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Abstract In recent years, under the background of exam-oriented physical education reform, the government has issued a lot of physical education documents and policies. As a result, many schools have made fundamental changes in physical education activities. These policies are mainly aimed at getting young people to be more active and autonomous in school sports. This requires physical education training teachers must adhere to the people-oriented, student-oriented, so as to highlight the subject status of students. Based on this, students should establish a good sports values and ethics and form a good habit of lifelong sports, so as to further promote the sustainable development of youth sports activities. Based on the ecological theory of sustainable development as the background, this study constructs a unified theory of Unified Theory of Acceptance and Use of Technology (UTAUT) model for the sustainable training and development of youth skating sports training institutions. This study selects the youth skating sports training institutions in Beijing, China as the investigation object, covering small, medium and large institutions of different sizes, and analyzes based on the statistical data in 2023 and the results of field research. The results show that the application of this model not only increases the willingness of youth skating training institutions to continue to participate by 3.66%, but also promotes the diversified development of youth skating training. In addition, this study also discusses the environmental protection measures implemented in the process of skating training to ensure that the training activities are sustainable while reducing the impact on the environment, so as to build a sustainable development of the new ecology of skating sports training.

Abstract Background The association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study. Methods We retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan–Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios. Results In the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76–0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82–1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64–0.84), but no association observed in women (HR = 0.96, 95% CI 0.81–1.13, Pinteraction = 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores. Conclusions Obesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.

Abstract KDM6A (lysine demethylase 6A) has been reported to undergo inactivating mutations in colorectal cancer, but its function in the progression of colorectal cancer has not been evaluated using animal models of colorectal cancer. In this study, we found that knocking out KDM6A expression in mouse intestinal epithelium increased the length of villus and crypt, promoting the development of AOM (azoxymethane)/DSS (dextran sulfate sodium salt)-induced colorectal cancer. On the other hand, knocking down KDM6A expression promoted the growth of colorectal cancer cells. In molecular mechanism studies, we found that KDM6A interacts with HIF-1α; knocking down KDM6A promotes the binding of HIF-1α to the LDHA promoter, thereby promoting LDHA expression and lactate production, enhancing glycolysis. Knocking down LDHA reversed the malignant phenotype caused by KDM6A expression loss. In summary, this study using animal models revealed that KDM6A loss promotes the progression of colorectal cancer through reprogramming the metabolism of the colorectal cancer cells, suggesting that restoring the function of KDM6A is likely to be one of the strategies for colorectal cancer treatment.

Background Microangiogenesis and lymphangiogenesis are essential for tumor growth in the tumor microenvironment, contributing to tumor invasion and metastasis. Limited literature exists on these processes in esophageal squamous cell carcinoma (ESCC). Therefore, the purpose of this study is to explore the impacts of microangiogenesis and lymphangiogenesis on the occurrence, progression, and prognosis assessment of ESCC. Methods Surgical specimens and paraffin-embedded human tissues were procured from ESCC patients, encompassing 100 ESCC tissues and 100 cancer-adjacent normal (CAN) tissues. CD34 and D2-40 were utilized as markers for microvessel endothelial cells and lymphatic vessel endothelial cells, respectively. Microvascular density (MVD) and lymphatic vessel density (LVD) were evaluated through immunohistochemical quantification. Results We found that tumor tissues in ESCC patients had significantly higher MVD and LVD than cancer-adjacent normal (CAN) tissues. High MVD and LVD were associated with lymph node metastasis and advanced tumor clinical stages. Additionally, both high MVD and high LVD were strongly linked to poorer prognosis among cancer patients. Furthermore, a positive correlation was found between high MVD and high LVD (p < 0.05). The presence of these markers individually indicated a worse prognosis, with their combined assessment showcasing enhanced prognostic value. Conclusions Overall, the increased MVD and LVD indicates higher invasion and metastasis of ESCC, closely correlating with unfavorablefor poor prognosis of ESCC patients.

Background Esophageal squamous cell carcinoma (ESCC) is a malignant condition in humans. Anoikis-related genes (ARGs) are crucial to cancer progression. Therefore, more studies on the relationship between ARGs and ESCC are warranted.Methods The study acquired ESCC-related transcriptome data from TCGA. Differentially expressed ARGs (DE-ARGs) were obtained by differential analysis and candidates were filtered out by survival analysis. Prognostic genes were determined by Cox and LASSO regression. A risk model was constructed based on prognostic gene expressions. An immune infiltration study was done to explain how these genes contribute to ESCC development. The IC50 test was adopted to assess the clinical response of chemotherapy drugs. Single cell analysis was performed on the GSE145370 dataset. Moreover, the prognostic gene expressions were detected by qRT-PCR.Results 53 DE-ARGs were screened and four candidate genes including PBK, LAMC2, TNFSF10 and KL were obtained. Cox and LASSO regression identified the two prognostic genes, TNFSF10 and PBK. Immuno-infiltration analysis revealed positive associations of PBK with Macrophages M0 cells, and TNFSF10 with Macrophages M1 cells. The IC50 values of predicted drugs, in the case of Tozasertib 1096 and WIKI4 1940, were significantly variant between risk groups. Single cell analysis revealed that TNFSF10 and PBK levels were higher in epithelial cells than in other cells. The prognostic genes expression results by qRT-PCR were compatible with the dataset analysis.Conclusion The study established an ARG prognosis model of ESCC. It provided a reference for the research of ARGs in ESCC.

