Postweaning sodium citrate exposure induces long-lasting and sex-dependent effects on social behaviours in mice.

BACKGROUND: Postweaning is a pivotal period for brain development and individual growth. As an important chemical used in medicines, foods and beverages, sodium citrate (SC) is commonly available. Although some effects of SC exposure on individual physiology have been demonstrated, the potential long-lasting effects of postweaning dietary SC exposure on social behaviours are still elusive. METHODS: Both postweaning male and female C57BL/6 mice were exposed to SC through drinking water for a total of 3 weeks. A series of behavioural tests, including social dominance test (SDT), social interaction test (SIT), bedding preference test (BPT) and sexual preference test (SPT), were performed in adolescence and adulthood. After these tests, serum oxytocin (OT) levels and gut microbiota were detected. RESULTS: The behavioural results revealed that postweaning SC exposure decreased the social dominance of male mice in adulthood and female mice in both adolescence and adulthood. SC exposure also reduced the sexual preference rates of both males and females, while it had no effect on social interaction behaviour. ELISA results indicated that SC exposure decreased the serum OT levels of females but not males. 16S rRNA sequencing analysis revealed a significant difference in ß-diversity after SC exposure in both males and females. The correlation coefficient indicated the correlation between social behaviours, OT levels and dominant genera of gut microbiota. CONCLUSION: Our findings suggest that postweaning SC exposure may have enduring and sex-dependent effects on social behaviours, which may be correlated with altered serum OT levels and gut microbiota composition.

Dispersive Fourier transform based dual-comb ranging.

Laser-based light detection and ranging (LIDAR) offers a powerful tool to real-timely map spatial information with exceptional accuracy and owns various applications ranging from industrial manufacturing, and remote sensing, to airborne and in-vehicle missions. Over the past two decades, the rapid advancements of optical frequency combs have ushered in a new era for LIDAR, promoting measurement precision to quantum noise limited level. For comb LIDAR systems, to further improve the comprehensive performances and reconcile inherent conflicts between speed, accuracy, and ambiguity range, innovative demodulation strategies become crucial. Here we report a dispersive Fourier transform (DFT) based LIDAR method utilizing phase-locked Vernier dual soliton laser combs. We demonstrate that after in-line pulse stretching, the delay of the flying pulses can be identified via the DFT-based spectral interferometry instead of temporal interferometry or pulse reconstruction. This enables absolute distance measurements with precision starting from 262 nm in single shot, to 2.8 nm after averaging 1.5 ms, in a non-ambiguity range over 1.7 km. Furthermore, our DFT-based LIDAR method distinctly demonstrates an ability to completely eliminate dead zones. Such an integration of frequency-resolved ultrafast analysis and dual-comb ranging technology may pave a way for the design of future LIDAR systems.

Co-utilization of wastewater sludge and heavy metals for single-atom electrocatalytic reduction of gaseous CO2.

Synergetic management of waste activated sludge, heavy metals (HMs) and CO2 for their valorization and cyclic utilization is rarely reported. Herein, we employed sludge-derived extracellular polymeric substances (EPS) and HMs in wastewater to fabricate a gas diffusion electrode (GDE) for electrochemical CO2 reduction. This approach atomically dispersed Ni at each nanofiber of the GDE. Abundant N element in the EPS proved to play a key role in the formation of Nx-Ni (mixture of N3-Ni and N4-Ni) sites for highly efficient CO2 to CO conversion. The atomical Ni3+ shows high catalytic activity. Direct gaseous CO2 reduction in a membrane electrode assembly generated a current density up to 50 mA·cm-2 with CO:H2 ratio of ∼100 and ∼75% FECO under 2.69 cell voltage. This strategy takes advantage of all waste streams generated on site and consolidates traditionally separated treatment processes to save costs, produces value-added products and generates carbon benefits during wastewater treatment.

PI3K/AKT pathway modulation and cold acclimation alleviation concerning apoptosis and necroptosis in broiler thymus.

