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A new species, Lysimachia xuyongensis X.F.Gao & W.B.Ju, from China is described and illustrated. The new species morphologically resembles L. miyiensis, L. paridiformis var. stenophylla and L. phyllocephala var. polycephala, but it clearly differs by having stems prostrate at base, dense white multicellular hairs, leave 4, lower scalelike, leaf blades and calyx carrying sparsely reddish glandular punctation, pedicel less than 5 mm, corolla lobes without glandular and ovary glabrous.

Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder that affects women of reproductive age. Recent studies have demonstrated a close association between the gut microbiome and PCOS. Their microbial diversity may not significantly change, and the crucial role of Bacteroides spp. has been demonstrated in human PCOS. Furthermore, animal models of PCOS exhibit gut microbiome features different from those of humans with PCOS. The gut microbiome may differ in patients with PCOS because it can be affected by multiple PCOS-related factors. Dysbiosis of the gut microbiome may trigger PCOS symptoms via an underlying mechanism that may involve microbial metabolites, including bile acids, short-chain fatty acids, and lipopolysaccharides. The manipulation of the gut microbiome can affect PCOS phenotypes, and prebiotic or probiotic therapy has the potential to improve PCOS symptoms. Future mechanistic studies are required to identify the causative role of these microbes and their metabolites in the pathogenesis of PCOS.

Abnormal expressions of long noncoding RNAs (lncRNAs) and protein-encoding messenger RNAs (mRNAs) are important for the development of childhood acute lymphoblastic leukemia (ALL). This study developed an lncRNA-mRNA integrated classifier for the prediction of recurrence and prognosis in relapsed childhood ALL by using several transcriptome data. Weighted gene coexpression network analysis revealed that green, turquoise, yellow, and brown modules were preserved across the TARGET, GSE60926, GSE28460, and GSE17703 datasets, and they were associated with clinical relapse and death status. A total of 184 genes in these four modules were differentially expressed between recurrence and nonrecurrence samples. Least absolute shrinkage and selection operator analysis showed that seven genes constructed a prognostic signature (including one lncRNA: LINC00652 and six mRNAs: INSL3, NIPAL2, REN, RIMS2, RPRM, and SNAP91). Kaplan-Meier curve analysis observed that patients in the high-risk group had a significantly shorter overall survival than those of the low-risk group. Receiver operating characteristic curve analysis demonstrated that this signature had high accuracy in predicting the 5-year overall survival and recurrence outcomes, respectively. LINC00652 may function by coexpressing with the above prognostic genes (INSL3, SNAP91, and REN) and lipid metabolism-related genes (MIA2, APOA1). Accordingly, this lncRNA-mRNA-based classifier may be clinically useful to predict the recurrence and prognosis for childhood ALL. These genes represent new targets to explain the mechanisms for ALL.

The genus Similisinocarum Cauwet & Farille (Apiaceae, Apioideae), was first described by Cauwet & Farille in 1984, but it has been considered as a synonym of Sinocarum H.Wolff ex R.H. Shan & F.T. Pu. In this study, Simlisinocarum normanianum, the type species of Similisinocarum was found in China for the first time, and the molecular phylogenetic evidence based on ITS sequences reveals that Similisinocarum normanianum occupies an individual clade, which is sister to the clade comprising seven species of Acronema, Sinocarum, and Oreocomopsis in Acronema clade, the values of genetic distances (ITS) between Similisinocarum and Acronema, Similisinocarum and Oreocomopsis, Similisinocarum and Pternopetalum, Similisinocarum and Sinocarum are close (≥0.0916), while deviated from the values within Acronema, Sinocarum and Pternopetalum (≤0.0580). Morphologically, we found Similisinocarum normanianum develops reflex bracteoles with white membranous margin, petals with an entire margin and incurved apex, and mericarps with many vittae in the furrow (≥ 3) and commissure (6), which are distinguishable from other species of the Acronema clade. Consequently, results manifested in molecular and morphological analyses indicate that Similisinocarum should be treated as an independent genus distinct from Sinocarum.

Physospermopsis (Apiaceae) comprises about 10 species, but its taxonomy and phylogeny are disputed. The genus is mostly distributed in the Himalayas and Hengduan Mountains at high elevation. Earlier molecular studies involving six species of Physospermopsis indicated that this genus is not monophyletic and is nested in the East Asia Clade. Therefore, the aims of this study were to re-assess the phylogenetic position of, and interspecific relationships within, Physospermopsis based on two chloroplast loci (rpl16, rps16) and one nuclear region, the internal transcribed spacers of ribosomal DNA (ITS). Eight species involving 13 populations of Physospermopsis were collected. These were sequenced and analyzed with the sequences of 31 other Apiaceae species obtained from the NCBI to determine phylogenetic relationships using Bayesian inference (BI) and Maximum likelihood (ML). Our study found that Physospermopsis is monophyletic, nested in Pleurospermeae of Apiaceae, sister to Pleurospermum. And we propose that the Physospermopsis clade should be replaced by the East Asia Clade. However, the interspecific relationships within Physospermopsis were not well resolved and the positioning of species was unclear. Diagnostic characteristics to distinguish Physospermopsis species in the field and laboratory are provided for future Physospermopsis phylogenetic studies.

Sinocarum is a Sino-Himalayan endemic genus of Apiaceae and distributed in high-elevations from Nepal to SW China. In this study, morphological characteristics were combined with nuclear internal transcribed spacer (ITS) and two chloroplast DNA (cpDNA) intron sequences (rpl16 and rps16) to determine the phylogenetic placement of Sinocarum and the infrageneric relationships between five Sinocarum species. The results confirmed that Sinocarum was a polyphyletic group separated into two clades, Acronema and East Asia clades. S. coloratum, the generic type of Sinocarum, S. cruciatum, S. vaginatum and S. filicinum are in the Acronema clade. Among them, the first three species are clustered into a subclade and are closely related to the genus Acronema. While S. filicinum has a close affinity with Meeboldia. S. schizopetalum did not ally with its congeners we collected and is allied closely with members of the distantly related East Asia clade. In addition, the fruit of the Acronema clade Sinocarum species is usually oblong-ovoid or ovoid, and the pollen is super-rectangular, while the Sinocarum species in the East Asia clade have broad-ovoid fruit and sub-rhomboidal pollen. This study has furnished cumulative evidence to reduce phylogenetic uncertainty and provide a more comprehensive description of the plant morphology, fruit morphology and anatomy, and pollen morphology of these five Chinese Sinocarum species.

