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The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the adverse effects of UV-induced barrier disruption and photoaging remains poorly understood. In this study, we revealed that UVB exposure resulted in a decreased expression of FLG2 in HaCaT keratinocytes, which correlated with a compromised barrier function. The administration of recombinant filaggrin-2 (rFLG2) enhanced keratinocyte differentiation, bolstered barrier integrity, and offered protection against apoptosis and oxidative stress induced by UVB irradiation. Furthermore, in a UV-induced photodamage murine model, the dermal injection of rFLG2 facilitated the enhanced restoration of the epidermal barrier, decreased oxidative stress and inflammation, and mitigated the collagen degradation that is typical of photoaging. Collectively, our findings suggested that targeting FLG2 could be a strategic approach to prevent and treat skin barrier dysfunction and combat the aging effects associated with photoaging. rFLG2 emerges as a potentially viable therapy for maintaining skin health and preventing skin aging processes amplified by photodamage. [ABSTRACT FROM AUTHOR]

The absolute stereochemical configurations of acremolides A and B were predicted by a biochemistry-based rule and unambiguously confirmed through their total syntheses. The features of the total syntheses include sequential Krische's Ir-catalyzed crotylation, Brown's borane-mediated crotylation, Mitsunobu esterification reaction, and cross-metathesis reaction. The efficient total synthesis enabled clear validation of the predicted stereochemistry for acremolides A and B. [ABSTRACT FROM AUTHOR]

Detecting pathogenic bacteria and their phenotypes including microbial resistance is crucial for preventing infection, ensuring food safety, and promoting environmental protection. Raman spectroscopy offers rapid, seamless, and label-free identification, rendering it superior to gold-standard detection techniques such as culture-based assays and polymerase chain reactions. However, its practical adoption is hindered by issues related to weak signals, complex spectra, limited datasets, and a lack of adaptability for detection and characterization of bacterial pathogens. This review focuses on addressing these issues with recent Raman spectroscopy breakthroughs enabled by machine learning (ML), particularly deep learning methods. Given the regulatory requirements, consumer demand for safe food products, and growing awareness of risks with environmental pathogens, this study emphasizes addressing pathogen detection in clinical, food safety, and environmental settings. Here, we highlight the use of convolutional neural networks for analyzing complex clinical data and surface enhanced Raman spectroscopy for sensitizing early and rapid detection of pathogens and analyzing food safety and potential environmental risks. Deep learning methods can tackle issues with the lack of adequate Raman datasets and adaptability across diverse bacterial samples. We highlight pending issues and future research directions needed for accelerating real-world impacts of ML-enabled Raman diagnostics for rapid and accurate diagnosis and surveillance of pathogens across critical fields. [ABSTRACT FROM AUTHOR]

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic–pituitary–gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives. [ABSTRACT FROM AUTHOR]

Urbanization in China has led to a significant increase in surface water pollution, posing a threat to the health and safety of residents and hindering sustainable economic development. Individual traditional methods have been used to purify polluted water, including the use of bamboo-derived activated charcoal, microbial material, and zero-valent iron. However, these methods have been found to have certain limitations. This study investigates the effects of an activated charcoal material combined with beneficial microbes and chelated nano-iron in removing nitrates. The experiments were conducted at various scales, including a bench-scale study, and studies of a small river, sewage plant tailwater, and artificially constructed wetlands. The microbes used included Bacillus spp., Lactobacillus spp., and yeasts. During the fermentation process, nano-scale iron powder was added, resulting in the formation of bivalent iron ions under anaerobic conditions. These ions were subsequently chelated by organic acids. Bamboo-derived activated charcoal was then soaked in the fermented liquid, allowing the microbes, chelated iron ions, and organic acids to infiltrate the pores of the activated charcoal. This activated charcoal material, containing microbes and chelated iron ions, demonstrated effective nitrate removal in laboratory experiments and sewage plant tailwater treatment, and water purification in wetlands and rivers. It is important to note that this research solely focused on the removal of nitrates, and further studies are required to confirm its effectiveness in other aspects of water purification. [ABSTRACT FROM AUTHOR]

An autonomous place recognition system is essential for scenarios where GPS is useless, such as underground tunnels. However, it is difficult to use existing algorithms to fully utilize the small number of effective features in underground tunnel data, and recognition accuracy is difficult to guarantee. In order to solve this challenge, an efficient point cloud position recognition algorithm, named Dual-Attention Transformer Network (DAT-Net), is proposed in this paper. The algorithm firstly adopts the farthest point downsampling module to eliminate the invalid redundant points in the point cloud data and retain the basic shape of the point cloud, which reduces the size of the point cloud and, at the same time, reduces the influence of the invalid point cloud on the data analysis. After that, this paper proposes the dual-attention Transformer module to facilitate local information exchange by utilizing the multi-head self-attention mechanism. It extracts local descriptors and integrates highly discriminative global descriptors based on global context with the help of a feature fusion layer to obtain a more accurate and robust global feature representation. Experimental results show that the method proposed in this paper achieves an average F 1 score of 0.841 on the SubT-Tunnel dataset and outperforms many existing state-of-the-art algorithms in recognition accuracy and robustness tests. [ABSTRACT FROM AUTHOR]

