Spatiotemporal patterns and deposition of organophosphate esters (OPEs) in air, foliage and litter in a subtropical forest of South China.

Recent studies revealed the un-negligible impact of airborne organophosphate esters (OPEs) on phosphorus (P)-limited ecosystems. Subtropical forests, the global prevalence P-limited ecosystems, contain canopy structures that can effectively sequester OPEs from the atmosphere. However, little is known about the behavior and fate of OPEs in subtropical forest ecosystem, and the impact on the P cycling in this ecosystem. OPE concentrations in the understory air (at two heights), foliage, and litterfall were investigated in a subtropical forest in southern China. The median ∑OPE concentrations were 3149 and 2489 pg/m3 in the upper and bottom air, respectively. Foliage exhibited higher ∑OPE concentrations (median = 386 ng/g dry weight (dw)) compared to litter (median = 267 ng/g dw). The air OPE concentrations were ordered by broadleaved forest > mixed forest > coniferous forest, which corresponds to the results of canopy coverage or leaf area index. The spatial variation of OPEs in foliage and litter was likely caused by the leaf surface functional traits. Higher OPE concentrations were found in the wet season for understory air while in the dry season for foliage and litter, which were attributed to the changes in emission sources and meteorological conditions, respectively. The inverse temporal variation suggests the un-equilibrium partitioning of OPEs between leaf and air. The OPE concentrations during the litter-incubation presented similar temporal trends with those in foliage and litter, indicating the strong interaction of OPEs between the litter layer and the near-soil air, and the efficient buffer of litter layer played in the OPEs partitioning between soil and air. The median OPEs-associated P deposition fluxes through litterfall were 270, 186, and 249 µg P/m2·yr in the broadleaved, mixed, and coniferous forests, respectively. Although the fluxes accounted for approximately 0.2% of the total atmospheric P deposition, their significance to this P-limited ecosystem may not be negligible.

Enhancing rutin accumulation in Tartary buckwheat through a novel flavonoid transporter protein FtABCC2.

Tartary buckwheat (Fagopyrum tataricum) is an annual coarse cereal from the Polygonaceae family, known for its high content of flavonoid compounds, particularly rutin. But so far, the mechanisms of the flavonoid transport and storage in Tartary buckwheat (TB) remain largely unexplored. This study focuses on ATP-binding cassette transporters subfamily C (ABCC) members, which are crucial for the biosynthesis and transport of flavonoids in plants. The evolutionary and expression pattern analyses of the ABCC genes in TB identified an ABCC protein gene, FtABCC2, that is highly correlated with rutin synthesis. Subcellular localization analysis revealed that FtABCC2 protein is specifically localized to the vacuole membrane. Heterologous expression of FtABCC2 in Saccharomyces cerevisiae confirmed that its transport ability of flavonoid glycosides such as rutin and isoquercetin, but not the aglycones such as quercetin and dihydroquercetin. Overexpression of FtABCC2 in TB hairy root lines resulted in a significant increase in total flavonoid and rutin content (P < 0.01). Analysis of the FtABCC2 promoter revealed potential cis-acting elements responsive to hormones, cold stress, mechanical injury and light stress. Overall, this study demonstrates that FtABCC2 can efficiently facilitate the transport of rutin into vacuoles, thereby enhancing flavonoids accumulation. These findings suggest that FtABCC2 is a promising candidate for molecular-assisted breeding aimed at developing high-flavonoid TB varieties.

Tobacco toxins trigger bone marrow mesenchymal stem cells aging by inhibiting mitophagy.

Smoking disrupts bone homeostasis and serves as an independent risk factor for the development and progression of osteoporosis. Tobacco toxins inhibit the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), promote BMSCs aging and exhaustion, but the specific mechanisms are not yet fully understood. Herein, we successfully established a smoking-related osteoporosis (SROP) model in rats and mice through intraperitoneal injection of cigarette smoke extract (CSE), which significantly reduced bone density and induced aging and inhibited osteogenic differentiation of BMSCs both in vivo and in vitro. Bioinformatics analysis and in vitro experiments confirmed that CSE disrupts mitochondrial homeostasis through oxidative stress and inhibition of mitophagy. Furthermore, we discovered that CSE induced BMSCs aging by upregulating phosphorylated AKT, which in turn inhibited the expression of FOXO3a and the Pink1/Parkin pathway, leading to the suppression of mitophagy and the accumulation of damaged mitochondria. MitoQ, a mitochondrial-targeted antioxidant and mitophagy agonist, was effective in reducing CSE-induced mitochondrial oxidative stress, promoting mitophagy, significantly downregulating the expression of aging markers in BMSCs, restoring osteogenic differentiation, and alleviating bone loss and autophagy levels in CSE-exposed mice. In summary, our results suggest that BMSCs aging caused by the inhibition of mitophagy through the AKT/FOXO3a/Pink1/Parkin axis is a key mechanism in smoking-related osteoporosis.

