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SIRT6, a member of the sirtuin protein family, is recognized as a tumor suppressor. This study investigates the evolutionary history of the SIRT gene family and examines the selective pressures shaping their functional divergence. Insights into the evolution of these genes may enhance our understanding of their roles in disease pathology. Seventy-three amino acid sequences and full-length mRNA sequences from 22 vertebrate species and one invertebrate were retrieved from public databases. Phylogenetic relationships among the seven SIRT gene family members were reconstructed using Bayesian inference. Codon-based models were applied to detect site-specific positive selection, and likelihood ratio tests (LRTs) were used to compare model fits. Positively selected sites were identified using Bayesian empirical Bayes (BEB) methods. Phylogenetic analysis revealed that the seven SIRT gene family members in vertebrates originated from gene duplication events. Asymmetric evolutionary rates and natural selection were identified as the primary drivers of SIRT gene divergence. Eleven positively selected sites (23I, 310 S, 311I, 313 A, 316 K, 320 C, 321 A, 322Q, 323 H, 327E, 328P) were identified with high confidence (posterior probability ≥ 99%), suggesting critical roles in functional divergence. The evolution of the SIRT gene family is characterized by gene duplication and natural selection. The reconstructed phylogenetic tree elucidates the relationships among the seven members, with SIRT6 emerging as a key evolutionary node. Positively selected sites identified in this study may represent mutation hotspots, providing potential targets for future cancer therapy research. [ABSTRACT FROM AUTHOR]

Nonlinear Raman-Nath diffraction (NRND) is a unique diffraction pattern formed when a high-intensity laser interacts with a nonlinear microstructure bulky medium relying only on the transverse phase matching condition. Here, we report on the first experimental observation of NRND in a submicron-thick periodically poled lithium niobate thin film (PPLNTF) by geometric reflection pumped via a near-infrared femtosecond pulse laser. We further observe the evolution of the diffracted signals after broadening of the pump laser via a fused silica plate. We systematically analyze the spectral properties of multi-order second harmonic generation (SHG) diffracted signals exhibiting asymmetric distributions and explicitly clarify their phase matching conditions, simultaneously considering the impacts of the incident pump wavelength, the sample poling period, and the incident angle on the properties of the angular distribution diffracted beams. The realization of NRND phenomena with appreciable on-chip efficiency at a submicron interaction length is mainly attributed to the significant contribution of domain walls to enhance the nonlinear effects along with the modulation of second-order nonlinear susceptibilities χ (2) . This NRND scheme provides a high-resolution, non-destructive on-chip microstructure diagnostic method, and even has the potential to develop novel on-chip integrated optoelectronic devices for applications such as precision metrology, biosensing, and spectral analysis. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular disease (CVD) represents the primary cause of mortality in patients afflicted with end-stage renal disease and undergoing peritoneal dialysis (PD) treatment. Galectin-3 (Gal-3), a molecule known to exhibit a correlation with CVD mortality garners considerable interest. The objective of this study was to explore the potential association between serum Gal-3 levels and other CVD risk factors among PD patients. Methods: In this cross-sectional study, a total of 114 PD patients with a minimum of 3 months of PD treatment were enrolled. Serum Gal-3 levels were quantified using an enzyme-linked immunosorbent assay. The data of patients with Gal-3 levels higher and lower than 26.744 pg/ml were compared using Mann–Whitney U tests or t tests. Pearson's correlation or Spearman's correlation analysis and multivariate regression were used to assess the associations between the known risk factors for CVD and Gal-3. Results: In comparison to the inter-group baseline data, the low Gal-3 group exhibited a higher glomerular filtration rate (GFR). Gal-3 levels correlate positively with PD duration, B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15), interventricular septal thickness in diastolic (IVST), and left ventricular mass index (LVMI). Conversely, Gal-3 exhibited a negative correlation with albumin levels. Multivariate linear regression analysis demonstrated a positive correlation between Gal-3 levels and BNP, GDF-15, PD duration, IVST and LVMI. Gal-3 levels were negatively correlated with albumin levels. Conclusions: Gal-3 was strongly associated with BNP, GDF-15, IVST and LVMI in patients undergoing PD treatment. Prospective studies should be carried out to determine whether Gal-3 can be a promising biomarker in predicting increased risk of adverse cardiovascular events in PD patients. [ABSTRACT FROM AUTHOR]

This paper proposes a novel estimator for support vector machines with matrix-valued covariates in a high-dimensional setting. We assume that the underlying parameter matrix lies in a low-dimensional subspace that is simultaneously low-rank and row (column) sparse. We formulate the problem as a regularized hinge loss minimization problem using the nuclear and group lasso norms as penalties to exploit the low-dimensional structure. Our primary focus is deriving the statistical convergence rate of the regularized estimator for the unknown parameter matrix. To validate our theoretical findings, we conducted numerical experiments on both simulated and real-world datasets, demonstrating the efficacy of the regularized support matrix machines framework. [ABSTRACT FROM AUTHOR]

With climate change and anthropic influence on the coastal ecosystems, mangrove ecosystems are disappearing at an alarming rate. Accordingly, it becomes important to track, study, record and store the mangrove microbial community considering their ecological importance and potential for biotechnological applications. Here, we provide information on mangrove fungal community composition and diversity in mangrove ecosystems with different plant species and from various locations differing in relation to anthropic influences. We describe twelve newly assembled genomes, including four chromosomal-level genomes of fungal isolates from the mangrove ecosystems coupled with functional annotations. We envisage that these data will be of value for future studies including comparative genome analysis and large-scale temporal and/or spatial research to elucidate the potential mechanisms by which mangrove fungal communities assemble and evolve. We further anticipate that the genomes represent valuable resources for bioprospecting related to industrial or clinical uses. [ABSTRACT FROM AUTHOR]

