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This is a continuation of a previous study initiated by the third author on nonlocal vertex bialgebras and smash product nonlocal vertex algebras. In this paper, we study a notion of right H -comodule nonlocal vertex algebra for a nonlocal vertex bialgebra H and give a construction of deformations of vertex algebras with a right H -comodule nonlocal vertex algebra structure and a compatible H -module nonlocal vertex algebra structure. We also give a construction of ϕ -coordinated quasi modules for smash product nonlocal vertex algebras. As an example, we give a family of quantum vertex algebras by deforming the vertex algebras associated to non-degenerate even lattices. [ABSTRACT FROM AUTHOR]

Introduction: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods: All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results: Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (AE) (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study drug. The majority of AEs were mild to moderate in severity. Conclusions: Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting that this regimen could be a promising option for HCV treatment in China irrespective of genotype. Trial Registration: ClinicalTrial.gov identifier, NCT04070235. [ABSTRACT FROM AUTHOR]

The razor clam Sinonovacula constricta is the first marine mollusk demonstrated to possess the complete long-chain polyunsaturated fatty acids (LC-PUFA) biosynthetic pathway. This study explored the impact of different microalgae on growth, Fad and Elovl expressions, and fatty acid (FA) profiles in juvenile S. constricta. Results revealed that juveniles fed with Isochrysis galbana (rich in DHA) or Chaetoceros calcitrans (rich in EPA) consistently exhibited higher growth than those fed Chlorella sp. (rich in LA and ALA), underscoring the importance of dietary LC-PUFA in S. constricta's development. Expression of most Fad and Elovl in C. calcitrans and I. galbana-fed juveniles were initially up-regulated, then down-regulated, suggesting LC-PUFA demand for faster growth. Although Chlorella sp.-fed juveniles exhibited decreased mRNA levels for most genes, levels were notably higher lately compared to those fed C. calcitrans or I. galbana, hinting at potential LC-PUFA biosynthesis induction. FA profiles in S. constricta generally mirrored those in ingested microalgae, implying direct FA accumulation from diets. Some microalgal FA were absent in farmed S. constricta, while others emerged, indicating S. constricta's ability to selectively accumulate and synthesize FA. This study enhances the understanding of dietary FA metabolism in S. constricta, valuable for selecting appropriate microalgae in its farming practices. [ABSTRACT FROM AUTHOR]

Let U ħ (g ^) be the untwisted affinization of a symmetrizable quantum Kac-Moody algebra U ħ (g) . For ℓ ∈ C , we construct an ħ -adic quantum vertex algebra V g ^ , ħ (ℓ , 0) , and establish a one-to-one correspondence between ϕ -coordinated V g ^ , ħ (ℓ , 0) -modules and restricted U ħ (g ^) -modules of level ℓ . Suppose that ℓ is a positive integer. We construct a quotient ħ -adic quantum vertex algebra L g ^ , ħ (ℓ , 0) of V g ^ , ħ (ℓ , 0) , and establish a one-to-one correspondence between certain ϕ -coordinated L g ^ , ħ (ℓ , 0) -modules and restricted integrable U ħ (g ^) -modules of level ℓ . Suppose further that g is of finite type. We prove that L g ^ , ħ (ℓ , 0) / ħ L g ^ , ħ (ℓ , 0) is isomorphic to the simple affine vertex algebra L g ^ (ℓ , 0) . [ABSTRACT FROM AUTHOR]

Batch normalization is one of the most widely used components in deep neural networks. It can accelerate training, and boost model performance on normal samples. However, batch normalization induces vulnerability to models on adversarial examples, especially in medical images, and the reason is still not clear. In this paper, we aim to explain the vulnerability aroused by batch normalization under adversarial images. Specifically, we first discover that both natural and medical images contain a large number of trivial features, whose weights will be enlarged under adversarial attacks, and batch normalization can further enlarge their weights. Additionally, we find that batch normalization will reduce the inter-class margin of high-level features, leading to less tolerance to adversarial perturbations, thereby decreasing the model robustness. Moreover, we hypothesize that the smaller inter-class margin, the more difficult to attain the optimal classification space, which means batch normalization will restrict the performance of adversarial training. This further verifies that a narrower inter-class margin induced by batch normalization reduces the model robustness. Experiments on four benchmark datasets demonstrate our discovery, interpretation and hypothesis. [ABSTRACT FROM AUTHOR]

Background: To investigate the prognostic impact of the controlling nutritional status (CONUT) score in non-small-cell lung cancer (NSCLC) patients receiving first-line chemotherapy. Methods: We retrospectively reviewed 278 consecutive patients undergoing chemotherapy for stage III-IV NSCLC between May 2012 and July 2020. CONUT score was calculated by incorporating serum albumin, total cholesterol, and total lymphocyte count. The patients were divided into two groups: CONUT ≥ 3 and CONUT < 3, according to receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. Results: A high CONUT score was significantly associated with older age(P = 0.003), worse ECOG-PS(P = 0.018), advanced clinical stage(P = 0.006), higher systematic inflammation index (SII) (P < 0.001)and lower prognostic nutritional index (PNI) (P < 0.001).The high CONUT group had a significantly shorter progression-free survival(PFS) and overall survival(OS) than the low CONUT group. In the univariate analysis, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse PFS (Pall < 0.05). Worse ECOG-PS, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse OS (Pall < 0.05). In multivariate analysis, CONUT(HR, 2.487; 95%CI 1.818 ~ 3.403; P < 0.001) was independently associated with PFS, while PNI(HR, 0.676; 95%CI 0.494 ~ 0.927; P = 0.015) and CONUT(HR, 2.186; 95%CI 1.591 ~ 3.002; P < 0.001)were independently associated with OS. In ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 24-month PFS and OS than the SII or PNI. When the time-dependent AUC curve was used to predict PFS and OS, CONUT tended to maintain its predictive accuracy for long-term prognosis at a significantly higher level for an extended period after chemotherapy when compared with the other markers tested. The CONUT score showed better accuracy of predicting OS (C-index: 0.711) and PFS(C-index: 0.753). Conclusion: CONUT score is an independent prognostic indicator of poor outcomes for patients with stage III-IV NSCLC and is superior to the SII and PNI in terms of prognostic ability. [ABSTRACT FROM AUTHOR]

