The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention.

Introduction: Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer's disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention. Methods: We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed. Results: Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012). Discussion: Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.

Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study.

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19. Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes. Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2-46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84-1.40 or 1.09, 0.92-1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01-1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26-1.64; 0.95, 0.36-2.54; and 1.01, 0.53-1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82-1.66; 1.18, 0.78-1.77; and 1.22, 0.92-1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31-2.81; 0.97, 0.25-3.74 and 1.05, 0.44-2.49, respectively) compared to those not using medication. Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

Influence of Intermolecular Interactions on Crystallite Size in Crystalline Solid Dispersions.

Crystalline solid dispersions (CSDs) represent a thermodynamically stable system capable of effectively reducing the crystallite size of drugs, thereby enhancing their solubility and bioavailability. This study uses flavonoid drugs with the same core structures but varying numbers of hydroxyl groups as model drugs and poloxamer 188 as a carrier to explore the intrinsic relationships between drug-polymer interactions, crystallite size, and in vitro dissolution behavior in CSDs. Initially, we investigate the interactions between flavonoid drugs and P188 by calculating Hansen solubility parameters, determination of Flory-Huggins interaction parameters, and other methods. Subsequently, we explore the crystallization kinetics of flavonoid drugs and P188 in CSD systems using polarized optical microscopy and powder X-ray diffraction. We monitor the domain size and crystallite size of flavonoids in CSDs through powder X-ray diffraction and a laser-particle-size analyzer. Finally, we validate the relationship between crystallite size and in vitro dissolution behavior through powder dissolution. The results demonstrate that, as the number of hydroxyl groups increases, the interactions between drugs and polymers become stronger, making drug crystallization in the CSD system less likely. Consequently, reductions in crystalline domain size and crystallite size become more pronounced, leading to a more significant enhancement in drug dissolution.

Direct learning-based deep spiking neural networks: a review.

The spiking neural network (SNN), as a promising brain-inspired computational model with binary spike information transmission mechanism, rich spatially-temporal dynamics, and event-driven characteristics, has received extensive attention. However, its intricately discontinuous spike mechanism brings difficulty to the optimization of the deep SNN. Since the surrogate gradient method can greatly mitigate the optimization difficulty and shows great potential in directly training deep SNNs, a variety of direct learning-based deep SNN works have been proposed and achieved satisfying progress in recent years. In this paper, we present a comprehensive survey of these direct learning-based deep SNN works, mainly categorized into accuracy improvement methods, efficiency improvement methods, and temporal dynamics utilization methods. In addition, we also divide these categorizations into finer granularities further to better organize and introduce them. Finally, the challenges and trends that may be faced in future research are prospected.

PubPredict: Prediction of progression and survival in oncology leveraging publications and early efficacy data.

In oncology/hematology early phase clinical trials, efficacies were often observed in terms of response rate, depth, timing, and duration. However, the true clinical benefits that eventually support registrational purpose are progression-free survival (PFS) and/or overall survival (OS), the follow-up of which are typically not long enough in early phase trials. This gap imposes challenges in strategies for late phase drug development. In this article, we tackle the question by leveraging published study to establish a quantitative link between early efficacy outcomes and late phase efficacy endpoints. We used solid tumor cancer as disease model. We modeled the disease course of a RECISTv1.1 assessed solid tumor with a continuous Markov chain (CMC) model. We parameterize the transition intensity matrix of a CMC model based on published aggregate-level summary statistics, and then simulate subject-level time-to-event data. The simulated data is shown to have good approximation to published studies. PFS and/or OS could be predicted with the transition intensity matrix modified given clinical knowledge to reflect various assumptions on response rate, depth, timing, and duration. The authors have built a R shiny application named PubPredict, the tool implements the algorithm described above and allows customized features including multiple response levels, treatment crossover and varying follow-up duration. This toolset has been applied to advise phase 3 trial design when only early efficacy data are available from phase 1 or 2 studies.

Effectiveness and safety of Qingfei Dayuan granules for treating influenza and upper respiratory tract infections manifested by the pulmonary heat-toxin syndrome: A multicenter, randomized, double-blind, placebo-controlled trial.