Total synthesis of the proposed noursamycin A has been accomplished, which disproves the original structural assignments. The synthetic strategy described herein has also been employed in the first total synthesis of nicrophorusamide A, a cyclopeptide that is structurally related to noursamycin A. [ABSTRACT FROM AUTHOR]

The first total syntheses of cyclic depsipeptides colletopeptide A and colletotrichamide A, have been accomplished. The key advanced intermediate, a cyclic tridepsipeptide derivative, was constructed using a sequence of transformations that features asymmetric Brown crotylation, cross metathesis, Yamaguchi esterification, ozonolysis, and macrolactamization. A late-stage incorporation of the mannose fragment completed the synthesis of colletotrichamide A, and the desilylation of the common intermediate gave rise to colletopeptide A, which led to unambiguous confirmation of the absolute stereochemistry of the aforementioned natural products. [ABSTRACT FROM AUTHOR]

In the realm of China's bustling economy, a fascinating dynamic exists between family businesses and state-owned enterprises, characterized by a symbiotic relationship and collaboration. Many family firms today originate from state-owned enterprises. Hence, their earlier ownership institution can influence privatized family firms. However, the impact of this privatization on long-term strategic orientation is not clear. This study endeavors to shed light on this complex matter through meticulous examination, employing estimation and inference techniques through the use of a panel model with a discernible time trend. Combining both imprinting theory and institutional logic theory, this study finds that state ownership imprints intervene in the strategic outcomes of family firms: Privatized family firms induce a lower level of innovation as compared to non-privatized family firms. This research also finds that intergenerational succession weakens this effect while the proportion of state-owned shares strengthens it. Robustness tests, utilizing the PSM method, have been conducted to validate the credibility and reliability of the findings obtained through this study. The findings of this research serve as a testament to the ever-evolving dynamics and interconnectedness prevalent within the intricate tapestry of China's economic landscape. [ABSTRACT FROM AUTHOR]

The ovary is a highly susceptible organ to senescence, and granulosa cells (GCs) have a crucial role in oocyte development promotion and overall ovarian function maintenance. As age advances, GCs apoptosis and dysfunction escalate, leading to ovarian aging. However, the molecular mechanisms underpinning ovarian aging remain poorly understood. In this study, we observed a correlation between the age-related decline of fertility and elevated expression levels of miR-143-3p in female mice. Moreover, miR-143-3p was highly expressed in senescent ovarian GCs. The overexpression of miR-143-3p in GCs not only hindered their proliferation and induced senescence-associated secretory phenotype (SASP) but also impeded steroid hormone synthesis by targeting ubiquitin-conjugating enzyme E2 E3 (Ube2e3) and luteinizing hormone and human chorionic gonadotropin receptor (Lhcgr). These findings suggest that miR-143-3p plays a substantial role in senescence and steroid hormone synthesis in GCs, indicating its potential as a therapeutic target for interventions in the ovarian aging process. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 1 (HSV-1) is a leading cause of encephalitis and infectious blindness. The commonly used clinical therapeutic drugs are nucleoside analogues such as acyclovir. However, current drugs for HSV cannot eliminate the latent virus or viral reactivation. Therefore, the development of new treatment strategies against latent HSV has become an urgent need. To comprehensively suppress the proliferation of HSV, we designed the CLEAR strategy (coordinated lifecycle elimination against viral replication). VP16, ICP27, ICP4, and gD—which are crucial genes that perform significant functions in different stages of the HSV infection lifecycle—were selected as targeting sites based on CRISPR-Cas9 editing system. In vitro and in vivo investigations revealed that genome editing by VP16, ICP27, ICP4 or gD single gene targeting could effectively inhibit HSV replication. Moreover, the combined administration method (termed "Cocktail") showed superior effects compared to single gene editing, which resulted in the greatest decrease in viral proliferation. Lentivirus-delivered CRISPR-Cas9/gRNA editing could effectively block HSV replication. The CLEAR strategy may provide new insights into the potential treatment of refractory HSV-1-associated diseases, particularly when conventional approaches have encountered resistance. [ABSTRACT FROM AUTHOR]

