Search

Abstract Background Post-intensive care syndrome (PICS) is a term coined by the Society of Critical Care Medicine to describe the psychological, cognitive, and physical dysfunction that ICU survivors may experience. Although surgical patients represent a substantial proportion of ICU survivors, studies describing PICS in this specific population remain limited. This study aims to determine the incidence and independent risk factors associated with PICS among surgical ICU survivors in a Chinese cohort. Methods The study was a prospective cohort study of critically ill surgical patients who were discharged from the ICU at the First Affiliated Hospital of Sun Yat-sen University between August 2021 and June 2022. Demographic characteristics, disease-related information, and ICU treatment were collected, and enrolled participants were followed up within six months after ICU discharge. The Chinese version of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and the Short Memory Questionnaire (SMQ) were used to assess PICS. The physical component summary (PCS) and the mental component summary (MCS) were averaged from the corresponding four-dimension scores in the SF-36. PICS diagnosis was determined based on the presence of at least one of the following: physiological dysfunction (defined as PCS reductions greater than 10), psychological dysfunction (defined as MCS reductions greater than 10), or cognitive dysfunction (defined as SMQ reductions and scores less than 40 at six months). PICS diagnosis was based on the presence of at least one of the following: physiological, psychological, or cognitive dysfunction. Results A total of 565 patients were screened in this study, and 83 were enrolled after applying the inclusion and exclusion criteria. Overall, 65 surgical ICU survivors developed PICS within six months, with an incidence rate of 78.3%. The prevalences were 55.4% and 27.7% at the end of 3 and 6 months after ICU discharge, respectively. Univariate analysis showed that there was a correlation between the occurrence of PICS and the total bilirubin and creatinine levels at ICU admission, APACHE II score, ICU length of stay, and the presence of dialysis (P

The Chinese wheat landrace Kaixianluohanmai (KL) expresses the ph-like phenotype. A major QTL, QPh.sicau-3A (syn. phKL), responsible for this effect has been mapped to chromosome arm 3AL. This study presents some characteristics of homoeologous pairing and recombination induced by phKL. In KL haploids, the level of homoeologous pairing was elevated relative to Ph1 Chinese Spring (CS) haploids. There was a clear preference for A–D pairing and less frequent for A–B and B–D, reflecting the higher levels of affinity between genomes A and D in wheat. The characteristics of pairing were affected by temperature and magnesium ion supplementation. The suitability of phKL for chromosome engineering was tested on three pairs of homoeologues: 2Sv-2B, 2Sv-2D, and 2RL-2BL. The recombination rates were 1.68%, 0.17%, and 0%, respectively. The phKL locus in KL induced a moderate level of homoeologous chromosome pairing and recombination when the Ph1 locus of wheat was present, both in wheat haploids and hexaploids. The Ph1-imposed criteria for chromosome pairing and crossing over were relaxed to some degree, permitting homoeologous crossing over but only between closely related chromosomes; there was no crossing over between more differentiated chromosomes. Therefore, the phKL system (QPh.sicau-3A) can be a useful tool in chromosome engineering of wheat to transfer genes from closely related species with the benefit of reduced genomic chaos generated by the ph1b mutation.

BackgroundThyroid carcinoma (TC) is the most common malignant endocrine tumor worldwide. Several studies have documented that male patients with TC have a higher rate of metastasis and disease recurrence than female patients. However, the mechanism underlying this observation is not completely clear. The goal of our research was to investigate the potential key candidate genes and pathways related to TC progression in male patients at the molecular level.MethodsA total of 320 samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Hub genes were screened out using weighted gene coexpression network analysis (WGCNA) and a protein–protein interaction (PPI) network analysis. Survival analysis was used to identify hub genes associated with disease-free survival (DFS) rates. Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression (ESTIMATE) data were used to assess the relationship between hub genes and immune cell infiltration. The molecular mechanism and biological functions of hub genes were explored using RT-qPCR, Western blot, Cell Counting Kit-8 Assay, flow cytometry, Transwell assays, and scratch assays.ResultsForty-seven hub genes were identified, and the survival analysis demonstrated that anti-silencing function 1B (ASF1B) was the sole independent risk factor for poor DFS in male TC patients. Possible associations between the results from the ESTIMATE analysis showed that the ASF1B expression level was related to the ESTIMATE score, immune score, and T-cell regulatory (Treg) infiltration level. Through in vitro cell function experiments, we verified that knockdown of ASF1B inhibited KTC-1 cell proliferation, promoted cell apoptosis, and blocked cell cycle. The silencing of ASF1B reduced protein kinase B (AKT), phospho-AKT (p-AKT), and forkhead box p3 (FOXP3) in KTC-1 cells. Moreover, FOXP3 overexpression markedly restored the cell migration, invasion, and proliferation abilities repressed by ASF1B knockdown.ConclusionsOur results indicate that ASF1B can be considered a prognostic marker, therapeutic target, and predictor of immunotherapy response in male thyroid cancer patients. However, further in-depth studies are required to validate this finding.

Sulfate-reducing bacteria are a group of microorganisms that use sulfate as an electron acceptor. These bacteria are useful in the bioremediation of heavy metal pollution since they can reduce/precipitate metals. Previously, we identified the Alishewanella strain WH16-1 from soil of a copper and iron mine and determined that it can reduce sulfate and chromate and that it was tolerant to many heavy metals. In this study, we investigated the chromate reduction mechanism of strain WH16-1 through Tn5 transposon mutagenesis. A cytochrome bd (cytbd) Tn5 mutant was generated (Δcytbd), and a detail analysis showed that the following: (1) gene cydE (coding for a GbsR-type regulator) was co-transcribed with the two subunits coding genes of the Cytochrome bd complex (Cytbd), namely, cydA and cydB, based on RT-PCR analysis, and similar gene arrangements were also found in other Alteromonadaceae family strains; (2) the chromate resistance level was dramatically decreased and chromate reduction efficiency also decreased in strain Δcytbd compared to the wild-type and a complemented strain (Δcytbd-C); (3) Cytbd could catalyze the decomposition of H2O2 according to the analyses of H2O2 decomposition ability, cellular H2O2 contents, H2O2 inhibition zone, and H2O2 sensitivity tests; (4) surprisingly, chromate was not an inducer of the expression of Cytbd, but sulfate induced expression of Cytbd, and sulfate/sulfide resistance levels were also decreased in the Δcytbd strain; (5) the addition of sulfate enhanced the chromate resistance level and reduction efficiency; (6) Cytbd expression was repressed by CydE and derepressed by sulfate based on an in vivo bacterial one hybrid system and in vitro EMSA tests; and (7) DNA footprinting and short-fragment EMSA tests revealed two binding sites of CydE in its promoter region. All these results showed that Cytbd is negatively regulated by CydE and derepressed by sulfate. In addition, Cytbd contributes to the resistance of sulfate and sulfide, and sulfide could be used as a reductant to reduce chromate. Moreover, Cytbd is essential to decompose H2O2 to decrease cellular oxidative stress. Thus, the regulation and function of Cytbd may explain why sulfate could enhance chromate reduction.