Study question: To construct prediction models based on the Bayesian network (BN) learning method for the probability of fertilization failure (including low fertilization rate [LRF] and total fertilization failure [TFF]) in assisted reproductive technology (ART) treatment. Summary answer: A BN model was developed to predict TFF/LFR. The model showed relatively high calibration in external validation, which could facilitate the identification of risk factors for fertilization disorders and improve the efficiency of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. What is known already: The prediction of TFF/LFR is very complex. Although some studies attempted to construct prediction models for TFF/LRF, most of the reported models were based on limited variables and traditional regression-based models, which are unsuitable for analyzing real-world clinical data. Therefore, none of the reported models have been widely used in routine clinical practice. To date, BN modeling analysis is a prominent and increasingly popular machine learning method that is powerful in dealing with dynamic and complex real-world data. Study design, size, duration: A retrospective study was performed with 106,640 fresh embryo IVF/ICSI cycles from 2009 to 2019 in one of China's largest reproductive health centers. Participants/materials, setting, methods: A total of 106, 640 cycles were included in this study, including 97,102 controls, 4,339 LFR cases, and 5,199 TFF cases. Twenty-four predictors were initially included, including 13 female-related variables, five male-related variables, and six variables related to IVF/ICSI treatment. BN modeling analysis with tenfold cross-validation was performed to construct the predictive model for TFF/LFR. The receiver operating characteristic (ROC) curves and the corresponding area under the curves (AUCs) were used to evaluate the performance of the BN model. Main results and the role of chance: All twenty-four predictors were first organized into seven hierarchical layers in a theoretical BN model, according to prior knowledge from previous literature and clinical practice. A machine-learning BN model was generated based on real-world clinical data, containing a total of eighteen predictors, of which the infertility type, ART method, and number of retrieved oocytes directly influence the probabilities of LFR/TFF. The prediction accuracy of the BN model was 91.7%. The AUC of the TFF versus control groups was 0.779 (95% CI: 0.766-0.791), with a sensitivity of 71.2% and specificity of 70.1%; the AUC of of TFF versus LFR groups was 0.807 (95% CI: 0.790-0.824), with a sensitivity of 49.0% and specificity of 99.0%. Limitations, reason for caution: First, our study was based on clinical data from a single center, and the results of this study should be further verified by external data. In addition, some critical data (e.g., the detailed IVF laboratory parameters of the sperm and oocytes used for insemination) were not available in this study, which should be given full consideration when further improving the performance of the BN model. Wider implications of the findings: Based on extensive clinical real-world data, we developed a BN model to predict the probabilities of fertilization failures in ART, which provides new clues for clinical decision-making support for clinicians in formulating personalized treatment plans and further improving ART treatment outcomes. Study funding/competing interest(s): Dr. Y. Wang was supported by grants from the Beijing Municipal Science & Technology Commission (Z191100006619086). We declare that there are no conflicts of interest. Trial registration number: N/A. [ABSTRACT FROM AUTHOR]

Herein, we introduced a novel individual sperm freezing device named SpermCD, which consists of a right angular cryopiece (RA‐Cryopiece, or "C") and a grooved petri dish ("D"). SpermCD allows embryologists to transfer sperm and perform ICSI on the same focal plane. Thirty‐five patients underwent single sperm cryopreservation using SpermCD, including four patients with non‐obstructive azoospermia (NOA), 14 patients with virtual azoospermia and 17 patients with cryptozoospermia. One hundred and twenty‐five cryopreserved spermatozoa from nine patients were thawed on the day of the oocyte retrieval and 121 spermatozoa were found, with a sperm recovery rate of 97.1 ± 4.6%. Sixty‐five MII oocytes from their spouse were injected with thawed sperm. Normal fertilization and high‐quality embryo rates were 68.0% ± 33.2% and 24.4% ± 22.2%. Nineteen transplantable embryos were formed after fertilization with frozen sperm, eight of which were transplanted in five couples, resulting in four successful deliveries. SpermCD is a simple and practical individual sperm freezing device. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (IONPs) are mostly intended to be administrated intravenously, understanding the interaction of IONPs with vascular endothelial cells is extremely crucial for developing safe application regimes of IONPs. In this work, interactions of three kinds of IONPs to endothelial cells were investigated both in human umbilical vein endothelial cells (HUVECs) and in healthy mice. Both meso-2,3-dimercaptosuccinic acid (DMSA) coated Fe3O4 NPs (DMSA-Fe3O4 NPs) and DMSA-Fe2O3 NPs induced cell growth inhibition, while polyglucose sorbitol carboxymethyether coated Fe2O3 NPs(PSC-Fe2O3 NPs) did not. The PSC coating inhibited the cellular uptake of the IONPs. Both DMSA-Fe3O4 and DMSA-Fe2O3 NPs induced ferroptosis of HUVEC through upregulating phospholipid peroxides, which could be inhibited by typical ferroptosis inhibitors ferrostatin-1, Trolox and deferoxamine. Moreover, transforming growth factor beta 1 (TGFβ1) was upregulated by DMSA-Fe3O4 NPs at protein and gene level. The inhibitor of TGFβ1 receptor LY210 could reduce the effect. When being intravenously injected in mice, DMSA-Fe3O4 NPs were observed locating in the liver, increased the levels of lipid peroxidation (4-hydroxynonenal), acyl-CoA synthetase long-chain family member 4(ACSL4) and TGFβ1, indicating ferroptosis occurrence in vivo. The ferroptosis of vascular endothelial cells in exposure with IONPs depended on the surface coating and core chemistry of the NPs. Both DMSA-Fe3O4 NPs and DMSA-Fe2O3 NPs could induce the ferroptosis of endothelial cells, while PSC-Fe2O3 NPs did not induce ferroptosis and apoptosis possibly due to the very low cellular uptake. DMSA-Fe3O4 NPs and TGFβ1 formed feedforward loop to induce ferroptosis. [ABSTRACT FROM AUTHOR]

Based on the macroanalysis of the unbalanced development of the "demand side" and the "supply side" of clinical medicine in China, this paper elucidates the stakeholders, resources, and ecosystem of the strategic scientific and technological capacity-building and calls for a larger coverage, smoother supply chain, and more sustainable ecosystem to ensure the development of clinical medicine. Furthermore, focusing on the establishment and development of clinical reproductive health in China, the authors introduce the strategic scientific and technological capacity-building of reproductive medicine in Peking University Third Hospital, with an attempt to inform similar efforts in other fields and even the whole clinical medicine in China. [ABSTRACT FROM AUTHOR]

Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well‐tolerated and druggable in healthy subjects and HCV‐infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6. In this open‐label study, patients with chronic HCV infection were randomly assigned with a 1:1:1 ratio to receive 12 weeks of daclatasvir 60 mg plus alfosbuvir at a dose of 400, 600 or 800 mg (Cohort A, B or C) daily. Randomization was stratified by HCV genotype and the presence or absence of cirrhosis at screening. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A total of 124 patients were enrolled in the study, all of whom were available for post‐treatment week 12 assessments. SVR12 was achieved in 92.7% (38/41), 95.2% (40/42) and 100% (41/41) of patients in Cohort A, B and C respectively. The most common adverse events were hepatic steatosis, upper respiratory tract infection, hypercholesterolaemia, hypertriglyceridaemia, blood bilirubin increased, and total bile acids increased. There were no discontinuations due to adverse events, and no treatment‐related serious adverse events were reported. Once‐daily oral administration of alfosbuvir plus daclatasvir were highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3 or 6, suggesting this regimen could be a promising drug candidate for HCV treatment irrespective of genotype. (ClinicalTrials.gov number, NCT04070235). [ABSTRACT FROM AUTHOR]

