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Curcuma longa , known as the 'golden spice' and 'life spice', is one of the most commonly utilized spices in the world and also has medicinal, cosmetic, dye and flavoring values. Herein, we present the chromosomal-level genome for turmeric to explore the differences between tubers and rhizomes in the regulation of curcumin biosynthesis and the mechanism of tuber formation. We assembled the turmeric genome into 21 pseudochromosomes using Pacbio long reads complemented with Hi-C technologies, which has a total length of 1.11 Gb with scaffold N50 of 50.12 Mb and contains 49,612 protein-coding genes. Genomic evolutionary analysis indicated that turmeric and ginger have shared a recent WGD event. Contraction analysis of gene families showed possible roles for transcription factors, phytohormone signaling, and plant-pathogen interactions associated genes in adaptation to harsh environments. Transcriptomic data from tubers at different developmental stages indicated that candidate genes related to phytohormone signaling and carbohydrate metabolic responses may be associated with the induction of tuber formation. The difference in curcumin content between rhizomes and tubers reflected the remodeling of secondary metabolites under environmental stress, which was associated with plant defense in response to abiotic stresses. Overall, the availability of the C. longa genome provides insight into tuber formation and curcumin biosynthesis in turmeric as well as facilitating the understanding of other Curcuma species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yin, Xie, Zhou, Yin, Guo, Zhou, Li, Shi, Peng and Gao.)

Background: Fuzi's compatibilities with other medicines are effective treatments for chronic heart failure. Pre-clinical animal experiments have indicated many possible synergistic compatibility mechanisms of it, but the results were not reliable and reproducible enough. Therefore, we performed this systematic review and meta-analysis of pre-clinical animal studies to integrate evidence, conducted both qualitative and quantitative evaluations of the compatibility and summarized potential synergistic mechanisms. Method: An exhaustive search was conducted for potentially relevant studies in nine online databases. The selection criteria were based on the Participants, Interventions, Control, Outcomes, and Study designs strategy. The SYRCLE risk of bias tool for animal trials was used to perform the methodological quality assessment. RevMan V.5.3 and STATA/SE 15.1 were used to perform the meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions. Result: 24 studies were included in the systematic review and meta-analysis. 12 outcomes were evaluated in the meta-analysis, including BNP, HR, HWI, ALD, LVEDP, LVSP, EF, FS, +dP/dt max , -dP/dt max , TNF-α and the activity of Na + -K + -ATPase. Subgroup analyses were performed depending on the modeling methods and duration. Conclusion: The synergistic Fuzi compatibility therapeutic effects against CHF animals were superior to those of Fuzi alone, as shown by improvements in cardiac function, resistance to ventricular remodeling and cardiac damage, regulation of myocardial energy metabolism disorder and RAAS, alleviation of inflammation, the metabolic process in vivo , and inhibition of cardiomyocyte apoptosis. Variations in CHF modeling methods and medication duration brought out possible model-effect and time-effect relationships., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Xie, Luo, Zhao, Li, Peng and Peng.)

GRAS proteins are plant-specific transcription factors and play important roles in plant growth, development, and stress responses. In this study, a total of 48 GRAS genes in the eggplant ( S. melongena ) genome were identified. These genes were distributed on 11 chromosomes unevenly, with amino acid lengths ranging from 417 to 841 aa. A total of 48 GRAS proteins were divided into 13 subgroups based on the maximum likelihood (ML) model. The gene structure showed that 60.42% (29/48) of SmGRAS s did not contain any introns. Nine pairs of SmGRAS appeared to have a collinear relationship, and all of them belonged to segmental duplication. Four types of cis-acting elements, namely, light response, growth and development, hormone response, and stress response, were identified by a cis-acting element predictive analysis. The expression pattern analysis based on the RNA-seq data of eggplant indicated that SmGRAS s were expressed differently in various tissues and responded specifically to cold stress. In addition, five out of ten selected SmGRAS s ( SmGRAS2/28/32/41/44 ) were upregulated under cold stress. These results provided a theoretical basis for further functional study of GRAS genes in eggplant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Li, Zhang, Wang, Xie and Wen.)

Gliomas are a primary types of intracranial malignancies and are characterized by a poor prognosis due to aggressive recurrence profiles. Temozolomide (TMZ) is an auxiliary alkylating agent that is extensively used in conjunction with surgical resection and forms the mainstay of clinical treatment strategies for gliomas. However, the frequent occurrence of TMZ resistance in clinical practice limits its therapeutic efficacy. Accumulating evidence has demonstrated that long non‑coding RNAs (lncRNAs) can play key and varied roles in glioma progression. lncRNAs have been reported to inhibit glioma progression by targeting various signaling pathways. In addition, the differential expression of lncRNAs has also been found to mediate the resistance of glioma to several chemotherapeutic agents, particularly to TMZ. The present review article therefore summarizes the findings of previous studies in an aim to report the significance and function of lncRNAs in regulating the chemoresistance of gliomas. The present review may provide further insight into the clinical treatment of gliomas.

