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关键词： Rock fracture   Shear mechanical characteristics   Roughness index   DEM   Shear test  

摘要： Rough feature quantitatively described by the roughness indexes is the key to evaluating the shear mechanical characteristics of rock fractures in advance. However, the correspondence between roughness index and fracture shear mechanical characteristics has not been verified. In this study, the specific relationship between the roughness index theta*max/(C + 1) and the shear mechanical characteristics of rock fractures was discussed through numerical direct shear tests of fracture specimens based on the discrete element method (DEM). To explore this, rough rock fractures having the same theta*max/(C + 1) were established by adjusting the ten standard roughness profiles. The microscopic mechanics parameters of the rock and fracture in the numerical model were determined by calibrating the macroscopic parameters with physical model experiments. The test results show that fracture specimens with the same roughness grade exhibit varying shear mechanics indicators, with the degree of dispersion increasing as the roughness increases. However, due to differences in morphology, specimens with the same roughness grade exhibit distinct contact force distribution and failure characteristics. It has been observed that theta*max/(C + 1) can well reflect the roughness grade and even macroscopic shear properties of fractures when discretisation is not taken into account.

关键词： Absorption   Amino acid   Carbon capture   CESAR solvent   L-lysine  

摘要： Carbon capture technologies are vital for mitigating carbon dioxide (CO₂) emissions in bioenergy and energy-from-waste power plants. Among them, solvent-based absorption is the most widely used in above industries. Mono-ethanolamine (MEA) is the pre-dominant and an established solvent for absorption based-carbon capture. However, newer solvent blends, like mixtures of MEA and N-methyl diethanolamine (MDEA), and CESAR-1 (a blend of 2-amino-2-methyl-1-propanol and piperazine) are being considered for future plants as they offer 10–15% enhanced performance and ∼20% improved capacity. This study presents the first results of adding L-lysine as a co-promoter for CESAR-1, to improve its CO₂ capture efficiency and capacity. The proposed blend, Bio-CESAR (a blend of 2-amino-2-methyl-1-propanol, piperazine, and L-lysine), was experimentally tested for CO₂ solubility across a range of pressures (30–500 kPa, CO₂ partial pressure range of 3–50 kPa) and temperatures (298.15–343.15 K), and its performance was compared to conventional CESAR-1 and MEA solutions. Results show that Bio-CESAR offers 15% higher CO₂ loading and equilibrium CO₂ solubility at average compared to CESAR-1, suggesting potential for improved cyclic efficiency in industrial applications. The enhanced CO₂ absorption performance of Bio-CESAR is attributed to the incorporation of L-lysine, which modifies CO₂–solvent interactions and solution speciation within the CESAR-1 framework. Results from this macroscopic study suggest that the bio-derived amino acid act synergistically with the conventional amine components, leading to improved equilibrium CO₂ loading. This study provides a fundamental insight for the use of L-lysine (and not its alkaline salt) in enhancing solvent performance and reducing environmental risks in carbon capture systems.

摘要： To address the mass transfer limitations and adsorption constraints in deep desulfurization processes, a novel bifunctional catalyst, Ag₂O/HTS-1, was synthesized and evaluated for the oxidative desulfurization (ODS) of model fuels. The catalyst was prepared by hydrothermally synthesizing hierarchical titanosilicalite-1 (HTS-1) using polydiallyldimethylammonium chloride as a mesopore-directing agent, followed by the strategic impregnation of Ag₂O. Comprehensive physicochemical characterization confirmed the successful integration of Ag species onto a stable, hierarchically porous MFI framework. The resulting catalyst leverages a powerful synergistic effect. The enlarged mesopores of HTS-1 overcome diffusion barriers for bulky sulfur compounds, while the Ag sites serve as preferential adsorption sites. Consequently, under optimal conditions (60 °C, 2:1 oxidant-to-sulfur molar ratio), Ag₂O/HTS-1 demonstrated superior performance, achieving 100% desulfurization of DBT and 98% desulfurization of bulky 4,6-DMDBT, significantly surpassing conventional TS-1 and HTS-1 catalysts. Demonstrating industrial viability, the catalyst maintained robust performance in the presence of common interfering fuel components and exhibited high activity over five reaction cycles. These results highlight Ag₂O/HTS-1 as a highly efficient and reusable bifunctional catalyst, capable of simultaneously promoting oxidation and adsorption for the sustainable production of clean fuels.

