[Spatiotemporal Response of Ecosystem Service Value to Land Use Change in the Lanzhou-Xining Urban Agglomeration over the Past 20 Years].

With rapid urbanization and human activities exacerbating threats to the degradation of various ecosystem services in modern urban agglomerations, the exploration of the state of ecological security at the scale of urban agglomerations is of great significance. This study considered the Lanzhou-Xining Urban Agglomeration as the research area, based on the land use data in 2000, 2005, 2010, 2015, and 2020. At the same time, the landscape ecological risk index was introduced. The land use change characteristics of the Lanzhou-Xining Urban Agglomeration were analyzed by using the land use transfer matrix, the value per unit area equivalent factor method, and the bivariate spatial autocorrelation analysis method to elucidate the impacts of the changes in the ecological risk index induced by the land use transition on the value of ecosystem services. This study analyzed the land use change characteristics of the Lanzhou-Xining Urban Agglomeration and elucidated the impacts of changes in the ecological risk index on the value of ecosystem services caused by land use transformation. The results showed that:① During the period from 2000 to 2020, the land use types of the Lanzhou-Xining Urban Agglomeration were mainly dominated by grassland, cropland, and forest land. The construction land area had expanded significantly mainly from cropland and grassland, and the six land use types had strong cross-transformation. The total area of land use change was 6 646.05 km2. ② In terms of spatial changes, the spatial pattern of ecosystem service value in the Lanzhou-Xining Urban Agglomeration had not undergone obvious transformation. However, the regional variability was significant, generally showing the distribution characteristics of high in the northwest and low in the southeast. ③From the perspective of temporal change, the value of ecosystem services in the Lanzhou-Xining Urban Agglomeration showed an upward trend, with the total flow of value increasing from 186.459 billion yuan to 192.156 billion yuan, with a total value-added of 5.697 billion yuan. ④ There was a rising trend in the overall ecological risk index of the Lanzhou-Xining Urban Agglomeration over the past 20 years. Low ecological risk areas and lower ecological risk areas dominated the ecological risk areas. There was a significant positive correlation between the value of ecosystem services and the ecological risk index. This study aimed to reveal the understanding of the impacts of land-use practices on ecosystem service values and ecological risks, to provide important references for regional ecological risk management and land-use policy formulation, and thus to promote the high-quality development of the ecological environment in the Yellow River Basin.

Uptake of polycyclic aromatic hydrocarbons (PAHs) from PAH-contaminated soils to carrots and Chinese cabbages under the greenhouse and field conditions.

Polycyclic aromatic hydrocarbons (PAHs) with the properties of structural stability, semi-volatility, and hydrophobicity are toxic and persistent in environments; thus, their transport and fate in agroecosystems is essential for reducing PAH accumulation in the edible parts of crops. Here, we cultivated cabbages (Brassica pekinensis L.) and carrots (Daucus carota L.) in PAH-contaminated soils under the greenhouse and field conditions. After harvesting, we observed a 9.5-46% reduction in soil ∑PAH concentrations. There were 37% of bioconcentration factors (BCFbs) > 1 and 93% of translocation factors (TFab) > 1, while low-molecular-weight (LMW) PAHs had higher BCFbs than high-molecular-weight (HMW) PAHs. The PAH concentrations showed significant and positive correlations among soils, the belowground parts, and the aboveground parts. The toxicity equivalent concentration (TEQBaP) followed the order of cabbage (greenhouse) > cabbage (field) > carrot (greenhouse) > carrot (field), suggesting potentially higher health risks in cabbage relative to carrot and vegetables under the greenhouse relative to field condition. Our study suggested growing carrots under field conditions as a management strategy for reducing the risks of vegetables grown in PAH-contaminated soils.

Trypsin-treated chickpea protein hydrolysate enhances the cytoaffinity of microbeads for cultured meat application.