A novel hydrogen bond surrogate-based (HBS) α-helix mimetic was designed by the combination of covalent H-bond replacement and the use of an ether linkage to substitute an amide bond within a short peptide sequence. The new helix template could be placed in position other than the N-terminus of a short peptide, and the CD studies demonstrate that the template adopts stable conformations in aqueous buffer at exceptionally high temperatures. [ABSTRACT FROM AUTHOR]

Setting environmental regulation policy is an important practice to reach the goal of ecological environmental protection. By establishing fixed effects and spatial spillover models, this paper examines the relationship between the environmental regulation of carbon emissions and the impact on spatial spillovers. The results of our analysis show that: 1. environmental regulation has significant inhibitory effects on carbon emissions, which is beneficial to carbon dioxide emission reduction, and 2. environmental regulation has a significant inhibitory impact on local carbon emissions but increases carbon emissions in neighboring locations. Therefore, in order to achieve the aim of carbon emission reduction, appropriate environmental regulation policies should be established, which, in turn, would provide better coordination of the carbon emission relationship between different regions. Meanwhile, environmental regulation plays an important role in protecting the environment. To strengthen environmental governance and promote the coordinated development of regional carbon emission reduction, we need to implement a top-level design of environmental regulation and build a market-oriented environmental regulation system. [ABSTRACT FROM AUTHOR]

Spatially explicit crop yield datasets with continuous long-term series are essential for understanding the spatiotemporal variation of crop yield and the impact of climate change on it. There are several spatial disaggregation methods to generate gridded yield maps, but these either use an oversimplified approach with only a couple of ancillary data or an overly complex approach with limited flexibility and scalability. This study developed a spatial disaggregation method using improved spatial weights generated from machine learning. When applied to Chinese maize yield, extreme gradient boosting (XGB) derived the best prediction results, with a cross-validation coefficient of determination (R2) of 0.81 at the municipal level. The disaggregated yield at 1 km grids could explain 54% of the variance of the county-level statistical yield, which is superior to the existing gridded maize yield dataset in China. At the site level, the disaggregated yields also showed much better agreement with observations than the existing gridded maize yield dataset. This lightweight method is promising for generating spatially explicit crop yield datasets with finer resolution and higher accuracy, and for providing necessary information for maize production risk assessment in China under climate change. [ABSTRACT FROM AUTHOR]

The effects of freezing methods, including rapid freezing (RF) or slow freezing (SF), combined with thawing methods, e.g., water immersing thawing (WT) or cold thawing (CT), on the meat yield, drip loss, gel properties, and digestive properties of meat detached from red swamp crayfish were investigated. RF greatly reduced the freezing time compared to SF, and the thawing time of frozen crayfish was obviously shortened by WT in comparison to CT. RF and CT improved the meat yield but increased the drip loss, probably as a result of the greater protein denaturation or degradation. A soft and flexible gel was obtained by SF-CT, while a hard one was achieved by RF-WT. An SEM analysis showed that SF resulted in rough and irregular microstructures with larger pore sizes. Freeze-thawing led to an increase in the β-sheet content at the expense of α-helix and variations in the microenvironment of tyrosine and tryptophan residues in protein molecules of the gels, which was more pronounced in the SF-CT group. Moreover, freeze-thawing could cause enhanced protein digestibility but reduce the antioxidant activity of gels. These findings underline the promise of the freezing-thawing treatment in tuning the gel-based meat products of crayfish. [ABSTRACT FROM AUTHOR]

Traditional user research methods are challenged for the decision-making in product design and improvement with the updating speed becoming faster, considering limited survey scopes, insufficient samples, and time-consuming processes. This paper proposes a novel approach to acquire useful online reviews from E-commerce platforms, build a product evaluation indicator system, and put forward improvement strategies for the product with opinion mining and sentiment analysis with online reviews. The effectiveness of the method is validated by a large number of user reviews for smartphones wherein, with the evaluation indicator system, we can accurately predict the bad review rate for the product with only 9.9% error. And improvement strategies are proposed after processing the whole approach in the case study. The approach can be applied for product evaluation and improvement, especially for the products with needs for iterative design and sailed online with plenty of user reviews. [ABSTRACT FROM AUTHOR]

