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Following the relaxation of control measures for COVID-19 in China in December 2022, there was a resurgence of influenza A among children in Linyi. This research aims to analyze the epidemiology and genetic characteristics of influenza A viruses circulating among children in Linyi from April 2022 to March 2024. Throat swab specimens were collected from children with influenza-like illness (ILI), and the types of influenza were identified. The hemagglutinin (HA) genes of influenza A viruses were amplified using reverse transcription-polymerase chain reaction (RT-PCR) and then sequenced. Subsequently, the gene characteristics and phylogenetics of these sequences were analyzed. A total of 6258 cases of influenza A were tested from 54,926 children with ILI over two years, showing three epidemic waves: one in summer 2022 and two in spring and winter 2023. The epidemic waves in summer 2022 and winter 2023 were caused by influenza A(H3N2) viruses. In spring 2023, influenza A(H1N1)pdm09 viruses accounted for 77.1% and A(H3N2) viruses accounted for 22.9%, respectively. The influenza A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.2a, while the influenza A(H3N2) viruses evolved from clade 3C.2a1b.2a.1a to 3C.2a1b.2a.2a.3a.1. Compared with the vaccine strain of the Northern Hemisphere of the current year, multiple amino acid substitutions and glycosylation sites changes were observed in the HA protein that most likely resulted in antigenic drift. The influenza A viruses have been circulating and evolving persistently in Linyi from 2022 to 2024. Continuous surveillance is essential for comprehending the dynamics of influenza in the post-COVID-19 era. [ABSTRACT FROM AUTHOR]

Background: To investigate the accuracy of quantitative blood oxygen level-dependent (qBOLD) magnetic resonance imaging (MRI) in identifying hypoxia within glioblastoma and explore dynamic changes in oxygenation status of glioblastoma with and without metformin administration. Methods: Three healthy and seven C6-bearing rats underwent 7-T qBOLD MRI. Oxygen extraction fraction (OEF) and cerebral metabolism rate of O2 (CMRO2) were calculated from qBOLD data. Tumor tissues were stained using hypoxia-inducible factor-1 α (HIF-1 α ) and pimonidazole. The correlation between the hypoxia markers and corresponding qBOLD-based parameters was analyzed. Six C6-bearing rats were divided into metformin-treated and control groups for a longitudinal study of qBOLD imaging changes, with scans conducted on the 12th, 15th, and 18th day post-tumor implantation. Results: In healthy rats, gray matter showed higher values than white matter in T2, T2*, cerebral blood volume (CBV), and cerebral blood flow (CBF), whereas OEF was lower. Glioblastoma tissues exhibited elevated T2, T2*, CBV, and CBF but decreased OEF and CMRO2 relative to normal-appearing white matter. No significant correlation was found between staining scores from HIF-1 α and pimonidazole. T2* and T2 values were negatively correlated with pimonidazole scores in tumor regions. As the tumor progressed, OEF values increased with intra-tissue variations, whereas CMRO2 decreased. Metformin delayed the reduction of T2 and T2* values, with significant differences in OEF and CMRO2 values compared to controls on day 18. Conclusion: T2* and T2 values were significantly associated with the hypoxia status in glioma. Metformin could potentially mitigate the progression of hypoxia in glioblastoma, which can be tracked by qBOLD parameters. Relevance statement: This study demonstrates the potential of qBOLD parameters in assessing glioma dynamic oxygen metabolism and the efficacy of metformin as an anti-hypoxic agent, providing insights into improving glioblastoma treatment strategies. Key Points: The study investigated qBOLD imaging's accuracy in identifying hypoxia status within glioblastoma. qBOLD effectively assesses hypoxia and its dynamic evolution in glioblastoma. qBOLD parameters assist in identifying a suitable patient demographic for metformin treatment. [ABSTRACT FROM AUTHOR]

Climate change, earthquakes, and human activities are accelerating the degradation of permafrost, leading to loess failures and slope instability. Some engineering corridors (ECs)/infrastructures located on the northeastern margin of the Qinghai-Tibet Plateau (NE-QTP) of China are heavily influenced by landslide phenomena due to being built on permafrost, loess, and seasonally frozen ground. However, few systematic investigations have been carried out in this area. To compile a comprehensive landslide inventory, we visually interpreted 11,914 landslides in GaoFen-6 images taken from 2021 to 2022. We observe that approximately 44.85% of the infrastructures are affected by landslides. Then, based on the ground types and triggering factors, landslides are classified into three types: freeze‒thaw landslides (FTLs), loess landslides (LLs), and general landslides (GLs). More specifically, FTLs are mainly distributed in the boundary regions between permafrost and seasonally frozen ground. The LLs exhibit high-density clustered distribution characteristics. GLs have significant transitional characteristics and commonalities between FTLs and LLs. Furthermore, we apply the geographical detector to determine the controlling factors of the landslides that occurred. We find that the temperature change is the primary controller on the FTLs. The water exhibits a certain correlation with LLs. And the earthquake is the most important factor on the GLs. Our study provides a significant dataset for quantifying the analysis of landslides in NE-QTP. [ABSTRACT FROM AUTHOR]

Variable-frequency air injection and extraction is critical for salt cavern compressed air energy storage (CAES) power plants to smoothly integrate electricity into the power grid, and the magnitude of its effect on the mechanical properties and damage progression of the salt cavern surrounding rock determines the operation scheme of CAES power plants. To examine the impact of variable frequency, a series of monotonic loading tests with different rates and variable-frequency fatigue (VFF) tests with different upper limit stresses were carried out. Dilatancy stresses have a positive power function relationship with loading rate and frequency, but the fatigue loading process weakens this nonlinear tendency. The rate of change (CR) or the exponent of the fitted function can express it. From the initial stage to the steady stage, the CR of dilatancy stress increases about three times, and the CR of residual volumetric strain decreases about five to eight times. Increased upper-limit stress weakens this trend of change. Both high speed and high-frequency loading shift the damage acceleration point forward (e.g., b value accelerates earlier). The damage rate correlation is significant in the later stages of the VFF tests, the rate correlation of damage is significant. Both the upper stress and the extension of the main fracture zone enhance the rate dependence of fracture types. Moreover, the effect of rate on crystal penetrating cracks is more pronounced in the high-stress interval. The number of fractures significantly affects the dilatancy, rather than the type of fracture. This study serves as a guide for the design of variable frequency programs in different CAES salt cavern operation stages, as well as subsequent research. Highlights: The variable-frequency test, avoiding rock dispersion, is more reliable and more in line with engineering than fixed-frequency and fixed-speed tests. Crack amount, not type, decides dilatancy. Stress affects the high frequency-high amplitude signal. Fast speed and high-frequency advance damage. Dilatancy rate correlation is explained by the dislocation slip, crack extension type and the stress concentration. We propose some CAES power plant frequency conversion ideas based on the correlation between crack and dilatancy rates. [ABSTRACT FROM AUTHOR]

