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Abstract Bone marrow-derived mesenchymal stem cells (BMSCs) exhibit multi-lineage differentiation potential and robust proliferative capacity. The late stage of differentiation signifies the functional maturation and characterization of specific cell lineages, which is crucial for studying lineage-specific differentiation mechanisms. However, the molecular processes governing late-stage BMSC differentiation remain poorly understood. This study aimed to elucidate the key biological processes involved in late-stage BMSC differentiation. Publicly available transcriptomic data from human BMSCs were analyzed after approximately 14 days of osteogenic, adipogenic, and chondrogenic differentiation. Thirty-one differentially expressed genes (DEGs) associated with differentiation were identified. Pathway enrichment analysis indicated that the DEGs were involved in extracellular matrix (ECM)-receptor interactions, focal adhesion, and glycolipid biosynthesis, a ganglion series process. Subsequently, the target genes were validated using publicly available single-cell RNA-seq data from mouse BMSCs. Lamc1 exhibited predominant distribution in adipocytes and osteoblasts, primarily during the G2/M phase. Tln2 and Hexb were expressed in chondroblasts, osteoblasts, and adipocytes, while St3gal5 was abundantly distributed in stem cells. Cell communication analysis identified two receptors that interact with LAMCI. q-PCR results confirmed the upregulation of Lamc1, Tln2, Hexb, and St3gal5 during osteogenic differentiation and their downregulation during adipogenic differentiation. Knockdown of Lamc1 inhibited adipogenic and osteogenic differentiation. In conclusion, this study identified four genes, Lamc1, Tln2, Hexb, and St3gal5, that may play important roles in the late-stage differentiation of BMSCs. It elucidated their interactions and the pathways they influence, providing a foundation for further research on BMSC differentiation.

ObjectiveTo investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α (RORA) in the proliferation and progression of colorectal cancer (CRC) cells. MethodsThe expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR, FISH, and IHC. Cell proliferation capability was detected through EdU and CFSE assay, cell apoptosis by flow cytometry assay, and cell migration and invasion abilities by cell scratch and Transwell invasion assays, respectively. The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay, cell function rescue test, RT-PCR, and Western blot assay. Finally, bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation, invasion, and progression of CRC via regulating RORA. ResultsmiR-18a-5p exhibited a high expression in CRC tissues and cells (P

Abstract Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPS L.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPS L.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPS L. p -delivered OVA compared to OVA alone. Notably, NAPS L.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPS L.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPS L.p -based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPS L.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

With the widespread use of tetracycline antibiotics (TCs) and the application of manure fertilizer in farmland, TCs and their metabolites especially 4-epimers have been heavily detected in agricultural soil. However, existing studies have focused on the residual and environmental behavior of maternal TCs, and few studies have looked at the ecotoxicity of their 4-epimers in soil. In this study, the degradation and interconversion of tetracycline (TC), oxytetracycline (OTC) and their 4-epimers (4-epitetracycline, ETC; 4-epioxytetracycline, OTC) were revealed. Their effects on antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and bacterial community in soil were also investigated in comparison. The results showed that the 4-epimers could be substantially transformed to their parents and degraded as a whole. The degradation rates of four selected pollutants are followed: TC > OTC > ETC > EOTC. This indicated that when TCs entered the soil, part of TCs transformed into slower-degraded 4-epimers, and these 4-epimers could also be converted back to their antibiotic parents, causing the long-term residue of TCs in soil. When added to the soil alone, TC and OTC significantly promoted the proliferation of most ARGs and MGEs, among them, trb-C, IS1247 and IS1111 were the top three genes in abundance. ETC and EOTC had little effect at the beginning. However, as the 4-epimers continuously converted into their parents after one month of cultivation, ETC and EOTC treatments showed similar promoting effect on ARGs and MGEs, indicating that the effect of ETC and EOTC on soil resistome was lagged and mainly caused by their transformed parents. Nocardioides, unclassified_Rhizobiaceae, norank_Sericytochromatia, Microlunatus, Solirubrobacter and norank_67-14 were the most frequent hosts of ARGs, Most of which belong to the phylum Actinobacteria. Due to their large transformation to TCs, slow degradation rate and potential effects on soil microbes and ARGs, the harm of TCs’ 4-epimers on soil ecosystem cannot be ignored.

Abstract Whispering gallery mode (WGM) laser with single‐mode is important for optoelectronic applications because of the higher stability during the light signal transmission. But till now, for InGaN‐based WGM laser, most reports of lasing behavior are multimode lasing. To achieve single‐mode WGM laser, an InGaN‐based micro‐ring laser is proposed and demonstrated with lateral nanoporous distributed Bragg reflector (DBR), where the high‐order lasing modes are strongly suppressed. The side mode suppression ratio (SMSR) is more than 9 times larger than that of the micro‐disk laser with the same radius. Combined with FDTD simulation, the results show that the enhancements are originated from the suppression of the high‐order resonant mode because of the inner boundary of micro‐ring. This work provides a new solution to achieve stable single‐mode WGM laser for future photonic integration.

The biocurrent generated by soil extracellular electron transfer (EET) partly drives biogeochemical cycles and controls soil quality. However, it is unclear how the soil abiotic and biotic conditions affect the biocurrent conduction. In this study, the response relationship of soil microenvironment and in-situ biocurrent was studied. The results showed that red soil exhibited the optimal electron transfer efficiency, as evidenced by the maximum current density and accumulated charge output, with increments of 56–93 % and 80–2800 %, respectively, compared with the other five types of soils. Soil physicochemical properties were the most important factor on the biocurrent generation, and further the quantity and bioavailability of dissolved organic matter, NH4+-N content, and lower pH were predictive indicators for the exoelectrogenic processes of soils. In addition, the high soil biocurrent was likely determined by a complex synergistic network of the transformation of carbon and nitrogen, electroactive bacteria involving the functions of cell wall/membrane and cytochrome enzyme metabolism and transport related EET process. Overall, we provide an insight into the relationship among soil biocurrent conduction, physicochemical properties, bacteria community and metabolic function, and a support for bioelectrochemical technology application.

