YY1 mediated DCUN1D5 transcriptional activation promotes triple-negative breast cancer progression by targeting FN1/PI3K/AKT pathway.

Triple-negative breast cancer (TNBC) is more aggressive and has a higher metastasis rate compared with other subtypes of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is now the only available systemic treatment for TNBC. However, some patients might still develop drug resistance and have poor prognosis. Therefore, novel molecular biomarkers and new treatment targets are urgently needed for patients with TNBC. To provide molecular insights into TNBC progression, we investigated the function and the underlying mechanism of Defective in cullin neddylation 1 domain containing 5 (DCUN1D5) in the regulation of TNBC. By TCGA dataset and surgical specimens with immunohistochemical (IHC) staining method, DCUN1D5 was identified to be significantly upregulated in TNBC tumor tissues and negatively associated with prognosis. A series of in vitro and in vivo experiments were performed to confirm the oncogenic role of DCUN1D5 in TNBC. Overexpression of FN1 or PI3K/AKT activator IGF-1 could restore the proliferative and invasive ability induced by DCUN1D5 knockdown and DCUN1D5 could act as a novel transcriptional target of transcription factor Yin Yang 1 (YY1). In conclusion, YY1-enhanced DCUN1D5 expression could promote TNBC progression by FN1/PI3K/AKT pathway and DCUN1D5 might be a potential prognostic biomarker and therapeutic target for TNBC treatment.

Cucurbitacin B induces ferroptosis in oral leukoplakia via the SLC7A11/mitochondrial oxidative stress pathway.

BACKGROUND: Oral leukoplakia (OLK), characterized by abnormal epithelial hyperplasia, is the most common precancerous oral mucosa lesion and is closely related to oxidative stress. Cucurbitacin B (CuB), a tetracyclic triterpenoid molecule derived from plants, has shown promising anti-proliferative and antioxidant effects in preclinical studies. However, whether CuB can play an antiproliferative role in OLK by regulating oxidative stress remains elusive. PURPOSE: To investigate the role of CuB in inhibiting the malignant progression of oral leukoplakia and to further explore its underlying mechanisms of action. METHODS: In vitro, the effect of CuB on the proliferation, migration, apoptosis, and cell cycle of OLK cells DOK was detected. The core genes and key pathways of OLK and CuB were analyzed in the transcriptome database, by using immunofluorescence, qRT-PCR, and Western blot to evaluate the expression levels of the ferroptosis markers ROS, GSH, MDA, Fe2+, and marker genes SLC7A11, GPX4, and FTH1. Immunohistochemistry of human tissue was performed to investigate the expression of the SLC7A11. In vivo, the model of OLK was established in C57BL/6 mice and the biosafety of CuB treatment for OLK was further evaluated. RESULTS: CuB substantially suppressed the proliferation of DOK cells. Bioinformatics analysis showed that the core targets of OLK crossing with CuB include SLC7A11 and that the essential pathways involve ROS and ferroptosis. In vitro experiments indicated that CuB might promote ferroptosis by down-regulating the expression of SLC7A11. We observed a gradual increase in SLC7A11 expression levels during the progression from normal oral mucosa to oral leukoplakia with varying degrees of epithelial dysplasia. In vivo experiments demonstrated that CuB inhibited the malignant progression of OLK by promoting ferroptosis in OLK mice and exhibited a certain level of biosafety. CONCLUSION: This study demonstrated for the first time that CuB could effectively inhibit the malignant progression of OLK by inducing ferroptosis via activating the SLC7A11/ mitochondrial oxidative stress pathway. These findings indicate that CuB could serve as the lead compound for the future development of anti-oral leukoplakia drugs.

Joint optimization of headway and number of stops for bilateral bus rapid transit.

