Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1.

Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis. And overexpression of SPNS1 exhibited opposite functions. Furthermore, ESCC cells became more sensitive to 5-fluorouracil (5-FU) when SPNS1 was knocked down. Transcriptome sequencing revealed that NEU1 was one significant DEG affected by SPNS1 and positively correlated with SPNS1 expression. Oseltamivir phosphate (OP), one NEU1 inhibitor, markedly reversed 5-FU resistance, migration, and proliferation induced by high expression of SPNS1 both in vivo and in vitro. Our findings indicated that SPNS1 might promote the progression of ESCC by upregulating NEU1 expression and influencing chemotherapy sensitivity. These results provide new perceptions into potential therapeutic targets for ESCC treatment. The present study aimed to investigate the role and underlying mechanism of SPNS1 in ESCC.

Effects of N Acetylcysteine on the Expression of Genes Associated with Reproductive Performance in the Goat Uterus during Early Gestation.

N acetylcysteine (NAC) affects antioxidation and reactive oxygen species scavenging in the body and thereby promotes embryonic development and implantation and inhibits inflammation. The mechanism through which NAC regulates reproductive performance in the uteri of goats during early gestation remains unclear. In this study, the treatment group was fed 0.07% NAC for the first 35 days of gestation, whereas the control group received no NAC supplementation. The regulatory genes and key pathways associated with goat reproductive performance under NAC supplementation were identified by RNA-seq. RT-qPCR was used to verify the sequencing results and subsequently construct tissue expression profiles of the relevant genes. RNA-seq identified 19,796 genes coexpressed in the control and treatment groups and 1318 differentially expressed genes (DEGs), including 787 and 531 DEGs enriched in the treatment and control groups, respectively. A GO analysis revealed that the identified genes mapped to pathways such as cell activation, cytokine production, cell mitotic processes, and angiogenesis, and a KEGG enrichment analysis showed that the DEGs were enriched in pathways associated with reproductive regulation, immune regulation, resistance to oxidative stress, and cell adhesion. The RT-qPCR analysis showed that BDNF and CSF-1 were most highly expressed in the uterus, that WIF1 and ESR2 showed low expression in the uterus, and that CTSS, PTX3, and TGFß-3 were most highly expressed in the oviduct, which indicated that these genes may be directly or indirectly involved in the modulation of reproduction in early-gestation goats. These findings provide fundamental data for the NAC-mediated modulation of the reproductive performance of goats during early gestation.

A Proteomic Study of the Effect of N-acetylcysteine on the Regulation of Early Pregnancy in Goats.

Dietary supplementation with N-acetyl-L-cysteine (NAC) may support early pregnancy regulation and fertility in female animals. The purpose of this study was to investigate the effect of supplementation with 0.07% NAC on the expression of the uterine keratin gene and protein in Qianbei-pockmarked goats during early pregnancy using tandem mass spectrometry (TMT) relative quantitative proteomics. The results showed that there were significant differences in uterine keratin expression between the experimental group (NAC group) and the control group on day 35 of gestation. A total of 6271 proteins were identified, 6258 of which were quantified by mass spectrometry. There were 125 differentially expressed proteins (DEPs), including 47 upregulated and 78 downregulated proteins, in the NAC group. Bioinformatic analysis showed that these DEPs were mainly involved in the transport and biosynthesis of organic matter and were related to the binding of transition metal ions, DNA and proteins and the catalytic activity of enzymes. They were enriched in the Jak-STAT signalling pathway, RNA monitoring pathway, amino acid biosynthesis, steroid biosynthesis and other pathways that may affect the early pregnancy status of does through different pathways and thus influence early embryonic development. Immunohistochemistry, real-time quantitative PCR and Western blotting were used to verify the expression and localization of glial fibrillary acidic protein (GFAP) and pelota mRNA surveillance and ribosomal rescue factor (PELO) in uterine horn tissue. The results showed that both PELO and GFAP were localized to endometrial and stromal cells, consistent with the mass spectrometry data at the transcriptional and translational levels. Moreover, NAC supplementation increased the levels of the reproductive hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol (E2), progesterone (P4), superoxide dismutase (SOD), glutamate peroxidase (GSH-Px) and nitric oxide (NO) in the serum of does. These findings provide new insight into the mechanism by which NAC regulates early pregnancy and embryonic development in goats.

