Constraints on Ultraheavy Dark Matter Properties from Dwarf Spheroidal Galaxies with LHAASO Observations.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR, pirS, pirA, piuA, or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates (n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance.

Measurements of Normalized Differential Cross Sections of Inclusive η Production in e

Using data samples collected with the BESIII detector operating at the BEPCII storage ring, the cross section of the inclusive process e^{+}e^{-}→η+X, normalized by the total cross section of e^{+}e^{-}→hadrons, is measured at eight center-of-mass energy points from 2.0000 to 3.6710 GeV. These are the first measurements with momentum dependence in this energy region. Our measurement shows a significant discrepancy compared to the existing fragmentation functions. To address this discrepancy, a new QCD analysis is performed at the next-to-next-to-leading order with hadron mass corrections and higher twist effects, which can explain both the established high-energy data and our measurements reasonably well.

Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG.

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss. METHODS: We quantified genomic, metabolomic, and proteomic changes in cultured skeletal muscle cells and mouse models of IDH-mutant leukemia using RNA sequencing, mass spectrometry, and computational modeling. RESULTS: D2-HG impairs NADH redox homeostasis in myotubes. Increased NAD+ levels drive activation of nuclear deacetylase Sirt1, which causes deacetylation and activation of LC3, a key regulator of autophagy. Using LC3 mutants, we confirm that deacetylation of LC3 by Sirt1 shifts its distribution from the nucleus into the cytosol, where it can undergo lipidation at pre-autophagic membranes. Sirt1 silencing or p300 overexpression attenuated autophagy activation in myotubes. In vivo, we identified increased muscle atrophy and reduced grip strength in response to D2-HG in male vs. female mice. In male mice, glycolytic intermediates accumulated, and protein expression of oxidative phosphorylation machinery was reduced. In contrast, female animals upregulated the same proteins, attenuating the phenotype in vivo. Network modeling and machine learning algorithms allowed us to identify candidate proteins essential for regulating oncometabolic adaptation in mouse skeletal muscle. CONCLUSIONS: Our multi-omics approach exposes new metabolic vulnerabilities in response to D2-HG in skeletal muscle and provides a conceptual framework for identifying therapeutic targets in cachexia.

First Study of Antihyperon-Nucleon Scattering Λ[over ¯]p→Λ[over ¯]p and Measurement of Λp→Λp Cross Section.

Using (10.087±0.044)×10^{9} J/ψ events collected with the BESIII detector at the BEPCII storage ring, the processes Λp→Λp and Λ[over ¯]p→Λ[over ¯]p are studied, where the Λ/Λ[over ¯] baryons are produced in the process J/ψ→ΛΛ[over ¯] and the protons are the hydrogen nuclei in the cooling oil of the beam pipe. Clear signals are observed for the two reactions. The cross sections in -0.9≤cosθ_{Λ/Λ[over ¯]}≤0.9 are measured to be σ(Λp→Λp)=(12.2±1.6_{stat}±1.1_{syst}) and σ(Λ[over ¯]p→Λ[over ¯]p)=(17.5±2.1_{stat}±1.6_{syst}) mb at the Λ/Λ[over ¯] momentum of 1.074 GeV/c within a range of ±0.017 GeV/c, where the θ_{Λ/Λ[over ¯]} are the scattering angles of the Λ/Λ[over ¯] in the Λp/Λ[over ¯]p rest frames. Furthermore, the differential cross sections of the two reactions are also measured, where there is a slight tendency of forward scattering for Λp→Λp, and a strong forward peak for Λ[over ¯]p→Λ[over ¯]p. We present an approach to extract the total elastic cross sections by extrapolation. The study of Λ[over ¯]p→Λ[over ¯]p represents the first study of antihyperon-nucleon scattering, and these new measurements will serve as important inputs for the theoretical understanding of the (anti)hyperon-nucleon interaction.

Clinical Features and Genomic Epidemiology of Bloodstream Infections due to Enterococcal Species Other Than Enterococcus faecalis or E. faecium in Patients With Cancer.

Background: Non-Enterococcus faecium, non-E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described. Methods: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood culture <14 days after clearance). Whole-genome sequencing was performed on all available NFF (n = 65). Results: Patients with hematological malignancies made up 56% of the cohort (77% had leukemia). The majority of solid malignancies (87%) were gastrointestinal in origin. The majority of infections (83%) originated from an intra-abdominal source. The most common NFF species were E. gallinarum (50%) and E. casseliflavus (30%). Most (61%) patients received combination therapy. Bacteremia recurred in 4.3% of patients, there was a 30-day mortality of 23%, and 4.3% had microbiological failure. E. gallinarum and E. casseliflavus isolates were genetically diverse with no spatiotemporal clustering to suggest a single strain. Frequencies of ampicillin resistance (4.3%) and daptomycin resistance (1.9%) were low. Patients with hematologic malignancy had infections with NFF enterococci that harbored more resistance genes than patients with solid malignancy (P = .005). Conclusions: NFF bacteremia is caused by a heterogeneous population of isolates and is associated with significant mortality. Hematological malignancy is an important risk factor for infection with NFF resistant to multiple antibiotics.

