Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs.

GATA4 is a transcription factor known for its crucial role in the development of many tissues, including the liver; however, its role in adult liver metabolism is unknown. Here, using high-throughput sequencing technologies, we identified GATA4 as a transcriptional regulator of metabolism in the liver. GATA4 expression is elevated in response to refeeding, and its occupancy is increased at enhancers of genes linked to fatty acid and lipoprotein metabolism. Knocking out GATA4 in the adult liver (Gata4LKO) decreased transcriptional activity at GATA4 binding sites, especially during feeding. Gata4LKO mice have reduced plasma HDL cholesterol and increased liver triglyceride levels. The expression of a panel of GATA4 binding genes involved in hepatic cholesterol export and triglyceride hydrolysis was down-regulated in Gata4LKO mice. We further demonstrate that GATA4 collaborates with LXR nuclear receptors in the liver. GATA4 and LXRs share a number of binding sites, and GATA4 was required for the full transcriptional response to LXR activation. Collectively, these results show that hepatic GATA4 contributes to the transcriptional control of hepatic and systemic lipid homeostasis.

Oral frailty: A concept analysis.

AIM: To clarify the concept of oral frailty to provide a clear and standardized conceptual basis for further research in older people. DESIGN: Rodgers and Knafl's evolutionary concept analysis approach. METHODS: The narrative analysis detailedly extracted and synthesized the attributes of oral frailty, as well as its antecedents, consequences and related terms under the guidance of Rodgers' evolutionary method. DATA SOURCES: Multiple databases including Pubmed, CINAHL and Cochrane were searched using selected search terms 'oral frail*', 'oral health' and 'aged' respectively. Articles written between 2013 and 2023 were included, and grey literature was excluded. RESULTS: A total of 32 articles were included for further analysis and synthesis. The attributes of oral frailty were hypofunction, predisposing in nature, non-specific and multidimensional. Antecedents of prefrailty were classified into four categories, namely, sociodemographic characteristics, comorbidity, physical function and psychosocial factors. Consequences of oral frailty include three themes: increased risk of adverse outcomes, poor nutritional status and possibility of social withdrawal. Related terms that had shared attributes with oral frailty were oral health, functional dentition, oral hypofunction and deterioration of oral function. CONCLUSIONS: Oral frailty is an age-related phenomenon reflected in decreased oral function. The findings of this concept analysis are conducive to understanding and clarifying the oral frailty, which can help clinicians or other healthcare providers to consider how to distinguish oral frailty in older adults and further promote the development of this field. IMPACT: Oral frailty is increasingly recognized as an age-related phenomenon reflected in decreased oral function. As it is newly proposed, no consensus has been reached regarding the theoretical and operational concept of it. Through clarifying the concept, this paper will guide future healthcare research on oral frailty regarding the influencing factors, mechanisms and interventions, thus raising the awareness with regard to oral health among older adults. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: In the context of older adults, oral frailty is a concept that requires further research to guide future theoretical development, and the influencing factors, mechanisms and interventions need to be further studied. Raise awareness with regard to oral health among older people and more attention will be paid to the early identification and intervention of oral frailty, so as to further improve the quality of life of older adults.

Remnant cholesterol, but not other cholesterol parameters, is associated with gestational diabetes mellitus in pregnant women: a prospective cohort study.