Abstract How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno‐occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity‐based and pathological distortion‐independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single‐subject level. Thirty‐three machine‐learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature‐based model for long‐term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate “fingerprints” of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

ObjectiveTo explore the effects of walking pattern based intelligent electrical stimulation on lower limb function in out-patients with stroke.MethodsA total of 60 outpatients with stroke who met the inclusion criteria were randomly divided into real stimulation group, sham stimulation group and control group. Finally, 52 patients completed the evaluation, including 20 patients in the control group, 15 patients in the sham stimulation group and 17 patients in the real stimulation group. All patients in the three groups received routine outpatient rehabilitation treatment and home rehabilitation guidance. The control group was not given electrical stimulation. The real stimulation group received walking pattern-based intelligent electrical stimulation once a day for 10 minutes, once a day, five days a week, with a duration of 8 weeks. The stimulation electrodes were placed on the active points of lower limb muscles (quadriceps femoris, hamstring muscle, tibialis anterior and gastrocnemius) on the hemiplegic side. The stimulation frequency was 30 Hz, the wavelength was 200 μs, and the intensity was the minimum intensity of muscle contraction. The stimu- lation electrodes placed in the sham stimulation group were the same with the real stimulation group, and the intensities could only cause weak sensory stimulation but no real muscle contraction. Lower limb function was assessed by Fugl-Meyer assessment (FMA), and balance function was assessed by postural assessment scale for stroke (PASS) and Berg balance scale (BBS). In addition, the walking ability was assessed by time up and go test (TUGT). The differences were compared among the three groups before the treatment and 2, 4 and 8 weeks posttreatment.ResultsThere was no significant difference in the baseline data and the evaluation results of the three groups before treatment. After 2 weeks treatment, the scores of FMA were significantly better than those before treatment in three groups (PPPP

Introduction Deep neck space abscesses (DNAs) are serious surgical emergencies, associated with life-threatening complications. Surgical incision and drainage combined with antibiotics is the main treatment for DNAs, but drawbacks still exist. Ultrasound-guided puncture drainage is an alternative treatment for some DNAs with limited clinical evidence. Hence, the optimal drainage technique for the treatment of DNAs remains unclear. Therefore, we will perform a protocol for a systematic review and meta-analysis to identify the efficacy of ultrasound-guided puncture drainage for DNAs.Methods and analysis PubMed, Ovid Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, VIP database and trial registry databases will be searched from inception to September 2023 to identify randomised controlled trials of patients diagnosed with DNAs accepting ultrasound-guided puncture drainage. The primary outcome will be the length of hospital stay. The secondary outcomes will be the cure rate, incidence of retreatment, complications and overall cost to the healthcare system. Fixed-effects or random-effects model will be used according to the statistical heterogeneity. Mean differences or standardised mean differences with 95% CIs for continuous data and risk ratio (RR) with 95% CIs for dichotomous data. The Cochrane risk-of-bias tool 2, Grading of Recommendations Assessment, Development and Evaluation (GRADE) and trial sequential analysis will be conducted to evaluate the evidence quality and control the random errors. Funnel plots and Egger’s regression test will be performed to evaluate publication bias.Ethics and dissemination Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications.PROSPERO registration number CRD42023441031.

Ruminants such as cattle rely mainly on microbes in the rumen to digest cellulose and hemicellulose from forage, and the digestion products are mainly absorbed and utilized by the host in the form of short chain fatty acids (SCFAs). This study aimed to isolate acid-producing strains from the cattle rumen and investigate their functions. A total of 980 strains of acid-producing bacteria were isolated from cattle rumen contents using a medium supplemented with bromocresol green. Combined with the test of acid production ability and 16S rRNA amplicon sequencing technology, five strains were selected based on their ability to produce relatively high levels of acid, including Bacillus pumillus, Enterococcus hirae, Enterococcus faecium, and Bacillus subtilis. Sheep were treated by gavage with a mixed bacterial suspension. The results showed that mixed bacteria significantly increased the body weight gain and feed conversion rate of sheep. To investigate the function of acid-producing bacteria in sheep, we used 16S rDNA sequencing technology to analyze the rumen microbes of sheep. We found that mixed bacteria changed the composition and abundance of sheep rumen bacteria. Among them, the abundance of Bacteroidota, Actinobacteriota, Acidobacteriota, and Proteobacteria was significantly increased, and the abundance of Firmicutes was significantly decreased, indicating that the changes in gut microbiota changed the function of the sheep rumen. The acid-producing bacteria isolated in this study can effectively promote the growth of ruminants, such as cattle and sheep, and can be used as additives to improve breeding efficiency, which lays a foundation for subsequent research on probiotics.

Objective To learn the production efficient of platelet components among prefecture-level blood stations in China, to provide supporting data for those blood stations to optimize the production mode of platelet components and continuously improve production efficiency and supply capacity. Methods The data from 2017 to 2020 was obtained from 24 prefecture-level blood stations who were the members of the practice comparison network for blood institutes in China. The collection units of apheresis platelets, the number of dual-collections of apheresis platelets and plasma, the average apheresis units of one platelet apheresis procedure, the discarded rate of apheresis platelets, the amount of expired apheresis platelets and the amount of apheresis platelets issued were collected. For concentrated platelets, the prepared amount of platelet concentrates and the amount of expired platelet concentrates were collected; both the quantity of qualified and issued concentrated platelets were submitted for statistical analysis.The total output and efficiency of platelet components were calculated based on the collected data. Results The average annual growth rate of apheresis platelets collection in 24 prefecture-level blood stations was 12.23%, accounting for 99.80% of the total platelet output; the average collection unit of one platelets apheresis procedure was 1.75; from 2019 to 2020, only 5 blood stations performed dual-collection of platelet and plasma during one apheresis procedure; the discarded rate of apheresis platelets was 0.28%, of which 0.007% was due to expiration. A total of 1 621.2 therapeutic units of concentrated platelets were prepared, and 13.03% of them was discarded due to the expiration. The production efficiency of platelet components was 97.56%, of which the production efficiency of apheresis platelets was 97.61% and the production efficiency of concentrated platelets was 74.43%. Conclusion There are large regional differences in the supply capacity of platelet components in prefecture-level blood stations. Apheresis platelets are the main resource of platelet components product, and the collection capacity is increasing over the years with the characteristics of high production efficiency and low expiration scrapping rate. However, the preparation of concentrated platelets are still limited with relatively low production and high expiration discarded rate.

Abstract Background The overall survival (OS) of stage I operable lung cancer is relatively low, and not all patients can benefit from adjuvant chemotherapy. This study aimed to develop and validate a radiomic signature (RS) for prediction of OS and adjuvant chemotherapy candidates in stage I lung adenocarcinoma. Methods A total of 474 patients from 2 centers were divided into 1 training (n = 287), 1 internal validation (n = 122), and 1 external validation (n = 65) cohorts. We extracted 1218 radiomic features from preoperative CT images and constructed RS. We further investigated the prognostic value of the RS in survival analysis. Interaction between treatment and RS was assessed to evaluate its predictive value. Propensity score matching (PSM) was conducted. Results Overall, 474 eligible patients with stage I lung adenocarcinoma (214 men [45.1%]; median age, 60 years) were identified. The RS was significantly associated with OS in the training and two validation cohorts (hazard ratios [HRs] > = 3.22). In multivariable analysis, the RS remained an independent prognostic factor adjusting for clinicopathologic variables (adjusted HRs > = 2.63). The prognostic value of RS was also confirmed in PSM analysis. In stage I patients, the interaction between RS status and adjuvant chemotherapy was significant (interaction P = 0.020). Within the stratified analysis, good chemotherapy efficacy was only observed for patients with stage IB disease (interaction P

Abstract Background mTOR pathway is known to promote cancer malignancy and influence cancer immunity but is unknown for its role in immune checkpoint inhibitors (ICI) therapy. Methods Using Memorial Sloan-Kettering Cancer Center dataset (MSKCC), we extracted mTOR pathway gene mutations for stepwise Cox regression in 1661 cancer patients received ICI. We associated the mutation of the gene signature resulted from the stepwise Cox regression with the 1661 patients’ survival. Other 553 ICI-treated patients were collected from 6 cohorts for validation. We also performed this survival association in patients without ICI treatment from MSKCC as discovery (n = 2244) and The Cancer Genome Atlas (TCGA) as validation (n = 763). Pathway enrichment analysis were performed using transcriptome profiles from TCGA and IMvigor210 trial to investigate the potential mechanism. Results We identified 8 genes involved in mTOR pathway, including FGFR2, PIK3C3, FGFR4, FGFR1, FGF3, AKT1, mTOR, and RPTOR, resulted from stepwise Cox regression in discovery (n = 1661). In both discovery (n = 1661) and validation (n = 553), the mutation of the 8-gene signature was associated with better survival of the patients treated with ICI, which was independent of tumor mutation burden (TMB) and mainly attributed to the missense mutations. This survival association was not observed in patients without ICI therapy. Intriguingly, the mutation of the 8-gene signature was associated with increased TMB and PD1/PD-L1 expression. Immunologically, pathways involved in anti-tumor immune response were enriched in presence of this mutational signature in mTOR pathway, leading to increased infiltration of immune effector cells (e.g., CD8 + T cells, NK cells, and M1 macrophages), but decreased infiltration of immune inhibitory M2 macrophages. Conclusions These results suggested that mTOR pathway gene mutations were predictive of better survival upon ICI treatment in multiple cancers, likely by its association with enhanced anti-tumor immunity. Larger studies are warranted to validate our findings.

Abstract Background In non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs), higher blood tumor mutational burden (bTMB) was usually associated with better progression-free survival (PFS) and objective response rate (ORR). However, the association between bTMB and overall survival (OS) benefit remains undefined. It has been reported that patients harboring a high level of circulating tumor DNA (ctDNA) had poor survival. We hypothesized that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs. Methods Our study was retrospectively performed in three cohorts, including OAK and POPLAR cohort (n = 853), Shanghai and Wuhan (SH&WH) cohort (n = 44), and National Cancer Center (NCC) cohort (n = 47). Durable clinical benefit (DCB) was defined as PFS lasting ≥ 6 months. The cutoff value of ctDNA-adjusted bTMB for DCB prediction was calculated based on a receiver operating characteristic curve. Interaction between treatments and ctDNA-adjusted bTMB was assessed. Results The bTMB score was significantly associated with tumor burden, while no association was observed between ctDNA-adjusted bTMB with tumor burden. In the OAK and POPLAR cohort, significantly higher ORR (P = 0.020) and DCB (P

Abstract Knowledge of sex determination has important implications in physiology, ecology and genetics, but the evolutionary mechanisms of sex determination systems in turtles have not been fully elucidated, due to a lack of reference genomes. Here, we generate a high-quality genome assembly of Asian yellow pond turtle (Mauremys mutica) using continuous long-read (PacBio platform), Illumina, and high-throughput chromatin conformation capture (Hi-C) technologies. The M. mutica haplotype has a genome size of 2.23 Gb with a contig N50 of 8.53 Mb and scaffold N50 of 141.98 Mb. 99.98% sequences of the total assembly are anchored to 26 pseudochromosomes. Comparative genomics analysis indicated that the lizard-snake-tuatara clade diverged from the bird-crocodilian-turtle clade at approximately 267.0–312.3 Mya. Intriguingly, positive selected genes are mostly enriched in the calcium signaling pathway and neuroactive ligand-receptor interaction, which are involved in the process of temperature-dependent sex determination. These findings provide important evolutionary insights into temperature-dependent sex determination system.

Abstract Extrachromosomal DNA (ecDNA) is a type of circular and tumor specific genetic element. EcDNA has been reported to display open chromatin structure, facilitate oncogene amplification and genetic material unequal segregation, and is associated with poor cancer patients’ prognosis. The ability of immune evasion is a typical feature for cancer progression, however the tumor intrinsic factors that determine immune evasion remain poorly understood. Here we show that the presence of ecDNA is associated with markers of tumor immune evasion, and obtaining ecDNA could be one of the mechanisms employed by tumor cells to escape immune surveillance. Tumors with ecDNA usually have comparable TMB and neoantigen load, however they have lower immune cell infiltration and lower cytotoxic T cell activity. The microenvironment of tumors with ecDNA shows increased immune-depleted, decreased immune-enriched fibrotic types. Both MHC class I and class II antigen presentation genes’ expression are decreased in tumors with ecDNA, and this could be the underlying mechanism for ecDNA associated immune evasion. This study provides evidence that ecDNA formation is an immune escape mechanism for cancer cells.

ObjectiveTo observe the effect of transcranial direct current stimulation (tDCS) synchronized with normal walking pattern based on multi-channel functional electrical stimulation (FES) on lower limb motor and balance function in patients with traumatic brain injury hemiplegia.MethodsA total of 56 patients with TBI and hemiplegia were divided into synchronous group (n=21), FES group (n=20), and tDCS group (n=15) by using sealed-envelope randomization. The tDCS group was given head tDCS treatment and lower extremity sham FES treatment, the FES group was given head sham tDCS treatment and lower extremity FES treatment, and the synchronous group was given head tDCS treatment and lower extremity FES treatment. The treatment was 20 min/time, 1 time/d, for 12 days. Before treatment, after 6 days treatment and after 12 days treatment, the following scales were used to evaluate: Fugl-Meyer assessment of lower extremity (FMA-LE), Berg balance scale (BBS), and Neurocom Balance Manager System.ResultsThere was no significant differences among the evaluation results of the three groups before treatment. After treatment, compared with those before treatment, the FMA-LE scores of three groups were significantly different (PP>0.05). Compared with the three groups before and after treatment, BBS scores of the three groups were significantly different respectively (PPPPPPP>0.05).ConclusionThe three methods can effectively improve the lower limb motor and balance function of patients with traumatic brain injury in chronic period. The treatment of tDCS with FES is better than the treatment of tDCS or FES alone in terms of some evaluation indicators.

Abstract Background The differential effect of pre-pregnancy low BMI on macrosomia has not been fully addressed. Herein, we conducted a city-wide population-based cohort study to illuminate the association between pre-pregnancy low BMI and macrosomia, stratifying by maternal age, parity, and GDM status. Methods All pregnant women who paid their first prenatal visit to the hospital in Qingdao during August 1, 2018, to June 30, 2020, were recruited to this study. The interactive effect of maternal age and pre-pregnancy low BMI on macrosomia was evaluated using logistic regression models, followed by strata-specific analyses. Results A total of 105,768 mother-child pairs were included, and the proportion of fetal macrosomia was 11.66%. The interactive effect of maternal pre-pregnancy BMI and age was statistically significant on macrosomia irrespective of parity (nullipara: P adjusted =0.0265; multipara: P adjusted =0.0356). The protective effect of low BMI on macrosomia was most prominent among nullipara aged 35 years and above (aOR=0.16, 95% CI 0.05–0.49) and multipara aged 25 years and below (aOR=0.17, 95% CI 0.05–0.55). In nullipara without GDM, the risk estimates gradually declined with increasing conception age (20-to-24 years: aOR=0.64, 95% CI 0.51–0.80; 25-to-29 years: aOR=0.43 95% CI 0.36–0.52; 30-to-34 years: aOR=0.40 95% CI 0.29–0.53; and ≥35 years: aOR=0.19, 95% CI 0.06–0.60). A similar pattern could also be observed in nullipara with GDM, where the aOR for low BMI on macrosomia decreased from 0.54 (95% CI 0.32–0.93) in pregnant women aged 25–29 years to 0.30 (95% CI 0.12–0.75) among those aged 30–34 years. However, younger multiparous mothers, especially those aged 25 years and below without GDM (aOR=0.21, 95% CI 0.06–0.68), were more benefited from a lower BMI against the development of macrosomia. Conclusions Maternal low BMI is inversely associated with macrosomia irrespective of maternal age and parity. The impact of pre-pregnancy low BMI on macrosomia varied by maternal age and parity. The protective effect of a lower maternal BMI against fetal macrosomia was more prominent in nulliparous mothers aged 35 years and above, whereas multiparous mothers younger than 25 years of age were more benefited.

BackgroundHeart failure (HF) is a prevalent chronic disease and is associated with increases in mortality and morbidity. HF is a leading cause of hospitalizations and readmissions in the United States. A potentially promising area for preventing HF readmissions is continuous remote patient monitoring (CRPM). ObjectiveThe primary aim of this study is to determine the feasibility and preliminary efficacy of a CRPM solution in patients with HF at NorthShore University HealthSystem. MethodsThis study is a feasibility study and uses a wearable biosensor to continuously remotely monitor patients with HF for 30 days after discharge. Eligible patients admitted with an HF exacerbation at NorthShore University HealthSystem are being recruited, and the wearable biosensor is placed before discharge. The biosensor collects physiological ambulatory data, which are analyzed for signs of patient deterioration. Participants are also completing a daily survey through a dedicated study smartphone. If prespecified criteria from the physiological data and survey results are met, a notification is triggered, and a predetermined electronic health record–based pathway of telephonic management is completed. In phase 1, which has already been completed, 5 patients were enrolled and monitored for 30 days after discharge. The results of phase 1 were analyzed, and modifications to the program were made to optimize it. After analysis of the phase 1 results, 15 patients are being enrolled for phase 2, which is a calibration and testing period to enable further adjustments to be made. After phase 2, we will enroll 45 patients for phase 3. The combined results of phases 1, 2, and 3 will be analyzed to determine the feasibility of a CRPM program in patients with HF. Semistructured interviews are being conducted with key stakeholders, including patients, and these results will be analyzed using the affective adaptation of the technology acceptance model. ResultsDuring phase 1, of the 5 patients, 2 (40%) were readmitted during the study period. The study completion rate for phase 1 was 80% (4/5), and the study attrition rate was 20% (1/5). There were 57 protocol deviations out of 150 patient days in phase 1 of the study. The results of phase 1 were analyzed, and the study protocol was adjusted to optimize it for phases 2 and 3. Phase 2 and phase 3 results will be available by the end of 2022. ConclusionsA CRPM program may offer a low-risk solution to improve care of patients with HF after hospital discharge and may help to decrease readmission of patients with HF to the hospital. This protocol may also lay the groundwork for the use of CRPM solutions in other groups of patients considered to be at high risk. International Registered Report Identifier (IRRID)DERR1-10.2196/36741

Abstract Mucoepidermoid carcinoma (MEC) is the most common type of salivary gland cancers and patients with advanced, metastatic, and recurrent MECs have limited therapeutic options and poor treatment outcomes. MEC is commonly associated with a chromosomal translocation t(11;19) (q14-21;p12-13) that encodes the CRTC1-MAML2 oncogenic fusion. The CRTC1-MAML2 fusion is required for MEC growth in part through inducing autocrine AREG-EGFR signaling. Growing evidence suggests that MEC malignancy is maintained by cancer stem-like cells. In this study, we aimed to determine critical signaling for maintaining MEC stem-like cells and the effect of combined targeting of stem cell signaling and CRTC1-MAML2-induced EGFR signaling on blocking MEC growth. First, we evaluated the significance of Notch signaling in regulating MEC stem-like cells. Aberrantly activated Notch signaling was detected in human fusion-positive MEC cells. The inhibition of Notch signaling with genetic or pharmacological inhibitors reduced oncosphere formation and ALDH-bright population in vitro and blocked the growth of MEC xenografts in vivo. Next, we investigated the effect of co-targeting Notch signaling and EGFR signaling, and observed enhanced inhibition on MEC growth in vivo. Collectively, this study identified a critical role of Notch signaling in maintaining MEC stem-like cells and tumor growth, and revealed a novel approach of co-targeting Notch and EGFR signaling as a potential effective anti-MEC treatment.

Multimodal sentiment analysis is an essential task in natural language processing which refers to the fact that machines can analyze and recognize emotions through logical reasoning and mathematical operations after learning multimodal emotional features. For the problem of how to consider the effective fusion of multimodal data and the relevance of multimodal data in multimodal sentiment analysis, we propose an attention-based mechanism feature relevance fusion multimodal sentiment analysis model (AFR-BERT). In the data pre-processing stage, text features are extracted using the pre-trained language model BERT (Bi-directional Encoder Representation from Transformers), and the BiLSTM (Bi-directional Long Short-Term Memory) is used to obtain the internal information of the audio. In the data fusion phase, the multimodal data fusion network effectively fuses multimodal features through the interaction of text and audio information. During the data analysis phase, the multimodal data association network analyzes the data by exploring the correlation of fused information between text and audio. In the data output phase, the model outputs the results of multimodal sentiment analysis. We conducted extensive comparative experiments on the publicly available sentiment analysis datasets CMU-MOSI and CMU-MOSEI. The experimental results show that AFR-BERT improves on the classical multimodal sentiment analysis model in terms of relevant performance metrics. In addition, ablation experiments and example analysis show that the multimodal data analysis network in AFR-BERT can effectively capture and analyze the sentiment features in text and audio.

Summary: Food science and technology have a fundamental and considerable overlap with medicine, and many clinically important applications were borne out of translational food science research. Globally, the food industry - through various food processing technologies - generates huge quantities of agro-waste and food processing byproducts that retain a significant biochemical potential for upcycling into important medical applications. This review explores some distinct clinical applications that are fabricable from food-based biopolymers and substances, often originating from food manufacturing side streams. These include antibacterial wound dressings and tissue scaffolding from the biopolymers cellulose and chitosan and antimicrobial food phytochemicals for combating antibiotic-resistant nosocomial infections. Furthermore, fermentation is discussed as the epitome of a translational food technology that unlocks further therapeutic value from recalcitrant food-based substrates and enables sustainable large-scale production of high-value pharmaceuticals, including novel fermented food-derived bioactive peptides (BPs).

Lung cancer with loss-of-function of the LKB1 tumor suppressor is a common aggressive subgroup with no effective therapies. LKB1-deficiency induces constitutive activation of cAMP/CREB-mediated transcription by a family of three CREB-regulated transcription coactivators (CRTC1-3). However, the significance and mechanism of CRTC activation in promoting the aggressive phenotype of LKB1-null cancer remain poorly characterized. Here, we observed overlapping CRTC expression patterns and mild growth phenotypes of individual CRTC-knockouts in lung cancer, suggesting functional redundancy of CRTC1-3. We consequently designed a dominant-negative mutant (dnCRTC) to block all three CRTCs to bind and co-activate CREB. Expression of dnCRTC efficiently inhibited the aberrantly activated cAMP/CREB-mediated oncogenic transcriptional program induced by LKB1-deficiency, and specifically blocked the growth of human and murine LKB1-inactivated lung cancer. Collectively, this study provides direct proof for an essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer and proposes the CRTC-CREB interaction interface as a novel therapeutic target.

No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown. Here, we show that doxycycline-induced CRTC1-MAML2 knockdown blocked the growth of established MEC xenografts, validating CRTC1-MAML2 as a therapeutic target. We further generated a conditional transgenic mouse model and observed that Cre-induced CRTC1-MAML2 expression caused 100% penetrant formation of salivary gland tumors resembling histological and molecular characteristics of human MEC. Molecular analysis of MEC tumors revealed altered p16-CDK4/6-RB pathway activity as a potential cooperating event in promoting CRTC1-MAML2–induced tumorigenesis. Cotargeting of aberrant p16-CDK4/6-RB signaling and CRTC1-MAML2 fusion–activated AREG/EGFR signaling with the respective CDK4/6 inhibitor Palbociclib and EGFR inhibitor Erlotinib produced enhanced antitumor responses in vitro and in vivo. Collectively, this study provides direct evidence for CRTC1-MAML2 as a key driver for MEC development and maintenance and identifies a potentially novel combination therapy with FDA-approved EGFR and CDK4/6 inhibitors as a potential viable strategy for patients with MEC.

This study established a model to assess the capability of civil universities to support the development of China's space industry. Using linear scaling, data from 41 elite universities were assessed for three dimensions: education, research, and culture. Differences among the indicators and their correlations were examined. A k-means algorithm was employed to classify universities into four clusters. According to the results, high support potential for the space industry is concentrated in certain universities. With the outcomes, the study also provides recommendations to guide space industry authorities and university leaders in policymaking. Further, the model can be used as a feasible, simple, and practical tool for similar studies.

Abstract In contrast to the nearly error-free self-assembly of protein architectures in nature, artificial assembly of protein complexes with pre-defined structure and function in vitro is still challenging. To mimic nature’s strategy to construct pre-defined three-dimensional protein architectures, highly specific protein-protein interacting pairs are needed. Here we report an effort to create an orthogonally interacting protein pair from its parental pair using a bacteria-based in vivo directed evolution strategy. This high throughput approach features a combination of a negative and a positive selection. The newly developed negative selection from this work was used to remove any protein mutants that retain effective interaction with their parents. The positive selection was used to identify mutant pairs that can engage in effective mutual interaction. By using the cohesin-dockerin protein pair that is responsible for the self-assembly of cellulosome as a model system, we demonstrated that a protein pair that is orthogonal to its parent pair could be readily generated using our strategy. This approach could open new avenues to a wide range of protein-based assembly, such as biocatalysis or nanomaterials, with pre-determined architecture and potentially novel functions and properties.

Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα+ adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA-induced beige adipogenesis was blocked following vascular endothelial growth factor receptor (VEGFR) 2 knock out in PDGFRα+ cells, suggesting its mediatory role. Our data reveal an intrinsic link between maternal retinoid level and offspring health via promoting beige adipogenesis. Thus, enhancing maternal retinoids is an amiable therapeutic strategy to prevent obesity in offspring, especially for those born to obese mothers which account for one third of all pregnancies.

Background: Nontraumatic spontaneous subarachnoid hemorrhage (SAH) is associated with a high mortality. This study was conducted to investigate the epidemiological features of nontraumatic spontaneous SAH in China. Methods: From January 2006 to December 2008, the clinical data of patients with nontraumatic SAH from 32 major neurosurgical centers of China were evaluated. Emergent digital subtraction angiography (DSA) was performed for the diagnosis of SAH sources in the acute stage of SAH (≤3 days). The results and complications of emergent DSA were analyzed. Repeated DSA or computed tomography angiography (CTA) was suggested 2 weeks later if initial angiographic result was negative. Results: A total of 2562 patients were enrolled, including 81.4% of aneurysmal SAH and 18.6% of nonaneurysmal SAH. The total complication rate of emergent DSA was 3.9% without any mortality. Among the patients with aneurysmal SAH, 321 cases (15.4%) had multiple aneurysms, and a total of 2435 aneurysms were detected. The aneurysms mostly originated from the anterior communicating artery (30.1%), posterior communicating artery (28.7%), and middle cerebral artery (15.9%). Among the nonaneurysmal SAH cases, 76.5% (n = 365) had negative initial DSA, including 62 cases with peri-mesencephalic nonaneurysmal SAH (PNSAH). Repeated DSA or CTA was performed in 252 patients with negative initial DSA, including 45 PNSAH cases. Among them, the repeated angiographic results remained negative in 45 PNSAH cases, but 28 (13.5%) intracranial aneurysms were detected in the remaining 207 cases. In addition, brain arteriovenous malformation (AVM, 7.5%), Moyamoya disease (7.3%), stenosis or sclerosis of the cerebral artery (2.7%), and dural arteriovenous fistula or carotid cavernous fistula (2.3%) were the major causes of nonaneurysmal SAH. Conclusions: DSA can be performed safely for pathological diagnosis in the acute stage of SAH. Ruptured intracranial aneurysms, AVM, and Moyamoya disease are the major causes of SAH detected by emergent DSA in China.

Vascular cognitive impairment (VCI) defines an entire spectrum of neurologic disorders from mild cognitive impairment to dementia caused by cerebral vascular disease. The pathogenesis of VCI includes ischemic factors (e.g., large vessel occlusion and small vessel dysfunction); hemorrhagic factors (e.g., intracerebral hemorrhage and subarachnoid hemorrhage); and other factors (combined with Alzheimer’s disease). Clinical evaluations of VCI mainly refer to neuropsychological testing and imaging assessments, including structural and functional neuroimaging, with different advantages. At present, the main treatment for VCI focuses on neurological protection, cerebral blood flow reconstruction, and neurological rehabilitation, such as pharmacological treatment, revascularization, and cognitive training. In this review, we discuss the pathogenesis, neuroimaging evaluation, and treatment of VCI.

[This corrects the article DOI: 10.1371/journal.pone.0194915.].

Approximation algorithms with linear complexities are required in the treatments of big data, however, present algorithms cannot output the diameter of a set of points with arbitrary accuracy and near-linear complexity. By introducing the partition technique, we introduce a very simple approximation algorithm with arbitrary accuracy ε and a complexity of O(N + ε-1 log ε-1) for the cases that all points are located in an Euclidean plane. The error bounds are proved strictly, and are verified by numerical tests. This complexity is better than existing algorithms, and the present algorithm is also very simple to be implemented in applications.

This study aimed to locate the contributing factors of Catastrophic Health Expenditure (CHE), evaluate their impacts, and try to propose strategies for reducing the possibilities of CHE in the context of China's current public health insurance system. The financial data of all hospitalization cases from a sample hospital in 2013 were gathered and used to determine the pattern of household medical costs. A simulation model was constructed based on China's current public health insurance system to evaluate the financial burden for medical service on Chinese patients, as well as to calculate the possibilities of CHE. Then, by adjusting several parameters, suggestions were made for China's health insurance system in order to reduce CHE. It's found with China's current public health insurance system, the financial aid that a patient may receive depends on whether he is from an urban or rural area and whether he is employed. Due to the different insurance policies and the wide income gap between urban and rural areas, rural residents are much more financially vulnerable during health crisis. The possibility of CHE can be more than 50% for low-income rural families. The CHE ratio can be dramatically lowered by applying different policies for different household income groups. It's concluded the financial burden for medical services of Chinese patients is quite large currently, especially for those from rural areas. By referencing different healthcare policies in the world, applying different health insurance policies for different income groups can dramatically reduce the possibility of CHE in China.

Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.

Foot-and-mouth disease virus (FMDV) is an economically devastating viral disease leading to a substantial loss to the swine industry worldwide. A novel alternative strategy is to develop pigs that are genetically resistant to infection. Here, we produce transgenic (TG) pigs that constitutively expressed FMDV-specific short interfering RNA (siRNA) derived from small hairpin RNA (shRNA). In vitro challenge of TG fibroblasts showed the shRNA suppressed viral growth. TG and non-TG pigs were challenged by intramuscular injection with 100 LD50 of FMDV. High fever, severe clinical signs of foot-and-mouth disease and typical histopathological changes were observed in all of the non-TG pigs but in none of the high-siRNA pigs. Our results show that TG shRNA can provide a viable tool for producing animals with enhanced resistance to FMDV.

