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Abstract As a highly salt-resistant mangrove, Avicennia marina can thrive in the hypersaline water. The leaves of Avicennia marina play a crucial role in salinity stress adaptability by secreting salt. Although the functions of long non-coding RNAs (lncRNAs) in leaves remain unknown, they have emerged as regulators in leaf development, aging and salt response. In this study, we employed transcriptomic data of both short-term and long-term salt treated leaves to identify salt-associated lncRNAs of leaf tissue. As a result, 687 short-term and 797 long-term salt-associated lncRNAs were identified. Notably, both short-term and long-term salt-associated lncRNAs exhibited slightly longer lengths and larger exons, but smaller introns compared with salt-non-associated lncRNAs. Furthermore, salt-associated lncRNAs also displayed higher tissue-specificity than salt-non-associated lncRNAs. Most of the salt-associated lncRNAs were common to short- and long-term salt treatments. And about one fifth of the downregulated salt-associated lncRNAs identified both in two terms were leaf tissue-specific lncRNAs. Besides, these leaf-specific lncRNAs were found to be involved in the oxidation–reduction and photosynthesis processes, as well as several metabolic processes, suggesting the noticeable functions of salt-associated lncRNAs in regulating salt responses of Avicennia marina leaves.

Abstract Backgrounds Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. Methods We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. Results Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p

Abstract Background Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) provide more comprehensive and informative perspective on microstructural alterations of cerebral white matter (WM) than single-shell diffusion tensor imaging (DTI), especially in the detection of crossing fiber. However, studies on systemic lupus erythematosus patients without neuropsychiatric symptoms (non-NPSLE patients) using multi-shell diffusion imaging remain scarce. Methods Totally 49 non-NPSLE patients and 41 age-, sex-, and education-matched healthy controls underwent multi-shell diffusion magnetic resonance imaging. Totally 10 diffusion metrics based on DKI (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis and radial kurtosis) and NODDI (neurite density index, orientation dispersion index and volume fraction of the isotropic diffusion compartment) were evaluated. Tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analyses were performed to determine group differences in brain WM microstructure. The associations of multi-shell diffusion metrics with clinical indicators were determined for further investigation. Results TBSS analysis revealed reduced FA, AD and RK and increased ODI in the WM of non-NPSLE patients (P

Abstract Background Certain studies have indicated a link between obstructive sleep apnea and insulin resistance in specific populations. To gain more clarity, extensive research involving a broad sample of the overall population is essential. The primary objective of this study was to investigate this correlation by utilizing data from the National Health and Nutrition Examination Survey database. Methods The analysis incorporated data from the National Health and Nutrition Examination Survey database spanning the time periods from 2005 to 2008 and from 2015 to 2018, with a focus on American adults aged 18 years and older after applying weight adjustments. Key variables such as obstructive sleep apnea, triglyceride glucose index, and various confounding factors were considered. A generalized linear logistic regression model was used to investigate the association between obstructive sleep apnea and the triglyceride glucose index, with additional exploration of the consistency of the results through hierarchical analysis and other techniques. Results The study included participants aged between 18 and 90 years, with an average age of 46.75 years. Among the total sample, 50.76% were male. The triglyceride glucose index demonstrated a diagnostic capability for obstructive sleep apnea, with an AUC of 0.701 (95% CI: 0.6619–0.688). According to the fully adjusted model, individuals in the fourth quartile of the triglyceride glucose index showed an increased likelihood of having obstructive sleep apnea compared to those in the first quartile (OR: 1.45; 95% CI: 1.02–2.06; P

Abstract Background Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. Methods We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. Results Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. Conclusions Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

Abstract Objective The purpose of this article is to systematically review the association between dry eye and sleep quality. Methods PubMed, EMBASE, Cochrane, Web of Science, and grey literature databases were searched for observational studies published before April 2023. Meta-analysis was performed using STAT15 software. Results A total of 21 studies with 419,218 participants were included. The results showed that the dry eye subjects had a worse sleep quality than the healthy population, with poorer subjective sleep quality, longer sleep latency, and a higher risk of unhealthy sleep duration such as insufficient sleep or excessive sleep. The Pittsburgh Sleep Quality Index (PSQI) scores of the dry eye subjects were significantly higher than those of the control subjects (WMD = 1.78, 95%CI: 1.06, 2.50, P

