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Objective: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. β-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of β-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism. Methods: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and β-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis. Results: The loss of β-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1β) factors in condylar cartilage were increased in β-arrestin2 null mice compared with WT mice. Moreover, the loss of β-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA. Conclusion: In conclusion, we demonstrated for the first time that β-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, β-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage. [ABSTRACT FROM AUTHOR]

Fungal non-ribosomal peptide synthetase (NRPS)-encoding products play a paramount role in new drug discovery. Fusarium, one of the most common filamentous fungi, is well-known for its biosynthetic potential of NRPS-type compounds with diverse structural motifs and various biological properties. With the continuous improvement and extensive application of bioinformatic tools (e.g., anti-SMASH, NCBI, UniProt), more and more biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) have been identified in Fusarium strains. However, the biosynthetic logics of these SMs have not yet been well investigated till now. With the aim to increase our knowledge of the biosynthetic logics of NPRS-encoding products in Fusarium, this review firstly provides an overview of research advances in elucidating their biosynthetic pathways. [ABSTRACT FROM AUTHOR]

Selective dehydrogenative silylation is one of the most valuable tools for synthesizing organosilicon compounds. In this study, a regio- and stereoselective ruthenium-catalyzed dehydrogenative intermolecular silylation was firstly developed to access (E)-alkenyl silyl-ether derivatives and silyl-ether heterocycles with good functional group tolerance. Furthermore, two pathways for RuH2(CO)(PPh3)3/NBE-catalyzed dehydrogenative intermolecular silylation of alcohols and alkenes as well as intermolecular silylation of naphthol derivatives were investigated with H2SiEt2 as the hydrosilane reagent. [ABSTRACT FROM AUTHOR]

Fluorescence imaging flow cytometry (IFC) has been demonstrated as a crucial biomedical technique for analyzing specific cell subpopulations from heterogeneous cellular populations. However, the high-speed flow of fluorescent cells leads to motion blur in cell images, making it challenging to identify cell types from the raw images. In this study, we present a real-time single-cell imaging and classification system based on a fluorescence microscope and deep learning algorithm, which is able to directly identify cell types from motion-blur images. To obtain annotated datasets of blurred images for deep learning model training, we developed a motion deblurring algorithm for the reconstruction of blur-free images. To demonstrate the ability of this system, deblurred images of HeLa cells with various fluorescent labels and HeLa cells at different cell cycle stages were acquired. The trained ResNet achieved a high accuracy of 96.6% for single-cell classification of HeLa cells in three different mitotic stages, with a short processing time of only 2 ms. This technology provides a simple way to realize single-cell fluorescence IFC and real-time cell classification, offering significant potential in various biological and medical applications. [ABSTRACT FROM AUTHOR]

Fungal microbes are important in the creation of new drugs, given their unique genetic and metabolic diversity. As one of the most commonly found fungi in nature, Fusarium spp. has been well regarded as a prolific source of secondary metabolites (SMs) with diverse chemical structures and a broad spectrum of biological properties. However, little information is available concerning their derived SMs with antimicrobial effects. By extensive literature search and data analysis, as many as 185 antimicrobial natural products as SMs had been discovered from Fusarium strains by the end of 2022. This review first provides a comprehensive analysis of these substances in terms of various antimicrobial effects, including antibacterial, antifungal, antiviral, and antiparasitic. Future prospects for the efficient discovery of new bioactive SMs from Fusarium strains are also proposed. [ABSTRACT FROM AUTHOR]

The market-oriented real estate development model has occupied a leading position in the urban renewal activities in Shenzhen and the regeneration of the old city has shown serious stagnation under the intertwined interests of multiple subjects. This study took the Mutoulong Community (Shenzhen, China), Luohu District as an example to resolve and analyze the project promotion process and explore the core problems of the old city regeneration in Shenzhen. The results showed that the internal contradictions and conflicts between the owners of different factions were the core problem of stagnation in the old city regeneration. In addition, from the case study on the application of a third-party professional force in Hubei New Village (Shenzhen, China), Shenzhen and the project that funded the building in Macao Special Administrative Region (SAR), the results show that the third-party professional forces are professional, nonprofit, and prioritized public interests, which could effectively balance the cognitive differences between the owners of different factions in the planning policy, design scheme, and implementation, which helped to build trust between the owners and other subjects. In addition, the third-party professional forces with a resident composition will help to resolve the complex ownership relationships and effectively promote the development of the old city regeneration projects. [ABSTRACT FROM AUTHOR]

The development of the county economy in China is a complicated process that is influenced by many factors in different ways. This study is based on multi-source big data, such as Tencent user density (TUD) data and point of interest (POI) data, to calculate the different influencing factors, and employed a multiscale geographically weighted regression (MGWR) model to explore their spatial non-stationarity impact on China's county economic development. The results showed that the multi-source big data can be useful to calculate the influencing factor of China's county economy because they have a significant correlation with county GDP and have a good models fitting performance. Besides, the MGWR model had prominent advantages over the ordinary least squares (OLS) and geographically weighted regression (GWR) models because it could provide covariate-specific optimized bandwidths to incorporate the spatial scale effect of the independent variables. Moreover, the effects of various factors on the development of the county economy in China exhibited obvious spatial non-stationarity. In particular, the Yangtze River Delta, the Pearl River Delta, and the Beijing-Tianjin-Hebei urban agglomerations showed different characteristics. The findings revealed in this study can furnish a scientific foundation for future regional economic planning in China. [ABSTRACT FROM AUTHOR]

Feeding time is an important factor affecting the physiological activity and feeding rhythm of crustaceans. However, little is known about the factors and mechanisms contributing to variations in feeding time in aquatic species or their impacts. Moreover, the gut microbiome largely affects host physiology and is associated with diet. To investigate the effects of different feeding times on the composition of intestinal bacterial communities, high-throughput 16S rRNA sequencing was used to monitor the gut bacteria of the Chinese mitten crab Eriocheir sinensis over a 10-day period under different feeding times: 06:00 h, 12:00 h, 18:00 h, and 24:00 h. Weight gain of the day-fed groups was significantly higher than that of the night-fed groups. Two probiotics, Akkermansia muciniphila and Faecalibacterium prausnitzii, were detected in the intestines of crabs in the 12:00 group. In addition, the diversity and richness of the flora in the 12:00 group were slightly higher than those in the other treatment groups. These results collectively indicate that different feeding times change the intestinal flora composition of Chinese mitten crabs, and further identified specific feeding times associated with a more significant weight gain effect. Our findings provide important insights into improving farming strategies for Chinese mitten crabs. [ABSTRACT FROM AUTHOR]