Protein lysine acetylation (Kac) modification plays important roles in diverse physiological functions. However, there is little evidence on the role of Kac modification in bacterial antibiotic resistance. Here, we compared the differential expressions of whole-cell proteins and Kac peptides in oxytetracycline sensitive and oxytetracycline resistance (OXY R ) strains of Aeromonas hydrophila using quantitative proteomics technologies. We observed a porin family protein Aha1 downregulated in the OXY R strain, which may have an important role in the OXY resistance. Interestingly, seven of eight Kac peptides of Aha1 decreased abundance in OXY R as well. Microbiologic assays showed that the K57R, K187R, and K197R Aha1 mutants significantly increased antibiotic resistance to OXY and reduced the intracellular OXY accumulation in OXY stress. Moreover, these Aha1 mutants displayed multidrug resistance features to tetracyclines and β-lactam antibiotics. The 3D model prediction showed that the Kac states of K57, K187, and K197 sites located at the extracellular pore vestibule of Aha1 may be involved in the uptake of specific types of antibiotics. Overall, our results indicate a novel antibiotic resistance mechanism mediated by Kac modification, which may provide a clue for the development of antibiotic therapy strategies., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

D-Allulose, a low-calorie rare sugar with various physiological functions, is mainly produced through the isomerization of D-fructose by ketose 3-epimerases (KEases), which exhibit various substrate specificities. A novel KEase from a Clostridia bacterium (CDAE) was identified to be a D-allulose 3-epimerase and was further characterized as thermostable and metal-dependent. In order to explore its structure-function relationship, the crystal structure of CDAE was determined using X-ray diffraction at 2.10 Å resolution, revealing a homodimeric D-allulose 3-epimerase structure with extensive interactions formed at the dimeric interface that contribute to structure stability. Structural analysis identified the structural features of CDAE, which displays a common (β/α) 8 -TIM barrel and an ordered Mn 2+ -binding architecture at the active center, which may explain the positive effects of Mn 2+ on the activity and stability of CDAE. Furthermore, comparison of CDAE and other KEase structures revealed several structural differences, highlighting the remarkable differences in enzyme-substrate binding at the O4, O5 and O6 sites of the bound substrate, which are mainly induced by distinct hydrophobic pockets in the active center. The shape and hydrophobicity of this pocket appear to produce the differences in specificity and affinity for substrates among KEase family enzymes. Exploration of the crystal structure of CDAE provides a better understanding of its structure-function relationship, which might provide a basis for molecular modification of CDAE and further provides a reference for other KEases.

Hypervirulent Klebsiella pneumoniae (hvKP) is an evolving infectious pathogen associated with high mortality. The convergence of hypervirulence and multidrug resistance further challenges the clinical treatment options for K. pneumoniae infections. The QseBC two-component system (TCS) is a component of quorum-sensing regulatory cascade and functions as a global regulator of biofilm growth, bacterial motility, and virulence in Escherichia coli . However, the functional mechanisms of QseBC in hvKP have not been reported, and we aim to examine the role of QseBC in regulating virulence in hvKP strain ATCC43816. The CRISPR-Cas9 system was used to construct qseB , qseC , and qseBC knockout in ATCC43816. No significant alterations in the growth and antibiotic susceptibility were detected between wild-type and mutants. The deletion of qseC led to an increase of biofilm formation, resistance to serum killing, and high mortality in the G. mellonella model. RNAseq differential gene expression analysis exhibited that gene-associated biofilm formation ( glgC, glgP, glgA, gcvA, bcsA, ydaM, paaF, ptsG ), bacterial type VI secretion system ( virB4, virB6, virB10, vgrG, hcp ), and biosynthesis of siderophore ( entC, entD, entE ) were significantly upregulated in comparison with the wild-type control. In addition, qseB , ygiW (encode OB-family protein), and AraC family transcriptional regulator IT767_23090 genes showed highest expressions in the absence of QseC, which might be related to increased virulence. The study provided new insights into the functional importance of QseBC in regulating the virulence of hvKP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Zhu, Wang, Xie, Wang, Zhu, Chen, Zhong and Du.)

