Inflammation-induced subcutaneous neovascularization for the long-term survival of encapsulated islets without immunosuppression.

Cellular therapies for type-1 diabetes can leverage cell encapsulation to dispense with immunosuppression. However, encapsulated islet cells do not survive long, particularly when implanted in poorly vascularized subcutaneous sites. Here we show that the induction of neovascularization via temporary controlled inflammation through the implantation of a nylon catheter can be used to create a subcutaneous cavity that supports the transplantation and optimal function of a geometrically matching islet-encapsulation device consisting of a twisted nylon surgical thread coated with an islet-seeded alginate hydrogel. The neovascularized cavity led to the sustained reversal of diabetes, as we show in immunocompetent syngeneic, allogeneic and xenogeneic mouse models of diabetes, owing to increased oxygenation, physiological glucose responsiveness and islet survival, as indicated by a computational model of mass transport. The cavity also allowed for the in situ replacement of impaired devices, with prompt return to normoglycemia. Controlled inflammation-induced neovascularization is a scalable approach, as we show with a minipig model, and may facilitate the clinical translation of immunosuppression-free subcutaneous islet transplantation.

Mechanistic insights into dissolved organic matter-driven protistan and bacterial community dynamics influenced by vegetation restoration.

Vegetation restoration projects can not only improve water quality by absorbing and transferring pollutants and nutrients from non-vegetation sources, but also protect biodiversity by providing habitat for biological growth. However, the mechanism of the protistan and bacterial assembly processes in the vegetation restoration project were rarely explored. To address this, based on 18 S rRNA and 16 S rRNA high-throughput sequencing, we investigated the mechanism of protistan and bacterial community assembly processes, environmental conditions, and microbial interactions in the rivers with (out) vegetation restoration. The results indicated that the deterministic process dominated the protistan and bacterial community assembly (94.29% and 92.38%), influenced by biotic and abiotic factors. For biotic factors, microbial network connectivity was higher in the vegetation zone (average degree = 20.34) than in the bare zone (average degree = 11.00). For abiotic factors, the concentration of dissolved organic carbon ([DOC]) was the most important environmental factor affecting the microbial community composition. [DOC] was lower significantly in vegetation zone (18.65 ± 6.34 mg/L) than in the bare zone (28.22 ± 4.82 mg/L). In overlying water, vegetation restoration upregulated the protein-like fluorescence components (C1 and C2) by 1.26 and 1.01-folds and downregulated the terrestrial humic-like fluorescence components (C3 and C4) by 0.54 and 0.55-folds, respectively. The different DOM components guided bacteria and protists to select different interactive relationships. The protein-like DOM components led to bacterial competition, whereas the humus-like DOM components resulted in protistan competition. Finally, the structural equation model was established to explain that DOM components can affect protistan and bacterial diversity by providing substrates, facilitating microbial interactions, and promoting nutrient input. In general, our study provides insights into the responses of vegetation restored ecosystems to the dynamics and interactives in the anthropogenically influenced river and evaluates the ecological restoration performance of vegetation restoration from a molecular biology perspective.

[An optimization method of weighted network module partition based on TCM theory of "monarch, minister, assistant and guide"].

The disease-gene-drug multi-level network constructed by network pharmacology can predict drug targets and has been widely used in the study of material basis and mechanism of action of Chinese medicinal prescriptions. However, most of the current studies have normalized the efficacies of Chinese herbal medicines in the compounds during the construction of the network. There is also a lack of in-depth exploration of the mechanism of synergy among multiple components. This study proposed a network module partition method based on group collaboration and the pharmacological network was weighed according to the traditional Chinese medicine(TCM) theory of "monarch, minister, assistant and guide". Taking the Tanyu Tongzhi Prescription as an example, we constructed its pharmacological network for the treatment of myocardial ischemia-reperfusion injury. The group collaboration module in the network was identified and the network changes before and after the weighting were compared based on the network topology analysis to explore a new method to find the core nodes of the network as well as the core drugs that affected the efficacy of the compounds. The results showed that the module partition method based on group collaboration could be used to identify and partition group collaboration mo-dules in pharmacological networks of compounds. The proposed weighted network based on the TCM theory of "monarch, minister, assistant, and guide" could identify and partition the modules based on the characteristics of the pharmacological network. The identification and partition results of modules of Tanyu Tongzhi Prescription in the weighted network were superior to those in the unweighted network. The weighted closeness centrality(WCC) evaluation method was conducive to finding key nodes and relations in the network as compared with traditional methods, thereby providing a basis for analyzing the core components of drugs and extracting more accurate drug components and targets.

[Hotspots and trends of Ophiopogonis Radix based on CiteSpace knowledge map].

