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Abstract Background Although national policies in China are comprehensive and instructive, a wide disparity exists between different cities. The current status of public mental health services by region in China remains unclear. This study aimed to investigate policies related to public mental health services, the contact coverage of public mental health services and outcomes of service users. Methods A cross-sectional study was carried out in Southern China, between April 2021 and March 2022. Considering the geographical location, socioeconomic development levels, and prevalence of severe mental illness, four cities including Wuhan, Changsha, Guangzhou, and Shenzhen were selected. Relevant service providers were asked to report data on mental health policies and facility-related information, including mental health resources, registration rates of patients, management rates of patients, and medication rates of patients. Eligible patients were invited to report service user-related data, including contact coverage of public mental health services and their outcomes. SPSS 26.0 was used for data analysis. Results The four cities in Southern China have made different efforts to develop public mental health services, primarily focusing on socio-economically disadvantaged individuals. Community health centers in Guangzhou and Shenzhen reported having more professional human resources on mental health and higher mental health budgets for patients. The contact coverage rates of most public mental services were higher than 80%. Patients in Changsha (B = 0.3; 95%CI: 0.1–0.5), Guangzhou (B = 0.2; 95%CI: 0.1–0.3), and Shenzhen (B = 0.3; 95%CI: 0.1–0.4) who received social medical assistance services reported higher levels of medication adherence. Patients in Wuhan (B = -6.5; 95%CI: -12.9--0.1), Guangzhou (B = -2.8; 95%CI: -5.5--0.1), and Shenzhen who received community-based rehabilitation services reported lower levels of disability (B = -2.6; 95%CI: -4.6--0.5). Conclusions There have been advances in public mental health services in the four Southern cities. The contact coverage rates of most public mental health services were higher than 80%. Patients’ utilization of public mental services was associated with better health outcomes. To improve the quality of public mental health services, the government should try to engage service users, their family members, and supporters in the design, delivery, operationalization, and evaluation of these public mental health services in the future.

ABSTRACT Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

Abstract Pleiotropy is frequently detected in agronomic traits of wheat (Triticum aestivum). A locus on chromosome 4B, QTn/Ptn/Sl/Sns/Al/Tgw/Gl/Gw.caas-4B, proved to show pleiotropic effects on tiller, spike, and grain traits using a recombinant inbred line (RIL) population of Qingxinmai × 041133. The allele from Qingxinmai increased tiller numbers, and the allele from line 041133 produced better performances of spike traits and grain traits. Another 52 QTL for the eight traits investigated were detected on 18 chromosomes, except for chromosomes 5D, 6D, and 7B. Several genes in the genomic interval of the locus on chromosome 4B were differentially expressed in crown and inflorescence samples between Qingxinmai and line 041133. The development of the KASP marker specific for the locus on chromosome 4B is useful for molecular marker-assisted selection in wheat breeding.

Abstract Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36, originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance.

An active chitosan (CS) film containing a nano-hydroxyapatite–tea polyphenol (HAP-TP) complex was designed and prepared. The effects of HAP-TP loading on the structural and physicochemical properties of the CS-based film were evaluated. The mechanical and thermal properties of the film were significantly improved by the resulting intermolecular interactions and formation of hydrogen bonds between HAP-TP and CS, which reduced the water vapor and oxygen permeabilities of the film by 29.78 and 35.59 %, respectively. The CS-HAP-TP film exhibited excellent slow-release behavior and antioxidant activity, with a cumulative release rate at 700 h 6.79 % lower than that of CS-TP films. The CS-HAP-TP film significantly inhibited the deterioration of semi-dried golden pompano, and thus helped to retain the taste of umami and sweet amino acids in fish samples, while reducing off-flavor generation. The film therefore shows considerable potential as an active packaging material for the preservation of semi-dried fish products.

IntroductionObservational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation.MethodsFor Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments.ResultsOur results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34–4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32–3.43]), benign neoplasm of the larynx (2.01 [1.36–2.96]), melanoma (1.74 [1.17–2.59]), follicular lymphoma (1.50 [1.06–2.11]), autoimmune thyroiditis (2.47 [1.49–4.08]), and autoimmune hyperthyroidism (1.93 [1.17–3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland.ConclusionCasting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

The utilization of in-situ resources will be crucial for the survival of astronauts in space. Therefore, plants and crops will be important for humans in space as they serve as food, provide oxygen, and remove carbon dioxide, enhancing habitability. The aim of this research is to explore the growth of crops on celestial bodies prior to human arrival. The paper outlines the creation of a novel capsule by Green Moon Project (GMP) designed to meet essential criteria for monitoring and enhancing crop cultivation on the lunar terrain, tackling key obstacles such as self-propagation, fluctuating light patterns, water provision, and monitoring germination and growth stages. The Center of Space Exploration (hereafter COSE) managed to sprout the first seed on another celestial body during the Chang’e 4 mission on the Moon in January 2019. This achievement means an important step in space agriculture and widens the biological research of crops that will sustain future crewed missions and human bases in space. Space farming requires greater understanding if humans are to survive in space without constant contact from Earth and that is why GMP goals are aligned COSE’s. Therefore, GMP and COSE work in synergy to boost the research of space farming, future crops, habitability, and close controlled environmental systems. Due to the similarities between both projects, both teams decided to join efforts and cooperate in future space missions. To provide scientific support and technical solutions for future long-term crewed exploration missions, it is mandatory to conduct ground verification experiments of controllable extraterrestrial ecosystems.

Abstract This study aimed to investigate the associations between the clinical characteristics and effectiveness of anti-PD-1 inhibitors in patients with EGFR-sensitive mutations, aiming to identify the potential subgroup of patients who might benefit from anti-PD-1 inhibitor treatment. Patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-sensitive mutations who received subsequent anti-PD-1 inhibitors in combination with chemotherapy/antiangiogenic agents or alone after progression to tyrosine kinase inhibitors (TKIs) were screened. Clinical characteristics, including hematological parameters, were investigated for potential correlations with clinical outcomes. Subgroup and multivariate analyses were used for further confirmation of the relationship. Kaplan–Meier curves and Cox survival regression models using the log-rank test were used for progression-free survival (PFS) and overall survival (OS) assessments between the groups. Multiple regression analysis was performed using the standard regression coefficient values. The Wilcoxon test was used for the analysis of the variation in NLR. P ≤ 0.05 was considered to indicate statistical significance. This study was a retrospective study. Twenty-two patients met the inclusion criteria and were included in the study. The median PFS was 3.05 months (95% CI, 2.9–10.2 months). The median OS was 7.30 months (95% CI, 5.2–18.1 months). PFS in low neutrophil to lymphocyte ratio (NLR ≤ 4) was significantly longer than high NLR (NLR > 4, 5.7 months versus 2.0 months, HR, 0.35, 95% CI, 0.08–0.63, P = 0.0083). The OS in the low NLR group was also significantly better than that in the high NLR group (OS, 21.3 months versus 5.0 months, HR, 0.33; 95% CI, 0.09–0.74; P = 0.0163). In the multivariate analysis, NLR was the only significant factor for OS benefits (β = 3.535, 95% CI, 1.175–10.636, P = 0.025). Further investigation revealed that front-line TKIs exposure may contribute to the elevation or decrease of NLR, and finally lead to different efficacy outcomes by anti-PD-1 inhibitors. The findings suggest that a portion of advanced NSCLC patients with low NLR characteristics (NLR ≤ 4), even those harboring EGFR-sensitive mutations, could benefit from anti-PD-1 inhibitors as further line treatment after progression to EGFR-TKIs.

