Dual Infection of Different Clusters of HIV in People Living with HIV Worldwide: A Meta-Analysis Based on Next-Generation Sequencing Studies.

To understand the global dual HIV infection (DI) profiles comprehensively, the databases Cochrane Library, Embase, PubMed, and Web of Science were the data sources up to March 31, 2024 (PROSPERO: CRD42023388328). Stata and R-language software were used to analyze the extracted data. Publication bias was assessed using Egger's test. Sensitivity analysis was conducted to evaluate the stability of the combined effect values. Data from 17 eligible studies across four continents (Africa, Asia, Europe, and North America) with 1,475 subjects were used. The combined dual infection rate (DIR) was 10.47% (95% CI: 7.11%-14.38%) without a time trend (p = 0.105). The DIRs of target population groups differed significantly, with FSWs having the highest DIR (15.14%), followed by general population (12.08%), MSM (11.84%), and DUs (9.76%). The subtype profiles of 122 patients with dual infection were extracted, and the results showed that intrasubtype infections were predominant in coinfection (16/22, 72.73%) and superinfection (68/100, 68.00%) groups, with the subtype pattern B and B accounts for the largest proportion. The global dual infection rate may be underestimated, even though the data fluctuated around 10% and showed no time trend. The occurrence of DI indicated that individuals still do not acquire sufficient resistance to HIV even after primary infection, which could potentially compromise the patient's treatment effect and lead to the emergence of new subtypes, posing a significant challenge to HIV prevention, control, and treatment, suggesting that behavioral counseling and health education for all HIV-infected individuals are still crucial during the antiviral therapy.

The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism.

N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Real-world performance of HIV low viral load values in diagnosing acute HIV infection in a tertiary care hospital in Beijing, China.

BACKGROUND: Early diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the Diagnosis and Treatment of HIV/AIDS (2021 edition) state that an HIV RNA level > 5,000 copies/mL is the threshold for diagnosing HIV infection. The impact of low viral load values on HIV diagnosis needs to be investigated. METHODS: There were 3455 human immunodeficiency virus (HIV1 + 2) antibody results (immunoblotting method) and 65,129 HIV viral load values at Beijing Youan Hospital from 2019 to 2022. A total of 2434 patients had both antibody confirmatory results and viral load results. The confirmatory antibody results and HIV viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis. RESULTS: Of the 2434 patients who had both confirmatory antibody results and viral load results, the viral load values of 140 patients (5.8%) had viral loads ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody result, and of these 140 patients, the sample receipt time for the viral load tests of 96 (66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, 34 patients (1.4%) had low viral loads ranging from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody result. CONCLUSION: This study revealed that there is a risk of missed diagnosis if a threshold of 5000 copies/mL is used for the diagnosis of HIV infection. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.

Prognostic Impact of Mucin Expression in Curatively Resected Ampulla of Vater Cancer.

Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods: Using samples from 68 patients with AoV cancer, we performed immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 using a tissue microarray. Subsequently, we analyzed their expression patterns in relation to clinicopathological parameters and patient outcomes. Results: Of the patients, 98.5% exhibited positive expression for MUC1, while MUC2, MUC5AC, and MUC6 were expressed in 44.1%, 47.1%, and 41.2% of the patients, respectively. Correlation analyses between mucin expression and clinicopathological factors revealed no significant associations, except between MUC5AC expression and N stage. Univariate analysis demonstrated significant associations between MUC5AC expression and overall survival (OS). Multivariate analysis further confirmed that MUC5AC expression was a significant predictor of OS, along with the N stage. However, MUC5AC expression was not meaningfully associated with recurrence-free survival (RFS). The patients positive for MUC5AC expression had a considerably shorter OS than those with negative expression. Conclusions: Our study provides insights into the clinical impact of mucins on AoV cancer, regardless of the histological subtype. Although MUC1 expression is universal, MUC5AC expression is a significant prognostic indicator that correlates with lymph node metastasis and poor OS. These results emphasize the possible utility of MUC5AC as a biomarker for extensive lymph node dissection and the prognostic evaluation of patients with AoV cancer.