关键词： tuberculosis infection   1HP   rifapentine concentration   pediatrics   safety  

摘要： Background : One month of daily rifapentine plus isoniazid (1HP) is a new regimen for tuberculosis (TB) infection to lower the incidence of active TB. However, it has not been prescribed for Chinese children, and the optimal dosage of daily rifapentine for children remains controversial. We aimed to assess the feasibility and safety of 1HP in young Chinese children with TB infection and to provide evidence for extrapolating dosing strategies to children. Methods : An open-label, prospective, single-arm clinical trial was conducted among eligible participants (aged <= 14 years). Completion rate, safety, and rifapentine concentrations of the 1HP regimen were analyzed. Results : Eighty children were enrolled in our study;79 of the participants (98.75%) completed the treatment, with only 1 case of noncompletion (1.25%) in the age group 6-14 years because of rash. Five of 80 participants (6.25%) experienced grade >= 3 adverse events, with no serious adverse events or deaths reported. The relationship between rifapentine concentration (mg/L) and time (days) in children stratified by age and weight demonstrated the lowest rifapentine concentration in participants <= 2 years old and those weighing <= 15 kg when compared to the other subgroups. Conclusions : The 1HP regimen is safe and feasible for young Chinese children with TB infection. Weight-based daily rifapentine (10-15 mg/kg) might not be enough for young children, particularly for those aged <= 2 years or weighing <= 15 kg. Clinical Trials Registration : ChiCTR2200066411.

关键词： Apoptosis   spheroid   PAC-1   glioma   caspase  

摘要： Glioblastoma multiforme (GBM) is the most common form of malignant brain cancer and is generally approached with palliative intent. Preclinical studies suggest that short-term fasting may be an effective tool for enhancing existing cancer therapies by disrupting the glucose-dependent, oncogenic phenotype of many cancers. In this study, we investigated whether a fasting-mimicking environment (FME) enhances the efficacy of an emerging proapoptotic drug, procaspase-activating compound 1 (PAC-1), in 2D and 3D GBM cell models. Ad libitum food consumption (Fed) and FME conditions were simulated in vitro by modifying glucose, ketone and serum concentrations. The FME conditions enhanced PAC-1 in U87-MG, T98G and 9L-GS monolayer experiments by significantly reducing the PAC-1 50% inhibitory concentration (IC50), delaying cell growth and increasing apoptosis. Similarly, in the 3D spheroid models, the minimum concentration of PAC-1 required to reduce U87-MG and 9L-GS spheroid area was lower in the FME conditions than the Fed conditions. Additionally, we discovered that serum restriction was primarily responsible for the FME-induced PAC-1 enhancement. These finding are the first to demonstrate that fasting-mimicking conditions sensitize 2D and 3D glioma cell models to PAC-1, supporting the use of short-term fasting as a low-cost and widely accessible strategy for enhancing cancer therapies.

关键词： mcr-1   Multidrug-resistant   Plasmid   Salmonella  

摘要： We conducted genomic analysis of a Chinese beef-derived, mcr-1-positive, multidrug-resistant monophasic Salmonella enterica serovar Typhimurium isolate. Antimicrobial resistance determinants were located on both its chromosome and plasmid. The multidrug resistance was primarily mediated by a novel IncHI2-IncHI2A plasmid harboring 18 resistance genes, including mcr-1, in contrast to only five resistance genes and one resistance-associated mutation detected on the chromosome. These findings underscore the need for enhanced surveillance of this pathogen. © The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia 2026.

关键词： Acute cholangitis   Antibiotic therapy   Clinical trial   ERCP   Treatment duration  

