TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration.

Coordinated migration of the mesoderm is essential for accurate organization of the body plan during embryogenesis. However, little is known about how mesoderm migration influences posterior neural tube closure in mammals. Here, we show that spinal neural tube closure and lateral migration of the caudal paraxial mesoderm depend on transmembrane protein 132A (TMEM132A), a single-pass type I transmembrane protein, the function of which is not fully understood. Our study in Tmem132a-null mice and cell models demonstrates that TMEM132A regulates several integrins and downstream integrin pathway activation as well as cell migration behaviors. Our data also implicates mesoderm migration in elevation of the caudal neural folds and successful closure of the caudal neural tube. These results suggest a requirement for paraxial mesodermal cell migration during spinal neural tube closure, disruption of which may lead to spina bifida.

Strategic protection of landslide vulnerable mountains for biodiversity conservation under land-cover and climate change impacts.

Natural disasters impose huge uncertainty and loss to human lives and economic activities. Landslides are one disaster that has become more prevalent because of anthropogenic disturbances, such as land-cover changes, land degradation, and expansion of infrastructure. These are further exacerbated by more extreme precipitation due to climate change, which is predicted to trigger more landslides and threaten sustainable development in vulnerable regions. Although biodiversity conservation and development are often regarded as having a trade-off relationship, here we present a global analysis of the area with co-benefits, where conservation through expanding protection and reducing deforestation can not only benefit biodiversity but also reduce landslide risks to human society. High overlap exists between landslide susceptibility and areas of endemism for mammals, birds, and amphibians, which are mostly concentrated in mountain regions. We identified 247 mountain ranges as areas with high vulnerability, having both exceptional biodiversity and landslide risks, accounting for 25.8% of the global mountainous areas. Another 31 biodiverse mountains are classified as future vulnerable mountains as they face increasing landslide risks because of predicted climate change and deforestation. None of these 278 mountains reach the Aichi Target 11 of 17% coverage by protected areas. Of the 278 mountains, 52 need immediate actions because of high vulnerability, severe threats from future deforestation and precipitation extremes, low protection, and high-population density and anthropogenic activities. These actions include protected area expansion, forest conservation, and restoration where it could be a cost-effective way to reduce the risks of landslides.

Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis.

Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism-related gene expression in global ApoH-/- C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH-/- and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH-/- mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH-/- mice than in those of WT mice. Microbial beta diversity was lower in ApoH-/- mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH-/- mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction-associated steatohepatitis livers reinforced a significant association between metabolic dysfunction-associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease.

Syngeneic murine models with distinct immune microenvironments represent subsets of human intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a poorly immunogenic malignancy associated with limited survival. Syngeneic immunocompetent mouse models of CCA are an essential tool to elucidate the tumor immune microenvironment (TIME), understand mechanisms of tumor immune evasion, and test novel immunotherapeutic strategies. The scope of this study was to develop and characterize immunocompetent CCA models with distinct genetic drivers, and correlate tumor genomics, immunobiology, and therapeutic response. METHODS: A multifaceted approach including scRNA-seq, CITE-seq, whole exome and bulk RNA sequencing was employed. FDA-approved PD-1/PD-L1 antibodies were tested in humanized PD-1/PD-L1 mice (HuPD-H1). RESULTS: A genetic mouse model of intrahepatic CCA (iCCA) driven by intrabiliary transduction of Fbxw7ΔF/Akt that mimics human iCCA was generated. From the Fbxw7ΔF/Akt tumors, a murine cell line (FAC) and syngeneic model with genetic and phenotypic characteristics of human iCCA were developed. Established SB1 (YAPS127A/Akt) and KPPC (KrasG12Dp53L/L) models were compared to the FAC model. Although the models had transcriptomic similarities, they had substantial differences as well. Mutation patterns of FAC, SB1, and KPPC cells matched different mutational signatures in Western and Japanese CCA patient cohorts. KPPC tumors had a high tumor mutation burden. FAC tumors had a T cell-infiltrated TIME, while SB1 tumors had a preponderance of suppressive myeloid cells. FAC, SB1, and KPPC tumors matched different immune signatures in human iCCA cohorts. Moreover, FAC, SB1, and KPPC tumor-bearing HuPD-H1 mice displayed differential responses to nivolumab or durvalumab. CONCLUSIONS: Syngeneic iCCA models display a correlation between tumor genotype and TIME phenotype, with differential responses to FDA-approved immunotherapies. This study underscores the importance of leveraging multiple preclinical models to understand responses to immunotherapy in different genetic subsets of human CCA. IMPACT AND IMPLICATIONS: Understanding the relationship between tumor genotype and the phenotype of the immune microenvironment is an unmet need in cholangiocarcinoma (CCA). Herein, we use syngeneic murine models of intrahepatic CCA with different genetic drivers to demonstrate a correlation between tumor genotype and immune microenvironment phenotype in murine models, which is associated with differential responses to FDA-approved immunotherapies. This information will help guide other preclinical studies. Additionally, it emphasizes that immune checkpoint inhibition in patients with CCA is not a "one-size-fits-all" approach. Our observations suggest that, as for targeted therapies, patients should be stratified and selected for treatment according to their tumor genetics.