Background Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. Methods Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. Results A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group. Conclusions Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated. Clinical Trials registration NCT00230503 and China Drug Trials CTR2018042 [ABSTRACT FROM AUTHOR]

This article provides an overview of assisted reproductive technology (ART) in China. It highlights the rapid development of ART in China over the past 30 years, with over 1 million ART cycles and 300,000 ART babies born annually. The article also discusses the challenges faced by reproductive medicine in China, such as the aging population and increasing infertility rates. It presents several studies conducted in China on topics such as polycystic ovary syndrome, luteal phase deficiency, cervical cancer, chromosome aberrations, and premature ovarian insufficiency. The article concludes by expressing gratitude to the authors, reviewers, and editors for their contributions to reproductive medicine in China. [Extracted from the article]

Myocardial ischemia/reperfusion (MI/R) injury is a common clinical problem after myocardial infarction without effective therapy. Loureirin B (LrB) is a kind of flavonoid with anti-inflammatory and antifibrotic activities. However, the effect of LrB on MI/R and its underlying mechanism remains elusive. In the present study, a mouse model of MI/R was established by coronary artery occlusion. Administration of LrB (0.5 mg/kg or 1 mg/kg) for 4 weeks effectively improved left ventricular (LV) function and reduced myocardial infarction in MI/R mice. MI/R-induced expression of IL-6, TNF-α, and IL-1β in the hearts was reduced by LrB treatment. Histological analysis showed that LrB attenuated myocardial collagen deposition. LrB downregulated fibronectin, collagen I, collagen III, and α-SMA expression. Notably, LrB inhibited the expression of profibrotic plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-β1, TGF-β1R, and p-Smad2/3. Consistently, LrB inhibited the activation of TGF-β1/Smad signaling pathway and the expression of fibrosis-related proteins in angiotensin (Ang) II-treated cardiac fibroblasts (CFs). Overexpression of PAI-1 abolished the effects of LrB on Ang II-treated CFs, suggesting that LrB may function through regulating PAI-1. These results indicated that LrB may alleviate MI/R-induced myocardial fibrosis by inhibiting PAI-1/TGF-β1/Smad signaling pathway. Thus, LrB may be a potential drug in the treatment of MI/R injury. [ABSTRACT FROM AUTHOR]

External light-independent antitumor PDT is successfully realized with a covalent organic framework (COF)-based host–guest nanosystem. Its highly effective antitumor behavior is fully demonstrated by both H2O2-overexpressed 4T1 and H2O2-less expressed HCT116 and MCF-7 xenograft models. [ABSTRACT FROM AUTHOR]

The nesting activity of the Chinese softshell turtle (Pelodiscus sinensis) in its natural habitat is largely undocumented despite its broad geographical distribution across East Asia. Here, we report on female nesting behaviors, egg incubation, and hatchling emergence of P. sinensis on the Yellow River in northwestern China. In this region, the turtle is currently threatened by overharvesting, and successful conservation strategies should include strict monitoring of hunting and trade activities. [ABSTRACT FROM AUTHOR]

Background and Aim: This single‐arm, open‐label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis. Methods: Treatment‐naive or interferon‐experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12). Results: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post‐treatment course and 3 discontinued follow‐up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention. Conclusions: The all‐oral, ribavirin‐free regimen of seraprevir and sofosbuvir is an effective and well‐tolerated treatment option for Chinese patients mono‐infected with HCV, including those with a history of interferon treatment. [ABSTRACT FROM AUTHOR]

Since graph learning could preserve the structure information of the samples to improve the learning ability, it has been widely applied in both shallow learning and deep learning. However, the current graph learning methods still suffer from the issues such as outlier influence and model robustness. In this paper, we propose a new dynamic graph neural network (DGCN) method to conduct semi-supervised classification on multi-view data by jointly conducting the graph learning and the classification task in a unified framework. Specifically, our method investigates three strategies to improve the quality of the graph before feeding it into the GCN model: (i) employing robust statistics to consider the sample importance for reducing the outlier influence, i.e. assigning every sample with soft weights so that the important samples are with large weights and outliers are with small or even zero weights; (ii) learning the common representation across all views to improve the quality of the graph for every view; and (iii) learning the complementary information from all initial graphs on multi-view data to further improve the learning of the graph for every view. As a result, each of the strategies could improve the robustness of the DGCN model. Moreover, they are complementary for reducing outlier influence from different aspects, i.e. the sample importance reduces the weights of the outliers, both the common representation and the complementary information improve the quality of the graph for every view. Experimental result on real data sets demonstrates the effectiveness of our method, compared to the comparison methods, in terms of multi-class classification performance. [ABSTRACT FROM AUTHOR]

Background: Ischaemic preconditioning elicited by brief periods of coronary occlusion and reperfusion protects the heart from a subsequent prolonged ischaemic insult. Here, we test the hypothesis that short‐term non‐ischaemic stimulation of hypertrophy renders the heart resistant to subsequent ischaemic injury. Methods and Results: Transient transverse aortic constriction (TAC) was performed for 3 days in mice and then withdrawn for 4 days by aortic debanding, followed by subsequent exposure to myocardial ischaemia‐reperfusion (I/R) injury. Following I/R injury, myocardial infarct size and apoptosis were significantly decreased, and cardiac dysfunction was markedly improved in the TAC preconditioning group compared with the control group. Mechanistically, TAC preconditioning markedly suppressed I/R‐induced autophagy and preserved autophagic flux by deacetylating SOD2 via a SIRT3‐dependent mechanism. Moreover, treatment with an adenovirus encoding SIRT3 partially mimicked the effects of hypertrophic preconditioning, whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning. Furthermore, in vivo lentiviral‐mediated knockdown of Beclin 1 in the myocardium ameliorated the I/R‐induced impairment of autophagic flux and was associated with a reduction in cell death, whereas treatment with a lentivirus encoding Beclin 1 abolished the cardioprotective effect of TAC preconditioning. Conclusions: The present study identifies TAC preconditioning as a novel strategy for induction of an endogenous self‐defensive and cardioprotective mechanism against cardiac injury. Specifically, TAC preconditioning reduced myocardial autophagic cell death in a SIRT3/SOD2 pathway‐dependent manner. [ABSTRACT FROM AUTHOR]

