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Abstract Background The increasing incidence of diabetes mellitus has established diabetic cataracts (DC) as a significant worldwide public health issue. The mechanisms underlying DC remain unknown, and effective prevention and treatment strategies are lacking. Accordingly, we aimed to explore the role and mechanism behind N6-methyladenosine (m6A) in DC progression. Methods Methyltransferase-like 3 (METTL3), p21, Beclin1, LC3, and p62 expression levels were measured in human tissues. This study assessed total m6A levels and common m6A-regulated biomarkers in both in vitro and in vivo DC models. Autophagy flux was detected in vitro through Ad-mCherry-GFP-LC3B and Monodansylcadaverine (MDC) staining. Cellular senescence was assessed utilizing the senescence-associated β-galactosidase (SA-β-Gal) assay. Furthermore, the effect of METTL3 on SIRT1 mRNA modification was demonstrated, and its mechanism was elucidated using RT-qPCR, western blot, RNA stability assays, and RIP analysis. Results METTL3, p21, and p62 expression levels were elevated in lens epithelial cells (LECs) from DC patients, while Beclin1 and LC3 levels were reduced. Silencing METTL3-mediated m6A modifications restored high-glucose-induced autophagy inhibition and prevented premature senescence in LECs. Notably, SIRT1720 and Metformin significantly enhanced autophagosome generation and delayed cellular senescence. The m6A-reading protein YTHDF2 bound to m6A modifications, and YTHDF2 silencing significantly reduced METTL3-mediated SIRT1 inactivation. Conclusions METTL3 induces senescence in DC by destabilizing SIRT1 mRNA in an m6A-YTHDF2-dependent manner. The METTL3-YTHDF2-SIRT1 axis is a key target and potential pathogenic mechanism in DC.

Abstract Background Magnetic Resonance Imaging (MRI) is extensively utilized in clinical diagnostics and medical research, yet the imaging process is often compromised by noise interference. This noise arises from various sources, leading to a reduction in image quality and subsequently hindering the accurate interpretation of image details by clinicians. Traditional denoising methods typically assume that noise follows a Gaussian distribution, thereby neglecting the more complex noise types present in MRI images, such as Rician noise. As a result, denoising remains a challenging and practical task. Method The main research work of this paper focuses on modifying mask information based on a global mask mapper. The mask mapper samples all blind spot pixels on the denoised image and maps them to the same channel. By incorporating perceptual loss, it utilizes all available information to improve performance while avoiding identity mapping. During the denoising process, the model may mistakenly remove some useful information as noise, resulting in a loss of detail in the denoised image. To address this issue, we train a generative adversarial network (GAN) with adaptive hybrid attention to restore the detailed information in the denoised MRI images. Result The two-stage model NRAE shows an improvement of nearly 1.4 dB in PSNR and approximately 0.1 in SSIM on clinical datasets compared to other classic models. Specifically, compared to the baseline model, PSNR is increased by about 0.6 dB, and SSIM is only 0.015 lower. From a visual perspective, NRAE more effectively restores the details in the images, resulting in richer and clearer representation of image details. Conclusion We have developed a deep learning-based two-stage model to address noise issues in medical MRI images. This method not only successfully reduces noise signals but also effectively restores anatomical details. The current results indicate that this is a promising approach. In future work, we plan to replace the current denoising network with more advanced models to further enhance performance.

Abstract Background Parasitic diseases remain a serious public health problem in China. Health education aimed at disseminating health-related knowledge and promoting healthy behaviours, plays a crucial role in the prevention and control of parasitic diseases. This study aims to develop a tool to measure the parasitic disease health literacy of residents in China. Methods Scale development was based on qualitative and quantitative methods. Qualitative method included focus group discussions and Delphi consultations. A methodological design with multistage sampling and a pilot study was used to evaluate the questionnaire. The scale’s reliability was tested using Cronbach’s α and split-half reliability, while its construct validity was assessed using confirmatory factor analysis. The scale’s passing score was determined using the receiver operating characteristic curve. A cross-sectional survey was conducted in six districts of the prefecture of Jiangsu and residents aged 14–69 years in the participating townships were randomly selected based on their location. Results The health literacy indicator system for parasitic diseases included 3 first-level, 9 s-level and 23 third-level indicators. The 23-item questionnaire demonstrated good internal consistency (Cronbach’s alpha = 0.774) and split-half reliability (Spearman-Brown coefficient = 0.778). The questionnaire’s passing score was 60. A total of 990 valid questionnaires were collected from participants in three cities. The percentage of participants with health literacy regarding parasitic diseases was 15.8%. Their scores were influenced by age, income, employment, and educational level. Conclusions Health literacy of parasitic diseases is an integrated indicator rather than just knowledge or behavior information. The correlation between knowledge and behavior is weak. The capacity for healthy behavior of parasitic disease is associated with the location and culture of the city. For neglected diseases, it is important for people to talk positively about their behaviors with a doctor.

