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HLA-DRB1*14:246 differs from HLA-DRB1*14:18 by one nucleotide in exon 2.

Background: Therapeutics of urticaria in Chinese outpatients remain to be illustrated.Objectives: To investigate clinical treatment of outpatients with urticaria, and provide theoretical evidence for selection of medication regimens.Methods: In this hospital-based multicenter study, urticaria outpatients filled in a questionnaire at initial visit and were followed-up (once per week, for 4 weeks).Results: 1715 urticaria outpatients were recruited and 647 completed 4- week’s follow-up. Their total UAS7 was reduced (27.44 at baseline, 16.87 in 1 week, 12.39 in 2 weeks, 7.21 in 3 weeks, 4.2 in 4 weeks). 71.8% patients recovered from urticaria (therapy was highly effective in 11%, whereas effective in 14.2%). The second-generation H1 antihistamines (sgAHs) (at conventional dose) were the most commonly prescribed drugs, with ebastine, levocetirizine and olopatadine being the leading ones (41.1%, 36.2%, and 16%, respectively). Combinations of several antihistamines (649 cases, 37.8%) at conventional dose were far more common than a single drug at escalated dose (59 cases, 3.4%). The combination of ebastine with levocetirizine was the most frequent options (18.25%, 313 cases), followed by combination of ebastine with compound glycyrrhizin (18.2%, 312 cases). The usage rates of tripterygium glycoside (19.6%), hydroxychloroquine (17.2%) and system application glucocorticoids (5.5%) in angioneurotic edema were much higher than in dermographic urticaria and chronic spontaneous urticaria. Conclusions: This study identifies curative therapy for Chinese outpatients with urticaria. The sgAHs, especially ebastine, are the most commonly prescribed drugs. Olopatadine has fast-acting and curative effects. Compound glycyrrhizin holds potential as a versatile collaborator.Combinations of several antihistamines at conventional dose is common.

Galeaspida is an endemic clade of jawless stem-gnathostomes (‘ostracoderms’), known exclusively from the Silurian and Devonian of China and Vietnam. Among galeaspids, the family Sanqiaspidae is of particular interest for providing the first information on the galeaspid trunk and caudal fin; however, the cranial morphology of sanqiaspids remains poorly known. Here we report the first occurrence of Sanqiaspis in the Xujiachong Formation of Qujing, East Yunnan, and describe new material of Sanqiaspis from two other sites in South China. The new data corroborate the presence of the two median transverse canals in Sanqiaspis as a possible synapomorphy of the Sanqiaspidae. As a key member of the Xujiachong Assemblage, Sanqiaspis is known from the Xujiachong, Guanshanpo, Posongchong, and Si Ka formations. Stratigraphic correlation of eight Early Devonian sections in South China and North Vietnam indicates that the Sanqiaspis-bearing layers can be correlated with the transitional beds between the Lianhuashan and Nahkaoling formations in Liujing, Guangxi. Therefore, the middle-upper part of the Si Ka Formation in northern Vietnam and the upper part of the Lianhuashan Formation in Guangxi should be dated as Pragian, rather than Lochkovian. The fish assemblage from the Pragian of the South China Block documents the diversification of galeaspids, notably Huananaspidiformes, and exhibits much the same endemic pattern as that of early vascular plants and brachiopods. This endemism might be linked with the semi-closed epicontinental nature of the South China Sea during the Early Devonian, which formed a biodiversity hotspot as in the modern Red Sea.

Background This study aimed to analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH). Methods Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) during the same period were also analyzed. Results In group R, three patients who did not respond to methylprednisolone (MP) pulse and intravenous immunoglobulin (IVIG) therapies were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment (dexamethasone and etoposide, with or without cyclosporine A), but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperatures of eleven patients decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The glucocorticoid dosage in group R was significantly lower than that in group C. Both groups were followed-up for 2–2.5 years. No obvious adverse drug reactions to ruxolitinib were observed during treatment and follow-up. Conclusion Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for glucocorticoid therapy for HLH treatment in children, thereby reducing or avoiding glucocorticoid-related adverse reactions.

A new genus and species of the Galeaspida Qushiaspis elaia gen. et sp. nov. is described from the Lower Devonian Xujiachong Formation of Qujing, Yunnan Province, southwestern China. The new genus d...

