In December 2019, a new coronavirus was found in Wuhan, Hubei Province, China, and spread rapidly throughout the country, attracting global attention. On February 11, the World Health Organization ...(WHO) officially named the disease caused by 2019-nCoV coronavirus disease 2019 (COVID-19). With the increasing number of cases, health care workers (HCWs) from all over China volunteered to work in Hubei Province. Because of the strong infectivity of COVID-19, HCWs need to wear personal protective equipment (PPE), such as N95 masks, latex gloves, and protective clothing. Due to the long-term use of PPE, many adverse skin reactions may occur. Therefore, the purpose of this study is to explore the adverse skin reactions among HCWs using PPE.Questionnaires were used for the research; a quantitative study was carried out to determine the incidence of adverse skin reactions among HCWs using PPE.A total of 61 valid questionnaires were collected. The most common adverse skin reactions among HCWs wearing N95 masks were nasal bridge scarring (68.9%) and facial itching (27.9%). The most common adverse skin reactions among HCWs wearing latex gloves were dry skin (55.7%), itching (31.2%), and rash (23.0%). The most common adverse skin reactions among HCWs wearing protective clothing were dry skin (36.1%) and itching (34.4%).When most HCWs wear PPE for a long period of time, they will experience adverse skin reactions. The incidence of adverse skin reactions to the N95 mask was 95.1%, that to latex gloves was 88.5%, and that to protective clothing was 60.7%.
Human glucose transporters (GLUTs) are responsible for cellular uptake of hexoses. Elevated expression of GLUTs, particularly GLUT1 and GLUT3, is required to fuel the hyperproliferation of cancer ...cells, making GLUT inhibitors potential anticancer therapeutics. Meanwhile, GLUT inhibitor-conjugated insulin is being explored to mitigate the hypoglycemia side effect of insulin therapy in type 1 diabetes. Reasoning that exofacial inhibitors of GLUT1/3 may be favored for therapeutic applications, we report here the engineering of a GLUT3 variant, designated GLUT3exo, that can be probed for screening and validating exofacial inhibitors. We identify an exofacial GLUT3 inhibitor SA47 and elucidate its mode of action by a 2.3 Å resolution crystal structure of SA47-bound GLUT3. Our studies serve as a framework for the discovery of GLUTs exofacial inhibitors for therapeutic development.
The spread of coronavirus disease 2019 (COVID-19) around the world has put a heavy burden on human society and is also a great challenge facing medical staff. This study aimed to assess the ...difficulties faced by health care personnel (HCP) in using personal protective equipment (PPE) in clinical practice during the COVID-19 outbreak in Wuhan, China. One hundred twenty medical staff from the First Affiliated Hospital of Chongqing Medical University presented to the Wuhan First Hospital to provide medical assistance, from whom 20 HCP volunteered to participate in a focus group discussion attended by infection control nurse leaders. Participants' responses and discussions were recorded, and the content was analyzed for themes. Observed difficulties included inappropriate PPE sizes, the design of the PPE and its complexity of use, doubts related to the quality and effectiveness of PPE, potential risks during doffing, space layout between clean and contaminated area, and poor comfort with PPE use. Other factors, such as the support environment, management, processes, preparedness, HCP, and equipment can also have a positive or negative impact on the use of PPE. Future efforts to optimize PPE use should focus on strengthening training for HCP using real items for increasing compliance with standardized protocols, improving PPE design, and performing further research on the risks, benefits, and best practices of PPE use.
Due to its high infectivity and concealment, the coronavirus disease 2019 (COVID-19) outbreak that occurred in Wuhan attracted global attention. A special nursing group of transdisciplinary nurses ...(TNs) who had not worked in respiratory medicine, infection departments, or emergency and intensive medicine but who accounted for a large proportion of all nurses also drew our attention. Few studies have examined this special group of TNs. Therefore, this study collected the experiences and views of TNs at the forefront of the COVID-19 outbreak to investigate their potential problems.
Twenty-five TNs and 19 nurses with experience in infectious diseases (non-TNs) were enrolled in the study. Compared with non-TNs, TNs showed higher levels of perceived stress and relatively less perceived social support. For TNs, the ambiguous roles, transition of operating mode, unfamiliar work content, and reversal of their daily schedule were the most common vocational problems. Additionally, most TNs had psychological problems such as anxiety, pain and insomnia. The incomprehension of parents, concern for family members and long-term isolation were the most common causes of psychological stress.
This survey is the first to focus on the group of TNs at the forefront of the COVID-19 outbreak and to investigate their experiences, vocational issues and psychological stresses qualitatively and quantificationally. We found that TNs had more perceived stress and less perceived social support than non-TNs. The vocational and psychological issues of TNs should be highlighted. These findings identify important issues and offer insights into the underlying issues to help TNs ultimately win the battle against novel coronavirus epidemics.
Semi-structured and face-to-face individual interviews and quantitative assessments were conducted. The Braun Clarke Thematic Analysis method and the strategy outlined by Miles and Huberman were used in the data analysis process of the qualitative study. The perceived stress scale and perceived social support scale were utilized to quantificationally evaluate the perceived stress level and the amount of perceived social support. Both qualitative and quantitative methods were adopted to assess the vocational and psychological perceptions and issues.
Artificial municipal wastewater was treated successfully by the bioaugmentation of Bacillus sp. K5 capable of simultaneous nitrification and denitrification (SND) within a sequencing batch reactor ...(SBR). During the long-term operation, the bioaugmentation system exhibited an excellent and steady COD and NH4+-N removal without nitrite and nitrate accumulation. The average removal efficiency for COD and NH4+-N achieved to 98% and 95%, respectively. PCR-DGGE, SEM and FISH revealed that the introduced Bacillus sp. K5 should be an important functional strain and exerted a critical influence on the structure of microbial community. qPCR analysis indicated that the strain K5 facilitated aerobic nutrients removal capabilities and SND might be the primary pathway for the nitrogen removal in the SBR. Overall, the SBR system used in our study should be very promising for the future wastewater treatment.
is one of the main industrially cultivated varieties of edible fungi, with a delicious taste and high nutritional value. However, the long harvest period of 130-150 days greatly limits its ...large-scale expansion. This study aimed to investigate the effects of central carbon metabolism (CCM) on the mycelial growth performance and fruiting body formation of
. Nine edible fungi with different harvest periods were collected and used to evaluate their intracellular carbon metabolic differences in the CCM, which revealed that the imbalanced distribution of intracellular carbon metabolic levels in the CCM of
might be one of the key factors resulting in a slow mycelial growth rate and a long harvest period. Further analysis by three strategies, including metabolomics, adaptation of different carbon sources, and chemical interference, confirmed that low carbon flux into the pentose phosphate pathway (PPP) limited the supply of raw materials, reduced power, and thus influenced the mycelial growth of
. Furthermore, four transformants with increased expression levels of glucose-6-phosphate dehydrogenase (G6PDH), a key rate-limiting enzyme in the PPP of
, were developed and showed more extracellular soluble protein secretion and higher sugar assimilation rates, as well as improved mycelial growth rates in bottle substrate mixtures. Finally, cultivation experiments indicated that the maturation periods of the fruiting body with ~4-5 days in advance and the maximum fruiting body yield of 574.8 g per bag with an increase of 7.4% were achieved by improving the G6PDH expression level of the PPP in
. This study showed that CCM played an important role in the mycelial growth and development of
, which provided new insights for future advancements in cultivating and breeding edible fungi.
Aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway promotes prostate cancer (PC) growth and progression by regulating cancer‐related genes through its downstream effectors GLI1 and ...GLI2. Therefore, targeting the SHH‐GLI pathway provides an alternative approach to avoid cancer progression. The aim of this study was to delineate the underlying molecular mechanisms by which GDC‐0449 (a SMO receptor inhibitor) and GANT‐61 (a GLI transcription factor inhibitor) regulate cellular proliferation and self‐renewal in human PC stem cells (ProCSCs). Inhibition of the SHH signaling pathway by GANT‐61 induced apoptosis with more efficacy than by GDC‐0449 in ProCSCs and PC cell lines. GLI1 and GLI2 expression, promoter‐binding activity and GLI‐responsive luciferase reporter activity were all decreased with either GDC‐0449 or GANT‐61 treatment. Expression of Fas, DR4, DR5, and cleavage of caspase‐3 and PARP were increased, whereas levels of PDGFR‐α and Bcl‐2 were reduced. Double knockout of GLI1 and GLI2 using shRNA abolished the effects observed with either GDC‐0449 or GANT‐61 treatment. Collectively, our results showed that GANT‐61 and GDC‐0449 induced ProCSC apoptosis by directly or indirectly inhibiting the activities of the GLI family transcription factors, may enhance the efficacy of PC treatment.
We demonstrated that GDC‐0449 and GANT‐61 inhibited prostate cancer stem cell (ProCSC) proliferation by inducing apoptotic genes through the SHH signaling pathway. Moreover, we showed that GLI1/GLI2 played a significant role in this regulation, as double knockdown of GLI1/GLI2 in ProCSCs almost completely eliminated the anti‐proliferative/pro‐apoptotic effects by GANT‐61 and GDC‐0449. Although GDC‐0449 has been approved by the FDA and EMA for treating breast cancer patients and has shown promising preclinical tumor suppressing effects in multiple other cancers, much less information has been reported for GANT‐61 function in cancer. Also, this is the first study demonstrating the effect of these two drugs on ProCSCs. In our study, GANT‐61 exhibited greater efficacy than GDC‐0449 in inhibiting proliferation and inducing apoptosis, providing an alternative targeting approach that may be more effective in therapeutic treatment.
In this study, a novel laccase gene (
) from
was isolated and its functions were characterized in detail. The results showed that
has the highest expression activity during mycelium development and ...fruit body maturation based on the analysis of
RNA transcripts at different developmental stages of
. To investigate the exact contribution of
to mycelium and fruit body development in
,
transgenic strains were constructed by targeted gene replacement and over-expression approaches. The results showed that the lignin degradation rate in
deletion mutant was much lower than the degradation efficiency of the wild-type (WT), over-expression and rescue strains. The lignin degradation activity of
is dependent on
and the deletion of
exerted detrimental influences on the development of mycelium branch. Furthermore, the study uncovered that
deletion mutants generated much shorter pale grey fruit bodies, suggesting that
contributes directly to pigmentation and stipe elongation during fruit body development in
. The information obtained in this study provides a novel and mechanistic insight into the specific role of
during growth and development of
.
Specification and maturation of insulin+ cells accompanies a transition in expression of Maf family of transcription factors. In development, MafA is expressed after specification of insulin+ cells ...that are expressing another Maf factor, MafB; after birth, these insulin+ MafA+ cells stop MafB expression and gain glucose responsiveness. Current differentiation protocols for deriving insulin-producing β-cells from stem cells result in β-cells lacking both MafA expression and glucose-stimulated insulin secretion. So driving expression of MafA, a β-cell maturation factor in endocrine precursors could potentially generate glucose-responsive MafA+ β cells. Using inducible transgenic mice, we characterized the final stages of β-cell differentiation and maturation with MafA pause/release experiments. We found that forcing MafA transgene expression, out of its normal developmental context, in Ngn3+ endocrine progenitors blocked endocrine differentiation and prevented the formation of hormone+ cells. However, this arrest was reversible such that with stopping the transgene expression, the cells resumed their differentiation to hormone+ cells, including α-cells, indicating that the block likely occurred after progenitors had committed to a specific hormonal fate. Interestingly, this delayed resumption of endocrine differentiation resulted in a greater proportion of immature insulin+MafB+ cells at P5, demonstrating that during maturation the inhibition of MafB in β-cell transitioning from insulin+MafB+ to insulin+MafB− stage is regulated by cell-autonomous mechanisms. These results demonstrate the importance of proper context of initiating MafA expression on the endocrine differentiation and suggest that generating mature Insulin+MafA+ β-cells will require the induction of MafA in a narrow temporal window to achieve normal endocrine differentiation.
•Enforced expression of MafA in endocrine progenitors inhibits their differentiation.•MafA blocks differentiation after progenitors commit to a specific hormonal fate.•Stopping MafA expression relieves the block and cells resume their differentiation.•Cell‐autonomous mechanisms regulate the loss of MafB in maturing insulin+ cells.
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