Abstract Magnetic tunnel junctions (MTJs) with conventional bulk ferromagnets separated by a nonmagnetic insulating layer are key building blocks in spintronics for magnetic sensors and memory. A radically different approach of using atomically-thin van der Waals (vdW) materials in MTJs is expected to boost their figure of merit, the tunneling magnetoresistance (TMR), while relaxing the lattice-matching requirements from the epitaxial growth and supporting high-quality integration of dissimilar materials with atomically-sharp interfaces. We report TMR up to 192% at 10 K in all-vdW Fe3GeTe2/GaSe/Fe3GeTe2 MTJs. Remarkably, instead of the usual insulating spacer, this large TMR is realized with a vdW semiconductor GaSe. Integration of semiconductors into the MTJs offers energy-band-tunability, bias dependence, magnetic proximity effects, and spin-dependent optical-selection rules. We demonstrate that not only the magnitude of the TMR is tuned by the semiconductor thickness but also the TMR sign can be reversed by varying the bias voltages, enabling modulation of highly spin-polarized carriers in vdW semiconductors.

Surface roughness and low surface energy are key elements for the artificial preparation of biomimetic superhydrophobic materials. However, the presence of micro-/nanostructures and the corresponding increase in roughness can increase light scattering, thereby reducing the surface transparency. Therefore, designing and constructing superhydrophobic surfaces that combine superhydrophobicity with high transparency has been a continuous research focus for researchers and engineers. In this study, a transparent superhydrophobic coating was constructed on glass substrates using hydrophobic fumed silica (HF-SiO2) and waterborne polyurethane (WPU) as raw materials, combined with a simple spray-coating technique, resulting in a water contact angle (WCA) of 158.7 ± 1.5° and a sliding angle (SA) of 6.2 ± 1.8°. Characterization tests including SEM, EDS, LSCM, FTIR, and XPS revealed the presence of micron-scale protrusions and a nano-scale porous network composite structure on the surface. The presence of HF-SiO2 not only provided a certain roughness but also effectively reduced surface energy. More importantly, the coating exhibited excellent water-repellent properties, extremely low interfacial adhesion, self-cleaning ability, and high transparency, with the light transmittance of the coated glass substrate reaching 96.1% of that of the bare glass substrate. The series of functional characteristics demonstrated by the transparent superhydrophobic HF-SiO2@WPU coating designed and constructed in this study will play an important role in various applications such as underwater observation windows, building glass facades, automotive glass, and goggles.

Limosilactobacillus pontis (L. pontis) is a species of lactic acid bacteria (LAB) found in various products, including fermented milk, sourdough, and broiler chickens’ gastrointestinal tracts. However, the evolutionary strategies and genomic features of the species remain unknown, which limits its application. In this study, whole-genome sequencing was carried out to investigate the genomic characteristics and evolutionary strategies of L. pontis, combined with a comparative genomic approach, providing the necessary theoretical basis for its application. The genomic sequences in this study included three published genomic sequences and two strains isolated from fermented milk in our lab in Inner Mongolia, China. The mean genome size of the five L. pontis strains was 1.70 Mb, and the mean DNA G + C content was 53.06%. L. pontis was a species with higher G + C content in LAB. The phylogenetic evolutionary tree for the core genes showed that the strains from the same sources were aggregated into a cluster. There were some differences in the genomic information and phylogenetic relationships amongst L. pontis from different sources. An analysis of the annotation results identified differences in the functional genes, carbohydrate-active enzymes, and bacteriocins amongst different isolated strains, which were related to the environment. L. pontis was rich in glycosyltransferases, especially in strains isolated from fermented milk, indicating that they had higher sugar synthesis abilities. It is worth mentioning that only the L. pontis strains isolated in our laboratory identified the bacteriocin operon, which may increase its application potential. The genomic characteristics and evolutionary process of L. pontis were analyzed by comparative genomics, and this study explored the differences in the functional genes amongst the strains, aiming to provide new insights into the genetic characteristics and niche adaptations of L. pontis.

Obesity, characterized by the excessive accumulation of adipose tissue, has emerged as a major public health concern worldwide. To develop effective strategies for treating obesity, it is essential to comprehend the biological properties of different adipose tissue types and their respective roles in maintaining energy balance. Adipose tissue serves as a crucial organ for energy storage and metabolism in the human body, with functions extending beyond simple fat storage to encompass the regulation of energy homeostasis and the secretion of endocrine factors. This review provides an overview of the key characteristics, functional differences, and interconversion processes among white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue. Moreover, it delves into the molecular mechanisms and recent research advancements concerning the browning of WAT, activation of BAT, and whitening of BAT. Although targeting adipose tissue metabolism holds promise as a potential approach for obesity treatment, further investigations are necessary to unravel the intricate biological features of various adipose tissue types and elucidate the molecular pathways governing their interconversion. Such research endeavors will pave the way for the development of more efficient and targeted therapeutic interventions in the fight against obesity.