Pleiotropic Role of Rainbow Trout CXCRs in Response to Disease and Environment: Insights from Transcriptional Signatures and Structure Analysis.

Chemokines are cytokines with chemoattractant capacities that exert their physiological functions through the binding of chemokine receptors. Thus, chemokine and receptor complexes exert important roles in regulating development and homeostasis during routine immune surveillance and inflammation. Compared to mammals, the physiology and structure of chemokine receptors in fish have not been systematically studied. Furthermore, the salmonid-specific whole genome duplication has significantly increased the number of functional paralogs of chemokine receptors. In this context, in the current study, trout exhibited 17 cxcr genes, including 12 newly identified and 5 previously identified receptors. Interestingly, gene expression of brain cxcr1 and cxcr4, kidney cxcr3 and cxcr4, and spleen cxcr3, cxcr4, and cxcr5 subtypes were altered by bacterial infection, whereas brain cxcr1, kidney cxcr1 and cxcr7, and liver cxcr2, cxcr3, and cxcr4 subtypes were changed in response to environmental changes. Based on protein structures predicted by ColabFold, the conserved amino acids in binding pockets between trout CXCR4.1 subtypes and human CXCR4 were also analyzed. Our study is valuable from a comparative point of view, providing new insights into the identification and physiology of salmonid chemokine receptors.

Peptide-based non-viral gene delivery: A comprehensive review of the advances and challenges.

Gene therapy is the most effective treatment option for diseases, but its effectiveness is affected by the choice and design of gene carriers. The genes themselves have to pass through multiple barriers in order to enter the cell and therefore require additional vectors to carry them inside the cell. In gene therapy, peptides have unique properties and potential as gene carriers, which can effectively deliver genes into specific cells or tissues, protect genes from degradation, improve gene transfection efficiency, and enhance gene targeting and biological responsiveness. This paper reviews the research progress of peptides and their derivatives in the field of gene delivery recently, describes the obstacles encountered by foreign materials to enter the interior of the cell, and introduces the following classes of functional peptides that can carry materials into the interior of the cell, and assist in transmembrane translocation of carriers, thus breaking through endosomal traps to enable successful entry of genetic materials into the nucleus of the cell. The paper also discusses the combined application of peptide vectors with other vectors to enhance its transfection ability, explores current challenges encountered by peptide vectors, and looks forward to future developments in the field.

Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress.

Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.

Construction of novel 7 integrin-related gene signatures in thyroid cancer construction of model based on integrin genes.

Advanced and metastatic THCA patients usually have a poor prognosis. Thus, this study aimed to establish a risk model to discriminate the high risk population. The expression and clinical data were obtained from TCGA database. The cluster analysis, lasso, univariate and multivariate cox analyses were used to construct risk model. K-M, ROC and DCA were applied to validate the efficiency and stability of the model. GO, KEGG, and ssGSEA analysis were performed to identify the potential mechanism of signatures. The 7-gene prognosis model was constructed, including FAM27E3, FIGN, GSTM4, BEX5, RBPMS2, PHF13, and DCSTAMP. ROC and DCA results showed our model had a better prognosis prediction performance than other risk models. The high risk score was associated with the poor prognosis of THCA patients with different clinical characteristics. The risk score was closely related to cell cycle. Further, we found that the expressions of signatures were significantly dysregulated in THCA and associated with prognosis. These gene expressions were affected by some clinical characteristics, methylation and CNV. Some signatures played a role in drug sensitivity and pathway activation. We constructed a 7-gene signature model based on the integrin-related genes, which showed a great prognostic value in THCA.

Tobacco toxins induce osteoporosis through ferroptosis.