Abstract Objective The aim of this study was to investigate the influence of osthole (OS) on asthma-induced airway epithelial cell apoptosis and inflammation by restraining Th2 differentiation through suppressing TSLP/NF-κB. Methods An asthma mouse model and an inflammation cell model were constructed with ovalbumin (OVA) and lipopolysaccharide (LPS), respectively. CD4 + T cells were treated with IL-4 to induce Th2 differentiation. Model mice were treated with OS (15,40 mg/kg) for 7 days, and 10 µg/mL OS was added to cell treatment groups. The levels of relevant indices were detected by RT‒qPCR, HE and Masson staining, Western blotting, ELISA and flow cytometry. Results In a mouse asthma model, TSLP expression was elevated, and the NF-κB pathway was activated. Therefore, OS could restrain the apoptosis and inflammation of airway epithelial cells. Downstream mechanistic studies revealed that OS can suppress Th2 differentiation by restraining the level of TSLP and NF-κB nuclear translocation, thus facilitating the proliferation of airway epithelial cells, restraining their apoptosis and inflammation, and alleviating airway inflammation in asthmatic mice. Conclusion OS can inhibit Th2 differentiation by inhibiting the TSLP and NF-κB pathways, which can reduce the apoptosis and inflammation of airway epithelial cells caused by asthma.

CD7-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL). In this study, we reported a case of a 34-year-old male patient with T-ALL who finally developed multi-line drug resistance and refractoriness after multiple lines of high-intensity chemotherapy. After physician evaluation, this patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Then, The patient remained in complete remission (CR) for four months before a relapse with 26.64% chimerism rate, so he was treated with allogeneic anti-CD7 CAR-T cells after chemotherapy reducing the tumor burden. The CAR-T product was a novel anti-CD7 CAR-T based on retroviral vectors (RV). After infusion, the patient achieved CR within 1 month after anti-CD7 CAR-T infusion and the remission has been ongoing for 9 months to date. Cytokine release syndrome (CRS) 1 was experienced while no immune effector cell-associated neurotoxicity syndrome (ICANS) was found. In addition, CAR copy number peaked at 350, 758 copies/μg on day 6. This case report of clinical treatment of T-ALL with anti-CD7 CAR-T cells prepared using a retroviral vector without gene editing and combined with chemotherapy, which demonstrated that the RV-based anti-CD7 CAR-T cells had good therapeutic effect and high safety in triple-refractory T-ALL patients.

Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.

Background: Although studies in China have found that school bullying is prevalent among adolescents, most relevant research has focused on southern China, while research in northern China is limited. This study aimed to explore ethnic disparities in the socio-demographic determinants of school bullying in Inner Mongolia, a northern region of China. Methods: A cross-sectional study was conducted among 2891 adolescents in Inner Mongolia, China, from September to December 2022. Data on participants' sociodemographic characteristics and school bullying experiences were collected through questionnaires. Multivariate logistic regression analyses, stratified by ethnicity, were employed to examine factors associated with school bullying. Furthermore, subgroup analyses and interaction tests were conducted to explore potential effect modifiers of the relationship between ethnicity and bullying. Results: The prevalence of school bullying was 18.99 % (549/2891) overall, with 17.96 % (420/2339) among Han and 23.37 % (129/552) among ethnic minorities. Minority adolescents faced a higher risk of bullying compared to Han (OR = 1.35, 95 % CI: 1.08–1.69, P 0.05). Limitations: This cross-sectional study has limitations in establishing causal relationships between identified associated factors and school bullying. Conclusions: Ethnic minority adolescents in Inner Mongolia, China, especially middle school students, face a higher risk of school bullying than their Han peers. The differential impact of maternal education, family economic status, and family structure on bullying risk between Han and minority adolescents underscores the need for culturally sensitive, targeted interventions that consider the unique challenges faced by ethnic minority students.

Ischemic stroke (IS) is a cerebrovascular sickness, and cerebral ischemia-reperfusion (I/R) damage often occurs, but there is still a lack of drugs that can significantly alleviate it. Curcumin (Cur) exerts pharmacological effects such as antioxidative stress, anti-inflammation, and the promotion of apoptosis through regulating various pathways, but its efficacy and specific mechanism of action in IS have not been fully clarified. The purpose of this paper is to study the influence of Cur on IS. Brain microvascular endothelial cells (BMECs) were used to create an oxygen-glucose deprivation/reoxygenation (OGD/R) model to simulate I/R damage. The cell viability was assessed using an MTT assay. The LDH level and ROS positive rate were measured using commercial kits. The cell invasion was examined using a transwell assay. The apoptosis was assessed by flow cytometry. The contents of GMFB, Bax, and Bcl2 were measured using western blot. We confirmed that in the OGD/R-induced IS cell model, the abundance of GMFB was enhanced in the OGD/R group versus the control group. GMFB overexpression promoted OGD/R-induced cell viability diminution, increased LDH and ROS levels, lessened cell invasion ability, enhanced cell apoptosis, enhanced Bax levels, and decreased Bcl2 levels. Silencing GMFB ameliorated OGD/R-induced cell damage. Cur ameliorated OGD/R-induced cell damage. Cur curbed OGD/R-induced cell damage by downregulating GMFB expression. In conclusion, Cur cured ischemic stroke-induced cell damage by downregulating GMFB expression.

Drawing on two theoretical frameworks–positive psychology theory and conservation of resources theory–the relationship and underlying mechanism between team-level service-oriented human resource practice (SO-HRP) bundles and team performance were explored by constructing a team-level serial mediation model. Survey data were collected from 424 employees at 80 branches of five financial holding companies in Northern Taiwan. The team-level serial-mediated model and hypotheses were examined using SPSS version 24 and the PROCESS macro for SPSS. The results indicate that team psychological capital (PsyCap) and team work engagement serially mediated the relationship between SO-HRP bundles and team performance. These results imply that managers should plan and implement SO-HRP bundles in detail, reinforce team PsyCap, and increase engagement within their financial service teams to enhance team performance.