Ophiopogonis Radix is an important Yin-nourishing drug in traditional Chinese medicine(TCM), with the effects of nourishing Yin, promoting fluid production, clearing away heart-fire, and relieving restlessness. It is widely used in clinical practice due to its multiple chemical components and pharmacological effects. The technique "mapping knowledge domains" is an effective tool to quantitatively and objectively visualize the development frontiers and trends of certain disciplines. In this study, TCM research papers related to Ophiopogonis Radix were retrieved from Web of Science(WoS) and CNKI, and the research institutions, journals, and keywords involved were visualized and analyzed using the scientometric software CiteSpace. The co-occurrence network of related research on Ophiopogonis Radix was constructed, and the Ophiopogonis Radix-disease-target network was plotted using Cytoscape 3.8.2. The hot topics in Chinese and English papers were analyzed and the shortcomings in the research on Ophiopogonis Radix were summed up. Furthermore, the development trends were discussed. A total of 1 403 Chinese papers and 292 English papers were included in this study. The analysis of research institutions showed that Beijing University of Chinese Medicine and China Pharmaceutical University were the two research institutions with the largest numbers of papers published. The analysis of journals showed that Hebei Journal of Traditional Chinese Medicine and Journal of Asian Natural Products Research were the two journals with the highest numbers of papers concerning Ophiopogonis Radix. The keyword analysis showed that the research contents of Chinese papers focused on the analysis of medication regularity and clinical observation trials, while the English papers focused on component analysis and pharmacological investigation. Data mining and apoptosis-based pharmacological mechanism might be the research trends in the future.

Optimization of the Convolutional Neural Networks for Automatic Detection of Skin Cancer.

Convolutional neural networks (CNNs) are a branch of deep learning which have been turned into one of the popular methods in different applications, especially medical imaging. One of the significant applications in this category is to help specialists make an early detection of skin cancer in dermoscopy and can reduce mortality rate. However, there are a lot of reasons that affect system diagnosis accuracy. In recent years, the utilization of computer-aided technology for this purpose has been turned into an interesting category for scientists. In this research, a meta-heuristic optimized CNN classifier is applied for pre-trained network models for visual datasets with the purpose of classifying skin cancer images. However there are different methods about optimizing the learning step of neural networks, and there are few studies about the deep learning based neural networks and their applications. In the present work, a new approach based on whale optimization algorithm is utilized for optimizing the weight and biases in the CNN models. The new method is then compared with 10 popular classifiers on two skin cancer datasets including DermIS Digital Database Dermquest Database. Experimental results show that the use of this optimized method performs with better accuracy than other classification methods.

Independent relationship between body mass index and LH peak value of GnRH stimulation test in ICPP girls: A cross-sectional study.

The effect of obesity on idiopathic central precocious puberty (ICPP) girls is still under discussion. The relationship between body mass index (BMI) and sexual hormone levels of gonadotropin-releasing hormone (GnRH) stimulation test in ICPP girls is controversial and the underlying mechanism is unclear. This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone (LH) level of stimulation test in ICPP girls and the role of other related factors. A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP, including 355 cases of normal weight, 99 cases of overweight and 164 cases of obese. The results showed that obese group had more progressed Tanner stage and no significant difference (P=0.28) in LH peak was found as basal LH value was used as a covariate. The obese group had higher total testosterone (TT), adrenocorticotrophic hormone (ACTH), 17-α hydroxyprogesterone (17-αOHP) and androstendione (AN), with significantly increased fasting insulin (FIN) and homeostasis model of assessment for insulin resistance index (HOMA-IR). Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score (BMI-SDS) and LH peak in different Tanner stages (P for interaction=0.017). Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages. Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages, with and without different confounding factors being adjusted. In B2 stage, BMI-SDS was negatively associated with LH peak. In B3 stage, when BMI-SDS <1.5, as BMI-SDS increased, the level of LH peak decreased (model I: ß=-1.8, 95% CI=-4.7 to 1.1, P=0.214). When BMI-SDS ≥1.5, BMI-SDS was significantly positively associated with LH peak (model I: ß=4.5, 95% CI=1.7 to 7.4, P=0.002). In B4 stage, when BMI-SDS <1.5, BMI-SDS was negatively associated with LH peak (model I: ß=-11.6, 95% CI=-22.7 to-0.5, P=0.049). When BMI-SDS ≥1.5, BMI-SDS was positively associated with LH peak (model I: ß=-4.2, 95% CI=-3.3 to 11.7, P=0.28). It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls, their relationships are different in different Tanner stages, and the effect of BMI-SDS can be affected by adrenal androgens, estradiol and glucose metabolism parameters.