A WeChat-based self-compassion training to improve the treatment adherence of patients with schizophrenia in China: Protocol for a randomized controlled trial.

Background: At present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent studies have demonstrated that increasing a patient's level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia. Methods: The protocol for the randomized controlled trial (RCT) is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline (T0), immediately after the intervention (T1), and 3 weeks after the intervention (T2). Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention (T1). Expected results: The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients' desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries.

CYP19A1 May Influence Lambing Traits in Goats by Regulating the Biological Function of Granulosa Cells.

Abnormal expression of CYP19A1, a gene related to steroid hormone synthesis, causes steroid hormone disruption and leads to abnormal ovulation in granulosa cells. However, the exact mechanism of CYP19A1 regulation is unclear. In this study, we confirmed the localization of CYP19A1 in goat ovarian tissues using immunohistochemistry. Subsequently, we investigated the effects of CYP19A1 on granulosa cell proliferation, steroid hormone secretion, and expression of candidate genes for multiparous traits by overexpressing and silencing CYP19A1 in goat granulosa cells (GCs). The immunohistochemistry results showed that CYP19A1 was expressed in all types of follicular, luteal, and granulosa cells, with subcellular localization results revealing that CYP19A1 protein was mainly localized in the cytoplasm and nucleus. Overexpression of CYP19A1 significantly increased the mRNA levels of CYP19A1, FSHR, and INHBA, which are candidate genes for multiple birth traits in goats. It also promoted cell proliferation, PCNA and Cyclin E mRNA levels in granulosa cells, and secretion of estrogen and progesterone. However, it inhibited the mRNA levels of STAR, CYP11A1, and 3ßSHD, which are genes related to steroid synthesis. Silencing CYP19A1 expression significantly reduced CYP19A1, FSHR, and INHBA mRNA levels in granulosa cells and inhibited granulosa cell proliferation and PCNA and Cyclin E mRNA levels. It also reduced estrogen and progesterone secretion but enhanced the mRNA levels of STAR, CYP11A1, and 3ßSHD. CYP19A1 potentially influenced the lambing traits in goats by affecting granulosa cell proliferation, hormone secretion, and expression of candidate genes associated with traits for multiple births.

Association between self-care disability and depressive symptoms among middle-aged and elderly Chinese people.

OBJECTIVE: In the context of an increased focus on geriatric depression in recent years, this study examined the associations between different types of self-care disability, the number of self-care disabilities, and depressive symptoms among middle-aged and elderly Chinese people. METHOD: The data for this study were extracted from the follow-up survey (conducted in 2018) of the China Health and Retirement Longitudinal Study (CHARLS). The sample comprised 10808 participants aged 45 years and older. The Activities of Daily Living (ADL) scale and the Center for Epidemiological Studies Depression (CESD-10) Scale were used to assess self-care disability and depressive symptoms, respectively. RESULT: The prevalence of depressive symptoms and self-care disability among the surveyed residents was 45.1% and 23.4%, respectively. Overall, there was a significant positive association between self-care disability and depressive symptoms. Participants who reported having a self-care disability in relation dressing, bathing, transferring in and out of bed, using the toilet, and controlling urination and defecation were found to have a significantly higher risk of depressive symptoms. In addition, participants with a greater cumulative quantity of self-care disabilities had a higher risk of depressive symptoms, and higher CESD-10 scores. CONCLUSION: Self-care disability is a risk factor for depressive symptoms among middle-aged and elderly Chinese people. A positive correlation between the number of self-care disabilities and the risk of depressive symptoms was found.

TIMP1 may affect goat prolificacy by regulating biological function of granulosa cells.