Background: Patients diagnosed with influenza and upper respiratory tract infections (URTIs) have similar clinical manifestations and biochemical indices and a low detection rate of viral pathogens, mixed infection with diverse respiratory viruses, and targeted antiviral treatment difficulty in the early stage. According to the treatment strategy of "homotherapy for heteropathy" in traditional Chinese medicine (TCM), different diseases with the same clinical symptoms can be treated with the same medicines. Qingfei Dayuan granules (QFDY), a type of Chinese herbal preparation included in the TCM Diagnosis and Treatment Protocol for COVID-19 of Hubei Province issued by the Health Commission of Hubei Province in 2021, are recommended for patients suffering from COVID-19 with symptoms of fever, cough, and fatigue, among others. Additionally, recent studies have shown that QFDY effectively alleviates fever, cough, and other clinical symptoms in patients with influenza and URTIs. Materials and methods: The study was designed as a multicenter, randomized, double-blind, placebo-controlled clinical trial for treatment for influenza and URTIs manifested by pulmonary heat-toxin syndrome (PHTS) with QFDY. A total of 220 eligible patients were enrolled from eight first-class hospitals in five cities of Hubei Province in China and randomly assigned to receive either 15 g of QFDY or a placebo three times a day for 5 days. The primary outcome was the complete fever relief time. Secondary outcomes included efficacy evaluation of TCM syndromes, scores of TCM syndromes, cure rate of each single symptom, incidence of comorbidities and progression to severe conditions, combined medications, and laboratory tests. Safety evaluations mainly involved adverse events (AEs) and changes in vital signs during the study. Results: Compared with the placebo group, the complete fever relief time was shorter in the QFDY group, 24 h (12.0, 48.0) in the full analysis set (FAS) and 24 h (12.0, 49.5) in the per-protocol set (PPS) (p ≤ 0.001). After a 3-day treatment, the clinical recovery rate (22.3% in the FAS and 21.6% in the PPS) and cure rate of cough (38.6% in the FAS and 37.9% in the PPS), a stuffy and running nose, and sneezing (60.0% in the FAS and 59.5% in the PPS) in the QFDY group were higher than those in the placebo group (p < 0.05). The number of patients taking antibiotics for more than 24 h in the placebo group (nine cases) was significantly higher than that in the QFDY group (one case) (p < 0.05). There were no significant differences between the two groups in terms of scores of TCM syndromes, incidence of comorbidities or progression to severe conditions, combined use of acetaminophen tablets or phlegm-resolving medicines, and laboratory tests (p > 0.05). Meanwhile, no significant difference was found in the incidence of AEs and vital signs between the two groups (p > 0.05). Conclusion: The trial showed that QFDY was an effective and safe treatment modality for influenza and URTIs manifested by PHTS because it shortened the complete fever relief time, accelerated clinical recovery, and alleviated symptoms such as cough, a stuffy and running nose, and sneezing during the course of treatment. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=131702, identifier ChiCTR2100049695.

Effect of lifestyle intervention on HbA1c levels in overweight and obese adults with type 2 diabetes across ethnicities: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Weight reduction is fundamental for the management and remission of diabetes. We aimed to assess ethnic differences in the effects of lifestyle weight-loss interventions on HbA1c levels in overweight or obese adults with type 2 diabetes mellitus (T2DM). METHODS: We systematically searched PubMed/MEDLINE and Web of Science online databases up to 31 Dec 2022. Randomized controlled trials using lifestyle weight-loss interventions in overweight or obese adults with T2DM were selected. We performed subgroup analyses to explore the heterogeneity across different ethnicities (Asians, White/Caucasians, Black/Africans and Hispanics). A random effects model was applied to calculate weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: Thirty studies including 7580 subjects from different ethnicities were identified according to the predefined inclusion and exclusion criteria. HbA1c levels were significantly reduced by lifestyle weight-loss intervention. Notably, a significantly beneficial effect on HbA1c was observed in White/Caucasians (WMD = -0.59, 95% CI: -0.90, -0.28, P < 0.001) and Asians (WMD = -0.48, 95% CI: -0.63, -0.33, P < 0.001), but not in the Black/African or Hispanic group (both P > 0.05). The findings remained essentially unchanged in the sensitivity analysis. CONCLUSIONS: Lifestyle weight-loss interventions had distinct beneficial effects on HbA1c levels in different ethnic groups with T2DM, especially in Caucasians and Asians.