Clinical epidemiological studies have confirmed that tobacco smoking disrupts bone homeostasis and is an independent risk factor for the development of osteoporosis. The low viability and inferior osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) are important etiologies of osteoporosis. However, few basic studies have elucidated the specific mechanisms that tobacco toxins devastated BMSCs and consequently induced or exacerbated osteoporosis. Herein, our clinical data showed the bone mineral density (BMD) values of femoral neck in smokers were significantly lower than non-smokers, meanwhile cigarette smoke extract (CSE) exposure led to a significant decrease of BMD in rats and dysfunction of rat BMSCs (rBMSCs). Transcriptomic analysis and phenotype experiments suggested that the ferroptosis pathway was significantly activated in CSE-treated rBMSCs. Accumulated intracellular reactive oxygen species activated AMPK signaling, furtherly promoted NCOA4-mediated ferritin-selective autophagic processes, increased labial iron pool and lipid peroxidation deposition, and ultimately led to ferroptosis in rBMSCs. Importantly, in vivo utilization of ferroptosis and ferritinophagy inhibitors significantly alleviated BMD loss in CSE-exposed rats. Our study innovatively reveals the key mechanism of smoking-related osteoporosis, and provides a possible route targeting on the perspective of BMSC ferroptosis for future prevention and treatment of smoking-related bone homeostasis imbalance.

Quercetin promotes autophagy to alleviate cigarette smoke-related periodontitis.

BACKGROUND AND OBJECTIVES: Cigarette smoking has been reported as an independent risk factor for periodontitis. Tobacco toxins affect periodontal tissue not only locally but also systemically, leading to the deterioration and recurrence of periodontitis. However, the mechanism of cigarette smoke-related periodontitis (CSRP) is unclear and thus lacks targeted treatment strategies. Quercetin, a plant-derived polyphenolic flavonoid, has been reported to have therapeutic effects on periodontitis due to its documented antioxidant activity. This study aimed to evaluate the effects of quercetin on CSRP and elucidated the underlying mechanism. METHODS: The cigarette smoke-related ligature-induced periodontitis mouse model was established by intraperitoneal injection of cigarette smoke extract (CSE) and silk ligation of bilateral maxillary second molars. Quercetin was adopted by gavage as a therapeutic strategy. Micro-computed tomography was used to evaluate the alveolar bone resorption. Immunohistochemistry detected the oxidative stress and autophagy markers in vivo. Cell viability was determined by Cell Counting Kit-8, and oxidative stress levels were tested by 2,7-dichlorodihydrofluorescein diacetate probe and lipid peroxidation malondialdehyde assay kit. Alkaline phosphatase and alizarin red staining were used to determine osteogenic differentiation. Network pharmacology analysis, molecular docking, and western blot were utilized to elucidate the underlying molecular mechanism. RESULTS: Alveolar bone resorption was exacerbated and oxidative stress products were accumulated during CSE exposure in vivo. Oxidative stress damage induced by CSE caused inhibition of osteogenic differentiation in vitro. Quercetin effectively protected the osteogenic differentiation of human periodontal ligament cells (hPDLCs) and periodontal tissue by upregulating the expression of Beclin-1 thus to promote autophagy and reduce oxidative stress damage. CONCLUSION: Our results established a role of oxidative stress damage and autophagy dysfunction in the mechanism of CSE-induced destruction of periodontal tissue and hPDLCs, and provided a potential application value of quercetin to ameliorate CSRP.

Identification, characterization, and transcription of serotonin receptors in rainbow trout (Oncorhynchus mykiss) in response to bacterial infection and salinity changes.