Abstract Background The sustainable supply of medicinal plants is important, and cultivating and domesticating them has been suggested as an optimal strategy. However, this can lead to a loss of genetic diversity. Tripterygium wilfordii Hook. f. is a medicinal plant commonly used in traditional Chinese medicine, but its wild populations are dwindling due to excessive harvesting. To protect the species and meet the increasing demand, it is urgent to cultivate it on a large scale. However, distinguishing between T. wilfordii and T. hypoglaucum, two similar species with different medicinal properties, is challenging. Therefore, it is crucial to understand the genetic diversity and population structure of these species for their sustainable utilization. Results In this study, we investigated the genetic diversity and population structure of the two traditional medicinal semiwoody vines plant species, Tripterygium wilfordii and T. hypoglaucum, including wild and cultivated populations using chloroplast DNA (cpDNA) sequences and microsatellite loci. Our results indicated that the two species maintain a high level of genetic divergence, indicating possible genetic bases for the different contents of bioactive compounds of the two species. T. wilfordii showed lower genetic diversity and less subdivided population structures of both markers than T. hypoglaucum. The potential factors in shaping these interesting differences might be differentiated pollen-to-seed migration rates, interbreeding, and history of population divergence. Analyses of cpDNA and microsatellite loci supported that the two species are genetically distinct entities. In addition, a significant reduction of genetic diversity was observed for cultivated populations of the two species, which mainly resulted from the small initial population size and propagated vegetative practice during their cultivation. Conclusion Our findings indicate significant genetic divergence between T. wilfordii and T. hypoglaucum. The genetic diversity and population structure analyses provide important insights into the sustainable cultivation and utilization of these medicinal plants. Accurate identification and conservation efforts are necessary for both species to ensure the safety and effectiveness of crude drug use. Our study also highlighted the importance of combined analyses of different DNA markers in addressing population genetics of medicinal plants because of the contrasts of inheritance and rates of gene flow. Large-scale cultivation programs should consider preserving genetic diversity to enhance the long-term sustainability of T. wilfordii and T. hypoglaucum. Our study proposed that some populations showed higher genetic diversity and distinctness, which can be considered with priority for conservation and as the sources for future breeding and genetic improvement.

Abstract Background Parenting is both a complex and stressful endeavor, so parents sometimes experience parenting burnout. The main objective of this study was to provide an overview of factors related to general parental burnout (PB) among parents with at least one child based on the Ecological Systems Theory (EST). Methods PubMed, Web of Science, EBSCO, CNKI and WanFang were systematically searched for studies published from 2010 to July 2023 for peer-reviewed articles using keywords extracted from Medical Subject Headings such as “parenting”, “parental”, “burnout”, “psychological burnout”, “burn-out syndrome”. Studies were included if they described associations between factors and PB among parents of children aged 0-18 years old in the general population, and published in an English or Chinese language peer-reviewed journal. The Quality Assessment Tool for Studies with Diverse Designs (QATSDD) was employed to assess the risk of bias of included studies. Results Of 2037 articles, 26 articles met the inclusion criteria. Based on the Ecological Systems Theory (EST), we found that microsystem-individual factors such as gender, educational level, income, parental personality, internalization of maternal parental motivation, unmitigated communion, self-compassion and concern for others, alexithymia, anxiety and depressive symptoms, parental perfectionism, resilience, low self-esteem and high need for control, mother's attachment style were identified as being associated with parenting burnout. Mesosystem-interpersonal factors involve parent-child relationship and marital satisfaction. The exosystem-organizational or community factors include the number of children in the household, neighborhood and the number of hours spent with children, child's illness, child's behavior problems and social support. The macrosystem-society/policy or culture factors are mainly personal values and cultural values. Conclusions This systematic review found several factors that have been investigated in relation to PB. However, the majority of the factors were reported by one or two studies often implementing a cross-sectional design. Nevertheless, we still recommend that health policymakers and administrators relieve parenting burnout among parents with children by adjusting these modifiable factors.