Background: Endometrial carcinoma (EC) is a prevalent gynecological malignancy, necessitating accurate preoperative staging for effective treatment planning. This study explores the application value of multi-parameter MRI in diagnosing and staging endometrial cancer. Methods: Seventy-six patients diagnosed with endometrial cancer underwent 3.0 T pelvic MRI within two weeks before surgery. Imaging data were analyzed based on FIGO clinical staging criteria. The study assessed the sensitivity, specificity, positive predictive value, and negative predictive value of MRI for each stage. Results: Postoperative pathology confirmed 71 cases of endometrial adenocarcinoma, 3 serous adenocarcinoma, and 2 clear cell carcinomas. MRI staging showed a high consistency (Kappa value = 0.786) with postoperative pathology. The overall accuracy of MRI diagnosis was 86.8%. Sensitivity and specificity varied for each stage: IA (91.3%, 96.2%), IB (88.6%, 93.8%), II (97.4%, 89.2%), and III (84.2%, 100%). Conclusion: While there was a slight misdiagnosis rate, the overall accuracy of preoperative MRI for endometrial cancer was high, aiding in precise diagnosis and clinical staging. MRI effectively identified myometrial infiltration, cervical involvement, paracentral extension, and lymph node metastasis. Further research with larger sample sizes is recommended for enhanced reliability.

Abstract Purpose To investigate the influence of β-arrestin2 on the docetaxel resistance in castration-resistant prostate cancer (CRPC) and elucidate the underlying molecular mechanisms. Methods PC3 and DU145 cells with stable β-arrestin2 overexpression and C4-2 cells with stable β-arrestin2 knockdown, were constructed via using lentivirus and puromycin selection. MTT and colony formation assays were carried out to investigate the effect of β-arrestin2 expression on the docetaxel resistance of CRPC cells. Glycolysis analysis was used to assess the glycolytic capacity modulated by β-arrestin2. GO enrichment analysis, gene set enrichment analysis and Spearman correlation test were carried out to explore the potential biological function and mechanism via using public data from GEO and TCGA. The expressions of PKM2, Phospho-PKM2, Phospho-ERK1/2 and hnRNP A1 were detected by western blot. Functional blocking experiments were carried out to confirm the roles of PKM2 and hnRNP A1 in the regulation of β-arrestin2’s biological functions via silencing PKM2 or hnRNP A1 expression in cells with stable β-arrestin2 overexpression. Finally, nude mice xenograft models were established to confirm the experimental results of cell experiments. Results β-Arrestin2 significantly decreased the sensitivity of CRPC cells to docetaxel stimulation, through enhancing the phosphorylation and expression of PKM2. Additionally, β-arrestin2 increased PKM2 phosphorylation via the ERK1/2 signaling pathway and induced PKM2 expression in a post-transcriptional manner through an hnRNP A1-dependent PKM alternative splicing mechanism, rather than by inhibiting its ubiquitination degradation. Conclusion Our findings indicate that the β-arrestin2/hnRNP A1/PKM2 pathway could be a promising target for treating docetaxel-resistant CRPC.

Abstract Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. HER2-low breast cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, the characteristic remains unknown. Our aim was to explore the differences of clinicopathological indicators and survival outcomes between HER2-low and HER2-0 breast cancers. We retrospectively analyzed 501 invasive breast cancer patients with complete data on HER2 status from 2017 to 2021 in our single center, of whom 415 HER2 negative patients were included for subsequent analysis. Each cohort was further divided into hormone receptor (HR) positive and HR negative subgroup. Clinicopathological factors and survival outcomes were collected and compared between HER2-low BCs and HER2-0 BCs. HER2-low BCs was obviously higher in HR positive BCs, with 277 (90.5%) HER2-low HR positive patients, 29 (9.5%) HER2-low HR negative patients, 68 (62.4%) HER2-0 HR positive patients and 41 (37.6%) HER2-0 HR negative patients (P

Due to the high cost for exploration and development of tight oil reservoirs, it is an urgent problem to achieve profitable development of tight oil. According to the characteristics of tight oil reservoir in the eighth member of Triassic Yanchang Formation (Chang 8) in Honghe oil field, Ordos Basin, this paper highlighted single well information, started with the key parameters affecting the economic benefit of tight reservoir-single well economically recoverable reserves, and established a series of determination methods and process of geological evaluation parameters for profitable development of tight oil reservoirs based on single well economically recoverable reserves. Considering the particularity that the single well recoverable reserves of Chang 8 tight oil reservoir in Honghe oil field was controlled by fractures, the fracture development degree was added in the study of determination of the geological evaluation parameters. Five parameters, including single well technically recoverable reserves, net pay thickness, effective porosity, oil saturation and fracture development degree, were selected for classification and subdivided into six types. By compiling the intersection diagram of single well technically recoverable reserves and net pay thickness, the cutoffs of geological parameters were determined comprehensively by comparing the economic cutoffs and the classification of reservoir geological parameters under two scenarios. The method was applied to Chang 8 reservoir in Honghe oil field, and its feasibility was verified. The practical application shows that this method can provide effective technical support for sweet spot screening and development and deployment optimization in tight reservoirs.

Prostaglandin E2 (PGE2) signaling through its EP4 receptor regulates hematopoietic stem and progenitor cell (HSPC) functions. Here we generated mouse strains with conditional and inducible deletion of EP4 in stromal cell populations, including osteolineage cells, mesenchymal progenitor cells, perivascular stromal cells, and endothelial cells, to evaluate the role of EP4 in HSPC regulation through signaling in each of these niche cell populations. We found that EP4 deletion in different stromal cells had distinct effects on HSPC proliferation, long-term repopulating capacity, and the peripheral blood stem cell mobilization response. Lack of EP4 signaling in osteolineage cells increased HSPC number but impaired their long-term engraftment and mobilization. EP4 deletion in mesenchymal progenitor cells and endothelial cells reduced HSPC number and function, while EP4 deletion in perivascular stromal cells had sex-specific effects on HSPC engraftment. Our results demonstrate that PGE2/EP4 signaling in bone marrow stromal cells plays a significant and complex role in HSPC regulation, with both positive and negative effects depending on the stromal cell type.