Abstract Evidence on the associations between patient’s disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia is lacking. This study aimed at explore the underlying mechanisms between patient’s disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia. A cross-sectional study was carried out in four Chinese cities (Wuhan, Changsha, Guangzhou, and Shenzhen), between April, 2021 and March, 2022. A total of 493 patients and their family caregivers were invited to report related data. The Zarit burden interview, WHODAS 2.0, the Potentially harmful behavior scale, the Affiliate Stigma Scale, and the Multidimensional Scale of perceived social support were used to collect data. Linear regression analysis and bootstrapping analysis were conducted. The adjusted regression results showed that patients’ disability (B = 0.616; 95% CI: 0.479–0.753), potentially harmful behavior on caregivers (B = 0.474; 95% CI: 0.232–0.716), and caregiver’s low social support (B = −0.079; 95% CI: −0.158– −0.002), high level of affiliate stigma (B = 13.045; 95% CI: 10.227–15.864) were associated with higher level of caregiver burden (p

A recombinant inbred line (RIL) population derived from wheat landrace Qingxinmai and breeding line 041133 exhibited segregation in resistance to powdery mildew and stripe rust in five and three field tests, respectively. A 16K genotyping by target sequencing (GBTS) single-nucleotide polymorphism (SNP) array-based genetic linkage map was used to dissect the quantitative trait loci (QTLs) for disease resistance. Four and seven QTLs were identified for adult-plant resistance (APR) against powdery mildew and stripe rust. QPm.caas-1B and QPm.caas-5A on chromosomes 1B and 5A were responsible for the APR against powdery mildew in line 041133. QYr.caas-1B, QYr.caas-3B, QYr.caas-4B, QYr.caas-6B.1, QYr.caas-6B.2, and QYr.caas-7B detected on the five B-genome chromosomes of line 041133 conferred its APR to stripe rust. QPm.caas-1B and QYr.caas.1B were co-localized with the pleiotropic locus Lr46/Yr29/Sr58/Pm39/Ltn2. A Kompetitive Allele Specific Polymorphic (KASP) marker KASP_1B_668028290 was developed to trace QPm/Yr.caas.1B. Four lines pyramiding six major disease resistance loci, PmQ, Yr041133, QPm/Yr.caas-1B, QPm.caas-2B.1, QYr.caas-3B, and QPm.caas-6B, were developed. They displayed effective resistance against both powdery mildew and stripe rust at the seedling and adult-plant stages.

This research explores the application of an Empathy Design Thinking (EDT) curriculum within primary education, guided by the principles of Experience, Empathy, Exploration, and Evaluation, to examine its effect on fostering student creativity in a Chinese context. The curriculum was redesigned into a streamlined, modular format for ease of integration into existing educational frameworks. Findings demonstrate a positive impact on students' creative thinking abilities, particularly in enhancing fluency and flexibility, with notable mentions of empathy's vital role in the educational process. This study aligns with global educational trends emphasizing the need for empathetic and comprehensive learning experiences, offering insights into the potential of EDT to enrich creative education for primary students, educators, curriculum developers, and policymakers.

Abstract Family caregiving of people living with schizophrenia (PLS) can be burdensome, and some family caregivers may perpetrate abusive behavior that could be harmful to PLS. This study aims to examine the association of family caregivers’ abusive behavior with internalized stigma of PLS and draw attention to this problem. PLS were recruited from four cities across China and completed measures of abusive behavior and internalized stigma. Linear regression analyses were used to determine the association between family caregivers’ abusive behavior and internalized stigma of PLS. A total of 693 PLS were include in this study. 22.7% of the participants had experienced one or more of the abusive behaviors perpetrated by family caregivers. The most common type of abusive behavior towards PLS was verbal abuse and 4.2% of the participants reported physical abuse. 44.6 % of participants reported a high level of internalized stigma. PLS who experienced any abusive behavior by family caregivers had significantly higher levels of internalized stigma. Family caregivers’ abusive behavior is positively associated with alienation and social withdrawal but not with stereotype endorsement and discrimination of PLS. To end all forms of stigma and discrimination against PLS, more attention needs to be paid to the families of PLS.

Two-dimensional [Formula: see text]-In2Se3 exhibits simultaneous intercorrelated in-plane and out-of-plane polarization, making it a highly promising material for use in memories, synapses, sensors, detectors, and optoelectronic devices. With its narrow bandgap, [Formula: see text]-In2Se3 is particularly attractive for applications in photodetection. However, relatively little research has been conducted on the out-of-plane photoconductive and bulk photovoltaic effects in [Formula: see text]-In2Se3. This limits the potential of [Formula: see text]-In2Se3 in the device innovation and performance modification. Herein, we have developed an [Formula: see text]-In2Se3-based heterojunction with a transparent electrode of two-dimensional Ta2NiS5. The out-of-plane electric field can effectively separate the photo-generated electron–hole pairs in the heterojunction, resulting in an out-of-plane responsivity (R), external quantum efficiency (EQE), and specific detectivity ([Formula: see text]) of 0.78[Formula: see text]mA/W, 10[Formula: see text]% and [Formula: see text] Jones, respectively. The out-of-plane bulk photovoltaic effect has been demonstrated by changes in the short circuit current (SCC) and open circuit voltage ([Formula: see text]) with different optical power intensity and temperature, which indicates that [Formula: see text]-In2Se3-based heterojunctions has application potential in mid-far infrared light detection based on its out-of-plane photoconductive and bulk photovoltaic effects. Although the out-of-plane photoconductive and bulk photovoltaic effects are relatively lower than that of traditional materials, the findings pave the way for a better understanding of the out-of-plane characteristics of two-dimensional [Formula: see text]-In2Se3 and related heterojunctions. Furthermore, the results highlight the application potential of [Formula: see text]-In2Se3 in low-power device innovation and performance modification.

Abstract Objective This study aimed to explore the molecular mechanism underlying the role of Pin1 in cognitive dysfunction in diabetic mice. Methods Using a streptozotocin‐induced diabetic mouse model, an adeno‐associated virus carrying the Pin1 gene was used to upregulate Pin1 expression in the hippocampus of diabetic mice. Animal behavior tests and molecular biology techniques were further used to explore the role of Pin1 in cognitive dysfunction in diabetic mice. Results Our study demonstrated that upregulation of Pin1 expression increased the phosphorylation of AKT and insulin receptor substrate 1 downstream signaling molecules of the IR‐IGF1R pathway, increased the phosphorylation of GSK‐3β, and concomitantly decreased the phosphorylation of Tau in the hippocampus of diabetic mice, thereby improving the ultrastructural pathology of the hippocampus and further alleviating diabetes‐related cognitive impairment. Conclusion Pin1 can improve cognitive dysfunction in diabetic mice.

IntroductionThe lower respiratory tract microbiome is widely studied to pinpoint microbial dysbiosis of diversity or abundance that is linked to a number of chronic respiratory illnesses. However, it is vital to clarify how the microbiome, through the release of microbial metabolites, impacts lung health and oncogenesis.MethodsIn order to discover the powerful correlations between microbial metabolites and disease, we collected, under electronic bronchoscopy examinations, samples of paired bronchoalveolar lavage fluids (BALFs) from tumor-burden lung segments and ipsilateral non-tumor sites from 28 lung cancer participants, further performing metagenomic sequencing, short-chain fatty acid (SCFA) metabolomics, and multiomics analysis to uncover the potential correlations of the microbiome and SCFAs in lung cancer.ResultsIn comparison to BALFs from normal lung segments of the same participant, those from lung cancer burden lung segments had slightly decreased microbial diversity in the lower respiratory tract. With 18 differentially prevalent microbial species, including the well-known carcinogens Campylobacter jejuni and Nesseria polysaccharea, the relative species abundance in the lower respiratory tract microbiome did not significantly differ between the two groups. Additionally, a collection of commonly recognized probiotic metabolites called short-chain fatty acids showed little significance in either group independently but revealed a strong predictive value when using an integrated model by machine learning. Multiomics also discovered particular species related to SCFAs, showing a positive correlation with Brachyspira hydrosenteriae and a negative one with Pseudomonas at the genus level, despite limited detection in lower airways. Of note, these distinct microbiota and metabolites corresponded with clinical traits that still required confirmation.ConclusionsFurther analysis of metagenome functional capacity revealed that genes encoding environmental information processing and metabolism pathways were enriched in the lower respiratory tract metagenomes of lung cancer patients, further supporting the oncogenesis function of various microbial species by different metabolites. These findings point to a potent relationship between particular components of the integrated microbiota-metabolites network and lung cancer, with implications for screening and diagnosis in clinical settings.