The atmospheric CO2 concentration continues a rapid increase to its current record high value of 416 ppm for the time being. It calls for advanced CO2 capture technologies. One of the attractive technologies is physical adsorption-based separation, which shows easy regeneration and high cycle stability, and thus reduced energy penalties and cost. The extensive research on this topic is evidenced by the growing body of scientific and technical literature. The progress spans from the innovation of novel porous adsorbents to practical separation practices. Major CO2 capture materials include the most widely used industrially relevant porous carbons, zeolites, activated alumina, mesoporous silica, and the newly emerging metal-organic frameworks (MOFs) and covalent-organic framework (COFs). The key intrinsic properties such as pore structure, surface chemistry, preferable adsorption sites, and other structural features that would affect CO2 capture capacity, selectivity, and recyclability are first discussed. The industrial relevant variables such as particle size of adsorbents, the mechanical strength, adsorption heat management, and other technological advances are equally important, even more crucial when scaling up from bench and pilot-scale to demonstration and commercial scale. Therefore, we aim to bring a full picture of the adsorption-based CO2 separation technologies, from adsorbent design, intrinsic property evaluation to performance assessment not only under ideal equilibrium conditions but also in realistic pressure swing adsorption processes.

Recent evidence highlights the role of adiponectin in the pathophysiology of autism spectrum disorder (ASD), yielding conflicting results. The aims of this study were (1) To assess the adiponectin levels of children with ASD and typical developing (TP); (2) To investigate the relationship between adiponectin levels and symptom severity of children with ASD. This is a single-center cross-sectional study from China. From December 2017 to November 2019, first-diagnosis and drug-naive children with ASD were included. Same TP children who were matched with clinical groups by gender and age were included as the control group. The enzyme-linked immunosorbent assay (ELISA) kit was used to determine serum concentrations of adiponectin. We recorded 176 children (88 were ASD and 88 were TP children) and 77.3% (n = 136) were boys and the mean age was 4.3 years (standard deviations [S.D.]: 1.2). The mean (S.D.) levels of adiponectin were 9.01(2.19) and 11.55(2.32) μg/ml for those with ASD and TP subjects. The difference between those two groups was significant (t = 7.169, p

To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS）.From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed.Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×10Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.ATG联合PTCy的Haplo-HSCT方案治疗儿童骨髓增生异常综合征.探讨ATG联合后置环磷酰胺（PTCy）诱导免疫耐受的单倍体型造血干细胞移植（haplo-HSCT）方案治疗儿童骨髓增生异常综合征（MDS）的疗效及安全性.回顾并分析2016年7月至2020年11月在本中心接受ATG联合PTCy诱导免疫耐受的Haplo-HSCT方案治疗的8例儿童MDS患者的临床资料.8例儿童MDS患者中，男1例，女7例，中位年龄6.4岁（10个月-15岁），病史中位数27年（3个月-8年），7例诊断为难治性血细胞减少症，1例诊断为难治性贫血伴原始细胞增多。供者为患者父亲、母亲或哥哥，HLA配型（6-9）/12位点相合，供者经筛查均为健康供者，未携带受者致病基因，中位年龄364（25-49）岁，回输单个核细胞中位数 19.8(13.2-47.3) ×10ATG联合PTCy诱导免疫耐受的Haplo-HSCT方案是治疗儿童MDS安全有效的方法.

We report a feasibility study of pure leptonic decay $D_s^+\to\mu^+\nu_\mu$ by using a fast simulation software package at STCF. With an expected luminosity of $1~\mathrm{ab}^{-1}$ collected at STCF at a center-of-mass energy of 4.009 GeV, the statistical sensitivity of the branching fraction is determined to be 0.3\%. Combining this result with the $c\rightarrow s$ quark mixing matrix element $|V_{cs}|$ determined from the current global Standard Model fit, the statistical sensitivity of $D_s^+$ decay constant, $f_{D_s^+}$, is estimated to be 0.2\%. Alternatively, combining the current results of $f_{D_s^+}$ calculated by lattice QCD, the statistical sensitivity of $|V_{cs}|$ is determined to be 0.2\%, which helps probe possible new physics beyond. The unprecedented precision to be achieved at STCF will provide a precise calibration of QCD and rigorous test of Standard Model., Comment: 8pages, 7 figures

A simple method based on a thiamonomethinecyanine dye (dye2) and duplex DNA system was constructed to detect Pb2+ by UV–Vis spectra. The absorption spectra of dye2 show dimers and monomers peak and the monomer–dimer equilibrium could be regulated with environmental change. Duplex DNA as a template was used to regulate distinct aggregates of cyanine dye in the presence of Pb2+. This system shows a specific absorption signal for Pb2+ detection.