Tissue inhibitor of metalloproteinase 1 (TIMP1) is associated with animal reproductive processes, such as follicular growth, ovulation, luteinization, and embryo development in mammals. The purposes of this study were to explore the expression and localization of TIMP1 in the ovarian tissues and determine the effect of TIMP1 on the function of granulosa cells and the association of TIMP1 with lambing-related genes of the goats. Immunohistochemical analysis showed that TIMP1 protein was strongly expressed by granulosa cells. Enzyme-linked immunosorbent assay (ELISA) results showed that TIMP1 overexpression promoted the secretion of estradiol of granulosa cells after 12, 24, and 48 h of transfection. Moreover, in vitro experiments indicated that TIMP1 had the ability to promote the cell proliferation and elevate the transcriptional levels of four genes associated with goat prolificacy, including BMPR-1B, BMP15, GDF9, and FSHB, in granulosa cells. In conclusion, TIMP1 could be an important molecule in regulating reproductive performance of the goats by affecting estrogen secretion and cell proliferation, as well as the expression of lambing-related genes of granulosa cells in the goats.

Cathepsin D knockdown regulates biological behaviors of granulosa cells and affects litter size traits in goats.

Cathepsin D (CTSD), the major lysosomal aspartic protease that is widely expressed in different tissues, potentially regulates the biological behaviors of various cells. Follicular granulosa cells are responsive to the increase of ovulation number, hence indirectly influencing litter size. However, the mechanism underlying the effect of CTSD on the behaviors of goat granulosa cells has not been fully elucidated. This study used immunohistochemistry to analyze CTSD localization in goat ovarian tissues. Moreover, western blotting was applied to examine the differential expression of CTSD in the ovarian tissues of monotocous and polytocous goats. Subsequently, the effects of CTSD knockdown on cell proliferation, apoptosis, cell cycle, and the expression of candidate genes of the prolific traits, including bone morphogenetic protein receptor IB (BMPR-IB), follicle-stimulating hormone (FSHR), and inhibin α (INHA), were determined in granulosa cells. Results showed that CTSD was expressed in corpus luteum, follicle, and granulosa cells. Notably, CTSD expression in the monotocous group was significantly higher than that in the polytocous group. In addition, CTSD knockdown could improve granulosa cell proliferation, inhibit cell apoptosis, and significantly elevate the expression of proliferating cell nuclear antigen (PCNA) and B cell lymphoma 2 (Bcl-2), but it lowered the expression of Bcl-2-associated X (Bax) and caspase-3. Furthermore, CTSD knockdown significantly reduced the ratios of cells in the G0/G1 and G2/M phases but substantially increased the ratio of cells in the S phase. The expression levels of cyclin D2 and cyclin E were elevated followed by the obvious decline of cyclin A1 expression. However, the expression levels of BMPR-IB, FSHR, and INHA clearly increased as a result of CTSD knockdown. Hence, our findings demonstrate that CTSD is an important factor affecting the litter size trait in goats by regulating the granulosa cell proliferation, apoptosis, cell cycle, and the expression of candidate genes of the prolific trait.

Dignity and its related factors among older adults in long-term care facilities: A cross-sectional study.

OBJECTIVES: This study aimed to explore the dignity and related factors among older adults in long-term care facilities. METHODS: Cross-sectional data were obtained from a sample of 253 Chinese older adults dwelling in long-term care facilities. Dignity among older adults was measured using the Dignity Scale, and its potential correlates were explored using multiple linear regressions. RESULTS: Results showed that the total score of the Dignity Scale is 151.95 ± 11.75. From high to low, the different factors of dignity among older adults in long-term care facilities were as follows: caring factors (4.83 ± 0.33), social factors (4.73 ± 0.41), psychological factors (4.66 ± 0.71), value factors (4.56 ± 0.53), autonomous factors (4.50 ± 0.57), and physical factors (4.38 ± 0.55). A higher score of the Dignity Scale was associated with higher economic status, fewer chronic diseases, less medication, better daily living ability and long-time lived in cities. CONCLUSION: Older adults with low economic status, more chronic diseases, and poor daily living ability, taking more medications, or the previous residence in rural areas seem to be most at low-level dignity in long-term care facilities and thus require more attention than their peers.

Sodium Danshensu promotes the healing of stage 2 pressure injury wounds in ischemia/reperfusion injury rat models: possible regulation of apoptosis and inflammatory response.

