tiller number, were characterized. Tiller-related traits play an important role in determining the yield potential of wheat. Therefore, it is important to elucidate the genetic basis for tiller number when attempting to use genetic improvement as a tool for enhancing wheat yields. In this study, a quantitative trait locus (QTL) analysis of three tiller-related traits was performed on the recombinant inbred lines (RILs) of a mapping population, referred to as KJ-RILs, that was derived from a cross between the Kenong 9204 (KN9204) and Jing 411 (J411) lines. A total of 38 putative additive QTLs and 55 pairwise putative epistatic QTLs for spike number per plant (SNPP), maximum tiller number (MTN), and ear-bearing tiller rate (EBTR) were detected in eight different environments. Among these QTLs with additive effects, three major and stable QTLs were first documented herein. Almost all but two pairwise epistatic QTLs showed minor interaction effects accounting for no more than 3.0% of the phenotypic variance. The genetic effects of two colocated major and stable QTLs, i.e., qSnpp-KJ-5D.1 and qMtn-KJ-5D, for yield-related traits were characterized. The breeding selection effect of the beneficial allele for the two QTLs was characterized, and its genetic effects on yield-related traits were evaluated. The candidate genes underlying qMtn-KJ-5D were predicted based on multi-omics data, and TraesKN5D01HG00080 was identified as a likely candidate gene. Overall, our results will help elucidate the genetic architecture of tiller-related traits and can be used to develop novel wheat varieties with high yields.

Implementation of a Quorum-Sensing System for Highly Efficient Biosynthesis of Lacto-N-neotetraose in Engineered Escherichia coli MG1655.

Lacto-N-neotetraose (LNnT), a prominent neutral human milk oligosaccharide (HMO), serves as a pivotal structural element in complex HMO biosynthesis. Given its promising health effects for infants, the biosynthesis of LNnT is garnering greater interest. Using a previously engineered strain as a chassis, a highly effective LNnT producer was constructed. First, LNnT synthesis in Escherichia coli MG1655 was achieved by introducing ß1,3-N-acetylglucosaminyltransferase LgtA and ß1,4-galactosyltransferase CpsIaJ, coupled with the optimization of enzyme expression levels using various promoters. Subsequently, ugd underwent disruption, and the galE gene was enhanced by replacing its promoter with PJ23119 or Ptac. Then, a lux-type quorum sensing (QS) system was applied to achieve varied metabolic regulation. Additionally, systematic optimization of the QS promoters was conducted to further improve the LNnT titer in the shake flask. Finally, the extracellular titer of LNnT was 20.33 g/L, accompanied by a productivity of 0.41 g/L/h.

Microbial Synthesis of Lacto-N-fucopentaose I with High Titer and Purity by Screening of Specific Glycosyltransferase and Elimination of Residual Lacto-N-triose II and Lacto-N-tetraose.

Lacto-N-fucopentaose I (LNFP I) has recently been approved as generally recognized as safe, demonstrating its great commercial potential in the food industry. Microbial synthesis through metabolic engineering strategies is an effective approach for large-scale production of LNFP I. Biosynthesis of LNFP I requires consideration of two key points: high titer with low byproduct 2'-fucosyllactose (2'-FL) generation and high purity with low lacto-N-triose II (LNTri II) and lacto-N-tetraose (LNT) residues. Herein, α1,2-fucosyltransferase from Thermoanaerobacterium sp. RBIITD was screened from 16 selected LNFP I-producing glycosyltransferase candidates, showing the highest in vivo LNFP I productivity. Chromosomal integration of wbgO enhanced the LNFP I production by improving the precursor conversion from LNTri II to LNT. The best engineered strain produced 4.42 and 35.1 g/L LNFP I in shake-flask and fed-batch cultivation, respectively. The residual LNTri II and LNT were eliminated by further cultivation with a recombinant strain coexpressing Bifidobacterium bifidum ß-N-acetylhexosaminidase and lacto-N-biosidase. A strategy for LNFP I biosynthesis with high yield and purity was finally realized, providing support for its practical application in large-scale production.