Moderate cold stimulation regulates the thymus's growth and function and facilitates cold acclimatization in broilers. However, the underlying mechanism remains unknown. To explore the possible mechanism of the thymus in cold-acclimated broilers against cold stress, 240 one-day-old Arbor Acres (AA) broilers were assigned to 2 groups randomly. The control group (C) was housed at conventional temperatures. The temperature during the first week was 33°C to 34°C. Between the ages of 8 and 32 d, the temperature was lowered by 1°C every 2 d, i.e., gradually from 32°C to 20°C, and then maintained at 20°C until 42 d of age. The cold-acclimated group (C-3) was housed at the same temperature as C from 1 to 7 d after birth. Between 8 and 42 d, the temperature of C-3 was 3°C colder than C. After 24 h exposure to acute cold stress (ACS) at 42 d, C and C-3 were named as S and S-3. The results showed that ACS was able to induce oxidation stress, modulate PI3K/AKT signal, and cause necroptosis and apoptosis in broiler thymus. By contrast, cold acclimation could alleviate apoptosis and necroptosis induced by cold stress via alleviating oxidative stress, efficiently activating the PI3K/AKT signal, as well as decreasing apoptotic and necrotic genes' levels. This study offers a novel theoretical basis for cold acclimation to improve the body's cold tolerance.

The Impact of Water Potential and Temperature on Native Species' Capability for Seed Germination in the Loess Plateau Region, China.

Global warming is increasing the frequency and intensity of heat waves and droughts. One important phase in the life cycle of plants is seed germination. To date, the association of the temperature and water potential thresholds of germination with seed traits has not been explored in much detail. Therefore, we set up different temperature gradients (5-35 °C), water potential gradients (-1.2-0 MPa), and temperature × water potential combinations for nine native plants in the Loess Plateau region to clarify the temperature and water combinations suitable for their germination. Meanwhile, we elucidated the temperature and water potential thresholds of the plants and their correlations with the mean seed mass and flatness index by using the thermal time and hydrotime models. According to our findings, the germination rate was positively correlated with the germination percentage and water potential, with the former rising and the latter decreasing as the temperature increased. Using the thermal time and hydrotime models, the seed germination thresholds could be predicted accurately, and the germination thresholds of the studied species varied with an increase in germination percentage. Moreover, temperature altered the impact of water potential on the germination rate. Overall, the base water potential for germination, but not the temperature threshold, was negatively correlated with mean seed mass and was lower for rounder seeds than for longer seeds. This study contributes to improving our understanding of the seed germination characteristics of typical plants and has important implications for the management and vegetation restoration of degraded grasslands.

Postweaning stress affects behavior, brain and gut microbiota of adolescent mice in a sex-dependent manner.

Aggression is an instinctive behavior that has been reported to be influenced by early-life stress. However, the potential effects of acute stress during the postweaning period, a key stage for brain development, on defensive aggression and the associated mechanism remain poorly understood. In the present study, aggressive behaviors were evaluated in adolescent mice exposed to postweaning stress. Serum corticosterone and testosterone levels, neural dendritic spine density, and gut microbiota composition were determined to identify the underlying mechanism. Behavioral analysis showed that postweaning stress reduced locomotor activity in mice and decreased defensive aggression in male mice. ELISA results showed that postweaning stress reduced serum testosterone levels in female mice. Golgi staining analysis demonstrated that postweaning stress decreased neural dendritic spine density in the medial prefrontal cortex of male mice. 16S rRNA sequencing results indicated that postweaning stress altered the composition of the gut microbiota in male mice. Combined, these results suggested that postweaning stress alters defensive aggression in male mice, which may be due to changes in neuronal structure as well as gut microbiota composition. Our findings highlight the long-lasting and sex-dependent effects of early-life experience on behaviors.

Changes in frailty and incident cardiovascular disease in three prospective cohorts.

