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The Himalaya Terrane of southern Tibet exposes successive shallow-marine carbonate deposits from the Lower to Upper Triassic, and is a key region for studying the Triassic conodont biostratigraphy at the northern margin of the Indian Plate. On the basis of newly collected samples from the Kangshare and Laibuxi formations at the Tulong section, 11 conodont species of 7 genera were identified, and four conodont zones were established, namely, the Novispathodus abruptus Zone (lower Spathian, first reported in Tibet), the Columbitella jubata Zone (middle Spathian), the Triassospathodus symmetricus Zone (upper Spathian), and the Chiosella timorensis Zone (lowermost Anisian) in ascending order. The first occurrence (FO) of Chiosella timorensis indicates the Olenekian–Anisian boundary (OAB) at Bed 25, upper part of the Kangshare Formation. The regional and global correlation of these conodont zones is synthesized.

Multi-factors have been reported to affect the gut microbiome, including genotype, age, diet, and nutrition. However, few reports have investigated the relative capacity of different factors to shape the gut microbiome in a single study. Our design used a genetic Vitamin A deficient mouse model, the Rbp4-/- mouse, feeding with the low Vitamin A diets at different ages of initiation (4 or 7 weeks) for 28 days. Fecal samples were collected for bacterial profiling at seven time points after diet controlling. With RBP4 depletion, Akkermansia decreased and Bacteroides increased, while Desulfovibrio, Barnesiella, Clostridium_XlVa, and Lactobacillus fluctuated. The bacterial community swiftly adjusted with the Vitamin A-deficient diet administration and gradually changed (e.g., decrease of Barnesiella and increase of Desulfovibrio). Age exerted a relatively weaker but long-last influence. At an earlier age to feed a Vitamin-A deficient diet, a higher microbial dysbiosis index (MDI) will be valued. Of note, the shaping effects of diet and age on the bacterial community varied with the difference of genotype, which might indicate a greater role of genotype than diet and age in shaping the gut microbiome.

EBV-encoded circular RNA LMP2A (ebv-circLMP2A) was found to be expressed in EBV-associated gastric carcinoma (EBVaGC) and associated with distant metastasis and poor prognosis. Angiogenesis is a key step in tumor invasion and metastasis and plays a crucial role in tumor progression. However, it is unclear whether and how ebv-circLMP2A is involved in angiogenesis. In this study, we showed that MVD, HIF1α, and VEGFA expression was increased in EBVaGC mouse xenografts with high expression of ebv-circLMP2A. The expression of ebv-circLMP2A was positively correlated with MVD, HIF1α, and VEGFA expression in clinical samples of EBVaGC. Knockdown of ebv-circLMP2A repressed tube formation and migration of HUVECs and decreased VEGFA and HIF1α expression in cancer cells under hypoxia, while ectopic expression of ebv-circLMP2A reversed these effects. Additionally, knockdown of HIF1α blocked the upregulation of ebv-circLMP2A by hypoxia, and ebv-circLMP2A interacted with KHSRP to enhance KHSRP-mediated decay of VHL mRNA, leading to the accumulation of HIF1α under hypoxia. There was a positive feedback loop between HIF1α and ebv-circLMP2A that promotes angiogenesis under hypoxia. ebv-circLMP2A was essential in regulating tumor angiogenesis in EBVaGC and might provide a valuable therapeutic target for EBVaGC.

Objective To evaluate the clinical outcome of manual reduction combined with pedicle fixation through Wiltse paraspinal approach (WPA) in the treatment of thoracolumbar fractures. Methods From May 2017 to May 2019, 48 thoracolumbar fractures patients without neurological symptoms were enrolled in this study. Forty‐eight patients were randomly divided into two groups based on the different surgical treatment. Group 1 was manual reduction combined with pedicle screw fixation through Wiltse paraspinal approach treatment group. Group 2 was pedicle screw fixation through traditional posterior approach treatment group. The operation time (OT), intraoperative blood loss (BL), postoperative drainage (PD), time of brace (TB) and the cobb angle recovery of the injured kyphosis in the prone position were obtained and compared between the two groups, respectively. Comparison of cobb angle changes, serum creatine kinase (CK) level, pain visual analogue score (VAS), Oswestry disability index (ODI), and multifidus cross‐sectional (MCS) area changes were achieved between the two groups, respectively. Results Forty‐eight patients were enrolled in this study and each group had 24 patients. There was no significant difference between the two groups in patient's age, height, weight, and body mass index (BMI). There were 20 males and four females in group 1. The mean age, height, weight, and BMI of patients were 61.99 ± 11.00 years (range, 42–75 years), 175.21 ± 4.49 cm, 76.71 ± 4.87 kg, and 24.98 ± 1.03 kg/m2 in group 1, respectively. Group 2 had 18 males and six females, and the mean age, height, weight, and BMI of patients were 57.95 ± 9.22 years (range, 44–77 years), 176.37 ± 4.56 cm, 77.42 ± 4.61 kg, and 24.87 ± 1.10 kg/m2 in group 2, respectively. The mean bleeding volume of group 1 was significantly less than group 2 (64.13 ± 9.77 ml and 152.13 ± 10.73 ml, respectively) (P, In this study, the results showed that preoperative manual reduction could help restore the height of injured vertebrae. Wiltse intermuscular approach has less intraoperative blood loss, shorter operation time and paraspinal muscle damage.

The genus Eutrichosomella Girault is recorded for the first time from China (Yunnan Province), and Eutrichosomella yunnanensissp. nov. (♀, ♂) is described and illustrated. A distribution map of this genus is presented.

Two strains HN-1T and 39 were isolated from rhizospheres of different plants grown in different regions of PR China. The two strains exhibited high nitrogenase activities and possessed almost identical 16S rRNA gene sequences. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between the two strains were 99.9 and 93.8% respectively, suggesting that they belong to one species. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strains HN-1T and 39 are the members of the genus Paenibacillus and both strains exhibited 99.5% similarity to Paenibacillus stellifer DSM 14472T and the both strains represented a separate lineage from all other Paenibacillus species. However, the ANI of type strain HN-1T with P. stellifer DSM 14472T was 90.69, which was below the recommended threshold value (T and P. stellifer DSM 14472T, which was lower than the recommended threshold value (dDDH T contain anteiso-C15:0 as major fatty acids and MK-7 as predominant isoprenoid quinone. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four aminophospholipids and an unidentified glycolipid. Unlike the most closely related P. stellifer DSM 14472T, strain HN-1T or 39 was positive for catalase reaction. Distinct phenotypic and genomic characterisations from previously described taxa support the classification of strains HN-1T or 39 as representatives of a novel species of the genus Paenibacillus, for which the name Paenibacillus sinensis is proposed, with type strains HN-1T (= CGMCC 1.18902, JCM 34620), and reference strain 39 (= CGMCC 1.18879, JCM 34616), respectively.

