Pembrolizumab-Induced Steven-Johnson Syndrome in an NSCLC Patient: A Case Report

Background: Immune checkpoints inhibitors (ICIs) are widely used in various therapy of tumors. With the increasing usage of them, immune-related adverse events (irAEs) have been known and become common events, especially in the dermatologic system. However, the rare and severe immune-related cutaneous adverse events (irCAEs) still lack enough knowledge. Case presentation: We described a rare case of Steven-Johnson syndrome (SJS) induced by pembrolizumab in an advanced squamous non-small cell lung cancer (NSCLC) patient. SJS is a rare irCAE that could happen at any time after immunotherapy while this case happened from the 3rd day. The patient had influence-like symptoms and several mucous lesions including oral, eye, and skin. With a gradually severer condition, a stoss therapy of intravenous immunoglobulin (IVIG) had a mild effect. It was a long process and failed to respond to usual dermatologic treatment. Conclusion: We share this case in order to enhance clinicians’ ability to early recognition and diagnosis in severe irCAEs. Early recognition and appropriate management are important to evade the termination of immunotherapy. Such severe irCAE should be paid more attention to in clinical medicine when using ICIs.

高等教育数字化转型的国际经验:基于CIPP模型的实践案例

数字化转型对于高校创新人才培养以及国际竞争力提升均具有重要的意义与价值,已成为我国高等教育创新变革的重要趋势。为借鉴国际高校的数字化转型创新经验,文章基于CIPP模型,构建了高等教育数字化转型实践案例的分析理论框架,包含背景、投入、过程和成果四个维度,并基于该框架对四所高校的典型案例进行分析。结果发现:在国际范围内,高校进行数字化转型的背景与该校建立竞争优势或解决现实问题的基本需求相关联。在此背景下,进行构建数字化领导力和建设数字化学习环境等方面的投入。高校数字化转型实践过程是在数字化领导力引领下的改进或创新教学运营模式和学习模式,并通过深挖数据价值,逐步实现更包容、更有效、更深入的教学的过程。数字化转型成果为高校增加了附加价值,促进教学资源的可持续利用,为教师和学习者提供了新的角色以及更为灵活和个性化的教与学体验,进而为创新人才培养提供了有力条件。

马来西亚产业结构转型研究

产业是国家经济发展的根基,不同国家不同产业的发展路径是不一样的。根据政府实施的产业政策,马来西亚产业结构转型过程可以划分为三个阶段:重点鼓励劳动密集型工业发展阶段、大力促进资金技术密集型工业发展阶段以及大力发展现代服务业和高新技术产业阶段。随着经济全球化的发展,中国对马来西亚的投资不断增加,中国资本的流入能够为马来西亚的产业结构转型提供良好的基础设施环境和有利的融资环境,完善制造业的产业链条,促进合作产业向产业链的中高端方向发展,此外还能促进马来西亚的主导产业升级。中国应该吸取马来西亚产业结构转型过程中的教训,提防过早地去工业化,提高自主创新能力,增强民间资本的活力,促进金融市场的发展。

基于贪心迭代算法的网络信息传输安全威胁动态识别方法

网络信息传输安全威胁识别过程中易出现漏检现象,影响网络入侵特征检测的准确性,为此,提出基于贪心迭代算法的网络信息安全威胁识别方法。采用动态网关入口节点监测方法,采集网络信息传输的动态数据集,提取多帧频谱特征量;结合网络拓扑结构重组方法,实现对网络传输信息的动态特征分布式重构,根据组合频域因素分布式融合技术,实现对网络信息传输的动态迭代处理,采用离散傅里叶变换,实现对网络性安全威胁的时间序列频域转换控制,根据网络攻击类型进行网络入侵特征检测和分类识别,根据贪心算法迭代结果,实现对网络信息安全威胁的动态识别和监测。实验结果表明,该方法在网络信息安全威胁识别方面具有优秀的特征检测能力,能够根据不同的入侵威胁程度对安全威胁进行有效的分组识别,该方法的漏检率最低仅为0.021。

Embryonic Growth and Yolk Depletion during Incubation in the Chinese Skink, Plestiodon chinensis

We collected 24 gravid female Chinese skinks(Plestiodon chinensis) to study embryonic growth and yolk depletion during incubation. Females laid eggs between late May and mid-June. Eggs were incubated at 24(± 0.3) ℃. One egg from each clutch was dissected at 5-d intervals starting at laying. Embryonic stages at laying varied from Dufaure and Hubert's(1961) Stage 30-35, with a mean stage of 32.6. Incubation lengths at 24 ℃ varied from 35.1 to 48.3 d, with a mean of 41.5 d. Based on the derived functions describing instantaneous changes in embryo dry mass and yolk dry mass, we identified three phases of embryonic growth or yolk depletion in P. chinensis. Phase 1, from Day 0(at laying) to Day 15(～36% of the way through incubation), was one of minimal transfer of material from yolk to embryo. Phase 2, from Day 15 to Day 32-33(～77%-80% of the way through incubation), was characterized by increasingly rapid embryonic growth or yolk depletion. Phase 3, from Day 32-33 to hatching, was characterized by reduced embryonic growth or yolk depletion. The length of the last embryonic stage(Stage 40 = completely differentiated embryos) accounted for about 28% of incubation length, and the dry mass of the smallest embryos of Stage 40 accounted for only ～48% of the hatchling dry mass. Our study adds evidence to the idea that oviposition is not timed to coincide with the onset of rapid embryonic growth in oviparous reptiles, and is first to demonstrate that ～50% embryonic growth occurs in the last quarter of incubation in P. chinensis.

