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Susu Feng,1 Lin Guo,1 Sijing Wang,1 Lijuan Chen,1 Hang Chang,2 Bo Hang,2,3 Jianhua Mao,2 Antoine M Snijders,2 Yibing Lu,1 Dafa Ding1 1Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; 3Department of Biomaterials, Berkeley-Nanjing Research Center, Nanjing, People’s Republic of ChinaCorrespondence: Dafa Ding, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, People’s Republic of China, Tel +86 15850514014, Email dingdafa@njmu.edu.cnAim: We aimed to identify the ability of serum bile acids (BAs) and unsaturated fatty acids (UFAs) profiles to predict the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients.Methods: We first used univariate and multivariate analysis to compare 15 serum BA and 11 UFA levels in healthy control (HC) group (n = 82), T2DM patients with DR (n = 58) and T2DM patients without DR (n = 60). Forty T2DM patients were considered for validation. Then, the receiver operating characteristic curve (ROC) and decision curve analysis were used to assess the diagnostic value and clinical benefit of serum biomarkers alone, clinical variables alone or in combination, and the area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to further assess whether the addition of biomarkers significantly improved the predictive ability of the model.Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) of serum BAs and UFAs separated the three cohorts including HC, T2DM patients with or without DR. The difference in serum BA and UFA profiles of T2DM patients with or without DR was mainly manifested in the three metabolites of taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA) and arachidonic acid (AA). Together, they had an AUC of 0.785 (0.918 for validation cohort) for predicting DR in T2DM patients. After adjusting for numerous confounding factors, TLCA, TUDCA, and AA were independent predictors that differentiated T2DM with or without DR. The results of AUC, IDI, and NRI demonstrated that adding these three biomarkers to a model with clinical variables statistically increased their predictive value and were replicated in our independent validation cohort.Conclusion: These findings highlight the association of three metabolites, TLCA, TUDCA and AA, with DR and may indicate their potential value in the pathogenesis of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, serum bile acid, unsaturated fatty acid

Yazhuo Li, Dewu Zhang, Bing Hang, Hao Wang Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University (Xibei Hospital), Xi’an, People’s Republic of ChinaCorrespondence: Hao Wang, Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University (Xibei Hospital), No. 157, West 5th Road, Xi’an, Shaanxi Province, 710004, People’s Republic of China, Tel +86 182 9183 9156, Email wanghaonxyc@xjtu.edu.cnBackground: Combined therapy for keloids is currently recommended. Surgery is one of the main options, but the measures to prevent recurrence after excision are still being explored.Objective: The randomized controlled study aimed at evaluating the efficacy of excision followed by intralesional low concentrations of 5-fluorouracil (5-FU)(12.5 mg/mL) and betamethasone.Methods: Sixty patients were randomly assigned to three groups. Patients in group A had excision followed by 5-FU and betamethasone intralesional injections, group B had 5-FU and betamethasone intralesional injections, and group C had excision followed by radiotherapy. Efficacy parameters were assessed from 8 to 12 months, including improvement on the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Scale (POSAS), as well as side effects and recurrence. Trial registration number: ChiCTR2100046025.Results: After 4 months’ treatment, the improvement of the VSS and POSAS scores in group A was not different from that in group C (P > 0.05) but was superior to that in group B (P < 0.05); the pain and pruritus of the three groups were relieved more than 50%. After 8 to 12 months’ follow-up, there was no statistical difference in the incidence of side effects and recurrence among the groups (P > 0.05).Conclusion: Excision followed by intralesional low concentrations of 5-FU (12.5mg/mL) with betamethasone is a safe and sustainable treatment for keloid, with no significant difference from excision followed by radiotherapy.Keywords: keloid, excision, 5-fluorouracil, betamethasone, radiotherapy

Xue Li,1 Feng Shi,2 Liping Gong,2 Baojian Hang,2 Daoyuan Li,1 Lianli Chi1 1National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, and State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong, People’s Republic of China; 2Scientific Research Division, Shandong Institute for Food and Drug Control, Jinan, Shandong, People’s Republic of China Abstract: Colla corii asini (CCA) is a protein-based traditional Chinese medicine made from donkey skins. Because it has the ability to nourish blood, its demand is increasing rapidly. The shortage of donkey skins increases the risk of the adulteration of CCA products with other animal skins. To ensure the drug efficacy and safety of CCA products, a proteomics technique was applied to reveal proteins in the skins of donkey, horse, cattle, and pig. Species-specific peptides for each animal species were predicted using bioinformatics, and their presence in the skins and gelatin samples was examined by nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS). One unique marker peptide for each animal species was selected to develop an LC-MS/MS multiple reaction monitoring method. The capability of this method to identify donkey, horse, cattle, and pig materials was demonstrated by analyzing in-house-made donkey gelatins containing different amounts of other animal skins and commercial CCA products. The adulteration of non-donkey species could be sensitively detected at a low level of 0.5%. Hybrid animals, such as mules and hinnies, were also differentiated from donkeys. We provide a practical tool for the quality control of CCA products. The strategy can also be used to study other important traditional Chinese medicines which contain animal proteins. Keywords: Colla corii asini, collagen, proteomics, adulteration, mass spectrometry

