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Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the accumulation of fat in the liver, excluding excessive alcohol consumption and other known causes of liver injury. Animal models are often used to explore different pathogenic mechanisms and therapeutic targets of MASLD. The aim of this study is to apply an artificial intelligence (AI) system based on second-harmonic generation (SHG)/two-photon-excited fluorescence (TPEF) technology to automatically assess the dynamic patterns of hepatic steatosis in MASLD mouse models. Methods: We evaluated the characteristics of hepatic steatosis in mouse models of MASLD using AI analysis based on SHG/TPEF images. Six different models of MASLD were induced in C57BL/6 mice by feeding with a western or high-fat diet, with or without fructose in their drinking water, and/or by weekly injections of carbon tetrachloride. Results: Body weight, serum lipids, and liver enzyme markers increased at 8 and 16 weeks in each model compared to baseline. Steatosis grade showed a steady upward trend. However, the non-alcoholic steatohepatitis (NASH) Clinical Research Network (CRN) histological scoring method detected no significant difference between 8 and 16 weeks. In contrast, AI analysis was able to quantify dynamic changes in the area, number, and size of hepatic steatosis automatically and objectively, making it more suitable for preclinical MASLD animal experiments. Conclusions: AI recognition technology may be a new tool for the accurate diagnosis of steatosis in MASLD, providing a more precise and objective method for evaluating steatosis in preclinical murine MASLD models under various experimental and treatment conditions.

Abstract Apiose is a natural pentose containing an unusual branched-chain structure. Apiosides are bioactive natural products widely present in the plant kingdom. However, little is known on the key apiosylation reaction in the biosynthetic pathways of apiosides. In this work, we discover an apiosyltransferase GuApiGT from Glycyrrhiza uralensis. GuApiGT could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, and exhibits strict selectivity towards UDP-apiose. We further solve the crystal structure of GuApiGT, determine a key sugar-binding motif (RLGSDH) through structural analysis and theoretical calculations, and obtain mutants with altered sugar selectivity through protein engineering. Moreover, we discover 121 candidate apiosyltransferase genes from Leguminosae plants, and identify the functions of 4 enzymes. Finally, we introduce GuApiGT and its upstream genes into Nicotiana benthamiana, and complete de novo biosynthesis of a series of flavonoid apiosides. This work reports an efficient phenolic apiosyltransferase, and reveals mechanisms for its sugar donor selectivity.

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5′-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

The Shuangjianzishan super-large Ag-Pb-Zn deposit is situated in the southern Great Xing’an Range (SGXR), which is part of the eastern Central Asian Orogenic Belt (CAOB) and the northeastern Xing’an-Mongolia Orogenic Belt (XMOB). The host rock of this deposit is the Dashizhai Formation, characterized by a widely distributed, extremely thick slate in the Shuangjianzishan basin. Petrographically, the slate contains secondary minerals such as secondary quartz, biotite, sphalerite, pyrite, galena, and chalcopyrite, in addition to primary quartz, feldspar, and rock fragment. The whole-rock geochemical analysis indicates that the slate was deposited in an oxygen-deficient shale basin, influenced by calcium-rich volcanic ash and magmatic-hydrothermal fluids. The mineralogical characteristics of sulfide minerals and the in-situ sulfur isotopic composition of pyrites suggest that the sulfide minerals were likely formed before the primary metallogenic epoch, indicating pre-enrichment of metals. The color variation from black to green observed in the drilling core of the slate is attributed to differences in feldspar content, with the denser “black” slate marking the metallogenic horizon. Based on previous research, it is inferred that the slate is a product of the post-orogenic extensional tectonic setting of the XMOB in the Late Carboniferous, and it underwent alteration by epithermal magmatic-hydrothermal fluids during the Mesozoic metallogenic episode.