A high-intensity muon source driven by a continuous-wave superconducting linac holds the potential to significantly advance the intensity frontier of muon sources. Alongside advancements in accelerator technologies, breakthroughs in muon production target and collection schemes are essential. After a brief introduction to the development of the accelerator-driven system superconducting linac, a novel muon production target is proposed, utilizing a free-surface liquid lithium jet capable of handling the heat power generated by a proton beam with an energy of 600 MeV and a current of 5 mA. It is predicted by our simulation studies that the lithium target is more efficient in surface muon production compared to the rotating graphite target. The parameter space of the front end consisting of a lithium target and a large-aperture capture solenoid is explored, from the perspective of production efficiency, capture efficiency, and characteristics of the surface muon beam.

China’s delayed retirement policy will be prudently rolled out at the appropriate time, yet the public’s acceptance of this policy is concerning. To address this issue, our endeavor explores the impact of framing and anchoring effects on policy acceptance, aiming to mitigate the populace’s resistance to the new policy. We conducted two survey studies on the Chinese population aged 16–65. Achieved through an online survey, Study 1 (N = 225) demonstrated that information framing significantly influences the public’s acceptance of the delayed retirement policy. It was found that perceived fairness plays a mediating role between information framing and policy acceptance. Notably, the positive frame had a more pronounced effect on acceptance than its negative counterpart, with the positive presentation being perceived as more fair. Study 2 (N = 383), utilizing a combination of online and offline approaches, revealed that the anchoring effect moderates the relationship between information framing and perceived fairness. The interaction of anchoring and framing effects significantly influences perceived fairness, subsequently promoting public policy acceptance. The interplay between anchoring and framing effects significantly shapes perceived fairness, in turn bolstering the public’s receptiveness to policy. These insights offer reasonable communication strategies for the smooth advancement of new policies, further enriching the field of behavioral science.

Bioelectric field is a stimulated force to degrade xenobiotic pollutants in soils. However, the effect of bioelectric field on microplastics (MPs) aging is unclear. The degradation behavior of polyvinyl chloride (PVC), polyethylene (PE) and polylactic acid (PLA) was investigated in an agricultural soil microbial electrochemical system in which bioelectric field was generated in-situ by native microbes. Based on the density function theory, the energy gaps between the highest and the lowest occupied molecular orbitals of the three polymers with periodic structure were 4.20, 7.24 and 10.09 eV respectively, and further decreased under the electric field, indicating the higher hydrolysis potential of PLA. Meanwhile, the mass loss of PLA in the closed-circuit group (CC) was the highest on day 120, reaching 8.94%, which was 3.01–3.54 times of that without bioelectric field stimulation. This was mainly due to the enrichment of plastic-degrading bacteria and a robust co-occurrence network as the deterministic assembly process, e.g., the abundance of potential plastic-degrading bacteria on the surface of PLA and PVC in the CC increased by 1.92 and 1.30 times, respectively, compared to the open-circuit group. In terms of functional genes, the xenobiotic biodegradation and metabolism capacity of plasticsphere in the CC were stronger than that in soil, and determined by the bioaccessibility of soil nitrogen and carbon. Overall, this study explored the promoting effect of bioelectric field on the degradation of MPs and reveled the mechanism from quantum chemical calculations and microbial community analysis, which provides a novel perception to the in-situ degradation of MPs.

The incomplete silencing of exogenous transcription factors (TFs) and the lack of endogenous counterpart activation hampers the application of porcine induced pluripotent stem cells (piPSCs). We used porcine, bovine and murine TFs to reprogram porcine fetal fibroblasts. Porcine TFs-derived piPSCs (ppiPSCs) showed the highest levels of endogenous pluripotency markers activation, were able to differentiate into three germ layers and primordial germ cell-like cells (PGCLCs) and integrated into neural ectoderm of E7.5 mouse embryos in vitro. The bovine TFs derived piPSCs (bpiPSCs) expressed endogenous pluripotency markers higher than murine TFs derived piPSCs (mpiPSCs), but both had limited differentiation ability in vitro and depended on continuous expression of exogenous TFs for the maintenance. RNA sequencing confirmed ppiPSCs had distinct global transcriptional profiling, upregulated Hippo, PI3K-Akt, MAPK and relevant pluripotency signaling pathways as porcine blastocyst inner cell mass and expressed PGC early related genes. In addition, a positive and a negative correlation between exogenous and endogenous TFs’ expression level were observed in ppiPSCs and bpiPSCs lines, respectively. The TFs’ protein structures in pig were more similar to cattle than to mouse. In conclusion, the species affinity of the exogenous TFs is a key element, and the own species origin of TFs is optimal for iPSCs generation and application.

It is necessary to assess the appropriate dietary protein level of the forest musk deer (FMD), as nutritional needs are unclear. The microbiome in gastrointestinal tracts plays an important role in regulating nutrient utilization, absorption and host growth or development. Thus, we aimed to evaluate growth performance, nutrient digestibility and fecal microbiome of growing FMD supplied with different protein levels of diets. Eighteen 6-month-old male FMD with an initial weight 5.0 ± 0.2 kg were used in a 62-day trial. The animals were randomly distributed to three groups, the dietary crude protein (CP) level was 11.51% (L), 13.37% (M), and 15.48% (H). The results showed that the CP digestibility decreased as dietary CP level increased (p