University faculty in Southeast Asia (SEA) is being required to take on new roles and responsibilities resulting from rapid changes in higher education. To date, a range of faculty development (FD) initiatives has been implemented, but little has been uncovered concerning the effectiveness of these FD activities. Using a predetermined review protocol, we conducted a systematic literature review to identify the current foci and trends of faculty development in SEA higher education. We found that Vietnam, Singapore, and Malaysia were the leading providers of empirical evidence about FD activities. Teacher education and training were found to rank first among the disciplines that performed FD. This aligns with results of the focus and type of FD which primarily concerned improvement of pedagogical competence and self-directed learning. In addition, the findings suggested that most FD outcomes were found to be predominantly at levels 1 and 2 of Kirkpatrick's taxonomy (adapted from Hendricson et al. in "J Dent Educ" 71(12):1513-1533, 2007). Based on this review, we offered relevant recommendations for FD practice and research in this region.

The Internet of Things (IoT) technology connects the real and network worlds by integrating sensors and internet technology, which has greatly changed people’s lifestyles, showing its broad application prospects. However, traditional materials for the sensors and power components used in the IoT limit its development for high-precision detection, long-term endurance, and multi-scenario applications. Metal halide perovskite, with unique advantages such as excellent photoelectric properties, an adjustable bandgap, flexibility, and a mild process, exhibits enormous potential to meet the requirements for IoT development. This paper provides a comprehensive review of metal halide perovskite’s application in sensors and energy supply modules within IoT systems. Advances in perovskite-based sensors, such as for gas, humidity, photoelectric, and optical sensors, are discussed. The application of indoor photovoltaics based on perovskite in IoT systems is also discussed. Lastly, the application prospects and challenges of perovskite-based devices in the IoT are summarized.

Abstract Prostate cancer (PCa) patients with lymph node involvement (LNI) constitute a single-risk group with varied prognoses. Existing studies on this group have focused solely on those who underwent prostatectomy (RP), using statistical models to predict prognosis. This study aimed to develop an easily accessible individual survival prediction tool based on multiple machine learning (ML) algorithms to predict survival probability for PCa patients with LNI. A total of 3280 PCa patients with LNI were identified from the Surveillance, Epidemiology, and End Results (SEER) database, covering the years 2000–2019. The primary endpoint was overall survival (OS). Gradient Boosting Survival Analysis (GBSA), Random Survival Forest (RSF), and Extra Survival Trees (EST) were used to develop prognosis models, which were compared to Cox regression. Discrimination was evaluated using the time-dependent areas under the receiver operating characteristic curve (time-dependent AUC) and the concordance index (c-index). Calibration was assessed using the time-dependent Brier score (time-dependent BS) and the integrated Brier score (IBS). Moreover, the beeswarm summary plot in SHAP (SHapley Additive exPlanations) was used to display the contribution of variables to the results. The 3280 patients were randomly split into a training cohort (n = 2624) and a validation cohort (n = 656). Nine variables including age at diagnosis, race, marital status, clinical T stage, prostate-specific antigen (PSA) level at diagnosis, Gleason Score (GS), number of positive lymph nodes, radical prostatectomy (RP), and radiotherapy (RT) were used to develop models. The mean time-dependent AUC for GBSA, RSF, and EST was 0.782 (95% confidence interval [CI] 0.779–0.783), 0.779 (95% CI 0.776–0.780), and 0.781 (95% CI 0.778–0.782), respectively, which were higher than the Cox regression model of 0.770 (95% CI 0.769–0.773). Additionally, all models demonstrated almost similar calibration, with low IBS. A web-based prediction tool was developed using the best-performing GBSA, which is accessible at https://pengzihexjtu-pca-n1.streamlit.app/ . ML algorithms showed better performance compared with Cox regression and we developed a web-based tool, which may help to guide patient treatment and follow-up.