In this work, we focus on investigating electrothermal flow in rotating electric fields (ROT-ETF), with primary attention paid to the horizontal traveling-wave electrothermal (TWET) vortex induced at the center of the electric field. The frequency-dependent flow profiles in the microdevice are analyzed using different heat transfer models. Accordingly, we address in particular the importance of electrode cooling in ROT-ETF as metal electrodes of high thermal conductivity, while substrate material of low heat dissipation capability is employed to develop such microfluidic chips. Under this circumstance, cooling of electrode array due to external natural convection on millimeter-scale electrode pads for external wire connection occurs and makes the internal temperature maxima shift from the electrode plane to a bit of distance right above the cross-shaped interelectrode gaps, giving rise to reversal of flow rotation from a typical repulsion-type to attraction-type induction vortex, which is in good accordance with our experimental observations of co-field TWET streaming at frequencies in the order of reciprocal charge relaxation time of the bulk fluid. These results point out a way to make a correct interpretation of out-of-phase electrothermal streaming behavior, which holds great potential for handing high-conductivity analytes in modern microfluidic systems. [ABSTRACT FROM AUTHOR]

On-chip immuno-sensors are a hot topic in the microfluidic community, which is usually limited by slow diffusion-dominated transport of analytes in confined microchannels. Specifically, the antigen-antibody binding reaction at a functionalized area cannot be provided with enough antigen source near the reaction surface, since a small diffusion flux cannot match with the quick rate of surface reaction, which influences the response time and sensitivity of on-chip heterogeneous immunoassay. In this work, we propose a method to enhance the transportation of biomolecules to the surface of an antibody-immobilized electrode with induce charge electroosmotic (ICEO) convection in a low concentration suspension, so as to improve the binding efficiency of microfluidic heterogeneous immunoassays. The circular stirring fluid motion of ICEO on the surface of a floating gate electrode at the channel bottom accelerates the transport of freely suspended antigen towards the wall-immobilized antibodies. We investigate the dependence of binding efficiency on voltage magnitude and field frequency of the applied alternate current (AC) electrical field. The binding rate yields a factor of 5.4 higher binding for an applied voltage of 4 V at 10 Hz when the Damkohler number is 1000. The proposed microfluidic immuno-sensor technology of a simple electrode structure using ICEO convective fluid flow around floating conductors could offer exciting opportunities for diffusion-limited on-chip bio-microfluidic sensors. [ABSTRACT FROM AUTHOR]

In this work, we proposed a novel design of a microfluidic mixer utilizing the amplified Marangoni chaotic advection induced by alternating current (AC) continuous electrowetting of a metal droplet situated in electrolyte solution, due to the linear and quadratic voltage-dependence of flow velocity at small or large voltages, respectively. Unlike previous researchers exploiting the unidirectional surface stress with direct current (DC) bias at droplet/medium interface for pumping of electrolytes where the resulting flow rate is linearly proportional to the field intensity, dominance of another kind of dipolar flow pattern caused by local Marangoni stress at the drop surface in a sufficiently intense AC electric field is demonstrated by both theoretical analysis and experimental observation, which exhibits a quadratic growth trend as a function of the applied voltage. The dipolar shear stress merely appears at larger voltages and greatly enhances the mixing performance by inducing chaotic advection between the neighboring laminar flow. The mixer design developed herein, on the basis of amplified Marangoni chaotic advection around a liquid metal droplet at larger AC voltages, has great potential for chemical reaction and microelectromechanical systems (MEMS) actuator applications because of generating high-throughput and excellent mixing performance at the same time. [ABSTRACT FROM AUTHOR]

Streptococcus mutans (S. mutans) is the major clinical pathogen responsible for dental caries. Its acid tolerance has been identified as a significant virulence factor for its survival and cariogenicity in acidic conditions. Small RNAs (sRNAs) are recognized as key regulators of virulence and stress adaptation. Here, we constructed three libraries of sRNAs with small size exposed to acidic conditions for the first time, followed by verification using qRT-PCR. The levels of two sRNAs and target genes predicted to be bioinformatically related to acid tolerance were further evaluated under different acid stress conditions (pH 7.5, 6.5, 5.5, and 4.5) at three time points (0.5, 1, and 2 h). Meanwhile, bacterial growth characteristics and vitality were assessed. We obtained 1879 sRNAs with read counts of at least 100. One hundred and ten sRNAs were perfectly mapped to reported msRNAs in S. mutans. Ten out of 18 sRNAs were validated by qRT-PCR. The survival of bacteria declined as the acid was increased from pH 7.5 to 4.5 at each time point. The bacteria can proliferate under each pH except pH 4.5 with time. The levels of sRNAs gradually decreased from pH 7.5 to 5.5, and slightly increased in pH 4.5; however, the expression levels of target mRNAs were up-regulated in acidic conditions than in pH 7.5. These results indicate that some sRNAs are specially induced at acid stress conditions, involving acid adaptation, and provide a new insight into exploring the complex acid tolerance for S. mutans. [ABSTRACT FROM AUTHOR]