The bilateral Bus Rapid Transit (BRT) system is a kind of BRT system in which the stops are located in the middle of the transit lane. By simultaneously serving transit lines in opposite directions, it is particularly designed to save space resources and enhance service quality. To improve the operational efficiency of the bilateral BRT, this paper optimizes the operational performance of bilateral BRT with elastic demand. The objective is to minimize the generalized time cost per passenger of the system by jointly optimizing the headway and number of stops of bilateral BRT. The cost includes the agency operating and user travel. The optimal design model is formulated as a mixed-integer program and solved using a fuzzy analytic hierarchy process (FAHP) and a genetic algorithm (GA). We conduct a case study and sensitivity analysis to show the effectiveness and reliability of the proposed approach. We conclude that the optimized minimum generalized cost per passenger is lower than the actual case for all demand levels, especially at off-peak hours, by about 22.5%. In addition, we find that the weights of agency and user costs have the most significant impact on headway, whereas the influence of walking, vehicle speed, and route length is minimal. In contrast, the optimal number of BRT stops is mostly influenced by the route length, and walking speed has essentially no effect on the optimal number of stops. Finally, we find that the generalized cost per passenger at peak hours is 10% to 15% smaller than at off-peak hours in various scenarios.

Effect of repetitive transcranial magnetic stimulation-assisted training on lower limb motor function in children with hemiplegic cerebral palsy.

OBJECTIVE: To explore the effect of repetitive transcranial magnetic stimulation (rTMS)-assisted training on lower limb motor function in children with hemiplegic cerebral palsy (HCP). METHOD: Thirty-one children with HCP who met the inclusion criteria were selected and randomly divided into a control group (n = 16) and an experimental group (n = 15). The control group received routine rehabilitation treatment for 30 min each time, twice a day, 5 days a week for 4 weeks. Based on the control group, the experimental group received rTMS for 20 min each time, once a day, 5 days a week for 4 weeks. The outcome measures included a 10-metre walk test (10MWT), a 6-minute walk distance (6MWD) test, D- and E-zone gross motor function measurements (GMFM), the symmetry ratio of the step length and stance time and the muscle tone of the triceps surae and the hamstrings (evaluated according to the modified Ashworth scale), which were obtained in both groups of children before and after treatment. RESULTS: After training, the 10MWT (P < 0.05), 6MWD (P < 0.01), GMFM (P < 0.001) and the symmetry ratio of the step length and stance time of the two groups were significantly improved (P < 0.05), there was more of an improvement in the experimental group compared with the control group. There was no significant change in the muscle tone of the hamstrings between the two groups before and after treatment (P > 0.05). After treatment, the muscle tone of the triceps surae in the experimental group was significantly reduced (P < 0.05), but there was no significant change in the control group (P > 0.05). CONCLUSION: Repetitive TMS-assisted training can improve lower limb motor function in children with HCP.

Room-Temperature Processed Annealing-Free Printable Carbon-Based Mesoscopic Perovskite Solar Cells with 17.34% Efficiency.

Carbon-based printable mesoscopic perovskite solar cells (MPSCs) have promising commercial development due to the use of easily scalable printing processes and low-cost carbon material electrodes. Simplifying the preparation process of MPSCs will undoubtedly contribute to their practical application. Here, we demonstrate that efficient and stable MPSCs can be prepared at room temperature without annealing by using low boiling point 2-methoxyethanol (2-ME) and strongly coordinated N-methyl-2-pyrrolidone (NMP) as a novel mixed solvent under the synergistic effect of ammonium chloride (NH4Cl). The results show that the 2-ME/NMP mixed solvent can generate an optimized coordination environment so that uniform nucleation and crystallization of perovskites in mesopores can be achieved at room temperature without annealing by forming uniform small-sized colloids in the precursor solution. Moreover, our work for the first time introduces NH4Cl as a crystallization modulator during a room-temperature annealing-free process, effectively regulating the crystallization behavior of perovskite in mesopores and obtaining high-quality perovskites. Finally, MPSCs prepared synergistically by a room-temperature annealing-free process based on a low boiling point 2-ME/NMP mixed solvent and NH4Cl modulator achieved a champion power conversion efficiency of 17.34% while demonstrating excellent long-term air stability for over half a year. This work provides a new approach to simplifying the preparation process of MPSCs and preparing efficient and stable MPSCs through a room-temperature annealing-free process.

Inclusion of frailty improved performance of delirium prediction for elderly patients in the cardiac intensive care unit (D-FRAIL): A prospective derivation and external validation study.

