VirBot: an RNA viral contig detector for metagenomic data.

SUMMARY: Without relying on cultivation, metagenomic sequencing greatly accelerated the novel RNA virus detection. However, it is not trivial to accurately identify RNA viral contigs from a mixture of species. The low content of RNA viruses in metagenomic data requires a highly specific detector, while new RNA viruses can exhibit high genetic diversity, posing a challenge for alignment-based tools. In this work, we developed VirBot, a simple yet effective RNA virus identification tool based on the protein families and the corresponding adaptive score cutoffs. We benchmarked it with seven popular tools for virus identification on both simulated and real sequencing data. VirBot shows its high specificity in metagenomic datasets and superior sensitivity in detecting novel RNA viruses. AVAILABILITY AND IMPLEMENTATION: https://github.com/GreyGuoweiChen/RNA_virus_detector. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Low-cost and efficient all group-IV visible/shortwave infrared dual-band photodetector.

Low-cost broadband photodetectors (PDs) based on group-IV materials are highly demanded. Herein, a vertical all group-IV graphene-i-n (Gr-i-n) structure based on sputtering-grown undoped Ge0.92Sn0.08/Ge multiple quantum wells (MQWs) on n-Ge substrate was proposed to realize efficient visible/shortwave infrared (VIS/SWIR) dual-band photoresponse. Harnessing Gr-germanium tin (GeSn)/Ge MQWs van der Waals heterojunctions, an extended surface depletion region was established, facilitating separation and transportation of photogenerated carriers at VIS wavelengths. Consequently, remarkable VIS/SWIR dual-band response ranging from 400 to 2000 nm with a rapid response time of 23 µs was achieved. Compared to the PD without Gr, the external quantum efficiency at 420, 660, and 1520 nm was effectively enhanced by 10.2-, 5.2-, and 1.2-fold, reaching 40, 42, and 50%, respectively. This research paves the way for the advancement of all group-IV VIS/SWIR broadband PDs and presents what we believe to be a novel approach to the design of low-cost broadband PDs.

Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen.

Despite the importance of lipid mediators in stress and depression and their link to inflammation, the influence of stress on these mediators and their role in inflammation is not fully understood. This study used RNA-seq, LC-MS/MS, and flow cytometry analyses in a mouse model subjected to chronic social defeat stress to explore the effects of acute and chronic stress on lipid mediators, gene expression, and cell population in the bone marrow and spleen. In the bone marrow, chronic stress induced a sustained transition from lymphoid to myeloid cells, accompanied by corresponding changes in gene expression. This change was associated with decreased levels of 15-deoxy-d12,14-prostaglandin J2, a lipid mediator that inhibits inflammation. In the spleen, chronic stress also induced a lymphoid-to-myeloid transition, albeit transiently, alongside gene expression changes indicative of extramedullary hematopoiesis. These changes were linked to lower levels of 12-HEPE and resolvins, both critical for inhibiting and resolving inflammation. Our findings highlight the significant role of anti-inflammatory and pro-resolving lipid mediators in the immune responses induced by chronic stress in the bone marrow and spleen. This study paves the way for understanding how these lipid mediators contribute to the immune mechanisms of stress and depression.

Sulfur Free Crosslinking of EPDM Composites via Silane Grafting and Silica Incorporation.

This study aims at evaluating and developing an environmental-friendly and sulfur-free cured ethylene propylene diene monomer (EPDM) composites. Silane grafted EPDM (SiEPDM) composites incorporated with silica is prepared via a solvent-free, one-step reactive mixing process. The silane grafting and silica filler bonding are characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The mechanical properties of the developed composites are examined. The fracture morphology is observed using an environmental scanning electron microscopy. The rheology and thermomechanical properties are evaluated by using a rotational rheometer and dynamic mechanical analyzer. Notably, a robust bonding between silica and the grafted silane is established, yielding a crosslinking network within the composite structure. This phenomenon is substantiated by the observed gel efficiency and rheology behavior. Consequently, a pronounced augmentation of up to 75% in tensile strength and 29% in tear strength are observed in the optimized SiEPDM-silica composites, distinguishing them from their EPDM-silica counterparts. The introduction of paraffin oil contributes to enhanced processability; however, it is concomitant with a reduction in gel efficiency and associated mechanical properties. Furthermore, subsequent UV weathering test unveils that the SiEPDM-silica composites exhibit the highest levels of residual tensile strength and modulus, indicative of their exceptional UV stability.