Etheno adducts in DNA arise from multiple endogenous and exogenous sources. Of these adducts we have reported that, 1,[N.sup.6]-ethenoadenine ([Epsilon]A) and 3,[N.sup.4]-ethenocytosine ([Epsilon]C) are removed from DNA by two separate DNA glycosylases. We later confirmed these results by using a gene knockout mouse lacking alkylpurine-DNA-N-glycosylase, which excises [Epsilon]A. The present work is directed toward identifying and purifying the human glycosylase activity releasing [Epsilon]C. HeLa cells were subjected to multiple steps of column chromatography, including two [Epsilon]C-DNA affinity columns, which resulted in >1,000-fold purification. Isolation and renaturation of the protein from SDS/polyacrylamide gel showed that the [Epsilon]C activity resides in a 55-kDa polypeptide. This apparent molecular mass is approximately the same as reported for the human G/T mismatch thymine-DNA glycosylase. This latter activity copurified to the final column step and was present in the isolated protein band having [Epsilon]C-DNA glycosylase activity. In addition, oligonucleotides containing [Epsilon]C.G or G/T(U), could compete for [Epsilon]C protein binding, further indicating that the [Epsilon]C-DNA glycosylase is specific for both types of substrates in recognition. The same substrate specificity for [Epsilon]C also was observed in a recombinant G/T mismatch DNA glycosylase from the thermophilic bacterium, Methano-bacterium thermoautotrophicum THF.

The enzymatic and biochemical properties of 3,N4-benzetheno-dC toward p-BQ-dC and an AP site in a defined oligonucleotide were compared. The comparative analysis of the specificity constants (Kcat/Km) for p-BQ-dC and an AP site suggests that the AP site is the preferred substrate. Results indicate that the enzyme does not cleave other structurally related exocyclic adducts and modified nucleosides.

Objective: To screen novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from camel milk lactoferrin (LF) combined with bioinformatics. Network pharmacology was used to explore the potential mechanism of action of screened peptides on diabetes. Methods: Multiple peptides were generated by simulated enzymatic cleavage of lactoferrin using the BIOPEP website. Screening target peptides by combining peptide databases and molecular docking. Four of them were selected for solid-phase synthesis to verify their DPP-IV inhibitory activity. Molecular docking was performed to analyze the interaction between the peptide and DPP-IV molecules, and the Lineweaver-Burk method was used to analyze the inhibition mode of the peptide. Then, GPQY with stronger inhibition was selected for network pharmacological analysis to predict its potential mechanism of action on diabetes. Furthermore, the active targets of GPQY and diabetes were mined from the Swiss Target Prediction and Gene Cards databases, and the String database was used to obtain protein-protein interaction relationships. The PPI networks were built by Cytoscape 3.9.0 software, and the DAVID database was exploited for enrichment analysis of GO and KEGG signaling pathways for key targets. Results: Two DPP-IV inhibitory peptides were obtained with semi-inhibitory concentration (IC50) values of 348.27±16.11 and 1024.89±19.67 μmol/L. Inhibition pattern analysis indicated competitive inhibition of GPQY and mixed-type inhibition of EACAF. Molecular docking results revealed two peptides bound to the active pocket of DPP-IV through hydrogen bonding, hydrophobic interactions and electrostatic interactions. From the PPI network analysis, GPQY had 25 core-acting targets, including STAT3, MMP9, SRC, and MAPK1. The enrichment results were based on KEGG pathways, which showed that GPQY was involved in the IL-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, renin-angiotensin system, apoptosis, etc. Conclusion: Camel milk lactoferrin is a good source of DPP-IV inhibitor peptide. GPQY could prevent diabetes and its complications through multiple targets and pathways involved in the inflammatory response and cell proliferation and differentiation.

Fano resonators have attracted great attention due to their high extinction ratio and sharp asymmetric line shape. And Fano-like resonators have also been investigated and analyzed in plenty of fields, such as optical sensing, signal processing and so on. We propose and demonstrate a Fano-like resonator with a high slope rate (SR) and low-complexity fabrication processing. Our scheme is based on a symmetrical 2 × 2 multimode interferometer (MMI) and two parallel microring resonators (MRRs) which are sandwiched between the two branches of MMI. By appropriately tuning the voltages are applied on the lower branch of MMI and the right MRR, tunable SRs can be obtained. The SR of our scheme can vary from -115.04 dB/nm to -247.54 dB/nm, and the maximum SR is obtained when the power consumption of the micro-heater integrated on right MRR is 6.79 mW. Besides, the SR of our Fano-like resonator can be tuned between positive and negative within a wavelength range of 0.06 nm. Our scheme has the advantages of compact structure, low-complexity fabrication processing, and high flexibility. And it can be widely used in color filters, all-optical switches, and optical sensing.

