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Abstract Background Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation. Methods Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis. Results Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria. Conclusion This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.

Abstract Background This retrospective study aimed to compare the efficacy and safety of one-stage computed tomography (OSCT)- to that of two-stage computed tomography (TSCT)-guided localization for the surgical removal of small lung nodules. Methods We collected data from patients with ipsilateral pulmonary nodules who underwent localization before surgical removal at Veteran General Hospital Kaohsiung between October 2017 and January 2022. The patients were divided into the OSCT and TSCT groups. Results We found that OSCT significantly reduced the localization time and risky time compared to TSCT, and the success rate of localization and incidence of pneumothorax were similar in both groups. However, the time spent under general anesthesia was longer in the OSCT group than in the TSCT group. Conclusions The OSCT-guided approach to localize pulmonary nodules in hybrid operation room is a safe and effective technique for the surgical removal of small lung nodules.

Abstract In our previous work (Zhang and Shu in Eur Phys J. C 84(3):256, 2024), we have explored quantum gravity induced entanglement of masses (QGEM) in curved spacetime, observing entanglement formation between particles moving along geodesics in a Schwarzschild spacetime background. We find that long interaction time induces entanglement, even for particles with microscopic mass, addressing decoherence concerns. In this work, we build upon our previous work (Zhang and Shu 2024) by extending our investigation to a time-dependent spacetime. Specifically, we explore the entanglement induced by the mutual gravitation of massive particles in the Friedmann–Lemaître–Robertson–Walker (FLRW) universe. With the help of the phase shift and the QGEM spectrum, our proposed scheme offers a potential method for observing the formation of entanglement caused by the quantum gravity of massive particles as they propagate in the FLRW universe. Consequently, it provides insights into the field of entanglement in cosmology.

Abstract Background It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. Main body Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1β (IL-1β) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. Conclusion Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Abstract The experiment involving the entanglement of two massive particles through gravitational fields has been devised to discern the quantum attributes of gravity. In this paper, we present a scheme to extend this experiment’s applicability to more generalized curved spacetimes, with the objective of validating universal quantum gravity within broader contexts. Specifically, we direct our attention towards the quantum gravity induced entanglement of masses (QGEM) in astrophysical phenomena, such as particles traversing the interstellar medium. Notably, we ascertain that the gravitational field within curved spacetime can induce observable entanglement between particle pairs in both scenarios, even when dealing with particles significantly smaller than mesoscopic masses. Furthermore, we obtain the characteristic spectra of QGEM across diverse scenarios, shedding light on potential future experimental examinations. This approach not only establishes a more pronounced and extensive manifestation of the quantum influences of gravity compared to the original scheme but also opens avenues for prospective astronomical experiments. These experiments, aligned with our postulates, hold immense advantages and implications for the detection of quantum gravity and can be envisioned for future design.

Abstract The capability to gather heterogeneous data, alongside the increasing power of artificial intelligence to examine it, leading a revolution in harnessing multimodal data in the life sciences. However, most approaches are limited to unimodal data, leaving integrated approaches across modalities relatively underdeveloped in computational pathology. Pathogenomics, as an invasive method to integrate advanced molecular diagnostics from genomic data, morphological information from histopathological imaging, and codified clinical data enable the discovery of new multimodal cancer biomarkers to propel the field of precision oncology in the coming decade. In this perspective, we offer our opinions on synthesizing complementary modalities of data with emerging multimodal artificial intelligence methods in pathogenomics. It includes correlation between the pathological and genomic profile of cancer, fusion of histology, and genomics profile of cancer. We also present challenges, opportunities, and avenues for future work.

Abstract It is believed that gravity can be considered as a quantum coherent mediator. In this study, we propose a plan to test the existence of extra dimensions using the quantum gravity induced entanglement of masses (QGEM) experiment. This experiment involves two freely falling test masses passing through a Stern–Gerlach-like device. We investigate the entanglement witness between these masses within the framework of the Randall–Sundrum II model (RS-II). Our findings indicate that the system reaches entanglement more rapidly in the presence of extra dimensions, particularly when the radius of the extra dimension is large.

Objective Distal femoral physeal fractures (DFPF) are rare but severe injuries in children, and there is no consensus on treatments for Salter–Harris (S–H) IV and V type of DFPF yet. This study aimed to introduce a minimally invasive technique using percutaneous leverage reduction combined with Kirschner wires fixation in treating pediatric DFPF with S–H IV and V type of injury and evaluate the clinical results. Methods From July 2008 to June 2018, the authors' institute (Union Hospital, Tongji Medical College) retrospectively reviewed all patients diagnosed with pediatric DFPF. They were divided into two groups according to received treatment: children in the minimally invasive technique group were treated with a minimally invasive percutaneous leverage reduction technique, and the traditional technique group included the other children who received the conventional open reduction with internal fixation (ORIF). The surgical and clinical results of the two groups were collected and analyzed. The independent sample t‐test analysis and the chi‐square test were applied to compare continuous and categorical variables. Results A total of 14 pediatric patients were recruited, including five females and nine males with DFEF. All eight patients in the minimally invasive technique group and four of the six patients in the ORIF group were treated successfully. One patient in the minimally invasive technique group opted for conservative treatment due to his good functional recovery, while the other two patients in the ORIF group needed further surgery because of the limb length discrepancy. There was a difference in surgery duration (p

