Lipid Metabolic Disorders Induced by Organophosphate Esters in Silver Carp from the Middle Reaches of the Yangtze River.

The Yangtze River fishery resources have declined strongly over the past few decades. One suspected reason for the decline in fishery productivity, including silver carp (Hypophthalmichthys molitrix), has been linked to organophosphate esters (OPEs) contaminant exposure. In this study, the adverse effect of OPEs on lipid metabolism in silver carp captured from the Yangtze River was examined, and our results indicated that muscle concentrations of the OPEs were positively associated with serum cholesterol and total lipid levels. In vivo laboratory results revealed that exposure to environmental concentrations of OPEs significantly increased the concentrations of triglyceride, cholesterol, and total lipid levels. Lipidome analysis further confirmed the lipid metabolism dysfunction induced by OPEs, and glycerophospholipids and sphingolipids were the most affected lipids. Hepatic transcriptomic analysis found that OPEs caused significant alterations in the transcription of genes involved in lipid metabolism. Pathways associated with lipid homeostasis, including the peroxisome proliferator-activated receptor (PPAR) signal pathway, cholesterol metabolism, fatty acid biosynthesis, and steroid biosynthesis, were significantly changed. Furthermore, the affinities of OPEs were different, but the 11 OPEs tested could bind with PPARγ, suggesting that OPEs could disrupt lipid metabolism by interacting with PPARγ. Overall, this study highlighted the harmful effects of OPEs on wild fish and provided mechanistic insights into OPE-induced metabolic disorders.

Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.

Rhizospheric Lactobacillus spp. contribute to the high Cd-accumulating characteristics of Phytolacca spp. in acidic Cd-contaminated soil.

Screening high Cd-accumulating plants and understanding the interactions between plants, rhizospheric microbes and Cd are important in developing microbe-assisted phytoremediation techniques for Cd-contaminated soils. In this study, the Cd tolerance and accumulation characteristics of Phytolacca americana L., P. icosandra L. and P. polyandra Batalin growing in acidic Cd-contaminated soil were compared to evaluate their phytoremediation potential. According to Cd concentrations (root: 8.26-37.09 mg kg-1, shoot: 2.80-9.26 mg kg-1), bioconcentration factors (BCFs) and translocation factors (TFs), the three Phytolacca species exhibited high Cd-accumulation capacities, ranked in the following order: P. icosandra (root BCF: 1.25, shoot BCF: 0.31, TF: 0.25) > P. polyandra (root BCF: 0.68, shoot BCF: 0.26, TF: 0.44) > P. americana (root BCF: 0.28, shoot BCF: 0.09, TF: 0.38). Phytolacca icosandra and P. polyandra can thus be considered as two new Cd accumulators for phytoremediation. Soil pH, available Cd (ACd) concentration and certain bacterial taxa (e.g. Lactobacillus, Helicobacter, Alistipes, Desulfovibrio and Mucispirillum) were differentially altered in the rhizospheres of the three Phytolacca species in comparison to unplanted soil. Correlation analysis showed that there were significant interactions between rhizospheric ACd concentration, pH and Lactobacillus bacteria (L. murinus, L. gasseri and L. reuteri), which affected Cd uptake by Phytolacca plants. The mono- and co-inoculation of L. murinus strain D51883, L. gasseri strain D51533 and L. reuteri strain D24591 in the rhizosphere of P. icosandra altered the rhizospheric pH and ACd concentrations, in addition to increasing the shoot Cd contents by 31.9%-44.6%. These results suggest that recruitment of rhizospheric Lactobacillus spp. by Phytolacca plants contributes to their high Cd-accumulating characteristics. This study provides novel insights into understanding the interactions between plants, rhizobacteria and heavy metals.

Tris(1,3-dichloro-2-propyl) Phosphate Inhibits Early Embryonic Development by Binding to Gsk-3ß Protein in Zebrafish.