Deletion of Nox from Listeria monocytogenes Strain EGDe Enhances Bacterial Virulence and Reduces the Production of Reactive Oxygen Species and Inflammatory Factors In Vivo.

The foodborne pathogens have a serious threat to human health, especially Listeria monocytogenes. NADPH oxidase (NOX) is involved in cellular respiration and the production of reactive oxygen species (ROS), acting as messengers to host cells during the infection. However, the role of nox in the process of L. monocytogenes infection is unclear. In this study, we examined the impact of nox in L. monocytogenes by gene deletion. The results of cell experiment showed that knocking out nox from L. monocytogenes strain EGDe resulted in a twofold increase invasion ability to Caco-2 cells compared with that of wild-type strain (WT), but did not affect adhesion ability. Animal infection assays also showed that bacterial loads in the liver and spleen of mice challenged with EGDe-Δnox were approximately two times higher compared with those challenged with the WT strain. On the one hand, quantitative real-time polymerase chain reaction revealed that deletion of nox leads to upregulation of genes related to the internalization of L. monocytogenes (inlA, inlB, and inlC). More importantly, the expression of listeriolysin-positive regulatory (prfA) gene increased by three times in vivo compared with that of WT. On the other hand, the deletion of nox resulted in a reduction of the upregulation of proinflammatory factors in EGDe-Δnox compared with the WT and complementary strains. Thus, our study revealed that nox affected the virulence of L. monocytogenes by upregulating the expression of virulence genes and regulating the production of ROS and inflammatory factors in vivo.

Synergetic Modulation of Steric Hindrance and Excited State for Anti-Quenching and Fast Spin-Flip Multi-Resonance Thermally Activated Delayed Fluorophore.

Multi-resonance thermally activated delayed fluorescence (MR-TADF) materials hold great promise for advanced high-resolution organic light-emitting diode (OLED) displays. However, persistent challenges, such as severe aggregation-caused quenching (ACQ) and slow spin-flip, hinder their optimal performance. We propose a synergetic steric-hindrance and excited-state modulation strategy for MR-TADF emitters, which is demonstrated by two blue MR-TADF emitters, IDAD-BNCz and TIDAD-BNCz, bearing sterically demanding 8,8-diphenyl-8H-indolo[3,2,1-de]acridine (IDAD) and 3,6-di-tert-butyl-8,8-diphenyl-8H-indolo[3,2,1-de]acridine (TIDAD), respectively. These rigid and bulky IDAD/TIDAD moieties, with appropriate electron-donating capabilities, not only effectively mitigate ACQ, ensuring efficient luminescence across a broad range of dopant concentrations, but also induce high-lying charge-transfer excited states that facilitate triplet-to-singlet spin-flip without causing undesired emission redshift or spectral broadening. Consequently, implementation of a high doping level of IDAD-BNCz resulted in highly efficient narrowband electroluminescence, featuring a remarkable full-width at half-maximum of 34 nm and record-setting external quantum efficiencies of 34.3 % and 31.8 % at maximum and 100 cd m-2, respectively. The combined steric and electronic effects arising from the steric-hindered donor introduction offer a compelling molecular design strategy to overcome critical challenges in MR-TADF emitters.

Isolation, characterization and genomic analysis of the novel Arthrobacter sp. phage SWEP2.

A new virulent phage, SWEP2, infecting the Arthrobacter sp. 5B strain, was isolated from black soil samples in northeastern China. SWEP2 has a latent period of 80 min and a burst size of 45 PFU (evaluated at an MOI of 0.1). Genomic analysis revealed that the 43,398-bp dsDNA genome of phage SWEP2 contains 64 open reading frames (ORFs) and one tRNA gene. Phylogenetic analysis indicated a close relationship between SWEP2 and Arthrobacter phage Liebe, with 82.98% identity and a query coverage of 48%. Based on its distinct phenotypic and genetic characteristics, SWEP2 is identified as a novel Arthrobacter phage.

Comparative efficacy of silicon and iron oxide nanoparticles towards improving the plant growth and mitigating arsenic toxicity in wheat (Triticum aestivum L.).