OBJECTIVE: No evidence has been found of a relationship between remnant cholesterol (RC) and the likelihood of gestational diabetes mellitus (GDM) in pregnant women. The aim of our study was to investigate the link between serum RC at 12-14 weeks of gestation and the risk of GDM. METHODS: This was a secondary analysis with data from a prospective cohort study in Korea. A total of 590 single pregnant women attending two hospitals in Korea, up to 14 weeks gestation, from November 2014 to July 2016 were included in the study. The formula used to calculate RC in detail was RC (mg/dL) = TC (mg/dL)-HDL-c (mg/dL)-LDL-c (mg/dL). Logistic regression models were employed to examine the relationship between RC and GDM and explore the association between other lipoprotein cholesterol parameters and the risk of GDM. Furthermore, receiver operating characteristic (ROC) analysis was performed to assess the ability of RC to identify GDM. Additionally, sensitivity and subgroup analyses were conducted. RESULTS: The mean age of participants was 32.06 ± 3.80 years. The median of RC was 34.66 mg/dL. 37 pregnant women (6.27%) were eventually diagnosed with GDM. Multivariate adjusted logistic regression analysis showed that RC was positively associated with the risk of GDM (OR = 1.458, 95% CI 1.221, 1.741). There was no significant association between other lipoprotein cholesterols (including TC, LDL-c, HDL-c) and the risk of GDM. The area under the ROC curve for RC as a predictor of GDM was 0.8038 (95% CI 0.7338-0.8738), and the optimal RC cut-off was 24.30 mg/dL. Our findings were demonstrated to be robust by performing a series of sensitivity analyses. CONCLUSION: Serum RC levels at 12-14 weeks of gestation are positively associated with GDM risk in pregnant women. RC in early pregnancy is an early warning indicator of GDM in pregnant women, especially those with normal HDL-c, LDL-c, and TC that are easily overlooked. There is a high risk of developing GDM in pregnant women whose RC is more than 24.30 mg/dL. This study may help optimize GDM prevention in pregnant women and facilitate communication between physicians, pregnant patients, and their families.

circS100A11 enhances M2a macrophage activation and lung inflammation in children with asthma.

BACKGROUND: Dysregulation of circRNAs is associated with a variety of human diseases; however, its role in childhood asthma is undefined. METHODS: The differential expression profiles of circRNAs were analyzed by microarray. The effects and mechanisms by which circRNAs influence macrophage activation were detected by quantitative real-time PCR, RNA immunoprecipitation assay, and chromatin immunoprecipitation assay, among others. The roles of circRNA and its host gene in asthma were tested in a cockroach allergen extract (CRE)-induced murine asthma model. RESULTS: We identified 372 circRNAs that were differentially expressed in PBMCs of children with asthma as compared with healthy controls. A circRNA with unknown function, circS100A11, was dominantly expressed in monocytes and significantly upregulated in children with asthma. circS100A11 facilitated M2a macrophage activation by enhancing translation of its host gene, S100A11, and exacerbated lung inflammation in a CRE-induced murine asthma model with macrophage-specific overexpression of circS100A11. Mechanistically, circS100A11 promoted S100A11 translation by competitively binding to CAPRIN1 to decrease the suppression of CAPRIN1 upon S100A11 translation. Then, S100A11 liberated SP3 from nucleolin and promoted SP3 binding to the STAT6 promoter to enhance STAT6 expression and M2a macrophage activation. Macrophage-specific knockdown of S100A11 could alleviate lung inflammation in a CRE-induced murine asthma model in vivo. CONCLUSIONS: circS100A11 and S100A11 promote M2a macrophage activation and lung inflammation in asthma model and may serve as potential therapeutic and diagnostic targets in children with asthma.

Single-cell RNA-sequencing of zebrafish hair cells reveals novel genes potentially involved in hearing loss.

Hair cells play key roles in hearing and balance, and hair cell loss would result in hearing loss or vestibular dysfunction. Cellular and molecular research in hair cell biology provides us a better understanding of hearing and deafness. Zebrafish, owing to their hair cell-enriched organs, have been widely applied in hair cell-related research worldwide. Similar to mammals, zebrafish have inner ear hair cells. In addition, they also have lateral line neuromast hair cells. These different types of hair cells vary in morphology and function. However, systematic analysis of their molecular characteristics remains lacking. In this study, we analyzed the GFP+ cells isolated from Tg(Brn3c:mGFP) larvae with GFP expression in all hair cells using single-cell RNA-sequencing (scRNA-seq). Three subtypes of hair cells, namely macula hair cell (MHC), crista hair cell (CHC), and neuromast hair cell (NHC), were characterized and validated by whole-mount in situ hybridization analysis of marker genes. The hair cell scRNA-seq data revealed hair cell-specific genes, including hearing loss genes that have been identified in humans and novel genes potentially involved in hair cell formation and function. Two novel genes were discovered to specifically function in NHCs and MHCs, corresponding to their specific expression in NHCs and MHCs. This study allows us to understand the specific genes in hair cell subpopulations of zebrafish, which will shed light on the genetics of both human vestibular and cochlear hair cell function.

Effectiveness of photobiomodulation for people with age-related cognitive impairment: a systematic review and meta-analysis.

