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The response to immune checkpoint inhibitors (ICIs) monotherapy remains unsatisfactory in patients with NSCLC. Thus, combining ICIs with other potential modalities is of great significance to enhance the response of single drug alone. Here, we identified that HIF-1α inhibition was capable of promoting anti-tumor immunity in NSCLC. We applied NSCLC cell lines and mouse models to evaluate the synergy of combined HIF-1α inhibition and PD-1 blockade on tumor growth and the function of tumor infiltrating lymphocytes (TILs). Public datasets were utilized to investigate patients' prognosis based on expressions of HIF-1α and LOXL2 as well as EMT-associated markers and CD8

During the transition from sexual to asexual reproduction, a suite of reproduction‐related sexual traits become superfluous, and may be selected against if costly. Female functional virginity refers to asexual females resisting to mate or not fertilizing eggs after mating. These traits appear to be among the first that evolve during transitions from sexual to asexual reproduction. The genetic basis of female functional virginity remains elusive. Previously, we reported that female functional virginity segregates as expected for a single recessive locus in the asexual parasitoid wasp Asobara japonica. Here, we investigate the genetic basis of this trait by quantitative trait loci (QTL) mapping and candidate gene analyses. Consistent with the segregation of phenotypes, we found a single QTL of large effect, spanning over 4.23 Mb and comprising at least 131 protein‐coding genes, of which 15 featured sex‐biased expression in the related sexual species Asobara tabida. Two of the 15 sex‐biased genes were previously identified to differ between related sexual and asexual population/species: CD151 antigen and nuclear pore complex protein Nup50. A third gene, hormone receptor 4, is involved in steroid hormone mediated mating behaviour. Overall, our results are consistent with a single locus, or a cluster of closely linked loci, underlying rapid evolution of female functional virginity in the transition to asexuality. Once this variant, causing rejection to mate, has swept through a population, the flanking region does not get smaller owing to lack of recombination in asexuals.

Meiotic drivers are selfish genetic elements that tinker with gametogenesis to bias their own transmission into the next generation of offspring. Such tinkering can have significant consequences on gametogenesis and end up hampering the spread of the driver. In Drosophila affinis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are typically more than 95% female. Interestingly, D. affinis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons - effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 750X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.

In systems with early stage sex-chromosome evolution, climate gradients can largely explain changes in the sex-determining systems (i.e., genetic or environmental factors). However, in the common frog Rana temporaria, Phillips et al. found that phylogeography, rather than elevation (used as a proxy for climate), was associated with homomorphic sex-chromosome differentiation levels.

Background Elders' disability severity and caregiver health could predict elders' informal care time, but the mechanism by which the degree of disability in the elderly affects informal care time is unclear. Aim The aim of this works is to explore the mediating roles of caregiver health and home-based care quality between disability severity of elders and informal care time in far north-western low-income areas in China. Method From September 2017 to February 2018, three hundred fifty-two dyads of Kazakh disabled elders and informal caregivers in Xinjiang were interviewed. Structural equation modelling analyses were applied. Results Significant positive correlations were observed between elders' disability severity and informal care time, caregiver health and informal care time, elders' disability severity and caregiver health. Significant negative correlations were observed between home-based care quality and informal care time, elders' disability severity and home-based care quality, caregiver health and home-based care quality. Elders' disability severity had 71.94% direct effect on informal care time, 28.06% indirect effect on informal care time mediated by home-based care quality and caregiver health. Conclusion Caregiver health and home-based care quality play mediating roles on the path relationship between the elders' disability severity and informal care time.

Background Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. Methods NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. Results Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). Conclusions Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis, with an unfavorable response to palliative chemotherapy. Unfortunately, there are few effective therapeutic regimens. Therefore, we require novel treatment strategies with enhanced efficacy. The present study aimed to investigate the antitumor efficacy of APG-1252-M1, a dual inhibitor of BCL-2/BCL-XL, as a single agent and combined with gemcitabine. We applied various apoptotic assays and used subcutaneous transplanted NPC model to assess the in vitro and in vivo antitumor activity. Moreover, phospho-tyrosine kinase array was used to investigate the combined therapy’s potential synergistic mechanism. In addition, further validation was performed using immunohistochemistry and western blotting. In vitro, we observed that APG-1252-M1 had moderate antitumor activity toward NPC cells; however, it markedly improved gemcitabine’s ability to promote NPC cell apoptosis and suppress invasion, migration, and proliferation. Specifically, APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo. Mechanistically, the drug combination synergistically suppressed NPC by activating caspase-dependent pathways, blocking the phospho (p)-JAK-2/STAT3/MCL-1 signaling pathway, and inhibiting epithelial-mesenchymal transition. In conclusion, the results indicated that the combination of APG-1252 and gemcitabine has synergistic anticancer activities against NPC, providing a promising treatment modality for patients with NPC.