In clinical treatment, Pleione bulbocodioides (Franch.) Rolfe (PB) has been widely used as an anti-tumor drug. However, low productivity impeded its extensive application. The lack of endosperm in the seeds of PB led to a low natural germination rate, causing inefficient production and long reproductive cycle. Improving production and retaining clonal fidelity are the challenges in its efficient micropropagation. This study is to optimize medium and evaluate clonal fidelity on induction and differentiation of Protocorm-like Body (PLB) from PB. The effects of plant growth regulators (PGR) and natural additives on the formation and proliferation of protocorms from seeds and the induction and proliferation of PLBs were investigated. The ultra-structural were performed via a scanning electron microscope (SEM) and transmission electron microscope (TEM) and clonal fidelity assessment was conducted using histochemical assays, DNA electrophoresis analysis and Inter-simple sequence repeat (ISSR) molecular marker analysis. The optimum medium for inducing protocorm was that the Murashige and Skoog (MS) medium supplemented with 2.0 mg/L 2,4-D, 2.0 mg/L KT (Kinetin), 2.0 mg/L AgNO3, and 50 mL/L coconut water in the orthogonal experiments and validation experiments, and for inducing PLBs was that MS medium with 0.3 mg/L indole-3-butyric acid (IBA), 0.3 mg/L KT, 100 mg/L potato extract, and 1 g/L activated charcoal. The SEM and TEM showed the ultra-structural of PB had no change from protocorm to PLBs, and the DNA electrophoresis showed the total DNA did not change in different stages of PB by induction and differentiation and ISSR analysis revealed no DNA polymorphisms included bulb, PLBS, and the differentiated tissue of PLBs. In conclusion, the DNA hereditary character and ultra-structural of PB was retained using our optimum medium induction and differentiation of PLBs from PB, which will be useful for the efficient micropropagation popularization for PB. The present work reports the DNA hereditary stability character and optimum medium for induction and differentiation of PLBs from Pleione bulbocodioides (Franch.) Rolfe (PB), which will be useful for the efficient micropropagation popularization for PB.

Meeboldia H.Wolff, Sinodielsia H.Wolff and their relatives (Apiaceae: Apioideae) are similar in morphology, of which taxonomic treatments were controversial. In this study, the nuclear ribosomal DNA sequence (ITS) and two plastid DNA markers (rps16 and rpl16) were applied to reconstruct phylogenetic trees. The results demonstrated that Meeboldia and Sinodielsia formed a monophyletic group in phylogenetic trees and their highly similar morphological characteristics in taproot, basal leaves, calyx teeth, ribs, and vittae of fruits also confirmed their close relationships. Consequently, the following results were obtained: (1) Sinodielsia should be merged into Meeboldia; (2) Sinodielsia delavayi was confirmed conspecific with Meeboldia yunnanensis and renamed as Meeboldia delavayi (Franch.) W.Gou & X.J.He; (3) Sinodielsia thibetica was away from other Sinodielsia species; (4) Sinodielsia microloba was a member of Meeboldia and renamed as Meeboldia microloba (Kljuykov) W.Gou & X.J.He; (5) The name of Sinodielsia clade was suggested to be replaced by Hymenidium clade. We applied multiple approaches to explore the relationship of morphologically similar taxa, which will facilitate a deep understanding of taxonomy and species diversity of Apiaceae.

Antheraea pernyi and Bombyx mori silk fibres, the most important and the subjects of several studies, have attracted widespread attention due to their exceptional mechanical properties and promising applications. However, the determinants behind the variations of mechanical property between these two fibres still remains unknown. In this paper, the nanocrystalline structures of these two silk fibres were tuned by thermal treatment in order to understand how the structure affects the mechanical properties of fibres. It has been found that, along with an increase in temperature for thermal treatment, the increase in the intramolecular β-sheet leads to progressive increase in longitudinal modulus and radial hardness, whilst the reduction in crystallinity results in great reduction in breaking tensile strength. The yield strength is proportional to the average crystallite size which increases along with the annealing temperature. Compared to B. mori, A. pernyi silk fibres have more obvious temperature-dependant structural changes. These findings explain how size effects can be exploited to create bioinspired materials with tuneable mechanical properties.

In order to solve the poor self-purification ability of low temperature water in winter, the microbial community structure in the sediment of Pi River water (located in West Anhui) was investigated experimentally in this study. Firstly, the sediment was sampled in the lower reaches of Pi River and prepared with the different pH (5.0, 5.5, 7.0 and 8.5); secondly, the prepared samples were tested by the high-throughput sequencing technology and the tested results showed that more than 40% of the bacteria in the sediment samples had an average relative abundance of less than 1.5% and the bacterial community was relatively dispersed and diversified; the relative abundance of Acidobacteria was the lowest, while Proteobacteria and Bacteroidetes were the opposite; additionally, the abundances of Nitrosomonadaceae, Nitrospirae and Nitrosomonadales samples (pH = 5.5, 7.0 and 8.5) were all less than 5%, while the abundance in pH = 5.0 samples was less than 1%; the specific species of alkaline sample is 0, because acidity had a great influence on the structure of microbial community, especially nitrifying bacteria, furthermore, the optimal environment for bacterial growth in sediments had an acidity threshold. Accordingly, this paper will provide a reference for the poor self-purification of water at low temperature in winter.

Semenovia thomsonii is a perennial herb native to India. In this study, we assembled and annotated the complete chloroplast (cp) genome of a specimen collected from Xizang, China, using whole genome next-generation sequencing. The cp genome is circular in structure and 147,137 bp in length, consisting of one large single-copy (LSC) region of 92,885 bp, one small single-copy (SSC) region of 17,448 bp, and a pair of inverted repeat regions of 36,804 bp. The overall GC content of the genome is 37.6%. The cp genome was predicted to contain 129 genes, including 85 protein-coding, 36 tRNA, and eight rRNA. Phylogenetic analysis of S. thomsonii and 21 cp genomes in the Apiaceae fully resolved S. thomsonii in a clade with S. gyirongensis, and S. transiliensis. These genetic data represent the first confirmed report of S. thomsonii from Xizang, China and provide useful information to the phylogenetic history of the genus Semenovia.

Notholirion campanulatum and N. bulbuliferum are parapatrically distributed in the Qinghai-Tibetan Plateau and adjacent regions, however, their relationship has been controversial for a long time. In this study, six morphological characters including colour of corolla/ovary/bulblet, corolla shape, tepal size, and pollen form, together with nuclear ITS and four cpDNA markers (matK, ndhA, ndhG-I, and petL-G) were selected to perform a comprehensive analysis on 23 populations. Our results indicate that morphological characters of N. campanulatum and N. bulbuliferum are congruent with each other, and the phylogenetic analysis revealed that N. campanulatum closely nested with N. bulbuliferum. Therefore, we propose that these two species should be regarded as synonyms.

Integrating morphological and phylogenetic evidence is important for the taxonomy of Apiaceae. Here, we employed morphology of mericarps and molecular evidence to corroborate that two species of Haplosphaera are members of Hansenia. The results showed that Haplosphaera and Hansenia are similar carpologically. Phylogenetic analysis based on ITS data revealed that Haplosphaera is not monophyletic and the two species are embedded in Hansenia. Therefore, the two species of Haplosphaera are transferred to Hansenia, and reasonable taxonomical treatments are proposed.

A new species Tongoloa arguta (Apiaceae) is described and illustrated in this article. The new species grows in alpine bushes and meadows in south-western China. It resembles T. silaifolia, but differs from the latter by the length of the stem, ultimate segments of leaf and rays of the umbel. Phylogenetic analysis, based on nuclear ribosomal DNA internal transcribed spacer (ITS) sequences, is provided, as well as comparative morphology between related species.

