Elucidating the modulatory role of dietary hydroxyproline on the integrity and functional performance of the intestinal barrier in early-weaned piglets: A comprehensive analysis of its interplay with the gut microbiota and metabolites.

Piglets receive far less hydroxyproline (Hyp) from a diet after weaning than they obtained from sow's milk prior to weaning, suggesting that Hyp may play a protective role in preserving intestinal mucosal homeostasis. This study aimed to evaluate the effect of Hyp on intestinal barrier function and its associated gut microbiota and metabolites in early-weaned piglets. Eighty weaned piglets were divided into four groups and fed diets containing different Hyp levels (0 %, 0.5 %, 1 %, or 2 %) for 21 days. Samples, including intestinal contents, tissues, and blood, were collected on day 7 for analysis of microbial composition, intestinal barrier function, and metabolites. We demonstrated that dietary supplementation with 2 % Hyp improved the feed conversion ratio and reduced the incidence of diarrhea in early-weaned piglets compared to the control group. Concurrently, Hyp enhanced intestinal barrier function by facilitating tight junction protein (zonula occludens (ZO)-1 and occludin) expression and mucin production in the jejunal, ileal, and colonic mucosas. It also improved mucosal immunity (by increasing the amount of secretory IgA (sIgA) and the ratio of CD4+/CD8+ T lymphocytes and decreasing NF-κB phosphorylation) and increased antioxidant capacity (by raising total antioxidant capacity (T-AOC) and glutathione levels) in the intestinal mucosa. In addition, Hyp supplementation resulted in an increase in the levels of glycine, glutathione, and glycine-conjugated bile acids, while decreasing the concentrations of cortisol and methionine sulfoxide in plasma. Intriguingly, piglets fed diet containing Hyp exhibited a remarkable increase in the abundance of probiotic Enterococcus faecium within their colonic contents. This elevation occurred alongside an attenuation of pro-inflammatory responses and an enhancement in intestinal barrier integrity. Further, these changes were accompanied by a rise in anti-inflammatory metabolites, specifically glycochenodeoxycholic acid and guanosine, along with a suppression of pro-inflammatory lipid peroxidation products, including (12Z)-9,10-dihydroxyoctadec-12-enoic acid (9,10-DHOME) and 13-L-hydroperoxylinoleic acid (13(S)-HPODE). In summary, Hyp holds the capacity to enhance the intestinal barrier function in weaned piglets; this effect is correlated with changes in the gut microbiota and metabolites. Our findings provide novel insights into the role of Hyp in maintaining gut homeostasis, highlighting its potential as a dietary supplement for promoting intestinal health in early-weaned piglets.

Effect of various different pretreatment methods on infrared combined hot air impingement drying behavior and physicochemical properties of strawberry slices.

In current work, the effect of freezing (F), ultrasound (U), and freeze- ultrasound (FU) pretreatment on infrared combined with hot air impingement drying kinetics, cell ultrastructure, enzyme activity, and physicochemical properties of strawberry slices were explored. Results showed that FU pretreatment enhanced cell membrane permeability via forming micropores, altered water status by transforming bound water into free water and thus promoted moisture diffusivity and decreased drying time by 50% compared to the control group. FU pretreatment also extensively decreased pectin methylesterase enzyme activity and maintained quality. The contents of total phenols, anthocyanins, vitamin C, antioxidant activity, and a* value of dried strawberries pretreated by FU were extensively increased compared to the control group. U and FU pretreatments were beneficial for retaining aromatic components and organic sulfides according to e-nose analyses. The findings indicate that FU is a promising pretreatment technique as it enhances drying process and quality of strawberry slices.

[Characteristics of Epiphytic Bacterial Community on Submerged Macrophytes in Water Environment Supplemented with Reclaimed Water].

