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ObjectiveAiming at the problem that it is difficult to model user requirements with fuzzy characteristics in existing ship conceptual scheme design (SCSD), this study focuses on a rapid SCSD system based on a fuzzy inference system (FIS) that can quickly obtain ship performance values that meet the user requirements and generate the corresponding ship hull design parameter values.MethodsFirst, the existing ship hull parameter data is collected and sorted as prior knowledge for hyper-parameter initialization in the process of user requirement modeling. Second, based on the fuzzy set theory, the user requirements are quantitatively mapped to the fuzzy space, and the sorted prior knowledge is used to infer the ship performance values that meet the user requirements in an interpretable way. Finally, the best ship hull design parameters are matched for each ship performance value that meets the user requirements, and through the "AND" principle in fuzzy set theory, the ship design parameters that meet all the user requirements for ship performance are further inferred and taken as the SCSD. ResultsThe experimental results show that the intelligent FIS can quickly infer multiple SCSDs with deviations within 3.5% according to the fuzzy user requirements within 30 seconds. ConclusionsThe intelligent FIS quantifies the fuzziness in user requirements, and after two stages of inference, the SCSD that meets the various user requirements is efficiently generated. The results of this study can provide useful references for rapid intelligent SCSD generation.

Summary: Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β′s metastatic response but not its anti-growth response. ERBB4 directly phosphorylates Tyr162 in the linker region of SMAD4, which enables SMAD4 to achieve a higher DNA-binding ability and potentiates TGF-β-induced gene transcription associated with epithelial-to-mesenchymal transition (EMT), cell migration, and invasion without affecting the genes involved in growth inhibition. These selective effects facilitate lung cancer metastasis in mouse models. This discovery sheds light on the previously unrecognized role of SMAD4 as a substrate of ERBB4 and highlights the selective involvement of the ERBB4-SMAD4 regulatory axis in tumor metastasis.

Mural cells are essential for maintaining the proper functions of microvasculatures. However, a key challenge of microvascular tissue engineering is identifying a cellular source for mural cells. We showed that in vitro , circulating fibrocytes (CFs) can (1) shear and stabilize the microvasculatures formed by vascular endothelial cells (VECs) in a collagen gel, (2) form gap junctions with VECs and (3) induce basement membrane formation. CFs transplanted into nude mice along with VECs in either collagen gel or Matrigel exhibited activities similar to those mentioned above, that is, sheathing microvasculatures formed by VECs, inducing basement membrane formation and facilitating the connection of the engineered microvasculatures with the host circulation. Interestingly, the behaviour of CFs also differs from that of human brain vascular pericytes (HBVPs) in vitro , which often infiltrate the lumen of capillary-like structures in a mosaic pattern, actively proliferate and exhibit lower endocytosis and migration capacities. We concluded that CFs are a suitable cellular source for mural cells in the construction of tissue-engineered microvasculatures.

Abstract Background Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). Methods We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein–protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. Results We identified 35 protein targets for migraine and its subtypes (p

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.

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.

Golden-flower fungus, the only dominant microorganism determining the Fu-brick tea quality through fermentation and the important microbe in Liupao tea, is considered a potential probiotic fungus based on its anti-obesity effect. However, the classif ication of golden-f lower fungi is still controversial; the anti-obesity effect of golden-f lower fungus polysaccharides remains unknown. In this study, we identify a golden-f lower strain as Aspergillus cristatus based on morphological characteristics and multigene phylogeny analysis, which resolves the controversy of classif ication. Moreover, we f ind A. cristatus polysaccharides (ACPS) attenuate obesity in rats. ACPS modulate gut bacterial composition, in which Akkermansia, Akkermansia muciniphila, Bacteroides, Romboutsia, Blautia, and Desulfovibrio are considered the core microbes regulated by ACPS.ACPS increase fecal total short-chain fatty acid content and serum, hepatic, and fecal total bile acid content. Furthermore, ACPS-induced gut microbiota alteration plays a causal role in the protection from obesity, according to a fecal transplantation experiment. Thus, ACPS ameliorate obesity by regulating gut microbiota and gut microbiota-related metabolites.

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.

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 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.