IntroductionIn today’s digital economy, data resources have gained strategic recognition. Enterprises view data analytic capabilities as a core organizational competitiveness. This study explored factors influencing college students’ continuance learning intention in data analysis technology courses to inform the role of self-efficacy on the relationship between interactivity and continuance learning intention.MethodsThe research model underpinning the study was based on the Stimulus-Organism-Response model and flow theory. The model was validated using SmartPLS. A total of 314 valid questionnaires were collected via the standard online survey approach.ResultsAmong internal factors, study results showed both cognitive interest and self-efficacy had significant positive effects on continuance learning intention. Also, cognitive interest had a significant positive effect on self-efficacy. Among external stimuli, content quality, software quality, and interactivity had significant positive effects on self-efficacy. Software quality did not have a significant effect on cognitive interest. Importantly, self-efficacy registered a significant moderating role on the relationship between interactivity and continuance learning intention.

Breast cancer ranks first among female cancers and has become a major public health problem in the current society. More studies indicated that these cancers are related to the change in the gut microbiome that can cause metabolic and immune system disorders in the body. However, there are few studies on the changes in gut microbiome caused by the onset of breast cancer, and the relationship between breast cancer and gut microbiome needs to be further clarified. In this study, we inoculated 4T1 breast cancer cells to induce breast cancer tumorigenesis in mice and collected their feces samples at different stages during this process. These intestinal florae were analyzed using 16S rRNA gene amplicon sequencing, and the results showed that at the phylum level, the ratio of Firmicutes/Bacteroidetes decreased with the development of the tumor; at the family level, the intestinal microbiome had obvious variations of Lachnospiraceae, Bacteroidaceae, Erysipelotrichaceae, etc. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated that decreased abundance of cancer-related signaling pathways. This study elucidated the relationship between breast cancer and intestinal microbiome, and the research results can be used as an important biomarker for the diagnosis of breast cancer.

The main purpose of this study is to explore the influence of leadership empowering behavior (personal development support, participative decision making and delegation of authority) and thriving at work (vigor, learning) on employee innovation behavior and analyze the moderating effect of personal development support on participative decision making and innovation behavior. The questionnaire survey method is used to survey Chinese industrial workers, and a total of 290 valid questionnaires are collected. The model is verified using SmartPLS. Results show that the personal development support and participative decision making dimensions of leadership empowering behavior have a significant positive influence on employee innovation behavior. Vigor and learning has a significant positive influence on employee innovation behavior, and personal development support has a significant moderating effect on the relationship between participative decision making and innovative behavior.

BackgroundCompared with urban areas, old adults in rural areas have limited access to medical and health resources in China. Active of daily living ability (ADL) decline and depressive symptoms are common in rural older adults. In particular, the depressive symptoms of the elderly in rural areas are often ignored. Thus, it is difficult to realize high-level active aging at the individual level. In order to explore the effects of ADL and depressive symptoms on the active aging of rural elderly, we conducted a survey and analyzed the mediation and interaction effects of depressive symptoms of ADL on active aging.MethodsFrom July to November 2019, a cross-sectional study of 945 elderly rural individuals was conducted in three townships in Xiangtan County, China. Active aging, ADL, and depressive symptoms were assessed using the positive aging questionnaire (PAEQ), ADL scale, and depression in old age scale (DIA-S), respectively. PROCESS macro program model 4 and logistic regression were used to explore the mediation and interaction between ADL and depressive symptoms on active aging.ResultsThe proportions of rural elderly with an active aging level were 23.5% (well above average), 50.9% (above average), 24.1% (below average), 1.5% (well below average), respectively. The rates of ADL decline and depressive symptoms were 44.7 and 19.7%, respectively. Mediated effect analysis showed that the relationship between ADL and active aging could be partly mediated by depressive symptoms (ab = −0.2382, boot SE = 0.0437), and the 95% confidence interval was [−0.3311, −0.1584]. The mediating effect proportion of the total effect was 30.7%. Logistic regression showed that ADL and depressive symptoms have an interactive additive effect on active aging. The relative excess risk of interaction (RERI), the attributable proportion due to interaction (API), and the synergy index (SI) scores were 13.109, 0.621, and 2.871, respectively. Older adults with ADL decline and depressive symptoms had higher (OR = 21.115) odds of well-below-average active aging compared with older adults with ADL decline (OR = 3.258) or only depressive symptoms (OR = 5.749).ConclusionThe findings suggest that the association between ADL and active aging is persistent and partly mediated by depressive symptoms, and comorbid depressive symptoms and ADL decline have an additive effect on active aging. Maintaining independence is an important factor for realizing active aging. However, for the rural elderly with ADL decline and low-level active aging, we can promote the realization of high-level active aging at the individual level through the prevention and treatment of depressive symptoms based on multidisciplinary care.

Most of the initial in-place and undeveloped OOIP are low-grade reserves, and how to evaluate their potential is an urgent problem. There are many uncertainties in low-grade reserves, such as complex geological conditions, strong reservoir heterogeneity, limited data and limited geological knowledge. The reliability of the conventional evaluation method is poor. Therefore, a series of systematic evaluation methods for initial in-place and undeveloped OOIP on the basis of quantitative uncertainty was proposed, which mainly focused on three improvements. Firstly, the range value was used to describe the uncertainty of OOIP, which changed the unique value estimated by the certainty method in the past. The degree of certainty was proposed to quantitatively characterize the risk of reserves. Secondly, the evaluation index system, the evaluation method and the evaluation process of uncertainty of the key parameters were established. Thirdly, the new method was changed from the previous emphasis on reserve scale to reserve value, established a three-factor model of "the degree of certainty-unit reserves/resources value and the scale of reserves/resources" by applying risk-value assessment technology. Potential blocks were divided into four categories, namely type Ⅰ with low risk and high value, type Ⅱ with low risk and low value, type Ⅲ with high risk and high value, and type Ⅳ with high risk and low value. In this way, a potential evaluation platform combining reserves, production and value evaluation was proposed. The application of the method showed that it can effectively evaluate the reserve upgrading and development potential and optimize the blocks, and the selected blocks are basically consistent with the subsequent upgrading and development of potential blocks, which verified the reliability and rationality of the method.