Tongoloa tagongensis (Apiaceae), is proposed as a new species from the Hengduan Mountains in Sichuan, western China. It is most similar to T. elata, but the new species’ roots are short conic to tuberous, lower leaves 2–3-ternate/pinnate, rays 4–11, and ribs more obvious. Description and illustrations are provided.

Cognitive deficit is one of the most serious complications of cranial radiotherapy of head and neck cancers. However, the underlying mechanism of this cognitive impairment remains unclear. In the present study, the role of tropomyosin receptor kinase A (TrkA) and its ligand neurotrophin nerve growth factor (NGF) were investigated following whole‑brain irradiation (WBI). Young male Sprague‑Dawley rats underwent WBI at a single dose of 10 Gy. WBI was determined to result in notable memory decline and substantial neurogenesis impairment in the hippocampus 3 months post‑irradiation. Compared with the control group, TrkA protein expression was greater in irradiated rats 1 week after WBI, which then decreased significantly by the 3‑month time‑point. However, no difference in NGF expression was observed from 1 day to 3 months post‑WBI. Overexpression of hippocampal TrkA in rats using adeno‑associated virus ameliorated memory decline induced by irradiation. Additionally, upregulating TrkA expression rescued irradiation‑induced hippocampal precursor cell proliferation and promoted neurogenesis. PI3K, Akt and ERK1/2 phosphorylation were also revealed to be significantly inhibited by WBI, which was ameliorated by TrkA overexpression. Findings of the present study indicated that the TrkA‑dependent signaling pathway may serve a critical role in radiotherapy‑induced cognitive deficit and impairments in neurogenesis.

Isoflurane, an anesthetic, can aggravate the progression of Alzheimer's disease (AD). Long non-coding RNA β-secretase 1 (BACE1)-antisense transcript (BACE1-AS) and miR-214-3p are related to AD progression. Nevertheless, it is unclear whether BACE1-AS is involved in the development of isoflurane-mediated AD via miR-214-3p. Amyloid beta peptide (Aβ) was employed to construct the AD cell model. The expression of BACE1-AS and miR-214-3p in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aβ and isoflurane was assessed through quantitative reverse transcription polymerase chain reaction (qRT-PCR). The proliferation and apoptosis of Aβ-treated SK-N-SH and SK-N-AS cells were determined via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) or flow cytometry assays, respectively. Protein levels of B cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), CyclinD1, microtubule-associated protein A1/1B-light chain3 (LC3 I/LC3 II), p62 and Beclin1 were detected via western blot analysis. The relationship between BACE1-AS and miR-214-3p was verified by dual-luciferase reporter assay. We found that BACE1-AS was upregulated and miR-214-3p was downregulated in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aβ and isoflurane. Both BACE1-AS depletion and miR-214-3p augmentation restored the suppression of proliferation and the facilitation of apoptosis and autophagy of Aβ-treated SK-N-SH and SK-N-AS cells induced by isoflurane. Importantly, BACE1-AS acted as a sponge for miR-214-3p. Additionally, miR-214-3p silencing reversed the influence of BACE1-AS knockdown on isoflurane-mediated proliferation, apoptosis and autophagy in Aβ-induced SK-N-SH and SK-N-AS cells. In conclusion, BACE1-AS aggravated isoflurane-induced neurotoxicity to AD via sponging miR-214-3p.

Hymenidium dentatum (Wall. ex DC.) Pimenov & Kljuykov was a little-known species that was regarded as endemic to the Himalayan region. It is known that many species are under-collected impeded taxonomic studies and the traditionally recognized genera Pleurospermum (Hymenidium and Pterocyclus) were polyphyletic group. In this study, two naturally occurring populations of H. dentatum were discovered in China and morphological traits and ITS sequence data were studied to confirm the phylogenetic position of H. dentatum, which was located in Sinodielsia clade and close to the generic type of Hymendium. A comprehensive description of H. dentatum along with distribution, habitats and specimens examined and discuss suggestions for the conservation of this species were carried out comprehensively referring to our fieldwork.

The section Pallasia is one of the components of the genus Allium subgenus Allium (Amaryllidaceae), and species relationship in this section is still not resolved very well, which hinders further evolutionary and adaptive studies. Here, the complete chloroplast genomes of five sect. Pallasia species were reported, and a comparative analysis was performed with other three related Allium species. The genome size of the eight species ranged from 151,672 bp to 153,339 bp in length, GC content changed from 36.7% to 36.8%, and 130 genes (except Allium pallasii), 37 tRNA, and 8 rRNA were identified in each genome. By analyzing the IR/LSC and IR/SSC boundary, A. pallasii exhibited differences compared with other seven species. Phylogenetic analysis achieved high supports in each branch, seven of the eight Allium species cluster into a group, and A. pallasii exhibit a close relationship with A. obliquum. Higher pairwise Ka/Ks ratios were found in A. schoenoprasoides compared to A. caeruleum and A. macrostemon while a lower value of Ka/Ks ratios was detected between A. caeruleum and A. macrostemon. This study will be a great contribution to the future phylogenetic and adaptive research in Allium.

Background and AimsThe genus Allium L., one of the largest monocotyledonous genera and one that includes many economically important crops with nutritional and medicinal value, has been the focus of classification or phylogeny studies for centuries. Recent studies suggested that the genus can be divided into 15 subgenera and 72 sections, which were further classified into three evolutionary lineages. However, the phylogenetic relationships reconstructed by one or two loci showed weaker support, especially for the third evolutionary lineage, which might not show the species relationships very clearly and could hinder further adaptive and evolutionary study.MethodsIn this study, a total of 39 complete chloroplast genomes of Allium (covering 12 Allium subgenera) were collected, and combining these with 125 species of plastomes from 19 other families of monocots, we reconstructed the phylogeny of the genus Allium, estimated the origin and divergence time of the three evolutionary lineages and investigated the adaptive evolution in this genus and related families.ResultsOur phylogenetic analysis confirmed the monophyly and three evolutionary lineages of Allium, while new species relationships were detected within the third evolutionary lineage. The divergence time of the three evolutionary lineages was estimated to be in the early Eocene to the middle Miocene, and numerous positive selected genes (PSGs) and PSGs with high average Ka/Ks values were found in Allium species.ConclusionsOur results detected a well-supported phylogenetic relationship of Allium. The PSGs and PSGs with high Ka/Ks values, as well as diversified morphologies, complicated chromosome characteristics and unique reproductive modes may play important roles in the adaptation and evolution of Allium species. This is the first study that conducted phylogenetic and evolutionary analyses on the genus Allium combined with the plastome and morphological and cytological data. We hope that this study can contribute to further analysis of Allium for other researchers.

