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Abstract Localized magnetic moments in non-magnetic materials, by interacting with the itinerary electrons, can profoundly change the metallic properties, developing various correlated phenomena such as the Kondo effect, heavy fermion, and unconventional superconductivity. In most Kondo systems, the localized moments are introduced through magnetic impurities. However, the intrinsic magnetic properties of materials can also be modulated by the dimensionality. Here, we report the observation of Kondo effect in a heterodimensional superlattice VS2-VS, in which arrays of the one-dimensional (1D) VS chains are encapsulated by two-dimensional VS2 layers. In such a heterodimensional Kondo superlattice, we observe the typical Kondo effect but with intriguing anisotropic field dependence. This unique anisotropy is determined to originate from the magnetic anisotropy which has the root in the unique 1D chains in the structure, as corroborated by the first-principles calculation. Our results open up a novel avenue of studying exotic correlated physics in heterodimensional materials.

Abstract Background Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). Methods We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer’s disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. Results The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. Discussion This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.

Summary: Pyroptosis, a pro-inflammatory form of programmed cell death, is crucial for host defense against pathogens and danger signals. Proteolytic cleavage of gasdermin proteins B–E (GSDMB–GSDME) is well established as a trigger for pyroptosis, but the intracellular activation mechanism of GSDMA remains elusive. Here, we demonstrate that severe starvation induces pyroptosis through phosphorylation-induced activation of GSDMA. Nutrient stresses stimulate GSDMA activation via phosphorylation mediated by Unc-51-like autophagy-activating kinase 1 (ULK1). Phosphorylation of Ser353 on human GSDMA by ULK1 or the phospho-mimetic Ser353Asp mutant of GSDMA liberates GSDMA from auto-inhibition, facilitating its membrane targeting and initiation of pyroptosis. To further validate the significance of GSDMA phosphorylation, we generated a constitutively active mutant Ser354Asp of mouse Gsdma, which induced skin inflammation and hyperplasia in mice, reminiscent of phenotypes with activated Gsdma. This study uncovers phosphorylation of GSDMA as a mechanism underlying pyroptosis initiation and cellular response to nutrient stress.

Abstract Aqueous zinc‐ion batteries (AZIBs) are highly promising for grid‐scale energy storage due to their high‐safety and low‐cost characteristics. Nevertheless, the progress in AZIBs has been impeded due to challenges encompassing corrosion, hydrogen evolution reaction, and the formation of dendrites on Zn anodes. These issues arise from the decomposition of active water molecules in the Zn2+ solvation structure in the electrolyte. Various strategies have been proposed to regulate the electrode/electrolyte interface to effectively address these problems. In spite of remarkable headway, an inadequacy of comprehensive studies addressing the mechanisms and evolutionary dynamics of the electrode/electrolyte interface is evident within scientific literature. This overview aims to provide a comprehensive overview of the strategies for regulating the electrode/electrolyte interface, focusing on dendrite‐free and side reactions‐suppressed AZIBs. These strategies include the introduction of metal ion additives, inorganic additives, surfactant additives, polymer additives and organic additives. Furthermore, a detailed examination is made on the effects and underlying mechanisms associated with modifying the electrolyte at the interface between the electrode and electrolyte. Moreover, an appraisal is provided on the performance metrics of diverse strategies and prospective research directions are recommended as well.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.

Abstract Lysosomal Storage Disorders (LSDs), which share common phenotypes, including enlarged lysosomes and defective lysosomal storage, are caused by mutations in lysosome-related genes. Although gene therapies and enzyme replacement therapies have been explored, there are currently no effective routine therapies against LSDs. During lysosome reformation, which occurs when the functional lysosome pool is reduced, lysosomal lipids and proteins are recycled to restore lysosome functions. Here we report that the sorting nexin protein SNX8 promotes lysosome tubulation, a process that is required for lysosome reformation, and that loss of SNX8 leads to phenotypes characteristic of LSDs in human cells. SNX8 overexpression rescued features of LSDs in cells, and AAV-based delivery of SNX8 to the brain rescued LSD phenotypes in mice. Importantly, by screening a natural compound library, we identified three small molecules that enhanced SNX8–lysosome binding and reversed LSD phenotypes in human cells and in mice. Altogether, our results provide a potential solution for the treatment of LSDs.

To balance the nutrition and improve quality of sausages. This research investigated quality improvements of Sichuan sausages by 41.5% poultry, rabbit meat and fish addition. The moisture, crude fat, crude protein contents, pH, Aw, colour, texture, TBARS, protein carbonyl, free thiol groups, fatty acids composition and sensory attributes of pork, poultry, rabbit meat and fish mixture group sausages were evaluated. The results showed that the hardness of pork and rabbit meat mixture group sausages (76.37, 68.01 kg) was significant (P

This paper primarily investigates the effect of the tilt of corner cube reflector (CCR) arrays on lunar laser ranging (LLR). A mathematical model was established to study the random errors caused by the tilt of the CCR arrays. The study found that, ideally, when the laser ranging pulse width is 10 picoseconds or less, it is possible to distinguish from which specific corner cubes within the CCR array each peak in the echo signal originates. Consequently, partial data from the echo can be extracted for signal processing, significantly reducing random errors and improving the single-shot precision of LLR. The distance obtained by extracting part of the echo can be reduced to the center position of the array, thereby providing multiple higher-precision ranging results from each measurement. This not only improves the precision of LLR but also increases the data volume. A simulation experiment based on the 1.2 m laser ranging system at Yunnan Observatories was conducted. By extracting one peak for signal processing, the single-shot precision improved from 32.24 mm to 2.52 mm, validating the theoretical analysis results. Finally, an experimental laser ranging system based on a 53 cm binocular telescope system was established for ground experiments. The experimental results indicated that the echo signal could identify the tilt state of the CCR array. By extracting the peak returned by the central CCR for signal processing, the ranging precision was greatly improved. Through theoretical analyses, simulation experiments, and ground experiments, a solution to reduce the random errors caused by the tilt of the CCR array was provided. This offers an approach to enhance the single-shot precision of future LLR and provides a reference for upgrading ground-based equipment at future laser ranging stations.

The aim of individuals consuming health supplements is to attain a robust state through nutritional regulation. However, some unscrupulous manufacturers, motivated by profit, fraudulently incorporate drugs or unauthorized components with therapeutic effects into the product for instant product performance enhancement. The long-term use of these products may inadvertently inflict harm on human health and fail to promote nutritive healthcare. The illegal inclusion of these substances is prevalent in kidney-tonifying and sexuality-enhancing products. Developing effective analytical methods to identify these products and screen for illegal added ingredients can effectively prevent such products from reaching and remaining on the market. A target screening method for the detection and quantification of 90 phosphodiesterase type 5 inhibitors (PDE-5is) in 5 kinds of health products was developed and validated. The type of dietary supplements varied from tablets, capsules, and protein powder to wine and beverages. Sample preparation was completed with a one-step liquid phase extraction. The screening process of 90 PDE-5is was done efficiently within 25 min by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using the dynamic multiple reaction monitoring (dMRM) technique. The LODs of 90 PDE-5is were detected at levels ranging from 25 to 85 ng/g or ng/mL. This novel targeting methodology was effective and can be applied to routine market supervision. Among 286 batches of samples, 8 batches were found to be positive. Three kinds of PDE-5is were first detected in healthy products. The screening method demonstrated herein will be a promising and powerful tool for rapid screening of PDE-5is.