Quercitrin is a naturally available type of flavonoid that commonly functions as the dietary ingredient and supplement. So far, a wide spectrum of bioactivities of quercitrin have been revealed, including antioxidative stress, antiinflammation, anti-microorganisms, immunomodulation, analgesia, wound healing, and vasodilation. Based on these various pharmacological activities, increasing studies have focused on the potency of quercitrin in diverse diseases in recent years, such as bone metabolic diseases, gastrointestinal diseases, cardiovascular and cerebrovascular diseases, and others. In this paper, by collecting and summarizing publications from the recent years, the natural sources, pharmacological activities and roles in various diseases, pharmacokinetics, structure-activity relationship, as well as the toxicity of quercitrin were systematically reviewed. In addition, the underlying molecular mechanisms of quercitrin in treating related diseases, the dose-effect relationships, and the novel preparations were discussed on the purpose of broadening the application prospect of quercitrin as functional food and providing reference for its clinical application. Notably, clinical studies of quercitrin are insufficient at present, further high-quality studies are needed to firmly establish the clinical efficacy of quercitrin., (© 2022 John Wiley & Sons Ltd.)

Aconitine is one of the main bioactive and toxic ingredients of Aconitum species. Increasingly, aconitine has been reported to induce neurotoxicity. However, whether aconitine has effects on the dopaminergic nervous system remains unclear. In this study, zebrafish embryos at 6-days postfertilization were exposed to aconitine at doses of 0.5, 1, and 2 μM for 24 h, and SH-SY5Y cells were treated with 50, 100, and 200 μM of aconitine for 24 h. Results demonstrated that aconitine treatment induced deformities and enhanced the swimming behavior of zebrafish larvaes. Aconitine exposure suppressed cell proliferation and increased the number of reactive oxygen species and apoptosis in zebrafish larvaes and SH-SY5Y cells. Aconitine altered the levels of dopamine and its metabolites by regulating the expression of genes and proteins related to dopamine synthesis, storage, degradation, and reuptake in vivo and in vitro . Moreover, aconitine activated the AC/cAMP/PKA pathway by activating the dopamine D1 receptor (D1R) and inhibiting the dopamine D2 receptor (D2R) to disturb intracellular calcium homeostasis, eventually leading to the damage of nerve cells. Furthermore, the D1R antagonist SCH23390 and D2R agonist sumanirole pretreatment effectively attenuated the excitatory state of larvaes. Sumanirole and PKA antagonist H-89 pretreatment effectively decreased intracellular Ca 2+ accumulation induced by aconitine in vivo . SCH23390 and sumanirole also reduced aconitine-induced cytotoxicity by inhibiting the AC/cAMP/PKA pathway in vitro . These results suggested that dopamine homeostasis imbalance and dopamine receptors (DRs)-mediated AC/cAMP/PKA pathway activation might be vital mechanisms underlying aconitine-induced neurological injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Peng, Li, Yan, Yang, Li, Cao, Xie, Chen, Rao, Huang, Peng and Pan.)

Breast cancer has an extremely high incidence in women, and its morbidity and mortality rank first among female tumors. With the increasing development of molecular biology and genomics, molecular targeted therapy has become one of the most active areas in breast cancer treatment research and has also achieved remarkable achievements. However, molecular targeted therapy is mainly aimed at HER2-positive breast cancer and has not yet achieved satisfactory curative effect on HER2-negative breast cancer. This article describes the potential targets that may be used for breast cancer treatment from the aspects of PI3K/AKT signaling pathway, DDR, angiogenesis, the cell cycle, breast cancer stem cells, etc. , and explores possible inhibitors for the treatment of HER2-negative breast cancer, such as PI3K inhibitors, AKT inhibitors and m-TOR inhibitors that inhibit the PI3K/AKT signaling pathway, small molecule tyrosine kinase inhibitors that restrain angiogenesis, CDK inhibitors, aurora kinase inhibitors and HDAC inhibitors that block cell cycle, as well as the drugs targeting breast cancer stem cells which have been a hit, aiming to provide a new idea and strategy for the treatment of HER2-negative breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 An, Peng, Xie and Peng.)

Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO 3- X ) for healing the DUs are reported. The ROS scavenging ability of MoO 3- X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO 3- X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO 3- X nanodots for diabetic wound therapy., (© 2021 Wiley-VCH GmbH.)