Since the identification of microRNAs (miRNAs), empirical research has demonstrated their crucial involvement in the functioning of organisms. Investigating miRNAs significantly bolsters efforts related to averting, diagnosing, and treating intricate human maladies. Yet, exploring every conceivable miRNA–disease association consumes significant resources and time within conventional wet experiments. On the computational front, forecasting potential miRNA–disease connections serves as a valuable source of preliminary insights for medical investigators. As a result, we have developed a novel matrix factorization model known as Hessian-regularized L 2 , 1 nonnegative matrix factorization in combination with deep learning for predicting associations between miRNAs and diseases, denoted as H R L 2 , 1 -NMF-DF. In particular, we introduce a novel iterative fusion approach to integrate all similarities. This method effectively diminishes the sparsity of the initial miRNA–disease associations matrix. Additionally, we devise a mixed model framework that utilizes deep learning, matrix decomposition, and singular value decomposition to capture and depict the intricate nonlinear features of miRNA and disease. The prediction performance of the six matrix factorization methods is improved by comparison and analysis, similarity matrix fusion, data preprocessing, and parameter adjustment. The AUC and AUPR obtained by the new matrix factorization model under fivefold cross validation are comparative or better with other matrix factorization models. Finally, we select three diseases including lung tumor, bladder tumor and breast tumor for case analysis, and further extend the matrix factorization model based on deep learning. The results show that the hybrid algorithm combining matrix factorization with deep learning proposed in this paper can predict miRNAs related to different diseases with high accuracy. [ABSTRACT FROM AUTHOR]

Pyroptosis is a novel type of cell death observed in various diseases. Our study aimed to investigate the relationship between pyroptosis-associated-long non-coding RNAs (lncRNAs), immune infiltration, and expression of immune checkpoints in the setting of lung adenocarcinoma and the prognostic value of pyroptosis-related lncRNAs. RNA-seq transcriptome data and clinical information from The Cancer Genome Atlas (TCGA) were downloaded, and consensus clustering analysis was used to separate the samples into two groups. Least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature. The association between pyroptosis-associated lncRNAs, immune infiltration, and expression of immune checkpoints were analysed. The cBioPortal tool was used to discover genomic alterations. Gene set enrichment analysis (GSEA) was utilized to investigate downstream pathways of the two clusters. Drug sensitivity was also examined. A total of 43 DEGs and 3643 differentially expressed lncRNAs were identified between 497 lung adenocarcinoma tissues and 54 normal samples. A signature consisting of 11 pyroptosis-related lncRNAs was established as prognostic for overall survival. Patients in the low-risk group have a significant overall survival advantage over those in the high-risk group in the training group. Immune checkpoints were expressed differently between the two risk groups. Risk scores were validated to develop an independent prognostic model based on multivariate Cox regression analysis. The area under time-dependent receiver operating characteristic curve (AUC of the ROC) at 1-, 3-, and 5-years measured0.778, 0.757, and 0.735, respectively. The high-risk group was more sensitive to chemotherapeutic drugs than the low-risk group. This study demonstrates the association between pyroptosis-associated lncRNAs and prognosis in lung adenocarcinoma and enables a robust predictive signature of 11 lncRNAs to inform overall survival. [ABSTRACT FROM AUTHOR]

In applications involving, e.g., panel data, images, genomics microarrays, etc., trace regression models are useful tools. To address the high-dimensional issue of these applications, it is common to assume some sparsity property. For the case of the parameter matrix being simultaneously low rank and elements-wise sparse, we estimate the parameter matrix through the least-squares approach with the composite penalty combining the nuclear norm and the l1 norm. We extend the existing analysis of the low-rank trace regression with i.i.d. errors to exponential β-mixing errors. The explicit convergence rate and the asymptotic properties of the proposed estimator are established. Simulations, as well as a real data application, are also carried out for illustration. [ABSTRACT FROM AUTHOR]

In this paper, a new reverse half-discrete Mulholland-type inequality with the nonhomogeneous kernel of the form h (v (x) ln n) and the best possible constant factor is obtained by using the weight functions and the technique of real analysis. The equivalent reverses are considered. As corollaries, we deduce some new equivalent reverse inequalities with the homogeneous kernel of the form k λ (v (x) , ln n) . A few particular cases are provided. Our new reverse half-discrete Mulholland-type inequality which has a nonhomogeneous kernel is more general than in the previous homogeneous kernel work. The harmonized integration will have more applications. [ABSTRACT FROM AUTHOR]

In flash flood events, predicting the impact loads of rushing water is helpful to detect the possible and direct damage to the downstream structures. The present study conducted three-dimensional numerical simulations for three typical laboratory experiments with emphasis on the hydrodynamic impact. Two RANS-based k-ε models and the LES model were chosen for the turbulence closure. The VOF method was applied to track the free surface. The numerical model provided satisfactory results of the temporal variations of both water depth and hydrodynamic load, which are in great agreement with the experimental data. Further quantitative comparisons also show that the deviations between simulations and experiments are small. The values of performance indicators mean-absolute deviation (MAD), root-mean-squared deviation (RMSD) and mean-absolute percentage deviation (MAPD) are respectively lower than 0.05 (0.03 m), 0.08 (0.048 m) and 19% for depth prediction, lower than 0.05 (0.03 kPa), 0.11 (0.06 kPa) and 11% for pressure prediction, and lower than 0.7 N, 1N and 15% for net force prediction. The absolute values of relative percent deviation (RPD) are less than 27% and 25% for the prediction of peak pressure and peak net force, respectively. The values of Nash–Sutcliffe efficiency (NSE) for depth and pressure are higher than 0.8. Moreover, the impulse of pressure or net force exhibits better predictability than its instantaneous values. Additional investigation shows that the time-varying behaviour of the impact force are significantly affected by the upstream initial depth, and the maximum impact force has a quadratic relationship with the initial depth. [ABSTRACT FROM AUTHOR]

Although relevant literature investigates the economic value of online sales channel (OSC) from the perspective of the stock market, knowledge on this topic remains insufficient or unclear because existing studies are conducted under an extremely turbulent market environment and have not considered different aspects. This study aims to examine the topic by focusing on the market reactions to OSC investment from three aspects (namely, the innovativeness, business model and goods types) in a relatively stable market environment to fill in the research gap. Empirical results, obtained using 69 firm-level OSC announcements from October 2002 to September 2007, show that the stock market reacts positively to OSC investment by firms. Additionally, the stock market reactions to OSC investment mainly depend on two key characteristics, namely investment innovativeness and business model applied. [ABSTRACT FROM AUTHOR]