Background and objectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has broad tissue tropism and high transmission, which are likely to perpetuate the pandemic. The study aim to analyze the clinicopathogenic characteristics in paediatric patients.MethodsIn this single-centre study, we retrospectively included all confirmed cases infected by SARS-CoV-2 infection at Xi’an Children's Hospital, China, from 1 December to 31 December 2022. The demographic, clinical, laboratory, and radiological features of the patients were analysed.ResultsA total of 4,520 paediatric patients with SARS-CoV-2 omicron variant infections were included. Of these, 3,861 (85.36%) were outpatients, 659 (14.64%) were hospitalised patients, and nine patients (0.20%) died. Of the nine patients who died, five were diagnosed with acute necrotising encephalopathy (ANE). The most common symptoms were fever in 4,275 (94.59%) patients, cough in 1,320 (29.20%) patients, convulsions in 610 (13.50%) patients, vomiting in 410 (9.07%) patients, runny nose/coryza in 277 (6.13%) patients, hoarseness of voice in 273 (6.04%) patients. A blood cell analysis showed a slight elevation of monocytes (mean: 11.14 ± 0.07%). The main diagnoses for both outpatients and inpatients were respiratory infection with multisystem manifestations.ConclusionsA high incidence of convulsions is a typical characteristic of children infected with SARS-CoV-2. Five of the nine COVID-19 fatalities were associated with ANE. This indicates that nervous system damage in children with SARS-CoV-2 infection is more significant.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the infiltration of inflammatory cells and proliferation of synovial cells. It can cause cartilage and bone damage as well as disability and is regarded as an incurable chronic disease. Available therapies cannot prevent the development of diseases due to the high toxicity of the therapeutic agents and the inefficient drug delivery. Ferroptosis, an iron-dependent manner of lipid peroxidative cell death, indicates great potential for RA therapy due to ability to damage the infiltrated inflammatory cells and proliferated fibroblast-like synoviocytes. Here, we use macrophages as vector to deliver Fe3O4 nanoparticles and sulfasalazine (SSZ) for ferroptosis and photothermal therapy of RA. The inherent property of migration towards the inflamed joints under the guidance of inflammatory factors enables macrophages to targetedly deliver the payload into the RA. Upon the irradiation of the near infrared light, the Fe3O4 nanoparticles convert the light into heat to damage the proliferated synovium. Meanwhile, the iron released from Fe3O4 nanoparticles works with SSZ to generate synergetic ferroptosis effect. The resident inflammatory cells and proliferated synovium are efficiently damaged by the ferroptosis and photothermal effect, showing pronounced therapeutic effect for RA.

Abstract Background Traditional estimates can only provide static predictions of cancer outcomes and cannot assess the evolving effect of race on patient survival. This study aims to reveal the dynamic survival of patients with bladder cancer and to explore the evolving effect of race on patient prognosis. Methods Using data from the Surveillance, Epidemiology, and End Results (SEER) registry, 99,590 white, 6,036 African American, and 4,685 Asian/Pacific Islander (API) patients with bladder cancer were identified. Conditional cancer-specific survival (CSS) rates, which could reflect the dynamic survival prediction of cancer patients, represented the primary outcomes, and were estimated by the Kaplan-Meier algorithm. The evolving effect of race on patient survival was evaluated by multivariable Cox regression in combination with conditional survival (CS) estimates. Results The 5-year CSS for African American patients who had survived 1, 2, 3, 4, or 5 years after definitive therapy improved from the baseline calculation by + 5.8 (84.4%), + 9.5 (87.4%), + 12.8 (90.0%), + 14.4 (91.3%), and + 14.7% (91.5%), respectively. The increasing trend also held for overall white and API patients, and for all patient subsets when CS was calculated according to different levels of sex, age, and disease stage. African Americans, despite having the worst survival at baseline, could have CSS comparable to their white and API counterparts after 4 years of survivorship. In addition, the risk of death for African Americans tended to decrease with increasing survival, and the risk was no longer significantly different from that of whites after 4 years of survival. Conclusions While having the worst initial predicted outcomes, African Americans may eventually achieve comparable survival to white and API patients given several years of survivorship. As patient survival increases, African American race may lose its role as an indicator of poorer prognosis.

Abstract Background Currently, immune checkpoint blockers (ICB) and radiotherapy (RT) combination therapy is broadly applied in non‐small cell lung cancer (NSCLC) patients. However, meta‐analysis about safety and efficacy of RT + ICB versus ICB has not yet been reported. To evaluate safety and efficacy of the combination therapy of ICB and RT in patients with recurrent or metastatic NSCLC and explore factors related to higher response rates, longer lifetime, and lower toxicity, meta‐analysis of previous clinical data will be presented in this article. Methods A literature search on patients with recurrent or metastatic NSCLC treated with RT + ICB versus ICB was performed using the Cochrane Library, Embase and PubMed up to December 10, 2022. Suitable quality assessment checklists were selected corresponding to various types of research studies. Comparative and single‐arm studies were analyzed using Stata 14.0. Results 10 comparative studies and 15 arms of combination therapy were included for this meta‐analysis. RT significantly improved objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and progression‐free survival (PFS) of ICB (I‐square value (I2) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09–1.49, I2 = 0.00%, OR 1.12, 95% CI 1.00–1.25, I2 = 42.1%, OR 0.81, 95% CI 0.72–0.92, I2 = 34.5%, OR 0.80, and 95% CI 0.71–0.89, respectively). Toxicity between combination therapy and ICB monotherapy did not significantly differ in any grade or in ≥3 grade of tr‐AEs (I2 = 0.00%, OR 1.05, 95% CI 0.91–1.22, I2 = 0.00%, OR 1.46, 95% CI 0.90–2.37, respectively). Subgroup analyses based on single‐arm studies showed that applications of SRS/SBRT, PD‐1 inhibitor, and administration of ICB after RT were conducive to a better DCR, longer OS and mild adverse events (heterogeneity between groups (HBG) all p

Naturally occurring substances and their derivatives function as vital resources for pesticides that can be used in fields, such as insecticide production and fungicide development. As a botanical entity displaying multifaceted biological functions, wormwood has received thorough scrutiny across multiple sectors. The insect repellency potency combined with antibacterial and antifungal activities of wormwood position it as a potential candidate for prospective development into eco-friendly chemical pesticides. In this research, Wormwood essential oil was procured via ethanol water under ultrasonic scenarios and subsequently diluted with PEG 400 to formulate green chemical pesticides. The defensive efficacy of this green pesticide on plants was validated through 2 weeks of clustered plant growth experiments. Active constituents that exerted their effects were scrutinized by GC-MS. Furthermore, this green pesticide also displays efficacious effects on the prevention and management of aphids, exhibiting a dose-dependent relationship. 4-terpenol, eucalyptol, carvacrol, and L-borneol were identified by GC-MS as the predominant active constituents in this green chemical pesticide. Wormwood can be leveraged to develop green chemical pesticides, which can protect plants without contaminating the environment.

We derive the analytical expressions for root-mean-square (rms) beam wander (BW) and relative BW of a twisted electromagnetic elliptical vortex (TEEV) beam propagating through non-Kolmogorov atmospheric turbulence with the help of the extended Huygens–Fresnel principle and the second-order moments of the Wigner distribution function (WDF). Our numerical findings demonstrate that the BW of a TEEV beam with a small ellipticity, a large topological charge as well as a small waist width and initial coherent length is less affected by the turbulence. It can be also found that the effect of turbulence with a larger outer scale of turbulence, a generalized exponent parameter, and a generalized structure parameter on BW is more obvious. It is interesting to find that the effect of atmospheric turbulence on BW for a TEEV beam can be effectively reduced by regulating jointly the symbols and sizes of the twisted factor and topological charge. Therefore, modulation of the structure parameters of a TEEV beam provides a new way to mitigate turbulence-induced beam wander. Our work will be useful for free-space optical communications, remote sensing, and lidar distance measurement.