BACKGROUND AND AIMS: Previous studies found that frailty was an important risk factor for cardiovascular disease (CVD). However, previous studies only focused on baseline frailty status, not taking into consideration the changes in frailty status during follow-up. The aim of this study was to investigate the associations of changes in frailty status with incident CVD. METHODS: This study used data of three prospective cohorts: China Health and Retirement Longitudinal Study (CHARLS), English Longitudinal Study of Ageing (ELSA), and Health and Retirement Study (HRS). Frailty status was evaluated by the Rockwood frailty index and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty status at baseline and the second survey which was two years after the baseline. Cardiovascular disease was ascertained by self-reported physician-diagnosed heart disease (including angina, heart attack, congestive heart failure, and other heart problems) or stroke. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders. RESULTS: A total of 7116 participants from CHARLS (female: 48.6%, mean age: 57.4 years), 5303 from ELSA (female: 57.7%, mean age: 63.7 years), and 7266 from HRS (female: 64.9%, mean age: 65.1 years) were included according to inclusion and exclusion criteria. The median follow-up periods were 5.0 years in the CHARLS, 10.7 years in the ELSA, and 9.5 years in the HRS. Compared with stable robust participants, robust participants who progressed to pre-frail or frail status had increased risks of incident CVD (CHARLS, HR = 1.84, 95% CI: 1.54-2.21; ELSA, HR = 1.53, 95% CI: 1.25-1.86; HRS, HR = 1.59, 95% CI: 1.31-1.92). In contrast, frail participants who recovered to robust or pre-frail status presented decreased risks of incident CVD (CHARLS, HR = 0.62, 95% CI: 0.47-0.81; ELSA, HR = 0.49, 95% CI: 0.34-0.69; HRS, HR = 0.70, 95% CI: 0.55-0.89) when compared with stable frail participants. These decreased risks of incident CVD were also observed in pre-frail participants who recovered to robust status (CHARLS, HR = 0.66, 95% CI: 0.52-0.83; ELSA, HR = 0.65, 95% CI: 0.49-0.85; HRS, HR = 0.71, 95% CI: 0.56-0.91) when compared with stable pre-frail participants. CONCLUSIONS: Different changes in frailty status are associated with different risks of incident CVD. Progression of frailty status increases incident CVD risks, while recovery of frailty status decreases incident CVD risks.

Drug Repositioning for Amyloid Transthyretin Amyloidosis by Interactome Network Corrected by Graph Neural Networks and Transcriptome Analysis.

Amyloid transthyretin (ATTR) amyloidosis caused by transthyretin misfolded into amyloid deposits in nerve and heart is a progressive rare disease. The unknown pathogenesis and the lack of therapy make the 5-year survival prognosis extremely poor. Currently available ATTR drugs can only relieve symptoms and slow down progression, but no drug has demonstrated curable effect for this disease. The growing volume of pharmacological data and large-scale genome and transcriptome data bring new opportunities to find potential new ATTR drugs through computational drug repositioning. We collected the ATTR-related in the disease pathogenesis and differentially expressed (DE) genes from five public databases and Gene Expression Omnibus expression profiles, respectively, then screened drug candidates by a corrected protein-protein network analysis of the ATTR-related genes as well as the drug targets from DrugBank database, and then filtered the drug candidates on the basis of gene expression data perturbed by compounds. We collected 139 and 56 ATTR-related genes from five public databases and transcriptome data, respectively, and performed functional enrichment analysis. We screened out 355 drug candidates based on the proximity to ATTR-related genes in the corrected interactome network, refined by graph neural networks. An Inverted Gene Set Enrichment analysis was further applied to estimate the effect of perturbations on ATTR-related and DE genes. High probability drug candidates were discussed. Drug repositioning using systematic computational processes on an interactome network with transcriptome data were performed to screen out several potential new drug candidates for ATTR.

Polysaccharides from Dendrobium officinale improve obesity-induced insulin resistance through the gut microbiota and the SOCS3-mediated insulin receptor substrate-1 signaling pathway.

BACKGROUND: Obesity induces insulin resistance and chronic inflammation, impacting human health. The relationship between obesity, gut microbiota, and regulatory mechanisms has been studied extensively. Dendrobium officinale polysaccharide (DOP), a traditional Chinese herbal medicine, potentially reduces insulin resistance. However, the mechanism through which DOP affects gut microbiota and alleviates obesity-induced insulin resistance in rats requires further investigation. RESULTS: The current study aimed to assess the impact of DOP on gut microbiota and insulin resistance in rats on a high-fat diet. The results revealed that DOP effectively reduced blood lipids, glucose disorders, oxidative stress, and inflammatory infiltration in the liver of obese Sprague Dawley rats. This was achieved by downregulating SOCS3 expression and upregulating insulin receptor substrate-1 (IRS-1) by regulating the JAK/STAT/SOCS3 signaling pathway. Notably, DOP intervention enhanced the abundance of beneficial gut microbiota and reduced harmful microbiota. Correlation analysis demonstrated significant associations among intestinal microbiota, SOCS3-mediated IRS-1 expression, and inflammatory factors. CONCLUSION: Dendrobium officinale polysaccharide regulated the gut microbiota, enhanced IRS-1 expression, and mitigated liver injury and insulin resistance due to a high-fat diet. These findings depict the potential anti-insulin resistance properties of DOP and offer further evidence for addressing obesity and its complications. © 2023 Society of Chemical Industry.

