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The PandaX-4T experiment, a 4-ton scale dark matter direct detection experiment, is being planned at the China Jinping Un- derground Laboratory. In this paper we present a simulation study of the expected background in this experiment. In a 2.8-ton fiducial mass and the signal region between 1–10 keV electron equivalent energy, the total electron recoil background is found to be 4:9 × 10 −5 kg −1 d −1 keV −1 . The nuclear recoil background in the same region is 2:8 × 10 −7 kg −1 d −1 keV −1 . With an exposure of 5.6 ton-years, the sensitivity of PandaX-4T could reach a minimum spin-independent dark matter-nucleon cross section of 6 × 10 −48 cm 2 at a dark matter mass of 40 GeV/ c 2 .

Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health and attracted the attention of the World Health Organization (WHO) and the governments of various countries. Therefore, the establishment of measures against bacterial resistance and the discovery of new antibacterial drugs are increasingly urgent to better contain the emergence of bacterial resistance and provide a reference for the development of new antibacterial drugs. In this review, we discuss some antibiotic drugs that have been approved for clinical use and a partial summary of the meaningful research results of anti-drug resistant bacterial drugs in different fields, including the antibiotic drugs approved by the FDA from 2015 to 2020, the potential drugs against drug-resistant bacteria, the new molecules synthesized by chemical modification, combination therapy, drug repurposing, immunotherapy and other therapies.

A bstract PandaX-4T is a ton-scale dark matter direct detection experiment using a dual-phase TPC technique at the China Jinping Underground Laboratory. Various ultra-low background technologies have been developed and applied to material screening for PandaX-4T, including HPGe gamma spectroscopy, ICP-MS, NAA, radon emanation measurement system, krypton assay station, and alpha detection system. Low background materials were selected to assemble the detector. Surface treatment procedures were investigated to further suppress radioactive background. Combining measured results and Monte Carlo simulation, the total material background rates of PandaX-4T in the energy region of 1–25 keV ee are estimated to be (9.9 ± 1.9) × 10 − 3 mDRU for electron recoil and (2.8 ± 0.6) × 10 − 4 mDRU for nuclear recoil. In addition, nat Kr in the detector is estimated to be < 8 ppt.

Introduction: Phellinus igniarius (P. igniarius) (Sanghuang) is a widely used traditional Chinese medicine fungus, and its natural products have great potential for clinical application in immune enhancement. This study aimed to explore the immune-enhancing activity and underlying mechanisms of the polysaccharides and flavonoids derived from Phellinus igniarius ( P. igniarius ) and to provide a theoretical and experimental basis for the development of novel drugs. Methods: Wild P. igniarius YASH1 from the Loess Plateau in Yan’an region was collected, and polysaccharides and total flavonoids were extracted, isolated and identified from mycelium and sporophore. In vitro antioxidant activity was detected through the scavenging activity of hydroxyl radicals and total antioxidant capacity. Cell Counting Kit-8 and trypan blue detection kit were used to detect the effect of extract polysaccharides and flavonoids on the proliferation and phagocytosis ability of immune cells. To assess the effect of the drugs on cytokine secretion by immune cells and immune recovery in immunocompromised mice, the expression of interleukin (IL)-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were examined at the cellular and animal levels. The species composition, abundance of gut microbiota and the altered content of short-chain fatty acids in the feces were analyzed to elucidate the possible mechanisms of drugs by 16S ribosomal RNA (rRNA) amplifiers sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both polysaccharides and flavonoids derived from mycelium or sporophore had antioxidant activity and may stimulate the expression and secretion of IL-2, IL-6, and IFN-γ in immune cells while inhibiting TNF-α expression and secretion and increasing IL-2, IL-6, and IFN- γ expression levels in mice. Furthermore, polysaccharides and flavonoids from mycelium and sporophore showed different effects on the metabolic response of intestinal short-chain fatty acids (SCFAs) in mice, and the use of these drugs remarkably changed the species composition and abundance of intestinal flora in mice. Discussion: Polysaccharides and flavonoids from P. igniarius YASH1 mycelium and sporophore have in vitro antioxidant activity, and they affect the promotion of cell proliferation, stimulation of IL-2, IL-6, and IFN-γ secretion, and inhibition of TNF-α expression in immune cells. Polysaccharides and flavonoids from P. igniarius YASH1 may enhance immunity in immunocompromised mice and remarkably affect the intestinal flora and content of SCFAs.

PandaX is a large liquid-xenon detector experiment usable for direct dark-matter detection and 136Xe double-beta decay search. The central vessel was designed to accommodate a staged target volume increase from initially 120 kg （stage I） to 0.5 t （stage II） and eventually to a multi-ton scale. The experiment is located in the Jinping Deep-Underground Laboratory in Sichuan, China. The detector operates in dual-phase mode, allowing detection of both prompt scintillation, and ionization charge through proportional scintillation. In this paper a detailed description of the stage I detector design and performance as well as results established during the commissioning phase are presented.

