A sandwich-type photoelectrochemical biosensor based on Ru(bpy)32+ sensitized In2S3 for aflatoxin B1 detection.

Aflatoxin B1 (AFB1), classified as a class I carcinogen, is a widespread mycotoxin that poses a serious threat to public health and economic development, and the food safety problems caused by AFB1 have aroused worldwide concern. The development of accurate and sensitive methods for the detection of AFB1 is significant for food safety monitoring. In this work, a sandwich-type photoelectrochemical (PEC) biosensor for AFB1 detection was constructed on the basis of an aptamer-antibody structure. A good photocurrent response was obtained due to the sensitization of In2S3 by Ru(bpy)32+. In addition, this sandwich-type sensor constructed by modification with the antibody, target detector, and aptamer layer by layer attenuated the migration hindering effect of photogenerated carriers caused by the double antibody structure. The aptamer and antibody synergistically recognized and captured the target analyte, resulting in more reliable PEC response signals. CdSe@CdS QDs-Apt were modified as a signal-off probe onto the sensor platform to quantitatively detect AFB1 with a "signal-off" response, which enhanced the sensitivity of the sensor. The PEC biosensor showed a linear response range from 10-12 to 10-6 g mL-1 with a detection limit of 0.023 pg mL-1, providing a feasible approach for the quantitative detection of AFB1 in food samples.

Beneficial action of cinnamic acid against ovarian cancer via network pharmacology analysis and the pharmacological activity assessment.

Naturally occurring cinnamic acid (CA) shows the beneficial potential in the suppression of ovarian cancer (OC). Currently, the in-depth molecular mechanisms of CA to suppress OC are still undescribed entirely. Thus, our research used the preclinical methodology through network pharmacology approach and pharmacological evaluation in vitro to unshroud the anti-OC targets and mechanisms of CA. Our data primarily identified 202 CA targets and 495 OC targets, and additional 45 shared targets in CA and OC were screened as presented in interaction network map. All 11 core targets in CA against OC were identified completely. The enrichment analysis of core targets revealed the biological functions and molecular mechanisms of CA against OC in details, including metabolic recombination and immune microenvironment regulation. Additionally, pharmacological evaluation data in vitro suggested that CA inhibited human OC cell proliferation in the time- and dose-dependent manners. In conclusion, CA can exert antineoplastic effects against OC effectively, and the pharmacological functions may directly actualize through a multi-target and multi-pathway avenue for suppressing OC.

Discovery of Multitarget Inhibitors against Insect Chitinolytic Enzymes via Machine Learning-Based Virtual Screening.

Multitarget inhibitors of insect chitinolytic enzymes are promising sources of green insecticides. Machine learning (ML) is an emerging virtual screening method that can accelerate drug discovery and reduce costs. Taking advantage of the data from our previous high-throughput screening work, we established a strategy integrating ML and molecular docking to screen a large natural product library (17 600 compounds) to identify novel multitarget inhibitors of four chitinolytic enzymes from the insect Ostrinia furnacalis (OfChtI, OfChtII, OfChi-h, and OfHex1). 3,5-Di-O-caffeoylquinic acid and γ-mangostin were identified as inhibitors of all of these enzymes with Ki values at the µM level. Moreover, they showed significant biological activities against lepidopteran pests. Transcriptomic analysis of compound-treated insects suggested the physiological relationship between these compounds and chitinolytic enzymes. This study highlights the potential of ML for insecticide discovery and provides novel and low-cost scaffolds of multitarget inhibitors against insect chitinolytic enzymes as potential pesticide leads.

Chitinase is a Potent Insecticidal Molecular Target of Camptothecin and Its Derivatives.

Camptothecin (CPT) is a prominent molecule in natural product research because of its application prospects in medicine and agriculture. In this study, CPT and its derivatives were discovered to be competitive inhibitors of group II and group h insect chitinases, both of which are key components of insect chitinolytic systems. CPT and 7-ethyl-10-hydroxycamptothecin (SN-38) inhibited group II chitinase from Ostrinia furnacalis (OfChtII) with Ki values of 5.1 and 2.0 µM, respectively. Results from tryptophan fluorescence spectroscopy, molecular docking analysis, and molecular dynamics simulations revealed that both CPT and SN-38 inhibit OfChtII-C1 by interacting with solvent-exposed tryptophan residues in a substrate-binding cleft. CPT exhibited high insecticidal activity toward the orthopteran pest Locusta migratoria, possibly because of the midgut metabolism of CPT, with only moderate activities toward lepidopteran pests. Even though SN-38 exhibited much lower insecticidal activities than CPT, it still showed higher inhibitory activity toward chitinase. This study reports a new molecular target of CPT and provides insights into molecular design of CPT-based insecticides against different kinds of pests.