BACKGROUND: The elderly patients admitted to cardiac intensive care unit (CICU) are at relatively high risk for developing delirium. A simple and reliable predictive model can benefit them from early recognition of delirium followed by timely and appropriate preventive strategies. OBJECTIVE: To explore the role of frailty in delirium prediction and develop and validate a delirium predictive model including frailty for elderly patients in CICU. DESIGN: A prospective, observational cohort study. SETTINGS: CICU at China-Japan Friendship Hospital from March 1, 2022 to August 25, 2022 (derivation cohort); CICU at Beijing Anzhen Hospital affiliated to Capital Medical University from March 14, 2023 to May 8, 2023 (external validation cohort). PARTICIPANTS: A total of 236 and 90 participants were enrolled in the derivation and external validation cohorts, respectively. Participants in the derivation cohort were assigned into either the delirium (n = 70) or non-delirium group (n = 166) based on the occurrence of delirium. METHODS: The simplified Chinese version of the Confusion Assessment Method for the Diagnosis of Delirium in the Intensive Care Unit was used to assess delirium twice a day at 8:00-10:00 and 18:00-20:00 until the onset of delirium or discharge from the CICU. Frailty was assessed using the FRAIL scale during the first 24 h in the CICU. Other possible risk factors were collected prospectively through patient interviews and medical records review. After processing missing data via multiple imputations, univariate analysis and bootstrapped forward stepwise logistic regression were performed to select optimal predictors and develop the models. The models were internally validated using bootstrapping and evaluated comprehensively via discrimination, calibration, and clinical utility in both the derivation and external validation cohorts. RESULTS: The study developed D-FRAIL predictive model using FRAIL score, hearing impairment, Acute Physiology and Chronic Health Evaluation-II score, and fibrinogen. The area under the receiver operating characteristic curve (AUC) was 0.937 (95% confidence interval [CI]: 0.907-0.967) and 0.889 (95%CI: 0.840-0.938) even after bootstrapping in the derivation cohort. Inclusion of frailty was demonstrated to improve the model performance greatly with the AUC increased from 0.851 to 0.937 (p < 0.001). In the external validation cohort, the AUC of D-FRAIL model was 0.866 (95%CI: 0.782-0.907). Calibration plots and decision curve analysis suggested good calibration and clinical utility of the D-FRAIL model in both the derivation and external validation cohorts. CONCLUSIONS: For elderly patients in the CICU, FRAIL score is an independent delirium predictor and the D-FRAIL model demonstrates superior performance in predicting delirium.

Development of a Pathomics-Based Model for the Prediction of Malignant Transformation in Oral Leukoplakia.

Accurate prognostic stratification of oral leukoplakia (OLK) with risk of malignant transformation into oral squamous cell carcinoma is crucial. We developed an objective and powerful pathomics-based model for the prediction of malignant transformation in OLK using hematoxylin and eosin (H&E)-stained images. In total, 759 H&E-stained images from multicenter cohorts were included. A training set (n = 489), validation set (n = 196), and testing set (n = 74) were used for model development. Four deep learning methods were used to train and validate the model constructed using H&E-stained images. Pathomics features generated through deep learning combined with machine learning algorithms were used to develop a pathomics-based model. Immunohistochemical staining of Ki67, p53, and PD-L1 was used to interpret the black box of the model. Pathomics-based models predicted the malignant transformation of OLK (validation set area under curve [AUC], 0.899; testing set AUC, 0.813) and significantly identified high-risk and low-risk populations. The prediction performance of malignant transformation from dysplasia grading (validation set AUC, 0.743) was lower than that of the pathomics-based model. The expressions of Ki67, p53, and PD-L1 were correlated with various pathomics features. The pathomics-based model accurately predicted the malignant transformation of OLK and may be useful for the objective and rapid assessment of the prognosis of patients with OLK.

Differences in Pathogenicity and Vaccine Resistance Discovered between Two Epidemic Strains of Marek's Disease Virus in China.

