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Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Abstract Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G–Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

At room temperature, the conversion of greenhouse gases into valuable chemicals using metal-free catalysts for dry reforming of methane (DRM) is quite promising and challenging. Herein, we developed a novel covalent organic porous polymer (TPE-COP) with rapid charge separation of the electron–hole pairs for DRM driven by visible light at room temperature, which can efficiently generate syngas (CO and H2). Both electron donor (tris(4-aminophenyl)amine, TAPA) and acceptor (4,4′,4″,4‴-((1 E,1′E,1″E, 1‴E)-(ethene-1,1,2,2-tetrayltetrakis (benzene-4,1-diyl))tetrakis (ethene-2,1-diyl))tetrakis (1-(4-formylbenzyl)quinolin-1-ium), TPE-CHO) were existed in TPE-COP, in which the push–pull effect between them promoted the separation of photogenerated electron–hole, thus greatly improving the photocatalytic activity. Density functional theory (DFT) simulation results show that TPE-COP can form charge-separating species under light irradiation, leading to electrons accumulation in TPE-CHO unit and holes in TAPA, and thus efficiently initiating DRM. After 20 h illumination, the photocatalytic results show that the yields reach 1123.6 and 30.8 μmol g−1 for CO and H2, respectively, which are significantly higher than those of TPE-CHO small molecules. This excellent result is mainly due to the increase of specific surface area, the enhancement of light absorption capacity, and the improvement of photoelectron-generating efficiency after the formation of COP. Overall, this work contributes to understanding the advantages of COP materials for photocatalysis and fundamentally pushes metal-free catalysts into the door of DRM field.

Abstract Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL’s therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.

Abstract Quantum networks comprised of entangled end nodes serve stronger than the classical correlation for unparalleled quantum internet applications. However, practical quantum networking is affected by noise, which at its worst, causes end nodes to be described by pre-existing classical data. In such untrusted networks, determining quantum network fidelity and genuine multi-node entanglement becomes crucial. Here, we show that determining quantum network fidelity and genuine N-node entanglement in an untrusted star network requires only N + 1 measurement settings. This method establishes a semi-trusted framework, allowing some nodes to relax their assumptions. Our network determination method is enabled by detecting genuine N-node Einstein-Podolsky-Rosen steerability. Experimentally, using spontaneous parametric down-conversion entanglement sources, we demonstrate the determinations of genuine 3-photon and 4-photon quantum networks and the false positives of the widely used entanglement witness, the fidelity criterion of 1/2. Our results provide a scalable method for the determination of multipartite entanglement in realistic quantum networks.

ObjectiveTo explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group.MethodsForty healthy subjects （12 males and 28 females） were recruited. A portable digital quantitative muscle strength tester, Micro FET2TM, was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension, 0° neutral, and 30° flexion, respectively. Palmar abduction strength of the thumb was measured at 30° and 60°, respectively. Ten subjects were randomly selected from the 40 subjects, and the quantitative muscle strength of each muscle group was tested again by the same operator after an interval of 10 to 15 days.ResultsExcept for the fact that in males, there was no significant difference in flexor muscle strength of thumb and wrist joint between 30° of wrist extension and neutral 0° position, the muscle strength of the other fingers flexion and wrist palmar flexor showed the following characteristics： 30° of wrist extension > neutral 0° position > 30° of flexion, and the PAST was 30°>60°; The flexor muscle strength of all the subjects was thumb > index finger > middle finger > ring finger > little finger; All muscle strength values of male were greater than those of female, and the difference was statistically significant （P0.05）. The reliability of muscle strength values measured at different times in 10 subjects was good.ConclusionThe quantitative muscle strength of each muscle group of the hand and wrist is affected by the test position, and a standardized and uniformed test position should be adopted in the actual identification. Micro FET2TM has good reliability for hand and wrist quantitative muscle strength testing. The 30° extension of the wrist can be used as the best standardized test position for the flexion muscle strength of each finger and wrist joint. The 30° position can be used as the best standardized test position for PAST.

Abstract Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.