Recent Advances in Electrochemiluminescence Visual Biosensing and Bioimaging.

Electrochemiluminescence (ECL) is one of the most powerful techniques that meet the needs of analysis and detection in a variety of scenarios, because of its highly analytical sensitivity and excellent spatiotemporal controllability. ECL combined with microscopy (ECLM) offers a promising approach for quantifying and mapping a wide range of analytes. To date, ECLM has been widely used to image biological entities and processes, such as cells, subcellular structures, proteins and membrane transport properties. In this review, we first introduced the mechanisms of several classic ECL systems, then highlighted the progress of visual biosensing and bioimaging by ECLM in the last decade. Finally, the characteristics of ECLM were summarized, as well as some of the current challenges. The future research interests and potential directions for the application of ECLM were also outlooked.

Exoskeleton rehabilitation robot training for balance and lower limb function in sub-acute stroke patients: a pilot, randomized controlled trial.

PURPOSE: This pilot study aimed to investigate the effects of REX exoskeleton rehabilitation robot training on the balance and lower limb function in patients with sub-acute stroke. METHODS: This was a pilot, single-blind, randomized controlled trial. Twenty-four patients with sub-acute stroke (with the course of disease ranging from 3 weeks to 3 months) were randomized into two groups, including a robot group and a control group. Patients in control group received upright bed rehabilitation (n = 12) and those in robot group received exoskeleton rehabilitation robot training (n = 12). The frequency of training in both groups was once a day (60 min each) for 5 days a week for a total of 4 weeks. Besides, the two groups were evaluated before, 2 weeks after and 4 weeks after the intervention, respectively. The primary assessment index was the Berg Balance Scale (BBS), whereas the secondary assessment indexes included the Fugl-Meyer Lower Extremity Motor Function Scale (FMA-LE), the Posture Assessment Scale for Stroke Patients (PASS), the Activities of Daily Living Scale (Modified Barthel Index, MBI), the Tecnobody Balance Tester, and lower extremity muscle surface electromyography (sEMG). RESULTS: The robot group showed significant improvements (P < 0.05) in the primary efficacy index BBS, as well as the secondary efficacy indexes PASS, FMA-LE, MBI, Tecnobody Balance Tester, and sEMG of the lower limb muscles. Besides, there were a significant differences in BBS, PASS, static eye-opening area or dynamic stability limit evaluation indexes between the robotic and control groups (P < 0.05). CONCLUSIONS: This is the first study to investigate the effectiveness of the REX exoskeleton rehabilitation robot in the rehabilitation of patients with stroke. According to our results, the REX exoskeleton rehabilitation robot demonstrated superior potential efficacy in promoting the early recovery of balance and motor functions in patients with sub-acute stroke. Future large-scale randomized controlled studies and follow-up assessments are needed to validate the current findings. CLINICAL TRIALS REGISTRATION: URL: https://www.chictr.org.cn/index.html.Unique identifier: ChiCTR2300068398.

Population pharmacokinetics of Ainuovirine and exposure-response analysis in human immunodeficiency virus-infected individuals.

BACKGROUND: Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV. METHODS: Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses. RESULTS: ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for CL/F was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). CONCLUSIONS: Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure. TRIAL REGISTRATION: Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Electrochemical Lateral Flow Immunoassay with Built-In Electrodes for Ultrasensitive and Wireless Detection of Inflammatory Biomarkers.

