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This study reports the development and evaluation of yttrium-90 (90Y) radiolabeled silica-coated iron oxide (SiO 2 -Fe 3 O 4) resin microspheres for potential theranostic application in cancer radiation therapy. Iron oxide nanoparticles of average diameter 29.7 nm were synthesized via optimized co-precipitation and displayed superparamagnetic behavior ideal for MRI. Aminosilane surface functionalization enabled covalent conjugation of 1 mmol/g DTPA/DOTA chelators for labeling 2 mCi 90Y per 150 μg nanoparticles with 92 % efficiency when incubated for 45 mins at pH 5.5 and 50°C. In vitro stability assays in buffers and human serum showed excellent 90Y retention (>95 %) up to 48 hours. In vivo biodistribution in Wistar rats revealed extended nanoparticle circulation half-life of 5.2 hours and peak exposure of 22.4 %ID/g compared to rapid clearance of unconjugated 90Y chloride within 1 hour. Complete renal recovery by 72 hours and minimal bone accumulation (<2 %) proves in vivo stability and biocompatibility of the 90Y-radiolabeled theranostic platform. [ABSTRACT FROM AUTHOR]

Tumors reprogram their metabolism to generate complex neoplastic ecosystems. Here, we demonstrate that glioblastoma (GBM) stem cells (GSCs) display elevated activity of the malate-aspartate shuttle (MAS) and expression of malate dehydrogenase 2 (MDH2). Genetic and pharmacologic targeting of MDH2 attenuated GSC proliferation, self-renewal, and in vivo tumor growth, partially rescued by aspartate. Targeting MDH2 induced accumulation of alpha-ketoglutarate (αKG), a critical co-factor for dioxygenases, including the N6-methyladenosine (m6A) RNA demethylase AlkB homolog 5, RNA demethylase (ALKBH5). Forced expression of MDH2 increased m6A levels and inhibited ALKBH5 activity, both rescued by αKG supplementation. Reciprocally, targeting MDH2 reduced global m6A levels with platelet-derived growth factor receptor-β (PDGFRβ) as a regulated transcript. Pharmacological inhibition of MDH2 in GSCs augmented efficacy of dasatinib, an orally bioavailable multi-kinase inhibitor, including PDGFRβ. Collectively, stem-like tumor cells reprogram their metabolism to induce changes in their epitranscriptomes and reveal possible therapeutic paradigms. [Display omitted] • GSCs exhibit high activity of the malate-aspartate shuttle (MAS) • Targeting malate dehydrogenase 2 (MDH2) reduces GSC proliferation and stemness • MDH2 regulates m6A modifications of PDGFRB mRNA via αKG-dependent ALKBH5 inhibition • MDH2 inhibition augments the efficacy of dasatinib against GSCs Lv et al. find that stem-like tumor cells preferentially activate the malate-aspartate shuttle (MAS), which represses levels of α-ketoglutarate, a metabolite co-factor for the mRNA demethylase ALKBH5, to reprogram the epitranscriptome and maintain tumor stemness. Targeting this tumor-associated metabolic pathway through malate dehydrogenase 2 sensitizes highly resistant cancer cells to targeted therapeutics. Collectively, tumors reprogram their metabolic states to promote RNA diversity and maintenance of cancer stem cells, providing therapeutic vulnerabilities. [ABSTRACT FROM AUTHOR]

The rise of multidrug-resistant bacteria (MDRB) has made bacterial infection one of the biggest health threats, causing numerous antibiotics to fail. Real-time monitoring of bacterial disease treatment efficacy at the infection site is required. Herein, we report a versatile Raman tag 3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated star-shaped Au-MoS 2 @hyaluronic acid (AMD@HA) nanocomposite as a surface-enhanced Raman scattering (SERS) nanoprobe for quick bacterial identification and in-situ eradication. Localized surface plasmon resonance (LSPR) from the hybrid metallic nanostructure makes AMD@HA highly responsive to the near-infrared laser, enabling it to demonstrate a photothermal (PTT) effect, increased SERS activity, and peroxidase-like catalytic reaction to release reactive oxygen species. The tail vein injection of AMD@HA nanoprobes is invasive, however SERS imaging for bacterial identification is non-invasive and sensitive, making it an efficient residual bacteria monitoring method. The detection limit for methicillin-resistant Staphylococcus aureus (MRSA) is as low as 102 CFU·mL-1, and the substrates allow for taking 120 s to acquire a Raman image of 1600 (40 × 40) pixels. In mouse models of MRSA-induced wound infection and skin abscess, the combination of AMD@HA-mediated PTT and catalytic therapy demonstrates a synergistic effect in promoting wound healing through rapid sterilization. This SERS-guided therapeutic approach exhibits little toxicity and does not cause considerable collateral damage, offering a highly promising intervention for treating diseases caused by MDRB. This research introduces a SERS nanoprobe, AMD@HA, for the rapid identification and eradication of multidrug-resistant bacteria (MDRB), a critical health threat. The nanoprobe leverages localized surface plasmon resonance for photothermal therapy and enhanced Raman signals, offering a sensitive, non-invasive diagnostic tool. With a low detection limit for MRSA and a synergistic therapeutic effect in mouse models, our approach holds significant promise for treating MDRB-driven infections with minimal toxicity, advancing the field of antimicrobial strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Postoperative adhesions commonly form in various tissues, resulting in serious implications and an increased risk of secondary surgery. The application of anti-adhesion films as physical barriers has proven effective in reducing adhesion incidence and severity. However, existing anti-adhesion films require manual deployment during minimally invasive surgery, posing inconvenience and possibility of further injury. To address these limitations, we have developed an intelligent anti-adhesion film based on shape memory polyurethane. In this work, a linear shape memory polyurethane (ISO2-PU), incorporating hexamethylene isocyanate and isosorbitol as hard segments and poly(D, L-lactic acid) macrodiol as soft segments, was fabricated into an anti-adhesion film. The favorable shape memory effect of the ISO2-PU film ensures its convenient delivery and automatic unfolding, as revealed by a simulation experiment for endoscopic surgical implantation. Furthermore, the glass transition temperature (T g) close to body temperature endows the ISO2-PU film with good mechanical compliance, thus ensuring a reliable fit with the wounded tissue to avoid undesired folding. Finally, in vivo experiments using a rat cecal abdominal wall injury model demonstrated that the combination of reliable fit, appropriate degradation rate, and good cytocompatibility promises the ISO2-PU film with high anti-adhesion efficacy. This work validates the concept of shape memory anti-adhesion barrier and expands future directions for advanced anti-adhesion biomaterials. Postoperative adhesions are a common complication that occurs widely after various surgeries. This work developed an intelligent anti-adhesion film based on a linear shape memory polyurethane (ISO2-PU). This film is featured with remarkable shape memory effect and mechanical compliance at body temperature, appropriate degradability, and good cytocompatibility. These merits ensure convenient delivery and smart unfolding of ISO2-PU film during minimally invasive surgery and favorable postoperative anti-adhesion efficacy. The results validate the concept of shape memory anti-adhesion barrier and paves a way for designing next-generation anti-adhesion biomaterials. [Display omitted] [ABSTRACT FROM AUTHOR]