Despite highly effective vaccines, Marek's disease (MD) causes great economic loss to the poultry industry annually, largely due to the continuous emergence of new MD virus (MDV) strains. To explore the pathogenic characteristics of newly emerged MDV strains, we selected two strains (AH/1807 and DH/18) with clinically different pathotypes. We studied each strain's infection process and pathogenicity and observed differences in immunosuppression and vaccine resistance. Specific pathogen-free chickens, unvaccinated or vaccinated with CVI988, were challenged with AH/1807 or DH/18. Both infections induced MD damage; however, differences were observed in terms of mortality (AH/1807: 77.8%, DH/18: 50%) and tumor rates (AH/1807: 50%, DH/18: 33.3%). The immune protection indices of the vaccine also differed (AH/1807: 94.1, DH/18: 61.1). Additionally, while both strains caused interferon-ß and interferon-γ expression to decline, DH/18 infection caused stronger immunosuppression than AH/1807. This inhibition persisted even after vaccination, leading to increased replication of DH/18 that ultimately broke through vaccine immune protection. These results indicate that both strains have different characteristics, and that strains such as DH/18, which cause weaker pathogenic damage but can break through vaccine immune protection, require further attention. Our findings increase the understanding of the differences between epidemic strains and factors underlying MD vaccination failure in China.

Advances in the study of regulators of ferroptosis in head and neck squamous cell carcinoma (Review).

Head and neck squamous cell carcinoma (HNSCC), a common malignancy of the head and neck, is associated with a rapid progression, a high mortality rate and unsatisfactory curative effects. The treatment efficacy is unsatisfactory due to chemotherapeutic drug resistance, the lack of ideal therapeutic agents, as well as the absence of clinical prognostic models. Thus, the identification of novel potential therapeutic targets for its diagnosis and treatment is vital. Ferroptosis is an iron­dependent regulatory cell death mode different from traditional cell death modes, such as apoptosis and autophagy, and has notable therapeutic potential in cancer treatment. The study of ferroptosis in HNSCC is expected to solve this bottleneck problem. In the present review, the findings, characteristics and regulatory mechanisms of ferroptosis are summarized, with emphasis on the factors and drugs that regulate ferroptosis in HNSCC, in order to provide theoretical basis for the targeted therapy of ferroptosis in HNSCC.

KNOX transcription factor VvHB63 affects grape seed development by interacting with protein VvHB06.

The fast-growing demand for seedless table grapes has attracted the attention of scientists for the development of new seedless cultivars. Various genes and pathways have been identified which affect seedlessness. However, the detail of the mechanism(s) regulating seedless traits in grape is still unclear, and genes related to seedlessness in grape require further study. Transcriptomic and genomic analyses of Homeobox (HB) transcription factors have suggested the involvement of HB genes, especially of HB-KNOX members, in grape seed development. Here, we functionally characterize VvHB63 gene in grape and report its role in fruit and seed development. VvHB63 showed higher expressions levels in the chalaza and integument of ovules in seedless grapes, than in seeded ones. However, no differences were observed in the sequences of seedless and seeded grape cultivars. In situ hybridization (ISH) analysis showed that VvHB63 gene was expressed in the episperm cells and ovules of 'Thompson Seedless'. Conserved domains KNOX1 and KNOX2 were important for the interaction of VvHB63 with VvHB06. Heterologous over-expression of VvHB63 (35 S::VvHB63-OE) in tomato induced smaller fruits and seeds than in wild type or SlTkn1-KO. The synergistic cooperation between VvHB63 and related proteins play an important role in ovule development.

Understanding the effect of sociodemographic and psychological latent characteristics on flex-route transit acceptance.