First Observation of a Three-Resonance Structure in e

We report the measurement of the inclusive cross sections for e^{+}e^{-}→nOCH (where nOCH denotes non-open charm hadrons) with improved precision at center-of-mass (c.m.) energies from 3.645 to 3.871 GeV. We observe three resonances: R(3760), R(3780), and R(3810) with significances of 8.1σ, 13.7σ, and 8.8σ, respectively. The R(3810) state is observed for the first time, while the R(3760) and R(3780) states are observed for the first time in the nOCH cross sections. Two sets of resonance parameters describe the energy-dependent line shape of the cross sections well. In set I [set II], the R(3810) state has mass (3805.7±1.1±2.7) [(3805.7±1.1±2.7)] MeV/c^{2}, total width (11.6±2.9±1.9) [(11.5±2.8±1.9)] MeV, and an electronic width multiplied by the nOCH decay branching fraction of (10.9±3.8±2.5) [(11.0±3.4±2.5)] eV. In addition, we measure the branching fractions B[R(3760)→nOCH]=(25.2±16.1±30.4)%[(6.4±4.8±7.7)%] and B[R(3780)→nOCH]=(12.3±6.6±8.3)%[(10.4±4.8±7.0)%] for the first time. The R(3760) state can be interpreted as an open-charm (OC) molecular state, but containing a simple four-quark state component. The R(3810) state can be interpreted as a hadrocharmonium state.

Determination of Spin-Parity Quantum Numbers of X(2370) as 0

Based on (10087±44)×10^{6} J/ψ events collected with the BESIII detector, a partial wave analysis of the decay J/ψ→γK_{S}^{0}K_{S}^{0}η^{'} is performed. The mass and width of the X(2370) are measured to be 2395±11(stat)_{-94}^{+26}(syst) MeV/c^{2} and 188_{-17}^{+18}(stat)_{-33}^{+124}(syst) MeV, respectively. The corresponding product branching fraction is B[J/ψ→γX(2370)]×B[X(2370)→f_{0}(980)η^{'}]×B[f_{0}(980)→K_{S}^{0}K_{S}^{0}]=(1.31±0.22(stat)_{-0.84}^{+2.85}(syst))×10^{-5}. The statistical significance of the X(2370) is greater than 11.7σ and the spin parity is determined to be 0^{-+} for the first time. The measured mass and spin parity of the X(2370) are consistent with the predictions of the lightest pseudoscalar glueball.

Observation of Structures in the Processes e

We present measurements of the Born cross sections for the processes e^{+}e^{-}→ωχ_{c1} and ωχ_{c2} at center-of-mass energies sqrt[s] from 4.308 to 4.951 GeV. The measurements are performed with data samples corresponding to an integrated luminosity of 11.0 fb^{-1} collected with the BESIII detector operating at the Beijing Electron Positron Collider storage ring. Assuming the e^{+}e^{-}→ωχ_{c2} signals come from a single resonance, the mass and width are determined to be M=(4413.6±9.0±0.8) MeV/c^{2} and Γ=(110.5±15.0±2.9) MeV, respectively, which is consistent with the parameters of the well-established resonance ψ(4415). In addition, we also use one single resonance to describe the e^{+}e^{-}→ωχ_{c1} line shape and determine the mass and width to be M=(4544.2±18.7±1.7) MeV/c^{2} and Γ=(116.1±33.5±1.7) MeV, respectively. The structure of this line shape, observed for the first time, requires further understanding.

Coupled-Channel Analysis of the χ_{c1}(3872) Line Shape with BESIII Data.

We perform a study of the χ_{c1}(3872) line shape using the data samples of e^{+}e^{-}→γχ_{c1}(3872), χ_{c1}(3872)→D^{0}D[over ¯]^{0}π^{0}, and π^{+}π^{-}J/ψ collected with the BESIII detector. The effects of the coupled channels and the off-shell D^{*0} are included in the parametrization of the line shape. The line shape mass parameter is obtained to be M_{X}=(3871.63±0.13_{-0.05}^{+0.06}) MeV. Two poles are found on the first and second Riemann sheets corresponding to the D^{*0}D[over ¯]^{0} branch cut. The pole location on the first sheet is much closer to the D^{*0}D[over ¯]^{0} threshold than the other, and is determined to be 7.04±0.15_{-0.08}^{+0.07} MeV above the D^{0}D[over ¯]^{0}π^{0} threshold with an imaginary part -0.19±0.08_{-0.19}^{+0.14} MeV.