Soil salinization–alkalization is a major hindrance to agricultural development globally. Tea crabapple is widely used in China. However, little remains known regarding the molecular mechanisms used to withstand mixed saline–alkali stress (MSAS). Herein, we exposed tea crabapple seedlings to MSAS, and RNA-seq was performed for the transcriptome analysis of roots. Between 43.26 million and 43.37 million clean reads were thus obtained. In comparison with the control group (day 0), 2931, 2335, and 3746 genes were differentially expressed at day 1, day 3, and day 6 of MSAS exposure, respectively, and 1022 genes were common in the three comparison groups. On functional annotation, we observed that numerous differentially expressed genes were involved in "global and overview maps"; "carbohydrate metabolism"; "folding, sorting, and degradation"; "biosynthesis of other secondary metabolites"; "environmental adaptation"; and "signal transduction." Heat shock proteins, cytochrome P450s, disease-resistant proteins, non-specific lipid-transfer proteins, pectate lyase, and beta-glucosidases were also induced in response to MSAS, in addition to nitrogen, phosphorus, and potassium absorption and metabolism-related genes. Transcription factor-coding genes appear to regulate the response of tea crabapple roots to MSAS by participating in, for example, plant hormone signal transduction and heat shock response. We also performed quantitative real-time PCR to validate the expression of six differentially expressed genes. Our findings provide new insights into the molecular mechanisms used by tea crabapple to cope with MSAS. [ABSTRACT FROM AUTHOR]

Background: Anti-angiogenic drugs increase anti-tumor efficacy of immune checkpoint inhibitors (ICIs). However, the optimal dose of anti-angiogenic drugs remains unclear. Methods: We retrospectively analyzed efficacy and safety data from patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) that received PD-1 blockade with low-doses of anlotinib, a highly selective receptor tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptors, as second or later line therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety profile. Univariate and multivariate analyses were used to identify prognostic factors. Results: A total of 40 eligible patients were included. The median PFS was 11.4 months. The median OS of the entire cohort was 27.0 months. ORR was achieved in 16 patients (40.0%) and DCR was maintained in 33 patients (82.5%). The overall incidence of adverse events (AEs) was 52.5%, and the most common all grade AE was gastrointestinal reactions, which occurred in four patients (10.0%). Treatment-related grade 3/4 toxicity was observed in one patient (2.5%). Conclusions Low-dose anlotinib may be an effective and well-tolerated anti-angiogenesis partner for combination therapy with ICIs in second-line and later settings for advanced NSCLC. [ABSTRACT FROM AUTHOR]

This paper investigates the Lasso method for sparse linear models with exponential φ -mixing errors under a fixed design, where the number of covariates p is large, or even much larger than the sample size n. The non-asymptotic concentration inequalities for the estimation and prediction errors of the Lasso estimators are given when the errors follow the Gaussian distribution and the sub-exponential distribution, respectively. The prediction and variable selection performance of Lasso estimators are further illustrated through numerical simulations. Finally, the results of the empirical application show that the Index Tracking Fund based on the sparse selection of Lasso can closely track the trend of the target index, and thus provide some useful guidance for the investors. [ABSTRACT FROM AUTHOR]

Saline–alkali stress is a universal abiotic stress factor limiting fruit tree cultivation worldwide. Apple (Malus×domestica Borkh.) is one of the fruits with the largest yields worldwide. Tea crabapple (Malus hupehensis Rehd. var. pingyiensis Jiang) is a type of common apple rootstock in China. Because facultative apomixis occurs in this species, it is often used in molecular research. The present study investigated the molecular mechanism of the response of indoleacetic acid (IAA) and cytokinins [zeatin, trans-zeatin riboside (tZR), isopentenyladenine (iP), and isopentenyladenosine (iPA)] to mixed saline–alkali stress (MSAS) in tea crabapple leaves. The endogenous hormone content of tea crabapple leaves under MSAS was measured, and the expression of stress response-related genes was analyzed by RNA sequencing. The results showed that the concentration of IAA was initially higher and then lower than that in the control, whereas the concentration of zeatin, tZR, iP, and iPA was higher than that in the control. A total of 1262 differentially expressed genes were identified in the three comparison groups. Further analyses suggested that IAA and cytokinin biosynthetic genes were mostly upregulated in tea crabapple leaves, indicating that auxin and cytokinin signaling pathway regulation occurred in response to MSAS. These findings suggest that IAA and cytokinins play an important role in the response of tea crabapple to MSAS. [ABSTRACT FROM AUTHOR]

