脑舒胶囊对衰老小鼠免疫功能的调节作用

Objective: To observe the effects of NaoShu capsule on immune function of aging mice. Methods: Aging mice was induced by subcutaneous injections model was induced by subcutaneous injections with 5% D-galactose at the neck for 6 weeks, IL-2 and IL-6 content in serum were detected by means of radio-immunity, and calculating the index of organ by a ratio of the weight of thymus and spleen and the weight of mice. Results: Compared with the control group, the thymus and spleen index of mice was decreased obvious; the IL-2 content was obvious decreased, and the IL-6 content was obvious increased in aging model group. Compared with the model group, the the IL-2 content was enhanced and the IL-6 content was obvious decreased in the therapeutic group with 1.33g/kg and 2.66g/kg Naoshu capsule (P<0.05, 0.01). Conclusion: There has a certain correlation between aging and immune, and there are obvious accommodation of Naoshu capsule on immune function of aging mice.目的  观察脑舒胶囊对衰老小鼠免疫功能的调节作用。方法  5%D-半乳糖颈背部皮下注射连续6周制备衰老小鼠模型；放射免疫法测小鼠血清IL-2和IL-6含量；胸腺、脾脏重量比小鼠体重，计算脏器指数。结果  与对照组比较，衰老模型组小鼠胸腺、脾脏指数明显下降，血清IL-2含量明显降低，IL-6的含量明显提高。与模型组比较，1.33g/kg和2.66g/kg脑舒胶囊可明显提高衰老小鼠的胸腺和脾指数（P<0.05，0.01），升高衰老小鼠血清IL-2含量（P<0.05，0.01），降低血清IL-6含量（P<0.05，0.01）。结论  衰老与免疫存在相关性，脑舒胶囊对衰老小鼠的免疫功能具有明显的调节作用

Lini0.5mn1.5o4 spinel cathode using room temperature ionic liquid as electrolyte

In this study, LiNi0.5Mn1.5O4 (LNMO) nanoparticles were prepared as a 5 V cathode material via a rheological phase method and annealed at different temperatures: 680 ◦C, 750 ◦C, and 820 ◦C. The sample annealed at 750 ◦C shows the best performance. A room temperature ionic liquid (RTIL) containing 1 M lithium bis(trifluoromethanesulfonyl) imide (LiNTf2) in N-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesulfonyl) imide (C4mpyrNTf2) was used as novel electrolyte in conjunction with the LNMO cathodes and their electrochemical properties have been investigated. The results show that the LNMO using RTIL as electrolyte has better coulombic efficiency and comparable discharge capacities to those of the cells assembled with standard liquid electrolyte (1 M LiPF6 in ethylene carbonate/diethyl carbonate). Electrochemical impedance spectroscopy shows that the RTIL is much more stable as the electrolyte for LiNi0.5Mn1.5O4 than the conventional electrolyte

In-situ tunable giant electrical anisotropy in a grating gated AlGaN/GaN two-dimensional electron gas

Materials with in-plane electrical anisotropy have great potential for designing artificial synaptic devices. However, natural materials with strong intrinsic in-plane electrical anisotropy are rare. We introduce a simple strategy to produce extremely large electrical anisotropy via grating gating of a semiconductor two-dimensional electron gas (2DEG) of AlGaN/GaN. We show that periodically modulated electric potential in the 2DEG induces in-plane electrical anisotropy, which is significantly enhanced in a magnetic field, leading to an ultra large electrical anisotropy. This is induced by a giant positive magnetoresistance and a giant negative magnetoresistance under two orthogonally oriented in-plane current flows, respectively. This giant electrical anisotropy is in-situ tunable by tailoring both the grating gate voltage and the magnetic field. Our semiconductor device with controllable giant electrical anisotropy will stimulate new device applications, such as multi-terminal memtransistors and bionic synapses

Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1 -positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study