Pathological features of Alzheimer's Disease (AD) include alterations in the structure and function of neurons as well as of myelin sheaths. Accumulated evidence shows that aerobic type of exercise can enhance neuroplasticity in mouse models of AD. However, whether and how aerobic exercise can affect myelin sheath repair and neuroprotection in the AD models remains unclear. In this study we tested the hypotheses that 1) myelin structural alterations in 3xTg-AD mice would be related to abnormalities in oligodendrocyte lineage cells, resulting in impaired learning and memory, and 2) a 6-month aerobic exercise intervention would have beneficial effects on such alterations. Two-month-old male 3xTg-AD mice were randomly assigned to a control (AC) or an exercise (AE) group, and age-matched male C57BL/6;129 mice were also randomly assigned to a normal control (NC) or an exercise (NE) group, with n = 12 in each group. Mice in the exercise groups were trained on a motor-drive treadmill, 60 min per day, 5 days per week for 6 months. Cognitive function was assessed at the end of the intervention period. Then, brain specimens were obtained for assessments of morphological and oligodendrocyte lineage cell changes. The results of electron microscopy showed that myelin ultrastructure demonstrated a higher percentage of loose and granulated myelin sheath around axons in the temporal lobe in the AC, as compared with the NC group, along with greater cognitive dysfunction at 8-months of age. These differences were accompanied by significantly greater myelin basic protein (MBP) expression and less neuron-glial antigen-2 (NG2) protein and mRNA levels in the AC, compared to the NC. However, there were no significant between-group differences in the G-ratio (the ratio of axon diameter to axon plus myelin sheath diameter) and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) protein and mRNA levels. The aerobic exercise ameliorated cognitive deterioration and appeared to keep components of myelin sheath and oligodendrocyte precursor cells stabilized, resulting in a decrease in the percentage of loose and granulated myelin sheath and MBP protein, and an increase in NG2 protein and mRNA levels in the AE group. Therefore, the 6-month exercise intervention demonstrated beneficial effects on myelin lesions, abnormal differentiation of oligodendrocytes and general brain function in the 3xTg-AD mice, providing further insights into the role of aerobic exercise in management of neurodegeneration in AD by maintaining intact myelination.

Taking Fenghua taro starch as raw materials, and octenyl succinic anhydride (OSA) as esterifying agent, octenyl succinate taro starch ester (OSTS) was prepared in this work. The degree of substitution (DS) of starch esters was determined by high performance liquid chromatography, and the esterification conditions were optimized by single-factor experiments and response surface methodology using the degree of substitution as the response value, and then the physicochemical properties of OSTS, such as surface hydrophobicity, X-ray diffraction and morphology were measured. The results showed that the optimal process was: Starch concentration 40% (w/v), pH8.5, reaction time 2.5 h, reaction temperature 41℃, and the degree of substitution of OSTS obtained under these conditions was 0.02069. After esterification, the contact angle of taro starch changed from 86.2° to 120.9°, which meant the hydrophobicity of starch surface increased. Starch crystal shape was not affected after esterification, indicating that the esterification reaction between OSA and taro starch preferred to the surface of starch particles. The relative crystallinity decreased from 19.04% to 15.20%. This study would provide a theoretical basis for the effective reaction between OSA and small granular starch.

BackgroundHalf of the population of non-small cell lung cancer (NSCLC) patients are older than 70 years and have limited therapeutic options due to poor tolerance and being excluded in most clinical trials. Anlotinib hydrochloride, a novel oral multi-target tyrosine kinase inhibitor, has been approved for the standard third-line treatment for NSCLC in China. Herein we report an elderly NSCLC patient without any driver gene mutations who was undergoing anlotinib as a front-line treatment and who achieved long-term survival.Case summaryThe 77-year-old male patient was admitted to the hospital for chest tightness after engaging in physical activity for a week. The patient has been diagnosed with stage IIIB driver gene-negative squamous cell lung carcinoma. After that, he was treated with anlotinib for 2 years and 10 months from the first diagnosis until the last disease progression. Briefly, anlotinib combined with platinum-based chemotherapy was performed as the first-line therapy over six cycles. After 6 more cycles of anlotinib monotherapy maintenance, disease progression occurred. Then, anlotinib combined with tegafur was administered as a salvage treatment, and the disease was controlled again. After 29 cycles of anlotinib combined with tegafur regimens, the disease progressed finally. The patient achieved a total of 34 months of progression-free survival after anlotinib was used as the front-line treatment. He is still alive with a good performance status now (performance status score: 1).ConclusionThis patient achieved long-term survival using anlotinib as a front-line regimen combined with chemotherapy.

Abstract Background Previous studies have shown that polycystic ovary syndrome is a predictor of gestational diabetes mellitus, but we do not know exactly how many polycystic ovary syndrome patients may develop gestational diabetes mellitus. Currently, the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome varies greatly across studies, ranged from 4.12% to 59.50%. Besides, many factors have been found to be related to the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, but the results among different studies are not consistent. The possible causes of inconsistencies between the current estimates were unclear. This review aimed at exploring the pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, summarizing possible causes of the inconsistencies in the current estimates, try to provide a reference for prevention of gestational diabetes mellitus and polycystic ovary syndrome in the future. Methods Systematic searches of different databases (including EMBASE, Web of Science, MEDLINE, The Cochrane Library, CNKI and PubMed) were conducted for studies published until 31 May 2021. Statistical analyses were performed using R software, the pooled incidence of gestational diabetes mellitus among polycystic ovary syndrome patients was combined using random effects model. Cochrane’s “Tool to Assess Risk of Bias in Cohort Studies” was used for quality assessment. Results Twenty-two longitudinal studies were included. A total of 24,574 women with polycystic ovary syndrome were identified in the 22 articles, of which 4478 were reported with gestational diabetes mellitus. The pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome was 20.64%, with a 95% CI of 14.64% to 28.30%. In the meta-regression model, several variables including age, area, quality score and sample size were suggested as significant sources of heterogeneity, accounted for 77.57% of the heterogeneity across studies. Conclusions Evidence in this review suggests that gestational diabetes mellitus were common among women with polycystic ovary syndrome. More research is needed to found effective interventions for preventing gestational diabetes mellitus among women with polycystic ovary syndrome.

Puccinia striiformis Westend. f. sp. tritici (Pst) pathotype CYR34 is widely virulent and prevalent in China. Here, we report identification of a strpie rust resistance (Yr) gene, designated Yr041133, in winter wheat line 041133. This line produced a hypersensitive reaction to CYR34 and conferred resistance to 13 other pathotypes. Resistance to CYR34 in line 041133 was controlled by a single dominant gene. Bulked segregant RNA sequencing (BSR-Seq) was performed on a pair of RNA bulks generated by pooling resistant and susceptible recombinant inbred lines. Yr041133 was mapped to a 1.7 cM genetic interval on the chromosome arm 7BL that corresponded to a 0.8 Mb physical interval (608.9–609.7 Mb) in the Chinese Spring reference genome. Based on its unique physical location Yr041133 differred from the other Yr genes on this chromosome arm.

Problemsγδ T cells are essential for anti-leukemia function in immunotherapy, however, γδ T cells have different functional subsets, including regulatory cell subsets expressing the Foxp3. Whether they are correlated with immune-checkpoint mediated T cell immune dysfunction remains unknown in patients with acute myeloid leukemia (AML).MethodsIn this study, we used RNA-seq data from 167 patients in TCGA dataset to analyze the correlation between PD-1 and FOXP3 genes and these two genes’ association with the prognosis of AML patients. The expression proportion of Foxp3+/PD-1+ cells in γδ T cells and two subgroups Vδ1 and Vδ2 T cells were performed by flow cytometry. The expression level of FOXP3 and PD-1 genes in γδ T cells were sorted from peripheral blood by MACS magnetic cell sorting technique were analyzed by quantitative real-time PCR.ResultsWe found that PD-1 gene was positively correlated with FOXP3 gene and highly co-expressed PD-1 and FOXP3 genes were associated with poor overall survival (OS) from TCGA database. Then, we detected a skewed distribution of γδ T cells with increased Vδ1 and decreased Vδ2 T cell subsets in AML. Moreover, significantly higher percentages of PD-1+ γδ, Foxp3+ γδ, and PD-1+Foxp3+ γδ T cells were detected in de novo AML patients compared with healthy individuals. More importantly, AML patients containing higher PD-1+Foxp3+ γδ T cells had lower OS, which might be a potential therapeutic target for leukemia immunotherapy.ConclusionA significant increase in the PD-1+Foxp3+ γδ T cell subset in AML was associated with poor clinical outcome, which provides predictive value for the study of AML patients.

Abstract Background The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells. Methods In the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h. Results The pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P

It has been shown that multidrug and toxic compound extrusion/detoxification (MATE/DTX) family transporters are involved in the regulation of plant development and stress response. Here, we characterized the mini body1 (mib1) mutants in mungbean, which gave rise to increased branches, pentafoliate compound leaves, and shortened pods. Map-based cloning revealed that MIB1 encoded a MATE/DTX family protein in mungbean. qRT-PCR analysis showed that MIB1 was expressed in all tissues of mungbean, with the highest expression level in the young inflorescence. Complementation assays in Escherichia coli revealed that MIB1 potentially acted as a MATE/DTX transporter in mungbean. It was found that overexpression of the MIB1 gene partially rescued the shortened pod phenotype of the Arabidopsis dtx54 mutant. Transcriptomic analysis of the shoot buds and young pods revealed that the expression levels of several genes involved in the phytohormone pathway and developmental regulators were altered in the mib1 mutants. Our results suggested that MIB1 plays a key role in the control of plant architecture establishment in mungbean.

Broad diversity of flowers in Fabaceae provides a good system to investigate development and evolution of floral symmetry in higher plants. Many studies have demonstrated a conserved mechanism controlling development of zygomorphic flower during last decades. However, the molecular basis of how asymmetric flower established is largely unknown. In this study, we characterized mutants named keeled wings (kw) in mungbean (Vigna radiata L.), which is a legume species with asymmetric flowers. Compared to those in the wild type plants, the lateral petals were ventralized in the kw mutants. Map-based cloning showed that KW was VrCYC3 gene in mungbean, the ortholog of Lotus japonicus CYC3 (LjCYC3) and Pisum sativum CYC3 (PsCYC3). In addition, another two CYC-like genes named VrCYC1 and VrCYC2 were identified from mungbean genome. The three CYC-like genes displayed distinct expression patterns in dorsal, lateral and ventral petals. It was found that VrCYC3 was located in nucleus. Further analysis showed that VrCYC3 had transcription activity and could interact with VrCYC1 and VrCYC2 in yeast cell. Moreover, the deletion of two amino acid residues in the R domain of VrCYC3 protein could decrease its interaction with VrCYC1 and VrCYC2 proteins. Our results suggest that LjCYC3/VrCYC3 orthologs play conserved roles determining the lateral petal shape and identity of zygomorphic flower as well as asymmetric flower in Papilionoideae.

BackgroundCurrently, evidence on the role of stressful life events in fatigue among the Chinese working adults is lacking. This study aimed at exploring the prospective associations between stressful life events and chronic fatigue among Chinese government employees.MethodsFrom January 2018 to December 2019, a total of 16206 government employees were included at baseline and they were followed-up until May 2021. A digital self-reported questionnaire platform was established to collect information on participants' health and covariates. Life events were assessed by the Life Events Scale (LES), fatigue was assessed by using a single item, measuring the frequency of its occurrence. Binary logistic regression analysis was used for the data analysis.ResultsOf the included 16206 Chinese government employees at baseline, 60.45% reported that they experienced negative stressful life events and 43.87% reported that they experienced positive stressful life events over the past year. Fatigue was reported by 7.74% of the sample at baseline and 8.19% at follow-up. Cumulative number of life events at baseline, and cumulative life events severity score at baseline were positively associated with self-reported fatigue at follow up, respectively. After adjusting sociodemographic factors, occupational factors and health behavior related factors, negative life events at baseline (OR: 2.06, 95% CI: 1.69–2.51) were significantly associated with self-reported fatigue at follow-up. Some specific life events including events related to work and events related to economic problems were significantly associated with self-reported fatigue. Specifically, work stress (OR = 1.76, 95%CI: 1.45–2.13), as well as not satisfied with the current job (OR = 1.95, 95%CI: 1.58–2.40), in debt (OR = 1.75, 95%CI: 1.40–2.17) were significantly associated with self-reported fatigue. The economic situation has improved significantly (OR = 0.62, 95%CI: 0.46–0.85) at baseline was significantly associated with lower incidence of self-reported fatigue.ConclusionNegative stressful life events were associated with fatigue among Chinese government employees. Effective interventions should be provided to employees who have experienced negative stressful life events.

Wheat genotypes resistant to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) provide a sustainable means for disease control. We developed a pair of near-isogenic lines H962R and H962S with contrasting reactions to powdery mildew from a residue heterozygous line. H962R was resistant to 127 out of the 136 Bgt isolates collected from the major wheat-producing regions of China and showed a similar virulence/avirulence pattern as Fuzhuang 30, Xiaobaidong, and Hongquanmang carrying resistance allele of Pm5e, but H962S was resistant to none of them. A dominant gene was responsible for the powdery mildew resistance of H962R as revealed by the genetic analysis using segregating populations derived from a cross between H962R and H962S. Molecular marker analysis detected a resistance locus, designated PmH962, on a genetic interval of the chromosome arm 7BL where Pm5e resides. This locus was co-segregated with the functional marker of Pm5e. The PCR-based sequence alignment of Pm5e demonstrated that H962R had an identical sequence as Fuzhuang 30 (haplotype HapGA), and H962S possessed the same sequence as the powdery mildew susceptible cultivar Kenong 199. The genomic compositions of lines H962R and H962S were highly comparable as evidenced by only a small percentage of SNP variations detected by the 16K Genotyping by Target Sequencing (GBTS) SNP array and the 90K Illumina iSelect Wheat SNP array. The two lines performed similarly in the yield-related and plant growth traits investigated, except for greater kernel weight in H962R than in H962S. This indicates that Pm5e has no deleterious effect and can be served as an excellent disease resistance gene in wheat breeding.