Multifunctional Biodegradable Conductive Hydrogel Regulating Microenvironment for Stem Cell Therapy Enhances the Nerve Tissue Repair.

The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstrates that the rationally designed biodegradable multifunctional hydrogel significantly enhances nerve tissues repair.

LncRNA FGD5-AS1 Alleviates Inflammation in Allergic Rhinitis through the miR-223-3p/COX11 Axis.

INTRODUCTION: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of allergic rhinitis (AR). The current investigation is focused on elucidating the functional impact of a specific lncRNA, FGD5 antisense RNA 1 (FGD5-AS1), on the development and progression of AR through its interaction with miR-223-3p. METHODS: An experimental framework for AR was constructed in both cellular and animal models. Quantitative assessment of FGD5-AS1, miR-223-3p, and COX11 mRNA expression was conducted using real-time quantitative reverse transcription PCR. The expression of inflammatory factors, immunoglobulin E, LTC4, and ECP, was examined using ELISA. Apoptosis in human nasal epithelial cells was assessed by the flow cytometry method. The protein expression of COX11 was examined using Western blotting. Nasal mucosal function was further evaluated by hematoxylin and eosin staining. Furthermore, bioinformatics evaluations, dual-luciferase reporter assays, and a series of experimental procedures unveiled a putative competitive endogenous RNA regulatory mechanism. RESULTS: We found the expression of lncRNA FGD5-AS1 was decreased in AR. In vitro lncRNA FGD5-AS1 attenuated the production of inflammatory cytokines in nasal epithelial cells. Furthermore, elevated FGD5-AS1 expression significantly alleviated AR symptoms by reducing nasal epithelial apoptosis and inflammation. MiR-223-3p was identified as a direct target of FGD5-AS1. Moreover, miRNA-223-3p directly downregulated the expression of COX11 mRNA. Subsequent experiments confirmed that FGD5-AS1 regulated AR through the miR-223-3p/COX11 axis, thereby inhibiting inflammation. CONCLUSION: The FGD5-AS1/miR-223-3p/COX11 axis plays a pivotal role in the pathogenesis of AR, suggesting that FGD5-AS1 could serve as a potential diagnostic biomarker and therapeutic target for AR.

Exploring the role of lactylation-related genes in osteosarcoma: A deep dive into prognostic significance and therapeutic potential.