Abstract Sub-Saharan Africa (SSA) has experienced a high economic growth rate over the last two decades, which has been accompanied by concerns about increasing carbon dioxide (CO2) emissions. This study aims to find out whether renewable energy and agriculture can help reduce CO2 emissions for selected SSA countries. A balanced dataset incorporating CO2 emissions, renewable energy consumption, agricultural land per capita, GDP per capita, urbanization level and energy intensity of 38 SSA countries covering the period 2000–2019 is utilized. The differentiated-generalized method of moments (GMM) is employed as a benchmark estimation method to estimate the effects of renewable energy and agriculture on CO2. The regional heterogeneity analysis of countries at different income levels is then carried out. The moderating role of government governance in the energy-agriculture-environment nexus is also investigated. The following conclusions are highlighted: (1) the consumption of renewable energy can reduce CO2 emissions, while agriculture increases them; (2) the mitigating effect of renewable energy on CO2 emissions is relatively larger in countries at a low income level countries than in high-income countries, while agriculture aggravates CO2 emissions in lower middle-income and low-income regions, but mitigates emissions in upper middle-income regions; and (3) governance quality turns the mitigating role of renewable energy use on CO2 emissions into an increasing one, and exaggerates the polluting effect of agriculture. Finally, the study proposes policy implications for improving renewable energy use and green agricultural growth to achieve sustainable development in SSA.

Abstract Background Loneliness and social isolation are increasingly recognised as prevalent among people with mental health problems, and as potential targets for interventions to improve quality of life and outcomes, as well as for preventive strategies. Understanding the relationship between quality and quantity of social relationships and a range of mental health conditions is a helpful step towards development of such interventions. Purpose Our aim was to give an overview of associations between constructs related to social relationships (including loneliness and social isolation) and diagnosed mental conditions and mental health symptoms, as reported in systematic reviews of observational studies. Methods For this umbrella review (systematic review of systematic reviews) we searched five databases (PsycINFO, MEDLINE, EMBASE, CINAHL, Web of Science) and relevant online resources (PROSPERO, Campbell Collaboration, Joanna Briggs Institute Evidence Synthesis Journal). We included systematic reviews of studies of associations between constructs related to social relationships and mental health diagnoses or psychiatric symptom severity, in clinical or general population samples. We also included reviews of general population studies investigating the relationship between loneliness and risk of onset of mental health problems. Results We identified 53 relevant systematic reviews, including them in a narrative synthesis. We found evidence regarding associations between (i) loneliness, social isolation, social support, social network size and composition, and individual-level social capital and (ii) diagnoses of mental health conditions and severity of various mental health symptoms. Depression (including post-natal) and psychosis were most often reported on, with few systematic reviews on eating disorders or post-traumatic stress disorder (PTSD), and only four related to anxiety. Social support was the most commonly included social construct. Our findings were limited by low quality of reviews and their inclusion of mainly cross-sectional evidence. Conclusion Good quality evidence is needed on a wider range of social constructs, on conditions other than depression, and on longitudinal relationships between social constructs and mental health symptoms and conditions.

Abstract Background Leonurus japonicus, a significant medicinal plant known for its therapeutic effects on gynecological and cardiovascular diseases, has genetic diversity that forms the basis for germplasm preservation and utilization in medicine. Despite its economic value, limited research has focused on its genetic diversity and divergence. Results The avg. nucleotide diversity of 59 accessions from China were 0.00029 and hotspot regions in petN-psbM and rpl32-trnL (UAG) spacers, which can be used for genotype discrimination. These accessions divided into four clades with significant divergence. The four subclades, which split at approximately 7.36 Ma, were likely influenced by the Hengduan Mountains uplift and global temperature drop. The initial divergence gave rise to Clade D, with a crown age estimated at 4.27 Ma, followed by Clade C, with a crown age estimated at 3.39 Ma. The four clades were not showed a clear spatial distribution. Suitable climatic conditions for the species were identified, including warmest quarter precipitation 433.20 mm ~ 1,524.07 mm, driest month precipitation > 12.06 mm, and coldest month min temp > -4.34 °C. The high suitability distribution showed contraction in LIG to LGM, followed by expansion from LGM to present. The Hengduan Mountains acted as a glacial refuge for the species during climate changes. Conclusions Our findings reflected a clear phylogenetic relationships and divergence within species L. japonicus and the identified hotspot regions could facilitate the genotype discrimination. The divergence time estimation and suitable area simulation revealed evolution dynamics of this species and may propose conservation suggestions and exploitation approaches in the future.