Detailed analysis of continuous time-series data from regions undergoing rapid urbanization can accurately reveal spatial variations on short time scales. This study used the city of Changchun in Jilin Province, China, as a case study to analyze total and annual changes in area--especially decreases in rural settlement area--as well as regional differences in these changes and driving forces of rural settlement evolution. Quantitative analytical techniques include a dynamic percentage of rural settlements, the distribution index of rural settlements, the regression correlation analysis, and other spatial analysis methods. Data were derived from a variety of sources, including land-use databases and social and economic statistics. The results show that the area of rural settlements decreased between 2009 and 2014, with the urban construction land expansion and decreases in cultivated lands. Rural settlements also became increasingly fragmented after 2009. Most of the rural settlements were located close to the urban construction land, and changes in rural settlement area were more pronounced with decreasing distance to the closest urban construction land, illustrating the effect of urban sprawl on rural settlement changes. The analysis also shows that the decreasing area of rural settlements between 2009 and 2014 is directly caused by urban sprawl. Regional development strategies and urban planning indirectly contribute to changes in the scale and spatial distribution of rural settlements by guiding urban development. The geographical environment and strict cultivated-land-protection policies also indirectly restrict changes in rural settlements by determining the restrictive area of urban expansion. No significant changes were found in the influence of population change on changing areas of rural settlements. In conclusion, the interaction of strategy for social-economic development, natural geography environments, and human demand jointly caused changes in rural settlements. [ABSTRACT FROM AUTHOR]

Satellite-based models have tremendous potential for monitoring crop production because satellite data can provide temporally and spatially continuous crop growth information at large scale. This study used a satellite-based vegetation production model (i.e., eddy covariance light use efficiency, EC-LUE) to estimate national winter wheat gross primary production, and then combined this model with the harvest index (ratio of aboveground biomass to yield) to convert the estimated winter wheat production to yield. Specifically, considering the spatial differences of the harvest index, we used a cross-validation method to invert the harvest index of winter wheat among counties, municipalities and provinces. Using the field-surveyed and statistical yield data, we evaluated the model performance, and found the model could explain more than 50% of the spatial variations of the yield both in field-surveyed regions and most administrative units. Overall, the mean absolute percentage errors of the yield are less than 20% in most counties, municipalities and provinces, and the mean absolute percentage errors for the production of winter wheat at the national scale is 4.06%. This study demonstrates that a satellite-based model is an alternative method for crop yield estimation on a larger scale. [ABSTRACT FROM AUTHOR]

Although China is the largest producer of rice, accounting for about 25% of global production, there are no high-resolution maps of paddy rice covering the entire country. Using time-weighted dynamic time warping (TWDTW), this study developed a pixel- and phenology-based method to identify planting areas of double-season paddy rice in China, by comparing temporal variations of synthetic aperture radar (SAR) signals of unknown pixels to those of known double-season paddy rice fields. We conducted a comprehensive evaluation of the method's performance at pixel and regional scales. Based on 145,210 field surveyed samples from 2018 to 2020, the producer's and user's accuracy are 88.49% and 87.02%, respectively. Compared to county-level statistical data from 2016 to 2019, the relative mean absolute errors are 34.11%. This study produced distribution maps of double-season rice at 10 m spatial resolution from 2016 to 2020 over nine provinces in South China, which account for more than 99% of the planting areas of double-season paddy rice of China. The maps are expected to contribute to timely monitoring and evaluating rice growth and yield. [ABSTRACT FROM AUTHOR]

Crop rotations, the farming practice of growing crops in sequential seasons, occupy a core position in agriculture management, showing a key influence on food security and agro-ecosystem sustainability. Despite the improvement in accuracy of identifying mono-agricultural crop distribution, crop rotation patterns remain poorly mapped. In this study, a hybrid convolutional neural network (CNN) and long short-term memory (LSTM) architecture, namely crop rotation mapping (CRM), were proposed to synergize the synthetic aperture radar (SAR) and optical time series in a rotational mapping task. The proposed end-to-end architecture had reasonable accuracies (i.e., accuracy > 0.85) in mapping crop rotation, which outperformed other state-of-the-art non-deep or deep-learning solutions. For some confusing rotation types, such as fallow-single rice and crayfish-single rice, CRM showed substantial improvements from traditional methods. Furthermore, the deeply synergistic SAR-optical, time-series data, with a corresponding attention mechanism, were effective in extracting crop rotation features, with an overall gain of accuracy of four points compared with ablation models. Therefore, our proposed method added wisdom to dynamic crop rotation mapping and yields important information for the agro-ecosystem management of the study area. [ABSTRACT FROM AUTHOR]