Striped catfish (Pangasianodon hypophthalmus), a freshwater species cultured mainly in the Mekong Delta region in Southern Vietnam, is facing a significant challenge due to salinity intrusion as a result of climatic changes. Given these evolving environmental conditions, selecting new strains with a higher salinity tolerance could make production of striped catfish economically feasible in brackish environments. In this study, we carried out a selection program aimed at developing a striped catfish strain able to survive and grow fast in a saline environment. To implement the selection program, we first collected males and females from different provinces in the Mekong delta. We next performed a factorial cross of these breeders to produce half- and full-sib families. When fish reached fry stage (47 dph), we put them in a saline environment (10 ppt) and subsequently kept 50 % of the fastest-growing fish after 143 days post hatching (dph). We repeated this mass selection procedure after 237 dph and 340 dph. We maintained in parallel a randomly selected group in saline conditions and a group of fish reared in freshwater to serve as controls. After crossing the selected individuals, we performed several tests on the next generation of fish to evaluate the effectiveness of selection after one generation in saline conditions. Average direct responses to selection were 18.0 % for growth and 11.4 % for survival rate after one generation of selection. We estimated a moderate realized heritability (0.29) for body weight. The genetic gains obtained in our study for body weight and survival rate after one generation of selection under saline conditions suggest that selection can be effective to improve ability of striped catfish to cope with saline stress. We conclude that our selection program has succeeded in developing a productive strain of striped catfish with better tolerance to salinity.

Abstract Background Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. In recent years, many plants have been explored in order to discover new bioactive secondary metabolites to treat cancers or enhance treatment efficiency. Aspiletrein A (AA) is a steroidal saponin isolated from the whole endemic species Aspidistra letreae in Vietnam. Previously, elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. However, the antitumor activities and mechanisms of action have not yet been elucidated. In this study, we demonstrated the anti-proliferative, anti-migrative and anti-invasive effects of AA on H460, H23 and A549 human lung cancer cells. Methods MTT, wound healing and Transwell invasion assays were used to evaluate the anti-proliferation, anti-migration and anti-invasion effects of AA, respectively. Moreover, the inhibitory effect of AA on the activity of protein kinase B (Akt), a central mediator of cancer properties, and apoptotic regulators in the Bcl-2 family proteins were investigated by Western blotting. Results AA exhibits antimetastatic effects in human lung cancer cells through the inhibition of the pAkt/Akt signaling pathway, which in turn resulted in a significant inhibitory effect of AA on the migration and invasion of the examined lung cancer cells. Conclusions Aspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound.

Natural gas hydrates as sustainable energy resources are inherently affected by mineral surfaces and confined spaces in reservoirs. However, the habits of hydrates in geological sediments are still an open question. In this work, we systemically studied the process of hydrate formation and dissociation in sediments from the Shenhu area of the South China Sea to examine the evolution of hydrate saturation and permeability in sediments and their relationship. Characterization of samples indicates that sediments of the Shenhu area are mainly composed of clay and fine sand grains and provide a large number of nanopores for hydrate accumulation. For in situ observations enabled by low-field nuclear magnetic resonance methods, the formation of hydrates shows a different kinetic behavior with an induction time compared to hydrate dissociation. Estimated by variations of hydrate saturation (%) over time, the rate of hydrate formation is around 12%/min, while the dissociation rate increases to 3%/min with the higher temperature. With the presence of hydrates, pore space and thus permeability of sediments decreased obviously by one and three orders of magnitude when the hydrate saturation is 20 and 45%, respectively. Compared to models with the assumption of grain-coating and pore-filling hydrates, the tendency of permeability evolution from NMR measurements is between fitted lines from models. It highlights that the existing models considering a single pattern of hydrate growth cannot precisely describe the relationship between permeability and hydrate saturation. Hybrid hydrate habits coexist in sediments resulting from heterogeneous pore structures and thus complex gas–water distributions.

Since teachers and their psychological factors have a significant share of variance in accounting for success in educational contexts, significant number of empirical studies have investigated the associations among intrapsychic variables of teachers. To further examine the inter-connections between individual teacher constructs in English as a Foreign Language (EFL) contexts, this study explored the role of emotion regulation and teacher self-efficacy in predicting teacher burnout in the Chinese EFL context. In so doing, a sample of 174 EFL teachers completed a survey containing the three valid scales measuring these constructs. Structural Equation Modeling was employed to examine the structural model of the variables under investigation. The findings revealed that teacher self-efficacy accounted for 20% of the variance in burnout, whereas emotion regulation represented 11.2% of the teacher burnout variance. Overall, it was revealed that although both variables exerted a significant unique contribution to teacher burnout, teacher self-efficacy seemed to be a stronger predictor of burnout than emotion regulation of teachers. The results might have remarkable implications for EFL teacher development programs.