Background The mcr-1 gene confers transferable colistin resistance. mcr-1-positive Enterobacteriaceae (MCRPE) have attracted substantial medical, media, and political attention; however, so far studies have not addressed their clinical impact. Herein, we report the prevalence of MCRPE in human infections and carriage, clinical associations of mcr-1-positive Escherichia coli (MCRPEC) infection, and risk factors for MCRPEC carriage. Methods We undertook this study at two hospitals in Zhejiang and Guangdong, China. We did a retrospective cross-sectional assessment of prevalence of MCRPE infection from isolates of Gram-negative bacteria collected at the hospitals from 2007 to 2015 (prevalence study). We did a retrospective case-control study of risk factors for infection and mortality after infection, using all MCRPEC from infection isolates and a random sample of mcr-1-negative E coli infections from the retrospective collection between 2012 and 2015 (infection study). We also did a prospective case-control study to assess risk factors for carriage of MCRPEC in rectal swabs from inpatients with MCRPEC and mcr-1 negative at the hospitals and collected between May and December, 2015, compared with mcr-1-negative isolates from rectal swabs of inpatients (colonisation study). Strains were analysed for antibiotic resistance, plasmid typing, and transfer analysis, and strain relatedness. Findings We identified 21 621 non-duplicate isolates of Enterobacteriaceae, Acinetobacter spp, and Pseudomonas aeruginosa from 18 698 inpatients and 2923 healthy volunteers. Of 17 498 isolates associated with infection, mcr-1 was detected in 76 (1%) of 5332 E coli isolates, 13 (<1%) of 348 Klebsiella pneumoniae, one (<1%) of 890 Enterobacter cloacae, and one (1%) of 162 Enterobacter aerogenes. For the infection study, we included 76 mcr-1-positive clinical E coli isolates and 508 mcr-1-negative isolates. Overall, MCRPEC infection was associated with male sex (209 [41%] vs 47 [63%], adjusted p=0·011), immunosuppression (30 [6%] vs 11 [15%], adjusted p=0·011), and antibiotic use, particularly carbapenems (45 [9%] vs 18 [24%], adjusted p=0·002) and fluoroquinolones (95 [19%] vs 23 [30%], adjusted p=0·017), before hospital admission. For the colonisation study, we screened 2923 rectal swabs from healthy volunteers, of which 19 were MCRPEC, and 1200 rectal swabs from patients, of which 35 were MCRPEC. Antibiotic use before hospital admission (p<0·0001) was associated with MCRPEC carriage in 35 patients compared with 378 patients with mcr-1-negative E coli colonisation, whereas living next to a farm was associated with mcr-1-negative E coli colonisation (p=0·03, univariate test). mcr-1 could be transferred between bacteria at high frequencies (10−1 to 10−3), and plasmid types and MCRPEC multi-locus sequence types (MLSTs) were more variable in Guangdong than in Zhejiang and included the human pathogen ST131. MCRPEC also included 17 unreported ST clades. Interpretation In 2017, colistin will be formally banned from animal feeds in China and switched to human therapy. Infection with MRCPEC is associated with sex, immunosuppression, and previous antibiotic exposure, while colonisation is also associated with antibiotic exposure. MLST and plasmid analysis shows that MCRPEC are diversely spread throughout China and pervasive in Chinese communities

Antagonist Effect of Triptolide on AKT Activation by Truncated Retinoid X Receptor-alpha

