Search

Every fifth individual with type 1 diabetes (T1D) suffers from an additional autoimmune disorder due to shared genetic factors and dysregulated immunity. Here we report an extremely rare case of T1D complicated with cyclic vomiting and hypoglycaemia. A 27-year-old Chinese woman with 14-year history of T1D was periodically hospitalized for severe vomiting of more than 30 times a day without apparent organic causes. The vomiting developed acutely and remitted spontaneously after 2-3 days, followed with intractable hypoglycaemia for another 3-4 days during the hospitalization. A few weeks after discharge, she was admitted once again with the same symptoms and disease course. Cyclic vomiting syndrome (CVS) was diagnosed according to the Rome IV criteria, a system developed to define the functional gastrointestinal disorders. Dynamic association and disassociation of exogenous insulin and insulin antibodies (IAs) were identified in her blood during hypoglycaemia, leading to the diagnosis of exogenous insulin antibody syndrome (EIAS). Treatment with rituximab to suppress the IAs was associated with a striking amelioration of hypoglycaemia. Unexpectedly, the episodes of cyclic vomiting were also dramatically reduced. In conclusion, we identified the first case with alternating CVS and EIAS in the setting of T1D. Dynamic measurements of free and total insulin are helpful for the diagnosis of EIAS. CVS is likely to be a latent autoimmune disorder considering the good response to rituximab treatment.

Abstract Background Emerging studies have revealed the potent functions of circRNAs in breast cancer tumorigenesis. However, the biogenesis, biofunction and mechanism of circRNAs in triple-negative breast cancer (TNBC) are largely unknown. Methods High-throughput RNA sequencing was applied to identify dysregulated circRNAs in TNBCs and paired normal tissues. RNA pulldown and luciferase assays were performed to investigate the interaction between circular CD44 (circCD44, also annotated as hsa_circ_0021735) and miR-502–5p. RNA pulldown and RIP assays were used to investigate the interaction between circCD44 and IGF2BP2. Cell viability, colony formation, migration/invasion assays and in vivo tumorigenesis were used to investigate circCD44 biological functions. Results CircCD44 is an uncharacterized circRNA, which is highly expressed in TNBC, and its expression is negatively correlated with the prognosis of TNBC patients. CircCD44 promotes TNBC proliferation, migration, invasion and tumorigenesis at least partially by sponging miR-502–5p and interacting with IGF2BP2. Conclusion Our data suggested that overexpressed circCD44 promotes TNBC progression. CircCD44 is potentially a novel diagnostic and therapeutic marker for TNBC patients.

Abstract Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins. However, the precise molecular mechanism and function of TRIM3 in SUMOylation and the response to tamoxifen remain unclear. In the present study, we observed that TRIM3 was dramatically overexpressed in breast cancer, which correlated with tamoxifen resistance. Furthermore, TRIM3 overexpression significantly correlated with poor survival of patients with ER+ breast cancer treated with tamoxifen. TRIM3 overexpression conferred cell survival and tumorigenesis, whereas knocking down of TRIM3 reduced these capabilities. Moreover, TRIM3, as a ubiquitin carrier protein 9 (UBC9) binding protein, promoted SUMO modification of estrogen receptor 1 (ESR1) and activated the ER pathway. Silencing UBC9 abolished the function of TRIM3 in regulating tamoxifen resistance. These results suggest TRIM3 as a novel biomarker for breast cancer therapy, indicating that inhibiting TRIM3 combined with tamoxifen might provide a potential treatment for breast cancer.

Abstract Pyrite nodules up to 20 cm in diameter are found at the top of the Marinoan (~ 635 Ma) Nantuo glacial diamictite as well as in the cap dolostones and shale/siltstones in the lower Doushantuo Formation in eastern Guizhou, southern China. Field occurrences, petrography, and stable sulfur isotopic compositions of pyrite nodules were studied from a section at Taoying, eastern Guizhou, China. Pyrite δ34S values from different nodules varied from 7.3 to 60.5‰ at different stratigraphic levels. No stratigraphic trend existed for the δ34S, supporting the scenario of pyrite formation in sediments before the precipitation of the cap dolostone. Pyrite δ34S values were also homogeneous within individual nodules at a 0.3 to 1 cm sampling scale, but were more heterogeneous at a 2 mm sampling scale. Homogeneity was not expected from the particular model for pyrite nodule formation in a largely closed or semi-closed environment. Thus, differential cementation and compaction of the pyrite-bearing sediments may have produced the nodular shape of the pyrite deposit.

Abstract Background Biogenic volatile organic compounds (BVOCs) play an essential role in tropospheric atmospheric chemical reactions. There are few studies conducted on BVOCs emission of dominant forest species in the Jing-Jin-Ji area of China. Based on the field survey, forest resources data and the measured standard emission factors, the Guenther model developed in 1993 (G93) was applied in this paper to estimate the emission of BVOCs from several dominant forest species (Platycladus orientalis, Quercus variabilis, Betula platyphylla, Populus tomentosa, Pinus tabuliformis, Robinia pseudoacacia, Ulmus pumila, Salix babylonica and Larix gmelinii) in the Jing-Jin-Ji area in 2017. Then the spatiotemporal emission characteristics and atmospheric chemical reactivity of these species were extensively evaluated. Results The results showed that the total annual BVOCs emission was estimated to be 70.8 Gg C·year− 1, consisting 40.5 % (28.7 Gg C·year− 1) of isoprene, 36.0 % (25.5 Gg C·year− 1) of monoterpenes and 23.4 % (16.6 Gg C·year− 1) of other VOCs. The emissions from Platycladus orientalis, Quercus variabilis, Populus tomentosa and Pinus tabulaeformis contributed 56.1 %, 41.2 %, 36.0 % and 31.1 %, respectively. The total BVOCs emission from the Jing-Jin-Ji area accounted for 61.9 % and 1.8 % in summer and winter, respectively. Up to 28.8 % of emission was detected from Chengde followed by Beijing with 24.9 %, that mainly distributed in the Taihang Mountains and the Yanshan Mountains. Additionally, the Robinia pseudoacacia, Populus tomentosa, Quercus variabilis, and Pinus tabulaeformis contributed mainly to BVOCs reaction activity. Conclusions The BVOCs emission peaked in summer (June, July, and August) and bottomed out in winter (December, January, and February). Chengde contributed the most, followed by Beijing. Platycladus orientalis, Quercus variabilis, Populus tomentosa, Pinus tabulaeformis and Robinia pseudoacacia represent the primary contributors to BVOCs emission and atmospheric reactivity, hence the planting of these species should be reduced.