Abstract Pancreatic ductal adenocarcinoma (PDAC) poses challenges due to late-stage diagnosis and limited treatment response, often attributed to the hypoxic tumor microenvironment (TME). Sonoporation, combining ultrasound and microbubbles, holds promise for enhancing therapy. However, additional preclinical research utilizing commercially available ultrasound equipment for PDAC treatment while delving into the TME's intricacies is necessary. This study investigated the potential of using a clinically available ultrasound system and phase 2-proven microbubbles to relieve tumor hypoxia and enhance the efficacy of chemotherapy and immunotherapy in a murine PDAC model. This approach enables early PDAC detection and blood-flow-sensitive Power-Doppler sonoporation in combination with chemotherapy. It significantly extended treated mice's median survival compared to chemotherapy alone. Mechanistically, this combination therapy enhanced tumor perfusion and substantially reduced tumor hypoxia (77% and 67%, 1- and 3-days post-treatment). Additionally, cluster of differentiation 8 (CD8) T-cell infiltration increased four-fold afterward. The combined treatment demonstrated a strengthening of the anti-programmed death-ligand 1(αPDL1) therapy against PDAC. Our study illustrates the feasibility of using a clinically available ultrasound system with NH-002 microbubbles for early tumor detection, alleviating hypoxic TME, and improving chemotherapy and immunotherapy. It suggests the development of an adjuvant theragnostic protocol incorporating Power-Doppler sonoporation for pancreatic tumor treatment.

Abstract Background Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. Methods We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. Results The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. Conclusions The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.

Abstract Despite docetaxel combined with cisplatin and 5‐fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48‐linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)‐like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG‐like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7‐USP10‐G3BP1 axis contains potential targets and biomarkers for NPC treatment.

Lower extremity peripheral artery disease (PAD) is a growing global health problem. New methods to diagnose PAD have been explored in recent years. At present, the majority of imaging methods for PAD focus on the macrovascular blood flow, and the exploration of microcirculation and tissue perfusion of PAD remains largely insufficient. In this report, we applied three new imaging technologies, i.e., second near-infrared region (NIR-II, 900–1,880 nm wavelengths) imaging, optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG), in a PAD patient with a healthy human subject as control. Our results showed that the PAD patient had poorer tissue perfusion than the control without observed adverse effects. Moreover, compared with the first near-infrared region (NIR-I, 700–900 nm wavelengths) imaging results, NIR-II imaging had a higher signal-to-background ratio and resolution than NIR-I imaging and detected microvessels that were not detected by NIR-I imaging. These observations suggested that NIR-II imaging, OCTA, and LSFG are potentially safe and effective methods for diagnosing PAD.

Abstract Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. Trial registration ClinicalTrials.gov (NCT 04401800).

Abstract Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions. Graphical Abstract

Abstract Background Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. Methods This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. Results (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. Conclusions Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

Abstract On 18 September 2022, the MW 6.9 Chihshang earthquake struck the south half of the Longitudinal Valley, Taiwan, and caused severe damage. A precise and rapid report for the distribution of aftershock sequence after a devastating earthquake provides key information for deciphering the seismogenic structure in the source region. The utilization of deep-learning methodologies for earthquake event detection offers a significant acceleration in data analysis. In this study, we use SeisBlue, a deep-learning platform/package, to extract the whole earthquake sequence from September to October 2022, including the MW 6.5 Guanshan foreshock, the MW 6.9 mainshock, over 14,000 aftershocks, and 866 foal mechanisms from two sets of broadband networks. After applying hypoDD for earthquakes, the distribution of aftershock sequence clearly depicts not only the Central Range Fault and the Longitudinal Valley Fault but also several local, shallow tectonic structures that have not been observed along the southern Longitudinal Valley.

Abstract Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients’ survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

BackgroundAtherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic’s anti-atherosclerotic effects remain unclear.AimsThis study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis.MethodsThe study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets.ResultsThe integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis.ConclusionGarlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

BackgroundPrevious research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study.MethodsGenetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test.ResultsWe identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08–2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42–0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25–3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P