Mung bean contains various neuroprotective polyphenols, so it might be a healthy food for Alzheimer's disease (AD) prevention. Totally, 19 major phenolic compounds were quantified in mung bean, including 10 phenolic acids and 9 flavonoids. After summarizing their contents and effective doses in rodent AD models, it was speculated that vitexin, isovitexin, sinapic acid, and ferulic acid might be the major bioactive compounds for mung bean-mediated neuroprotection. The mechanisms involved inhibition of β-amyloidogenesis, tau hyperphosphorylation, oxidative stress, and neuroinflammation, and promotion of autophagy and acetylcholinesterase enzyme activity. Notably, the neuroprotective phenolic profile in mung bean changed after germination, with decreased vitexin and isovitexin, and increased rutin, isoquercitrin, isorhamnetin, and caffeic acid detected. However, only studies of individual phenolic compounds in mung bean are published at present. Hence, further studies are needed to elucidate the neuroprotective activities and mechanisms of extractions of mung bean seeds and sprouts, and the synergism between different phenolic compounds.

Although all cancers share common hallmarks, we have long realized that there is no silver-bullet treatment for the disease. Many clinical oncologists specialize in a single cancer type, based predominantly on the tissue of origin. With advances brought by genetics and cancer genomic research, we now know that cancers are profoundly different, both in origins and in genetic alterations. At the same time, commonalities such as key driver mutations, altered pathways, mutational, immune and microbial signatures and other areas (many revealed by pan-cancer studies) point to the intriguing possibility of targeting common traits across diverse cancer types with the same therapeutic strategies. Studies designed to delineate differences and similarities across cancer types are thus critical in discerning the basic dynamics of oncogenesis, as well as informing diagnoses, prognoses and therapies. We anticipate growing emphases on the development and application of therapies targeting underlying commonalities of different cancer types, while tailoring to the unique tissue environment and intrinsic molecular fingerprints of each cancer type and subtype. Here we summarize the facets of pan-cancer research and how they are pushing progress toward personalized medicine. Ding and colleagues discuss the era of pan-cancer analysis, covering the fundamental insights gained, unique opportunities and challenges, and the future of such approaches in the basic and clinical space.

Clear‐cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy. The pathogenesis of the disease is currently poorly understood, and the prognosis is poor. Therefore, in this study, we focused on exploring and identifying genes and signal transduction pathways that are closely related to ccRCC. Differentially expressed genes (DEGs) were analyzed using the renal cell oncogene expression profiles GSE100666 and GSE68417. DAVID evaluation of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses was used. We constructed a protein–protein interaction (PPI) network of DEGS using Cytoscape software and analyzed the submodules with the CytoHubba plugin. Finally, we performed western blot, immunohistochemistry, and PCR validation by collecting tissues, and also utilized cells for in vitro functional analysis of ceruloplasmin (CP). In total, 202 DEGs (52 upregulated and 150 downregulated genes) were identified. Upregulated DEGs are significantly rich in angiogenesis, cell adhesion, and response to hypoxia, whereas downregulated DEGs are involved in intracellular pH regulation, excretion, coagulation, and chloride transmembrane transport. We selected the interactions of the top 20 hub genes provided by the PPI network, all of which are involved in important physiological pathways in vivo, such as complement and coagulation cascades. Tissue protein assays demonstrated that renal cancer highly expressed CP, while in vitro experiments showed that CP could promote the invasion of renal cancer cells. Our study suggests that ALB, C3, LOX, HRG, CXCR4, GPC3, SLC12A3, CP, and CASR may be involved in the development of ccRCC, and is expected to provide theoretical support for future studies on the diagnosis and targeted therapy of ccRCC., DEGs in clear cell renal cell carcinoma (ccRCC) were identified and their expression analyzed in ccRCC patient tissues and an RCC cell line. Tissue protein assays demonstrated that renal cancer highly expressed ceruloplasmin (CP), and in vitro experiments showed that CP could promote the invasion of renal cancer cells. Overall, CP may promote the poor prognosis of renal cancer.

The Patched 1 (PTCH1) gene encodes a membrane receptor involved in the Hedgehog (Hh) signaling pathway, an abnormal state of which may result in congenital defects or human tumors. In this study, we conducted whole-exome sequencing on a three-generation Chinese family characterized with variable penetrance of orofacial clefts. A rare heterozygous variant in the PTCH1 gene (c.2833C > T p.R945X) was identified as a disease-associated mutation. Structural modeling revealed a truncation starting from the middle of the second extracellular domain of PTCH1 protein. This may damage its ligand recognition and sterol transportation abilities, thereby affecting the Hh signaling pathway. Biochemical assays indicated that the R945X protein had reduced stability compared to the wild-type in vitro. In addition, we reviewed the locations and mutation types of PTCH1 variants in individuals with clefting phenotypes, and analyzed the associations between clefts and locations or types of variants within PTCH1. Our findings provide further evidence that PTCH1 variants result in orofacial clefts, and contributed to genetic counseling and clinical surveillance in this family.

Purpose This paper studies the characteristics of the seedling regeneration, stand structures, undergrowth biomasses, litter amounts and soil water contents of planted forests of Pinus tabuliformis in the Liaoheyuan Nature Reserve after a fire disturbance in 2014 and analyzes the significant factors affecting seedling regeneration to offer a scientific basis for the ecological restoration of vegetation in burned areas. Methods Plots of forest stands that experienced different fire severities (high severity, moderate severity, low severity) and control sample plots were used to study the significance of differences in seedling regeneration, stand structure, undergrowth biomass, litter amount and soil water content characteristics among stands under the effects of different fire severities by using single element variance analysis. The major factors affecting seedling regeneration characteristics were also analyzed here by using correlation and principal component analyses. Results (1) There was no significant difference in the density and growth characteristics (base diameter, plant height and crown diameter) of regenerated seedlings of Pinus tabuliformis under the different fire severities (P ​> ​0.05), and the spatial distribution of regenerated seedlings fit the aggregated distribution pattern. (2) There was no significant difference in diameter at breast height (DBH), plant height or crown diameter of Pinus tabuliformis under different fire severities (P ​> ​0.05), but there were highly significant differences in scorch height, biomass of undergrowth woody plants, biomass of undergrowth herbs, undecomposed litter amount, semidecomposed litter amount and soil water content under different the fire severities (P ​ Conclusion In the 5th year after a fire disturbance, the seedling regeneration of Pinus tabuliformis in a burned area was influenced by factors such as the stand structure, undergrowth plants, litter and soil. Low- and moderate-severity fires promote the natural regeneration of stands and are conducive to the stable balance of ecosystems.