Abstract Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

Abstract Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI’s robust and consistent performance.

Abstract Intercellular cell adhesion molecule-1 (ICAM-1) is frequently overexpressed in non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the mechanism underlying the negative effects of neoplastic ICAM-1 remains obscure. Herein, we demonstrate that the survival of NSCLC cells but not normal human bronchial epithelial cells requires an anti-apoptosis signal triggered by fibrinogen γ chain (FGG)–ICAM-1 interaction. ICAM-1–FGG ligation preserves the tyrosine phosphorylation of ICAM-1 cytoplasmic domain and its association with SHP-2, and subsequently promotes Akt and ERK1/2 activation but suppresses JNK and p38 activation. Abolishing ICAM-1–FGG interaction induces NSCLC cell death by activating caspase-9/3 and significantly inhibits tumor development in a mouse xenograft model. Finally, we developed a monoclonal antibody against ICAM-1–FGG binding motif, which blocks ICAM-1‒FGG interaction and effectively suppresses NSCLC cell survival in vitro and tumor growth in vivo. Thus, suppressing ICAM-1–FGG axis provides a potential strategy for NSCLC targeted therapy.

Abstract Non-iatrogenic trauma of the iliac artery is rarely reported but is always life-threatening. In this report, we describe the case of a child with complete transection and partial disappearance of the iliac artery caused by bicycle handlebar impalement. He experienced catastrophic hemorrhage, malignant arrhythmia, and difficulty in exploring transected vessel stumps. Aggressive infusion, blood transfusion in time, and pediatric vascular characteristics help delay the deterioration during anesthesia induction. Eventually he was successfully rescued by performing interventional balloon occlusion and open revascularization after more than 7 h post-trauma. A series of interventions and precautionary methods may benefit such severely injured patients; thus, these methods should be highlighted.

Abstract One question in lymphocyte homing is how integrins are rapidly activated to enable immediate arrest of fast rolling lymphocytes upon encountering chemokines at target vascular beds given the slow chemokine-induced integrin inside-out activation. Herein we demonstrate that chemokine CCL25-triggered Ca2+ influx induces T cell membrane-proximal external Ca2+ concentration ([Ca2+]ex) drop in 6 s from physiological concentration 1.2 mM to 0.3 mM, a critical extracellular Ca2+ threshold for inducing αLβ2 activation, triggering rapid αLβ2 activation and T cell arrest before occurrence of αLβ2 inside-out activation. Talin knockdown inhibits the slow inside-out activation of αLβ2 but not [Ca2+]ex drop-triggered αLβ2 quick activation. Blocking Ca2+ influx significantly suppresses T cell rolling-to-arrest transition and homing to skin lesions in a mouse psoriasis model, thus alleviating skin inflammation. [Ca2+]ex decrease-triggered rapid integrin activation bridges the gap between initial chemokine stimulation and slow integrin inside-out activation, ensuring immediate lymphocyte arrest and subsequent diapedesis on the right location.