Mycotoxins are a class of exogenous metabolites that are major contributors to foodborne diseases and pose a potential threat to human health. However, little attention has been paid to trace mycotoxin co-exposure situations in vivo. To address this, we devised a novel analytical strategy, both highly sensitive and comprehensive, for quantifying 67 mycotoxins in human plasma samples. This method employs isotope dilution mass spectrometry (IDMS) for approximately 40% of the analytes and utilizes internal standard quantification for the rest. The mycotoxins were classified into three categories according to their physicochemical properties, facilitating the optimization of extraction and detection parameters to improve analytical performance. The lowest limits of detection and quantitation were 0.001–0.5 μg/L and 0.002–1 μg/L, respectively, the intra-day precision ranged from 1.8% to 11.9% RSD, and the intra-day trueness ranged from 82.7–116.6% for all mycotoxins except Ecl, DH-LYS, PCA, and EnA (66.4–129.8%), showing good analytical performance of the method for biomonitoring. A total of 40 mycotoxins (including 24 emerging mycotoxins) were detected in 184 plasma samples (89 from infertile males and 95 from healthy males) using the proposed method, emphasizing the widespread exposure of humans to both traditional and emerging mycotoxins. The most frequently detected mycotoxins were ochratoxin A, ochratoxin B, enniatin B, and citrinin. The incidence of exposure to multiple mycotoxins was significantly higher in infertile males than in healthy subjects, particularly levels of ochratoxin A, ochratoxin B, and citrinin, which were significantly increased. It is necessary to carry out more extensive biological monitoring to provide data support for further study of the relationship between mycotoxins and male infertility.

Artemisinin has an endoperoxide bridge structure, which can be cleaved by ferrous ions to generate various carbonyl radicals in an oxygen-independent manner, highlighting its potential for treating hypoxic tumors. In our study, we fabricated Tween 80 micelles loaded with Fe3O4 nanoparticles and artemisinin for cancer therapy. The synthesized Fe3O4 nanoparticles and drug-loaded micelles have particle sizes of about 5 nm and 80 nm, respectively, both exhibiting excellent dispersibility and stability. After uptake by MCF-7 cells, drug-loaded micelles release Fe2+ and ART into the cytoplasm, effectively inducing the generation of reactive oxygen species (ROS) in hypoxic conditions, thereby enhancing toxicity against cancer cells. In vitro and in vivo studies have demonstrated that ART and Fe3O4 nanoparticles are encapsulated in Tween 80 to form micelles, which effectively prevent premature release during circulation in the body. Although free ART and Fe3O4 nanoparticles can inhibit tumor growth, TW80-Fe3O4-ART micelles demonstrate a more pronounced inhibitory effect, with a tumor suppression rate of up to 85%. A novel strategy based on artemisinin and ferroptosis is thus offered, holding a favorable prospect for hypoxic cancer therapy.

With increasing health awareness and the accelerating pace of life, whole-grain prepared foods have gained popularity due to their health benefits and convenience. However, the potential risk of type B trichothecene toxins has also increased, and these mycotoxins in such foods are rarely regulated. In this study, a quantitative method combining a single-valve dual-column automatic online solid-phase extraction system with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) was developed for the first time using restricted-access media columns. This method can simultaneously determine trace residues of seven type B trichothecenes within 15 min. The method is convenient, sensitive (limit of detection and quantification of 0.05–0.6 μg/kg and 0.15–2 μg/kg, respectively), accurate (recovery rates of 90.3%–106.6%, relative standard deviation < 4.3%), and robust (>1000 times). The established method was applied to 160 prepared food samples of eight categories sold in China. At least one toxin was detected in 70% of the samples. Whole-wheat dumpling wrappers had the highest contamination rate (95%) and the highest total content of type B trichothecenes in a single sample (2077.3 μg/kg). Exposure risk assessment indicated that the contamination of whole-grain prepared foods has been underestimated. The total health risk index of whole-wheat dumpling wrappers, which are susceptible to deoxynivalenol, reached 136.41%, posing a significant threat to human health. Effective measures urgently need to be taken to control this risk.

(1) Background: The adulteration of cosmetics has become increasingly common, which seriously harms ordinary consumers. The counterfeit cosmetics pointed out in this study mainly refer to imitating genuine products in terms of ingredients and packaging. Ordinary consumers cannot distinguish their authenticity solely based on appearance and daily use. If there is a convenient and low-cost detection method that can expose this phenomenon of adulteration, it will be able to expose adulteration and protect the interests of consumers quickly and conveniently. (2) Methods: MALDI-TOF, GC-MS, and mid-IR were used to develop low-cost and fast methods for identifying the authenticity of cosmetics. Five types of liquid and five types of emulsion cosmetics purchased from container and wholesale markets were analyzed using the three instruments mentioned above, and their spectra and acquired data were carefully compared to determine their authenticity. MALDI-TOF and GC-MS directly tested cosmetic samples, and mid-IR spectroscopy tested the ink on the outer packaging of cosmetics. (3) Results: The data procured by MALDI-TOF can provide a representation of its product attributes; two liquid samples and one paste sample demonstrated inconsistent test outcomes with the corresponding reference samples, suggesting contamination. The results of GC-MS can illustrate the substance count within cosmetic samples; the comparison outcomes of the total ion chromatogram indicate that one paste sample was a counterfeit. The results attained from mid-IR were consonant with those acquired from the MALDI-TOF analysis and GC-MS. (4) Conclusions: These three newly developed techniques can all be effectively utilized for the task of detecting cosmetic adulteration and quality control in the manufacturing process. With regard to user-friendliness and rapidity, both MALDI-TOF and mid-IR outperform GC-MS, demonstrating consistently superior levels of detection. Conversely, GC-MS has unique advantages in identifying emulsion cosmetics containing a high amount of weak polarity and volatile substances. Consequently, these corresponding methods could serve as efficient and cost-effective ways to detect authenticity issues in real-world cosmetic products.

Abstract Backgrounds The respiratory microbiota and radiomics correlate with the disease severity and prognosis of chronic obstructive pulmonary disease (COPD). We aim to characterize the respiratory microbiota and radiomics features of COPD patients and explore the relationship between them. Methods Sputa from stable COPD patients were collected for bacterial 16 S rRNA gene sequencing and fungal Internal Transcribed Spacer (ITS) sequencing. Chest computed tomography (CT) and 3D-CT analysis were conducted for radiomics information, including the percentages of low attenuation area below − 950 Hounsfield Units (LAA%), wall thickness (WT), and intraluminal area (Ai). WT and Ai were adjusted by body surface area (BSA) to WT/ $$\sqrt{\text{B}\text{S}\text{A}}$$ and Ai/BSA, respectively. Some key pulmonary function indicators were collected, which included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion lung carbon monoxide (DLco). Differences and correlations of microbiomics with radiomics and clinical indicators between different patient subgroups were assessed. Results Two bacterial clusters dominated by Streptococcus and Rothia were identified. Chao and Shannon indices were higher in the Streptococcus cluster than that in the Rothia cluster. Principal Co-ordinates Analysis (PCoA) indicated significant differences between their community structures. Higher relative abundance of Actinobacteria was detected in the Rothia cluster. Some genera were more common in the Streptococcus cluster, mainly including Leptotrichia, Oribacterium, Peptostreptococcus. Peptostreptococcus was positively correlated with DLco per unit of alveolar volume as a percentage of predicted value (DLco/VA%pred). The patients with past-year exacerbations were more in the Streptococcus cluster. Fungal analysis revealed two clusters dominated by Aspergillus and Candida. Chao and Shannon indices of the Aspergillus cluster were higher than that in the Candida cluster. PCoA showed distinct community compositions between the two clusters. Greater abundance of Cladosporium and Penicillium was found in the Aspergillus cluster. The patients of the Candida cluster had upper FEV1 and FEV1/FVC levels. In radiomics, the patients of the Rothia cluster had higher LAA% and WT/ $$\sqrt{\text{B}\text{S}\text{A}}$$ than those of the Streptococcus cluster. Haemophilus, Neisseria and Cutaneotrichosporon positively correlated with Ai/BSA, but Cladosporium negatively correlated with Ai/BSA. Conclusions Among respiratory microbiota in stable COPD patients, Streptococcus dominance was associated with an increased risk of exacerbation, and Rothia dominance was relevant to worse emphysema and airway lesions. Peptostreptococcus, Haemophilus, Neisseria and Cutaneotrichosporon probably affected COPD progression and potentially could be disease prediction biomarkers.