OBJECTIVE: To investigate the protective effect and possible mechanism of sodium Danshensu (SDSS) against pressure injury caused by ischemia/reperfusion (I/R) injury. METHODS: Sprague-Dawley rats were randomly divided into five groups of eight rats each: control group, model group, 10 mg/kg SDSS-treated group, 20 mg/kg SDSS-treated group, and 40 mg/kg SDSS-treated group. We used two round ferrite magnetic plates of 15 mm diameter and 3 mm thickness to establish stage 2 pressure injury model rats. Each rat was subjected to five cycles of ischemia and reperfusion to induce pressure injury. One cycle consisted of 2 h of ischemia and 0.5 h of reperfusion, which meant that each cycle included 2 h of pressure and 0.5 h of pressure relief. The outline of the wound was delineated by butter paper and marker pen, and histopathological changes were observed by hematoxylin and eosin staining. In addition, the number of apoptotic cells and the activity of caspase-3 were assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling and caspase-3 assay kits, respectively. The expression of apoptosis-regulatory proteins and inflammatory mediators was investigated by enzyme-linked immunosorbent assay. RESULTS: Results showed that treatment with SDSS for 7 d after establishing the pressure injury model remarkably improved the healing rate of the wound. SDSS also inhibited the levels of tumor ne- crosis factor-α, myeloperoxidase, and intercellular cell adhesion molecule-1; decreased the number of apoptotic cells; increased the ratio of B-cell lymphoma-2 (Bcl-2) / Bcl-2-associated X (Bax); and regulated the expression and activity of caspase-3. CONCLUSION: Our results suggest that SDSS exhibits a treatment efficacy for pressure injury caused by I/R injury possibly by inhibiting apoptosis and inflammatory response.

[Cloning and expression of the growth hormone gene and its effect on the proliferation of skeletal muscle cells of Guizhou cattle].

The aim of this study was to investigate the expression of growth hormone (GH) gene on skeletal muscle cell proliferation of Guizhou cattle. The coding sequence of cattle GH gene was amplified by reverse transcription PCR, cloned into the pUCM-T vector and then used to construct the GH gene overexpression vector pEGFP-N3-GH. The expression of the GH gene in skeletal muscle-related tissues (psoas major and longissimus dorsi) of Guizhou cattle was determined by real-time fluorescent quantitative PCR (RT-qPCR). This was followed by culturing and identification of the bovine primary skeletal muscle cells. Subsequently, we introduced the GH gene overexpression vector into the cells to investigate its effect on the proliferation of bovine skeletal muscle cells and the expression of insulin like growth factor 1 and 2 genes related to skeletal muscle growth and development. RT-qPCR results showed that the expression level of GH gene was higher in the psoas major than in the longissimus dorsi of Guizhou cattle, and the expression level in the psoas major of Guanling cattle and Weining cattle was significantly higher than in the longissimus dorsi (P<0.05). The transfection and proliferation results showed that pEGFP-N3-GH significantly increased the expression of GH, IGF-1, and IGF-2 genes in skeletal muscle cells compared to pEGFP-N3 (PP<0.05), and that overexpression of the GH gene also significantly increased the proliferation rate of skeletal muscle cells at the four periods examined (PP<0.01). Our results suggest that GH gene can promote the proliferation of skeletal muscle cells of Guizhou cattle and exerts a positive regulatory effect. This lays the foundation for further exploring the mechanism by which the GH gene affects the growth and development of Guizhou cattle.

A Systems Vaccinology Approach Reveals Temporal Transcriptomic Changes of Immune Responses to the Yellow Fever 17D Vaccine.

In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays. At 4 h postvaccination, genes associated with innate cell differentiation and cytokine pathways were dramatically downregulated, whereas receptor genes were upregulated, compared with their baseline levels at 0 h. Immune response pathways were primarily upregulated on days 5 and 7, accompanied by the upregulation of the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust activation of innate immunity within 2 d postvaccination and a durable adaptive response, as assessed by transcriptional profiling. Coexpression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell (DC) and CD4+ T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for Abs against another flavivirus exhibited significantly impaired DC, NK cell, and T cell function in response to YF-17D vaccination. Overall, our findings indicate that YF-17D vaccination induces a prompt innate immune response and DC activation, a robust Ag-specific T cell response, and a persistent B cell/memory B cell response.