Planktonic microorganisms have been recognized as important components in biogeochemical cycling in lakes. However, research into the impact of phyllosphere microorganisms, particularly those involved in carbon cycling, on CO2 fluxes in macrophyte-dominated lakes within the context of global environmental changes remains scarce. Here, by employing high-throughput sequencing techniques, we experimentally tested how nutrient enrichment, top-down effects of fish and increases in dissolved organic carbon (DOC) affect CO2 exchange flux at the water-air interface by altering the community structure and functioning of phyllosphere bacteria on macrophytes. We found that our mesocosm ecosystems exhibited a net absorption of CO2, but nutrient enrichment significantly decreased the absorption ability. Mantel tests and multiple regression modeling also showed that eutrophication-associated parameters (total nitrogen, total phosphorus and ammonium nitrogen), pH, and extinction coefficient were the key drivers influencing abundance of phyllosphere functional microorganisms. In addition, these experimental treatments significantly altered the composition, diversity and co-occurrence networks of carbon cycling-associated phyllosphere microorganisms, which impacted the CO2 flux. Structural equation models and linear regression further showed that the Shannon Index of phyllosphere functional microorganisms related to carbon cycling (rather than plant volume inhabited - PVI) had a significant positive impact on CO2 fixation. This means that environmental changes—especially eutrophication—may hinder carbon sequestration by decreasing the diversity of phyllosphere microorganisms rather than reducing the abundance of submerged macrophytes. This study increases our understanding of carbon cycling processes in aquatic environments from a management perspective by emphasizing the importance of protecting the diversity of phyllosphere microorganisms in macrophyte-dominated lakes.

Background: Neutrophil extracellular trap (NET) is associated with host response, tumorigenesis, and immune dysfunction. However, the link between NET and the tumor microenvironment (TME) of gastric cancer (GC) remains unclear. Our study aims to characterize the expression patterns of NET-related genes and their relationships with clinicopathological characteristics, prognosis, TME features, and immunotherapy efficacy in GC cohorts. Methods: Transcriptomic and single-cell RNA sequencing profiles of GC with annotated clinicopathological data were obtained from TCGA-STAD (n = 415), GSE62254 (n = 300), GSE15459 (n = 192), and GSE183904 (n = 26). The consensus cluster algorithm was used to classify tumor samples into different NET-related clusters. A NET-related signature was constructed using LASSO regression and verified in four immunotherapy cohorts. ROC and Kaplan-Meier analyses were conducted to evaluate the predictive and prognostic value of the model for immunotherapy efficacy. Results: This study identified two NET-related clusters with distinct clinicopathological features, prognosis, and TME landscapes. The high NET-related cluster, characterized by increased NET-related gene expression, exhibited more aggressive behavior and a worse prognosis (HR = 1.63, P = 0.004) than the low NET-related cluster. DEGs were primarily involved in the chemokine/cytokine-associated pathways. Moreover, the high NET-related cluster had significantly higher levels of TME scores, immune infiltration, and immune effectors (all P

During pipe installation, compacting soil at pipe sides causes an initial pipe deformation which is known as the “peaking” effect. However, in conventional pipe design codes, only pipe deformation caused by vertical overburden is considered while the “peaking” effect is ignored. In this study, a full-scale test was conducted on a Grade X52 steel pipe with a diameter of 600 mm to investigate the impacts of both soil compaction and vertical overburden on pipe deformation. Soil compaction and external load were found to elongate and shorten the vertical pipe diameter, respectively. The “peaking” effect was observed during the installation procedure accompanied by the highest pipe stress measured at the pipe crown. Then, a two-dimensional finite element model was created and validated based on the calculated pipe stresses from the experimental study. A parametric study was performed thereafter to numerically study the impacts of soil water content, pipe wall thickness, compaction pressure, and lift thickness on pipe responses due to soil compaction and external load. An increase in the “peaking” effect is observed with increasing soil water content and compaction pressure, while an increase in pipe wall thickness or lift thickness would cause a decrease in the “peaking” effect.

Upland crop-rice cropping systems (UCR) facilitate sustainable agricultural intensification. Accurate UCR cultivation mapping is needed to ensure food security, sustainable water management, and rural revitalization. However, datasets describing cropping systems are limited in spatial coverage and crop types. Mapping UCR is more challenging than crop identification and most existing approaches rely heavily on accurate phenology calendars and representative training samples, which limits its applications over large regions. We describe a novel algorithm (RRSS) for automatic mapping of upland crop–rice cropping systems using Sentinel-1 Synthetic Aperture Radar (SAR) and Sentinel-2 Multispectral Instrument (MSI) data. One indicator, the VV backscatter range, was proposed to discriminate UCR and another two indicators were designed by coupling greenness and pigment indices to further discriminate tobacco or oilseed UCR. The RRSS algorithm was applied to South China characterized by complex smallholder rice cropping systems and diverse topographic conditions. This study developed 10-m UCR maps of a major rice bowl in South China, the Xiang-Gan-Min (XGM) region. The performance of the RRSS algorithm was validated based on 5197 ground-truth reference sites, with an overall accuracy of 91.92%. There were 7348 km2 areas of UCR, roughly one-half of them located in plains. The UCR was represented mainly by oilseed-UCR and tobacco-UCR, which contributed respectively 69% and 15% of UCR area. UCR patterns accounted for only one-tenth of rice production, which can be tripled by intensification from single rice cropping. Application to complex and fragmented subtropical regions suggested the spatiotemporal robustness of the RRSS algorithm, which could be further applied to generate 10-m UCR datasets for application at national or global scales.