Baicalin ameliorates multidrug-resistant Pseudomonas aeruginosa induced pulmonary inflammation in rat via arginine biosynthesis.

Multidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus, Lactobacillus and Bacteroides, but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection.

Effect of a family-involvement combined aerobic and resistance exercise protocol on cancer-related fatigue in patients with breast cancer during postoperative chemotherapy: study protocol for a quasi-randomised controlled trial.

INTRODUCTION: Cancer-related fatigue (CRF) is one of the most common and debilitating side effects experienced by patients with breast cancer (BC) during postoperative chemotherapy. Family-involvement combined aerobic and resistance exercise has been introduced as a promising non-pharmacological intervention for CRF symptom relief and improving patients' muscle strength, exercise completion, family intimacy and adaptability and quality of life. However, evidence for the practice of home participation in combined aerobic and resistance exercise for the management of CRF in patients with BC is lacking. METHODS AND ANALYSIS: We present a protocol for a quasi-randomised controlled trial involving an 8-week intervention. Seventy patients with BC will be recruited from a tertiary care centre in China. Participants from the first oncology department will be assigned to the family-involvement combined aerobic and resistance exercise group (n=28), while participants from the second oncology department will be assigned to the control group that will receive standard exercise guidance (n=28). The primary outcome will be the Piper Fatigue Scale-Revised (R-PFS) score. The secondary outcomes will include muscle strength, exercise completion, family intimacy and adaptability and quality of life, which will be evaluated by the stand-up and sit-down chair test, grip test, exercise completion rate, Family Adaptability and Cohesion Scale, Second Edition-Chinese Version (FACESⅡ-CV) and Functional Assessment of Cancer Therapy -Breast (FACT-B) scale. Analysis of covariance will be applied for comparisons between groups, and paired t-tests will be used for comparison of data before and after exercise within a group. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (PJ-KS-KY-2021-288). The results of this study will be published via peer-reviewed publications and presentations at conferences. TRAIL REGISTRATION NUMBER: ChiCTR2200055793.

Synthetic bacterial therapies for intestinal diseases based on quorum-sensing circuits.

Bacterial therapy has become a key strategy against intestinal infectious diseases in recent years. Moreover, regulating the gut microbiota through traditional fecal microbiota transplantation and supplementation of probiotics faces controllability, efficacy, and safety challenges. The infiltration and emergence of synthetic biology and microbiome provide an operational and safe treatment platform for live bacterial biotherapies. Synthetic bacterial therapy can artificially manipulate bacteria to produce and deliver therapeutic drug molecules. This method has the advantages of solid controllability, low toxicity, strong therapeutic effects, and easy operation. As an essential tool for dynamic regulation in synthetic biology, quorum sensing (QS) has been widely used for designing complex genetic circuits to control the behavior of bacterial populations and achieve predefined goals. Therefore, QS-based synthetic bacterial therapy might become a new direction for the treatment of diseases. The pre-programmed QS genetic circuit can achieve a controllable production of therapeutic drugs on particular ecological niches by sensing specific signals released from the digestive system in pathological conditions, thereby realizing the integration of diagnosis and treatment. Based on this as well as the modular idea of synthetic biology, QS-based synthetic bacterial therapies are divided into an environmental signal sensing module (senses gut disease physiological signals), a therapeutic molecule producing module (plays a therapeutic role against diseases), and a population behavior regulating module (QS system). This review article summarized the structure and function of these three modules and discussed the rational design of QS gene circuits as a novel intervention strategy for intestinal diseases. Moreover, the application prospects of QS-based synthetic bacterial therapy were summarized. Finally, the challenges faced by these methods were analyzed to make the targeted recommendations for developing a successful therapeutic strategy for intestinal diseases.

Identification of Kinetic Abnormalities in Male Patients after Anterior Cruciate Ligament Deficiency Combined with Meniscal Injury: A Musculoskeletal Model Study of Lower Limbs during Jogging.