Effects of environmental tobacco smoke (ETS) exposure on children and adolescent health outcomes have been attracted more and more attention. In the present study, we seek to examine the gender-specific difference association of environmental smoke exposure biomarkers and developmental disorders in children and adolescents aged 6–15 years. US nationally representative sample collected from the National Health and Nutrition Examination Survey (NHANES) 2007–2014 was enrolled (N = 4428). Developmental disorders (DDs) are defined as a positive answer to the question, "Does your child receive special education or early intervention services?" Serum cotinine and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were utilized as acute and chronic exposure biomarkers of ETS, respectively. Participants with serum cotinine >0.015 ng/mL were considered as with acute ETS exposure, and participants with creatinine-adjusted NNAL >0.0006 ng/mL were considered as with chronic ETS exposure. A survey logistic regression model was used to estimate the association between ETS exposure biomarkers and DDs. Additive interaction was utilized to examine the interaction of gender and biomarkers of ETS. Overall, approximately 9% of children were defined as DDs, and 65% of children had serum cotinine and urinary NNAL levels above the limit of detection. In the adjusted models, the association of ETS exposure biomarkers with DDs was only observed in girls. Girls with low cotinine levels and high urinary NNAL levels had 2.074 (95% CI: 1.012–4.247) and 1.851 (95% CI: 1.049–3.265) times higher odds of being DDs than those without ETS exposure, respectively. However, the effects of boys and NNAL exposure on DDs have additively interacted. Our findings first provided strong evidence for gender differences in the association between two tobacco metabolites and DDs in children, disclosing the public health implications and economic burdens of environmental tobacco smoke exposure. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is one of the aggressive malignant tumors with high mortality, and the proliferation of myeloid-derived suppressor cells (MDSCs) could promote the metastasis of NPC through inhibiting the function of T cells. Meanwhile, SPLUNC1 was known to inhibit the malignant behavior of NPC cells, while the detailed function of SPLUNC1 in LPS-modified immune microenvironment of NPC remains unclear. To assess the impact of SPLUNC1 in immune microenvironment during the progression of NPC, NPC cells were exposed to LPS and then co-cultured with MDSCs for 48 h. RT-qPCR and western blot were performed to evaluate the mRNA and protein level of SPLUNC1, CXCL-2 and CXCR-2, respectively. The level of IL-1β, IL-6, TNF-α, PD-L1, Arg-1 and iNOS were tested by ELISA. Meanwhile, the expression of CD33+ was tested by flow cytometry. The expression of CXCL-2 and CXCR-2 in NPC cells was higher, compared to that in NP69 cells. In contrast, SPLUNC1 level in NPC cells was much lower than that in NP69 cells. SPLUNC1 level was negatively correlated with CXCL-2 and CXCR-2. Overexpression of SPLUNC1 reversed LPS-induced inflammatory responses and proliferation in NPC cells. In addition, SPLUNC1 upregulation could reverse LPS-induced proliferation of MDSCs in tumor microenvironment. Meanwhile, SPLUNC1 overexpression could regulate CXCL-2/CXCR-2 axis through decreasing CXCL-2 and CXCR-2 protein and mRNA expression. SPLUNC1 regulates LPS-induced progression of nasopharyngeal carcinoma and proliferation of MDSCs. Thus, our study might provide a theoretical basis for discovering new strategies against NPC. [ABSTRACT FROM AUTHOR]

Accurate organ-at-risk (OAR) segmentation is critical to reduce radiotherapy complications. Consensus guidelines recommend delineating over 40 OARs in the head-and-neck (H&N). However, prohibitive labor costs cause most institutions to delineate a substantially smaller subset of OARs, neglecting the dose distributions of other OARs. Here, we present an automated and highly effective stratified OAR segmentation (SOARS) system using deep learning that precisely delineates a comprehensive set of 42 H&N OARs. We train SOARS using 176 patients from an internal institution and independently evaluate it on 1327 external patients across six different institutions. It consistently outperforms other state-of-the-art methods by at least 3–5% in Dice score for each institutional evaluation (up to 36% relative distance error reduction). Crucially, multi-user studies demonstrate that 98% of SOARS predictions need only minor or no revisions to achieve clinical acceptance (reducing workloads by 90%). Moreover, segmentation and dosimetric accuracy are within or smaller than the inter-user variation. Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Here, the authors develop an automated OAR segmentation system to delineate a comprehensive set of 42 H&N OARs. [ABSTRACT FROM AUTHOR]

Purpose: As a novel antiangiogenic multi-target tyrosine kinase inhibitor recently approved in China, anlotinib has exhibited promising anticancer efficacy and acceptable safety profile in the salvage treatment of small cell lung cancer (SCLC) in clinical trials. Here we retrospectively investigated the efficacy and safety of anlotinib as third- or further-line treatment in patients with refractory SCLC. Patients and methods: A total of 40 patients with refractory SCLC treated with anlotinib monotherapy were included in this study. The clinicopathological data, treatment information, survival data and safety data were retrospectively collected. Survival curves were constructed using the Kaplan–Meier method. Univariate analysis was performed by log-rank testing. Results: Altogether, 40 patients of extensive-stage SCLC or progressive limited-stage SCLC received anlotinib monotherapy as third- or further-line treatment from July 2018 to June 2020. Four patients achieved partial response (PR), 14 patients achieved stable disease (SD), no complete response (CR) was recorded, and 22 patients experienced progressive disease (PD). The disease control rate (DCR) was 45.0%. The median progression-free survival (PFS) was 3.0 months (95% CI 2.241–3.759), and the median overall survival (OS) was 7.8 months (95% CI 3.190–12.410). The common adverse effects (AEs) included hypertension, fatigue, anorexia, cough, rash and nausea. Grade 3 treatment-related AEs occurred in 3 (7.5%) patients. One patient interrupted anlotinib treatment due to repeated grade 1 epistaxis. Univariate analysis revealed that patients without liver metastases, previously treated with radiotherapy or with Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1 had longer OS with anlotinib treatment. Cox regression analysis demonstrated that patients without liver metastases and patients with ECOG score ≤ 1 had longer PFS, while patients without liver metastases had longer OS. Conclusion: Anlotinib is beneficial to refractory SCLC as third- or further-line treatment, especially in patients without liver metastasis and with better physical status. Related adverse effects are tolerable and manageable. [ABSTRACT FROM AUTHOR]

Landslide susceptibility prediction is a key step in preventing and managing landslide hazards. As a classical supervised non-parametric machine learning model, support vector machine (SVM) has been widely used in landslide susceptibility prediction in recent years. However, most studies focus on the application of general SVM methods, or compare SVMs as benchmark methods. SVMs with different kernel functions are rarely used in this field. In this study, we apply the general SVM and its popular variants (i.e., multiple kernel learning, infinite ensemble SVM and semi-supervised SVM) to predict landslide susceptibility, and compare their prediction performance. The experimental results show that the Laplacian-SVM has the highest prediction performance (AUC = 0.8815) among SVM-based methods. SVMs with RBF kernel can achieve higher performance than SVMs with linear kernel, indicating that RBF kernel is more suitable for solving susceptibility prediction problems. Furthermore, SVM-based methods have higher sensitivity (0.8543–0.9288) than deep learning methods (0.8237–0.8271), which proves the advantage of SVMs in finding potential landslide areas. [ABSTRACT FROM AUTHOR]

