Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.

P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3ß domain of the ICD. PSFL77 modulated pain perception in P2rx3+/+, but not in P2rx3-/-, mice, indicating that the 1α3ß, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.

Mechanism underlying the therapeutic effects of effective component compatibility of Bufei Yishen formula III combined with exercise rehabilitation on chronic obstructive pulmonary disease.

OBJECTIVE: To explore the mechanism underlying the therapeutic effect of Bufei Yishen Formula III combined with exercise rehabilitation (ECC-BYF III + ER) on chronic obstructive pulmonary disease (COPD) and further identify hub genes. MATERIALS AND METHODS: Gene Set Enrichment Analysis was used to identify the COPD-associated pathways and reversal pathways after ECC-BYF III + ER treatment. Protein-protein interaction network analysis and cytoHubba were used to identify the hub genes. These genes were verified using independent datasets, molecular docking and quantitative real-time polymerase chain reaction experiment. RESULTS: Using the high-throughput sequencing data of COPD rats from our laboratory, 49 significantly disturbed pathways were identified in COPD model compared with control group via gene set enrichment analysis (false discovery rate < 0.05). The 34 pathways were reversed after ECC-BYF III + ER treatment. In the 2306 genes of these 34 pathways, 121 of them were differentially expressed in COPD rats compared with control samples. A protein-protein interaction network comprising 111 nodes and 274 edges was created, and 34 candidate genes were identified. Finally, seven COPD hub genes (Il1b, Ccl2, Cxcl1, Apoe, Ccl7, Ccl12, and Ccl4) were well identified and verified in independent COPD rat data from our laboratory and the public dataset GSE178513. The area under the receiver operating characteristic curve values ranged from 0.86 to 1 and from 0.67 to 1, respectively. The reliability of the mentioned genes, which can bind to the active ingredients of ECC-BYF III through molecular docking, were further verified through qRT-PCR experiments. CONCLUSION: Thirty-four COPD-related pathways and seven hub genes that may be regulated by ECC-BYF III + ER were identified and well verified. The findings of this study may provide insights into the treatment and mechanism underlying COPD.

GSEA method can circumvent the limitations of the preacquisition of DEGs for ORA and is suitable for small sample data.34 COPD-related pathways that can be regulated by ECC-BYF III + ER were identified.Seven COPD hub genes were identified and well verified in independent RNA-seq data and PCR experiment, and they may play a crucial role in TCM treatment.

Formation Mechanisms, Interrelationships, and Effects of Cognitive Factors on Diet and Physical Activity During the Post-Bariatric Surgery Period: A Cross-Sectional Study Based on Compensatory Carry-Over Action Model.

Background: Diet and physical activity (PA) are pivotal behaviors for managing energy balance post-bariatric surgery. Given the need for dual behavioral management, understanding the interplay of cognitive factors influencing these behaviors is crucial. This study applied the compensatory carry-over action model (CCAM) to explore the impact of cognitive factors on behaviors and their subsequent effects on subjective health outcomes. Methods: This cross-sectional study was conducted among patients at the third month after bariatric surgery in China. Data on diet and PA status, behavioral cognitive factors (intention, self-efficacy, compensatory belief, transfer cognition), and subjective health outcomes (perceived stress, well-being, quality of life) were collected. Structural equation model (SEM) was employed to test hypotheses in CCAM and assess mediation relationships. Results: Analysis of data from 239 patients revealed the following: (1) Among antecedent cognitive factors, only compensatory belief significantly influenced diet (P<0.001). (2) Intention and self-efficacy directly correlated with their respective behaviors, while compensatory belief affected intention, and transfer cognition impacted self-efficacy (P<0.05), aligning with CCAM hypotheses. (3) PA demonstrated significant influence only on perceived stress (P=0.004), whereas diet significantly affected all subjective health outcomes (P<0.05). (4) Mediation analysis indicated intention partially mediated the relationship between compensatory belief and diet and fully mediated the relationship between compensatory belief and PA. Self-efficacy completely mediated the relationship between transfer cognition and diet and PA. Conclusion: Transfer cognition's carry-over effect did not directly influence behaviors among antecedent cognitions. Interventions should primarily target improving diet by mitigating compensatory belief. Moreover, diet exhibited a more pronounced impact on overall health compared to PA. Consequently, prioritizing dietary intervention over PA intervention is warranted based on the analysis of CCAM and the aim of promoting joint behaviors post-bariatric surgery.