Abstract Loss of TGF-β-mediated growth suppression is a major contributor to the development of cancers, best exemplified by loss-of-function mutations in genes encoding components of the TGF-β signaling pathway in colorectal and pancreatic cancers. Alternatively, gain-of-function oncogene mutations can also disrupt antiproliferative TGF-β signaling. However, the molecular mechanisms underlying oncogene-induced modulation of TGF-β signaling have not been extensively investigated. Here, we show that the oncogenic BCR-ABL1 of chronic myelogenous leukemia (CML) and the cellular ABL1 tyrosine kinases phosphorylate and inactivate Smad4 to block antiproliferative TGF-β signaling. Mechanistically, phosphorylation of Smad4 at Tyr195, Tyr301, and Tyr322 in the linker region interferes with its binding to the transcription co-activator p300/CBP, thereby blocking the ability of Smad4 to activate the expression of cyclin-dependent kinase (CDK) inhibitors and induce cell cycle arrest. In contrast, the inhibition of BCR-ABL1 kinase with Imatinib prevented Smad4 tyrosine phosphorylation and re-sensitized CML cells to TGF-β-induced antiproliferative and pro-apoptotic responses. Furthermore, expression of phosphorylation-site-mutated Y195F/Y301F/Y322F mutant of Smad4 in Smad4-null CML cells enhanced antiproliferative responses to TGF-β, whereas the phosphorylation-mimicking Y195E/Y301E/Y322E mutant interfered with TGF-β signaling and enhanced the in vivo growth of CML cells. These findings demonstrate the direct role of BCR-ABL1 tyrosine kinase in suppressing TGF-β signaling in CML and explain how Imatinib-targeted therapy restored beneficial TGF-β anti-growth responses.

Objective: To establish a method for the determination of shrimp allergens in meat products by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Methods: Meat products (cooked ham, sausages and meatballs) with complex matrix components were selected as the detection target. The samples were extracted by ultrasonic in phosphate buffer solution (PBS) for 30 min, and acetonitrile was added to remove fat after centrifugation (10000 r/min, 15 ℃, 10 min). Finally, trypsin (1 mg/mL, 10 μL) was added to the sample diluents which had been mixed with internal peptide (2.5 μmol/L, 40 μL), and the enzymolysis process lasted 16 h at 37 ℃ before UPLC-MS/MS analysis. The samples were separated on a T3 column, and eluted by gradient elution with 0.1% formic acid aqueous solution and acetonitrile. The data was collected by multiple reaction monitoring (MRM) in positive ion mode, and quantified by internal standard method. Results: The method was used to determine the content of shrimp allergen in meat products, and the quantitative peptide had a good linear relationship with the determination coefficients 1.0000 in the range of 0.001~2.0 μmol/L. The limits of detection was 0.67 mg/kg, and the limits of quantification was 2.00 mg/kg. The recovery was 83.2%~104.5% and the precision was 2.63%~7.92% at three spiked levels. Conclusion: The method has the advantages of strong specificity, high sensitivity and good recovery. It was suitable for the screening and quantification of shrimp allergens in meat products.

With the characteristics of large space-time and satellite-ground network integration, the space integrated ground network has attracted much attention.Satellites can not only be used as emergency communication supplements, but also serve as air stations to expand the coverage of terrestrial networks, occupying an important position in both military and civilian scenarios.The entity authentication and key negotiation mechanism can prevent the malicious entities from joining the integrated network to steal users’ privacy, and guarantee network information security.In view of the characteristics of the high satellite-ground transmission delays, exposed links, limited processing capability and dynamic topology of the integrated network, a lightweight authentication scheme between satellites and ground suitable for double-layer satellite network was proposed to achieve a secure satellite networking architecture with session keys to protect data transmission.The scheme was based on symmetric cryptographic system, using lightweight cryptographic algorithms and introducing group key and hierarchical management mechanisms.The proposed scheme included three parts: inter-satellite authentication for geostationary earth orbit satellites, layer and inter-satellite authentication for same low earth orbit, and inter-satellite authentication for adjacent low earth orbit satellites.The group key and hierarchical management mechanism improved the efficiency of inter-group information transfer, reduced the authentication pressure on the ground control center, and enhanced the authentication security strength by realizing double verification in the three-entities authentication protocol.Different from the previous single scene authentication, the proposed authentication protocol took the form of multiplexing authentication parameters, which can realize the authentication requirements of dual scenes in one process.The results of Scyther, a protocol formal security simulation tool, show that the proposed scheme achieves secure access authentication.Compared with existing protocols, the proposed scheme improves authentication security and reduces communication and computational overhead.

Abstract Background Migraine is a disabling neurological disorder with the pathophysiology yet to be understood. The microstructural alteration in brain white matter (WM) has been suggested to be related to migraine in recent studies, but these evidence are observational essentially and cannot infer a causal relationship. The present study aims to reveal the causal relationship between migraine and microstructural WM using genetic data and Mendelian randomization (MR). Methods We collected the Genome-wide association study (GWAS) summary statistics of migraine (48,975 cases / 550,381 controls) and 360 WM imaging-derived phenotypes (IDPs) (31,356 samples) that were used to measure microstructural WM. Based on instrumental variables (IVs) selected from the GWAS summary statistics, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between migraine and microstructural WM. In forward MR analysis, we inferred the causal effect of microstructural WM on migraine by reporting the odds ratio (OR) that quantified the risk change of migraine for per 1 standard deviation (SD) increase of IDPs. In reverse MR analysis, we inferred the causal effect of migraine on microstructural WM by reporting the β value that represented SDs of changes in IDPs were caused by migraine. Results Three WM IDPs showed significant causal associations (p

We present here the first systematic search of short-timescale γ -ray flares from 29 high Galactic latitude BL Lac objects over 14 yr of Fermi Large Area Telescope data. Using a combined Bayesian Blocks and HOP algorithm, we identified seven high-quality orbital timescale flare segments from three sources and quantified 24 short-timescale flare structures. We then performed a comprehensive analysis of flare symmetry, power spectral density (PSD) of variability, and flux–photon index relation. The main results are as follows. (1) The flare symmetry parameter A shows a “U-shaped” distribution. Short-timescale flares are symmetric while long-timescale flares are asymmetric. The number of fast-rise, slow-decay and slow-rise, fast-decay type flares are equal. No correlation is found between A and peak/integral flux. No parameter evolution is seen between consecutive flares, either. The observations support a scenario where longer-timescale flares originate from the superposition of short, symmetric subhour flares. (2) PSD from yearly to hourly timescales is modeled using the CARMA process. At lower frequencies, the PSD follows the typical broken power-law form. The high-frequency region of the PSD exhibits a continuous power-law shape, indicating that γ -ray variability originates from a single physical process across all probed timescales. (3) The flux–photon index distribution shows a pattern of “harder-when-brighter” or “softer-when-brighter,” but becomes flat above a certain critical flux, with Γ ≈ 2. This behavior cannot be simply explained by a two-component or blazar sequence model, and we speculate it may be related to complex interplay between electron acceleration and cooling.

