Changes in Hole and Electron Injection under Electrical Stress and the Rapid Electroluminescence Loss in Blue Quantum-Dot Light-Emitting Devices.

Blue quantum dot light-emitting devices (QLEDs) suffer from fast electroluminescence (EL) loss when under electrical bias. Here, it is identified that the fast EL loss in blue QLEDs is not due to a deterioration in the photoluminescence quantum yield of the quantum dots (QDs), contrary to what is commonly believed, but rather arises primarily from changes in charge injection overtime under the bias that leads to a deterioration in charge balance. Measurements on hole-only and electron-only devices show that hole injection into blue QDs increases over time whereas electron injection decreases. Results also show that the changes are associated with changes in hole and electron trap densities. The results are further verified using QLEDs with blue and red QDs combinations, capacitance versus voltage, and versus time characteristics of the blue QLEDs. The changes in charge injection are also observed to be partially reversible, and therefore using pulsed current instead of constant current bias for driving the blue QLEDs leads to an almost 2.5× longer lifetime at the same initial luminance. This work systematically investigates the origin of blue QLEDs EL loss and provides insights for designing improved blue QDs paving the way for QLEDs technology commercialization.

Prognosis and personalized treatment prediction in TP53-mutant hepatocellular carcinoma: an in silico strategy towards precision oncology.

TP53 mutation is one of the most common genetic changes in hepatocellular carcinoma (HCC). It is of great clinical significance to tailor specialized prognostication approach and to explore more therapeutic options for TP53-mutant HCCs. In this study, a total of 1135 HCC patients were retrospectively analyzed. We developed a random forest-based prediction model to estimate TP53 mutational status, tackling the problem of limited sample size in TP53-mutant HCCs. A multi-step process was performed to develop robust poor prognosis-associated signature (PPS). Compared with previous established population-based signatures, PPS manifested superior ability to predict survival in TP53-mutant patients. After in silico screening of 2249 drug targets and 1770 compounds, we found that three targets (CANT1, CBFB and PKM) and two agents (irinotecan and YM-155) might have potential therapeutic implications in high-PPS patients. The results of drug targets prediction and compounds prediction complemented each other, presenting a comprehensive view of potential treatment strategy. Overall, our study has not only provided new insights into personalized prognostication approaches, but also thrown light on integrating tailored risk stratification with precision therapy.

Exploring subclass-specific therapeutic agents for hepatocellular carcinoma by informatics-guided drug screen.

Almost all currently approved systemic therapies for hepatocellular carcinoma (HCC) failed to achieve satisfactory therapeutic effect. Exploring tailored treatment strategies for different individuals provides an approach with the potential to maximize clinical benefit. Previously, multiple studies have reported that hepatoma cell lines belonging to different molecular subtypes respond differently to the same treatment. However, these studies only focused on a small number of typical chemotherapy or targeted drugs across limited cell lines due to time and cost constraints. To compensate for the deficiency of previous experimental researches as well as link molecular classification with therapeutic response, we conducted a comprehensive in silico screening, comprising nearly 2000 compounds, to identify compounds with subclass-specific efficacy. Here, we first identified two transcriptome-based HCC subclasses (AS1 and AS2) and then made comparison of drug response between two subclasses. As a result, we not only found that some agents previously considered to have low efficacy in HCC treatment might have promising therapeutic effects for certain subclass, but also identified novel therapeutic compounds that were not routinely used as anti-tumor drugs in clinic. Discovery of agents with subclass-specific efficacy has potential in changing the status quo of population-based therapies in HCC and providing new insights into precision oncology.

Ribosomal DNA copy number alteration in blood sample from gastric cancer patients.

BACKGROUND: Ribosomal DNA (rDNA) is the most abundant and important housekeeping gene in the cell. It usually acted as DNA damage sensor in DNA damage reaction. Gastric cancer (GC) as a tumor with high morbidity and mortality, it is hard to diagnosis in an early stage. METHODS: In this study, we collected and test the copy number of rDNA in blood sample of 42 GC patients and 56 healthy controls (HC) to explore the relationship between rDNA and GC. Besides, we make a correlation between the copy number of rDNA and ten biomarkers (CYFR21-1, CA15-3, CA72-4, NSE, CEA, CA125, ProGRP, AFP, SCC, CA19-9). RESULTS: The copy number of 18 S, 5.8 S, 28 S rDNA in GC is less than HC and 5 S is more than HC in their blood sample. And the expression of H-cox-1 and ND1 in GC is higher than HC in blood sample. it shows the expression of CA15-3 is related to ND1 and H-cox-1. CONCLUSION: We found for the first time the changes of rDNA and mtDNA expression in the blood of patients with gastric cancer. All these finding suggests rDNA may have potential in diagnosing GC.