A novel meroterpenoid, named meroterpenthiazole A (1), was isolated from the deep-sea-derived Penicillium allii-sativi. Its structure was established by extensive spectroscopic and computational methods. Meroterpenthiazole A bears a rare benzothiazole moiety in nature. Compound 1 significantly inhibited retinoid X receptor (RXR)-α transcriptional effect (KD = 12.3 μmol/L) through a novel binding mechanism.

ObjectiveTo profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals.DesignIntegrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort.ResultsIn total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93).ConclusionGut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection.

G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design. In this review, we summarize the detection method and the structure of G4, highlighting some non-canonical G4 DNA structures, such as G4 with a bulge, a vacancy, or a hairpin. Subsequently, the functions of G4 DNA in physiological processes are discussed, especially their regulation of DNA replication, transcription of disease-related genes (c-MYC, BCL-2, KRAS, c-KIT et al.), telomere maintenance, and epigenetic regulation. Typical G4 ligands that target promoters and telomeres for drug design are also reviewed, including ellipticine derivatives, quinoxaline analogs, telomestatin analogs, berberine derivatives, and CX-5461, which is currently in advanced phase I/II clinical trials for patients with hematologic cancer and BRCA1/2-deficient tumors. Furthermore, since the long-term stable existence of G4 DNA structures could result in genomic instability, we summarized the G4 unfolding mechanisms emerged recently by multiple G4-specific DNA helicases, such as Pif1, RecQ family helicases, FANCJ, and DHX36. This review aims to present a general overview of the field of G-quadruplex DNA that has progressed in recent years and provides potential strategies for drug design and disease treatment.

Camellia nitidissima Chi (CNC) is a traditional Chinese medicine (TCM) with anticancer property. However, its underlying mechanisms of anti-colon cancer (CC) remain unknown. Therefore, a systematic approach is proposed in the present study to elucidate the anticancer mechanisms of CNC based on network pharmacology and experimental validation. Initially, the potential active ingredients of CNC were verified via the TCMSP database based on the oral bioavailability (OB) and drug-likeness (DL) terms. Hub targets of CNC were acquired from SwissTarget prediction and TCMSP databases, and target genes related to CC were gathered from GeneCards and OMIM databases. Cytoscape was used to establish the compound-target networks. Next, the hub target genes collected from the CNC and CC were parsed via GO and KEGG analysis. Results of GO and KEGG analysis reveal that quercetin and luteolin in CNC, VEGFA and AKT1 targets, and PI3K-Akt pathway were associated with the suppression of CC. Besides, the result of molecular docking unveils that VEGFA demonstrates the most powerful binding affinity among the binding outcomes. This finding was successfully validated using in vitro HCT116 cell model experiment. In conclusion, this study proved the usefulness of integrating network pharmacology with in vitro experiments in the elucidation of underlying molecular mechanisms of TCM.

Indirect defense is an important strategy employed by sessile plants to defend against herbivorous insects by recruiting the natural enemies of herbivores mediated by herbivore-induced plant volatiles (HIPVs). We aimed to determine whether indirect defense occurs in Compositae with Chrysanthemum morifolium as the model and elucidate the mechanisms underlying the biosynthesis of HIPVs. Using two-choice olfactometer bioassays, we showed that C. morifolium plants following infestation by larvae of the tobacco cutworm (Spodoptera litura, TCW) were significantly more attractive to two natural enemies of TCW larvae than control plants, indicating that indirect defense is an active defense strategy of C. morifolium. The chemical cue responsible for indirect defense in C. morifolium was identified as a complex blend of volatiles predominated by sesquiterpenes and monoterpenes. A total of 11 candidate terpene synthase (TPS) genes were identified by comparing the transcriptomes of healthy and TCW-infested plants. Gene expression analysis confirmed that up-regulated CmjTPS genes are consistent with the elevated emission of terpenes after herbivory treatment. Our study showed that the herbivore-induced emission of JA-dependent volatile terpenes attracted both predatory and parasitic enemies of herbivores. Generally, our findings indicate that indirect defense might be an important defense mechanism against insects in C. morifolium.

Background In recent years, the rate of immunosuppressed patients has increased rapidly. Invasive fungal infections usually occur in these patients, especially those who have had hematological malignances and received chemotherapy. Fusariosis is a rare pathogenic fungus, it can lead to severely invasive Fusarium infections. Along with the increased rate of immune compromised patients, the incidence of invasive Fusarium infections has also increased from the past few years. Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection. Case summary We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin, eyeball, and knee joint during the course of chemotherapy. We performed skin biopsy, microbial cultivation, and molecular biological identification, and the pathogenic fungus was finally confirmed to be Fusarium solani. The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily, and surgical debridement. Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery. The disseminated Fusarium solani infection eventually resolved, and there was no recurrence at the 3 mo follow-up. Conclusion Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection. These are important to prevent progression to a more aggressive infection. Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy. Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.

Summary Azalea belongs to Rhododendron, which is one of the largest genera of flowering plants and is well known for the diversity and beauty in its more than 1000 woody species. Rhododendron contains two distinct groups: the most high‐altitude and a few low‐altitude species; however, the former group is difficult to be domesticated for urban landscaping, and their evolution and adaptation are little known. Rhododendron ovatum has broad adaptation in low‐altitude regions but possesses evergreen characteristics like high‐altitude species, and it has floral fragrance that is deficient in most cultivars. Here we report the chromosome‐level genome assembly of R. ovatum, which has a total length of 549 Mb with scaffold N50 of 41 Mb and contains 41 264 predicted genes. Genomic micro‐evolutionary analysis of R. ovatum in comparison with two high‐altitude Rhododendron species indicated that the expansion genes in R. ovatum were significantly enriched in defence responses, which may account for its adaptability in low altitudes. The R. ovatum genome contains much more terpene synthase genes (TPSs) compared with the species that lost floral fragrance. The subfamily b members of TPS are involved in the synthesis of sesquiterpenes as well as monoterpenes and play a major role in flora scent biosynthesis and defence responses. Tandem duplication is the primary force driving expansion of defence‐responsive genes for extensive adaptability to the low‐altitude environments. The R. ovatum genome provides insights into low‐altitude adaptation and gain or loss of floral fragrance for Rhododendron species, which are valuable for alpine plant domestication and floral scent breeding.