Recently, several studies have reported that exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) results in abnormal development of zebrafish embryos in blastocyst and gastrula stages, but molecular mechanisms are still not clear. This lacking strongly affects the interspecific extrapolation of embryonic toxicity induced by TDCIPP and hazard evaluation. In this study, zebrafish embryos were exposed to 100, 500 or 1000 µg/L TDCIPP, and 6-bromoindirubin-3'-oxime (BIO, 35.62 µg/L) was used as a positive control. Results demonstrated that treatment with TDCIPP or BIO caused an abnormal stacking of blastomere cells in mid blastula transition (MBT) stage, and subsequently resulted in epiboly delay of zebrafish embryos. TDCIPP and BIO up-regulated the expression of ß-catenin protein and increased its accumulation in nuclei of embryonic cells. This accumulation was considered as a driver for early embryonic developmental toxicity of TDCIPP. Furthermore, TDCIPP and BIO partly shared the same modes of action, and both of them could bind to Gsk-3ß protein, and then decreased the phosphorylation level of Gsk-3ß in TYR·216 site and lastly inhibited the activity of Gsk-3ß kinase, which was responsible for the increased concentrations of ß-catenin protein in embryonic cells and accumulation in nuclei. Our findings provide new mechanisms for clarifying the early embryonic developmental toxicity of TDCIPP in zebrafish.

Gamma-Aminobutyric Acid Enhances Cadmium Phytoextraction by Coreopsis grandiflora by Remodeling the Rhizospheric Environment.

Gamma-aminobutyric acid (GABA) significantly affects plant responses to heavy metals in hydroponics or culture media, but its corresponding effects in plant-soil systems remain unknown. In this study, different GABA dosages (0-8 g kg-1) were added to the rhizosphere of Coreopsis grandiflora grown in Cd-contaminated soils. Cd accumulation in the shoots of C. grandiflora was enhanced by 38.9-159.5% by GABA in a dose-dependent approach because of accelerated Cd absorption and transport. The increase in exchangeable Cd transformed from Fe-Mn oxide and carbonate-bound Cd, which may be mainly driven by decreased soil pH rather than GABA itself, could be a determining factor responsible for this phenomenon. The N, P, and K availability was affected by multiple factors under GABA treatment, which may regulate Cd accommodation and accumulation in C. grandiflora. The rhizospheric environment dynamics remodeled the bacterial community composition, resulting in a decline in overall bacterial diversity and richness. However, several important plant growth-promoting rhizobacteria, especially Pseudomonas and Sphingomonas, were recruited under GABA treatment to assist Cd phytoextraction in C. grandiflora. This study reveals that GABA as a soil amendment remodels the rhizospheric environment (e.g., soil pH and rhizobacteria) to enhance Cd phytoextraction in plant-soil systems.

Mutation of barley HvPDIL5-1 improves resistance to yellow mosaic virus disease without growth or yield penalties.

The soil-borne yellow mosaic virus disease, which is caused by the bymoviruses barley yellow mosaic virus (BaYMV) and/or barley mild mosaic virus (BaMMV), seriously threatens winter barley production in Europe and East Asia. Both viruses are transmitted by the soil-borne plasmodiophorid Polymyxa graminis and are difficult to eliminate through chemical or physical measures in the field, making breeding for resistant cultivars the optimal strategy for disease control. The resistance locus rym1/11 was cloned encoding the host factor gene Protein Disulfide Isomerase Like 5-1 (PDIL5-1), whose loss-of-function variants confer broad-spectrum resistance to multiple strains of BaMMV/BaYMV. Most resistance-conferring variants have been identified in six-rowed barley landraces/historic cultivars, and their introgression into modern two-rowed malting cultivars is difficult because PDIL5-1 is located in a peri-centromeric region with suppressed recombination. In this study, we used CRISPR/Cas9 genome editing to modify PDIL5-1 in the BaYMV/BaMMV-susceptible elite malting barley cv. 'Golden Promise' and obtained the mutants pdil5-1-a and pdil5-1-b. PDIL5-1 in the pdil5-1-a mutant encodes a protein lacking a cysteine residue, and pdil5-1-b contains a protein-coding frameshift. Both mutants were completely resistant to BaYMV. The knockout mutant pdil5-1-b showed complete BaMMV resistance, while pdil5-1-a showed decreased viral accumulation but no disease symptoms if compared to 'Golden Promise'. Both PDIL5-1 edited lines, as well as the previously produced EMS-induced pdil5-1 mutant '10253-1-5' in the elite malting barley cv. 'Barke' background, displayed no growth or yield penalties in garden experiments or bymovirus-free field trials. Line '10253-1-5' showed improved resistance and yield performance compared to the wild-type and its sibling line when grown in infectious fields. Therefore, genome editing of the host factor gene PDIL5-1 could facilitate the breeding of barley varieties with resistance to bymoviruses.