Associations between maternal occupational exposures and pregnancy outcomes among Chinese nurses: a nationwide study.

BACKGROUND: Several studies have provided evidence about adverse pregnancy outcomes of nurses involved in occupational exposure. However, the pregnancy outcomes among nurses in middle-income countries are not well demonstrated. The main aim of this study is to present the prevalence and influencing factors of pregnancy outcomes among female nurses in China. METHODS: We included 2243 non-nurse health care workers, and 4230 nurses in this national cross-sectional study in China. Information on occupational exposures and pregnancy outcomes was collected using a face-to-face investigation. Odds ratios (ORs) were estimated through logistic regression. RESULTS: The proportion of threatened abortion, spontaneous abortion, and stillbirth of female nurses was 2.6%, 7%, and 2.1%, respectively. We found an increased risk of threatened abortion among nurses with overtime work (OR = 1.719, 95% CI 1.158-2.550). The risk of threatened abortion and spontaneous abortion was elevated among nurses handling disinfectant (OR = 2.293 and 1.63, respectively). We found a nearly twofold increased risk of premature birth (OR = 2.169, 95% CI 1.36-3.459) among nurses handling anti-cancer drugs. CONCLUSIONS: Our findings suggested that maternal occupational exposures might be associated with the risk of adverse pregnancy outcomes among female nurses in China. We recommend that policy-markers and hospital managers work together to reduce exposure to occupational hazards and improve pregnancy outcomes among female nurses.

WeChat as a platform for blending problem/case-based learning and paper review methods in undergraduate paediatric orthopaedics internships: a feasibility and effectiveness study.

BACKGROUND: Paediatric orthopaedics is a significant and difficult for undergraduate students to master. During the COVID-19 pandemic, we used the WeChat platform to combine the advantages offered by problem-based learning (PBL), case-based learning (CBL) and paper review teaching methods to establish a new blended online teaching model and demonstrated its feasibility and effectiveness. OBJECTIVE: This study aims to demonstrate the feasibility and effectiveness of a new blended pedagogical method that uses the WeChat platform and combines PBL, CBL and paper review. METHODS: We enrolled 22 students participating in the Department of Paediatric Orthopaedics. They participated in the WeChat blended pedagogy mode. Their departmental rotation examination scores were compared with those of 23 students who participated in the traditional teaching method. Moreover, an anonymous questionnaire was used to evaluate students' perceptions and experiences. RESULTS: The total average scores of students who participated in the WeChat blended pedagogy mode and the traditional teaching method were 47.27 and 44.52, respectively. There were no statistically significant differences between the online teaching mode and the traditional teaching method in terms of possessing professional accomplishment, gaining knowledge and promoting interpersonal skills (P = 0.07, P = 0.12 and P = 0.65, respectively). In terms of independent clinical thinking, self-improving capability and improving clinical skills, the scores associated with the WeChat blended pedagogy mode were 8.00, 8.00 and 6.00, whereas those associated with the traditional teaching method were 6.70, 6.87 and 7.48. The overall satisfaction with the WeChat blended pedagogy mode reached 100%. A total of 64%, 86%, 68%, 64% and 59% of students chose very large or large in response to the items concerning professional accomplishment, knowledge absorption, independent clinical thinking skills, English reading and literature exploring capacity, as well as interpersonal skills, respectively. Fifteen participants claimed that the WeChat blended pedagogy mode was less helpful to them with regard to promoting the improvement of their clinical skills. Nine students claimed that the WeChat blended pedagogy mode was time-consuming. CONCLUSIONS: Our study verified the feasibility and effectiveness of the WeChat blended pedagogy mode for undergraduate paediatric orthopaedics internships. TRIAL REGISTRATION: Retrospectively registered.

Spatiotemporal evolution and trend prediction of regional water-energy-food-ecology system vulnerability: a case study of the Yangtze River Economic Belt, China.

The vulnerability study of the water-energy-food-ecosystem (WEFE) system in the Yangtze River Economic Belt (YREB) is of great significance for ensuring water, energy, food, and ecological security. In this study, the concept of vulnerability of WEFE systems is explained, and then its mechanism is analyzed. Based on the vulnerability concept of the WEFE system and combined with the pressure-state-response (PSR) framework and the exposure-sensitivity-adaptability (ESA) capacity model, this study constructs an evaluation index system for the vulnerability of the WEFE system. The cross-efficiency data envelopment analysis (CE-DEA) method, which considers both self-evaluation and peer evaluation efficiency, is used to calculate the vulnerability from 2005 to 2020. The spatiotemporal dynamic characteristics are explored using the hot spot analysis and spatial autocorrelation model. The results show that the overall vulnerability of the WEFE system in the YREB has fluctuated and increased during the study period, with a spatial pattern characterized by "high in the middle and low on both sides." Over time, the spatial evolution tends to be centralized and non-equilibrium, forming a relatively independent spatial pattern.

Current Challenges and Strategies for Chimeric Antigen Receptor-T-Cell Therapy for Solid Tumors.

Chimeric antigen receptor (CAR)-T-cell therapy has resulted in remarkable responses in patients with certain hematological malignancies. However, its efficacy in solid tumors is disappointing. Many factors can limit the effect of CAR-T-cell therapy on solid tumors. CAR-T-cell infiltration, survival, and persistence face numerous challenges in solid tumors. Vasculature and stromal barriers, hypoxia and high metabolism of solid tumors, tumor microenvironment immunosuppression, and high numbers of heterogeneous tumor cells all are closely related to cancer progression and immune escape. These factors usually contribute to form an environment wherein tumor cells have an advantage over CAR-T cells for survival. It is thus necessary to improve immune CAR-T-cell function in solid tumors by developing strategies to reconstruct the environment or modify the CAR-T cells. In this review, we outline major obstacles of CAR-T-cell therapy for solid tumors. We also propose strategies to overcome the above challenges and barriers against CAR-T antitumor efficacy.

Urban flood resilience assessment using RAGA-PP and KL-TOPSIS model based on PSR framework: A case study of Jiangsu province, China.

The research on urban flood resilience will contribute to building a more resilient city and provide valuable reference for municipal decision-makers. There are many frameworks and approaches for empirical studies on what constitutes urban flood resilience and how to evaluate it. In this study, a typical region suffering from flood disaster in China-Jiangsu Province was selected as the study area, including 13 prefecture-level cities. The pressure-state-response (PSR) framework, the projection pursuit based on real-coded accelerated genetic algorithm (RAGA-PP) and the technique for order preference by similarity to an ideal solution based on the Kullback-Leibler distance (KL-TOPSIS) were combined to develop a hybrid multi-criteria approach for assessing urban flood resilience. Then the grey relational analysis obtained the important factors. The results illustrate that (1) the development of each subsystem in the city is uncoordinated, that is, the pressure-subsystem has little influence on urban flood resilience, while the state-subsystem and the response-subsystem have great influence. (2) The urban flood resilience in Jiangsu Province presents obvious polarization trend, that is, Southern Jiangsu is more resilient than Northern Jiangsu. The underlying factors are closely related to the level of economic development. Furthermore, the proposed method provides a practical evaluation approach for other fields.

Performance improvements in all-solution processed inverted QLEDs realized by inserting an electron blocking layer.

Highly efficient, all-solution processed inverted quantum dot light-emitting diodes (QLEDs) are demonstrated by employing 1,3,5-tri(m-pyrid-3-yl-phenyl)benzene (TmPyPB) layer as electron blocking layer. Electron injection from ZnO electron transport layer to quantum dots (QDs) emission layer (EML) can be adjusted by thickness of TmPyPB layer, enabling the balanced charge carriers in QDs EML. With optimal thickness of this TmPyPB adjuster, 59.7% increment in the device current efficiency (from 8.2 to 13.1 cd A-1) and 46.2% improvement in the maximum luminance (from 31916 to 46674 cd m-2) are achieved, compared with those of the control QLED which has double hole transport layer structure. On the other hand, we find luminescence quenching process, which often happens at the interface of ZnO nanoparticles and QDs, is not obvious in our QLEDs, in which the ZnO layer is fabricated in precursor method, and this conclusion is verified through Time Resolution Photoluminescence test. In a word, this strategy provides a direction for optimizing charge carrier balance in all-solution processed inverted QLED.

Synergistic function of doping and ligand engineering to enhance the photostability and electroluminescence performance of CsPbBr3quantum dots.