There is little known about kinetic changes in anterior cruciate ligament deficiency (ACLD) combined with meniscal tears during jogging. Therefore, 29 male patients with injured ACLs and 15 healthy male volunteers were recruited for this study to investigate kinetic abnormalities in male patients after ACL deficiency combined with a meniscal injury during jogging. Based on experimental data measured by an optical tracking system, a subject-specific musculoskeletal model was employed to estimate the tibiofemoral joint kinetics during jogging. Between-limb and interpatient differences were compared by the analysis of variance. The results showed that decreased knee joint forces and moments of both legs in ACLD patients were detected during the stance phase compared to the control group. Meanwhile, compared with ACLD knees, significantly fewer contact forces and flexion moments in ACLD combined with lateral and medial meniscal injury groups were found at the mid-stance, and ACLD with medial meniscal injury group showed a lower axial moment in the loading response (p < 0.05). In conclusion, ACLD knees exhibit reduced tibiofemoral joint forces and moments during jogging when compared with control knees. A combination of meniscus injuries in the ACLD-affected side exhibited abnormal kinetic alterations at the loading response and mid-stance phase.

Quantitative evaluation method of smoke exhaust performance and application on exhaust volume optimization in tunnel fires under lateral centralized mode.

This study investigated the indicators in the quantitative method of evaluating the smoke exhaust performance, which provided a theoretical basis for the optimization of the smoke extraction system under the lateral centralized mode in tunnel fires. The criterion was proposed for plug-holing, and the theoretical models of smoke exhaust efficiency were established to distinguish whether the plug-holing occurs or not. The relationship between efficiency, effectiveness, and efficacy was analyzed from the perspective of smoke and heat exhaust. Meanwhile, this evaluation method was applied to the optimization of exhaust volume in a practical engineering through FDS numerical simulation. The results show that Ri is a vital basis for reflecting the movement form of smoke and the exhaust effect. The critical value of Ri is 1.09 when plug-holing occurs in a standard three-lane immersed tunnel, resulting in a significant reduction in the efficiency of smoke exhaust. The greater the exhaust volume of the exhaust fan, the greater the Ri value, the higher the total smoke and heat exhaust efficiency, and the better the exhaust effectiveness of smoke inlets without plug-holing. Under longitudinal ventilation, the optimal exhaust volume is 180 m3/s at 20 MW and 360 m3/s at 50 MW in the application case.

Viral Metagenomics Reveals Diverse Viruses in Tissue Samples of Diseased Pigs.

The swine industry plays an essential role in agricultural production in China. Diseases, especially viral diseases, affect the development of the pig industry and threaten human health. However, at present, the tissue virome of diseased pigs has rarely been studied. Using the unbiased viral metagenomic approach, we investigated the tissue virome in sick pigs (respiratory symptoms, reproductive disorders, high fever, diarrhea, weight loss, acute death and neurological symptoms) collected from farms of Anhui, Jiangsu and Sichuan Province, China. The eukaryotic viruses identified belonged to the families Anelloviridae, Arteriviridae, Astroviridae, Flaviviridae, Circoviridae and Parvoviridae; prokaryotic virus families including Siphoviridae, Myoviridae and Podoviridae occupied a large proportion in some samples. This study provides valuable information for understanding the tissue virome in sick pigs and for the monitoring, preventing, and treating of viral diseases in pigs.

Synergistic effects on itaconic acid production in engineered Aspergillus niger expressing the two distinct biosynthesis clusters from Aspergillus terreus and Ustilago maydis.

BACKGROUND: Itaconic acid (IA) is a versatile platform chemical widely used for the synthesis of various polymers and current methods for IA production based on Aspergillus terreus fermentation are limited in terms of process efficiency and productivity. To construct more efficient IA production strains, A. niger was used as a chassis for engineering IA production by assembling the key components of IA biosynthesis pathways from both A. terreus and Ustilago maydis. RESULTS: Recombinant A. niger S1596 overexpressing the A. terreus IA biosynthesis genes cadA, mttA, mfsA produced IA of 4.32 g/L, while A. niger S2120 overexpressing the U. maydis IA gene cluster adi1, tad1, mtt1, itp1 achieved IA of 3.02 g/L. Integration of the two IA production pathways led to the construction of A. niger S2083 with IA titers of 5.58 g/L. Increasing cadA copy number in strain S2083 created strain S2209 with titers of 7.99 g/L and deleting ictA to block IA degradation in S2209 created strain S2288 with IA titers of 8.70 g/L. Overexpressing acoA to enhance the supply of IA precursor in strain S2288 generated strain S2444 with IA titers of 9.08 g/L in shake flask. CONCLUSION: Recombinant A. niger overexpressing the U. maydis IA biosynthesis pathway was capable of IA accumulation. Combined expression of the two IA biosynthesis pathways from A. terreus and U. maydis in A. niger resulted in much higher IA titers. Furthermore, increasing cadA copy number, deleting ictA to block IA degradation and overexpressing acoA to enhance IA precursor supply all showed beneficial effects on IA accumulation.