Abstract The origins of Cenozoic granites in the Himalaya are key to understanding the evolution of the Himalayan orogen. However, it is unclear whether these granites represent primary melts, and the nature of their magma source is controversial. Here, we present a systematic element and Sr–Nd–B–Mo isotope study of Cenozoic granites from the Yardoi area in the eastern Tethyan Himalaya, China. These granites can be divided into two groups: mid‐Eocene porphyritic two‐mica granites with low SiO2 contents (65.9−69.6 wt.%) and adakitic geochemical signatures, and mid‐Eocene to Miocene equigranular granites with high SiO2 contents (71.6−75.5 wt.%). The high‐SiO2 granites (HSG) have similar Sr−Nd isotope compositions to the low‐SiO2 granites (LSG), but they have distinct δ11B values of −19.4‰ to −11.4‰ and −10.6‰ to −6.89‰. This indicates that the two groups have different sources, with the LSG derived by partial melting dominantly of metamafic rocks at thickened lower crustal conditions, and the HSG generated by partial melting of the mid‐crust metasedimentary rocks with less enriched Nd isotope compositions. The δ98/95Mo of the LSG and HSG are highly variable with values of −0.68‰ to 0.12‰ and −1.13‰ to 0.46‰, respectively. δ11B values of the HSG correlate positively with δ98/95Mo and Sr/Y values and correlate negatively with K2O, Rb, Zr, and Rb/Sr, reflecting the addition of external metamorphic fluids during anatexis of the metapelites. The B–Mo isotope data robustly suggest source‐controlled compositional diversity of the Himalayan granites, which could provide clues to the physical and geochemical responses during the evolution of a large orogen.

C-glycosides are an important class of bioactive natural products, and the C-glycosidic bonds are usually catalyzed by C-glycosyltransferases. In this work, an efficient and rare CGT, LaCGT1, was discovered from the aquatic plant Lemna aequinoctialis. LaCGT1 could accept five sugar donors (UDP-Glc/-Xyl/-Gal/-GlcNAc/-Ara) to catalyze C-glycosylation, and showed strong preference to uridine 5′-diphosphate xylose (UDP-Xyl). LaCGT1 catalyzed at least six substrates using UDP-Xyl as sugar donor, with conversion rates of > 95%. Three xylosides were obtained by scaled-up enzymatic catalysis, and their structures were identified by 1D NMR, 2D NMR, and HR-ESIMS data analyses. Molecular modeling and site-directed mutagenesis indicated that R271, W357, D378, and Q379 residues were key amino acids contributing to sugar donor recognition of UDP-Xyl. LaCGT1 could be a promising catalyst to prepare bioactive flavonoid C-xylosides.

Honey bees are typical model organisms for the study of caste differentiation, and the juvenile hormone (JH) is a crucial link in the regulatory network of caste differentiation in honey bees. To investigate the mechanism of JH-mediated caste differentiation, we analyzed the effect of the JH response gene AmKr-h1 on this process. We observed that AmKr-h1 expression levels were significantly higher in queen larvae than in worker larvae at the 48 h, 84 h, and 120 h larval stages, and were regulated by JH. Inhibiting AmKr-h1 expression in honey bee larvae using RNAi could lead to the development of larvae toward workers. We also analyzed the transcriptome changes in honey bee larvae after AmKr-h1 RNAi and identified 191 differentially expressed genes (DEGs) and 682 differentially expressed alternative splicing events (DEASEs); of these, many were related to honey bee caste differentiation. Our results indicate that AmKr-h1 regulates caste differentiation in honey bees by acting as a JH-responsive gene.

Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may “wake up” immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the “dominant population” for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.

RNA interference (RNAi) has been used successfully to reduce target gene expression and induce specific phenotypes in several species. It has proved useful as a tool to investigate gene function and has the potential to manage pest populations and reduce disease pathogens. However, it is not known whether different administration methods are equally effective at interfering with genes in bees. Therefore, we compared the effects of feeding and injection of small interfering RNA (siRNA) on the messenger RNA (mRNA) levels of alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1), 4-coumarate-CoA ligase (4CL), and heat shock protein 70 (HSP70). Both feeding and injection of siRNA successfully knocked down the gene but feeding required more siRNA than the injection. Our results suggest that both feeding and injection of siRNA effectively interfere with brain genes in bees. The appropriateness of each method would depend on the situation.

BackgroundApproximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (biCEBPA) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.MethodsIn this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (N =111) and a validation cohort (N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method.ResultsAt least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R, KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P

Sex determination and caste differentiation are two crucial processes for morphology building in honeybees. It is unclear whether there is an interaction between these two processes. Here, we investigated the expression of fem and Amdsx genes between female castes of honeybees. We found that the expression of fem and Amdsx is significantly higher in queens than in workers, and this expression was positively regulated by juvenile hormone (JH). Our results suggest that sex-determining genes fem and Amdsx are also involved in honeybee caste differentiation.

In this paper, a novel temperature field tailored broadband terahertz absorber is proposed, which consists of the metallic mercury resonance units. When the ambient temperature (T) alters, the mercury can be expanded through the vertebral body channel, middle cross glass cavities, cylindrical hole and fill the upper cross glass cavities of such an absorber, which leads to the absorption bands changed. The simulated results indicate that when T = −30 ℃, the wideband absorption (WBA) regions over 90% can be achieved, which are located at 4.53–5.79 THz and 8.15–9.49 THz, and their relative bandwidths (RBs) are 24% and 15.5%, respectively. If T is increased to 300 ℃, such two WBA areas will move to 2.83–3.39 THz and 5.90–7.74 THz, whose RBs are changed to 18% and 13.3%. To investigate the performance of such an absorber, the effects of incident angle, polarization angle and structural parameters on the absorption are discussed. Similarly, the electric and magnetic field intensity distributions, the surface current distributions, power flow and power loss density of the presented absorber are also given to expound the physical mechanism of absorption. The scheme put forward in this paper will provide a new idea for the study of tunable absorbers.

Apis cerana is one of the main honeybee species in artificial farming, which is widely distributed in Asian countries. The genome of A. cerana has been sequenced by several different research groups using second generation sequencing technologies. However, it is still necessary to obtain more complete and accurate genome sequences. Here we present a chromosome-scale assembly of the A. cerana genome using single-molecule real-time (SMRT) Pacific Biosciences sequencing and high-throughput chromatin conformation capture (Hi-C) genome scaffolding. The updated assembly is 215.67 Mb in size with a contig N50 of 4.49 Mb, representing an 212-fold improvement over the previous Illumina-based version. Hi-C scaffolding resulted in 16 pseudochromosomes occupying 97.85% of the assembled genome sequences. A total of 10,741 protein-coding genes were predicted and 9,627 genes were annotated. Besides, 314 new genes were identified compared to the previous version. The improved high-quality A. cerana reference genome will provide precise sequence information for biological research of A. cerana.

Context: Scutellaria baicalensis Georgi (Lamiaceae) is a popular medicinal plant. Its roots are used as the famous traditional Chinese medicine Huang-Qin, which is recorded in Chinese Pharmacopoeia, European Pharmacopoeia, and British Pharmacopoeia. Objective: This review comprehensively summarizes research progress in phytochemistry, pharmacology, and flavonoid biosynthesis of S. baicalensis. Methods: English and Chinese literature from 1973 to March 2018 was collected from databases including Web of Science, SciFinder, PubMed, Elsevier, Baidu Scholar (Chinese), and CNKI (Chinese). Scutellaria baicalensis, chemical constituents, phytochemistry, biological activities, and biosynthesis were used as the key words. Results: A total of 126 small molecules (1–126) and 6 polysaccharides have been isolated from S. baicalensis. The small molecules can be classified into four structural types, namely, free flavonoids, flavonoid glycosides, phenylethanoid glycosides, and other small molecules. Extracts of S. baicalensis and its major chemical constituents have been reported to possess anti-viral, anti-tumor, anti-bacterial, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective activities. Key steps in the biosynthetic pathways of Scutellaria flavonoids have also been summarized. Conclusions: This article could be helpful for researchers who are interested in the chemical constituents, bioactivities, biosynthesis, and clinical applications of S. baicalensis.