Background: Comparisons between high intensity interval training (HIIT) and continuous training (CT) regarding improvements of adolescents’ cardiac function are scarce and the preferred intensity for cardiac improvement with restricted myocardial damage remains unknown. This study conducted a 4-weeks training in male adolescent rats under moderate (MI) or high intensity (HI) HIIT and CT programs, aiming to discover and compare exercise-induced myocardial adaptations towards these two training methods.Methods: 39 male adolescent Sprague-Dawley rats (aged 4 weeks) were randomly assigned to high intensity HIIT (HI-HIIT, n = 8), moderate intensity HIIT (MI-HIIT, n = 8), high intensity CT (HI-CT, n = 8), moderate intensity CT (MI-CT, n = 8) and sedentary control (SC, n = 7) groups. Rats in training groups were trained for 4 weeks and echocardiography was performed at baseline and after the final training. Serum creatine kinase myocardial band (CK-MB), cardiac troponin T (cTn-T) and untargeted metabolomics analysis were measured from blood samples collected 24 h after the final training.Results: HIIT groups had greater cardiac output improvement than CT groups while no significant difference was found between the HI-HIIT and the MI-HIIT groups. HI-CT group showed higher serum CK-MB and cTn-T levels compared to MI-HIIT, MI-CT and control groups. Untargeted metabolomics analysis identified eleven HI-HIIT-related metabolites, five MI-HIIT-related metabolites and two HICT-related metabolites. The majority of the identified metabolites were phospholipid-related. Phosphatidylglyceride 18 level was significantly different between the HI-CT and MI-CT groups, and was negatively associated with cTn-T in CT groups.Conclusion: HIIT and CT improve cardiac function of adolescent rats while the HIIT demonstrates better improvement and less myocardial damage. High and moderate training intensities in HIIT exert similar cardiac benefits. HI-CT induced myocardial damage might be associated with serum phospholipids.

SCFFBXW7 E3 ubiquitin ligase complex is a crucial enzyme of the ubiquitin proteasome system that participates in variant activities of cell process, and its component FBXW7 (F-box and WD repeat domain–containing 7) is responsible for recognizing and binding to substrates. The expression of FBXW7 is controlled by multiple pathways at different levels. FBXW7 facilitates the maturity and function maintenance of immune cells via functioning as a mediator of ubiquitination-dependent degradation of substrate proteins. FBXW7 deficiency or mutation results in the growth disturbance and dysfunction of immune cell, leads to the resistance against immunotherapy, and participates in multiple illnesses. It is likely that FBXW7 coordinating with its regulators and substrates could offer potential targets to improve the sensitivity and effects of immunotherapy. Here, we review the mechanisms of the regulation on FBXW7 and its tumor suppression role in immune filed among various diseases (mostly cancers) to explore novel immune targets and treatments.

ObjectiveThe purpose of the study was to test whether primary lifestyles mediate associations of SES with incidence of dyslipidemia and to explore interaction relations of lifestyles and SES with incidence of dyslipidemia.MethodsWe included 9,901 individuals at baseline from January 2018 to November 2019, and incidence data were updated to 31 December 2020. Dyslipidemia was defined as total cholesterol (TC) 6.2 mmol/L TC ≥ or triglycerides (TG) ≥2.3 mmol/L or low-density lipoprotein cholesterol (LDL-C) ≥4.1 mmol/L or high-density lipoprotein cholesterol (HDL-C)

A novel composite edible film was synthesized by grafting gelatin chain onto hydroxypropyl methyl cellulose (HPMC) in the presence of glycerol (used as a plasticizer) using a solution polymerization technique. The reaction was carried out in homogeneous aqueous medium. Thermal properties, chemical structure, crystallinity, surface morphology, and mechanical and hydrophilic performance changes of HPMC caused by the addition of gelatin were investigated by differential scanning calorimetry, thermogravimetric, Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, universal testing machine and water contact angle. The results shows that HPMC and gelatin are miscible and the hydrophobic property of the blending film can be enhanced with the introduction of the gelatin. Moreover, the HPMC/gelatin blend films are flexible, and exhibit excellent compatibility, good mechanical properties and also thermal stability, and could be promising candidates for food packaging materials.

Collagen (Col) hydrogels are an important biomaterial with many applications in the biomedical sector. However, deficiencies, including insufficient mechanical properties and a rapid rate of biodegradation, hamper their application. In this work, nanocomposite hydrogels were prepared by combining a cellulose nanocrystal (CNC) with Col without any chemical modification. The high-pressure, homogenized CNC matrix acts as nuclei in the collagen’s self-aggregation process. The obtained CNC/Col hydrogels were characterized in terms of their morphology, mechanical and thermal properties and structure by SEM, rotational rheometer, DSC and FTIR, respectively. Ultraviolet-visible spectroscopy was used to characterize the self-assembling phase behavior of the CNC/Col hydrogels. The results showed an accelerated assembling rate with the increasing loading of CNC. The triple-helix structure of the collagen was preserved with a dosage of CNC of up to 15 wt%. The CNC/Col hydrogels demonstrated an improvement in both the storage modulus and thermal stability which is attributed to the interaction between the CNC and collagen by the hydrogen bonds.

BackgroundHypertension (HTN) is a global public health concern. However, the association between life events (LEs) and HTN is complex. Thus, we conducted a prospective cohort study to explore this complex association.MethodsA total of 8,077 government employees without HTN were recruited through cluster sampling between 2018 and 2019 in Hunan Province, China. At baseline, information regarding sociodemographic characteristics, LEs, and behavioral factors was collected. After the 1-year follow-up, the participants were revisited to obtain the HTN diagnosis. Crude and adjusted Poisson regression models were constructed to calculate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Cubic regression spline models were used to visualize the trends between LEs and HTN IRRs. Interactive and subgroup analyses were also performed.ResultsThe 1-year HTN incidence rate among government employees in Hunan province was 4.30% (95% CI: 3.86–4.74%). LEs were associated with a higher HTN risk (IRR, 1.02; 95% CI, 1.00–1.04). When calculating positive and negative LEs scores separately, only the latter was a risk factor for HTN incidence (IRR, 1.04; 95% CI, 1.03–1.06); conversely, positive LEs reduced the risk (IRR, 0.90; 95% CI, 0.85–0.96). Compared with patients in the lowest quartile of LEs score, those in quartiles two (IRR, 1.28; 95% CI, 0.96–1.71), three (IRR, 1.43; 95% CI, 1.04–1.96), and four (IRR, 1.73; 95% CI, 1.26–2.37) were at progressively higher risk. In restricted spline curves, a non-linear association was noted between LEs and HTN risk. Regarding the subcategories of LEs, work-related LEs, personal LEs, and all subcategories of negative LEs were associated with an increased risk of HTN. However, among positive LEs, only the family-related cases were associated with a lower risk of HTN.ConclusionLEs had a non-linear association with an increased risk of HTN. Negative LEs were risk factors for HTN incidence, whereas positive LEs reduced the risk of HTN. Thus, the importance of LEs should be highlighted in the development of HTN prevention strategies and initiatives.