Abstract Phase change materials (PCMs) can be used for efficient thermal energy harvesting, which has great potential for cost-effective thermal management and energy storage. However, the low intrinsic thermal conductivity of polymeric PCMs is a bottleneck for fast and efficient heat harvesting. Simultaneously, it is also a challenge to achieve a high thermal conductivity for phase change nanocomposites at low filler loading. Although constructing a three-dimensional (3D) thermally conductive network within PCMs can address these problems, the anisotropy of the 3D framework usually leads to poor thermal conductivity in the direction perpendicular to the alignment of fillers. Inspired by the interlaced structure of spider webs in nature, this study reports a new strategy for fabricating highly thermally conductive phase change composites (sw-GS/PW) with a 3D spider web (sw)-like structured graphene skeleton (GS) by hydrothermal reaction, radial freeze-casting and vacuum impregnation in paraffin wax (PW). The results show that the sw-GS hardly affected the phase transformation behavior of PW at low loading. Especially, sw-GS/PW exhibits both high cross-plane and in-plane thermal conductivity enhancements of ~ 1260% and ~ 840%, respectively, at an ultra-low filler loading of 2.25 vol.%. The thermal infrared results also demonstrate that sw-GS/PW possessed promising applications in battery thermal management.

Abstract Background Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), explore the mechanisms of its progression, and lay the foundation for the search for new biological markers. Methods We analyzed overlapping differentially expressed genes (DEGs) from three datasets; a protein–protein interaction (PPI) network was subsequently constructed and analyzed using Cytoscape. We then selected NCAPG for validation because of its poor prognosis and because it has not been sufficiently studied in the context of LUAD. Immunohistochemical analysis was used to detect the expression of NCAPG in LUAD tissues, and the relationships between NCAPG and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to verify the role of NCAPG in LUAD. Finally, we studied the specific mechanism of action of NCAPG in LUAD. Results Through comprehensive analysis of the GSE43458, GSE75037, and The Cancer Genome Atlas databases, we identified 517 overlapping DEGs. Among them, NCAPG was identified as a hub gene. Immunohistochemical analysis revealed that NCAPG was strongly associated with the clinical stage, M-classification, and N-classification. Univariate and multivariate Cox regression analyses indicated that NCAPG was a prognostic risk factor for LUAD, while the in vitro experiments showed that NCAPG overexpression promoted proliferation, migration, invasion, and epithelial-mesenchymal transition. Furthermore, knockdown of NCAPG inhibited LUAD progression, both in vitro and in vivo. Mechanistically, NCAPG overexpression increased p-Smad2 and p-Smad3 expressions in the transforming growth factor β (TGF-β) signaling pathway. Additionally, rescue experiments indicated that TGF-β signaling pathway inhibitors could restore the effect of NCAPG overexpression in LUAD cells. Conclusions NCAPG may promote proliferation and migration via the TGF-β signaling pathway in LUAD.

Introduction: The timely alleviation of symptoms is essential for managing community-acquired pneumonia (CAP). Juhongtanke oral solution is a traditional marketed Chinese patent medicine believed to ease CAP symptoms. The currently available evidence is based on a few retrospective studies of patients with various types of pneumonia, whereas robust randomized controlled trials (RCTs) that support this notion are lacking.Material and methods: In this multi-center, prospective RCT, patients were randomly allocated to receive routine treatment alone or a combination of Juhongtanke oral solution (20 mL q8h) for 5 days and maintained for an additional 3-day safety observation period. The primary outcome was Breathlessness, Cough, and Sputum Scale (BCSS) score evaluated on day 5. Secondary outcomes included the evaluation of cough and dyspnea items in the Visual Analogue Scale (VAS) from days 1–5, remission rate in BCSS and VAS during the treatment course, and the length of hospitalization and in-hospital mortality.Results: Of 272 patients assessed for eligibility, 240 were enrolled in the study (n =120 per group). The mean difference in BCSS evaluated on day 5 was a median 1 point [95%CI (1.00, 2.00)], significantly lower in the treatment group compared with the control group (p < 0.001). Similar results were observed in VAS on day 5, with statistics of a median 2 points [95%CI (1.40, 2.50)] in the cough item and a median 1 point [95%CI (0.50, 2.00)] in the dyspnea item, significantly lower in the treatment group compared with the control group (both p < 0.001). The treatment group had a favorable outcome in BCSS and VAS remission rate assessments compared with the control group, with 99.50% vs. 89.17% in BCSS (p = 0.01), 98.33% vs. 75% in the cough item of VAS (p < 0.001), and 88.33% vs. 62.50% in the dyspnea item of VAS (p < 0.001), respectively. No notable adverse effects were observed during the study. No differences were observed in the length of hospitalization between groups (with a median of 7 days for both groups, p = 0.871).Conclusion: Juhongtanke oral solution may be considered to alleviate the clinical symptoms of CAP.

Differential diagnosis of hypoglycaemia can at times be challenging for patients who appear to be well. Here we identify the case of a 66-year-old Chinese man presenting with recurrent episodes of fasting hypoglycaemia and confusion without any other manifestations. He had no personal or family history of diabetes, nor was he on any hypoglycaemic drugs. The fasting insulin levels were elevated while the C-peptide and pro-insulin levels were slightly low or normal. Antibodies against insulin were negative and levels of insulin-like growth factors were normal. A series of imaging diagnosis excluded the presence of insulinoma or ectopic insulin-secreting neuroendocrine tumor. Ultimately, insulin receptor autoantibodies (IRAb) were detected by both immunoprecipitation assay and enzyme-linked immunosorbent assay (ELISA) developed in house. In a cell study, the immunoglobulins isolated from this patient exerted insulin-like effects on stimulation of post-insulin receptor signaling and glucose uptake as well as inhibited 125I-insulin binding with insulin receptors. Collectively, this patient was diagnosed with IRAb-induced autoimmune hypoglycaemia. Although this patient had no obvious immune disorders, several autoantibodies were identified in his plasma samples, suggesting the patient might have mild aberrant autoimmunity and therefore generated IRAb. IRAb-related disease is uncommon and possibly underdiagnosed or missed due to the lack of simple detection methods for IRAb. Our in-house user-friendly ELISA kit provides a valuable tool for diagnosis of this disease.

The flowers of tea plants (Camellia sinensis), as well as tea leaves, contain abundant secondary metabolites and are big potential resources for the extraction of bioactive compounds or preparation of functional foods. However, little is known about the biosynthesis and transcriptional regulation mechanisms of those metabolites in tea flowers, such as terpenoid, flavonol, catechins, caffeine, and theanine. This study finely integrated target and nontarget metabolism analyses to explore the metabolic feature of developing tea flowers. Tea flowers accumulated more abundant terpenoid compounds than young leaves. The transcriptome data of developing flowers and leaves showed that a higher expression level of later genes of terpenoid biosynthesis pathway, such as Terpene synthases gene family, in tea flowers was the candidate reason of the more abundant terpenoid compounds than in tea leaves. Differently, even though flavonol and catechin profiling between tea flowers and leaves was similar, the gene family members of flavonoid biosynthesis were selectively expressed by tea flowers and tea leaves. Transcriptome and phylogenetic analyses indicated that the regulatory mechanism of flavonol biosynthesis was perhaps different between tea flowers and leaves. However, the regulatory mechanism of catechin biosynthesis was perhaps similar between tea flowers and leaves. This study not only provides a global vision of metabolism and transcriptome in tea flowers but also uncovered the different mechanisms of biosynthesis and transcriptional regulation of those important compounds.