Identification of idiopathic pulmonary fibrosis hub genes and exploration of the mechanisms of action of Jinshui Huanxian formula.

Idiopathic pulmonary fibrosis (IPF) is a common and heterogeneous chronic disease, and the mechanism of Jinshui Huanxian formula (JHF) on IPF remains unclear. For a total of 385 lung normal tissue samples from the Gene Expression Omnibus database, 37,777,639 gene pairs were identified through microarray and RNA-seq platforms. Using the individualized differentially expressed gene (DEG) analysis algorithm RankComp (FDR < 0.01), we identified 344 genes as DEGs in at least 95 % (n = 81) of the IPF samples. Of these genes, IGF1, IFNGR1, GLI2, HMGCR, DNM1, KIF4A, and TNFRSF11A were identified as hub genes. These genes were verified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in mice with pulmonary fibrosis (PF) and MRC-5 cells, and they were highly effective at classifying IPF samples in the independent dataset GSE134692 (AUC = 0.587-0.788) and mice with PF (AUC = 0.806-1.000). Moreover, JHF ameliorated the pathological changes in mice with PF and significantly reversed the changes in hub gene expression (KIF4A, IFNGR1, and HMGCR). In conclusion, a series of IPF hub genes was identified, and validated in an independent dataset, mice with PF, and MRC-5 cells. Moreover, the abnormal gene expression was normalized by JHF. These findings provide guidance for further exploration of the pathogenesis and treatment of IPF.

Effectiveness and Safety of Radiofrequency Ablation versus Liver Resection in the Treatment of Early-stage Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of radiofrequency ablation and liver resection in the therapeutic management of early-stage hepatocellular carcinoma. METHOD: We conducted a comprehensive search of domestic and foreign databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang to retrieve literature on radiofrequency ablation and liver resection for the treatment of early hepatocellular carcinoma. The retrieved literature underwent thorough screening, and relevant data were extracted. Following the evaluation of the literature's quality, Meta-analysis was performed using RevMan 5.4 software. RESULTS: In this study, a total of 11 documents were selected, comprising 1334 patients with hepatocellular carcinoma. Meta-analysis results indicated that there was no statistically significant difference in the 1-year overall survival rate [Relative risk (RR) = 1.01, 95% confidence intervals (CI) (0.98; 1.04)] and the 3-year overall survival rate [RR = 0.95, 95% CI (0.90; 1.01)] between the radiofrequency ablation and liver resection groups (p > 0.05). Similarly, there was no statistically significant difference in the 1-year disease-free survival rate [RR = 0.94, 95% CI (0.87; 1.01)] between the two groups. However, the 3-year disease-free survival rate [RR = 0.84, 95% CI (0.74; 0.96)] of patients in the radiofrequency ablation group was significantly lower than that in the hepatectomy group (p < 0.05). Notably, the incidence of complications [RR = 0.42, 95% CI (0.33; 0.55)] was significantly lower in the radiofrequency ablation group compared to the hepatectomy group. Conversely, the local recurrence rate [RR = 1.45, 95% CI (1.22; 1.73)] was significantly higher in the radiofrequency ablation group compared to the hepatectomy group (p < 0.05). CONCLUSION: During the treatment of hepatocellular carcinoma, hepatectomy demonstrates superior clinical efficacy compared to radiofrequency ablation, particularly in its ability to control tumor recurrence. However, radiofrequency ablation presents with fewer complications and a higher level of safety. These findings can serve as a valuable foundation for clinicians when selecting the most suitable treatment approaches for liver cancer.

Individual, family and social-related factors of eating behavior among Chinese children with overweight or obesity from the perspective of family system.