Leukemia is a fatal disease that requires the counting of White Blood Cells (WBCs) in bone marrow for diagnosis. However, bone marrow blood contains many types of leukocytes, some of which have subtle differences. To address this issue, we propose the WBC-GLAformer model, which comprises three parts: Low-level Feature Extractor (LFE), Global–Local Attention based Encoder (GLAE), and Discrimination Part Select (DPS). The LFE uses a convolutional neural network (CNN) to tokenize patches from the extracted low-level features. The GLAE combines the ability of the CNN to extract local features with the ability of the transformer to extract global features, thereby enriching the features of leukocyte images. The DPS improves the accuracy of leukocyte classification by selecting the discriminative regions. Our method achieves state-of-the-art results in the bone marrow leukocyte fine-grained classification dataset. Experimental results demonstrate that the model has good generalization on different datasets and is more robust to the optimizer. And visualization results show that the model can effectively focus on the discriminative parts of different cells. Code is available at https://github.com/ywj1/WBC-GLAformer

Rheumatoid arthritis (RA) is a progressive autoimmune disease characterized by chronic synovitis and articular destruction. Pain is the earliest and most important symptom. The Janus kinase/stat signaling pathway not only participates in the physiological processes such as the growth and differentiation of normal cells, but also plays a significant role in the pathological mechanisms such as pain in RA patients. Pain in RA patients is mediated by both inflammatory and non-inflammatory factors, including central sensitization and peripheral sensitization. Cytokines can regulate the nociceptor threshold through the JAK pathway, which leads to sensitization. In this review, we provide an overview of the physiological basis of pain modulation, the underlying importance of cytokines and JAK/STAT pathway in pain modulation, and finally introduce the performance of JAK inhibitors in clinical research. Having a better understanding of the mechanism of pain in RA may provide new therapeutic ideas and directions for the clinical improvement of pain in RA patients.

Generally, binary immiscible alloys have poor plasticity due to weak interfacial bonding. In this study, an amorphous interlayer was introduced between Mo and Cu phases in Mo-Cu alloys by using the high-temperature infiltration method. With the increase of infiltrated temperature from 1300 °C to 1450 °C, the thickness of the amorphous interlayer wad increased from 2 nm to 13 nm. The formation process, thermodynamic driving force, stability of the amorphous interlayer in Mo-Cu alloy, and its contribution to mechanical properties were systematically investigated. By using the “macroscopic atom approach” Miedema's model, the thermodynamic driving force and stability of the amorphous interlayer were proved. It was found that the thickening of the amorphous interlayer can significantly improve the interfacial bonding, thus leading to an increase in the tensile strength of the Mo-Cu alloy from 520 to 600 MPa and failure strain from 0.15 to 0.31 The deformation behavior of the Mo-Cu alloy shows that the amorphous interlayer can effectively absorb interfacial dislocations during deformation, and relieve the stress concentration at the interface by crystallization, thus delaying the initiation and propagation of cracks at phase boundaries, which broke through the limitation of the trade-off between strength and plasticity of such Mo-Cu immiscible materials.

Abstract Electrospinning is a promising technique for preparing bioartificial blood vessels. Nanofibers prepared by electrospinning can simulate the structure of extracellular matrix to promote cell adhesion and proliferation. However, thorn-like protrusions can appear as defects on electrospun scaffolds and coaxial electrospun nanofibers often have no clear core/shell structure, which can seriously affect the quality of bioartificial blood vessels. To address these problems, Tween 80 is added to the electrospinning solution, which results in a stable Taylor cone, eliminates the thorn-like protrusions on electrospun bioartificial blood vessels, and reduces interfacial effects due to different core/shell solutions during coaxial electrospinning. Simulations, biomechanical tests, and in vivo studies were performed. The results demonstrate the excellent mechanical properties and biocompatibility of the bioartificial blood vessel. This research provides a useful reference for optimizing the electrospinning process for fabricating bioartificial blood vessels. Graphical Abstract

The charging station malfunction may deny the charging service for the electric vehicles at the station. As a result, the vehicles need to select other stations. How to make an optimal selection is difficult for the owners. An optimal charging guidance strategy based on a weighted complex network is proposed for the owners to select the optimal station. All the charging stations are modelled as a complex network in which the stations and the roads among them are defined as nodes and edges, respectively. Furthermore, each edge is weighted by the state of charge (SOC) of the vehicle, the charging price, and the distance and traffic conditions between these two stations. The bigger edge weight indicates the smaller probability that the owner at one node of the edge select the other node of the edge for charging, and vice versa. Based on the weighted complex network model, the local load redistribution method is presented to guide the charging of vehicles at the malfunctioning station. Consequently, the optimal scheduling of the vehicles is realized under the guidance strategy proposed in this paper. Finally, some contrast experiments are carried out to illustrate the effectiveness and the superiority of the proposed method.

Post-drilling evaluation is an important part of prospect evaluation in the oil and gas exploration processes. With the comparative analysis of pre-drilling prediction and post-drilling results, the experience is summarized, and the deficiencies in pre-drilling evaluation and prediction are corrected and improved, so that the pre-drilling evaluation and prediction results of exploration targets are more accurate, and the success rate for the coming oil and gas exploration can be improved. Based on introducing the main contents and methods of post-drilling evaluation, the problems and solutions that need to be focused on in post-drilling evaluation are summarized in this paper. By analyzing the geological risk factors and reserve parameters of both successful and failed drilling, the key elements of large deviation between pre-drilling prediction and post-drilling estimation are compared, and the causes for the deviation are discussed and improved, which can be helpful on improving the geological explorers' ability of prediction and enhancing the success ratio of exploration in the following work.

Abstract Introduction A portable spirometer is a promising alternative to a traditional pulmonary function test (PFT) spirometer for respiratory function evaluation. Objectives This study aimed to investigate the accuracy of automated interpretation of the PFT measured by a portable Yue Cloud spirometer in Chinese adults. Methods The PFT was performed to evaluate subjects prospectively enrolled at Ruijin Hospital (n = 220). A Yue Cloud spirometer and a conventional Jaeger MasterScreen device were applied to each patient with a 20‐min quiescent period between each measurement. Pulmonary function parameters, including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), maximal expiratory flow at 25%, 50%, and 75% of the FVC (MEF25, MEF50, and MEF75, respectively), and maximal mid‐expiratory flow (MMEF), were compared by correlation analyses and Bland–Altman methods. The Yue Cloud spirometer automatically interpreted the PFT results, and a conventional strategy was performed to interpret the PFT results obtained by the Jaeger machine. Concordance of the categorization of pulmonary dysfunction, small airway dysfunction, and severity was analyzed by the kappa (κ) statistic. Results Significantly similar correlations of all variables measured with the two spirometers were observed (all p 0.80). Conclusion The portable Yue Cloud spirometer not only yields reliable measurements of pulmonary function but also can automatically interpret the PFT results.

Abstract In order to solve the problem that the current charging load forecasting accuracy is not high, it is difficult to simulate the actual charging load distribution of Electric Vehicles (EVs), and it is impossible to reasonably predict the future load, a charging load forecasting model based on Sparrow Search Algorithm (SSA) improved Random Forest Regression (RFR) is proposed. The SSA is used to enhance the ability of global optimization and local exploration. Combined with the advantages of the RFR model, such as low generalization error, fast convergence speed, and few adjustment parameters, the SSA was used to optimize the parameters of the decision tree number and the number of split nodes in the RFR, and the optimal value of the parameters is obtained, so as to obtain the optimal performance of the RFR. Firstly, based on the concept of travel chain and conditional probability distribution, the user's travel habits are described. Monte Carlo simulation method was used to simulate the driving, parking, and charging behaviours of a large number of EVs in different regions, so as to obtain the charging load of EVs in different regions. Then, a charging load forecasting model based on SSA improved RFR is established. Monte Carlo simulation results are used as sample data to predict the charging load of EVs in different regions. Finally, taking a certain area as an example, the experimental results show that the charging load prediction model based on Sparrow Search Algorithm improved Random Forest Regression (SSA‐RFR) can accurately predict the charging load of EVs in different regions, and the charging load of different regional types is obviously different. Compared with the RFR model and other literature models, the SSA‐RFR model has better prediction accuracy, which verifies the feasibility and superiority of SSA‐RFR model in EVs charging load prediction.