Introduction: Rydberg atoms are ideal for measuring electric fields due to their unique physical properties. However, low-frequency electric fields below MHz can be challenging due to the accumulation of ionized free electrons on the atomic vapor cell’s surface, acting as a shield.Method: This paper proposes a Cavity-enhanced three-photon system (CETPS) measurement scheme, which uses a long-wavelength laser to excite the Rydberg state, reducing atomic ionization and enhancing detection spectrum resolution. A theoretical model is proposed to explain the quantum coherence effect of the light field, measured electric field, and the atomic system.Result: The results show that the proposed scheme significantly increases the electromagnetically induced transparency (EIT) spectral peak and narrows the spectral width, resulting in the maximum slope increasing by more than an order of magnitude.Discussion: The paper also discusses the impact of the Rabi frequency of the two laser fields and the coupling coefficient of the optical cavity on the transmission spectrum amplitude and linewidth, along with the optimal configuration of these parameters in the CEPTS scheme.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

In response to the challenge of mitigating flight delays, this study introduces an innovative solution that encompasses the prediction of delay durations for existing flights and the subsequent optimization of ground service processes based on these predictions. The indirect forecasting of flight delays is achieved through the construction of a random forest model, exhibiting a remarkable 100% accuracy when considering a 15-minute standard for flight delays. In light of the delay prediction outcomes, distinct delay coefficients are assigned to individual flights, facilitating the development of a ground service optimization model through the application of a genetic algorithm. Within the genetic algorithm optimization framework, significant enhancements have been implemented in the gene encoding of the initial population, incorporating a segmented encoding approach. Employing this refined model to optimize the service sequence and duration of ground service vehicles for all flights culminates in the notable accomplishment of achieving zero delays for the entire set of flights.

Abstract Background It is well known that tumor-associated macrophages (TAMs) play essential roles in brain tumor resistance to chemotherapy. However, the detailed mechanisms of how TAMs are involved in brain tumor resistance are still unclear and lack a suitable analysis model. Methods A BV2 microglial cells with ALTS1C1 astrocytoma cells in vitro co-culture system was used to mimic the microglia dominating tumor stroma in the tumor invasion microenvironment and explore the interaction between microglia and brain tumor cells. Results Our result suggested that microglia could form colonies with glioma cells under high-density culturing conditions and protect glioma cells from apoptosis induced by chemotherapeutic drugs. Moreover, this study demonstrates that microglia could hijack drug substances from the glioma cells and reduce the drug intensity of ALTS1C1 via direct contact. Inhibition of gap junction protein prevented microglial-glioma colony formation and microglia-mediated chemoresistance. Conclusions This study provides novel insights into how glioma cells acquire chemoresistance via microglia-mediated drug substance transferring, providing a new option for treating chemo-resistant brain tumors.

Abstract Background Among the safest procedures for anastomosis in pancreaticoduodenectomy, Blumgart pancreaticojejunostomy is associated with low rates of postoperative pancreatic fistula (POPF) and postoperative complications. However, this technique is difficult to perform during laparoscopic pancreaticoduodenectomy (LPD). This study presents a modified Blumgart method using a homemade crochet needle to facilitate laparoscopic pancreaticojejunostomy and evaluates its safety and reliability. Methods From February 2019 to October 2022, 96 LPD surgeries with the new technique were performed by the same surgeons in the Second Affiliated Hospital of Zhejiang University School of Medicine. The operative details (operative time, pancreaticojejunostomy time, POPF rate, postoperative complication rate, mortality rate) were analyzed along with clinical and pathological indicators (pancreatic duct diameter, pancreatic texture, and histopathological findings). Results There were 54 men and 42 women with a mean age of 63.38 ± 10.41 years. The intraoperative bleeding volume, operative time and postoperative length of hospital stay were 198.43 ± 132.97 mL, 445.30 ± 87.05 min and 13.68 ± 4.02 days, respectively. The operation time of pancreaticojejunostomy was 66.28 ± 10.17 min. Clinically relevant POPFs (grades B and C) occurred in 14.6% of patients. Only one patient had postoperative abdominal hemorrhage and was cured after reoperation. There were no operative or in-hospital deaths. With our proposed modification, the pancreatic duct and jejunal orifice are aligned correctly during duct-to-mucosa (DTM) after the application of external traction through the homemade crochet needle. The space between the posterior wall of pancreatic remnant and jejunal loop can be exposed by adjusting the tension of the external threads, which can facilitate DTM. Conclusions A modified Blumgart method using a homemade crochet needle could be technically feasible and safe during LPD. A randomized control trial is needed to confirm these findings.

Abstract Background Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood. Methods Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3. Results The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells. Conclusions Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.