Flex-route transit (FRT) has significant advantages in low-demand areas. Existing studies have focused on practical experience, strategic planning, and operational planning. Few studies have addressed the effect of sociodemographic and psychological latent characteristics on the acceptance of FRT. This study aims at exploring the effect of sociodemographic and psychological latent characteristics on FRT acceptance. To finish the goal, a household survey is conducted from April to May 2020 in Nanjing, China. The survey includes sociodemographic characteristics and observed variables of individuals. Firstly, the study extracts six psychological latent characteristics to reflect individuals' attitudes based on previous and mature researches in the field of technology acceptance model (TAM) and theory of planned behavior (TPB). Then, a multiple indicators and multiple causes (MIMIC) is applied to calculate six psychological latent characteristics. Finally, an integrated model, consisting of the MIMIC and a binary logit model (BLM), is applied to match sociodemographic and psychological latent characteristics. The BLM with sociodemographic characteristics is developed as the reference model to compare the effects of psychological latent characteristics. Results show that psychological latent factors play a significant role in estimating the effect on FRT acceptance. Results of the integrated model show that the parameter of car is -0.325, displaying individuals with private cars are more reluctant to use FRT. Therefore, restricting private cars is an effective measure to facilitate FRT. Improving flexibility (0.241) is a significant measure to facilitate FRT. Findings are expected to facilitate decision-making of transport planners and engineers, and therefore enhance the service of the FRT system.

Nanosheet-hydrogel composites: from preparation and fundamental properties to their promising applications.

Hydrogels are an important class of soft materials with elastic and intelligent properties. Nevertheless, these traditional hydrogels usually possess poor mechanical properties and limited functions, which greatly restrict their further applications. With the rapid development of nanotechnology, there have been significant advances in the design and fabrication of functional nanocomposite hydrogels with unique properties and functions. Among various materials, nanosheets with planar topography, large specific surface areas, and versatile physicochemical properties have attracted intense research interest. Herein, this review summarises the synthesis mechanisms, fundamental properties, and promising applications of nanosheet-incorporated hydrogels. In particular, how the nanosheet structure is applied to improve the overall performance of the hydrogel in each application is emphasized. Additionally, the current challenges and prospects are briefly discussed in this area. We expect that the combination of nanosheets and hydrogels can attract more researchers' interest and bring new opportunities in the future.

Chromosome-scale genomics, metabolomics, and transcriptomics provide insight into the synthesis and regulation of phenols in Vitis adenoclada grapes.

Vitis adenoclada is a wild grape unique to China. It exhibits well resistance to heat, humidity, fungal disease, drought, and soil infertility. Here, we report the high-quality, chromosome-level genome assembly of GH6 (V. adenoclada). The 498.27 Mb genome contained 221.78 Mb of transposable elements, 28,660 protein-coding genes, and 481.44 Mb of sequences associated with 19 chromosomes. GH6 shares a common ancestor with PN40024 (Vitis vinifera) from approximately 4.26-9.01 million years ago, whose divergence occurred later than Vitis rotundifolia and Vitis riparia. Widely-targeted metabolome and transcriptome analysis revealed that the profiles and metabolism of phenolic compounds in V. adenoclada varieties significantly were differed from other grape varieties. Specifically, V. adenoclada varieties were rich in phenolic acids and flavonols, whereas the flavan-3-ol and anthocyanin content was lower compared with other varieties that have V. vinifera consanguinity in this study. In addition, ferulic acid and stilbenes content were associated with higher expressions of COMT and STSs in V. adenoclada varieties. Furthermore, MYB2, MYB73-1, and MYB73-2 were presumably responsible for the high expression level of COMT in V. adenoclada berries. MYB12 (MYBF1) was positively correlated with PAL, CHS, FLS and UFGT.Meanwhile, MYB4 and MYBC2-L1 may inhibit the synthesis of flavan-3-ols and anthocyanins in two V. adenoclada varieties (YN2 and GH6). The publication of the V. adenoclada grape genome provides a molecular foundation for further revealing its flavor and quality characteristics, is also important for identifying favorable genes of the East Asian species for future breeding.

Inhibition of integrated stress response protects against lipid-induced senescence in hypothalamic neural stem cells in adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. METHODS: Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. RESULTS: htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood-brain barrier. CONCLUSIONS: Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.

Widely Targeted Metabolomics Profiling Reveals the Effect of Powdery Mildew on Wine Grape Varieties with Different Levels of Tolerance to the Disease.