Recent studies have revealed the important role of long noncoding RNAs (lncRNAs) in heart development and pathogenesis. This study was aimed to investigate the role of NEAT1 in hypoxia-induced cardiac injury and explore its possible molecular mechanism. Real-time PCR (RT-PCR) was used to determine the relative RNA expression of NEAT1 and its potential target microRNA, miR-129-5p, in the plasma of patients with acute myocardial infarction, heart failure, and angina, as well as in H2O2-treated H9c2 cells. The role of NEAT1 overexpression or inhibition in H9c2 cell migration and proliferation was assessed by transwell assay and Edu staining, respectively. Collagen deposition and apoptosis were evaluated by Western blot detection of collagen and apoptotic proteins, including Capase3, Bax, and Bcl2. We showed that H2O2 treatment significantly decreased H9c2 cell migration and proliferation while increasing H9c2 cell apoptosis. Inhibition of NEAT1 attenuated the cell apoptosis and alleviated proliferation inhibition induced by hypoxia. Bioinformatics analysis showed that miR-129-5p was the direct target of NEAT1, which was confirmed by luciferase assay. NEAT1 upregulation aggravated apoptosis by downregulating miR-129-5p. In conclusion, we uncovered a novel NEAT1-miR-129 axis and its implication in H2O2-induced heart failure.

To investigate the effeicacy of Yishen Huoxue decoction (YSHX) on renal fibrosis induced by unilateral ureteric obstruction (UUO), and on reactive oxygen species (ROS) homeostasis in human umbilical vein endothelial cells (HUVECs).Forty male mice were randomly divided into six groups, sham group, UUO group, UUO+ resveratrol (RSV) (15 mg/kg) group, UUO + YSHX 20 mg/kg group (UUO + YSHX-L), UUO + YSHX 40 mg/kg group (UUO + YSHX-M), UUO + YSHX 80 mg/kg group (UUO + YSHX-H). Western blotting was used to measure protein expression levels. Reverse transcription-quantitative polymerase chain reaction was used to measure the mRNA expression. Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample. Cell apoptosis was measured by Annexin V/PI staining. Cell viability was measured using CCK-8/WST-8 assay.YSHX treatment reduced α-SMA and Col-4 expressions, and increased CD31 and VE-cadherin expressions in UUO model mice. In vitro, YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions. YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor coactivator-1α (PGC-1α)/silent mating-type information regulation 2 homolog 3 (Sirt3) signaling.YSHX treatment reduced 109KJ UUO-induced renal injury and fibrosis. Furthermore, YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.

Hermiticity is the fundamental property of the physical systems, for which it should obey the laws of energy conservation and time-reversal symmetry. Parity-time symmetry is introduced to study the non-Hermitian system with real energy spectra. Considering the coupling dissipation of the practical system, there would be phase-related terms on the non-diagonal elements of the Hermitian matrix. Here in this work, we present a coupled circuit model of the system and investigate the dynamics of parity-time-anyonic Hamiltonian related to an arbitrary phase of the system. We find that parity-time symmetry can be achieved under the tunable phases in the quasi-parity-time symmetric circuit system.

Metabolic reprogramming occurs in the clonal evolution of acute myeloid leukemia (AML), which contributes to cell survival under metabolic stress and the development of drug resistance. Leukemic cells exhibit various metabolic profiles, which involve multiple metabolic pathways due to the heterogeneity of AML. However, studies on metabolic targets for AML treatment are mostly focused on glycolysis at present. In this work, we established conditional knock-in AML mouse models harboring Dnmt3aR878H/WT, NrasG12D/WT, and both of the mutations, respectively. Transcriptomic analysis of Gr1+ cells from bone marrow was performed afterward to screen interested metabolic pathways and target genes. Candidate genes were studied using the CRISPR/Cas9 technique, quantitative real-time RT-PCR, and flow cytometric analyses. We revealed that multiple metabolic pathways were affected in AML mice, including lipid metabolism. Endothelial lipase (LIPG) was obviously upregulated in leukemic cells from AML mice with Dnmt3a mutation. We performed knockout of LIPG in OCI-AML3 cells carrying DNMT3A R882C mutation by using the CRISPR/Cas9 technique. Depletion of LIPG led to proliferation inhibition, apoptosis, damage of antioxidant capacity, and myeloid differentiation in OCI-AML3 cells. LIPG might serve as a potential metabolic target for the treatment of AML with abnormal lipid metabolism.

Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis.qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes.Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1.Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.

We report a sensitive study of measuring $$b\rightarrow s\gamma $$ b → s γ photon polarisation in $$D^{0}\rightarrow K_1(1270)^-e^+\nu _e$$ D 0 → K 1 ( 1270 ) - e + ν e with an integrated luminosity of $$\mathscr {L}$$ L = 1 ab$$^{-1}$$ - 1 at a center-of-mass energy of 3.773 GeV at a future Super Tau Charm Facility. More than 61,000 signals of $$D^{0}\rightarrow K_1(1270)^-e^+\nu _e$$ D 0 → K 1 ( 1270 ) - e + ν e are expected. Based on a fast simulation software package, the statistical sensitivity for the ratio of up-down asymmetry is estimated to be $$1.5\times 10^{-2}$$ 1.5 × 10 - 2 by performing a two-dimensional angular analysis in $$D^{0}\rightarrow K_1(1270)^-e^+\nu _e$$ D 0 → K 1 ( 1270 ) - e + ν e . Combining with measurements of up-down asymmetry in $$B\rightarrow K_1\gamma $$ B → K 1 γ , the photon polarisation in $$b\rightarrow s\gamma $$ b → s γ can be determined model-independently.