Cultured meat is believed to be a promising alternative to conventional meat production that can reduce environmental impacts, animal suffering, and food safety risks. However, one of the major challenges in producing cultured meat is to provide suitable microcarriers that can support cell attachment, proliferation, and differentiation. In this study, we developed novel microcarriers based on chickpea protein hydrolysates functionalized with trypsin. These microcarriers exhibited superior cytoaffinity and proliferation for various types of cultured cells, including C2C12, porcine myoblasts, chicken satellite cells, and 3T3-L1. Moreover, these microcarriers enabled cell differentiation into muscle or fat cells under appropriate conditions. We propose that trypsin treatment enhances the cytoaffinity of chickpea protein hydrolysates by exposing lysine and arginine residues that can interact with cell surface receptors. Our results suggest that chickpea protein hydrolysate functionalized microcarrier is a promising substrate for cultured meat production with cost-effectiveness and scalability.

Environmental profile, potential sources, and ecological risk of polycyclic aromatic hydrocarbons in a typical coastal bay and outer bay area.

As a class of persistent organic pollutants, polycyclic aromatic hydrocarbons (PAHs) are widely present and accumulate in multimedia environments. The pollution characteristics, spatiotemporal distribution, potential sources, influencing factors, and ecological risks of 16 PAHs were investigated in the water-sediment system of the Hangzhou Bay and outer bay area (HZB and OBA, respectively). The total concentrations of 16 PAHs (∑PAHs) were 220 ± 97.0 and 130 ± 36.0 ng/L in the seawater and 343 ± 179 and 505 ± 415 µg/kg (dry weight) in the sediments of the HZB and OBA, respectively. The pollution level of PAHs in the HZB seawater was higher than that in the OBA seawater, but the opposite result was found in the sediments. Moreover, ∑PAHs exhibited high temporal variability in the HZB seawater (rainy season > dry season), whereas ∑PAHs in the sediments showed no significant difference between seasons. The molecular diagnostic ratio method was used to identify pollution sources and showed that the PAHs in seawater came from different pollution sources (fuel combustion and petroleum), whereas the PAHs in the sediments originated from coincident sources (mixed combustion). Correlation analysis revealed that temperature was positively related to ∑PAHs, whereas salinity was negatively related to seawater ∑PAHs values. Ecological risk assessment demonstrated that the potential for adverse ecological effects was low to moderate in seawater but moderate to high in the sediments.

Epigenetic effects of herbal medicine.

Epigenetic memory is essential for life that governs the predefined functional features of cells. Recent evidence has indicated that the epigenetic modification provides a potential link to gene expression changes that may be involved in the development of various chronic diseases, and targeting the epigenome becomes a plausible method for treating diseases. Traditional herbal medicine has gradually entered the vision of researchers due to its low toxicity and its effectiveness in treating diseases. As a matter of fact, researchers found that the possessed epigenetic modification capacity of herbal medicine had the ability to combat the progression of the disease, such as various types of cancer, diabetes, inflammation, amnesia, liver fibrosis, asthma, and hypertension-induced renal injury. Studies on the epigenetic effects of herbal medicine will provide valuable insights into the molecular mechanisms of human diseases, which may lead to new therapeutic approaches and diagnoses. Thus, this review summarized the impact of herbal medicine and its bioactive components on disease epigenome as examples of how utilization of epigenetic plasticity could be useful as the basis for the future development of targeted therapies in chronic diseases.

Comparison of Human Eukaryotic Translation Initiation Factors 5A1 and 5AL1: Identification of Amino Acid Residues Important for EIF5A1 Lysine 50 Hypusination and Its Protein Stability.

The human eukaryotic translation initiation factor 5A (EIF5A) family consists of three members, namely EIF5A1, EIF5A2, and EIF5AL1. Recent studies have shown that the expression of EIF5As is related to many human diseases, such as diabetes, viral infection, central nervous system injury, and cancer. Among them, EIF5A1 plays different functions in various cancers, possibly as a tumor-suppressor or oncogene, while EIF5A2 promotes the occurrence and development of cancer. Yet, the biological function of EIF5AL1 is not being studied so far. Interestingly, although there are only three amino acid (at residues 36, 45, and 109) differences between EIF5A1 and EIF5AL1, we demonstrate that only EIF5A1 can be hypusinated while EIF5AL1 cannot, and EIF5AL1 has a tumor-suppressor-like function by inhibiting cell proliferation and migration. We also show that EIF5AL1 protein turnover is mediated through the proteasomal pathway, and EIF5AL1 protein turnover is much faster than that of EIF5A1, which may explain their differential protein expression level in cells. By engineering single and double mutations on these three amino acids, we pinpoint which of these amino acids are critical for hypusination and protein stability. The data of this work should fill in the gaps in EIF5As research and pave the way for future studies on EIF5AL1.

