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Abstract Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Abstract Background The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. Methods The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. Results PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. Conclusions Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.

Abstract Background Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20–50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. Methods PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). Results Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39–10.98, p

For ultra-high-resolution (UHR) image semantic segmentation, striking a balance between computational efficiency and storage space is a crucial research direction. This paper proposes a Feature Fusion Network (EFFNet) to improve UHR image semantic segmentation performance. EFFNet designs a score map that can be embedded into the network for training purposes, enabling the selection of the most valuable features to reduce storage consumption, accelerate speed, and enhance accuracy. In the fusion stage, we improve upon previous redundant multiple feature fusion methods by utilizing a transformer structure for one-time fusion. Additionally, our combination of the transformer structure and multibranch structure allows it to be employed for feature fusion, significantly improving accuracy while ensuring calculations remain within an acceptable range. We evaluated EFFNet on the ISPRS two-dimensional semantic labeling Vaihingen and Potsdam datasets, demonstrating that its architecture offers an exceptionally effective solution with outstanding semantic segmentation precision and optimized inference speed. EFFNet substantially enhances critical performance metrics such as Intersection over Union (IoU), overall accuracy, and F1-score, highlighting its superiority as an architectural innovation in ultra-high-resolution remote sensing image semantic segmentation.

Abstract The current generation of wearable sensors often experiences signal interference and external corrosion, leading to device degradation and failure. To address these challenges, the biomimetic superhydrophobic approach has been developed, which offers self‐cleaning, low adhesion, corrosion resistance, anti‐interference, and other properties. Such surfaces possess hierarchical nanostructures and low surface energy, resulting in a smaller contact area with the skin or external environment. Liquid droplets can even become suspended outside the flexible electronics, reducing the risk of pollution and signal interference, which contributes to the long‐term stability of the device in complex environments. Additionally, the coupling of superhydrophobic surfaces and flexible electronics can potentially enhance the device performance due to their large specific surface area and low surface energy. However, the fragility of layered textures in various scenarios and the lack of standardized evaluation and testing methods limit the industrial production of superhydrophobic wearable sensors. This review provides an overview of recent research on superhydrophobic flexible wearable sensors, including the fabrication methodology, evaluation, and specific application targets. The processing, performance, and characteristics of superhydrophobic surfaces are discussed, as well as the working mechanisms and potential challenges of superhydrophobic flexible electronics. Moreover, evaluation strategies for application‐oriented superhydrophobic surfaces are presented.

Let $ G $ be a finite abelian group with exponent $ \exp(G) $ and $ S $ be a sequence with elements of $ G $. We say $ S $ is a zero-sum sequence if the sum of the elements in $ S $ is the zero element of $ G $. For a positive integer $ t $, let $ \mathtt{s}_{t\exp(G)}(G) $ (respectively, $ \mathtt{s}'_{t\exp(G)}(G) $) denote the smallest integer $ \ell $ such that every sequence (respectively, zero-sum sequence) $ S $ over $ G $ with $ |S|\geq \ell $ contains a zero-sum subsequence of length $ t\exp(G) $. The invariant $ \mathtt{s}_{t\exp(G)}(G) $ (respectively, $ \mathtt{s}'_{t\exp(G)}(G) $) is called the Generalized Erdős-Ginzburg-Ziv constant (respectively, Modified Erdős-Ginzburg-Ziv constant) of $ G $. In this paper, we discuss the relationship between Generalized Erdős-Ginzburg-Ziv constant and Modified Erdős-Ginzburg-Ziv constant, and determine $ \mathtt{s}'_{t\exp(G)}(G) $ for some finite abelian groups.

Based on numerical simulations, the heat transfer and flow field of a turbine vane are analyzed and the film cooling is improved. The optimization objective is increasing the overall cooling effectiveness with cascade pressure loss factors staying almost unchanged. Thus, cylindrical film holes were replaced by laidback holes and V-crater holes. To analyze the effect of structural adjustment on the vane, pressure distributions, mass flow distributions, and heat transfer coefficients were investigated for internal and external cooling systems. To explain the advantages of shaped holes over cylindrical holes, the flow mechanisms, film superposition, discharge coefficients, blow ratios, and film cooling effectiveness were compared. Meanwhile, the influence of mass flow ratios and mainstream Reynolds numbers was analyzed. After optimization, at the design condition, the overall cooling effectiveness increased by 4.19% on the pressure surface and 1.78% on the suction surface. However, the cascade pressure loss factor increased by 0.26% only.