Background Immunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, however, its relationship with NPC remains unclear. This study aimed to evaluate LAG-3 expression in NPC and its association with CD3+ tumor-infiltrating lymphocytes (TILs), Granzyme B (GZMB), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) expression. Methods A total of 182 patients with NPC from Sun Yat-sen University Cancer Center, China, were included in this retrospective study. LAG-3 expression in 15 NPC cell lines and LAG-3, CD3+ TILs, GZMB, PD-L1 and PD-1 in clinical samples were estimated using immunohistochemistry. The Chi-square test was used to estimate the association between LAG-3, other biomarkers, and clinical characteristics. Survival analysis was performed using the Kaplan–Meier method and the Cox regression model. Results LAG-3 was negatively expressed in all of the 15 NPC cell lines, whereas, 147 patients with NPC (80.8%) exhibited high LAG-3 expression on TILs from tumor tissues. Male patients and those who were EBV-positive presented higher LAG-3 expression. Correlation analyses showed that LAG-3 expression was related to PD-1 expression on TILs, as well as, PD-L1 expression on tumor cells (TCs) and TILs. Both the univariate and multivariate Cox models indicated that pathological type III (P = 0.036), higher LAG-3 on TILs (P P = 0.027), and higher PD-1 on TILs (P P = 0.002). Conclusion Higher LAG-3 and PD-1 on TILs, and higher PD-L1 expression on TCs, and pathological type III were identified as independent risk factors for poorer DFS in NPC patients. Our data demonstrate that LAG-3 is a promising inhibitory receptor that may play an important role in anti-NPC therapy.

Objectives To identify the cooperation of authors, countries, and institutions and explore the hot topics and future prospects regarding programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) research. Materials and methods Publications on PD-1 and PD-L1 research were retrieved from the Web of Science Core Collection. Bibliometric analyses were performed using VOSviewer 1.6.9, HistCite 2.1, and CiteSpace V software. Network maps were generated to evaluate the collaborations between different authors, countries, and institutions. Results A total of 7359 articles related to PD-1 and PD-L1 research in the field of cancer were identified. We observed rapid growth in the number of publications since 2014. Oncoimmunology (326, 4.43%) had the highest number of publications, while N Engl J Med (18,828 co-citations, 6.30%) was the most co-cited journal. Hodi FS and Wolchok JD were key researchers. There were active collaborations among the top authors. The USA was the leading contributor in this field with 3496 publications. Active cooperations between countries and between institutions were observed. The main hot topics included matters related to the efficacy and prognosis of various tumors after treatment with PD-1 and/or PD-L1 inhibitors, as well as the activation or expression of important immunological factors targeted at tumors. Conclusion PD-1 and PD-L1 studies have significantly increased after 2014. The USA contributed the most publications. There were active cooperations between authors, countries, and institutions. Further research should expand and develop new topics such as those likely to boost therapeutic strategies for cancer.

Background and Aims Polyploidy has played a major role in the origin of new plant species, probably because of the expansion of polyploid populations in the species’ ecological niche, and because reproductive isolation can be established between a new polyploid population and its diploid progenitor species. It is well established that most polyploid species are polyphyletic, with multiple independent origins, and that polyploid genomes may undergo rapid change after their duplication and hybridization associated with their origin. We considered whether multiple independent origins and rapid genomic change might lead to reproductive isolation between polyploid populations of the same ploidy but with potentially different evolutionary histories. Methods We tested our hypothesis by assessing differences in DNA content and morphology, the evolution of reproductive isolation, and the phylogenetic placement of two broadly sympatric hexaploid lineages of the wind-pollinated annual plant Mercurialis annua hitherto regarded as populations of the same species. Key Results The two hexaploid lineages of M. annua have slightly divergent DNA content, and distinct inflorescence morphology. They also fall into largely different clades of a chloroplast phylogeny and are reproductively isolated from one another. Conclusions The distinct evolutionary histories of the two hexaploid lineages of M. annua have contributed to the remarkable reproductive diversity of the species complex. It seems likely that reproductive interference between them will eventually lead to the displacement of one lineage by the other via pollen swamping. Thus, whereas polyploidization can contribute to speciation, diversification might also be compromised by reproductive interference.