A convenient and practical pathway to 2-cyano and 2-ester anilines is described via efficient and selective copper(II)-catalyzed reductive amination via hydrosilylation process. Both 2-cyano and 2-ester anilines were successfully synthesized with good functional group tolerance and high selectivity. The application of the 2-cyano and -iodine containing anilines was developed in the synthesis of indoloindole derivatives via CuSO4-catalyzed N -benzylation and cyclization reaction in 'one pot'. More interestingly, the photophysical property investigations of these 2-cyano and 2-ester containing anilines exhibit excellent fluorescent properties, which have great potential application in the development of interesting near-ultraviolet optical devices in the near future. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3) combustion has received increasing attention for its carbon-free nature. However, the utilization of ammonia in engines is constrained by its relatively low reactivity. To overcome this shortcoming, ammonia blending with high-reactivity fuels has been used. In the present work, direct numerical simulation (DNS) of ammonia/n-heptane dual-fuel combustion was performed to understand the effects of ammonia addition on the combustion behavior of n-heptane sprays. Three DNS cases with NH 3 energy ratios of 0%, 20%, and 40% were considered. Two-stage combustion was observed in all cases. It was found that both the first-stage and second-stage ignition delay times increase with increasing NH 3 energy ratio, and the peak of mean heat release rate (HRR) reduces with increasing NH 3 energy ratio. For low-temperature combustion, ignition kernels were observed in the case with pure n-heptane while ignition occurs almost volumetrically in the cases with NH 3 addition. The reaction zone of the cases with NH 3 addition is thicker compared to that of the case with pure n-heptane. The reactions of NH 3 involve radicals, such as OH, which affects the low-temperature combustion of n-heptane. In the stage of high-temperature combustion, individual ignition kernels with significant heat release rate were observed in the cases with NH 3 addition, where the reaction zones are thin. In contrast, for the case with pure n-heptane, large heat release rate occurs simultaneously over the entire domain with thick reaction zones. Ignition occurs in regions characterized by low scalar dissipation rate for both low-temperature and high-temperature combustion in all cases. It was found that, though the contributions of NH 3 -related reactions to the total HRR are noticeable, the contributions of important elementary reactions to the total HRR in pure n-heptane combustion still prevail in the cases with NH 3 addition, which indicates that n-heptane chemistry dominates that of NH 3 in this work. • DNS of turbulent ammonia/n-heptane dual-fuel combustion were studied for the first time. • The impact of NH 3 addition on the combustion behavior of n-heptane sprays was examined. • The evolutions of the reaction zones in various cases were analyzed. • The interactions of ammonia and n-heptane were explored in terms of elementary reactions. [ABSTRACT FROM AUTHOR]

This paper proposes a novel general sixth-generation (6G) irregular-shaped geometry-based stochastic model (IS-GBSM) for millimeter wave (mmWave) massive multiple-input multiple-output (MIMO) wireless communication systems. The proposed IS-GBSM can model spherical wavefront propagation, high delay resolution, and three-dimensional (3D) space-time-frequency non-stationarity of channels with time-space consistency, and thus can be applied to integrated communication and sensing systems. To capture the 3D non-stationarity with channel consistency, a new hybrid method combining geometric and parametric methods is developed. Based on the geometric method, i.e., visibility region (VR), the smooth and consistent appearance and disappearance of clusters during array-time evolution are modeled. With the help of the parametric method, a frequency-dependent path gain is introduced, and a visible factor based on uniform continuity theorem and bounded variation function is further proposed to capture the soft cluster power handover during cluster array-time evolution. Key channel statistics of the proposed IS-GBSM are derived and investigated. Simulation results demonstrate that the space-time-frequency non-stationarity is modeled and time-space consistency is captured. Finally, the utility of the proposed IS-GBSM is verified by the excellent agreement between simulation results and measurement. [ABSTRACT FROM AUTHOR]

In this paper, we propose a three-dimensional (3D) cluster-based model for the fifth generation (5G)/beyond 5G (B5G) vehicle-to-vehicle (V2V) massive multiple-input multiple-output (MIMO) wideband channels. It is the first cluster-based irregular shaped geometry-based stochastic model (IS-GBSM) to distinguish the dynamic clusters and static clusters in vehicular massive MIMO communication scenarios. This model not only considers the high time-variance, the time non-stationarity, and the vehicular traffic density (VTD) of V2V channels, but also models the massive MIMO channel characteristics, such as spherical wavefronts by 3D vector calculation and space non-stationarity. Meanwhile, this model for the first time integrates the VTD into birth-death process to model the channel characteristics of V2V and massive MIMO jointly and deeply, where a novel VTD-combined time-array cluster evolution algorithm for 5G/B5G V2V massive MIMO channel model is developed. Based on the proposed model, we derive some expressions of channel statistical properties, including time-space-frequency correlation function (STF-CF) and Doppler power spectral density (DPSD). The influence of several parameters, e.g., VTDs, vehicle moving directions, and antenna spacings, on the channel characteristics are sufficiently explored, which can provide assistance for the design of vehicular massive MIMO communication systems. Finally, the utility of the proposed model is verified by the close agreement between simulation results and measurement data. [ABSTRACT FROM AUTHOR]

Unsupervised Domain Adaptation (UDA) makes predictions for the target domain data while labels are only available in the source domain. Lots of works in UDA focus on finding a common representation of the two domains via domain alignment, assuming that a classifier trained in the source domain can be generalized well to the target domain. Thus, most existing UDA methods only consider minimizing the domain discrepancy without enforcing any constraint on the classifier. However, due to the uniqueness of each domain, it is difficult to achieve a perfect common representation, especially when there is low similarity between the source domain and the target domain. As a consequence, the classifier is biased to the source domain features and makes incorrect predictions on the target domain. To address this issue, we propose a novel approach named reducing bias to source samples for unsupervised domain adaptation (RBDA) by jointly matching the distribution of the two domains and reducing the classifier's bias to source samples. Specifically, RBDA first conditions the adversarial networks with the cross-covariance of learned features and classifier predictions to match the distribution of two domains. Then to reduce the classifier's bias to source samples, RBDA is designed with three effective mechanisms: a mean teacher model to guide the training of the original model, a regularization term to regularize the model and an improved cross-entropy loss for better supervised information learning. Comprehensive experiments on several open benchmarks demonstrate that RBDA achieves state-of-the-art results, which show its effectiveness for unsupervised domain adaptation scenarios. • A novel method named RBDA is proposed for domain adaptation. • RBDA focuses on reducing the classifier's bias to source samples. • Comprehensive experiments demonstrate the effectiveness of RBDA. [ABSTRACT FROM AUTHOR]

This study aimed to develop a prognostic model for clear cell renal cell carcinoma (ccRCC) based on transcriptome analysis. We screened Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database for gene expression data and clinical characteristics of ccRCC. After differentially expression analysis, we identified 533 key genes of the development of ccRCC. Next, a weighted gene co-expression network analysis (WGCNA) was executed to investigate the association between differentially expressed genes and clinical characteristics. Then, based on protein–protein interaction (PPI) network, least absolute shrinkage and selection operator (LASSO) regression and Cox regression, a four-gene (COL4A5, ABCB1, NR3C2 and PLG) prognostic model has been constructed in TCGA training cohort. Finally, we examined the predictive power of this model with survival analysis and receiver operating characteristic (ROC) curve both in training cohort and in validation cohorts. And we found this model was significantly correlated with infiltrating immune cells. The four-gene prognosis model could be a potential prediction tool with high accuracy and reliability for ccRCC patients. • The differentially expressed genes between ccRCC and normal tissues were analyzed across different transcriptomic platforms. • A four-gene prognostic model was constructed for the first time and could be a potential prediction tool for ccRCC patients. • The four-gene prognostic model was correlated with the infiltration of immune cells and immune checkpoint molecules. [ABSTRACT FROM AUTHOR]

In this study, Polyethyleneimine (PEI) was utilized to modulate the electronegativity of carbon nanotubes (CNTs) through a mild method to promote its electrocatalytic performance for electrosynthesis of H2O2. The characterization results indicate the co-doping of oxygen and nitrogen elements and the CNTs-80 (modification temperature was 80 °C) catalyst exhibited the highest content of nitrogen (4.05%) and OII functional groups (73.5%). Accordingly, the GF/CNTs-80/PTFE cathode exhibited the highest H2O2 yield of 116.34 mg L−1 at pH 7, suggesting that the introduction of nitrogen and oxygen-containing functional groups (carboxyl and ether groups) effectively enhances its 2e− ORR performance. Furthermore, a more positive surface potential and reduced diffusion resistance were conducive to the electrochemical generation of H2O2. This research contributes to the understanding of surface potential modulation and highlights the potential of PEI-modified CNTs cathodes for efficient H2O2 electrogeneration. Highlights: PEI-modified CNTs catalysts for electrochemical production of H2O2 were synthesized. The introduction of O-containing functional groups enhanced the catalytic activity of the composite cathode. The positive surface potential enhanced the catalytic activity of the composite cathode. The GF/CNTs-80/PTFE composite cathode achieved the highest H2O2 yield of 116.34 mg·L−1at pH 7. [ABSTRACT FROM AUTHOR]