Proteomic, cellular and biochemical analysis of the stress protein NUPR1 reveals that it binds to PARP1 into the nucleus and inhibits PARP1 activity in vitro. Mutations on residues Ala33 or Thr68 of NUPR1 or treatment with its inhibitor ZZW-115 inhibits this effect. PARylation induced by 5-fluorouracil (5-FU) treatment is strongly enhanced by ZZW-115 and associated with a decrease of NAD+/NADH ratio and rescued by the PARP inhibitor olaparib. Cell death induced by ZZW-115 treatment of pancreas cancer-derived cells is rescued by olaparib and improved with PARG inhibitor PDD00017273. The mitochondrial catastrophe induced by ZZW-115 treatment or by genetic inactivation of NUPR1 is associated to a hyperPARylation of the mitochondria, disorganization of the mitochondrial network, mitochondrial membrane potential decrease, and with increase of superoxide production, intracellular level of reactive oxygen species (ROS) and cytosolic levels of Ca2+. These features are rescued by olaparib or NAD+ precursor nicotinamide mononucleotide in a dose-dependent manner and partially by antioxidants treatments. In conclusion, inactivation of NUPR1 induces a hyperPARylation, which in turn, induces a mitochondrial catastrophe and consequently a cell death through a non-canonical Parthanatos, since apoptosis inducing-factor (AIF) is not translocated out of the mitochondria. NUPR1 binds to PARP1 and inhibits PARP1 activity in pancreatic cancer cells, with the NUPR1 inhibitor ZZW-115 abolishing the protective effect of NUPR1, inducing strong hyperPARylation and cell death by mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

We provide a tool for diagnosing preference heterogeneity (e.g., present bias) in a resource game. This game constitutes of two present-biased players, i.e., resource harvesters. Each resource harvester has three decision-making mechanisms: naive, precommitted and sophisticated paradigms. It is proven that (i) the harvester's decision to extract resource follows not only from her own present bias, but also from another harvester's present bias; (ii) the harvester under the sophisticated paradigm enjoys a higher resource than under naive and precommitted paradigms. [ABSTRACT FROM AUTHOR]

As crowdfunding has emerged as a popular source of funding for new ventures, budding entrepreneurs often struggle to deliver a convincing pitch to attract backers. We adopt an n-gram language model to analyze narratives of over 21,000 film projects from Kickstarter and find that the choice of words is critical to crowdfunding success. Using penalized logistic regression, we identify the relative power of phrases to predict funding outcome, resulting in a dramatic reduction in error rate. Consistent with the language expectancy theory, the linguistic analyses show that successful projects usually include words that reflect the credibility of project creators and meaningful social interactions, whereas failed projects exude negativism or uncertainty. While good word choices vary among movie genres, words of lower cognitive complexity dampen the chances of funding. These findings have broad implications for text analysis and natural language generation for persuasive marketing communications. [ABSTRACT FROM AUTHOR]

Multilevel thresholding image segmentation has always been a popular issue and attracted the attention of many researchers in recent years since it has many applications. However, the process of determining the optimal thresholds in the case of multilevel thresholding is time-consuming. To address this problem, in this paper, the optimal thresholds for multilevel thresholding image segmentation are obtained by maximizing the Rényi entropy using the Lévy flight firefly algorithm (FAFA), in which an adaptive parameter strategy based on Lévy flight is used to improve the performance of the standard firefly algorithm (FA). The performance of the proposed algorithm has been evaluated using several benchmark images and has been compared with five different heuristic algorithms. The experimental results showed that the proposed algorithm prevailed over the other five competitive algorithms in terms of the objective function value, image quality measures, and computational efficiency. [ABSTRACT FROM AUTHOR]

Small heat-shock proteins (sHSPs/HSP20s) are closely related to algae and plant thermotolerance, but studies on HSP20 family in Neoporphyra haitanensis are scarce. In this study, a total of eight HSP20 members were identified from the genome of N. haitanensis. It was predicted that most of them encode acidic hydrophilic proteins, locating in various organelles as chloroplasts and endoplasmic reticulum. Phylogenetically, the HSP20 genes of N. haitanensis were closely related to that of other species of Porphyra sensu lato, which evolved independently from that of land plants. In addition, their promoter regions contain a large number of cis-acting elements related to stress response. Based on the expression analysis of six HSP20 genes, it showed that the expression patterns of these genes were different among three conditions of dehydration, heat stress and co-stresses of heat and dehydration, with some genes being very sensitive to heat stress. These results initially indicated that HSP20 genes in N. haitanensis could specifically response to heat stress under gene expression level, suggesting their involvement in the process of thermotolerance of N. haitanensis, which is valuable for further studies on the molecular function of HSP20s in N. haitanensis. [ABSTRACT FROM AUTHOR]

Gene therapy using small interfering RNA (siRNA) is emerging as a novel therapeutic approach to treat various diseases. However, safe and efficient siRNA delivery still constitutes the major obstacle for clinical implementation of siRNA therapeutics. Here we report an ionizable supramolecular dendrimer vector, formed via self-assembly of a small amphiphilic dendrimer, as an effective siRNA delivery system with a favorable safety profile. By virtue of the ionizable tertiary amine terminals, the supramolecular dendrimer has a low positively charged surface potential and no notable cytotoxicity at physiological pH. Nonetheless, this ionizable feature imparted sufficient surface charge to the supramolecular dendrimer to enable formation of a stable complex with siRNA via electrostatic interactions. The resulting siRNA/dendrimer delivery system had a surface charge that was neither neutral, thus avoiding aggregation, nor too high, thus avoiding cytotoxicity, but was sufficient for favorable cellular uptake and endosomal release of the siRNA. When tested in different cancer cell lines and patient-derived cancer organoids, this dendrimer-mediated siRNA delivery system effectively silenced the oncogenes Myc and Akt2 with a potent antiproliferative effect, outperforming the gold standard vector, Lipofectamine 2000. Therefore, this ionizable supramolecular dendrimer represents a promising vector for siRNA delivery. The concept of supramolecular dendrimer nanovectors via self-assembly is new, yet easy to implement in practice, offering a new perspective for supramolecular chemistry in biomedical applications. [ABSTRACT FROM AUTHOR]