Cerebral ischemia-reperfusion injury produces excessive reactive oxygen and nitrogen species, including superoxide, nitric oxide, and peroxynitrite (ONOO-). We recently developed a new ONOO--triggered metal-free carbon monoxide donor (PCOD585), exhibiting a notable neuroprotective outcome on the rat middle cerebral artery occlusion model and rendering an exciting intervention opportunity toward ischemia-induced brain injuries. However, its therapeutic mechanism still needs to be addressed. In the pharmacological study, we found PCOD585 inhibited neuronal Bcl2/Bax/caspase-3 apoptosis pathway in the peri-infarcted area of stroke by scavenging ONOO-. ONOO- scavenging further led to decreased Acyl-CoA synthetase long-chain family member 4 and increased glutathione peroxidase 4, to minimize lipoperoxidation. Additionally, the carbon monoxide release upon the ONOO- reaction with PCOD585 further inhibited the neuronal Iron-dependent ferroptosis associated with ischemia-reperfusion. Such a synergistic neuroprotective mechanism of PCOD585 yields as potent a neuroprotective effect as Edaravone. Additionally, PCOD585 penetrates the blood-brain barrier and reduces the degradation of zonula occludens-1 by inhibiting matrix metalloproteinase-9, thereby protecting the integrity of the blood-brain barrier. Our study provides a new perspective for developing multi-functional compounds to treat ischemic stroke. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a lethal cardiovascular disease worldwide. Emerging evidence has revealed the critical role of gut dysbiosis and impaired gut-brain axis in the pathological progression of MI. Tanshinone IIA (Tan IIA), a traditional Chinese medicine, has been demonstrated to exert therapeutic effects for MI. However, the effects of Tan IIA on gut-brain communication and its potential mechanisms post-MI are still unclear. In this study, we initially found that Tan IIA significantly reduced myocardial inflammation, apoptosis and fibrosis, therefore alleviating hypertrophy and improving cardiac function following MI, suggesting the cardioprotective effect of Tan IIA against MI. Additionally, we observed that Tan IIA improved the gut microbiota as evidenced by changing the α-diversity and β-diversity, and reduced histopathological impairments by decreasing inflammation and permeability in the intestinal tissues, indicating the substantial improvement of Tan IIA in gut function post-MI. Lastly, Tan IIA notably reduced lipopolysaccharides (LPS) level in serum, inflammation responses in paraventricular nucleus (PVN) and sympathetic hyperexcitability following MI, suggesting that restoration of Tan IIA on MI-induced brain alterations. Collectively, these results indicated that the cardioprotective effects of Tan IIA against MI might be associated with improvement in gut-brain axis, and LPS might be the critical factor linking gut and brain. Mechanically, Tan IIA-induced decreased intestinal damage reduced LPS release into serum, and reduced serum LPS contributes to decreased neuroinflammation with PVN and sympathetic inactivation, therefore protecting the myocardium against MI-induced injury. [ABSTRACT FROM AUTHOR]

The urgent need for integrated molding and sintering across various industries has inspired the development of additive manufacturing (AM) ceramics. Among the different AM technologies, direct laser additive manufacturing (DLAM) stands out as a group of highly promising technology for flexibly manufacturing ceramics without molds and adhesives in a single step. Over the last decade, significant and encouraging progress has been accomplished in DLAM of high-performance ceramics, including Al2O3, ZrO2, Al2O3/ZrO2, SiC, and others. However, high-performance ceramics fabricated by DLAM face challenges such as formation of pores and cracks and resultant low mechanical properties, hindering their practical application in high-end equipment. Further improvements are necessary before they can be widely adopted. Methods such as field-assisted techniques and post-processing can be employed to address these challenges, but a more systematic review is needed. This work aims to critically review the advancements in direct selective laser sintering/melting (SLS/SLM) and laser directed energy deposition (LDED) for various ceramic material systems. Additionally, it provides an overview of the current challenges, future research opportunities, and potential applications associated with DLAM of high-performance ceramics. [ABSTRACT FROM AUTHOR]

Although rotating blades are designed to operate away from structural frequencies, internal resonance can still occur at certain rotation speeds, significantly affecting the blades' stiffness. Therefore, a detailed investigation of the resonance mechanisms of rotating blades, especially those introduced by nonlinearities, is crucial for structural design and optimization. To address this, a dynamic model of a functionally graded graphene/titanium alloy composite trapezoid plate is established to investigate the nonlinear dynamics of a rotating blade with varying cross-sections. The ordinary differential equations of the plate are formulated based on the energy method and Lagrange equations. The occurrence of 1:3 internal resonance in the trapezoid plate is identified through the analysis of linear and nonlinear free vibrations. Subsequently, the steady-state responses of the rotating plate in the case of 1:3 internal resonance are numerically calculated and verified using the approximation solution of the multiple scales method. Parametric studies are conducted to investigate the effects of rotation speed, taper ratio, excitation amplitude, and excitation frequency on the amplitude–frequency and amplitude–force curves. [ABSTRACT FROM AUTHOR]

Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5–11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a prevalent autosomal dominant disorder caused by mutations in the NF1 gene, leading to multisystem disorders. Given the critical role of cysteine residues in protein stability and function, we aimed to identify key NF1 mutations affecting cysteine residues that significantly contribute to neurofibromatosis pathology. To identify the most critical mutations in the NF1 gene that contribute to the pathology of neurofibromatosis, we employed a sophisticated computational pipeline specifically designed to detect significant mutations affecting the NF1 gene. Our approach involved an exhaustive search of databases such as the Human Gene Mutation Database (HGMD), UniProt, and ClinVar for information on missense mutations associated with NF1. Our search yielded a total of 204 unique cysteine missense mutations. We then employed in silico prediction tools, including PredictSNP, iStable, and Align GVGD, to assess the impact of these mutations. Among the mutations, C379R, R1000C, and C1016Y stood out due to their deleterious effects on the biophysical properties of the neurofibromin protein, significantly destabilizing its structure. These mutations were subjected to further phenotyping analysis using SNPeffect 4.0, which predicted disturbances in the protein’s chaperone binding sites and overall structural stability. Furthermore, to directly visualize the impact of these mutations on protein structure, we utilized AlphaFold3 to simulate both the wild-type and mutant NF1 structures, revealing the significant effects of the R1000C mutation on the protein’s conformation. In conclusion, the identification of these mutations can play a pivotal role in advancing the field of precision medicine and aid in the development of effective drugs for associated diseases. [ABSTRACT FROM AUTHOR]