Abstract Object This study aimed to investigate the changes in the translucency and color of four different multi-layered zirconia materials when the sintering temperature were inaccurate. Materials and methods Two hundred zirconia samples (11 × 11 × 1.0 mm) of four multi-layered zirconia, Upcera TT-GT (UG), Upcera TT-ML (UM), Cercon xt ML (CX), and Lava Esthetic (LE), were divided into five subgroups according to the sintering temperature: L1 (5% lower temperature), L2 (2.5% lower temperature), R (recommended sintering temperature), H2 (2.5% higher temperature), H1 (5% higher temperature). After sintering, color coordinates were measured. Then the translucency parameter (TP) values, and the color differences (between the inaccurate sintering temperature and the recommended temperature) of each zirconia specimen were calculated. Statistical analysis was performed by using three-way ANOVA tests, the one-way ANOVA, and Tukey’s post hoc test. Results Three-way ANOVA results showed that material type, sintering temperature, specimen section, and their interactions significantly influenced the TP values (except for the interactions of specimen section and sintering temperature) (P .05). Compared with recommended sintering temperature, higher sintering temperature caused higher TP values for CX, but lower for LE. Three-way ANOVA results showed that material type, sintering temperature, and their interactions significantly influenced the ∆E 00 values (P

To achieve the high-value utilization of squid skin obtained from squid processing, this study utilized an enzymatic approach to prepare protein peptides. The enzymatic hydrolysis parameters were optimized using single factor and response surface tests, with the concentration of peptide and trichloroacetic acid-nitrogen soluble index (TCA-NSI) serving as evaluation criteria. The amino acid composition, molecular weight distribution, peptide sequence, antioxidant activity, and in vitro simulated digestive properties of the prepared protein peptides were also thoroughly characterized. The results showed that the optimal conditions for enzymatic hydrolysis were as follows: Enzymatic temperature of 43.50 ℃, enzymatic time of 100 minutes, enzymatic pH of 7.50, trypsin to alkaline protease ratio of 2:1, and enzyme dosage of 4000 U/g. Under these specified conditions, the TCA-NSI achieved a value of 89.02%±0.66%. The prepared protein peptides exhibited a well-balanced amino acid composition, with an essential amino acid index (EAAI) value of 0.90. Furthermore, the prepared protein peptides encompassed a total of 43 polypeptide sequences, with 38 of these segments exhibiting molecular weights below 1800 Da. The IC50 values for scavenging DPPH radical, ABTS+ radical, and hydroxyl radical were determined to be 0.61, 0.28 and 1.95 mg/mL, respectively. Notably, the antioxidant activity remained favorable even after undergoing simulated gastrointestinal digestion in vitro. These findings serve to establish a solid theoretical basis for the advancement and exploitation of byproducts derived from squid processing, as well as their subsequent value-added utilization.

Abstract Obstruction and/or reflux compromise during venous emptying can facilitate different pathophysiologies in chronic venous insufficiency (CVI). We present a patient with persistent lower limb CVI edema caused by post-thrombotic syndrome (PTS), who responded well to femoral vein valve therapy via axillary vein bypass after unsuccessful valvuloplasty, and led a normal life. During a 12 month observation period, bridging vessels completely restored original anatomical structures. In a literature study, no similar surgeries were reported, but we show that this operation may be feasible in selected patients.

