NνDEx-100 conceptual design report

Observing nuclear neutrinoless double beta (0vββ) decay would be a revolutionary result in particle physics.Observing such a decay would prove that the neutrinos are their own antiparticles,help to study the absolute mass of neutrinos,explore the origin of their mass,and may explain the matter-antimatter asymmetry in our universe by lepton number violation.We propose developing a time projection chamber (TPC) using high-pressure ^(82)SeF_(6) gas and Topmetal silicon sensors for readout in the China Jinping Underground Laboratory (CJPL) to search for neutrinoless double beta decay of82Se,called the NvDEx experiment.Besides being located at CJPL with the world’s thickest rock shielding,NvDEx combines the advantages of the high Qββ(2.996 MeV) of82Se and the TPC’s ability to distinguish signal and background events using their different topological characteristics.This makes NvDEx unique,with great potential for low-background and high-sensitivity 0 vββsearches.NvDEx-100,a NvDEx experiment phase with 100 kg of SeF_(6)gas,is being built,with plans to complete installation at CJPL by 2025.This report introduces 0 vββ physics,the NvDEx concept and its advantages,and the schematic design of NvDEx-100,its subsystems,and background and sensitivity estimation.

Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers

Gastric cancer and liver cancer are among the most common malignancies and the leading causes of death worldwide,due to late detection and high recurrence rates.Today,these cancers have a heavy socioeconomic burden,for which a full understanding of their pathophysiological features is warranted to search for promising biomarkers and therapeutic targets.Osteopontin (OPN) is overexpressed in most patients with gastric and liver cancers.Over the past decade,emerging evidence has revealed a correlation of OPN level and clinicopathological features and prognosis in gastric and liver cancers,indicating its potential as an independent prognostic indicator in such patients.Functional studies have verified the potential of OPN knockdown as a therapeutic approach in vitro and in vivo .Furthermore,OPN mediates multifaceted roles in the interaction between cancer cells and the tumor microenvironment,in which many details need further exploration.OPN signaling results in various functions,including prevention of apoptosis,modulation of angiogenesis,malfunction of tumor-associated macrophages,degradation of extracellular matrix,activation of phosphoinositide 3-kinase-Akt and nuclear factor-κB pathways,which lead to tumor formation and progression,particularly in gastric and liver cancers.This editorial aims to review recent findings on alteration in OPN expression and its clinicopathological associations with tumor progression,its potential as a therapeutic target,and putative mechanisms in gastric and liver cancers.Better understanding of the implications of OPN in tumorigenesis might facilitate development of therapeutic regimens to benefit patients with these deadly malignancies.

Using bovine pituitary extract to increase proliferation of keratocytes and maintain their phenotype in vitro

AIM:To investigate the effects of bovine pituitary extract on the proliferation of keratocytes and maintaining the keratocyte phenotype/n v/tro.METHODS:Single keratocytes were isolated by enzyme digestion for in vitro culture.Three groups were designed according to the different culture media:a bovine pituitary extract(BPE)group,a fetal bovine serum(FBS)group and the control group.The phenotypes and proliferation of cultured cells were evaluated by morphology,immunofluorescent staining and mRNA expression of CD34,Lumican,VSX1,α-SMA and proliferating cell nuclear antigen(PCNA).in the BPE group,cells underwent serial subcultivation,and their phenotypes were identified by immunofluorescent staining.To analyze the proliferation of keratocytes in different concentrations of BPE,six different concentrations were designed to ascertain the most appropriate amount.RESULTS:In the BPE group,the cells spread out and presented dendritic morphology,and their dendrites connected to one another to form networks.On the third passage,most cells maintained their phenotype.In the FBS group,the cells exhibited a dendritic appearance in early cultured stages,but their morphology subsequently changed into a fibroblast-like shape.The number ofdendritic cells in BPE group was more than FBS and control groups.Immunofluorescent staining and realtime polymerase chain reaction(PCR)confirmed that few keratocytes underwent fibroblastic transformation in the BPE and control groups,and that proliferation was higher in the BPE group than in the control group.Although the proliferation was higher in the FBS group,many keratocytes underwent fibroblastic transformation.The analysis of cell morphology and mRNA expressions of CD34,PCNA and VSX1 in six group showed that different concentrations of BPE affected the proliferation obviously but didn’t affect the keratocyte phenotype,and the concentration of 40μg/mL was the most appropriate one.CONCLUSION:BPE can improve the proliferation of keratocytes and maintain their phenotype in vitro.Many keratocytes can be harvested rapidly and provide seeds for the construction of corneal stroma.

Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect

Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis.Methods: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide(LPS). We screened for potential protein targets of Cel using activity-based protein profiling(ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays(CETSA) and surface plasmon resonance(SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown.Results: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS(P <0.05). Cel bound to Cys424 of pyruvate kinase M2(PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis(Warburg effect). Cel also bound to Cys106 in high mobility group box 1(HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin(IL)-1β. Cel bound to the Cys residues in lactate dehydrogenase A(LDHA).Conclusions: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.

Identification of antimalarial targets of chloroquine by a combined deconvolution strategy of ABPP and MS-CETSA

Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.

HDAC-selective Inhibitor Cay10603 Has Single Anti-tumour Effect in Burkitfs Lymphoma Cells by Impeding the Cell Cycle

Histone deacetylases(HDACs)inhibitors are novel in cancer therapy nowadays.HDAC6-selective inhibitors exert advantageous effects due to higher selectivity and less toxicity.We explored the anti-tumor effect and the molecular mechanism of cay 10603,a potent HDAC6 inhibitor in Burkitt's lymphoma cells.Our study revealed cay 10603 inhibited the proliferation of Burkitt's lymphoma cell lines,and induced caspase-dependent apoptosis.Cayl0603 inhibited the expression of CDKs and cyciins to impede cell cycle progression in both Burkitt's lymphoma cell lines.Cay 10603 also showed the additive effect with vpl 6 notably.Our data presented the promising anti-tumor effect of cay 10603 in the Burkitt's lymphoma therapy.

肠道真菌菌群失调对小鼠角膜创伤修复的影响

目的:观察抗真菌药物诱导的肠道真菌菌群失调对小鼠角膜创伤修复的影响。方法:选用健康无眼疾的C57BL/6J雄性小鼠,将实验小鼠随机分为两组:对照组和两性霉素B组。对照组给予正常饮食,两性霉素B组给予添加两性霉素B的饮食,以诱导小鼠肠道真菌菌群失调,4wk后对两组小鼠角膜进行上皮创伤,使用荧光素钠染色角膜创伤区域,动态观察上皮修复情况,并利用免疫荧光染色观察角膜上皮细胞、炎症细胞变化,通过HE染色观察角膜厚度的变化。结果:两性霉素B组与对照组相比,再上皮化速度和创伤修复延迟,炎症细胞明显减少,角膜上皮厚度变薄。结论:肠道真菌菌群失调延迟角膜创伤的修复,降低角膜创伤后的炎症反应。

The clinical and immunological features of pediatric COVID-19 patients in China

In December 2019,the corona virus disease 2019(COVID-19)caused by novel coronavirus(SARS-CoV-2)emerged in Wuhan,China and rapidly spread worldwide.Few information on clinical features and immunological profile of COVID-19 in paediatrics.The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed.The immunological features of children patients was investigated and compared with twenty adult patients.The median age was 14.5-years(range from 0.64 to 17),and six of the patients were male.The average incubation period was 8 days.Clinically,cough(9/12,75%)and fever(7/12,58.3%)were the most common symptoms.Four patients(33.3%)had diarrhea during the disease.As to the immune profile,children had higher amount of total T cell,CD8t T cell and B cell but lower CRP levels than adults(P<0.05).Ground-glass opacity(GGO)and local patchy shadowing were the typical radiological findings on chest CT scan.All patients received antiviral and symptomatic treatment and the symptom relieved in 3e4 days after admitted to hospital.The paediatric patients showed mild symptom but with longer incubation period.Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level,which might ascribed to the mild clinical symptom.We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

Linear dipole behavior of single quantum dots encased in metal oxide semiconductor nanoparticles films

Understanding of charge/energy exchange processes and interfacial interactions that occur between quantum dots (QDs) and the metal oxides is of critical importance to these QD-based optoelectronic devices. This work reports on linear dipole behavior of single near-infrared emitting CdSeTe/ZnS core/shell QDs which are encased in indium tin oxide (ITO) semiconductor lianoparticles films. A strong polarization anisotropy in photohiminescence emission is observed by defocused wide-field imaging and polarization measuremen11echniques, and the average polarization degree is up to 0.45. A possible mechanism for the observation is presented in which the electrons, locating at single QD surface from ITO by electron transfer due to the equilibration of the Fermi levels, result in a significant Stark distortion of the QD electron/hole wavefunctions. The Stark distortion results in the linear polarization property of the single QDs. The investigation of linear dipole behavior for single QDs encased in ITO films would be helpful for further improving QD-based device performance.