The increasing incident of age-related cognitive impairment worldwide and the lack of pharmaceutical treatments emphasizes the value of non-pharmaceutical therapy. Emerging evidence suggested photobiomodulation (PBM) is a popular intervention to brain disorder; however, it remains unclear the efficacy of PBM for patients with age-related cognitive impairment. The purpose of this systematic review is to compare the different parameters used in PBM, analyze the beneficial effects of PBM as a potential therapy for age-related cognitive impairment. Five electronic database, PubMed, Web of Science, Cochrane Library, CINAHL, and PsycINFO, were systematically searched from inception to November 2021. Relevant randomized controlled trials (RCTs) were screened and assessed for risk of bias. Eleven RCTs evaluating PBM interventions were included. The systematic review and meta-analysis has been registered in PROSPERO(CRD42022374562). Results showed that PBM had a significant moderated effect on global cognition function (SMD=0.51, 95% CI [0.162, 0.864], p=0.004). We found that multiple wavelength PBM (SMD=0.648, 95% CI [0.220, 1.075], p=0.003) had significant effects while single wavelength PBM was non-significant (SMD=0.385, 95% CI [-0.168, 0.987], p=0.172). Laser effect (SMD=0.682, 95% CI [0.37, 0,994], p<0.001) was larger than LED effect (SMD=0.582, 95% CI [0.269, 0.895], p<0.001). PBM in clinical setting (SMD=0.468, 95% CI [0.050, 0.887], p=0.028) had significant effect, but there was no significant effect of home-used PBM (SMD=0.616, 95% CI [-0.121, 1.354], p=0.101). The pool effect of multi-modality PBM (SMD=0.720, 95% CI [0.027, 1.414], p=0.040) was significantly higher in the studies of transcranial irradiation (SMD=0.616, 95% CI [-0.121, 1.354], p=0.010). Cumulative irradiation time was a moderator between the PBM and cognitive function improvement. Photobiomodulation have the potential to improve cognitive function in aging adults. Cumulative irradiation duration, light source, device type, penetration modality, and intervention site can affect the effectiveness of PBM intervention.

Dyadic profiles of family resilience among patients with first-episode stroke: A longitudinal study of the first 6 months after stroke.

BACKGROUND: The importance of family resilience in the recovery of stroke patients has been demonstrated in numerous studies. However, little is known about post-stroke family resilience. AIMS: To investigate the family resilience of stroke patients from a patient-caregiver dyadic perspective during the first 6 months after stroke. METHODS: A total of 288 dyads of patients diagnosed with a first-episode stroke and their principal caregivers were recruited from neurology departments of 7 tertiary hospitals in Shanghai and Shangqiu, China. Family resilience and family function were assessed during hospitalisation and at 1, 3 and 6 months after stroke. K-means cluster analysis was used to identify different clusters of family resilience based on family resilience of patients and caregivers during hospitalisation. The STROBE guidelines for observational studies were followed. RESULTS: Three clusters of family resilience were identified with distinct trajectories: cluster of high resilience (HR), cluster of low resilience (LR) and cluster of discrepant resilience (DR). The level of family function was consistently highest in cluster HR and lowest in cluster with LR at four time points. Most (69.8%) families fell into the cluster with low resilience and low family function. Characteristics such as the Rankin scores and education level of patients, education level of caregivers, family monthly income and living district were different among the three clusters. CONCLUSIONS: We concluded that family resilience was linked to the family functioning of patients with a first-episode stroke, however, the levels of resilience in most families were low. Factors, including the education level, family income and stroke severity of patients were revealed to influence the family resilience and its development. RELEVANCE TO CLINICAL PRACTICE: A resilience-focused approach to family-related treatment is beneficial for families. Therefore, understanding family resilience among stroke survivors is needed to inform the development of interventions for enhancing the recovery of stroke families.

Hsa_circ_0004287 inhibits macrophage-mediated inflammation in an N6-methyladenosine-dependent manner in atopic dermatitis and psoriasis.