Glutenite reservoirs are one of the major targets for petroleum exploration, and some important breakthroughs have been made in many oil-bearing basins in recent years. Through 2019 glutenite reservoirs in the Jiyang Depression of Bohai Bay Basin accounted for 15% of the total low permeability controlled reserves of SINOPEC. However, due to the lack of upgrade standards and the unclear main control factors, which of these controlled reserves can be upgraded is also unclear. Based on the status analysis of upgraded reserves and the characteristics of proved reserves in low permeability glutenite reservoirs, it is suggested that reservoir effectiveness, productivity and economy are the main factors that influence the controlled reserve upgrade. The key parameters for characterizing and controlling reserve upgrading were determined, and the methods for determining rational production and decline rate were studied in detail. A two-level standard for the upgrading of controlled reserves in low permeabilityglutenite reservoirs was established under different geological conditions and oil prices. First, the lowest limit for reservoir effectiveness was assessed under different permeability and burial depth, such as in situ crude oil viscosity, effective thickness, effective porosity and oil saturation. Second, the lowest limit for single well productivity and minimum economic recoverable reserves of individual wells under different burial depth and oil price was considered. The results provide a basis to evaluate the upgrading potential of controlled reserves of low permeability glutenites in the middle and deep layers of Jiyang Depression. The selected upgrade potential of a block is basically consistent with the subsequent upgrade effect of that block, which verifies the reliability and rationality of the above upgrade standard.

Abstract Background A growing number of patients continue to receive total knee replacement (TKR) surgery. Nevertheless, such surgeries result in moderate to severe postoperative pain and difficulty in managing it. Musical interventions are regarded as a type of multimodal analgesia, achieving beneficial results in other clinical treatments. This study aims to evaluate the effect of musical interventions in improving short-term pain outcomes following TKR in order to determine a more reasonable and standard way of delivering musical intervention. Methods A systematic search was conducted to identify available and relevant randomized controlled trials (RCTs) regarding musical interventions compared against non-musical interventions in patients treated with TKR in Embase, MEDLINE, Cochrane Library, Web of Science, CNKI, and Wanfang Med Online up to 8 January 2020. The authors independently assessed study eligibility and risk of bias and collected the outcomes of interest to analyze. The statistical analysis was conducted using the Review Manager (RevMan) version 5.30 software. Results Eight RCTs comprised of 555 patients satisfied the inclusion criteria and were enrolled in the present study. The results showed no significant difference between the music and control groups in pain of the visual analog scale (VAS), during postoperative recovery room, back to the ward after surgery; anxiety degree of VAS; heart rate; respiratory rate; oxygen saturation; blood pressure, systolic blood pressure, and diastolic blood pressure. Nevertheless, significant differences were observed between the two groups in average increase in continuous passive motion (CPM) angles and LF/HF ratio (one kind index of heart rate variability). Conclusions Musical interventions fail to demonstrate an obvious effect in improving short-term pain outcomes following TKR. A reasonable standardization of musical interventions, including musical type, outcome measures used, outcomes measured, duration, timing and headphones or players, may improve pain outcomes with certain advantages and should be further explored after TKR.

Abstract Background Porous-coated metaphyseal sleeves are designed to fill bone loss and facilitate osseo-integration when bone loss occurs during revision total knee arthroplasty (TKA). The purpose of this paper was to evaluate the clinical and radiographic outcomes of porous-coated metaphyseal sleeves for severe bone loss in revision TKA. Methods Form December 2014 to March 2018, we retrospectively analyzed 36 patients receiving revision TKAs. They had Anderson Orthopaedic Research Institute (AORI) Type II and III tibial bone loss and were treated with metaphyseal sleeve. The patients were followed up for a mean time of 28.5 months. The Knee Society Score (KSS), the Hospital for Special Surgery (HSS) Knee Score, Visual Analog Scale (VAS) score and the range of motion (ROM), radiographic findings of sleeve osteo-integration were also recorded. The paired t test was used to compare the KSS, the HSS knee score and VAS score before and after the revision TKAs. A value of P

Following COVID-19 outbreak, Internet public opinion has tended to proliferate. From a theoretical perspective, however, the spread law of Internet public opinion in major epidemic prevention and control may provide optimization strategies on how best to channel Internet public opinion. Specifically, this article aims at exploring key factors affecting our theoretical understanding on the spread of Internet public opinion on a major epidemic situation amongst college students. A questionnaire survey on college students was conducted via online research data collection platform located in Changsha, China, amassing three hundred and nineteen valid questionnaires. Smart PLS was applied to verify a theoretical model vis-à-vis the reliability and validity of the measuring instrument. Results show that adult attachment and social motivation have significant positive influences on the consciousness of social participation. Evidently, adult attachment, emotional orientation and risk perception also have significant positive influences on emotional motivation. Emotional motivation plays a mediating role in the relationship between affective disposition and dissemination willingness. Additionally, social motivation, consciousness of social participation and emotional motivation significantly influence one's dissemination willingness in a positive way. The consciousness of social participation plays a mediating role in the relationship between social motivation and dissemination willingness. Social motivation plays a moderating role in the relationship between risk perception and dissemination willingness. Altogether, theoretical rationalization to enhance understanding and guide the initiation and spread of Internet public opinion of major public health emergencies accurately has now been provided by this work.

Eosinophilic/T-cell chorionic vasculitis (ETCV) is an inflammatory lesion of placental fetal vessels. In contrast to acute chorionic vasculitis, inflammation in ETCV is seen in chorionic vessel walls opposite the amnionic surface. It is not known whether inflammation in ETCV consists of maternal cells from the intervillous space or fetal cells migrating from the vessel. We used fluorescent in situ hybridization (FISH) to differentiate fetal versus maternal cells in ETCV. Placentas with ETCV, previously identified for a published study, were used. Infant sex in each case was identified using the electronic medical record. For male infants, 3-pm sections were cut from archived tissue blocks from placentas involving ETCV and stained with fluorescent X- and Y-chromosome centromeric probes. A consecutive hematoxylin/eosinstained section was used for correlation. FISH analysis was performed on 400 interphase nuclei at the site of ETCV to determine the proportion of XX, XY, X, and Y cells. Of 31 ETCV cases, 20 were female and 10 were male (1 sex not recorded). Six of 10 cases with male infants had recuts with visible ETCV. In these 6 cases the average percentages (ranges) of XY cells, X-only cells, and Y-only cells in the region of inflammation were 81 (70-90), 11 (6-17), and 8 (2-14), respectively. There was a 2:1 female:male infant ratio in ETCV. Similar to acute chorionic vasculitis, the inflammation in ETCV is of fetal origin. It is still unknown, however, whether the stimulus for ETCV is of fetal or maternal origin. [ABSTRACT FROM AUTHOR]

Summary: Here we identify human Kinesin-5, Kif11/HsEg5, as a cellular target of Zika protease. We show that Zika NS2B-NS3 protease targets several sites within the motor domain of HsEg5 irrespective of motor binding to microtubules. The native integral ER-membrane protease triggers mitotic spindle positioning defects and a prolonged metaphase delay in cultured cells. Our data support a model whereby loss of function of HsEg5 is mediated by Zika protease and is spatially restricted to the ER-mitotic spindle interface during mitosis. The resulting phenotype is distinct from the monopolar phenotype that typically results from uniform inhibition of HsEg5 by RNAi or drugs. In addition, our data reveal novel inter-organelle interactions between the mitotic apparatus and the surrounding reticulate ER network. Given that Kif11 is haplo-insufficient in humans, and reduced dosage results in microcephaly, we propose that Zika protease targeting of HsEg5 may be a key event in the etiology of Zika syndrome microcephaly.

