Butenyl-spinosyn, produced by Saccharopolyspora pogona, is a promising biopesticide due to excellent insecticidal activity and broad pesticidal spectrum. Bacterioferritin (Bfr, encoded by bfr) regulates the storage and utilization of iron, which is essential for the growth and metabolism of microorganisms. However, the effect of Bfr on the growth and butenyl-spinosyn biosynthesis in S. pogona has not been explored.

Programmed cell death protein-1 (PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. We generated PD-1 and T cell receptor (TCR) deficient mesothelin-specific CAR-T (MPTK-CAR-T) cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study. A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion. No dose-limiting toxicity or unexpected adverse events were observed in any of the 15 patients. The best overall response was stable disease (2/15 patients). Circulating MPTK-CAR-T cells peaked at days 7-14 and became undetectable beyond 1 month. TCR-positive CAR-T cells rather than TCR-negative CAR-T cells were predominantly detected in effusion or peripheral blood from three patients after infusion. We further confirmed the reduced persistence of TCR-deficient CAR-T cells in animal models. Our results establish the preliminary feasibility and safety of CRISPR-engineered CAR-T cells with PD-1 disruption and suggest that the natural TCR plays an important role in the persistence of CAR-T cells when treating solid tumors.

Triticum aestivum xylanase inhibitor (TaXI) gene plays an important role in plant defense. Recently, TaXI-III inhibitor has been shown to play a dual role in wheat resistance to Fusarium graminearum infection. Thus, identifying the members of the TaXI gene family and clarifying its role in wheat resistance to stresses are essential for wheat resistance breeding. However, to date, no comprehensive research on TaXIs in wheat (Triticum aestivum L.) has been conducted. In this study, a total of 277 TaXI genes, including six genes that we cloned, were identified from the recently released wheat genome database (IWGSC RefSeq v1.1), which were unevenly located on 21 chromosomes of wheat. Phylogenetic analysis divided these genes into six subfamilies, all the six genes we cloned belonged to XI-2 subfamily. The exon/intron structure of most TaXI genes and the conserved motifs of proteins in the same subfamily are similar. The TaXI gene family contains 92 homologous gene pairs or clusters, 63 and 193 genes were identified as tandem replication and segmentally duplicated genes, respectively. Analysis of the cis-acting elements in the promoter of TaXI genes showed that they are involved in wheat growth, hormone-mediated signal transduction, and response to biotic and abiotic stresses. RNA-seq data analysis revealed that TaXI genes exhibited expression preference or specificity in different organs and developmental stages, as well as in diverse stress responses, which can be regulated or induced by a variety of plant hormones and stresses. In addition, the qRT-PCR data and heterologous expression analysis of six TaXI genes revealed that the genes of XI-2 subfamily have double inhibitory effect on GH11 xylanase of F. graminearum, suggesting their potential important roles in wheat resistance to F. graminearum infection. The outcomes of this study not only enhance our understanding of the TaXI gene family in wheat, but also help us to screen more candidate genes for further exploring resistance mechanism in wheat.

As well as their ion transportation function, the voltage-dependent potassium channels could act as the cell signal inducer in a variety of pathogenic processes. However, their roles in neurogenesis after stroke insults have not been clearly illustrated. In our preliminary study, the expressions of voltage-dependent potassium channels Kv4.2 was significantly decreased after stroke in cortex, striatum and hippocampus by real-time quantitative PCR assay. To underlie the neuroprotection of Kv4.2 in stroke rehabilitation, recombinant plasmids encoding the cDNAs of mouse Kv4.2 was constructed. Behavioral tests showed that the increased Kv4.2 could be beneficial to the recovery of the sensory, the motor functions and the cognitive deficits after stroke. Temozolomide (TMZ), an inhibitor of neurogenesis, could partially abolish the mentioned protections of Kv4.2. The immunocytochemical staining showed that Kv4.2 could promote the proliferations of neural stem cells and induce the neural stem cells to differentiate into neurons in vitro and in vivo. And Kv4.2 could up-regulate the expressions of ERK1/2, p-ERK1/2, p-STAT3, NGF, p-TrkA, and BDNF, CAMKII and the concentration of intracellular Ca2+. Namely, we concluded that Kv4.2 promoted neurogenesis through ERK1/2/STAT3, NGF/TrkA, Ca2+/CAMKII signal pathways and rescued the ischemic impairments. Kv4.2 might be a potential drug target for ischemic stroke intervention.