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) have been identified as predictors of treatment response in a variety of cancers. We conducted a retrospective analysis to investigate the usefulness of NLR, PLR and SII at baseline and at 6 weeks post-treatment as predictors of response to anti-PD-1/PD-L1 antibody treatment in small cell lung cancer (SCLC). Data of 41 SCLC patients receiving immunotherapy as second- or later-line treatment were analyzed. The overall median progression-free survival (PFS) was 5.1 months (95% CI 3.2–6.2). The median PFS was significantly longer in patients with NLR < 5 than in patients with NLR ≥ 5 at 6 weeks post treatment (HR = 0.29, 95%CI 0.09–0.96, P = 0.04). However, median PFS was comparable between patients with NLR < 5 and patients with NLR ≥ 5 at baseline (HR = 0.75, 95% CI 0.24–2.26, P = 0.56). The median PFS was similar between patients with PLR < 169 and those with PLR ≥ 169 at baseline (HR = 0.67, 95% CI 0.25–1.80, P = 0.43) and at 6 weeks post treatment (HR = 0.69, 95% CI 0.25–1.86, P = 0.46). No statistically different PFS was found between patients with SII < 730 and those with SII ≥ 730 at baseline (HR = 0.70, 95% CI 0.26–1.89, P = 0.48) and at 6 weeks post treatment (HR = 0.38, 95% CI 0.013–1.09, P = 0.07). In conclusion, NLR at 6 weeks after start of treatment appears to be a biomarker of response in the early phase in SCLC patients treated with anti-PD-1/PD-L1 antibodies as second- or later-line treatment. [ABSTRACT FROM AUTHOR]

The aim of this paper was to investigate the protective effects of bromodomain containing 4 (BRD4) inhibition on the temporomandibular joint osteoarthritis (TMJ OA) induced by compressive mechanical stress and to explore the underlying mechanism. In vivo, a rat model of TMJ compressive loading device was used and BRD4 inhibitor was injected into the TMJ region. HE staining and micro-CT analysis were used for histological and radiographic assessment. Immunohistochemistry and qPCR were performed to detect inflammatory cytokines expressions. High-throughput ChIP-sequencing screening was performed to compare the BRD4 and H3K27ac binding patterns between condylar cartilage from control and mechanical force groups. In vitro, the mandibular condylar chondrocytes were treated with IL-1β. Small Interference RNA (siRNA) infection was used to silencing BRD4 or TREM1. qPCR was performed to detect inflammatory cytokines expressions. Our study showed that BRD4 inhibition can alleviate the thinning of condylar cartilage and subchondral bone resorption, as well as decrease the inflammatory factors expression both in vivo and in vitro. ChIP-seq analysis showed that BRD4 was more enriched in the promoter region of genes related to the stress and inflammatory pathways under mechanical stress in vivo. Trem1, a pro-inflammatory gene, was screened out from the overlapped BRD4 and H3K27ac increased binding sites, and Trem1 mRNA was found to be regulated by BRD4 inhibition both in vivo and in vitro. TREM1 inhibition reduced the expression of inflammatory factors induced by IL-1β in vitro. In summary, we concluded that BRD4 inhibition can protect TMJ OA-like pathological changes induced by mechanical stress and attenuate TREM1-mediated inflammatory response. [ABSTRACT FROM AUTHOR]

The aim of this paper was to investigate the protective effects of bromodomain containing 4 (BRD4) inhibition on the temporomandibular joint osteoarthritis (TMJ OA) induced by compressive mechanical stress and to explore the underlying mechanism. In vivo, a rat model of TMJ compressive loading device was used and BRD4 inhibitor was injected into the TMJ region. HE staining and micro-CT analysis were used for histological and radiographic assessment. Immunohistochemistry and qPCR were performed to detect inflammatory cytokines expressions. High-throughput ChIP-sequencing screening was performed to compare the BRD4 and H3K27ac binding patterns between condylar cartilage from control and mechanical force groups. In vitro, the mandibular condylar chondrocytes were treated with IL-1β. Small Interference RNA (siRNA) infection was used to silencing BRD4 or TREM1. qPCR was performed to detect inflammatory cytokines expressions. Our study showed that BRD4 inhibition can alleviate the thinning of condylar cartilage and subchondral bone resorption, as well as decrease the inflammatory factors expression both in vivo and in vitro. ChIP-seq analysis showed that BRD4 was more enriched in the promoter region of genes related to the stress and inflammatory pathways under mechanical stress in vivo. Trem1, a pro-inflammatory gene, was screened out from the overlapped BRD4 and H3K27ac increased binding sites, and Trem1 mRNA was found to be regulated by BRD4 inhibition both in vivo and in vitro. TREM1 inhibition reduced the expression of inflammatory factors induced by IL-1β in vitro. In summary, we concluded that BRD4 inhibition can protect TMJ OA-like pathological changes induced by mechanical stress and attenuate TREM1-mediated inflammatory response. [ABSTRACT FROM AUTHOR]

• The hollow-sphere g-C 3 N 4 was used as a substrate material for uniformly dispersing Pd nanoparticles to expose more active sites. • The synergistic effect of the 3D g-C 3 N 4 and Pd nanoparticles promoted efficient separation of photogenerated carriers. • According to TAS, it was estimated that the charge separated state lifetime of Pd/g-CN (10 h) was shortened to 1.4 ns ± 338.0 ps. Herein, 3D hollow-sphere structure graphitic carbon nitride (g-C 3 N 4) with large specific surface area and high porosity is synthesized through a mild, heat polymerization, template-free route. The as-prepared hollow-sphere structure can be used as a substrate material for uniformly dispersing Pd nanoparticles to enhance the absorption of visible light and expose more active sites. Pd nanoparticles as electron acceptor are implanted into g-C 3 N 4 , which increases the trapping capability of capturing transition electrons to gain more photogenerated carriers participating in surface reactions. Therefore, the estimated charge separation lifetime of Pd/SCN (10 h) investigated by transient absorption spectroscopy was 1.4 ns ± 338.0 ps, which is only half of SCN. Benefiting from the unique structure and the excellent optical performance, the obtained Pd/SCN composites exhibited prominent photocatalytic hydrogen evolution performance under visible light irradiation. Especially, the photocatalytic hydrogen rate of Pd/SCN (10 h) reached 267.9 µmol/h, almost 10 times higher than the Pd/2D g-C 3 N 4. Simultaneously, a possible mechanism for photocatalytic H 2 reaction was proposed based on the characterization results. [ABSTRACT FROM AUTHOR]

GLO:1XW/01oct19:bjh16127-fig-0001.jpg PHOTO (COLOR): HC4319 binds to the surface of AML cells, inhibits SDF-1 -induced migration and signalling pathways, and reverses BMSC-mediated chemoresistance of AML cells in vitro. (C) U937 and HL-60 cells serum-starved overnight were pre-treated with or without HC4319 (20 µmol/l) for 1 h, followed by stimulation with SDF-1 (30 ng/ml for U937 cells, 100 ng/ml for HL-60 cells) for 10 min. This result indirectly suggested that HC4319 bound to the surface of AML cells when administrated into the AML xenograft mouse and the effect upon this binding peaked at 1 to 3 h, then HC4319 was gradually eliminated from the AML cells surface. [Extracted from the article]