Problematic mobile phone use and time management disposition in Chinese college students: the chain mediating role of sleep quality and cognitive flexibility.

BACKGROUND: With the widespread adoption of smartphones, there has been a notable increase in problematic mobile phone use (PMPU), particularly prevalent among college students. Research suggests that apart from being associated with various problematic behaviors, this excessive mobile phone use might also have an impact on individual personality traits, such as time management disposition (TMD), which plays a significant role in individual motivation and psychological well-being. While previous literature has identified a negative relationship between PMPU and TMD, few studies have delved into the underlying mediating mechanism. Thus, the main aim of this study was to examine the chain mediating effect of sleep quality and cognitive flexibility on the relationship between PMPU and TMD. METHODS: A total of 921 Chinese college students completed the questionnaire. We collected basic information about the participants and assessed their PMPU, TMD, sleep quality, and cognitive flexibility using the Problematic Mobile Phone Use Scale-10, Adolescence Time Management Disposition Inventory, Pittsburgh Sleep Quality Index scale and Cognitive Flexibility Inventory. RESULTS: The results indicated a significant correlation among all the variables. Moreover, we noted that both sleep quality and cognitive flexibility fully mediated the association between PMPU and TMD. Additionally, a chain mediating effect involving sleep quality and flexibility in this relationship was also identified. CONCLUSION: We found that sleep quality and cognitive flexibility had a series of multiple mediating effects in the pathway from PMPU to TMD, and both significantly mediated TMD. These findings indicated that impaired cognitive function and sleep quality may contribute to time management difficulties resulting from PMPU, suggesting that problematic behaviors like PMPU can impact one's personality traits. Therefore, interventions should be enhanced to mitigate the adverse effects of PMPU.

Zero-Velocity Update-Based GNSS/IMU Tightly Coupled Algorithm with the Constraint of the Earth's Rotation Angular Velocity for Cableway Bracket Deformation Monitoring.

Cableways have been widely used in industrial areas, cities, and scenic spots due to their advantages, such as being a convenient mode of transportation, time-saving, labor-saving, and low cost, as well as offering environmental protection. To ensure the safe operation of a cableway, based on the characteristic that the velocity of the cableway bracket is approximately zero in a static deformation monitoring environment, a deformation monitoring method called zero velocity update (ZUPT)-based GNSS/IMU tightly coupled algorithm with the constraint of the Earth's rotation angular velocity was proposed. The proposed method can effectively solve the problem of a single GNSS being unable to output attitude, which is directly related to the status of wire ropes and cable cars. Meanwhile, ZUPT is used to restrain the Kalman filter's divergence when IMU is stationary. However, the improvements of ZUPT on attitude are not obvious, so the constraint of the Earth's rotation angular velocity was applied. The performance of the proposed method was evaluated through monitoring the cableway bracket of the Yimeng Mountain Tourism area in Shandong. Compared with the ZUPT-based GNSS/IMU tightly coupled algorithm (ZUPT-TC), the proposed method can further constrain the error accumulation of IMU while stationary and, therefore, it can provide reliable position and attitude information on cableway brackets.

Healthy lifestyle scores associate with incidence of type 2 diabetes mediated by uric acid.