Abstract Background With aging, body mass index (BMI) increases and muscle strength declines, resulting in dynapenic obesity. It remains unknown whether and how sleep duration contributes to the sequence of BMI and muscle strength change in the progression of dynapenic obesity. Methods Data were derived from the first two waves of China Health and Retirement Longitudinal Study. Sleep duration was self-reported. BMI was calculated and grip strength (GS) was measured to reflect muscle strength. The effect of baseline sleep duration on the sequential change of BMI and GS was assessed using two mediation models considering the nonlinear associations between them. The moderating effect of metabolic disorder was also tested. Results Totally 4986 participants aged ≥ 50 years (50.8% females) with complete information on variables were included. Baseline BMI fully mediated the nonlinear association between sleep duration and follow-up GS change, but baseline GS did not mediate between sleep duration and follow-up BMI change for older men and women. Short sleep duration positively affected BMI-induced GS change (β = 0.038; 95%CI, 0.015–0.074), while this favorable effect became nonsignificant for moderate sleep duration (β = 0.008; 95% CI, -0.003–0.024) and turned negative with prolonged sleep duration (β = − 0.022; 95%CI, − 0.051 to − 0.003). This nonlinear mediation effect was more pronounced in older women who are relatively metabolically healthy at baseline. Conclusion For older adults in China, the influence of sleep duration on BMI-induced GS change but not the GS-induced BMI change suggested the contribution of sleep duration to the sequential course in the progression of dynapenic obesity. Sleep duration deviated either above or below normal range may confer adverse impact on GS through BMI. Strategies addressing sleep and obesity jointly to improve muscle function and delay the progression of dynapenic obesity are required.

Abstract Background Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis and drug-resistance. Disheveled3 (DVL3) is involved in malignant behaviors of cancer. However, the role and potential mechanism of DVL3 remain elusive in EMT and CSLCs of colorectal cancer (CRC). Methods UALCAN and PrognoScan databases were employed to evaluate DVL3 expression in CRC tissues and its correlation with CRC prognosis, respectively. Transwell, sphere formation and CCK8 assay were used to assess metastasis, stemness and drug sensitivity of CRC cells, respectively. Western blotting and dual luciferase assay were performed to analyze the protein expression and Wnt/β-catenin activation, respectively. Lentiviral transfection was used to construct the stable cell lines. Animal studies were performed to analyze the effect of silencing DVL3 on tumorigenicity and metastasis of CRC cells in vivo. Results DVL3 was overexpressed in CRC tissues and several CRC cell lines. DVL3 expression was also higher in CRC tissues with lymph node metastasis than tumor tissues without metastasis, and correlated with poor prognosis of CRC patients. DVL3 positively regulated the abilities of migration, invasion and EMT-like molecular changes in CRC cells. Moreover, DVL3 promoted CSLCs properties and multidrug resistance. We further identified that Wnt/β-catenin was crucial for DVL3-mediated EMT, stemness and SOX2 expression, while silencing SOX2 inhibited DVL3-mediated EMT and stemness. Furthermore, c-Myc, a direct target gene of Wnt/β-catenin, was required for SOX2 expression and strengthened EMT and stemness via SOX2 in CRC cells. Finally, knockdown of DVL3 suppressed tumorigenicity and lung metastasis of CRC cells in nude mice. Conclusion DVL3 promoted EMT and CSLCs properties of CRC via Wnt/β-catenin/c-Myc/SOX2 axis, providing a new strategy for successful CRC treatment.

Abstract Hematopoietic stem cells (HSCs) are the common and essential precursors of all blood cells, including immune cells, and they are responsible for the lifelong maintenance and damage repair of blood tissue homeostasis. The vast majority (> 95%) of HSCs are in a resting state under physiological conditions and are only activated to play a functional role under stress conditions. This resting state affects their long-term survival and is also closely related to the lifelong maintenance of hematopoietic function; however, abnormal changes may also be an important factor leading to the decline of immune function in the body and the occurrence of diseases in various systems. While the importance of resting HSCs has attracted increasing research attention, our current understanding of this topic remains insufficient, and the direction of clinical targeted treatments is unclear. Here, we describe the functions of HSCs, analyze the regulatory mechanisms that affect their resting state, and discuss the relationship between resting HSCs and different diseases, with a view to providing guidance for the future clinical implementation of related targeted treatments.

Abstract Background Sleep is conducive to the elimination of brain metabolites and the recovery of brain function. However, the relationship between sleep disturbance and Mild Cognitive Impairment is not fully been determined. Methods This was a community population-based cross-sectional study. A total of 1,443 participants from a village in the suburbs of Xi’an, China were enrolled in 2017. Sleep quality was evaluated using the Pittsburgh sleep quality index (PSQI), and sleep disturbance was defined as a PSQI score > 5. Mini-Mental State Examination (MMSE) was used to assess cognitive function and Mild Cognitive Impairment(MCI) was defined as the MMSE score less than cutoff values and meets the diagnostic criteria. Univariate and multivariate analyses were used to analyze the relationships between sleep disturbance and MCI. Results Among 1,443 subjects, 69(4.78%) had MCI, and 830 (57.52%) had sleep disturbance. In bivariate analysis, MCI was associated with sleep disturbance (ρ = 0.094, P