Serotonergic system is involved in the regulation of physiological functions and behavioral traits including cognition, memory, aggression, stress coping, appetite and immunomodulation. Serotonin exerts its functions via binding distinct serotonin receptors which are classified into 7 groups. Salmonid exhibits expanded functional gene copies due to salmonid-specific whole genome duplication. However, serotonin receptor (htr) repertoire is not fully identified in rainbow trout (Oncorhynchus mykiss). In this study, we identified 39 htr genes, including 14 htr1, 4 htr2, 4 htr2 like, 3 htr3, 4 htr4, 2 htr5, 2 htr6, and 6 htr7 subtypes. We investigated physiological functions of serotonin receptors in response to bacterial pathogens exposure and salinity changes. We showed htr1, htr2, htr4 and htr7 subtypes were associated with immunomodulation in response to Vibrio anguillarum or Aeromonas salmonicida infection. Saltwater (salinity of 15) transfer significantly altered htr1, htr2, htr4, and htr7 subtypes, suggesting trout Htr was associated with osmoregulation. We further showed residues interacted with inverse agonist (methiothepin) and serotonin analogue (5-Carboxamidotryptamine) were conserved between trout and human, suggesting exogenous ligands targeting human HTRs might have a role in aquaculture. This study showed duplicated trout Htrs might be physiologically neofunctionalized and potentially exhibit pleiotropic effects in regulating immunomodulation and osmoregulation.

Vibration for enhancement of electrochemical analysis of biomolecules in a droplet on the rough surface of a disposable working electrode.

Although electrochemical detection of microliters-level solutions is attractive for analysis of low-amount biological samples, its performance could be weakened by limited mass transfer due to low Reynolds number and laminar flow. Herein we designed a 3D-printed electroanalytical device to apply vibration for improvement of mass transfer during electrochemical detection. In our approach, the droplet-size sample solution containing Indole-3-acetic acid (IAA, as a model) was directly applied on the effective surface of a disposable working electrode. We demonstrated that vibration could enhance electrochemical responses of IAA more on the rough surface than on the smooth surface of the working electrodes. After optimization, the sensitivity for electrochemical detection of a 20-µL droplet under vibration with the voltage of 7 V increased more than 100% compared with the static condition. The enhanced electrochemical responses brought by vibration could be achieved reproducibly, which could be ascribed to improved mass transfer. Our strategy could be practically applied for differentiation of IAA in different tissues of Marchantia polymorpha with enhanced responses. This study suggested that vibration might become a simple and effective method to improve mass transfer in analysis of microliter-volume solutions, which might be extended for more biochemical assays.

Polycyclic aromatic hydrocarbons (PAHs) in air, foliage, and litter in a subtropical forest: Spatioseasonal variations, partitioning, and litter-PAH degradation.

Forest canopies play a vital role in scavenging airborne semi-volatile organic compounds. The present study measured polycyclic aromatic hydrocarbons (PAHs) in the understory air (at two heights), foliage, and litterfall in a subtropical rainforest (the Dinghushan mountain) in southern China. ∑17PAH concentrations in the air ranged from 2.75 to 44.0 ng/m3 (mean = 8.91 ng/m3), showing a spatial variation depending on the forest canopy coverage. Vertical distributions of the understory air concentrations also indicated PAH inputs from the above-canopy air. The concentrations of PAHs in fresh litter (with a mean of 261 ± 163 ng/g dry weight (dw)) were slightly lower than those in the foliage (362 ± 291 ng/g dw). Unlike the stable air PAH concentrations for most of the time of the year, the temporal variations of foliage and litter concentrations were remarkable but generally similar. Higher or comparable leaf/litter-air partition coefficients (KLA) in fresh litter compared with living KLA in leaves suggest that the forest litter layer is an efficient storage media for PAHs. Degradation of three-ring PAHs in litter under the field conditions follows first-order kinetics (R2 = 0.81), while the degradation is moderate for four-ring PAHs and insignificant for five- and six-ring PAHs. The yearly net cumulative deposition of PAHs through forest litterfall in the whole Dinghushan forest area over the sampling year was about 1.1 kg, 46% of the initial deposition (2.4 kg). This spatial variations study provides the results of in-field degradation of litter PAHs and makes a quantitative assessment of the litter deposition of PAHs, deducing their residence dynamics in the litter layer in a subtropical rainforest.

miR-22-3p Suppresses Cell Proliferation and Migration of Gastric Cancer by Targeting ENO1.

Background and Objective: miR-22-3p functions as a tumor suppressor by targeting a variety of downstream genes, while its role and downstream targets in gastric cancer (GC) remain to be determined. We aimed to explore the role of miR-22-3p in gastric cancer and the potential mechanism. Methods: miR-22-3p mimic and inhibitor were used to overexpress or knockdown the expression of miR-22-3p separately. Quantitative real-time PCR (RT-qPCR) and Western blot were used to analyse the abundance of mRNA or protein level respectively. CCK-8 assay, cell colony formation assay, and flow cytometry were implemented to investigate the effect of miR-22-3p on gastric cancer cell proliferation and apoptosis. Luciferase assay was used to evaluate the role of miR-22-3p on the expression of glycolytic enzyme enolase 1 (ENO1). Results: In this study, we found that miR-22-3p was downregulated in GC cells. By transfecting the cells with miR-22-3p inhibitors or mimics, we showed that miR-22-3p suppressed GC cell proliferation and migration, as well as triggered cell death. In addition, we discovered that miR-22-3p was engaged in glycolysis by controlling the generation of lactate as well as the consumption of glucose. TargetScan database suggested that the ENO1 may be a target of the miR-22-3p, and the luciferase experiment verified this hypothesis. Recovery assays showed that the proliferation and migration of GC cells suppressed by miR-22-3p could be rescued by overexpression of ENO1. Conclusion: Collectively, we identified a new axis of miR-22-3p/ENO1 for GC development, which could be investigated as a therapeutic target for GC.

Transcriptome analysis of liver, gill and intestine in rainbow trout (Oncorhynchus mykiss) symptomatically or asymptomatically infected with Vibrio anguillarum.

Rainbow trout (Oncorhynchus mykiss), an important economic cold-water fish worldwide, is severely threatened by viruses and bacteria in the farming industry. The vibriosis outbreak has caused a significant setback to aquaculture. Vibrio anguillarum, one of the common disease-causing vibriosis associated with severe lethal vibriosis in aquaculture, infects fish mainly by adsorption and invasion of the skin, gills, lateral line and intestine. To investigate the defense mechanism of rainbow trout against the pathogen after infection with Vibrio anguillarum, trout were intraperitoneally injected by Vibrio anguillarum and divided into symptomatic group (SG) and asymptomatic group (AG) according to the phenotype. RNA-Seq technology was used to evaluate the transcriptional signatures of liver, gill and intestine of trout injected with Vibrio anguillarum (SG and AG) and corresponding control groups (CG(A) and CG(B)). The GO and KEGG enrichment analyses were used to investigate the mechanisms underlying the differences in susceptibility to Vibrio anguillarum. Results showed that in SG, immunomodulatory genes in the cytokine network were activated and tissue function-related genes were down-regulated, while apoptosis mechanisms were activated. However, AG responded to Vibrio anguillarum infection by activating complement related immune defenses, while metabolism and function related genes were up-regulated. Conclusively, a rapid and effective immune and inflammatory response can successfully defend Vibrio anguillarum infection. However, a sustained inflammatory response can lead to tissue and organ damage and cause death. Our results may provide a theoretical basis for breeding rainbow trout for disease resistance.

Comparison of the chronic and multigenerational toxicity of racemic glufosinate and l-glufosinate to Caenorhabditis elegans at environmental concentrations.

Glufosinate-ammonium, the second largest transgene crop resistant herbicide, is classified as a mobile persistent pollutant by the U.S. Environmental Protection Agencybecause of its slow decomposition and easy mobile transfer in a water environment. The chronic and multigeneration toxicity of this compound to environmental organisms are alarming. In this study, racemic glufosinate-ammonium and the effective isomer, l-glufosinate-ammonium, were used as the test agents. The developmental, neurotoxic and reproductive toxicities of Caenorhabditis elegans to their parents and progeny were studied by continuous exposure in water at concentrations of 0.1, 1, 10 and 100 µg/L. The causes of toxicity differences were analysed from oxidative stress and transcription levels. Through oxidative stress of C. elegans, racemic glufosinate-ammonium and l-glufosinate-ammonium both mediated the developmental toxicity (shortened developmental cycle, reduced body length and width, promoted ageingand decreased longevity), neurotoxicity (inhibited head swinging, body bending frequency and acetylcholinesterase [AchE] activity) and reproductive toxicity (significant reductions in the number of eggs and offspring in vivo and induced apoptosis of gonadal cells). These phenomena caused oxidative damage (protein and membrane lipid peroxidation) and further induced apoptosis. The changes in various indicators caused by racemic glufosinate-ammonium exposure were more significant than those caused by l-glufosinate-ammonium exposure, and the reproduction-related indicators were more significant than the developmental and neurological indicators. A continuous accumulation of toxicity was observed after multiple generations of continuous exposure. These research results provide a data reference for the ecotoxicological evaluation and risk assessment of glufosinate-ammonium and contribute to the revision and improvement of the related environmental policies of glufosinate-ammonium.