In order to solve the problems of slow convergence and easiness to fall into local optimal solution in solving vehicle routing problem,an improved ant colony algorithm was proposed.Firstly,the saving matrix updating selection probability formula was introduced to guide ant search;Secondly,the piecewise function was used to improve the volatilization factor and adjust the convergence speed of the algorithm;Thirdly,the 2-opt method was used to improve the local search ability of the algorithm;Finally,the international general data set of vehicle routing problem was selected for simulation,and the control variable method was used to find the appropriate values of pheromone factor and heuristic function factor.The improvement effect of the algorithm was tested with class P data,and compared with basic ant colony algorithm,genetic algorithm,simulated annealing algorithm and particle swarm optimization algorithm.The results show that compared with the basic ant colony algorithm,the total length of the optimal path of the improved ant colony algorithm is reduced by [BF]6.97%[BFQ];Compared with genetic algorithm,simulated annealing algorithm and particle swarm optimization algorithm,the improved ant colony algorithm has stronger optimization ability and faster convergence speed.Therefore,the improved ant colony algorithm can effectively reduce the path length,jump out of the local optimization and accelerate the convergence speed.Especially in the case of a single route that allows more service points and discrete distribution of points,its advantages are more obvious,which provides a certain reference for solving the vehicle routing problem.[HQ]

With the development of network and the popularity of e-commerce, the network service industry has shown strong development potential, and many community e-commerce platforms have emerged as the times require. In order to ensure the profit of the supply chain of community e-commerce platform and supervise whether the suppliers of enterprises and grid station service providers try their best to participate in value co-creation, this paper introduces the delay parameter a of community e-commerce platform, constructs a three-party evolutionary game model of "community e-commerce platform-grid station service provider-supplier", simulates the strategies of each agent with matlab, studies the behaviours of community e-commerce platform under different delay parameters, and concludes that the delay parameter a of community e-commerce platform has a great influence on the timing of community e-commerce platform supervision. Finally, three suggestions are put forward for the supervision of the supply chain of community e-commerce platform: (1) encourage consumers to report; (2) formulate the reward and punishment system for the settled enterprises; (3) formulating a reasonable supervision system.

Followership is as crucial as leadership for organizational success. Significant efforts have been made by numerous researchers to examine how leadership influences followership; however, not enough attention has been paid to the influence of internal factors of followers on followership from the followers’ perspective. This study relies on identity theory to understand the relationship between the influence of followers’ perceived self-following traits (FTP) and followership prototype (FP) on followership, and the mediation role of self-efficacy in the relationship between FTP-FP consistency and followership. In order to avoid common method bias and ensure good discriminant validity of the variables, a two-wave time-lagged data collection design was used to collect 276 valid questionnaires from front-line business staff and junior supervisors in private and public sector organizations of China. Polynomial regression and response surface analysis were used to investigate the effect of FTP-FP consistency on followership. The empirical findings indicated that (1) the more consistent FTP-FP, the stronger the followership; (2) compared to the ‘low FTP-low FP’, employees with ‘high FTP-high FP’ had stronger followership; (3) employees with ‘high FTP-low FP’ had stronger followership than ‘low FTP-high FP’; (4) self-efficacy played a mediating role between FTP-FP consistency and followership. These findings contribute to management practice by revealing antecedents to followership from the perspective follower identity and the effect of follower identity on followership.

ObjectiveLymphagioma, which in most cases as benign tumors, occurs in head, neck, axilla, and mediastinum. Lymphangioma is exceedingly rare in the upper gastrointestinal tract including esophagus, stomach, and duodenum. However, the clinical characteristics, natural history, and recurrence rate after endoscopic resection remain unclear. This study aims to evaluate the characteristic findings and assess the efficacy of endoscopic techniques in the management of this disease.MethodsIn this systematic retrospective analysis, we evaluated all 24 cases of upper gastrointestinal lymphangioma resected by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and diagnosed by histopathology at our hospital from January 2012 to May 2021. We analyzed the results of endoscopy, endoscopic ultrasonography (EUS), CT, histologic examination, and follow-up assessments.Results9 male and 15 female patients with esophageal lymphangioma were enrolled in this study, with a mean age of 54.17 ± 11.60 years (range 30-71 years). The lesions’ size varied from 2.20 to 40.10 mm, with the median size of 7.83 mm. All patients were evaluated preoperatively, whose endoscopic appearance typically appears as dilated lymphatic channels beneath the surface epithelium of the protrude mucosal or sub-mucosal lesion. Endoscopic ultrasonography revealed the presence of a honeycomb-like or grid-like mass with a heterogeneous echo pattern, and a clear boundary between the lesion and the muscularis propria layer may be helpful for the primary diagnosis of this disease. 22 patients underwent EMR and 2 patient were treated with ESD. Histologic examination revealed that the lesions contained many dilated lymphatic vessels, which confirmed the initial diagnosis of lymphangioma in all patients. No major adverse events were found during the operation or a median follow-up of 43 months (range 13–92).ConclusionsEndoscopic ultrasonography has important clinical value for the primary diagnosis of lymphangioma in the upper gastrointestinal tract. This study also suggests that endoscopic resection should be considered as a more minimally invasive, safe, feasible, and effective therapeutic option comparing to laparoscopic surgery.

Ecological corridors (ECs) are important management tools to protect biodiversity by linking fragile habitats, especially for highly mobile organisms. ECs in terrestrial landscapes work as passages on land or in water. However, the significance of ECs to migratory species in estuaries has not been well elucidated. Based on annual fishery investigation in the Yangtze estuary and their dominance index rank, three of the top five species, including Larimochthys polyactis, Coilia mystus, and Gobiidae, exhibited absolute dominance in spring during the past 5 years. The temporal and spatial density variance of C. mystus supported its short-distance migration pattern. Redundancy analysis and the MaxEnt model predicted optimum habitats for C. mystus. C. mystus larvae survival was significantly related to salinity, total nitrogen, pH, reactive silicate, dissolved oxygen, surface water temperature, and chlorophyll-a in May and to salinity, surface water temperature, permanganate index, suspended particles, total nitrogen, and total phosphorus in August. The MaxEnt model predicted a broader longitudinal distribution range from offshore to the upstream freshwater area but narrower latitudinal distribution in the southern branch in May than in August. Finally, we delineated migratory corridors connecting optimum habitats for C. mystus using the least-cost route method. Optimum habitats close to the coastlines in the south branch might play a significant role in maintaining population or community connectivity in the Yangtze estuary. Our findings provide a perspective and method to quantify and facilitate the harmonious development of socioeconomy and fishery biodiversity conservation.