[Display omitted] • A naphthalimide-based fluorescent probe for relay recognition of Cu2+ and S2− has been designed and synthesized. • The sensor has lower detection limit for Cu2+ and S2−. • Fluorescence behavior in the presence of Cu2+ and S2− could be manufactured to IMPLICATION type logic gate. • Intracellular fluorescence imaging in living cells were developed. A fluorescent chemosensor based on naphthalimide derivative (HL) was prepared and characterized. HL exhibited strong fluorescence emission at 528 nm, which was attributed to naphthalimide moiety, while the addition of Cu2+ almost completely quenched the fluorescence emission. However, with the addition of S2−, the fluorescence at 528 nm reoccurred remarkably. The detection limits for Cu2+ and S2− were measured to be 1.72 × 10−7 M and 2.66 × 10−7 M, respectively. As determined, the fluorescence behavior of HL in the presence of Cu2+ and S2− could be manufactured to IMPLICATION type logic gate. Moreover, confocal fluorescence imaging in HepG2 cells indicated that the HL could act as a useful fluorescent probe for intracellular Cu2+ and S2− detection with negligible cytotoxicity. [ABSTRACT FROM AUTHOR]

The protein shortage for the world's population in the near future has prompted scientists to develop novel methods for the sustainable production of dietary proteins from various alternative sources. In this study, the application of the bioseparation technique known as microwave-assisted three phase partitioning (MATPP) was explored to simultaneously extract and separate proteins from brewer's spent grain (BSG) after fungal fermentation. The results of the study indicated that MATPP (82.2%) recovered twice the amounts of proteins from fermented BSG compared to three phase partitioning (TPP) (41.8%). Besides, no significant differences (p > 0.05) were observed in terms of amino acid composition, protein pattern, and some functional properties between the fermented BSG proteins (FBPs) obtained via TPP and MATPP. Additionally, MATPP was found to increase the antioxidant activities of FBPs. These findings suggest that MATPP holds great potential for industrial-scale protein recovery attributed to its effectiveness, simplicity, and speed. Microwave-assisted three phase partitioning (MATPP) is an emerging bioseparation technique that could simultaneously extract, separate, and partially purify proteins from protein-rich plant materials effectively within a relatively short timeframe. The fact that the microwave used does not significantly alter most of the physicochemical properties of the plant protein hydrolysates certainly supports the adoption of the technique in industry settings. MATPP demonstrates significant potential for industrial-scale utilization due to its efficiency, simplicity and potential cost reduction in production. • TPP and MATPP were employed to extract proteins from BSG after fungal fermentation. • The protein yield doubled by using MATPP compared to TPP. • MATPP- and TPP-extracted protein hydrolysates showed no differences in most properties. • Higher antioxidant activities were exhibited by MATPP-extracted protein hydrolysates. • MATPP shows great promise for implementation in industrial settings. [ABSTRACT FROM AUTHOR]

In the present study, we explored the effects of seven light treatments (white, violet, blue, cyan, green, yellow, and red) on juvenile Sinonovacula constricta (length, 693.79 ± 82.91 μm), employing dark treatment as a control. A rearing experiment was conducted for one week in which the feeding rate was examined daily, e.g., one, two and three h after feeding. At the conclusion of the experiment, overall growth was calculated, and enzymatic activity related to digestion, superoxide dismutase, catalase, and glutathione peroxidase pertaining to antioxidant biomarkers, as well as expression levels of genes related to antioxidation and stress response, were examined. The results showed that the highest growth rates were observed in the yellow light group, while the lowest growth rates were found in the violet and blue light groups; on the other hand, no significant differences were found among the other groups. Meanwhile, when exposed to white, yellow, or green light, juveniles exhibited high feeding rates, while those in the violet and blue light groups showed low feeding rates. Regarding enzymatic activity related to digestion, those of α -amylase, lipase, pepsin, and trypsin were relatively higher in the yellow light group than in the other groups. Regarding oxidative stress, the yellow light group showed higher superoxide dismutase, catalase, and glutathione peroxidase activities than the other groups. In contrast, the lowest malonaldehyde level was found in the white light group, followed by yellow light, while there were no significant differences among the other groups. In addition, the expression levels of genes related to antioxidation and stress response (heat shock protein 70 and glucose-regulated protein 78) in juveniles generally exhibited higher levels in the red light group, whereas they showed relatively lower levels in the yellow light group. Collectively, these results suggest that the application of yellow light may facilitate the growth of juvenile S. constricta , while red and violet light have opposite effects. • Light spectrum differently influenced the growth of juvenile S. constricta. • Yellow light facilitated the growth of juvenile S. constricta. • Yellow light induced less stress to S. constricta. • Red and violet lights impaired the growth of juvenile S. constricta. [ABSTRACT FROM AUTHOR]

Sinonovacula constricta is an important bivalve with strong photosensitivity and a robust circadian rhythm. To elucidate the light entrainment of the molecular circadian clock in this species, this study identified the clock genes, characterized their tissue distribution, and investigated their transcriptional variations under different light regimes: LD (12 h light/12 h dark cycle), LL (continuous light), and DD (continuous dark). The results showed that the S. constricta clock system consists of seven genes [ Circadian locomotor output cycles kaput (ScClock), Brain and muscle ARNT-like protein (ScBmal), Cryptochrome (ScCry1 and 2), Period (ScPer), and Timeless (ScTimeless1 and 2)] that are closely related to their orthologs in marine mollusks and contained corresponding conserved functional regions, indicating the conserved evolution of the circadian clock among organisms. These genes were expressed in all tissues, with high expression in the labial palps and hepatopancreas, suggesting a complex peripheral biological clock in S. constricta and the critical role of these two tissues in circadian functions. When exposed to different light regimes in labial palps, genes from the positive loop (ScClock and ScBmal) displayed a daily/circadian rhythm under both LD and DD and their acrophases were shifted by 5–7 h, whereas genes from the negative loop displayed daily rhythms (ScCry1 and ScPer) under LD and circadian rhythms (ScCry2 and ScTimeless2) under DD. However, only one gene (ScTimeless2) displayed a circadian rhythm under LL conditions. These results suggest that the S. constricta circadian system may be regulated by different clock genes to adapt to various light environments. Although similar phenomena were observed in the hepatopancreas, markedly different clock gene expression patterns occurred between the two tissues, indicating a tissue-specific regulated circadian system. Collectively, this study reveals how the circadian oscillators of S. constricta respond to light and may promote light environment optimization in the S. constricta farming industry. • The molecular circadian clock was conserved in S. constricta. • A peripheral and tissue-specific clock might exist in S. constricta. • The S. constricta circadian clock was synchronized by photoperiod. • A functional clock exists in S. constricta. [ABSTRACT FROM AUTHOR]

A chemical kinetic model is developed to study the decomposition of tetraethoxysilane (TEOS) in O2/Ar atmospheric pressure dielectric barrier discharge and compared with gas chromatography and optical emission spectroscopy results. The calculations indicate that the excited Ar dominates the fragmentation of TEOS in the absence of oxygen and mainly breaks the carbon–carbon bonds in TEOS. However, in the presence of oxygen, the primary decomposition process of TEOS is the substitution of ethoxy (–OC2H5) by hydroxyl (–OH). The variation of these two reactions with oxygen composition could explain the transition of the deposition layer from organic to norganic. The model and its results provide a theoretical basis for further modeling and regulating the quality of the deposition layer. [ABSTRACT FROM AUTHOR]