Freshwater fish populations are facing multiple stressors, including climate change, species invasion, and anthropogenic interference. Temporal studies of fish functional diversity and community assembly rules based on trait-environment relationships provide insights into fish community structure in riverine ecosystems.

Severe coronavirus disease 2019 (COVID-19) is often indicated by lymphopenia and increased myelopoiesis; however, the underlying mechanism is still unclear, especially the alteration of hematopoiesis. It is important to explore to what extent and how hematopoietic stem cells contribute to the impairment of peripheral lymphoid and myeloid compartments in COVID-19 patients. In this study, we used single-cell RNA sequencing to assess bone marrow mononuclear cells from COVID-19 patients with peripheral blood mononuclear cells as control. The results showed that the hematopoietic stem cells in these patients were mainly in the G1 phase and prone to apoptosis, with immune activation and anti-viral responses. Importantly, a significant accumulation of immature myeloid progenitors and a dramatic reduction of lymphoid progenitors in severe cases were identified, along with the up-regulation of transcription factors (such as SPI1, LMO4, ETS2, FLI1, and GATA2) that are important for the hematopoietic stem cell or multipotent progenitor to differentiate into downstream progenitors. Our results indicate a dysregulated hematopoiesis in patients with severe COVID-19.

Ginger (Zingiber officinale), the type species of Zingiberaceae, is one of the most widespread medicinal plants and spices. Here, we report a high-quality, chromosome-scale reference genome of ginger 'Zhugen', a traditionally cultivated ginger in Southwest China used as a fresh vegetable, assembled from PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture (Hi-C) reads. The ginger genome was phased into two haplotypes, haplotype 1 (1.53 Gb with a contig N50 of 4.68 M) and haplotype 0 (1.51 Gb with a contig N50 of 5.28 M). Homologous ginger chromosomes maintained excellent gene pair collinearity. In 17,226 pairs of allelic genes, 11.9% exhibited differential expression between alleles. Based on the results of ginger genome sequencing, transcriptome analysis, and metabolomic analysis, we proposed a backbone biosynthetic pathway of gingerol analogs, which consists of 12 enzymatic gene families, PAL, C4H, 4CL, CST, C3'H, C3OMT, CCOMT, CSE, PKS, AOR, DHN, and DHT. These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs. Overall, this study serves as an excellent resource for further research on ginger biology and breeding, lays a foundation for a better understanding of ginger evolution, and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.

Nucleotide-binding leucine-rich-repeat (NLR) genes comprise the largest family of plant disease-resistance genes. Angiosperm NLR genes are phylogenetically divided into the TNL, CNL, and RNL subclasses. NLR copy numbers and subclass composition vary tremendously across angiosperm genomes. However, the evolutionary associations between genomic NLR content and ecological adaptation, or between NLR content and signal transduction components, are poorly characterized because of limited genome availability. In this study, we established an angiosperm NLR atlas (ANNA, https://biobigdata.nju.edu.cn/ANNA/) that includes NLR genes from over 300 angiosperm genomes. Using ANNA, we revealed that NLR copy numbers differ up to 66-fold among closely related species owing to rapid gene loss and gain. Interestingly, NLR contraction was associated with adaptations to aquatic, parasitic, and carnivorous lifestyles. The convergent NLR reduction in aquatic plants resembles the lack of NLR expansion during the long-term evolution of green algae before the colonization of land. A co-evolutionary pattern between NLR subclasses and plant immune pathway components was also identified, suggesting that immune pathway deficiencies may drive TNL loss. Finally, we identified a conserved TNL lineage that may function independently of the EDS1-SAG101-NRG1 module. Collectively, these findings provide new insights into the evolution of NLR genes in the context of ecological adaptation and genome content variation.

Various circular RNAs (circRNAs) are dysregulated in the placenta of fetal growth restriction (FGR) fetuses, but their roles and regulatory mechanisms have not been fully elucidated. Herein, we aimed to elucidate the role of hsa_circ_0081343 in regulating the migration, invasion, and apoptosis of human extravillous trophoblast HTR-8 cells.