Background: We conducted a study on radiation exposure in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) treated with [177Lu]Lu-DOTA-TATE in China for the first time, aiming to provide guidance and reference for radiation protection in this regard. A total of 30 GEP-NENs patients who received [177Lu]Lu-DOTA-TATE therapy were recruited in the study. We measured the external dose rate (EDR) values of each patient during the injection and 0–6 h post-administration period, as well as the radiation dose (RD) values to healthcare nurses and the surrounding environment. We performed a double exponential curve fitting and estimated the RD to the public from patients discharged at different times after [177Lu]Lu-DOTA-TATE therapy. Results: Among the 30 patients, 27 patients completed 4 cycles of [177Lu]Lu-DOTA-TATE treatments, the estimated RD to the public indicated that for adult family members, children above 10 years old, children aged 3–10 and coworkers of the patients, patients could begin daily contact at least 24 h, 48 h, 144 h and 192 h after injection to ensure that the total RD values after four treatments not exceed the limit. During the hospitalization of patients receiving [177Lu]Lu-DOTA-TATE, the cumulative dose received by the administering nurses and to the ward environment were both well below the national RD limits. Conclusions: This study conducted a fitting analysis of the decay pattern of EDR values in GEP-NENs patients undergoing [177Lu]Lu-DOTA-TATE therapy, in order to establish guidelines for patient discharge timing and provide recommendations for radiation protection for the general public after patient discharge. Trial registration A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs, NCT05459844. https://clinicaltrials.gov/study/NCT05459844?cond=NCT05459844&rank=1. Registered 5 July 2022. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant tumors globally, characterized by high incidence and mortality rates. Despite ongoing research, the underlying molecular mechanisms of HCC development are not yet fully understood. Utilizing bioinformatic analysis, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot assays, we identified that the expression of specificity protein 1 (Sp1) was significantly elevated in HCC cells compared to normal cells. Knockdown of the Sp1 gene led to a marked reduction in the viability and clonogenic potential of HCC cells. Further investigation revealed that the succinylation level of Sp1 was also increased in HCC cells. The upregulation of Sp1 expression was attributed to its succinylation, mediated by KAT2A, with lysine (K)562 identified as the succinylation site. Additionally, KAT2A and Sp1 were found to influence the upregulation of mTOR phosphorylation. Collectively, these findings suggest that KAT2A-promoted succinylation of Sp1 enhances the proliferative capacity of HCC cells by activating the mTOR pathway, providing a theoretical foundation for potential therapeutic strategies against HCC. [ABSTRACT FROM AUTHOR]

This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios. [ABSTRACT FROM AUTHOR]

Background: Recurrent gliomas rapidly progress and have high mortality and poor prognosis in the central nervous system. Therefore, further investigation of prognostic and therapeutic markers is needed. Methods: The mRNA expression, clinical data, and coagulation-related genes (CRGs) associated with recurrent glioma were obtained and calculated from the Chinese Glioma Genome Atlas and Kyoto Encyclopedia of Genes and Genomes databases. The significant CRGs were calculated by Weighted gene co-expression network analysis and PPI network. A prediction model was constructed using the least absolute shrinkage and selection operator regression analysis. Recurrent gliomas were stratified into high and low-risk groups based on the median risk score (RS). The Kaplan–Meier curve was used to analyze the difference in overall survival (OS) between these groups, while the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of the gene model at 1-, 3-, and 5-years. Clinical factors, including age, gender, MGMT methylation status, radiotherapy, chemotherapy, and RS, were included in the univariate and multivariate regression analysis. A prognostic nomogram and calibration curve were established based on these factors. Results: Overall, seven CRGs associated with the prognosis were identified, including BTK, ITGB1, GNAI3, CFH, LYN, CFI, and F3. OS and survival rates were lower in the high-risk group compared with the low-risk group. The ROC curve demonstrated the area under the curve values >0.65 at 1-, 3-, and 5-years, confirming the reliability of the prognostic model. The univariate regression analysis indicated that tumor grade (grades 2, 3, and 4), histopathology (GBM or not), chemotherapy, IDH mutation, and 1p19q co-deletion status were independent prognostic indicators. Univariate and multivariate regression analyses indicated that RS was an independent prognostic factor for patients with recurrent glioma. Immune analysis revealed low infiltration of resting dendritic cells and high expression of programmed death receptor 1 in the high-risk group. Conclusion: This study comprehensively investigated the correlation between CRGs and recurrent glioma prognosis, offering crucial insights for further research into glioma recurrence mechanisms and treatment strategies. [ABSTRACT FROM AUTHOR]

Crystalline silica (CS) particle exposure leads to silicosis which is characterized as progressive fibrosis. Fibroblasts are vital effector cells in fibrogenesis. Emerging studies have identified immune sentinel roles for fibroblasts in chronic disease, while their immune-modulatory roles in silicosis remain unclear. Herein, we show that group 2 innate lymphoid cell (ILC2) conversion to ILC1s is closely involved in silicosis progression, which is mediated by activated fibroblasts via interleukin (IL)−18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulates IL-18 production via caspase 1 activity. The mouse-specific Notch3 knockout in fibroblasts retards pulmonary fibrosis progression that is linked to attenuated ILC conversion. Our results indicate that activated fibroblasts in silicotic lungs are regulators of ILC2–ILC1 conversion, associated with silicosis progression via the Notch3–IL-18 signaling axis. This finding broadens our understanding of immune-modulatory mechanisms in silicosis, and indicates potential therapeutic targets for lung fibrotic diseases. Crystalline silica particle exposure in the airways can lead to lung silicosis and progressive fibrosis. Here the authors use mouse silicosis models to show mechanics activated fibroblasts promote conversion of ILC2 to ILC1-like cells pulmonary fibrosis and that this is associated with a Notch3-IL-18 signalling pathway. [ABSTRACT FROM AUTHOR]

Objectives: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC). Methods: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors. Results: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = −0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = −0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02). Conclusions: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment. Clinical relevance statement: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy. Key Points: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment. [ABSTRACT FROM AUTHOR]