Rhizoma Coptidis (RC), the dried rhizome of Coptis Chinensis Franch., can dispel dampness and heat within the body and has been traditionally used for the treatment of cardiovascular disease (CVD)-associated problems including hyperlipidemia in China. Berberine (BBR) is the main active component of RC, which has been shown to possess significant therapeutic potential. However, only 0.14% of BBR is metabolized in the liver, and the extremely low bioavailability (<1%) and blood concentration of BBR in experimental and clinical settings is insufficient to achieve the effects as observed under in vitro conditions, which imposes challenges to explain its excellent pharmacological actions. Intense efforts are currently being devoted to defining its specific pharmacological molecular targets, while the exploration from the perspective of its pharmacokinetic disposition has rarely been reported to date, which could hardly make a comprehensive understanding of its hypolipidemic enigma. This study made a pioneering endeavor to unveil the hypolipidemic mechanism of BBR from RC focusing on its unique intestines-erythrocytes-mediated bio-disposition. The fate of BBR in intestines and erythrocytes was probed by a rapid and sensitive LC/MS-IT-TOF method. To analyze the disposition of BBR, a reliable HPLC method was subsequently developed and validated for simultaneous determination of BBR and its key active metabolite oxyberberine (OBB) in whole blood, tissues, and excreta. Meanwhile, the enterohepatic circulation (BDC) of BBR and OBB was verified by bile duct catheterization rats. Finally, lipid overloading models of L02 and HepG2 cells were employed to probe the lipid-lowering activity of BBR and OBB at in vivo concentration. The results showed that BBR underwent biotransformation in both intestines and erythrocytes, and converted into the major metabolite oxyberberine (OBB). The AUC 0-t ratio of total BBR to OBB was approximately 2:1 after oral administration. Besides, the AUC 0-t ratio of bound BBR to its unbound counterpart was 4.6:1, and this ratio of OBB was 2.5:1, indicative of abundant binding-type form in the blood. Liver dominated over other organs in tissue distribution. BBR was excreted in bile, while the excretion of OBB in feces was significantly higher than that in bile. Furthermore, the bimodal phenomenon of both BBR and OBB disappeared in BDC rats and the AUC 0-t was significantly lower than that in the sham-operated control rats. Interestingly, OBB significantly decreased triglycerides and cholesterol levels in lipid overloading models of L02 and HepG2 cells at in vivo -like concentration, which was superior to the prodrug BBR. Cumulatively, BBR underwent unique extrahepatic metabolism and disposition into OBB by virtue of intestines and erythrocytes. BBR and OBB were mainly presented and transported in the protein-bound form within the circulating erythrocytes, potentially resulting in hepatocyte targeting accompanied by obvious enterohepatic circulation. The unique extrahepatic disposition of BBR via intestines and erythrocytes conceivably contributed enormously to its hypolipidemic effect. OBB was the important material basis for the hypolipidemic effect of BBR and RC. [Display omitted] • BBR could be metabolized into its active hypolipidemic form OBB coupled with intestines and erythrocytes. • BBR and OBB were mainly presented and transported in the protein-bound form within the circulating erythrocytes. • BBR and OBB exhibited hepatocyte-targeting and enterohepatic circulation, which increased the hypolipidemic efficacy. • OBB might be the major bioactive metabolite obligatory for the hypolipidemic efficacy of BBR. [ABSTRACT FROM AUTHOR]

Objective To examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS). Methods We used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague–Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5 Hz, 24 h vs 20%, 0.5 Hz, 24 h) on chondrocytes. For hypoxia experiment, the concentration of O 2 was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF-1α, and HIF-2α were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method. Results Tunicamycin, 20% mechanical forces and hypoxia (1% O 2 ) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers. Conclusion We confirmed that mechanical stress and local hypoxia both contributed to the chondrocytes apoptosis. Mechanical stress can cause OA-like pathological change in rat mandibular condylar cartilage via ERS activation and hypoxia existed in the meantime. Both mechanical forces and hypoxia can induce ERS and cause chondrocytes apoptosis only if the stimulate was in higher level. Salubrinal can protect chondrocytes from apoptosis, and relieve OA-liked pathological change on mandibular condylar cartilage under mechanical stress stimulation. [ABSTRACT FROM AUTHOR]

Paper has been used to engineer many types of bio-diagnostics. A major issue to most paper-based bio-diagnostics is the biomolecule instability causing the short shelf-life of the diagnostics. Commercial papers contain various polymeric additives. Polyamidoamine-epichlorohydrin (PAE), a polyelectrolyte typically used as wet-strength agent, is commonly used in filter papers and paper towels, which are often used as substrate in bioactive paper. However, the effect of cellulose or polymeric additives on antibody bioactivity is unknown. This limits paper optimization for diagnostic applications. In this study, model papers were made with and without PAE addition. IgM Anti-A blood typing antibody was physisorbed and dried on paper, aged for up to 9 weeks at different relative humidity (RH) conditions and the antibody activity was measured. The antibody bioactivity was represented as blood typing efficiency measured by image analysis. The surface chemical composition was measured using X-ray photoelectron spectroscopy (XPS). Antibody bioactivity loss was promoted by elevated RH, corresponding to increased paper water content. PAE significantly reduces the paper water content under ambient environment. Antibody bioactivity is higher on paper made with PAE under the high humidity conditions (57.6%–84.3% RH). However, under conditions of humidity saturation (100%RH), PAE shows little effect on reducing paper water content nor on protecting antibody bioactivity. These results demonstrate the water content of paper to be associated with antibody bioactivity loss. [ABSTRACT FROM AUTHOR]

Cell delivery therapy holds great prospects in regenerative medicine. However, low cell survival and retention are still the main problems in current studies. To address these challenges, a temperature-sensitive hydrogel suitable for cell encapsulation was developed by mixing methylcellulose (MC) and polyvinyl alcohol (PVA) solution simply in this work. Based on the physical hydrogen bonds between MC and PVA chains, porous hydrogels with excellent water-retention ability were achieved at 37 °C. The hydrogels exhibited superior performances such as fast-gelling, stable modulus, great injectability, and high light transmittance. Additionally, cell viability analysis showed MC/PVA hydrogels were cytocompatible. More importantly, cell encapsulation experiments demonstrated that rabbit adipose-derived stem cells (rADSCs) cultured within the MC/PVA hydrogels remain in high viability. Taken together, these results indicated the potential of MC/PVA hydrogels as a clinically translatable delivery system for stem cells. • The MC/PVA hydrogels were developed via a simple and environmentally friendly method. • Fast curing at 37 °C was achieved. • The integration of MC and PVA resulted in excellent injectability. • The MC/PVA hydrogels were biocompatible and suitable for cell encapsulation. [ABSTRACT FROM AUTHOR]

Objective: To assess the anti-caries effect of arginine-containing formulations in vivo on caries lesions compared with fluorides or placebo.Methods: Randomized or quasi-randomized human clinical trials wherein arginine was delivered by any method were considered. The MEDLINE, Web of Science, EMBASE, Cochrane Library, and CBM databases were searched to identify relevant articles published up to December 2014. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using data collection forms. Each included study was assessed using the Cochrane risk of bias assessment tool.Results: Of the 470 studies screened, 31 full articles were scrutinized and assessed for eligibility. Ten studies (n = 15,546 participants) were selected for final inclusion. The meta-analysis results (n = 7 studies) demonstrated a synergistic effect of arginine when used in conjunction with fluoride on early coronal and root caries compared with placebo or fluoride alone. No specific side effects related to arginine usage were identified.Conclusions: When used in combination with a calcium compound and fluoride, arginine potentially provides a superior anti-caries effect compared with matched formulations of fluoride alone. However, the level of evidence was downgraded because of risks of bias and potential publication bias. In the future, more high quality, non-industry-supported clinical studies in this research area are required before any definitive recommendations can be made. [ABSTRACT FROM AUTHOR]