MicroRNAs (miRNAs) are known to play a part in regulating important cellular processes. They generally perform their regulatory function through their binding with mRNAs, ultimately leading to a repression of target protein expression levels. However, their roles in cellular processes are poorly understood due to the limited understanding of their specific cellular targets. Aberrant levels of miRNAs have been found in hepatocellular carcinoma (HCC) including miR-181a. Using bioinformatics analysis, cyclin-dependent kinase inhibitor 1B (CDKN1β) and transcriptional factor E2F7 were identified as potential targets of miR-181a. Validation analysis using surface plasmon resonance (SPR) showed a positive binding between miR-181a and the 3'UTRs of these two potential mRNA targets. In vivo luciferase assay further confirmed the positive miR-181a:mRNA bindings, where a significant decrease in luciferase activity was detected when HepG2 cells were co-transfected with the 3'UTR-containing reporter plasmids and miR-181a. The potential impact of miR-181a binding to its specific targets on the general cellular behavior was further investigated. Results showed that miR-181a significantly activated the MAPK/JNK pathway which regulates cell proliferation, supporting our recently reported findings. Inhibition of miR-181a, on the other hand, abolished the observed activation. Our findings open up a new approach in designing targeted functional analysis of miRNAs in cellular processes, through the identification of their cellular targets.

Fatty acid-derived biofuels and biochemicals can be produced in microbes using β-oxidation pathway engineering. In this study, the β-oxidation pathway of Saccharomyces cerevisiae was engineered to accumulate a higher ratio of medium chain fatty acids (MCFAs) when cells were grown on fatty acid-rich feedstock. For this purpose, the haploid deletion strain Δpox1 was obtained, in which the sole acyl-CoA oxidase encoded by POX1 was deleted. Next, the POX2 gene from Yarrowia lipolytica, which encodes an acyl-CoA oxidase with a preference for long chain acyl-CoAs, was expressed in the Δpox1 strain. The resulting Δpox1 [pox2+] strain exhibited a growth defect because the β-oxidation pathway was blocked in peroxisomes. To unblock the β-oxidation pathway, the gene CROT, which encodes carnitine O-octanoyltransferase, was expressed in the Δpox1 [pox2+] strain to transport the accumulated medium chain acyl-coAs out of the peroxisomes. The obtained Δpox1 [pox2+, crot+] strain grew at a normal rate. The effect of these genetic modifications on fatty acid accumulation and profile was investigated when the strains were grown on oleic acids-containing medium. It was determined that the engineered strains Δpox1 [pox2+] and Δpox1 [pox2+, crot+] had increased fatty acid accumulation and an increased ratio of MCFAs. Compared to the wild-type (WT) strain, the total fatty acid production of the strains Δpox1 [pox2+] and Δpox1 [pox2+, crot+] were increased 29.5% and 15.6%, respectively. The intracellular level of MCFAs in Δpox1 [pox2+] and Δpox1 [pox2+, crot+] increased 2.26- and 1.87-fold compared to the WT strain, respectively. In addition, MCFAs in the culture medium increased 3.29-fold and 3.34-fold compared to the WT strain. These results suggested that fatty acids with an increased MCFAs ratio accumulate in the engineered strains with a modified β-oxidation pathway. Our approach exhibits great potential for transforming low value fatty acid-rich feedstock into high value fatty acid-derived products.

ObjectivesRecent neuroimaging studies have identified a potentially critical role of the amygdala in disrupted emotion neurocircuitry in individuals after total sleep deprivation (TSD). However, connectivity between the amygdala and cerebral cortex due to TSD remains to be elucidated. In this study, we used resting-state functional MRI (fMRI) to investigate the functional connectivity changes of the basolateral amygdala (BLA) and centromedial amygdala (CMA) in the brain after 36 h of TSD.Materials and methodsFourteen healthy adult men aged 25.9 ± 2.3 years (range, 18-28 years) were enrolled in a within-subject crossover study. Using the BLA and CMA as separate seed regions, we examined resting-state functional connectivity with fMRI during rested wakefulness (RW) and after 36 h of TSD.ResultsTSD resulted in a significant decrease in the functional connectivity between the BLA and several executive control regions (left dorsolateral prefrontal cortex [DLPFC], right dorsal anterior cingulate cortex [ACC], right inferior frontal gyrus [IFG]). Increased functional connectivity was found between the BLA and areas including the left posterior cingulate cortex/precuneus (PCC/PrCu) and right parahippocampal gyrus. With regard to CMA, increased functional connectivity was observed with the rostral anterior cingulate cortex (rACC) and right precentral gyrus.ConclusionThese findings demonstrate that disturbance in amygdala related circuits may contribute to TSD psychophysiology and suggest that functional connectivity studies of the amygdala during the resting state may be used to discern aberrant patterns of coupling within these circuits after TSD.

Proteomics study was performed to investigate the specific protein expression profiles of HepG2 cells transfected with mutant HBV compared with wildtype HBV genome, aiming to identify the specific functions of SH3 binding domain (proline rich region) located in HBx. In addition to the cell movement and kinetics changes due to the expression of HBV genome we have observed previously, here we further targeted to explore the specific changes of cellular proteins and potential intracellular protein interactions, which might provide more information of the potential cellular mechanism of the differentiated cell movements. Specific changes of a number of proteins were shown in global protein profiling in HepG2 cells expressing wildtype HBV, including cell migration related proteins, and interestingly the changes were found recovered by SH3 binding domain mutated HBV. The distinctive expressions of proteins were validated by Western blot analysis.

The phytochemical content, antioxidant activity and antiproliferative properties of three diverse varieties of proso millet are reported. The free phenolic content ranged from 27.48 (Gumi 20) to 151.14 (Mi2504-6) mg gallic acid equiv/100 g DW. The bound phenolic content ranged from 55.95 (Gumi20) to 305.81 (Mi2504-6) mg gallic acid equiv/100 g DW. The percentage contribution of bound phenolic to the total phenolic content of genotype samples analyzed ranged between 62.08% and 67.05%. Ferulic acid and chlorogenic acid are the predominant phenolic acid found in bound fraction. Caffeic acid and p-coumaric acid were also detected. Syringic acid was detected only in the free fraction. The antioxidant activity was assessed using the hydrophilic peroxyl radical scavenging capacity (PSC) assay. The PSC antioxidant activity of the free fraction ranged from 57.68 (Mi2504-6) to 147.32 (Gumi20) µmol of vitamin C equiv/100 g DW. The PSC antioxidant activity of the bound fraction ranged from 95.38 (Mizao 52) to 136.48 (Gumi 20) µmol of vitamin C equiv/100 g DW. The cellular antioxidant activity (CAA) of the extract was assessed using the HepG2 model. CAA value ranged from 2.51 to 6.10 µmol equiv quercetin/100 g DW. Antiproliferative activities were also studied in vitro against MDA human breast cancer and HepG2 human liver cancer cells. Results exhibited a differential and possible selective antiproliferative property of the proso millet. These results may be used to direct the consumption of proso millet with improved health properties.

The CRISPR/Cas9 system has been adapted as an efficient genome editing tool in laboratory animals such as mice, rats, zebrafish and pigs. Here, we report that CRISPR/Cas9 mediated approach can efficiently induce monoallelic and biallelic gene knockout in goat primary fibroblasts. Four genes were disrupted simultaneously in goat fibroblasts by CRISPR/Cas9-mediated genome editing. The single-gene knockout fibroblasts were successfully used for somatic cell nuclear transfer (SCNT) and resulted in live-born goats harboring biallelic mutations. The CRISPR/Cas9 system represents a highly effective and facile platform for targeted editing of large animal genomes, which can be broadly applied to both biomedical and agricultural applications.

Using a small near-Earth object (NEO) to impact a larger and potentially threatening NEO has been suggested as an effective method to avert a collision with Earth. This paper develops a procedure for analysis of the technique for specific NEOs. First, an optimization method is used to select a proper small body from the database. Some principles of optimality are achieved with the optimization process. Then, the orbit of the small body is changed to guarantee that it flies toward and impacts the big threatening NEO. Kinetic impact by a spacecraft is chosen as the strategy of deflecting the small body. The efficiency of this method is compared with that of a direct kinetic impact to the big NEO by a spacecraft. Finally, a case study is performed for the deflection of the Apophis NEO, and the efficiency of the method is assessed.

A new protocol was established for the regeneration of Solanum nigrum by frog egg-like bodies (FELBs), which are novel somatic embryogenesis (SE) structures induced from the root, stem, and leaf explants. The root, stem, and leaf explants (93.33%, 85.10%, and 100.00%, respectively) were induced to form special embryonic calli on Murashige and Skoog (MS) medium containing 1.0 mg/L 2,4-dichlorophenoxyacetic acid, under dark condition. Further, special embryonic calli from the root, stem, and leaf explants (86.97%, 83.30%, and 99.47%, respectively) were developed into FELBs. Plantlets of FELBs from the three explants were induced in vitro on MS medium supplemented with 5.0 mg/L 6-benzylaminopurine and 0.1 mg/L gibberellic acid, and 100.00% plantlet induction rates were noted. However, plantlet induction in vivo on MS medium supplemented with 20 mg/L thidiazuron showed rates of 38.63%, 15.63%, and 61.30% for the root, stem, and leaf explants, respectively, which were lower than those of the in vitro culture. Morphological and histological analyses of FELBs at different development stages revealed that they are a novel type of SE structure that developed from the mesophyll (leaf) or cortex (stem and root) cells of S. nigrum.

BackgroundSeveral studies evaluated the associations of tumor necrosis factor-α (TNF-α) polymorphisms with pneumonia in different populations. However, the results were conflicting and controversial.MethodsDatabases including PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Data were extracted independently by two investigators. Crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated.ResultsTwelve case-control studies and one cohort study were included. Overall, no association between TNF-α -308A/G polymorphism and pneumonia risk was observed for AA +AG vs. GG (OR = 1.13; 95% CI 0.99-1.30; P = 0.07). In addition, TNF-α -308A/G polymorphism was not associated with pneumonia mortality (OR = 1.96; 95% CI 0.94-4.09; P = 0.07). Furthermore, there was no association of TNF-α -238A/G polymorphism with the risk of pneumonia (OR = 1.38; 95% CI 0.84-2.28; P = 0.20).ConclusionsTNF-α -308A/G, -238A/G polymorphisms were not associated with pneumonia risk. Moreover, TNF-α -308A/G polymorphism did not play a role in the pneumonia mortality risk.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has recently emerged as potential therapeutic agents for cerebral ischemia-reperfusion (I/R) injury because of anti-neuronal apoptotic actions. However, whether PPAR-γ activation mediates neuronal autophagy in such conditions remains unclear. Therefore, in this study, we investigated the role of PPAR-γ agonist 15-PGJ(2) on neuronal autophagy induced by I/R. The expression of autophagic-related protein in ischemic cortex such as LC3-II, Beclin 1, cathepsin-B and LAMP1 increased significantly after cerebral I/R injury. Furthermore, increased punctate LC3 labeling and cathepsin-B staining occurred in neurons. Treatment with PPAR-γ agonist 15d-PGJ(2) decreased not only autophagic-related protein expression in ischemic cortex, but also immunoreactivity of LC3 and cathepsin-B in neurons. Autophagic inhibitor 3-methyladenine (3-MA) decreased LC3-II levels, reduced the infarct volume, and mimicked some protective effect of 15d-PGJ(2) against cerebral I/R injury. These results indicate that PPAR-γ agonist 15d-PGJ(2) exerts neuroprotection by inhibiting neuronal autophagy after cerebral I/R injury. Although the molecular mechanisms underlying PPAR-γ agonist in mediating neuronal autophagy remain to be determined, neuronal autophagy may be a new target for PPAR-γ agonist treatment in cerebral I/R injury.

BackgroundThe associations between the interleukin-4 receptor α chain (IL4RA) I50V and Q551R polymorphisms and asthma risk remained controversial.MethodsWe searched the Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases for studies published before February 2013. The strengths of the associations were calculated using odds ratios (ORs) with 95% confidence intervals (CIs).ResultsA total of 50 studies were included in this meta-analysis. There was a significant association between the IL4RA I50V polymorphism and asthma risk in a dominant genetic model (OR = 1.13, 95% CI 1.04-1.23, P = 0.005). The IL4RA Q551R polymorphism was associated with a significantly elevated asthma risk in a recessive genetic model (OR = 1.46, 95% CI 1.22-1.75, PConclusionsThe results of this meta-analysis suggested that the IL4RA I50V and Q551R polymorphisms may be risk factors for developing asthma.