There are few data favoring the need for septotomy at the time of peroral endoscopic myotomy (POEM) or if POEM alone is sufficient. Our aim was to compare POEM outcomes with and without septotomy (POEM+S or POEM-S) in patients with symptomatic epiphrenic diverticula (ED) and an underlying motility disorder. This was an international, multicenter retrospective study involving 21 centers between January 2014 and January 2023. Patients with ED and an underlying motility disorder who underwent POEM were included. The primary outcome was clinical success (Eckardt score [ES] ≤3 or a 1-point drop in ES for patients with baseline ES <3) without the need for repeat surgical/endoscopic interventions during follow-up. A total of 85 patients (mean age, 64.29 ± 17.1 years; 32 [37.6%] female) with ED and underlying motility disorder underwent POEM+S (n = 47) or POEM–S (n = 38). Patients in the POEM+S group had a significantly higher mean pre-POEM ES (7.3 ± 2.1 vs 5.8 ± 2; P =.002). The most common indication for POEM was achalasia (51% in the POEM+S cohort and 51.8% in the POEM–S cohort; P =.7). A posterior approach was favored in the POEM+S group (76.6% vs 52.6%; P =.02). A similar rate of technical success was seen in both groups (97.9% vs 100%; P =.1). The rate of adverse events was similar between the 2 cohorts (4.2% vs 8.1%; P =.6). The median length of hospital stay after POEM–S was significantly longer compared with POEM+S (2 days [interquartile range (IQR), 1-4 days] vs 1 day [IQR, 1-2 days]; P =.005). Clinical success was equivalent between the 2 groups (83% vs 86.8%; P =.6) at a median follow-up duration of 8 months (IQR, 3-19 months). In patients with ED and an underlying motility disorder, both POEM+S and POEM–S are equally safe and effective, with similar procedure duration and a low recurrence rate at short-term follow-up. Future comparative prospective studies with long-term follow-up are required to validate these findings. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD. [ABSTRACT FROM AUTHOR]

[Display omitted] • LPS-activated MSCs promote the expression of NLRP3 and the production of IL-10. • NLRP3 upregulates Glut1 expression and promotes glycolysis in MSCs. • Overexpression of Glut1 enhanced the therapeutic effect of Nlrp3 KO MSCs against DSS-induced colitis. • NLRP3 activation promotes IL-10 production by upregulating glycolysis levels, heightening the protective effects of MSCs treatment on DSS-induced colitis. Numerous studies demonstrated that NLRP3 has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) regulated the NLRP3 inflammasome, which has emerged as a novel therapeutic approach for treating IBD. The exact role of NLRP3 in regulating MSCs' function is unclear. Our study aimed to explore how NLRP3 affects the therapeutic effects of MSCs in colitis. We extracted MSCs from the bone marrow of C57BL/6 mice and Nlrp3 KO mice, and identified them using differentiation assays and flow cytometry. In vitro , Both WT MSCs and Nlrp3 KO MSCs were stimulated with inflammatory factor Lipopolysaccharide (LPS), and only WT MSCs were stimulated with varying concentrations of the NLRP3 inhibitor MCC950, then, quantified IL-10 levels in the supernatant. RNA-seq was performed to examine gene expression patterns and Seahorse was used to assess oxidative phosphorylation (OXPHOS) and glycolysis levels. Western blot was used to evaluate protein expression. In vivo , we treated DSS-induced colitis with either WT or Nlrp3 KO MSCs, monitoring weight, measuring colon length, and further evaluation. We also treated DSS-induced colitis with pretreated MSCs (BAY876, oe-Glut1, or oe-NLRP3), following the same experimental procedures as described above. Our results demonstrate that Nlrp3 deletion did not affect MSC phenotypes, but rather promoted osteogenic differentiation. However, the absence of Nlrp3 reduced IL-10 production in MSCs in the presence of LPS, leading to impaired protection on DSS-induced colitis. Conversely, overexpression of NLRP3 promotes the production of IL-10, enhancing therapeutic effects. Further investigation revealed that Nlrp3 deficiency downregulated Glut1 expression and glycolysis activation in MSCs, resulting in decreased IL-10 production. Notably, overexpressing Glut1 in Nlrp3 KO MSCs restored their therapeutic effect that was previously dampened due to Nlrp3 deletion. Our findings demonstrate that NLRP3 heightens the therapeutic effects of MSC treatment on DSS-induced colitis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The coexistence of mutant and wild-type mtDNA constitutes the heteroplasmy of mtDNA. • The ovary is a highly energy-intensive organ, and it relies heavily on mitochondrial function. • Mitochondrial heteroplasmy can potentially contribute to a variety of significant ovarian disorders. • Current strategies related to mitochondrial heteroplasmy are untargeted and have low bioavailability. • The exploration of new mitochondria-targeted therapeutic strategies may offer promising paths towards these diseases. The reportedly high mutation rate of mitochondrial DNA (mtDNA) may be attributed to the absence of histone protection and complete repair mechanisms. Mitochondrial heteroplasmy refers to the coexistence of wild-type and mutant mtDNA. Most healthy individuals carry a low point mutation load (<1 %) in their mtDNA, typically without any discernible phenotypic effects. However, as it exceeds a certain threshold, it may cause the onset of various diseases. Since the ovary is a highly energy-intensive organ, it relies heavily on mitochondrial function. Mitochondrial heteroplasmy can potentially contribute to a variety of significant ovarian disorders. In this review, we have elucidated the close relationship between mtDNA heteroplasmy and ovarian diseases, and summarized novel avenues and strategies for the potential treatment of these ovarian diseases. Mitochondrial heteroplasmy can potentially contribute to a variety of significant ovarian disorders, including polycystic ovary syndrome, premature ovarian insufficiency, and endometriosis. Current strategies related to mitochondrial heteroplasmy are untargeted and have low bioavailability. Nanoparticle delivery systems loaded with mitochondrial modulators, mitochondrial replacement/transplantation therapy, and mitochondria-targeted gene editing therapy may offer promising paths towards potentially more effective treatments for these diseases, despite ongoing challenges. [ABSTRACT FROM AUTHOR]

Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)–dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. Peritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a deep learning radiomics nomogram (DLRN) based on B-mode ultrasound (BMUS) and color doppler flow imaging (CDFI) images for preoperative assessment of lymphovascular invasion (LVI) status in invasive breast cancer (IBC). In this multicenter, retrospective study, 832 pathologically confirmed IBC patients were recruited from eight hospitals. The samples were divided into training, internal test, and external test sets. Deep learning and handcrafted radiomics features reflecting tumor phenotypes on BMUS and CDFI images were extracted. The BMUS score and CDFI score were calculated after radiomics feature selection. Subsequently, a DLRN was developed based on the scores and independent clinic-ultrasonic risk variables. The performance of the DLRN was evaluated for calibration, discrimination, and clinical usefulness. The DLRN predicted the LVI with accuracy, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI 0.90–0.95), 0.91 (95% CI 0.87–0.95), and 0.91 (95% CI 0.86–0.94) in the training, internal test, and external test sets, respectively, with good calibration. The DLRN demonstrated superior performance compared to the clinical model and single scores across all three sets (p < 0.05). Decision curve analysis and clinical impact curve confirmed the clinical utility of the model. Furthermore, significant enhancements in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indicated that the two scores could serve as highly valuable biomarkers for assessing LVI. The DLRN exhibited strong predictive value for LVI in IBC, providing valuable information for individualized treatment decisions. [ABSTRACT FROM AUTHOR]