Ligusticum chuanxiong Hort. (CX) is a medicinal and edible plant with a wide range of constituents of biological interest. Since the biomass of the non-medicinal parts of CX is huge, discarding them will cause a waste of resources. To expand the medicinal uses of CX, we comprehensively investigated the chemical diversity and efficacy of its different parts (rhizomes, fibrous roots, stems and leaves). 75 compounds in the volatile oil and 243 compounds in the methanol extracts (including 95 phthalides) obtained from CX were characterized by GC-MS and UHPLC/Q-Orbitrap MS analysis, respectively. Of 95 phthalides, 14 potential new compounds and 5 phthalide trimers were identified from CX for the first time. Phthalide monomers were more abundant in rhizomes and fibrous roots, and phthalide dimers or even phthalide trimers mainly in stems and leaves. By multivariate and univariate analyses, 22 and 24 different compounds were found in the volatile oils and the methanol extracts, respectively. In the bioactivity evaluation of different parts, stems and leaves showed the best antioxidant activity, fibrous roots showed the strongest vasodilator activity, and rhizomes showed the most significant anticoagulant activity, which was related to the different metabolites in different parts. Ultimately, this work revealed the similarities and differences of phytochemicals and bioactivities in different anatomical parts of CX. It might provide helpful evidence for the rational application of non-medicinal resources.

Ethnopharmacological Relevance: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear., Aim of the Study: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment., Materials and Methods: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting., Results: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01)., Conclusion: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2., (Copyright © 2021. Published by Elsevier B.V.)

Gliomas are tumors of the primary central nervous system associated with poor prognosis and high mortality. The 5-year survival rate of patients with gliomas received surgery combined with chemotherapy or radiotherapy does not exceed 5%. Although temozolomide is commonly used in the treatment of gliomas, the development of resistance limits its use. MicroRNAs are non-coding RNAs involved in numerous processes of glioma cells, such as proliferation, migration and apoptosis. MicroRNAs regulate cell cycle, PI3K/AKT signal pathway, and target apoptosis-related genes (e.g., BCL6), angiogenesis-related genes (e.g., VEGF) and other related genes to suppress gliomas. Evidence illustrates that microRNAs can regulate the sensitivity of gliomas to temozolomide, cisplatin, and carmustine, thereby enhancing the efficacy of these agents. Moreover, traditional Chinese medicine (e.g., tanshinone IIA, xanthohumol, and curcumin) exert antiglioma effects by regulating the expression of microRNAs, and then microRNAs inhibit gliomas through influencing the process of tumors by targeting certain genes. In this paper, the mechanisms through which microRNAs regulate the sensitivity of gliomas to therapeutic drugs are described, and traditional Chinese medicine that can suppress gliomas through microRNAs are discussed. This review aims to provide new insights into the traditional Chinese medicine treatment of gliomas.

Leaf senescence is an important process of growth and development in plant, and it is a programmed decline controlled by a series of genes. In this study, the biochemical properties and transcriptome at five maturity stages (M1∼M5) of tobacco leaves were analyzed to reveal the dynamic changes in leaf senescence of tobacco. A total of 722, 1,534, 3,723, and 6,933 genes were differentially expressed (DEG) between M1 and M2, M1 and M3, M1 and M4, and M1 and M5, respectively. Significant changes of nitrogen, sugars, and the DEGs related to metabolite accumulation were identified, suggesting the importance of energy metabolism during leaf senescence. Gene Ontology (GO) analysis found that DEGs were enriched in biosynthetic, metabolic, photosynthesis, and redox processes, and especially, the nitrogen metabolic pathways were closely related to the whole leaf senescence process (M1∼M5). All the DEGs were grouped into 12 expression profiles according to their distinct expression patterns based on Short Time-series Expression Miner (STEM) software analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that these DEGs were enriched in pathways of carbon metabolism, starch and sucrose metabolism, nitrogen metabolism, and photosynthesis among these expression profiles. A total of 30 core genes were examined by Weight Gene Co-expression Network Analysis (WGCNA), and they appeared to play a crucial role in the regulatory of tobacco senescence. Our results provided valuable information for further functional investigation of leaf senescence in plants., Competing Interests: BZ and GG were employed by the Fujian Provincial Tobacco Company. LJ and ZL were employed by the Yanping Branch of Nanping Tobacco Company. CC was employed by the Jianning Branch of Sanming Tobacco Company. JS was employed by the Nanping Tobacco Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Yang, Gu, Jin, Chen, Lin, Song and Xie.)