Osteosarcoma (OS), notorious for its complex pathogenesis and formidable prognosis, represents a significant medical quandary. This research embarked on a quest to unravel the implications of lactylation-related genes (LRGs) in OS, offering a novel lens through which to interpret its intricacies. A meticulous evaluation of 329 LRGs within the TARGET dataset spotlighted 27 paramount genes, intricately intertwined with survival. These genes highlighted metabolic processes-particularly amino acid metabolism-as key players, as evidenced in both GO and KEGG analyses. Utilizing consensus clustering and principal component analysis, the 93 OS samples were segmented into two distinct groups, differing notably in overall and event-free survival. Cluster 2 demonstrated a heightened immune response, contrasting the other cluster. Machine learning techniques, like generalized boosted model, CoxBoost, and RSF, spotlighted MYC and GOT2 as critical genes. Using multivariate Cox regression, a risk model was developed, categorizing patients into high and low-risk groups, each displaying varied survival patterns. Additionally, a contrast was observed between MYC and GOT2's associations with HLA molecules, emphasizing their distinct roles in antigen presentation. Potential therapeutic avenues were identified for each risk group, with special attention to mutations in MYC, particularly amplifications, hinting at its role in tumor progression. Finally, delving deeper into the role of MYC, Western blot analyses exhibited amplified myc protein levels in OS cells U-2 and MG-63 when juxtaposed against human osteoblastic cells Hfob1.19. A focused knockdown of myc in OS cells subsequently confirmed its influence on cell proliferation and migration, with reduced myc expression resulting in inhibited cell activities. Furthermore, immunofluorescence assays corroborated myc's heightened expression in OS cells relative to normal osteoblastic cells. In summary, this study accentuates the vital role of LRGs and specifically MYC in OS, ushering in a horizon of tailored therapeutic strategies.

A transcriptional landscape underlying sugar import for grain set in maize.

Developing seed depends on sugar supply for its growth and yield formation. Maize (Zea mays L.) produces the largest grains among cereals. However, there is a lack of holistic understanding of the transcriptional landscape of genes controlling sucrose transport to, and utilization within, maize grains. By performing in-depth data mining of spatio-temporal transcriptomes coupled with histological and heterologous functional analyses, we identified transporter genes specifically expressed in the maternal-filial interface, including (i) ZmSWEET11/13b in the placento-chalazal zone, where sucrose is exported into the apoplasmic space, and (ii) ZmSTP3, ZmSWEET3a/4c (monosaccharide transporters), ZmSUT1, and ZmSWEET11/13a (sucrose transporters) in the basal endosperm transfer cells for retrieval of apoplasmic sucrose or hexoses after hydrolysis by extracellular invertase. In the embryo and its surrounding regions, an embryo-localized ZmSUT4 and a cohort of ZmSWEETs were specifically expressed. Interestingly, drought repressed those ZmSWEETs likely exporting sucrose but enhanced the expression of most transporter genes for uptake of apoplasmic sugars. Importantly, this drought-induced fluctuation in gene expression was largely attenuated by an increased C supply via controlled pollination, indicating that the altered gene expression is conditioned by C availability. Based on the analyses above, we proposed a holistic model on the spatio-temporal expression of genes that likely govern sugar transport and utilization across maize maternal and endosperm and embryo tissues during the critical stage of grain set. Collectively, the findings represent an advancement towards a holistic understanding of the transcriptional landscape underlying post-phloem sugar transport in maize grain and indicate that the drought-induced changes in gene expression are attributable to low C status.

Metal-enriched HSP90 nanoinhibitor overcomes heat resistance in hyperthermic intraperitoneal chemotherapy used for peritoneal metastases.

Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after cytoreductive surgery. However, treated tumor cells are prone to becoming heat resistant to HIPEC therapy through high expression of heat shock proteins (HSPs). Here, a carrier-free bifunctional nanoinhibitor was developed for HIPEC therapy in the management of peritoneal metastases. Self-assembly of the nanoinhibitor was formed by mixing Mn ion and epigallocatechin gallate (EGCG) in a controllable manner. Such nanoinhibitor directly inhibited HSP90 and impaired the HSP90 chaperone cycle by reduced intracellular ATP level. Additionally, heat and Mn ion synergistically induced oxidative stress and expression of caspase 1, which activated GSDMD by proteolysis and caused pyroptosis in tumor cells, triggering immunogenic inflammatory cell death and induced maturation of dendritic cells through the release of tumor antigens. This strategy to inhibit heat resistance in HIPEC presented an unprecedented paradigm for converting "cold" tumors into "hot" ones, thus significantly eradicating disseminated tumors located deep in the abdominal cavity and stimulating immune response in peritoneal metastases of a mouse model. Collectively, the nanoinhibitor effectively induced pyroptosis of colon tumor cells under heat conditions by inhibiting heat stress resistance and increasing oxidative stress, which may provide a new strategy for treatment of colorectal peritoneal metastases.

Macrocycle Self-Assembly Hydrogel for High-Efficient Oil-Water Separation.