Human activity recognition (HAR) has recently become a popular research field in the wearable sensor technology scene. By analyzing the human behavior data, some disease risks or potential health issues can be detected, and patients’ rehabilitation progress can be evaluated. With the excellent performance of Transformer in natural language processing and visual tasks, researchers have begun to focus on its application in time series. The Transformer model models long-term dependencies between sequences through self-attention mechanisms, capturing contextual information over extended periods. In this paper, we propose a hybrid model based on the channel attention mechanism and Transformer model to improve the feature representation ability of sensor-based HAR tasks. Extensive experiments were conducted on three public HAR datasets, and the results show that our network achieved accuracies of 98.10%, 97.21%, and 98.82% on the HARTH, PAMAP2, and UCI-HAR datasets, respectively, The overall performance is at the level of the most advanced methods.

COVID-19 is an acute respiratory infectious disease caused by SARS-CoV-2. It was first reported in Wuhan, China in December 2019 and rapidly spread globally in early 2020, triggering a global pandemic. In December 2022, China adjusted the dynamic COVID-zero strategy that lasted for three years. The number of positive cases in China increased rapidly in the short term. Weihai was also affected during this period. We conducted genomic surveillance of SARS-CoV-2 variants in Weihai during this period, hoping to understand the changes in the genomic characteristics of SARS-CoV-2 before and after the adjustment of the epidemic policy. In this study,we collected SARS-CoV-2 positive samples from March 2022 to March 2023 in Weihai and performed SARS-CoV-2 whole genome sequencing on these samples using next-generation sequencing technology. we obtained a total of 704 SARS-CoV-2 whole genome sequences, and selected 581 high-quality sequences for further analysis. The analysis results showed that from March 2022 to November 2022, before the adjustment of epidemic policy, the COVID-19 cases in Weihai were mainly from four local clusters,which were caused by four variants, including BA.2,BA.1.1,P.1.15 and BA.5.2.1. Phylogenetic analysis showed that: In the same cluster,the sequences between each other were highly homologous, and the whole genome sequence were almost identical. After December 2022, the epidemic policy was adjusted, BF.7 and BA.5.2 became the dominant variants in Weihai, consistent with the main domestic strains in China during the same period. Phylodynamic analysis showed that BF.7 and BA.5.2 had a large amount of genetic diversities in December, and the effective population size of BF.7 and BA.5.2 also showed explosive growth in December. In conclusion, we reported the composition and dynamic trend of SARS-CoV-2 variants in Weihai from March 2022 to March 2023. We found that there have been significant changes in the variants and expansion patterns of SARS-CoV-2 before and after the adjustment of epidemic policies. But the dominant variants in Weihai were the same as the SARS-CoV-2 variants circulating globally at the same time and we found no persistently dominant variants or new lineages during this period.

Abstract High-speed visualization of three-dimensional (3D) processes across a large field of view with cellular resolution is essential for understanding living systems. Light-field microscopy (LFM) has emerged as a powerful tool for fast volumetric imaging. However, one inherent limitation of LFM is that the achievable lateral resolution degrades rapidly with the increase of the distance from the focal plane, which hinders the applications in observing thick samples. Here, we propose Spherical-Aberration-assisted scanning LFM (SAsLFM), a hardware-modification-free method that modulates the phase-space point-spread-functions (PSFs) to extend the effective high-resolution range along the z-axis by ~ 3 times. By transferring the foci to different depths, we take full advantage of the redundant light-field data to preserve finer details over an extended depth range and reduce artifacts near the original focal plane. Experiments on a USAF-resolution chart and zebrafish vasculatures were conducted to verify the effectiveness of the method. We further investigated the capability of SAsLFM in dynamic samples by imaging large-scale calcium transients in the mouse brain, tracking freely-moving jellyfish, and recording the development of Drosophila embryos. In addition, combined with deep-learning approaches, we accelerated the three-dimensional reconstruction of SAsLFM by three orders of magnitude. Our method is compatible with various phase-space imaging techniques without increasing system complexity and can facilitate high-speed large-scale volumetric imaging in thick samples.