Single-gene knockout-coupled omics analysis identifies C9orf85 and CXorf38 as two uncharacterized human proteins associated with ZIP8 malfunction.

Human transmembrane protein metal cation symporter ZIP8 (SLC39A8) is a member of the solute carrier gene family responsible for intracellular transportation of essential micronutrients, including manganese, selenium, and zinc. Previously, we established a ZIP8-knockout (KO) human cell model using the CRISPR/Cas9 system and explored how the expression of ZIP8 could possibly contribute to a wide range of human diseases. To further assess the biophysiological role of ZIP8, in the current study, we employed isobaric tags for relative and absolute quantitation (iTRAQ) and detected the changes of the proteome in ZIP8-KO cells (proteomic data are available via ProteomeXchange with identifier PXD036680). A total of 286 differentially expressed proteins (206 downregulated and 80 upregulated proteins) were detected in the ZIP8-KO cell model, and subsequent bioinformatics analyses (GO, KEGG, KOG, and PPI) were performed on these proteins. Interestingly, four "uncharacterized" proteins (proteins with unknown biological function) were identified in the differentially expressed proteins: C1orf198, C9orf85, C17orf75, and CXorf38-all of which were under-expressed in the ZIP8-KO cells. Notably, C9orf85 and CXorf38 were amongst the top-10 most downregulated proteins, and their expressions could be selectively induced by essential micronutrients. Furthermore, clinical-based bioinformatic analysis indicated that positive correlations between the gene expressions of ZIP8 and C9orf85 or CXorf38 were observed in multiple cancer types. Overall, this study reveals the proteomic landscape of cells with impaired ZIP8 and uncovers the potential relationships between essential micronutrients and uncharacterized proteins C9orf85 and CXorf38. The differentially expressed proteins identified in ZIP8-KO cells could be the potential targets for diagnosing and/or treating human ZIP8-associated diseases, including but not limited to malnutrition, viral infection, and cancers.

Molecular dynamics simulation of hyaluronic acid hydrogels: Effect of water content on mechanical and tribological properties.

BACKGROUND AND OBJECTIVE: Recently conducted biomedical studies have shown that the drug diffusivity of hyaluronic acid hydrogel plays an important role in the treatment of joint diseases. The drug diffusivity is closely related to the water content of hydrogel. In addition, different water content will not only affect its mechanical and tribological properties, but also change the effect of drug release. METHODS: In this work, a Molecular dynamics simulation was used to investigate the effect of water content on spatial distribution, tribological and mechanical properties of a hyaluronic acid hydrogel network. This paper focuses on the analysis and calculation of the radial distribution function of 20, 40, 60, and 80% water content model and the friction force and mechanical parameters under the influence of different load and friction speed. RESULTS: The results show that at 20 and 40% water content, the spatial distribution is loose and the intermolecular force is not strong, resulting in a major lack in tribological and mechanical properties; whereas at 60 and 80% water content, the spatial distribution becomes gradually compact and the intermolecular force is gradually increased. The tribological and mechanical properties manifest a marked improvement. CONCLUSIONS: The calculations reveal that the hydrogel model has the best wear resistance, pressure resistance, and plastic deformation resistance at 80% water content. In the range of 20-80% water content, the mechanical properties and friction properties of hydrogels become better and better with the increase of water content.

Multi-omics analysis reveals the metabolic regulators of duodenal low-grade inflammation in a functional dyspepsia model.