Powdery mildew is an economic threat for viticulture because it not only affects grape yield, but also causes a series of impacts on the qualities of fruit and wine, especially the flavors and various metabolites. Different grape varieties may have different levels of powdery mildew resistance/tolerance and their components of their metabolome are also various. In this study, two wine grape varieties, Guipu No.6 (GP6) and Marselan (Mar) with different levels of powdery mildew tolerance, were used to compare the quality differences in metabolism level by using the widely targeted metabolomics method. The results show that GP6 has a better powdery mildew leaf tolerance than Mar. A total of 774 metabolites were detected by using a UPLC-QQQ-MS-based metabolomics approach, and 57 differential metabolites were identified as key metabolites that were accumulated after infection with powdery mildew in GP6 and Mar, including phenolic acids, flavonoids, terpenoids, stilbenes, lipids, nucleotides and derivatives, lignans and coumarins, and quinones. This finding indicates that the defense mechanisms of grape fruit are mainly associated with phenylpropane-flavonoid metabolism. Specifically, stilbenes had greater variations after powdery mildew infection in GP6; while in Mar, the variations of flavonoids, especially kaempferol-3-O-glucuronide and luteolin-7-O-glucuronide, were more remarkable. The above results demonstrate that stilbenes may play a more important role than flavonoids in resisting powdery mildew infection in GP6's fruits, and the drastic variations of these phenolic compounds in different wine grapes after powdery mildew infection might also lead to quality difference in the flavors. This study can provide new insights into the understanding of the cause of powdery mildew tolerance in different grape varieties and the effects on the quality of wine grapes infected with the disease exerted by metabolism level.

Recent advances in multi-mechanism design of crack-resistant hydrogels.

For conventional hydrogels, the phenomenon of crack generation and propagation caused by high-stress concentration is ubiquitous. However, this phenomenon is unfavorable in many applications, such as wearable electronics, tissue engineering, and tunable adhesion. Fortunately, many hydrogels that can suppress crack growth during deformation and maintain the original mechanical properties during deformation, called crack-resistant hydrogels, have been published. Herein, the state-of-the-art of crack-resistant hydrogels is comprehensively reviewed. Starting from the principle of designing a crack-resistant hydrogel, we first survey the relevant crack-resistant strategies. The latest crack-resistant hydrogels are then categorized according to their crack-resistant mechanisms (including energy dissipation at the molecular level, multiscale structure, crack pinning, crack deflection, and sliding of chain), and their crack-resistant processes are described in detail. Furthermore, we summarize the current challenges and make an outlook for crack-resistant hydrogels, which might lead to substantial progress in the future design and development of these high-performance materials.

Mapping developmental paths of monkey primordial germ-like cells differentiation from pluripotent stem cells by single cell ribonucleic acid sequencing analysis†.

The induction of primordial germ-like cells (PGCLCs) from pluripotent stem cells (PSCs) provides a powerful system to study the cellular and molecular mechanisms underlying germline specification, which are difficult to study in vivo. The studies reveal the existence of a species-specific mechanism underlying PGCLCs between humans and mice, highlighting the necessity to study regulatory networks in more species, especially in primates. Harnessing the power of single-cell RNA sequencing (scRNA-seq) analysis, the detailed trajectory of human PGCLCs specification in vitro has been achieved. However, the study of nonhuman primates is still needed. Here, we applied an embryoid body (EB) differentiation system to induce PGCLCs specification from cynomolgus monkey male and female PSCs, and then performed high throughput scRNA-seq analysis of approximately 40 000 PSCs and cells within EBs. We found that EBs provided a niche for PGCLCs differentiation by secreting growth factors critical for PGCLC specification, such as bone morphogenetic protein 2 (BMP2), BMP4, and Wnt Family Member 3. Moreover, the developmental trajectory of PGCLCs was reconstituted, and gene expression dynamics were revealed. Our study outlines the roadmap of PGCLC specification from PSCs and provides insights that will improve the differentiation efficiency of PGCLCs from PSCs.

Temperature dependent developmental time for the larva stage of Aedes aegypti.