Nano-enabled agriculture has emerged as an attractive approach for facilitating soil pollution mitigation and enhancing crop production and nutrition. In this study, we conducted a greenhouse experiment to explore the efficacy of silicon oxide nanoparticles (SiONPs) and iron oxide nanoparticles (FeONPs) in alleviating arsenic (As) toxicity in wheat (Triticum aestivum L.) and elucidated the underlying mechanisms involved. The application of SiONPs and FeONPs at 25, 50, and 100 mg kg-1 soil concentration significantly reduced As toxicity and concurrently improved plant growth performance, including plant height, dry matter, spike length, and grain yield. The biochemical analysis showed that the enhanced plant growth was mainly due to stimulated antioxidative enzymes (catalase, superoxide dismutase, peroxidase) and reduced reactive oxygen species (electrolyte leakage, malondialdehyde, and hydrogen peroxide) in wheat seedlings under As stress upon NPs application. The nanoparticles (NPs) exposure also enhanced the photosynthesis efficiency, including the total chlorophyll and carotenoid contents as compared with the control treatment. Importantly, soil amendments with 100 mg kg-1 FeONPs significantly reduced the acropetal As translocation in the plant root, shoot and grains by 74%, 54% and 78%, respectively, as compared with the control treatment under As stress condition, with relatively lower reduction levels (i.e., 64%, 37% and 58% for the plant root, shoot and grains, respectively) for SiONPs amendment. Overall, the application of NPs especially the FeONPs as nanoferlizers for agricultural crops is a promising approach towards mitigating the negative impact of HMs toxicity, ensuring food safety, and promoting future sustainable agriculture.

Anaerobic sludge digestion elevates dissemination risks of bacterial antibiotic resistance in effluent supernatant.

Anaerobic digestion following a variety of pretreatments is a promising technique for the reduction of excess sludge in municipal wastewater treatment plants (MWWTPs), and eliminations of possible pathogens, viruses, protozoa, and other disease-causing organisms. Notwithstanding a rapidly increasing health concern of antibiotic resistant bacteria (ARB) in MWWTPs, dissemination risks of ARB in anaerobic digestion processes are still poorly understood, especially in the digested supernatant. Taking the representative ARB with respect to the common tetracycline-, sulfamethoxazole-, clindamycin- and ciprofloxacin resistance, we investigated the compositions of ARB in the sludge and supernatant, and quantified their variations along the entire anaerobic sludge digestion process following ultrasonication-, alkali-hydrolysis- and alkali-ultrasonication pretreatments, respectively. Results showed that the abundance of ARB was diminished by up to 90% from the sludge along anaerobic digestion coupling with the pretreatments. Surprisingly, pretreatments clearly boosted the abundance of specific ARB (e.g., 2.3 × 102 CFU/mL of tetracycline-resistant bacteria) in the supernatant that otherwise remained relatively low value of 0.6 × 102 CFU/mL from the direct digestion. Measurements of the soluble-, loosely-bound- and tightly-bound extracellular polymeric substances components revealed a gradually intensified destruction of the sludge aggregates along the entire anaerobic digestion processes, which could be likely responsible to the increase of the ARB abundance in the supernatant. Furthermore, analysis of the bacterial community components showed that the ARB populations were strongly correlated with the occurrence of Bacteroidetes, Patescibacteria, and Tenericutes. Interestingly, intensified conjugal transfer (0.015) of antibiotic resistance genes (ARGs) was observed upon returning of the digested supernatant to the biological treatment system. It implies the likelihood of ARGs spreading and subsequent ecological risks upon anaerobic digestion towards reducing excess sludge, and therefore requires further attentions for the excess sludge treatments especially of supernatant.

Efficient Intersystem Crossing and Long-lived Charge-Separated State Induced by Through-Space Intramolecular Charge Transfer in a Parallel Geometry Carbazole-Bodipy Dyad.

The design of efficient heavy atom-free triplet photosensitizers (PSs) based on through bond charge transfer (TBCT) features is a formidable challenge due to the criteria of orthogonal donor-acceptor geometry. Herein, we propose using parallel (face-to-face) conformation carbazole-bodipy donor-acceptor dyads (BCZ-1 and BCZ-2) featuring through space intramolecular charge transfer (TSCT) process as efficient triplet PS. Efficient intersystem crossing (ΦΔ =61 %) and long-lived triplet excited state (τT =186 µs) were observed in the TSCT dyad BCZ-1 compared to BCZ-3 (ΦΔ =0.4 %), the dyad involving TBCT, demonstrating the superiority of the TSCT approach over conventional donor-acceptor system. Moreover, the transient absorption study revealed that TSCT dyads have a faster charge separation and slower intersystem crossing process induced by charge recombination compared to TBCT dyad. A long-lived charge-separated state (CSS) was observed in the BCZ-1 (τCSS =24 ns). For the first time, the TSCT dyad was explored for the triplet-triplet annihilation upconversion, and a high upconversion quantum yield of 11 % was observed. Our results demonstrate a new avenue for designing efficient PSs and open up exciting opportunities for future research in this field.