Summary: Liver injury stimulates hepatocyte replication and hepatic stellate cell (HSC) activation, thereby driving liver regeneration. Aberrant HSC activation induces liver fibrosis. However, mechanisms underlying liver regeneration and fibrosis remain poorly understood. Here, we identify hepatic Snai1 and Snai2 as important transcriptional regulators for liver regeneration and fibrosis. Partial hepatectomy or CCl4 treatment increases occupancies of Snai1 and Snai2 on cyclin A2 and D1 promoters in the liver. Snai1 and Snai2 in turn increase promoter H3K27 acetylation and cyclin A2/D1 expressions. Hepatocyte-specific deletion of both Snai1 and Snai2, but not one alone, suppresses liver cyclin A2/D1 expression and regenerative hepatocyte proliferation after hepatectomy or CCl4 treatments but augments CCl4-stimulated HSC activation and liver fibrosis. Conversely, Snai2 overexpression in the liver enhances hepatocyte replication and suppresses liver fibrosis after CCl4 treatment. These results suggest that hepatic Snai1 and Snai2 directly promote, via histone modifications, reparative hepatocyte replication and indirectly inhibit liver fibrosis.

ObjectiveThis study aimed to analyze the growth patterns of height and foot length (FL) among Chinese children aged 3–18 and examine their associations with puberty development.MethodsA cross-sectional survey was conducted in September 2022 in Beijing. Data were collected through questionnaires and on-site physical examinations. The growth patterns and velocity of height and FL in different age groups were described, and their associations with puberty development were analyzed.ResultsFrom an age perspective, the peak FL growth occurred between 9 and 11 years (boys were 11 years and girls were 9 years), while the peak height growth occurred at 11 ~ 13 years for boys and 9 ~ 11 years for girls. Additionally, boys and girls reached 99.0% of their final FL at the ages of 14 and 13, respectively, while they reached 99.0% of their final height at the ages of 16 and 15, respectively. From the perspective of Tanner stage, the age of peak FL growth in boys coincided with the age of the G2 stage, while in girls it occurred slightly earlier than the mean age of the B2 stage. The peak height growth for both boys and girls occurred between Tanner stages 2 and 3.ConclusionBoys and girls reach their peak FL growth at 11 and 9 years old, respectively, which were both 2 years earlier than their peak height growth. The peak FL growth occurred around the onset of puberty, while the peak height growth occurred between Tanner stages 2 and 3.

Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)− 18, IL-1β, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K+) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.

The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow–Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

In this work, we investigate an alternative channel for the formation of fast-spinning black hole–neutron star (BHNS) binaries, in which super-Eddington accretion is expected to occur in accreting BHs during the stable mass transfer phase within BH-stripped helium (BH–He-rich) star binary systems. We evolve intensive MESA grids of close-orbit BH–He-rich star systems to systematically explore the projected aligned spins of BHs in BHNS binaries, as well as the impact of different accretion limits on the tidal disruption probability and electromagnetic (EM) signature of BHNS mergers. Most of the BHs in BHNS mergers cannot be effectively spun up through accretion if the accretion rate is limited to $\lesssim 10\,{\dot{M}}_{\mathrm{Edd}}$ , where ${\dot{M}}_{\mathrm{Edd}}$ is the standard Eddington accretion limit. In order to reach high spins (e.g., χ _BH ≳ 0.5), the BHs are required to be born less massive (e.g., ≲3.0 M _⊙ ) in binary systems with initial periods of ≲0.2–0.3 days and accrete material at $\sim 100\,{\dot{M}}_{\mathrm{Edd}}$ . However, even under this high accretion limit, ≳6 M _⊙ BHs are typically challenging to significantly spin up and generate detectable associated EM signals. Our population simulations suggest that different accretion limits have a slight impact on the ratio of tidal disruption events. However, as the accretion limit increases, the EM counterparts from the cosmological BHNS population can become bright overall.

Leukemia stem cells (LSC) represent a crucial and rare subset of cells present in acute myeloid leukemia (AML); they play a pivotal role in the initiation, maintenance, and relapse of this disease. Targeting LSC holds great promise for preventing AML relapse and improving long-term outcomes. However the precise molecular mechanisms governing LSC self-renewal are still poorly understood. Here, we present compelling evidence that the expression of miR-30e-5p, a potential tumor-suppressive microRNA, is significantly lower in AML samples than in healthy bone marrow samples. Forced expression of miR- 30e effectively inhibits leukemogenesis, impairs LSC self-renewal, and delays leukemia progression. Mechanistically, Cyb561 acts as a direct target of miR-30e-5p in LSC, and its deficiency restricts the self-renewal of LSC by activating reactive oxygen series signaling and markedly prolongs recipients' survival. Moreover, genetic or pharmacological overexpression of miR-30e-5p or knockdown of Cyb561 suppresses the growth of human AML cells. In conclusion, our findings establish the crucial role of the miR-30e-5p/Cyb561/ROS axis in finely regulating LSC self-renewal, highlighting Cyb561 as a potential therapeutic target for LSC-directed therapies.