Soil nematode communities can provide valuable information about the structure and functions of soil food webs, and are sensitive to agricultural practices, including short-term straw incorporation. However, currently, such effects under long-term straw incorporation conditions at different fertility levels are largely unknown. Thus, we conducted a 13-year ongoing experiment to evaluate the effects of long-term straw incorporation on the structure and functions of the soil food web in low and high fertility soils through analyzing its effects on nematode communities, food web indices and metabolic footprints. Four treatments were included: straw removal (–S) under non-fertilized (–NPK) or fertilized (+NPK) conditions; and straw incorporation (+S) under –NPK or +NPK conditions. Soil samples from a 0–20 cm depth layer were collected when wheat and rice were harvested. Compared with straw removal, straw incorporation increased the abundances of total nematodes, bacterivores, plant-parasites and omnivores-predators, as well the relative abundances of omnivores-predators with increases of 73.06, 89.29, 95.31, 238.98, and 114.61% in –NPK soils and 16.23, 2.23, 19.01, 141.38, and 90.23% in +NPK soils, respectively. Regardless of sampling times and fertilization effects, straw incorporation increased the diversity and community stability of nematodes, as indicated by the Shannon-Weaver diversity index and maturity index. Enrichment and structure index did not show significant responses to straw incorporation, but a slight increase was observed in the structure index. The analysis of nematode metabolic footprints showed that straw incorporation increased the plant-parasite footprint and structure footprint by 97.27 and 305.39% in –NPK soils and by 11.29 and 149.56% in +NPK soils, but did not significantly influence enrichment, bacterivore and fungivore footprints. In conclusion, long-term straw incorporation, particularly under a low fertility level, favored the soil nematodes and regulated the soil food web mainly via a top-down effect.

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors., Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Aims Klebsiella pneumoniae has been reported to develop increased antibiotic resistance. Ceftazidime-avibactam (CZA) is a novel antibiotic with activity against serine-lactamase. Here, we investigated the sensitivity of carbapenem-resistant K. pneumoniae (CRKP) to CZA and the mechanisms of drug resistance in our hospital. Methods and results Patient characteristics were obtained from medical records. K. pneumoniae and its antibiotic susceptibility were determined using the Vitek-2 Compact instrument. The antibiotic resistance genes KPC, NDM, OXA-48, VIM, IMP, CIM, SPM, TMB, SMB, SIM, AIM and DIM were detected using real-time PCR. Multilocus sequence typing was used for genetic RELATEDNESS analysis. In total, 121 CRKP strains were isolated from patients in the intensive care unit (51·2%), senior ward (12·4%) and neurosurgery department (10%). With an average age of 72·5 years, most patients were in care for respiratory (34·7%), brain (20·7%), digestive tract (13·2%) and cardiovascular (8·3%) diseases. Specimens were predominantly obtained from sputum (39·67%), urine (29·75%) and blood (6·61%). Conclusion Of 23 CZA-resistant CRKP strains (19·01%), ST11 being the most common at 56·52%, 11 NDM-1-positive (47·83%) and four NDM-5-positive (17·39%) strains were detected. Significance and impact of the study Our study indicates that CZA resistance occurs in ~19·01% CRKP strains and that blaNDM-1 and blaNDM-5 might be critical for resistance.

SET domain protein 3 (SETD3) is an actin-specific methyltransferase, a rare post-translational modification with limited known biological functions. Till now, the function of SETD3 in cerebral ischemia-reperfusion (I/R)-induced injury remains unknown. Here, we show that the protein level of SETD3 is decreased in rat neurons after cerebral I/R injury. SETD3 promotes neuronal survival after both glucose and oxygen deprivation/reoxygenation (OGD/R) and cerebral I/R injury, and knockdown of SETD3 increases OGD/R-induced neuronal death. We further show that OGD/R-induced downregulation of SETD3 leads to the decrease of cellular ATP level, the reduction of mitochondrial electric potential and the increase of ROS production, thereby promoting mitochondrial dysfunction. We found that SETD3 reduction-induced mitochondrial dysfunction is mediated by the suppression of actin polymerization after OGD/R. Furthermore, we demonstrate that I/R-induced upregulation of PTEN leads to the downregulation of SETD3, and suppressing PTEN protects against ischemic neuronal death through downregulation of SETD3 and enhancement of actin polymerization. Together, this study provides the first evidence suggesting that I/R-induced downregulation of SETD3 mediates PTEN upregulation-induced ischemic neuronal death through downregulation of SETD3 and subsequent suppression of actin polymerization. Thus, upregulating SETD3 is a potential approach for the development of ischemic stroke therapy.

The long reads of Nanopore sequencing permit accurate transcript assembly and ease in discovering novel transcripts with potentially important functions in cancers. The wide adoption of Nanopore sequencing for transcript quantification, however, is largely limited by high costs. To address this issue, we developed a bioinformatics software, NovelQuant, that can specifically quantify long‐read‐assembled novel transcripts with short‐read sequencing data. Nanopore Direct RNA Sequencing was carried out on three hepatocellular carcinoma (HCC) patients’ tumor, matched portal vein tumor thrombus, and peritumor to reconstruct the HCC transcriptome. Then, based on the reconstructed transcriptome, NovelQuant was applied on Illumina RNA sequencing data of 59 HCC patients’ tumor and paired peritumor to quantify novel transcripts. Our further analysis revealed 361 novel transcripts dysregulated in HCC and that 101 of them were significantly associated with prognosis. There were 19 novel prognostic transcripts predicted to be long noncoding RNAs (lncRNAs), and some of them had regulatory targets that were reported to be associated with HCC. Additionally, 42 novel prognostic transcripts were predicted to be protein‐coding mRNAs, and many of them could be involved in xenobiotic metabolism. Moreover, the tumor‐suppressive roles of two representative novel prognostic transcripts, CDO1‐novel (lncRNA) and CYP2A6‐novel (protein‐coding mRNA), were further functionally validated during HCC progression. Overall, the current study shows a possibility of combining long‐ and short‐read sequencing to explore functionally important novel transcripts in HCC with accuracy and cost‐efficiency, which expands the pool of molecular biomarkers that could enhance our understanding of the molecular mechanisms of HCC., We used Nanopore RNA sequencing to discover novel transcripts in hepatocellular carcinoma (HCC), and developed NovelQuant to specifically quantify novel transcripts. Many of these novel transcripts were further found to be predictive of prognosis and have functional roles in HCC.