Paper-based lateral flow immunoassays (LFIAs) are cost-effective, portable, and simple methods for detection of diverse analytes, which however only provide qualitative or semiquantitative results and lack sufficient sensitivity. A combination of LFIA and electrochemical detection, namely, electrochemical lateral flow immunoassay (eLFIA), enables quantitative detection of analytes with high sensitivity, but the integration of external electrodes makes the system relatively expensive and unstable. Herein, the working, counter, and reference electrodes were prepared directly on the nitrocellulose membrane using screen printing, which remarkably simplified the structure of eLFIA and decreased the cost. Moreover, a horseradish peroxidase (HRP)-based electrochemical signal amplification strategy was used for further increasing the analytical sensitivity. HRP captured on the working electrode can catalyze the oxidation of tetramethylbenzidine (TMB) to form the TMB-TMBox precipitate on the electrode surface, which as an electrochemically active product can output an amplified current for quantification. We demonstrated that the eLFIA could detect low-abundant inflammatory biomarkers in human plasma samples with limits of detection of 0.17 and 0.54 pg mL-1 for interleukin-6 and C-reactive protein, respectively. Finally, a fully portable system was fabricated by integrating eLFIA with a flexible and wireless electrochemical workstation, realizing the point-of-care detection of interleukin-6.

Synthesis and biological evaluation of orally active anti-Trypanosoma agents.

In previous studies, we developed anti-trypanosome tubulin inhibitors with promising in vitro selectivity and activity against Human African Trypanosomiasis (HAT). However, for such agents, oral activity is crucial. This study focused on further optimizing these compounds to enhance their ligand efficiency, aiming to reduce bulkiness and hydrophobicity, which should improve solubility and, consequently, oral bioavailability. Using Trypanosoma brucei brucei cells as the parasite model and human normal kidney cells and mouse macrophage cells as the host model, we evaluated 30 new analogs synthesized through combinatorial chemistry. These analogs have fewer aromatic moieties and lower molecular weights than their predecessors. Several new analogs demonstrated IC50s in the low micromolar range, effectively inhibiting trypanosome cell growth without harming mammalian cells at the same concentration. We conducted a detailed structure-activity relationship (SAR) analysis and a docking study to assess the compounds' binding affinity to trypanosome tubulin homolog. The results revealed a correlation between binding energy and anti-Trypanosoma activity. Importantly, compound 7 displayed significant oral activity, effectively inhibiting trypanosome cell proliferation in mice.

SIRT1 regulates the localization and stability of telomerase protein by direct interaction.

Telomerase reverse transcriptase (TERT) not only upholds telomeric equilibrium but also plays a pivotal role in multiple non-canonical cellular mechanisms, particularly in the context of aging, cancer, and genomic stability. Though depletion of SIRT1 in mouse embryonic fibroblasts has demonstrated telomere shortening, the impact of SIRT1 on enabling TERT to regulate telomeric homeostasis remains enigmatic. Here, we reveal that SIRT1 directly interacts with TERT, and promotes the nuclear localization and stability of TERT. Reverse transcriptase (RT) domain of TERT and N-terminus of SIRT1 mainly participated in their direct interaction. TERT, concomitantly expressed with intact SIRT1, exhibits nuclear localization, whereas TERT co-expressed with N-terminal-deleted SIRT1 remains in the cytosol. Furthermore, overexpression of SIRT1 enhances the nuclear localization and protein stability of TERT, akin to overexpression of deacetylase-inactive SIRT1, whereas N-terminal-deleted SIRT1 has no effect on TERT. These findings suggest a novel regulatory role of SIRT1 for TERT through direct interaction. This interaction provides new insights into the fields of aging, cancer, and genome stability governed by TERT and SIRT1.

The effect of fine particulate matter (PM2.5) pollution on health inequality: an intergenerational perspective.