Background and Aim: Alzheimer's disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD. Methods: We recruited 107 participants including 23 healthy controls (HC), 21 amnestic mild cognitive impairment (aMCI), 24 non-amnestic mild cognitive impairment (naMCI) and 39 AD patients. Via liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis, we compared differences in serum lipid metabolites among these patient groups and further elucidated biomarkers that differentiate aMCI from HC. Results: There were significant differences of serum lipid metabolites among the groups, and 20 metabolites were obtained under negative ion mode from HC and aMCI comparison. Notably, 16:3 cholesteryl ester, ganglioside GM3 (d18:1/9z-18:1) and neuromedin B were associated with cognition and increased the predictive effect of aMCI to 0.98 as revealed by random forest classifier. The prediction model composed of MoCA score, 16:3 cholesteryl ester and ganglioside GM3 (d18:1/9z-18:1) had good predictive performance for aMCI. Glycerophospholipid metabolism was a pathway common among HC/aMCI and aMCI/AD groups. Conclusion: This study provides preliminary evidence highlighting that 16:3 cholesteryl ester were useful for AD disease monitoring while ganglioside GM3 (d18:1/9z-18:1) and neuromedin B discriminated aMCI from HC, which can probably be applied in clinic for early predicting of AD.

Copy number variations (CNVs) in cell-free DNA (cfDNA) are emerging as noninvasive biomarkers for various cancers. However, multiple-level analysis of cfDNA CNVs for hepatocellular carcinoma (HCC) patients with radical treatments remains uninvestigated. Here, CNVs at genome-wide, chromosomal-arm, and bin levels were analyzed in cfDNA from 117 HCC patients receiving radical treatments. Then, the relationship between cfDNA CNVs and clinical outcomes was explored. Our results showed that a concordant profile of CNVs was observed between cfDNA and tumor tissue DNA. Three genome-wide CNV indicators including tumor fraction (TFx), prediction score (P-score), and stability score (S-score) were calculated and demonstrated to exhibit significant correlation with poorer overall survival (OS) and recurrence-free survival (RFS). Furthermore, the high-frequency cfDNA CNVs at chromosomal-arm level including the loss of 4q, 17p, and 19p and the gain of 8q and 1q clearly predicted HCC prognosis. Finally, a bin-level risk score was constructed to improve the ability of CNVs in predicting prognosis. Altogether, our study indicates that the multiple-level cfDNA CNVs are significantly associated with OS and RFS in HCC patients with radical treatments, suggesting that cfDNA CNVs detected by low-coverage whole-genome sequencing (WGS) may be used as potential prognostic biomarkers of HCC patients.

Hand pose estimation from RGB images has always been a difficult task, owing to the incompleteness of the depth information. Moon et al. improved the accuracy of hand pose estimation by using a new network, InterNet, through their unique design. Still, the network still has potential for improvement. Based on the architecture of MobileNet v3 and MoGA, we redesigned a feature extractor that introduced the latest achievements in the field of computer vision, such as the ACON activation function and the new attention mechanism module, etc. Using these modules effectively with our network, architecture can better extract global features from an RGB image of the hand, leading to a greater performance improvement compared to InterNet and other similar networks.

Almost all surfaces sensitive to the ambient environment are covered by water, whereas the impacts of water on surface-dominated colloidal quantum dot (CQD) semiconductor electronics have rarely been explored. Here, strongly hydrogen-bonded water on hydroxylated lead sulfide (PbS) CQD is identified. The water could pilot the thermally induced evolution of surface chemical environment, which significantly influences the nanostructures, carrier dynamics, and trap behaviors in CQD solar cells. The aggravation of surface hydroxylation and water adsorption triggers epitaxial CQD fusion during device fabrication under humid ambient, giving rise to the inter-band traps and deficiency in solar cells. To address this problem, meniscus-guided-coating technique is introduced to achieve dense-packed CQD solids and extrude ambient water, improving device performance and thermal stability. Our works not only elucidate the water involved PbS CQD surface chemistry, but may also achieve a comprehensive understanding of the impact of ambient water on CQD based electronics.

Atherosclerosis is the main cause of myocardial infarction and stroke, and the morbidity and mortality rates of cardiovascular disease are among the highest of any disease worldwide. Excessive plasma trimethylamine-N-oxide (TMAO), an intestinal metabolite, promotes the development of atherosclerosis. Therefore, effective measures for reducing plasma TMAO production can contribute to preventing atherosclerosis. Probiotics are living microorganisms that are beneficial to the human body, and some of them can attenuate plasma TMAO production. To explore the effects of probiotic supplementation on plasma TMAO in choline-fed mice, we intragastrically administered eight strains of Bifidobacterium breve and eight strains of Bifidobacterium longum to mice for 6 weeks. B. breve Bb4 and B. longum BL1 and BL7 significantly reduced plasma TMAO and plasma and cecal trimethylamine concentrations. However, hepatic flavin monooxygenase (FMO) activity, flavin-containing monooxygenase 3 (FMO3), farnesoid X receptor (FXR) protein expression and TMAO fractional excretion were not significantly affected by Bifidobacterium supplementation. The treatment of Bifidobacterium strains modulated the abundances of several genera such as Ruminococcaceae UCG-009, Ruminococcaceae UCG-010, which belong to the Firmicutes that has been reported with cut gene clusters, which may be related to the reduction in intestinal TMA and plasma TMAO. Additionally, a reduction in Ruminococcaceae indicates a reduction in circulating glucose and lipids, which may be another pathway by which Bifidobacterium strains reduce the risk of atherosclerosis. The effect of Bifidobacterium strains on Bacteroides also suggests a relationship between the abundance of this genus and TMA concentrations in the gut. Therefore, the mechanism underlying these changes might be gut microbiota regulation. These Bifidobacterium strains may have therapeutic potential for alleviating TMAO-related diseases.