Plant monovalent cation/proton antiporters (CPAs), types of transmembrane transporters, play important roles in resistance to salt stress. In this study, 37 CPA genes from moso bamboo (Phyllostachys edulis) were identified and characterised. The expression profiles of 10 CPA1 genes (PheNHXs) of moso bamboo were detected by qRT-PCR, which showed that they were specifically expressed in six tissues. In addition, the expression of 10 PheNHXs in leaves and roots changed significantly under 150/200 mM NaCl and 100 μM ABA treatments. In particular, the expression of PheNHX2 in leaves and roots was significantly upregulated under NaCl treatment, thus, we cloned PheNHX2 and analysed its function. Subcellular localisation analysis showed that PheNHX2 was located on the vacuolar membrane. Overexpression of PheNHX2 reduced seed germination and root growth of Arabidopsis thaliana under salt stress, as well as severely affecting cellular Na+ and K+ content, which in turn reduced the salt tolerance of transgenic Arabidopsis. Measurements of physiological indicators, including chlorophyll content, malondialdehyde content, peroxidase and catalase enzyme activities and relative electrical conductivity, all supported this conclusion. Under salt stress, PheNHX2 also inhibited the expression of some stress-related and ion transport-related genes in transgenic Arabidopsis. Overall, these results indicate that overexpression of PheNHX2 reduces the salt tolerance of transgenic Arabidopsis. This investigation establishes a foundation for subsequent functional studies of moso bamboo CPA genes, and it provides a deeper understanding of PheNHX2 regulation in relation to the salt tolerance of moso bamboo.

Background The Gram-negative intracellular bacterium Mycoplasma anatis is a pathogen of respiratory infectious diseases in ducks and has caused significant economic losses in the poultry industry. Objective This study, as the first report of the structure and function of the pan-genome of Mycoplasma anatis, may provide a valuable genetic basis for many aspects of future research on the pathogens of waterfowl. Methods We sequenced the whole genomes of 15 Mycoplasma anatis isolated from ducks in China. Draft genome sequencing was carried out and whole-genome sequencing was performed by the sequencers of the PacBio Sequel and an IonTorrent Personal Genome Machine (PGM). Then the common genic elements of protein-coding genes, tRNAs, and rRNAs of Mycoplasma anatis genomes were predicted by using the pipeline Prokka v1.13.7. To investigate homologous protein clusters across Mycoplasma anatis genomes, we adopted Roary v3.13.0 to cluster orthologous genes (OGs) based on the following criteria. Results We obtained one complete genome and 14 genome sketches. Microbial mobile genetic element analysis revealed the distribution of insertion sequences (IS30, IS3, and IS1634), prophage regions, and CRISPR arrays in the genome of Mycoplasma anatis. Comparative genomic analysis decoded the genetic components and functional classification of the pan-genome of Mycoplasma anatis that comprised 646 core genes, 231 dispensable genes and among them 110 was strain-specific. Virulence-related gene profiles of Mycoplasma anatis were systematically identified, and the products of these genes included bacterial ABC transporter systems, iron transport proteins, toxins, and secretion systems. Conclusion A complete virulence-related gene profile of Mycoplasma anatis has been identified, most of the genes are highly conserved in all strains. Sequencing results are relevant to the molecular mechanisms of drug resistance, adaptive evolution of pathogens, population structure, and vaccine development. Supplementary Information The online version contains supplementary material available at 10.1007/s13258-021-01129-5.

Late Mesozoic–Cenozoic non-marine deposits are well developed in the Jiaolai Basin, eastern Shandong Province, China, yielding abundant fossils including ostracods. In order to further understand the geological settings of the basin during the Late Cretaceous–Paleogene, three boreholes (JK-1, JZK-01 and JZK-02) were drilled in the city of Jiaozhou. Nine genera and sixteen species (including six indeterminate species) of ostracods are described from the Jiaozhou Formation in the three boreholes, including Cypridea, Mongolocypris, Talicypridea, Candona, Eucypris, Cyprois, Porpocypris, Sinocypris and Timiriasevia. Of these, Porpocypris sphaeroidalis Guan, 1978 is reported from northern China for the first time, indicating that this species has great potential to be an indicator of the K/Pg boundary. Correlation of these species with the known Cretaceous–Paleogene ostracod assemblages suggests that the age of the Jiaozhou Formation could be latest Cretaceous–Paleocene in borehole JK-1, Campanian–Maastrichtian in borehole JZK-01, and Maastrichtian–Danian in borehole JZK-02. The exact position of K/Pg boundary, however, is unavailable for the present in the Jiaozhou Formation from boreholes JK-1 and JZK-01.

This study aimed to develop an energy- and resource-efficient process for the coproduction of edible mushroom, fermentable sugar and solid biofuel from wood residues. A promising potential was revealed for wood ear fungus (Auricularia auricular-judae), which yielded about 200 g mushroom per kg dry birch-based substrate, with concomitant degradation of 76.8 and 85.7% of lignin and xylan, respectively, in the substrate. Substrate pasteurisation by hot-air (85–100 °C) was as effective as by energy intensive autoclaving (121 °C), resulting comparable mushroom growth and degradation of lignocellulose. The spent mushroom substrate (SMS) contained 28–33% glucan, which upon analytical enzymatic saccharification released around 46% of the potentially-achievable glucose, corresponding to a 2.3–fold enzymatic digestibility compared with that of the raw substrate. The solid leftover generated after enzymatic hydrolysis revealed high thermal energy value and promising combustion characteristics, showing a plausibility to be recycled as solid fuel for self-supporting energy system and space heating.

Past researches have shown that pluripotency maintenance of naive and primed-state pluripotent stem cells (PSCs) depends on different signaling pathways, and naive-state PSCs possess the ability to produce chimeras when they are introduced into a blastocyst. Considering porcine is an attractive model for preclinical studies, many researches about pig induced pluripotent stem cells (piPSCs) have been reported. Some cytokines and small molecule compounds could transform primed piPSCs into naive state. However, there are no suitable culture conditions for generation of naive-state piPSCs with high efficiency; other small molecule compounds need further exploration. In this study, we investigated whether p38 MAPK and JNK signal pathway inhibitor SB203580 and SP600125 could be of benefit for acquiring naive-state piPSCs. By comparing reprogramming efficiencies under conditions of different donor cells and culture environment, we found that porcine bone marrow mesenchymal stem cells (PBMSCs) have higher efficiency on piPSC induction, and the culture condition of CHIR99021+PD0325901(2i)+Lif+bFGF is more suitable for subculturing of piPSCs. Our results also indicate that SB203580 and SP600125 could promote reprogramming of PBMSCs into naive-like state piPSCs. These results provide guidance for choosing donor cells, culture conditions, and research of different state iPSCs during the process of reprogramming pig somatic cells.