To identify relationships between busulfan (Bu) exposure and outcomes of a cohort pediatric patients receiving hematopoietic stem cell transplantation (HSCT), along with a targeted busulfan-based conditioning regimen. We retrospectively evaluated targeted busulfan concentrations in 53 pediatric patients (age 0.4-16 years) who received busulfan 4 times daily according to recommended weight-based doses in a single-center analysis between 2018 and 2020. In this trial, individual busulfan pharmacokinetics were performed following dose 5 of the conditioning regimen. Twenty four of 53 patients (45.3%) studies did not require dose adjustments. Equal number of patients (24/53) required one dose adjustments while two-dose adjustment applied for 5 of 53 (9.4%). Twenty-one percent of the patients exhibited ll-lV aGVHD. The incidence of veno-occlusive disease (VOD) was in 3.8% of the 53 patients, while incidence of hemorrhagic cystitis (II-III) reached to 9.7%. Engraftment was successful in 98% of the 53 patients with relapse in 2% of cases. The probability of overall survival and disease-free survival at day 100 was 96% and 94%, respectively. In conclusion, therapeutic drug monitoring (TDM) and individualization of Bu dosage are essential to improve the efficacy and safety of busulfan-based regimen in Chinese pediatric HSCT recipients.

The atmospheric CO

Retinoic acid-inducible gene I (RIG-I) is up-regulated during granulocytic differentiation of acute promyelocytic leukemia (APL) cells induced by all- trans retinoic acid (ATRA). It has been reported that RIG-I recognizes virus-specific 5′-ppp-double-stranded RNA (dsRNA) and activates the type I interferons signaling pathways in innate immunity. However, the functions of RIG-I in hematopoiesis remain unclear, especially regarding its possible interaction with endogenous RNAs and the associated pathways that could contribute to the cellular differentiation and maturation. Herein, we identified a number of RIG-I–binding endogenous RNAs in APL cells following ATRA treatment, including the tripartite motif-containing protein 25 ( TRIM25 ) messenger RNA (mRNA). TRIM25 encodes the protein known as an E3 ligase for ubiquitin/interferon (IFN)-induced 15-kDa protein (ISG15) that is involved in RIG-I–mediated antiviral signaling. We show that RIG-I could bind TRIM25 mRNA via its helicase domain and C-terminal regulatory domain, enhancing the stability of TRIM25 transcripts. RIG-I could increase the transcriptional expression of TRIM25 by caspase recruitment domain (CARD) domain through an IFN-stimulated response element. In addition, RIG-I activated other key genes in the ISGylation pathway by activating signal transducer and activator of transcription 1 (STAT1), including the modifier ISG15 and several enzymes responsible for the conjugation of ISG15 to protein substrates. RIG-I cooperated with STAT1/2 and interferon regulatory factor 1 (IRF1) to promote the activation of the ISGylation pathway. The integrity of ISGylation in ATRA or RIG-I–induced cell differentiation was essential given that knockdown of TRIM25 or ISG15 resulted in significant inhibition of this process. Our results provide insight into the role of the RIG-I-TRIM25-ISGylation axis in myeloid differentiation.

Rationale: Myelodysplastic syndrome (MDS) can be complicated with Crohn disease (CD). Irritable bowel disease (IBD) associated with MDS has already been reported in the past; however, hematopoietic stem cell transplantation (HSCT) is rarely performed. Herein, we report a case of CD with MDS for HSCT. Patient concerns: A 41-year-old man was hospitalized due to abdominal pain and intermittent fever for 40 days. Two years later, he was readmitted due to abdominal pain and diarrhea with fever for 10 days. Diagnosis: Symptoms, laboratory examinations, and imaging findings of the patient were indicative of CD complicated with MDS. Interventions: An allogeneic HSCT was performed. Outcomes: He died of severe lung infection 125 days post-transplantation. Lessons: The number of cases of CD combined with MDS remains insufficient, and no consensus opinions are available to date. Hence, HSCT is a very potential treatment method. Additional experiences are needed to determine its effectiveness.