Meleagrin and oxaline, which belong to the roquefortine alkaloids with a unique dihydroindole spiroamide framework, have significant bioactivities, especially tumor cell inhibitory activity. In order to discover the requefortine alkaloids, Penicillium sp. OUCMDZ-1435 was fished and identified from marine fungi using molecular probe technology. Meleagrin (1) and oxaline (2) were isolated from it. In addition, we first reported that compounds 1 and 2 could effectively inhibit the proliferation and metastasis of the human HepG2 cell and induce HepG2 cell apoptosis and cell cycle arrest in the G2/M phase. Additionally, the fermentation of Meleagrin (1) was optimized to increase its yield to 335 mg/L. These results provided bioactive inspiration and fungus resources for roquefortine alkaloid development. [ABSTRACT FROM AUTHOR]

The coincidence of hatching and emergence events with favorable conditions is crucial for turtle survival. Nocturnal emergence has been widely documented across marine and freshwater turtles, and has long been suggested as an adaptive behavior that reduces risks of heat stress and predation. To our knowledge, however, studies related to nocturnal emergence have mainly focused on the post‐hatching behaviors of turtles, and very few experimental studies have been performed to investigate the effects of hatching time on the distribution of emergence times over the course of a day. Here, we visually monitored the activity of the Chinese softshell turtle (Pelodiscus sinensis)—a shallow‐nesting freshwater turtle—from hatching to emergence. Our study provides evidence for the novel finding that (i) the timing of synchronous hatching events in P. sinensis coincides with the time of day when nest temperatures decrease, (ii) the synchrony between hatching and emergence may further facilitate their nocturnal emergence, and (iii) synchronous behaviors of hatchlings in the nest may be effective in reducing the risk of hatchling predation, and predation is more likely to occur in the asynchronous hatching groups. This study suggests that the hatching of shallow‐nesting P. sinensis in response to temperature changes in the nest might be an adaptive nocturnal emergence strategy. [ABSTRACT FROM AUTHOR]

In this paper, for an arbitrary Kac-Moody Lie algebra {\mathfrak g} and a diagram automorphism \mu of {\mathfrak g} satisfying certain natural linking conditions, we introduce and study a \mu-twisted quantum affinization algebra {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right) of {\mathfrak g}. When {\mathfrak g} is of finite type, {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right) is Drinfeld's current algebra realization of the twisted quantum affine algebra. When \mu =\mathrm {id} and {\mathfrak g} in affine type, {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right) is the quantum toroidal algebra introduced by Ginzburg, Kapranov and Vasserot. As the main results of this paper, we first prove a triangular decomposition for {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right). Second, we give a simple characterization of the affine quantum Serre relations on restricted {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right)-modules in terms of "normal order products". Third, we prove that the category of restricted {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right)-modules is a monoidal category and hence obtain a topological Hopf algebra structure on the "restricted completion" of {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right). Last, we study the classical limit of {\mathcal U}_\hbar \left (\hat {\mathfrak g}_\mu \right) and abridge it to the quantization theory of extended affine Lie algebras. In particular, based on a classification result of Allison-Berman-Pianzola, we obtain the \hbar-deformation of all nullity 2 extended affine Lie algebras. [ABSTRACT FROM AUTHOR]

Objective: Adenoidectomy is a surgical procedure most frequently performed by otolaryngologists. However, there are no universally accepted guidelines for the choice of the surgical approach in specific circumstances. Therefore, a network meta-analysis (NMA) is needed to summarize existing studies and provide more evidence-based medical guidelines. Methods: A systematic search of the literature was conducted in the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases from inception to 31 July 2021. A network meta-analysis of operating time, intraoperative blood loss, postoperative pain score, and incidence of postoperative residual tissue was performed. Results: A total of 20 studies with 2329 patients were included. Four common surgical approaches, including powered vacuum shaver adenoidectomy (PVSA), plasma field ablation adenoidectomy (PFAA), curettage adenoidectomy (CUA), and suction diathermy adenoidectomy (SDA), were compared for operative time, intraoperative blood loss, postoperative pain score, and incidence of postoperative residual tissue. There were no significant differences between the surgical techniques for the 3 endpoints, operative time, intraoperative blood loss, and incidence of postoperative residual tissue. The data showed lower postoperative pain scores for PFAA than for CUA (MD = −3.45, 95% CI [−6.01, −0.95]). There were no significant differences in other surgical approaches for postoperative pain scores. Conclusion: There were no significant differences between PVSA, PFAA, CUA, and SDA for operative time, intraoperative blood loss, and incidence of postoperative residual tissue. PFAA had advantages over CUA for postoperative pain scores. [ABSTRACT FROM AUTHOR]

Adenoid or adenotonsillar hypertrophy (AATH) adversely affects cardiovascular function, leading to pulmonary hypertension (PH). This meta-analysis of observational studies aimed to estimate the prevalence of PH in children with AATH. A meta-analysis was performed by searching the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases from their inception to 1 July 2021, for all studies that extracted data about PH prevalence in children with AATH. PH prevalence was calculated for each included study and as a pooled estimate with a 95% confidence interval. A total of eight studies were included in this analysis. The pooled prevalence of PH in children with AATH was 35.0% (95% CI [18.0%, 52.0%]). The subgroup analysis demonstrated that the prevalence of PH in children with adenotonsillar hypertrophy was higher than that with adenoid hypertrophy with or without tonsillar hypertrophy (39.0%, 95% CI [14.0%, 65.0%] vs. 22.0%, 95% CI [17.0%, 28.0%], respectively). The prevalence derived from the prospective and cross-sectional studies were 45.0% (95% CI [13.0%, 76.0%]) and 20.0% (95% CI [14.0%, 25.0%]), respectively. America and Africa had lower prevalence rates than Asia (24.0%, 95% CI [1.0%, 46.0%], 27.0%, 95% CI [17.0%, 38.0%], and 48.0%, 95% CI [-2.0%, 98.0%]), respectively. The prevalence of studies with diagnostic criterion (a mean pulmonary artery pressure higher than 20 mmHg) was 50.0% (95% CI [6.0%, 94.0%]). The pooled prevalence of studies with diagnostic criterion (a mean pulmonary artery pressure higher than 25 mmHg) was 25.0% (95% CI [13.0%, 36.0%]). The meta-analysis showed a prevalence of PH in children with AATH of 35.0%, demonstrating that this condition is a frequent complication of AATH. To better understand its clinical impact, more prospective evaluations are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR). Methods: A nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions. Results: The DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67–4.43)], Li [OR: 1.89 (1.06–3.42)], and Cs [OR: 1.97 (1.10–3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect. Conclusion: This study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Respiratory infectious viruses, including SARS‐CoV‐2, undergo rapid genetic evolution, resulting in diverse subtypes with complex mutations. Detecting and differentiating these subtypes pose significant challenges in respiratory virus surveillance. To address these challenges, we integrated ARMS‐PCR with molecular beacon probes, allowing selective amplification and discrimination of subtypes based on adjacent mutation sites. The method exhibited high specificity and sensitivity, detecting as low as 104 copies/mL via direct fluorescence analysis and ~106 copies/mL using real‐time PCR. Our robust detection approach offers a reliable and efficient solution for monitoring evolving respiratory infections, aiding early diagnosis and control measures. Further research could extend its application to other respiratory viruses and optimize its implementation in clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Adenoid or adenotonsillar hypertrophy (AATH) causes upper airway obstruction, leading to cardiovascular complications. This meta-analysis was conducted to evaluate the efficacy of adenoidectomy or adenotonsillectomy (AATE) on the cardiovascular system. Methods: Using the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases, we identified studies involving a comparison of preoperative and postoperative cardiovascular function in children with AATH. The Cochrane Collaboration's Review Manager 5.3 software was used for meta-analysis. Results: A total of 13 studies with 706 participants were included. The meta-analysis demonstrated a significant reduction in mean pulmonary artery pressure (mPAP) of patients after AATE compared with preoperative values. The left ventricular myocardial function index (LVMPI) and the right ventricular myocardial function index (RVMPI) showed a significant decrease after the operation. Moreover, AATE prominently increased left ventricular ejection time (LVET) and right ventricular ejection time (RVET) and reduced the left ventricular interventricular septum diameter (LVIVSD) and the right ventricular end-diastolic diameter (RVedD). There was no significant difference in mPAP, LVMPI, RVMPI, LVET, RVET, LVIVSD, and RVedD between postoperative patients and healthy children (P > 0.05). Conclusion: AATE can improve cardiovascular function in pediatric patients with AATH. Specifically, it reduces mPAP and LVMPI/RVMPI in pediatric patients. Furthermore, AATE increases LVET and RVET and reduces LVIVSD and RVedD. [ABSTRACT FROM AUTHOR]

Does blastocyst biopsy for preimplantation genetic testing (PGT) increase the risk of adverse maternal and neonatal outcomes? Retrospective cohort study of 5097 single vitrified–warmed blastocyst transfer cycles from January 2016 to December 2018, with 2061 cycles in the biopsied group and 3036 cycles in the unbiopsied group enrolled in the analyses. Maternal and neonatal outcomes were compared between the two groups. The live birth rate in the biopsied group (41.1%) was significantly higher than that in the unbiopsied group (35.6%, adjusted odds ratio [aOR] 1.27, 95% confidence interval [CI] 1.05–1.54, P = 0.012) after adjusting for maternal age, maternal body mass index, gravidity, parity, infertility diagnosis, timing of blastocyst transfer, blastocyst quality, regimen of endometrial preparation, endometrial thickness before transfer and treatment year. The rates of total pregnancy loss (25.4% versus 32.2%, aOR 0.69, 95% CI 0.52–0.91, P = 0.008) and early miscarriage (12.1% versus 17.3%, aOR 0.56, 95% CI 0.38–0.83, P = 0.004) were significantly lower in the biopsied group than in the unbiopsied group. No significant differences were found in sex ratio or the risks of hypertensive disorders in pregnancy, diabetes in pregnancy, placenta previa, preterm premature rupture of membranes, low birthweight, very low birthweight, macrosomia, small for gestational age, large for gestational age or birth defects between the two groups. When the subgroup analyses were conducted based on different types of PGT, similar patterns were found for all types. Blastocyst biopsy might not increase the risks of adverse maternal and neonatal outcomes in the short term. [ABSTRACT FROM AUTHOR]

Herin, we report a Cu(II)-porphyrin-derived nanoscale COF, which can be triggered by endogenous H2S via an intracellular sulfidation reaction to generate a metal-free COF-photosensitizer for PDT against H2S-enriched colon tumors with controllable singlet oxygen release; meanwhile in situ generated CuS can be synchronously used as a photothermal agent for PTT. [ABSTRACT FROM AUTHOR]

Sichuan taimen (Hucho bleekeri Salmonidae) populations are declining, and the status of remnant populations in the Qinling Mountains is poorly known. In this study, eDNA and creel netting were used to estimate the distributions of Sichuan taimen in two upper tributaries of the Hanjiang River. A qPCR assay was applied to detect the eDNA of H. bleekeri, and the presence of Sichuan taimen in the Taibai River, but not in the Xushui River, was confirmed. Sampling during summer achieved a relatively higher detection rate. The utility of eDNA techniques for detecting low-density Sichuan taimen was demonstrated in intricate stream ecosystems. The eDNA method can increase the efficiency of the management of endangered freshwater species, such as Sichuan taimen, by providing reliable distribution data. [ABSTRACT FROM AUTHOR]

Engineering light-controlled K+ pumps from Na+-pumping rhodopsins (NaR) greatly expands the scope of optogenetic applications. However, the limited knowledge regarding the kinetic and selective mechanism of K+ uptake has significantly impeded the modification and design of light-controlled K+ pumps, as well as their practical applications in various fields, including neuroscience. In this study, we presented K+-dependent photocycle kinetics and photocurrent of a light-driven Na+ pump called Nonlabens dokdonensis rhodopsin 2 (NdR2). As the concentration of K+ increased, we observed the accelerated decay of M intermediate in the wild type (WT) through flash photolysis. In 100 mM KCl, the lifetime of the M decay was approximately 1.0 s, which shortened to around 0.6 s in 1 M KCl. Additionally, the K+-dependent M decay kinetics were also observed in the G263W/N61P mutant, which transports K+. In 100 mM KCl, the lifetime of the M decay was approximately 2.5 s, which shortened to around 0.2 s in 1 M KCl. According to the competitive model, in high KCl, K+ may be taken up from the cytoplasmic surface, competing with Na+ or H+ during M decay. This was further confirmed by the K+-dependent photocurrent of WT liposome. As the concentration of K+ increased to 500 mM, the amplitude of peak current significantly dropped to approximately ~60%. Titration experiments revealed that the ratio of the rate constant of H+ uptake (kH) to that of K+ uptake (kK) is >108. Compared to the WT, the G263W/N61P mutant exhibited a decrease of approximately 40-fold in kH/kK. Previous studies focused on transforming NaR into K+ pumps have primarily targeted the intracellular ion uptake region of Krokinobacter eikastus rhodopsin 2 (KR2) to enhance K+ uptake. However, our results demonstrate that the naturally occurring WT NdR2 is capable of intracellular K+ uptake without requiring structural modifications on the intracellular region. This discovery provides diverse options for future K+ pump designs. Furthermore, we propose a novel photocurrent-based approach to evaluate K+ uptake, which can serve as a reference for similar studies on other ion pumps. In conclusion, our research not only provides new insights into the mechanism of K+ uptake but also offers a valuable point of reference for the development of optogenetic tools and other applications in this field. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) techniques have emerged as a cost-effective and non-invasive strategy for monitoring the distribution of endangered aquatic species. Despite their numerous advantages, operational uncertainty at each step of the process represents a significant challenge that can impact the reliability of results. Hence, the optimization of the eDNA analytic protocol is of utmost importance. In this study, the rare and endangered fish species Sichuan taimen was chosen as the target species to evaluate the concordance between different approaches (tissue, pond, and field water samples) for eDNA detection. The results showed that membrane filtration, collection of a 2-L water sample, and utilization of the DNeasy Tissue and Blood DNA extraction kit were suitable for the analysis of DNA in water samples. Furthermore, the mtDNA D-loop region demonstrated potential as a specific molecular marker for the precise identification of Sichuan taimen. Our results indicated that TaqMan fluorescence PCR can serve as the optimal detection method for reliable identification of target DNA even at extremely low concentrations in the field. This study established an optimized eDNA analysis protocol for Sichuan taimen detection, which will provide the basis for future resource investigations aimed at protection of this endangered aquatic species. [ABSTRACT FROM AUTHOR]