Abstract Background Aortoesophageal fistula (AEF) is a rare condition characterized by communication between the aorta and esophagus. AEF caused by an esophageal foreign body is even rare, and there is currently no recommended standard treatment protocol. We report a case of delayed aortic rupture after the endoscopic removal of a fish bone, which was successfully treated with a combined approach of vascular stenting and thoracic surgery. Case presentation A 33-year-old man presented to the hospital after experiencing chest discomfort for 3 days following the accidental ingestion of a fish bone. Under endoscopic guidance, the fish bone was successfully removed, and the patient was subsequently admitted for medical therapy. On the fourth postoperative day, the patient suddenly developed hematemesis, and chest computed tomography angiography revealed the presence of an AEF. This necessitated urgent intervention; hence, thoracic surgery was performed and a vascular-covered stent was placed. Following the surgical procedure, the patient received active medical treatment, recovered well, and was successfully discharged from the hospital. Conclusions In patients with esophageal perforation caused by foreign bodies, hospitalization for observation, computed tomography angiography examination, early use of antibiotics, and careful assessment of aortic damage are advised. Thoracic endovascular aortic repair and esophageal rupture repair may have benefits for the treatment of AEF.

Abstract In China, according to the ‘Technical Operating Procedures for Blood Stations (2019 Edition),’ blood stations are authorized to utilize Chemiluminescence Immunoassay (CLIA) to detect pathogen markers linked with transfusion-transmissible infections. However, currently, there is no approved CLIA reagent for the screening of blood-borne diseases in China, specifically for the detection of Hepatitis B surface antigen. The objective of this research project is to conduct a comprehensive evaluation of the performance of the Wantai Chemiluminescent Microparticle Hepatitis B surface antigen reagent. This study evaluates the performance of the Wantai Chemiluminescent Microparticle Immunoassay (CMIA) on the Wan200 + analyzer in screening for Hepatitis B Surface Antigen (HBsAg) in blood samples. The clinical trial component of this evaluation is included as part of the documentation submitted to the National Medical Products Administration (NMPA) of China for the approval of blood screening reagents. The evaluation plan of this study encompasses two main components: clinical trials and performance assessment. We adopted a controlled trial design, utilizing the WanTai Chemiluminescent Microparticle Immunoassay (CMIA) on the Wan200 + analyzer and the Enzyme-Linked Immunosorbent Assay (ELISA) to screen for Hepatitis B Surface Antigen (HBsAg) in routine blood donor samples and reference serum panel samples. To ensure the accuracy of the screening, we additionally employed Abbott's ELISA reagents and HBV DNA for validation. The assessment primarily focused on key performance indicators such as sensitivity, specificity, and analytical sensitivity. Moreover, this clinical trial data has been included as part of the submission to China's National Medical Products Administration (NMPA). In the clinical trials of this study, a total of 10,470 blood donor samples underwent simultaneous testing using both CMIA and ELISA methods. Across two clinical trials, there was remarkable concordance between CMIA and the two ELISA reagents, with Kappa values exceeding 0.82. Among the 269 samples that were double-reactive in the enzyme immunoassay (ELISA) tests, CMIA exhibited a 100% reactivity detection rate. However, CMIA produced 14 and 6 false-positive results in the respective clinical trials, resulting in specificities of 99.73% and 99.89%. In contrast, the specificities for Wantai ELISA and Xin Chuang ELISA were both greater than 99.94%.When testing samples in the gray zone serum plates, CMIA's detection limit significantly exceeded that of the two ELISA assays. CMIA had a detection cutoff of 0.05 IU/mL, while the two ELISA reagents had cutoffs of 0.1 IU/mL and 0.09 IU/mL, respectively. CMIA's detection limits for the adr and adw subtypes were 0.05 IU/mL, and for the ay subtype, it was 0.1 U/mL. The detection limit for 10 HBV mutant samples was 0.5 U/mL. In 165 cases where ELISA tested negative but HBV DNA tested positive, CMIA detected 5 HBsAg-positive samples. This study evaluated the performance of the Wantai CMIA in screening for HBsAg among blood donors. The results demonstrate outstanding performance of CMIA in both clinical trials and performance assessments, detecting all true positive samples with a sensitivity of 100%. It exhibits excellent concordance with the two ELISA assays. Of particular note is its superiority in early detection of HBsAg in the screening of early-stage hepatitis B infections, reducing the window period compared to ELISA. CMIA achieves a specificity exceeding 99.73% for negative blood donors, aligning with the European Union's standards for blood screening assay specificity. In summary, Wantai's CMIA displays high sensitivity and specificity in blood donor screening, making it suitable for screening blood donors in China.