Systemic sclerosis is a chronic multisystem autoimmune disease that is associated with polyclonal B cell hyperreactivity. The CDR3 of BCRs is the major site of antigen recognition. Therefore, we analyzed the BCR repertoire of patients with SSc. The BCR repertoires in 12 subjects including eight SSc patients and four healthy controls were characterized by high-throughput sequencing, and bioinformatics analysis were studied. The average CDR3 length in the SSc group was significantly shorter. The SSc patient displayed more diverse BCR. Moreover, SSc patients with mild skin sclerosis, anti-Scl70, interstitial lung disease or female sex were more diversified. B cells from the SSc patients showed a differential V and J gene usage. SSc patients had distinct BCR repertoires.These findings reflected the differences of BCR repertoires between SSc patients and controls. The higher-usage genes for the BCR sequence might be potential biomarkers of B cell-targeted therapies or diagnosis for SSc.

$CP$ violation is an excellent tool for probing flavor dynamics as we learned first with ${K}_{L}\ensuremath{\rightarrow}2\ensuremath{\pi}$ and later also with the weak decays of beauty mesons. LHCb 2019 data have shown $CP$ violation for the first time in ${D}^{0}\ensuremath{\rightarrow}{K}^{\ensuremath{-}}{K}^{+}$ vs ${D}^{0}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}$. Searching for $CP$ asymmetries is of great interest in the charm quark sector in the Standard Model (SM) or even more beyond it. In charm hadron decays, lots of work had focused on two-body final states, and the measurements of $CP$ asymmetries in three- or four-body final states are rare. Dalitz plots have shown an excellent record for three-body final states, and more results are desired for four-body ones. In this work we study $CP$ asymmetries in the decays ${\mathrm{\ensuremath{\Lambda}}}_{c}^{+}\ensuremath{\rightarrow}p{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{0}/\mathrm{\ensuremath{\Lambda}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}/p{K}_{S}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$, where the SM gives zero values for the first two channels, while $3.3\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}$ is given for the last one due to ${K}^{0}\ensuremath{-}{\overline{K}}^{0}$ oscillation. We performed a fast Monte Carlo simulation study by using electron-positron annihilation data of $1\text{ }\text{ }{\mathrm{ab}}^{\ensuremath{-}1}$ at center-of-mass energy $\sqrt{s}=4.64\text{ }\text{ }\mathrm{GeV}$. The data is expected to be available by the next generation Super Tau Charm Facility proposed by China and Russia with one year (or even less) of the data taking operation. The results indicate that a sensitivity at the level of $0.2\ensuremath{\sim}0.5%$ is accessible for these processes, which would be enough to measure nonzero $CP$-violating asymmetries as large as 1%. Furthermore ${A}_{T\text{-odd}}\ensuremath{\ne}0$ can establish parity violation by themselves and likewise for ${\overline{A}}_{T\text{-odd}}\ensuremath{\ne}0$. The SM is based on ${W}^{+/\ensuremath{-}}$ being 100% left handed. One can compare decay asymmetry parameters ${a}_{\text{P}}$ from ${\mathrm{\ensuremath{\Lambda}}}_{c}^{+}\ensuremath{\rightarrow}\mathrm{\ensuremath{\Lambda}}{e}^{+}\ensuremath{\nu}$ vs ${\overline{a}}_{\text{P}}$ from ${\overline{\mathrm{\ensuremath{\Lambda}}}}_{c}^{\ensuremath{-}}\ensuremath{\rightarrow}\overline{\mathrm{\ensuremath{\Lambda}}}{e}^{\ensuremath{-}}\overline{\ensuremath{\nu}}$. In the SM one gets ${a}_{\text{P}}=1$ and ${\overline{a}}_{\text{P}}=\ensuremath{-}1$ in the SM, while present data give the following: $({a}_{\mathrm{P}}+{\overline{a}}_{\mathrm{P}})/2=0.00\ifmmode\pm\else\textpm\fi{}0.04$. Probing these nonleptonic decays of ${\mathrm{\ensuremath{\Lambda}}}_{c}^{+}$ would give new lessons about nonperturbative QCD or even indirect impact of new dynamics on parity violation.