We aimed to validate the prognostic implication of uncertain resection, R(un), proposed by International Association for the Study of Lung Cancer (IASLC) and evaluate the prognostic value of spread through air spaces (STAS) in reclassifying the R classification among patients with lung adenocarcinoma after segmentectomy. We enrolled 1007 patients who underwent segmentectomy for c-stage IA lung adenocarcinoma between 2014 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were compared to evaluate the prognostic value of IASLC-R(un) and STAS. Whether STAS would skip into complementary lobectomy was evaluated in a prospective cohort. The current IASLC-R(un) failed to significantly stratify the RFS (P =.078) in segmentectomy, and STAS was a stronger risk factor of poor prognosis for both RFS and OS (P <.001). Moreover, the presence of STAS was associated with increased locoregional recurrence in patients undergoing segmentectomy (P <.001) but not in those treated with lobectomy (P =.187), indicating that only STAS-positive segmentectomy was consistent with the concept of R(un) in relapse pattern. After reclassifying STAS-positive segmentectomy into the R(un) category, the proposed R(un) showed an improvement in prognosis stratification. In addition, 2 of 30 patients (6.2%) in the prospective cohort who underwent initial segmentectomy and complementary lobectomy had STAS clusters in the complementary lobectomy specimens. Unfavorable prognosis, relapse patterns consistent with R(un), and pathologic verification that saltatory spread of STAS observed in complementary lobectomy specimens supported reclassifying STAS-positive segmentectomy as R(un). STAS is a critical concern for the surgical completeness evaluation after segmentectomy. [Display omitted] [ABSTRACT FROM AUTHOR]

Mitochondria, pivotal organelles crucial for energy generation, apoptosis regulation, and cellular metabolism, have spurred remarkable advancements in targeted material development. This review surveys recent breakthroughs in targeted mitochondrial nanomaterials, illuminating their potential in drug delivery, disease management, and biomedical imaging. This review approaches from various application perspectives, introducing the specific applications of mitochondria-targeted materials in cancer treatment, probes and imaging, and diseases treated with mitochondria as a therapeutic target. Addressing extant challenges and elucidating potential therapeutic mechanisms, it also outlines future development trajectories and obstacles. By comprehensively exploring the diverse applications of targeted mitochondrial nanomaterials, this review aims to catalyze innovative treatment modalities and diagnostic approaches in medical research. This review presents the latest advancements in mitochondria-targeted nanomaterials for biomedical applications, covering diverse fields such as cancer therapy, bioprobes, imaging, and the treatment of various systemic diseases. The novelty and significance of this work lie in its systematic analysis of the intricate relationship between mitochondria and different diseases, as well as the ingenious design strategies employed to harness the therapeutic potential of nanomaterials. By providing crucial insights into the development of mitochondria-targeted nanomaterials and their applications, this review offers a valuable resource for researchers working on innovative treatment modalities and diagnostic approaches. The scientific impact and interest to the readership lie in the identification of promising avenues for future research and the potential for clinical translation of these cutting-edge technologies. [Display omitted] [ABSTRACT FROM AUTHOR]

A bimodal-structured Mg–15Gd binary alloy with 45% volume fraction of elongated grains and 55% of dynamically recrystallized (DRXed) grains is fabricated by the extrusion process. The precipitating behavior correlating with the evolution of mechanical properties is systematically characterized during the subsequent aging treatment at 200 °C. The extruded alloy presents an outstanding strength with tensile yield strength of 466 MPa and ultimate tensile strength of 500 MPa at peak aging condition, while the elongation drops from 9.2% in extrusion state to 3.1%. It is found there obviously exist a rapidly decreasing range of ductility at the early stage of aging. Just during this time, the nano precipitates form preferentially at lamellar dislocation boundaries (LDBs) within the elongated grains, but there is no dense and uniform precipitation in the matrix. The results suggest that the low elongation in the aged Mg–15Gd alloy is mainly attributed to the nano precipitates prior formed at the LDBs with a high density in the elongated grains. The related mechanism has been clarified. [ABSTRACT FROM AUTHOR]

Skeletal muscle is an important contributor to joint health. Previous studies have shown that age-related muscle mass and strength loss are closely associated with the development of knee osteoarthritis. The objective of this study is to investigate whether a high plant protein/peptide nutrition supplementation can alleviate knee osteoarthritis by improving muscle mass and strength. This randomized, double-blind, placebo-controlled trial that included participants aged 50–70 years diagnosed with knee osteoarthritis and sarcopenia was conducted in China from February 2022 to September 2022 (ChiCTR2200056415). Participants were randomly assigned to receive either a 12-week high plant protein/peptide nutrition supplementation or a placebo twice daily, with one serving each after breakfast and dinner, respectively. The primary outcome analyzed using intention-to-treat analysis was difference in Short Physical Performance Battery (SPPB) from baseline to week 12 between the two groups. The secondary outcomes included changes in muscle mass, strength, symptom and imaging of knee osteoarthritis, body composition, biochemical parameters, and health quality scores. After 12 weeks, a total of 124 participants (38.7% male) completed the trial and were included in the final analysis. Over the 12-week follow-up, the experimental group showed a significant improvement in the SPPB total score (1.03, 95% CI, 0.69 to 1.38, P < 0.0001) compared with the placebo group. Grip strength (2.83 kg, 95% CI, 2.13 to 3.53, P < 0.0001) and skeletal muscle mass index (0.66 kg/m2, 95% CI, 0.45 to 0.86, P < 0.0001) were also significantly increased in the experimental group relative to the placebo group. The mean change in Western Ontario and McMaster Universities Osteoarthritis Index total score was −3.95 points (95% CI, −5.02 to −2.89, P < 0.0001) in the experimental group and 0.23 points (95% CI, −0.17 to 0.63, P = 0.253) in the placebo group. Additionally, within the experimental group, nine participants experienced an improvement in osteophyte magnetic resonance imaging results, while no improvement was observed in the placebo group. The experimental group also exhibited significant improvements in health quality compared with the placebo group as assessed by Short Form 36, the World Health Organization Quality of Life Brief Scale, and the Chalder Fatigue Scale. No serious adverse events were reported during the trial. Oral supplementation with high levels of plant protein/peptides can alleviate symptoms of osteoarthritis in elderly individuals with minor or mild knee osteoarthritis and sarcopenia. This improvement may be attributed to the enhancements of muscle mass, strength, and physical performance. [ABSTRACT FROM AUTHOR]

This work applies a bootstrap multivariate panel Granger causality test to examine the causal relationship between the coronavirus disease 2019, Delta and Omicron pandemic eras and the maritime shipping freight industry across 15 Chinese marine transportation freight stocks through the data from Jannuary 23, 2020 to December 6, 2022. After accounting for both dependency and heterogeneity across these industries, we find support for six of the 15 maritime shipping freight enterprises which display a unidirectional Granger relationship between stock returns and pandemic-related shocks and five of them which demonstrate a bidirectional association. On the other hand, the stock values of three firms in this cohort Granger "lead" the epidemic, suggesting that the adjustment of expectations to external shocks and the efficient market hypothesis could elucidate apparent causal connections. The empirical findings of this work provide important policy implications for the maritime shipping freight industry. [ABSTRACT FROM AUTHOR]