Purpose: The purpose of the present study is to examine the factors contributing to the development of eating behavior in overweight and obese children from the perspective of the family system. Methods: A cross-sectional survey was conducted by using convenience sampling method to select 388 participants in two primary schools in Jiangsu, China. Individual, family and social-related factors were collected. Individual factors included age, gender, ethnicity, single child, social anxiety, depression, physical activity, sleep duration, screen time. Family factors included family environment, family structure, family function, family income, parenting style, parental feeding behavior, home food environment and marital satisfaction. Social-related factors included place of residence, number of surrounding restaurants and social support. Univariate analysis, correlation analysis and multivariate analysis were used to identify factors of eating behavior among Chinese children with overweight and obese. Results: In this study, 388 participants took part with a 94.865% response rate. In the univariate analysis, the significant differences regarding Dutch Eating Behavior Questionnaire (DEBQ) scores were found between children aged 6-9 years and those aged >9 years. Correlation analysis indicated that parent's nutrition literacy (r = 0.118, P < 0.05), pressure to eat (r = 0.212, P < 0.01), perception of child weight (r = -0.112, P < 0.05) and family function (r = -0.563, P < 0.01) were associated with children's eating behavior. With regard to psychosocial factors, children's social anxiety (r = 0.299, P < 0.01) and depressive symptoms (r = 0.081, P < 0.05) were in positive correlation with eating behavior. The independent variables included in the initial model were age, father's employment status, social anxiety, maternal punishment and harshness, parents' nutrition literacy, pressure to eat, family function and perception of child weight. These variables in the final model accounted for 20.7% of the variance. Conclusion: We found that age, father's employment status, social anxiety, maternal punishment and harshness, parents' nutrition literacy, pressure to eat, family function and perception of child weight have great effect on children's eating behavior who are overweight or obese. As early childhood is a critical timeline for child development, children's social anxiety, parenting style, parent's nutrition literacy, parent's feeding behavior and family function should be intervened to promote eating behavior. Intervention programs aimed at promoting healthy eating behaviors among children, thereby mitigating the risk of pediatric obesity, should primarily target parents.

A shared mechanism for TNP-ATP recognition by members of the P2X receptor family.

P2X receptors (P2X1-7) are non-selective cation channels involved in many physiological activities such as synaptic transmission, immunological modulation, and cardiovascular function. These receptors share a conserved mechanism to sense extracellular ATP. TNP-ATP is an ATP derivative acting as a nonselective competitive P2X antagonist. Understanding how it occupies the orthosteric site in the absence of agonism may help reveal the key allostery during P2X gating. However, TNP-ATP/P2X complexes (TNP-ATP/human P2X3 (hP2X3) and TNP-ATP/chicken P2X7 (ckP2X7)) with distinct conformations and different mechanisms of action have been proposed. Whether these represent species and subtype variations or experimental differences remains unclear. Here, we show that a common mechanism of TNP-ATP recognition exists for the P2X family members by combining enhanced conformation sampling, engineered disulfide bond analysis, and covalent occupancy. In this model, the polar triphosphate moiety of TNP-ATP interacts with the orthosteric site, while its TNP-moiety is deeply embedded in the head and dorsal fin (DF) interface, creating a restrictive allostery in these two domains that results in a partly enlarged yet ion-impermeable pore. Similar results were obtained from multiple P2X subtypes of different species, including ckP2X7, hP2X3, rat P2X2 (rP2X2), and human P2X1 (hP2X1). Thus, TNP-ATP uses a common mechanism for P2X recognition and modulation by restricting the movements of the head and DF domains which are essential for P2X activation. This knowledge is applicable to the development of new P2X inhibitors.

Family characteristics in adolescents with overweight or obesity: a network analysis.

Background: Rates of overweight and obesity continue to grow in adolescents. Overweight and obesity in adolescence are associated with numerous immediate and long-term adverse health conditions. Throughout adolescence, parents and the family have an important and central influence on adolescents' health and lifestyle. The home environment may be a major factor in shaping children's weight. However, our current understanding of the interplay between family-related variables in adolescents with overweight or obesity is limited and fragmented. This study aimed to assess the relationship between family-related variables in adolescents who are overweight or obese using network analysis and inform future health promotion for family-based intervention. Methods: Participants (n = 488) were recruited from middle schools in Nanjing from October 2022 to March 2023. Participants, together with their parents, completed a questionnaire at school about the family food environment, family size, family APGAR index, family physical activity facilities, parental mental health, rearing behavior, parental weight status, drinking history, marital satisfaction, and sociodemographic characteristics. Results: The network split into three distinct communities of items. Network analysis showed that parental mental health and paternal rearing styles-rejection were the most central nodes in the network. In contrast, maternal weight status was the most peripheral and least connected nodes. Conclusion: Family-related variables constituted a connected network in adolescents with overweight or obesity. The pattern of network node connections supports that interventions could prioritize targeting changing parental mental health and paternal rearing styles in adolescents with overweight or obesity.