Itching is a leading symptom of eczema or dermatitis and has a great impact on patients’ lives. Previous studies on itching have focused mostly on atopic dermatitis (AD). A cross-sectional multicenter study was conducted among outpatients with eczema from 39 tertiary hospitals in mainland China from July 1 to September 30, 2014. This work elaborates on itching in different types of eczema. Itching was very common (97%, 8499/8758) in outpatients with eczema. The severity of the itch increased with age and disease duration (P P P P P

Significance DNMT3A is a critical epigenetic modifier and tumor suppressor in the hematopoietic system. This gene is frequently mutated in hematopoietic malignancies, including acute myeloid leukemia (AML), with Dnmt3a R878H being the most common mutant. By using a conditional knockin approach, this study shows that Dnmt3a R878H is sufficient to initiate AML and recapitulate human leukemic features in mice. The leukemia-initiating cells are enriched in hematopoietic stem/progenitor cells. Through gene expression profiling, DNA methylation and histone modification analysis, and functional tests on important regulators for cell proliferation and differentiation in an animal model, this study has not only discovered mTOR pathway activation as a key player in the disease mechanism but also revealed the potential therapeutic effects of mTOR inhibition on DNMT3A mutation-related leukemia.

Astemizole has gained attention as an antineoplastic drug that targets important ion channels. The present study aimed to investigate the protective effects of astemizole against hydrogen peroxide (H2O2)‑induced oxidative damage to human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated with astemizole (0.5 and 1 µM) for 12 h, then exposed to H2O2 (200 µM) for 12 h. Cell viability was measured using the MTT assay. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px), reactive oxygen species (ROS) and apoptotic percentage were determined. Additionally, the protein expression of p53, p21Cip1/Waf1 and p16INK4a was measured by western blot analysis The results demonstrated that astemizole (0.5‑1 µM) was able to significantly restore the viability of HUVECs under oxidative stress and scavenge intracellular ROS induced by H2O2. Astemizole also suppressed the production of lipid peroxides, such as MDA, and restored the activities of endogenous antioxidants, including SOD and GSH‑Px, indicating that cell apoptosis may be inhibited. In addition, astemizole significantly increased p53, p21Cip1/Waf1 and p16INK4a protein expression. In conclusion, astemizole effectively protected endothelial cells against oxidative stress induced by H2O2, a function that may involve ROS/p53/p21Cip1/Waf1/ p16INK4a signaling pathways. The present study therefore served as a preliminary investigation into the ROS‑protective effects of astemizole, and may pave the way for future studies into the development of this compound as a novel therapy for atherosclerosis.

A Super Tau Charm Facility (STCF) is one of the major options for the accelerator-based high energy project in China in the post-BEPCII era, and its R&D program is underway. The proposed STCF will span center of mass energies (√(s)) ranging from 2 to 7 GeV with a peaking luminosity above 0.5× 1035 cm−2 s−1 at √(s)=4.0 GeV, and will provide a unique platform for tau-charm physics and hadron physics. In order to evaluate the physical potential capabilities and optimize the detector design, a fast simulation package has been developed. This package takes as inputs the response of physical objects in each sub-system of the detector including resolution, efficiency as well as related variables for the kinematic fit and the secondary vertex reconstruction algorithm. It can flexibly adjust the responses of each sub-detector system and is a critical tool for the STCF R&D program.

Soluble amyloid-β (Aβ) oligomers, also known as Aβ-derived diffusible ligands (ADDLs), are thought to be the key pathogenic factor in Alzheimer's disease (AD), but there is still no effective treatment for preventing or reversing the progression of the disease. Targeting NMDA receptor trafficking and regulation is a new strategy for early treatment of AD. Aβ oligomers have been found to bind to the fibronectin (FN) type III repeat domain of EphB2 to trigger EphB2 degradation, thereby impairing the normal functioning of NMDA receptors and resulting in cognitive deficits. Here, we identified for the first time the interaction sites of the EphB2 FN domain with ADDLs by applying the peptide array method to design and synthesize four candidate peptides (Pep21, Pep25, Pep32, and Pep63) that might be able to block the EphB2–ADDL interaction. Among them, Pep63 was found to be the most effective at inhibiting the binding between EphB2 and ADDLs. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2- and GluN2B-containing NMDA receptors from the neuronal surface in cultured hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic mice and the phosphorylation and surface expression of GluN2B-containing NMDA receptors in cultures. Together, these results suggest that blocking the EphB2–ADDL interaction by small interfering peptides may be a promising strategy for AD treatment.SIGNIFICANCE STATEMENTAlzheimer's disease (AD) is an age-dependent neurodegenerative disorder and amyloid β-derived diffusible ligands (ADDLs) play a key role in triggering the early cognitive deficits that constitute AD. ADDLs may bind EphB2 and alter NMDA receptor trafficking and synaptic plasticity. Here, we identified the interaction sites of the EphB2 FN domain with ADDLs for the first time to develop a small (10 aa) peptide (Pep63) capable of blocking the EphB2–ADDL interaction. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2 and GluN2B-containing NMDA receptors from the neuronal surface in cultured hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic mice. Our results suggest that blocking the EphB2–ADDL interaction with Pep63 may be a promising strategy for AD treatment.