Design and synthesis of N-(1-(6-(substituted phenyl)-pyridazin-3-yl)-piperidine-3-yl)-amine derivatives as JMJD6 inhibitors.

JMJD6 is a member of the JmjC domain-containing family and has been identified as a promising therapeutic target for treating estrogen-induced and triple-negative breast cancer. To develop novel anti-breast cancer agents, we synthesized a class of N-(1-(6-(substituted phenyl)-pyridazine-3-yl)-piperidine-3-yl)-amine derivatives as potential JMJD6 inhibitors. Among them, the anti-cancer compound A29 was an excellent JMJD6 binder (KD = 0.75 ± 0.08 µM). It could upregulate the mRNA and protein levels of p53 and its downstream effectors p21 and PUMA by inhibiting JMJD6. Besides, A29 displayed potent anti-proliferative activities against tested breast cancer cells by the induction of cell apoptosis and cell cycle arrest. Significantly, A29 also promoted a remarkable reduction in tumor growth, with a TGI value of 66.6% (50 mg/kg, i.p.). Taken together, our findings suggest that A29 is a potent JMJD6 inhibitor bearing a new scaffold acting as a promising drug candidate for the treatment of breast cancer.

Polyaspartic acid enhances the Cd phytoextraction efficiency of Bidens pilosa by remolding the rhizospheric environment and reprogramming plant metabolism.

The green soil chelator polyaspartic acid (PASP) can enhance heavy metal phytoextraction efficiency, but the potential mechanisms are not clearly understood from the whole soil-plant system. In this study, we explored the effects and potential mechanisms of PASP addition in soils on plant growth and cadmium (Cd) uptake in the Cd hyperaccumulator Bidens pilosa by analysing variations in chemical elements, rhizospheric microbial community, and plant metabolomics. The results showed that PASP significantly promoted the biomass yield and Cd concentration in B. pilosa, leading to an increase in the total accumulated Cd by 46.4% and 76.4% in shoots and 124.7% and 197.3% in roots under 3 and 6 mg kg-1 PASP addition, respectively. The improved soil-available nutrients and enriched plant growth-promoting rhizobacteria (e.g., Sphingopyxis, Sphingomonas, Cupriavidus, Achromobacter, Nocardioides, and Rhizobium) were probably responsible for the enhanced plant growth after PASP addition. The increase in Cd uptake by plants could be due to the improved rhizosphere-available Cd, which was directly activated by PASP and affected by the induced rhizobacteria involved in immobilizing/mobilizing Cd (e.g., Sphingomonas, Cupriavidus, Achromobacter, and Rhizobium). Notably, PASP and/or these potassium (K)-solubilizing rhizobacteria (i.e., Sphingomonas, Cupriavidus, and Rhizobium) highly activated rhizosphere-available K to enhance plant growth and Cd uptake in B. pilosa. Plant physiological and metabolomic results indicated that multiple processes involving antioxidant enzymes, amino acids, organic acids, and lipids contributed to Cd detoxification in B. pilosa. This study provides novel insights into understanding how soil chelators drive heavy metal transfer in soil-plant systems.

Physiological and rhizospheric response characteristics to cadmium of a newly identified cadmium accumulator Coreopsis grandiflora Hogg. (Asteraceae).

Screening for superior cadmium (Cd) phytoremediation resources and uncovering the mechanisms of plant response to Cd are important for effective phytoremediation of Cd-polluted soils. In this study, the characteristics of Coreopsis grandiflora related to Cd tolerance and accumulation were analyzed to evaluate its Cd phytoremediation potential. The results revealed that C. grandiflora can tolerate up to 20 mg kg-1 of Cd in the soil. This species showed relatively high shoot bioconcentration factors (1.09-1.85) and translocation factors (0.46-0.97) when grown in soils spiked with 5-45 mg kg-1 Cd, suggesting that C. grandiflora is a Cd accumulator and can potentially be used for Cd phytoextraction. Physiological analysis indicated that antioxidant enzymes (i.e., superoxide dismutase, peroxidase, and catalase) and various free amino acids (e.g., proline, histidine, and methionine) participate in Cd detoxification in C. grandiflora grown in soil spiked with 20 mg kg-1 of Cd (Cd20). The overall microbial richness and diversity remained similar between the control (Cd0) and Cd20 soils. However, the abundance of multiple rhizospheric microbial taxa was altered in the Cd20 soil compared with that in the Cd0 soil. Interestingly, many plant growth-promoting microorganisms (e.g., Nocardioides, Flavisolibacter, Rhizobium, Achromobacter, and Penicillium) enriched in the Cd20 soil likely contributed to the growth and vitality of C. grandiflora under Cd stress. Among these, some microorganisms (e.g., Rhizobium, Achromobacter, and Penicillium) likely affected Cd uptake by C. grandiflora. These abundant plant growth-promoting microorganisms potentially interacted with soil pH and the concentrations of Cd and AK in soil. Notably, potassium-solubilizing microbes (e.g., Rhizobium and Penicillium) may effectively solubilize potassium to assist Cd uptake by C. grandiflora. This study provides a new plant resource for Cd phytoextraction and improves our understanding of rhizosphere-associated mechanisms of plant adaptation to Cd-contaminated soil.