Integrated bioinformatics analysis for the identification of idiopathic pulmonary fibrosis-related genes and potential therapeutic drugs.

OBJECTIVE: The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. We sought to identify IPF-related genes that may participate in the pathogenesis and predict potential targeted traditional Chinese medicines (TCMs). METHODS: Using IPF gene-expression data, Wilcoxon rank-sum tests were performed to identify differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks, hub genes, and competitive endogenous RNA (ceRNA) networks were constructed or identified by Cytoscape. Quantitative polymerase chain reaction (qPCR) experiments in TGF-ß1-induced human fetal lung (HFL) fibroblast cells and a pulmonary fibrosis mouse model verified gene reliability. The SymMap database predicted potential TCMs targeting IPF. The reliability of TCMs was verified in TGF-ß1-induced MRC-5 cells. MATERIALS: Multiple gene-expression profile data of normal lung and IPF tissues were downloaded from the Gene Expression Omnibus database. HFL fibroblast cells and MRC-5 cells were purchased from Wuhan Procell Life Science and Technology Co., Ltd. (Wuhan, China). C57BL/12 mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). RESULTS: In datasets GSE134692 and GSE15197, DEGs were identified using Wilcoxon rank-sum tests (both p < 0.05). Among them, 1885 DEGs were commonly identified, and 87% (1640 genes) had identical dysregulation directions (binomial test, p < 1.00E-16). A PPI network with 1623 nodes and 8159 edges was constructed, and 18 hub genes were identified using the Analyze Network plugin in Cytoscape. Of 18 genes, CAV1, PECAM1, BMP4, VEGFA, FYN, SPP1, and COL1A1 were further validated in the GeneCards database and independent dataset GSE24206. ceRNA networks of VEGFA, SPP1, and COL1A1 were constructed. The genes were verified by qPCR in samples of TGF-ß1-induced HFL fibroblast cells and pulmonary fibrosis mice. Finally, Sea Buckthorn and Gnaphalium Affine were predicted as potential TCMs for IPF. The TCMs were verified by qPCR in TGF-ß1-induced MRC-5 cells. CONCLUSION: This analysis strategy may be useful for elucidating novel mechanisms underlying IPF at the transcriptome level. The identified hub genes may play key roles in IPF pathogenesis and therapy.

Efficacy and Adverse Reactions of Transcatheter Arterial Chemoembolization Combined with Apatinib in the Treatment of HCC with PVTT: A Meta-Analysis.

Background: Hepatocellular carcinoma is a major contributor to cancer-related deaths in China and ranks among the most prevalent malignant tumors. . The study aimed to assess the efficacy and adverse reactions of transcatheter arterial chemoembolization combined with apatinib in treating hepatocellular carcinoma with portal vein tumor thrombus. Methods: When treating hepatocellular carcinoma with a portal vein tumor thrombus, the computer retrieves eight databases to find controlled trials on the effects of transcatheter arterial chemoembolization combined with apatinib. The Cochrane Library, WanFang databases EMbase, PubMed, Web of Science, China Biomedical Literature Database (CBM), & CNKI are all retrieved by the computer. "Transcatheter arterial chemoembolization", "apatinib", & "hepatocellular carcinoma" are the search terms. As this a meta-analysis, Utilizing RevMan 5.3 software, data analysis was carried out following a thorough assessment of the quality of the literature. Results: This meta-analysis finally contained 7 papers. According to a meta-analysis, the disease control rate of the test category was considerably greater than that of the control category (odd Ratio OR: 1.65; 95% Cl: 1.17,2.33; P = .01). The experimental cohort's level of VEGF was substantially lower than that of the control group (standardized mean difference SMD:-25.38; 95% Cl: -28.69,-21.79; P < .01). According to a meta-analysis, caspase-8 levels in the group that underwent the experiment were substantially greater than those in the control category (SMD: 15.12; 95% Cl: 12.09, 18.15; P < .01). The test control experienced considerably less pain than the control sample (OR: 0.86; 95% Cl: 0.75,0.99; P = .033). Conclusion: The findings of this trial indicate that individuals with HCC & PVTT may benefit from TACE & apatinib together, as evidenced by disease control rate, VEGF, Caspase-8, pain, hypertension, nausea and vomiting, and more reputable studies are required to support the aforementioned conclusions.