Caenorhabditis elegans (C. elegans) is increasingly used as a model organism to screen probiotics for ageing research. In this study, a C. elegans lifespan analysis model exposed to H2O2 and juglone (for chronic and acute assays) was used to preselect lactic acid bacteria (LAB) with resistance to oxidative stress. The mechanism of oxidative stress protection was analyzed. Seven out of ten LAB strains screened for namely 427, X13, 9-5, 422, Z5, G14 and H29M-8M demonstrated higher levels of protection to C. elegans, ranging from 70% to 85% survival rate, in comparison to the inactive strains 408, 13-7 and 430 (35% to 45% survival rate). The survival rates of the seven oxidative stress tolerant strains were correlated to increase in catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) levels and decrease in reactive oxygen species (ROS) expression in C. elegans during H2O2 and juglone exposure. In addition, the transcription of mitogen-activated protein kinase (MAPK) and Nrf2-Keap1-ARE pathway related genes was elevated in the oxidative stress protection of LAB isolates. Finally, a significant correlation was found between the ability of these LAB strains to protect C. elegans from H2O2 or juglone exposure and their antioxidative ability in Campylobacter jejuni-infected mice. Thus the results indicated that the oxidative stress-based lifespan model of C. elegans is useful for screening of LAB with antioxidant efficacy in pathogen-infected mammals.

Nephron endowment is defined by fetal kidney growth and critically dictates renal health in adults. Despite the advances in understanding the molecular regulation of nephron progenitors, the causes for low congenital nephron count and contribution of basic metabolism to nephron progenitor biology remain poorly understood. Here we characterized the metabolic consequences of MAPK/ERK-deficiency in nephron progenitors, whose maintenance and propagation in developing kidney critically depends on ERK activation. Our LC/MS-based metabolomics profiling identified 42 reduced metabolites, of which 26 were further supported by in vivo transcriptional characterization of MAPK/ERK-deficient nephron progenitors. This revealed a severe shortage of energy and nucleotide biosynthesis precursors, blockage in glycolysis and diminished pyruvate and proline metabolism. Utilization of in vitro kidney cultures demonstrated a dosage-specific function for glycolytic pyruvate as an energy source that controls the shape of the ureteric bud tip kwon to serve as a niche for nephron progenitor regulation. Analysis of the proline biosynthesis effects in developing kidney in vivo revealed premature loss of nephron progenitor maintenance in the absence of Pycr1/2 functions. Our results suggest that MAPK/ERK-dependent nephron progenitor metabolism functionally contributes to progenitor preservation by controlling pyruvate availability and proline metabolism in developing kidneys.

Objectives To explore the clinical features, molecular characteristics, and immune landscape of lung adenocarcinoma patients with KEAP1/NFE2L2/CUL3 mutations. Methods The multi‐omics data from the GDC‐TCGA LUAD project of The Cancer Genome Atlas (TCGA) database were downloaded from the Xena browser. The estimate of the immune infiltration was implemented by using the GSVA analysis and CIBERSORT. The status of KEAP1/NFE2L2/CUL3 mutation in 50 LUAD samples of our department was detected by using Sanger sequencing, following the relative expression level of differentially expressed genes (DEGs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was validated by IHC and real‐time quantitative polymerase chain reaction (RT‐qPCR). Results The Kaplan–Meier and multivariable Cox regression analyses demonstrated that KEAP1/NFE2L2/CUL3 mutations had independent prognostic value for OS and PFS in LUAD patients. The differential analysis detected 207 upregulated genes (like GSR/UGT1A6) and 447 downregulated genes (such as PIGR). GO, KEGG, and GSEA analyses demonstrated that DEGs were enriched in glutamate metabolism and the immune response. The constructed ceRNA network shows the linkage of differential lncRNAs and mRNAs. Three hundred and nine somatic mutations were detected, alterations in immune infiltration DNA methylations and stemness scores were also founded between the two groups. Eight mutated LUAD patients were detected by Sanger DNA sequencing in 50 surgical patients. GSR and UGT1A6 were validated to express higher in the Mut group, whereas the expression of PIGR was restrained. Furthermore, the IHC staining conducted on paraffin‐embedded tissue emphasizes the consistency of our result. Conclusion This research implemented the comprehensive analysis of KEAP1/NFE2L2/CUL3 somatic mutations in the LUAD patients. Compared with the wild type of LUAD patients, the Mut group shows a large difference in clinical features, RNA sequence, DNA methylation, and immune infiltrations, indicating complex mechanism oncogenesis and also reveals potential therapeutic targets., For the first time, an integrated multi‐mics analysis of KEAP1/NFE2L2/CUL3 mutated LUAD patients was performed. Based on several independent database, we validated the clinical value of KEAP1/NFE2L2/CUL3 in univiarate and multiviarate analyses. Our research shed light on the significance of potential therapeutical target via bioinformatics analyses and experimental verification.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC., 1. A new molecular feature of ESCC that involves both active posttranscriptional and posttranslational regulation was unveiled. 2. ESCC‐related signaling and metabolic pathways, networks among omics data, and common cancer/testis antigens along with established cancer drivers and kinases were delineated. 3. Proteins with close linkage to ESCC prognosis were discovered, and a new prognostic protein, fibrillarin (FBL), was further validated, functionally studied, and found to correlate negatively with patient outcomes.

Microtubule target agents (MTAs) are widely-used clinical anti-cancer drugs for decades, but the acquired drug resistance severely restricted their application. Thioredoxin reductases (TrxR) was reported to be overexpressed in most tumors and closely related to high risk of cancer recurrence and drug resistance, making it a potential target for anticancer drug discovery. Multi-target-directed ligands (MTDLs) by a single molecule provide a logical and alternative approach to drug combinations. In this work, based on the structure-activity relationships obtained in our previous study, some structure modifications were performed. On one hand, the retained skeleton structure of MTAs endowed its tubulin polymerization inhibition activity, on the other hand, the selenium-containing structure and α,β-unsaturated ketone moiety endowed the TrxR inhibition activity. As results, the newly obtained compounds exhibited superior anti-proliferative activities towards various human cancer cells and drug-resistance cells, and displayed high selectivity towards various human normal cells. The mechanism study revealed that the dual effect of cell cycle arrest triggered by targeting tubulin and the abnormal accumulation of ROS caused by TrxR inhibition eventually lead to cell apoptosis. Notably, compared with the MTA agents CA-4P, and the TrxR inhibitor Ethaselen, the optimized compound 14c, which served as dual-targeting inhibitor of tubulin and TrxR, exerted greatly improved in vivo anti-tumor activity. In summary, 14c deserved further consideration for cancer therapy.

Background/Aims: SMG9 participates in the nonsense-mediated mRNA decay process that degrades mRNA harboring nonsense mutations introduced either at the level of transcription or RNA processing. However, little is known about the role of SMG9 in hepatocellular carcinoma (HCC). The objective of this research was to clarify the effects of SMG9 expression on HCC progression.Methods: Microarray data were acquired from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to bioinformatically analyze the differential expression of SMG9 between HCC patients and normal controls. SMG9 mRNA level was measured in sixteen sets of fresh tumor tissues and adjacent non-cancerous liver tissues (ANLTs) via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SMG9 protein expression was analyzed in ninety-five sets of paired formalin-fixed and paraffin-embedded tissue specimens by immunohistochemistry (IHC). In addition, clinicopathological features of SMG9 in HCC were checked. For in vitro studies, small interfering RNA (siRNA) was used to silence SMG9 expression for exploring biological functions and underlying mechanisms of SMG9 in SMMC-7721 and HepG2.Results: We found that SMG9 was upregulated in HCC tissues and SMG9 levels were closely related to TNM stage, tumor number and tumor size. Cox regression and Kaplan–Meier proportional hazards analyses showed that high expression of SMG9 was associated with poor patient survival. Furthermore, proliferation, apoptosis resistance, migration and invasion of both SMMC-7721 and HepG2 cells were suppressed by SMG9 inhibition. In addition, EMT and the Wnt/β-catenin signaling pathway were involved in SMG9-mediated HCC progression.Conclusions: SMG9 may serve as a potential novel prognostic biomarker and therapeutic target in HCC patients.

The karst environment is characterized by low soil water content, periodic water deficiency, and poor nutrient availability, which provides an ideal natural laboratory for studying the adaptive evolution of its inhabitants. However, how species adapt to such a special karst environment remains poorly understood. Here, transcriptome sequences of two Urophysa species (Urophysa rockii and Urophysa henryi), which are Chinese endemics with karst-specific distribution, and allied species in Semiaquilegia and Aquilegia (living in non-karst habitat) were collected. Single-copy genes (SCGs) were extracted to perform the phylogenetic analysis using concatenation and coalescent methods. Positively selected genes (PSGs) and clusters of paralogous genes (Mul_genes) were detected and subsequently used to conduct gene function annotation. We filtered 2,271 SCGs and the coalescent analysis revealed that 1,930 SCGs shared the same tree topology, which was consistent with the topology detected from the concatenated tree. Total of 335 PSGs and 243 Mul_genes were detected, and many were enriched in stress and stimulus resistance, transmembrane transport, cellular ion homeostasis, calcium ion transport, calcium signaling regulation, and water retention. Both molecular and morphological evidences indicated that Urophysa species evolved complex strategies for adapting to hostile karst environments. Our findings will contribute to a new understanding of genetic and phenotypic adaptive mechanisms of karst adaptation in plants.

Background Campylobacter jejuni is the major micro-bacillary pathogen responsible for human coloenteritis. Lactic acid bacteria (LAB) have been shown to protect against Campylobacter infection. However, LAB with a good ability to inhibit the growth of C. jejuni in vitro are less effective in animals and animal models, and have the disadvantages of high cost, a long cycle, cumbersome operation and insignificant immune response indicators. Caenorhabditis elegans is increasingly used to screen probiotics for their anti-pathogenic properties. However, no research on the use of C. elegans to screen for probiotic candidates antagonistic to C. jejuni has been conducted to date. Results This study established a lifespan model of C. elegans, enabling the preselection of LAB to counter C. jejuni infection. A potential protective mechanism of LAB was identified. Some distinct LAB species offered a high level of protection to C. elegans against C. jejuni. The LAB strains with a high protection rate reduced the load of C. jejuni in C. elegans. The transcription of antibacterial peptide genes, MAPK and Daf-16 signalling pathway-related genes was elevated using the LAB isolates with a high protection rate. The reliability of the lifespan model of C. elegans was verified using mice and chickens infected with C. jejuni. Conclusions The results showed that different LAB had different abilities to protect C. elegans against C. jejuni. C. elegans provides a reliable model for researchers to screen for LAB that are antagonistic to C. jejuni on a large scale.

The species Tetrataenium yunnanense is a medicinal herb exhibiting excellent anti-tumor activity in vitro and mainly distributed in northwest Yunnan, China. The assembled genome is 142,739 ...

Hansenia pinnatiinvolucellata and H. weberbaueriana have been recorded to co-occur in Hengduan Mountains and adjacent regions. However, there were no reliable distinguishing characters to identify them. In our research, we explored key morphological characters through field work, specimen examinations and original literature reviews and reconstructed the phylogeny based on nuclear ITS regions, to determine the relationship between H. pinnatiinvolucellata and H. weberbaueriana. Morphological results indicated that the key, unique morphological characters (entire or pinnati bracteoles longer than pedicels and fruit with 3 ribs) of H. pinnatiinvolucellata were occurs simultaneously in some populations of H. weberbaueriana. Phylogenetic analyses also reveal that H. pinnatiinvolucellata and H. weberbaueriana are nested together. So, H. pinnatiinvolucellata should be a synonym of H. weberbaueriana.

Our integrated evidence indicates morphological and genetic polymorphisms in Allium cyathophorum and thus the need for a taxonomic revision. First, A. cyathophorum var. farreri is reinstated as A. farreri. Second, a cryptic allotetraploid population geographically confined to the intermediate zone between A. cyathophorum and A. farreri is described here as a new species named A. tetraploideum. Morphological characters that differentiate these three species from each other, as well as information on their distribution range and habitat, are provided.

Glycogen synthase (GS) and glycogen phosphorylase (GP) are two key enzymes in the glycogen synthesis pathway, which catalyze trehalose and glucose transformation in insects. GS and GP can be regulated by trehalose metabolism, which plays an important role in insect growth. However, it is not known whether these genes can be targeted for pest control through regulation of chitin metabolism. We studied the function of Nilaparvata lugens GS and GP (NLGS and NLGP, respectively) using RNA interference, and reported that trehalose and the chitin biosynthesis pathways are regulated by GP and GS, especially TPS3, TRE1-1, and G6PI1, which decreased following knockdown of these two genes. The expression levels of TPS1, TPS2, and several chitin synthesis pathway family genes were significantly increased following dsNlGP injection. Additionally, despite there being no apparent change to the chitin content, an abnormal molting phenotype and wing deformity appeared, and close to 25% insects died. These results demonstrate that silencing of NLGP or NLGS can lead to molting deformities and an elevated mortality rate through the regulation of chitin pathway genes and chitinase genes. NLGP may play a key role in chitin synthesis due to the number of genes regulated, and higher deformity and mortality rates resulting from its knockdown.

l-Tyrosine is an essential aromatic amino acid required for the synthesis of proteins and a diverse array of plant natural products; however, little is known on how the levels of tyrosine are controlled in planta and linked to overall growth and development. Most plants synthesize tyrosine by TyrA arogenate dehydrogenases, which are strongly feedback-inhibited by tyrosine and encoded by TyrA1 and TyrA2 genes in Arabidopsis thaliana. While TyrA enzymes have been extensively characterized at biochemical levels, their in planta functions remain uncertain. Here we found that TyrA1 suppression reduces seed yield due to impaired anther dehiscence, whereas TyrA2 knockout leads to slow growth with reticulate leaves. The tyra2 mutant phenotypes were exacerbated by TyrA1 suppression and rescued by the expression of TyrA2, TyrA1 or tyrosine feeding. Low-light conditions synchronized the tyra2 and wild-type growth, and ameliorated the tyra2 leaf reticulation. After shifting to normal light, tyra2 transiently decreased tyrosine and subsequently increased aspartate before the appearance of the leaf phenotypes. Overexpression of the deregulated TyrA enzymes led to hyper-accumulation of tyrosine, which was also accompanied by elevated aspartate and reticulate leaves. These results revealed that TyrA1 and TyrA2 have distinct and overlapping functions in flower and leaf development, respectively, and that imbalance of tyrosine, caused by altered TyrA activity and regulation, impacts growth and development of Arabidopsis. The findings provide critical bases for improving the production of tyrosine and its derived natural products, and further elucidating the coordinated metabolic and physiological processes to maintain tyrosine levels in plants.