We first verify that the time from the emergence of larva to the emergence of pupa (i.e., the duration of the larva stage) for Aedes aegypti is approximately gamma distributed, provided that the pupation process is successful. This is illustrated by fitting a multi-stage model to temperature-controlled pupation rate data of Aedes aegypti. We then determine the temperature dependent gamma distribution parameters, and found that both the shape and rate parameters and the survival probability are unimodal functions of temperature. We then use a Gaussian unimodal function to describe the dependence of these parameters on temperature, and fit the model to the pupation rate data. We found that the optimal pupation temperature is about 28℃, with a mean time from the emergence of larva to the emergence of pupa about 3.8 days, and standard deviation of 0.5 days. For very high and very low temperatures, the death rate is 1.

Mediating Role of Depressive Symptoms on the Association Between Neighborhood Social Cohesion and Quality of Life in Individuals with Type 2 Diabetes Mellitus.

Purpose: Few studies have explored the association between neighborhood social cohesion (NSC), a type of social capital, and the quality of life of patients with type 2 diabetes mellitus (T2DM). In addition, the potential mechanism for this association remains unclear. The current study examined the mediation effect of depressive symptoms on the relationship between NSC and quality of life among diabetes patients in China. Patients and Methods: A cross-sectional study of 1747 T2DM patients was conducted. The specific quality of life (DSQL), Center for Epidemiological Survey Depression (CES-D), and social capital scales were administered using a face-to-face survey. Partial correlation analysis and a linear regression model were employed to explore the relationship between NSC, depressive symptoms, and quality of life. Bootstrap analysis using PROCESS was used to test the mediation model. Results: After controlling for covariates, NSC was negatively correlated with depressive symptoms (r=-0.24, P<0.01) and DSQL score (r=-0.20, P<0.01) while depressive symptoms were positively correlated with DSQL score (r=0.46, P<0.01). Linear regression analysis also found that NSC was negatively associated with the DSQL score, while depressive symptoms were positively associated with the DSQL score. Depressive symptoms mediated the relationship between NSC and quality of life in T2DM patients (explaining 50.7% of the total variance). Conclusion: NSC was positively associated with improved quality of life among Chinese T2DM patients in this study, and depressive symptoms were likely to partially explain this relationship. These findings may be used to help maintain a good quality of life among at-risk individuals. Additional prospective studies are needed to confirm these findings.

Emerging natural recombinant Marek's disease virus between vaccine and virulence strains and their pathogenicity.

Marek's disease virus (MDV), an oncogenic virus belonging to the subfamily Alphaherpesvirinae, causes Marek's disease (MD). Vaccines can control MD but cannot block the viral infection; they are considered imperfect vaccines, which carry the risk of recombination. In this study, six natural recombinant MDV strains were isolated from infected chickens in commercial flocks in China. We sequenced and analysed the genetic characteristics of the isolates (HC/0803, CH/10, SY/1219, DH/1307, DH/1504 and Hrb/1504). We found that the six strains resulted from recombination between the vaccine CVI988/Rispens (CVI988) strain skeleton and the virulence strain's partial unique short region. Additionally, a pathogenicity study was performed on recombinant strains (HC/0803 and DH/1307) and reference strains (CVI988 and LHC2) to evaluate their virulence. LHC2 induced 84.6% mortality in infected chickens; however, no mortality was recorded in chickens inoculated with HC/0803, DH/1307 or CVI988. However, HC/0803 and DH/1307 induced a notable spleen enlargement, and mild thymus and bursa atrophy at 11-17 days post-challenge (dpc). The viral genome load in the HC/0803- and DH/1307-challenged chickens peaked at approximately 107 viral copies per million host cells at 17 dpc and was similar to that in LHC2-challenged chickens, but significantly higher than that of CVI988-challenged chickens. In summary, HC/0803 and DH/1307 displayed mild virulence with temporal damage to the immune organs of chicken and a higher reproduction capability than the vaccine strain CVI988. Our study provides direct evidence of the emergence of recombinant MDV strains between vaccine and virulence strains in nature. The emergence of natural recombinant strains suggests that live vaccines can act as genetic donors for genomic recombination, and recombination may be a safety concern when administering live vaccines. These findings demonstrate that recombination promotes genetic diversity and increases the complexity of disease diagnosis, prevention and control.