Deficits in hippocampal cellular and synaptic plasticity are frequently associated with cognitive and mood disorders, and indeed common mechanisms of antidepressants are thought to involve neuroplastic processes. Here, we investigate hippocampal adult-born cell survival and synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in serotonin transporter (5-HTT) knockout (KO) mice. From 8 weeks of age, mice either continued in standard-housing conditions or were given access to voluntary running wheels for 1 month. Electrophysiology was performed on hippocampal slices to measure LTP and LTD, and immunohistochemistry was used to assess cell proliferation and subsequent survival in the dentate gyrus. The results revealed a reduced LTP in 5-HTT KO mice that was restored to wild-type (WT) levels after chronic exercise. While LTD appeared normal in 5-HTT KO, exercise decreased the magnitude of LTD in both WT and 5-HTT KO mice. Furthermore, although 5-HTT KO mice had normal hippocampal adult-born cell survival, they did not benefit from the pro-proliferative effects of exercise observed in WT animals. Taken together, these findings suggest that reduced 5-HTT expression is associated with significant alterations to functional neuroplasticity. Interestingly, 5-HTT appeared necessary for exercise-induced augmentation of adult-born hippocampal cell survival, yet exercise corrected the LTP impairment displayed by 5-HTT KO mice. Together, our findings further highlight the salience of serotonergic signalling in mediating the neurophysiological benefits of exercise.

BACKGROUND Exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for asthma prevalence. This study aims to explore whether PAHs exposure is associated with childhood asthma by altering microbial diversity and metabolic profiles. METHODS Thirty children with asthma and 30 children as control in Nanjing, China were recruited. Urinary 1-hydroxypyrene (1-OHPyr) level was determined by UPLC-Orbitrap-MS as a PAHs exposure biomarker. Logistic regression was conducted to investigate the association between 1-OHPyr and childhood asthma. Microbial diversity was analyzed by 16S rRNA gene sequencing. Metabolic profiles were obtained by UPLC-Orbitrap-MS methods. Differential microbiota and metabolites were screened and selected as response biomarkers or intermediates. Mediation analysis was conducted to assess the association between PAHs and asthma mediated by intermediates. RESULTS Participating children with and without asthma aged 6.43 ± 2.23 years. The urinary 1-OHPyr level ranged from 0.10 to 1.51 μmol/mol (creatinine corrected) in the participants. The urinary 1-OHPyr level was associated with childhood asthma (OR = 7.21, 95% CI: 1.03-50.42 per 1 μmol/mol unit). Microbial diversity was decreased in the group with asthma and there was a significant shift in the abundance of Proteobacteria (at the phylum level), Veillonella and Prevotella (at the genus level). The enrichment pathway analysis showed that differentially expressed metabolites were involved in purine metabolism, amino acid metabolism, and lipid and fatty acid metabolism. The urinary 1-OHPyr level was associated with the abundance of Actinomyces sp. oral clone IO076 and 7-methylguanine that showed a mediation effect on the association between urinary 1-OHPyr levels and childhood asthma by mediation analysis. CONCLUSIONS Urinary 1-OHPyr exposure was associated with childhood asthma, microbial diversity, and metabolic profiles. Microbial diversity and metabolic profiles may be intermediates as response biomarkers to PAHs exposure in childhood asthma. Further research is needed to confirm these study results and determine the underlying mechanism.

Background Oxidized LDL(Ox-LDL) mediated endothelial dysfunction is involved in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Azilsartan is a potent agent for the treatment of hypertension as the antagonist of the angiotensin II receptor. This study will investigate whether Azilsartan possesses a beneficial effect against endothelial cell dysfunction induced by ox-LDL and explore the underlying preliminary mechanism. Methods Ox-LDL was applied to construct an in vitro endothelial dysfunction model in human umbilical vascular endothelial cells (HUVECs). The expression of lectin-type oxidized LDL receptor 1 (LOX-1), endothelial nitric oxide synthase (eNOS), tight junction protein occludin, and transcriptional factor Kruppel-like factor 2 (KLF2) was detected using qRT-PCR and Western blot. ELISA and qRT-PCR were utilized to evaluate the production of chemokine monocyte chemotactic protein 1 (MCP-1) and chemokine (C-X-C motif) Ligand 1 Protein (CXCL1) in treated HUVECs. The generation of nitro oxide (NO) was determined using DAF-FM DA staining assay. KLF2 was silenced by transfecting the cells with specific Small interfering RNA (siRNA). FITC-dextran permeation assay was used to check the endothelial monolayer permeability of treated HUVECs. Results Firstly, the elevated expressions of LOX-1, MCP-1, and CXCL-1 induced by stimulation with ox-LDL were significantly suppressed by Azilsartan. The downregulated eNOS and reduced production of NO induced by ox-LDL were reversed by the introduction of Azilsartan. Secondly, enlarged endothelial monolayer permeability and decreased expression of occludin stimulated with ox-LDL were greatly reversed by treatment with Azilsartan but were abolished by silencing the expression of KLF2. Lastly, the inhibited expression of KLF2 induced by ox-LDL was significantly elevated by the introduction of Azilsartan. Conclusion Azilsartan might ameliorate ox-LDL-induced endothelial damage via elevating the expression of KLF2.

Phytochemical investigation on the 90% EtOH extract of the seeds of Cipadessa cinerascensa led to the isolation of three new limonoids, cinerascenoids A-C (1-3). Structural elucidation of all the c...

Rb1-inducible coiled-coil 1 (RB1CC1) has been demonstrated to function as an inhibitor of proline-rich/Ca-activated tyrosine kinase 2 (PYK2) by binding to the kinase domain of PYK2, which promotes the proliferation, invasion, and migration of renal cell carcinoma (RCC) cells. Additionally, in breast cancer, PYK2 positively regulates the expression of transcriptional co-activator with PDZ-binding motif (TAZ) which in turn can enhance PDL1 levels in breast and lung cancer cells. The current study was performed to decipher the impact of RB1CC1 in the progression of RCC via regulation of the PYK2/TAZ/PDL1 signaling axis. Expression of RB1CC1 and PYK2 was quantified in clinical tissue samples from RCC patients. The relationship between TAZ and PYK2, TAZ and PDL1 was then validated. The cellular processes of doxorubicin (DOX)-induced human RCC cell lines including the abilities of proliferation, colony formation, sphere formation and apoptosis, as well as the tumorigenicity of transfected cells, were evaluated after the alteration of RB1CC1 expression. RB1CC1 exhibited decreased expression in RCC tissues and was positively correlated with patient survival. RB1CC1 could inhibit the activity of PYK2, which in turn stimulated the stability of TAZ protein by phosphorylating TAZ. Meanwhile, TAZ protein activated PDL1 transcription by binding to the promoter region of PDL1. RB1CC1 overexpression or PYK2 knockdown could help everolimus (EVE) to inhibit tumor proliferation and activate immune response. Taken together, RB1CC1 can potentially augment the response of RCC cells to immunotherapy by suppressing the PYK2/TAZ/PDL1 signaling axis.