In situ online observation of surface morphology during degradation processes is of paramount importance for exploring the stability of organic photovoltaic materials. In this study, we designed an in situ online characterization system based on hyperspectral and neural network technologies, and observed the degradation processes of P3HT:PCBM thin film materials. The system is capable of collecting hyperspectral image data from 101 channels within the 400–700 nm wavelength range for characterizing detailed surface features of materials. Additionally, to automate the processing of hyperspectral image data, we designed a spectral image segmentation algorithm based on neural networks and proposed a foreground attention mechanism to improve the segmentation accuracy of the algorithm. The experimental results indicate that the system can achieve high spectral characterization of P3HT:PCBM thin film materials and automate image data processing through artificial intelligence algorithms, with an image segmentation accuracy of 99.62 %. Furthermore, owing to the higher spectral resolution of this system and its computer-assisted analysis capabilities for material image data, not only are the in-situ variations in size, density, and formation rate of aggregates formed during the thermal degradation process of P3HT:PCBM thin film materials experimentally analyzed, but also the fluorescence changes at the edges of aggregates during the photodegradation process are revealed. The reliable code can be found at the following link: https://github.com/HyperSystemAndImageProc/IONFMDP-UHHNN.

Abstract During myocardial ischaemia‒reperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis‐mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low‐intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI‐induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome‐dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F‐actin pathway. Meanwhile, F‐actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS‐induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome‐dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non‐invasive treatment for MIRI.

This in vitro study was to evaluate the effect of different non-thermal atmospheric pressure plasma (NTP) on shear bond strength (SBS) between yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and self-adhesive resin cement. In this study, The Y-TZP specimens were divided into 4 groups according to the surface treatment methods as follows: Control (no surface treatment), Sb (Sandblasting), AP(argon NTP), and CP(20 % oxygen and 80 % argon combination NTP). Y-TZP specimens were randomly selected from each group to observe and test the following indexes: scanning electron microscope to observe the surface morphology; atomic force microscope to detect the surface roughness; contact angle detector to detect the surface contact angle; energy spectrometer to analyze the surface elements. Then, resin cement (Rely X–U200) was bonded to human isolated teeth with Y-TZP specimens to measure SBS. The results showed that for the SE test, the NTP group was significantly higher than the control group (p 0.05). This study shows that non-thermal atmospheric pressure plasma can improve the shear bond strength of Y-TZP by increasing the surface energy. The addition of oxygen ratio to argon is more favorable to increase the shear bond strength and is worth further investigation.

Hyperspectral image (HSI) classification has become a popular research topic in recent years, and transformer-based networks have demonstrated superior performance by analyzing global semantic features. However, using transformers for pixel-level HSI classification has two limitations: ineffective capture of spatial-spectral correlations and inadequate exploitation of local features. To address these challenges, we propose a dual-dimension self-attention (D2SA) mechanism that fully exploits HIS's high spectral-spatial correlation by using two separate branches to model the global dependence of features from the spectral and spatial dimensions. Additionally, we develop a multilayer residual convolution module that extracts local features and introduces shallow-deep feature interactions to obtain more discriminative representations. Based on these components, we propose a dual-dimension spectral-spatial bottleneck transformer (D2S2BoT) framework for HSI classification that simultaneously models the local interactions and global dependencies of HSI pixels to achieve high-precision classification. By virtue of the D2SA mechanism, the introduced D2S2BOT framework can produce competitive classification results with a limited number of training samples on three well-known datasets, which we hope will provide a strong baseline for future research on transformers in the field of HSI.