Abstract Background Immunization to prevent infectious diseases is a core strategy to improve childhood health as well as survival. It remains a challenge for some African countries to attain the required childhood immunization coverage. We aim at identifying individual barriers confronting parents/caretakers, providers, and health systems that hinder childhood immunization coverage in Sub-Saharan Africa. Method This systematic review searched PubMed/MEDLINE, Web of Science and EMBASE. We restricted to published articles in English that focused on childhood immunization barriers in sub-Saharan Africa from January 1988 to December 2019. We excluded studies if: focused on barriers to immunization for children in other regions of the world, studied adult immunization barriers; studies not available on the university library, they were editorial, reports, reviews, supplement, and bulletins. Study designs included were cross-sectional, second-hand data analysis; and case control. Results Of the 2652 items identified, 48 met inclusion criteria. Parents/caretakers were the most common subjects. Nine articles were of moderate and 39 were of high methodological quality. Nine studies analyzed secondary data; 36 used cross-sectional designs and three employed case control method. Thirty studies reported national immunization coverage of key vaccines for children under one, eighteen did not. When reported, national immunization coverage of childhood vaccines is reported to be low. Parents/caretaker’ barriers included lack of knowledge of immunization, distance to access point, financial deprivation, lack of partners support, and distrust in vaccines and immunization programs. Other associated factors for low vaccine rates included the number of off-springs, lifestyle, migration, occupation and parent’s forgetfulness, inconvenient time and language barrier. Barriers at health system level cited by healthcare providers included limited human resources and inadequate infrastructures to maintain the cold chain and adequate supply of vaccines. Conclusion In this review we identified more thoroughly the parents/caretakers’ barriers than those of providers and health systems. Factors that influenced decisions to get children vaccinated were mainly their gender, beliefs, socio-culture factors in the communities in which they live. Thus it is vital that immunization programs consider these barriers and address the people and societies in their communities across sub-Saharan Africa.

Abstract Background Conflicting evidence exists on whether parent or spouse caregivers experience better outcomes when caring for family members with schizophrenia. The current study aims to examine relative caregiving experiences and impacts of spouse and parent caregivers for people living with schizophrenia (PLS) in China. Methods A cross-sectional study was conducted in a sample of 264 community-dwelling primary family caregivers of PLS. Face-to-face interviews were conducted to collect information on family caregiving activities; negative caregiving impacts including objective and subjective burden, and caregiver psychological distress such as depression and anxiety; positive caregiving impacts including caregiving rewarding feelings, and family functioning for spouse and parent caregivers. Results Both types of caregivers report engaging in similar caregiving activities and report comparable levels of objective burden. However, parent caregivers report significantly higher subjective burden than spouse caregivers (b = 7.94, 95%CI:2.08, 13.80, P

Resistance to powdery mildew is an important trait of interest in many wheat breeding programs. The information on genes conferring resistance to powdery mildew in wheat cultivars is useful in parental selection. Winter wheat breeding line DH51302 derived from Liangxing 99 and cultivar Shimai 26 derived from Jimai 22 showed identical infection patterns against 13 isolates of Blumeria graminis f. sp. tritici (Bgt) that causes wheat powdery mildew. DH51302 and Shimai 26 were crossed to a powdery mildew susceptible cultivar Zhongzuo 9504 and the F2:3 families were used in molecular localization of the resistance genes. Fourteen polymorphic markers, which were linked to Pm52 from Liangxing 99, were used to establish the genetic linkage maps for the resistance genes PmDH51302 and PmSM26 in DH51302 and Shimai 26, respectively. These genes were placed in the same genetic interval where Pm52 resides. Analysis of gene-linked molecular markers indicated that PmDH51302 and PmSM26 differed from other powdery mildew resistance genes on chromosome arm 2BL, such as Pm6, Pm33, Pm51, MlZec1, MlAB10, and Pm64. Based on the results of reaction patterns to different Bgt isolates and molecular marker localization, together with the pedigree information, DH51302 and Shimai 26 carried the same gene, Pm52, which confers their resistance to powdery mildew.

Powdery mildew is a major threat to world wheat yields. Here the authors describe the map-based cloning of Pm24, a gain-of-function powdery mildew resistance allele that encodes a tandem kinase-pseudokinase protein with a deletion in a kinase domain that is endemic to certain wheat landraces.

BackgroundIncreasing evidence shows that the ubiquitin–proteasome system has a crucial impact on lung adenocarcinoma. However, reliable prognostic signatures based on ubiquitination and immune traits have not yet been established.MethodsBioinformatics was performed to analyze the characteristic of ubiquitination in lung adenocarcinoma. Principal component analysis was employed to identify the difference between lung adenocarcinoma and adjacent tissue. The ubiquitin prognostic risk model was constructed by multivariate Cox regression and least absolute shrinkage and selection operator regression based on the public database The Cancer Genome Atlas, with evaluation of the time-dependent receiver operating characteristic curve. A variety of algorithms was used to analyze the immune traits of model stratification. Meanwhile, the drug response sensitivity for subgroups was predicted by the “pRRophetic” package based on the database of the Cancer Genome Project.ResultsThe expression of ubiquitin genes was different in the tumor and in the adjacent tissue. The ubiquitin model was superior to the clinical indexes, and four validation datasets verified the prognostic effect. Additionally, the stratification of the model reflected distinct immune landscapes and mutation traits. The low-risk group was infiltrating plenty of immune cells and highly expressed major histocompatibility complex and immune genes, which illustrated that these patients could benefit from immune treatment. The high-risk group showed higher mutation and tumor mutation burden. Integrating the tumor mutation burden and the immune score revealed the patient’s discrepancy between survival and drug response. Finally, we discovered that the drug targeting ubiquitin and proteasome would be a beneficial prospective treatment for lung adenocarcinoma.ConclusionThe ubiquitin trait could reflect the prognosis of lung adenocarcinoma, and it might shed light on the development of novel ubiquitin biomarkers and targeted therapy for lung adenocarcinoma.

In the classification and typing of breast cancer, triple-negative breast cancer (TNBC) is one type of refractory breast cancer, while chemotherapy stays in the traditional treatment methods. However, the impact of chemotherapy is short-lived and may lead to recurrence due to incomplete killing of tumor cells. The occurrence, development, and relapse of breast cancer are relevant to T cell dysfunction, multiplied expression of related immune checkpoint molecules (ICIs) such as programmed death receptor 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) produce immunosuppressive effect. Immunotherapy (namely, immune checkpoint inhibitors, adoptive cellular immunotherapy, CAR-T immunotherapy and some potential treatments) provides new hope in TNBC. This review focuses on the new immune strategies of TNBC patients.

Ruyan Neixiao Cream (RUc) is a traditional Chinese herbal formula which can effectively inhibit the angiogenesis of breast precancerous lesions. In order to reveal the specific mechanism, we carried out experiments in vitro and in vivo. We found that the conditioned medium of MCF-10AT cells treated with RUc transdermal solution (RUt) could significantly inhibit the proliferation, migration, invasion, tube formation of HUVECs and the capillary formation of rat aortic rings. RUt may down-regulate the expression of VEGF, MMP2, and MMP9 in MCF-10AT medium by down-regulating miR-21 and up-regulating TIMP-3 and RECK. We further confirmed in rats that the microvascular density of precancerous lesions decreased significantly after external use of RUc, which may be related to the inhibition of Ras/Raf/MEK/ERK signaling pathway related proteins. Presumptively, RUc may inhibit the angiogenesis of breast precancerous lesions by inhibiting Ras/Raf/MEK/ERK signaling pathway, thus relieving the inhibition of miR-21 on TIMP-3 and RECK, then down-regulating the secretion of angiogenic factors.

The eighteenth data release (DR18) of the Sloan Digital Sky Survey (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs or “Mappers”: the Milky Way Mapper (MWM), the Black Hole Mapper (BHM), and the Local Volume Mapper. This data release contains extensive targeting information for the two multiobject spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration and scientifically focused components. DR18 also includes ∼25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.