The adjustable bandgap, single crystal structure, and strong chemical inertness of GaN materials make them excellent candidates for water splitting applications. The fabrication of GaN nanostructures can enhance their water splitting performance by increasing their surface area, improving photon absorption, and accelerating photocatalytic reactions. Developing cost-effective methods to fabricate GaN nanostructures is crucial to promote the development of GaN-based materials in water splitting applications. In this review, we introduce the main cost-effective techniques for the fabrication of GaN nanostructures and highlight future development directions.

Although a high-quality homoepitaxial layer of 4H‑silicon carbide (4H-SiC) can be obtained on a 4° off-axis substrate using chemical vapor deposition, the reduction of defects is still a focus of research. In this study, several kinds of surface defects in the 4H-SiC homoepitaxial layer are systemically investigated, including triangles, carrots, surface pits, basal plane dislocations, and step bunching. The morphologies and structures of surface defects are further discussed via optical microscopy and potassium hydroxide-based defect selective etching analysis. Through research and analysis, we found that the origin of surface defects in the 4H-SiC homoepitaxial layer can be attributed to two aspects: the propagation of substrate defects, such as scratches, dislocation, and inclusion, and improper process parameters during epitaxial growth, such as in-situ etch, C/Si ratio, and growth temperature. It is believed that the surface defects in the 4H-SiC homoepitaxial layer can be significantly decreased by precisely controlling the chemistry on the deposition surface during the growth process.

The 2020–2025 Dietary Guidelines for Americans (DGA) recommends less than 10% of total daily calories come from added sugars. However, many adults overconsume added sugars putting them at risk for poor health outcomes. We examined characteristics of high added sugars consumers among US adults (≥20 years) and described their top 10 sources of added sugars intake using National Health and Nutrition Examination Survey 2015–2018 data (n = 9647). We defined high consumers as consuming >15% of daily calories from added sugars (1.5 times higher than the DGA). We used the National Cancer Institute method to estimate usual intake of energy and percent of calories from added sugars. Top 10 sources were identified based on their percentage contribution to total added sugars intake on a given day. T-tests were used to examine differences by age, sex, race/ethnicity, education, income, marital status, and weight status. Overall, mean usual total energy intake and added sugars intake was 2068 kcal/day and 264 kcal/day, respectively, and 30% of adults were classified as high consumers. The prevalence of high added sugars consumers was significantly higher among 20–30-year-olds (29%), 31–50-year-olds (33%), and 51–70-year-olds (29%) than those aged ≥70 years (22%); non-Hispanic Black (39%) and non-Hispanic White (31%) adults than Hispanics (26%); adults with

Background: High consumption of added sugars is related to adverse health consequences. Objective: The objective of this study was to examine characteristics of US youth who report high intakes of added sugars, as well as the eating occasions and top sources of added sugars that contributed to intakes among consumers with high added sugars intake. Design and participants/setting: We conducted a cross-sectional study using 2015–2018 NHANES data among 5280 US youths (2–19 years). Main outcome measures: Outcome measure was usual percent of calories from added sugars using 2 days of dietary recall based on the National Cancer Institute method. High consumers were defined as consuming greater than 15% of total daily calorie intake from added sugars (1.5 times higher than the 2020–2025 Dietary Guidelines for Americans recommendation of t-tests to compare mean differences between sociodemographic groups. Results: Overall, 34% of US youths were classified as high consumers of added sugars. The prevalence of high consumers of added sugars significantly varied by some sociodemographics (i.e., age, race/ethnicity, and head of household’s education level). The prevalence of high added sugars consumers was significantly greater among 12–19-year-olds (41%) and 6–11-year-olds (37%) compared to 2–5-year-olds (19%), non-Hispanic Black (42%) and non-Hispanic White (42%) persons compared to Hispanic persons (19%), and those with a head of household’s education level of high school/some college (40%) compared to households with college degree or higher (29%). The prevalence of high consumers did not differ by sex, income, or weight status. Of eating occasions, the amount of added sugars youths consumed was highest during snack occasions among high consumers. Top five sources of added sugars among high consumers on a given day were sweetened beverages, sweet bakery products, candy, other desserts, and ready-to-eat cereals. Conclusion: One in three US youths consumed more than 15% of total calories from added sugars. High added sugars intake was more prevalent among certain subgroups such as 12–19-year-olds and non-Hispanic Black or non-Hispanic White youth. Our findings can provide information for intervention efforts to decrease added sugars intake to promote child health.

In this study, Co-doped TiO2 was synthesized using waste tobacco stem silk (TSS) as a template via a one-pot impregnation method. These samples were characterized using various physicochemical techniques such as N2 adsorption/desorption analysis, diffuse reflectance UV–visible spectroscopy, X-ray diffraction, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, photoluminescence spectroscopy, and electron paramagnetic resonance spectroscopy. The synthesized material was used for the photodegradation of tetracycline hydrochloride (TCH) under visible light (420–800 nm). No strong photodegradation activity was observed for mesoporous TiO2 synthesized using waste TSS as a template, mesoporous Co-doped TiO2, or TiO2. In contrast, Co-doped mesoporous TiO2 synthesized using waste TSS as a template exhibited significant photocatalytic degradation, with 86% removal of TCH. Moreover, owing to the unique chemical structure of Ti-O-Co, the energy gap of TiO2 decreased. The edge of the absorption band was redshifted, such that the photoexcitation energy for generating electron–hole pairs decreased. The electron–hole separation efficiency improved, rendering the microstructured biotemplated TiO2 a much more efficient catalyst for the visible-light degradation of TCH.