CAF promotes chemoresistance through NRP2 in gastric cancer.

BACKGROUND: Fibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored. METHODS: Primary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques. RESULTS: CAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ. CONCLUSIONS: The present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.

Validation of the functional assessment of anorexia/cachexia therapy instrument to assess quality of life in maintenance hemodialysis patients with cachexia.

BACKGROUND: Many patients on maintenance hemodialysis (MHD) eventually suffer from cachexia. The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) is a tool used to evaluate the quality of life of patients with cachexia related to various diseases, but its suitability for use in MHD patients has yet to be verified. This study aimed to explore the validation of the FAACT in MHD patients by conducting reliability and validity tests. METHODS: Qualified MHD patients were selected to complete the FAACT and Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaires, and their demographic data and biochemical test results were collected from electronic medical records. Next, the Cronbach's alpha coefficient, paired sample t test and ICC were used to analyze the scale consistency. Additionally, the association between the KDQOL-36 and FAACT was analyzed using Bland-Altman plots and Pearson correlation analysis. Finally, the patients were divided into groups to evaluate discriminant validity. RESULTS: A total of 299 patients were included in this study. The Cronbach's alpha coefficients of the FAACT and its anorexia-cachexia subscale (ACS) were 0.904 and 0.842, respectively, and their ICC exceeded 0.90. The correlation coefficients between the FAACT and its items ranged from 0.146 to 0.631, and the correlation coefficients between the FAACT and KDQOL-36 dimensions ranged from 0.446 to 0.617. The Bland-Altman plots between the FAACT and KDQOL-36 showed that only 3.3% of the points were outside the 95% limits of agreement. The effects of cachexia status (present or absent) on FAACT and ACS scores had effect sizes of 0.54 (P < 0.001) and 0.60 (P < 0.001), respectively. The FAACT and ACS also significantly discriminated between patients with and without inflammation (P < 0.001). CONCLUSIONS: The FAACT and ACS have acceptable reliability and validity in MHD patients and are suitable for measuring the quality of life of MHD patients with cachexia.

MiR-205-5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1.

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205-5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. We investigated miR-205-5p expression and microvessel densities (MVDs) in GC tissues and liver metastases from patients. The function and mechanisms of miR-205-5p were examined in human cell lines and in xenograft mouse models. Associations between miR-205-5p expression and clinical characteristics were analyzed using either Pearson's χ2 test or Fisher's exact test. Differences in overall survival (OS) distributions were evaluated using the log-rank test. Differences in measurement data were compared using Student's t-test and one-way ANOVA. We found that miR-205-5p expression was downregulated in GC tissues and was negatively correlated with CD31 expression in both TCGA and our clinical samples. GC cell lines expressed low levels of miR-205-5p, and miR-205-5p upregulation significantly impaired the proliferation and angiogenesis of GC cells. Moreover, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) expression and activation of extracellular-related kinase (ERK) signaling were suppressed by miR-205-5p. MiR-205-5p inhibition promoted malignant phenotypes by enhancing VEGFA and FGF1 expression, as well as the activation of ERK signaling. Angiogenesis and ERK signaling were decreased in response to VEGFA and FGF1 downregulation induced by miR-205-5p overexpression. The dual-luciferase reporter assay showed that VEGFA and FGF1 were direct targets of miR-205-5p. Xenograft mouse models revealed that miR-205-5p suppressed tumor growth by inhibiting neovascularization. Altogether, these results demonstrate that miR-205-5p suppresses angiogenesis in GC by attenuating the expression of VEGFA and FGF1, indicating that upregulation of miR-205-5p may represent as an antiangiogenic therapy for GC.

Retracted: The Nephroprotective Effect of TNF Receptor-Associated Factor 6 (TRAF6) Blockade on LPS-Induced Acute Renal Injury Through the Inhibition if Inflammation and Oxidative Stress.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Xuemei Chen, Yiqing Zhao, Jiajun Xu, Jiachun Bao, Junyao Zhao, Jingfeng Chen, Guowei Chen, Jibo Han. The Nephroprotective Effect of TNF Receptor-Associated Factor 6 (TRAF6) Blockade on LPS-Induced Acute Renal Injury Through the Inhibition if Inflammation and Oxidative Stress. Med Sci Monit, 2020; 26: e919698. DOI: 10.12659/MSM.919698.