Design and synthesis of adamantyl-substituted flavonoid derivatives as anti-inflammatory Nur77 modulators: Compound B7 targets Nur77 and improves LPS-induced inflammation in vitro and in vivo.

In continuing our study on discovering new Nur77-targeting anti-inflammatory agents with natural skeletons, we combined adamantyl group and hydroxamic acid moiety with flavonoid nucleus, synthesized three series of flavonoid derivatives with a similar structure like CD437, and evaluated their activities against LPS-induced inflammation. Compound B7 was found to be an excellent Nur77 binder (Kd = 3.55 × 10-7 M) and a potent inhibitor of inflammation, which significantly decreased the production of cytokines in vitro, such as NO, IL-6, IL-1ß, and TNF-α, at concentrations of 1.25, 2.5, and 5 µM. Mechanistically, B7 modulated the colocalization of Nur77 at mitochondria and inhibited the lipopolysaccharides (LPS)-induced inflammation via the blockade of NF-κB activation in a Nur77-dependent manner. Additionally, B7 showed in vivo anti-inflammatory activity in the LPS-induced mice model of acute lung injury (ALI). These data suggest that the Nur77-targeting flavonoid derivatives can be particularly useful for further pharmaceutical development for the treatment of inflammatory diseases such as ALI.

Phytoremediation potential evaluation of three rhubarb species and comparative analysis of their rhizosphere characteristics in a Cd- and Pb-contaminated soil.

Screening or breeding exceptional plant species for heavy metal phytoremediation is as important as adopting feasible measures to enhance phytoremediation efficiency, which are largely based on clarifying the mechanisms of heavy metal tolerance and accumulation by plants. In this study, cadmium (Cd) and lead (Pb) tolerance and accumulation characteristics of Rheum officinale, R. palmatum, and R. tanguticum were analysed to assess their phytoremediation potential. The seed germination test indicated that these three rhubarb species could tolerate 10 mg L-1 Cd and 100 mg L-1 Pb. However, when sown in Cd- and Pb-contaminated soil, all three rhubarb species exhibited a relatively high Cd accumulation capacity but a considerably low Pb accumulation capacity according to the bioconcentration factors of Cd (0.42-0.47 in shoots and 0.11-0.15 in roots) and Pb (0.004-0.008 in shoots and 0.007-0.013 in roots). The high Cd translocation factors (3.04-4.24) indicated that these three rhubarb species were suitable for Cd phytoextraction. The changes in rhizospheric physicochemical indices were generally similar among the three rhubarb plants in comparison with those of the unplanted soil. However, differential indicator rhizobacteria were identified for the three rhubarb plants, which may be primarily attributed to their different root system characteristics. These enriched rhizobacteria included many plant growth-promoting bacteria, and several of them were also involved in regulating heavy metal uptake by plants, indicating that three rhubarb species likely recruit differentially beneficial rhizobacteria to maintain plant growth and vitality and to regulate heavy metal uptake in the Cd- and Pb-polluted soil. This study identifies new candidate plant resources for the phytoremediation of Cd-polluted soils and provides novel insights into understanding the interactions among heavy metals, rhizobacteria, and plants.

Rhizospheric microbiomics integrated with plant transcriptomics provides insight into the Cd response mechanisms of the newly identified Cd accumulator Dahlia pinnata.