Exploring the effects of orographic events and climatic shifts on geographic distribution of organism in the Hengduan Mountains Region (HMR) and its eastern adjacent area is crucial to the understanding of the environmental changes to organismal evolution. To gain further insight into these processes, we reconstruct evolutionary history of ten species in Allium section Sikkimensia, distributed across regions abovementioned. Using chloroplast and nuclear sequence variation of 79 populations of these ten Allium species with known morphological preferences, we elucidate the phylogenetic relationship, divergence time, ancestral area and genetic structures. Climatic variables analysis, Isolation by distance (IBD) and environment (IBE) and Species distribution modeling (SDM) were analyzed along different genetic clades. These analyses indicated that the initial split of Sikkimensia was triggered by climate changes following Qinghai-Tibet Plateau sensu lato (QTPsl) uplift during the late Miocene. Subsequently, divergences within lineage (lineage A)/among lineages (lineage C and D) in Sikkimensia may be induced by the intense uplift of the HMR around 3–4 Ma and abrupt intensifying of the Asian monsoon regimes. Furthermore, Sikkimensia populations exhibited lopsided demographic history in the Last Glacial Maximum (LGM), as was indicated by the expansion of their range in the QDM and contraction in the HMR. Our findings appear to suggest that the HMR uplift could have strengthened the orographic difference between the HMR and its eastern adjacent area and led to a colder climate in the HMR, while geological topography also played an important role for taxa to respond the climate change that had taken place in the HMR and its eastern adjacent area during the Pleistocene.

Alkaline phosphatase (ALP) excreted from lactic acid bacteria (LAB) showed the ability to degrade organophosphorus pesticides. This study reported the first purification and characterization of ALP from LAB. The molecular weight of ALP was estimated to be 43 kDa measured by SDS-PAGE. The activity of purified enzyme was determined with the binding of p-nitrophenyl phosphate as the substrate. The results showed that the optimal temperature for ALP activity was 37 °C, and the optimal pH was 8.5. But ALP was stable at temperatures below 32 °C. The ALP activity remained at 80% when the pH was 8–9.5. The enzyme activity could be activated by Mg2+, Ca2+, and inhibited by Cu2+, Zn2+, and EDTA. The Michaelis–Menten constant was 6.05 mg kg−1 with dimethoate as the substrate according to the Lineweaver–Burk plots. These results highlight an important potential use of ALP from LAB for the cleanup of pesticide pollution in raw materials for the food industry.

Leuconostoc mesenteroides can be used to produce mannitol by fermentation, but the mannitol productivity is not high. Therefore, in this study modify the chromosome of Leuconostoc mesenteroides by genetic methods to obtain high-yield strains of mannitol production. In this study, gene knock-out strains and gene knock-in strains were constructed by a two-step homologous recombination method. The mannitol productivity of the pat gene (which encodes phosphate acetyltransferase) deleteon strain (Δpat::amy), fk gene (which encodes fructokinase) deleteon strain (Δfk::amy) and stpk gene (which encodes serine-threonine protein kinase) deleteon strain (Δstpk::amy) were all increased compared to the wild type, and the productivity of mannitol for each strain was 84.8%, 83.5% and 84.1% respectively. The mannitol productivity of the mdh gene (which encodes mannitol dehydrogenase) knock-in strains (Δpat::mdh, Δfk::mdh and Δstpk::mdh) was increased to a higher level than that of the single-gene deletion strains, and the productivity of mannitol for each was 96.5%, 88% and 93.2%, respectively. The multi-mutant strain ΔdtsΔldhΔpat::mdhΔstpk::mdhΔfk::mdh had mannitol productivity of 97.3%. This work shows that multi-gene knock-out and gene knock-in strains have the greatest impact on mannitol production, with mannitol productivity of 97.3% and an increase of 24.7% over wild type. This study used the methods of gene knock-out and gene knock-in to genetically modify the chromosome of Leuconostoc mesenteroides. It is of great significance that we increased the ability of Leuconostoc mesenteroides to produce mannitol and revealed its broad development prospects.

Exploring the effects of orographic events and climatic shifts on the geographic distribution of organisms in the Himalayas-Hengduan Mountains (HHM) region and Qinghai-Tibetan Plateau (QTP) is crucial to understand the impact of environmental changes on organism evolution. To gain further insight into these processes, we reconstructed the evolutionary history of nine Chamaesium species distributed across the HHM and QTP regions. In total, 525 individuals from 56 populations of the nine species were analyzed based on three maternally inherited chloroplast fragments (rpl16, trnT-trnL, and trnQ-rps16) and one nuclear DNA region (internal transcribed spacer, ITS). Fifty-two chloroplast DNA (cpDNA) and 47 ITS haplotypes were identified in nine species. All of the cpDNA and ITS haplotypes were species-specific. Phylogenetic analysis suggested that all nine species form a monophyletic clade with high support. Dating analysis and ancestral area reconstruction revealed that the ancestral group of Chamaesium originated in the southern Himalayan region at the beginning of the Paleogene (60.85 Ma). The nine species of Chamaesium then separated well during the last 25 million years started in Miocene. Our maxent modeling indicated the broad-scale distributions of all nine species remained fairly stable from LIG to the present and predicted that it will remain stable into the future. The initial split of Chamaesium was triggered by climate changes following the collision of the Indian plate with the Eurasia plate during the Eocene. Subsequently, divergences within Chamaesium may have been induced by the intense uplift of the QTP, the onset of the monsoon system, and Central Asian aridification. Long evolutionary history, sexual reproduction, and habitat fragmentation could contribute to the high level of genetic diversity of Chamaesium. The higher genetic differentiation among Chamaesium populations may be related to the drastic changes of the external environment in this region and limited seed/pollen dispersal capacity.