• Forest resilience to soil drought stress under global warming can be retrieved from the soil microbiota. • How internal workings within the soil microbiota change with forest management aimed to maintain forest production is little known due to the lacking of powerful network models. • We describe an advanced network model for reconstructing informative, dynamic, omnidirectional and personalized networks (idopNetworks) from big static data. • idopNetworks reveal the topological structure of the soil microbiota and its causal relationship with soil physical and chemical properties under forest management. • The model can chart the global and detailed atlas of how the soil microbiota change their structure and organization in response to reduced precipitation due to global warming and thinning used to leverage forest resilience. Forest management by thinning can mitigate the detrimental impact of increasing drought caused by global warming. Growing evidence shows that the soil microbiota can coordinate the dynamic relationship between forest functions and drought intensity, but how they function as a cohesive whole remains elusive. We outline a statistical topology model to chart the roadmap of how each microbe acts and interacts with every other microbe to shape the dynamic changes of microbial communities under forest management. To demonstrate its utility, we analyze a soil microbiota data collected from a two-way longitudinal factorial experiment involving three stand densities and three levels of rainfall over a growing season in artificial plantations of a forest tree – larix (Larix kaempferi). We reconstruct the most sophisticated soil microbiota networks that code maximally informative microbial interactions and trace their dynamic trajectories across time, space, and environmental signals. By integrating GLMY homology theory, we dissect the topological architecture of these so-called omnidirectional networks and identify key microbial interaction pathways that play a pivotal role in mediating the structure and function of soil microbial communities. The statistical topological model described provides a systems tool for studying how microbial community assembly alters its structure, function and evolution under climate change. [ABSTRACT FROM AUTHOR]

Due to severe deformation, noise, and occlusion, the registration problem of non-rigid point sets in rolling formed metal workpieces poses challenges, and the demand for real-time data storage and registration during the rolling forming process makes this problem even more prominent. This paper proposes an enhanced nonrigid point set registration algorithm based on the Coherent Point Drift (CPD) framework, introducing novel methods to improve accuracy and efficiency. A refined local distance calculation method combining spatial distance has been proposed to improve matching accuracy. In contrast, an optimized shape context method introduces a new driving force criterion to expedite initial registration and reduce subsequent errors. Leveraging the Expectation-Maximization (EM) algorithm, the approach iteratively solves point correspondences, demonstrating robustness in handling complex scenarios like non-rigid deformation and noise. Experimental validation using real production datasets shows superior accuracy and efficiency over classical algorithms, showcasing a practical solution for non-rigid point set registration challenges in roll forming applications. [ABSTRACT FROM AUTHOR]

Heatstroke (HS), associated with the early activation of the coagulation system and frequently presenting with thrombocytopenia, poses a significant healthcare challenge. Understanding the relationship of nadir platelet count (PLT) within 24 h for adverse outcomes in HS patients is crucial for optimizing management strategies. This retrospective cohort study, conducted in six tertiary care hospitals, involved patients diagnosed with HS and admitted to the emergency departments. The primary and secondary outcomes included in-hospital mortality and various acute complications, respectively, with logistic regression models utilized for assessing associations between nadir PLT and outcomes. The PLT count change curve was described using a generalized additive mixed model (GAMM), with additional analyses involving body temperature (BT) at 2 h also conducted. Of the 152 patients included, 19 (12.5%) died in-hospital. The median nadir PLT within 24 h was 99.5 (58.8–145.0)*10^9/L. Notably, as a continuous variable (10*10^9/L), nadir PLT was significantly associated with in-hospital mortality (OR 0.76; 95% CI 0.64–0.91; P = 0.003) and other adverse outcomes like acute kidney and liver injury, even after adjustment for confounders. GAMM revealed a more rapid and significant PLT decline in the non-survival group over 24 h, with differential PLT dynamics also observed based on BT at 2 h. Nadir PLT within 24 h were tied to in-hospital mortality and various adverse outcomes in HS patients. Early effective cooling measures demonstrated a positive impact on these associations, underscoring their importance in patient management. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? The present study sought to understand whether the presence of the APOE -ε4 allele results in differential cognitive outcomes following the interacting effects of decreasing in PM 2.5 levels over time and aging. • What is the main finding of this study? The results showed high levels of PM 2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. Participants demonstrated cognitive decline with an average MMSE score decline of 1.11 per year. Carriers of ε4/ε4 alleles in APOE had significantly 3.68-fold risks of MMSE decline. • What is the meaning of the finding? Although the annual PM 2.5 levels decreased over time, the results still indicated that long-term exposure to PM 2.5 , was associated with an increased risk of MMSE decline. Limited research has explored the long-term effect of reduced PM 2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM 2.5 exposure and the interactions of PM 2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE -ε4 allele. Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM 2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM 2.5 on MMSE decline, further stratified by the presence of APOE -ε4 alleles. After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM 2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM 2.5 decreased over time, the impact of PM 2.5 on MMSE decline also slowly diminished. Long-term PM 2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM 2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools. [ABSTRACT FROM AUTHOR]

Patients with stage III or IV of operative link for gastric intestinal metaplasia assessment (OLGIM) are at a higher risk of gastric cancer (GC). We aimed to construct a deep learning (DL) model based on magnifying endoscopy with narrow-band imaging (ME-NBI) to evaluate OLGIM staging. This study included 4473 ME-NBI images obtained from 803 patients at three endoscopy centres. The endoscopic expert marked intestinal metaplasia (IM) regions on endoscopic images of the target biopsy sites. Faster Region-Convolutional Neural Network model was used to grade IM lesions and predict OLGIM staging. The diagnostic performance of the model for IM grading in internal and external validation sets, as measured by the area under the curve (AUC), was 0.872 and 0.803, respectively. The accuracy of this model in predicting the high-risk stage of OLGIM was 84.0%, which was not statistically different from that of three junior (71.3%, p = 0.148) and three senior endoscopists (75.3%, p = 0.317) specially trained in endoscopic images corresponding to pathological IM grade, but higher than that of three untrained junior endoscopists (64.0%, p = 0.023). This DL model can assist endoscopists in predicting OLGIM staging using ME-NBI without biopsy, thereby facilitating screening high-risk patients for GC. [ABSTRACT FROM AUTHOR]

While the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic. We aimed to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated. AR was induced in mice with ovalbumin. Toluidine blue staining, liquid chromatography–tandem mass spectrometry analysis, real-time quantitative PCR, and immunoblotting were performed with AR and control mice. Ovalbumin-induced AR is diurnally rhythmic and associated with clock gene disruption in nasal mucosa. In particular, Rev-erbα is generally downregulated and its rhythm retained, but with a near-12-hour phase shift. Furthermore, global knockout of core clock gene Bmal1 or Rev-erbα increases the susceptibility of mice to AR and blunts AR rhythmicity. Importantly, nasal solitary chemosensory cells (SCCs) are rhythmically activated, and inhibition of the SCC pathway leads to attenuated AR and a loss of its rhythm. Moreover, rhythmic activation of SCCs is accounted for by diurnal expression of ChAT (an enzyme responsible for the synthesis of acetylcholine) and temporal generation of the neurotransmitter acetylcholine. Mechanistically, Rev-erbα trans-represses Ch at through direct binding to a specific response element, generating a diurnal oscillation in this target gene. SCCs, under the control of Rev-erbα , are a driver of AR rhythmicity; targeting SCCs should be considered as a new avenue for AR management. [ABSTRACT FROM AUTHOR]