Abstract Background As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that Poria cocos polysaccharides (PCP), a traditional Chinese herbal medicine with various bioactivities and prebiotic effects, might improve the therapeutic effect of 5-FU by restoring the homeostasis of the gut microenvironment and the commensal gut microflora. Methods Apc Min/+ mice were employed to evaluate the anti-cancer effect of 5-FU in conjunction with PCP treatment. Body weight and food consumption were monitored weekly. Polyp count was used to assess the anti-cancer effect of PCP and 5-FU. Expressions of mucosal cytokines and gut epithelial junction molecules were measured using qRT-PCR. 16S rRNA gene sequencing of fecal DNAs was used to evaluate the compositional changes of gut microbiota (GM). Transplantation of Lactobacillus johnsonii and Bifidobacterium animalis were performed to verify the prebiotic effects of PCP in improving the efficacy of 5-FU. Results The results showed that PCP treatment alleviated the weight loss caused by 5-FU treatment and reduced the polyp burden in Apc Min/+ mice. Additionally, PCP treatment eased the cytotoxic effects of 5-FU by reducing the expressions of pro-inflammatory cytokines, increasing the anti-inflammatory cytokines; and significantly improving the gut barriers by enhancing the tight junction proteins and associated adhesion molecules. Furthermore, 16S rRNA gene sequencing data showed that PCP alone or with 5-FU could stimulate the growth of probiotic bacteria (Bacteroides acidifaciens, Bacteroides intestinihominis, Butyricicoccus pullicaecorum, and the genera Lactobacillus, Bifidobacterium, Eubacterium). At the same time, it inhibited the growth of potential pathogens (e.g., Alistipes finegoldii, Alistipes massiliensis, Alistipes putredinis., Citrobacter spp., Desulfovibrio spp., and Desulfovibrio desulfuricans). Moreover, the results showed that transplantation of L.johnsonii and B.animalis effectively reduced the polyp burden in Apc Min/+ mice being treated with 5-FU. Conclusion Our study showed that PCP could effectively improve the anti-cancer effect of 5-FU by attenuating its side effects, modulating intestinal inflammation, improving the gut epithelial barrier, and modulating the gut microbiota of ApcMin/+ mice.

Abstract Background Coffin-Siris syndrome-8 (CSS8) is a rare autosomal dominant disorder caused by variants in SMARCC2, a core subunit of the chromatin-remodeling complex BRG1-associated factor (BAF). The clinical characteristics of this disorder have not been entirely determined because of the rarity of clinical reports. The BAF complex plays a crucial role in embryogenesis and cardiac development, and pathogenic variants in genes encoding the components of the BAF complex have been associated with congenital heart disease (CHD). However, variants in SMARCC2 have not been reported in patients with CHD. Case presentation A 28-year-old primigravida was referred at 24 weeks gestation for prenatal echocardiography. The echocardiographic findings were consistent with a prenatal ultrasound diagnosis of tetralogy of Fallot (TOF). After detailed counseling, the couple decided to terminate the pregnancy and undergo genetic testing. A trio (fetus and the parents) whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. CNV-seq identified no chromosomal abnormalities. WES analysis revealed a pathogenic, de novo heterozygous frameshift variant in SMARCC2 (NM_003075.5: c.3561del, p.Leu1188fs). The genetic diagnosis of CSS8 was considered given the identification of the SMARCC2 pathogenic variant. Conclusions We report the first prenatal case with the SMARCC2 variant. The presence of CHD further broadens the phenotypic spectrum of SMARCC2-related disease.

Abstract Background Taxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants. Results Here, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs. Conclusions Our results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.