Reduced graphene oxide (rGO) has been widely used to modify the mechanical performance of alkali activated slag composites (AASC); however, the mechanism is still unclear and the electrical properties of rGO reinforced AASC are unknown. Here, the rheological, mechanical, and electrical properties of the AASC containing rGO nanosheets (0, 0.1, 0.2, and 0.3% wt.) are investigated. Results showed that rGO nanosheets addition can significantly improve the yield stress, plastic viscosity, thixotropy, and compressive strength of the AASC. The addition of 0.3% wt. rGO nanosheets increased the stress, viscosity, thixotropy, and strength by 186.77 times, 3.68 times, 15.15 times, and 21.02%, respectively. As for electrical properties, the impedance of the AASC increased when the rGO content was less than 0.2% wt. but decreased with the increasing dosage. In contrast, the dielectric constant and electrical conductivity of the AASC containing rGO nanosheets decreased and then increased, which can be attributed to the abundant interlayer water and the increasing structural defects as the storage sites for charge carriers, respectively. In addition, the effect of graphene oxide (GO) on the AASC is also studied and the results indicated that the agglomeration of GO nanosheets largely inhibited the application of it in the AASC, even with a small dosage. [ABSTRACT FROM AUTHOR]

The first total synthesis of the thiazole-containing cyclic depsipeptide pagoamide A, is detailed. The longest linear sequence of the liquid-phase synthesis comprises 9 long linear steps from simple known starting materials, which led to the unambiguous structural confirmation of pagoamide A. [ABSTRACT FROM AUTHOR]

The asymmetric total synthesis of four diastereomers of laingolide A was achieved, which led to the unambiguous assignment of the stereochemistry of the natural product. The salient features of the convergent, fully stereocontrolled approach were a copper-catalysed stereospecific Kumada-type coupling, a Julia-Kocienski olefination and an RCM/alkene migration sequence to access the desired macrocyclic enamide. [ABSTRACT FROM AUTHOR]

Insulin resistance decreases the ability of insulin to inhibit hepatic gluconeogenesis, a key step in the development of metabolic syndrome. Metabolic alterations, fat accumulation, and fibrosis in the liver are closely related and contribute to the progression of comorbidities, such as hypertension, type 2 diabetes, or cancer. Omega 3 (n-3) polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), were identified as potent positive regulators of insulin sensitivity in vitro and in animal models. In the current study, we explored the effects of a transgenerational supplementation with EPA in mice exposed to an obesogenic diet on the regulation of microRNAs (miRNAs) and gene expression in the liver using high-throughput techniques. We implemented a comprehensive molecular systems biology approach, combining statistical tools, such as MicroRNA Master Regulator Analysis pipeline and Boolean modeling to integrate these biochemical processes. We demonstrated that EPA mediated molecular adaptations, leading to the inhibition of miR-34a-5p, a negative regulator of Irs2 as a master regulatory event leading to the inhibition of gluconeogenesis by insulin during the fasting–feeding transition. Omics data integration provided greater biological insight and a better understanding of the relationships between biological variables. Such an approach may be useful for deriving innovative data-driven hypotheses and for the discovery of molecular–biochemical mechanistic links. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is the most aggressive brain tumor and most resistant to therapy. The identification of novel predictive biomarkers or targets to counteract chemoresistance, requires a better understanding of the GBM primary response to therapy. The aim of our study was to assess the molecular response of GBM to the standard of care chemotherapy by temozolomide (TMZ). We established a comprehensive map of gene expression changes after treatment and discovered that GBM cells elicit a coordinated gene expression program after chemotherapy that differs between sensitive and resistant cells. We found that a novel class of genes expressed as long non-coding RNAs (lncRNAs) is involved in gene regulatory circuits in GBM and could represent novel markers of GBM patient prognosis. By shedding light on the involvement of the non-coding genome in GBM, our results may provide new mechanistic insight on lncRNAs and their importance in chemoresistance. Resistance to chemotherapy by temozolomide (TMZ) is a major cause of glioblastoma (GBM) recurrence. So far, attempts to characterize factors that contribute to TMZ sensitivity have largely focused on protein-coding genes, and failed to provide effective therapeutic targets. Long noncoding RNAs (lncRNAs) are essential regulators of epigenetic-driven cell diversification, yet, their contribution to the transcriptional response to drugs is less understood. Here, we performed RNA-seq and small RNA-seq to provide a comprehensive map of transcriptome regulation upon TMZ in patient-derived GBM stem-like cells displaying different drug sensitivity. In a search for regulatory mechanisms, we integrated thousands of molecular associations stored in public databases to generate a background "RNA interactome". Our systems-level analysis uncovered a coordinated program of TMZ response reflected by regulatory circuits that involve transcription factors, mRNAs, miRNAs, and lncRNAs. We discovered 22 lncRNAs involved in regulatory loops and/or with functional relevance in drug response and prognostic value in gliomas. Thus, the investigation of TMZ-induced gene networks highlights novel RNA-based predictors of chemosensitivity in GBM. The computational modeling used to identify regulatory circuits underlying drug response and prioritizing gene candidates for functional validation is applicable to other datasets. [ABSTRACT FROM AUTHOR]

