Implication of GRB 221009A: Can TeV Emission Come from the GRB Prompt Phase?

Recently, the B.O.A.T. ("brightest of all time") gamma-ray burst, dubbed GRB 221009A, was detected by various instruments. Unprecedentedly, the GRB presented very-high-energy (VHE, energy above 0.1 TeV) gamma-ray emission with energy extending above 10 TeV, as reported by the Large High Altitude Air Shower Observatory (LHAASO). We here demonstrate that the VHE and especially >10 TeV emission may originate from the internal hadronic dissipation of the GRB, without the need of invoking any exotic processes as suggested by some previous studies. We also discuss the constraints on the properties of the GRB ejecta from multiwavelength and multi-messenger observations, which favors a magnetically dominated GRB ejecta. The suggested Poynting-flux-dominated GRB ejecta in this work supports the Blandford & Znajek (BZ) mechanism as the possible central engine model of GRB.Comment: 13 pages, 7 figures, 3 tables, accepted versio

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. PROSPERO, CRD42023396828. [Abstract copyright: © 2023 Korea Institute of Oriental Medicine. Published by Elsevier B.V.

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy

Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure

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

Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved

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