Since the discovery of NDM-1 and the worldwide reporting of different variants have raised alarms concerning global health, the problem of carbapenem-resistant Enterobacterales (CRE) has become increasingly serious. Therefore, research on the hydrolytic activity and molecular structure of NDM variants is beneficial to the development of antibacterial drugs. NDM has been evolving into variants that possess different hydrolysis activities toward β-lactam antibiotics. Here, we characterized a novel bla NDM variant, named bla NDM-33 , identified from a multidrug-resistant Escherichia coli strain from hospital sewage. NDM-33 differed from NDM-5 with a single-amino-acid substitution (A72T). bla NDM-5 was located in the Tn 125 -related bla NDM-33 region from an IncX3-type plasmid, pHD6415-NDM, that can be transferred horizontally. The genetic construct of bla NDM-33 showed higher MICs of carbapenems than a bla NDM-5 construct. Enzyme kinetics showed that NDM-33 had higher enzymatic activity for meropenem and cefazolin than NDM-5. The emergence of this novel NDM variant could pose a threat to public health because of its transferability and enhanced carbapenem activity. IMPORTANCE Our study described a novel NDM-33 variant from an E. coli strain isolated from hospital sewage, where it was associated with human disease and antibiotic exposure. Importantly, hospital sewage was increasingly considered to be related to CRE hosts. Pathogens were transmitted from reservoirs through direct and indirect contact, ingestion, and inhalation of contaminated water or aerosols. In addition, under the selective pressure of antibiotics, NDM variants will become the main strain in the hospital water system and evolve into high virulence and high resistance. The monitoring of NDM mutants is of great significance for preventing and controlling the evolution of superbugs.

Bacterial leaf streak (BLS) is a devastating rice disease caused by the bacterial pathogen, Xanthomonas oryzae pv. oryzicola ( Xoc ), which can result in severe damage to rice production worldwide. Based on a total of 510 rice accessions, trialed in two seasons and using six different multi-locus GWAS methods (mrMLM, ISIS EM-BLASSO, pLARmEB, FASTmrMLM, FASTmrEMMA and pKWmEB), 79 quantitative trait nucleotides (QTNs) reflecting 69 QTLs for BLS resistance were identified (LOD > 3). The QTNs were distributed on all chromosomes, with the most distributed on chromosome 11, followed by chromosomes 1 and 5. Each QTN had an additive effect of 0.20 (cm) and explained, on average, 2.44% of the phenotypic variance, varying from 0.00-0.92 (cm) and from 0.00-9.86%, respectively. Twenty-five QTNs were detected by at least two methods. Among them, qnBLS11.17 was detected by as many as five methods. Most of the QTNs showed a significant interaction with their environment, but no QTNs were detected in both seasons. By defining the QTL range for each QTN according to the LD half-decay distance, a total of 848 candidate genes were found for nine top QTNs. Among them, more than 10% were annotated to be related to biotic stress resistance, and five showed a significant response to Xoc infection. Our results could facilitate the in-depth study and marker-assisted improvement of rice resistance to BLS.

Cancer is still an insurmountable problem for humans and critically attacking human health. In recent years, natural products have gained increasing attention in the field of anti-tumor due to their extensive sources and minimal side effects. Maslinic acid (MA), a pentacyclic triterpene acid mainly derived from the olive tree ( Olea europaea L.) has been confirmed to possess great anti-cancer effects. This paper reviewed the inhibitory effect of MA and its derivatives on lung cancer, colon cancer, ovarian cancer, gastric cancer, lymphatic, leukemia, breast cancer, pancreatic cancer, melanoma, prostate cancer, renal cell carcinoma, gallbladder cancer, and bladder cancer, among others. MA inhibited the proliferation of various tumor cells and showed lower IC 50 values in melanoma 518A2 cells and gastric cancer MKN28 cells compared with other cell lines. A series of semi-synthetic derivatives obtained by modifying MA chemical structure have been shown to have high cytotoxicity to human tumor cell lines, but low cytotoxicity to non-malignant cells, which is conducive to developing its potential as a chemotherapeutic agent. These studies suggest that MA derivatives have broad prospects in the development of antitumor therapeutics in the future and warrant further study., Competing Interests: The authors declare no conflicts of interest for this work., (© 2021 Yu et al.)