Event-triggered H∞ consensus for uncertain nonlinear systems using integral sliding mode based adaptive dynamic programming.

This paper studies a robust optimal consensus problem for uncertain nonlinear multi-agent systems, where the uncertainties include both input and external disturbances. Adaptive distributed observer, integral sliding mode control and H∞ adaptive dynamic programming are integrated to obtain a sub-optimal control protocol for each follower. Firstly, an adaptive distributed observer is designed for state estimation of the leader, which serves as the reference of the ADP algorithm. Then, an H∞ ADP algorithm is presented to make each follower track the reference in real-time. An integral sliding manifold-based discontinuous control is designed to eliminate the matched uncertainty, and continuous control is obtained by solving the Hamilton-Jacobi-Isaac equation under the H∞ tracking framework. Two event-triggered rules are developed to relieve the communication pressure. For simplicity, a critic-only structure is used to numerically implement the proposed algorithm, and a concurrent learning technique is employed to update weights of neural networks. All signals in the closed-loop system are proven to be uniformly ultimately bounded. Finally, a simulation is conducted to demonstrate demonstrates the effectiveness of the method.

Secondary Structural Ensemble Learning Cluster for Estimating the State of Health of Lithium-Ion Batteries.

Accurate online state-of-health (SOH) estimation can improve the operational efficiency of lithium-ion batteries (LIBs) and ensure the safety of energy storage systems. However, the complex electrochemical properties of LIBs make accurate SOH estimation challenging. To overcome this challenge, we propose a secondary structural ensemble learning (SSEL) cluster. The proposed SSEL cluster includes multiple SSEL frameworks established separately within different SOH data intervals, allowing the identification of stable feature-SOH relationships. The adaptability and basic accuracy of each SSEL framework are guaranteed by various base learners and the corresponding stacking model and bagging model fusion. Each framework remains unique and specialized owing to the adoption of back propagation neural networks, which adjust learner weights based on the feature-SOH relationship at each interval. The effectiveness of the SSEL cluster was verified using the Oxford Battery Degradation Dataset 1. Comparisons showed that the proposed estimation method performs better than traditional machine learning methods.

Universal Adversarial Attack on Attention and the Resulting Dataset DAmageNet.

Adversarial attacks on deep neural networks (DNNs) have been found for several years. However, the existing adversarial attacks have high success rates only when the information of the victim DNN is well-known or could be estimated by the structure similarity or massive queries. In this paper, we propose to Attack on Attention (AoA), a semantic property commonly shared by DNNs. AoA enjoys a significant increase in transferability when the traditional cross entropy loss is replaced with the attention loss. Since AoA alters the loss function only, it could be easily combined with other transferability-enhancement techniques and then achieve SOTA performance. We apply AoA to generate 50000 adversarial samples from ImageNet validation set to defeat many neural networks, and thus name the dataset as DAmageNet. 13 well-trained DNNs are tested on DAmageNet, and all of them have an error rate over 85 percent. Even with defenses or adversarial training, most models still maintain an error rate over 70 percent on DAmageNet. DAmageNet is the first universal adversarial dataset. It could be downloaded freely and serve as a benchmark for robustness testing and adversarial training.

Validation of the DIGIROP-birth model in a Chinese cohort.

BACKGROUND: We aimed to validate the predictive performance of the DIGIROP-Birth model for identifying treatment-requiring retinopathy of prematurity (TR-ROP) in Chinese preterm infants to evaluate its generalizability across countries and races. METHODS: We retrospectively reviewed the medical records of preterm infants who were screened for retinopathy of prematurity (ROP) in a single Chinese hospital between June 2015 and August 2020. The predictive performance of the model for TR-ROP was assessed through the construction of a receiver-operating characteristic (ROC) curve and calculating the areas under the ROC curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: Four hundred and forty-two infants (mean (SD) gestational age = 28.8 (1.3) weeks; mean (SD) birth weight = 1237.0 (236.9) g; 64.7% males) were included in the study. Analyses showed that the DIGIROP-Birth model demonstrated less satisfactory performance than previously reported in identifying infants with TR-ROP, with an area under the receiver-operating characteristic curve of 0.634 (95% confidence interval = 0.564-0.705). With a cutoff value of 0.0084, the DIGIROP-Birth model showed a sensitivity of 48/93 (51.6%), which increased to 89/93 (95.7%) after modification with the addition of postnatal risk factors. In infants with a gestational age < 28 weeks or birth weight < 1000 g, the DIGIROP-Birth model exhibited sensitivities of 36/39 (92.3%) and 20/23 (87.0%), respectively. CONCLUSIONS: Although the predictive performance was less satisfactory in China than in developed countries, modification of the DIGIROP-Birth model with postnatal risk factors shows promise in improving its efficacy for TR-ROP. The model may also be effective in infants with a younger gestational age or with an extremely low birth weight.