Phytoremediation that depends on excellent plant resources and effective enhancing measures is important for remediating heavy metal-contaminated soils. This study investigated the cadmium (Cd) tolerance and accumulation characteristics of Dahlia pinnata Cav. to evaluate its Cd phytoremediation potential. Testing in soils spiked with 5-45 mg kg-1 Cd showed that D. pinnata has a strong Cd tolerance capacity and appreciable shoot Cd bioconcentration factors (0.80-1.32) and translocation factors (0.81-1.59), indicating that D. pinnata can be defined as a Cd accumulator. In the rhizosphere, Cd stress (45 mg kg-1 Cd) did not change the soil physicochemical properties but influenced the bacterial community composition compared to control conditions. Notably, the increased abundance of the bacterial phylum Patescibacteria and the dominance of several Cd-tolerant plant growth-promoting rhizobacteria (e.g., Sphingomonas, Gemmatimonas, Bryobacter, Flavisolibacter, Nocardioides, and Bradyrhizobium) likely facilitated Cd tolerance and accumulation in D. pinnata. Comparative transcriptomic analysis showed that Cd significantly induced (P < 0.001) the expression of genes involved in lignin synthesis in D. pinnata roots and leaves, which are likely to fix Cd2+ to the cell wall and inhibit Cd entry into the cytoplasm. Moreover, Cd induced a sophisticated signal transduction network that initiated detoxification processes in roots as well as ethylene synthesis from methionine metabolism to regulate Cd responses in leaves. This study suggests that D. pinnata can be potentially used for phytoextraction and improves our understanding of Cd-response mechanisms in plants from rhizospheric and molecular perspectives.

Discovery of new chalone adamantyl arotinoids having RXRα-modulating and anticancer activities.

In the present study, a new series of chalcone adamantly arotinoids (chalcone AdArs) derived from RAR antagonist MX781, are synthesized, characterized, and evaluated for the biological activities in vitro. The studies of antiproliferative activity and RXRα-binding affinity of target compounds result in the discovery of a lead candidate (WA15), which is a good RXRα binder (Kd = 2.89 × 10-6 M) with potent antiproliferative activity against human cancer cell lines (IC50 ≈ 10 µM) and low toxic to normal LO2 and MRC-5 cells (IC50 > 50 µM). Different from MX781, WA15 eliminates RARα antagonist activity but inhibits 9-cis-RA-induced RXRα transactivation activity in a dose-dependent manner. Compound WA15 is found to be a good apoptosis inducer in various cancer cells and promotes cell apoptosis in an RXRα-independent manner. Besides, WA15 shows the induction of proteasome-dependent RXRα degradation which might enhance the WA15-induced apoptosis. Finally, the immunoblotting indicates that WA15 can inhibit the TNFα-induced IKK activation and IκBα degradation, suggesting that the anticancer activity of WA15 might be related to the inhibition of IKK/NF-κB signal pathway.

[Cadmium Accumulation Characteristics of Four Herbs].

A pot-based experiment was conducted to study the Cd tolerance and accumulation characteristics of four invasive herbs (Galinsoga quadriradiata, Panicum dichotomiflorum, Setaria geniculata, and Lolium persicum) under exposures of 0 (T0), 5 (T5), 25 (T25), and 50 mg·kg-1 (T50) soil Cd concentrations to screen for potential Cd accumulators for phytoremediation. The results showed that the biomasses of both shoots and roots of G. quadriradiata had no significant changes compared to the control (T0) samples under all Cd treatments, whereas the biomass of the other three Poaceae species significantly decreased under the T25 or T50 treatment. The results indicate that G. quadriradiata had stronger Cd tolerance than the other three species. The Cd concentrations in the shoots and roots of the four herbs significantly increased with an increase in soil Cd concentrations, but the shoot bioconcentration factors (SBCF) of the four plant species significantly decreased under T5, T25, and T50 treatment. The SBCF of G. quadriradiata and P. dichotomiflorum were greater than 1 whereas those of S. geniculata and L. persicum were lower than 1. The translocation factors (TF) of G. quadriradiata were 0.93, 0.73, and 1.04 under T5, T25, and T50 treatment, respectively, which were significantly higher than those of the other three plants under the same soil Cd concentration. In addition, both the total Cd and shoot Cd contents of G. quadriradiata were notably higher than in the other three species under the same Cd treatment. Moreover, 90% of the Cd in G. quadriradiata could be transferred aboveground, which was significantly higher than for the other three plants. Based on our comprehensive comparison of Cd tolerance and accumulation capacity, we suggest that G. quadriradiata is a high-Cd accumulator with considerable phytoremediation potential.