Pluripotent stem cells (PSCs) have the potential to differentiate to all cell types of an adult individual and are useful for studying mammalian development. Establishing induced pluripotent stem cells (iPSCs) capable of expressing pluripotent genes and differentiating to three germ layers will not only help to explain the mechanisms underlying somatic reprogramming but also lay the foundation for the establishment of sheep embryonic stem cells (ESCs) in vitro. In this study, sheep somatic cells were reprogrammed in vitro into sheep iPSCs with stable morphology, pluripotent marker expression, and differentiation ability, delivered by piggyBac transposon system with eight doxycycline (DOX)-inducible exogenous reprogramming factors: bovine OCT4, SOX2, KLF4, cMYC, porcine NANOG, human LIN28, SV40 large T antigen, and human TERT. Sheep iPSCs exhibited a chimeric contribution to the early blastocysts of sheep and mice and E6.5 mouse embryos in vitro. A transcriptome analysis revealed the pluripotent characteristics of somatic reprogramming and insights into sheep iPSCs. This study provides an ideal experimental material for further study of the construction of totipotent ESCs in sheep.

Abstract Interest Flooding Attack (IFA) is one of the main security threats for the Named Data Networking (NDN). Most of its existing countermeasures enable intermediate routers near the attackers to independently detect the attack and consider the typical attack scenario in which attackers directly send malicious Interests at a constant and relatively high rate after the attack starts. Moreover, they may also throttle legitimate Interests when enforcing the existing defense measures at intermediate routers as it is still difficult for them to distinguish the Interests issued by attackers from those issued by legitimate consumers. Instead, this work aims at a more sophisticated attack scenario in which attackers start the attack at a relatively lower rate but gradually speed up to keep the Pending Interest Tables (PITs) of the victims increasing to finally deplete the PIT resources for legitimate consumers. It is relatively difficult for intermediate routers to independently and timely detect such a sophisticated IFA. To solve this problem, we propose a mechanism to detect and mitigate the sophisticated IFA from the network-wide view, dubbed as DMNWV. In DMNWV, a central controller monitors the network and makes a comprehensive and prompt decision on whether there is an ongoing IFA based on the overall state of the whole network collected from the abnormity information reports sent by the first-hop routers of attackers. Attack sources can be directly located after an IFA is determined, and then the routers directly connected to attackers (i.e., access routers) can take targeted measures based on the located attackers to prevent malicious Interest from entering the network without throttling legitimate Interests. We conduct an experimental study to evaluate the performance of DMNWV, explore the parameter settings of the attack detection algorithm at access routers, and measure the communication overhead of the central controller. The experimental results validate that DMNWV can timely detect and mitigate the sophisticated IFA without throttling requests from legitimate consumers with significantly low communication overhead of the central controller, which will not bring about too much burden to the network.

Summary: Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca2+, warm temperature, and oxidative stress. It is critically involved in physiological and pathological processes ranging from inflammation to stroke to neurodegeneration. At present, the channel’s gating and ion permeation mechanisms, such as the location and identity of the selectivity filter, remain ambiguous. Here, we report the cryo-electron microscopy (cryo-EM) structure of human TRPM2 in nanodisc in the ligand-free state. Cryo-EM map-guided computational modeling and patch-clamp recording further identify a quadruple-residue motif as the ion selectivity filter, which adopts a restrictive conformation in the closed state and acts as a gate, profoundly contrasting with its widely open conformation in the Nematostella vectensis TRPM2. Our study reveals the gating of human TRPM2 by the filter and demonstrates the feasibility of using cryo-EM in conjunction with computational modeling and functional studies to garner structural information for intrinsically dynamic but functionally important domains.

As a leading cause of vision impairment of the retina, macular edema (ME) has one of the highest clinical demands for treatment. Current treatment of ME relies heavily on invasive techniques resulting in complications and poor patient compliance. To enhance the efficiency of triamcinolone acetonide as eye drop to the posterior segment of the eye, we developed and characterized a novel formulation, namely, triamcinolone acetonide chitosan-coated liposomes (TA-CHL), prepared by the calcium acetate gradient method with some modifications. TA-CHL provided the mean particle size of 135.46 ± 4.49 nm and high entrapment efficiency (90.66 ± 3.21%), exhibited a sustained release profile, excellent physical stability, and no significant toxicity on cornea, conjunctiva, and retina. Optical coherence tomography system (OCT) was used to detect pharmacokinetics of CHL in vivo, indicating that CHL had good potency for drug delivery. Cellular uptake experiments showed CHL had the higher transduction efficiency into HCEC and ARPE-19 than liposomes. TA-CHL was shown to be potentially effective eye drop to contribute to the posterior segment of the eye.

Wheat germ and fish skin usually has not been completely utilized and sometimes may be discarded, thus causing a lot of waste. Here, we aim at exploring the therapeutic anti-inflammatory effects of protease hydrolysates of wheat germ and fish skin on the ulcerative colitis (UC) mice. In the current study, wheat germ protein hydrolysates (WGPH) and fish skin gelatin hydrolysates (FSGH) treated mice had a longer colon than the DSS-induced mice. Moreover, protease hydrolysates reversed DSS-induced gut dysbiosis. Protease hydrolysates were likely to shift the balance of the intestinal flora on inflammation. In summary, these findings suggested that protease hydrolysates might serve as a latent therapy for UC treatment.