The curing rate of epoxy resins is a critical parameter that significantly influences the curing properties of polymer matrix composites (PMCs). It plays a vital role in meeting high-performance requirements, particularly in achieving rapid development of high modulus. The paper reviews the current state of research on the curing of epoxy resins in PMCs, including theoretical studies on the curing kinetics of the curing rate. The effects of curing methods, curing agents, accelerators, functional fillers and composite curing processes on the curing rate and mechanical properties are also reviewed. In addition, the relationship between curing rate and mechanical properties of epoxy composites under different influencing factors is reviewed. The review aims to provide research ideas for obtaining advanced structural composites with fast curing and excellent mechanical properties. [ABSTRACT FROM AUTHOR]

As a cathode material for potassium-ion batteries (PIBs), manganese-based layered oxides have attracted widespread attention due to their low cost, ease of synthesis, and high performance. However, the Jahn-Teller effect caused by Mn3+ and the irreversible phase transformation of the structure leads to poor cycle stability, limiting the development of layered oxides in PIBs. Herein, we demonstrate the use of phase-transition-free CaTiO3 as rivets in K0.5Mn0.9Ti0.1O2 by a simple solid-state method. As verified by the in situ X-ray diffraction, the CaTiO3 rivets effectively prevent the slippage of the transition metal layer during charge and discharge, inhibiting structural degradation. As a result, the obtained K0.5Mn0.9Ti0.1O2-0.02CaTiO3 shows excellent cycling stability and rate performance, with high capacities of 119.3 and 70.1 mAh·g-1 at 20 and 1000 mA·g-1, respectively. At 200 mA·g-1, the capacity retention remains 94.7% after more than 300 cycles. This work represents a new avenue for designing and optimizing layered cathode materials for PIBs and other batteries. [ABSTRACT FROM AUTHOR]

In order to measure the migration parameters of nuclides in bentonite more conveniently, an improved through-discharge electromigration method was developed. In this method, the nuclides first were driven by the electric field to migrate through the bentonite column fast, then discharged with the carrier fluid, and finally collected automatically for measurement. Meanwhile, based on the analysis of the important process in the method, the solution equation for deriving the migration parameters of nuclides was established. Furthermore, two kinds of through-discharge electromigration devices were designed in term of the different nuclide sorption behaviors onto the bentonite, and the electromigration breakthrough curves of 88Sr and 239Pu in bentonite were obtained for the first time. The result indicated that the improved electromigration technology was quite efficient for acquiring the migration parameters of 88Sr with weak adsorption capacity. However, it was found that more experimental data were needed to support the analysis of 239Pu migration behavior because of its complex electrochemistry reaction with bentonite. [ABSTRACT FROM AUTHOR]

Coalition formation (CF) refers to reasonably organizing robots and/or humans to form coalitions that can satisfy mission requirements, attracting more and more attention in many fields such as multirobot collaboration and human-robot collaboration. However, the analysis on CF problems remains limited. To provide a valuable study reference for researchers interested in CF, this paper proposed a capability-centric analysis of the CF problem. The key problem elements of CF are firstly extracted by referencing the concepts of the 5W1H method. That is, objects (who) form coalitions (what) to accomplish missions (why) by aggregating capabilities (how) in a specific environment (where-when). Then, a multi-view analysis of these elements and their correlation in terms of capabilities is proposed through various logic diagrams, structure charts, etc. Finally, to facilitate a deeper understanding of capability-centric CF, a general mathematical model is constructed, demonstrating how the different concepts discussed in this analysis contribute to the overall model. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD. [ABSTRACT FROM AUTHOR]

Silica microspheres have been demonstrated as the optical micro-cavity for laser generation based on whispering-gallery modes (WGM). They can achieve a high-quality factor (Q) within a tiny volume. Traditionally, complex processes are needed to process a coating containing photoluminescent elements, with enough thickness and uniformity, for laser generation. We developed a novel sol-gel fabrication method of Er3+/Yb3+doped silica microspheres with a homogeneous doping concentration over the entire microsphere volume. The sol-gel precursors were doped with 1–2 mol% Er3+ and/or Yb3+. The viscosity of the precursor was controlled at around 4000 cP, and gel fibers can be conveniently drawn from the precursor. After firing at 1000 °C for 1 h, transparent fibers with diameters of 40–180 µm were obtained. The fiber tips were quickly melted into microspheres using a CO2 laser. The diameters of microspheres were determined by the fiber diameter and laser parameters, such as laser power and irradiation time duration. Typically, the microspheres had diameters between 90 to 160 µm. The emission spectrum under 357 nm and 527 nm excitation showed characteristic Er3+ emission peaks, that match the literature well. The UV-VIS spectra confirm the photoluminescence results and showed both Er3+ and Yb3+ characteristic absorptions. The optical behaviors of the microspheres indicate that the Er3+ and Yb3+ were well dispersed in the silica matrix and the microspheres had typical optical activities of Er3+/Yb3+ glasses. Highlights: Silica microspheres, fabricated using laser melting, with homogeneously doped Er3+/Yb3+. No need for multiple layers of Er3+/Yb3+ sol-gel coatings. Microspheres demonstrated strong optical activities with Er3+/Yb3+ doping. [ABSTRACT FROM AUTHOR]

The discovery of "mismatch repair deficient (MMRd)-crypt foci" in non-neoplastic intestinal mucosa in Lynch syndrome (LS) has significantly enhanced our understanding of how tumors and tumor immunity form and evolve in LS. In this study, we report the frequent presence of "mismatch repair proficient (MMRp)-crypt foci" in both non-neoplastic and neoplastic intestinal mucosa in a patient with constitutional MMR deficiency (CMMRD), who carried a germline MSH6 pathogenic variant (c.3261dupC) in trans with an MSH6 likely pathogenic variant (c.3724_3726del) and whose tissues were otherwise deficient in MMR globally. The MMRp-crypts occurred at a rate of 1.1/100 crypts in non-neoplastic intestinal mucosa and were readily discernible in adenomas > 1 cm. Sequencing analysis revealed normalization of the MSH6c.3261dupC variant in MMRp-adenoma crypts, indicating reverse frameshifting of the exon 5 C8 microsatellite. Interestingly but not surprisingly, the MMRp-adenoma crypts remained microsatellite-instability-high (MSI-H), and shared oncogenic APC mutations with the background MMRd-adenoma. Contrasting with MSH6-CMMRD, no PMS2-CMMRD individuals (0/5) harbored MMRp-crypts. In conclusion, our study documents distinct MMRp-crypts in MSH6-CMMRD, a phenomenon in keeping with MSH6 being a frequent target of MSI-H due to its coding microsatellite and suggesting that MSH6-CMMRD can potentially serve as a unique model system to further our understanding of MSH6's role in MSI-H tumor formation and evolution. Our findings also bear diagnostic implications; when using MMR immunohistochemistry as an ancillary tool in detecting CMMRD, awareness of these MMRp crypts can help avoid diagnostic pitfalls. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza, which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis. Methods: An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway. Results: The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines. Conclusions: Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by significant hypoxemia, which impairs the oxygen supply necessary for optimal lung function. This study aimed to investigate the effects of sodium propionate (SP), the primary end product of intestinal flora fermentation of dietary fiber, on lipopolysaccharide (LPS)-induced ARDS in rats. The rats were treated with SP, after which the lung wet/dry ratio, arterial partial oxygen pressure (PaO2), levels of pro- and anti-inflammatory cytokines, tight junction proteins ZO-1 and Occludin, as well as LC3 and phosphorylated PI3K (p-PI3K)/p-AKT/p-mTOR protein levels, were measured. Additionally, histopathological analysis was conducted. The results indicated that SP effectively alleviated arterial hypoxemia in rats and mitigated the pathological damage to both intestinal and lung tissues caused by LPS. Notably, SP significantly reduced the levels of inflammatory factors TNF-α and IL-6 in the blood and bronchoalveolar lavage fluid (BALF) of ARDS rats, while increasing the concentration of the anti-inflammatory factor IL-10. Furthermore, SP inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the LC3II/LC3I ratio in lung tissue. Therefore, SP may improve LPS-induced ARDS in rats by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway, promoting autophagy, decreasing the production and release of inflammatory markers, and reducing alveolar epithelial damage. [ABSTRACT FROM AUTHOR]

This study investigates global extreme precipitation events (EPEs) during warm seasons, with a particular focus on EPEs preceded by extreme heat stress (EPE-Hs) and a comparative analysis with those not (EPE-NHs). Using reanalysis product and Earth System Model data, the spatiotemporal characteristics and temperature sensitivities of EPEs are analyzed. Results show that EPE-Hs, while less frequent, have longer duration and greater magnitude compared to EPE-NHs, particularly in high latitude regions. In the future, a significant increase is projected in the characteristics of EPE-Hs, in contrast to the stable duration and magnitude of EPE-NHs. EPE-Hs demonstrate substantially higher temperature sensitivity than EPE-NHs, especially in low latitudes. The precipitation-temperature scaling relationships diverge markedly between EPE-Hs and EPE-NHs, with notable regional variations. These insights are pivotal for crafting region-specific early warning and adaptation strategies to mitigate the risks associated with extreme precipitation under the backdrop of global warming. [ABSTRACT FROM AUTHOR]

Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn., that has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and evaluated for their in vitro cytotoxic activity against five human cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, and H1975). Among these compounds, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3- methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the most potent cytotoxic activity against the five cancer cells, with IC50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays showed that compound 8 inhibited the migration and invasion of MDA-MB-231 cells by down-regulation HIF-1α, MMP-2 and MMP-9 protein expression. We further demonstrated that compound 8 induced apoptosis of MDA-MB-231 cells by increasing of Bax/Bcl-2 ratio and down-regulation of Akt protein expression. [ABSTRACT FROM AUTHOR]

Achieving ideal abdominal wall reconstruction in giant ventral incisional hernia has been a challenging for surgeons. This study aimed to verify the safety and efficacy of bridging repair by comparing it with primary fascial closure (PFC) repair in the treatment of giant ventral incisional hernia. We retrospectively analyzed the clinical data of 92 patients with giant ventral incisional hernia who underwent mesh repair at our medical institution from January 1, 2014 to December 31, 2020. Patients were divided into 2 groups: the bridging repair group with 40 patients in whom repair was completed using the bridging technique and the PFC group with 52 patients in whom primary fascial closure was achieved and all patients underwent mesh reinforcement during the operation. The main outcome measures were recurrence rate and morbidity, especially intra-abdominal hypertension (IAH). Follow-up time of both groups lasted at least 24 months after surgery. After a median of 46 months and 65 months of follow-up, respectively, in the two groups, bridging repair did not increase the long-term recurrence rate (2.56%) in the larger defect area group compared to the PFC group (1.96%). There were no significant differences in perioperative morbidity, IAH, incidence of postoperative chronic pain, and sensory impairment of the abdominal wall between both groups. The application of bridging surgery in the treatment of complex giant ventral incisional hernias is safe and effective and does not significantly increase the postoperative recurrence rate. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) can adversely affect surgical outcomes, and the impact on revision total knee arthroplasty (TKA) outcomes is unclear. This study aimed to explore the impact of SLE on in-patient outcomes of revision TKA. The Nationwide Inpatient Sample (NIS) database from 2005 to 2018 was searched for patients aged ≥ 18 years old who received revision TKA. Patients with and without SLE were propensity score matched (PSM) at a 1:4 ratio. Associations between SLE and in-hospital outcomes were examined using regression analyses. The study included 133,054 patients, with 794 having SLE. After 1:4 PSM, data of 3,970 patients were analyzed (SLE, 794; non-SLE, 3,176). Multivariate-adjusted analyses revealed that SLE patients had a significantly higher risk of postoperative complications (adjusted odds ratio [aOR] = 1.23, 95% confidence interval [CI]: 1.05–1.44, p = 0.011), non-routine discharge (aOR = 1.22, 95% CI: 1.02–1.46, p = 0.028), major blood loss (aOR = 1.19), respiratory failure/mechanical ventilation (aOR = 1.79), acute kidney injury (AKI) (aOR = 1.47), and wound dehiscence (aOR = 2.09). SLE patients also had a longer length of hospital stay (aBeta = 0.31) and greater total hospital costs (aBeta = 6.35) compared to non-SLE patients. Among those with aseptic failure, SLE patients had a significantly higher risk of postoperative complications (aOR = 1.23) and non-routine discharge (aOR = 1.36). SLE is independently associated with worse in-hospital outcomes in patients undergoing revision TKA. This study highlights the importance of heightened vigilance and tailored perioperative management for patients undergoing major surgeries in the background of SLE. Key Points • SLE significantly increases the risk of non-routine discharge, major blood loss, respiratory failure, acute kidney injury, and wound dehiscence, in patients undergoing aseptic and septic revision TKA. • Patients with SLE experience longer hospital stays and higher hospital costs compared to those without SLE. • The study's findings highlight the necessity for healthcare providers to consider the presence of SLE as a critical factor in preoperative planning and postoperative care to improve outcomes in revision TKA patients. [ABSTRACT FROM AUTHOR]