Abstract Background The cause and underlying molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) are unclear. Our study aims to identify the key genes associated with HNSCC and reveal potential biomarkers. Methods In this study, the expression profile dataset GSE83519 of the Gene Expression Omnibus database and the RNA sequencing dataset of HNSCC of The Cancer Genome Atlas were included for analysis. Sixteen differentially expressed genes were screened from these two datasets using R software. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was then adopted for survival analysis, and finally, three key genes related to the overall survival of HNSCC patients were identified. Furthermore, we verified these three genes using the Oncomine database and from real-time PCR and immunohistochemistry results from HNSCC tissues. Results The expression data of 44 samples from GSE83519 and 545 samples from TCGA-HNSC were collected. Using bioinformatics, the two databases were integrated, and 16 DEGs were screened out. Gene Ontology (GO) enrichment analysis showed that the biological functions of DEGs focused primarily on the apical plasma membrane and regulation of anoikis. Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathway analysis showed that these DEGs were mainly involved in drug metabolism-cytochrome P450 and serotonergic synapses. Survival analysis identified three key genes, CEACAM5, CEACAM6 and CLCA4, that were closely related to HNSCC prognosis. The Oncomine database, qRT–PCR and IHC verified that all 3 key genes were downregulated in most HNSCC tissues compared to adjacent normal tissues. Conclusions This study indicates that integrated bioinformatics analyses play an important role in screening for differentially expressed genes and pathways in HNSCC, helping us better understand the biomarkers and molecular mechanism of HNSCC.

Abstract Background Loneliness is a frequent and distressing experience among people with mental health problems. However, few longitudinal studies have so far investigated the trajectories of loneliness and objective social isolation, and the extent to which both issues may impact mental health outcomes among mental health service users. Therefore, this study aims to describe the trajectories of loneliness and objective social isolation and their associations with self-rated personal recovery among people leaving crisis resolution teams (CRTs). Methods A total of 224 participants receiving care from CRTs (recruited for a large multi-site randomised controlled trial) were included in this longitudinal cohort study. They completed the eight-item University of California at Los Angeles Loneliness Scale (ULS-8), Lubben-Social Network Scale (LNSN-6), and the Questionnaire about the Process of Recovery (QPR) (primary outcome) at baseline, 4- and 18-month follow-up, as well as baseline sociodemographic and clinical variables. Results We compared groups who were persistently lonely (at all time points), intermittently lonely (at one or two time points) and never lonely. After adjusting for all potential confounders and baseline predictive variables, persistent severe loneliness was associated with worse personal recovery at 18-month follow-up compared with the never lonely (reference group) (coef. = − 12.8, 95% CI -11.8, − 3.8, p

Abstract Background Little is known about the prevalence of and risk factors for adolescent mental health problems during the COVID-19 outbreak. We aimed to investigate the prevalence of depressive symptoms, their association with study-relevant problems, and the moderating effect of parent-child relationship among Chinese adolescents during the school closures. Methods We performed a cross-sectional analysis with data collected in middle and high schools in Taizhou, China. Students completed an online survey between April 16 and May 14, 2020. Depressive symptoms were assessed using the Children’s Depression Inventory. Three types of study problems were recorded, including having difficulty in studying at home, dislike of remote learning, and excessive screen entertainment time. Parental relationships were categorized into good or normal relationship and poor relationship. Linear regression and logistic regression analyses were conducted to investigate the associations between study-relevant problems and depressive symptoms. Results Using data from 6435 adolescents, we found that the prevalence of depressive symptoms was 17.7%. All the study problem measures were associated with more severe depressive symptoms. There was a moderating effect of the parental relationship on the associations between study problems and depressive symptoms. The association between number of study problems and depressive symptoms was stronger in adolescents with a poor parent-child relationship (regression coefficient 4.34 [95% CI 2.97, 5.72]) than those with a good or normal relationship (2.55 [2.35, 2.75]), p for interaction 0.002, on multivariable adjustment. Conclusions Study problems due to school closures were particularly problematic for adolescents who had poor parent-child relationships. Public health initiatives could help students to adjust study habits and improve parent-child relationships, thereby protecting against the development of depression.

Abstract Background Loneliness is an important public health problem with established adverse effects on physical and mental health. Although people with psychosis often experience high levels of loneliness, relatively little is known about the relationship between loneliness and early psychosis. Potential interventions to address loneliness might be easier to implement early in the illness when social networks and social skills may be more intact than at a later stage. We investigated the views of mental health practitioners about the context and causes of loneliness in people with early psychosis, and about potential interventions. Methods Semi-structured face-to-face interviews were conducted with mental health practitioners (n = 20). Participants were purposively recruited from four early intervention services for first-episode psychosis in the UK. Interviews were transcribed verbatim and thematic analysis was conducted. Results Participants believed that the majority of service users with early psychosis experience feelings of loneliness. They often saw socially isolated and disconnected clients and believed them to be lonely, but rarely discussed loneliness explicitly in clinical interactions. A combination of symptoms, stigma and negative sense of self were believed to underpin loneliness. Participants could not identify any specific current interventions delivered by their services for tackling loneliness, but thought some routinely provided interventions, including social groups and psychological treatments, could be helpful. They favoured making a wider range of loneliness interventions available and believed that community agencies beyond mental health services should be involved to make these effective and feasible to deliver. They suggested social participation interventions without an explicit mental health focus as potentially promising and valued a co-produced approach to intervention development. Conclusions This study suggests that loneliness is not routinely discussed in early intervention services, and a targeted strategy for tackling it is lacking. Co-produced, individualised community approaches, and interventions that target symptoms, stigma and negative self-schemas might be beneficial in alleviating loneliness for people with early psychosis. Empirical research is needed to develop and test such interventions.