In recent years, deep-learning-based hyperspectral unmixing techniques have garnered increasing attention and made significant advancements. However, relying solely on the use of convolutional neural network (CNN) or transformer approaches is insufficient for effectively capturing both global and fine-grained information, thereby compromising the accuracy of unmixing tasks. In order to fully harness the information contained within hyperspectral images, this article explores a dual-stream collaborative network, referred to as TCCU-Net. It end-to-end learns information in four dimensions: spectral, spatial, global, and local, to achieve more effective unmixing. The network comprises two core encoders: one is a transformer encoder, which includes squeeze-launch modules, DSSCR–vision transformer modules, and stripe pooling modules, while the other one is a CNN encoder, which is composed of two-dimensional (2-D) pyramid convolutions and 3-D pyramid convolutions. By fusing the outputs of these two encoders, the semantic gap between the encoder and decoder is bridged, resulting in improved feature mapping and unmixing outcomes. This article extensively evaluates TCCU-Net and seven hyperspectral unmixing methods on four datasets (Samson, Apex, Jasper Ridge, and Synthetic dataset). The experimental results firmly demonstrate that the proposed approach surpasses others in terms of accuracy, holding the potential to effectively address hyperspectral unmixing tasks.

Abstract Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their α-C−H bonds are unreactive towards electrophiles due to their extremely low acidity (pK a ~57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary alkyl amines by increasing the acidity of the α-amino C−H bonds by up to 1044 times. This makes the α-amino C−H bonds acidic enough to be deprotonated under mild conditions. By combining DFO with an iridium catalyst, direct asymmetric α-C−H alkylation of NH2-unprotected primary alkyl amines with allylic carbonates has been achieved. This reaction produces a wide range of chiral homoallylic amines with high enantiopurities. The approach has successfully switched the reactivity between primary alkyl amines and allylic carbonates from intrinsic allylic amination to the α-C−H alkylation, enabling the construction of pharmaceutically significant chiral homoallylic amines from readily available primary alkyl amines in a single step.

Abstract Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer–immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.

Abstract Hepatocarcinogenesis is a multi-step process. However, the regulators of hepatocellular carcinoma (HCC) initiation are understudied. Adult liver-specific gene expression was globally downregulated in HCC. We hypothesize that adult liver-specific genes, especially adult liver-enriched transcription factors may exert tumor-suppressive functions in HCC. In this study, we identify ZBTB7B, an adult liver-enriched transcription factor as a permissive regulator of HCC initiation. ZBTB7B is highly expressed in hepatocytes in adult livers, compared to fetal livers. To evaluate the functions of ZBTB7B in hepatocarcinogenesis, we performed hepatocyte-specific ZBTB7B knockout in hydrodynamic oncogene transfer-induced mouse liver cancer models. Hepatocyte-specific knockout of ZBTB7B promotes activated Akt and N-Ras-induced HCC development. Moreover, ZBTB7B deficiency sensitizes hepatocytes to a single oncogene Akt-induced oncogenic transformation and HCC initiation, which is otherwise incompetent in inducing HCC. ZBTB7B deficiency accelerates HCC initiation by down-regulating adult liver-specific gene expression and priming livers to a fetal-like state. The molecular mechanism underlying ZBTB7B functions in hepatocytes was investigated by integrated transcriptomic, phosphoproteomic, and chromatin immunoprecipitation-sequencing analyses. Integrative multi-omics analyses identify c-Jun as the core signaling node in ZBTB7B-deficient liver cancer initiation. c-Jun is a direct target of ZBTB7B essential to accelerated liver cancer initiation in ZBTB7B-deficient livers. Knockdown of c-Jun expression or dominant negative c-Jun expression delays HCC development in ZBTB7B-deficient livers. In addition, ZBTB7B competes with c-Jun for chromatin binding. Ectopic ZBTB7B expression attenuates the tumor-promoting functions of c-Jun. Expression of ZBTB7B signature, composed of 140 genes co-regulated by ZBTB7B and c-Jun, is significantly downregulated in early-stage HCCs compared to adjacent normal tissues, correlates to liver-specific gene expression, and is associated with good prognosis in human HCC. Thus, ZBTB7B functions as a permissive regulator of HCC initiation by directly regulating c-Jun expression and function.