En Route to High-Density Chiral Single-walled Carbon Nanotube Arrays using Solid Trojan Catalysts.

Solid catalyst is widely recognized as an effective strategy to control the chirality of single-walled carbon nanotubes (SWNTs). However, it is still not compatible with high density in horizontal arrays. "Trojan" catalysts strategy is one of the most effective methods to realize SWNTs with high density and has great potential in chirality control. Here, the co-realization of high density and chirality controlling for SWNTs in a low-temperature growth process is reported based on the developed solid "Trojan" catalyst. High temperature "Trojan" catalyst formation process provides sufficient catalyst number to acquire high density. These liquid "Trojan" catalysts are cooled to solid state by adopting low growth temperature (540 °C), which can be good template to realize the chirality controlling of SWNTs with exposing six-fold symmetry face, (111). Finally, (9, 6) and (13, 1) SWNTs enriched horizontal array with the purity of ≈90% and density of 4 tubes µm-1 is realized. The comparison between the distribution of initial catalysts and the density of as-grown tubes indicates no sacrificing on catalysts number to improve chirality selectivity. This work opens a new avenue on the catalyst's design and chirality controlling in SWNTs growth.

HipBST Toxin-antitoxin System of Prokaryotes / 中国生物化学与分子生物学报

Toxin-antitoxin system (TA) is a genetic element widely found in chromosomes and plasmids of bacteria, archaea and prophages. TA usually consists a toxin that inhibits the growth of bacteria and an antitoxin that neutralizes its toxicity. Since the discovery of the first CcdB / CcdA TA in the 1980s, TA has been proved to exist in almost all sequenced microorganisms and plays an important role in maintaining plasmid stability, anti-phage and promoting biofilm formation. At present, TA is divided into type I-VIII, among which type IITA is the most widely studied. HipBA is a type II TA. The toxin HipA in Escherichia coli HipBA is a serine / threonine kinase, which inhibits protein translation by phosphorylating bacterial Glutamyl tRNA synthetase (GltX), and its toxicity can be specifically neutralized by HipB. Recently, it has been found that Escherichia coli HipA homologous proteins exist widely in microorganisms, and they form a potential novel TA with genes of the same promoter, in which HipBST has been confirmed by experiments. The toxin HipT and the antitoxin HipS in this TA are similar to the C-terminal and N-terminal of E. coli HipA respectively, and the neutralization mechanism and the substrate of the toxin are different from that of E. coli toxin HipA. This study summarizes the recent discovery of special TA, especially the neutralization mechanism of HipBST which widely exists in prokaryotes.

Preparation of thioamides from alkyl bromides, nitriles, and hydrogen sulfide through a thio-Ritter-type reaction.

A novel thio-Ritter-type reaction of alkyl bromides, nitriles, and hydrogen sulfide has been explored, providing a straightforward approach toward functionally important thioamides. This transformation features a broad substrate scope, operational simplicity, use of available feedstock chemicals, and late-stage functionalizations of bioactive molecules. The reaction mechanism is also proposed.

Improved runoff forecasting based on time-varying model averaging method and deep learning.

In order to improve the accuracy and stability of runoff prediction. This study proposed a dynamic model averaging method with Time-varying weight (TV-DMA). Using this method, an integrated prediction model framework for runoff prediction was constructed. The framework determines the main variables suitable for runoff prediction through correlation analysis, and uses TV-DMA and deep learning algorithm to construct an integrated prediction model for runoff. The results demonstrate that the current monthly runoff, the runoff of the previous month, the current monthly temperature, the temperature of the previous month and the current monthly rainfall were the variables suitable for runoff prediction. The results of runoff prediction show that the TV-DMA model has the highest prediction accuracy (with 0.97 Nash-efficiency coefficient (NSE)) and low uncertainty. The interval band of uncertainty was 33.3%-65.5% lower than single model. And the prediction performance of the single model and TV-DMA model in flood season is obviously lower than that in non-flood season. In addition, this study indicate that the current monthly runoff, rainfall and temperature are the important factor affecting the runoff prediction, which should be paid special attention in the runoff prediction.