Development of Cost-Effective Fatty Liver Disease Prediction Models in a Chinese Population: Statistical and Machine Learning Approaches.

BACKGROUND: The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in China presents a significant public health concern. Traditional ultrasound, commonly used for fatty liver screening, often lacks the ability to accurately quantify steatosis, leading to insufficient follow-up for patients with moderate-to-severe steatosis. Transient elastography (TE) provides a more quantitative diagnosis of steatosis and fibrosis, closely aligning with biopsy results. Moreover, machine learning (ML) technology holds promise for developing more precise diagnostic models for NAFLD using a variety of laboratory indicators. OBJECTIVE: This study aims to develop a novel ML-based diagnostic model leveraging TE results for staging hepatic steatosis. The objective was to streamline the model's input features, creating a cost-effective and user-friendly tool to distinguish patients with NAFLD requiring follow-up. This innovative approach merges TE and ML to enhance diagnostic accuracy and efficiency in NAFLD assessment. METHODS: The study involved a comprehensive analysis of health examination records from Suzhou Municipal Hospital, spanning from March to May 2023. Patient data and questionnaire responses were meticulously inputted into Microsoft Excel 2019, followed by thorough data cleaning and model development using Python 3.7, with libraries scikit-learn and numpy to ensure data accuracy. A cohort comprising 978 residents with complete medical records and TE results was included for analysis. Various classification models, including logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost), were constructed and evaluated based on the area under the receiver operating characteristic curve (AUROC). RESULTS: Among the 916 patients included in the study, 273 were diagnosed with moderate-to-severe NAFLD. The concordance rate between traditional ultrasound and TE for detecting moderate-to-severe NAFLD was 84.6% (231/273). The AUROC values for the RF, LightGBM, XGBoost, SVM, KNN, and LR models were 0.91, 0.86, 0.83, 0.88, 0.77, and 0.81, respectively. These models achieved accuracy rates of 84%, 81%, 78%, 81%, 76%, and 77%, respectively. Notably, the RF model exhibited the best performance. A simplified RF model was developed with an AUROC of 0.88, featuring 62% sensitivity and 90% specificity. This simplified model used 6 key features: waist circumference, BMI, fasting plasma glucose, uric acid, total bilirubin, and high-sensitivity C-reactive protein. This approach offers a cost-effective and user-friendly tool while streamlining feature acquisition for training purposes. CONCLUSIONS: The study introduces a groundbreaking, cost-effective ML algorithm that leverages health examination data for identifying moderate-to-severe NAFLD. This model has the potential to significantly impact public health by enabling targeted investigations and interventions for NAFLD. By integrating TE and ML technologies, the study showcases innovative approaches to advancing NAFLD diagnostics.

Development of Novel Star-Like Branched-Chain Acrylamide (AM)-Sodium Styrene Sulfonate (SSS) Copolymers for Heavy Oil Emulsion Viscosity Reduction and Its Potential Application in Enhanced Oil Recovery.

Injecting water with chemicals to generate emulsions in the reservoir is a promising method for enhancing heavy oil recovery because oil-in-water (O/W) emulsions significantly reduce oil viscosity. To enhance heavy oil recovery efficiency, we developed new star-like branched AM-SSS copolymers (SB-PAMs) with reduction in the viscosity of the heavy oil emulsion, which was synthesized by reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization. The core structure of the branched polymer was RAFT polymerization of acrylamide (AM) and N,N'-methylene bis-acrylamide (BisAM), in the presence of 3-(((benzylthio)carbonothioyl)thio)propanoic acid as a chain transfer agent, followed by chain extension with AM and SSS. The core structures were achieved by incorporation of total monomer ratios [BisAM]/[AM] of 1:11. The expansion of the core structures by copolymerization of AM and SSS resulted in star-like branched polymer SB-PAM-co-SSS with apparent molecular weights ranging from 240 to 2381 kDa. 1H-nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FTIR) confirmed the synthesized polymer structure. The molecular weight was determined by gel permeation chromatography (GPC). The polydispersity coefficient was between 1 and 7, which has a broad molecular weight distribution. The polymer dissolves only 0.75 h in deionized water, faster than conventional polyacrylamide. At 50 °C, the viscosity of the 1000 mg/L SB-polymer solution can reach up to 45 mPa·s. First, heavy oil viscosity reduction by 800 mg/L SB polymer can reach 91.7%, at a water dehydration rate of 90.4%; second, with 0.6 PV injection, 800 mg/L SB polymer improved oil recovery up to 23.66% after water flooding; and third, SB-polymer-assisted hot water flooding shows that heavy oil recovery improved by 19.46% at 110 °C with 0.6 pore volume (PV) SB-polymer injection. This novel branched chain polymer with heavy oil emulsion capability will shed light on high-temperature polymer flooding and the development of a new candidate structure for heavy oil viscosity reduction.