Microbial community composition in urban riverbank sediments: response to municipal effluents over spatial gradient.

Municipal effluents have adverse impacts on the aquatic ecosystem and especially the microbial community. This study described the compositions of sediment bacterial communities in the urban riverbank over the spatial gradient. Sediments were collected from seven sampling sites of the Macha River. The physicochemical parameters of sediment samples were determined. The bacterial communities in sediments were analyzed by 16S rRNA gene sequencing. The results showed that these sites were affected by different types of effluents, leading to regional variations in the bacterial community. The higher microbial richness and biodiversity at SM2 and SD1 sites were correlated with the levels of NH4+-N, organic matter, effective sulphur, electrical conductivity, and total dissolved solids (p < 0.01). Organic matter, total nitrogen, NH4+-N, NO3-N, pH, and effective sulphur were identified to be important drivers for bacterial community distribution. At the phylum level, Proteobacteria (32.8-71.7%) was predominant in sediments, and at the genus level, Serratia appeared at all sampling sites and accounted for the dominant genus. Sulphate-reducing bacteria, nitrifiers, and denitrifiers were detected and closely related to contaminants. This study expanded our understanding of municipal effluents on microbial communities in riverbank sediments, and also provided valuable information for further exploration of microbial community functions.

Effects of sacubitril-valsartan in the treatment of chronic heart failure patients with end-stage renal disease undergoing dialysis.

BACKGROUND: The data on the effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (LCZ696) in chronic heart failure (CHF) patients with end-stage renal disease (ESRD) requiring dialysis are lacking. This study assessed the efficacy and safety of LCZ696 in CHF patients with ESRD on dialysis. HYPOTHESIS: LCZ696 treatment can reduce rehospitalization rate for HF, delay the occurrence of rehospitalization for HF, and prolong the survival time. METHODS: We retrospectively analyzed the clinical data of CHF patients with ESRD on dialysis who were admitted to the Second Hospital of Tianjin Medical University from August 2019 to October 2021. RESULTS: Sixty-five patients had primary outcome during the follow-up. The incidence of rehospitalization for HF in the control group was significantly higher than that in the LCZ696 group (73.47% vs. 43.28%, p = .001). There was no significant difference in mortality between the two groups (8.96% vs. 10.20%, p = 1.000). Our study included a time-to-event analysis through 1 year for the primary outcome-Kaplan-Meier curve showed that the LCZ696 group had significantly longer free-event survival time than the control group over 1-year follow-up (median survival time 139.0 days vs. 116.0 days, p = .037). CONCLUSIONS: Our study found that LCZ696 treatment was associated with a reduction in HF rehospitalization without significant effects on serum creatinine and serum potassium levels. LCZ696 is effective and safe in CHF patients with ESRD on dialysis.

An Improved Time Delay Measurement Method for the Long-Distance Underwater Environment.

With the development of underwater navigation and underwater communication, it remains difficult to obtain time delay measurements after propagating long distance. This paper proposes an improved high-accuracy time delay measuring method for long distance underwater channel propagation. First, by sending an encoded signal, the signal acquisition is carried out at the receiving end. Then, to improve signal to noise ratio (SNR), bandpass filtering is carried out on the receiving end. Next, considering the random changes in the underwater sound propagation channel, a strategy is proposed to select the optimal time window for cross-correlation. Then, new regulations are proposed to calculate the cross-correlation results. To verify the effectiveness of the algorithm, we compared it with other algorithms under low SNR conditions using Bellhop simulation data. Finally, the accurate time delay is obtained. With underwater experiments over different distances, the method proposed by the paper achieves high accuracy. The error is about 10-3 s. The proposed method makes a contribution to underwater navigation and communication.