Air pollution poses a serious challenge to public health and simultaneously exacerbating regional & intergenerational health inequality. This research introduces PM2.5 pollution into the intergenerational health transmission model, and estimates its impact on health inequality in China using Ordered Logit Regression (OLR) and Multi-scale Geographically Weighted Regression (MGWR) model. The results indicate that PM2.5 pollution exacerbate the intergenerational health inequality, and its impacts show inconsistency across family income levels, parental health insurance status, and area of residence. Specifically, it is more difficult for offspring in low-income families to escape from the influence of unhealthy family to become upwardly mobile. Additionally, this health inequality is more significant in households in which at least one parent does not have health insurance. Moreover, the intergenerational solidification caused by PM2.5 pollution is higher in the east and lower in the west. Both the PM2.5 level and solidification effect are high in Beijing-Tianjin-Hebei region, Yangtze River Delta region and central areas of China, which is the focus of air pollution management. These findings suggest that more emphasis should be placed on family-based health promotion. In areas with high PM2.5 pollution levels, resources, subsidies and air pollution protection should be provided for less healthy families with lower incomes and no health insurance.

Regulation of Hippo-YAP signaling axis by Isoalantolactone suppresses tumor progression in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a devastating malignancy characterized by aggressive tumor growth and limited treatment options. Dysregulation of the Hippo signaling pathway and its downstream effector, Yes-associated protein (YAP), has been implicated in CCA development and progression. In this study, we investigated the effects of Isoalantolactone (IALT) on CCA cells to elucidate its effect on YAP activity and its potential clinical significance. Our findings demonstrate that IALT exerts cytotoxic effects, induces apoptosis, and modulates YAP signaling in SNU478 cells. We further confirmed the involvement of the canonical Hippo pathway by generating LATS1/LATS2 knockout cells, highlighting the dependence of IALT-mediated apoptosis and YAP phosphorylation on the Hippo-LATS signaling axis. In addition, IALT suppressed cell growth and migration, partially dependent on YAP-TEAD activity. These results provide insights into the therapeutic potential of targeting YAP in CCA and provide a rationale for developing of YAP-targeted therapies for this challenging malignancy.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

MPC motion control of boom descending of unmanned excavator based on regenerative valve.

The control precision of the working device has always been a challenging aspect in unmanned excavator research due to the adoption of a triangular drive mode and a complex hydraulic system in the working mechanism. The article focuses on the research of autonomous control for the downward motion of a robotic arm in an unmanned excavator equipped with a regeneration valve. The study aims to achieve precise tracking of fast movement trajectories during operator manipulation, utilizing Model Predictive Control (MPC). Furthermore, the exceptional disturbance rejection capability of the MPC algorithm is demonstrated through interference application. A comprehensive model considering mechanical, hydraulic, and electrical factors is established for the excavator boom. The MPC algorithm is applied to achieve precise control over the boom descent process, providing a foundation for motion control in unmanned excavators. This article presents a theoretical analysis to elucidate the robustness principle of MPC in the descent control of uncertain dynamic arms. By incorporating real parameters, we successfully track predetermined planned paths at different speeds and validate them on a 20-ton hydraulic excavator. The results demonstrate that the MPC control algorithm accurately manipulates the boom descent motion while exhibiting excellent disturbance rejection performance. Compared to PID control algorithms, MPC offers wider target adaptability range and better disturbance rejection performance, making it suitable for rapid application in controlling working devices of unmanned excavators.

Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

Quantifying US air pollution policy: How political and regional factors influence pollutant mitigation.

Air pollution control in the United States has evolved into a comprehensive policy system spanning from the federal to the state level over time. A unified quantitative analysis of policy intensity can shed light on the policy evolution across different levels, the influence of partisan and regional factors on policy, and the relationships with emissions of major pollutants. By harnessing the policy text of the Clean Air Act (CAA) at the federal level and State Implementation Plans (SIPs) at the state governments (1955-2020), we deployed a Natural Language Processing approach to define a policy intensity index to systematically quantify the US air policy landscape. Our findings highlight that the 1970 CAA amendment carries the most vigorous intensity as it established a holistic control system for the first time. Subsequent years witnessed a general trend of partisan polarization, eventually leading to a graduate convergence between red and blue states. Blue states demonstrated a closer alignment with federal directives and a superior efficacy in pollutant reduction. Regionally, the Northeast displays the highest overall policy intensity, and the West exhibits the highest coordination with the federal benchmarks, making these regions outperform others in air pollution control. Our study not only discusses policy implications for air pollutant reductions considering partisan and regional differences but also provides a novel measurement tool to quantify policies for assessing disparities and synergies.