Summary: Robust patient-derived platforms that recapitulate the cellular and molecular fingerprints of glioblastoma are crucial for developing effective therapies. Here, we describe a chemically defined protocol for 3D culture and propagation of glioblastoma in 3D gliospheres, patient-derived organoids (PDOs), mouse brain orthotopic xenografts (PDOXs), and downstream drug and immunofluorescence assays. This simple-to-follow protocol allows assessing drug sensitivity, on-target activity, and combined drug synergy. Promising therapies can then be validated in PDOXs for translation in precision medicine oncology trials.For complete details on the use and execution of this protocol, please refer to Chadwick et al. (2020) and Patrizii et al. (2018).

The emergence of immune checkpoint inhibitors (ICIs), mainly based on PD-1/PD-L1 blockade has revolutionized the therapeutic landscape of cancer. Despite the huge clinical success ICIs have achieved, about 70% of patients still showed de novo and adaptive resistance. Exploring novel and complementary immune checkpoint molecules in addition to PD-1/PD-L1 is in great urgency. T cell immunoglobulin and ITIM domain (TIGIT) is a co-inhibitory molecule containing an immunoreceptor tyrosine-based inhibition motif (ITIM) within its cytoplasmic tail, and is highly expressed on regulatory T cells and activated CD4+ T, CD8+ T, and NK cells. We generated a novel single chain Fab heterodimeric bispecific IgG antibody format targeting PD-L1 and TIGIT with one binding site for each target antigen. The bispecifc antibody BiAb-1 is based on “knob-into-hole” technology for heavy chain heterodimerization with a glycine serine linker connecting the 3′ end of Cκand the 5′ end of VH to prevent wrong pairing of light chains. BiAb-1 was produced with high expression yields and show simultaneous binding to PD-L1 and TIGIT with high affinity. Importantly, cytokine production was enhanced by BiAb-1 from staphylococcal enterotoxin B (SEB) stimulated PBMCs. BiAb-1 also demonstrated potent anti-tumor efficacy in multiple tumor models and superior activity to PD-1/PD-L1 blockade molecules. In conclusion, we have applied rational antibody engineering technology to develop a monovalent heterodimeric bispecifc antibody, which combines the blockade of both PD-1/PD-L1 and TIGIT/CD155 pathways simultaneously and results in superior anti-tumor efficacy in multiple tumor models over existing anti PD-1/PD-L1 molecules.

Summary: Glioblastoma is the most common and deadly primary brain malignancy. Despite advances in precision medicine oncology (PMO) allowing the identification of molecular vulnerabilities in glioblastoma, treatment options remain limited, and molecular assays guided by genomic and expression profiling to inform patient enrollment in life-saving trials are lacking. Here, we generate four-dimensional (4D) cell-culture arrays for rapid assessment of drug responses in glioblastoma patient-derived models. The arrays are 3D printed with thermo-responsive shape memory polymer (SMP). Upon heating, the SMP arrays self-transform in time from 3D cell-culture inserts into histological cassettes. We assess the utility of these arrays with glioblastoma cells, gliospheres, and patient derived organoid-like (PDO) models and demonstrate their use with glioblastoma PDOs for assessing drug sensitivity, on-target activity, and synergy in drug combinations. When including genomic and drug testing assays, this platform is poised to offer rapid functional drug assessments for future selection of therapies in PMO.

The purpose of this paper is to aggregate the topic information of online review text and clarify the user needs. We conducted the study on online reviews of women’s clothing store of Taobao.com with semantic analysis and text mining. Online reviews were collected by means of web crawler. Using Chinese word segmentation tool and data analysis tool, the word frequency statistics was realized. The statistical software was used for the clustering analysis and multidimensional scaling analysis of high frequency keywords. The results show that the content of online reviews mainly includes four topics: basic features of products, additional features of products, user experience and product display. It reveals the potential user needs of women’s clothing store of Taobao.com, which cannot only help consumers to make rational decisions, but also provide guidance to merchants and manufacturers.

ABSTRACT DNA phosphorothioate (PT) modification, in which the nonbridging oxygen in the sugar-phosphate backbone is substituted by sulfur, is catalyzed by DndABCDE or SspABCD in a double-stranded or single-stranded manner, respectively. In Dnd and Ssp systems, mobilization of sulfur in PT formation starts with the activation of the sulfur atom of cysteine catalyzed by the DndA and SspA cysteine desulfurases, respectively. Despite playing the same biochemical role, SspA cannot be functionally replaced by DndA, indicating its unique physiological properties. In this study, we solved the crystal structure of Vibrio cyclitrophicus SspA in complex with its natural substrate, cysteine, and cofactor, pyridoxal phosphate (PLP), at a resolution of 1.80 Å. Our solved structure revealed the molecular mechanism that SspA employs to recognize its cysteine substrate and PLP cofactor, suggesting a common binding mode shared by cysteine desulfurases. In addition, although the distance between the catalytic Cys314 and the substrate cysteine is 8.9 Å, which is too far for direct interaction, our structural modeling and biochemical analysis revealed a conformational change in the active site region toward the cysteine substrate to move them close to each other to facilitate the nucleophilic attack. Finally, the pulldown analysis showed that SspA could form a complex with SspD, an ATP pyrophosphatase, suggesting that SspD might potentially accept the activated sulfur atom directly from SspA, providing further insights into the biochemical pathway of Ssp-mediated PT modification. IMPORTANCE Apart from its roles in Fe-S cluster assembly, tRNA thiolation, and sulfur-containing cofactor biosynthesis, cysteine desulfurase serves as a sulfur donor in the DNA PT modification, in which a sulfur atom substitutes a nonbridging oxygen in the DNA phosphodiester backbone. The initial sulfur mobilization from l-cysteine is catalyzed by the SspA cysteine desulfurase in the SspABCD-mediated DNA PT modification system. By determining the crystal structure of SspA, the study presents the molecular mechanism that SspA employs to recognize its cysteine substrate and PLP cofactor. To overcome the long distance (8.9 Å) between the catalytic Cys314 and the cysteine substrate, a conformational change occurs to bring Cys314 to the vicinity of the substrate, allowing for nucleophilic attack.