Characteristics and Treatment of Pediatric Tracheobronchial Foreign Bodies: A Retrospective Analysis of 715 Cases.

BACKGROUND This study aimed to analyze the clinical characteristics of tracheobronchial foreign bodies in children in Shenzhen and to explore the diagnosis and treatment methods for special cases. MATERIAL AND METHODS This study included a total of 715 children who were diagnosed with tracheobronchial foreign bodies at Shenzhen Children's Hospital between October 2016 and October 2021. Data on sex, age, inducement, symptoms, foreign body type, foreign body location, foreign body retention time, foreign body history, and complications were recorded and analyzed. RESULTS Tracheal foreign bodies were found to occur primarily in children aged 0-2 years (90.6%). The overall incidence rates were 69.1% and 30.9% in boys and girls, respectively. Among them, 42.5% of the foreign bodies were detected in the left bronchus and 45.6% in the right bronchus. Inducements included playing while eating (n=398, 55.7%) and also crying (n=209, 29.2%). Operations were performed on 710 (99.3%) children, including 80 (11.2%) immediate surgeries and 2 tracheotomies. One child had no vital signs upon admission and died after emergency foreign body removal. All of the other children who underwent surgery recovered well postoperatively. CONCLUSIONS This study presents the characteristics and methods of diagnosis and treatment of tracheobronchial foreign bodies in pediatric patients in Shenzhen. Tracheobronchial foreign bodies are a major cause of accidental injury in infants and young children. In critical cases, airways should be immediately and rapidly cleared with multidisciplinary collaboration. In addition, public safety awareness should be strengthened, particularly among parents, teachers, and other child caregivers, to reduce and prevent instances of tracheobronchial foreign body accidents in children.

DrLLPS: a data resource of liquid-liquid phase separation in eukaryotes.

Here, we presented an integrative database named DrLLPS (http://llps.biocuckoo.cn/) for proteins involved in liquid-liquid phase separation (LLPS), which is a ubiquitous and crucial mechanism for spatiotemporal organization of various biochemical reactions, by creating membraneless organelles (MLOs) in eukaryotic cells. From the literature, we manually collected 150 scaffold proteins that are drivers of LLPS, 987 regulators that contribute in modulating LLPS, and 8148 potential client proteins that might be dispensable for the formation of MLOs, which were then categorized into 40 biomolecular condensates. We searched potential orthologs of these known proteins, and in total DrLLPS contained 437 887 known and potential LLPS-associated proteins in 164 eukaryotes. Furthermore, we carefully annotated LLPS-associated proteins in eight model organisms, by using the knowledge integrated from 110 widely used resources that covered 16 aspects, including protein disordered regions, domain annotations, post-translational modifications (PTMs), genetic variations, cancer mutations, molecular interactions, disease-associated information, drug-target relations, physicochemical property, protein functional annotations, protein expressions/proteomics, protein 3D structures, subcellular localizations, mRNA expressions, DNA & RNA elements, and DNA methylations. We anticipate DrLLPS can serve as a helpful resource for further analysis of LLPS.

GLW7.1, a Strong Functional Allele of Ghd7, Enhances Grain Size in Rice.

Grain size is a key determinant of both grain weight and grain quality. Here, we report the map-based cloning of a novel quantitative trait locus (QTL), GLW7.1 (Grain Length, Width and Weight 7.1), which encodes the CCT motif family protein, GHD7. The QTL is located in a 53 kb deletion fragment in the cultivar Jin23B, compared with the cultivar CR071. Scanning electron microscopy analysis and expression analysis revealed that GLW7.1 promotes the transcription of several cell division and expansion genes, further resulting in a larger cell size and increased cell number, and finally enhancing the grain size as well as grain weight. GLW7.1 could also increase endogenous GA content by up-regulating the expression of GA biosynthesis genes. Yeast two-hybrid assays and split firefly luciferase complementation assays revealed the interactions of GHD7 with seven grain-size-related proteins and the rice DELLA protein SLR1. Haplotype analysis and transcription activation assay revealed the effect of six amino acid substitutions on GHD7 activation activity. Additionally, the NIL with GLW7.1 showed reduced chalkiness and improved cooking and eating quality. These findings provide a new insight into the role of Ghd7 and confirm the great potential of the GLW7.1 allele in simultaneously improving grain yield and quality.

[Analysis of clinical phenotype and variant of SLC2A1 gene in a Chinese pedigree affected with glucose transporter 1 deficiency syndrome].