Ground glass opacity is observed frequently in the early stages of lung adenocarcinoma and is associated with a favorable prognosis and a low incidence of lymph node metastasis. However, the necessity of lymph node sampling in these patients is questionable, although current guidelines still recommend it. Radiologic and clinical data were retrospectively collected and analyzed for 2,298 patients with lung cancer who underwent surgical resection for lesions ≤15 mm during 2022. Based on the consolidation tumor ratios, patients were categorized into 4 groups (pure ground glass opacity, ground glass opacity-predominant, solid-predominant, and pure solid). The incidence of lymph node metastasis in each group was examined. A total of 2,298 patients with a median age of 54.0 years were enrolled in this study. Tumors were categorized into 4 types: 1,427 (62.1%) were pure ground glass opacity, which constituted the majority, while 421 (18.3%) were ground glass opacity-predominant, 330 (14.4%) were solid-predominant, and the remaining 120 (5.2%) were pure solid. Significant positive correlations were revealed between the consolidation tumor ratio group and pathologic grade (P <.001, ρ = 0.307), T stage (P <.001, ρ = 0.270), and N stage (P <.001, ρ = 0.105). Among the included cases, only 7 cases with metastasis were in the pure solid group. Within this group, 113 cases (94.2%) were N0, 5 cases (4.2%) were N1, and 2 cases (1.7%) were N2. Lymph node metastasis exclusively occurred in the pure solid group, suggesting that for nodules <15 mm, lymph node sampling may be crucial for pure solid nodules but less so for those containing ground glass opacities. [Display omitted] [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a discharge assessment scale tailored for outpatients undergoing sedative anesthesia treatment in the ambulatory postanesthesia care unit and validate its agreement with the Post-Anesthetic Discharge Scoring System. The Delphi method. A Delphi survey was conducted with 30 experts focusing on the evaluation of outpatient discharges following treatment under ambulatory anesthesia. Subsequently, a cross-sectional observational study employing convenience sampling selected 2,579 outpatients who had undergone painless ambulatory gastrointestinal endoscopy at a tertiary hospital to analyze the level of agreement with the Post-Anesthesia Discharge Scoring System. The study conducted three rounds of expert consultations to create the ambulatory discharge assessment scale. Twenty-five experts from 12 provinces and municipalities in our country were interviewed. The discharge assessment form encompassed five aspects: consciousness level, vital signs, directional stability, mobility, and adverse reactions. According to the scale, if the total score exceeded 9 points, with none of the items scoring 0 points, the ambulatory patient could be discharged from the hospital with the accompaniment of family members. Patients assessed using this newly constructed scale were able to leave the hospital earlier compared to those assessed using the comparative scale. No significant differences were observed in vital signs at the time of discharge or the occurrence of adverse events within 24 hours after the procedure. This assessment tool for discharging ambulatory patients after the ambulatory anesthesia from the postanesthesia outpatient care unit can be considered a valuable addition to formalize the discharge process in outpatient services. [ABSTRACT FROM AUTHOR]

Desmoid tumors (DTs) are rare benign neoplasms but cause significant mortality due to their locally infiltrative nature and propensity to recur. Most DTs occur in the extremities and trunk. Head and neck DTs are uncommon but can have a significant impact on a patient's facial appearance. However, there is limited information available about the diagnosis and treatment for multiple DTs located in head and neck. We report the first case of multiple maxillofacial DTs in a 14-year-old boy. He had painless submandibular masses for three months and MRI imaging reveals abnormal high signals on the submandibular and bilateral zygomatic regions. Considering facial aesthetics, via intraoral incision we obtained a biopsy from the largest mass. Pathological examination confirmed a diagnosis of DT. We selected the wait-and-see strategy and clinically monitored the rest of the masses. During the subsequent 1-year follow-up, the masses were stagnant and appeared to involute. According to the development and outcome of this case, a conservative treatment for craniofacial DTs is suggested; however, greater clarity concerning management and prognosis could derive from prospective study of a larger patient cohort in the future. [ABSTRACT FROM AUTHOR]

To develop a nomogram by integrating B-mode ultrasound (US), strain ratio (SR), and radiomics signature (RS) effectively differentiating between benign and malignant lesions in the Breast Imaging Reporting and Data System (BI-RADS) 4. We retrospectively recruited 709 consecutive patients who were assigned a BI-RADS 4 and underwent curative resection or biopsy between 2017 and 2022. US images were collected before surgery. A RS was developed through a multistep feature selection and construction process. Histology findings served as the gold standard. Univariate and multivariate regression analysis were employed to analyze the clinical and US characteristics and identify variables for developing a nomogram. The calibration and discrimination of the nomogram were conducted to evaluate its performance. The study included a total of 709 patients, with 497 in the training set and 212 in the validation set. In the training set, the B-mode US had an AUC of 0.84 (95% confidence interval [CI], 0.80, 0.87). The SR demonstrated an AUC of 0.78 (95% CI, 0.74, 0.82), while the RS showed an AUC of 0.85 (95% CI, 0.81, 0.88). Notably, the nomogram exhibited superior performance compared to the conventional US, SR, and RS (AUC = 0.93, both p < 0.05, as per the Delong test). The clinical usefulness of the nomogram was favorable. The calibrated nomogram can be specifically designed to predict the malignancy of breast lesions in the BI-RADS 4 category. [ABSTRACT FROM AUTHOR]