Cancer Rehabilitation,A New Discipline Based upon Multidisciplinary Collaboration

Cancer Rehabilitation is a new discipline,a combination of tumor medication,immunology,psychology,nutritional science and exercise physiology etc..The core of cancer rehabilitation is the therapy of natural immunology,which aims at activating T-cells,and restoring the bone marrow function impaired during chemo-radiation therapy.Cancer rehabilitation seeks to achieve the gradual recovery of the immune system,which in turn hinders recurrence and metastasis.In addition,with the help of psychological consultation,nutritional and physical exercise guidance,cancer patients may have a better chance at managing the risk of recurrence and metastasis,extending life expectancy with an improved quality of life.

A suspicious role of interferon in the pathogenesis of SARS-CoV-2 by enhancing expression of ACE2

Based on a number of published and unpublished single-cell RNAsequencing(scRNA-seq)datasets,a recent study identified putative specific cell subtypes targeted by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)and a possible role of interferon(IFN)in its pathogenesis.The rapid spread of SARS-CoV-2,the causative pathogen of COVID-19,has had global public health and economic consequences.The molecular mechanism(s)underlying the high transmissibility of SARS-CoV-2 remain(s)elusive.Therefore,we must follow a pragmatic and stepwise path to determine the specific target cell subsets and factors that regulate SARS-CoV-2 infection to elucidate true targets for treatment.In a recent issue of Cell,Carly and co-workers1 identified the cell subsets targeted by SARS-CoV-2 in certain tissues.In addition,they found that IFN-αenhanced the expression of angiotensin-converting enzyme 2(ACE2),the receptor for SARS-CoV-2,in primary human upper airway basal cells.However,we know that IFN is cell-type-and host speciesspecific,indicating the need for more preclinical and clinical data to clarify the role of IFN in the pathogenesis of COVID-19.

β-adrenoreceptor-triggered PKA activation negatively regulates the innate antiviral response

Upon viral infection, cytoplasmic pattern recognition receptors detect viral nucleic acids and activate the adaptor protein VISA/MAVS- or MITA/STING-mediated innate antiviral response. Whether and how the innate antiviral response is regulated by neuronal endocrine functions is unclear. Here, we show that viral infection reduced the serum levels of the β-adrenergic hormones epinephrine and norepinephrine as well as the cellular levels of their receptors ADRB1 and ADRB2. We further show that an increase in epinephrine/norepinephrine level inhibited the innate antiviral response in an ADRB1-/2-dependent manner. Mechanistically, epinephrine/norepinephrine stimulation activated the downstream kinase PKA, which catalyzed the phosphorylation of MITA at S241, S243 and T263, inhibiting MITA activation and suppressing the innate immune response to DNA virus. In addition, phosphorylation of VISA at T54 by PKA antagonized the innate immune response to RNA virus. These findings reveal the regulatory mechanisms of innate antiviral responses by epinephrine/norepinephrine and provide a possible explanation for increased host susceptibility to viral infection in stressful and anxiety-promoting situations.

The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin

Dear Editor,The rapid spread of SARS-CoV-2(also known as 2019-nCoV and HCoV-191),a novel lineage B betacoronavirus(βCoV),has caused a global pandemic of coronavirus disease(COVID-19).It has been speculated that RRAR,a unique furin-like cleavage site(FCS)in the spike protein(S),which is absent in other lineage BβCoVs,such as SARS-CoV,is responsible for its high infectivity and transmissibility.

A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases

The development of broad-spectrum antivirals against human coronaviruses(HCoVs)is critical to combat the current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,as well as future outbreaks of emerging CoVs.We have previously identified a polyethylene glycol-conjugated(PEGylated)lipopeptide,EK1C4,with potent pan-CoV fusion inhibitory activity.However,PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo.Therefore,we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment(HR2-CF)of HCoV-OC43.Among these lipopeptides,EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike(S)mutants,as well as other HCoVs and some bat SARS-related coronaviruses(SARSr-CoVs)tested.The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes,better metabolic stability in mouse serum,higher thermostability than the PEGylated lipopeptide EK1C4,suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

Enhancement of endocytic uptake of H IV-1 virions into CD4-negative epithelial cells by HIV-1 gp41 via its interaction with POB1

We previously used recombinant soluble gp41 （rsgp41） as a targetto screen a ntnnan oone marrow cul,~n library by the yeast two-hybrid assay, and we identified an HW-1 gp41-binding protein, human POB1 （the partner of RalBP1）. We found that the gp41- binding site was located at the C-term- inal region （aa462-521） of POB1 and the POBl-binding site was on the N-term- inal heptad repeat （NHR） region of HIV-1 gp41.

Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone

Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic.We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice.Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice,whereas knockout of the progesterone receptor PGR has opposite effects.Mechanistically,stimulation of PGR by progesterone activates the tyrosine kinase SRC,which phosphorylates the transcriptional factor IRF3 at Y107.