Biofilms attached to submerged macrophytes play an important role in improving the water quality of the water environment supplemented with reclaimed water. In order to explore the effects of reclaimed water quality and submerged macrophyte species on the characteristics of an epiphytic bacterial community, different types of submerged macrophytes were selected as research objects in this study. 16S rRNA high-throughput sequencing technology was used on the epiphytic bacteria and the surrounding environmental samples to analyze the bacterial community structure and functional genes. The results showed that approximately 20%-35% of the nitrogen and phosphorus nutrients were absorbed and utilized in the water environment supplemented with reclaimed water. However, the COD, turbidity, and chroma of the downstream water were significantly increased. The bacterial community of the biofilms attached to submerged macrophytes was significantly different from that in the surrounding environment (soil, sediment, and water body) and in the activated sludge that was treated by reclaimed water. In terms of bacterial community diversity, the richness and diversity were significantly lower than those of soil and sediment but higher than those of plankton bacteria in water. In terms of bacterial community composition, dominant genera and corresponding abundances were also different from those of other samples. The main dominant bacterial genera were Sphingomonas, Aeromonas, Pseudomonas, and Acinetobacter, accounting for 7%-40%, respectively. Both macrophyte species and the quality of reclaimed water (BOD5, TN, NH4+-N, and TP) could affect the bacterial community. However, the effect of water quality of the bacterial community was greater than that of macrophytes species. Additionally, the quality of reclaimed water also affected the abundance of functional genes in the bacterial community, and the relative abundance of nitrogen and phosphorus cycling functional genes was higher in areas with higher nitrogen and phosphorus concentrations.

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization.

BACKGROUND: Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma (PDAC) metastasis. AIM: To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis. Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis. METHODS: Cell culture and various experiments, including protein analysis, immunohistochemistry, and animal model experiments, were conducted. We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features. Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers. Finally, we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms. RESULTS: Our research showed that there was a significant increase in FAM53B levels in PDAC tissues, which was linked to adverse tumor features. Experimental findings indicated that FAM53B can enhance macrophage M2 polarization, leading to increased anti-inflammatory factor release. The results from the mouse model further supported the role of FAM53B in PDAC metastasis, as blocking FAM53B prevented tumor cell invasion and metastasis. CONCLUSION: FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization. This discovery could lead to the development of new strategies for treating PDAC. For example, interfering with the FAM53B signaling pathway may prevent cancer spread. Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.

Negative interactions and marital satisfaction across adulthood: The moderating role of affect valuation.

Older adults report higher marital satisfaction than younger adults even after negative interactions. The current study examined affect valuation as a potential moderator to explain age-related differences in the relationship between negative interactions and marital satisfaction. We conducted a 14-day daily diary study among 66 heterosexual couples (132 participants) aged from 21 to 80 years. At both person and daily levels, we found that valuing negative affect weakened the negative association between negative interactions and marital satisfaction in husbands. The moderating effect of negative affect valuation was stronger in older than younger husbands at the person but not daily level. Valuing positive affect more was associated with a stronger negative association between negative interactions and marital satisfaction in husbands at the person but not daily level. Such effect was again stronger in older than younger husbands. No significant results were found in wives. These findings shed light on the importance of affect valuation in understanding age-related differences in marital dynamics.

Cells in the liver microenvironment regulate the process of liver metastasis.

The research of liver metastasis is a developing field. The ability of tumor cells to invade the liver depends on the complicated interactions between metastatic cells and local subpopulations in the liver (including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells, and immune-related cells). These interactions are mainly mediated by intercellular adhesion and the release of cytokines. Cell populations in the liver microenvironment can play a dual role in the progression of liver metastasis through different mechanisms. At the same time, we can see the participation of liver parenchymal cells and nonparenchymal cells in the process of liver metastasis of different tumors. Therefore, the purpose of this article is to summarize the relationship between cellular components of liver microenvironment and metastasis and emphasize the importance of different cells in the occurrence or potential regression of liver metastasis.

Study protocol of the 'HEAL-HOA' dual randomized controlled trial: Testing the effects of volunteering on loneliness, social, and mental health in older adults.

Background: Interventions to reduce loneliness in older adults usually do not show sustained effects. One potential way to combat loneliness is to offer meaningful social activities. Volunteering has been suggested as one such activity - however, its effects on loneliness remain to be tested in randomized controlled trials (RCT). Methods: This planned Dual-RCT aims to recruit older adults experiencing loneliness, with subsequent randomization to either a volunteering condition (6 weeks of training before delivering one of three tele-based loneliness interventions to older intervention recipients twice a week for 6 months) or to an active control condition (psycho-education with social gatherings for six months). Power analyses require the recruitment of N = 256 older adults to detect differences between the volunteering and the active control condition (128 in each) on the primary outcome of loneliness (UCLA Loneliness Scale). Secondary outcomes comprise social network engagement, perceived social support, anxiety and depressive symptoms, self-rated health, cognitive health, perceived stress, sleep quality, and diurnal cortisol (1/3 of the sample). The main analyses will comprise condition (volunteering vs. no-volunteering) × time (baseline, 6-, 12-, 18-, 24-months follow-ups) interactions to test the effects of volunteering on loneliness and secondary outcomes. Effects are expected to be mediated via frequency, time and involvement in volunteering. Discussion: If our trial can show that volunteers delivering one of the three telephone-based interventions to lonely intervention recipients benefit from volunteer work themselves, this might encourage more older adults to volunteer, helping to solve some of the societal issues involved with rapid demographic changes.