OBJECTIVE: To analyze the clinical phenotype and variant of SLC2A1 gene in a Chinese pedigree affected with glucose transporter type 1 deficiency syndrome (GLUT1-DS). METHODS: Clinical data of a child who was treated due to delayed motor and language development and his family members were collected. DNA was extracted from peripheral blood samples and subjected to high-throughput medical exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and sister. The genotype-phenotype correlation was explored. RESULTS: The child, his mother and sister had common manifestations such as delayed mental and motor development, poor exercise tolerance, easy fatigue and paroxysmal dystonia, but the difference was that the child and his mother had microcephaly and seizures, while his sister did not. A heterozygous missense SLC2A1 c.191T>C (p.L64P) variant was identified in all affected members, which was unreported previously. CONCLUSION: The missense SLC2A1 c.191T>C (p.L64P) variant probably underlay the disease in the proband and his mother and sister. Variability of the clinical phenotypes has reflected the genetic and phenotypic diversity of GLUT1-DS. Detection of the novel variant has enriched the spectrum of GLUT1-DS mutations.

SPARC enhances 5-FU chemosensitivity in gastric cancer by modulating epithelial-mesenchymal transition and apoptosis.

Previous studies have shown that secreted protein acidic and rich in cysteine (SPARC) proteins can inhibit the development of cancer cells in various ways, such as by inhibiting angiogenesis and inhibiting cell proliferation. In fact, SPARC proteins may have an effect on the chemoresistance of gastric cancer cells to 5-Fluorouracil (5-FU), which needs further research in the future. Therefore, the purpose of this study was to explore the relationship between SPARC proteins and the chemosensitivity of gastric cancer cells to 5-FU. In vitro, after SPARC protein levels were regulated by plasmid, siRNA and human recombinant SPARC protein transfection in MGC-803, SGC-7901 and BGC-823 cells, we detected epithelial-mesenchymal transition (EMT), apoptosis markers and cell viability after 5-FU treatment. In vivo, we implanted BGC-823 cells with stable SPARC overexpression into nude mice. Tumour size was measured to assess the effect of SPARC protein on tumour formation and 5-FU chemosensitivity. In SGC-7901 and BGC-823 cells, both endogenous and exogenous upregulation of SPARC protein levels decreased cell viability, destroyed cytoskeletal F-actin, inhibited cell migration, and downregulated a series of transcription factors to inhibit cell EMT; it also upregulated cell apoptosis-related proteins to promote cell apoptosis. However, we obtained opposite results in SPARC knockdown MGC-803 cells. In vivo, compared with the control group, the group engrafted with BGC-823 cells stably overexpressing SPARC had a significant smaller tumour size. After 5-FU treatment, the new tumour gradually decreased in size. Our results show that the SPARC protein could enhance 5-FU chemosensitivity in gastric cancer cell lines by inhibiting EMT and promoting cell apoptosis.

Urine proteomics identifies biomarkers for diabetic kidney disease at different stages.

BACKGROUND: Type 2 diabetic kidney disease is the most common cause of chronic kidney diseases (CKD) and end-stage renal diseases (ESRD). Although kidney biopsy is considered as the 'gold standard' for diabetic kidney disease (DKD) diagnosis, it is an invasive procedure, and the diagnosis can be influenced by sampling bias and personal judgement. It is desirable to establish a non-invasive procedure that can complement kidney biopsy in diagnosis and tracking the DKD progress. METHODS: In this cross-sectional study, we collected 252 urine samples, including 134 uncomplicated diabetes, 65 DKD, 40 CKD without diabetes and 13 follow-up diabetic samples, and analyzed the urine proteomes with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We built logistic regression models to distinguish uncomplicated diabetes, DKD and other CKDs. RESULTS: We quantified 559 ± 202 gene products (GPs) (Mean ± SD) on a single sample and 2946 GPs in total. Based on logistic regression models, DKD patients could be differentiated from the uncomplicated diabetic patients with 2 urinary proteins (AUC = 0.928), and the stage 3 (DKD3) and stage 4 (DKD4) DKD patients with 3 urinary proteins (AUC = 0.949). These results were validated in an independent dataset. Finally, a 4-protein classifier identified putative pre-DKD3 patients, who showed DKD3 proteomic features but were not diagnosed by clinical standards. Follow-up studies on 11 patients indicated that 2 putative pre-DKD patients have progressed to DKD3. CONCLUSIONS: Our study demonstrated the potential for urinary proteomics as a noninvasive method for DKD diagnosis and identifying high-risk patients for progression monitoring.