Abstract Background Extracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release. Methods Human monocyte-derived macrophage primary cultures and a BV2 microglia cell line were used to represent the innate immune cells in the CNS. Transmission electron microscopy, nanoparticle tracking analysis, and Western blots were used to determine the EV regulation. GLS1 overexpression was performed using an adenovirus vector in vitro and transgenic mouse models in vivo. Data were evaluated statistically by ANOVA, followed by the Bonferroni post-test for paired observations. Results Our data revealed an increased release of EVs in GLS1-overexpressing HeLa cells. In HIV-1-infected macrophages and immune-activated microglia BV2 cells, treatment with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) or CB839, two specific GLS inhibitors, significantly decreased EV release, suggesting a critical role of GLS1 in EV release. Furthermore, addition of α-ketoglutarate or ceramide rescued EV release during BPTES treatment, implicating α-ketoglutarate and ceramide as critical downstream effectors for GLS inhibitors. These findings were further corroborated with the investigation of brain tissues in GLS1-transgenic mice. The EV levels were significantly higher in GLS1 transgenic mice than those in control mice, suggesting that GLS1 increases EV release in vivo. Conclusions These findings suggest that GLS1-mediated glutaminolysis and its downstream production of α-ketoglutarate are essential in regulating EV release during HIV-1 infection and immune activation. These new mechanistic regulations may help understand how glutamine metabolism shapes EV biogenesis and release during neuroinflammation.

The coexistence of pollutants presents a great challenge to the implementation of photocatalysts. In this work, a novel MIL-101(Fe)/TiO2 composite prepared by in situ growth of MIL-101(Fe) on TiO2 was developed for the synergetic oxidation of MC-LR and Cr(VI) reduction. The heterojunction material shows elevated photocatalytic behavior under ultraviolet compared with the unary pollutant system. Furthermore, quenching experiments and electron spin resonance confirm that the enhanced photodegradation behavior is related to the synergistic effect between the photocatalytic reduction and oxidation process, in which MC-LR consumes the holes and Cr(VI) captures electrons, followed by efficient charge separation through the conventional double-transfer mechanism between MIL-101(Fe) and TiO2. This investigation provides a deeper understanding of the construction of MOFs/semiconductor heterojunctions for the pollutants removal in multi-component contaminants system.

Metolachlor is extensively used and the most persistent chloroacetamide herbicide, thereby which its metabolites have been frequently detected in soils and surface and groundwaters. Microbial degradation is predominantly responsible for the removal of metolachlor from soil and water. However, few microbial strains reported previously are highly efficient in degrading potentials for metolachlor. We isolated the fungal strain MET-F-1 from an activated sludge, characterized as Penicillium oxalicum, which could degrade 88.6% of 50 mg/L metolachlor coupled with 0.1% glucose plus 0.1% yeast extract within 384 h under optimal conditions. Compared with metabolites produced by previously isolated microorganisms, different degradation products, i.e., MOXA, M2H, and MDES, detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), were produced through hydrolytic and reductive dechlorination by MET-F-1. This is the first report on the degradation of metolachlor by Penicillium oxalicum sp. Furthermore, field plot experiments using the wheat bran inoculum method were performed and demonstrated good metolachlor-degrading activity of this strain. This study serves as a steppingstone to promote MET-F-1 strain usage as a promising agent for metolachlor-contaminated soil remediation.

Most hinnies (female donkey×male horse) and mules (female horse×male donkey) are sterile with few reports of equine fertile hybrids. The main cause of this sterility is thought to be a meiotic block to spermatogenesis and oogenesis. This study compared the developmental features of the testes and a histological analyses of spermatogenesis in a male hinny with those of a normal, fertile stallion and Jack donkey. Hinny testes showed a thicker tunica albuginea, fewer blood vessels and more connective tissue in the testis parenchyma than those of the stallion and Jack donkey. Although the mean number of seminiferous tubules was significantly higher in stallion and hinny than Jack donkey (p

ABSTRACT G protein-coupled receptors (GPCRs) are involved in all human physiological systems where they are responsible for transducing extracellular signals into cells. GPCRs signal in response to a diverse array of stimuli including light, hormones, and lipids, where these signals affect downstream cascades to impact both health and disease states. Yet, despite their importance as therapeutic targets, detailed molecular structures of only 30 GPCRs have been determined to date. A key challenge to their structure determination is adequate protein expression. Here we report the quantification of protein expression in an insect cell expression system for all 826 human GPCRs using two different fusion constructs. Expression characteristics are analyzed in aggregate and among each of the five distinct subfamilies. These data can be used to identify trends related to GPCR expression between different fusion constructs and between different GPCR families, and to prioritize lead candidates for future structure determination feasibility.

The degradation mechanism of mid-power GaN-based white LEDs were investigated by using the in-situ multi-functional accelerated aging tests. The changes of the luminous flux and the chromaticity shift during the stress time show some correlations. To quantitatively analyze the degradation behavior, a composite model considering the luminous flux increasing and decreasing mechanisms was proposed and the results agree well with the experiments in the entire aging time. Furthermore, different analytical technologies have been used to understand the cause of luminous flux degradation and chromaticity shift. The results show that the chromaticity shift was mainly due to the phosphors deterioration, while the serious degradation of luminous flux was the overall effects from the package, including the phosphors deterioration and oxidation of silicone encapsulant.

Lung cancer is the leading cause of death from cancer in the world. The treatment remains one of the most challenging tasks in the medical world. The discovery and development of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) have had a major impact in the treatment of non small cell lung cancer (NSCLC). But the efficacy of EGFR-TKI in EGFR wild-type patients is limited, and the limited EGFR mutation incidence also prompts researchers to study what is the best treatment choice for patients with NSCLC who are negative for EGFR mutations. This review will discuss the research status in treatment choice for EGFR wild-type NSCLC.