Frogs are ideal organisms for studying sex chromosome evolution because of their diversity in sex chromosome differentiation and sex-determination systems. We review 222 anuran frogs, spanning ~220 Myr of divergence, with characterized sex chromosomes, and discuss their evolution, phylogenetic distribution and transitions between homomorphic and heteromorphic states, as well as between sex-determination systems. Most (~75%) anurans have homomorphic sex chromosomes, with XY systems being three times more common than ZW systems. Most remaining anurans (~25%) have heteromorphic sex chromosomes, with XY and ZW systems almost equally represented. There are Y-autosome fusions in 11 species, and no W-/Z-/X-autosome fusions are known. The phylogeny represents at least 19 transitions between sex-determination systems and at least 16 cases of independent evolution of heteromorphic sex chromosomes from homomorphy, the likely ancestral state. Five lineages mostly have heteromorphic sex chromosomes, which might have evolved due to demographic and sexual selection attributes of those lineages. Males do not recombine over most of their genome, regardless of which is the heterogametic sex. Nevertheless, telomere-restricted recombination between ZW chromosomes has evolved at least once. More comparative genomic studies are needed to understand the evolutionary trajectories of sex chromosomes among frog lineages, especially in the ZW systems.

Degenerative mutations in non-recombining regions, such as in sex chromosomes, may lead to differential expression between alleles if mutations occur stochastically in one or the other allele. Reduced allelic expression due to degeneration has indeed been suggested to occur in various sex-chromosome systems. However, whether an association occurs between specific signatures of degeneration and differential expression between alleles has not been extensively tested, and sexual antagonism can also cause differential expression on sex chromosomes. The anther-smut fungus Microbotryum lychnidis-dioicae is ideal for testing associations between specific degenerative signatures and differential expression because 1) there are multiple evolutionary strata on the mating-type chromosomes, reflecting successive recombination suppression linked to mating-type loci; 2) separate haploid cultures of opposite mating types help identify differential expression between alleles; and 3) there is no sexual antagonism as a confounding factor accounting for differential expression. We found that differentially expressed genes were enriched in the four oldest evolutionary strata compared with other genomic compartments, and that, within compartments, several signatures of sequence degeneration were greater for differentially expressed than non-differentially expressed genes. Two particular degenerative signatures were significantly associated with lower expression levels within differentially expressed allele pairs: upstream insertion of transposable elements and mutations truncating the protein length. Other degenerative mutations associated with differential expression included nonsynonymous substitutions and altered intron or GC content. The association between differential expression and allele degeneration is relevant for a broad range of taxa where mating compatibility or sex is determined by genes located in large regions where recombination is suppressed.

To explore the potential environmental and dietary factors during pregnancy affecting low-level prenatal lead exposure, we conducted a longitudinal study in Wujiang City, China. A total of 1976 mother-infant pairs were included from 2009 to 2010. An interviewed questionnaire was conducted and cord blood samples were collected. The geometric means of cord blood lead level was 30.3 μg/L (95% CI, 29.8–30.8) with 99.24% below 100 μg/L. Maternal age, passive smoking, and living in the countryside were significantly associated with cord blood lead concentrations. Multiple logistic models showed that some family environmental factors including using firewood and electricity as kitchen fuel were positively correlated with increased cord blood lead levels. Among dietary sources recorded in this study, meat consumption (> 3 times/week), fish consumption (1–3 times/week), vegetables consumption (> 1 times/day), and fruit intake (> 1 times/day) had inverse relationship with cord blood lead levels. In general, our findings may have important implications for family environmental and dietary direction during pregnancy to decrease prenatal lead exposure.