Diagnostic Value of Portal Vein Velocity for Portal Hypertension in Patients with Hepatitis B Virus-related Cirrhosis.

BACKGROUND: Portal vein velocity (PVV) has shown a reasonable correlation with the presence of portal hypertension in patients with cirrhosis. This study aims to evaluate the value of PVV for diagnosing clinically significant portal hypertension (CSPH) and predicting the risk of variceal hemorrhage (VH) in patients with hepatitis B virus (HBV)-related cirrhosis. MATERIALS AND METHODS: A cohort of 166 consecutive adult patients with HBV-related cirrhosis was recruited in this retrospective study from two high-volume liver centers in China between April 2015 and April 2017. The performance of PVV and other non-invasive parameters for diagnosing CSPH and predicting the risk of VH was studied. RESULTS: PVV demonstrated the best performance for diagnosing CSPH (defined as an HVPG ≥10 mmHg) in patients with HBV-related cirrhosis among the included non-invasive predictors with the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of 0.745, 50%, and 93.5%, respectively. Other non-invasive markers, including APRI, AAR, LS, FIB-4, and diameter of the portal vein, did not show sufficient performance with the AUCs of 0.565, 0.560, 0.544, 0.529, and 0.474, respectively. With regard to predicting the risk of VH (defined as an HVPG ≥12 mmHg), PPV also exhibited a moderate performance with an AUC of 0.762, which was superior to that of the aforementioned markers. By using two cutoff values of PVV to rule-out (11.65 cm/s) and rule-in (20.20 cm/s) CSPH, 30 (33.7%) patients showed definite results categories, with 23 (76.7%) patients were well classified and 7 (23.3%) were misclassified. Fifty-nine (66.3%) patients were with indeterminate results. By using PVV values of 13.10 cm/s and 21.40 cm/s to rule-out and rule-in HVPG ≥ 12mmHg, 34 (38.2%) patients has definite results, among whom 26 (76.5%) were well classified and 8 (23.5%) were misclassified. And 55 (61.8%) patients required further evaluation. CONCLUSION: PPV is insufficient to serve as a non-invasive parameter for identifying CSPH and predicting the risk of VH in patients with HBV-related cirrhosis.

Efficacy of the WINROP algorithm for retinopathy of prematurity screening in Southern China.

AIM: To evaluate the predicting efficacy of severe retinopathy of prematurity (ROP) by the WINROP algorithm (http://winrop.com) in Southern China. METHODS: All preterm infants with the gestational age (GA) less than 32wk were included. Their ROP screening results and serial postnatal body weight were analysed retrospectively. Weekly body weight was entered into and measured by the WINROP system. The outcomes were analysed, and the sensitivity, specificity, positive predictive value and negative predictive value (NPV) were calculated. RESULTS: Totally 432 infants with a median GA of 30.0 (24.0-31.9)wk, and a median birth weight (BW) of 1360 (540-2700) g were included. Among these 432 infants, 50 were diagnosed as type 1 ROP but only 28 were identified by the WINROP algorithm. The sensitivity was 56% (28/50) and the NPV was 92% (252/274). However, for infants with BW <1000 g or GA <28wk, the sensitivity was 93.8% (15/16) and 93.3% (14/15), respectively. Meanwhile, with several postnatal complications added as additional risk factors, the sensitivity was increased to 96% (48/50). CONCLUSION: The sensitivity of the WINROP algorithm from the Southern Chinese cohort is not as high as that reported in developed countries. This algorithm is effective for detecting severe ROP from extremely small or preterm infants. Modification of the algorithm with additional risk factors could improve the predictive value for infants with a GA>28wk in China.

Self-assembling hydrogel loaded with 5-FU PLGA microspheres as a novel vitreous substitute for proliferative vitreoretinopathy.

The vitreous substitute for proliferative vitreoretinopathy (PVR) surgery remains an unmet clinical need in ophthalmology. In our study, we developed an in situ formed hydrogel by crosslinking polyvinyl alcohol (PVA) and chitosan as a potential vitreous substitute. 5-fluorouracil (5-FU) Poly (lactic-co-glycolic acid) (PLGA) microspheres were developed and loaded onto the PVA/chitosan hydrogels to treat PVR. In vitro, PVA/chitosan hydrogels at four concentrations were subjected to morphological, physical, rheological analyses, and cytotoxicity was evaluated together with the characterization of 5-FU PLGA microspheres. In vivo, pharmacologically induce PVR rabbits were performed a vitrectomy. In the PVA group, 3% PVA/chitosan hydrogel was injected into the vitreous cavity. In the PVA/MS group, 3% PVA/chitosan hydrogel and 5-FU PLGA microspheres were injected. In the Control group, phosphate-buffered saline was injected. Therapeutic efficacy was evaluated with postoperative examinations and histological analyses. This study demonstrated that the 3% PVA/chitosan hydrogel showed properties similar to those of the human vitreous and could be a novel in situ crosslinked vitreous substitute for PVR. Loading 5-FU PLGA microspheres onto this hydrogel may represent an effective strategy to improve the prognosis of PVR.