Interleukin-37 (IL-37) is a newly identified anti-inflammatory cytokine, owning immunosuppressive activity in infectious diseases. The aim of this study was to investigate the regulatory function of IL-37 on CD8+ T cells during hepatitis B virus (HBV) infection. Eighteen acute hepatitis B (AHB) patients, thirty-nine chronic hepatitis B (CHB) patients, and twenty controls were enrolled. IL-37 concentration was measured by ELISA. IL-37 receptor subunits expressions on CD8+ T cells were assessed by flow cytometry. Purified CD8+ T cells were stimulated with HBV peptides and recombinant IL-37. Perforin and granzyme B secretion was investigated by ELISPOT. Programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) mRNA expressions were semi-quantified by real-time PCR. CD8+ T cell cytotoxicity was assessed in direct contact and indirect contact coculture with HepG2.2.15 cells. Plasma IL-37 level was down-regulated and negatively correlated with aminotransferase levels in AHB patients. There were no significant differences of IL-37 receptor subunits among AHB patients, CHB patients, and controls. Exogenous IL-37 stimulation suppressed HBV peptides-induced perforin and granzyme B secretion by CD8+ T cells in AHB patients, but not in CHB patients. Exogenous IL-37 stimulation did not affect proinflammatory cytokines secretion as well as PD-1/CTLA-4 mRNA expressions in CD8+ T cells in AHB and CHB patients. Exogenous IL-37 stimulation dampened HBV peptide-induced CD8+ T cell cytotoxicity in a cell-to-cell contact manner. The current data indicated that acute HBV infection might induce down-regulation of IL-37, which might be associated with enhanced CD8+ T cell cytotoxicity and liver damage.

The catalytic production of higher alcohols (HAs) is a promising path for converting CO2 into value-added chemical products. The application is still limited by the low selectivity of HAs (less than 10%) on most catalysts. Here, we report a tandem catalyst consisting of Mn-Cu-K modified iron carbide and CuZnAlZr catalyst. The modification of iron carbide with Mn, Cu and K promoters improves the formation of HAs (13.5% Sel.), and the construction of tandem catalysts with CuZnAlZr can further enhance the catalytic performance. By examining different catalyst filling methods and the filling ratio of the tandem catalyst, it was found that the powder mixing resulted in a higher selectivity of HAs with a mass ratio of the two components of 1:1, and a synergistic effect leads to a higher selectivity of HAs (15.5%) with about 40% of propanol and butanol among HAs.

Aiming at the shortcomings of low real-time, low applicability, and low welding precision of automatic welding system, a seam tracking system based on laser vision is designed. Use the laser vision sensor to collect the weld image and transmits it to the industrial control computer for processing. Using a median filter to eliminate noise impacts such as arc and splash. Then, this paper focuses on the combination of an improved image threshold segmentation algorithm is used to solve the optimal threshold to obtain the binary image. And the information of laser stripe and the background are separated, overcomes the problems that the researchers have encountered before, such as the unrecognized global optimal solution, and the inaccuracy of the segmentation caused by system jitter. Finally, combined with the improved upper and lower average method, least square method, and Hough transform, the weld feature points are identified and more ideal real-time weld tracking is realized. The experimental results show that the method can accurately track the weld feature points, and improve the detection speed.

Tight gas makes up a significant portion of the natural gas resources. There are tight gas reservoirs with great reserve and economic potential in the west Sichuan Basin, China. Due to the complex mineral component and heterogeneity of the thick tight sand formations, the reservoir parameters are challenging to evaluate from well logs using conventional methods, even the fundamental porosity. The mineral components must be considered. In this study, based on the analysis of different logging responses of varying lithologies, we introduced the complex reservoir analysis (CRA) method. CRA is always used in the carbonate reservoirs to calculate the different rock component volume fractions and can be used to classify the lithology and calculate the porosity simultaneously. By analyzing the component, a new equivalent component method (CRAE) is proposed based on the CRA method in this paper. In this method, the AC-CNL equation-calculated porosity is calibrated according to the core porosity data to set the rock components’ physical parameters. After calibration, the rock component fractions and porosity can be calculated accurately. Also, according to the relationship between the grain size and natural gamma-ray, a granularity median model was established. Six lithology types, including coarse-grained quartz sandstone and coarse-grained lithic sandstone, are distinguished, and the porosity is estimated in the study area. The identification results are compared with the mud logging data and other methods. It shows that this method is very well adequate in the tight sandstone gas reservoirs in the study area.