Stress fractures are rare, occurring in 1.5/100,000 high school athletes. High impact, repetitive loading participation in woman's sports, and being a white athlete have been identified as risk factors for stress fractures. Mostly treated conservatively, they are more common in the tibia (33%). Stress fractures requiring surgery, which are extremely rare, have been reported in the scaphoid, fifth metatarsal, and neck of femur. Herein, a 16-year-old adolescent patient with obesity presented with atypical knee pain after prolonged exercise. Advanced imaging revealed a stress fracture of the left tibia with a Salter–Harris type V fracture and varus deformity of the knee. We initially managed the fatigue fracture conservatively, followed by surgical correction of the varus deformity in the knee joint. The patient made a satisfactory recovery with equal limb length and no evidence of claudication. This is the first case of a proximal tibial metaphyseal stress fracture requiring surgery. The clinical manifestations of proximal tibial metaphyseal stress fractures and potential treatment strategies and the use of magnetic resonance for tibial stress fractures have been discussed. Understanding the location of unusual stress fractures can improve early diagnostic efficiency and reduce complication rates, healthcare costs, and recovery time.

BackgroundSelf-rated health (SRH), interviewer-rated health (IRH), and objective health reflect the overall health status from different aspects. This study aimed to investigate the associations of SRH, IRH, and objective health with mortality among Chinese older adults.MethodsThis study used data from the 2008 (baseline), 2011, 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. SRH and IRH were evaluated by questionnaire. Objective health was evaluated by the Chinese multimorbidity-weighted index (CMWI), which incorporated 14 diagnosed chronic diseases. SRH, IRH, and CMWI were assessed as: (1) baseline levels; (2) longitudinal changes by subtracting the values obtained in 2008 from the corresponding values in 2014; (3) trajectories by Group-Based Trajectory Modeling, respectively. The Cox proportional hazards model was used to explore the associations of baseline SRH, IRH, and CMWI, their changes, and trajectories with mortality.ResultsA total of 13,800 participants were included at baseline (2008). The baseline SRH ([hazard ratio] 0.93, [95% confidence interval] 0.91–0.96), IRH (0.84, 0.81–0.87), and CMWI (0.99, 0.98–1.00) in 2008 were significantly associated with 10-year mortality (2008 to 2018). Among 3,610 participants, the changes of SRH (0.93, 0.87–0.98), IRH (0.77, 0.71–0.83), and CMWI (0.97, 0.95–0.99) from 2008 to 2014 were significantly associated with 4-year mortality (2014–2018). The trajectories were divided into “high SRH/IRH/CMWI” and “low and declining SRH/IRH/CMWI.” Compared with “low and declining SRH/IRH/CMWI,” “high SRH” (0.58, 0.48–0.70), “high IRH” (0.66, 0.55–0.80), and “high CMWI” (0.74, 0.61–0.89) from 2008 to 2014 were significantly associated with 4-year mortality (2014–2018).ConclusionBaseline SRH, IRH, and CMWI, their changes and trajectories are all associated with mortality in Chinese older adults. It is possibly necessary to promote the use of cost-effective indicators in primary medical institutions to improve the health management of the older adults.

ObjectivesThis study aimed to identify the bacterial composition in the pancreatic fluid of severe and critical acute pancreatitis (SAP and CAP) patients.MethodsA total of 78 pancreatic fluid samples were collected from 56 SAP and CAP patients and analyze using aerobic culture and 16S rRNA gene next-generation sequencing. The clinical data of the patients were obtained from the electronic medical records.ResultsAmong the total 78 samples, 16S rRNA gene NGS identified a total of 660 bacterial taxa, belonging to 216 species in 123 genera. The dominant aerobic bacteria included Klebsiella pneumoniae, Acinetobacter baumannii, and Enterococcus faecium, while the dominant anaerobic bacteria included Bacteroides, Dialister invisus, and Olsenella uli. As compared to aerobic culturing, 95.96% (95/99) of the aerobic cultured bacteria were detected using the 16S rRNA gene NGS.ConclusionThe pancreatic infections in SAP and CAP patients might originate not only from the gut but also from the oral cavity and airways as well as related environments. Dynamic analysis of bacterial profile and abundance showed that some bacteria with low abundance might become the main pathogenic bacteria. There were no significant differences in the bacterial diversity between SAP and CAP.

BackgroundMedication is commonly used to treat migraine. However, patients may experience adverse events or fail to respond to medication. In recent years, neuromodulation techniques have emerged as potential non-pharmacological therapy for migraine. This article focuses on a systematic review and meta-analysis of randomized controlled trials of non-invasive vagus nerve stimulation (n-VNS) for migraine to determine the efficacy, safety and tolerability of n-VNS.MethodsWe searched PUBMED, EMBASE, and Cochrane Center Register of Controlled Trials databases up to July 15, 2022. Primary outcomes were monthly reduced migraine/headache days, and pain-free rates within 2 h. Secondary outcomes were ≥ 50% responder rate, headache intensity, monthly acute medication reduction days, and adverse events.ResultsMeta-analysis shows that non-invasive cervical vagus nerve stimulation (n-cVNS) significantly impacted ≥50% responder rate (OR, 1.64; 95% CI, 1.1 to 2.47; p = 0.02), but had no significant effect on reducing migraine days (MD, −0.46; 95% CI, −1.21 to 0.29; p = 0.23) and headache days (MD, −0.68; 95% CI, −1.52 to 0.16; p = 0.11). In contrast, low-frequency non-invasive auricular vagus nerve stimulation (n-aVNS) was found to significantly reduce the number of migraine days (MD, −1.8; 95% CI, −3.34 to −0.26; p = 0.02) and headache intensity (SMD, −0.7; 95% CI, −1.23 to −0.17; p = 0.009), but not the number of acute medication days per month (MD, −1.1; 95% CI, −3.84 to 1.64; p = 0.43). In addition, n-cVNS was found safe and well-tolerated in most patients.ConclusionThese findings show that n-VNS is a promising method for migraine management.

OBJECTIVES This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

IntroductionBladder cancer (BLCA) is a highly heterogeneous disease influenced by the tumor microenvironment, which may affect patients' response to immune checkpoint blockade therapy. Therefore, identifying molecular markers and therapeutic targets to improve treatment is essential. In this study, we aimed to investigate the prognostic significance of LRP1 in BLCA.MethodsWe analyzed TCGA and IMvigor210 cohorts to investigate the relationship of LRP1 with BLCA prognosis. We utilized gene mutation analysis and enrichment to identify LRP1-associated mutated genes and biological processes. Deconvolution algorithms and single-cell analysis were used to understand the tumor-infiltrated cells and biological pathways associated with LRP1 expression. Immunohistochemistry was conducted to validate the bioinformatics analysis.ResultsOur study revealed that LRP1 was an independent risk factor for overall survival in BLCA patients and was associated with clinicopathological features and FGFR3 mutation frequency. Enrichment analysis demonstrated that LRP1 was involved in extracellular matrix remodeling and tumor metabolic processes. Furthermore, the ssGSEA algorithm revealed that LRP1 was positively correlated with the activities of tumor-associated pathways. Our study also found that high LRP1 expression impaired patients' responsiveness to ICB therapy in BLCA, which was predicted by TIDE prediction and validated by IMvigor210 cohort. Immunohistochemistry confirmed the expression of LRP1 in Cancer-Associated Fibroblasts (CAFs) and macrophages in the tumor microenvironment of BLCA.DiscussionOur study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy.