The risk of abnormal placentation and hemorrhage in subsequent pregnancy following primary elective cesarean delivery.

Objective: We aimed to evaluate the relationship between mode of first delivery with subsequent placenta previa, placenta accreta/increta, and significant postpartum hemorrhage (PPH).Method: This retrospective cohort study included women with two consecutive singleton deliveries between 2007 and 2017 at our institution if the women were nulliparous and delivered at term at the time of first delivery. The first pregnancy delivery mode was classified as (1) vaginal delivery, (2) antepartum cesarean delivery (CD) without labor, or (3) intrapartum CD after the onset of labor. Within these three groups, rates of placenta previa, placenta accreta/increta, and significant PPH at the time of the second delivery were compared. Significant PPH was defined as hemorrhage requiring a blood transfusion.Results: A total of 8208 women were analyzed. Most first deliveries were vaginal (n = 5210, 63.5%), followed by antepartum CD (n = 2432, 29.6%) and intrapartum CD (n = 566, 6.9%). The incidence of placenta previa in subsequent deliveries differed by previous delivery mode: vaginal, 0.9%; antepartum CD, 2.0%; intrapartum CD, 1.6% (p < .001). Similar differences were also observed with respect to placenta accreta/increta (0.5 versus 1.5 versus 0.9%, p < .001) and PPH (0.6 versus 1.2 versus 0.4%, p = .017). Compared to the previous vaginal delivery group, the antepartum CD group had increased risks of placenta previa (aORs 2.02, 95% CI 1.35-3.05), placenta accreta/increta (aOR 2.52; 95% CI 1.53-4.14) and PPH (aOR 1.78, 95% CI 1.14-2.98) in subsequent pregnancies. However, the previous intrapartum CD was not significantly associated with increased risks of these complications.Conclusion: Previous antepartum CD was associated with two-fold increased risks of placenta previa, placenta accreta/increta, and significant PPH in the second delivery compared to women with a prior vaginal delivery. The increased risks of subsequent abnormal placentation following primary antepartum CD may be important for counseling concerning nonmedically indicated elective cesarean.Condensation: Previous antepartum cesarean delivery (CD) was associated with two-fold increased risks of placenta previa, placenta accreta/increta, and significant PPH in the second delivery.

The prognostic value of CXC chemokine receptor 2 (CXCR2) in cancers: a meta-analysis.

BACKGROUND & AIMS: Quite a few studies had investigated the correlation between CXC chemokine receptor 2 (CXCR2) and cancer. This meta-analysis was aimed to comprehensively summarize the previous studies and to explore the prognostic value of CXCR2 in patients with cancer. MATERIALS AND METHODS: An adequate literature search in EMBASE and PubMed was conducted. Articles in English which have reported CXCR2 expression in patients and enough data to calculate hazard ratio (HR) were included. Effect estimates were analyzed with Review Manager 5.2. The endpoint was overall survival (OS) and recurrence-free survival (RFS). RESULT: Twelve studies from 10 publications with a total of 2,461 patients were identified. It was shown that high level of CXCR2 was significantly associated with poorer overall survival (OS) (HR = 1.69, 95% CI = 1.46-1.96, p < 0.0001, I2 = 45%) and RFS (HR = 1.50, 95% CI = 1.25-1.80, p < 0.0001, I2 = 6%). The analyses of different analysis models (univariate or multivariate models), sample size (< 300 or ≥ 300) and ethnicity (Asian and Caucasian) have indicated the negative impact of CXCR2 over-expression on survival of patients with cancer. Stratified by cancer type, high-expression of CXCR2 was associated with unfavorable OS in laryngeal squamous cell carcinoma, lung cancer, pancreatic ductal carcinoma, clear-cell renal cell carcinoma and hepatocellular carcinoma; however, there was significant difference between high- and low-expression of CXCR2 in digestive tract cancer (esophageal adenocarcinoma and squamous cell carcinoma procession, resected esophageal carcinoma, esophageal cancer and gastric cancer). CONCLUSIONS: CXCR2 is an unfavorable predictor in terms of OS and RFS in patients with cancer except for digestive tract cancer and is related with poorer prognostic.