ObjectivesClear cell renal cell carcinoma (ccRCC) is highly prevalent, prone to metastasis, and has a poor prognosis after metastasis. Therefore, this study aimed to develop a prognostic model to predict the individualized prognosis of patients with metastatic clear cell renal cell carcinoma (mccRCC).Patients and MethodsData of 1790 patients with mccRCC, registered from 2010 to 2015, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The included patients were randomly divided into a training set (n = 1253) and a validation set (n = 537) based on the ratio of 7:3. The univariate and multivariate Cox regression analyses were used to identify the important independent prognostic factors. A nomogram was then constructed to predict cancer specific survival (CSS). The performance of the nomogram was internally validated by using the concordance index (C-index), calibration plots, receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). We compared the nomogram with the TNM staging system. Kaplan–Meier survival analysis was applied to validate the application of the risk stratification system.ResultsDiagnostic age, T-stage, N-stage, bone metastases, brain metastases, liver metastases, lung metastases, chemotherapy, radiotherapy, surgery, and histological grade were identified as independent predictors of CSS. The C-index of training and validation sets are 0.707 and 0.650 respectively. In the training set, the AUC of CSS predicted by nomogram in patients with mccRCC at 1-, 3- and 5-years were 0.770, 0.758, and 0.757, respectively. And that in the validation set were 0.717, 0.700, and 0.700 respectively. Calibration plots also showed great prediction accuracy. Compared with the TNM staging system, NRI and IDI results showed that the predictive ability of the nomogram was greatly improved, and DCA showed that patients obtained clinical benefits. The risk stratification system can significantly distinguish the patients with different survival risks.ConclusionIn this study, we developed and validated a nomogram to predict the CSS rate in patients with mccRCC. It showed consistent reliability and clinical applicability. Nomogram may assist clinicians in evaluating the risk factors of patients and formulating an optimal individualized treatment strategy.

The presence of arabinoxylan in wholewheat flour affects its quality significantly. Here, an efficient arabinoxylan hydrolytic enzyme, Hmxyn, from Halolactibacillus miurensis was identified and heterologously expressed in pichia pastoris. Moreover, its relevant properties, including potential application in the wholewheat bread were evaluated. Recombinant Hmxyn exhibited maximal activity at 45°C and pH 6.5, and was stable at mid-range temperature (

Aluminium hydroxide (ATH) filled silicone rubber working in a wide temperature range has to experience the crystallization process in many cases, in which mechanical properties would change greatly and its safety operation is threatened. In this paper, the structure-tensile properties relationship study of ATH filled silicone rubber from melting to crystallized state was carried out. By the differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS), it was found that ATH promoted heterogeneous nucleation in silicone rubber. With the increase of ATH, the proportion of rigid amorphous phase decreases. Meanwhile, the over doped ATH reduces the perfection of crystals during isothermal crystallization at −60 °C. Consequently, the elongation at break of high-content ATH filled silicone rubber with less crystalline and rigid amorphous phase dropped sharply by about 97% due to the failure of lamellae slips, which should arouse great attention for safety operation of ATH filled silicone rubber. It is thereby suggested to take the elongation at break as one of the criteria for the selection of ATH filled silicone rubber used in extremely low temperature.

Clinical significance and biological functions of the ferroptosis pathway were addressed in all aspect of cancer regarding multi-omics level; however, the overall status of ferroptosis pathway alteration was hard to evaluate. The aim of this study is to comprehensively analyze the putative biological, pathological, and clinical functions of the ferroptosis pathway in breast cancer on a pathway level. By adopting the bioinformatic algorithm “pathifier”, we quantified five programmed cell death (PCD) pathways (KO04210 Apoptosis; KO04216 Ferroptosis; KO04217 Necroptosis; GO:0070269 Pyroptosis; GO:0048102 Autophagic cell death) in breast cancer patients, and we featured the clinical characteristics and prognostic value of each pathway in breast cancer and found significantly activated PCD in cancer patients, among which ferroptosis demonstrated a significant correlation with the prognosis of breast cancer. Correlation analysis between PCD pathways identified intra-tumor heterogeneity of breast cancer. Therefore, clustering of patients based on the status of PCD pathways was done. Comparisons between subgroups highlighted specifically activated ferroptosis in cluster 2 patients, which showed the distinct status of tumor immunity and microenvironment from other clusters, indicating putative correlations with ferroptosis. NDUFA13 was identified and selected as a putative biomarker for cluster 2 patients. Experimental validations were executed on cellular level and NDUFA13 showed an important role in regulating ferroptosis activation and can work as a biomarker for ferroptosis pathway status. In conclusion, the status of the ferroptosis pathway significantly correlated with the clinical outcomes and intra-tumor heterogeneity of breast cancer, and NDUFA13 expression was identified as a positive biomarker for ferroptosis pathway activation in breast cancer patients.

Background: Curcumin (CUR) displays the capability of suppressing the proliferation and metastasis of various cancer cells. However, the effects and underline mechanisms of CUR to treat triple-negative breast cancer (TNBC) have not been systematically elucidated with an appropriate method.Methods: In the present research, a combination method of network pharmacology, molecular docking, and in vitro bio-experiment was used to investigate the pharmacological actions and underline mechanisms of CUR against TNBC. First, common targets of CUR and TNBC were screened via Venny 2.1.0 after potential CUR-related targets and targets of TNBC were got from several public databases. Then, the Gene Ontology (GO) function and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on the Metascape website, and the network of compound-targets-pathways was constructed via Cytoscape software. Moreover, the network of protein-protein interaction was constructed by the STRING database to screen potential targets. Moreover, molecular docking was applied to affirm the interaction of CUR with the screened top 10 potential targets. Finally, in vitro experiments were used to further verify the effects and mechanisms of CUR and its nano-formulation (CUR-NPs) against TNBC.Results: Forty potential targets of CUR against TNBC were obtained. STAT3, AKT1, TNF, PTGS2, MMP9, EGFR, PPARG, NFE2L2, EP300, and GSK3B were identified as the top 10 targets of CUR against TNBC. In vitro experiment verified that CUR and CUR-NPs could not only restrain the invasion, migration, and proliferation of MDA-MB-231 cells but also induce their apoptosis. In addition, molecular docking demonstrated that CUR could bind spontaneously with the screened top 10 targeted proteins, and a real-time PCR experiment demonstrated that both CUR and CUR-NPs could downregulate the genetic expression levels of the 10 targets. Moreover, according to the CUR-targets-pathways network, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance, JAK-STAT, Foxo, and HIF-1 signaling pathways were identified as the important pathways of CUR effects on TNBC. Among them, the inhibiting effects of CUR and CUR-NPs on the JAK-STAT signaling pathway were further verified by the western blot analysis.Conclusion: Taken together, the present research demonstrates that CUR and CUR-NPs have pharmacological effects against TNBC via a multi-target and multi-pathway manner.

Background and aimsInflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear.MethodsAcute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg−1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation.ResultsGML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1β and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-β). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus.ConclusionsWe showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.