BACKGROUND: Whether and to what extent serum uric acid (SUA) mediates the association between combined lifestyle behaviors and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the role of SUA in the relationship between healthy lifestyle scores (HLS) and the incidence of T2DM. METHODS: This prospective study used data from Zhejiang Metabolic Syndrome cohort. A HLS (5-point scale including healthy waist circumference (WC), never smoking, high physical activity, healthy diet and moderate alcohol intake) was estimated in 13,919 participants, who had SUA at baseline examination in 2009-2014, and were followed-up to 2021-2022 to ascertain incident of T2DM. Cox proportional hazards models and mediation analysis were used to examine the associations between HLS, SUA and T2DM. RESULTS: We included 13,919 participants aged 18 years or older without diabetes at baseline (mean age 54.6 [SD 13.9] years, 58.7% female). During a median follow-up of 9.94 years, 645 cases of T2DM occurred. Compared with participants with a poor HLS, those with 4-5 low-risk lifestyle factors showed a 60% reduction in the risk of developing T2DM (adjusted HR, 0.40; 95% CI: 0.28-0.57). Further, the population-attributable risk percent (95% CI) of T2DM for poor adherence to the overall healthy lifestyle (< 4 low-risk factors) was 43.24% (30.02%, 56.46%). The HLS was inversely associated with SUA level. With per score increased in HLS, the beta (95% CI) of SUA (log transformed) was - 0.03 (- 0.03, - 0.02), and the odds ratio (95% CI) of hyperuricemia was 0.82 (0.77, 0.86). The relationship between the HLS and risk of T2DM was mediated by SUA with a 13.06% mediation effect. There was no significant combined effect of HLS and SUA on risk of T2DM (P = 0.097). CONCLUSIONS: The relationship between overall healthy lifestyle behaviors and T2DM was reconfirmed and the association appeared to be mediated by SUA. The mediation effect of baseline SUA was more pronounced among women who were below 60 years old.

Global distribution and climatic controls of natural mountain treelines.

Mountain treelines are thought to be sensitive to climate change. However, how climate impacts mountain treelines is not yet fully understood as treelines may also be affected by other human activities. Here, we focus on "closed-loop" mountain treelines (CLMT) that completely encircle a mountain and are less likely to have been influenced by human land-use change. We detect a total length of ~916,425 km of CLMT across 243 mountain ranges globally and reveal a bimodal latitudinal distribution of treeline elevations with higher treeline elevations occurring at greater distances from the coast. Spatially, we find that temperature is the main climatic driver of treeline elevation in boreal and tropical regions, whereas precipitation drives CLMT position in temperate zones. Temporally, we show that 70% of CLMT have moved upward, with a mean shift rate of 1.2 m/year over the first decade of the 21st century. CLMT are shifting fastest in the tropics (mean of 3.1 m/year), but with greater variability. Our work provides a new mountain treeline database that isolates climate impacts from other anthropogenic pressures, and has important implications for biodiversity, natural resources, and ecosystem adaptation in a changing climate.

MESP1-knockdown inhibits the proliferation and epithelial mesenchymal transition of hepatocellular carcinoma and enhances the tumor-suppressive effect of 5-fluorouracil.

Primary liver hepatocellular carcinoma (HCC) is the third most deadly malignancy worldwide,in part, because it is often diagnosed at an advanced stage. Thus, molecular markers are needed to aid in the early diagnosis and treatment of HCC. Expression of abnormal mesoderm posterior-1 (MESP1) promotes tumorigenesis; however,its role in the regulation of HCC proliferation, apoptosis,and invasion is unknown. Here,we analyzed data in The Cancer Genome Atlas (TCGA)and Genotype Tissue Expression (GTEx) databases on the pan-cancer expression of MESP1 and its relationship with clinical characteristics and prognosis of patients with HCC. The expression of MESP1 was measured in 48 HCC tissues using immunohistochemical staining,and the results were correlated with clinical stage, tumor differentiation, tumor size,and metastasis. MESP1 expression was downregulated using small interfering RNA (siRNA) in the HCC cell lines HepG2 and Hep3B,and cell viability, proliferation,cell cycle, apoptosis,and invasion were analyzed. Finally,we also evaluated the tumor suppression effect of MESP1 downregulation combined with 5-fluorouracil (5-FU) treatment. Our results showed that MESP1 is a pan-oncogene associated with poor prognosis in patients with HCC. siRNA-induced downregulation of MESP1 expression in HepG2 and Hep3B cells exhibited downregulation of ß-catenin and GSK3ß expression 48h after transfection, along with an increase in apoptosis rate, arrest in the G1-S phase,and a decrease in mitochondrial membrane potential. Moreover,the expression levels of c-Myc, PARP1, bcl2, Snail1, MMP9, and immune checkpoint genes (TIGIT, CTLA4,LAG3,CD274,and PDCD1) were downregulated, while those of caspase3 and E-cadherin were upregulated. Tumor cells also showed decreased migration ability. Furthermore, siRNA interference of MESP1 expression combined with 5-FU-treatment of HCC cells significantly enhanced the G1-S phase block and apoptosis. MESP1 showed an aberrant high expression in HCC and was associated with poor clinical outcomes; therefore, MESP1 may be a potential target for the diagnosis and treatment of HCC.