Abstract Background Post-extubation stridor (PES) is one of the most common complications of invasive respiratory support, with severe cases leading to possible extubation failure (reintubation within 48 h) and increased mortality. Previous studies confirmed that prophylactic corticosteroids play an important role in reducing the risk of PES and extubation failure. However, few studies have looked at the efficacy of corticosteroids on preventing PES in patients after an emergency intubation. Aim To evaluate whether a single dose of methylprednisolone given over a set timeframe before extubation is effective in preventing PES in patients after an emergency intubation. Methods A multicenter, randomized, placebo-controlled trial will be performed in an emergency department (ED) setting. The trial will include 132 patients who fail a cuff-leak test (CLT) prior to the intervention. Patients will be randomly assigned to either intravenous methylprednisolone (40 mg) or placebo 4 h prior to extubation. Other eligible patients who pass the CLT will be included in a non-intervention (observation) group. The primary endpoint is the incidence of PES within 48 h after extubation. Secondary endpoints include oxygen therapy, respiratory support requirements, reintubation secondary to PES, adverse effects within 48 h after extubation, hospital length of stay, and hospital mortality. Discussion Patients who are intubated on an emergency basis have a higher risk of intubation-related complications. Previous studies have examined treatment regimens involving more than 10 different variations on corticosteroid treatments for PES prevention, while for ED therapy, only a simple and effective treatment would be appropriate. Corticosteroid administration is usually accompanied by adverse effects; thus, this study will be important for further risk stratification among intubated ED patients. Trial registration Chictr.org.cn ChiCTR2000030349 . Registered on 29 February 2020.

Abstract Background Loneliness has not until recently been a prominent focus in research on outcomes of mental illness. The aim of this study was to determine whether loneliness at baseline predicts poor outcomes at 4-month follow-up for individuals who have experienced mental health crises. The outcomes in this study included overall symptom severity, affective symptoms, self-rated recovery and health-related quality of life. Methods Our study reports a secondary analysis of data from a randomised controlled trial. The sample (n = 399) was taken from patients who received treatment from community crisis services. Respondents (n = 310) completed the follow-up measurement 4 months after baseline. Loneliness at baseline was assessed using an eight-item UCLA Loneliness Scale. The four mental health outcomes were measured at both baseline and follow-up. Two scales (or part thereof) assessed objective social isolation and neighbourhood social capital at baseline. Regression analyses were conducted to investigate longitudinal associations between loneliness at baseline and mental health outcomes at follow-up. Results Loneliness at baseline was associated with all four mental health outcomes at 4-month follow-up, adjusting for psychosocial, socio-demographic and clinical characteristics. A one-point higher loneliness score was associated with 0.74-point (95% CI 0.45, 1.02) and 0.34-point (95% CI 0.21, 0.47) increase in overall symptom severity score and affective symptoms score respectively, and with 1.08-point (95% CI -1.45, − 0.71) and 1.27-point (95% CI -1.79, − 0.75) decrease in self-rated recovery score and health-related quality of life score respectively. Loneliness was a better predictor of clinical outcomes than objective social isolation and social capital, even though the associations with clinical outcomes were reduced and no longer statistically significant following adjustment for their baseline values. A significant association with quality of life persisted after adjustment for its baseline score. Conclusions Greater loneliness at baseline predicted poorer health-related quality of life at follow-up. There were cross-sectional associations between loneliness and clinical outcomes, but their longitudinal relationship cannot be confirmed. Further research is needed to clearly establish their underpinning pathways. Reducing loneliness may be a promising target to improve recovery for mental health community crisis service users.