Supramolecular hydrogels involved macrocycles have been explored widely in recent years, but it remains challenging to develop hydrogel based on solitary macrocycle with super gelation capability. Here, the construction of lantern[33 ]arene-based hydrogel with low critical gelation concentration (0.05 wt%), which can be used for efficient oil-water separation, is reported. The lantern[33 ]arenes self-assemble into hydrogen-bonded organic nanoribbons, which intertwine into entangled fibers to form hydrogel. This hydrogel which exhibits reversible pH-responsiveness characteristics can be coated on stainless-steel mesh by in situ sol-gel transformation. The resultant mesh exhibits excellent oil-water separation efficiency (>99%) and flux (>6 × 104 L m-2 h-1 ). This lantern[33 ]arene-based hydrogel not only sheds additional light on the gelation mechanisms for supramolecular hydrogels, but also extends the application of macrocycle-based hydrogels as functional interfacial materials.

Aquiflexum gelatinilyticum sp. nov., isolated from river water.

Two Gram-stain-negative, strictly aerobic, rod-shaped, non-motile and non-gliding bacteria, designated as XJ19-10T and XJ19-11, were isolated from river water in Xinjiang Uygur Autonomous Region, PR China. Cells of these strains were catalase-, oxidase- and gelatinase-positive and contained carotenoids but no flexirubins. Growth occurred at 10-30 °C, pH 7.0-9.0 and with 0-2.5% (w/v) NaCl. On the basis of the results of 16S rRNA gene sequence and genome analyses, the two isolates represented members of the genus Aquiflexum, and the closest relative was Aquiflexum aquatile Z0201T with 16S rRNA gene sequence pairwise similarities of 97.9-98.1%. Furthermore, the average nucleotide identities and digital DNA-DNA hybridization identities between the two isolates and other relatives were all less than 82.9 and 28.2 %, respectively, all below the species delineation thresholds. The results of pan-genomic analysis indicated that the type strain XJ19-10T shared 2813 core gene clusters with other three type strains of members of the genus Aquiflexum, as well as having 623 strain-specific clusters. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, an unidentified aminolipid and unidentified lipids. The predominant fatty acids (>10% of the total contents) were iso-C15 : 0, iso-C15 : 1G, iso-C17 : 0 3-OH and summed feature 9, and MK-7 was the respiratory quinone. On the basis of the results of phenotypic, physiological, chemotaxonomic and genotypic characterization, strains XJ19-10T and XJ19-11 are considered to represent a novel species, for which the name Aquiflexum gelatinilyticum sp. nov. is proposed. The type strain is XJ19-10T (=CGMCC 1.19385T =KCTC 92266T).

A rare case of severe leptospirosis infection presenting as septic shock in a non-endemic area: a case report and literature review.

BACKGROUND: Leptospirosis is a zoonosis caused by spirochete "genus" leptospira. The clinical presentations of leptospirosis range from an influenza-like presentation of fever and myalgia, to severe forms. Leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis when clinical similarities exist. CASE PRESENTATION: A 63-year-old man presented with fever, shock and thrombocytopenia followed by diffuse pulmonary hemorrhage. Peripheral blood Metagenomic Next-generation Sequencing (mNGS) reported Leptospira interrogans. The patient was treated with piperacillin-tazobactam (TZP) plus doxycycline and improved dramatically after 7 days. CONCLUSION: We conclude that leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis. Correctly evaluation of thrombocytopenia in acute febrile illnesses facilitates the differential diagnosis of leptospirosis. mNGS can accurately detect Leptospira DNA during the early stage of the infection.

Updates of liquid biopsy in oral cancer and multiomics analysis.

Liquid biopsy is a method sampled from body fluids, such as blood, saliva, urine, pleural effusion, cerebrospinal fluid, and so on. It is minimally invasive and reproducible and therefore can build a dynamic, real-time monitoring of oral squamous cell carcinoma patient's conditions and treatment responses. Circulating tumor cells, circulating tumor DNA and exosomes are three main detection objects of liquid biopsy, having different detection methods and features involving cost, sensitivity, specificity and output. Blood and saliva are the options of liquid biopsy in oral cancer. Then we reviewed the studies of liquid biopsy in oral cancer, integrating multiomics analysis of these results. The multiomics analysis of genomics, transcriptomics, proteomics, metabolomics, and DNA methylation have shown potential for the early screening, diagnosis, staging, prognosis, personalized medicine therapy, and monitoring of recurrence (minimal residual disease). Besides, we concluded some problems to be solved, such as the lack of the standard of the measurement methods and procedures of samples, the insufficient connection among different omics, and how to improve the sensitivity and specificity. And we also put up rough assumptions to these problems. However, the analysis of multiomics of liquid biopsy in oral cancer still shows great clinical value in the diagnosis and treatment of oral squamous cell carcinoma.