Objective: This study aimed to explore the relationships and the underlying mechanisms between work stress and mental health problems, and potential mediation effects through job dissatisfaction in a working population.Methods: A large population-based study among workers in China was conducted. The self-reported scales of assessing job dissatisfaction and work stress were included in the questionnaire. Generalized Anxiety Disorder-2 and Patient Health Questionnaire-2 were used for assessment of mental health. Univariate logistic regression was conducted to test the associations between work stress and mental health. Path analysis was conducted to test the proposed mediation model.Results: Of the 6,190 included employees, 27.72% reported that they perceived work stress, 14.84% of them reported that they were not satisfied with their work, 5.01% of the employees reported depressive symptoms, and 3.75% of the employees reported anxiety symptoms. The results of univariate logistic regression showed that employees who perceived work stress were more likely to report anxiety symptoms (adjusted odds ratio (AOR) = 2.78; 95% CI: 2.03–3.79) or depressive symptoms (AOR = 1.61; 95% CI: 1.22–2.12). The path analysis showed that work stress was positively associated with job dissatisfaction. Job dissatisfaction mediated the relationship between work stress and mental health problems among Chinese working adults.Conclusion: This study suggests the importance of psychosocial work environment for mental health among Chinese working adults. Work dissatisfaction is a stressor that may induce negative consequences on the mental health among Chinese workers. Interventions to help workers with stress management may be beneficial for their mental health.

Background: High suicide rate in the elderly is an important global public health problem but has not received the attention it deserves. This study aimed to examine time trends of suicide mortality for people aged 70 years and over by sex, age, and location from 1990 to 2017, and to provide predictions up to 2030.Methods: Using data from the Global Burden of Disease study 2017, we presented elderly suicide mortality changes and compared the patterns for the elderly with that for all ages. We estimated associations between socio-demographic index (SDI) and suicide mortality rates using a restricted cubic spline smoother, and predicted suicide mortality rates up to 2030.Results: In 2017, 118,813 people aged 70 years and over died from suicide, indicating a mortality rate of 27.5 per 100,000, with the highest rates in Eastern Sub-Saharan Africa, Western Sub-Saharan Africa, and Central Sub-Saharan Africa, and for countries and territories, the highest were in South Korea, Zimbabwe, Lesotho, Mozambique, and Senegal. Between 1990 and 2017, suicide mortality rate for the elderly aged 70 years and over decreased globally (percentage change −29.1%), and the largest decreases occurred in East Asia, Southern Latin America, and Western Europe. Nationally, the largest decrease was found in Chile, followed by Czech Republic, Hungary, Turkey, and Philippines. For most countries, the elderly mortality rate was higher than the age-standardized rate, with the largest percentage differences in China and countries in Sub-Saharan Africa. The elderly suicide mortality rate decreased as SDI increased, except for a slight rebound at mid to high SDI. According to projections, 10 out of 195 countries were expected to meet the SDGs indicator of a third reduction by 2030.Conclusions: Variability in suicide mortality rates for the elderly aged 70 years and over by sex, age, region, country, and SDI can guide preventive policies, but causes of the variability need further study. Comprehensive strategies should be adopted to reduce suicide rates and close the gap to the 2030 SDGs.

Background: Smell and taste dysfunctions are common and have been reported as an early indicator of COVID-19. The prevalence of smell and taste dysfunctions among children with COVID-19 varies greatly across studies, which remains to be summarized quantitatively. This review aimed at examining the pooled prevalence of smell or taste dysfunctions among children with COVID-19, summarizing possible causes of the inconsistencies in the current estimates.Methods: Systematic searches of databases were conducted for literature published until 12 January 2021. Statistical analyses were performed using R software, the pooled prevalence was combined using random effects model. The Loney criteria were used for quality assessment.Results: A total of 18 eligible studies were included. The results showed that the pooled prevalence of smell dysfunction among children with COVID-19 was 15.97% (95% CI: 8.18–23.77%), the pooled prevalence of taste dysfunction among children with COVID-19 was 9.20% (95% CI: 4.25–14.16%), the pooled prevalence of smell or taste dysfunction among children with COVID-19 was 15.50% (95% CI: 10.30–20.70%) and the pooled prevalence of smell and taste dysfunction among children with COVID-19 was 20.21% (95% CI: 14.14–26.28%). Higher smell or taste dysfunction rates were associated with being female, younger age, smaller sample size, patients in Asia, and with comorbidities.Conclusions: Evidence suggests that smell or taste dysfunctions were common among children with COVID-19. Further research is needed to identify effective strategies for preventing and treating smell and taste dysfunctions among children with COVID-19.

Background: As one of the most widely researched consequence of traumatic events, the prevalence of post-traumatic stress symptoms (PTSS) among people exposed to the trauma resulting from infectious disease outbreak varies greatly across studies. This review aimed at examining the pooled prevalence of PTSS among people exposed to the trauma resulting from infectious disease outbreak, summarizing the possible causes of the inconsistencies in the current estimates.Methods: Systematic searches of databases were conducted for literature published on PubMed, EMBASE, Web of Science, the Cochrane Library, PsycArticles, and Chinese National Knowledge Infrastructure (CNKI) until 14 October 2020. Statistical analyses were performed using R software (registration number: CRD42020182366).Results: About 106 studies were included. The results showed that the pooled prevalence of PTSS among the general population exposed to the trauma resulting from infectious disease outbreak was 24.20% (95% CI: 18.54–30.53%), the pooled prevalence of PTSS among healthcare workers was 24.35% (95% CI: 18.38–1.51%), the pooled prevalence of PTSS among patients with infectious disease was 28.83% (95% CI: 18.53–44.86%), and the pooled prevalence of PTSS among suspected cases of infectious disease was 25.04% (95% CI: 18.05–34.73%). Mortality rate was a significant contributor to heterogeneity.Conclusions: Evidence suggests that PTSS were very common among people exposed to the trauma resulting from infectious disease outbreak. Health policymakers should consider both short-term and long-term preventive strategy of PTSS.

Objective We aimed to estimate the distribution of health-related behaviours and dietary habits by sociodemographics among public workers in China.Design Cross-sectional study.Setting A representative sample was obtained from 10 government-run institutions in Hunan province of China.Participants A total of 5029 public workers were included in this study.Primary and secondary outcome measures Prevalence on their sociodemographic characteristics, health-related behaviours and dietary habits. Socioeconomic status (SES) scores were calculated by multiplying ordinal numerical values assigned to consecutive categories of education level and annual household income. Multivariate logistic regression analysis and categorical principal component analysis were used to estimate differences in health-related behaviours and dietary habits by sociodemographics.Results The distribution of health-related behaviours and dietary habits was varied by sociodemographic groups. Middle-aged groups (41–60 years) were more likely to smoke (for men, 34.5%), use alcohol (for men, 22.5%), and have short sleep duration (for men, 36.3%; for women, 39.6%). Young participants (≤30 years) were more likely to have multiple unhealthy behaviours and dietary habits. Those in low-SES have a significant higher rate of smoking (ORadj=1.46, 95% CI: 1.15 to 1.85) and leisure-time physical inactivity (ORadj=1.18, 95% CI: 1.02 to 1.37), but a lower rate of late sleeping (ORadj=0.69, 95% CI: 0.57 to 0.83) than those in high-SES. Notably, older men (≥51 years) with low-SES preferred the ‘smoked and pickled foods and dessert’ and ‘fish and nut’ pattern. In high-SES groups, 41–50 year old people preferred the ‘traditional foods’ and ‘cereals and dairy product’ pattern. No difference in dietary patterns by sociodemographics was found among women (p

Abstract Background Tetrastigma hemsleyanum Diels et Gilg is a valuable medicinal herb, whose main bioactive constituents are flavonoids. Chilling sensitivity is the dominant environmental factor limiting growth and development of the plants. But the mechanisms of cold sensitivity in this plant are still unclear. Also, not enough information on genes involved in flavonoid biosynthesis in T. hemsleyanum is available to understand the mechanisms of its physiological and pharmaceutical effects. Results The electrolyte leakage, POD activity, soluble protein, and MDA content showed a linear sustained increase under cold stress. The critical period of cold damage in T. hemsleyanum was from 12 h to 48 h. Expression profiles revealed 18,104 differentially expressed genes (DEGs) among these critical time points. Most of the cold regulated DEGs were early-response genes. A total of 114 unigenes were assigned to the flavonoid biosynthetic pathway. Fourteen genes most likely to encode flavonoid biosynthetic enzymes were identified. Flavonols of T. hemsleyanum might play a crucial role in combating cold stress. Genes encoding PAL, 4CL, CHS, ANR, FLS, and LAR were significantly up-regulated by cold stress, which could result in a significant increase in crucial flavonols (catechin, epicatechin, rutin, and quercetin) in T. hemsleyanum. Conclusions Overall, our results show that the expression of genes related to flavonol biosynthesis as well as flavonol content increased in T. hemsleyanum under cold stress. These findings provide valuable information regarding the transcriptome changes in response to cold stress and give a clue for identifying candidate genes as promising targets that could be used for improving cold tolerance via molecular breeding. The study also provides candidate genes involved in flavonoid biosynthesis and may be useful for clarifying the biosynthetic pathway of flavonoids in T. hemsleyanum.