PurposeAging is a process associated with degeneration and dysfunction of peripheral vestibular system or apparatus. This study aimed to investigate the influence of aging on ocular vestibular-evoked myogenic potential (oVEMP) response rates and recording parameters using the B81 bone vibrator and compare them with air conduction stimuli (ACS) oVEMP response characteristics.MethodsIn 60 healthy participants aged 10–71 years (mean age 39.9; 29 male participants), the oVEMP response was elicited using a B81 bone vibrator and an ER-3A insert earphone. The effects of age and stimulus on oVEMP response rates and recording parameters were evaluated.ResultsResponse rates and amplitudes declined with aging using either ACS or bone-conducted vibration (BCV) stimulation, particularly in individuals over 60 years of age, whereas thresholds increased and N1 latencies were prolonged. BCV showed fewer risks of absent oVEMP response than ACS (p = 0.002). BCV acquired higher amplitudes (p < 0.001), lower thresholds, and shorter N1 and P1 latencies (all p < 0.001) than ACS.ConclusionsThe absence of an oVEMP response may be attributed to aging rather than a concurrent vestibular disorder. B81-BCV likely produces higher mechanical drives to the vestibular hair cells at safer and non-traumatic levels compared with ACS and therefore may be more likely to evoke a response in the elderly cohort, whose vestibular function and mechanical sensitivity have declined. Thus, B81-BCV stimulation is more effective and safer to elicit oVEMPs, and it should be recommended when ACS fails in the clinic, particularly in the elderly population.

As an approach to feature estimation, exponential fitting has attracted research interests in mathematical modeling. Semantic networks are used for numerous applications in computers, physics, and biology. However, such applications may have fitting troubles with various mathematical tools. Therefore, we present a novel method of fitting 2n data points of a signal to a sum of n exponential functions. The experiments proved that the proposed method operated well for linear and nonlinear functions, as its algorithm was straightforward, practical, and easy to determine. At the same time, the computational intricacy was considerably low, which has specific worth in use.

Butterflies are key indicators of urban biodiversity and one of the most vulnerable organism groups to environmental changes. Studying how butterflies are distributed and what factors might influence them in urban green spaces is crucial. In this study, from July 2022 to September 2022, we examined and analyzed the butterfly diversity in nine parks in Fuzhou, China, along three different levels of urbanization (urban, peri-urban, and suburban). We investigated how butterfly communities respond to increasing urbanization. The findings revealed that: (1) A total of 427 butterfly individuals from 4 families and 13 species were observed; (2) Shannon diversity, richness, and abundance of the overall butterfly community were lower in the more urbanized parks. Urbanization had significant effects on Shannon diversity (p = 0.003) and abundance (p = 0.007) but no significant effects on the whole butterfly community richness (p = 0.241); (3) non-metric multidimensional scaling revealed that there were differences in the overall number of butterfly species in urban parks among different geographic regions.

Southern China is a major rice-producing region where mixed rice cropping systems (single cropping rice (SCR) and double-cropping rice (DCR)) are widely practiced. An accurate estimation of the spatiotemporal changes in cropping systems is important for understanding the dynamic of paddy rice system and for developing suitable agricultural policies. However, few studies focus on mapping long-term changes in cropping systems in this subtropical region. The objective of this research is 1) to improve the phenology- and pixel-based paddy rice mapping (PPPM) algorithm by simultaneously considering the phenology signatures in the rice transplanting and heading periods; 2) to better identify different rice cropping systems and analyze their changes. Based on the improved PPPM method, we generated annual maps of SCR and DCR in southern China with image collection of Landsat 5, 7, and 8 from 1999 to 2019 using the Google Earth Engine platform. The overall accuracies of cropping system results for the study regions range from 81.0% to 98.1% depending on the areas of interest created in our study area. Then, the spatiotemporal patterns of the annual SCR and DCR time series were analyzed. In 2000, the total rice area was 208,614.6 km2, decreased sharply in 2003, and thereafter, the total increase in the paddy rice area fluctuated until 2011. From 2000 to 2019, the total rice area decreased to 171,474.3 km2 in 2019. The results showed that relatively stable SCR mainly distributed in Anhui, Hubei, and Jiangsu provinces whereas DCR occurred in Guangdong, Hunan and Jiangxi provinces. DCR-to-SCR conversion occurred drastically in Hunan, Hubei, and Jiangxi provinces. Rice-to-non-rice conversion was more prevalent in Hunan and Hubei provinces. Detailed spatiotemporal information over 20 years suggested that the plans for agricultural resources utilization in some specific provinces should be proposed, which is of great significance for food security in the major rice-producing area in southern China.

Abstract Background The apple snail, Pomacea canaliculata, is one of the world’s 100 worst invasive alien species and vector of some pathogens relevant to human health. Methods On account of the importance of gut microbiota to the host animals, we compared the communities of the intestinal microbiota from P. canaliculata collected at different developmental stages (juvenile and adult) and different sexes by using high-throughput sequencing. Results The core bacteria phyla of P. canaliculata gut microbiota included Tenericutes (at an average relative abundance of 45.7 %), Firmicutes (27.85 %), Proteobacteria (11.86 %), Actinobacteria (4.45 %), and Cyanobacteria (3.61 %). The female group possessed the highest richness values, whereas the male group possessed the lowest bacterial richness and diversity compared with the female and juvenile group. Both the developmental stages and sexes had important effects on the composition of the intestinal microbiota of P. canaliculata. By LEfSe analysis, microbes from the phyla Proteobacteria and Actinobacteria were enriched in the female group, phylum Bacteroidetes was enriched in the male group, family Mycoplasmataceae and genus Leuconostoc were enriched in the juvenile group. PICRUSt analysis predicted twenty-four metabolic functions in all samples, including general function prediction, amino acid transport and metabolism, transcription, replication, recombination and repair, carbohydrate transport and metabolism, etc. Conclusions This study provided a general understanding of the diversity characteristics of intestinal microbial communities of P. canaliculata, and indicated that developmental stage and gender could both influence the intestinal microbes of P. canaliculata. Further study may focus on the interaction between the gut microbiota and their host.

Abstract Heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of hospitalizations and mortality when diagnosed at the age of ≥ 65 years. HFpEF represents multifactorial and multisystemic syndrome and has different pathophysiology and phenotypes. Its diagnosis is difficult to be established based on left ventricular ejection fraction and may benefit from individually tailored approaches, underlying age-related changes and frequent comorbidities. Compared with the rapid development in the treatment of heart failure with reduced ejection fraction, HFpEF presents a great challenge and needs to be addressed considering the failure of HF drugs to improve its outcomes. Further extensive studies on the relationships between HFpEF, aging, and comorbidities in carefully phenotyped HFpEF subgroups may help understand the biology, diagnosis, and treatment of HFpEF. The current review summarized the diagnostic and therapeutic development of HFpEF based on the complex relationships between aging, comorbidities, and HFpEF.

Hongxin Huang and Yongfei Hu et al. develop Tag-seq, a streamlined sequencing method to examine off-target editing by CRISPR-Cas systems. The authors validate Tag-seq in multiple cell lines, demonstrating its broad utility and flexibility in identifying off-target genome editing.