Sustained retina drug delivery and rational drug combination are considered essential for enhancing the efficacy of therapy for wet age-related macular degeneration (wAMD) due to the conservative structure of the posterior ocular segment and the multi-factorial pathological mechanism. Designing a drug co-delivery system that can simultaneously achieve deep penetration and long-lasting retention in the vitreous is highly desired, yet remains a huge challenge. In this study, we fabricated Bor/RB-M@TRG as an intravitreal-injectable hydrogel depot for deep penetration into the posterior ocular segment and long-lasting distribution in the retinal pigment epithelium (RPE) layer. The Bor/RB-M@TRG consisted of borneol-decorated rhein and baicalein-coloaded microemulsions (Bor/RB-M, the therapy entity) and a temperature-responsive hydrogel matrix (the intravitreal depot). Bor/RB-M exhibited the strongest in vitro anti-angiogenic effects among all the groups studied, which is potentially associated with improved cellular uptake, as well as the synergism of rhein and baicalein, acting via anti-angiogenic and anti-oxidative stress pathways, respectively. Importantly, a single intravitreal (IVT) injection with Bor/RB-M@TRG displayed significant inhibition against the CNV of wAMD model mice, compared to all other groups. Particularly, coumarin-6-labeled Bor/RB-M@TRG (Bor/C6-M@TRG) could not only deeply penetrate into the retina but also stably accumulate in the RPE layer for at least 14 days. Our design integrates the advantages of borneol-decorated microemulsions and hydrogel depots, offering a promising new approach for clinically-translatable retinal drug delivery and synergistic anti-wAMD treatment. [ABSTRACT FROM AUTHOR]

Glioma treatment remains a challenge owing to unsatisfactory targeted chemotherapy, where the blood–brain barrier (BBB) hinders the efficient uptake of therapeutics into the brain. Vasculogenic mimicry (VM) formed by invasive glioma cells negatively affects the treatment of glioma. Herein, we developed a targeted biomimetic drug delivery system comprising a doxorubicin-loaded platelet membrane-coated nanogel (DOX@PNGs). The nanogels provide great redox/pH dual responsiveness, while the platelet membrane (PLTM) promotes stability and circulation time. In vitro cellular uptake and in vivo imaging experiments demonstrated that the DOX@PNGs delivery system could penetrate the BBB, target gliomas, and destruct VM. DOX@PNGs increased drug penetration and prolonged mouse survival time during the treatment of orthotopic gliomas. These results indicate this biomimetic drug delivery system to be promising for glioma treatment and may be clinically translated in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • HL-Cys showed red-emission fluorescence and its Stokes shift was more than 100 nm. • HL-Cys with hypotoxicity and low detection limit (0.58 µM) was successfully used to the imaging of Cys in vitro and in vivo. In this work, a novel red-emission fluorescent probe (HL-Cys) based on benzothiazole moiety was designed and synthesized for the detection of cysteine (Cys). HL-Cys could display specific fluorescence response toward Cys over other analytes including amino acids and GSH at 620 nm (E x = 513 nm) because of the Michael addition reaction between Cys and HL-Cys, leading to the cleavage of acryloyl group from the parent ligand (HL). Moreover, HL-Cys with hypotoxicity and low detection limit was successfully used to the imaging of Cys in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The Chinese giant salamander (Andrias davidianus) is the biggest extant and endangered amphibian, which has an incongruous sex ratio during the artificial breeding process and is sex indistinguishable in appearance. The sex development mechanism of this rare species thus needs to be explored. We therefore conducted this study to explore the molecular mechanisms of sex hallmarks or gonad maintenance genes for CGS. In this study, we sequenced and analyzed the sexually mature male and female gonads of Chinese giant salamanders (CGSs) using RNA-seq technology and found a total of 15,063 differentially expressed genes (DEGs) in the testicular and ovarian tissues, of which 7973 (52.93%) were expressed in testicular and 7090 (47.07%) in ovarian tissues. Thirteen gonad DEGs were selected based on gene expression abundance and quantified in the muscle and skin tissues of both male and female CGSs. The results showed that these 13 DEGS, out of the 20 analyzed DEGs, were expressed in both the muscle and skin tissues and only two of them (Bmp15 and ZP3) were consistent in the muscle and skin compared to the gonads of CGSs of the two sexes. Overall, our study should provide an important reference for the sex-characteristics-related genes in this type of species, shedding new light on future research on this topic. [ABSTRACT FROM AUTHOR]

The probe plays a pivotal role in the early diagnosis of tumor, especially tumor microenvironment (TME)-responsive probe, which could exploit differences between tumor and normal tissue to achieve better signal-to-noise ratio. In view of overexpressed glutathione (GSH) in microenvironment considered as one of the important characteristics of tumor distinct from normal tissue, we constructed a GSH activated near-infrared fluorescent (NIRF) and photoacoustic (PA) dual-modal probe (Probe-GSH) based on the hybrid of xanthene-based hemicyanines and dicyanoisophorone. The activated Probe-GSH could exhibit 8-fold PA signal/10-fold NIRF intensity enhancement. Besides, compared with the existing xanthene-based hemicyanines (XBH), Probe-GSH possessed longer absorbance/emission wavelength and larger Stokes shift. More importantly, Probe-GSH has been successfully applied to the image of 4T1-bearing tumor mice under NIRF and PA dual modality. [Display omitted] • Compared with the reported xanthene-based hemicyanines, Probe-GSH possess longer the absorbance/ emission wavelength. • Compared with the reported xanthene-based hemicyanines, Probe-GSH has larger Stokes shift. • Probe-GSH was capable for imaging of tumor mouse under NIRF and PA dual modality image. [ABSTRACT FROM AUTHOR]