One-pot production of butyl butyrate from glucose using a cognate "diamond-shaped" E. coli consortium.

Esters are widely used in plastics, textile fibers, and general petrochemicals. Usually, esters are produced via chemical synthesis or enzymatic processes from the corresponding alcohols and acids. However, the fermentative production of esters from alcohols and/or acids has recently also become feasible. Here we report a cognate microbial consortium capable of producing butyl butyrate. This microbial consortium consists of two engineered butyrate- and butanol-producing E. coli strains with nearly identical genetic background. The pathways for the synthesis of butyrate and butanol from butyryl-CoA in the respective E. coli strains, together with a lipase-catalyzed esterification reaction, created a "diamond-shaped" consortium. The concentration of butyrate and butanol in the fermentation vessel could be altered by adjusting the inoculation ratios of each E. coli strain in the consortium. After optimization, the consortium produced 7.2 g/L butyl butyrate with a yield of 0.12 g/g glucose without the exogenous addition of butanol or butyrate. To our best knowledge, this is the highest titer and yield of butyl butyrate produced by E. coli reported to date. This study thus provides a new way for the biotechnological production of esters.

Epidemiology of myopia and unaided visual impairment of primary and secondary school students of Han and minorities in Mangshi City in Yunnan / 中国学校卫生

Objective@#To investigate the prevalence and associated factors of unaided visual impairment and myopia among primary and secondary school students in Yunnan Province, and to provide scientific basis for myopia prevention.@*Methods@#The study was conducted among primary and secondary school students in Mangshi, Yunnan Province from March to August, 2014. All the 7 681 subjects underwent detailed eye examinations and a questionnaire survey. Myopia was defined as spherical equivalent value of less than -0.5 diopters. Unaided visual impairment was analyzed on the basis of the better and the worse-seeing eye, respectively.@*Results@#The prevalence of myopia and high myopia were 39.1% and 0.6%. The prevalence of unaided visual impairment was 11.4% based on the worse-seeing eye. Refractive errors accounted for 87.3% of the participants with unaided visual impairment. Prevalence of myopia was higher in girls than in boys (χ2=29.74, P<0.01), but there was no gender difference in high myopia (P=0.19). The prevalence of myopia and high myopia increased significantly with increasing age (χ2=351.23, 22.56, P<0.01). Besides, prevalence of myopia was 63.7% in Dai nationality students and 36.6% in Yi nationality students (χ2=78.14, P<0.01), which was higher than other ethnic minorities. After adjusting for the effects of sex, age and ethnicity, the presence of myopia was associated with increasing height (OR=1.02, 95%CI=1.01-1.03), computer use (OR=1.17, 95%CI=1.03-1.32), having a myopic father (OR=1.56, 95%CI=1.24-1.94), having a myopic mother (OR=1.33, 95%CI=1.08-1.63) and more time reading(OR=1.18, 95%CI=1.09-1.28). High myopia was found to be more prevalent in children who had a myopic father (OR=3.98, 95%CI=1.72-9.22) and using computers (OR=2.31, 95%CI=1.17-4.57).@*Conclusion@#Myopia and unaided visual impairment is prevalent in school students in rural China (Yunnan), though the prevalence is relatively lower compared with other areas in China. Attention should be paid to the formulation and input of primary eye care policies.