Several gastrointestinal phenotypes and impairment of duodenal mucosal barrier have been reported in clinical studies in patients with functional dyspepsia (FD). Due to the preferential colonization of the mucosa, intestinal microbes and their metabolites are commonly involved in host metabolism and immune responses. However, there are no studies on the intertwined correlation among multi-level data. For more comprehensive illustrating, a multi-omics analysis focusing on the duodenum was performed in the FD rat model. We found that differential microbiomes in the duodenum were significantly correlated with the biosynthesis of lipopolysaccharide and peptidoglycan. The innate immune response-related genes, which were upregulated in the duodenum, were associated with the TLR2/TLR4-NFκB signaling pathway. More importantly, arachidonyl ethanolamide (anandamide, AEA) and endocannabinoid analogues showed linear relationships with the FD phenotypes. Taken together, multi-level data from microbiome, transcriptome and metabolome reveal that AEA may regulate duodenal low-grade inflammation in FD. These results suggest an important cue of gut microbiome-endocannabinoid system axis in the pathogenesis of FD.

Constant frequency reconfigurable terahertz metasurface based on tunable electromagnetically induced transparency-like approach.

A terahertz constant frequency reconfigurable metasurface based on tunable electromagnetically induced transparency (EIT)-like property was designed, whose transparency window frequency did not vary with Fermi energy. This structure was composed of two single-layer graphene resonators, namely, left double big rings and right double small rings. An evident transparency window (EIT-like phenomenon) was caused by the near-field coupling between bright modes of the two resonators in the transmission spectrum, in which amplitude over 80% was acquired at 1.98 THz. By individually reconfiguring the Fermi energy of each resonator, the EIT-like effects, transparency window amplitude, modulation speed and group delay could be actively controlled while the frequency of EIT-like window remained constant. Significantly, the transparency window was fully modulated without changing the frequency, and the maximum modulation depth reached 78%. Furthermore, the modulation speed also increased because the total graphene areaAwas effectively reduced in the proposed structure. Compared with other metasurface structures, the modulation properties of the proposed structure showed higher performance while the EIT-like window frequency remained static. This research provides an alternative method for developing constant frequency reconfigurable modulation terahertz devices (such as optical switches and modulators), as well as a potential approach for miniaturization of terahertz devices.

Virtual patient-specific QA with DVH-based metrics.

We demonstrate a virtual pretreatment patient-specific QA (PSQA) procedure that is capable of quantifying dosimetric effect on patient anatomy for both intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). A machine learning prediction model was developed to use linear accelerator parameters derived from the DICOM-RT plan to predict delivery discrepancies at treatment delivery (defined as the difference between trajectory log file and DICOM-RT) and was coupled with an independent Monte Carlo dose calculation algorithm for dosimetric analysis. Machine learning models for IMRT and VMAT were trained and validated using 120 IMRT and 206 VMAT fields of prior patients, with 80% assigned for iterative training and testing, and 20% for post-training validation. Various prediction models were trained and validated, with the final models selected for clinical implementation being a boosted tree and bagged tree for IMRT and VMAT, respectively. After validation, these models were then applied clinically to predict the machine parameters at treatment delivery for 7 IMRT plans from various sites (61 fields) and 10 VMAT multi-target intracranial radiosurgery plans (35 arcs) and compared to the dosimetric effect calculated directly from trajectory log files. Dose indices tracked for targets and organs at risk included dose received by 99%, 95%, and 1% of the volume, mean dose, percent of volume receiving 25%-100% of the prescription dose. The average coefficient of determination (r2 ) when comparing intra-field predicted and actual delivery error was 0.987 ± 0.012 for IMRT and 0.895 ± 0.095 for VMAT, whereas r2 when comparing inter-field predicted versus actual delivery error was 0.982 for IMRT and 0.989 for VMAT. Regarding dosimetric analysis, r2 when comparing predicted versus actual dosimetric changes for all dose indices was 0.966 for IMRT and 0.907 for VMAT. Prediction models can be used to anticipate the dosimetric effect calculated from trajectory files and have potential as a "delivery-free" pretreatment analysis to enhance PSQA.

Contaminant occurrence, spatiotemporal variation, and ecological risk of organophosphorus flame retardants (OPFRs) in Hangzhou Bay and east China sea ecosystem.