Data-independent acquisition mass spectrometry reveals comprehensive plasma protein profiles in the natural history of patients with hereditary transthyretin amyloidosis (ATTRv).

OBJECTIVES: Hereditary transthyretin amyloidosis (ATTRv) is a rare, fatal, autosomal dominant disease with more than 140 mutations discovered. Three phenotypes of amyloid infiltration are neuropathy (ATTRv-PN), cardiopathy (ATTRv-CM), and neuropathy + cardiopathy (ATTRv-MIX). The lack of ATTR-specific biomarkers, difficulties in biopsy evidence, and limited known pathogenic mechanisms have made diagnosis difficult. Newly emerging noninvasive measures for monitoring progression and disease-modifying therapies have improved early diagnosis and patient management. METHODS: Our research applies the latest technology, Data-Independent Acquisition-Based Quantitative Proteomics (DIA), to reveal comprehensive plasma protein profiles in the natural history of Chinese patients with hereditary transthyretin amyloidosis (ATTRv). We analyzed differentially expressed proteins (DEPs) in three phenotypes (ATTRv-PN, ATTRv-CM, and ATTRv-MIX). RESULTS: Serum samples were collected from a total of 18 patients (6 ATTRv-PN, 5 ATTRv-CM, and 7 ATTRv-MIX patients) and 20 healthy participants as a control group. Combined with the results of the proteomic and bioinformatic analyses, we found 30 DEPs and protein interaction networks clustered in KRT family proteins and DSC3 between ATTRv-PN and the control, which were rich in the estrogen signaling pathway and the cell adhesion molecule (CAM) pathway. CONCLUSION: This study demonstrates a global and significant proteomic profile in different stages of ATTRv.

Long-lasting and sex-dependent effects of late lactational maternal deprivation on socioemotional behaviors in adult mice.

The lactation period is an important period for individual development and a sensitive period for the behavioral phenotypes and plasticity of individual offspring. Early life experiences (e.g., maternal deprivation (MD) and neglect) have significant long-lasting and dual effects on individual stress reactivities during adulthood. Theoretically, stress inoculation can improve the adaptive capacity of the body, but overstress can lead to dysfunction when adaptive mechanisms fail.To date, the potential effects of late lactational MD on the socioemotional behaviors of mouse offspring during adulthood are still not fully understood. In the present study, mice were subjected to early deprivation by individually separating pups from their dam for 0 min, 15 min, and 3 h per day from PND 13-25. The social dominance test (SDT), social interaction test (SI), open field test (OFT), and forced swim test (FST) were carried out during adulthood. The results showed that the social dominance of male mice in the 15 min/d MD group significantly increased, especially in low-rank mice. In the 3 h/d MD group, the social dominance of female mice was decreased, especially in the lower-rank mice. The anxiolytic and antidepressant-like effects of the 15 min/d MD group were significantly increased in male mice. Our study provides direct evidence that MD during late lactation period results in long-lasting effects on social dominance as well as on anxiety and depression phenotypes in a sex-dependent manner.

Comparison of anti-tumor activities and underlying mechanisms of glucuronomannan oligosaccharides and its sulfated derivatives on the hepatocarcinoma Huh7.5 cells.

Hepatocellular carcinoma (HCC) is an aggressive tumor triggered by various factors such as virus infection and alcohol abuse. Glucuronomannan polysaccharide (Gx) is a subtype of fucoidans that possesses many bioactivities, but its anti-tumor activities in HCC have not been reported. In this paper, the anti-tumor effects of glucuronomannan oligosaccharides (Gx) and its sulfated derivatives (GxSy) on hepatocarcinoma Huh7.5 cells were investigated. The anti-proliferation, anti-metastasis activities, and underlying mechanism of Gx and GxSy on Huh7.5 cells were analyzed and compared by MTT, wound healing, transwell, and western blotting assays, respectively. Results showed that the best anti-proliferation effects were G4S1 and G4S2 among 13 drugs, which were 38.67% and 30.14%, respectively. The cell migration rates were significantly inhibited by G2S1, G4S2, G6S2, and unsulfated Gn. In addition, cell invasion effects treated with G4S1, G4S2, and G6S1 decreased to 48.62%, 36.26%, and 42.86%, respectively. Furthermore, sulfated G4 regulated the expression of (p-) FAK and MAPK pathway, and sulfated G6 down-regulated the MAPK signaling pathway while activating the PI3K/AKT pathway. On the contrary, sulfated G2 and unsulfated Gx had no inhibited effects on the FAK-mTOR pathway. These results indicated that sulfated Gx derivatives have better anti-tumor activities than unsulfated Gx in cell proliferation and metastasis process in vitro, and those properties depend on the sulfation group levels. Moreover, degrees of polymerization of Gx also played a vital role in mechanisms and bioactivities. This finding shows the structure-activity relationship for developing and applying the marine oligosaccharide candidates.