Lithium-sulfur (Li-S) batteries are deemed to be one of the most optimal solutions for the next generation of high-energy-density and low-cost energy storage systems. However, the low volumetric energy density and short cycle life are a bottleneck for their commercial application. To achieve high energy density for lithium-sulfur batteries, the concept of synergistic adsorptive–catalytic sites is proposed. Base on this concept, the TiN@C/S/Ta2O5 sulfur electrode with about 90 wt% sulfur content is prepared. TiN contributes its high intrinsic electron conductivity to improve the redox reaction of polysulfides, while Ta2O5 provides strong adsorption capability toward lithium polysulfides (LiPSs). Moreover, the multidimensional carbon structure facilitates the infiltration of electrolytes and the motion of ions and electrons throughout the framework. As a result, the coin Li-S cells with TiN@C/S/Ta2O5 cathode exhibit superior cycle stability with a decent capacity retention of 56.1% over 300 cycles and low capacity fading rate of 0.192% per cycle at 0.5 C. Furthermore, the pouch cells at sulfur loading of 5.3 mg cm−2 deliver a high areal capacity of 5.8 mAh cm−2 at low electrolyte/sulfur ratio (E/S, 3.3 μL mg−1), implying a high sulfur utilization even under high sulfur loading and lean electrolyte operation.

Trust plays an important role in pervasive social networking (PSN) for reciprocal activities among strang-ers.It helps people overcome perceptions of uncertainty and risk and engages in trust-related social behaviors.The current literature on trust management in PSN was reviewed.The advantages and disadvantages of existing solutions were analyzed.Furthermore,key research issues were presented.A research model was also proposed to achieve trustworthy pervasive social networking comprehensively.

The mechanism of sex determination is common for all honeybee species (Apis spp.) by the complementary sex determi-nation (csd) gene. The csd gene has been studied in the Western honey bee (Apis mellifera L.), the Eastern honey bee (Apis cerana F.) and the giant honey bee (Apis dorsata F.), whereas no studies had been conducted on the high altitude Himalayan or black giant honey bee, Apis laboriosa Smith. In the present study, we cloned the genomic exon 6 to exon 9 region of the A. laboriosa csd gene, and identified 13 csd haplotypes. The data was analyzed and compared with the other aforementioned three honeybee species. The results showed that, as with the other three Apis species, region 3 of the csd gene contains an RS domain at the N terminal, a proline-rich domain at the C terminal, and a hypervariable region in the middle. A phylogenetic tree showed that the csd haplotypes from A. laboriosa fell into one clade with those from A. dorsata, and were separated from those from the other two species, A. mellifera and A. cerana. The network map also showed that the csd haplotypes from A. laboriosa and A. dorsata are well mixed among each other, and do not form two separate branches. Pairwise Fst analysis revealed that the value between A. laboriosa and A. dorsata was very low (0.098), confirming a close relationship to exist between them.

Royal jelly has many important biological functions, however the molecular mechanism of royal jelly secretion in hypopharyngeal gland (HG) is still not well understood. In our previously study, six genes (SV2C, eIF-4E, PDK1, IMP, cell growth-regulating nucleolar protein and TGF-βR1) have been shown to might be associated with royal jelly secretion. In this study, the relative expression levels of these genes were examined in the hypopharyngeal gland of workers at different developmental stages (nurse, forager and reversed nurse stages). The results indicated that the relative expression levels of SV2C, eIF-4E, IMP, cell growth-regulating nucleolar protein and TGF-βR1 were reversed at reversed nurse stage compared to forager stage. We concluded that these genes are possibly candidates related to hypopharyngeal gland development or royal jelly secretion.