Background: Significant progress has been made in the diagnosis and treatment of pediatric syncope since the publication of the "2018 Chinese Pediatric Cardiology Society (CPCS) guideline for diagnosis and treatment of syncope in children and adolescents" ("2018 Edition Guidelines"). Therefore, we have revised and updated it to assist pediatricians in effectively managing children with syncope. Data sources: According to the "2018 Edition Guidelines", the expert groups collected clinical evidence, evaluated preliminary recommendations, and then organized open-ended discussions to form the recommendations. This guideline was developed by reviewing the literature and studies in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to April 2024. Search terms included "syncope", "children", "adolescents", "diagnosis", and "treatment." Results: The guidelines were based on the latest global research progress and were evidence-based. The classification of syncope etiology, diagnostic procedures, postural tests, such as the active standing test, head-up tilt test, and active sitting test, clinical diagnosis, and individualized treatment for neurally mediated syncope in pediatric population were included. Conclusions: The guidelines were updated based on the latest literature. The concepts of sitting tachycardia syndrome and sitting hypertension were introduced and the comorbidities of neurally mediated syncope were emphasized. Some biomarkers used for individualized treatment were underlined. Specific suggestions were put forward for non-pharmacological therapies as well as the follow-up process. The new guidelines will provide comprehensive guidance and reference for the diagnosis and treatment of neurally mediated syncope in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. Methods: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography–tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. Conclusion: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes. [ABSTRACT FROM AUTHOR]

Empagliflozin is currently known to decrease blood glucose levels, delay renal failure, and reduce the risk of cardiovascular death and all-cause mortality in patients with type 2 diabetes with cardiovascular disease. However, the effects of empagliflozin on the lifespan and health of naturally aged organisms are unclear. This study was designed to investigate the impacts and potential mechanisms of empagliflozin on lifespan and liver senescence in naturally aged mice. Our study revealed that empagliflozin improved survival and health in naturally aged mice. Empagliflozin extended the median survival of male mice by 5.9%. Meanwhile, empagliflozin improved learning memory and motor balance, decreased body weight, and downregulated the hepatic protein expression of P21, P16, α-SMA, and COL1A1. Empagliflozin modulates the structure of the intestinal flora, increasing the relative abundance of Lachnospiraceae, Ruminococcaceae, Lactobacillus, Blautia, and Muribaculaceae and decreasing the relative abundance of Erysipelotrichaceae, Turicibacter, and Dubosiella in naturally aged mice. Further exploration discovered that empagliflozin increased the concentration of SCFAs, decreased the levels of the inflammatory factors TNF-α, IL-6, and CXCL9, and regulated the PI3K/AKT/P21 and AMPK/SIRT1/NF-κB pathways, which may represent the underlying mechanisms involved in these beneficial hepatic effects. Taken together, the above results indicated that empagliflozin intervention could be considered a potential strategy for extending lifespan and slowing liver senescence in naturally aged mice. Treatment with empagliflozin extended longevity, improved learning memory and motor balance, regulated the gut microbiota and SCFAs, ameliorated the level of inflammation and delayed liver senescence. [ABSTRACT FROM AUTHOR]

Proximal gradient algorithms are popularly implemented to achieve convex optimization with nonsmooth regularization. Obtaining the exact solution of the proximal operator for nonsmooth regularization is challenging because errors exist in the computation of the gradient; consequently, the design and application of inexact proximal gradient algorithms have attracted considerable attention from researchers. This paper proposes computationally efficient basic and inexact proximal gradient descent algorithms with random reshuffling. The proposed stochastic algorithms take randomly reshuffled data to perform successive gradient descents and implement only one proximal operator after all data pass through. We prove the convergence results of the proposed proximal gradient algorithms under the sampling-without-replacement reshuffling scheme. When computational errors exist in gradients and proximal operations, the proposed inexact proximal gradient algorithms can converge to an optimal solution neighborhood. Finally, we apply the proposed algorithms to compressed sensing and compare their efficiency with some popular algorithms. [ABSTRACT FROM AUTHOR]

Background: Nasal tip refinement is a challenging step of East Asian rhinoplasty due to complex anatomical defects. Autologous costal cartilage grafts are commonly used to provide nasal tip support. This study aims to evaluate the efficacy and safety of a modified technique using a lollipop-like cartilage graft with a peach-shaped head. Methods: A retrospective review was conducted on Chinese patients who underwent primary rhinoplasty with the modified technique between November 2018 and March 2021 at our center. Preoperative and postoperative facial photographs, patient-reported outcome measures including the visual analog scale (VAS) and the rhinoplasty outcome evaluation (ROE), as well as surgery-related complications, were collected for outcome assessment. Results: A total of 31 adult patients were included in this retrospective cohort study, with a mean follow-up period of 17.12 ± 3.89 months. The majority of patients (28/31; 90.3%) expressed satisfaction with the aesthetic outcomes, as evidenced by a significant increase in mean VAS score from 3.97 ± 1.52 preoperatively to 7.39 ± 0.22 postoperatively (P < 0.01), and a significant increase in mean ROE score from 11.77 ± 2.33 to 17.22 ± 2.47 (P < 0.01). Photogrammetric analysis also demonstrated significant improvements in nasal anatomical measurements. Among the three patients with unsatisfactory feedback, two had mild columella deviations and one had a mild dorsum deviation. No other notable complications were reported. Conclusion: The current study supports the safety and utility of the modified technique utilizing the lollipop-like costal cartilage graft with a peach-shaped head for major tip refinement in East Asian patients. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Extreme events with increasing frequency and intensity are significantly affecting the permafrost environment. Analysis using the ERA5-Land reanalysis data revealed that the permafrost region of the central Qinghai-Tibet Plateau (QTP) experienced the summer heat wave in 2022. Four active layer sites experienced maximum active layer thicknesses (ALT) in 2022 (mean: 207.7 cm), which was 20% higher than the mean ALT during 2000–2021 (mean: 175.9 cm). The mean annual ground temperature (MAGT) observed in 2022 was also the highest, exceeding the average of the previous years by 10%. The contribution fraction of heat wave to the seasonal thaw depth of active layer was quantified using Stefan model with ranging from 6.6% to 13.6%, and the maximum contribution fraction occurs in 2022. These findings are helpful to better understand the impact processes of extreme events on the active layer and permafrost. [ABSTRACT FROM AUTHOR]