Suppressive effects of pterostilbene on human cytomegalovirus (HCMV) infection and HCMV-induced cellular senescence.

BACKGROUND: Human cytomegalovirus (HCMV), a member of the ß-herpesvirus family, causes the establishment of a latent infection that persists throughout the life of the host and can be reactivated when immunity is weakened. To date, there is no vaccine to prevent HCMV infection, and clinically approved drugs target the stage of viral replication and have obvious adverse reactions. Thus, development of novel therapeutics is urgently needed. METHODS: In the current study, we identified a naturally occurring pterostilbene that inhibits HCMV Towne strain replication in human diploid fibroblast WI-38 cells through Western blotting, qPCR, indirect immunofluorescence assay, tissue culture infective dose assays. The time-of-addition experiment was carried out to identify the stage at which pterostilbene acted. Finally, the changes of cellular senescence biomarkers and reactive oxygen species production brought by pterostilbene supplementation were used to partly elucidate the mechanism of anti-HCMV activity. RESULTS: Our findings revealed that pterostilbene prevented lytic cytopathic changes, inhibited the expression of viral proteins, suppressed the replication of HCMV DNA, and significantly reduced the viral titre in WI-38 cells. Furthermore, our data showed that pterostilbene predominantly acted after virus cell entry and membrane fusion. The half-maximal inhibitory concentration was determined to be 1.315 µM and the selectivity index of pterostilbene was calculated as 26.73. Moreover, cell senescence induced by HCMV infection was suppressed by pterostilbene supplementation, as shown by a decline in senescence-associated ß-galactosidase activity, decreased production of reactive oxygen species and reduced expression of p16, p21 and p53, which are considered biomarkers of cellular senescence. CONCLUSION: Together, our findings identify pterostilbene as a novel anti-HCMV agent that may prove useful in the treatment of HCMV replication.

Gender-related differences in the effects of Inonotus obliquus polysaccharide on intestinal microorganisms in SD rats model.

Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. The effects of sex on intestinal microbiota after IOP absorption was determined. In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases.

Clinical phenotypes and genetic features of hereditary transthyretin amyloidosis patients in China.

BACKGROUND: Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This retrospective analysis study aimed to report the genotypes and phenotypes of herediary transthyretin amyloidosis (hATTR) in Chinese through a systematic review of published literature. METHODS: The systematic review included structured searches of peer-reviewed literature published from 2007 to 2020 of following online reference databases: PubMed, Web of Science and the literature database in China. Extracted data included sample size, personal information (sex, age, natural course, family history), mutation type, clinical milestones and reason of death. RESULTS: We described 126 Chinese patients with hereditary transthyretin amyloidosis identified through a systematic review of 30 studies. The most common genotype in the Chinese population was Gly83Arg (25, 19.8%), which most likely presented visual and neurological abnormalities without reported death. The second and third most common genotypes were Val30Met (20, 15.9%) and Val30Ala (10, 7.9%). Peripheral neurological manifestations (91, 72%) were dominant in 126 patients. The followed manifestation was autonomic neurological abnormalities (73, 58%). Half of the cases were reported to have visual disorders, and nearly one-third of the cases presented cardiac abnormalities. Among all 126 reported patients, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. In addition. Chinese patients were mostly early onset, with age of onset at 41.8 (SD: 8.9) years, and the median time from onset to death was 7.5 [IQR: 5.3] years. Patients with cardiac involvement had a shorter survival duration (log Rank (Mantel-Cox), χ2 = 26.885, P < 0.001). CONCLUSIONS: This study focused on 126 Chinese hATTR patients obtained from a literature review. A total of 26 kinds of TTR mutations were found and the most common one was Gly83Arg. As for phenotype, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. Chinese hATTR patients were mostly early onset (AO 41.8 years), and the median time from onset to death was 7.5 years.