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 solve the privacy-preserving problem of both the user and the server in indoor positioning, outsourcing part of the calculation to cloud server in the process of using Paillier encryption was considered.The scheme not only protected the privacy of the user and the positioning server, but also avoided excessive computing and communication overhead.The main idea of the scheme was that the fingerprint database in the offline stage was established by the server firstly.The k-anonymity algorithm was combined with Paillier encryption in the online stage by the user, and the encrypted Wi-Fi fingerprints were sent to the positioning server.An aggregation of the received Wi-Fi fingerprints and database fingerprints were performed by the server.Then they were outsourced to the cloud server for decryption and distance calculation by the positioning server.Finally, the positioning result was obtained.Theoretical analysis and experimental results show that the proposed scheme is safe, effective and practical.

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

Aiming at the efficiency issue of handover authentication for a large number of vehicles in the 5G-V2X scenario, a secure and efficient group handover authentication protocol based on trajectory prediction was proposed.Firstly, the effect of completing key agreement protocol in advance was achieved by predicting vehicle trajectories.Secondly, vehicles with mobility relevance were treated as the same group through user grouping algorithms, and then all vehicles within the group were batch verified using certificateless aggregation signature technology.In addition, to address the vulnerability of aggregated signature technology to DoS attacks, a binary search method was used to quickly locate malicious users and improve the efficiency of group handover authentication protocol.Finally, the security analysis of the protocol was conducted using the formal verification tool Scyther, and compared with the existing optimal protocol, the computational efficiency is improved by 30%.

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

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.

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.

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.

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.

For the current user device access authentication mechanism requires ground participation to bring about large communication delays and poor scalability, a user device access authentication and re-authentication protocol in the ground default scenario in the space-ground integrated network was proposed, and further for the user device authentication process may occur in the power outage reconnection and AV asynchronization and other problems, a user device fast authentication mechanism and AV fast security synchronization mechanism under power failure reconnection scenario were proposed to ensured that users could safely accessed the satellite network and obtain related services.In the proposed scheme, the AV vector generated in the initial access authentication was used to assisted the re-authentication process to completed the authentication between entities without the involvement of the network control center, which guaranteed the communication system resilience.The formal verification tool Scyther showed that the proposed protocol was resistant to common protocol attacks, guaranteed the confidentiality and integrity of the communication process, and had a small signaling, computational, and bandwidth overhead, made it suitable for the satellite internet.

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.

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.

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.

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

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.

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.

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.

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.

(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.

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.

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

In order to solve the shortcomings of the existing Beidou user equipment access solutions such as prolonged authentication, and in response to the need of user privacy protection, a user equipment access authentication protocol based on location key was proposed, which realized the mutual authentication and session key negotiation between entities.Combining Beidou’s location information and master key to form a two-factor, the proposed protocol solved the security problem of the master key leaking due to the equipment being captured during the authentication process to some extent.The proposed protocol can meet different security requirements through the verification of the Scyther formal tool.Compared with other similar schemes, it has better performance overhead, and is suitable for Beidou satellite navigation system with limited node resources.

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.

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 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.

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.

In order to solve the current problems of electronic invoices, such as anti-counterfeiting, privacy leakage and low verification efficiency, an electronic invoice public verification architecture based on the national signature algorithm was proposed.Electronic invoice documents have complex data sources, sensitive user information on the ticket surface, frequent data flow and other characteristics as well as the demand for efficient public verification.Based on these motivations, the e-invoice generation and verification protocol was designed.Besides, a signature code generation scheme for invoice anti-counterfeiting was proposed based on certificate-free joint signature.Then multiple data verification and signatures of the invoicing party and the taxation authority can be realized.All kinds of invoice holders can not only verify the authenticity and data integrity of electronic invoices, but also publicly check the authenticity and data integrity of electronic invoices.The integration of data encryption algorithms protects user privacy data in electronic invoices, and at the same time can fulfill the requirements for authenticity or status verification under various invoice application scenarios.The checking party only needs to verify one signature to confirm the authenticity of the electronic invoice signed by both parties.Scyther security simulation tools were used to analyze the security of the proposed solution, which can verify the integrity and authenticity of the data source and check the confidentiality of the privacy data under various types of attacks.Compared with a typical overseas e-invoice checking scheme and a similar digital signature-based e-invoice checking scheme, the proposed scheme has obvious advantages in terms of checking efficiency and invoice file size.

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.

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.

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.

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.

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.

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.

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.