Background The prevalence of preterm birth in Bangladesh is estimated to be 19.1%, the highest in the world. Although prenatal exposure to several metals has been linked with preterm birth, fewer prospective studies have investigated the socioeconomic factors that affect metal exposure, leading to preterm birth risk. Objective We aim to identify novel metal biomarkers and their critical exposure windows, as well as the upstream socioeconomic risk factors for preterm birth in rural Bangladeshi, to shed light for future interventional strategies. Methods This study included data from 780 mother–offspring pairs, who were recruited to participate in a prospective birth cohort in Bangladesh (2008–2011). Serum concentrations of 19 metals were measured in the first and second trimesters using inductively coupled plasma mass spectrometry. Mediation analysis was performed to explore the upstream socioeconomic factors that affect the risk of preterm birth mediated via metal exposure concentrations. Results Early pregnancy exposure to serum zinc, arsenic, and strontium and mid-pregnancy exposure to barium were significantly associated with risk of preterm birth. Furthermore, younger marriage age was associated with an exponential increase in the risk of preterm birth, and women who married after 18 years old had a considerably lower risk of preterm birth. Mediation analysis indicated that these four elements mediated 30.2% of the effect of marriage age on preterm birth. Conclusion This study indicated that maternal serum metal exposure mediates the impact of child marriage on the increased risk of preterm birth via metal exposures. The findings shed light on the mechanisms underlying such association and provide insights into future interventional strategies.

The roles of RNA modification during organ metastasis of cancer cells are not known. Here we established breast cancer lung metastasis cells by three rounds of selection of lung metastatic subpopulations in vivo and designated them as BCLMF3 cells. In these cells, mRNA N6-methyladenosine (m6A) and methyltransferase METTL3 were increased, while the demethylase FTO was decreased. Epi-transcriptome and transcriptome analyses together with functional studies identified keratin 7 (KRT7) as a key effector for m6A-induced breast cancer lung metastasis. Specifically, increased METTL3 methylated KRT7-AS at A877 to increase the stability of a KRT7-AS/KRT7 mRNA duplex via IGF2BP1/HuR complexes. Furthermore, YTHDF1/eEF-1 was involved in FTO-regulated translational elongation of KRT7 mRNA, with methylated A950 in KRT7 exon 6 as the key site for methylation. In vivo and clinical studies confirmed the essential roles of KRT7, KRT7-AS, and METTL3 for lung metastasis and clinical progression of breast cancer. Collectively, m6A promotes breast cancer lung metastasis by increasing the stability of a KRT7-AS/KRT7 mRNA duplex and translation of KRT7. Significance: This study suggests that N6-methyladenosine is a key driver and potential therapeutic target in breast cancer metastasis.

N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-021-01362-2.

African swine fever virus (ASFV), as a member of the large DNA viruses, may regulate autophagy and apoptosis by inhibiting programmed cell death. However, the function of ASFV proteins has not been fully elucidated, especially the role of autophagy in ASFV infection. One of three Pyrroline-5-carboxylate reductases (PYCR), is primarily involved in conversion of glutamate to proline. Previous studies have shown that depletion of PYCR2 was related to the induction of autophagy. In the present study, we found for the first time that ASFV E199L protein induced a complete autophagy process in Vero and HEK-293T cells. Through co-immunoprecipitation coupled with mass spectrometry (CoIP-MS) analysis, we firstly identified that E199L interact with PYCR2 in vitro. Importantly, our work provides evidence that E199L down-regulated the expression of PYCR2, resulting in autophagy activation. Overall, our results demonstrate that ASFV E199L protein induces complete autophagy through interaction with PYCR2 and down-regulate the expression level of PYCR2, which provide a valuable reference for the role of autophagy during ASFV infection and contribute to the functional clues of PYCR2. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00375-x.

Background The incidence of infection with Mycobacterium abscessus (M. abscessus) has increased in recent years. This increase is partly associated with invasive cosmetic procedures. Case summary The purpose of this case summary is to increase clinicians' awareness of M. abscessus infection and reduce mycobacterial infection caused by cosmetic procedures. We report the case of a 45-year-old woman who received acetyl hexapeptide-8 (argireline) injections in the forehead and temples, and erythema, nodules, and abscesses appeared at the injection sites after one week. The pus specimens were examined by microbiological culture and confirmed to be positive for M. abscessus. Clarithromycin 500 mg twice daily and moxifloxacin 400 mg once daily were administered for 5 mo and the lesions gradually subsided. Conclusion We report here for the first time a case of infection with M. abscessus after argireline injection. This condition is easily misdiagnosed as a common bacterial infection. Microbiological examinations are helpful for diagnosis and standardized cosmetic procedures can prevent infection with M. abscessus.

One undescribed lignan, one new natural product, along with fourteen known compounds, were isolated from the roots of Ficus hirta. The structures of the isolates were elucidated by comprehensive spectroscopic technologies, including UV, IR, HRESIMS, and NMR. The absolute configuration of 1 was determined by comparison of experimental and calculated ECD data. The cytotoxicity of all the compounds against HeLa and HepG2 cell lines was evaluated and compound 7 showed considerable cytotoxic effect towards HepG2 cells. Also, the apoptotic effect of 7 on HepG2 cells and the effect of 7 on the key proteins (p-JNK and p-p38) in MAPK (Mitogen-activated protein kinases) pathways were studied by flow cytometry and western blotting experiment. As a result, compound 7 induced the apoptosis of HepG2 cells, and dose-dependently increased the phosphorylation of JNK and p38. Thus, 7 might trigger HepG2 cells apoptosis via JNK/p38 MAPK signaling pathway.