The additive effects of bioactive glasses and photobiomodulation on enhancing bone regeneration.

Bioactive glasses (BG) have been generally used in bone defects repair for its good osteoinductivity and osteoconductivity. However, the early angiogenesis of BG in the repair of large-sized bone defects may not be sufficient enough to support new bone formation, resulting in the failure of bone repair. Photobiomodulation (PBM) therapy, which is superior on promoting early angiogenesis, may contribute to the angiogenesis of BG and further enhance the repair of bone defects. Therefore, we applied BG and PBM in combination and preliminarily investigated their additive effects on bone regeneration both in vitro and in vivo. The in vitro results revealed that BG combined with PBM remarkably enhanced human bone marrow mesenchymal stem cells proliferation, osteogenic-related genes expression and mineralization, which was better than applying BG or PBM respectively. For in vivo studies, the histological staining results showed that BG induced new bone formation in the interior of defects and promoted new bone reconstruction at 6 weeks post-operation. The micro-computed tomography results further confirmed that BG combined with PBM accelerated bone formation and maturation, improved the speed and quality of bone regeneration, and promoted bone repair. In conclusion, with the optimum BG and PBM parameters, BG combined with PBM generated additive effects on promoting bone regeneration.

The additive effects of photobiomodulation and bioactive glasses on enhancing early angiogenesis.

Bioactive glasses (BG) have been widely utilized as a biomaterial for bone repair. However, the early angiogenesis of BG may be inadequate, which weakens its osteogenic effects in large-sized bone defects and often leads to the failure of bone regeneration. In this study, we explored the effects of photobiomodulation (PBM) combined with BG on early angiogenesis to solve this bottleneck problem of insufficient early angiogenesis.In vitro, human umbilical vein endothelial cells (HUVECs) were cultured with BG extracts and treated with PBM using 1 J cm-2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and tubule formation assay were utilized to detect HUVECs' proliferation, vascular growth factor genes expression and tubules formation.In vivo, bone defects at the femoral metaphysis in Sprague-Dawley rats were treated with BG particulates and PBM at 120 J cm-2. Hematoxylin-eosin staining was used to observe the inflammatory response, tissue formation and biomaterial absorption of bone defects. Immunohistochemical staining was applied to observe the vascular-like structure formation. Thein vitroresults showed that PBM combined with BG significantly promoted HUVECs' proliferation, genes expression and mature tubules formation. On days 2, 4 and 7, the mRNA expression of VEGF in BG + PBM group was 2.70-, 2.59- and 3.05-fold higher than control (P< 0.05), and significantly higher than PBM and BG groups (P< 0.05). On days 4 and 7, the bFGF gene expression in BG + PBM group was 2.42- and 1.82-fold higher than control (P< 0.05), and also higher than PBM and BG groups (P< 0.05). Tube formation assay showed that mature tubules were formed in BG + PBM and PBM groups after 4 h, and the number in BG + PBM group was significantly higher than other groups (P< 0.05).In vivoresults further confirmed PBM induced early angiogenesis, with more vascular-like structures observed in BG + PBM and PBM groups 2 week post-surgery. With the optimum PBM fluence and BG concentration, PBM combined with BG exerted additive effects on enhancing early angiogenesis.

The Minimum AC Signal Model of Bipolar Transistor in Amplification Region for Weak Signal Detection.

This paper presents a minimum signal model via the AC small-signal model and the uncertainty principle, which reveals the minimum AC signal that can be amplified by a bipolar transistor. The Ebers-Moll model (EM3) can describe the small signal amplification process, but it is difficult to define the minimum amplifiable signal of the bipolar transistor. In this study, the correspondence relationship between the non-equilibrium carrier and the electric injection is proved, and the relationship between the life of the non-equilibrium carrier and the measurable signal is proposed by the uncertainty principle. Next, the limit of perceived minimum voltage is also derived in this paper. Then, combining with EM3 model, the minimum AC signal model of bipolar transistor is presented to calculate the minimum voltage signal of bipolar transistor that can be amplified. Finally, a number of the simulation and experiment results show that when the minimum signal in the model is used as input, the carrier concentration of the bipolar transistor does not change and the base electrode cannot perceive the signal, which verifies the validity of the minimum AC signal model.