A new enantioselective open‐tubular capillary electrochromatography was developed employing poly(glycidyl methacrylate) nanoparticles/β‐cyclodextrin covalent organic frameworks chemically immobilized on the inner wall of the capillary as a stationary phase. A pretreated silica‐fused capillary reacted with 3‐aminopropyl‐trimethoxysilane followed by poly(glycidyl methacrylate) nanoparticles and β‐cyclodextrin covalent organic frameworks through a ring‐opening reaction. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The electroosmotic flow was studied to evaluate the variation of the immobilized columns. The chiral separation performance of the fabricated capillary columns was validated by the analysis of the four racemic proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, and omeprazole. The influences of bonding concentration, bonding time, bonding temperature, buffer type and concentration, buffer pH, and applied voltage on the enantioseparation of four proton pump inhibitors were investigated. Good enantioseparation efficiencies were achieved for all enantiomers. In the optimum conditions, the enantiomers of four proton pump inhibitors were fully resolved within 10 min with high resolutions of 9.5–13.9. The column‐to‐column and inter‐ to intra‐day repeatability of the fabricated capillary columns through relative standard deviation were found better than 9.54%, exhibiting satisfactory stability and repeatability of the fabricated capillary columns. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic inflammatory disease associated with lipid deposition, which could be converted into acute clinical events by thrombosis or plaque rupture. Adipose-derived mesenchymal stem cell (ADSC)-encapsulated repair units could be an effective cure for the treatment of AS patients. In this study, we encapsulate human adipose-derived mesenchymal stem cells (hADSCs) in collagen microspheres to fabricate stem cell repair units. Besides, we show that encapsulation in collagen microspheres and cultured in vitro for 14 days maintain the viability and stemness of hADSCs. Moreover, we generate AS progression model and niche in vitro by combining hyperlipemia serum of AS patients with AS cell models. We further systematically demonstrate that hADSC-based microspheres could ameliorate AS progression by inhibiting oxidative stress injury, cell apoptosis, endothelial dysfunction, inflammation, and lipid accumulation. In addition, we perform transcriptomic analysis and functional studies to demonstrate how hADSCs (three dimensional cultured in microspheres) respond to AS niche compared with healthy microenvironment. These findings reveal a role for ADSC-based microspheres in the treatment of AS and provide new ideas for stem cell therapy in cardiovascular disease. The results may have implications for improving the efficiency of hADSC therapies by illuminating the mechanisms of hADSCs exposed in special pathological niche. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three small molecule donors based on asymmetric BDT core were synthesized. • Effects of side chains and ending groups on properties of donors were investigated. • 2D-2D asymmetric SMD3 ending capped by rhodanine showed best photovoltaic property. In this work, we employed symmetry-breaking strategy to construct A-π-D-π-A typed small molecule donors SMD1, SMD2 and SMD3 to reduce the self-aggregation in blends and form ideal phase separation morphology. The effect of different side chains and terminal groups on the photovoltaic properties of these asymmetric small molecule donors were investigated in detail. SMD3 shows more red-shifted absorption and weaker self-aggregation than SMD1 and SMD2. Consequently, SMD3:PC 71 BM blend films show homogenous morphology, which is beneficial for exciton dissociation and charge transport. As a result, SMD3:PC 71 BM based devices exhibit the highest power conversion efficiency (PCE) of 4.67%. Our investigation proved that the benzene-alkoxyl and thiophene-alkylthiol are ideal candidates for side chains on BDT and 3-isooctyl rhodanine is an ideal terminal group for asymmetric small molecular donors. [ABSTRACT FROM AUTHOR]

Norbornene modified hyaluronic acid (NorHA) has attracted enormous attention in biological research for its ability to form hydrogels in a cell-friendly way. However, traditional routes to synthesis NorHA are involved with laboring and cumbersome steps. In this study, an alternative single-step approach to fabricate NorHA is reported. NorHA was first synthesized by conjugating carbic anhydride (CA) with hyaluronic acid (HA) directly and NorHA with various norbornene substitution degrees (SD) was obtained by adjusting the reaction pH, time, and the amounts of CA easily. Porous NorHA hydrogels were prepared via orthogonal thiol-norbornene reaction under blue light irradiation. Furthermore, the resulting gelation performances, swelling behaviors, and transmittance of NorHA hydrogels were adjusted by varying the content of crosslinker or NorHA. The cytocompatibility evaluation suggests that the obtained NorHA were suitable for cell encapsulation. Finally, we show that this approach also can be extended to other natural or synthesized biopolymers to prepare cytocompatible photo-crosslinked hydrogels. [Display omitted] • A facile route to synthesize NorHA by conjugating carbic anhydride with HA directly was established. • Basic conditions are essential for esterification between carbic anhydride and HA. • NorHA preserved the merits of thiol-norbornene cross-linking. • NorHA hydrogels were biocompatible and suitable for cell encapsulation. • Biocompatible GelNB and PVANB were also synthesized by using carbic anhydride. [ABSTRACT FROM AUTHOR]

[Display omitted] • 0D/1D/2D structure is in-situ coupled by Co 2 Mo 3 O 8 nanosheets and Co nanoparticles. • The Co 2 Mo 3 O 8 exists in the form of single-crystal regular hexagonal nanosheets. • 3 mmol H 2 can be completely released within 4 min at 25 °C in the hydrolysis of AB. • The 0D/1D/2D mutual-supported spatial structure contribute to the high performance. • O vacancies also boost adsorption and dissociation process for enhanced activity. Recently, hydrolysis of ammonia borane (AB) is a promising way of producing and employing hydrogen in mild conditions. Nonetheless, the failure to develop inexpensive and high-performance catalyst impedes the further scale hydrogen energy application of AB. Given the fact that ex-situ formed nanocatalysts could be prone to abscission and agglomeration for insufficient dispersion and support, 1D composite microrods with 0D/1D/2D spatial structure constructed by mutual-supported 2D single-crystal Co 2 Mo 3 O 8 nanosheets and 0D Co nanoparticles (denoted as Co@Co 2 Mo 3 O 8) have been in-situ synthesized and introduced into the hydrolysis of AB for the first time. Excitingly, the novel Co@Co 2 Mo 3 O 8 exhibits one of the best catalytic performances in the hydrolysis of AB for non-noble metal/metal oxide heterojunction catalysts with TOF value reaching 17.28 m o l H 2 m o l ca t - 1 m i n - 1 at 25 °C, which is 3.95 and 24.0 times that of the single Co 2 Mo 3 O 8 and Co. Meanwhile, two kinds of catalytic components with high intrinsic activity (Co 2 Mo 3 O 8 and Co) and supporting each other in the 0D/1D/2D spatial structure (nanoparticles, microrods, and nanosheets) along with plentiful O vacancies induce the outstanding catalytic activity of Co@Co 2 Mo 3 O 8. The large-scale controllable preparation method for in-situ fabrication of non-noble metal 0D/1D/2D composite catalysts with high performances would be an accelerator for great potential application for hydrolysis of AB. [ABSTRACT FROM AUTHOR]