IGT family genes function critically to regulate lateral organ orientation in plants. However, little information is available about this family of genes in Brassica napus. In this study, 27 BnIGT genes were identified on 16 chromosomes and divided into seven clades, namely LAZY1∼LAZY6 and TAC1 (Tiller Angle Control 1), based on their phylogenetic relationships. Duplication analysis revealed that 91.1% of the gene pairs were derived from whole-genome duplication. Most BnIGT genes had a similar structural pattern with one or two very short exons followed by a long and a shorter exon. Common and specific motifs were identified among the seven clades, and motif 1, containing the family-specific GφL(A/T)IGT sequence, was observed in all clades except LAZY5. Three types of cis-elements pertinent to transcription factor binding, light responses, and hormone signaling were detected in the BnIGT promoters. Intriguingly, more than half of the BnIGT genes exhibited no or very low expression in various tissues, and the LAZY1 and TAC1 clade members showed distinct tissue expression preferences. Coexpression analysis revealed that the LAZY1 members had strong associations with cell wall biosynthesis genes. This analysis provides a deeper understanding of the BnIGT gene family and will facilitate further deduction of their role in regulating plant architecture in B. napus.

There is accumulating evidence suggesting that an autoimmune component is involved in esophageal achalasia. An increase in immune cells, cytokines, chemokines, and autoimmune antibodies in serum and infiltration of immune cells in tissues support the view that immune-mediated inflammation is a crucial pathogenesis of inhibitory neuron degeneration in the lower esophageal sphincter. Infection of viruses such as the herpes virus family has been suspected of provoking the autoimmune reaction. Meanwhile, previous reports on immunogenetics have proposed that specific risk alleles on the human leukocyte antigen complex define the susceptible population to achalasia. In this study we reviewed current knowledge regarding the immune-related factors of achalasia, including immunology, viral infection and immunogenetic variations.

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 μm microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

The interferon gamma-inducible protein 16 (IFI16) and its murine homologous protein p204 function in non-sequence specific dsDNA sensing; however, the exact dsDNA recognition mechanisms of IFI16/p204, which harbour two HIN domains, remain unclear. In the present study, we determined crystal structures of p204 HINa and HINb domains, which are highly similar to those of other PYHIN family proteins. Moreover, we obtained the crystal structure of p204 HINab domain in complex with dsDNA and provided insights into the dsDNA binding mode. p204 HINab binds dsDNA mainly through α2 helix of HINa and HINb, and the linker between them, revealing a similar HIN:DNA binding mode. Both HINa and HINb are vital for HINab recognition of dsDNA, as confirmed by fluorescence polarization assays. Furthermore, a HINa dimerization interface was observed in structures of p204 HINa and HINab:dsDNA complex, which is involved in binding dsDNA. The linker between HINa and HINb reveals dynamic flexibility in solution and changes its direction at ∼90° angle in comparison with crystal structure of HINab:dsDNA complex. These structural information provide insights into the mechanism of DNA recognition by different HIN domains, and shed light on the unique roles of two HIN domains in activating the IFI16/p204 signaling pathway.

Ferroptosis is a newly discovered form of programmed cell death, which has unique biological effects on metabolism and redox biology. In this study, the prognostic value of ferroptosis‐related genes was investigated in lower‐grade gliomas (LGG). We downloaded the ferroptosis‐related genes from the FerrDb dataset. Univariate Cox and LASSO regression analyses were applied to identify genes correlated with overall survival (OS). Subsequently, 12 ferroptosis‐related genes were screened to establish the prognostic signature using stepwise multivariate Cox regression. According to the median value of risk scores, patients were divided into low‐ and high‐risk subgroups. The Kaplan‐Meier curves showed the high‐risk group had a lower OS. The predictive power of the risk model was validated using the CGGA. Functional analysis revealed that the terms associated with plasma membrane receptor complex, immune response and glutamate metabolic process were primarily related to the risk model. Moreover, we established a nomogram that had a strong forecasting ability for the 1‐, 3‐ and 5‐year OS. In addition, we compared the risk scores between different clinical features. We also detected infiltration of macrophages and monocytes in different subgroups. Overall, our study identified the prognostic signature of 12 ferroptosis‐related genes, which has the potential to predict the prognosis of LGG.

Ischemia-reperfusion (I/R) injury causes cardiac dysfunction through several mechanisms including the irregular expression of some long noncoding RNA. However, the role of SNHG12 in myocardial I/R injury remains unclear. Here, we found the increase of the SNHG12 level in hypoxia-reoxygenation (H/R)-injured-H9c2 cells. SNHG12 silencing enhanced the apoptosis of H/R-injured H9c2 cells, while SNHG12 overexpression relieved the cardiomyocyte apoptosis induced by H/R stimulation. Additionally, the suppression of SNHG12 significantly boosted the H/R-induced expression and the production of TNF-α, IL-6, and IL-1β, as well as the activation of NF-κB, which were fully reversed after overexpression of SNHG12. Mechanistically, SNHG12 adversely regulated the production of receptor for advanced glycation end products (RAGE) in H/R-stimulated H9c2 cells. Antibody blocking of RAGE alleviated the apoptosis of H/R-injured H9c2 cells. Collectively, we have determined a valuable mechanism by which the high level of SNHG12 contributes to H9c2 cells against H/R injury through the reduction of RAGE expression.

Background Mixotrophy can confer a higher growth rate than the sum of photoautotrophy and heterotrophy in many microalgal species. Thus, it has been applied to biodiesel production and wastewater utilization. However, its carbon and energy metabolic mechanism is currently poorly understood. Results To elucidate underlying carbon and energy metabolic mechanism of mixotrophy, Chromochloris zofingiensis was employed in the present study. Photosynthesis and glucose metabolism were found to operate in a dynamic balance during mixotrophic cultivation, the enhancement of one led to the lowering of the other. Furthermore, compared with photoautotrophy, non-photochemical quenching and photorespiration, considered by many as energy dissipation processes, were significantly reduced under mixotrophy. Comparative transcriptome analysis suggested that the intermediates of glycolysis could directly enter the chloroplast and replace RuBisCO-fixed CO2 to provide carbon sources for chloroplast organic carbon metabolism under mixotrophy. Therefore, the photosynthesis rate-limiting enzyme, RuBisCO, was skipped, allowing for more efficient utilization of photoreaction-derived energy. Besides, compared with heterotrophy, photoreaction-derived ATP reduced the need for TCA-derived ATP, so the glucose decomposition was reduced, which led to higher biomass yield on glucose. Based on these results, a mixotrophic metabolic mechanism was identified. Conclusions Our results demonstrate that the intermediates of glycolysis could directly enter the chloroplast and replace RuBisCO-fixed CO2 to provide carbon for photosynthesis in mixotrophy. Therefore, the photosynthesis rate-limiting enzyme, RuBisCO, was skipped in mixotrophy, which could reduce energy waste of photosynthesis while promote cell growth. This finding provides a foundation for future studies on mixotrophic biomass production and photosynthetic metabolism.