To review, summarize, and analyze both similarities and differences of pharmacoeconomic (PE) guidelines, to enable researchers to access their characteristics and the current state of PE guidelines; furthermore, to learn which methodological issues still remain contested and to promote the methodological development of PE guidelines.The authors performed a search for PE guidelines using PubMed, the Cochrane library database, and the websites of the International Society for Pharmacoeconomics and Outcomes Research. Information of each guideline was extracted using a pre-designed extraction template, which included 22 aspects; the guidelines were summarized in the forms of charts, and their characteristics have been described.A total of 40 PE guidelines were studied. The most common methodological issues include the types of analysis, sources for effectiveness, use of quality-adjusted life-years (QALYs) to measure outcomes, and use of incremental cost effectiveness ratios to present results. The majority of the guidelines preferred a cost utility analysis with outcomes expressed in terms of QALYs. Most of the guidelines preferred meta-analysis or meta-analysis of the randomized controlled trials, and required a systematic review of all evidence. Issues that varied most in the guidelines were the choice of the comparator, recommended costs to be included, methods related to indirect cost calculations, methods of sensitivity analysis, and discounting rate.A comparison of these guidelines revealed that a number of differences exist among them in several key aspects, and some critical methodological issues still exist, for which no best solution is available. Furthermore, efforts need to be made to develop harmonious methods for the PE, and to improve the transferability of the outcomes of PE evaluations.

Sex-determination mechanisms vary both within and among populations of common frogs, opening opportunities to investigate the molecular pathways and ultimate causes shaping their evolution. We investigated the association between sex-chromosome differentiation (as assayed from microsatellites) and polymorphism at the candidate sex-determining gene Dmrt1 in two Alpine populations. Both populations harbored a diversity of X-linked and Y-linked Dmrt1 haplotypes. Some males had fixed male-specific alleles at all markers (‘differentiated’ Y chromosomes), others only at Dmrt1 (‘proto-’ Y chromosomes), while still others were genetically indistinguishable from females (undifferentiated X chromosomes). Besides these XX males, we also found rare XY females. The several Dmrt1 Y haplotypes differed in the probability of association with a differentiated Y chromosome, which we interpret as a result of differences in the masculinizing effects of alleles at the sex-determining locus. From our results, the polymorphism in sex-chromosome differentiation and its association with Dmrt1, previously inferred from Swedish populations, are not just idiosyncratic features of peripheral populations, but also characterize highly diverged populations in the central range. This implies that an apparently unstable pattern has been maintained over long evolutionary times. This article is protected by copyright. All rights reserved.

The canonical model of sex-chromosome evolution assigns a key role to sexually antagonistic (SA) genes on the arrest of recombination and ensuing degeneration of Y chromosomes. This assumption cannot be tested in organisms with highly differentiated sex chromosomes, such as mammals or birds, owing to the lack of polymorphism. Fixation of SA alleles, furthermore, might be the consequence rather than the cause of recombination arrest. Here we focus on a population of common frogs (Rana temporaria) where XY males with genetically differentiated Y chromosomes (nonrecombinant Y haplotypes) coexist with both XY° males with proto-Y chromosomes (only differentiated from X chromosomes in the immediate vicinity of the candidate sex-determining locus Dmrt1) and XX males with undifferentiated sex chromosomes (genetically identical to XX females). Our study finds no effect of sex-chromosome differentiation on male phenotype, mating success or fathering success. Our conclusions rejoin genomic studies that found no differences in gene expression between XY, XY° and XX males. Sexual dimorphism in common frogs might result more from the differential expression of autosomal genes than from sex-linked SA genes. Among-male variance in sex-chromosome differentiation seems better explained by a polymorphism in the penetrance of alleles at the sex locus, resulting in variable levels of sex reversal (and thus of X-Y recombination in XY females), independent of sex-linked SA genes.