[Display omitted] • Osteoprotegerin (OPG) significantly upregulates during the development of obesity. • Hyperlipidaemia-induced Cbfa1 is responsible for OPG transactivation and overexpression. • Up-regulation of OPG is responsible for the adipocyte differentiation and lipid storage. • Targeting OPG by electroacupuncture improved obesity in mice. • Single blinded, randomized, sham-controlled clinical trials revealed that electroacupuncture improved obesity and suppressed OPG in patients. Adipogenesis, the process of white adipose tissue expansion, plays a critical role in the development of obesity. Osteoprotegerin (OPG), known for its role in bone metabolism regulation, emerges as a potential regulator in mediating adipogenesis during obesity onset. This study aims to elucidate the involvement of OPG in adipogenesis during the early phases of diet-induced obesity and explore its therapeutic potential in obesity management. Using a diet-induced obesity model, we investigated OPG expression patterns in adipocytes and explored the mechanisms underlying its involvement in adipogenesis. We also assessed the effects of targeted silencing of OPG and recombinant OPG administration on obesity progression and insulin resistance. Additionally, the impact of electroacupuncture treatment on OPG levels and obesity management was evaluated in both animal models and human participants. OPG expression was prominently activated in adipocytes of white adipose tissues during the early phase of diet-induced obesity. Hyperlipidemia induced Cbfa1-dependent OPG transcription, initiating and promoting adipogenesis, leading to cell-size expansion and lipid storage. Intracellular OPG physically bound to RAR and released the PPARɤ/RXR complex, activating adipogenesis-associated gene expression. Targeted silencing of OPG suppressed obesity development, while recombinant OPG administration promoted disease progression and insulin resistance in obese mice. Electroacupuncture treatment suppressed obesity development in an OPG-dependent manner and improved obesity parameters in obese human participants. OPG emerges as a key regulator in mediating adipogenesis during obesity development. Targeting OPG holds promise for the prevention and treatment of obesity, as evidenced by the efficacy of electroacupuncture treatment in modulating OPG levels and managing obesity-related outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Using genetic mouse models and a synthetic small molecule activator to demonstrate that Piezo1 activation promotes OA development and progression. • Utilizing biochemical and histological approaches to reveal that Piezo1 activation promotes Runx2 expression and chondrocyte catabolism through a PI3K-AKT dependent manner. • Demonstrated that artemisinin protects against OA lesions by inactivating Piezo1 in mice. Osteoarthritis (OA) is a devastating whole-joint disease affecting a large population worldwide with no cure; its mechanism remains poorly defined. Abnormal mechanical stress is the main pathological factor of OA. To investigate the effects of Piezo1 activation on OA development and progression and to explore Piezo1-targeting OA treatment. The expression levels of Piezo1 were determined in human OA cartilage and experimental OA mice. Mice with genetic Piezo1 deletion in chondrocytes or intra-articular injection of the Piezo1 activator Yoda1 were utilized to determine the effects on DMM-induced OA progression. Effects of artemisinin (ART), a potent antimalarial drug, on Piezo1 activation, chondrocyte metabolism and OA lesions were determined. Piezo1 expression was elevated in articular chondrocytes in human OA and DMM-induced mouse OA cartilage. Piezo1 deletion in chondrocytes largely attenuates DMM-induced OA-like phenotypes. In contrast, intra-articular injection of Yoda1 aggravates the knee joint OA lesions in mice. PIEZO1 activation increases, while PIEZO1 siRNA knockdown decreases, expression of RUNX2 and catabolic enzymes MMP13 and ADAMTS5 in primary human articular chondrocytes in a PI3K-AKT dependent manner. We have provided strong evidence supporting that ART is a novel and potent inhibitor of Piezo1 activation in primary OA-HACs and all cell lines examined, including human endothelial HUVEC cells, ATDC5 chondrocyte-like cells and MLO-Y4 osteocytes-like cells. Results from in vitro experiments confirmed that ART decreases the Yoda1-induced increases in the levels of OA-related genes and p-PI3K and p-AKT proteins in OA-HACs and alleviates DMM-induced OA lesions in mice. We establish a critical role of Piezo1 in promoting OA development and progression and define ART as a potential OA treatment. [ABSTRACT FROM AUTHOR]

Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US. The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999–2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively. Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them. • The prevalence of one or less ideal CVH metrics increased in CHD in the US, while the prevalence of three and more than four ideal CVH metrics decreased. • Ideal CVH metrics were inversely associated with all-cause and CVD mortality in CHD. • Effective measures are needed to improve the CVH for people with CHD. [ABSTRACT FROM AUTHOR]

Since the global burden of chronic kidney disease (CKD) is rising rapidly, the study aimed to assess the association of cardiovascular health (CVH) metrics with all-cause and cardiovascular disease (CVD) mortality among individuals with CKD. The cohort study included 5834 participants with CKD from the National Health and Nutrition Examination Survey 1999–2018. A composite CVH score was calculated based on smoking status, physical activity, body mass index, blood pressure, total cholesterol, diet quality, and glucose control. Primary outcomes were all-cause and CVD mortality as of December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between CVH metrics and deaths in CKD patients. During a median follow-up of 7.2 years, 2178 all-cause deaths and 779 CVD deaths were documented. Compared to participants with ideal CVH, individuals with intermediate CVH exhibited a 46.0% increase in all-cause mortality (hazard ratio, 1.46; 95% confidence interval: 1.17, 1.83), while those with poor CVH demonstrated a 101.0% increase (2.01; 1.54, 2.62). For CVD mortality, individuals with intermediate CVH experienced a 56.0% increase (1.56; 1.02, 2.39), and those with poor CVH demonstrated a 143.0% increase (2.43; 1.51, 3.91). Linear trends were noted for the associations of CVH with both all-cause mortality (P for trend <0.001) and CVD mortality (P for trend = 0.02). Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD, which highlights the importance of maintaining good CVH in CKD patients. • Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD. • Maintaining a better CVH status is beneficial for reducing the risk of premature death in patients with chronic kidney disease. • The benefits of ideal cardiovascular health were particularly evident in younger participants and those at an early stage of CKD. [ABSTRACT FROM AUTHOR]

Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-β) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC. [ABSTRACT FROM AUTHOR]

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, which is crucial for innate immunity. This pathway responds to mitochondrial DNA and is associated with cellular stress response. Our review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS–STING pathway. We critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions, primarily through the accumulation of damaged mitochondria, which activates the cGAS–STING pathway. This activation prompts the production of pro-inflammatory cytokines, exacerbating neuroinflammation. This review emphasizes the interaction between mitophagy and the cGAS–STING pathways. Effective mitophagy may suppress the cGAS–STING pathway, offering protection against neuroinflammation. Conversely, impaired mitophagy may activate the cGAS–STING pathway, leading to chronic neuroinflammation. Additionally, we explored how this interaction influences neurodegenerative disorders, suggesting a common mechanism underlying these diseases. In conclusion, there is a need for additional targeted research to unravel the complexities of mitophagy–cGAS–STING interactions and their role in neurodegeneration. This review highlights potential therapies targeting these pathways, potentially leading to new treatments for neuroinflammatory and neurodegenerative conditions. This synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research. Crosstalk between autophagy and cGAS–STING in microglia activation is vital for neurodegeneration, orchestrating shifts from M0 to M1/M2 phenotypes, crucial for maintaining neuronal survival and blood–brain barrier integrity. [Display omitted] [ABSTRACT FROM AUTHOR]

The periodical impulses caused by localized defects of components are the vital characteristic information for fault detection and diagnosis of rotating machines. In recent years, multitudinous spectrum analysis-based signal processing methods have been developed and authenticated as the powerful tools for excavating fault-related repetitive transients from the measured complex signals. Nonetheless, in practice, their applications can be severely confined by the constraints of limited system signal availability and incomplete information extraction under intricate noise interferences. To tackle the aforementioned issues, this paper proposes a periodic-modulation-oriented noise resistant correlation (PMONRC) method for target period detection and fault diagnosis of rotating machinery. Firstly, the envelope of raw signal is obtained via a novel sequential procedure of signal element-wise squaring, spectral Gini index-guided adaptive low-pass filtering, and signal element-wise square root computation, to highlight the modulated wave component that is more likely to be related to the potential fault-induced periods. Subsequently, a series of sub-signals, which can encode the fault-related repetitive information and enhance noise resistance, are constructed utilizing the envelope signal. Based upon the envelope signal and the obtained sub-signals, a weighted envelope noise resistant correlation function can be derived with the assistance of the L-moment ratio-based indicator and Sigmoid transformation. Finally, the specific fault type of the rotating machinery can be identified and affirmed accordingly. The proposed PMONRC method, which is nonparametric and completely adaptive to the signal being processed itself, overcomes the deficiencies of spectral analysis-based approaches, and is applicable for the engineering circumstances of system signal limitation and low signal-to-noise ratio (SNR), possessing immense practical merit. Both simulation analyses and experimental validations profoundly demonstrate that the proposed method is superior to other existing state-of-the-art time-domain correlation methods. Moreover, as an attempt as well as exemplar to apply this method, the PMONRC-based incipient fault diagnostic results of rolling bearing data from the well-known experimental platform PRONOSTIA are presented and discussed as well, to further elucidate the effectiveness and practical engineering significance of the proposed method. • A weighted envelope noise-resistant correlation approach coined PMONRC is developed. • An adaptive enveloping-demodulation method is proposed for AM-FM signature enhancing. • Fault information of sub-signals are appraised for more rational weights allocation. • The PMONRC is effective for fault-induced hidden periods detection and extraction. • The PMONRC is applicative for the scenarios of limited system signal availability. [ABSTRACT FROM AUTHOR]

Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease. We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes. Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14–4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14–4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents. In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan. [Display omitted] • Cesarean section delivery disrupts microbiota and immune regulation but its association with Kawasaki disease is uncertain. • This study examined the association between Cesarean section and Kawasaki disease in 15,796 mother-infant pairs in Taiwan. • Cesarean section increased Kawasaki disease risk, while it was not associated with the risk of negative control outcomes. [ABSTRACT FROM AUTHOR]

• The hierarchical structure was fabricated by a novel thermomechanical treatment. • The combination of grain-twin-precipitation hierarchical structure was realized on Mg-15Gd-1Zn-0.4Zr alloy. • The hierarchical structure had the effect of synergistically improving the strength and ductility of Mg-15Gd-1Zn-0.4Zr alloy. Currently, the hierarchical structure is one of the most effective means to enhance the strength and plasticity of metal materials, since the strain localization can be effectively delayed by the coordination of the unique microstructure. In this study, a hierarchical structure of Mg-15Gd-1Zn-0.4Zr (GZ151K) alloys containing grain, twin, and precipitation structural units was prepared by ultrasonic surface rolling process (USRP) and recrystallization annealing (RU). The results showed that the stress gradient generated by USRP formed a twin gradient structure, which will activate the twin-assisted precipitation (TAP) effect and twin-induced recrystallization (TIR) effect during RU. Then, the twin gradient structure transformed into a twin-precipitation gradient structure, and finally into a hierarchical structure with grain-twin-precipitation as the increasement of recrystallization degree. Besides, the dual gradient structure with twin and precipitation structural units had the highest strength and microhardness owing to the precipitation strengthening. However, the hierarchical structure with grain, twin, and precipitation structural units exhibited the most excellent combination of strength and plasticity under grain refinement and precipitation strengthening. [ABSTRACT FROM AUTHOR]

Clinical Practice Guideline on Acupuncture and Moxibustion: Migraine (WFAS 007.9-2023) is a clinical practice guideline officially released by the World Federation of Acupuncture-Moxibustion Societies (WFAS) on October 9, 2023, and is the first international guideline on the treatment of migraine with acupuncture. This international standard was developed under the guidance of rigorous evidence-based methodology, and it contains guideline purpose, scope, applicable population, applicable settings, overview of acupuncture for migraine, guideline development process and recommendations. For promoting the understanding and application of this guideline, this article summarizes a total of 18 recommendations in order to assist clinical decisions for migraine with acupuncture. [ABSTRACT FROM AUTHOR]

To evaluate whether ultrasound-based radiomics features can effectively predict HER2-low expression in patients with breast cancer (BC). Between January 2021 and June 2023, patients who received US scans with pathologically confirmed BC in this multicenter study were included. In total, 383 patients from institution 1 were comprised of training set, 233 patients from institution 2 were comprised of validation set and 149 patients from institution 3 were comprised of external validation set. Radiomics features were derived from conventional ultrasound (US) images. The minimum redundancy and maximum relevancy and the least absolute shrinkage and selector operation algorithm were used to generate an US-based radiomics score (RS). Multivariable logistic regression analysis was used to select variables associated with HER2 expressions. The diagnostic performance of the RS was evaluated through the area under the receiver operating characteristic curve (AUC). In the training set, the RS yield an AUC of 0.81 (95%CI: 0.76–0.84) for differentiation HER2-zero from HER2-low and -positive cases, and performed well in validation set (AUC 0.84, 95%CI: 0.78–0.88) and external validation set (AUC 0.82, 95%CI: 0.73–0.90). In the subgroups analysis, the RS showed good performance in distinguishing HER2-zero from HER2 1 + , HER2 2 + and HER2-low tumors (AUC range, 0.79–0.87). The RS based on conventional US is proven effective for predicting HER2-low expression in BC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. • Cis-trans isomerization of TRIM32 recruit PIN1, which resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. • Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in triple-negative breast cancer (TNBC). • Regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC, which is important for TNBC therapy. Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis–trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC. [ABSTRACT FROM AUTHOR]

Optical atrophy 1 (OPA1), a protein accountable for mitochondrial fusion, facilitates the restoration of mitochondrial structure and function following cerebral ischemia/reperfusion (I/R) injury. The OPA1-conferred mitochondrial protection involves its expression and activity, which can be improved by SIRT3 in non-cerebral ischemia. Nevertheless, it remains obscure whether SIRT3 enhances the expression and activity of OPA1 after cerebral I/R injury. Mature male Sprague Dawley rats were intracranially injected with adeno-associated viral-Sirtuin-3(AAV-SIRT3) and AAV-sh_OPA1, followed by a 90-min temporary blockage of the middle cerebral artery and subsequent restoration of blood flow. Cultured cortical neurons of rats were transfected with LV-SIRT3 or LV-sh_OPA1 before a 2-h oxygen-glucose deprivation and reoxygenation. The rats and neurons were subsequently treated with a selective OPA1 activity inhibitor (MYLS22). The interaction between SIRT3 and OPA1 was assessed by molecular dynamics simulation technology and co-immunoprecipitation. The expression, function, and specific protective mechanism of SIRT3 were examined by various analyses. SIRT3 interacted with OPA1 in the rat cerebral cortex before and after cerebral I/R. After cerebral I/R damage, SIRT3 upregulation increased the OPA1 expression, which enhanced deacetylation and OPA1 activity, thus alleviating cerebral infarct volume, neuronal apoptosis, oxidative pressure, and impairment in mitochondrial energy production; SIRT3 upregulation also improved neuromotor performance, repaired mitochondrial ultrastructure and membrane composition, and promoted the mitochondrial biogenesis. These neuroprotective effects were partly reversed by OPA1 expression interference and OPA1 activity inhibitor MYLS22. In rats, SIRT3 enhances the expression and activity of OPA1, facilitating the repair of mitochondrial structure and functional recovery following cerebral I/R injury. These findings highlight that regulating SIRT3 may be a promising therapeutic strategy for ischemic stroke. [ABSTRACT FROM AUTHOR]

Metastasis and recurrence are the main causes of death in post-operative bladder cancer (BC), emphasizing the importance of exploring early-stage diagnostic markers. Serum biomarkers constitute a promising diagnostic approach for asymptomatic stage cancer as they are non-invasive, have high accuracy and low cost. To correlate concentrations of plasma amino acids with BC progression to assess their utility as an early-stage diagnostic. Newly diagnosed BC patients (n = 95) and normal controls (n = 96) were recruited during the period from 1 December 2018 to 30 December 2020. General and food frequency questionnaires established their basic information and dietary intake data. Venous blood samples were collected from fasting subjects and used to detect levels of plasma amino acids by liquid chromatography-mass spectrometry. Verification was performed on the GSE13507 transcriptome gene expression matrix of BC from Gene Expression Omnibus (GEO) database. Eleven amino acids have been identified as altered in the plasma of newly diagnosed BC patients compared to controls (P < 0.05). Adjusted by gender, education, smoking and other factors, plasma ornithine level (OR = 0.256, 95% CI: 0.104–0.630) is a protective factor for BC, plasma levels of methionine (OR = 3.460, 95% CI: 1.384–8.651), arginine (OR = 3.851, 95% CI: 1.542–9.616), and glutamate (OR = 3.813, 95% CI: 1.543–9.419) are all risk factors for BC. ROC analysis demonstrated that the combination of plasma ornithine, methionine, arginine and glutamate could accurately diagnose BC (AUC = 0.84, 95% CI: 0.747–0.833). In addition, the mRNA level of arginase 1 was decreased (P < 0.05), while the inducible nitric oxide synthase was increased significantly, which may be linked with the disturbance of arginine metabolism in BC patients. Further analysis of GEO database confirmed the role of arginine metabolism. A biomarker panel containing four amino acids may provide a feasible strategy for the early diagnosis of BC. However, further validation is required through prospective studies. [ABSTRACT FROM AUTHOR]