Processed Meat Characteristics between Commercial Duroc-Sired and Heritage Breed Large Black Pigs.

This study examined the meat processing characteristics between Duroc-sired (DS) and heritage breed Large Black (LB) pigs fed high forage (FIB) or commercial diets (CON). Fifty pigs (DS, n = 25; LB, n = 25) were used in a 2 × 2 factorial design with breed and diet as fixed effects. Processing traits were measured for fresh bellies, bacon slices, and sausage patties. Results showed that DS bellies were longer (p < 0.001) but thinner (p = 0.026). CON bellies were longer (p = 0.005) and thicker (p < 0.001). LB bellies had decreased lean area (p < 0.001) and processing yield (p = 0.001). DS patties were lighter (L*, p < 0.001) and less red (a*, p < 0.001). LB had increased belly firmness (p = 0.053). The CON diet resulted in better particle definition (p = 0.010) in patties as well as a larger slice area (p = 0.048) in bacon slices. A breed × diet interaction was observed for lipid oxidation (p = 0.001). The findings provided novel insight into the comparison between these breeds and diets. While LB pork may have niche market value, the integration of this breed into commercial bacon processing has limitations in composition that need to be further evaluated to improve the product desirability.

Single reader between-cases AUC estimator with nested data.

The area under the receiver operating characteristic curve (AUC) is widely used in evaluating diagnostic performance for many clinical tasks. It is still challenging to evaluate the reading performance of distinguishing between positive and negative regions of interest (ROIs) in the nested-data problem, where multiple ROIs are nested within the cases. To address this issue, we identify two kinds of AUC estimators, within-cases AUC and between-cases AUC. We focus on the between-cases AUC estimator, since our main research interest is in patient-level diagnostic performance rather than location-level performance (the ability to separate ROIs with and without disease within each patient). Another reason is that as the case number increases, the number of between-cases paired ROIs is much larger than the number of within-cases ROIs. We provide estimators for the variance of the between-cases AUC and for the covariance when there are two readers. We derive and prove the above estimators' theoretical values based on a simulation model and characterize their behavior using Monte Carlo simulation results. We also provide a real-data example. Moreover, we connect the distribution-based simulation model with the simulation model based on the linear mixed-effect model, which helps better understand the sources of variation in the simulated dataset.

Impacts of COVID-19 on Nutritional Intake in Rural China: Panel Data Evidence.

The COVID-19 pandemic introduced risks and challenges to global food and nutrition security. In this paper, we examine the impact of the COVID-19 pandemic on the nutritional intake of China's rural residents using panel data and a fixed effects model. The data were collected in 2019 and 2020 and covered nine provinces and 2631 households in rural China. The results reveal that an increase of 100 confirmed cases in a county resulted in a 1.30% (p < 0.01), 1.42% (p < 0.01), 1.65% (p < 0.01), and 1.15% (p < 0.01) decrease in per capita intake of dietary energy, carbohydrates, fats, and proteins, respectively. Moreover, the COVID-19 pandemic had a significant and negative effect on dietary macronutrient intake in the low-income group at the 5% level of significance. Our study indicates that the potential insufficient nutrition situation, nutritional imbalance, and dietary imbalance of low-income rural residents should be addressed appropriately.

The Effect of Leucine Supplementation on Sarcopenia-Related Measures in Older Adults: A Systematic Review and Meta-Analysis of 17 Randomized Controlled Trials.