Independent Relationship between Body Mass Index and LH Peak Value of GnRH Stimulation Test in ICPP Girls: A Cross-sectional Study / 华中科技大学学报（医学）（英德文版）

The effect of obesity on idiopathic central precocious puberty (ICPP) girls is still under discussion.The relationship between body mass index (BMI) and sexual hormone levels of gonadotropin-releasing hormone (GnRH) stimulation test in ICPP girls is controversial and the underlying mechanism is unclear.This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone (LH) level of stimulation test in ICPP girls and the role of other related factors.A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP,including 355 cases of normal weight,99 cases of overweight and 164 cases of obese.The results showed that obese group had more progressed Tanner stage and no significant difference (P=0.28) in LH peak was found as basal LH value was used as a covariate.The obese group had higher total testosterone (TT),adrenocorticotrophic hormone (ACTH),17-α hydroxyprogesterone (17-αOHP) and androstendione (AN),with significantly increased fasting insulin (FIN) and homeostasis model of assessment for insulin resistance index (HOMA-IR).Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score (BMI-SDS) and LH peak in different Tanner stages (P for interaction=0.017).Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages.Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages,with and without different confounding factors being adjusted.In B2 stage,BMI-SDS was negatively associated with LH peak.In B3 stage,when BMI-SDS ＜1.5,as BMI-SDS increased,the level of LH peak decreased (model Ⅰ:β=-1.8,95％ CI=-4.7 to 1.1,P=0.214).When BMI-SDS ≥1.5,BMI-SDS was significantly positively associated with LH peak (model Ⅰ:β=4.5,95％ CI=1.7 to 7.4,P=0.002).In B4 stage,when BMI-SDS ＜1.5,BMI-SDS was negatively associated with LH peak (model Ⅰ:β=-11.6,95％ CI=-22.7 to-4.5,P=0.049).When BMI-SDS ≥1.5,BMI-SDS was positively associated with LH peak (model Ⅰ:β=-4.2,95％ CI=-3.3 to 11.7,P=0.28).It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls,their relationships are different in different Tanner stages,and the effect of BMI-SDS can be affected by adrenal androgens,estradiol and glucose metabolism parameters.

Comparison of the photoconversion of para-chlorophenol under simulated sunlight and UV irradiation in ice.

The photochemistry of para-chlorophenol (4-CP) was studied under simulated sunlight (lambda > 300 nm) and UV irradiation by using a 125 W high-pressure mercury lamp with or without a hard glass as light source in an ice matrix. The experiments were carried out in a photochemical cold chamber reactor at -14 to -12 degrees C. The photoconversion rate, photoproducts and photoconversion mechanism of 4-CP were all inspected and compared. The results show that the 4-CP photoconversion obeys the first order kinetic model and its photoconversion rate is highly affected by the initial concentration of 4-CP, light intensity and water quality. It is found that the conversion rate of 4-CP under UV irradiation is higher than that under simulated sunlight irradiation. The intermediate products of 4-CP were characterized by GC-MS, HPLC-ESI-MS and HPLC techniques and the possible photoconversion mechanism was proposed accordingly. It is concluded that the mechanism and photoproducts of 4-CP photolysis in ice are different from those in water, and the photoproducts and photoconversion pathways of 4-CP in ice varied with different light sources.

[Forming processes of micro-ecology in anaerobic sludge granulation].

By use of the fluorescence in situ hybridization (FISH) and the polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) methods, the diversity and similarity of microbial community during anaerobic sludge granulation were studied. The relative abundance and their succession of H2-producing acetogens (HPA), homoacetoges (HOMA) and methanogens were monitored. And the whole forming processes of micro-ecology were investigated correspondingly. The results showed that for an anaerobic reactor during normal startup, only through 33-days continuous operation, the healthy microecology of granular sludge could be formed, which is much less than the growth period of granular sludge ( > 180 d) and the time for achieving good COD removal (about 50 d). During the granulation processes of anaerobic sludge, the Shannon-Wiener diversity index of the microbial community increased firstly to 3.11 and then decreased to 2.88, and their similarity increased from 44% to 86% continuously. It is through these three stages, namely the adaptive stage, the growth stage and the stabilization stage in turn, the stable microecology could be formed gradually. In the initial granulation stage, the methanogens had a higher growth speed, resulting in methanogens, HPA and HOMA studied being produced in a ratio of approximately 42: 2: 1, respectively. However, with the healthy mocroecology been formed gradually, the ratio of methanogens to HPA and HOMA decreased to 2.8: 2.4: 1.0 finally.

Kinetics and mechanism of para-chlorophenol photoconversion with the presence of nitrite in ice.

The photochemistry of para-chlorophenol (4-CP) under UV irradiation by using a 125-W high-pressure mercury lamp as light source with the presence of nitrite in a solid water ice matrix had been studied. The experiments were carried out in a photochemical cold chamber reactor at -14 to -12 degrees C. Each influence factor of the 4-CP photoconversion kinetics in the water ice was inspected. The results show that the 4-CP photoconversion obeys the first-order kinetics model and the initial concentration of 4-CP, the initial concentration of nitrite, pH value, light intensity, inorganic ions and the water quality all have significant influence on the photoconversion rate. In addition, nine intermediate products were characterized by GC-MS, HPLC-ESI-MS and HPLC techniques and the possible photoconversion mechanism was proposed accordingly. It is concluded that the mechanism and photoproducts of 4-CP photolysis in ice are changed due to the presence of NO(2)(-).