The canonical model of sex-chromosome evolution assigns a key role to sexually antagonistic (SA) genes on the arrest of recombination and ensuing degeneration of Y chromosomes. This assumption cannot be tested in organisms with highly differentiated sex chromosomes, such as mammals or birds, owing to the lack of polymorphism. Fixation of SA alleles, furthermore, might be the consequence rather than the cause of recombination arrest. Here we focus on a population of common frogs (Rana temporaria) where XY males with genetically differentiated Y chromosomes (non-recombinant Y haplotypes) coexist with both XY° males with proto-Y chromosomes (only differentiated from X chromosomes in the immediate vicinity of the candidate sex-determining locus Dmrt1) and XX males with undifferentiated sex chromosomes (genetically identical to XX females). Our study shows no effect of sex-chromosome differentiation on male phenotype, mating success or fathering success. Our conclusions rejoin genomic studies that found no differences in gene expression between XY, XY° and XX males. Sexual dimorphism in common frogs seems to result from the differential expression of autosomal genes rather than sex-linked SA genes. Among-male variance in sex-chromosome differentiation is better explained by a polymorphism in the penetrance of alleles at the sex locus, resulting in variable levels of sex reversal (and thus of X-Y recombination in XY females), independent of sex-linked SA genes.Impact SummaryHumans, like other mammals, present highly differentiated sex chromosomes, with a large, gene-rich X chromosome contrasting with a small, gene-poor Y chromosome. This differentiation results from a process that started approximately 160 Mya, when the Y first stopped recombining with the X. How and why this happened, however, remain controversial. According to the canonical model, the process was initiated by sexually antagonistic selection; namely, selection on the proto-Y chromosome for alleles that were beneficial to males but detrimental to females. The arrest of XY recombination then allowed such alleles to be only transmitted to sons, not to daughters. Although appealing and elegant, this model can no longer be tested in mammals, as it requires a sex-chromosome system at an incipient stage of evolution. Here we focus on a frog that displays within-population polymorphism is sex-chromosome differentiation, where XY males with differentiated chromosomes coexist with XX males lacking Y chromosomes. We find no effect of sex-chromosome differentiation on male phenotype or mating success, opposing expectations from the standard model. Sex linked genes do not seem to have a disproportionate effect on sexual dimorphism. From our results, sexually antagonistic genes show no association with sex-chromosome differentiation in frogs, which calls for alternative models of sex-chromosome evolution.

Background and Purpose. Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation. Methods. We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses. Key Results. A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P<0.001; I2=0%) and clinical response (OR, 2.75 [1.33, 5.67]; P=0.006; I2=49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P=0.37; I2=69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P=0.44; I2=0%). Conclusions and Inferences. Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.

The integration of Chinese medicine (CM) and Western medicine (WM) has obvious advantages. However, basic theories of CM and WM are hard to integrate at the present stage due to radical difference in world view and methodology between them. CM and WM share the same objective, i.e., saving life and treating disease, so they can be integrated technologically. And only in this way can focus the integration of CM and WM on solving practical problems and obtaining clinical efficacy. The integration in this way is firmly and valuable.

Nonrecombining sex chromosomes are widely found to be more differentiated than autosomes among closely related species, due to smaller effective population size and/or to a disproportionally large-X effect in reproductive isolation. Although fungal mating-type chromosomes can also display large nonrecombining regions, their levels of differentiation compared with autosomes have been little studied. Anther-smut fungi from the Microbotryum genus are castrating pathogens of Caryophyllaceae plants with largely nonrecombining mating-type chromosomes. Using whole genome sequences of 40 fungal strains, we quantified genetic differentiation among strains isolated from the geographically overlapping North American species and subspecies of Silene virginica and S. caroliniana. We inferred that gene flow likely occurred at the early stages of divergence and then completely stopped. We identified large autosomal genomic regions with chromosomal inversions, with higher genetic divergence than the rest of the genomes and highly enriched in selective sweeps, supporting a role of rearrangements in preventing gene flow in genomic regions involved in ecological divergence. Unexpectedly, the nonrecombining mating-type chromosomes showed lower divergence than autosomes due to higher gene flow, which may be promoted by adaptive introgressions of less degenerated mating-type chromosomes. The fact that both mating-type chromosomes are always heterozygous and nonrecombining may explain such patterns that oppose to those found for XY or ZW sex chromosomes. The specific features of mating-type chromosomes may also apply to the UV sex chromosomes determining sexes at the haploid stage in algae and bryophytes and may help test general hypotheses on the evolutionary specificities of sex-related chromosomes.