Chelerythrine (CHE) is a natural benzophenanthridine alkaloid, which has shown its anti-fibrosis activity in kidney and liver, while the impact of CHE in pulmonary fibrosis is still unclear. This study is developed to explore the impact and mechanism of CHE in pulmonary fibrosis. Pulmonary fibrosis mouse models were established through intratracheal injection of bleomycin (BLM), after which the mice were intraperitoneally injected with CHE (0.375 or 0.75 mg/kg/d) every other day. The mice were sacrificed at the 28th day to collect blood serum, bronchoalveolar lavage fluid (BALF), and pulmonary tissues. Then, the severity of pulmonary fibrosis and the expression of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2) in the pulmonary tissues were detected. Western blot analysis quantified the expressions of fibronectin and alpha-smooth muscle actin (α-SMA). The levels of 4-hydroxynonenal (4-HNE), glutathione (GSH), superoxide dismutase (SOD), TGF-β and hydroxyproline (HP) in the BALF, and pulmonary tissues were measured. The expression levels of Nrf2 and its downstream genes, hemeoxygenase-1 (HO-1) and NAD (P) H: quinone oxidoreductase (NQO1) were examined. CHE at the concentration of 0.375 or 0.75 mg/kg/d could attenuate pulmonary fibrosis. CHE injection reduced the expression levels of fibronectin, α-SMA, and TGF-β, upregulated the levels of SOD and GSH and decreased the levels of 4-HNE and HP. Also, CHE increased the expressions of Nrf2, HO-1, and NQO1. Treatment of Nrf2/antioxidant response element (ARE) inhibitor could block the Nrf2/ARE signaling pathway, thus perturbing the inhibition of CHE on BLM-stimulated pulmonary fibrosis in mice. CHE alleviates BLM-induced pulmonary fibrosis in mice through activating the Nrf2/ARE pathway to increase the activity of antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Brain metastasis (BM) is associated with poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutation reportedly enhances the development of BM. However, the exact mechanism of how EGFR-mutant NSCLC contributes to BM remains unknown. Herein, we found the protein WNT5A, was significantly downregulated in BM tissues and EGFR-mutant samples. In addition, the overexpression of WNT5A inhibited the growth, migration, and invasion of EGFR-mutant cells in vitro and retarded tumor growth and metastasis in vivo compared with the EGFR wide-type cells. We demonstrated a molecular mechanism whereby WNT5A be negatively regulated by transcription factor E2F1, and ERK1/2 inhibitor (U0126) suppressed E2F1's regulation of WNT5A expression in EGFR-mutant cells. Furthermore, WNT5A inhibited β-catenin activity and the transcriptional levels of its downstream genes in cancer progression. Our research revealed the role of WNT5A in NSCLC BM with EGFR mutation, and proved that E2F1-mediated repression of WNT5A was dependent on the ERK1/2 pathway, supporting the notion that targeting the ERK1/2-E2F1-WNT5A pathway could be an effective strategy for treating BM in EGFR-mutant NSCLC. [ABSTRACT FROM AUTHOR]

When solving for optimal strategies, a financial engineer needs to take into consideration of preferences heterogeneities, which involve not only present bias, but also future-focused preferences. We provide a reusable tool (i.e. algorithm) for explicitly solving optimal strategy in the presence of preferences variation over time, decision-makers and goods. In this framework, a new discount function identifies many hitherto unknown preference heterogeneities, a non-standard HJB yields sophisticated solution, a behavior equation produces naive and precommitted solutions. An application of the framework shows that a decision-maker can be neither impatient nor patient, and that sophisticated paradigm engenders immediate gratification in earlier phases of life cycle and self-control in later phases of life cycle. [ABSTRACT FROM AUTHOR]

Organic electron-transport materials are an essential component to boost performances and stability of organic light-emitting diodes. We present a robust organic electron-transport compound 3-(6-(3-(4,6-bis(4-biphenylyl)-l,3,5-triazin-2-yl)phenyl)pyridin-2-yl)phenyldiphenylphosphine oxide by facilely coupling the triphenylphosphine oxide moiety to the 2-phenyl-4,6-bis(4-biphenylyl)-1,3,5-triazine unit via a 2,6-pyridinylene linker. It is well soluble in weakly polar solvents and possesses a high Tg of 123 °C with an exceptional Td≈470 °C at 1% weight loss and deep HOMO/LUMO levels of ca. −6.45/-3.06 eV. The phos-phorescent spectrum measured in solid state at 77 K reveals a notable triplet energy of 2.88 eV. n-Doping with 8-hydroxyquinolatolithium (Liq) produces the electron mobility value of 4.66×10−5-3.21×10−4 cm V−1s−1 @(2–5)×10−5 V cm−1. Moreover, the contrasting solubility of the bromo reaction intermediate and the new compound in alcoholic solvents facilitates separation. The characterizations of bottom- and top-emission green phosphorescent OLEDs involving this single Liq-doped electron-transport layer reveal long stability. In particular, the latter provides outstanding performances with 77.4 cd A−1 (corresponding to an EQE of 18.7%) and 86.8 lm W−1@ca. 1000 cd m−2, based on the green emitter bis(2-phenylpyridine)(2-(4-methyl-3-phenylphenyl)pyridine)iridium(III). Moreover, driven by a constant current for ca. 640 h, the initial luminance of 1000 cd m−2 appears almost no decay. [ABSTRACT FROM AUTHOR]

This study aimed to assess the technique of using transesophageal echocardiography (TEE) to detect gastric inflation and to determine the optimal level of inspiratory pressure during face mask ventilation (FMV). In this prospective and randomized trial, seventy-five adults scheduled for cardiac surgery were enrolled to one of the three groups (P12, P15, P20) defined by the applied inspiratory pressure during FMV. After induction, mask ventilation was performed with the corresponding level of pressure-control ventilation for 2 min in each patient. Respiratory and hemodynamic parameters were recorded every 15 s. Arterial blood gases were tested before induction and at the time of intubation. Gastric cross-section area was detected using transesophageal echocardiography after intubation. The gastric cross-section areas were 3.1 ± 0.81, 3.8 ± 1.37 and 4.8 ± 2.29 cm2 respectively. It statistically increased in group P20 compared with group P12 and P15. PaCO2 before intubation statistically increased compared with the baseline in groups P12 and P15, while decreased in group P20. The mean values of PaCO2 equaled to 44.4 mmHg (40-51.5), 42.9 mmHg (34-50.5) and 36.9 mmHg (30.9-46) respectively in three groups. Peak airway pressure of 12-20 cmH2O could provide acceptable sufficient ventilation during mask ventilation, but 20 cmH2O result in higher incidence of gastric inflation. TEE is useful to detect the gastric inflation related to the entry of air into the stomach during pressure-controlled face mask ventilation.Trial Registration Number ChiCTR-IOR-14005325. [ABSTRACT FROM AUTHOR]