Abstract Background It is believed that deposition of amyloid beta (Aβ) in the brain is the central pathological changes of Alzheimer’s disease (AD), which triggers a series of pathological processes. However, the relationship between dyslipidemia and AD is uncertain. Considering the peripheral Aβ levels are related to brain Aβ deposition, we explore the relationships between blood lipids and plasma Aβ. Methods Participants who lived in the selected village of Xi’an for more than 3 years were enrolled, aged 40–85 years (n = 1282, 37.9% male). Fasting blood lipid, plasma Aβ levels, basic information and living habits were measured. Multiple linear regressions were used. Results In total population, blood lipids were not associated with plasma Aβ. After stratified by blood pressure, serum total cholesterol (TC) and low-density lipoprotein (LDL-c) were positively associated with plasma Aβ42 levels (βTC = 0.666, P TC = 0.024; βLDL-c = 0.743, P LDL-c = 0.011, respectively) in normal blood pressure. LDL-c was negatively associated with plasma Aβ40 levels (β = − 0.986, P = 0.037) in high blood pressure. Conclusion Elevated plasma Aβ42 levels are associated with higher TC and LDL-c in normal blood pressure. Elevated plasma Aβ40 levels are associated with lower LDL-c in high blood pressure. This indicated that the relationships between blood lipids and plasma Aβ were confounded by blood pressure.

Abstract Background The objectives were to investigate the disparity in the prevalence of bone metastases (BM) between the sexes and to assess the effect of female sex on the development and prognosis of BM. Methods Cases of invasive non-sex-specific cancers diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) program were used. The prevalence of BM was calculated by combining the prevalence of BM among different cancers. Multivariable logistic regression and proportion hazard regression were conducted to investigate the effect of female sex, and the results were pooled by meta-analysis. Results The pooled prevalence of BM among male and female patients was 2.3% (95% CI: 1.6–3.2%) and 1.8% (95% CI: 1.2–2.6%), respectively. The pooled prevalence of BM dramatically decreased for patients aged 11–40 years old, plateaued for patients aged 41–90 years old and increased for patients aged > 90 years old in both male and female patients. Meta-analysis suggested that female sex had a protective effect on the development of BM (pooled OR = 0.80; 95% CI: 0.75–0.84; p

Abstract Background Serum lipids [total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG)] are risk factors for stroke, but the relationships between serum lipids and cognitive impairment have not been verified completely. In this study, we studied the relationships between serum lipids and cognitive impairment and explored whether gender and age had effects on the relationships. Methods In this cross-sectional study, we collected serum lipids and cognitive function information from 1762 participants (aged 40–85). Univariate analysis, multivariate analysis, and both gender- and age-based stratified multivariate analysis were used. Results In the entire sample set, there was no significant correlation between serum lipid parameters (TC, LDL-C, HDL-C and TG) and cognitive impairment. In both gender- and age-based stratified multivariate analysis, high serum TC was positively associated with cognitive impairment in the elderly (> 55) male participants (OR = 4.404, 95% CI = 1.264–15.344, p = 0.02), and high serum LDL-C was positively correlated with cognitive impairment in the elderly female subjects (OR = 2.496, 95% CI = 1.057–5.896, p = 0.037), while high serum TG was negatively associated with cognitive impairment in the middle-aged (≤ 55) male participants (OR = 0.157, 95% CI = 0.051–0.484, p = 0.001). Conclusions The relationships between serum lipids and cognitive impairment are gender- and age- dependent, with high serum TC and LDL-C may be risk factors of cognitive impairment in the elderly male and female subjects respectively, while high serum TG may be protector of cognitive impairment in the middle-aged male participants.

Abstract Background The adverse effects of loneliness and of poor perceived social support on physical health and mortality are established, but no systematic synthesis is available of their relationship with the outcomes of mental health problems over time. In this systematic review, we aim to examine the evidence on whether loneliness and closely related concepts predict poor outcomes among adults with mental health problems. Methods We searched six databases and reference lists for longitudinal quantitative studies that examined the relationship between baseline measures of loneliness and poor perceived social support and outcomes at follow up. Thirty-four eligible papers were retrieved. Due to heterogeneity among included studies in clinical populations, predictor measures and outcomes, a narrative synthesis was conducted. Results We found substantial evidence from prospective studies that people with depression who perceive their social support as poorer have worse outcomes in terms of symptoms, recovery and social functioning. Loneliness has been investigated much less than perceived social support, but there is some evidence that greater loneliness predicts poorer depression outcome. There is also some preliminary evidence of associations between perceived social support and outcomes in schizophrenia, bipolar disorder and anxiety disorders. Conclusions Loneliness and quality of social support in depression are potential targets for development and testing of interventions, while for other conditions further evidence is needed regarding relationships with outcomes.