Background: Programmed cell death-1 (PD-1) blockade has been shown to confer clinical benefit in cancer patients. Here, we assessed the level of serum interleukin 14α (IL14α) in patients receiving anti-PD-1 treatment. Methods: This prospective study recruited 30 patients with advanced solid cancer who received pembrolizumab treatment in Northern Jiangsu People’s Hospital between April 2016 and June 2018. The western blot analysis was used to assess the expression level of serum IL14α in patients at baseline and after 2 cycles of treatment. Interleukin 14α was performed using the unpaired 2-tailed Student test. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test. Results: The early change of IL14α after 2 cycles of anti-PD-1 therapy was calculated as delta IL14α % change = (IL14α level after 2 cycles − IL14α level before treatment)/IL14α level before treatment × 100%. Receiver operating characteristic (ROC) was analyzed to get a cutoff point of delta IL14α % change as 2.46% (sensitivity = 85.71%, specificity = 62.5%; area under the ROC curve [AUC] = 0.7277, P = .034). Using this cutoff to subgroup the patients, an improved objective response rate was observed in patients with a delta IL14α change higher than 2.46% ( P = .0072). A delta IL14α change over 2.46% was associated with a superior PFS ( P = .0039). Conclusions: Early changes of serum IL14α levels may be a promising biomarker to predict outcomes in patients with solid cancer following anti-PD-1 treatment.

In this paper, a specific type of Boron Carbide (B4C) with a high enrichment of 80 ± 0.3 at% 10B was prepared as an absorbing material for control rods in nuclear reactors. The enrichment of 10B was achieved using a chemical exchange method, followed by obtaining boron carbide powder through a carbothermal reduction method. Finally, B4C with a high enrichment of 68.3~74.2% theoretical density was obtained using a hot-pressed sintering process. This study focused on investigating the basic out-of-pile thermophysical properties of the high enrichment B4C compared to natural B4C reference pellets under non-irradiated conditions. These properties included the thermal expansion coefficient, thermal conductivity, emissivity, elastic limit, elastic modulus, and Poisson’s ratio. The research results indicate that the enriched B4C pellet exhibits good thermal stability and meets the technical requirements for mechanical capability. It was observed that porosity plays a significant role in determining the out-of-pile mechanical capability of B4C, with higher porosity samples having a lower thermal conductivity, elastic–plastic limit, and elastic modulus. In short, all the technical indexes studied meet the requirements of nuclear-grade Boron Carbide pellets for Pressurized Water Reactors.

Objectives: To assess the associations of the triglyceride and glucose (TyG) index with hypertension stages, phenotypes, and their progressions.Methods: The data originated from the China Health and Retirement Longitudinal Study. Multinomial logistic regression investigated the associations of the TyG index with hypertension stages (stage 1, stage 2), phenotypes (isolated systolic hypertension [ISH], isolated diastolic hypertension [IDH], systolic diastolic hypertension [SDH]), their progressions.Results: Compared with the lowest quartile of TyG index, the highest quartile was associated with increased risks of stage 1 hypertension (OR 1.71, 95% CI 1.38–2.13), stage 2 (1.74, 1.27–2.38), ISH (1.66, 1.31–2.11), IDH (2.52, 1.26–5.05), and SDH (1.65, 1.23–2.23). Similar results were found when TyG index was a continuous variable. From 2011 to 2015, a higher baseline TyG index was associated with normotension to stage 1 (per-unit: 1.39, 1.16–1.65), normotension to ISH (per-unit: 1.28, 1.04–1.56), and normotension to IDH (per-unit: 1.94, 1.27–2.97).Conclusion: The TyG index was associated with different hypertension stages, phenotypes, their progressions, and could be served as a surrogate indicator for early hypertension management.

Abstract Background Iron oxide nanoparticles have been approved by food and drug administration for clinical application as magnetic resonance imaging (MRI) and are considered to be a biocompatible material. Large iron oxide nanoparticles are usually used as transversal (T 2) contrast agents to exhibit dark contrast in MRI. In contrast, ultrasmall iron oxide nanoparticles (USPIONs) (several nanometers) showed remarkable advantage in longitudinal (T 1)-weighted MRI due to the brighten effect. The study of the toxicity mainly focuses on particles with size of tens to hundreds of nanometers, while little is known about the toxicity of USPIONs. Results We fabricated Fe3O4 nanoparticles with diameters of 2.3, 4.2, and 9.3 nm and evaluated their toxicity in mice by intravenous injection. The results indicate that ultrasmall iron oxide nanoparticles with small size (2.3 and 4.2 nm) were highly toxic and were lethal at a dosage of 100 mg/kg. In contrast, no obvious toxicity was observed for iron oxide nanoparticles with size of 9.3 nm. The toxicity of small nanoparticles (2.3 and 4.2 nm) could be reduced when the total dose was split into 4 doses with each interval for 5 min. To study the toxicology, we synthesized different-sized SiO2 and gold nanoparticles. No significant toxicity was observed for ultrasmall SiO2 and gold nanoparticles in the mice. Hence, the toxicity of the ultrasmall Fe3O4 nanoparticles should be attributed to both the iron element and size. In the in vitro experiments, all the ultrasmall nanoparticles (

The preparation and treatment of the sample has become an important part of the determination process, which directly affects the accuracy of detection. The preparation of the sample for final detection is actually a process of separation and transfer of the target to be tested from the sample matrix. The phase-transfer process of analysis and detection is the process of transferring the target substance to be measured from a complex multiphase system to a simple homogeneous system. This study shows a new phase-transfer process for food sample pretreatment in the determination of carbamate pesticides. Edible gum, xanthan gum, carrageenan, and gelatin were selected for purification testing from the perspective of eco-friendliness and safety. Phase-transfer purification process research was carried out on spinach and other foods. Compared with the commonly used QuEChERS method, the LC/MS results indicate that the straightforward carrageenan treatment process can significantly diminish the detection matrix effect and yield similarly superior detection parameters. The phase-transfer purification method with carrageenan has similar sensitivity and systematic error. The limits of detection and limits of quantitation of each pesticide compound in six plant sample substrates were 0.02–0.36 μg/kg and 0.06–1.9 μg/kg, respectively, which were lower than the residue limits here and abroad. Supplemental recoveries in six blank samples at 5, 20, and 100 μg/kg with the phase-transfer process method were better than those for the QuEChERS method. Positive determination results of actual samples using carrageenan phase-transfer purification proved that this method can be used for related detection from a practical point of view.

Objective To investigate the efficacy of modified percutaneous Achilles tendon lengthening for severe ankle joint deformity. Methods This retrospective case series study included 33 patients with an average age of 25.2 years who underwent surgery in our hospital from April 1, 2010 to March 1, 2018. Triple hemisection percutaneous Achilles tendon lengthening was performed. One stage surgery, other soft tissue surgery or bone correction surgery could be performed. After surgery, a plaster cast was used to fix the functional position, and rehabilitation training was carried out as planned. Complications during the perioperative period were recorded. Statistical analysis of the patients' visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) score before and at the last follow‐up was performed. The recurrence rate of Achilles tendon contracture at the last follow‐up and the patients' satisfaction rate were investigated. Results All patients were followed up, with an average follow‐up period of 56.31 months (8–104 months). All achieved good ankle joint function and appearance improvement And there were no infection or skin necrosis complications. In two cases, the incision was poorly healed at non‐Achilles tendon site and was cured by change of dressing. The average VAS score at the last follow‐up was reduced from (2 ± 1.48) points before surgery to (0.26 ± 0.51) points (P = 0.001), and the average AOFAS score was increased from (64.97 ± 13.56) points before surgery to (90.06 ± 10.06) points (P = 0.001). During the follow‐up period, there was no chronic rupture of Achilles tendon. There were two cases of recurrence of foot drop (5.7%), and the patients' satisfaction rate was 93.9%. Conclusion In the surgical treatment of severe ankle joint deformity, the application of triple hemisection percutaneous Achilles tendon lengthening for Achilles tendon contracture has the advantages of less trauma, beautiful incision, and reliable efficacy. The satisfaction rate of patients with this treatment is high, and it is worth promoting in the clinic.