Occurrence, spatiotemporal variation, sources, and ecological risks of 20 organophosphorus flame retardants (OPFRs) in water and sediments from Hangzhou Bay (HZB) and its adjacent East China Sea (ECS) were investigated in this study. The concentrations of OPFRs (∑OPFR) in water ranged from 0.51 ng/L to 885 ng/L, with chlorinated OPFRs having the highest value. For sediments, ∑OPFR ranged from 2.93 ng/g, dry weight (dw) to 37.8 ng/g, dw. The ∑OPFR in the water and sediments of HZB in summer was significantly (p < 0.05) higher than that in autumn. Additionally, the pollution of OPFRs in HZB was higher than that in ECS, and the high-concentration areas appeared in the north and south banks of HZB and near the coast of ECS. Principal component analysis-multiple linear regression showed that the OPFRs in this region were mainly from industrial products (e.g., polyurethane foam/paint/coating/textiles/product processing). In terms of aquatic environments, ecological risks were in a low (∑RQs<0.1) to moderate (0.1<∑RQs<1) level, with regard to median exposure levels, a moderate risk (0.1<∑RQs<1) was found in the sediments during autumn. This study can provide new insights into the OPFR pollution characteristic and ecological risk in a specific eco-environment.

Duodenal microbiota makes an important impact in functional dyspepsia.

Duodenal microbiota may have impact in Functional Dyspepsia. The aim of this study was to explore the difference of microbiota on duodenal mucosa between patients with Functional Dyspepsia and normal subjects. The duodenal mucosa of the subjects were collected under upper gastrointestinal endoscope and the contents of the descending duodenal intestine were extracted with cell brushes in 20 patients with Functional Dyspepsia and 5 healthy subjects. The microbiome on duodenal was studied by 16SrDNA gene sequencing. The differences of duodenal flora were analyzed and compared by LEfSe, FAPROTAX, SPSS and other software. There were significant differences in ACE index, shannon index and observedspecies index between patients with functional dyspepsia and healthy people (P < 0.05). PCoA analysis of the structure of bacteria between two groups found that the duodenal microbiome showed a separate trend. In further study, Amova analysis showed a significant difference (P < 0.05). We found that the there are obvious differences in the composition of duodenal microbiome in functional dyspepsia and healthy people. At the genus level, there were significant differences in Alloprevotella, Peptostreptococcus,Sutterella, Corynebacteriurn,Catonella, Faecalibacterium,Staphylococcus,Eubacteriumnodatumgro-up, Lachnoclostridiurn and Lautropia between the two groups (P < 0.05). The prediction results of Microflora function from FAPROTAX showed that the urea decomposing (ureolysis) and fumaric acid respiratory (fumaraterespiration) function of duodenal bacteria in patients with functional dyspepsia were significantly different from those in healthy people (P < 0.05). In conclusion, there is a significant difference in mucosal microflora of duodenum between patients with functional dyspepsia and healthy groups. It includes greater microflora diversity, different microflora structure, different microflora composition, specific taxa and specific microbiome function. The disorder of duodenal microecology may be the formation mechanism of functional dyspepsia.

Effects of CYP3A43 Expression on Cell Proliferation and Migration of Lung Adenocarcinoma and Its Clinical Significance.

The cytochrome P450s (CYP450s) include key oxidative enzymes involved in the metabolism of various carcinogens and anticancer drugs. Bioinformatic studies have demonstrated the association of CYP3A43 with liver cancer and ovarian cancer. However, the biological function of CYP3A43 in tumor progression remains unclear. To further reveal the role of CYP3A43 in tumor progression, we first analyzed the data from the UALCAN database and found that CYP3A43 was negatively correlated to the cancer staging and lymph node metastasis of lung adenocarcinoma (LUAD). We established stable CYP3A43-knockdown LUAD H1299 cell line and found that its knockdown enhanced cell proliferation, colony formation, and migration in vitro, and promoted the growth of tumor xenograft in vivo. Interestingly, when CYP3A43 was ectopically-expressed in the LUAD cell lines, decreased cell proliferation and ERK1/2 phosphorylation level were observed. Lastly, we also identified CYP3A43 co-expressed genes in LUAD from LinkedOmics database followed by GO and KEGG analyses. In conclusion, our results indicate the unprecedented role of CYP3A43 in the suppression of LUAD and provide new possibilities for targeted therapy of this life-threatening disease.