Background: The role of leucine in sarcopenia prevention remains unclear. We aimed to summarize the published data from randomized controlled trials (RCTs) to estimate the effect of leucine supplementation on sarcopenia-related measures in older adults. Methods: A systematic literature search was performed using the electronic databases PubMed, Embase, and Web of Science with restriction to randomized controlled trials design from January 1, 2009 to March 19, 2022. Sarcopenia-related measures included handgrip strength, total lean mass, gait speed, leg press, 6-min walk test, short-physical performance battery, timed up-and-go test and 30-s chair-stand test. Fixed- and random-effects meta-analysis models were used to generate pooled weighted mean differences (WMDs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses. Publication bias assessments were performed. Results: A total of 17 RCTs enrolling 1418 subjects were identified. Leucine-isolated supplementation showed no effect on total lean mass (WMD = 0.03 kg, 95% CI: -0.51, 0.57, P = 0.917), handgrip strength (WMD = 1.23 kg, 95% CI: -0.58, 3.03, P = 0.183) and leg press (WMD = -1.35 kg, 95% CI: -7.46, 4.77, P = 0.666). However, leucine-combined supplementation including vitamin D showed a significant improvement in handgrip strength (WMD = 2.17 kg, 95% CI: 0.24, 4.10, P = 0.027) and gait speed (WMD = 0.03 m/s, 95% CI: 0.01, 0.05, P = 0.008). Conclusion: Leucine-isolated supplementation did not improve muscle mass and strength in elderly. However, leucine-combined supplementation including vitamin D exhibited a significant benefit for muscle strength and performance including handgrip strength and gait speed in older adults. A combination of nutritional supplements would be a viable option for improving sarcopenia.

Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis.

BACKGROUND: The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer. RESULTS: First, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-κB-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients' fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph node metastasis status, and distant metastasis status. The receiver operating characteristic (ROC) curves showed that the relative abundance of Proteobacteria had better performance than the prostate-specific antigen (PSA) level in predicting the probability of distant metastasis in prostate cancer (area under the ROC curve, 0.860; p < 0.001). CONCLUSION: Collectively, this research demonstrated that gut dysbiosis, characterized by the enrichment of Proteobacteria due to antibiotic exposure, resulted in the elevation of gut permeability and intratumoral LPS, promoting the development of prostate cancer via the NF-κB-IL6-STAT3 axis in mice. Considering findings from human patients, Proteobacteria might act as an intestinal biomarker for progressive prostate cancer. Video Abstract.

Quality of Life in Mothers With Perinatal Depression: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of perinatal depression is high and its adverse effects on mothers and infants are extensive. Several studies have explored the relationship between perinatal depression and health-related quality of life (HRQoL), but little is known about the nature and magnitude of this effect. The objectives of this study were to evaluate the HRQoL of mothers with perinatal depression and compare the HRQoL of depressed mothers with that of non-depressed mothers. METHODS: A systematic review was performed according to the PRISMA guidelines. PubMed, EMBASE, Scopus, PsycINFO, Web of Science, Cochrane Central Register, the China National Knowledge Infrastructure, the VIP Database, and the Wan Fang Database were searched. The retrieval time was from the establishment of the database to July 2020. A series of meta-analyses were run for each outcome pertaining to HRQoL sub-measures. Subgroup analyses were conducted based on country income category and time period. RESULTS: Of 7,945 studies identified, 12 articles were included in the meta-analysis, providing HRQoL data for 4,392 mothers. Compared with non-depressed mothers, mothers with perinatal depression reported significantly poor scores across all the quality-of-life domains. Mixed-effects analysis showed that there was no difference in the HRQoL scores of mothers with antepartum and postpartum depression. Mothers with perinatal depression in higher-income countries reported higher disability on role-physical (p = 0.02) and social functioning domains (p = 0.001) than those from lower-income countries. LIMITATIONS: Due to insufficient data, no regression analysis was performed. The inability to accurately determine the difference in HRQoL between antepartum and postpartum depression was because of the restriction of the included studies. Moreover, most of the included studies were conducted in middle-income countries and may have an impact on the applicability of the results. Subgroup analyses are observational and not based on random comparisons. The results of subgroup analyses should be interpreted with caution. CONCLUSION: HRQoL is compromised in mothers with perinatal depression. Continuous efforts are required to improve the HRQoL of perinatal depressed mothers.Systematic Review Registration: CRD42020199488.