Abstract Background To determine the association of lymphatic vessel density (LVD) with the prognosis of Asian non-small cell lung cancer (NSCLC) patients via a meta-analysis. Methods Eligible studies were selected by searching PubMed and EMBASE from inception to July 25, 2017. The reference lists of the retrieved articles were also consulted. The information was independently screened by two authors. When heterogeneity was significant, a random-effects model was used to determine overall pooled risk estimates. Results A total of 15 studies with 1075 patients were finally included in the meta-analysis. LVD was positively associated with the prognosis of NSCLC in the overall analysis (hazard ratio (HR) 1.14, 95% confidence interval (95% CI): 1.02–1.27, p = 0.000, I2 = 73.2%). Subgroup analyses were performed on 5 VEGFR-3 groups (p = 0.709, I2 = 0.0%), 3 LYVE-1 groups (p = 0.01, I2 = 86.4%), 5 D2–40 groups (p = 0.019, I2 = 66.2%), and 2 podoplanin groups (p = 0.094, I2 = 64.5%). Sensitivity analysis indicated robust results. There was no publication bias. Conclusions LVD is an indicator of poor prognosis in Asian NSCLC patients.

Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a quarantine disease that seriously affects citrus production worldwide. The use of microorganisms and their products for biological control has been proven to be effective in controlling Xanthomonas disease. In this study, a novel Xcc antagonistic strain was isolated and identified as Bacillus amyloliquefaciens F9 by morphological and molecular analysis. The lipopeptide extract of B. amyloliquefaciens F9 (F9LE) effectively inhibited the growth of Xcc in an agar diffusion assay and restrained the occurrence of canker lesions in a pathogenicity test under greenhouse conditions. Consistent with these findings, F9LE treatment significantly inhibited the production of extracellular enzymes in Xcc cells and induced cell wall damage, with leakage of bacterial contents revealed by scanning electron microscopy and transmission electron microscopy analyses. In addition, F9LE also showed strong antagonistic activity against a wide spectrum of plant pathogenic bacteria and fungi. Furthermore, using electrospray ionization mass spectrometry analysis, the main antimicrobial compounds of strain F9 were identified as three kinds of lipopeptides, including homologues of surfactin, fengycin, and iturin. Taken together, our results show that B. amyloliquefaciens F9 and its lipopeptide components have the potential to be used as biocontrol agents against Xcc, and other plant pathogenic bacteria and fungi.

The urostylid family Pseudokeronopsidae Borror and Wicklow, 1983 was considered to be a well-outlined taxon. Nevertheless, recent evidence, including morphological, ontogenetic, and molecular information, has consistently revealed the polyphyly of this family. In the present work, a new population of Thigmokeronopsis stoecki Shao et al., 2008 was found and its binary divisional process was described for the fi rst time. In addition, the morphogenetic features of Thigmokeronopsis species and all the other pseudokeronopsids, for which detailed ontogenetic data are available, were rechecked and compared. This reveals that: (1) the ontogenetic process of T. stoecki corresponds well with its congeners T. jahodai and T. rubra except for the macronuclear behavior; (2) Apokeronopsis and Thigmokeronopsis share a similar ontogenetic mode despite of the differences in the number and origin of their buccal cirri; (3) most pseudokeronopsids share the same pattern in the origins of their oral primordia and fronto-ventral-transverse cirral anlagen, except for Pseudokeronopsis similis, which may not be a valid member of the family Pseudokeronopsidae. [ABSTRACT FROM AUTHOR]

The morphology and morphogenesis of a new marine hypotrichous ciliate Pseudoamphisiella elongata sp. nov. isolated from mussel-farming waters near Qingdao, China, are described based on living and protargol-impregnated specimens. Morphologically, the new species can be distinguished from its known congeners by its elongate body shape, narrow oral field, having fewer dorsal kineties and caudal cirri, more marginal cirri, and differentiated pretransverse cirri. The identification as a new species is firmly supported by the sequences of the small subunit ribosomal rRNA (SSU rRNA) gene, compared with other known Pseudoamphisiella species, and the phylogenetic analysis. The morphogenetic characteristics can be summarized as follows: (1) the parental adoral zone of membranelles and undulating membranes are entirely rebuilt by the oral primordium, which develops de novo in the outermost region of the cortex; (2) the oral primordium in the opisthe and the frontoventral–transverse (FVT) anlagen in both dividers are formed independently on the cell surface; (3) an ‘extra’ marginal anlage originates to the right of the right marginal anlage, and develops into two or three ‘extra’ marginal cirri; (4) the FVT anlagen develop in the primary mode, and the last FVT streak contributes two migratory cirri (frontoterminal cirri), which are probably resorbed; (5) the right marginal anlagen in both dividers occur close together, independent of the old structure. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 158, 231–243. [ABSTRACT FROM AUTHOR]

Leptoamphisiella vermis Gruber, 1888 n. g., n. comb. (basionym Epiclintes vermis Gruber, 1888 ) is an extraordinarily large and worm-like marine stichotrichous ciliate. Based on a population isolated recently from coastal waters of Qingdao, China, the living morphology and infraciliature are redescribed and its taxonomic position is defined. Accordingly, a new diagnosis for this species is suggested: large, marine Leptoamphisiella with a conspicuous layer of pellicular alveoli; 400–1000 μm × 40–70 μm in vivo; body band-like, highly flexible; about 40 membranelles; always three frontal and two buccal cirri; 52–80 transverse cirri (TC) extending to the posterior end of the buccal field; 57–79 left midventral and 44–62 right midventral cirri; 62–102 cirri in left and 63–91 cirri in right marginal rows (MR); 9–13 dorsal kineties that extend the full body length; about 100 macronuclear nodules and 5–13 micronuclei. The diagnosis for the new genus is as follows: vermiform Pseudoamphisiellidae with strongly contractile body, differentiated frontal, buccal, and highly developed TC; two remarkably separated midventral rows; one MR on each side of the body; frontoterminal and caudal cirri absent. Leptoamphisiella vermis n. comb. is fixed as the type species of the new genus. [ABSTRACT FROM AUTHOR]