Older adults experience better affective well-being in solitude: The moderating role of goal for conflict de-escalation.

Older adults report greater affective well-being in solitude than younger adults, but prior findings are based on correlational designs. We aim to examine age differences in affective well-being in solitude using an experimental design and to examine conflict de-escalation as a potential mechanism. In Study 1, 207 participants were randomly assigned to either a solitude or a social interaction condition. In Study 2, 128 participants were randomly assigned to one of four conditions: solitude-escalation, solitude-de-escalation, interaction-escalation, and interaction de-escalation. After a 15-min solitude or social interaction period, they reported their affective experiences. In Study 1, older (vs. younger) adults reported more positive affect overall. This age-related difference was greater in the solitude (vs. social interaction) condition; older adults reported less negative affect than younger adults in the solitude, but not the social interaction, condition. In Study 2, older (vs. younger) participants reported more high-arousal positive affect in the solitude-escalation condition. This difference was not significant in conflict de-escalation conditions. Our studies provide causal evidence of the relationship between solitude and affective well-being and advance our understanding of motivations that explain why older adults maintain better affective well-being in solitude.

Effects of volunteering over six months on loneliness, social and mental health outcomes among older adults: The HEAL-HOA Dual Randomized Controlled Trial.

OBJECTIVE: To determine the beneficial effects of volunteering as lay counselor via telephone on own loneliness, social network engagement, perceived social support, stress, anxiety, and depressive symptoms among Chinese older adults in Hong Kong during the COVID-19 pandemic. DESIGN, SETTING, INTERVENTION, AND PARTICIPANTS: "Helping Alleviate Loneliness in Hong Kong Older Adults" (HEAL-HOA), a dual randomized controlled trial, was implemented to test effects of telephone-based psychosocial interventions delivered by older-adult volunteers for low-income lonely older adults. To evaluate the effects of volunteering on loneliness, we randomized 375 individuals ages 50-70 into a volunteering condition versus an active control (psychoeducation with social gatherings). Following a 6-week training, participants in the volunteering condition, delivered tele-interventions to older intervention recipients. MEASUREMENT: The primary outcome was loneliness measured with the UCLA Loneliness Scale. Secondary outcomes were loneliness measured with the De Jong Gierveld Scale (DJG), social network engagement, perceived social support, perceived stress, anxiety, and depressive symptoms. Assessments were completed before training (baseline) and immediately after the 6-month volunteering period. RESULTS: Results from linear mixed models show significant positive effects of volunteering (significant interactions of condition × time) on both measures of loneliness (dppc2 = -0.41 ULCA Loneliness score, dppc2 = -0.70 total DJG score), social network engagement, stress and depressive symptoms as compared to control participants. CONCLUSIONS: The HEAL-HOA trial demonstrates beneficial effects of volunteer-delivered tele-interventions on decreasing loneliness on the volunteer interventionists themselves. Communicating these benefits for volunteers may attract more older adults into volunteering. This effective tele-based volunteer program is scalable for wider implementation. SUMMARY: This RCT tested effects of volunteering on loneliness in Hong Kong during the COVID-19-pandemic. Three hundred seventy-five individuals ages 50-70 were randomized into volunteering (delivering tele-interventions against loneliness) versus an active control condition. After 6 months, volunteers compared to controls, showed benefits on loneliness, social network engagement, stress and depressive symptoms. A program engaging lonely older adults in loneliness intervention delivery has beneficial effects on volunteers themselves and could be a scalable solution for our loneliness epidemic.

Rechallenge of immune checkpoint inhibitors in advanced non-small cell lung cancer.

Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Intergenerational Interactions and Relationship Quality: A Daily Study Among Mothers and Their Adult Children.