Observation of the Anomalous Shape of X(1840) in J/ψ→γ3(π

Using a sample of (10087±44)×10^{6} J/ψ events, which is about 45 times larger than that was previously analyzed, a further investigation on the J/ψ→γ3(π^{+}π^{-}) decay is performed. A significant distortion at 1.84 GeV/c^{2} in the line shape of the 3(π^{+}π^{-}) invariant mass spectrum is observed for the first time, which could be resolved by two overlapping resonant structures, X(1840) and X(1880). The new state X(1880) is observed with a statistical significance larger than 10σ. The mass and width of X(1880) are determined to be 1882.1±1.7±0.7 MeV/c^{2} and 30.7±5.5±2.4 MeV, respectively, which indicates the existence of a pp[over ¯] bound state.

Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis.

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized three gene operon (madEFG) that protects the E. faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.

Observation of Significant Flavor-SU(3) Breaking in the Kaon Wave Function at 12

We present cross sections for the reaction e^{+}e^{-}→K_{S}^{0}K_{L}^{0} at center-of-mass energies ranging from 3.51 to 4.95 GeV using data samples collected in the BESIII experiment, corresponding to a total integrated luminosity of 26.5 fb^{-1}. The ratio of neutral-to-charged kaon form factors at large momentum transfers (12

Observation of D

We perform for the first time an amplitude analysis of the decay D^{+}→K_{S}^{0}π^{+}η and report the observation of the decay D^{+}→K_{S}^{0}a_{0}(980)^{+} using 2.93 fb^{-1} of e^{+}e^{-} collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector. As the only W-annihilation-free decay among D to a_{0}(980) pseudoscalar, D^{+}→K_{S}^{0}a_{0}(980)^{+} is the ideal decay in extracting the contributions of the W-emission amplitudes involving a_{0}(980) and to study the final-state interactions. The absolute branching fraction of D^{+}→K_{S}^{0}π^{+}η is measured to be (1.27±0.04_{stat}±0.03_{syst})%. The branching fractions of intermediate processes D^{+}→K_{S}^{0}a_{0}(980)^{+} with a_{0}(980)^{+}→π^{+}η and D^{+}→π^{+}K[over ¯]_{0}^{*}(1430)^{0} with K[over ¯]_{0}^{*}(1430)^{0}→K_{S}^{0}η are measured to be (1.33±0.05_{stat}±0.04_{syst})% and (0.14±0.03_{stat}±0.01_{syst})%, respectively.

Study of the f_{0}(980) and f_{0}(500) Scalar Mesons through the Decay D_{s}

Using e^{+}e^{-} collision data corresponding to an integrated luminosity of 7.33 fb^{-1} recorded by the BESIII detector at center-of-mass energies between 4.128 and 4.226 GeV, we present an analysis of the decay D_{s}^{+}→π^{+}π^{-}e^{+}ν_{e}, where the D_{s}^{+} is produced via the process e^{+}e^{-}→D_{s}^{*±}D_{s}^{∓}. We observe the f_{0}(980) in the π^{+}π^{-} system and the branching fraction of the decay D_{s}^{+}→f_{0}(980)e^{+}ν_{e} with f_{0}(980)→π^{+}π^{-} measured to be (1.72±0.13_{stat}±0.10_{syst})×10^{-3}, where the uncertainties are statistical and systematic, respectively. The dynamics of the D_{s}^{+}→f_{0}(980)e^{+}ν_{e} decay are studied with the simple pole parametrization of the hadronic form factor and the Flatté formula describing the f_{0}(980) in the differential decay rate, and the product of the form factor f_{+}^{f_{0}}(0) and the c→s Cabibbo-Kobayashi-Maskawa matrix element |V_{cs}| is determined for the first time to be f_{+}^{f_{0}}(0)|V_{cs}|=0.504±0.017_{stat}±0.035_{syst}. Furthermore, the decay D_{s}^{+}→f_{0}(500)e^{+}ν_{e} is searched for the first time but no signal is found. The upper limit on the branching fraction of D_{s}^{+}→f_{0}(500)e^{+}ν_{e}, f_{0}(500)→π^{+}π^{-} decay is set to be 3.3×10^{-4} at 90% confidence level.