The photostability issue of CsPbX3(X = Cl, Br, I) quantum dots (QDs) is one of the key origins for the degradation of their luminescence performance, which hinders their application in lighting and displays. Herein, we report a new method combining doping and ligand engineering, which effectively improves the photostability of CsPbBr3QDs and the performance of QD light-emitting diodes (QLEDs). In this method, ZnBr2is doped into CsPbBr3QDs to reduce surface anion defects; didodecyldimethyl ammonium bromide (DDAB) and tetraoctylammonium bromide (TOAB) hybrid ligands, which have strong adsorption with QDs, are employed to protect the surface and enhance the conductivity of QD layer in QLEDs. The photoluminescence (PL) and transmission electron microscopy measurements prove the effectively improved photostability of CsPbX3QDs. Moreover, reduced defects and improved conductivity by doping and hybrid ligands treatment also enable the improved electroluminescence performance of CsPbX3QDs. The maximum luminance and external quantum efficiency of the QLED with optimized CsPbX3QDs are 3518.9 cd m-2and 5.07%, which are 3.6 and 2.1 times than that of the control device, respectively. Combining doping and hybrid ligands makes perovskite QDs have an extremely promising prospect in future applications of high-definition displays, high-quality lighting, as well as solar cells.

Color-Tunable Organic Light Emitting Diodes for Deep Blue Emission by Regulating the Optical Micro-Cavity.

Nowadays, most blue organic light emitting diodes (OLEDs) are fabricated by using sky-blue emitters which are more easily synthesized when compared with other deep blue emitters. Herein, we put forward a new idea of using an optical micro-cavity based on metal electrodes to regulate electroluminance (EL) spectra of sky-blue organic light emitting diodes to obtain a saturated deep blue emission with a narrowed full-width at half-maximum (FWHM). First, we simulate micro-cavity OLEDs and find that the transmission of the anode plays an important role in the forward emission. Meanwhile, the optical path of micro-cavity OLEDs as well as the phase shifting from electrodes influence the EL spectra and induce the extra intensity enhancement. The results show that when the resonant cavity optical path is regulated by changing the thickness of emitting layer (EML) from 25 nm to 75 nm in the micro-cavity, the EL peak of blue OLEDs has a redshift from 479 nm to 493 nm with FWHM shifting from 69.8 nm to 83.2 nm, when compared to the device without the micro-cavity, whose approximate EL peak and FWHM are 487 nm and 87 nm, respectively. However, the efficiency of electroluminescence decreases in micro-cavity OLEDs. We speculate that this is on account of the ohmic contact between ITO and Ag, the surface plasma effect and the rough morphology induced by Ag electrodes.

[Effects of fresh-cut on drying rate and quality of Panax notoginseng].

To study the effects of fresh-cut drying methods on the appearance and internal components of Panax notoginseng, and explore the feasibility of fresh-cut drying methods of P. notoginseng, so as to provide more effective processing methods for the production of P. notoginseng slices and Chinese patent medicines. In this study, we have compared the effects of 6 different drying methods on drying time, drying rate, density, appearance and internal components of P. notoginseng roots. It takes about 453 h to dry by whole-root drying in the sun, with a long constant speed period and a slow drying rate, the time of whole-root drying at 50 ℃ was shortened by 61.6% compared with whole-root drying in the sun, which resulted in the decrease of density and poor appearance of the medicinal material with hollow and crack appeared in the xylem, while the drying time of fresh-cut drying method was reduced by 61.82% to 91.58% and the drying rate increased greatly, due to the relatively slow drying process in the sun or in the shade after fresh-cut, salting-out and whitening appeared on the surface, and the internal components were all decreased to some extent. The drying time of fresh-cut drying at 50 ℃ was 91.58% and 68.83% shorter than that of whole-root drying in the sun and at 50 ℃, respectively. When drying at 50 ℃ after fresh-cut, the appearance and content of internal components of the medicinal materials were better, the appearance was yellowish green, the cut sections were clear with uniform pore distribution, and the content of saponin components was increased by 7.24% compared with that of the whole-root drying at 50 ℃, When drying at 40 ℃, the surface of slices has salting-out and whitening spots, and the loss of dencichine and total sugar was large, but at 60 ℃, this high temperature made the rate of dehydration of slices was extremely fast, which led to severe cracking and fragmentation, and the loss of total sugar and alcohol extract was large. By vacuum freeze drying after fresh-cut, the structure of medicinal materials slices was loose, the density was greatly reduced, and the appearance was different from those recorded in traditional books. The contents of total saponin components and dencichine were increased by 16.51% and 22.54%, respectively, compared with traditional whole-root drying. The fresh-cut process method is feasible in the production of P. notoginseng slices. In production, it is recommended that drying at 50 ℃ after fresh-cut can make the medicinal materials better in appearance and content of internal components, which is convenient for the subsequent processing and industrial feeding extraction. For the purpose of internal contents, it is better to adopt freeze-drying after fresh-cut processing method.