Regional economic development evaluation is essential for understanding social and environmental issues. Although the nighttime light (NTL) data have been proved to be effective in economic estimation, it cannot reflect the human activities that occur during the daytime. Recently, with the widespread use of smart mobile devices, the location based social media (LBSM) data are increasingly being used as a proxy for real-time human activities. However, little work was carried out to explore the potential of LBSM data in estimating economic development at different scales in China. This study filled this gap by evaluating the effectiveness of Tencent user density (TUD) data, a typical type of LBSM data in China, in Gross Domestic Product (GDP) modeling at the provincial, municipal, and county scales. In this study, we employed holiday and non-holiday TUD sample data to simulate the annual TUD data, and compared it with the new generation NTL data, NPP/VIIRS images. The results showed that although the simulated annual TUD data does not perform better than NPP/VIIRS-NTL data in provincial and municipal GDP estimation, it outperforms NPP/VIIRS-NTL data at the county scale. More importantly, the simulated annual TUD data are much more powerful and reliable than NPP/VIIRS-NTL data in underdeveloped areas with complex terrain, such as the Northwest and Southwest China, as well as in more developed areas with separation of work and housing, such as the North China and South China. This is mainly because TUD data can reduce the impact of natural factors such as terrain on data collection as well as reflect both daytime and nighttime human activities. This study confirmed that the LBSM-TUD data is a potential and promising data source for economic modeling in small scale areas of China, which will help to support China's regional economic evaluation. [Display omitted] • The ability of Tencent user density (TUD) data in economic modeling was explored. • Holiday and non-holiday TUD sample data was used to simulate the annual TUD data. • The Nighttime light (NTL) data was used to compared with TUD data in China. • TUD data does not perform better than NTL data at the provincial and municipal scale. • TUD data has potential at county scale, especially in less or more developed areas./. [ABSTRACT FROM AUTHOR]

The school's indoor environment significantly affects students' health and learning performance. Although related studies have been carried out in many regions, only a few have examined indoor classroom environments and proposed the energy-saving optimization of heating and ventilation in winter in China's hot summer and cold winter areas. This study aims to comprehensively investigate classroom indoor environmental quality in China's hot summer and cold winter areas, and propose targeted optimization strategies. It first examined the indoor environment, including indoor air, acoustic, visual, and thermal quality, of two typical middle schools. The indoor CO2 concentration in winter was found to be unsatisfactory. Subsequently, how the indoor layout, outdoor wind and occupancy density influence indoor CO2 concentration was examined through simulation, which indicated that high occupancy density is the main cause. Finally, this study proposed several ventilation optimization strategies and performed an energy analysis to maintain sufficient air quality and a comfortable thermal environment in high-density classrooms. The results show that compared with the intermittent mode, the fixed ventilation and heating mode could maintain a more comfortable indoor environment and achieve a 30% energy saving. A reference for the improvement of classroom indoor environment in hot summer and cold winter areas was provided. [ABSTRACT FROM AUTHOR]

Apoptosis, a fundamental process for both human health and disease, is initiated and regulated by protein-protein interactions, notable examples of which are the interactions involving Bcl-2 and IAP protein families. This article discusses recent advances in the use of chemical approaches in discovering and studying small molecules targeted to proteins of the Bcl-2 and IAP families. These small molecules and their complexes with receptors provide the tools and model systems to probe the basic mechanism of molecule recognition underling the life and death of cells and develop novel strategies for therapeutic intervention of the dysregulated apoptotic process. The review of these studies highlights the opportunity and challenge in this emerging area of chemical and chemical biological research. [Copyright &y& Elsevier]

Bcl-2 family proteins are key regulators of programmed cell death or apoptosis that is implicated in many human diseases, particularly cancer. In recent years, they have attracted intensive interest in both basic research to understand the fundamental principles of cell survival and cell death and drug discovery to develop a new class of anticancer agents. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions in either inhibiting or promoting cell death. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL commonly found in human cancers contributes to neoplastic cell expansion and interferes with the therapeutic action of many chemotherapeutic drugs. The functional blockade of Bcl-2 or Bcl-xL could either restore the apoptotic process in tumor cells or sensitize these tumors for chemo- and radiotherapies. This article reviews the recent progress in the design and discovery of small molecules that block the anti-apoptotic function of Bcl-2 or Bcl-xL. These chemical inhibitors are effective modulators of apoptosis and promising leads for the further development of new anticancer agents. Oncogene (2000) 19, 6627–6631. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel one-step calcination strategy to dispersed ultra-small CoO QDs in hollow-sphere g-C 3 N 4 (SCNO). • Volatile gas was used to avoid the aggregation of CoO quantum dots. • Results of photocatalytic hydrogen evolution revealed that the catalytic activity of the optimal sample SCNO/CoO (0.2) was up to 11495 μmol h−1g−1. • The electron transfer path and average fluorescence lifetime of the samples were measured by TA spectra. Highly dispersed ultra-small CoO QDs were successfully limited in hollow-sphere g-C 3 N 4 (SCNO) by a novel one-step calcination strategy using cyanuric acid-melamine supramolecular as a precursor. Meanwhile, the volatile gas provided the sufficient condition of confining CoO QDs to repulse its aggregation. TA spectroscopy verified that the photoproduction electrons of SCNO could be directionally transferred to the conduction band of CoO QDs. The density functional theory calculation further confirms the charge-carries transfer pathway of SCNO/CoO QDs. In addition, the results of photocatalytic hydrogen evolution revealed that the catalytic activity of the optimal sample SCNO/CoO (0.2) was up to 11495 μmol h−1 g−1, which may be due to the significantly accelerated rate of charge-carries. Meanwhile, the apparent quantum efficiency (AQE) of samples was tested at various monochromatic light wavelengths. Finally, a possible mechanism for photocatalytic hydrogen evolution was proposed according to the results. [ABSTRACT FROM AUTHOR]

Although it is known that the frequency and intensity of heatwaves are affected by the El Niño–Southern Oscillation (ENSO), unknown are the ENSO modulations on the moving properties (e.g., moving distance and speed) of spatiotemporally contiguous heatwaves. Here, we investigate the relationship between ENSO and the moving patterns of contiguous heatwaves. We show that contiguous heatwaves are likely more frequent, more persistent, and longer‐traveling, but slower‐moving during El Niño than La Niña episodes. The differences in the tropical contiguous heatwaves between El Niño and La Niña are influenced by persistent high‐pressure anomalies. During the following summers, El Niño can induce anomalous atmospheric circulation characterized by an intensified subsidence over the western North Pacific and ascending motion over the tropical Indian and Pacific Oceans. These features provide favorable conditions for the occurrence and maintenance of contiguous heatwaves. Plain Language Summary: The El Niño–Southern Oscillation (ENSO) is among the strongest climate variation phenomena, which has important effects on the frequency and intensity of heatwaves across the globe. However, how ENSO influences the joint evolution behaviors of heatwaves at both temporal and spatial dimensions (e.g., moving patterns including traveling distance and moving speed) is not fully understood. Here, we first track the spatiotemporally contiguous heatwaves that occur simultaneously in adjacent regions or consecutively in neighboring days, and investigate their moving patterns over global land areas during 1961–2020. Then, we examine the relationship between the ENSO and the moving properties of these contiguous heatwaves. The results show that contiguous heatwaves during El Niño years not only tend to be more frequent and more persistent, but also travel longer distances and at slower moving speed, especially in tropics. This relationship is likely due to persistent high‐pressure anomalies caused by El Niño, which can intensify subsidence over the western North Pacific and ascendance over the tropical Indian and Pacific Oceans. This knowledge is crucial for improving our predictions about heatwaves and adapting their potential impacts. Key Points: Contiguous heatwaves tend to be more frequent, more persistent, and longer‐traveling, but slower‐moving during El Niño than La NiñaDifferences in tropical contiguous heatwaves between El Niño and La Niña episodes are influenced by persistent high‐pressure anomaliesEl Niño intensifies contiguous heatwaves via inducing sinking over the western North Pacific (WNP) and rising over the tropical Indian Ocean [ABSTRACT FROM AUTHOR]