Background The lack of adequate medical care, healthcare, and older adult care in remote, low-income, rural Kazakh areas of China is a particular concern that should be prioritized for improvement. Purpose This study was designed to explore the relationship between the variables of disability severity, social support, and caregiver competence and the quality of home-based care in a population of Kazakh older adults with disabilities and to analyze the path between severity of disability and quality of home-based care in this population. Methods A cross-sectional survey was conducted on 335 Kazakh older adults with disabilities living in Xinjiang, China, and their primary informal caregivers. Disability severity was assessed using the Activities of Daily Living Scale, caregiver competence was assessed using the Family Caregiver Task Inventory, social support was assessed using the Social Support Rating Scale, and home-based care quality was assessed using the Family Caregiving Consequences Inventory Scale. Path analysis was used to check the effects of other variables on the quality of home-based care. Results Significant correlations were found among disability severity, caregiver competence, social support, and home-based care quality. Disability severity was shown to have a 29.28% direct effect on home-based care quality and a 70.72% indirect effect through social support and caregiver competence. Conclusions The results of this study confirm that better social support and caregiver competence improves the quality of home-based care available to older adults with disabilities. Policymakers should give priority to improving the quality of care provided to community-dwelling older adults with severe disabilities. Furthermore, health management departments should provide informal caregiver training that teaches care and rehabilitation knowledge and skills to improve the competencies of caregivers.

Despite the global abundance of studies on children’s lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children’s Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0–84 months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1 µg/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7 μg/L, with 8.6% of BLLs exceeding 50 µg/L. Boys had higher BLLs (GM 27.2 μg/L) compared to girls (GM: 25.9 μg/L) (p

Sex-biased genes are central to the study of sexual selection, sexual antagonism, and sex chromosome evolution. We describe a comprehensive de novo assembled transcriptome in the common frog Rana temporaria based on five developmental stages and three adult tissues from both sexes, obtained from a population with karyotypically homomorphic but genetically differentiated sex chromosomes. This allows the study of sex-biased gene expression throughout development, and its effect on the rate of gene evolution while accounting for pleiotropic expression, which is known to negatively correlate with the evolutionary rate. Overall, sex-biased genes had little overlap among developmental stages and adult tissues. Late developmental stages and gonad tissues had the highest numbers of stage- or tissue-specific genes. We find that pleiotropic gene expression is a better predictor than sex bias for the evolutionary rate of genes, though it often interacts with sex bias. Although genetically differentiated, the sex chromosomes were not enriched in sex-biased genes, possibly due to a very recent arrest of XY recombination. These results extend our understanding of the developmental dynamics, tissue specificity, and genomic localization of sex-biased genes.

To mainly analyze the prescription rules of Chinese herbal drugs for radiation induced lung injury, optimize the prescriptions, and provide a reference for the clinical treatment of radiation induced lung injury. The major Chinese databases CNKI, CBM and Wanfang data were searched to obtain the literature on Chinese herbal drugs for radiation induced lung injury. BICOMS 2 software was used to extract and collect all Chinese herbal drugs information and generate the co-occurrence matrix; NetDraw and Gcluto software were then used to make network map and visualization matrix for analysis. A total of 552 articles (19 types and 304 Chinese herbal drugs) were included. Ophiopogon japonicus had the highest frequency (229 times), followed by Astragalus membranaceus(181 times), Glycyrrhiza uralensis (166 times), and Scutellaria baicalensis (150 times). After the classification of efficacy, deficiency-supplementing medicinal (69 kinds of Chinese herbs), heat-clearing medicine (51 kinds of Chinese herbs) and phlegm cough medicine (42 kinds of Chinese herbs) accounted for 53.29% of all the Chinese herbs, acting in the main position. After the prescription analysis for the top 25 herbal prescriptions, six main structures of common prescriptions were found for the treatment of radiation induced lung injury. There are many kinds of Chinese herbal drugs for the treatment of radiation induced lung injury in clinical application. In the future, researchers can mainly focus on Ophiopogon japonicus etc. as the main drugs, combine with other high-frequency Chinese herbal drugs found in this study, or directly refer to the main structures of commonly used prescriptions found in this analysis.