Abstract Background The regulation of the transcription factor sex-determining region Y-box transcription factor 9 (SOX9) in lung development has been described in mouse, but the same principles apply to human lung development is unknown due to a lack of appropriate experimental approaches and models. Methods Here, we used gene editing technology to inactivate SOX9 in human embryonic stem cells that were then induced to differentiate into lung organoids to investigate the role of SOX9 in human lung epithelium development. Results Complete knockout of the transactivation domain of SOX9 by gene editing resulted in indels in both alleles of SOX9. SOX9−/− hESCs could be induced to differentiate into lung progenitor organoids. In vitro long-term expansion showed that SOX9 inactivation did not affect the differentiation of pulmonary epithelial cells, but promoted apoptosis and reduced proliferative capacity in the organoids. When lung progenitor organoids were transplanted under the kidney capsule of immunodeficient mice, expression of the club cell marker secretoglobin family 1A member 1 (SCGB1A1) was detected in SOX9−/− transplants but was absent in wild-type (WT) transplants. The maturation of goblet cells was also affected by SOX9 inactivation, as evidenced by the presence of mucin 5 AC (MUC5AC) in the cytoplasm of SOX9−/− grafts as compared to WT grafts in which most MUC5AC was secreted into the lumen. In vivo lung orthotopic transplantations showed that SOX9 inactivation had a limited effect on the differentiation of alveolar cells and lung regeneration in injured mice. Conclusions SOX9 modulates the proliferative capacity of lung epithelium but is not an indispensable transcription factor in the regulation of human lung epithelium development.

Abstract. Background:. One inevitable shortcoming of non-invasive prenatal screening (NIPS)/cell-free DNA (cfDNA) sequencing is the uninterpretable (“no-call”) result, which is mainly caused by an insufficient fetal fraction. This study was performed to investigate the factors associated with a successful second NIPS in these cases and determine the optimal management for women with initial no-call results. Methods:. We retrospectively analyzed the data of women who underwent NIPS with initial no-call results due to an insufficient fetal fraction from 2017 to 2019 in our center. We compared these women's maternal and pregnancy information with the data of women who had attained a successful second NIPS result and women who had received no-call results for a second time. Results:. Among the 33,684 women who underwent NIPS, 137 with a no-call result underwent a retest. Comparison between the 87 (63.50%) women with a successful retest and the other 50 (36.50%) women showed a significant difference in both the initial fetal fraction and maternal body mass index (BMI), whereas the other factors showed no significant differences. In addition, with an initial fetal fraction of

Abstract Background A reliable and effective method is required to deliver agent that can aid the in vivo imaging of retinal vessels. The aim of the present study was to evaluate retro-orbital (RO) injection of fluorescein-labeled isothiocyanate dextran (FITC-dextran) as a method of demonstrating retinal neovascularization (NV) and avascular areas in oxygen-induced retinopathy (OIR) mice. Methods Different concentrations of FITC-dextran were used to compare the efficacy of this agent in perfusing the retinal vessels. Hematoxylin–eosin (HE) staining was used to evaluate the safety of RO injection. The vitreous blood vessels and extent of NV were assessed in P17 OIR mice using FITC-dextran and compared with the corresponding measurements obtained following isolectin B4 staining or the combination of both methods. Results The fluorescence of small vessels and neovascular tufts could be observed clearly following RO injection of 0.05 ml of 25 mg/ml or 50 mg/ml FITC-dextran. No visible damage to tissues adjacent to the injection site was discovered. Vitreous blood flow was gradually reduced from P0 to P5 and eventually disappeared in P17 OIR mice, as demonstrated by FITC-dextran perfusion. The retinal NV areas assessed by isolectin B4 were larger than those assessed by FITC-dextran, but the retinal avascular areas were smaller. The combination of both methods could conduce to distinguish non-functional blood vessels. Conclusions RO injection of FITC-dextran combined with isolectin B4 is an effective, optimal method for assessing the NV area and avascular area.

With the rapid development of synthetic biology, a variety of biopolymers can be obtained by recombinant microorganisms. Polyhydroxyalkanoates (PHA) is one of the most popular one with promising material properties, such as biodegradability and biocompatibility against the petrol-based plastics. This study reviews the recent studies focusing on the microbial synthesis of PHA, including chassis engineering, pathways engineering for various substrates utilization and PHA monomer synthesis, and PHA synthase modification. In particular, advances in metabolic engineering of dominant workhorses, for example Halomonas, Ralstonia eutropha, Escherichia coli and Pseudomonas, with outstanding PHA accumulation capability, were summarized and discussed, providing a full landscape of diverse PHA biosynthesis. Meanwhile, we also introduced the recent efforts focusing on structural analysis and mutagenesis of PHA synthase, which significantly determines the polymerization activity of varied monomer structures and PHA molecular weight. Besides, perspectives and solutions were thus proposed for achieving scale-up PHA of low cost with customized material property in the coming future.

Introduction Hypertension is a common risk factor for cardiovascular disease. Transcutaneous electrical acupoint stimulation (TEAS) may be effective for hypertension, but the evidence remains limited. The aim of this study is to evaluate the effectiveness and safety of the smart phone-based TEAS as adjunctive therapy for hypertension.Methods and analysis This study is a 52-week cluster randomised controlled trial with 1600 hypertension patients in 32 community health service centres. Patients who meet the inclusion criteria will be randomised into usual care group or TEAS group in a 1:1 ratio. All patients will be provided with usual care as recommended by the guidelines. In addition to this, patients in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at home, 4 times weekly for 12 weeks. The primary outcome will be the mean difference in the changes in office systolic blood pressure from baseline to 12 weeks between TEAS and usual care groups. Secondary outcomes will include the change of mean diastolic blood pressure, proportion of patients with controlled blood pressure (blood pressure

Background: Ubiquitin specific protease 1 (USP1) tightly correlates with poor prognosis of multiple cancers. However, whether USP1 underlies ovarian cancer (OV) progression remains unclarified.Methods: First, GSEA strategy and WGCNA analysis were used to screen for anti-ovarian cancer drugs and furthern optimal module, respectively. In addition, functional enrichments of module genes were realized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Kaplan-Meier was then employed to analyze the prognostic impact of USP1 expression on OV patients. Cell proliferation and cell cycle assays were used to confirm biological functions of USP1 in the final.Results: Through the forementioned methods, we obtained five candidate drugs against OV from 353 anticancer drugs, and proposed ML323 as a novel anti-OV drug. As our hypothesized, ML323 significantly inhibited the proliferation of OV cells. Combined with WGCNA and KEGG analysis, the turquoise module was related to ML323, together with cell cycle. USP1 was subsequently identified as a target of ML323 and according to the TCGA database, USP1 negatively correlated with prognosis in OV, and its reduction and ML323-treatment both inhibited the proliferation of OV cells, blocking the S phase of cell cycle in vitro.Conclusion: Taken together, ML323 exerts its inhibitory effect on the proliferation of OV cells by targeting USP1-regulated cell cycle, providing a therapeutical strategy and potential target against OV.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P

Summary: This protocol describes how to generate lung organoids from human embryonic stem cells. Lung organoids form by self-assembly in Matrigel and contain lung epithelial cell types. The protocol presented in this study is simple and only uses 6 cytokines or small molecules. This protocol provides a promising tool to study human lung development, drug screening, regeneration, and disease modeling in vitro.For complete details on the use and execution of this protocol, please refer to Chen et al. (2018).