Neuropeptide FF (NPFF) is known to be an endogenous opioid-modulating peptide. Nevertheless, very few researches focused on the interaction between NPFF and endogenous opioid peptides. In the present study, we have investigated the effects of NPFF system on the supraspinal antinociceptive effects induced by the endogenous µ-opioid receptor agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2). In the mouse tail-flick assay, intracerebroventricular injection of EM-1 induced antinociception via µ-opioid receptor while the antinociception of intracerebroventricular injected EM-2 was mediated by both µ- and κ-opioid receptors. In addition, central administration of NPFF significantly reduced EM-1-induced central antinociception, but enhanced EM-2-induced central antinociception. The results using the selective NPFF1 and NPFF2 receptor agonists indicated that the EM-1-modulating action of NPFF was mainly mediated by NPFF2 receptor, while NPFF potentiated EM-2-induecd antinociception via both NPFF1 and NPFF2 receptors. To further investigate the roles of µ- and κ-opioid systems in the opposite effects of NPFF on central antinociception of endomprphins, the µ- and κ-opioid receptors selective agonists DAMGO and U69593, respectively, were used. Our results showed that NPFF could reduce the central antinociception of DAMGO via NPFF2 receptor and enhance the central antinociception of U69593 via both NPFF1 and NPFF2 receptors. Taken together, our data demonstrate that NPFF exerts opposite effects on central antinociception of endomorphins and provide the first evidence that NPFF potentiate antinociception of EM-2, which might result from the interaction between NPFF and κ-opioid systems.

Economic development usually leads to increased energy consumption, which in turn will result in an increase in carbon emissions. To break the relationship between economic development and carbon emissions, scholars have turned their attention to the phenomenon of decoupling. In this paper, we studied the decoupling relationship between carbon emissions and economic growth of the equipment manufacturing industry in China from 2000 to 2014. We adapted the LMDI decomposition method, and we used the Tapio decoupling evaluation model to analyze our data. We found that the decoupling relationship between carbon emissions and economic growth of China’s equipment manufacturing industry is weak, which indicates the industry is experiencing faster economic growth than carbon emission growth. We found the economic output is the factor that has the strongest influence on the industry’s carbon emission, and energy consumption intensity has the strongest relationship with the decoupling of economic growth and carbon emission. The indicators of the industry’s decoupling-effort are all less than 1.0, which indicates that the industry is in the state of weak decoupling, and we also observed an annual decreasing trend in the industry’s indicators. Toward the end of this paper, we used the Grey forecasting model to predict the decoupling relationship between carbon emission and economic growth for 2015–2024, and we discussed the implications of our research.

The low mature shale oil resources of Lucaogou Formation in Jimusar Sag have a great potential, but the heavy oil quality limits large-scale economic development significantly. Ultrasonic is a typical representative of heavy oil viscosity reduction and anhydrous fracturing technology, and how to understand the action characteristics and mechanism of ultrasonic effect on reservoir is a critical issue to enhance shale oil production in the industrialized application of power ultrasonic. Therefore, the comparative experiments with different time of power ultrasonic loading were conducted to analyze the response mechanism of reservoir characteristics and the change of fluid mobility. The results indicate that the ultrasonic treatment is ameliorative to the pore-fracture structure, and the improvement degree is controlled by the mechanical vibration and cavitation of ultrasound. Generally, the location with weak cementation strength or relatively developed microcrack is preferred to pore expansion. After the ultrasonic treatment, the shale oil quality becomes lighter, and the transformation of shale oil from adsorbed to free, is accelerated due to enhanced fluidity. Pore-expanding effect and fluid mobility enhancement are essential aspects of the power ultrasonic loading to improve the recovery of low mature shale oil. The results of this study support the feasibility analysis of ultrasonic enhanced shale oil exploitation theoretically. [ABSTRACT FROM AUTHOR]