Cholinesterase inhibitors (ChEIs), represented by donepezil, rivastigmine, and galantamine, used to be the only approved class of drugs for the treatment of Alzheimer’s disease. After the approval of memantine by the Food and Drug Administration (FDA), N-methyl-d-aspartic acid (NMDA) receptor antagonists have been recognized by authorities and broadly used in the treatment of Alzheimer’s disease. Along with complementary mechanisms of action, NMDA antagonists and ChEIs differ not only in therapeutic effects but also in adverse reactions, which is an important consideration in clinical drug use. And the number of patients using NMDA antagonists and ChEIs concomitantly has increased, making the matter more complicated. Here we used the FDA Adverse Event Reporting System for statistical analysis , in order to compare the adverse events of memantine and ChEIs. In general, the clinical evidence confirmed the safety advantages of memantine over ChEIs, reiterating the precautions of clinical drug use and the future direction of antidementia drug development.

Rationale In the course of endocarditis, the development of antineutrophil cytoplasmic antibody (ANCA)-mediated disease introduces the dilemma of determining the best treatment approach for immune conditions, whether immunosuppressant therapy should be added to antibiotic treatment has remained controversial. Patient concerns A 33-year-old man presented with progressive fever lasting for 7 months, and swelling, pain, and purpura in the arms and legs. The patient showed multiple autoantibodies including cytoplasmic ANCA, antiproteinase 3, rheumatoid factor, and anti-beta 2 glycoprotein I. Blood culture was positive for viridans streptococcus, and renal biopsy revealed glomerulonephritis and interstitial nephritis. Diagnosis Endocarditis caused by viridans streptococci, ANCA-associated vasculitis, and congenital ventricular septal defect. Interventions In addition to effective antibiotics, he also received twice intravenous corticosteroids and intravenous immunoglobulin therapy, and a low dose of cyclophosphamide. At last, the patient received congenital ventricular septal defect repair and debridement. Outcomes The abnormal clinical manifestations, including renal failure and loss of strength, recovered rapidly with corticosteroid therapy in addition to antibiotic treatment. After 6 months without any medications, he remained asymptomatic and was able to live normally. Lessons In this case with endocarditis and ANCA-associated vasculitis, we highlighted the importance of biopsy and immunosuppressive therapy. Histopathologic examination is required for diagnosis and treatment in such case. Identifying patients who have endocarditis and ANCA positivity with vasculitis pathologic features will require corticosteroid/immunosuppressives in addition to the antibiotics therapy.

Objective To evaluate the nutrition risks in Chinese elderly adults in community and provide the basis for malnutrition prevention.Methods The study population comprised of adults aged 60 years or older selected from communities. A stratified multi-stage cluster sampling method was used to investigate older adults in rural and urban areas with structured questionnaire. Nutrition Screening Initiative (NSI) checklist was used to screen nutritional status. Analyses were stratified according to age,gender,different regions,rural and urban areas,and income.Results A total of 3885 older adults with complete information were enrolled for final analyses,among whom 1894 (48.8%) were males and 1991 (51.2%) were females; 56.2% aged 60-69 years,28.8% aged 70-79 years,and 15% aged over 80 years; 1665(42.9%) were urban residents; 1592(41.0%) were in the eastern region,1211(31.2%) in the central region,and 1082(27.8%) in the western region. Up to 48.4% of the elderly adults were at high nutritional risk,and the nutritional risk was significantly higher in females (50.7%) than in males (46.0%),in individuals aged over 80 years (53.0%) than in other age groups,in urban area (41.7%) than in rural area (53.9%),and in eastern region (52.9%) than in other regions. Significant differences were found between nutritional status and the following variables: age (Χ

Background DNMT3A R882H, a frequent mutation in acute myeloid leukemia (AML), plays a critical role in malignant hematopoiesis. Recent findings suggest that DNMT3A mutant acts as a founder mutation and requires additional genetic events to induce full-blown AML. Here, we investigated the cooperation of mutant DNMT3A and NRAS in leukemogenesis by generating a double knock-in (DKI) mouse model harboring both Dnmt3a R878H and Nras G12D mutations. Methods DKI mice with both Dnmt3a R878H and Nras G12D mutations were generated by crossing Dnmt3a R878H knock-in (KI) mice and Nras G12D KI mice. Routine blood test, flow cytometry analysis and morphological analysis were performed to determine disease phenotype. RNA-sequencing (RNA-seq), RT-PCR and Western blot were carried out to reveal the molecular mechanism. Results The DKI mice developed a more aggressive AML with a significantly shortened lifespan and higher percentage of blast cells compared with KI mice expressing Dnmt3a or Nras mutation alone. RNA-seq analysis showed that Dnmt3a and Nras mutations collaboratively caused abnormal expression of a series of genes related to differentiation arrest and growth advantage. Myc transcription factor and its target genes related to proliferation and apoptosis were up-regulated, thus contributing to promote the process of leukemogenesis. Conclusion This study showed that cooperation of DNMT3A mutation and NRAS mutation could promote the onset of AML by synergistically disturbing the transcriptional profiling with Myc pathway involvement in DKI mice.