Periampullary tumors in a patient with pancreatic divisum and neurofibromatosis type 1: a case report.

INTRODUCTION: We present a case of a male patient with neurofibromatosis type 1 diagnosed with pancreatic divisum and several gastrointestinal tumors. A 55-year-old man was admitted to the hospital with recurrent chronic pancreatitis, indicating a large mass in the ampulla. In addition, genetic testing revealed two unique germline mutations in the neurofibromin (NF1) gene, and their potential interaction in promoting cancer was further investigated. CONCLUSION: The first similar case was reported in 2020. The current case was distinct from other cases since an additional two NF1 mutations were found in the patient. In conjunction with prior case reports, our findings imply that genetic testing in patients diagnosed with neurofibromatosis type 1 could be helpful in the development of effective treatments.

Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy.

INTRODUCTION: Sepsis is a medical condition characterized by acute organ dysfunction and uncontrolled inflammation. Organ dysfunction in sepsis is the primary cause of mortality in patients with myocardial dysfunction. Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients. Our main objective is to examine levosimendan's efficacy in treating severe sepsis complicated with septic cardiomyopathy. METHODS: We systematically searched five databases, PubMed, Web of Science, Embase, Cochrane Library and BioMed Central, for articles and publications from their inception to 2023. Our study adopted the PICOS approach in identifying suitable publications during the systematic search. Inclusion criteria included randomized, controlled trials utilizing levosimendan in adult patients diagnosed with septic shock or severe sepsis. We excluded non-English publications and non-randomized controlled trials. The Newcastle-Ottawa scale (NOS) scale was used to assess the methodological quality, while the risk of bias was assessed through the Cochrane Risk of bias tool. All statistical analyses were performed using RevMan version 5.4. RESULTS: Eight studies met the eligibility criteria and were included in the analysis. There was a statistically significant positive effect on cardiac input in patients treated with levosimendan compared to those treated with dobutamine (p < 0.001). Similarly, there were positive effects on left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular stroke work index (LVSWI) (p < 0.001). We observed a significant reduction in mortality (p < 0.01) and serum levels of lactic acid (p < 0.01). DISCUSSION: Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues. CONCLUSION: Levosimendan is highly efficacious and safe in the management of sepsis and sepsis-induced cardiomyopathy.

Long Non-coding RNAs (lncRNAs), A New Target in Stroke.

Stroke has become the most disabling and the second most fatal disease in the world. It has been a top priority to reveal the pathophysiology of stroke at cellular and molecular levels. A large number of long non-coding RNAs (lncRNAs) are identified to be abnormally expressed after stroke. Here, we summarize 35 lncRNAs associated with stroke, and clarify their functions on the prognosis through signal transduction and predictive values as biomarkers. Changes in the expression of these lncRNAs mediate a wide range of pathological processes in stroke, including apoptosis, inflammation, angiogenesis, and autophagy. Based on the exploration of the functions and mechanisms of lncRNAs in stroke, more timely, accurate predictions and more effective, safer treatments for stroke could be developed.

High concentration of Cas12a effector tolerates more mismatches on ssDNA.

Rapid pathogen detection is critical for prompt treatment, interrupting transmission routes, and decreasing morbidity and mortality. The V-type CRISPR system had been used for rapid pathogen detection. However, whether single-stranded DNA in CRISPR system can cause false positives remains undetermined. Herein, we show that high molar concentration of Cas12a effector tolerated more mismatches on ssDNA and activated its trans-cleavage activity at six base matches. Reducing Cas12a and crRNA molar concentration increased the minimal base-match number required for Cas12a ssDNA activation to 11, which reducing nonspecific activation. We then established a Cas12a-based M tuberculosis detection system with a primer having an 8 bp overlap with crRNA. This system did not exhibit primer-induced false positives, and minimum detection copy reached 1 copy/uL (inputting 1-µL sample) in standard strains. The Cas12a-based M tuberculosis detection system showed 80.0% sensitivity and 100.0% specificity in verification using clinical specimens, compared with Xpert MTB/RIF, which showed 72.0% sensitivity and 90.9% specificity. All these results prove that appropriate concentration of cas12a effector can effectively perform nucleic acid detection.