Two insufficiently described marine euplotids, Diophrys irmgard Mansfeld (1923) and Diophrys hystrix Buddenbrock (1920) , found in coastal waters near Qingdao, China, were reinvestigated with emphasis on their living morphology and infraciliature. Improved diagnoses and redescriptions are supplied for both organisms. Critical redefinitions of nine morphotypes are presented and the validities of the nominal species are discussed and briefly revised. Following Curds and Wu (1983) , and based on data obtained during the present study and a critical review of the literature, five additional nominal species are regarded as junior synonyms of known forms: Diophrys quadricaudatus Agamaliev (1967) , D. scutoides Agamaliev (1967) , and D. tetramacronucleata Kattar (1970) are synonymized with D. scutum ( Dujardin 1841 ), while D. pentacirratus Alekperov (1984) and D. multicirratus Alekperov (1984) are junior synonyms of D. oligothrix Borror (1965) . [ABSTRACT FROM AUTHOR]

Using oligonucleotide microarray analysis, THY1, mapping close to a previously defined 11q22–23 nasopharyngeal carcinoma (NPC) critical region was identified as showing consistent downregulated expression in the tumour segregants, as compared to their parental tumour-suppressing microcell hybrids (MCHs). Gene expression and protein analyses show that THY1 was not expressed in the NPC HONE1 recipient cells, tumour segregants, and other NPC cell lines; THY1 was exclusively expressed in the non-tumourigenic MCHs. The mechanism of THY1 gene inactivation in these cell lines was attributed to hypermethylation. Clinical study showed that in 65% of NPC specimens there was either downregulation or loss of THY1 gene expression. Using a tissue microarray and immunohistochemical staining, 44% of the NPC cases showed downregulated expression of THY1 and 9% lost THY1 expression. The frequency of THY1 downregulated expression in lymph node metastatic NPC was 63%, which was significantly higher than in the primary tumour (33%). After transfection of THY1 gene into HONE1 cells, a dramatic reduction of colony formation ability was observed. These findings suggest that THY1 is a good candidate tumour suppressor gene in NPC, which is significantly associated with lymph node metastases.Oncogene (2005) 24, 6525–6532. doi:10.1038/sj.onc.1208812; published online 20 June 2005 [ABSTRACT FROM AUTHOR]

Describes the isolation and functional characterization of two genes that together mediate organic solute and steroid transport in the liver of a marine vertebrate. Use of functional expression cloning in Xenopus oocytes; Limitations of expression cloning.

Background: At present, the mental health of rural left-behind children is a major social problem in China. Internet addiction, social anxiety, and loneliness are common psychological and behavioral problems among rural left-behind children, but the relationships among these issues have not been clearly identified. Methods: A total of 432 junior year 1 to senior year 3 students were randomly selected from 2 rural middle schools in Hunan Province of China as the research subjects. The Internet Addiction Disorder Diagnostic Scale, Social Anxiety Subscale of the Self-Consciousness Scale (SASS-CS), and University of California Los Angeles Loneliness Scale were employed to measure the degree of Internet addiction, feelings of social fear, social avoidance behavior, and the level of loneliness among the research subjects. Results: The rate of Internet addiction among rural left-behind middle school students was 18.27%, and was correlated with the length of time their parents spent at home as well as whether one or both parents migrated for work. Positive correlations were found among Internet addiction, social anxiety, and loneliness. Loneliness was found to play a mediating role in the relationship between social anxiety and Internet addiction among rural left-behind middle school students. Conclusion: Social anxiety and loneliness both increase the likelihood of Internet addiction in rural left-behind middle school students and social anxiety can affect Internet addiction through loneliness, implying an urgent need to strengthen care for rural left-behind children, reduce their loneliness, and thereby effectively alleviate the problem of Internet addiction among rural left-behind middle school students.

Kif5A is a neuronally-enriched isoform of the Kinesin-1 family of cellular transport motors. 23 separate mutations in the motor domain of Kif5A have been identified in patients with the complicated form of hereditary spastic paraplegia (HSP). We performed in vitro assays on dimeric recombinant Kif5A with HSP-causing mutations in the Switch I domain, which participates in the coordination and hydrolysis of ATP by kinesin. We observed a variety of significantly reduced catalytic and mechanical activities as a result of each mutation, with the shared phenotype from each that motility was significantly reduced. Substitution of Mn2+ for Mg2+ in our reaction buffers provides a dose-dependent rescue in both the catalytic and ensemble mechanical properties of the S203C mutant. This work provides mechanistic insight into the cause of HSP in patients with these mutations and points to future experiments to further dissect the root cause of this disease.

A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Background Chorionic histiocytic hyperplasia (CHH) is a cellular proliferation at the base of the chorion that was identified by the authors in examining placentas for chronic chorioamnionitis (CC). This study is a retrospective review of cases diagnosed with CHH, describing its incidence alone and with associated lesions, and the immunophenotype of lesional cells. Design In this retrospective study, a laboratory information system search over a 34-month period using the key phrase "chorionic stromal" was performed. Cases identified were reviewed for presence of the following: CC, chronic villitis (CV), chronic deciduitis (CD), maternal (MIR), and fetal (FIR) acute inflammatory responses, meconium deposition; and whether CD3 immunostaining was performed. Incidences were tabulated and compared with known prevalences in our population. Select cases were stained with various immunostains to identify cell lineage and X and Y fluorescent probes to identify fetal or maternal cell origin in cases with male infants. Results Eighty cases of CHH were identified during the study period. Incidences of inflammatory lesions associated with CHH were: CV (54/80, 68%), CD (32/80, 40%), CC (25/80, 31%), MIR (39/80, 49%), and FIR (9/80, 11%). Only chronic inflammatory lesions had a significant correlation with the co-incidence of CHH. CC was identified alongside CHH in 12 of 22 cases in which a CD3 immunostain was performed. The cell population in CHH was vimentin+, CD68+, CD3-, CD45-, CD56-, hPL-, SMA-, OCT 3/4- and, in some cases, variably mixed with CD3+ lymphocytes. The cells had a male genotype by fluorescent in situ hybridization analysis. Conclusion The association of CHH with acute and chronic inflammatory conditions and its immunophenotype suggest that it may be a reactive process. CD3 immunostaining is helpful to identify concurrent CC.