The disjunctive distribution (Europe–Caucasus–Asia) and species diversification across Eurasia for the genus Allium sect. Daghestanica has fascinating attractions for researchers aiming to understanding the development and history of modern Eurasia flora. However, no any studies have been carried out to address the evolutionary history of this section. Based on the nrITS and cpDNA fragments (trnL–trnF and rpl32–trnL), the evolutionary history of the third evolutionary line (EL3) of the genus Allium was reconstructed and we further elucidated the evolutionary line of sect. Daghestanica under this background. Our molecular phylogeny recovered two highly supported clades in sect. Daghestanica: the Clade I includes Caucasian–European species and Asian A. maowenense, A. xinlongense and A. carolinianum collected in Qinghai; the Clade II comprises Asian yellowish tepal species, A. chrysanthum, A. chrysocephalum, A. herderianum, A. rude and A. xichuanense. The divergence time estimation and biogeography inference indicated that Asian ancestor located in the Qinghai–Tibetan Plateau (QTP) and the adjacent region could have migrated to Caucasus and Europe distributions around the Late Miocene and resulted in further divergence and speciation; Asian ancestor underwent the rapid radiation in the QTP and the adjacent region most likely due to the heterogeneous ecology of the QTP resulted from the orogeneses around 4–3 million years ago (Mya). Our study provides a picture to understand the origin and species diversification across Eurasia for sect. Daghestanica.

Background Subtribe Angelicinae is a large and taxonomically complex group of Apiaceae, encompassing Angelica, Archangelica, Coelopleurum, Conioselinum, Czernaevia, Glehnia, Levisticum and Ostericum that are distributed in the Northern Hemisphere, and whether this taxa is natural is debatable, especially between Angelica and Ostericum. To determine genommic evolution and phylogenetic relationships between Angelica, Ostericum, and related species, we newly assembled the complete plastid genome sequences of eight subtribe Angelicinae species and Melanosciadium pimpinelloideum using next-generation sequencing technology. Results The nine plastid genomes we sequenced were conserved, and their size ranged from 146765 bp to 164329 bp, showing the typical quadripartite circular structure with an overall GC content of 37.5–37.8%. IR boundary analyses showed that the genes in the LSC region transfer into the IR regions and the SSC region was relatively stable. Codon usage patterns were similar among these species and we identified 66–86 SSRs, with the most abundant SSR being mononucleotide. The Pi analyses showed that petA-psbJ(0.02778), atpI-atpH(0.17333) and petA-psbJ(0.04726) intergenic regions had the highest Pi values in Angelica, Ostericum, and ten species, respectively. Conclusions Ostericum exhibited significant differences in size of genomes, content of genes and tRNAs, GC content, some type of SSRs, and IR boundaries to Angelica, and phylogenetic analyses found the relatedness between Angelica and Ostericum is more distant in protein-coding genes of the plastid genomes trees and nrITS trees.

The genus Allium is one of the world’s largest monocot genera. However, few reports on the complete chloroplast genome of Allium plants are reported. In this study, we reported the complete chloroplast genome of Allium prattii. The genome sequence was 154,482 bp in length, including a large single copy region (LSC) of 83,392 bp and a small single copy region (SSC) of 18,064 bp, which were separated by two inverted repeat (IR) regions of 26,513 bp. The complete chloroplast genome contains 131 genes, including 85 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analysis with several reported chloroplast genomes showed that A. prattii has a close genetic relationship with A. cepa and A. sativum.

Species of Tulipa (Liliaceae) are of great horticultural importance and are distributed across Europe, North Africa, and Asia. The Tien Shan Mountain is one of the primary diversity centres of Tulipa, but the molecular studies of Tulipa species from this location are lacking. In our study, we assembled four Tulipa plastid genomes from the Tien Shan Mountains, T. altaica, T. iliensis, T. patens, and T. thianschanica, combined with the plastid genome of T. sylvestris to compare against other Liliaceae plastid genomes. We focussed on the species diversity and evolution of their plastid genomes. The five Tulipa plastid genomes proved highly similar in overall size (151,691–152,088 bp), structure, gene order, and content. With comparative analysis, we chose 7 mononucleotide SSRs from the Tulipa species that could be used in further population studies. Phylogenetic analyses based on 24 plastid genomes robustly supported the monophyly of Tulipa and the sister relationship between Tulipa and Amana, Erythronium. T. iliensis, T. thianschanica, and T. altaica were clustered together, and T. patens was clustered with T. sylvestris, with our results clearly demonstrating the relationships between these five Tulipa species. Our results provide a more comprehensive understanding of the phylogenomics and comparative genomics of Tulipa.

Plants experience a wide array of environmental stimuli, some of which are frequent occurrences of cold weather, which have priming effects on agricultural production and agronomic traits. DNA methylation may act as an epigenetic regulator for the cold response of Tartary buckwheat (Fagopyrum tataricum). Combined with long-term field observation and laboratory experiments, comparative phenome, methylome, and transcriptome analyses were performed to investigate the potential epigenetic contributions for the cold priming of Tartary buckwheat variety Dingku1. Tartary buckwheat cv. Dingku1 exhibited low-temperature resistance. Single-base resolution maps of the DNA methylome were generated, and a global loss of DNA methylation was observed during cold responding in Dingku1. These sites with differential methylation levels were predominant in the intergenic regions. Several hundred genes had different DNA methylation patterns and expressions in different cold treatments (cold memory and cold shock), such asCuAO,RPB1, andDHE1. The application of a DNA methylation inhibitor caused a change of the free lysine content, suggesting that DNA methylation can affect metabolite accumulation for Tartary buckwheat cold responses. The results of the present study suggest important roles of DNA methylation in regulating cold response and forming agronomic traits in Tartary buckwheat.

Background Habrobracon hebetor (Hymenoptera: Braconidae) is a gregarious ectoparasitoid that attacks the larvae of several species of pyralid and noctuid moths. The reproduction and population dynamics of parasitoids in general are affected by host deprivation. However, how host deprivation affects H. hebetor is unknown. The effect of host deprivation on the parental generation, life table parameters, and the paralysis rate of the F1 generation of H. hebetor were evaluated using the age-stage, two-sex life table under laboratory conditions. Results The results indicated that the greatest longevity and the least lifetime fecundity of the F0 generation occurred after 19 days of host deprivation (PW-20 treatment). The life table parameters (intrinsic rate of increase, r; finite rate of increase, λ; and net reproductive rate, R0 ) and the paralysis rate parameters (net paralysis rate, C0 ; transformation rate, Qp ; stable paralysis rate, ψ; and finite paralysis rate, ω) of F1 individuals after PW-20 treatment were significantly higher than those of individuals subjected to the control treatment (no host deprivation). However, no difference was detected between the two host deprivation treatments: host deprivation after 1 day of host contact and immediate host deprivation (PW treatment). Conclusion Our results demonstrated that the effectiveness of H. hebetor did not decrease even during host deprivation for 19 days. Meanwhile, it was observed that mass rearing of the parasitoid could be improved by providing 10 individuals of 5th instar larvae of Ephestia elutella (Lepidoptera: Pyralidae) with a 20% honey-water solution. © 2020 Society of Chemical Industry.