BACKGROUND: Circular RNA (circRNA) has been implicated in various diseases; however, its role in atopic dermatitis (AD) or psoriasis remains unclear. OBJECTIVE: We sought to determine the differential expression profiles of circRNAs in peripheral blood mononuclear cells between healthy controls and AD patients, and explore the mechanisms underlying the effects of circRNAs on the pathogenesis of AD. METHODS: The differential expression profiles of circRNAs were analyzed by circRNA microarray. In vitro function and mechanisms by which circRNAs regulate macrophage-mediated inflammation were detected by reverse transcription quantitative PCR, Western blot analysis, RNA stability assay, immunoprecipitation, ELISA, and methylated RNA immunoprecipitation assay. In vivo roles of circRNAs were determined in 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis and imiquimod (IMQ)-induced psoriasis mouse model. RESULTS: We identified a functional unknown circRNA hsa_circ_0004287 from 88750 circRNAs, which was upregulated in peripheral blood mononuclear cells of both AD and psoriasis patients, and was mainly expressed by macrophages under inflammatory conditions. Hsa_circ_0004287 inhibited M1 macrophage activation in vitro, and macrophage-specific overexpression of hsa_circ_0004287 alleviated skin inflammation in both AD- and psoriasis-like mice. Mechanistically, hsa_circ_0004287 reduced the stability of its host gene metastasis associated lung adenocarcinoma transcript 1 (MALAT1) by competitively binding to IGF2BP3 with MALAT1 in an N6-methyladenosine (m6A)-dependent manner. Lower levels of MALAT1 promoted the ubiquitination degradation of S100A8/S100A9, thereby impeding p38/mitogen-activated protein kinase phosphorylation and macrophage-mediated inflammation. CONCLUSION: hsa_circ_0004287 inhibits M1 macrophage activation in an m6A-dependent manner in AD and psoriasis, and may serve as a general therapeutic candidate for AD and psoriasis.

Sensitisation of cancer cells to radiotherapy by serine and glycine starvation.

BACKGROUND: Cellular metabolism is an integral component of cellular adaptation to stress, playing a pivotal role in the resistance of cancer cells to various treatment modalities, including radiotherapy. In response to radiotherapy, cancer cells engage antioxidant and DNA repair mechanisms which mitigate and remove DNA damage, facilitating cancer cell survival. Given the reliance of these resistance mechanisms on amino acid metabolism, we hypothesised that controlling the exogenous availability of the non-essential amino acids serine and glycine would radiosensitise cancer cells. METHODS: We exposed colorectal, breast and pancreatic cancer cell lines/organoids to radiation in vitro and in vivo in the presence and absence of exogenous serine and glycine. We performed phenotypic assays for DNA damage, cell cycle, ROS levels and cell death, combined with a high-resolution untargeted LCMS metabolomics and RNA-Seq. RESULTS: Serine and glycine restriction sensitised a range of cancer cell lines, patient-derived organoids and syngeneic mouse tumour models to radiotherapy. Comprehensive metabolomic and transcriptomic analysis of central carbon metabolism revealed that amino acid restriction impacted not only antioxidant response and nucleotide synthesis but had a marked inhibitory effect on the TCA cycle. CONCLUSION: Dietary restriction of serine and glycine is a viable radio-sensitisation strategy in cancer.

Online Ethnography for People With Chronic Conditions: Scoping Review.

BACKGROUND: Online ethnography has been making a unique contribution to people with chronic conditions as a complement to offline ethnography. It can also be used to study the complexities and contingencies of people with chronic conditions in the context of the internet. Therefore, there is a need to synthesize existing knowledge on research activities concerning online ethnography for people with chronic conditions. OBJECTIVE: This scoping review aimed to profile the existing evidence on the application of online ethnography for people with chronic conditions, focusing on the characteristics, contributions, and implementation process. This will provide recommendations for the future use of online ethnography. METHODS: We followed the scoping review methodologies developed by Arksey and O' Malley and the Joanna Briggs Institute. A comprehensive search was conducted on the PubMed, CINAHL, Embase, Scopus, and PsycInfo databases using preselected keywords. The search was limited to documents written in English and published between January 1, 2000, and February 1, 2022. After removal of duplicates, articles were screened by 2 independent reviewers reading the title, abstract, and full text. One reviewer extracted data, which were descriptively analyzed to map the existing knowledge. RESULTS: After 2836 titles and abstracts and 51 full texts were screened, 27 publications were included in the analysis, published between 2009 and 2022. Most studies were from the United States (11/27, 40.7%), and most articles collected data from online forums (10/27, 37.0%). Moreover, the most commonly used type of researcher involvement was passive analysis (24/27, 88.9%), and 18.5% (5/27) of the topics concerned people with mental illness. Notably, the majority of articles did not report the immersion process in detail (17/25, 63.0%). Ethical issues were mentioned in 88.9% (24/27) of the included articles. CONCLUSIONS: We analyzed the current literature across fields and found that online ethnography can be exploited to explore the deeper experience of people with chronic conditions that are difficult to investigate using traditional ethnography. We found that there was diversity in researcher involvement, immersion process, data collection, and data analysis. However, most studies reported the insufficient immersion into the online environment. Researchers should determine the research approaches and data resources in order to complete culture immersion before researching. We also found that there was no uniform standard for ethical issues. Therefore, we recommend that researchers collect public and private data, obtain informed consent, and preserve the privacy and confidentiality of online users with chronic conditions. The findings can provide a practical reference for the use of online health care in studying chronic conditions.

lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma through stabilizing BAZ2B pre-mRNA.

BACKGROUND: Dysregulation of long noncoding RNAs (lncRNAs) is associated with a variety of human diseases; however, whether they have a role in childhood asthma is unknown. OBJECTIVE: We sought to determine the differential expression profiles of lncRNAs in PBMCs of children with asthma and the mechanisms underlying the effects of lncRNAs on the pathogenesis of asthma. METHODS: The differential expression profiles of lncRNAs were analyzed by transcriptome microarray. The effects and mechanisms by which lncRNAs influence macrophage activation were detected by real-time quantitative PCR, Western blot, RNase protection assay, and chromatin immunoprecipitation assay. The roles played by lncRNAs in asthma were tested in a cockroach allergen extract (CRE)-induced mouse model. RESULTS: We identified 719 lncRNAs that were differentially expressed in PBMCs of children with asthma, 502 of which were upregulated and 217 were downregulated. An lncRNA of unknown function, lnc-BAZ2B, was dominantly expressed in monocytes and significantly upregulated in children with asthma. lnc-BAZ2B promotes M2 macrophage activation by enhancing BAZ2B expression and exacerbated lung inflammation in an M2 macrophage-associated CRE-induced asthma model. Mechanistically, lnc-BAZ2B promoted the expression of its cis target gene BAZ2B by stabilizing its pre-mRNA. BAZ2B, a reader of H3K14ac modification, enhanced the transcription of IRF4 and promoted M2 macrophage activation. lnc-BAZ2B expression was correlated with that of BAZ2B in PBMCs from children with asthma. Baz2b knockdown could alleviate asthma severity in a CRE-induced asthma model. CONCLUSION: lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma and may serve as a potential therapeutic and diagnostic target in children with asthma.

Decisional control preference among Chinese patients with advanced kidney disease: the role of mastery, perceived social support and self-efficacy.

Although previous studies have shown a correlation between mastery, self-efficacy, and perceived social support among Chinese patients with advanced kidney disease, few studies have examined their relationship pathways. This study aimed to examine decisional control preference and the relationship between mastery, perceived social support, and self-efficacy among patients with advanced chronic kidney disease. A cross-sectional survey was conducted, and 350 participants were investigated using Control Preference Scale, Personal Mastery Scale, Perceived Social Support Scale, and Self-efficacy Scale. The mediating relationships were determined via structural equation modeling. Results showed that education and economic status were demographic factors influencing patients' decisional control preference. The model showed that mastery and self-efficacy had a direct effect on decisional control preference while perceived social support had an indirect effect mediated via mastery and self-efficacy. Therefore, improving self-efficacy can increase patient willingness to involve in medical decision-making. This study provides new interventions and future directions for promoting decisional control preference.

LKB1 Represses ATOH1 via PDK4 and Energy Metabolism and Regulates Intestinal Stem Cell Fate.