Patchmatch based stereo is an efficient method for stereo computation, and also has been extent to multiple-view stereo recently. In this paper we extend the two-view patchmatch stereo to multiple-views in the multiple-view stereo pipeline. The key of the proposed method is to first select multiple suitable neighboring images for a reference image and then combine them under the patchmatch stereo framework. Experimental results on benchmark data sets demonstrate the accuracy and efficiency of the proposed method.

Female-producing parthenogenesis can be induced by endosymbionts that increase their transmission by manipulating host reproduction. Our literature survey indicates that such endosymbiont-induced parthenogenesis is known or suspected in 124 host species from seven different arthropod taxa, with Wolbachia as the most frequent endosymbiont (in 56–75% of host species). Most host species (81%, 100 out of 124) are characterized by haplo-diploid sex determination, but a strong ascertainment bias likely underestimates the frequency of endosymbiont-induced parthenogenesis in hosts with other sex determination systems. In at least one taxon, hymenopterans, endosymbionts are a significant driver of transitions from sexual to parthenogenetic reproduction, with one-third of lineages being parthenogenetic as a consequence of endosymbiont infection. Endosymbiont-induced parthenogenesis appears to facilitate the maintenance of reproductive polymorphism: at least 50% of species comprise both sexual (uninfected) and parthenogenetic (infected) strains. These strains feature distribution differences similar to the ones documented for lineages with genetically determined parthenogenesis, with endosymbiont-induced parthenogens occurring at higher latitudes than their sexual relatives. Finally, although gamete duplication is often considered as the main mechanism for endosymbiont-induced parthenogenesis, it underlies parthenogenesis in only half of the host species studied thus far. We point out caveats in the methods used to test for endosymbiont-induced parthenogenesis and suggest specific approaches that allow for firm conclusions about the involvement of endosymbionts in the origin of parthenogenesis.

Background Although endoscopic nasopharyngectomy and intensity-modulated radiotherapy (IMRT) have been reported to be useful in treating isolated local recurrent nasopharyngeal carcinoma (NPC), their efficacy needs to be revaluated with comparison to 2D conventional radiotherapy (RT). Methods Four hundred ten patients with recurrent NPC were retrospectively analyzed, among whom the patients underwent IMRT, endoscopic nasopharyngectomy, and 2D conventional RT. Results The 5-year overall survival (OS) and distant metastasis-free survival were significantly higher in endoscopic nasopharyngectomy and IMRT groups than in 2D conventional RT group both in the entire series and in the subgroup of patients with recurrent T1 to 2 NPC (p

Tetranuclear square grids, namely, [Cd4(L–O)4]·1.5DMF (1), [Ni4(L–O)4]·H2O (2), [Zn4(L–O)4]·3H2O (3), [Zn4(L–O)4] (4), [Cu4(L–O)4]·H2O (5), and {[Cu4(L–O)4][Cu4(L–O)4]}·2.5DMF·1.5H2O (6) (DMF = N,N-dimethylformamide, H2L–O = 2,6-bis(pyrazine-2-carboxamido)pyridine-N-oxide), formed by the reactions of M ions (M = CdII, NiII, ZnII and CuII) with pyridyldicarboxamide ligands 2,6-bis(pyrazine-2-carboxamido)pyridine (H2L), was fully characterized. Notably, the central pyridines of ligands H2L were oxidized into pyridine-N-oxides under air conditions, producing the new anionic ligands (L–O)2− to fabricate those grids. In those square grids every octahedrally coordinated metal node is chelated by two doubly deprotonated ligands (L–O)2− in the mer configuration, and each ligand (L–O)2− acts as a rigid bis(tridentate) linker with the Ncarboxamide and one Npyrazine in each arm chelating metal ions plus the O atom in the pyridine-N-oxide group bridging the two bound M ions. The CdII and ZnII grids show uncommonly-excellent thermal stabilities and interesting green emissions. Magnetic studies upon grid [Ni4(L–O)4] suggest an antiferromagnetic coupling between the adjacent NiII mainly exchanged through μ–O with a coupling constant of J = −15.06 cm−1.