Maternal or post-weaning dietary fructo-oligosaccharide supplementation reduces stillbirth rate of sows and diarrhea of weaned piglets.

Fructo-oligosaccharides (FOS) are well-known prebiotics that have the potential to improve sow reproductive performance and increase piglet growth. However, previous studies were observed in sole FOS-supplemented diets of sows or weaned piglets and did not consider the sow-to-piglet transfer effect on the performance and diarrhea rate of weaned piglets. This study explores the effects of dietary FOS supplementation on the reproductive performance of sows, and the effects of FOS supplementation at different stages on the growth performance and diarrhea rate of weaned piglets. A split-plot experimental design was used with sow diet effect in the whole plot and differing piglet diet effect in the subplot. Fifty-two multiparous sows (223.24 ± 14.77 kg) were randomly divided into 2 groups (0 or 0.2% FOS). The experiment lasted from day 85 of gestation to day 21 of lactation. Reproductive performance, glucose tolerance, placental angiogenesis, and intestinal flora of sows were assessed. At weaning, 192 weaned piglets were grouped in 2 × 2 factorial designs, with the main effects of FOS supplemental level of sow diet (0 and 0.2%), and FOS supplemental level of weaned piglet diet (0 and 0.2%), respectively. The growth performance and diarrhea rate of the weaned piglets were analyzed during a 28-d experiment. Maternal dietary supplementation of FOS was shown to reduce the stillbirth and invalid piglet rates (P < 0.05), improve the insulin sensitivity (P < 0.05) and fecal scores (P < 0.05) of sows, increase the abundance of Akkermansia muciniphila (P = 0.016), decrease the abundance of Escherichia coli (P = 0.035), and increase the isovalerate content in feces (P = 0.086). Meanwhile, the placental angiogenesis marker CD31 expression was increased in sows fed FOS diet (P < 0.05). Moreover, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets (P < 0.05) and increased the content of short-chain fatty acids in feces (P < 0.05). Furthermore, only post-weaning dietary FOS supplementation could improve nutrient digestibility of weaned piglets (P < 0.05). Collectively, FOS supplementation in sows can reduce stillbirth rate, perinatal constipation, and insulin resistance, as well as improve placental vascularization barrier. Additionally, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets, but only FOS supplementation in piglets alone at weaning stage could improve their nutrient digestibility.

Antioxidant and Anti-Fatigue Effects of a Standardized Botanical Extract Fraction (HemoHIM) in Forced-Exercised Aged Mice.

HemoHIM is a standardized medicinal herbal preparation consisting of extracts of Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia lactiflora Pallas that possesses immune regulatory activities. This study aimed to research the potential antioxidant effects of HemoHIM and its capacity for reducing fatigue in aged mice subjected to forced exercise. After administering HemoHIM 125 (500 mg/kg orally) for 4 weeks in 8-month-old female C57BL/6 mice (4 groups of 10 mice), various parameters were evaluated. The analyses revealed that HemoHIM enhanced swimming time and grip strength. In addition, it significantly reduced serum lactate levels and increased liver glutathione peroxidase (GPx) levels after exercise challenge. The expression levels of antioxidant enzymes and factors, including nuclear factor erythroid 2-related factor-2 (Nrf-2), heme oxygenase 1, superoxide dismutase, GPx, and glutathione reductase, were significantly higher in liver and muscle tissues of mice treated with HemoHIM. These results indicate that HemoHIM might function as an anti-fatigue and antioxidant agent by modulating the Nrf-2 signaling pathway.