Microcomponent manipulation (MCM) technology plays a decisive role in assembling complex systems at the micro- and nanoscale. However, the existing micromanipulation methods are difficult to widely apply in the manufacturing of microelectromechanical systems (MEMSs) due to the limited manipulation space and complex application objects, and the manipulation efficiency is relatively low, which makes it difficult to industrialize these micromanipulating systems. To solve the above problems, this paper proposes an efficient metal MCM strategy based on the electrochemical method. To verify the feasibility and repeatability of the strategy, the finite element model (FEM) incorporating the hydrodynamic and electrochemical theories is used to calculate the local stress distribution of the contact position during the dynamic pick-up process. Based on the simulation results, we defined the relationship between the parameters, such as the optimal manipulating position and angle for picking, transferring and releasing. The failure behaviors of pick-up are built to realize the efficient three-dimensional manipulation of microcopper wire of 300 μm. By establishing a theoretical model and experimental verification, it was concluded that the middle point was the best manipulating position when picking up the microcopper wire, the most efficient picking angle was between 45 and 60 degrees for the pipette, and the average time was 480 s in three sets of picking–release manipulation experiments. This paper provides an achievable idea for different types of micro-object manipulations and promotes the rapid application of micromanipulation techniques in MEMSs.

The process of molecular evolution has many elements that are not yet fully understood. Evolutionary rates are known to vary among protein coding and noncoding DNAs, and most of the observed changes in amino acid or nucleotide sequences are assumed to be non-adaptive by the neutral theory of molecular evolution. However, it remains unclear whether fixed and standing missense changes in slowly evolving proteins are more or less neutral compared to those in fast evolving genes. Here, based on the evolutionary rates as inferred from identity scores between orthologs in human and Rhesus Macaques (Macaca mulatta), we found that the fraction of conservative substitutions between species was significantly higher in their slowly evolving proteins. Similar results were obtained by using four different methods of scoring conservative substitutions, including three that remove the impact of substitution probability, where conservative changes require fewer mutations. We also examined the single nucleotide polymorphisms (SNPs) by using the 1000 Genomes Project data and found that missense SNPs in slowly evolving proteins also had a higher fraction of conservative changes, especially for common SNPs, consistent with more non-conservative substitutions and hence stronger natural selection for SNPs, particularly rare ones, in fast evolving proteins. These results suggest that fixed and standing missense variants in slowly evolving proteins are more likely to be neutral.

Objective: To assess prognostic differences between primary and progressive muscle-invasive bladder cancer (MIBC) following radical cystectomy. Material and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to abstract MIBC data following radical cystectomy from 2000 to 2019. Patients were classified as either 'Primary' MIBC (defined as the presentation of muscle-invasive disease at initial diagnosis) or 'Progressive' MIBC (defined as a non-muscle invasive disease that later progressed to MIBC). Baseline characteristics for the two groups were balanced using a propensity score overlap weight (PSOW) technique. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Cox's proportional hazard regression was used to assess risk factors associated with overall survival (OS) and cancer-specific survival (CSS). Results: Six thousand six hundred thirty-two MIBC patients were identified in the SEER database. Among them, 83.3% (n=5658) were considered primaryMIBC patients, and 16.7% (n=974) were categorized as progressiveMIBC patients. Distribution of baseline covariates, including age, sex, race, T stage, N stage, tumour grade, marital status, and chemotherapy, were well-balanced after PSOWs were applied. After stable PSOW adjustments, Kaplan-Meier survival analysis showed that the CSS for progressive MIBC [hazard ratio (HR)=1.25, 95% confidence interval (CI): 1.12-1.38, P<0.001) was poorer than the primaryMIBC group. However, the difference in OS (HR=1.08, 95% CI: 0.99-1.18) was not significant (P=0.073). Multivariate analysis also suggested that patients with progressive MIBC have significantly poorer CSS (HR=1.24, 95% CI: 1.19-1.38, P<0.001) but not OS (HR=1.08, 95% CI: 0.99-1.18, P=0.089). Conclusion: CSS for progressive MIBC patients appears worse than for those with primary MIBC. This highlights the need to direct more resources for this patient population and particularly for high-risk cases of non-MIBC, where timely radical surgery will improve patients prognoses. [ABSTRACT FROM AUTHOR]