In this work, efficiency droop of InGaN/GaN multiple-quantum-well LEDs with super wide well (WW) is discussed by comparing the external quantum efficiency (EQE) of GaN grown on sapphire and FS-GaN substrates. The luminescence and electrical characteristics of these WW LEDs are also experimentally and theoretically analyzed. With the increase of well width from 3 nm to 6 nm, high V-pits density and more strain relaxation are found in WW LED on sapphire, which exhibits greatly reduced peak efficiency but almost negligible droop behavior. In contrast, despite a larger polarization field, WW LED on FS-GaN shows obviously enhanced peak efficiency and comparable droop compared to the counterpart with 3-nm well. The Auger recombination probably dominates the mechanism of efficiency droop rather than defect-related nonradiative recombination or polarization effect in the WW LED on both sapphire and FS-GaN, especially at high current density.

The degradation behaviors of high power GaN-based vertical blue LEDs on Si substrates were measured using in-situ accelerated life test. The results show that the dominant failure mechanism would be different during the operation. Besides that, the corresponding associated failure mechanisms were investigated systematically by using different analysis technologies, such as Scan Electron Microscopy, Reflectivity spectroscopy, Transient Thermal Analysis, Raman Spectra, etc. It is shown that initially, the failure modes were mainly originated from the semiconductor die and interconnect, while afterwards, the following serious deterioration of the radiant fluxes was attributed to the package. The interface material and quality, such as die attach and frame, play an important role in determining the thermal performance and reliability. In addition, the heating effect during the operation will also release the compressive strain in the chip. These findings will help to improve the reliability of GaN-based LEDs, especially for the LEDs with vertical structure.

Anoctamin 6 (Ano6) belongs to a conserved gene family (TMEM16) predicted to code for eight transmembrane proteins with putative Ca2+-activated chloride channel (CaCC) activity. Recent work revealed that disruption of ANO6 leads to a blood coagulation defect and impaired skeletal development. However, its function in skeletal muscle cells remains to be determined. By using a RNA interference mediated (RNAi) loss-of-function approach, we show that Ano6 regulates C2C12 myoblast proliferation. Ano6 is highly expressed in C2C12 myoblasts and its expression decreases upon differentiation. Knocking down Ano6 significantly reduces C2C12 myoblast proliferation but has minimal effect on differentiation. Ano6 deficiency significantly reduces ERK/AKT phosphorylation, which has been shown to be involved in regulation of cancer cell proliferation by another Anoctamin member. Taken together, our data demonstrate for the first time that Ano6 plays an essential role in C2C12 myoblast proliferation, likely via regulating the ERK/AKT signaling pathway.

Blastocyst injection and morula aggregation are commonly used to evaluate stem cell pluripotency based on chimeric contribution of the stem cells. To assess the protocols for generating chimeras from stem cells, 8-cell mouse embryos were either injected or cocultured with mouse embryonic stem cells and induced pluripotent stem cells, respectively. Although a significantly higher chimera rate resulted from blastocyst injection, the highest germline contribution resulted from injection of 8-cell embryos with embryonic stem cells. The fully agouti colored chimeras were generated from both injection and coculture of 8-cell embryos with embryonic stem cells. Additionally, microsatellite DNA screening showed that the fully agouti colored chimeras were fully embryonic stem cell derived mice. Unlike embryonic stem cells, the mouse chimeras were only generated from injection of 8-cell embryos with induced pluripotent stem cells and none of these showed germline transmission. The results indicated that injection of 8-cell embryos is the most efficient method for assessing stem cell pluripotency and generating induced pluripotent stem cell chimeras, embryonic stem cell chimeras with germline transmission, and fully mouse embryonic stem cell derived mice.

Mononuclear phagocytes (MP, macrophages and microglia), the main targets of HIV-1 infection in the brain, play a pathogenic role in HIV-associated neurocognitive disorders (HAND) through the production and release of various soluble neurotoxic factors including glutamate. We have previously reported that glutaminase (GLS), the glutamate-generating enzyme, is upregulated in HIV-1 infected MP and in the brain tissues of HIV dementia individuals, and that HIV-1 or interferon-α (IFN-α) regulates human glutaminase 1 (GLS1) promoter through signal transducer and activator of transcription 1 (STAT1) phosphorylation in macrophages. However, there are multiple putative STAT1 binding sites in human GLS1 promoter, the exact molecular mechanism of how HIV-1 or IFN-α regulates human GLS1 promoter remains unclear. To further study the function of the putative STAT1 binding sites, we mutated the sequence of each binding site to ACTAGTCTC and found that six mutants (mut 1,3,4,5,7,8) had significantly higher promoter activity and two mutants (mut 2 and mut 6) completely lost the promoter activity compared with the wild type. To determine whether sites 2 and 6 could interfere with other inhibitory sites, particularly the nearby inhibitory sites 3 and 5, we made double mutants dmut 2/3 and dmut 5/6, and found that both the double mutants had significantly higher activity than the wild type, indicating that sites 3 and 5 are critical inhibitory elements, while sites 2 and 6 are excitatory elements. ChIP assay verified that STAT1 could bind with sites 2/3 and 5/6 within human GLS1 promoter in IFN-α stimulated or HIV-1-infected monocyte-derived macrophages. Interestingly, we found that rat Gls1 promoter was regulated through a similar way as human GLS1 promoter. Together, our data identified critical elements that regulate GLS1 promoter activity.

HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN) α specifically activated the glutaminase 1 (GLS1) promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1) phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1) mRNA levels in HIV associated-dementia (HAD) individuals correlate with STAT1 (p