Low temperatures affect flower development in rose (Rosa hybrida), increasing petaloid stamen number and reducing normal stamen number. We identified the low-temperature-responsive R2R3-MYB transcription factor RhMYB17, which is homologous to Arabidopsis MYB17 by similarity of protein sequences. RhMYB17 was up-regulated at low temperatures, and RhMYB17 transcripts accumulated in floral buds. Transient silencing of RhMYB17 by virus-induced gene silencing decreased petaloid stamen number and increased normal stamen number. According to the ABCDE model of floral organ identity, class A genes APETALA 1 (AP1) and AP2 contribute to sepal and petal formation. Transcription factor binding analysis identified RhMYB17 binding sites in the promoters of rose APETALA 2 (RhAP2) and APETALA 2-LIKE (RhAP2L). Yeast one-hybrid assays, dual-luciferase reporter assays, and electrophoretic mobility shift assays confirmed that RhMYB17 directly binds to the promoters of RhAP2 and RhAP2L , thereby activating their expression. RNA sequencing further demonstrated that RhMYB17 plays a pivotal role in regulating the expression of class A genes, and indirectly influences the expression of the class C gene. This study reveals a novel mechanism for the homeotic transformation of floral organs in response to low temperatures. [ABSTRACT FROM AUTHOR]

Reports on the syntheses and conformations of somatostatin-related cyclic hexapeptides incorporating specific alpha- and beta-methylated residues. Syntheses of c[-Pro-Phe-(2R,3S)-beta-MeTrp-Lys-Thr-(2S,3S)-beta-MePhe-] and c[-Pro-Phe-(2S,3R)-beta-MeTrp-Lys-Thr-(2S,3S)-beta-MePhe-]; Binding procedures; (1)H NMR spectra; Computer simulations.

This article proposes a novel atmospheric data-driven Q-band satellite channel model using two artificial neural networks, i.e., multilayer perceptron and long short-term memory (LSTM), to estimate real-time channel attenuation at Q-band via a set of atmospheric parameters. Seven atmospheric parameters for modeling satellite channel attenuation are selected by the least absolute shrinkage and selection operator (LASSO) algorithm from 14 commonly used atmospheric parameters. Simulation results demonstrate that the multilayer perceptron-based atmospheric data-driven Q-band satellite channel model via those seven atmospheric parameters is more accurate and less complex than that via the 14 atmospheric parameters. Meanwhile, the accuracy performance of multilayer perceptron- and LSTM-based atmospheric data-driven Q-band satellite channel models, such as absolute errors and mean-squared errors (MSEs), is discussed and analyzed. The complexity of multilayer perceptron and LSTM in this model, such as training time, loading time, and estimation time, is also investigated. It can be seen that the estimated channel attenuation can well align with the measured channel attenuation. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Accurate and comprehensive immunochromatographic assay (ICA) data are urgently required in the daily supervision of plants, schools, testing institutions, and law-enforcing departments. Through pretreatment-integration and device-facilitated operation, a quantitative ICA with high sensitivity and throughput was realized on the basis of a commercialized semi-quantitative ICA strip. Three pretreatment methods, namely, acid base, heavy metal salt, and organic solvent methods, have less than three steps. The pretreatment was established for protein removal. A total of 17 pretreated ICA items in milk were considered for the identification of the most suitable pretreatment method. The items are composed of six items pretreated by the acid-base method, six by the heavy salt method, and five by the organic solvent method. Then, the ICA results with pretreatment were compared with those without pretreatment. After pretreatment, the signal intensity increased by 39%, the detection limit decreased to 12%, the half maximal inhibitory concentration decreased to 18%, and the detection range increased fourfold. A device with mixing and centrifugation functions was designed for the pretreatment-related operations. A pre-incubation sampling device was used to facilitate incubation in batch and high-throughput detection. An ICA reader was used. The detection throughput reached 8 samples per batch or 32 samples per hour. The designed devices were printed through 3D printing and rapid prototyping. [ABSTRACT FROM AUTHOR]

The activation of glycolysis, particularly in the context of reprogrammed energy metabolism, is increasingly recognized as a significant characteristic of cancer. However, the precise mechanisms by which glycolysis is promoted in metastatic gastric cancer cells under normal oxygen conditions remain poorly understood. MicroRNAs (miRNAs) play a crucial role in the development of malignant phenotypes in gastric cancer. Nevertheless, our understanding of the specific involvement of miRNAs in hypoxia-induced metabolic shifting and the subsequent metastatic processes is limited. Hypoxia-induced downregulation of miR-598-3p mechanistically leads to the upregulation of RMP and IGF1r, thereby promoting glycolysis. Either overexpression of miR-598-3p or R406 treatment effectively suppresses the metastasis of gastric cancer cells both in vitro and in vivo. Collectively, the depletion of miR-598-3p alters glucose metabolism from oxidative phosphorylation to glycolysis, thereby exacerbating the malignancy of gastric cancer cells. The present findings indicate a potential target for the development of therapeutics against gastric cancers with increased miR-598-3p expression. [ABSTRACT FROM AUTHOR]

Light is an indispensable factor in the healthy growth of living organisms, and alterations in the photoperiod can have consequences for body homeostasis. The eyestalk is a photosensitive organ that secretes various hormones to regulate the Chinese mitten crab (Eriocheir sinensis). However, the photoperiod-dependent eyestalk patterns of gene expression that may underlie changes in body homeostasis are unknown. In this study, we investigated the molecular mechanisms involved in eyestalk transcriptomic responses in E. sinensis under different photoperiod regimes on days 2, 4, and 6. The photoperiods tested were 12, 24, and 0 h light/day. In total, we obtained 110, 958, 348 clean datasets and detected 1809 differentially expressed genes (DEGs). Genes involved in the crustacean hyperglycemic hormone superfamily and juvenile hormones were observed, which play important roles in gonadal development, growth, and immunity in E. sinensis and may also be involved in photoperiod adaptation. In addition, the MAPK signaling pathway was the only signaling pathway identified in the continuous light group but was absent in the continuous darkness group. We suggest that the MAPK pathway is highly responsive to light input during the subjective night and insensitive to light during the middle of the subjective day. These results provide insight into the molecular mechanisms underlying the effects of photoperiod on the immune regulation of E. sinensis. [ABSTRACT FROM AUTHOR]

In order to meet the increasing requirements of epoxy resin matrix materials for the electrical and electronics industry, this paper presents the design and synthesis of Si–Mg–B oxides using Mg, Si and B organic monomers, and preparation of Si–Mg–B/EP nanocomposites by ultrasonic dispersion and thermal curing. Mainly study the effect of composite oxide introduction on the dielectric properties of epoxy resin composites. With an increase in doping amount, the Si–Mg–B/EP nanocomposites show an increase in dielectric constant under working frequency test conditions; a decrease in dielectric loss followed by an increase, and the lowest value of 0.00238 is obtained at a doping amount of 8 wt%. The volume resistivity initially increases and then decreases, with the maximum value of 5.64 × 1016 Ω cm obtained at a doping amount of 8 wt%. Furthermore, the corona resistance life of Si–Mg–B/EP nanocomposites increases, with a value of 401.8 min obtained at a doping amount of 8 wt%, which is 4.65 times that of pure EP. And the morphology near the breakdown point of corona breakdown was analyzed. These results suggest that Si–Mg–B oxide is effective in improving the dielectric loss and corona resistance of epoxy resin. [ABSTRACT FROM AUTHOR]