The α-amylases are the most widely used industrial enzymes, and are particularly useful as liquifying enzymes in industrial processes based upon starch. Since starch liquefication is carried out at evaluated temperatures, typically above 60 °C, there is substantial demand for thermostable α -amylases. Most naturally occurring α -amylases exhibit moderate thermostability, so substantial effort has been invested in attempts to increase their thermostability. One structural feature that has the potential to increase protein thermostability is the introduction of salt bridges. However, not every salt bridge contributes to protein thermostability. The salt bridges in amylases have their characteristics in terms of distribution, configuration and location. The summary of these features helps to introduce new salt bridges based on the characteristics. This review focuses on salt bridges of α-amylases, both naturally present and introduced using mutagenesis. Its aim is to provide a bird's eye view of distribution, configuration, location of desirable salt bridges., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Magnolia officinalis , a representative tall aromatic tree of the Magnoliaceae family, is a medicinal plant that is widely used in diverse industries from medicine to cosmetics. We report a chromosome-scale draft genome of M. officinalis , in which ∼99.66% of the sequences were anchored onto 19 chromosomes with the scaffold N50 of 76.62 Mb. We found that a high proportion of repetitive sequences was a common feature of three Magnoliaceae with known genomic data. Magnoliids were a sister clade to eudicots-monocots, which provided more support for understanding the phylogenetic position among angiosperms. An ancient duplication event occurred in the genome of M. officinalis and was shared with Lauraceae. Based on RNA-seq analysis, we identified several key enzyme-coding gene families associated with the biosynthesis of lignans in the genome. The construction of the M. officinalis genome sequence will serve as a reference for further studies of Magnolia, as well as other Magnoliaceae., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Objectives: Analyze the thermostability, mode of action, and product specificity of a maltooligosaccharide-forming amylase from Bacillus stearothermophilus STB04 (Bst-MFA) from the biochemical and structural point of view., Results: Using three-dimensional co-crystal structure of Bst-MFA with acarbose as a guide, experiments were performed to analyze the thermostability, mode of action and product specificity of Bst-MFA. The results showed that the Ca 2+ -Ca 2+ -Ca 2+ metal triad of Bst-MFA is responsible for its high thermostability. Multiple substrate binding modes, rather than one productive binding mode determined by non-reducing end recognition, are in accordance with an endo-type mode of action. Significant interactions between subsites - 5 and - 6 and glucosyl residues at the non-reducing end explain the maltopentaose (G5) and maltohexaose (G6) specificity of Bst-MFA., Conclusions: Bst-MFA is a thermostable enzyme that preferentially produces G5 and G6, with an endo-type mode. The understanding of structure-function relationships provides the foundation for future efforts to the modification of Bst-MFA.

The maltooligosaccharide-forming amylase from Bacillus stearothermophilus STB04 (Bst-MFA) randomly cleaves the α-1,4 glycosidic linkages of starch to produce predominantly maltopentaose and maltohexaose. The three-dimensional co-crystal structure of Bst-MFA with acarbose highlighted the stacking interactions between Trp139 and the substrate in subsites - 5 and - 6. Interactions like this are thought to play a critical role in maltopentaose/maltohexaose production. A site-directed mutagenesis approach was used to test this hypothesis. Replacement of Trp139 by alanine, leucine, or tyrosine dramatically increased maltopentaose production and reduced maltohexaose production. Oligosaccharide degradation indicated that these mutants also enhance productive binding of the substrate aglycone, leading to a high maltopentaose yield. Therefore, the aromatic stacking between Trp139 and substrate is suggested to control product specificity and the oligosaccharide cleavage pattern.

To better understand structure-function relationships, an X-ray crystal structure of the maltooligosaccharide-forming amylase from Bacillus stearothermophilus STB04 (Bst-MFA) with bound acarbose has been determined at 2.2 Å. The structure revealed a classical three-domain fold stabilized by four calcium ions, in which CaI-CaIII form an unprecedented linear metal triad in the interior of domain B. Catalytic residues are deduced to be two aspartic acids and one glutamic acid (Asp234, Glu264, Asp331), and the acarbose is bound to surrounding amino acid residues, mainly through extensive hydrogen bonds. Furthermore, analysis of the structure indicates the existence of at least 8 subsites in Bst-MFA, six glycone sites (-6, -5, -4, -3, -2, -1) and two aglycone sites (+1, +2). Subsite +3 remains to be further explored. Sugar-binding subsites contribute to further presentation of the oligosaccharide-binding mode, which explains the product specificity of Bst-MFA to some extent. In addition, we propose a mechanism by which maltooligosaccharide-forming amylases produce particular maltooligosaccharide products, a result different from that seen with typical α-amylases. Finally, the three-dimensional structure of Bst-MFA complexed with acarbose provides the basis for further studies, designed to increase product specificity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

With a high incidence and high mortality rate, ovarian cancer presents a challenge for clinical practice. It is thus extremely urgent to investigate new diagnosis and therapy methods for the treatment of ovarian cancer. Ternary copper-based chalcogenide nanomaterials are attractive owing to their near infrared (NIR) response for cancer theranostic fields. However, improving the theranostic efficiency of these nanomaterials is challenging. Herein, CuS-MnS2 nano-flowers were easily synthesized and under NIR irradiation exhibited a relatively high photothermal conversion efficiency of 67.5% and a simultaneous reactive oxygen species (ROS) generation effect. Owing to these outstanding photothermal/photodynamic effects, excellent tumor ablation results could be achieved by the combined use of CuS-MnS2 nano-flowers and 808 nm NIR laser treatments. The main anticancer mechanism of CuS-MnS2 nano-flowers + NIR was likely necroptosis. In addition, the nano-flowers showed remarkable contrast enhancement according to magnetic resonance imaging (MRI). These CuS-MnS2 nano-flowers could thus serve as a promising multifunctional nanotheranostic agent for MRI and as a photothermal/photodynamic cancer therapy agent through necroptosis.