Wheel-Like Icosanuclear Peroxotitanate-A Stable Water-Soluble Catalyst for Oxygen Transfer Reactions.

Water-soluble wheel-like icosanuclear peroxotitanate K16[Ti20(µ-O)8(HO2)8(O2)12( R, R-tart)12]·52H2O (1) chelated by tartrate has been successfully isolated. As the largest peroxotitanate reported, {Ti20} features 20 (hydro)peroxo groups with three kinds of coordination modes in µ-η1:η2, µ-η2:η2, and η2 fashions. The cluster is stable in solution and solid states. It has been tested for the catalytic oxidations of methyl phenyl sulfide and pyridine with hydrogen peroxide, respectively, which shows reversible elimination and the addition of peroxo groups. This provides a rare example of well-characterized titanium peroxide for homogeneous catalysis and mechanism research.

[Comparative and path analysis between underground tuber yield and agronomic traits in cultivation provenances of Gastrodia elata f. glauca from Zhaotong].

To provide guidance for quality control and variety breeding of Gastrodia elata f. glauca cultivated form in Zhaotong, nine agronomic traits of G. elata f. glauca cultivation form were measured and the traits were analyzed using multiple comparison,correlation analysis, multiple stepwise regression analysis and path analysis. The results of multiple comparison and analysis showed that the number of dot ring and the length-width ratio of tuber were no different in G. elata f. glauca cultivation form. The coefficient of variation about the single tuber fresh weigh, ring spacing and belly button diameter was about 20%. The coefficient of variation about the length of the tuber, the width of the tuber, the thickness of the tuber, the length-width ratio of tuber and the number of dot ring was near 10%. The correlation analysis results showed that the single tuber fresh weigh and the length,the width and the thickness of the tuber were extremely significant positive correlated. The results of multiple stepwise regression analysis and path analysis showed that the length, the width and the thickness of the tuber were the main factors affecting the fresh weight of single tuber,which were the best agronomic traits on high yield of G. elata f. glauca. The length of the tuber,the width of the tuber and the thickness of the tuber, which would be used as indicators of the characteristics of high yield varieties in Zhaotong. The number of dot ring and the length-width ratio of tuber, which would be selected as quality control indicators of the genuine Chinese medicinal materials in Zhaotong.

A novel process for obtaining pinosylvin using combinatorial bioengineering in Escherichia coli.

Pinosylvin as a bioactive stilbene is of great interest for food supplements and pharmaceuticals development. In comparison to conventional extraction of pinosylvin from plant sources, biosynthesis engineering of microbial cell factories is a sustainable and flexible alternative method. Current synthetic strategies often require expensive phenylpropanoic precursor and inducer, which are not available for large-scale fermentation process. In this study, three bioengineering strategies were described to the development of a simple and economical process for pinosylvin biosynthesis in Escherichia coli. Firstly, we evaluated different construct environments to give a highly efficient constitutive system for enzymes of pinosylvin pathway expression: 4-coumarate: coenzyme A ligase (4CL) and stilbene synthase (STS). Secondly, malonyl coenzyme A (malonyl-CoA) is a key precursor of pinosylvin bioproduction and at low level in E. coli cell. Thus clustered regularly interspaced short palindromic repeats interference (CRISPRi) was explored to inactivate malonyl-CoA consumption pathway to increase its availability. The resulting pinosylvin content in engineered E. coli was obtained a 1.9-fold increase depending on the repression of fabD (encoding malonyl-CoA-ACP transacylase) gene. Eventually, a phenylalanine over-producing E. coli consisting phenylalanine ammonia lyase was introduced to produce the precursor of pinosylvin, trans-cinnamic acid, the crude extraction of cultural medium was used as supplementation for pinosylvin bioproduction. Using these combinatorial processes, 47.49 mg/L pinosylvin was produced from glycerol.

[Ecological suitability regionalization for Gastrodia elata in Zhaotong based on Maxent and ArcGIS].

