Background and Objectives: This study aimed to find the optimal intervention available to both control blood glucose and improve physical function in the geriatric population with T2DM. Methods and ...Study Design: A systemic review and network meta-analysis (NMA) was conducted to assess and rank the comparative efficacy of different interventions on glycosylated hemoglobin A1c (HbAc1), fasting blood glucose (FBG), muscle mass, grip strength, gait speed, lower body muscle strength, and dynamic balance. A total of eight databases were searched for eligible randomized controlled trials (RCTs) that the elderly aged more than 60 years or with mean age >= 55 years, the minimal duration of the RCT intervention was 6 weeks, and those lacking data about glycemic level and at least one indicator of physical performance were excluded. The Cochrane risk of bias tool was used to assess the bias of each study included. Bayesian NMA was performed as the main results, the Bayesian meta regression and the frequentist NMA as sensitivity analysis. Results: Of the 2266 literature retrieved, 27 RCTs with a total of 2289 older adults were included. Health management provided by health workers exerts beneficial effects that is superior to other interventions at achieving glycemic control, but less marked improvement in physical performance. Exercise combined with cognitive training showed more pronounced improvement in muscle strength, gait speed, and dynamic balance, but ranked behind in decreasing the HbAc1 and FBG. Conclusions: Personalized health management combined with physical and cognitive training might be the optimal intervention to both accomplish glycemic control and improvement of physical performance. Further RCTs are needed to validate and assess the confidence of our results from this NMA.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. ...However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders.
This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations.
Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus
and genus
were protective, while the genus
was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders.
Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.
Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) ...therapy. In the present study, a set of novel indole ethylamine derivatives (
,
,
,
) were designed and synthesized. The target product (compound
) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound
reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound
supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Precise and reliable long-term streamflow prediction contributes to water resources planning and management. Artificial neural network (ANN) have shown its remarkable ability in forecasting ...non-linear hydrological processes without involvement of complex, dynamic, hydrological and hydro-climatologic physical process in the water shed. To improve its non-stationary responses, decomposition methods are adopted as pre-processing methods in this study including Empirical Mode Decomposition (EMD), Ensemble Empirical Mode Decomposition (EEMD) and Seasonal-Trend decomposition using Loess (STL). The original time sequence is decomposed to several components, which are then taken as the inputs of the ANN model. EMD and EEMD are data- adaptable methods, and thus the number of Intrinsic Mode Functions (IMFs) might differ for different sequences, leading to the discrepancy of the input number for ANN model in training and predicting. Fisher’s ordered clustering is thus used to classify the IMFs into a determined number of classes based on their frequency spectrum resulting from Maximum Entropy Spectral Analysis (MESA). The proposed methodology is applied on four important hydrological stations on the upper stream of the Yellow River and the Yangtze River in China, respectively, to forecast the streamflow of the next whole year with the historical daily data of the past 6 years. The Nash-Sutcliffe efficiencies of the monthly prediction are higher than 0.85 for all of the four cases, and various indicators indicates that the proposed hybrid method of STL-ANN performs better than other compared methods. The highlights of this study lies in that only historical daily streamflow data is used to derive an accurate long-term prediction by data mining based on decomposition technology and mapping relationships between the decomposed components and the original sequence in the future.
AIM： To explore precise deleted regions and screen the candidate tumor suppressor genes related to sporadic colorectal carcinoma. METHODS： Six markers on 1q31.1-32.1 were chosen. These polymorphic ...microsatellite markers in 83 colorectal cancer patients tumor and normal DNA were analyzed via PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for Loss of heterozygosity （LOH） scanning and analysis. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test. RESULTS： 1q31.1-32.1 exhibited higher LOH frequency in colorectal carcinoma. The average LOH frequency of 1q31.1-32.1 was 23.0%, with the highest frequency of 36.7% （18/49） at D1S2622, and the lowest of 16.4% （11/67） at D1S412, respectively. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622 （1q31.3-32.1）. There was no significant association between LOH of each marker on 1q31.1-32.1 and the clinicopathological data （patient sex, age, tumor size, growth pattern or Dukes stage）, which indicated that on 1q31.1-32.1, LOH was a common phenomenon in all kinds of sporadic colorectal carcinoma. CONCLUSION： Through our refined deletion mapping,the critical and precise deleted region was located within 2 cM chromosomal segment encompassing 2 loci （D1S413, D1S2622）. No significant association was found between LOH and clinicopathologic features in 1q31.1-32.1.
Objective The recent advent of robotically assisted surgery has enabled totally endoscopic repair of atrial septal defects and patent foramen ovale. This study investigates the feasibility and safety ...of totally endoscopic repair of an atrial septal defect through small incisions on the chest without robotic assistance. Methods Forty patients (23 female patients; average age, 15.4 ± 8.7 years; age range, 6–47 years) with secundum-type ASDs were selected for this study. Cardiopulmonary bypass was achieved peripherally. Through 3-port incisions in the right chest, pericardiotomy, bicaval occlusion, atriotomy, and ASD repair were performed by a surgeon through a thoracoscopy. Results The cardiopulmonary bypass and aortic crossclamp times were 56.2 ± 21.1 and 38.3 ± 8.6 minutes, respectively. The length of stay in the intensive care unit was 23.0 ± 4.1 hours. There were no mortalities and no major complications in this cohort. Patients were discharged from the hospital 4 to 6 days after the operation. Transesophageal echocardiographic analysis immediately after the operation and at 30 days showed complete closure of the defect without residual shunt. Conclusions Totally endoscopic atrial septal defect repair can be achieved without a robotically assisted surgical system. This technique is safe and effective and can be used as a therapeutic option for ASD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The brown planthopper (Nilaparvata lugens) is a major destructive rice pest in Asia. High levels of insecticide resistance have been frequently reported, and the G932C mutation in the chitin synthase ...1 (CHS1) gene has been found to mediate buprofezin resistance. However, there has been no direct evidence to confirm the functional significance of the single G932C substitution mutation leading to buprofezin resistance in N. lugens. Here, we successfully constructed a knock-in homozygous strain (Nl-G932C) of N. lugens using CRISPR/Cas9 coupled with homology-directed repair (HDR). Compared with the background strain susceptible to buprofezin (Nl-SS), the knock-in strain (Nl-G932C) showed a 94.9-fold resistance to buprofezin. Furthermore, resistant strains (Nl-932C) isolated from the field exhibited a 2078.8-fold resistance to buprofezin, indicating that there are other mechanisms contributing to buprofezin resistance in the field. Inheritance analysis showed that the resistance trait is incomplete dominance. In addition, the Nl-G932C strain had a relative fitness of 0.33 with a substantially decreased survival rate, emergence rate, and fecundity. This study provided in vivo functional evidence for the causality of G932C substitution mutation of CHS1 with buprofezin resistance and valuable information for facilitating the development of resistance management strategies in N. lugens. This is the first example of using CRISPR/Cas9 gene-editing technology in a hemipteran insect to directly confirm the role of a candidate target site mutation in insecticide resistance.
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•A knock-in strain (Nl-G932C) of Nilaparvata lugens was created using CRISPR/Cas9.•Nl-G932C showed a 94.9-fold resistance to buprofezin compared to susceptible strain.•Nl-G932C showed fitness disadvantage with low survivorship, emergence and fecundity.•The low fitness may help manage buprofezin resistance of N. lugens in the field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to ...mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec–CONH–BSA, blunted analgesia and attenuated hypothermia for arecoline.
An arecoline conjugate vaccine was first reported to treat betel-quid chewing addiction. The effects of linker attachment site were systematically evaluated in terms of the antibody affinity induced by arecoline conjugate vaccine. Vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec–CONH–BSA. This vaccination also blunted analgesia and attenuated hypothermia induced by arecoline. These results showed great promise of N-position on the tetrahydropyridine ring as an effective linker attachment site. Display omitted
•This is the first report of arecoline conjugate vaccine being used to treat betel-quid chewing addiction.•The arecoline conjugate vaccine candidate induced a potent immune response in mice, but the antibody induced by Arec-N-BSA (linker attachment site at N-position of the tetrahydropyridine ring) lead to a higher antibody affinity than Arec–CONH–BSA (linker attachment site at carboxyl group).•The conjugate vaccine candidate Arec-N-BSA generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine.•Vaccination with Arec-N-BSA blunted analgesia and attenuated hypothermia induced by arecoline in mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
Early recognition of coronavirus disease 2019 (COVID-19) severity can guide patient management. However, it is challenging to predict when COVID-19 patients will progress to critical ...illness. This study aimed to develop an artificial intelligence system to predict future deterioration to critical illness in COVID-19 patients.
Methods
An artificial intelligence (AI) system in a time-to-event analysis framework was developed to integrate chest CT and clinical data for risk prediction of future deterioration to critical illness in patients with COVID-19.
Results
A multi-institutional international cohort of 1,051 patients with RT-PCR confirmed COVID-19 and chest CT was included in this study. Of them, 282 patients developed critical illness, which was defined as requiring ICU admission and/or mechanical ventilation and/or reaching death during their hospital stay. The AI system achieved a C-index of 0.80 for predicting individual COVID-19 patients’ to critical illness. The AI system successfully stratified the patients into high-risk and low-risk groups with distinct progression risks (
p
< 0.0001).
Conclusions
Using CT imaging and clinical data, the AI system successfully predicted time to critical illness for individual patients and identified patients with high risk. AI has the potential to accurately triage patients and facilitate personalized treatment.
Key Point
• AI system can predict time to critical illness for patients with COVID-19 by using CT imaging and clinical data.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Metals are thought to have profound effects on the internal structures of the molecular clouds in which stars are born. The absence of metals is expected to prevent gas from efficient cooling and ...fragmentation in theory. However, this effect has not yet been observed in low-metallicity environments, such as in the early universe and local dwarf galaxies, because of the lack of high-spatial-resolution maps of gas. We carried out Atacama Large Millimeter/submillimeter Array observations of the carbon monoxide (CO) J = 2-1 emission line at 1.4 parsec resolutions of a molecular cloud in DDO 70 at 7% solar metallicity, the most metal-poor galaxy currently known with a CO detection. In total, five clumps have been identified and they are found to more or less follow Larson's law. Since the CO emission exists in regions with visual extinction AV around 1.0, we converted this AV to the gas-mass surface density using a gas-to-dust ratio of 4594 2848 for DDO 70. We found that the CO clumps in DDO 70 exhibit significantly larger (on average four times) sizes than those at the same gas-mass surface densities in the massive star formation regions of the Milky Way. The existence of such large clumps appears to be consistent with theoretical expectations that gas fragmentation in low-metallicity clouds is suppressed. While our observation is only for one cloud in the galaxy, if it is representative, the above result implies suppressed gas fragmentation during the cloud collapse and star formation in the early universe.
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