The indications for splenic hilar lymph node dissection in advanced proximal gastric cancer without invasion of the greater curvature are controversial. We aimed to develop a preoperative nomogram for individualized prediction of splenic hilar lymph node metastasis in non–greater curvature advanced proximal gastric cancer. From January 2014 to December 2021, 558 patients with non–greater curvature advanced proximal gastric cancer who underwent D2 lymphadenectomy (including splenic hilar lymph node) were retrospectively analyzed and divided into a training cohort (n = 361) and validation cohort (n = 197), depending on the admission time. A preoperative predictive nomogram of splenic hilar lymph node metastasis was established based on independent predictors identified by multivariate analysis, and the performance and prognostic value were confirmed. In the training and validation cohorts, 48 (13.3%) and 24 patients (12.2%) had pathologically confirmed splenic hilar lymph node metastasis, respectively. Tumor located in the posterior wall, tumor size ≥5 cm, Borrmann type IV, and splenic hilar lymph node lymphadenectasis on computed tomography were preoperative factors independently associated with splenic hilar lymph node metastasis. The nomogram developed based on these four parameters had a high concordance index of 0.850 (95% confidence interval, 0.793–0.907) and 0.825 (95% confidence interval, 0.743–0.908) in the training and validation cohorts, respectively, with well-fitting calibration plots and better net benefits in the decision curve analysis. In addition, disease-free survival and overall survival were significantly shorter in the high-risk group, with hazard ratios of 3.660 (95% confidence interval, 2.228–6.011; log-rank P <.0001) and 3.769 (95% confidence interval, 2.279–6.231; log-rank P <.0001), respectively. The nomogram has good performance in predicting the risk of splenic hilar lymph node metastasis in non–greater curvature advanced proximal gastric cancer preoperatively, which can help surgeons make rational clinical decisions. [ABSTRACT FROM AUTHOR]

• Metabolic PET radiomics features were strong predictors of seizure recurrence. • PET-based radiomics score, SGS, and Durmon were significant predictors of seizure-free outcomes. • A nomogram incorporating PET-based radiomics and clinical risk factors demonstrated good performance in predicting surgery outcomes. To establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). 234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). Eight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59–0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. A PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery. [ABSTRACT FROM AUTHOR]

Ground volume loss is an important parameter for settlement control and prediction in shield tunneling. This parameter is usually determined empirically, while its variation along the tunnel is not predictable. In this study, an analytical formula for ground volume loss is obtained based on physical derivation. The ground volume loss is divided into two components. Key operational parameters, i.e. face pressure, grouting pressure and grouting volume, are used to calculate the two components. The proposed formula is then validated against the field data collected from Changzhou Metro in thick silty clay layer. The validation shows that the new formula gives reasonable prediction of ground volume loss. Furthermore, the three model coefficients derived from physical calculation are very close to the regression coefficients based on statistical method. For EPB tunnels excavated in silty clay layer, the ground volume loss along a specific tunnel can be predicted by the new formula. The analysis also indicates that the surface settlement of EPB tunnel should be controlled by a balanced combination of varied operational parameters. [ABSTRACT FROM AUTHOR]

To investigate the feasibility of virtual monochromatic imaging (VMI) of dual-layer spectral detector computed tomography (SDCT) to reduce iodinated contrast material (CM) and radiation dose in craniocervical computed tomography angiography (CTA). A total of 280 consecutively selected patients performed craniocervical CTA with SDCT were prospectively selected and randomly divided into four groups (A, DoseRight index (DRI) 31, iopromide 370mgI/mL, volume 0.8 mL/kg; B, DRI 26, iopromide 370mgI/mL, volume 0.4 mL/kg; C, DRI 26, ioversol 320mgI/mL, volume 0.4 mL/kg; D, DRI 26, iohexol 300mgI/mL, volume 0.4 mL/kg). 50–70 kiloelectron volts (keV) VMIs in group B were reconstructed and compared to group A to select the optimal keV. Then, the optimal keV in groups B, C and D was reconstructed and compared. Objective image quality, including vascular attenuation, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), was evaluated. Subjective image quality was assessed using a 5-point Likert scale. In addition, the effective dose (ED), iodine load and iodine delivery rate (IDR) were compared between groups A and D. 55 keV VMI was the optimal VMI in group B. The objective and subjective image quality of 55 keV VMI in group B were equal to or better than those of the CI in group A. The SNR, CNR and subjective image quality in group D were similar to those in group B (P > 0.05). The ED, iodine load and IDR of group D were reduced by 44%, 59% and 19%, respectively, when compared to those of group A. Low dose iodinated CM and radiation for 55 keV VMI in craniocervical CTA using SDCT could still provide equivalent or better image quality than the conventional scanning protocol. [ABSTRACT FROM AUTHOR]

Air pollutants may aggravate atopic dermatitis (AD). However, the association between Air Quality Index (AQI) and incidence of AD remains unknown. To investigate association between AQI and incidence of AD, using the nationwide cohort in the Taiwan National Health Insurance Research Database (NHIRD). We included 21,278,938 participants from the NHIRD not diagnosed with AD before 2008. Long-term average AQI value, obtained from the Taiwan Air Quality Monitoring System Network, before AD diagnosis was calculated and linked for each participant. 199,205 incident cases of AD were identified from 2008 to 2018. Participants were classified into 4 quantiles (Q) by AQI value. With the lowest quantile, Q1, as reference, the AD risk increased significantly in the Q2 group (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.04-1.65), Q3 group (aHR: 4.71, 95% CI: 3.78-6.04), and was highest in the Q4 group (aHR: 13.20, 95% CI: 10.86-16.60). As AQI treated as a continuous variable, an increase of 1 unit of AQI value added 7% of AD risk (aHR, 1.07, 95% CI: 1.07-1.08). The NHIRD lacks detailed information on individual subjects. The results demonstrated a significant positive association between AQI and incidence of AD with a clear dose-response relationship. [ABSTRACT FROM AUTHOR]

This paper aims to analyze the impact of justice reform on entrepreneurship in China, utilizing a staggered difference-in-differences model. The research reveals that the implementation of justice reform has a sizable positive effect on entrepreneurship, both statistically and economically significant. The influence is more pronounced in areas with higher trust, lower legal environment, and in rural areas. Government quality and innovation are two possible mechanisms. This paper emphasizes the significant role of the justice environment in fostering business innovation and entrepreneurship, and highlights the economic significance of government quality, providing a new perspective for encouraging entrepreneurship. [ABSTRACT FROM AUTHOR]