In this multicenter study, we compared the performance of the Bruker Biotyper MS system and VITEK 2 YST systems for invasive yeast identification, investigated the distribution of isolated species, and evaluated the antifungal susceptibility profiles of Candida albicans, Candida parapsilosis, and Candida tropicalis. In cases of discrepant results lack of identification with either method, molecular identification techniques were employed. We tested 216 clinical isolates, and concordance between the two methods was observed for 192/216 isolates (88.9%). For five unidentified strains (2.3%), an internal transcribed spacer (ITS) sequencing approach was used. In brief, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) provided short turnaround times and more reliable results than those of Vitek 2 YST. In Wuhan, C. albicans, C. parapsilosis, Candida glabrata, and C. tropicalis were the most common pathogens (93.0%) in patients with candidemia. Cryptococcus neoformans was mainly detected in cerebrospinal fluid samples (88.9%). Trichosporon asahii were all isolated from drainage fluids in the Surgery. Candida albicans was clearly susceptible to azoles, while C. parapsilosis and C. tropicalis displayed differences in susceptibility to azoles. Our findings provide a basis for the practical application of MALDI-ToF MS for identification and for the use of ATB FUNGUS 3 to characterize the susceptibility of Candida spp., thereby providing significant data for therapeutic decisions.

Aim: The contribution of long non-coding RNAs (lncRNAs) to gastric cancer associated with Helicobacter pylori ( H. pylori ) infection remains largely unknown. Therefore, the present study aimed to investigate the expression of a lncRNA NR&#95;026827 in gastric epithelial cells infected with H. pylori , and demonstrate its expression characteristic in gastric cancer., Materials and Methods: Gastric epithelial cell line cells, GES-1, were cultured and infected with H. pylori . A microarray was used to analyze the lncRNA profile of gastric epithelial cells. Eighty fresh gastric cancer tissues and the paired adjacent non-cancerous tissue samples were randomly selected from patients. The expression of the lncRNA NR&#95;026827 was investigated using quantitative real-time polymerase chain reaction (qRT-PCR)., Results: The expression of several lncRNAs was significantly altered in GES-1 cells following infection with H. pylori . Of these lncRNAs, NR&#95;026827 was dramatically down-regulated in GES-1 cells infected with H. pylori . In addition, the expression of NR&#95;026827 was decreased in gastric cancer tissues in comparison to the corresponding adjacent non-cancerous tissues. Moreover, the expression of NR&#95;026827 did not change significantly in different gastric cancer stages., Conclusion: The lncRNA, NR&#95;026827, is down-regulated in all stages of gastric cancer associated with H. pylori infection and could represent a potential biomarker for the diagnosis of gastric cancer., Competing Interests: None.