摘要： Background: Acute cholangitis is an infection of the biliary tract that is managed with adequate biliary drainage combined with antibiotic treatment. The international Tokyo Guidelines 2018 recommend 4 to 7 days of antibiotic treatment after adequate biliary drainage, but observational data suggest shorter treatment may be sufficient. We assessed whether 1 day of antibiotic treatment is non-inferior to 4–7 days of antibiotic treatment for acute cholangitis after adequate biliary drainage. Methods: The COBRA-trial is a multicentre, open-label, parallel group randomized controlled non-inferiority trial with blinded outcome assessment. A total of 416 patients with acute cholangitis will be randomly assigned in a 1:1 ratio to the intervention group (1 day of antibiotic treatment after adequate biliary drainage) or to the control group (4–7 days of antibiotic treatment after adequate biliary drainage). Patients with acute cholangitis due to common bile duct stones, benign or malignant distal biliary obstruction, or distal biliary stent dysfunction are eligible. Randomization will take place once adequate biliary drainage is achieved by ERCP. Main exclusion criteria are concomitant pancreatitis, liver abscess, cholecystitis, and another infectious diagnosis at the time of randomization, use of systemic maintenance antibiotics, and specific immunosuppressants. Patients will be stratified for blood culture results at the time of randomization and aetiology of cholangitis. The primary endpoint is clinical cure, defined as the patient being symptom-free by day 14, with no relapse or death occurring by day 30. Secondary endpoints include 30-day and 90-day all-cause mortality, relapse of cholangitis by day 90, time from ERCP to first relapse, any other subsequent infection requiring antibiotic treatment within 90 days, duration of initial hospital stay, number of days treated with antibiotics by day 30, subsequent infections with multidrug resistant (MDR) bacteria, quality of l

关键词： Female fertility preservation   FOS/AP-1 pathway   Ovarian tissue cryopreservation   Single-cell RNA-seq   Spatial enhanced resolution omics sequencing  

摘要： Background: The ovary is a vital and dynamic reproductive organ. Ovarian tissue cryopreservation (OTC) plays a vital role in preserving female fertility. However, the cellular subtypes most susceptible to cryoinjury and the molecular mechanisms underlying cryopreservation-associated damage remain poorly understood. This study aimed to identify cell populations vulnerable to freezing-thawing and to elucidate the key transcriptomic alterations and signaling pathways associated with ovarian cryoinjury at the single-cell and spatial levels. Methods: Ovarian cortical tissues from patients undergoing three gender reassignment surgery (GRS) were divided into fresh and vitrification-rapid warming groups. Following collagenase IV digestion, 10x Genomics single-cell RNA-seq was used for dissociated ovarian cell suspensions (27,185 fresh and 25,480 frozen-thawed cells). Eight major cell clusters were identified. Additionally, 110 oocytes (66 fresh, 44 vitrification-rapid warming) were isolated and analyzed using the Smart-seq2 platform. Spatial transcriptomics was performed via BGI Stereo-seq. Molecular validation was performed via β-galactosidase staining, immunofluorescence, and qRT-PCR. Results: Cryopreservation significantly altered the activity of pathways related to focal adhesion, oxidative stress, and apoptosis, particularly in stromal and perivascular cells. The number of FOS-positive perivascular cells was notably increased after vitrification-rapid warming, whereas the number of PTGDS-positive stromal cells decreased. Oocyte analysis revealed that cryopreservation primarily disrupted pathways involved in the cell cycle and meiosis, although the damage was not irreversible, supporting the relative safety of long-term cryostorage. Spatial transcriptomics and functional validation further confirmed the rapid and robust activation of the FOS/AP-1 pathway after vitrification-rapid warming, particularly in perivascular and granulosa cells. Treatment with T-5224 (a FOS/AP-

关键词： Antigen-specific B cells   Beacon platform   Elite controller   HIV-1   Monoclonal antibody  

摘要： Elite controllers (ECs) are rare human immunodeficiency virus (HIV)-infected individuals who manage viral replication without antiretroviral therapy. While their cellular immunity is well characterized, humoral responses remain limited, which provides an uncommon window into antibody responses to HIV-1. Using single-cell functional screening, this study aimed to isolate and characterize HIV-1 envelope (Env)-specific monoclonal antibodies (mAbs) from ECs. The Beacon platform was used for enrichment, activation, and screening of cluster of differentiation 27⁺ (CD27⁺) memory B cells. Among ~ 12,000 single B cells, 40 Env-specific IgG-secreting cells were identified. Although 18 mAbs were recovered, six showed high-affinity binding to multiple Env trimers (average EC50 < 100 ng/mL). Notably, one mAb (#2) demonstrated broad reactivity, neutralizing 15 of the 17 pseudoviruses, albeit with limited potency (geometric mean IC50 of 46.53 μg/mL). Sequence analysis revealed predominant usage of IGHV1-69 and varied somatic hypermutation levels. However, the high binding affinity could not consistently predict neutralization potency. This study demonstrated the utility of integrated single-cell screening for rapid discovery of antibodies from rare donors. This study also highlights the need for functional assessment in HIV-1 antibody development and identification of mAb candidates for potential therapeutic applications. © The Author(s) 2026.