Mother-to-child transmission of hepatitis B virus (HBV) is the main route of transmission in Asia, and characterization of HBV quasispecies is needed to further understand virus evolution and adaptation. To understand changes in HBV during mother-to-child transmission, we enrolled nine pairs of mothers and children in the study, including a set of twins. Three groups were infected with HBV genotype C, and six groups were infected with HBV genotype B. The full-length HBV genome was amplified by PCR from serum samples before antiviral treatment, the whole viral genomes from each pair were sequenced, and the complexity and diversity of the quasispecies were analyzed. The entropy of transmitted HBV in children was found to be lower than their mothers, suggesting that there was a bottleneck effect during HBV transmission from the mother to the child. Selective evolution was shown by calculating πN and πS in the whole genomes, and the highest values were obtained for the X gene, which plays a role in viral replication and immune escape. All genotype C patients and only one genotype B pair had a πN/πS greater than 1 ratio, indicating that positive selection had occurred. In addition, quasispecies were found to be different between the twin children despite having the same mother, indicating that virus evolution is host-specific. [ABSTRACT FROM AUTHOR]

In amyotrophic lateral sclerosis (ALS), immune cells and glia contribute to motor neuron (MN) degeneration. We report the presence of NK cells in post-mortem ALS motor cortex and spinal cord tissues, and the expression of NKG2D ligands on MNs. Using a mouse model of familial-ALS, hSOD1G93A, we demonstrate NK cell accumulation in the motor cortex and spinal cord, with an early CCL2-dependent peak. NK cell depletion reduces the pace of MN degeneration, delays motor impairment and increases survival. This is confirmed in another ALS mouse model, TDP43A315T. NK cells are neurotoxic to hSOD1G93A MNs which express NKG2D ligands, while IFNγ produced by NK cells instructs microglia toward an inflammatory phenotype, and impairs FOXP3+/Treg cell infiltration in the spinal cord of hSOD1G93A mice. Together, these data suggest a role of NK cells in determining the onset and progression of MN degeneration in ALS, and in modulating Treg recruitment and microglia phenotype. Neuroimmune interactions are important in amyotrophic lateral sclerosis (ALS). Here the authors characterize the role of NK cells in mouse models of ALS, and in patient tissue. [ABSTRACT FROM AUTHOR]

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. [ABSTRACT FROM AUTHOR]

This work was to generate landslide susceptibility maps for the Three Gorges Reservoir (TGR) area, China by using different machine learning models. Three advanced machine learning methods, namely, gradient boosting decision tree (GBDT), random forest (RF) and information value (InV) models, were used, and the performances were assessed and compared. In total, 202 landslides were mapped by using a series of field surveys, aerial photographs, and reviews of historical and bibliographical data. Nine causative factors were then considered in landslide susceptibility map generation by using the GBDT, RF and InV models. All of the maps of the causative factors were resampled to a resolution of 28.5 m. Of the 486289 pixels in the area, 28526 pixels were landslide pixels, and 457763 pixels were non-landslide pixels. Finally, landslide susceptibility maps were generated by using the three machine learning models, and their performances were assessed through receiver operating characteristic (ROC) curves, the sensitivity, specificity, overall accuracy (OA), and kappa coefficient (KAPPA). The results showed that the GBDT, RF and InV models in overall produced reasonable accurate landslide susceptibility maps. Among these three methods, the GBDT method outperforms the other two machine learning methods, which can provide strong technical support for producing landslide susceptibility maps in TGR. [ABSTRACT FROM AUTHOR]

Both polychlorinated biphenyls (PCBs) and cadmium (Cd) can be frequently found in marine ecosystems and have detrimental effects on marine organisms, especially on filter-feeding marine mussels. Although biological responses to single metal or PCB exposure in mussels have been well-studied, information about oxidative stress is still limited, especially in different tissues in mussels. Considering the variety of contaminants existing in the actual marine environment, the exposures of the marine mussel Mytilus coruscus to Cd2+ alone (0.194, 0.388, and 0.775 mg/L) and Aroclor 1254 alone (0.005, 0.010, and 0.050 mg/L) and the co-exposures of the marine mussel Mytilus coruscus to Cd2+ (0.194 and 0.388 mg/L) and Aroclor 1254 (0.005 and 0.010 mg/L) were tested in an 8-day exposure experiment followed by a 7-day acclimation experiment. The alterations in superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde levels in the gills of the mussels were assessed. The effects of the depressed antioxidant were induced by the exposures of Cd2+ and Aroclor 1254 and their co-exposures. All exposures resulted in an initial increase and then a reduction in antioxidant enzyme activities. The range and rate of the antioxidant enzyme activities were positively correlated with stress duration and the concentration of the stress material. The effect of combined stress was stronger than that of each individual stressor. The valuable information for future investigations of stress response mechanisms, especially in relation to tissue functions in marine organisms, has been provided by the results and experimental model. The study of combined pollution effects has more scientific significance for marine pollution monitoring. [ABSTRACT FROM AUTHOR]

While online platforms often provide a single composite rating and the ratings of different attributes of a product, they largely ignore the attribute characteristics and customer criticality, which limits managerial action. We propose a multi-facet item response theory (MFIRT) approach to simultaneously examine the effects of product attributes, reviewer criticality, consumption situation, product type, and time in assessing latent customer satisfaction. Analyses of hotel ratings from TripAdvisor and beer ratings from BeerAdvocate suggest that product attributes differ with respect to their discriminating and threshold characteristics and that reviewer segments emphasize different attributes when rating various products over time. The MFIRT approach predicts product performance more accurately than alternative methods and provides novel insights to inform marketing strategies. The MFIRT framework can fundamentally advance how we analyze customer satisfaction and other consumer attitudes and improve marketing research and practice. [ABSTRACT FROM AUTHOR]