Taxus chinensis var. mairei is a national Category 1 protective species in China, with its northernmost natural distribution to the southeast of Shanxi Province, China. This study was conducted to investigate the natural distribution of T. chinensis var. mairei in Shanxi Province. The community classification, species diversity, population structure and competition intensity of T. chinensis var. mairei were studied. The results showed that T. chinensis var. mairei mainly formed four community types, including the community of T. chinensis var. mairei + Carpinus turczaninowii, the community of T. chinensis var. mairei - Vitex negundo var. heterophylla, the community T. chinensis var. mairei - Clerodendrum trichotomum and the community of T. chinensis var. mairei + Quercus variabilis. T. chinensis var. mairei was concentratedly distributed in Mohe of Linchuan County and Manghe Nature Reserve of Yangcheng County, and scattered in some other areas. The communities had an obviously vertical structure, with T. chinensis var. mairei trees growing into main canopy which were about 8-10 m high in mixed forests and 5-6 m high in pure forests. The species diversity index and evenness index had significant difference among the four community types. The average height of T. chinensis var. mairei was 5.16 m. The individuals in tree layer and succession layer were 43.4% and 56.6%, respectively, while they were scarce in the regeneration layer. 67.6% of the trees were small-diameter (DBH＜16 cm) and only 4.0% were large-diameter (32 cm≤DBH＜40 cm). T. chinensis var. mairei was considered to be lack of seedlings because only 4 seedlings were found, which might result in the declination of this species in future. T. chinensis var. mairei in Shanxi Province showed relatively concentrated distribution, with most individuals being small-diameter, resulting in tense intraspecific competition which accounted for 61.8% of the total intensity. The interspecific competition to T. chinensis var. mairei was mainly from C. turczaninowii and Q. variabilis, which were two dominant tree species with larger population in this area.南方红豆杉为国家Ⅰ级重点保护植物,山西省东南部为其自然分布最北界.本文调查了南方红豆杉在山西省的野生分布,对其进行了群落划分、物种多样性、结构特征和竞争特性的研究.结果表明: 山西省南方红豆杉主要形成南方红豆杉+鹅耳枥群落、南方红豆杉-荆条群落、南方红豆杉-海州常山群落和南方红豆杉+栓皮栎群落,集中分布于陵川县磨河和阳城县蟒河自然保护区,其他地区均为散生;群落垂直结构明显,南方红豆杉已进入主林层,混交林林冠层高8~10 m,纯林高5～6 m;群落间的总体物种多样性指数和均匀度指数存在显著差异.南方红豆杉植株矮小,平均高5.16 m,乔木层、演替层分别占43.4%和56.6%,更新层缺乏;胸径＜16 cm的个体占67.6%,胸径32～40 cm的个体占4.0%,幼苗稀少,仅发现4株幼苗;大量的小径级个体虽可保证南方红豆杉在一定时间内维持稳定的种群结构,但幼苗缺失必将引起未来种群的衰退.山西省野生南方红豆杉分布相对集中,多数是小径级个体,导致其种内竞争激烈,种内竞争强度占61.8%;鹅耳枥和栓皮栎是研究地区的主要组成树种,对南方红豆杉造成的种间竞争压力最大.

Effects of various concentrations of Cu(2+) and Zn(2+) (0.0, 0.1, 0.25, 0.5, or 1.0 mg/L) on the growth, malondialdehyde (MDA), the intracellular calcium, and physiological characteristics of green algae, Cladophora, were investigated. Low Zn(2+) concentrations accelerated the growth of Cladophora, whereas Zn(2+) concentration increases to 0.25 mg/L inhibited its growth. Cu(2+) greatly influences Cladophora growth. The photosynthesis of Cladophora decreased under Zn(2+) and Cu(2+) stress. Cu(2+) and Zn(2+) treatment affected the content of total soluble sugar in Cladophora and has small increases in its protein content. Zn(2+) induced the intracellular calcium release, and copper induced the intracellular calcium increases in Cladophora. Exposure to Cu(2+) and Zn(2+) induces MDA in Cladophora. The stress concent of Cu(2+) was strictly correlated with the total soluble sugar content, Chla+Chlb, and MDA in Cladophora, and the stress concent of Zn(2+) was strictly correlated with the relative growth rate (RGR) and MDA of Cladophora.