In this paper, the potential distribution information and ecological suitability regionalization for Gastrodia elata in Zhaotong were studied based on the climate, terrain, soil and vegetation factors analysis by Maxent and ArcGIS. The results showed that the highly potential distribution (suitability index>0.6) mainly located in Zhaotong, Yunnan province（Zhenxiong,Yiliang and Daguan county, with an area of 2 872 km²ï¼‰, and Bijie, Guizhou province （Hezhang,Bijie,Weining county, 1 251 km²ï¼‰. The AUC of ROC curve was above 0.99, indicating that the predictive results with the Maxent model were highly precise. The main ecological factors determining the potential distribution were the altitude, average rainfall in November, average rainfall in October, vegetation types, average rainfall in March, average rainfall in April,soil types,isothermal characteristic and average rainfall in June. The environmental variables in the highly potential areas were determined as altitude around 1 450-2 200 m,annual average temperature around 18.0-20.4 ℃,annual average precipitation around 900 mm,yellow soil or yellow brown soil,and acid sandy loam or slightly acidic sandy loam.The results will provide valuable references for plantation regionalization and the siting for imitation wild planting of G. elata in Zhaotong.

Influence of dextrans on the textural, rheological, and microstructural properties of acid-induced faba bean protein gels.

Dextrans (DXs) are a group of natural polysaccharides with different branching patterns. Previous studies examining the effects of DXs on plant protein gels have only focused on α-(1 â†’ 3)-branched DXs. Here, we compared the effects of α-(1 â†’ 3)-branched DX L12 with those of two α-(1 â†’ 2)-branched DXs on the properties of glucono-δ-lactone-induced faba bean protein isolate (FPI) gels. DX L12 showed stronger effects in decreasing gel hardness and enhancing gel viscoelasticity than the other two DXs. Moreover, DX L12 decreased the water-holding capacity of FPI gels, whereas the other DXs enhanced it. Microstructural analysis revealed that DX addition promoted phase separation during gel formation. However, FPI/L12 gels exhibited greater phase separation than the other two gels and contained larger void spaces. These differences could be attributed to the varying water adsorption and self-association properties of the DXs. These findings could guide the application of DX in the tailored preparation of plant protein gels.

Relationships among gut microbiota, plasma metabolites, and juvenile idiopathic arthritis: a mediation Mendelian randomization study.

Objective: The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators. Methods: Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization. Results: In our MR analysis, a positive correlation was observed between Rikenellaceae and the risk of juvenile idiopathic arthritis, while Dorea showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between Dorea and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%]. Conclusion: Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.

Aminopeptidase O Protein mediates the association between Lachnospiraceae and appendicular lean mass.

Objective: Investigating the causal relationship between Lachnospiraceae and Appendicular lean mass (ALM) and identifying and quantifying the role of Aminopeptidase O Protein (AOPEP) as a potential mediator. Methods: The summary statistics data of gut microbiota composition from the largest available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen Consortium (n = 13,266). Appendicular lean mass data were obtained from the UK-Biobank (n = 450,243). We conducted bidirectional two-sample Mendelian randomization (MR) analysis using summary-level data from GWAS to investigate the causal relationship between Lachnospiraceae and ALM. Additionally, we employed a drug-targeted MR approach to assess the causal relationship between AOPEP and ALM. Finally, a two-step MR was employed to quantitatively estimate the proportion of the effect of Lachnospiraceae on ALM that is mediated by AOPEP. Cochran's Q statistic was used to quantify heterogeneity among instrumental variable estimates. Results: In the MR analysis, it was found that an increase in genetically predicted Lachnospiraceae [OR = 1.031, 95% CI (1.011-1.051), P = 0.002] is associated with an increase in ALM. There is no strong evidence to suggest that genetically predicted ALM has an impact on Lachnospiraceae genus [OR = 1.437, 95% CI (0.785-2.269), P = 0.239]. The proportion of genetically predicted Lachnospiraceae mediated by AOPEP was 34.2% [95% CI (1.3%-67.1%)]. Conclusion: Our research reveals that increasing Lachnospiraceae abundance in the gut can directly enhance limb muscle mass and concurrently suppress AOPEP, consequently mitigating limb muscle loss. This supports the potential therapeutic modulation of gut microbiota for sarcopenia. Interventions such as drug treatments or microbiota transplantation, aimed at elevating Lachnospiraceae abundance and AOPEP inhibition, synergistically improve sarcopenia in the elderly, thereby enhancing the overall quality of life for older individuals.