Due to the influence of the errors of time difference of arrivals (TDOA) and the premeasured velocity in the propagation medium, the existing methods always hold the low location accuracy and efficiency. To increase the location accuracy, the joint inversion of AE/MS sources and propagation velocity is proposed using the full measurements and residual estimation. First, the control equation of the unknown wave velocity is constructed using sensor coordinates and full TDOA measurements, and it is linearized by introducing the additive variables. Second, considering the influence of TDOA errors, the residuals of the TDOA equations are calculated to obtain weights. Finally, the orthogonal projection is applied to separate the additive variables and solve the weighted linear equations for source coordinates. The pencil–lead breaks experiments are carried out to verify the effectiveness and accuracy of the proposed method. The results show that the novel method holds better accuracy and wave velocity inversion than the pre-existing methods. The average positioning error of the novel method is only 3.49 mm, while the errors of the traditional methods are 4.62 mm, 5.08 mm, 6.57 mm, and 11.93 mm, respectively. The positioning performance of the proposed method under different TDOA errors is further proved by simulation tests. The simulation results demonstrate that the positioning performance of the proposed method is better than that of the existing methods under different errors. Moreover, the blast vibration experiment validates that the proposed method holds the location accuracy of 16.65 m, which presents good prospects in engineering applications. Highlights No prior measurement of wave speeds and selection of reference sensors reduce the effect of velocity and arrival errors. Analytical solution being given by linearizing the control equation, complex computations and local convergence are circumvented. Estimating the noise term in the arrival time difference, the tolerance to TDOA errors is improved. Redundant time-difference-of-arrival measurements are fully used to provide new constraints. Blasting experiments reveal that positioning accuracy of the method is 72% more accurate than the traditional method. [ABSTRACT FROM AUTHOR]

The stable hydrogen isotope in precipitation is an effective environmental tracer for climatic and hydrologic studies. However, accurate and high-precision precipitation hydrogen isoscapes are currently unavailable in China. In this study, a data fusion method based on Convolutional Neural Networks (CNN) is used to fuse the hydrogen isotopic composition (δ2Hp) of observations and isotope-equipped general circulation model (iGCM) simulations. A precipitation hydrogen isoscape with a temporal resolution of monthly and a spatial resolution of 50–60 km is established for East China for the 1969–2017 period. Prior to building the isoscape, the performance of three data fusion methods (DFMs) and two bias correction methods (BCMs) is compared. The results indicate that the CNN fusion method performs the best with a correlation coefficient larger than 0.90 and root mean square error smaller than 10.5‰when using observation as a benchmark. The fusion methods based on back propagation and long short-term memory neural network perform similarly, while slightly outperforming the bias correction methods. Thus, the CNN method is used to generate the hydrogen isoscape, and the temporal and spatial distribution characteristics of the hydrogen isotope in precipitation are analyzed based on this dataset. The generated isoscape shows similar spatial and temporal distribution characteristics to observations. In general, the distribution pattern of δ2Hp is consistent with the temperature effect in northern China, and consistent with the precipitation amount effect in southern China. The trend of the δ2Hp time series is consistent with that of observed precipitation and temperature. Overall, the generated isoscape effectively reproduces the observations, and has the characteristics of time continuity and relative spatial regularity, which can provide valuable data support for tracking atmospheric and hydrological processes. [ABSTRACT FROM AUTHOR]

Crustal accretion at mid-ocean ridges governs the creation and evolution of the oceanic lithosphere. Generally accepted models1–4 of passive mantle upwelling and melting predict notably decreased crustal thickness at a spreading rate of less than 20 mm year−1. We conducted the first, to our knowledge, high-resolution ocean-bottom seismometer (OBS) experiment at the Gakkel Ridge in the Arctic Ocean and imaged the crustal structure of the slowest-spreading ridge on the Earth. Unexpectedly, we find that crustal thickness ranges between 3.3 km and 8.9 km along the ridge axis and it increased from about 4.5 km to about 7.5 km over the past 5 Myr in an across-axis profile. The highly variable crustal thickness and relatively large average value does not align with the prediction of passive mantle upwelling models. Instead, it can be explained by a model of buoyant active mantle flow driven by thermal and compositional density changes owing to melt extraction. The influence of active versus passive upwelling is predicted to increase with decreasing spreading rate. The process of active mantle upwelling is anticipated to be primarily influenced by mantle temperature and composition. This implies that the observed variability in crustal accretion, which includes notably varied crustal thickness, is probably an inherent characteristic of ultraslow-spreading ridges.Results from a high-resolution ocean-bottom seismometer experiment at the ultraslow-spreading Gakkel Ridge show unexpected highly variable crustal thickness and a relatively large average value, which can be explained by an active mantle upwelling model. [ABSTRACT FROM AUTHOR]

Introduction: Medical financial hardship in the United States is a growing public health concern. This study aims to assess the south vs. non-south disparities in medical financial hardship among US adults of different generations – Boomers (born between 1946 and 1964), Generation X (born between 1965 and 1980), and the Millennials (born between 1981 and 1996) across periods pre- and post- Affordable Care Act (ACA). Methods: This observational study utilizes data from multiple waves of the National Health Interview Survey (NHIS) split into three periods: pre–ACA (2011–2013), ii) post ACA (2015–2018), and iii) COVID-19 pandemic (2021–2022). Multivariable logistic regressions were fitted, separately for each generation in each period, to compare the extent of medical financial hardship among those from South to rest of the US, and Karlson-Holm-Breen (KHB) decomposition was applied to analyze whether there was a mediating impact of health insurance coverage. Results: Adults living in the South were more likely to experience medical financial hardship in all three periods. Residing in the South was associated with 1.7 to 2.6% points (pp) higher probability of medical financial hardship among boomers, 1.8 to 4.0 pp among generation Xers, and 1.7 to 2.8 pp among millennials. The relationship was robust after accounting for chronic comorbidities, sociodemographic and socioeconomic attributes and was partially mediated through differences in health insurance coverage. Conclusions: The problem of medical financial hardship has been deeply rooted in the South across generations, which was partly attributable to the regional differences in health insurance coverage. [ABSTRACT FROM AUTHOR]