Nowadays, natural polysaccharides-based hydrogels have achieved promising results as dressings to promote skin healing. In the present study, we prepared a novel hydrogel nanocomposite with poly(vinyl alcohol) (PVA) and sulfated heterosaccharide (UF), named UPH. The SEM results showed that the UPH had dense porous structures with a high porosity and a specific surface area. The UPH had a good swelling property, which can effectively adsorb exudate and keep the wound moist. The in vitro experiments results showed that the UPH was non-cytotoxic and could regulate the inflammatory response and promote the migration of fibroblasts significantly. The phenotypic, histochemistry, and Western blot analyses showed UPH treatment accelerated the wound healing and recovery of skin tissue at wound sites in a C57BL/6 mouse model. Furthermore, the UPH could promote the inflammation process to onset earlier and last shorter than that in a normal process. Given its migration-promoting ability and physicochemical properties, the UPH may provide an effective application for the treatment and management of skin wounds.

Lymph node ratio (LNR) has been increasingly reported as a prognostic factor in oral cavity squamous cell carcinoma (OCSCC). This study aimed to develop and validate a prognostic nomogram integrating LNR and to further assess its role in guiding adjuvant therapy for OCSCC.

To determine whether microRNA could be a therapy target of erectile dysfunction (ED) and the underlying mechanisms.

Obstructive sleep apnea (OSA) is common and independently associated with heart failure. This study aimed to investigate the impact of OSA on heart function in patients with dilated cardiomyopathy (DCM) as well as the possible mechanism related to exosomes regulated autophagy.

The pathological roles of long non-coding RNAs (lncRNAs) in colorectal carcinoma (CRC) have been corroborated. To date, the pathological contributions of LINC01315 in the epithelial-mesenchymal transition (EMT) property of CRC are still ambiguous. By silencing LINC01315, we disclosed that LINC01315 promoted the growth, metastatic characteristics, and the EMT of CRC cells in vitro. Mechanistically, LINC01315 activated Wnt/β-catenin signaling. LINC01315 bound to the β-catenin promoter and activated its transcription. In rescue experiments, ectopic overexpression of β-catenin counteracted the inhibiting effector-triggered by LINC01315 deletion. In summary, this preliminary study brings new insights to the pathological significance of the LINC01315/Wnt/β-catenin signaling pathway in CRC.

Drought is the primary disaster that endangers agricultural production, including animal husbandry, and affects the distribution, growth, yield, and quality of crops. Previous study had revealed that DIP, as a potential regulator of DBF activity, played an important role in response to drought stress in maize. In this study, a total of 67 DIPs were identified from seventeen land plants, including six tobacco DIPs (NtDIPs). NtDIP6 gene was further selected as a candidate gene for subsequent experiments based on the phylogenetic analysis and structural analysis. The transgenic tobacco and poplar plants over-expressing NtDIP6 gene were generated using the Agrobacterium- mediated method. Although there was not phenotypic difference between transgenic plants and wild-type plants under normal conditions, overexpression of the NtDIP6 gene in transgenic tobacco and poplar plants enhanced the drought tolerance under drought treatments in comparison with the wild type. The content of antioxidant defense enzymes peroxidase (POD), catalase (CAT), and the photosynthetic rate increased in NtDIP6-Ox transgenic tobacco and poplar plants, while the content of malondialdehyde decreased, suggesting that the overexpression of NtDIP6 enhances the antioxidant capacity of transgenic poplar. Furthermore, the results of qRT-PCR showed that the level of expression of drought-related response genes significantly increased in the NtDIP6-Ox transgenic plants. These results indicated that NtDIP6, as a positive response regulator, improves drought stress tolerance by scavenging superoxide via the accumulation of antioxidant defense enzymes.