Observation of D_{s}

By analyzing 7.33 fb^{-1} of e^{+}e^{-} annihilation data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector, we report the observation of the semileptonic decay D_{s}^{+}→η^{'}µ^{+}ν_{µ}, with a statistical significance larger than 10σ, and the measurements of the D_{s}^{+}→ηµ^{+}ν_{µ} and D_{s}^{+}→η^{'}µ^{+}ν_{µ} decay dynamics for the first time. The branching fractions of D_{s}^{+}→ηµ^{+}ν_{µ} and D_{s}^{+}→η^{'}µ^{+}ν_{µ} are determined to be (2.235±0.051_{stat}±0.052_{syst})% and (0.801±0.055_{stat}±0.028_{syst})%, respectively, with precision improved by factors of 6.0 and 6.6 compared to the previous best measurements. Combined with the results for the decays D_{s}^{+}→ηe^{+}ν_{e} and D_{s}^{+}→η^{'}e^{+}ν_{e}, the ratios of the decay widths are examined both inclusively and in several ℓ^{+}ν_{ℓ} four-momentum transfer ranges. No evidence for lepton flavor universality violation is found within the current statistics. The products of the hadronic form factors f_{+,0}^{η^{(')}}(0) and the c→s Cabibbo-Kobayashi-Maskawa matrix element |V_{cs}| are determined. The results based on the two-parameter series expansion are f_{+,0}^{η}(0)|V_{cs}|=0.452±0.010_{stat}±0.007_{syst} and f_{+,0}^{η^{'}}(0)|V_{cs}|=0.504±0.037_{stat}±0.012_{syst}, which help to constrain present models on f_{+,0}^{η^{(')}}(0). The forward-backward asymmetries are determined to be ⟨A_{FB}^{η}⟩=-0.059±0.031_{stat}±0.005_{syst} and ⟨A_{FB}^{η^{'}}⟩=-0.064±0.079_{stat}±0.006_{syst} for the first time, which are consistent with the theoretical calculation.

Determination of the Σ

Based on data samples collected with the BESIII detector at the BEPCII collider, the process e^{+}e^{-}→Σ^{+}Σ[over ¯]^{-} is studied at center-of-mass energies sqrt[s]=2.3960, 2.6454, and 2.9000 GeV. Using a fully differential angular description of the final state particles, both the relative magnitude and phase information of the Σ^{+} electromagnetic form factors in the timelike region are extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ=-0.67±0.29(stat)±0.18(syst) at sqrt[s]=2.3960 GeV, ΔΦ=55°±19°(stat)±14°(syst) at sqrt[s]=2.6454 GeV, and 78°±22°(stat)±9°(syst) at sqrt[s]=2.9000 GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.

Investigation of the ΔI=1/2 Rule and Test of CP Symmetry through the Measurement of Decay Asymmetry Parameters in Ξ

Using (10087±44)×10^{6} J/ψ events collected with the BESIII detector, numerous Ξ^{-} and Λ decay asymmetry parameters are simultaneously determined from the process J/ψ→Ξ^{-}Ξ[over ¯]^{+}→Λ(pπ^{-})π^{-}Λ[over ¯](n[over ¯]π^{0})π^{+} and its charge-conjugate channel. The precisions of α_{Λ0} for Λ→nπ^{0} and α[over ¯]_{Λ0} for Λ[over ¯]→n[over ¯]π^{0} compared to world averages are improved by factors of 4 and 1.7, respectively. The ratio of decay asymmetry parameters of Λ→nπ^{0} to that of Λ→pπ^{-}, ⟨α_{Λ0}⟩/⟨α_{Λ-}⟩, is determined to be 0.873±0.012_{-0.010}^{+0.011}, where the first and the second uncertainties are statistical and systematic, respectively. The ratio is smaller than unity more than 5σ, which signifies the existence of the ΔI=3/2 transition in Λ for the first time. Besides, we test for CP symmetry in Ξ^{-}→Λπ^{-} and in Λ→nπ^{0} with the best precision to date.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin.

The siderophore-cephalosporin cefiderocol(FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR , pirS , pirA , piuA or piuD from 498 unique isolates collected before the introduction of FDC from 4 clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates (n=15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance.

First Measurement of the Decay Asymmetry in the Pure W-Boson-Exchange Decay Λ_{c}

Based on 4.4 fb^{-1} of e^{+}e^{-} annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure W-boson-exchange decay Λ_{c}^{+}→Ξ^{0}K^{+} is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be α_{Ξ^{0}K^{+}}=0.01±0.16(stat)±0.03(syst). This result reflects the noninterference effect between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes has two solutions, which are δ_{p}-δ_{s}=-1.55±0.25(stat)±0.05(syst) rad or 1.59±0.25(stat)±0.05(syst) rad.