Development of low thermal conductivity and high strength building materials is an emerging strategy to solve the heavy energy consumption of buildings. This study develops sustainable alkali activated materials (AAMs) for structural members from waste expanded polystyrene (EPS) beads and reduced graphene oxide (rGO) to simultaneously meet the thermal insulation and mechanical requirements of building energy conservation. It was found that the thermal conductivity of AAMs with 80 vol.% EPS and 0.04 wt.% rGO (E8–G4) decreased by 74% compared to the AAMs without EPS and rGO (E0). The 28-day compressive and flexural strengths of E8–G4 increased by 29.8% and 26.5% with the addition of 80 vol.% EPS and 0.04 wt.% rGO, compared to the sample with 80 vol.% EPS without rGO (E8). In terms of compressive strength, thermal conductivity, and cost, the efficiency index of E8–G4 was higher than those of other materials. A building model made from AAMs was designed using building information modeling (BIM) tools to simulate energy consumption, and 31.78% of total energy consumption (including heating and cooling) was saved in the building operation period in Harbin City, China. Hence, AAMs made of waste EPS beads and rGO can realize the structural and functional integrated application in the future. [ABSTRACT FROM AUTHOR]

With the development of nanotechnology, reduced graphene oxide (rGO) has been used to improve the flexural strength of geopolymers. However, the reinforcing mechanism of rGO nanosheets on the flexural strength of geopolymers remains unclear. Here, this reinforcing mechanism was investigated from the perspectives of hydration and chemical composition. The effect of the reduction degree on rGO-reinforced geopolymers was also studied using isothermal calorimetry (IC), X-ray diffraction (XRD), and nuclear magnetic resonance (NMR) tests. Results show that the hydration degree and flexural strength of geopolymers effectively increase due to rGO addition. After alkali reduction at a temperature of 60 °C, rGO nanosheets have maximum reinforcement on the flexural strength of geopolymers with an increment of 51.2%. It is attributed to the promotion of slag hydration, as well as the simultaneous formation of calcium silicate hydrate with low Ca/Si ratio (C-S-H(I)) and calcium aluminosilicate hydrate (C-A-S-H) phases due to the inhibiting effect of rGO nanosheets on Al substitution on the end-of-chain silicates of C-S-H and C-A-S-H gels. In addition, different reduction degrees have almost no effect on the chemical composition of rGO-reinforced geopolymers, while excessive reduction impairs the improving effect of rGO nanosheets on the hydration process and flexural strength of geopolymers due to significant structural defects. [ABSTRACT FROM AUTHOR]

Calcium leaching is a degradation progress inside hardened cement composites, where Ca2+ ions in cement pore solution can migrate into the aggressive solution. In this work, calcium leaching of graphene oxide (GO) reinforced cement composites was effectively characterized by combined techniques of electrochemical impedance spectroscopy (EIS) and scanning electron microscope (SEM). Inhibiting mechanism of GO on calcium leaching of the composites was also examined. The obtained results show that the diameter of the semi-circle of the Nyquist curves of leached samples with GO addition decreased less than that of controlled samples. After leaching for 35 days, loss rate of model impedance RCCP of leached samples with 0, 0.05, 0.1, 0.15, and 0.2 wt.% GO addition was 94.85%, 84.07%, 79.66%, 75.34%, and 68.75%, respectively. Therefore, GO addition can significantly mitigate calcium leaching of cement composites, since it can absorb Ca2+ ions in cement pore solution, as well as improve the microstructure of the composites. In addition, coupling leaching depth and compressive strength loss were accurately predicted by using the impedance RCCP. [ABSTRACT FROM AUTHOR]

Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection of marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular ester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered compound via acyl migration at the 1,3-diol unit, and the transformation product was named lagunamide D'. The planar structures of both compounds were elucidated using a combination of nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectroscopy (HRMS). The absolute configurations were determined on the basis of enantioselective analysis, modified Mosher's analysis, Kishi NMR database, and direct comparison with lagunamide A, a structure closely resembling lagunamide D. Lagunamides A and D displayed low-nanomolar antiproliferative activity against A549 human lung adenocarcinoma cells, while the structural transformation from the 26-membered lagunamide D macrocycle to the 24-membered ring structure for lagunamide D' led to a 9.6-fold decrease in activity. Lagunamide D also displayed potent activity in triggering apoptosis in a dose- and time-dependent manner. Further investigation on the mechanism of action of the lagunamide scaffold is needed to fully explore its therapeutic potential as an anticancer agent. [ABSTRACT FROM AUTHOR]