Inclusion of molecular descriptors in predictive models improves pesticide soil-air partitioning estimates.

The soil-air exchange of pesticides is one potential fate and exposure pathways, and this process is generally thought to be governed by soil properties and environmental conditions. The experimental determination of soil-air partitioning coefficient (Ksa) is laborious and costly and typically, Ksa's are predicted from a semiempirical or a simple linear regression approach with soil and environmental variables. Here we developed a model that combined linear regression of soil, environmental and molecular parameters with the quantitative structural-property relationship (QSPR) to predict Ksa for pesticides. The values of theoretical descriptors of pesticides were calculated and the best descriptors selected using the Boruta Algorithm. Seventy-six experimental logKsa values for 17 pesticides were used in model development. Multiple linear regression (MLR) with a soil (organic carbon fraction), physicochemical (octanol-air partitioning coefficient), environmental (temperature and humidity) and molecular descriptor (Gmin, a 2D E-state molecular parameter), called as MLR-QSPR combined model exhibited better predictability (adj. r2 = 0.95) of logKsa compared to MLR (adj. r2 = 0.87) or QSPR (adj. r2 = 0.82) itself. MLR-QSPR also showed the best performance in five-fold cross-validation (adj. r2 = 0.94) and test set verification (adj. r2 = 0.96). The developed model was validated and characterized by the applicability domain. Results showed that the proposed MLR-QSPR approach is highly predictive and statistically robust with >95% of predictions within ±0.5 log unit of the measured Ksa. Therefore, this approach can be used in estimating the soil-air partitioning of pesticides to better predict it's fate and transport in environments.

Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors.

Although the extracellular ATP-gated cation channel purinergic receptor P2X5 is widely expressed in heart, skeletal muscle, and immune and nervous systems in mammals, little is known about its functions and channel-gating activities. This lack of knowledge is due to P2X5's weak ATP responses in several mammalian species, such as humans, rats, and mice. WT human P2X5 (hP2X5Δ328-349) does not respond to ATP, whereas a full-length variant, hP2X5 (hP2X5-FL), containing exon 10 encoding the second hP2X5 transmembrane domain (TM2), does. However, although rat P2X5 (rP2X5) has a full-length TM2, ATP induces only weak currents in rP2X5, which prompted us to investigate the mechanism underlying this small ATP response. Here, we show that single replacements of specific rP2X5 residues with the corresponding residues in hP2X5 (S191F or F195H) significantly enhance the current amplitude of rP2X5. Using a combination of engineered disulfide cross-linking, single-channel recording, and molecular modeling, we interrogated the effects of S191F and F195H substitutions on the allostery of the left flipper (LF) domain. On the basis of our findings, we propose that the bound ATP-induced distinct allostery of the LF domain with that of other functional subtypes has caused the weak ATP response of rP2X5 receptors. The findings of our study provide the prerequisite for future transgenic studies on the physiological and pathological functions of P2X5 receptors.

Assessing Space, Time, and Remediation Contribution to Soil Pollutant Variation near the Detection Limit Using Hurdle Models to Account for a Large Proportion of Nondetectable Results.

Many emerging, and some legacy, pollutants pose risks to humans and ecosystems near the detection limits (DL) of existing analytical systems. As a result, site assessments and management options are often presented with data sets that are sparse, highly skewed, and left-censored. Existing analysis methods are unable to differentiate effects of treatment from covariates, such as space, obscuring influences of site management. As a case study, we computed the mean and variance of censored soil benzene data across four sites over a three year period by gamma distribution with a maximum likelihood. Further, a combined hurdle model to accommodate left-censored concentrations was applied to analyze factors affecting benzene variation. This approach allowed us to assess the success and spatial dependency of a biostimulatory solution in reducing benzene concentrations at very low concentrations. Benzene concentrations decreased due to the addition of biostimulatory solution and spatial effects, but the detection of soil benzene after biostimulation was highly spatially dependent. By combining computed values for censored observations estimated by the hurdle-gamma model and uncensored observations, we can get the pseudocomplete data sets. The combined model is ideally suited to evaluate existing and emerging pollutants, that pose risks to humans and ecosystems but are typically at or near analytical detection limits.