Anti-Cancer and Medicinal Potentials of Moringa Isothiocyanate.

Moringa oleifera (M. oleifera), which belongs to the Moringaceae family, is a common herb, rich in plant compounds. It has a variety of bioactive compounds that can act as antioxidants, antibiotics, anti-inflammatory and anti-cancer agents, etc., which can be obtained in different body parts of M. oleifera. Isothiocyanates (ITCs) from M. oleifera are one class of these active substances that can inhibit cancer proliferation and promote cancer cell apoptosis through multiple signaling pathways, thus curbing cancer migration and metastasis, at the same time they have little adverse effect on normal cells. There are multiple variants of ITCs in M. oleifera, but the predominant phytochemical is 4-(α-L-rhamnosyloxy)benzyl isothiocyanate, also known as moringa isothiocyanate (MIC-1). Studies have shown that MIC-1 has the possibility to be used clinically for the treatment of diabetes, neurologic diseases, obesity, ulcerative colitis, and several cancer types. In this review, we focus on the molecular mechanisms underlying the anti-cancer and anti-chronic disease effects of MIC-1, current trends, and future direction of MIC-1 based treatment strategies. This review combines the relevant literature of the past 10 years, in order to provide more comprehensive information of MIC-1 and to fully exploit its potentiality in the clinical settings.

A calmodulin-binding transcription factor links calcium signaling to antiviral RNAi defense in plants.

RNA interference (RNAi) is an across-kingdom gene regulatory and defense mechanism. However, little is known about how organisms sense initial cues to mobilize RNAi. Here, we show that wounding to Nicotiana benthamiana cells during virus intrusion activates RNAi-related gene expression through calcium signaling. A rapid wound-induced elevation in calcium fluxes triggers calmodulin-dependent activation of calmodulin-binding transcription activator-3 (CAMTA3), which activates RNA-dependent RNA polymerase-6 and Bifunctional nuclease-2 (BN2) transcription. BN2 stabilizes mRNAs encoding key components of RNAi machinery, notably AGONAUTE1/2 and DICER-LIKE1, by degrading their cognate microRNAs. Consequently, multiple RNAi genes are primed for combating virus invasion. Calmodulin-, CAMTA3-, or BN2-knockdown/knockout plants show increased susceptibility to geminivirus, cucumovirus, and potyvirus. Notably, Geminivirus V2 protein can disrupt the calmodulin-CAMTA3 interaction to counteract RNAi defense. These findings link Ca2+ signaling to RNAi and reveal versatility of host antiviral defense and viral counter-defense.

D-galacturonic acid ameliorates the intestinal mucosal permeability and inflammation of functional dyspepsia in rats.

BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disease caused by imbalanced gastrointestinal function. Traditional treatments are deemed to be limited, and new therapeutic drugs are required. New study suggested that duodenal low-grade inflammation and increased intestinal permeability play an important role in the pathogenesis of FD. Previous studies have shown that polysaccharides containing D-galacturonic acid (GA) could modulate intestinal immune activity in vitro and in animal models. However, the ability of GA monomer to improve intestinal mucosal permeability and inflammation in FD has not been clearly elucidated. METHODS: A FD rat model was established using iodoacetamide (IA). FD Rats were administrated different doses of GA. Subsequently, the body weight and behavioral sensitivity of the rats were measured and evaluated; the permeability of the intestinal barrier was measured by determining D-lactose, lactulose/mannitol ratio (LMR), and permeability-related genes [desmocollin-2 (DSC2), TJP1, and OCLN] in FD rats. Also, inflammatory cells [cluster of differentiation (CD)3+ cells and mast cells] were assessed by immunohistochemistry, and the levels of immune-related factors, such as the Toll-like receptor-nuclear factor kappa B (TLR/NF-κB) pathway, were monitored by reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blot assays. RESULTS: Our results suggested that GA could markedly increase the body weight and attenuate the behavioral sensitivity of FD rats. Moreover, GA also has an obvious ameliorating effect on the intestinal mucosal permeability and inflammatory response of FD rats. Furthermore, we found that GA could markedly downregulate TLR2, TLR4, and NF-κB in FD rats. CONCLUSIONS: These findings indicate that GA could significantly attenuate the intestinal mucosal permeability and inflammation FD rats. The effect of GA was partially mediated by the TLR/NF-κB signaling pathway.