Background The genus Ligusticum consists of approximately 60 species distributed in the Northern Hemisphere. It is one of the most taxonomically difficult taxa within Apiaceae, largely due to the varied morphological characteristics. To investigate the plastome evolution and phylogenetic relationships of Ligusticum, we determined the complete plastome sequences of eight Ligusticum species using a de novo assembly approach. Results Through a comprehensive comparative analysis, we found that the eight plastomes were similar in terms of repeat sequence, SSR, codon usage, and RNA editing site. However, compared with the other seven species, L. delavayi exhibited striking differences in genome size, gene number, IR/SC borders, and sequence identity. Most of the genes remained under the purifying selection, whereas four genes showed relaxed selection, namely ccsA, rpoA, ycf1, and ycf2. Non-monophyly of Ligusticum species was inferred from the plastomes and internal transcribed spacer (ITS) sequences phylogenetic analyses. Conclusion The plastome tree and ITS tree produced incongruent tree topologies, which may be attributed to the hybridization and incomplete lineage sorting. Our study highlighted the advantage of plastome with mass informative sites in resolving phylogenetic relationships. Moreover, combined with the previous studies, we considered that the current taxonomy system of Ligusticum needs to be improved and revised. In summary, our study provides new insights into the plastome evolution, phylogeny, and taxonomy of Ligusticum species.

Hansenia Turcz., Haplosphaera Hand.-Mazz. and Sinodielsia H.Wolff are three Apiaceae genera endemic to the Hengduan Mountains and the Himalayas, which usually inhabit elevations greater than 2000 m. The phylogenetic relationships between and within the genera were uncertain, especially the placement of Hap. himalayensis and S. microloba. Therefore, we aimed to conduct comparative (simple sequence repeat (SSR) structure, codon usage bias, nucleotide diversity (Pi) and inverted repeat (IR) boundaries) and phylogenetic analyses of Hansenia, Haplosphaera and Sinodielsia (also compared with Chamaesium and Bupleurum) to reduce uncertainties in intergeneric and interspecific relationships. We newly assembled eight plastid genomes from Hansenia, Haplosphaera and Sinodielsia species, and analyzed them with two plastid genomes from GenBank of Hap. phaea,S. yunnanensis. Phylogenetic analyses used these ten genomes and another 22 plastid genome sequences of Apiaceae. We found that the newly assembled eight genomes ranged from 155,435 bp to 157,797 bp in length and all had a typical quadripartite structure. Fifty-five to 75 SSRs were found in Hansenia, Haplosphaera and Sinodielsia species, and the most abundant SSR was mononucleotide, which accounted for 58.47% of Hansenia, 60.21% of Haplosphaera and 48.01% of Sinodielsia. There was no evident divergence of codon usage frequency between the three genera, where codons ranged from 21,134 to 21,254. The Pi analysis showed that trnE(UUC)-trnT(GGU), trnH(GUG)-psbA and trnE(UUC)-trnT(GGU) spacer regions had the highest Pi values in the plastid genomes of Hansenia (0.01889), Haplosphaera (0.04333) and Sinodielsia (0.01222), respectively. The ndhG-ndhI spacer regions were found in all three genera to have higher diversity values (Pi values: 0.01028&ndash, 0.2), and thus may provide potential DNA barcodes in phylogenetic analysis. IR boundary analysis showed that the length of rps19 and ycf1 genes entering IRs were usually stable in the same genus. Our phylogenetic tree demonstrated that Hap. himalayensis is sister to Han. weberbaueriana, meanwhile, Haplosphaera and Hansenia are nested together in the East Asia clade, and S. microloba is nested within individuals of S. yunnanensis in the Acronema clade. This study will enrich the complete plastid genome dataset of the Apiaceae genera and has provided a new insight into phylogeny reconstruction using complete plastid genomes of Hansenia, Haplosphaera and Sinodielsia.

Tripterygium wilfordii Hook F (TwHF) is a traditional Chinese herb used in many medicinal applications, but the treatment of bullous pemphigoid (BP) with TwHF has never been reported. The aim of this study was to evaluate the efficacy and safety of TwHF in BP patients. A retrospective study was performed from January 2015 to September 2019 in the Department of Dermatology, Peking Union Medical College Hospital. A total of 10 patients with mild to moderate BP and treated with TwHF were enrolled in the study with 10 mild or moderate BP patients treated with systemic glucocorticoid randomly selected as controls. In the TwHF group, a major response was seen in seven patients, a minor response in one and no response was seen in two patients. In the glucocorticoid group, a major response was seen in nine patients and a minor response in one patient. Two patients experienced treatment failure. The time to disease control in the TwHF group (34 ± 11 days) was longer as compared to the glucocorticoid group (18 ± 8 days, P < .05). Ten patients relapsed during the follow-up period. The adverse events in the TwHF group were lower than those in the glucocorticoid group (13 vs 19). Low-dose TwHF may be effective and safe for treating mild and moderate BP.

Ubiquitin-specific protease 5 (USP5) is a deubiquitinating enzyme that functions as an oncoprotein in a variety of human cancers. However, the expression and role of USP5 in the metastasis of non-small cell lung cancer (NSCLC) have not been addressed. In this study, we examined the expression and prognostic significance of USP5 in NSCLC. The results revealed that USP5 was overexpressed and correlated with metastasis and overall survival in NSCLC tissues. A further in vitro study revealed that the levels of USP5 protein in NSCLC cells were associated with epithelial-mesenchymal transition (EMT) markers. Furthermore, USP5 overexpression significantly enhanced, whereas USP5 silencing significantly decreased the expression of EMT proteins and migration and invasion of NSCLC cells. In addition, the results from western blotting demonstrated that USP5 regulated EMT via the Wnt/β-catenin signaling pathway. Further immunohistochemical analysis revealed that USP5 was significantly associated with the expression of β-catenin and EMT markers in NSCLC tissues. Overall, USP5 upregulation is associated with tumor metastasis and poor prognosis in patients with NSCLC. USP5 promotes EMT and the invasion and migration of NSCLC cells. Therefore, USP5 may serve as a novel prognostic biomarker and provide a potential target for the treatment of metastasis in NSCLC.

Lung cancer (LC) is a leading cause of cancer-related deaths worldwide. Its rapid growth requires hyperactive catabolism of principal metabolic fuels. It is unclear whether fructose, an abundant sugar in current diets, is essential for LC. We demonstrated that, under the condition of coexistence of metabolic fuels in the body, fructose was readily used by LC cells in vivo as a glucose alternative via upregulating GLUT5, a major fructose transporter encoded by solute carrier family 2 member 5 (SLC2A5). Metabolomic profiling coupled with isotope tracing demonstrated that incorporated fructose was catabolized to fuel fatty acid synthesis and palmitoleic acid generation in particular to expedite LC growth in vivo. Both in vitro and in vivo supplement of palmitoleic acid could restore impaired LC propagation caused by SLC2A5 deletion. Furthermore, molecular mechanism investigation revealed that GLUT5-mediated fructose utilization was required to suppress AMPK and consequently activate mTORC1 activity to promote LC growth. As such, pharmacological blockade of in vivo fructose utilization using a GLUT5 inhibitor remarkably curtailed LC growth. Together, this study underscores the importance of in vivo fructose utilization mediated by GLUT5 in governing LC growth and highlights a promising strategy to treat LC by targeting GLUT5 to eliminate those fructose-addicted neoplastic cells.