Previous studies have demonstrated that the brain functional modular organization, which is a fundamental feature of the human brain, would change along the adult lifespan. However, these studies assumed that each brain region belonged to a single functional module, although there has been convergent evidence supporting the existence of overlap among functional modules in the human brain. To reveal how age affects the overlapping functional modular organization, this study applied an overlapping module detection algorithm that requires no prior knowledge to the resting-state fMRI data of a healthy cohort (N = 570) aged from 18 to 88 years old. A series of measures were derived to delineate the characteristics of the overlapping modular structure and the set of overlapping nodes (brain regions participating in two or more modules) identified from each participant. Age-related regression analyses on these measures found linearly decreasing trends in the overlapping modularity and the modular similarity. The number of overlapping nodes was found increasing with age, but the increment was not even over the brain. In addition, across the adult lifespan and within each age group, the nodal overlapping probability consistently had positive correlations with both functional gradient and flexibility. Further, by correlation and mediation analyses, we showed that the influence of age on memory-related cognitive performance might be explained by the change in the overlapping functional modular organization. Together, our results revealed age-related decreased segregation from the brain functional overlapping modular organization perspective, which could provide new insight into the adult lifespan changes in brain function and the influence of such changes on cognitive performance.

Abstract Background Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal diseases. Although acupuncture has become a common alternative therapy for IBS, there is insufficient evidence for its effectiveness. This study was designed to assess the efficacy and feasibility of acupuncture in the treatment of IBS. Methods/design This is a multicenter randomized controlled clinical trial. According to the ratio of 1:1:1, 90 patients with irritable bowel syndrome will be randomly divided into specific acupoints (SA) group, non-specific acupoints (NSA) group, and non-acupoints (NA) group. All patients will be treated with acupuncture 12 times within 4 weeks and followed up for 8 weeks. The primary outcome is the response rate, the percentage of patients whose average value of worst abdominal pain is 30% better and the days of loose stool is 50% less than the baseline, at week 4 after randomization. The secondary outcomes include the response rates at other time points, IBS Symptom Severity Scale (IBS-SSS), Patient Health Questionnaire-9 depression scale (PHQ-9), IBS-Quality of Life scale (IBS-QOL), IBS Adequate Relief (IBS-AR), Abdominal Pain Score, Abdominal Bloating Score, Bristol Stool Score (BBS), blinding assessment, and credibility evaluation. Adverse events will be monitored and recorded during the trial. Trial registration Chictr.org.cn ChiCTR2000030670. Registered on 9 March 2020.

Abstract One of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes. Phosphofructokinase (PFKM), one of the most important regulatory enzymes of glycolysis, was S-nitrosylated by nitric oxide synthase NOS1 at Cys351. S-nitrosylation at Cys351 stabilized the tetramer of PFKM, leading to resist negative feedback of downstream metabolic intermediates. The PFKM-C351S mutation decreased the proliferation rate of cultured cancer cells, and reduced tumor growth and metastasis in the mouse xenograft model. These findings indicated that S-nitrosylation at Cys351 of PFKM by NOS1 contributes to the metabolic reprogramming of ovarian cancer cells, highlighting a critical role of endogenous nitrogen oxide on metabolism regulations in tumor progression.

Abstract Background Delays in care-seeking for childhood illness may lead to more severe outcomes. We evaluated whether community distance from a primary healthcare facility was associated with decreased healthcare utilization in a rural district of northwestern Burkina Faso. Methods We conducted passive surveillance of all government-run primary healthcare facilities in Nouna District, Burkina Faso from March 1 through May 31, 2020. All healthcare visits for children under 5 years of age were recorded on a standardized form for sick children. We recorded the age, sex, and community of residence of the child as well as any diagnoses and treatments administered. We calculated healthcare utilization per 100 child-months by linking the aggregate number of visits at the community level to the community’s population of children under 5 months per a census that was conducted from August 2019 through February 2020. We calculated the distance between each community and its corresponding healthcare facility and assessed the relationship between distance and the rate of healthcare utilization. Results In 226 study communities, 12,676 primary healthcare visits were recorded over the three-month period. The median distance between the community and primary healthcare facility was 5.0 km (IQR 2.6 to 6.9 km), and median number of healthcare visits per 100 child-months at the community level was 6.7 (IQR 3.7 to 12.3). The rate of primary healthcare visits declined with increasing distance from clinic (Spearman’s rho − 0.42, 95% CI − 0.54 to − 0.31, P

In the submerged fermentation process, the introduction of novel nutrient media as sources of carbon and nitrogen can enhance antifungal activity. In this study, we used a submerged fermentation process to find the optimal media for the Bacillus velezensis BP-1 strain to grow in, and that would boost its antifungal activity against Peyronellaea arachidicola. By using a single-factor test and central composite design (CCD) in the response surface methodology, the optimal fermentation medium for the B. velezensis BP-1 strain was identified. The antagonistic potential of B. velezensis BP-1 was assayed against the P. arachidicola fungus to manage web blotch disease in peanut plant leaves. The LB medium was screened as the best medium, with a maximum antifungal activity of 90% in comparison to the other mediums. Semolina flour as the carbon source, peanut root extract as the nitrogen source, and magnesium sulfate as the inorganic salt were selected as the best nutrient components in comparison to the others. The response surface methodology was optimized by using 15 g/L of semolina flour as the carbon source, 13.68 g/L of peanut root extract as the nitrogen source, and 0.50 g/L of magnesium sulfate as the inorganic salt, achieving 90% inhibition of P. arachidicola. The in vitro bioassays showed that the optimized fermentation broth of B. velezensis BP-1 had significant antifungal activity, with an inhibition rate of 88.34% against P. arachidicola. In the pot experiments on disease control, the management effects revealed that the pre-inoculation spray of the B. velezensis BP-1 broth had significant efficiency (96%) when compared to the post-inoculation spray of the B. velezensis BP-1 broth. These findings suggest that the optimized fermentation broth of the B. velezensis BP-1 strain had strong antifungal activity. This could be a potent biocontrol tool for aiding in the early disease management of web blotch in peanut plants.

In Taiwan, oral cancer is the fourth most common cause of cancer death in men. The complications and side effects of oral cancer treatment pose a considerable challenge to family caregivers. The purpose of this study was to analyze the self-efficacy of the primary family caregivers of patients with oral cancer at home. A cross-sectional descriptive research design and convenience recruiting were adopted to facilitate sampling, and 107 patients with oral cancer and their primary family caregivers were recruited. The Caregiver Caregiving Self-Efficacy Scale-Oral Cancer was selected as the main instrument to be used. The primary family caregivers’ mean overall self-efficacy score was 6.87 (SD = 1.65). Among all the dimensions, managing patient-related nutritional issues demonstrated the highest mean score (mean = 7.56, SD = 1.83), followed by exploring and making decisions about patient care (mean = 7.05, SD = 1.92), acquiring resources (mean = 6.89, SD = 1.80), and managing sudden and uncertain patient conditions (mean = 6.17, SD = 2.09). Our results may assist professional medical personnel to focus their educational strategies and caregiver self-efficacy enhancement strategies on the dimensions that scored relatively low.

Brain metastasis (BM) is common in patients with non-small cell lung cancer (NSCLC) and is associated with a poor prognosis. Ceramide synthase 1 (CERS1) participates in malignancy development, but its potential role in NSCLC BM remains unclear. This study aimed to explore the physiological effects and molecular mechanism of CERS1 in NSCLC BM. CERS1 expression was evaluated in NSCLC tissues and cell lines, and its physiological roles were subsequently explored in vivo and in vitro. Mass spectrometry and co-immunoprecipitation were performed to explore CERS1-interacting proteins. The associated signaling pathways of CERS1 in NSCLC BM were further investigated using bioinformatics analysis and molecular biotechnology. We demonstrated that CERS1 was significantly downregulated in NSCLC cell lines and BM tissues, and its upregulation was associated with better prognoses. In vitro, CERS1 overexpression inhibited cell migration, invasion, and the ability to penetrate the blood-brain barrier. Moreover, CERS1 interacted with ubiquitin-specific protease 14 (USP14) and inhibited BM progression by downregulating the PI3K/AKT/mTOR signaling pathway. Further, CERS1 expression substantially suppressed BM tumor formation in vivo. This study demonstrated that CERS1 plays a suppressor role in NSCLC BM by interacting with USP14 and downregulating the PI3K/AKT/mTOR signaling pathway, thereby serving as a novel therapeutic target for NSCLC BM.

Abstract Background Atrial fibrillation (AF) is a common arrhythmia, which is closely related to cardiovascular morbidity and mortality. Although acupuncture is used in the treatment of AF, the evidence is insufficient. The objective of this pilot trial is to evaluate the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after catheter ablation (CA). Methods and design This will be a multi-center, 3-arm, pilot randomized controlled trial in China. Sixty patients in total will be randomly assigned to the specific acupoints group, the non-specific acupoints group, or the non-acupoints group in a 1:1:1 ratio. The whole study period is 6 months, including a 3-month treatment period and a 3-month follow-up period. All patients will receive 18 sessions of acupuncture over 12 weeks after CA and appropriate post-ablation routine treatment. The primary outcome is AF burden at 6 months after CA measured by electrocardiography patch that can carry out a 7-day continuous ambulatory electrocardiographic monitoring. The secondary outcomes include AF burden at 3 months after CA, recurrence of AF, quality of life, etc. The adverse events will also be recorded. Discussion This pilot study will contribute to evaluating the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after CA. The results will be used for the sample size calculation of a subsequent large-scale trial. Trial registration Chinese Clinical Trial Registry ChiCTR2000030576 . Registered on 7 March 2020.

Na0.5Bi0.5TiO3 (NBT)-based ceramics have been widely used as dielectric materials for energy storage capacitors because of their environmental friendliness and excellent ferroelectric properties. However, their energy storage performance still needs to be further improved to satisfy the increasing demand. Herein, we report a novel 0.90(Na0.5Bi0.5)0.7Sr0.3TiO3-0.10Bi(Ni0.5Sn0.5)O3 (0.90NBST-0.10BNS) ceramic with significantly improved energy density (5.0 J cm−3), enhanced recoverable energy density (4.18 J cm−3) and high energy efficiency (83.64%) through the incorporation of Bi(Ni0.5Sn0.5)O3 (BNS), due to the increased breakdown strength and the relaxation ferroelectric (RFE) properties. The first-order reversal curve (FORC) measurements confirm that the addition of BNS improves RFE properties by breaking the order of long-range ferroelectricity. The 0.90NBST-0.10BNS ceramic also possesses an outstanding temperature and frequency stability of energy storage properties in the range of 20 °C–140 °C and 1 Hz–100 Hz, respectively. More importantly, the discharge properties characterized by a preeminent power density (36.19 MW cm−3), transient energy release times (144.2 ns), and high discharge energy density (1.16 J cm−3) also synchronously observed in 0.90NBST-0.10BNS ceramic. These results show that the 0.90NBST-0.10BNS ceramic with outstanding comprehensive performances is a promising energy storage ceramic candidate for capacitors in high power systems.

Abstract Background The exploration of new therapeutic agents targeting 5-Fu resistance may open a new opportunity to gastric cancer treatment. The objective is to establish a 5-Fu resistant gastric cancer cell line and observe the effect of Jianpi Yangwei decoction (JPYW) on its apoptosis and drug-resistance related proteins. Methods MTT assay was used to measure the effect of JPYW on the BGC823 cells proliferation, and the apoptosis was observed by flow cytometry and Hoechst fluorescence staining. The BGC823 xenograft tumor nude mice models were established, the apoptosis was detected by Tunel method. BGC-823/5-Fu was established by repeated low-dose 5-Fu shocks, the drug resistance index and proliferation were detected by the MTT assay; MDR1 mRNA was detected by real-time RT-PCR; Western blot was used to detect the ratio of p-AKT to AKT; The BGC823/5-Fu xenograft tumor nude mice models were established and apoptosis was measured. The expressions of MRP1, MDR1, ABCG2, AKT, p-AKT, caspase-3 and bcl-2 were detected by immunohistochemistry and the AKT mRNA expression was detected by real-time RT-PCR. Results JPYW induced apoptosis in BGC823 cells; Drug-resistant cell line BGC-823/5-Fu was sucessfully established; JPYW induced apoptosis of BGC823/5-Fu cells, down-regulated the expression of MRP1, MDR1 and ABCG2 in vitro and in vivo, and further decreased MDR1 expression when combined with pathway inhibitor LY294002 (P

D-allulose is one sort of C-3 epimer of D-fructose with the low calorie (0.4 kcal/g) and high sweetness (70% of the relative sweetness of sucrose), which can be biosynthesized by D-allulose-3-epimerase (DAE). In this work, we report the characterization of a novel DAE from Ruminiclostridium papyrosolvens (RpDAE) by genome mining approach. The activity of RpDAE reached maximum at pH 7.5 and 60°C, supplemented with 1 mM Co2+. Using D-fructose (500 g/L) as the substrate for epimerization reaction, RpDAE produced D-allulose (149.5 g/L). In addition, RpDAE was immobilized within the microporous zeolite imidazolate framework, ZIF67, by in situ encapsulation at room temperature. The synthesized bio-composites were characterized by powder X-ray diffraction and Fourier transform infrared spectroscopy. RpDAE-ZIF67 maintained 56% of residual activity after five reaction cycles. This study provides helpful guidance for further engineering applications and industrial production of D-allulose.

Objective To develop and confirm an individualized predictive model to ascertain the probability of deep venous thrombosis in patients with acute poisoning after undergoing hemoperfusion. Methods Three hundred eleven patients with acute poisoning who were admitted to a hospital in China between October 2017 and February 2019 were included in the development group. Eighty patients with acute poisoning who were admitted between February and May 2019 were included in the validation group. The independent risk factors for deep venous thrombosis were examined. An individualized predictive model was developed using regression coefficients. Results The number of catheter indwelling days, having a catheter while being transported, elevated serum homocysteine concentrations, and dyslipidemia were independent risk factors for deep venous thrombosis following hemoperfusion in patients with acute poisoning. The areas under the receiver operating characteristic curve of the development and validation groups were 0.713 and 0.702, respectively, which suggested that the prediction model had good discrimination capacity. The calibration belts of the two groups were ideal. Conclusions Our prediction model has a moderate predictive effect for the occurrence of deep venous thrombosis in patients with acute poisoning. In clinical practice, this model could be combined with a common thrombosis risk assessment model.

Tobacco (Nicotiana tabacum) root affects the yield and quality of tobacco leaves. To gain insight into the responses of the tobacco root system to different soil types, we integrated morphological characteristics, the physiological index, the metabolic pathways of the root system, and the aboveground biomass of tobacco cultivated in limestone soil (LS), paddy soil (PS), and red soil (RS). Compared with plants growing in LS and PS, the chemical composition of tobacco leaves in RS tended to be coordinated. Red soil facilitated the accumulation of aboveground and belowground biomass of flue-cured tobacco and had the most significant effect on the dry matter quality of the roots. In addition, it promoted an increased root length, root surface area (RSA), root volume, and a higher number of root forks and improved root vigor and nitrate reductase (NR) activity; however, the activities of superoxide dismutase (SOD) and peroxidase (POD) were decreased. We studied differentially the abundant proteins (DAPs) of the flue-cured tobacco roots cultivated in different soil types by isobaric tags for the relative and absolute quantification (iTRAQ) of the proteomic profiles of cultivar. In total, 699, 650, and 569 differentially abundant proteins (DAPs) were identified from limestone soil (LS) vs. PS, LS vs. RS, and PS vs. RS, respectively, including 412/287, 291/359, and 323/246 up-/downregulated proteins, respectively. These DAPs were mainly involved in starch and sucrose metabolism, phenylalanine metabolism, the biosynthesis of secondary metabolites, microbial metabolism in different environments, and ribosomes. The parallel reaction monitoring (PRM) and quantitative reverse transcription PCR (qRT-PCR) analysis showed that the results of the iTRAQ proteomics were reliable. Overall, our study facilitates a new understanding of the responses of tobacco roots to different soil types at the protein level.

As a natural sweetener and sucrose substitute, the biosynthesis and application of steviol glycosides containing the component rebaudioside D have attracted worldwide attention. Here, a glycosyltransferase PgUGT from Panax ginseng was first reported for the biosynthesis of rebaudioside D. With the three-dimensional structures built by homology modeling and deep-learning–based modeling, PgUGT was semi-rationally designed by FireProt. After detecting 16 site-directed variants, eight of them were combined in a mutant Mut8 with both improved enzyme activity and thermostability. The enzyme activity of Mut8 was 3.2-fold higher than that of the wild type, with an increased optimum reaction temperature from 35 to 40°C. The activity of this mutant remained over 93% when incubated at 35°C for 2 h, which was 2.42 times higher than that of the wild type. Meanwhile, when the enzymes were incubated at 40°C, where the wild type was completely inactivated after 1 h, the residual activity of Mut8 retained 59.0% after 2 h. This study would provide a novel glycosyltransferase with great potential for the industrial production of rebaudioside D and other steviol glycosides.

Gentamicin ototoxicity can generate free radicals within the inner ear, leading to permanent damage to sensory hair cells (HCs) and eventually hearing loss. The following study examined the alterations of oxidative damage-related genes in the cochlea and important molecules responsible for oxidation following gentamicin injury in vitro. The RT2 Profiler polymerase chain reaction (PCR) array was used to screen candidate targets for treatment to prevent hearing loss caused by gentamicin. We found that during gentamicin-induced death in HCs, Heme oxygenase-1 (HO-1) had a high fold change in the HCs of the cochlea. Moreover, the use of CoPPIX to induce HO-1 inhibited gentamicin-induced HC death, while HO-1 inhibitors ZnPPIX after CoPPIX reversed this process. Furthermore, the inhibitors of NF-E2-related factor-2 (Nrf2) reduced the expression of HO-1 and inhibited the protective effect of HO-1 after gentamicin, thus suggesting that the Nrf2/HO-1 axis might regulate gentamicin-associated ototoxicity. We further demonstrated that induction of HO-1 up-regulated the expression of Nrf2 in both cochlear and HEI-OC1 cells. In summary, these findings indicated that HO-1 protects HCs from gentamicin by up-regulating its expression in HCs and interacting with Nrf2 to inhibit reactive oxygen species (ROS).

Melanoma is an aggressive malignant skin tumour with an increasing global incidence. However, current treatments have limitations owing to the acquired tumour drug resistance. Ferroptosis is a recently discovered form of programmed cell death characterised by iron accumulation and lipid peroxidation and plays a critical role in tumour growth inhibition. Recently, ferroptosis inducers have been regarded as a promising therapeutic strategy to overcome apoptosis resistance in tumour cells. In this study, we reported that nobiletin, a natural product isolated from citrus peel, and exhibited antitumour activity by inducing ferroptosis in melanoma cells. Subsequently, we further explored the potential mechanism of nobiletin-induced ferroptosis, and found that the expression level of glycogen synthase kinase 3β (GSK3β) in the skin tissue of patients with melanoma was significantly reduced compared to that in the skin of normal tissue. Additionally, nobiletin increased GSK3β expression in melanoma cells. Moreover, the level of Kelch-like Ech-associated protein-1 (Keap1) was increased, while the level of nuclear factor erythroid 2-related factor 2 (Nrf2), and haem oxygenase-1 (HO-1) was decreased in nobiletin-treated melanoma cells, suggesting that the antioxidant defence system was downregulated. Furthermore, knockdown of GSK3β significantly reduced nobiletin-induced ferroptosis and upregulated the Keap1/Nrf2/HO-1 signalling pathway, while the opposite was observed in cells overexpressing GSK3β. In addition, molecular docking assay results indicated that nobiletin showed strong binding affinities for GSK3β, Keap1, Nrf2, and HO-1. Taken together, our results demonstrated that nobiletin could induce ferroptosis by regulating the GSK3β-mediated Keap1/Nrf2/HO-1 signalling pathway in human melanoma cells. Hence, nobiletin stands as a promising drug candidate for melanoma treatment with development prospects.

To establish biosafety risk-management guidelines for clinical departments of military central hospitals in China. Using failure mode and effects analysis (FMEA), we assessed the biosafety risk priority number (RPN) of clinical departments of three military central hospitals. Nosocomial infection (NI), medical substance-associated accident (MSA), medical technology misuse (MTM), and synthetic RPN were 0.50 to 4.37, 0.50 to 2.91, 0.50 to 3.42, and 0.64 to 3.28, respectively. NI prevention investment was negatively correlated with NI risk, while NI RPN was positively correlated with MSA RPN. There were significant differences between groups of departments in synthetic and MTM RPN. NI, MSA, and MTM constitute a hospital biosafety risk. However, their risk factors are distributed differently among departments. Traditional NI prevention investment can reduce NI risk, but such investments were not effective for MSA and MTM. Targeted measures need to be taken by referring to RPN and risk levels derived from FMEA.