BACKGROUND & AIMS: In addition to the Notch and Wnt signaling pathways, energy metabolism also regulates intestinal stem cell (ISC) function. Tumor suppressor and kinase STK11 (also called LKB1) regulates stem cells and cell metabolism. We investigated whether loss of LKB1 alters ISC homeostasis in mice. METHODS: We deleted LKB1 from ISCs in mice using Lgr5-regulated CRE-ERT2 (Lkb1Lgr5-KO mice) and the traced lineages by using a CRE-dependent TdTomato reporter. Intestinal tissues were collected and analyzed by immunohistochemical and immunofluorescence analyses. We purified ISCs and intestinal progenitors using flow cytometry and performed RNA-sequencing analysis. We measured organoid-forming capacity and ISC percentages using intestinal tissues from Lkb1Lgr5-KO mice. We analyzed human Ls174t cells with knockdown of LKB1 or other proteins by immunoblotting, real-time quantitative polymerase chain reaction, and the Seahorse live-cell metabolic assay. RESULTS: Some intestinal crypts from Lkb1Lgr5-KO mice lost ISCs compared with crypts from control mice. However, most crypts from Lkb1Lgr5-KO mice contained functional ISCs that expressed increased levels of Atoh1 messenger RNA (mRNA), acquired a gene expression signature associated with secretory cells, and generated more cells in the secretory lineage compared with control mice. Knockdown of LKB1 in Ls174t cells induced expression of Atoh1 mRNA and a phenotype of increased mucin production; knockdown of ATOH1 prevented induction of this phenotype. The increased expression of Atoh1 mRNA after LKB1 loss from ISCs or Ls174t cells did not involve Notch or Wnt signaling. Knockdown of pyruvate dehydrogenase kinase 4 (PDK4) or inhibition with dichloroacetate reduced the up-regulation of Atoh1 mRNA after LKB1 knockdown in Ls174t cells. Cells with LKB1 knockdown had a reduced rate of oxygen consumption, which was partially restored by PDK4 inhibition with dichloroacetate. ISCs with knockout of LKB1 increased the expression of PDK4 and had an altered metabolic profile. CONCLUSIONS: LKB1 represses transcription of ATOH1, via PDK4, in ISCs, restricting their differentiation into secretory lineages. These findings provide a connection between metabolism and the fate determination of ISCs.

A photosynthesis-inspired supramolecular system: caging photosensitizer and photocatalyst in apoferritin.

Inspired by the bioinorganic structure of natural [FeFe]-hydrogenase ([FeFe]-H2ase) that possesses iron sulfur clusters to catalyze proton reduction to hydrogen (H2), we design a supramolecular photosystem by sequentially integrating hydrophobic ruthenium complex (as a photosensitizer) and diiron dithiolate complex (as a photocatalyst) into the inner surface or cavity of apoferritin via noncovalent interactions. This platform allows photosensitizer and catalyst to localize in a close proximity and short-distance electron transfer process to occur within a confined space. The resulted uniform core-shell nanocomposites were stable and well dispersed in water, and showed enhanced H2 generation activity in acidic solution as compared to the homogenous system without apoferritin participation.

MyD88 Signaling in T Cells Is Critical for Effector CD4 T Cell Differentiation following a Transitional T Follicular Helper Cell Stage.

Activation of CD4 T cells by dendritic cells leads to their differentiation into various effector lineages. The nature of the effector lineage is determined by the innate cues provided by dendritic cells to newly primed T cells. Although the cytokines necessary for several effector lineages have been identified, the innate cues that drive T follicular helper (Tfh) lineage cell development remain unclear. Here we found that following priming, CD4 T cells undergoing clonal expansion acquire a transient Tfh-like phenotype before differentiating into other effector lineages. In addition, we found that T cell-intrinsic myeloid differentiation antigen 88 (MyD88) signaling, which occurs downstream of interleukin-1 (IL-1) and IL-18 receptors, is critical for the primed CD4 T cells to transition out of the temporary Tfh lineage. Mice with T cell-specific deletion of MyD88 have a higher proportion of Tfh cells and germinal center (GC) B cells. These exaggerated Tfh cell and GC B cell responses, however, do not lead to protective immunity against infections. We demonstrate that T cell-intrinsic MyD88 is critical for effector lineage differentiation as well as production of the cytokines that are necessary for class switching. Overall, our study establishes that following priming and clonal expansion, CD4 T cells undergo a transitional Tfh-like phase and that further differentiation into effector lineages is dictated by T cell-intrinsic MyD88-dependent cues.

Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation.

Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation, a process involving up-regulation of MHC and costimulatory molecules and secretion of proinflammatory cytokines. All TLRs except TLR3 achieve these outcomes by using the signaling adaptor myeloid differentiation factor 88. TLR4 and TLR3 can both use the Toll-IL-1 receptor domain-containing adaptor inducing IFN-ß (TRIF)-dependent signaling pathway leading to IFN regulatory factor 3 (IRF3) activation and induction of IFN-ß and -α4. The TRIF signaling pathway, downstream of both of these TLRs, also leads to DC maturation, and it has been proposed that the type I IFNs act in cis to induce DC maturation and subsequent effects on adaptive immunity. The present study was designed to understand the molecular mechanisms of TRIF-mediated DC maturation. We have discovered that TLR4-TRIF-induced DC maturation was independent of both IRF3 and type I IFNs. In contrast, TLR3-mediated DC maturation was completely dependent on type I IFN feedback. We found that differential activation of mitogen-activated protein kinases by the TLR4- and TLR3-TRIF axes determined the type I IFN dependency for DC maturation. In addition, we found that the adjuvanticity of LPS to induce T-cell activation is completely independent of type I IFNs. The important distinction between the TRIF-mediated signaling pathways of TLR4 and TLR3 discovered here could have a major impact in the design of future adjuvants that target this pathway.

[Chemical Constituents of Salvia grandifolia].

Objective: To study the chemical constituents of Salvia grandifolia. Methods: The chemical constituents were isolated and purified by means of chromatographic techniques and their structures were elucidated by spectroscopic methods. Results: Eleven compounds were isolated from chloroform and ethyl acetate of ethanol extract, and identified as tanshinone Ⅵ( 1),tetrahydrotanshiquinone( 2),tanshinone ⅡB( 3),danshenol B( 4), ursolic acid( 5),2α-hydroxyursolic acid( 6),2α,3α-dihydroxyurs-12-en-28-oic acid( 7),salvianolic acid B(8),3,5-dihydroxycinnamic acid( 9),ethyl 3-( 3,4-dihydrophenyl) lactate( 10) and nepetoidin B( 11). Conclusion: All of them are isolated from this plant for the first time.

Passively Q-switched mode locking performance of Nd:GdTaO4 crystal by MoS2 saturable absorber at 1066 nm.

Passively Q-switched mode-locking performance of Nd:GdTaO4 crystal using molybdenum disulfide (MoS2) as a saturable absorber at 1066 nm was demonstrated for the first time. The MoS2 saturable absorber was prepared simply by transferring the MoS2 suspension onto a quartz substrate. By inserting the MoS2 saturable absorber into the Nd:GdTaO4 laser, stable Q-switched modelocked operation can be achieved. At the pump power of 4 W, the maximum average output power of 0.156 W was obtained with the optical conversion efficiency of 3.9%.

Barriers and facilitators to exercise adherence in community-dwelling older adults: A mixed-methods systematic review using the COM-B model and Theoretical Domains Framework.

BACKGROUND: Although the health benefits of exercise for older adults are widely recognized, physical inactivity is still common among older adults. Further clarification of the factors affecting exercise adherence is needed to develop more effective exercise interventions in community-dwelling older adults. OBJECTIVE: The purposes of this study were to identify (1) barriers and facilitators of exercise adherence in community-dwelling older adults and (2) behavior change techniques (BCTs) and implementation strategies that are potentially effective in improving adherence. METHODS: A total of eight databases were searched: PubMed, Web of Science, EMBASE, CENTRAL, PsycINFO, SPORTDiscus, MEDLINE, and Scopus. Studies published from database inception to April 2023 were searched. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool (MMAT). The Capabilities, Opportunities, Motivations, Behavior (COM-B) model and the Theoretical Domain Framework (TDF) were used to identify potential barriers and facilitators. The BCTs were used to identify potential intervention implementation strategies. RESULTS: A total of 64 studies were included, including 30 qualitative studies, 12 randomized controlled trials, 12 mixed methods studies, 6 quantitative descriptive studies, and 5 non-randomized trials. 54 factors influencing adherence and 38 potentially effective BCTs were identified from the included studies. The 38 BCTs were further categorized into 8 areas of implementation strategies (tailored exercise program, appropriate exercise environment, multidimensional social support, monitoring and feedback, managing emotional experiences and issues, participants education, enhancing self-efficacy, and exerting participants' autonomy). CONCLUSION: This study identified 54 influential factors affecting exercise adherence and identified 8 areas of intervention strategies (containing 38 BCTs). Further refinement, evaluation, and validation of these factors and strategies are needed in future studies.