Combined transcriptomic, proteomic and biochemical approaches to identify the cadmium hyper-tolerance mechanism of turnip seedling leaves.

Cadmium (Cd) pollution is a prominent environment problem, and great interests have been developed towards the molecular mechanism of Cd accumulation in plants. In this study, we conducted combined transcriptomic, proteomic and biochemical approaches to explore the detoxification of a Cd-hyperaccumulating turnip landrace exposed to 5 µM (T5) and 25 µM (T25) Cd treatments. A total of 1090 and 2111 differentially expressed genes (DEGs) and 161 and 303 differentially expressed proteins (DEPs) were identified in turnips under T5 and T25, respectively. However, poor correlations were observed in expression changes between mRNA and protein levels. The enriched KEGG pathways of DEGs with a high proportion (> 80%) of upregulated genes were focused on the flavonoid biosynthesis, sulphur metabolism and glucosinolate biosynthesis pathways, whereas those of DEPs were enriched on the glutathione metabolism pathway. This result suggests that these pathways contribute to Cd detoxification in turnips. Furthermore, induced antioxidant enzymes, heat stock proteins and stimulated protein acetylation modification seemed to play important roles in Cd tolerance in turnips. In addition, several metal transporters were found responsible for the Cd accumulation capacity of turnips. This study may serve as a basis for breeding low-Cd-accumulating vegetables for foodstuff or high-Cd-abstracting plants for phytoremediation.

Xuebijing injection in the treatment of COVID-19: a retrospective case-control study.

BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-α. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-α and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients.

Design, synthesis and biological evaluation of methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold: Novel potential CDK9 inhibitors.

In continuation of our previous work on the investigation of CDK9 inhibitors bearing indole moiety for the discovery of novel anticancer agents, novel methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold were designed, synthesized, and evaluated for the CDK9 inhibitory activity and anticancer activity. Biological activity results demonstrated that most of these derivatives possessed good inhibitory on the kinase activity of CDK9 such as blocking its phosphorylation function and inhibiting HIV-1 transcription. Compound 12i was found to be the most potent CDK9 inhibitor and exhibited excellent anticancer activity against HepG2, A375, MCF-7, and A549, but low toxic on normal cells including HaCaT and MCF-10A. Further studies revealed that as a result of CDK9 inhibition and subsequent inhibition of phosphorylation at Serine 2 of the RNAPII CTD, the representative compound 12i dose-dependently increased cleaved PARP level, exerting its antiproliferative effect through induction of apoptosis in cancer cells. Finally, the molecular docking analysis implied that 12i had a good binding affinity with CDK9. In summary, 12i is a potent CDK9 inhibitor and can be considered as a good lead-candidate for developing potential anticancer drugs.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.

Comparative expression analysis of heavy metal ATPase subfamily genes between Cd-tolerant and Cd-sensitive turnip landraces.

The heavy metal ATPase (HMA) subfamily is mainly involved in heavy metal (HM) tolerance and transport in plants, but an understanding of the definite roles and mechanisms of most HMA members are still limited. In the present study, we identified 14 candidate HMA genes named BrrHMA1-BrrHMA8 from the turnip genome and analyzed the phylogeny, gene structure, chromosome distribution, and conserved domains and motifs of HMAs in turnip (Brassica rapa var. rapa). According to our phylogenetic tree, the BrrHMAs are divided into a Zn/Cd/Co/Pb subclass and Cu/Ag subclass. The BrrHMA members show similar structural characteristics within subclasses. To explore the roles of BrrHMAs in turnip, we compared the gene sequences and expression patterns of the BrrHMA genes between a Cd-tolerant landrace and a Cd-sensitive landrace. Most BrrHMA genes showed similar spatial expression patterns in both Cd-tolerant and Cd-sensitive turnip landraces; some BrrHMA genes, however, were differentially expressed in specific tissue in Cd-tolerant and Cd-sensitive turnip. Specifically, BrrHMA genes in the Zn/Cd/Co/Pb subclass shared the same coding sequence but were differentially expressed in Cd-tolerant and Cd-sensitive turnip landraces under Cd stress. Our findings suggest that the stable expression and up-regulated expression of BrrHMA Zn/Cd/Co/Pb subclass genes under Cd stress may contribute to the higher Cd tolerance of turnip landraces.