Many accidents happen under shunting mode when the speed of a train is below 45 km/h. In this mode, train attendants observe the railway condition ahead using the traditional manual method and tell the observation results to the driver in order to avoid danger. To address this problem, an automatic object detection system based on convolutional neural network (CNN) is proposed to detect objects ahead in shunting mode, which is called Feature Fusion Refine neural network (FR-Net). It consists of three connected modules, i.e., the depthwise-pointwise convolution, the coarse detection module, and the object detection module. Depth-wise-pointwise convolutions are used to improve the detection in real time. The coarse detection module coarsely refine the locations and sizes of prior anchors to provide better initialization for the subsequent module and also reduces search space for the classification, whereas the object detection module aims to regress accurate object locations and predict the class labels for the prior anchors. The experimental results on the railway traffic dataset show that FR-Net achieves 0.8953 mAP with 72.3 FPS performance on a machine with a GeForce GTX1080Ti with the input size of 320 × 320 pixels. The results imply that FR-Net takes a good tradeoff both on effectiveness and real time performance. The proposed method can meet the needs of practical application in shunting mode. [ABSTRACT FROM AUTHOR]

In the field of investment, how to construct a suitable portfolio based on historical data is still an important issue. The second-order stochastic dominant constraint is a branch of the stochastic dominant constraint theory. However, only considering the second-order stochastic dominant constraints does not conform to the investment environment under realistic conditions. Therefore, we added a series of constraints into basic portfolio optimization model, which reflect the realistic investment environment, such as skewness and kurtosis. In addition, we consider two kinds of risk measures: conditional value at risk and value at risk. Most important of all, in this paper, we introduce Gray Wolf Optimization (GWO) algorithm into portfolio optimization model, which simulates the gray wolf’s social hierarchy and predatory behavior. In the numerical experiments, we compare the GWO algorithm with Particle Swarm Optimization (PSO) algorithm and Genetic Algorithm (GA). The experimental results show that GWO algorithm not only shows better optimization ability and optimization efficiency, but also the portfolio optimized by GWO algorithm has a better performance than FTSE100 index, which prove that GWO algorithm has a great potential in portfolio optimization. [ABSTRACT FROM AUTHOR]

Nostosins A and B were isolated from a hydrophilic extract of Nostoc sp. strain from Iran, which exhibits excellent tryps inhibitory activity. Nostosin A was the most potent natural tripeptide aldehyde as trypsin inhibitor up to now. Both R- and S-2-hydroxy-4-(4-hydroxy-phenyl) butanoic acid (Hhpba) were prepared and incorporated into the total synthesis of nostosin B, respectively. Careful comparison of the NMR spectra and optical rotation data of synthetic nostosin B (1a and 1b) with the natural product led to the unambiguous identification of the R-configuration of the Hhpba fragment, which was further confirmed by co-injection with the authentic sample on HPLC using both reversed phase column and the chiral AD-RH column.

Itralamides A and B were isolated from the lipophilic extract of Lyngbya majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic activity towards human embryonic kidney cells (HEK293, IC50 = 6 μM). Preliminary studies disapproved the proposed stereochemistry of itralamide. In this paper, we will provide a full account of the total synthesis of four stereoisomers of itralamide B and the results derived from biological tests of these structural congeners.

The complementary use of liquid chromatography (LC) and nuclear magnetic resonance (NMR) has shown high utility in a variety of fields. While the significant benefit of spectral simplification can be achieved for the analysis of complex samples, other limitations remain. For example, (1)H LC-NMR suffers from pH dependent chemical shift variations, especially during urine analysis, owing to the high physiological variation of urine pH. Additionally, large solvent signals from the mobile phase in LC can obscure lower intensity signals and severely limit the number of metabolites detected. These limitations, along with sample dilution, hinder the ability to make reliable chemical shift assignments. Recently, stable isotopic labeling has been used to detect quantitatively specific classes of metabolites of interest in biofluids. Here we present a strategy that explores the combined use of two-dimensional hydrophilic interaction chromatography (HILIC) and isotope tagged NMR for the unambiguous identification of carboxyl containing metabolites present in human urine. The ability to separate structurally related compounds chromatographically, in off-line mode, followed by detection using (1)H-(15)N 2D HSQC (two-dimensional heteronuclear single quantum coherence) spectroscopy, resulted in the assignment of low concentration carboxyl-containing metabolites from a library of isotope labeled compounds. The quantitative nature of this strategy is also demonstrated.