OBJECTIVES: The parent-child relationship is one of the most long-lasting relationships in human life. Such relationship is particularly adaptive during public health emergencies that threaten human life. However, few studies have examined the effects of daily exchanges in support between aging parents and adult children on the relationship quality during public health emergencies. Using data collected during the coronavirus disease 2019 pandemic, we examined the relationship between daily support and relationship quality among middle-aged and older mothers and adult children. METHODS: Seventy-seven dyads of middle-aged and older mothers (age range: 44-80 years, Mage = 53.78, SDage = 9.57) and adult children (age range: 18-54 years, Mage = 26.61, SDage = 9.46) participated in the study. They reported their daily exchanges with the other (i.e., support they had received from and given to each other) and daily relationship quality (i.e., relationship satisfaction and trust) each day for 14 consecutive days. RESULTS: The perception of being underbenefited on Day N was associated with daily relationship satisfaction on the concurrent day in children but not mothers. It was associated with daily trust toward the relationship partner in both mothers and children on Day N. Both providing and receiving more support on Day N was associated with better relationship satisfaction for both mothers and children on Day N. Only receiving (not providing) more support on Day N was associated with greater trust toward the partner on Day N for both mothers and children. The time-lagged associations were not significant. DISCUSSION: The findings highlight the importance of daily reciprocity and daily support exchanges on relationship quality during a public health emergency.

Distressed yet bonded: A longitudinal investigation of the COVID-19 pandemic's silver lining effects on life satisfaction.

It is a common understanding that the 2019 coronavirus pandemic (COVID-19) significantly harmed mental health. However, findings on changes in overall life satisfaction have been mixed and inconclusive. To address this puzzling phenomenon, we draw upon the domain-specific perspective of well-being and research on catastrophe compassion and propose that the pandemic can have opposing effects on mental health and communal satisfaction, which then differently relate to people's overall life satisfaction. Longitudinal analyses of the Household, Income and Labour Dynamics (HILDA) Survey of Australia (N = 12,093) showed that while there was a greater decrease in mental health in the first COVID-19 pandemic year (2019-2020) than in the previous years (2017-2019), an increase in communal satisfaction also occurred, demonstrating a potential silver lining effect of the pandemic on people's satisfaction with family, community, and neighborhood. Moreover, consistent with socioemotional selectivity theory, changes in mental health, communal satisfaction, and life satisfaction were related to age, such that older adults generally reported less harmful and more beneficial psychological changes. We further found that age was associated with stronger associations of mental health and communal satisfaction with life satisfaction during the pandemic year. Overall, our findings speak to the importance of communal life in life satisfaction during the pandemic and age-related differences in the process, shedding light on the need to devise customized support to address inequalities in pandemic effects on public well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Memory Trajectories and Disability Among Older Couples: The Mediating Role of Depressive Symptoms.

OBJECTIVES: Using a dyadic approach, this study examined the mediating effect of depressive symptoms on the longitudinal relationships between husbands' and wives' memory trajectories and their prospective disability status. METHODS: Longitudinal data from the Health and Retirement Study 2004-2018 were used. Older (aged 50+) heterosexual couples who had no limitations in the activity of daily living at the baseline (2004) were included (N = 1,310). Latent class growth analysis grouped wives and husbands into distinct memory trajectories in 2004-2014. A structural equation model examined the actor and partner effects of memory trajectories on depressive symptoms in 2016 and disability status in 2018. The mediating effect of depressive symptoms was tested. RESULTS: A total of 4 distinct memory trajectories were found: persistently high, high and slow decline, moderate and slow decline, and low and rapid decline. Only the wife's low and rapid decline memory trajectory predicted her own more depressive symptoms (ß = 0.588, 95% CI: 0.209, 0.967) and her husband's more depressive symptoms (ß = 0.326, 95% CI: 0.004, 0.648). Meanwhile, depressive symptoms had strong and significant actor effects on disability (ß = 0.046, 95% CI: = 0.036, 0.057 for wives; ß = 0.060, 95% CI: = 0.046, 0.074 for husbands). DISCUSSION: The wife's low and rapid decline trajectory was associated with her own and her husband's more depressive symptoms, which in turn increased the disability risk for both partners. Timely identification and treatment of memory decline among wives have the potential to mitigate couples' depressive symptoms and, ultimately, disability risks.

Age differences in the experience of everyday happiness: The role of thinking about the future.