Abstract Background Most of patients with dementia are cared for by family members. Caring for people with dementia is challenging; approximately 30–55% of caregivers suffered from anxiety or depressive symptoms. A range of studies have shown that psychosocial interventions are effective and can improve caregivers’ quality of life, reduce their care burden, and ease their anxiety or depressive symptoms. However, information on the acceptability of these interventions, despite being crucial, is under-reported. Methods Systematic searches of databases were conducted for literature published on EMBASE, PubMed, The Cochrane Library, Web of Science, and PsycARTICLES until August 2017 and the searches were updated on June 2018. The selection criteria included primary studies with data about the acceptability of psychosocial interventions for informal caregivers and publications written in English. Two authors independently selected studies, extracted study characteristics and data, assessed the methodological quality of the included studies by using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool and Critical Appraisal Skills Programme (CASP) Qualitative Research Checklist, and conducted a narrative synthesis of quantitative and qualitative data. Results A total of 10,610 abstracts were identified through systematic searches. Based on screening titles and abstracts, 207 papers were identified that met the criteria for full paper review, with 42 papers from 13 different countries meeting the inclusion criteria. We found high- and moderate-quality evidence showing psychosocial interventions were acceptable, with important benefits for caregivers. Facilitators of acceptability included caregivers’ need for intervention, appropriate content and organization of the intervention, and knowledge and professionalism of the staff. Barriers to acceptability included participants’ poor health status and low education levels, caregiving burden, change of intervention implementers, and poor system performance of interventions. Conclusion There is preliminary evidence to support the acceptability of psychosocial interventions for dementia caregivers. However, the available supporting evidence is limited, and there is currently no adequate information from these studies indicating that the acceptability has received enough attention from researchers. More well-designed studies assessing psychosocial interventions are needed to give specific statements about acceptability, and the measure of acceptability with psychosocial interventions should be more comprehensive.

A recessive gene PmQ conferring powdery mildew resistance was previously localized on the long arm of chromosome 2B in winter wheat landrace Qingxinmai. Breeder-friendly molecular markers are necessary for introgressing this gene into adapted wheat backgrounds for developing disease-resistant wheat cultivars. Three Kompetitive allele-specific PCR (KASP) markers were developed and validated based on SNP variants detected by Bulked segregant analysis-RNA-Seq (BSR-Seq) analysis using a recombinant inbred population derived from cross Qingxinmai × 041133. Two polymorphic SSR markers were also developed from the motifs in the Chinese Spring reference genome sequences of the target genomic region. Those markers were incorporated into a more saturated genetic linkage map for PmQ. The two flanking markers, Xicsq405 and Xicsk18, are 1.1 and 0.9 cM from PmQ, respectively. The KASP marker Xicsk19 produced unique amplification pattern in 158 out of 160 wheat cultivars or breeding lines. This marker with the gene-linked SSR markers Xicsqc, Xicsqd and Xicsq405 provides an efficient means in molecular marker-assisted selection for PmQ in wheat breeding. The corresponding genomic region of PmQ in the Chinese Spring reference genome has a conserved synteny with the genomes of sequenced wheat cultivars and Triticum durum, T. diccocoides, T. uratu, and barley. The annotation of the two genes, TraesCS2B01G517400.1 and TraesCS2B01G517700.1, associated with plant defense against pathogens placed a start for cloning PmQ.

AbstractBackgroundAs one of the most widely researched consequence of traumatic events, the prevalence of post-traumatic stress symptoms among people exposed to the trauma resulting from coronavirus disease 2019 (COVID-19) outbreak varies greatly across studies. This review aimed at examining the pooled prevalence of post-traumatic stress symptoms among people exposed to the trauma resulting from COVID-19 outbreak.MethodsSystematic searches of databases were conducted for literature published on PubMed, EMBASE, Web of Science, the Cochrane Library, PsycArticle, and Chinese National Knowledge Infrastructure until October 14, 2020. Statistical analyses were performed using R software (PROSPERO registration number: CRD42020180309).ResultsA total of 106,713 people exposed to the trauma resulting from the COVID-19 outbreak were identified in the 76 articles, of which 33,810 were reported with post-traumatic stress symptoms. The pooled prevalence of post-traumatic stress symptoms among people exposed to the trauma resulting from COVID-19 outbreak was 28.34%, with a 95% confidence interval of 23.03-34.32%. Subgroup analysis indicated that older age, male and bigger sample size were associated with higher prevalence of post-traumatic stress symptoms. After controlling for other factors, the results of meta-regression showed that the influence of gender and sample size on prevalence is no longer significant.ConclusionsSymptoms of post-traumatic stress disorder (PTSD) were very common among people exposed to the trauma resulting from COVID-19 outbreak. Further research is needed to explore more possible risk factors for post-traumatic stress symptoms and identify effective strategies for preventing PTSD-related symptoms among people exposed to the trauma resulting from COVID-19 outbreak.

Background: In response to the potentially concurrent mental health crisis due to the COVID-19 outbreak, there have been ongoing mental health policies put in place in China. This review aims to systematically synthesize the implemented national-level mental health policies released by the Chinese government during the COVID-19 outbreak, and summarize the implementation of those mental health policies.Methods: Six databases and two websites were systematically searched, including published studies and gray literature published between December 1, 2019 and October 29, 2020.Results: A total of 40 studies were included. Among them, 19 were national-level policies on mental health released by the Chinese government, and 21 studies reported data on the implementation of those mental health policies. Mental health policies were issued for COVID-19 patients, suspected cases, medical staff, the general population, patients with mental illness, and mental institutions. In the early stage of the COVID-19 epidemic, attention was paid to psychological crisis intervention. In the later stage of the epidemic, the government focused mainly on psychological rehabilitation. During the COVID-19 outbreak, more than 500 psychiatrists from all over China were sent to Wuhan, about 625 hotlines were notified in 31 provinces, several online psychological consultation platforms were established, social software such as TikTok, Weibo, and WeChat were used for psychological education, and many books on mental health were published. Responding quickly, maximizing the use of resources, and emphasizing the importance of policy evaluation and implementation quality were characteristics of the mental health policies developed during the COVID-19 outbreak. Challenges facing China include a low rate of mental health service utilization, a lack of evaluation data on policy effects, and no existing national-level emergency response system and designated workforce to provide psychological crisis interventions during a national emergency or disaster.Conclusions: This review suggests that China has responded quickly and comprehensively to a possible mental health crisis during the COVID-19 outbreak, appropriate mental health policies were released for different members of the population. As the epidemic situation continues to change, the focus of mental health policies has been adjusted accordingly. However, we should note that there has been a lack of separate policies for specific mental health issues during the COVID-19 outbreak.