Herein, all-trans retinoic acid-Hyaluronic acid prodrug nanoparticles (HA-ATRA NPs) were successfully prepared for improving the anti-psoriatic effect of ATRA. The HA-ATRA NPs were 146.7 ± 8.2 nm with a critical aggregation concentration of 92.6 µg/mL and a drug loading content of 8.3 %. Topically applied HA-ATRA NPs remarkably reduced the characteristic symptoms of psoriasis in imiquimod (IMQ)-induced psoriasis-like mice, including thickness of stratum corneum, epidermis hyperkeratosis, parakeratosis, and epidermal infiltrates induced by IMQ compared with ATRA. In addition, HA-ATRA NPs dramatically reduced the expressions of key inflammatory cytokines in psoriasis lesions without influence on the body weight of mice. • HA-ATRA prodrug nanoparticles were successfully prepared. • HA-ATRA NPs improved the anti-psoriatic effect of ATRA topically. • HA-ATRA NPs dramatically reduced application site inflammation. [ABSTRACT FROM AUTHOR]

The associations between metallic elements and ovarian reserve function have remained uncertain yet. In this case-control study, we involved 149 women with diminished ovarian reserve (DOR) and 151 women with normal ovarian reserve, and assessed the levels of six heavy metallic (Cr, Cd, As, Hg, Pb, and Mn) and seven trace essential (Se, Fe, Zn, Co, Mo, Cu, I) elements in their follicular fluid with inductively coupled plasma mass spectrometry. Associations were examined with logistic regressions and Bayesian kernel machine regression (BKMR). As a result, we found that the medium and the highest tertiles of Pb were significantly associated with an increased likelihood of DOR compared to the lowest tertile, while the medium or/an the highest tertiles of Cu, I, and Fe showed significantly lower likelihoods of DOR compared to the lowest tertiles. Cu and Pb showed significantly non-linear associations with ovarian reserve markers such as follicle-stimulating, anti-mullerian hormone levels, and antral follicle count. With the rising overall concentrations of heavy metals, the likelihood of DOR increased although not significant. There was a trend of a "U-shaped" association across the whole concentration range of trace essential elements and the likelihood of DOR. Our study revealed that avoiding heavy metallic elements and properly supplementing trace essential elements are conducive to ovarian function. [Display omitted] • Mixture of heavy metals are associated with higher likelihood of DOR. • Mixture of essential elements showed a "U-shaped" association with DOR. • Pb plays the most important toxic role in the heavy metals. • Highest tertiles of Cu, I, and Fe had lower odds of DOR than the lowest tertiles. [ABSTRACT FROM AUTHOR]

[Display omitted] • The excitation /emission wavelength of NIR dicyano-based fluorophoreare more than 650 nm. • The stokes shift of the NIR dicyano-based fluorophore is more than 100 nm. • Probe-Cys was used to visualize Cys in PC3 cells and PC3-xenograft tumor mice. • Probe-H 2 S has been applied in monitoring H 2 S releasing from the prodrug in vitro and in vivo. Near-infrared (NIR) fluorophores, especially dicyano-based fluorophores and xanthene-based hemicyanines, have been put high expectation in bioimaging application due to their excellent optical properties. However, they suffer from inherent shortages such as short excitation/emission wavelength (less than 700 nm) or small Stokes shift (20–50 nm). Herein, we constructed a novel NIR dicyano-based fluorophore (DCO-HBTN). To our knowledge, it is the first reported dicyano-based fluorophore of which the excitation/emission wavelength is more than 650 nm and Stokes shift is more than 100 nm. To demonstrate the feasibility of our efforts, we developed two NIR fluorescent probes (Probe-Cys and Probe-H 2 S) based on the fluorophore, Probe-Cys displayed good selective and highly sensitive (LOD = 0.28 μM) recognition of Cys over Hcy and GSH, which was used to visualize endogenous Cys in tumor tissue. Probe-H 2 S exhibited an. excellent specific and sensitive (LOD = 0.11 μM) response to H 2 S, which was applied in monitoring H 2 S releasing from the prodrug in vitro and in vivo. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to explore the optimal light intensity for the breeding of Sinonovacula constricta , and the effect of light intensity on the growth of S. constricta at different developmental stages was studied. Four developmental stages (spawning, fertilized eggs, planktonic larvae, and juveniles) and different light intensities were set up in our current experiments. The results showed that various light intensities had significantly different effects on spawning amount and initial spawning time, while it had little influence on the hatchability of fertilized eggs (P > 0.05). The spawning amount of the razor clam peaked at a light intensity of 44–250 lx (P < 0.05). In the planktonic larvae experiment, the highest survival rate appeared at 487 ± 31 lx (58.61 ± 4.0%).For juvenile S. constricta , two substratum thicknesses (1 and 5 mm) and four light intensities, including L 1 (14 ± 11 lx), L 2 (380 ± 145 lx), L 3 (3792 ± 2105 lx), and L 4 (12,244 ± 5290 lx), were set up in a 10-day experiment. When the substratum thickness of 1 mm was applied, the body length and survival rate of S. constricta juveniles (0.26 ± 0.02 mm) in the L 2 group were found to be the largest, which were significantly different compared with the other groups. When the substratum thickness was changed to 5 mm, the body length and survival rate among those groups showed no significant difference. However, when the shellfish samples were changed to a larger size of razor clam (1.45 ± 0.16 mm), a more obvious effect of light intensity on the growth was observed in a 1-mm substratum group compared with the 5-mm group. These results indicated that light intensity exerted a significant effect on the growth of S. constricta at different stages, and each stage exhibited a distinct sensitivity to light intensity. Further study from the aspects of photoreceptors and relevant genes is currently in progress in our laboratory. • Spawning, hatching and growth of S. constricta were affected by light intensity. • All developmental stages of S. constricta were photosensitive, except zygote. • Optimal light intensity is critical for S. constricta breeding and farming. [ABSTRACT FROM AUTHOR]

The targeted delivery of drugs to tumor cells and prevention of premature release before reaching the target is one of the key challenges to developing nanomedicines. In this paper, galactose decorated trimethyl chitosan (GT)–camptothecin (CPT) prodrug nanoparticles (GT-ss-CPT NPs) were prepared from GT-CPT conjugates linked by dithiodipropionic acid. The obtained GT-ss-CPT NPs were spherical with a particle size of 184.1 nm. GT-ss-CPT NPs displayed low drug release under physiological conditions, whereas efficient drug release was triggered by high GSH concentration. GT-ss-CPT NPs exhibited a higher antitumor effect both in vitro and in vivo than the free drug counterpart. More importantly, GT-ss-CPT NPs reduced the high systematic toxicity of CPT to tumor-bearing mice. In summary, GT-ss-CPT NPs can not only inhibit the premature release of CPT but also have a great potential for targeted hepatocellular carcinoma chemotherapy. [ABSTRACT FROM AUTHOR]