Happiness can be experienced differently in young as compared to older adulthood, possibly due to shifts in temporal focus and differences in preferences for high- versus low-arousal affective states. The current project aimed to replicate initial evidence on age-related differences in the experience of happiness by investigating the positive affective correlates of everyday happiness; we further explored the role of thinking about the future in moderating such associations. We used daily life assessments from 257 participants (Mage = 48.3, SDage = 24.6; 68% female; 77% Asian [East Asian, South Asian, and Southeast Asian]; 73% postsecondary educated), combining four data sets collected at two locations (Vancouver, Canada; Hong Kong) with different age samples (older and younger adults). Participants provided up to 30 repeated daily life assessments of momentary affective states and thoughts about the future, over 10 days. Results replicate previous findings by showing that happiness was more strongly associated with low-arousal positive affect and more weakly associated with high-arousal positive affect among older compared to younger adults. Engagement in thinking about the future was higher among younger compared to older adults in general, but its role in moderating the association between happiness and positive affect varying in arousal levels was confounded by the age moderation. Separate analyses conducted for each age group indicate different roles of everyday thinking about the future in shaping happiness experiences for different age groups. Age and future thinking-related contours of happiness are discussed in the context of emotional aging theories. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinical definition of secondary resistance to immunotherapy in non-small cell lung cancer.

Immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 blockade) have revolutionized the treatment landscape in non-small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO-IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Experimental Study on the Dilatancy and Energy Evolution Behaviors of Red-Bed Rocks under Unloading Conditions.

Surrounding rock deformation and consequent support failure are the most prominent issues in red-bed rock tunnel engineering and are mainly caused by the effects of unloading, rheology, and swelling. This study investigated the mechanical responses of two kinds of red-bed mudstone and sandstone under unloading conditions via laboratory observation. Volume dilation was observed on the rocks during unloading, and the dilatancy stress was linear with the initial confining pressure. However, the ratios of dilatancy stress to peak stress of the two rocks kept at a range from 0.8 to 0.9, regardless of confining pressures. Both the elastic strain energy and the dissipated energy evolved synchronously with the stress-strain curve and exhibited conspicuous confining pressure dependence. Special attention was paid to the evolution behavior of the dilatancy angle. The dilatancy angle changed linearly during unloading. When the confining pressure was 10 MPa, the dilatancy angle of mudstone decreased from 26.8° to 12.5° whereas the dilatancy angle of sandstone increased from 34.6° to 51.1°; when the confining pressure rose to 25 MPa, the dilatancy angle of mudstone and sandstone decreased from 45.8° to 17.4° and increased from 21.7° to 39.5°, respectively. To further understand the evolution of the dilatancy angle, we discussed the links between the variable dilatancy angle and the processes of rock deformation and energy dissipation.

Cold-water coral diversity along the continental shelf margin of northwestern South China Sea.

Scleractinian cold-water corals (CWCs) are one of the most important habitat engineers of the deep sea. Although the South China Sea (SCS) abuts the biodiversity center of scleractinian CWCs in the western Pacific, only a few sporadic records are available. We discovered new CWC sites by means of trawl sampling and video observation along the continental shelf of the northwestern SCS. All trawled scleractinian CWC specimens were identified to species level according to skeleton morphology and structure. The living CWCs and associated fauna recorded in the video were -identified to a higher level of classification. Scleractinian corals were identified to genus level, while non-scleractinian CWCs were identified to family level and given general names such as gorgonian corals, bamboo corals and black corals. Associated benthic dwellers were divided into major categories. A total of 28 scleractinian CWC species were identified to 7 families, 15 genera, and 1 additional subgenus. Among them, 13 species were colonial, including important habitat-forming species in the genera Eguchipsammia, Dendrophyllia and Cladopsammia. Non-scleractinian CWCs were identified to 7 families, including 4 families gorgonian corals, 1 family bamboo corals, and 2 families black corals. Gorgonian corals were the most abundant non-scleractinian CWCs in this region. Meanwhile, starfish, sea anemones, fish, gastropods, echinoderms, and other associated benthic fauna were recorded in the CWC habitats, with starfish belonging to the order Brisingida being most common. New scleractinian CWC assemblages were discovered along the continental seabed mounds in the northwestern SCS. This study highlights the remarkable diversity of cold-water scleractinian corals in the whole SCS, and shows the potential widespread distribution and conservation prospect of CWC habitats in this region.

Suppression of viral RNA polymerase activity is necessary for persistent infection during the transformation of measles virus into SSPE virus.

Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by measles virus (MV), which typically develops 7 to 10 years after acute measles. During the incubation period, MV establishes a persistent infection in the brain and accumulates mutations that generate neuropathogenic SSPE virus. The neuropathogenicity is closely associated with enhanced propagation mediated by cell-to-cell fusion in the brain, which is principally regulated by hyperfusogenic mutations of the viral F protein. The molecular mechanisms underlying establishment and maintenance of persistent infection are unclear because it is impractical to isolate viruses before the appearance of clinical signs. In this study, we found that the L and P proteins, components of viral RNA-dependent RNA polymerase (RdRp), of an SSPE virus Kobe-1 strain did not promote but rather attenuated viral neuropathogenicity. Viral RdRp activity corresponded to F protein expression; the suppression of RdRp activity in the Kobe-1 strain because of mutations in the L and P proteins led to restriction of the F protein level, thereby reducing cell-to-cell fusion mediated propagation in neuronal cells and decreasing neuropathogenicity. Therefore, the L and P proteins of Kobe-1 did not contribute to progression of SSPE. Three mutations in the L protein strongly suppressed RdRp activity. Recombinant MV harboring the three mutations limited viral spread in neuronal cells while preventing the release of infectious progeny particles; these changes could support persistent infection by enabling host immune escape and preventing host cell lysis. Therefore, the suppression of RdRp activity is necessary for the persistent infection of the parental MV on the way to transform into Kobe-1 SSPE virus. Because mutations in the genome of an SSPE virus reflect the process of SSPE development, mutation analysis will provide insight into the mechanisms underlying persistent infection.

Capsaicin improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the hypothalamic paraventricular nucleus.

BACKGROUND: Hypertension has seriously affected a large part of the adult and elderly population. The complications caused by hypertension are important risk factors for cardiovascular disease accidents. Capsaicin, a pungent component of chili pepper has been revealed to improve hypertension. However, its potential mechanism in improving hypertension remains to be explored. PURPOSE: In the present study, we aimed to investigate whether capsaicin could attenuate the SIRT1/NF-κB/MAPKs pathway in the paraventricular nucleus of hypothalamus (PVN). METHODS: We used spontaneous hypertensive rats (SHRs) as animal model rats. Micro osmotic pump was used to give capsaicin through PVN for 28 days, starting from age12-week-old. RESULTS: The results showed that capsaicin significantly reduced blood pressure from the 16th day of infusion onward. At the end of the experimental period, we measured cardiac hypertrophy index and the heart rate (HR), and the results showed that the cardiac hypertrophy and heart rate of rats was significantly improved upon capsaicin chronic infusion. Norepinephrine (NE) and epinephrine (EPI) in plasma of SHRs treated with capsaicin were also decreased. Additionally, capsaicin increased the protein expression and number of positive cells of SIRT1 and the 67-kDa isoform of glutamate decarboxylase (GAD67), decreased the production of reactive oxygen species (ROS), number of positive cells of NOX2, those of Angiotensin Converting Enzyme (ACE) and p-IKKß, tyrosine hydroxylase (TH), the gene expression levels of NOX4 and pro-inflammatory cytokines. Capsaicin also decreased the relative protein expressions of protein in MAPKs pathway. CONCLUSION: Current data indicated that capsaicin within the PVN improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the PVN of SHRs, supporting its potential as candidate drug for preventing and improving hypertension.

miRNA-186-5p inhibits migration, invasion and proliferation of breast cancer cells by targeting SBEM.

The paper aimed to investigate the effect of miR186-5p on invasion and migration of breast cancer cells and its molecular mechanism. MicroRNA-186-5p was found to be low expressed in breast cancer and highly expressed in SBEM by bioinformatics analysis. After transfecting MDA-MB-231 cells with miR-186-5p inhibitor NC, miR-186-5p inhibitor, miR-186-5p mimic NC and miR-186-5p mimic, respectively. The migration and invasive ability of breast cancer cells were detected by cell scratch test and Transwell test. Moreover, after adding 740 Y-P to the miR-186-5p mimic NC group and miR-186-5p mimic group cells, SBEM and PI3K pathway-related proteins were detected by Western blotting and proliferation of the cancer cells was evaluated by monoclonal cell experiment. Meanwhile, exogenous miR-186-5p mimic in MDA-MB-231 cells significantly inhibited the expression of SBEM, p-PI3K, p-AKT and their downstream pathways, MMP1, MMP3, MMP9, CyclinD1, PCNA and CyclinB1 proteins and reduced proliferation of breast cancer cells. Furthermore, the expression of SBEM protein in the miR-186-5p mimic + 740Y-P group was significantly lower than the miR-186-5p mimic NC + 740Y-P group after adding 740 Y-P. However, there were no significant changes in the protein's levels associated with PI3K pathway and the cancer cells proliferation. These results suggest that low expression of miR-186-5p in breast cancer results in an abnormally high expression of SBEM, activation of PI3K/AKT signaling pathway, promoting migration and invasion of human breast cancer cells.