Background: Retinoid X receptor-alpha (RXR alpha) is a key member of the nuclear receptor superfamily. We recently demonstrated that proteolytic cleavage of RXR alpha resulted in production of a truncated product, tRXR alpha, which promotes cancer cell survival by activating phosphatidylinositol-3-OH kinase (PI3K)/AKT pathway. However, how the tRXR alpha-mediated signaling pathway in cancer cells is regulated remains elusive. Methodology/Principal Findings: We screened a natural product library for tRXR alpha targeting leads and identified that triptolide, an active component isolated from traditional Chinese herb Trypterygium wilfordii Hook F, could modulate tRXR alpha-mediated cancer cell survival pathway in vitro and in animals. Our results reveal that triptolide strongly induces cancer cell apoptosis dependent on intracellular tRXR alpha expression levels, demonstrating that tRXR alpha serves as an important intracellular target of triptolide. We show that triptolide selectively induces tRXR alpha degradation and inhibits tRXR alpha-dependent AKT activity without affecting the full-length RXR alpha. Interestingly, such effects of triptolide are due to its activation of p38. Although triptolide also activates Erk1/2 and MAPK pathways, the effects of triptolide on tRXR alpha degradation and AKT activity are only reversed by p38 siRNA and p38 inhibitor. In addition, the p38 inhibitor potently inhibits tRXR alpha interaction with p85 alpha leading to AKT inactivation. Our results demonstrate an interesting novel signaling interplay between p38 and AKT through tRXR alpha mediation. We finally show that targeting tRXR alpha by triptolide strongly activates TNF alpha death signaling and enhances the anticancer activity of other chemotherapies Conclusions/Significance: Our results identify triptolide as a new xenobiotic regulator of the tRXR alpha-dependent survival pathway and provide new insight into the mechanism by which triptolide acts to induce apoptosis of cancer cells. Triptolide represents one of the most promising therapeutic leads of natural products of traditional Chinese medicine with unfortunate side-effects. Our findings will offer new strategies to develop improved triptolide analogs for cancer therapy.National Natural Science Foundation of China [NSFC: 30971445, 90913015, 91129302]; NSFC/Hong Kong Research Grants Council [NSFC/RGC: 30931160431/N_HKU 735/09]; Natural Science Foundation of Fujian Province [2009J01198

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.Improving the Ability of Diagnosis and Treatment of Difficult Disease

The Antibody Targeting the E314 Peptide of Human Kv1.3 Pore Region Serves as a Novel, Potent and Specific Channel Blocker

Selective blockade of Kv1.3 channels in effector memory T (TEM) cells was validated to ameliorate autoimmune or autoimmune-associated diseases. We generated the antibody directed against one peptide of human Kv1.3 (hKv1.3) extracellular loop as a novel and possible Kv1.3 blocker. One peptide of hKv1.3 extracellular loop E3 containing 14 amino acids (E314) was chosen as an antigenic determinant to generate the E314 antibody. The E314 antibody specifically recognized 63.8KD protein stably expressed in hKv1.3-HEK 293 cell lines, whereas it did not recognize or cross-react to human Kv1.1(hKv1.1), Kv1.2(hKv1.2), Kv1.4(hKv1.4), Kv1.5(hKv1.5), KCa3.1(hKCa3.1), HERG, hKCNQ1/hKCNE1, Nav1.5 and Cav1.2 proteins stably expressed in HEK 293 cell lines or in human atrial or ventricular myocytes by Western blotting analysis and immunostaining detection. By the technique of whole-cell patch clamp, the E314 antibody was shown to have a directly inhibitory effect on hKv1.3 currents expressed in HEK 293 or Jurkat T cells and the inhibition showed a concentration-dependence. However, it exerted no significant difference on hKv1.1, hKv1.2, hKv1.4, hKv1.5, hKCa3.1, HERG, hKCNQ1/hKCNE1, L-type Ca2+ or voltage-gated Na+ currents. The present study demonstrates that the antibody targeting the E314 peptide of hKv1.3 pore region could be a novel, potent and specific hKv1.3 blocker without affecting a variety of closely related Kv1 channels, KCa3.1 channels and functional cardiac ion channels underlying central nervous systerm (CNS) disorders or drug-acquired arrhythmias, which is required as a safe clinic-promising channel blocker

The Large High Altitude Air Shower Observatory (LHAASO) Science White Paper

The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously-operated gamma ray telescope in the energy range between 10$^{11}$ and $10^{15}$ eV. The experiment will be able of continuously surveying the TeV sky for steady and transient sources from 100 GeV to 1 PeV, t hus opening for the first time the 100-1000 TeV range to the direct observations of the high energy cosmic ray sources. In addition, the different observables (electronic, muonic and Cherenkov/fluorescence components) that will be measured in LHAASO will allow to investigate origin, acceleration and propagation of the radiation through a measurement of energy spec trum, elemental composition and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO in cosmic rays physics and gamma astronomy would play a key-role in the comprehensive general program to explore the High Energy Universe. LHAASO will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. In this document we introduce the concept of LHAASO and the main science goals, providing an overview of the project.Comment: This document is a collaborative effort, 185 pages, 110 figure

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements