In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. ...For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
A spiro‐axis skeleton not only introduces circularly polarized luminescence (CPL) into thermally activated delayed fluorescence (TADF) molecules but also enhances the intramolecular through space ...charge transfer (TSCT) process. Spiral distributed phenoxazine and 2‐(trifluoromethyl)‐9H‐thioxanthen‐9‐one‐10,10‐dioxide act as donor and acceptor units, respectively. The resulting TADF enantiomers, (rac)‐OSFSO, display emission maxima at 470 nm, small singlet‐triplet energy gap (ΔEST) of 0.022 eV and high photoluminescence quantum yield (PLQY) of 81.2 % in co‐doped film. The circularly polarized OLEDs (CP‐OLEDs) based on (R)‐OSFSO and (S)‐OSFSO display obvious circularly polarized electroluminescence (CPEL) signals with dissymmetry factor up to 3.0×10−3 and maximum external quantum efficiency (EQEmax) of 20.0 %. Moreover, the devices show remarkably low efficiency roll‐off with an EQE of 19.3 % at 1000 cd m−2 (roll‐off ca. 3.5 %), which are among the top results of CP‐OLEDs.
A chiral spiro‐axis skeleton introduced the circularly polarized luminescence property into TADF molecules and enhanced the intramolecular through space charge transfer process. The resulting TADF enantiomers display obvious CPEL signals with |gEL| factor up to 3.0×10−3 and EQE of 20.0 % with remarkably low efficiency roll‐off, which are among the top results of CP‐OLEDs.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and ...other countries. We investigated the effect of this deletion on the clinical features of infection.
We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study—a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed.
Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 0% of 29 patients) than in the wild-type only group (26 28% of 92; absolute difference 28% 95% CI 14–28). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 95% CI 0·00–0·48) compared with infection with wild-type virus only.
The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines.
National Medical Research Council Singapore.
In this study, we report the first circularly polarized white organic light‐emitting diodes (CP‐WOLEDs) based on all thermally activated delayed fluorescence (TADF) materials. Two pairs of spiro‐type ...TADF enantiomers, (R/S)‐SPOCN (5,5′‐((2,2′,3,3′‐tetrahydro‐1,1′‐spirobiindene‐7,7′‐diyl)bis(oxy))bis(4‐(10H‐phenoxazin‐10‐yl)phthalonitrile)) and (R/S)‐OSFSO (2′‐(trifluoromethyl)‐spiroquinolino3,2,1‐klphenoxazine‐9,9′‐thioxanthene‐10′,10′‐dioxide), serve as emitters with complementary emission. The CP‐OLEDs exhibit warm white emission with a CIE coordinate of (0.35, 0.46). Besides, decent device performances are observed with an external quantum efficiency of up to 21.6 % at maximum and 11.8 % at 1000 cd m−2. Obvious circularly polarized electroluminescence signals are detected with a dissymmetry factor |gEL| of around 3.0×10−3. This is the first report of CP‐WOLEDs that can harvest both singlet and triplet excitons, which provides a feasible strategy for the development of CP‐WOLEDs with remarkable device performances.
Circularly polarized white organic light‐emitting diodes that can harvest both singlet and triplet excitons have been developed by combining two pairs of spiro‐type circularly polarized delayed fluorescence enantiomers with complementary emissions as chiral emissive layers. Remarkable device performances are observed, with an external quantum efficiency of up to 21.6 % and intense circularly polarized luminescence having a |gEL| factor of 3.0×10−3.
Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic ...tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus.
The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only ...plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE
, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.
Since the number of server providing the facilities for the user is usually more than one, the authentication protocols for multi-server environment are required for practical applications. Most of ...password authentication schemes for multi-server environment are based on static ID, so the adversary can use this information to trace and identify the user's requests. It is unfavorable to be applied to special applications, such as e-commerce. In this paper, we develop a secure dynamic ID based remote user authentication scheme to achieve user's anonymity. The proposed scheme only uses hashing functions to implement a robust authentication scheme for the multi-server environment. It provides a secure method to update password without the help of third trusted party. The proposed scheme does not only satisfy all requirements for multi-server environment but also achieve efficient computation. Besides, our scheme provides complete functionality to suit with the real applications.
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing ...cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer. In syngeneic murine rhabdomyosarcoma models, we found that M3-9-M (MHC I high) but not 76-9 (MHC I low) tumors respond to oncolytic herpes simplex virus-1 (oHSV-1) and PD-1 blockade combination therapy. In addition, the therapeutic outcomes in M3-9-M tumor models correlated with the increased incidence of CD4
and CD8
T cells but not with the CD4
CD25
Foxp3
regulatory T cell populations in the tumor. Overall, our data suggest the combination of PD-1 blockade and oHSV-1 may be an effective treatment strategy for childhood soft tissue sarcoma.
Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin-9 (IL-9). However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility ...to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9- and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.
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•Multi-functional MMC9s produce prodigious amounts of IL-9 and mast cell mediators•MMC9 development increases in mice susceptible to IgE-mediated food allergy•Induction of MMC9s requires T cells and IL-4, not IL-9, signals•MMC9s amplify intestinal mastocytosis that drives IgE-mediated food allergy
Current knowledge cannot explain why only some patients and murine strains that acquire high amounts of dietary allergen-specific IgE develop life-threatening anaphylaxis. Wang and colleagues identify and characterize the IL-9-producing mucosal mast cells that amplify anaphylactic response to dietary proteins by producing large amounts of IL-9 and mast cell mediators.
This work reports a new strategy of introducing remote steric effect onto the electron donor for giving the better performance of the exciplex-based organic light-emitting device (OLED). The bulky ...triphenylsilyl group (SiPh3) was introduced onto the fluorene bridge of 4,4′-(9H-fluorene-9,9-diyl)bis(N,N-di-p-tolylaniline) (DTAF) to create remote steric interactions for increasing the possibility of effective contacts between electron-donating chromophores and acceptor molecules, rendering the resulting exciplex to have a higher photoluminescence quantum yield (PLQY). The green exciplex device based on DSDTAF:3N-T2T (1:1) as an emitting layer exhibits a low turn-on voltage of 2.0 V, high maximum efficiencies (13.2%, 42.9 cd A–1, 45.5 lm W–1), which are higher than the device employed DTAF (without SiPh3 groups) (11.6%, 35.3 cd A–1, 41.3 lm W–1) as donor under the same device structure. This strategy was further examined for blue exciplex, where the EQE was enhanced from 9.5% to 12.5% as the electron acceptor PO-T2T mixed with a tert-butyl group substituted carbazole-based donor (CPTBF) as the emitting exciplex in device. This strategy is simple and useful for developing high performance exciplex OLEDs.
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