Isolation and molecular characterization of NtMYB4a, a putative transcription activation factor involved in anthocyanin synthesis in tobacco.

The MYB transcription factors are involved in the regulation of plant secondary metabolism, cell development and morphogenesis, and stress response. Here, a full-length, 816-bp NtMYB4a cDNA, which encodes a protein comprising 271 amino acids, was isolated from tobacco leaves. Phylogenetic analysis revealed that NtMYB4a is most similar to Nicotiana. attenuata MYB4, followed by Eriobotrya japonica MYB4, and NtMYB4a clustered with transcriptional activators rather than repressors. Subcellular localization assays showed that NtMYB4 localized in the nucleus, membrane, and cytoplasm. Expression analyses revealed differential expression of NtMYB4a among different tissues and organs and between different developmental stages, with most expression occurring in the stems and leaves during the full-bloom stage. Moreover, NtMYB4a expression was induced by cold, NaCl, PEG, abscisic acid, methyl jasmonate, and dark stressors, and the expression patterns and maximum expression levels varied with the type of stress. Overexpression of NtMYB4a upregulated NtPAL, Nt4CL, NtCHS, NtCHI, NtF3H, NtDFR, NtANS, and NtUFGT, which resulted in increased anthocyanin content in the tobacco corolla and darker colors. However, CRISPR/Cas9-mediated knockout of NtMYB4a downregulated NtPAL, NtC4H, Nt4CL, NtCHS, NtCHI, NtF3H, NtANS, and NtUFGT, which resulted in reduced anthocyanin content, and lighter corolla colors. These results indicated that NtMYB4a positively regulates anthocyanin biosynthesis and is involved in abiotic stress responses in tobacco plants.

New hybridization coupling mechanism and enhanced sensitivity in a Cu2-xS@Au nanoparticle dimer.

To improve the refractive index sensitivity of a localized surface plasmon resonance (LSPR) sensor, we employ a new interparticle hybridization plasmon coupled resonance in a semiconductor-metal (Cu2-xS@Au) core-shell nanoparticle dimer (SMCSND), where the refractive index sensitivity can be improved by the generation of a tunable dual-band absorption spectrum at visible and near-infrared wavelengths. Owing to two LSPRs in different wavelength regions supported by the metal shell and semiconductor core, for the first time, we theoretically demonstrate that the new interparticle hybridization plasmon coupled mechanism in semiconductor-metal core-shell nanoparticle dimer depends not only on interparticle separation gap, but also on the nanoparticle shell thickness t. Electromagnetic model analysis reveals that there are two plasmon modes (Mode A and Mode C) associated with the interparticle hybridization plasmon coupled resonance, where the Mode C shows high sensitivity and figure of merit (FoM) to changes in the background dielectric medium. The tunability of the induced interparticle hybridization plasmon coupled resonance with different the separation distance and shell thickness can change the sensitivity and FoM of LSPR sensor in the visible to near-infrared region, which has broad application prospects.

Emerging targets and potential therapeutic agents in non-alcoholic fatty liver disease treatment.

Nonalcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease in the world, which is characterized by liver fat accumulation unrelated to excessive drinking. Indeed, it attracts growing attention and becomes a global health problem. Due to the complexity of the NAFLD pathogenic mechanism, no related drugs were approved by Food and Drug Administration (FDA) till now. However, it is encouraging that a series of candidate drugs have entered the clinical trial stage with expectation to treat NAFLD. In this review, we summarized the main pathways and pathogenic mechanisms of NAFLD, as well as introduced the main potential therapeutic targets and the corresponding compounds involved in metabolism, inflammation and fibrosis. Furthermore, we also discuss the progress of these compounds, such as drug design and optimization, the choice of pharmacological properties and druglikeness, and the analysis of structure-activity relationship. This review offers a medium on future drug design and development, to be beneficial to relevant studies.