The mechanical properties of rock mass under unloading conditions are essentially different from that under loading conditions. Triaxial compression tests and unloading confining pressure tests are conducted, and test results show that unloading failure is more brittle, and rock samples suffer more damage under unloading failure. The larger the initial confining pressure is, the easier of unloading failure is occurred. The increasing or decreasing values of rock deformation modulus under unloading conditions are within 10% of rock triaxial compressive strength. Unloading failure leads to deterioration of rock deformation modulus, which decreases gradually with confining pressure decreasing, and the decrease rates get bigger and bigger with unloading ratio of confining pressure increasing. Deformation modulus is only 24-34% of that under loading condition when rock strength goes down to residual strength.

The aim of this study was to assess the quality of clinical practice guidelines of traumatic brain injury (TBI) and investigate the evidence grading systems. A systematic search of relevant guideline websites and literature databases (including PubMed, NGC, SIGN, NICE, GIN, and Google) was undertaken from inception to May 2018 to identify and select TBI guidelines. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. The degree of agreement was evaluated with intraclass correlation coefficient (ICC). From 1802 records retrieved, 12 TBI guidelines were included. The mean scores for each AGREE II domain were as follows: scope and purpose (mean ± SD= 74.2 ± 9.09); stakeholder involvement (mean± SD= 54.6 ± 11.6); rigor of development (mean ± SD=70.1 ± 13.6); clarity and presentation (mean ± SD=78.4 ± 11.5); applicability (mean ± SD= 60.5 ± 13.6); and editorial independence (mean ± SD=61.7 ± 14.8). Ten guidelines were rated as “recommended.” The ICC values ranged from 0.73 to 0.95. Seven grading systems were used by TBI guidelines to rate the level of evidence and the strength of recommendation. Most TBI guidelines got a high-quality rating, whereas a standardized grading system should be adopted to provide clear information about the level of evidence and strength of recommendation in TBI guidelines.

Arthropods exhibit a large variety of sex determination systems both at the chromosomal and molecular level. Male heterogamety, female heterogamety, and haplodiploidy occur frequently, but partially different genes are involved. Endosymbionts, such as Wolbachia, Cardinium,Rickettsia, and Spiroplasma, can manipulate host reproduction and sex determination. Four major reproductive manipulation types are distinguished: cytoplasmic incompatibility, thelytokous parthenogenesis, male killing, and feminization. In this review, the effects of these manipulation types and how they interfere with arthropod sex determination in terms of host developmental timing, alteration of sex determination, and modification of sexual differentiation pathways are summarized. Transitions between different manipulation types occur frequently which suggests that they are based on similar molecular processes. It is also discussed how mechanisms of reproductive manipulation and host sex determination can be informative on each other, with a special focus on haplodiploidy. Future directions on how the study of endosymbiotic manipulation of host reproduction can be key to further studies of arthropod sex determination are shown.

In recent years, cucurbit[7]uril (CB[7]) has attracted great attention in drug delivery. Though the effect of CB[7] in enhancing the solubility of water insoluble drugs has been validated, the underlying mechanism remains poorly understood, particularly at a molecular level. This study is designed to evaluate a CB[7]-based pharmaceutical formulation to improve solubility and bioavailability of triamterene (a mild potassium-sparing diuretic). Two polymorphs of triamterene@CB[7] were obtained, and their crystal structures were determined by single crystal X-ray diffraction. The CB[7] molecule forms a stable host-guest complex with triamterene (Ka = 1.69 ± 0.34 × 10(4) M(-1)) in aqueous solution (pH = 1.0). The results of dissolution study demonstrate that the apparent solubility value of triamterene@CB[7] complex in 0.1 M HCl is 1.6 times as large as that of triamterene, while free triamterene was released from triamterene@CB[7] complex in phosphate buffer of pH 6.8. Pharmacokinetic studies in rats reveal that the AUC0-∞ value of triamterene@CB[7] complex increases 2.8-fold compared with that of free triamterene, and t1/2 is prolonged from 1.42 to 2.61 h (P0.05) after oral administration. The increased solubility and oral bioavailability are attributed to the formation of a hydrophilic capsule composed of two CB[7] molecules, in which two insoluble triamterene molecules are encapsulated. These results demonstrate that triamterene@CB[7] complex is a stable and effective pharmaceutical formulation.