Opportunities and challenges of polyphenols and polysaccharides for type 1 diabetes intervention.

Type 1 diabetes (T1D) is an autoimmune disorder characterized by the destruction of insulin-producing pancreatic ß cell. It contributes to high mortality, frequent diabetic complications, poor quality of life in patients and also puts a significant economic burden on health care systems. Therefore, the development of new therapeutic strategies is urgently needed. Recently, certain dietary compounds with potential applications in food industry, particularly polyphenols and polysaccharides, have gained increasing attention with their prominent anti-diabetic effects on T1D by modulating ß cell function, the gut microbiota and/or the immune system. In this review, we critically discuss the recent findings of several dietary polyphenols and polysaccharides with the potential to protect against T1D and the underlying anti-diabetic mechanisms. More importantly, we highlight the current trends, major issues, and future directions of industrial production of polyphenols- and polysaccharides-based functional foods for preventing or delaying T1D.

Devosia ureilytica sp. nov., isolated from Kuche River in China.

Two novel strains, designated XJ19-45T and XJ19-1, were isolated from water of Kuche River in Xinjiang Uygur Autonomous Region, China. Their cells were Gram-stain-negative, aerobic and motile rods. The phylogenetic analyses based on 16S rRNA genes and genomes showed that the two isolates belonged to the genus Devosia and the closest relative was Devosia subaequoris HST3-14T. The 16S rRNA genes sequences pairwise similarities, average nucleotide identities, digital DNA-DNA hybridizations and average amino acid identities between type strain XJ19-45T and other relatives were all less than 98.3, 80.3, 23.6 and 85.7 %, respectively, all below the species delineation thresholds. Pan-genomic analysis indicated that the novel isolate XJ19-45T shared 1594 core gene clusters with the 11 closely related type strains in Devosia, and the number of strain-specific clusters was 390. The major cellular fatty acids (>10 %) of the two isolates were summed feature 8, C18 : 1 ω7c 11-methyl and C16 : 0. Diphosphatidylglycerol, phosphatidylglycerol and glycolipids were the major polar lipids, and Q10 was the detected respiratory quinone. Based on the results of phenotypic, physiological, chemotaxonomic and genotypic characterizations, we propose that the isolates represent a novel species, for which the name Devosia ureilytica sp. nov. is proposed. The type strain is XJ19-45T (=CGMCC 1.19388T=KCTC 92263T).

Transcriptome analysis endoplasmic reticulum-stress response in Litopenaeus vannamei hemocytes.

Numerous studies have proved that endoplasmic reticulum (ER)-stress is an important cause of aquatic animal diseases. Therefore, for effectively preventing and controlling aquatic animal diseases, a systematic and in-depth understanding of the environmental stress response in aquatic animals is necessary. In present study, the influence of ER-stress in Litopenaeus vannamei was investigated using Illumina HiSeq based RNA-Seq. Comparing to the cDNA library of hemocytes treated with DMSO in L. vannamei, 286 unigenes were significantly upregulated and 473 unigenes were significantly down-regulated in the Thapsigargin treated group. KEGG analysis indicated that the differentially expressed genes (DEGs) are mainly related to ER-stress, immune as well as metabolism. Besides the classical ER-stress response pathways, the regulation of cell cycle and DNA replication are also important measures of ER-stress response. It has been suggested that the influence of ER-stress on immune genes might be an important factor in environmental stress inducing shrimp disease. Our investigation exhibited that immune-related DEG Prophenoloxidase activating enzyme 2 (LvPPAE2) roled in anti-pathogen immunity of shrimp. This study provides a solid foundation for uncovering the environmental adaptation response and especially its relationship with L. vannamei immune system.