Purpose: Anti-programmed cell death protein 1 or its ligand (anti-PD-1/L1) monotherapy has become the standard second-line treatment in advanced lung adenocarcinoma. However, the strategy treatment of anti-PD-1/L1 plus anti-angiogenesis therapy has not been evaluated. We conducted this retrospective study to assess the efficacy and safety of anti-PD-1/L1 plus anti-angiogenesis therapy in patients with advanced lung adenocarcinoma in the second-line or later setting. Methods: Patients with advanced lung adenocarcinoma who received anti-PD-1/L1 plus anti-angiogenesis therapy or anti-PD-1/L1 monotherapy in the second-line or later treatment from March 2015 to May 2019 in PLA General Hospital were retrospectively analyzed. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Multivariate analyses of PFS and OS were performed with Cox proportional hazard regression models. Results: Seventy-four patients were included in our study. Twenty-five patients were treated with anti-PD-1/L1 plus anti-angiogenesis therapy, and forty-nine patients were treated with anti-PD-1/L1 monotherapy. The disease control rate (DCR) was higher in the anti-PD-1/L1 plus anti-angiogenesis group than in the anti-PD-1/L1 monotherapy group (92.0% vs. 46.9%, P = 0.0004). The median progression-free survival (PFS) was 5.1 months vs. 2.0 months (HR 0.551 [95% confidence interval 0.337–0.902], P = 0.002) and median overall survival (OS) was 14.3 months vs. 8.4 months (HR 0.549 [95% CI 0.305–0.990], P = 0.046), respectively. Multivariate Cox proportional hazard regression models showed that anti-PD-1/L1 plus anti-angiogenesis group had prolonged PFS (HR 0.541 [95% CI 0.298–0.981], P = 0.033). The incidences of grade 3/4 adverse events were 12% (3/25) in anti-PD-1/L1 plus anti-angiogenesis group and 6% (3/49) in anti-PD-1/L1 monotherapy group. Conclusion: Compared with anti-PD-1/L1 monotherapy, anti-PD-1/L1 plus anti-angiogenesis therapy could significantly improve the clinical response and bring longer PFS and OS in patients with advanced lung adenocarcinoma who had failed first-line or later treatment. Further prospective studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver–gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites. [ABSTRACT FROM AUTHOR]

As the most prominent RNA modification, N6‐methyladenosine (m6A) participates in the regulation of tumour initiation and progression. Circular RNAs (circRNAs) also play crucial roles in ubiquitous life processes. Whether circRNAs are required for m6A regulation in renal cell carcinoma (RCC) remains unclear. Meta‐analysis and bioinformatics identified that IGF2BP3 was upregulated in RCC and indicated a worse prognosis. IGF2BP3 significantly promoted RCC progression in vitro and in vivo. Mechanistically, circRARS bound to KH1–KH2 domains of IGF2BP3 to enhance m6A modification recognition. A 12‐nt sequence (GUCUUCCAGCAA) was proven to be the IGF2BP3‐binding site of circRARS. Additionally, CAPN15, CD44, HMGA2, TNRC6A and ZMIZ2 were screened to be the target genes regulated by the IGF2BP3/circRARS complex in an m6A‐dependent manner. Stabiliser proteins, including HuR, Matrin3 and pAbPC1, were recruited by circRARS, thereby increasing the mRNA stability of the forementioned five target genes. Consequently, the IGF2BP3/circRARS complex facilitated the lipid accumulation of RCC cells and promoted sunitinib resistance via target genes. circRARS synergised with IGF2BP3 to facilitate m6A recognition, thereby promoting RCC progression. Thus, IGF2BP3 could be a potential biomarker for RCC diagnosis and prognosis and a therapeutic target. [ABSTRACT FROM AUTHOR]

[Display omitted] • The symmetry-breaking strategy was creatively used for PDx to fabricate PDx/g-C 3 N 4. • The asymmetric backbone TBF contributes to higher crystallinity in PD1 and PD3. • The BDT unit with asymmetric side chains promotes charge transfer in PD5/g-C 3 N 4. • The k for RhB degradation of PD5/g-C 3 N 4 was a record high 8 times that of g-C 3 N 4. Heterojunctions based on conjugated polymers (PHJs) are of promise as photocatalysts. Here, we fabricate the two-dimensional benzodithiophene (BDT) and thieno[2,3- f ]benzofuran (TBF) based conjugated polymers/g-C 3 N 4 PHJs creatively using the symmetry-breaking strategy. PD1 and PD3 with the asymmetric backbone TBF have better crystallinity. Moreover, PD3 utilizing fluorinated benzotriazole as the electron acceptor unit possesses more compact π − π stacking and higher charge mobility. The conjugated polymer PD5 with asymmetric side chains in the donor unit BDT guarantees more efficient charge transfer in the corresponding PD5/g-C 3 N 4 PHJ while maintaining comparable light utilization rate. Consequently, PD5/g-C 3 N 4 shows the champion performance with photocatalytic sterilization rates reaching 99.1% and 97.3% for S. aureus and E. coli. Notably, the reaction rate constant for Rhodamine B degradation of PD5/g-C 3 N 4 is 8 times that of g-C 3 N 4 , a record high among conjugated polymers/g-C 3 N 4. This study aims to reveal the structure − property correlation of asymmetric conjugated polymers/g-C 3 N 4 for potential photocatalysis applications. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-1 (HIV-1) recognizes one of its principal coreceptors, CXC chemokine receptor 4 (CXCR4), on the host cell via the third variable loop (V3 loop) of HIV-1 envelope glycoprotein gp120 during the viral entry process. Here, the mechanism of the molecular recognition of HIV-1 gp120 V3 loop by coreceptor CXCR4 was probed by synthetic peptides containing the full-length V3 loop. The two ends of the V3 loop were covalently linked by a disulfide bond to form a cyclic peptide with better conformational integrity. In addition, to probe the effect of the changed side-chain conformations of the peptide on CXCR4 recognition, an all-D-amino acid analog of the L-V3 loop peptide was generated. Both of these cyclic L- and D-V3 loop peptides displayed comparable binding recognition to the CXCR4 receptor, but not to another chemokine receptor, CCR5, suggesting their selective interactions with CXCR4. Molecular modeling studies revealed the important roles played by many negative-charged Asp and Glu residues on CXCR4 that probably engaged in favorable electrostatic interactions with the positive-charged Arg residues present in these peptides. These results support the notion that the HIV-1 gp120 V3 loop-CXCR4 interface is flexible for ligands of different chiralities, which might be relevant in terms of the ability of the virus to retain coreceptor recognition despite the mutations at the V3 loop. [ABSTRACT FROM AUTHOR]

Temporomandibular joint osteoarthritis (TMJ OA) is a common degenerative joint disease that has multiple causes. The abnormal stress distribution is known to be an important trigger of TMJ OA. This article explored the pathological changes of the condylar cartilage under 60 g mechanical force and whether the inhibition of Receptor-interacting protein 1 (RIP1) can protect stress-induced TMJ OA. We used a compressive mechanical force-induced-TMJ OA model and Lenti-virus targeting RIP1 to perform this study. A total of 72 male rats were used in the animal experiment. Each rat was injected with a negative control Lenti-shRNA in the right TMJ and Lenti-siRIP1 in the left TMJ and euthanized after 4 and 7 days, respectively. Quantitative real-time PCR, immunohistochemistry, Tunnel staining and Micro-CT were used to detect cartilage pathological changes and one way ANOVA with LSD analysis was used to determine statistical significance between groups. The results identified the characteristics of the spatio-temporal changes in stress-induced TMJ OA. Under mechanical force, inflammation and apoptosis, which occur in the whole layer of mandibular cartilage, appear on the 4th day and persist till the 7th day. Necroptosis arises in the later stage of mechanical force and is mainly located in the transition layer. RIP1 inhibition through Lenti-virus could protect stress-induced mandibular cartilage thinning by inhibiting persisted apoptosis and later-stage necroptosis in the transition layer. RIP1 plays an essential role in the destruction of mandibular cartilage under mechanical force. RIP1 inhibition through Lenti-virus could protect mechanical stress-induced TMJ OA. • Receptor-interacting protein 1 plays an essential role in the pathological change of mandibular cartilage under 60 g mechanical force. • Inflammation and apoptosis are continuous in the pathological changes of mandibular cartilage and necroptosis appears on the later stage. • Receptor-interacting protein 1 inhibition through Lenti-virus could protect mechanical stress-induced mandibular cartilage thinning. [ABSTRACT FROM AUTHOR]