Beijing’s Sub-Administrative Center (BSAC) is located in the South-eastern Beijing Plain, which exhibits severe subsidence. The rapid urban expansion in recent years has aggravated land subsidence and threatens the safe operation of Beijing. First, this study applied the persistent scatterer-interferometric synthetic aperture radar (PS-InSAR) to extract BSAC subsidence time series data. Second, combined with the index-based built-up index (IBI), expansion intensity index (EII), and expansion gradient index (EGI), the spatiotemporal characteristics of urban expansion were retrieved from optical data. Finally, we examined the urban expansion effects on land subsidence at the regional and single-building scales. The results showed that the maximum subsidence velocity in the BSAC reached 121 mm/year from 2015 to 2018, and the urban construction land area increased by 22%. At the regional scale, there existed a positive correlation between land subsidence and EGI or EII. This indicated that urban expansion had a certain impact on land subsidence. Therefore, we further explored the relationship between construction and land subsidence at the single-building scale. The engineering construction effects on land subsidence were divided into three periods, namely, rapid settlement, rebound, and stable periods. Although construction had a significant influence on land subsidence, it did not cause subsidence mutation.

Abstract Background Bladder cancer (BLCA) is the most common genitourinary tumor but lacks specific diagnostic biomarkers. Recent years have witnessed significant advances in the use and approval of immune checkpoint blockade (ICB) therapy to manage BLCA at advanced stages when platinum-based therapy has failed. The tumor microenvironment (TME) is essential in impacting BLCA patients' prognosis and responsiveness to ICB therapy. CXCL12 is a stromal secreted factor that was essentially involved in regulating the TME among cancers. In this article, we thoroughly investigated the TME regulating roles of CXCL12 in BLCA and revealed its critical involvement in the development of BLCA, which was closely correlated with inflammatory fibroblasts (iCAFs). Methods We examined the gene expression profiles in the TCGA and GEO database to reveal the potential association of CXCL12 with the carcinogenesis and prognosis of BLCA. The receiver operating characteristic curve was used to explore the accuracy of CXCL12 along with multiple iCAFs-associated genes in the diagnosis of BLCA. The MCP-COUNTER, ESTIMATE, and TIDE algorithms were applied to estimate the TME components and predict immunotherapy responsiveness. An iCAFs signature was constructed using the ssGSEA algorithm. The "maftool" R package analyzed the oncogenic mutations in BLCA patients. Bioinformatics analysis results were further validated through immunohistochemistry of clinical samples. IMvigor210 cohort was used to validate bioinformatic predictions of therapeutic responsiveness to immune checkpoint inhibitors. Results This manuscript revealed a significantly reduced expression of CXCL12 in BLCA compared with normal tissue. The expressions of various marker genes for iCAFs were also reduced considerably in BLCA tissues, highlighting the reduction of iCAFs in the pathogenesis of BLCA. Further studies revealed that CXCL12 and iCAFs were associated with pathological features, TME remodeling and aging in BLCA patients. The iCAFs signature further confirmed the intricate immunomodulatory roles of iCAFs in BLCA. Gene mutation analysis revealed the essential relationship between iCAFs and the mutation frequency of oncogenic genes, including TP53 and FGFR3. Meantimes, iCAFs levels also significantly affected BLCA patients' mutations in the TP53 and RTK-RAS pathways. Finally, our results confirmed the significant exclusion of CD8 + T cells by iCAFs, which further influenced the immunotherapy responsiveness in BLCA patients. Conclusions This article highlighted the impact of CXCL12 on the pathogenesis and progression of BLCA. The reduced expression levels of iCAFs markers, including CXCL12, were highly accurate in the diagnosis of BLCA, suggesting the reduction of iCAFs accompanied bladder carcinogenesis. However, both CXCL12 and iCAFs significantly impacted the prognosis and immunotherapy responsiveness for BLCA patients by remodeling the TME. Our results critically suggested the dual roles of iCAFs in the carcinogenesis and progression of BLCA. Further exploration of iCAFs might unravel potential diagnostic biomarkers and therapeutic targets for BLCA.

BackgroundThe unannounced standardized patient (USP) is the gold standard for primary health care (PHC) quality assessment but has many restrictions associated with high human and resource costs. Virtual patient (VP) is a valid, low-cost software option for simulating clinical scenarios and is widely used in medical education. It is unclear whether VP can be used to assess the quality of PHC. ObjectiveThis study aimed to examine the agreement between VP and USP assessments of PHC quality and to identify factors influencing the VP-USP agreement. MethodsEleven matched VP and USP case designs were developed based on clinical guidelines and were implemented in a convenience sample of urban PHC facilities in the capital cities of the 7 study provinces. A total of 720 USP visits were conducted, during which on-duty PHC providers who met the inclusion criteria were randomly selected by the USPs. The same providers underwent a VP assessment using the same case condition at least a week later. The VP-USP agreement was measured by the concordance correlation coefficient (CCC) for continuity scores and the weighted κ for diagnoses. Multiple linear regression was used to identify factors influencing the VP-USP agreement. ResultsOnly 146 VP scores were matched with the corresponding USP scores. The CCC for medical history was 0.37 (95% CI 0.24-0.49); for physical examination, 0.27 (95% CI 0.12-0.42); for laboratory and imaging tests, –0.03 (95% CI –0.20 to 0.14); and for treatment, 0.22 (95% CI 0.07-0.37). The weighted κ for diagnosis was 0.32 (95% CI 0.13-0.52). The multiple linear regression model indicated that the VP tests were significantly influenced by the different case conditions and the city where the test took place. ConclusionsThere was low agreement between VPs and USPs in PHC quality assessment. This may reflect the “know-do” gap. VP test results were also influenced by different case conditions, interactive design, and usability. Modifications to VPs and the reasons for the low VP-USP agreement require further study.

Purpose: The purpose of this study was to investigate the effect of MYC and TP53 comutations on the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in Chinese patients with advanced EGFR-positive nonsmall-cell lung cancer (NSCLC). Patients and methods: Tissue samples and information from 65 patients with advanced NSCLC in Northern Jiangsu People's Hospital were collected and analyzed by next-generation sequencing (NGS). Progression-free survival (PFS) and total survival (OS) were the main endpoints, and the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Result : Among 65 patients, 17 had TP53 and MYC wild-type mutations ( WT/WT ), 36 had TP53 mutant and MYC wild-type mutations ( TP53/WT ), and 12 had coexisting MYC/TP53 mutations ( MYC/TP53 ). When 12 patients with MYC/TP53 comutation were compared with the other two groups ( TP53/WT , WT/WT ), mPFS and mOS are significantly lower than those in the other two groups (mPFS: 4.1 months vs 6.0 months, 12.3 months, HR: 0.769, 95% CI: 4.592-7.608, P = .047. mOS: 14.6 months vs 24.1 months, 31.5 months, HR: 3.170, 95% CI: 18.786-31.214, P < .001), and the ORR, DCR of patients with MYC/TP53 comutation was lower than that of the other two groups (ORR, 25% vs 44.4%, 70.6%, P = .045. DCR, 58.3% vs 72.2%, 82.4%, P = .365). Conclusion: Patients with MYC/TP53 comutations with EGFR-positive advanced NSCLC are more likely to develop drug resistance after early treatment with EGFR-TKIs and have a worse clinical outcome.