Although accumulating evidence suggests that activated microglia are associated with deficits in neurogenesis and contribute to the physiopathology of major depressive disorder, the role of microglia in treating depression remains poorly understood. Our previous study showed that salvianolic acid (SalB) has the regulation of neuroinflammatory responses and antidepressant-like effects. Here, we hypothesized that SalB's therapeutic effects occur because it modulates microglial phenotypes that are associated with neurogenesis. To test this hypothesis, we treated CMS-exposed C57BL/6 mice with SalB (20mg/kg, intraperitoneally, once daily) for 3weeks and investigated microglial phenotypic profiles and hippocampal neurogenesis. The results showed that the SalB treatment skewed M1 microglial polarization toward M2 activation in the hippocampus and cortex and remedied CMS-induced deficits in hippocampal neurogenesis. SalB (40µM) inhibited LPS-stimulated microglial M1 activation as well as induced M2 activation in vitro, and the cultured microglia with the SalB treatment showed enhanced neural precursor cell proliferation, differentiation, and survival. SalB treatment also ameliorated the depressive-like behaviors of the CMS-treated mice in sucrose preference, forced swimming, and tail suspension tests. These findings suggest a possible antidepressive mechanism for anti-inflammatory agents that is correlated with microglial polarization and hippocampal neurogenesis and which may provide a new microglia-targeted strategy for depression therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Chronic cerebral hypoperfusion is a common pathophysiological state in various cerebrovascular diseases. Anisodine has been reported to exert neuroprotective effects in cerebral ischemia/reperfusion (I/R) animal model. However, it is unclear whether anisodine hydrobromide, the hydrobromide format of anisodine, one of the tropic alkanes alkaloids, exhibits the same neuroprotective effect on chronic cerebral hypoperfusion(CCH) rats. Herein, we tried to unravel these issues., Methods: CCH model in adult male Sprague-Dawley rats was established by permanent ligation of the bilateral common carotid arteries [two-vessel occlusion (2-VO)] surgery. Rats were randomly divided into six groups: sham, 2-VO, 2-VO + Butyl phthalide and sodium chloride injection (NBP, as positive control group), 2-VO + anisodine hydrobromide (AH)1.2mg/kg, 2-VO +AH0.6mg/kg, 2-VO +AH0.3mg/kg. Cognitive behavior was examined by Morris Water Maze Test. Neuronal survival and apoptosis were evaluated by Nissl staining and Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL staining). The relative monoamine neurotransmitter (5-hydroxytryptamine (5-HT), norepinephrine (NA)), the content of Ach, the activity of acetylcholin esterase (AchE) were measured in cholinergic system, and the protein expressions of Bcl-2, Bax, p-Akt and p-GSK-3βwere detected by Western blot assay., Results: The results showed that there is significant memory impairment and a remarkable neuron necrosis and apoptosis, along with the dysfunction of the neurotransmitter systems and central cholinergic system in CCH rats. AH treatment could significantly improve cognitive deficits, while reducing neuron necrosis and apoptosis, apart from increasing the content of 5-HT and decreasing the activity of AchE markedly. Further study revealed that AH could promote the protein expression of Bcl-2, phosphorylation of Akt and GSK-3β, and downregulate the protein of Bax., Conclusion: AH was demonstrated to ameliorate memory deficits by revising the imbalance of the monoamine neurotransmitter and cholinergic dysfunction. Moreover, AH can attenuate neuronal cell death and apoptosis by activating the Akt/GSK-3βsignaling pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Bacterial antimicrobial resistance has been associated with the up regulation of genes encoding efflux pumps and the down regulation of genes encoding outer membrane proteins (OMPs). Gene expression in bacteria is primarily initiated by sigma factors (σ factors) such as RpoE, which plays an important role in responding to many environmental stresses. Here, we report the first observation that RpoE serves as an antibiotic resistance regulator in Salmonella enteric serovar Typhi (S. Typhi). In this study, we found that the rpoE mutant (ΔrpoE) of S. Typhi GIFU10007 has elevated resistance to several antimicrobial agents, including β-lactams, quinolones, and aminoglycosides. Genomic DNA microarray analysis was used to investigate the differential gene expression profiles between a wild type and rpoE mutant in response to ampicillin. The results showed that a total of 57 genes displayed differential expression (two-fold increase or decrease) in ΔrpoE versus the wild-type strain. The expressions of two outer membrane protein genes, ompF and ompC, were significantly down-regulated in ΔrpoE (six and seven-fold lower in comparison to wild-type strain) and RamA, a member of the efflux pump AraC/XylS family, was up-regulated about four-fold in the ΔrpoE. Our results suggest RpoE is a potential antimicrobial regulator in S. Typhi, controlling both the down regulation of the OMP genes and up-regulating the efflux system.

Salmonella enterica serovar Typhi (S. Typhi) is a human-specific pathogen that causes typhoid fever. In this study, we constructed ΔygaE mutant and a microarray was performed to investigate the role of ygaE in regulation of gene expression changes in response to hyperosmotic stress in S. Typhi. qRT-PCR was performed to validate the microarray results. Our data indicated that ygaE was the repressor of gab operon in S. Typhi as in Escherichia coli (E. coli), though the sequence of ygaE is totally different from gabC (formerly ygaE) in E. coli. OmpF, OmpC, and OmpA are the most abundant out membrane proteins in S. Typhi. Here we report that YgaE is a repressor of both OmpF and OmpC at the early stage of hyperosmotic stress. Two-dimensional electrophoresis was applied to analyze proteomics of total proteins in wild-type strain and ΔygaE strain and we found that YgaE represses the expression of OmpA at the late stage of hyperosmotic stress. Altogether, our results implied that YgaE regulates out membrane proteins in a time-dependent manner under hyperosmotic stress in S. Typhi.