Background: Irinotecan administration can lead to severe delayed-onset diarrhea (SDOD) in clinical practice. Currently, there is no reliable surrogate predictor of intestinal exposure to SN-38 and subsequent diarrhea incidence. Methods: The relationship between fecal 7-ethyl-10-hydroxycamptothecin (SN-38) content and SDOD was investigated in Fisher 344 rats using a novel spectrofluorimetric method. Additionally, a pharmacokinetic study of irinotecan was performed to evaluate the biodistribution of SN-38 to establish the relationship between tissue and fecal SN-38 exposure. Results: The spectrofluorimetric method was successfully employed to measure fecal SN-38 and CPT-11 content from Day 3 to Day 6 post-irinotecan administration. Only fecal SN-38 content on Day 3 exhibited a significantly positive correlation with SDOD incidence on Days 4 and 5. A cutoff value of SN-38 ≥ 0.066 mg/g in feces was identified, predicting severe diarrhea incidence with 81% accuracy and 80% specificity. The positive correlation between fecal SN-38 content and SN-38 exposure in the ileum on Day 3 was also reflected in the changes of indicators during intestinal injury, such as prostaglandin E2 level and antioxidant activity. Conclusion: Fecal SN-38 content proves to be representative of intestinal exposure to SN-38, indicative of intestinal injury, and predictive of SDOD incidence in rats, while the spectrofluorimetric method demonstrates the translational potential. Fecal SN-38 content as a surrogate predictor for SN-38 intestinal tissue exposure and irinotecan-induced severe delayed-onset diarrhea The intestinal SN-38 exposure, involving both the distribution of SN-38 from the blood vessel and the reabsorption of SN-38 from intestinal lumen, was shown to be closely related to irinotecan-induced diarrhea. However, intestinal SN-38 exposure is hard to measure in humans. Fecal SN-38 content could serve as a surrogate predictor of intestinal SN-38 exposure, which is dependent on biliary excretion, intestinal excretion to intestinal lumen and bacteria β-glucuronidase activities that convert SN-38G to SN-38. [ABSTRACT FROM AUTHOR]

Podocyte damage plays a crucial role in the occurrence and development of diabetic nephropathy (DN). Accumulating evidence suggests that dysregulation of transcription factors plays a crucial role in podocyte damage in DN. However, the biological functions and underlying mechanisms of most transcription factors in hyperglycemia-induced podocytes damage remain largely unknown. Through integrated analysis of data mining, bioinformatics, and RT-qPCR validation, we identified a critical transcription factor forkhead box F1 (FOXF1) implicated in DN progression. Moreover, we discovered that FOXF1 was extensively down-regulated in renal tissue and serum from DN patients as well as in high glucose (HG)-induced podocyte damage. Meanwhile, our findings showed that FOXF1 might be a viable diagnostic marker for DN patients. Functional experiments demonstrated that overexpression of FOXF1 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and fibrosis in HG-induced podocytes damage. Mechanistically, we found that the downregulation of FOXF1 in HG-induced podocyte damage was caused by DNMT1 directly binding to FOXF1 promoter and mediating DNA hypermethylation to block FOXF1 transcriptional activity. Furthermore, we found that FOXF1 inhibited the transcriptional expression of miR-342-3p by binding to the promoter of miR-342, resulting in reduced sponge adsorption of miR-342-3p to E2F1, promoting the expression of E2F1, and thereby inhibiting HG-induced podocytes damage. In conclusion, our findings showed that blocking the FOXF1/miR-342-3p/E2F1 axis greatly alleviated HG-induced podocyte damage, which provided a fresh perspective on the pathogenesis and therapeutic strategies for DN patients. [ABSTRACT FROM AUTHOR]

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Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue. [ABSTRACT FROM AUTHOR]

Urolithin families are gut-microbial metabolites of ellagic acid (EA). Although urolithin A (UA) and urolithin B (UB) were reported to have antiproliferative activities in cancer cells, the role and related mechanisms of urolithin C (UC) in colorectal cancer (CRC) have not yet been clarified. In this study, we assess the antitumor activities of UC in vitro and in vivo and further explore the underlying mechanisms in CRC cell lines. We found that UC inhibited the proliferation and migration of CRC cells, induced apoptosis, and arrested the cell cycle at the G2/M phase in vitro, and UC inhibited tumor growth in a subcutaneous transplantation tumor model in vivo. Mechanically, UC blocked the activation of the AKT/mTOR signaling pathway by decreasing the expression of Y-box binding protein 1(YBX1). The AKT agonist SC79 could reverse the suppression of cell proliferation in UC-treated CRC cells. In conclusion, our research revealed that UC could prevent the progression of CRC by blocking AKT/mTOR signaling, suggesting that it may have potential therapeutic values. [ABSTRACT FROM AUTHOR]

In meet-in-the-middle (MITM) attacks, the sizes of the precomputation tables determine the effectiveness. In this paper, value constraints are presented to reduce the size of the precomputation table in MITM attacks on AES. Based on a differential property of linear combinations of multiple S-boxes, value constraints related to input or output in four and five rounds of AES are explored. Meanwhile, with these value constraints, a method of setting up non-linear equations is proposed to reduce the sizes of the precomputation tables by decreasing the number of byte parameters. Compared with the existing results, their sizes can be reduced by 2 8 , 2 16 , or 2 24 . Finally, some attacks are improved with lower time and memory complexities. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex, severe disorder related to brain development. It impairs patient language communication and social behaviors. In recent years, ASD researches have focused on a single-modal neuroimaging data, neglecting the complementarity between multi-modal data. This omission may lead to poor classification. Therefore, it is important to study multi-modal data of ASD for revealing its pathogenesis. Furthermore, recurrent neural network (RNN) and gated recurrent unit (GRU) are effective for sequence data processing. In this paper, we introduce a novel framework for a Multi-Kernel Learning Fusion algorithm based on RNN and GRU (MKLF-RAG). The framework utilizes RNN and GRU to provide feature selection for data of different modalities. Then these features are fused by MKLF algorithm to detect the pathological mechanisms of ASD and extract the most relevant the Regions of Interest (ROIs) for the disease. The MKLF-RAG proposed in this paper has been tested in a variety of experiments with the Autism Brain Imaging Data Exchange (ABIDE) database. Experimental findings indicate that our framework notably enhances the classification accuracy for ASD. Compared with other methods, MKLF-RAG demonstrates superior efficacy across multiple evaluation metrics and could provide valuable insights into the early diagnosis of ASD. [ABSTRACT FROM AUTHOR]