This study aimed to explore the efficacy of zunyimycin C in the immunological enhancement of hypoimmune mice and improvement of cognitive impairment in a mice model of Alzheimer’s disease (AD). Zunyimycin C was administered intranasally to interfere with AD mouse models or gavage to hypoimmune animals. Results of the Morris water maze (MWM) showed that zunyimycin may improve the learning and memory abilities of the AD mice model. The results of differential expression analysis of mRNA levels of inflammatory factors and pathways in brain tissues of the AD mouse model suggested that differential expression was more obvious under Zun-Int L. Western blot revealed that the relative expression of glial fibrillary acidic protein in the brain tissue of the AD mouse model in the Zun-Pre group was significantly higher than that in the other groups, and the difference was statistically significant. The relative expression of interleukin (IL)-6 protein in the brain tissue of mice in the low-dose intervention group was significantly lower than that in the other groups, and the difference was statistically significant. As for hypoimmune animals, short chain fatty acids (SCFAs) assay and intestinal flora assay results showed that zunyimycin C may change intestinal flora diversity and SCFA biosynthesis. The prophylactic administration of zunyimycin C could not inhibit acute neuroinflammation in AD mice. Zunyimycin C may participate in the immune response by activating the Ras-Raf-MEK-ERK signaling pathway to stimulate microglia to produce more inflammatory factors. Zunyimycin C may inhibit autophagy by activating the PI3K-AKT-mTOR signaling pathway, promote cell survival, mediate neuroprotective effects of reactive microglia and reactive astrocytes, and reduce IL-1β in brain tissue and IL-6 secretion, thereby attenuating neuroinflammation in AD mice and achieving the effect of improving learning and memory impairment. Zunyimycin C may play a role in immunological enhancement by changing intestinal flora diversity and SCFAs.

We report on the first dark-matter（DM）search results from PandaX-I,a low threshold dual-phase xenon experiment operating at the China JinPing Underground Laboratory.In the 37-kg liquid xenon target with 17.4 live-days of exposure,no DM particle candidate event was found.This result sets a stringent limit for low-mass DM particles and disfavors the interpretation of previously-reported positive experimental results.The minimum upper limit,3.7×10-44cm2,for the spin-independent isoscalar DM-particle-nucleon scattering cross section is obtained at a DM-particle mass of 49 GeV/c2at 90%confidence level.

It is commonly conjectured that dark matter is a charge neutral fundamental particle. However, it may still have minute photon-mediated interactions through millicharge 1 , 2 or higher-order multipole interactions 3 – 10 , resulting from new physics at a high energy scale. Here we report a direct search for effective electromagnetic interactions between dark matter and xenon nuclei that produce a recoil of the latter from the PandaX-4T xenon-based detector 11 , 12 . Using this technique, the first constraint on the charge radius of dark matter is derived with the lowest excluded value of 1.9 × 10 −10  fm 2 for a dark matter mass of 40 giga electron volts per speed of light in a vaccum squared (GeV/ c 2 ), more stringent than that for neutrinos by four orders of magnitude. Constraints on the magnitudes of millicharge, magnetic dipole moment, electric dipole moment and anapole moment are also improved substantially from previous searches 13 , 14 , with corresponding tightest upper limits of 2.6 × 10 −11  e, 4.8 × 10 −10  Bohr magnetons, 1.2 × 10 −23  ecm and 1.6 × 10 −33  cm 2 , respectively, for a dark matter mass of 20–40 GeV/ c 2 . A direct search for effective electromagnetic interactions between dark matter and xenon nuclei that produce a recoil of the latter is carried out and the first constraint on charge radius of dark matter is derived.

We propose a major upgrade to the existing PandaX-4T experiment at the China Jinping Underground Laboratory. The new experiment, PandaX-xT, will be a multi-ten-tonne liquid xenon, ultra-low background, and general-purpose observatory. The full-scaled PandaX-xT contains a 43-t liquid xenon active target. Such an experiment will significantly advance our fundamental understanding of particle physics and astrophysics. The sensitivity of dark matter direct detection will be improved by nearly two orders of magnitude compared to the current best limits, approaching the so-called “neutrino floor” for a dark matter mass above 10 GeV/c 2 , providing a key test to the Weakly Interacting Massive Particle paradigm. By searching for the neutrinoless double beta decay of 136 Xe isotope in the detector, the effective Majorana neutrino mass can be measured to a 10–41 meV/c 2 sensitivity, providing a key test to the Dirac/Majorana nature of neutrinos. Astrophysical neutrinos and other ultra-rare interactions can also be measured and searched for with an unprecedented background level, opening up new windows of discovery. Depending on the findings, PandaX-xT will seek the next stage upgrade utilizing isotopic separation of natural xenon.

A bstract Detailed studies of two-neutrino double electron capture (2 ν DEC) is a crucial step towards searching for the neutrinoless mode to explore the Majorana nature of neutrinos. We have measured precisely the half-life of the 2 ν DEC process in 124 Xe, utilizing a total exposure of 1.73 tonne year from the commissioning run and the first science run of the PandaX-4T experiment. A time-dependent background model in the O (10 keV) energy is constructed for the first time in PandaX-4T data. With an unbinned maximum likelihood fit, we determine the half-life of the 2 ν DEC process to be (1.03 ± 0.15 stat ± 0.08 sys ) × 10 22 yr. Furthermore, we have evaluated the capture fraction for both electrons captured from the K shell ( KK ) to be (65 ± 5)%, which aligns with the 124 Xe nuclear model calculations within 1.8 σ .