In this research, the antifungal role of hydrogen sulfide (H2S) on the postharvest pathogens Aspergillus niger and Penicillium italicum growing on fruits and under culture conditions on defined media ...was investigated. Our results show that H2S, released by sodium hydrosulfide (NaHS) effectively reduced the postharvest decay of fruits induced by A. niger and P. italicum. Furthermore, H2S inhibited spore germination, germ tube elongation, mycelial growth, and produced abnormal mycelial contractions when the fungi were grown on defined media in Petri plates. Further studies showed that H2S could cause an increase in intracellular reactive oxygen species (ROS) in A. niger. In accordance with this observation we show that enzyme activities and the expression of superoxide dismutase (SOD) and catalase (CAT) genes in A. niger treated with H2S were lower than those in control. Moreover, H2S also significantly inhibited the growth of Saccharomyces cerevisiae, Rhizopus oryzae, the human pathogen Candida albicans, and several food-borne bacteria. We also found that short time exposure of H2S showed a microbicidal role rather than just inhibiting the growth of microbes. Taken together, this study suggests the potential value of H2S in reducing postharvest loss and food spoilage caused by microbe propagation.
Accumulating evidence shows that hydrogen sulfide (H2S) acts as a multifunctional signaling molecule in plants, whereas the interaction between H2S and ethylene is still unclear. In the present study ...we investigated the role of H2S in ethylene-promoted banana ripening and senescence by the application of ethylene released from 1.0 g·L-1 ethephon solution or H2S with 1 mM sodium hydrosulfide (NaHS) as the donor or in combination. Fumigation with ethylene was found to accelerate banana ripening and H2S treatment effectively alleviated ethylene-induced banana peel yellowing and fruit softening in parallel with decreased activity of polygalacturonase (PG). Ethylene+H2S treatment also delayed the decreases in chlorophyll and total phenolics, and increased the accumulation of flavonoid, whereas decreased the contents of carotenoid, soluble protein in banana peel and reducing sugar in pulp compared with ethylene treatment alone. Besides, ethylene+H2S treatment suppressed the accumulation of superoxide radicals (·O2-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) which accumulated highly in ethylene-treated banana peels. Furthermore H2S enhanced total antioxidant capacity in ethylene-treated banana peels with the 2,2'-azobis(3-ethylbenz-thiazoline-6-sulfonic acid (ABTS) assay. The result of quantitative real-time PCR showed that the combined treatment of ethylene with H2S down-regulated the expression of ethylene synthesis genes MaACS1, MaACS2 and MaACO1 and pectate lyase MaPL compared with ethylene treatment, while the expression of ethylene receptor genes MaETR, MaERS1 and MaERS2 was enhanced in combination treatment compared with ethylene alone. In all, it can be concluded that H2S alleviates banana fruit ripening and senescence by antagonizing the effect of ethylene through reduction of oxidative stress and inhibition of ethylene signaling pathway.
Stretchable electrochemical sensors are conceivably a powerful technique that provides important chemical information to unravel elastic and curvilinear living body. However, no breakthrough was made ...in stretchable electrochemical device for biological detection. Herein, we synthesized Au nanotubes (NTs) with large aspect ratio to construct an effective stretchable electrochemical sensor. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allows for the first time, real‐time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching‐free and stretching states as well as sensing of the inner lining of blood vessels. The results demonstrate the great potential of this sensor in electrochemical detection of living body, opening a new window for stretchable electrochemical sensor in biological exploration.
Biomedical sensor: A highly controllable strategy has been developed for synthesizing Au nanotubes with a large aspect ratio. The nanotubes were used to construct an effective stretchable electrochemical sensor and to realize real‐time monitoring of mechanically sensitive cells and tissues.
Objective
To explore the experiences of front‐line nurses combating the coronavirus disease‐2019 epidemic.
Design and Sample
Fifteen front‐line nurses caring for COVID‐19 patients were recruited from ...two hospitals in Wuhan, China from January 26 to February 5, 2020. Data were collected through semi‐structured individual interviews and analyzed using standard qualitative methods.
Results
Four theme categories emerged from the data analysis: (a) “Facing tremendous new challenges and danger”; (b) “Strong pressure because of fear of infection, exhaustion by heavy workloads and stress of nursing seriously ill COVID‐19 patients”; (c) “Strong sense of duty and identity as a healthcare provider”; (d) “Rational understanding of the epidemic—the nurses believed that the epidemic would soon be overcome and would like to receive disaster rescue training.”
Conclusions
Although the intensive rescue work drained front‐line nurses, both physically and emotionally, they showed a spirit of dedication and felt a responsibility to overcome this epidemic. Their experiences provide useful insights into implementing a safer public health emergency rescue system in preparation for future outbreaks of infectious diseases. Specifically, psychological support and humanistic care should be provided to front‐line nurses to maintain their well‐being, and nationwide emergency rescue training and disaster education should be implemented.
Abstract
Motivation
Clustering analysis in a biological network is to group biological entities into functional modules, thus providing valuable insight into the understanding of complex biological ...systems. Existing clustering techniques make use of lower-order connectivity patterns at the level of individual biological entities and their connections, but few of them can take into account of higher-order connectivity patterns at the level of small network motifs.
Results
Here, we present a novel clustering framework, namely HiSCF, to identify functional modules based on the higher-order structure information available in a biological network. Taking advantage of higher-order Markov stochastic process, HiSCF is able to perform the clustering analysis by exploiting a variety of network motifs. When compared with several state-of-the-art clustering models, HiSCF yields the best performance for two practical clustering applications, i.e. protein complex identification and gene co-expression module detection, in terms of accuracy. The promising performance of HiSCF demonstrates that the consideration of higher-order network motifs gains new insight into the analysis of biological networks, such as the identification of overlapping protein complexes and the inference of new signaling pathways, and also reveals the rich higher-order organizational structures presented in biological networks.
Availability and implementation
HiSCF is available at https://github.com/allenv5/HiSCF.
Supplementary information
Supplementary data are available at Bioinformatics online.
Targeted integration of transgenes can be achieved by strategies based on homologous recombination （HR）, mi- crohomology-mediated end joining （MMEJ） or non-homologous end joining （NHEJ）. The more ...generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining （HMEJ）-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and -800 bp of homology arms, and the targeted genome. We found no significant improve- ment of the targeting efficiency by the HMEJ-based method in either mouse embryonic stem cells or the neuroblas- toma cell line, N2a, compared to the HR-based method. However, the HMEJ-based method yielded a higher knock- in efficiency in HEK293T cells, primary astrocytes and neurons. More importantly, this approach achieved transgene integration in mouse and monkey embryos, as well as in hepatocytes and neurons in vivo, with an efficiency much greater than HR-, NHEJ- and MMEJ-based strategies. Thus, the HMEJ-based strategy may be useful for a variety of applications, including gene editing to generate animal models and for targeted gene therapies.
Anthocyanins, which have important biological functions and have a beneficial effect on human health, notably account for pigmentation in purple-fleshed sweet potato tuberous roots. Individual ...regulatory factors of anthocyanin biosynthesis have been identified; however, the regulatory network of anthocyanin biosynthesis in purple-fleshed sweet potato is unclear.
We functionally determined that IbMYB340 cotransformed with IbbHLH2 in tobacco and strawberry receptacles induced anthocyanin accumulation, and the addition of IbNAC56a or IbNAC56b caused increased pigmentation. Furthermore, we confirmed the interaction of IbMYB340 with IbbHLH2 and IbNAC56a or IbNAC56b via yeast two-hybrid and firefly luciferase complementation assays; these proteins could form a MYB340-bHLH2-NAC56a or MYB340-bHLH2-NAC56b transcriptional complex to regulate anthocyanin biosynthesis by binding to the IbANS promoter rather than the IbUFGT promoter. Furthermore, it was found by a transient expression system in tobacco leaves that IbMYB44 could decrease anthocyanin accumulation. Moreover, the interaction of IbMYB44 with IbMYB340 and IbNAC56a or IbNAC56b was verified. This result suggested that IbMYB44 acts as a repressor of anthocyanin in sweet potato.
The repressor IbMYB44 affected anthocyanin biosynthesis by competitively inhibiting the IbMYB340-IbbHLH2-IbNAC56a or IbMYB340-IbbHLH2-IbNAC56b regulatory complex formation. Overall, the present study proposed a novel regulatory network whereby several vital TFs play key roles in regulating anthocyanin biosynthesis, and it provides strong insight into the potential mechanism underlying anthocyanin biosynthesis in sweet potato tuberous roots with purple color.
Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to ...control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism.
Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D
(VD
).
A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD
, other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316).
Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.
Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II–IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with ...EGFR-mutant stage IB–IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II–IIIA (N1–N2) NSCLC.
We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18–75 years with completely resected (R0), stage II–IIIA (N1–N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079.
Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8–44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months 95% CI 24·9–32·5) than with vinorelbine plus cisplatin (18·0 months 13·6–22·3; hazard ratio HR 0·60, 95% CI 0·42–0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two 2% patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 34% patients vs none with gefitinib), leucopenia (14 16% vs none), and vomiting (eight 9% vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related.
Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II–IIIA (N1–N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature.
Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.
Hepatitis B virus (HBV) infection is a common infectious disease, in which nuclear covalently closed circular DNA (cccDNA) plays a key role in viral persistence, viral reactivation after treatment ...withdrawal, and drug resistance. A recent genome‐wide association study has identified that the ubiquitin conjugating enzyme E2 L3 (UBE2L3) gene is associated with increased susceptibility to chronic HBV (CHB) infection in adults. However, the association between UBE2L3 and children with CHB and the underlying mechanism remain unclear. In this study, we performed two‐stage case–control studies including adults and independent children in the Chinese Han population. The rs59391722 allele in the promoter of the UBE2L3 gene was significantly associated with HBV infection in both adults and children, and it increased the promoter activity of UBE2L3. Serum UBE2L3 protein levels were positively correlated with HBV viral load and hepatitis B e antigen (HBeAg) levels in children with CHB. In an HBV infection cell model, UBE2L3 knockdown significantly reduced total HBV RNAs, 3.5‐kb RNA, as well as cccDNA in HBV‐infected HepG2‐Na+/taurocholate cotransporting polypeptide cells and human primary hepatocytes. A mechanistic study found that UBE2L3 maintained cccDNA stability by inducing proteasome‐dependent degradation of apolipoprotein B mRNA editing enzyme catalytic subunit 3A, which is responsible for the degradation of HBV cccDNA. Moreover, interferon‐α (IFN‐α) treatment markedly decreased UBE2L3 expression, while UBE2L3 silencing reinforced the antiviral activity of IFN‐α on HBV RNAs, cccDNA, and DNA. rs59391722 in UBE2L3 was correlated with HBV DNA suppression and HBeAg loss in response to IFN‐α treatment of children with CHB. Conclusion: These findings highlight a host gene, UBE2L3, contributing to the susceptibility to persistent HBV infection; UBE2L3 may be involved in IFN‐mediated viral suppression and serve as a potential target in the prevention and treatment of HBV infection.
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