A novel reinforced concrete (RC) vertical bent frame structure system consisting of a RC frame structure and RC bent structure has been proposed for the development of large-scale thermal power plants. To better understand the seismic performance of RC bent columns in vertical bent frame structures, a 1/5-scale representative component selected from a common vertical bent frame structure was tested by quasi-static testing (QST). The failure mode hysteretic characteristics, ductility, energy dissipation capacities of RC bent columns were investigated. Based on the experimental results, finite element models for the bent frame columns and vertical bent frame structures were developed and the nonlinear dynamic analyses were carried out. The results of finite element analysis indicate that the axial pressure ratio has significant effects on the seismic behaviour of RC bent columns. The relationship of drift angle for bent frame column under frequent earthquake and infrequent earthquake are investigated. The limitation values of axial compression ratios and the inter-storey drift angle for RC bent columns in vertical bent frame structures are suggested. [ABSTRACT FROM AUTHOR]

In infants, hepatitis B virus (HBV) infections are mainly acquired by mother-to-child transmission (MTCT). Current tests for the presence of HBV markers at birth can neither confirm nor exclude MTCT. The aim of this study was to find an early diagnostic marker of HBV MTCT. From 2011 to 2016, we studied a total of 5999 pregnant women who gave birth at our hospital in Shenzhen City, China. HBsAg-positive mothers and their offspring (n=386 pairs) were tested at birth for HBV markers, and 207 infants were followed up at 7-12 months after birth. The HBsAg-seropositive rate of the pregnant women was 12.5%. Additionally, 28.0%, 36.0%, 98.5% and 6.6% of umbilical cord (UC) blood samples of neonates were found to be positive for HBsAg, HBeAg, anti-HBc and HBV-DNA, respectively, whereas for neonatal femoral venous (FV) blood, the percentages were 16.2%, 38.0%, 98.8% and 2.6%, respectively. Mothers with high HBV DNA loads and those who were HBeAg positive were the most likely to have HBV-positive offspring. Immunoprophylaxis failed in five infants: the difference in median HBV DNA titer between UC blood from infants with and without HBV MTCT was statistically significant, and there was no significant difference in HBV DNA titer between UC blood and in peripheral blood of infants with HBV MTCT. In conclusion, we found that HBeAg positivity and high HBV loads are strong risk factors for MTCT of HBV and that the HBV DNA titer in the UC is a good predictor for HBV MTCT. [ABSTRACT FROM AUTHOR]

The effects of high-energy pipe whipping after rupturing are very important in an AP1000 nuclear power plant's conventional island and restraints of pipe whipping should be considered in the design. It is the first time in the country when reinforced concrete shear walls are used as restraint services. In this paper, the behaviors of walls and restraint services subjected to pipe whipping are analyzed through static and dynamic methods in the finite element software (ABAQUS), in which all kinds of nonlinearities are considered. In addition, a test study on the restraint of pipe whipping is conducted. The results show that the wall and the restraint service can prevent pipe whipping effectively under the design load, and anchor plates arranged around the wall opening can improve the local concrete compression performance of concrete to reduce the damage of concrete. Meanwhile, the study also provides the valuable reference for wall designing to prevent from pipe whipping. [ABSTRACT FROM AUTHOR]

Color rendering index and color temperature are the key factors for the LEDs application. The two points are closely related to the emission spectrum shape of phosphors. As the key factors for the LEDs application, both the above aspects are closely dependent on the emission spectrum shape of phosphors. In this study, the emission spectrum shape has been adjusted via a home designed route. A combination of structural, morphological, and optical characterization techniques has been used to study the shape evolution mechanism. The structural results show that the Sr2SiO4 phase has not been changed with the sintering temperature increasing, but the emission spectrum shape has changed dramatically, meanwhile, the colorimetric coordinate moves from blue-green to green region. Gaussian fitting method has been used to treat the emission spectrum, and the as-obtained results indicate the emission spectrum contains two single bands, which come from the 4f7(7S7/2)-4f6(7FJ)5d1 transition of Eu2+ on the different Sr sites in the Sr2SiO4 crystal. The intensity of the two single bands is driven by sintering temperature, because of the difference between the energy barrier of the Eu2+ occupying the different Sr sites in the matrix crystal. Moreover, the mechanism of the above phenomenon has also been studied by means of first principles method, and the obtained results agree well with the former deduction. [ABSTRACT FROM AUTHOR]

Purpose: To examine available data from randomized controlled trials to assess if the freeze-all embryo and subsequent frozen-thawed embryo transfer (FET) results in better clinical outcomes than fresh embryo transfer (ET).Methods: Meta-analysis.Results: We conducted an electronic literature search on PubMed and Embase databases and manually supplemented another 2 articles from relevant citations. Seven studies were finally included in the meta-analysis,including 1141 women who underwent fresh embryo transfer and 1079 who underwent frozen embryo transfer. The results of the meta-analysis suggested that the live birth rate [RR (95% CI) 1.18 (1.08-1.30), P = 0.0003] and clinical pregnancy rate [RR (95% CI) 1.10 (1.02-1.19), P = 0.02] were significantly higher in FET group. Miscarriage rate [RR (95% CI) 0.62 (0.48-0.80), P = 0.0002], and moderate to severe OHSS occurrence rate [RR (95% CI) 0.22 (0.12 to 0.39), P < 0.00001] were significantly lower in FET group. Differences of biochemical pregnancy rate, ongoing pregnancy rate and implantation rate between the two groups did not reach the statistical significance.Conclusions: Our results suggest that the IVF/ICSI with FET is more efficient and less risky for OHSS compared with ET. However, we should comprehensively inform patients with advantages, disadvantages and potential risks related to embryo cryopreservation, and carefully assess their fertility conditions to make the most beneficial clinical decision. [ABSTRACT FROM AUTHOR]

Small interfering RNA (siRNA) therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with covalent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types in vitro and in vivo, including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired structurally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating selfassembling amphiphilic dendrimers to construct supramolecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great promise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications. [ABSTRACT FROM AUTHOR]