Abstract Background Treating complex cases of spinal tuberculosis (STB) that involve multiple vertebral bodies and cause destruction of the spinal structure, kyphotic deformity, and acute nerve injury can be challenging. This report describes the course of treatment and 5-year follow-up of a complex case of multisegmental STB. Case presentation This report describes a case of tuberculosis affecting the vertebrae extending from thoracic 12 to lumbar 5 in a 60-year-old woman who suffered sudden paralysis in both lower extremities. The patient underwent emergency posterior paraspinal abscess clearance, laminectomy with spinal decompression. Partial correction of the kyphotic deformity via long-segment fixation from the T9 vertebral body to the ilium in a one-stage posterior procedure. The patient’s neurological status was diagnosed as grade E on the American Spinal Injury Association (ASIA) scale after the one-stage operation. Following standardized 4-combination anti-tuberculosis drug therapy for three months in postoperative patients, the patient underwent two-stage transabdominal anterior abscess removal, partial debridement of the lesion and bilateral fibula graft support. One year after the two-stage operation, the patient’s visual analog scale (VAS) score of back pain was 1 point, and the patient’s erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels returned to normal. Five years after the second-stage operation, the Oswestry disability index (ODI) of patient quality of life was 14 points. There was a 4-degree change in the Cobb angle over five years. During the five-year follow-up period, the grafted fibula did not experience any subsidence. Conclusion For patients with spinal tuberculosis and acute paralysis, it is essential to relieve spinal cord compression as soon as possible to recover spinal cord function. For lesions that cannot be debrided entirely, although limited debridement combined with anti-tuberculosis drug therapy has the risk of sinus formation and tuberculosis recurrence, it is much safer than the risk of thorough debridement surgery. In this case, an unconventional long-segment fibula graft, pelvis-vertebral support, was an effective reconstruction method.

Abstract Acquired resistance to chemotherapy is one of the major causes of mortality in advanced nasopharyngeal carcinoma (NPC). However, effective strategies are limited and the underlying molecular mechanisms remain elusive. In this study, through transcriptomic profiling analysis of 23 tumor tissues, we found that NOTCH3 was aberrantly highly expressed in chemoresistance NPC patients, with NOTCH3 overexpression being positively associated with poor clinical outcome. Mechanistically, using an established NPC cellular model, we demonstrated that enhancer remodeling driven aberrant hyperactivation of NOTCH3 in chemoresistance NPC. We further showed that NOTCH3 upregulates SLUG to induce chemo-resistance of NPC cells and higher expression of SLUG have poorer prognosis. Genetic or pharmacological perturbation of NOTCH3 conferred chemosensitivity of NPC in vitro and overexpression of NOTCH3 enhanced chemoresistance of NPC in vivo. Together, these data indicated that genome-wide enhancer reprogramming activates NOTCH3 to confer chemoresistance of NPC, suggesting that targeting NOTCH3 may provide a potential therapeutic strategy to effectively treat advanced chemoresistant NPC.

Traditional X-ray pulsar ranging and velocity measurement methods only estimate the radial position and velocity information of the pulsar. For non-linear orbits, errors in the transverse position and velocity of the pulsar lead to errors in the radial velocity of the pulsar, leading to distortion of the X-ray pulsar profile. Based on this, we propose using the distortion of the pulsar profile to infer the transverse position and velocity information of the pulsar. First, a model of the distortion of the pulsar profile due to errors in the transverse position and velocity is established, and the observable directions of the transverse position and velocity are given separately. Then, considering that the distortions in the pulsar profile caused by errors in the transverse position and velocity are indistinguishable, we establish a reactive motion state measure related to the observable directions for the transverse position and velocity errors as a new observable measure in X-ray pulsar navigation. The experimental results show that the precision of the reactive motion state measure reaches 0.57, equivalent to a position error of 284.50 m or a velocity error of 0.57 m/s.

In environments where silent communication is essential, such as libraries and conference rooms, the need for a discreet means of interaction is paramount. Here, we present a single-electrode, contact-separated triboelectric nanogenerator (CS-TENG) characterized by robust high-frequency sensing capabilities and long-term stability. Integrating this TENG onto the inner surface of a mask allows for the capture of conversational speech signals through airflow vibrations, generating a comprehensive dataset. Employing advanced signal processing techniques, including short-time Fourier transform (STFT), Mel-frequency cepstral coefficients (MFCC), and deep learning neural networks, facilitates the accurate identification of speaker content and verification of their identity. The accuracy rates for each category of vocabulary and identity recognition exceed 92% and 90%, respectively. This system represents a pivotal advancement in facilitating secure and efficient unobtrusive communication in quiet settings, with promising implications for smart home applications, virtual assistant technology, and potential deployment in security and confidentiality-sensitive contexts.

To construct a heterotrophic axenic system of Chlorella sorokiniana FZU60, the symbiotic bacteria were isolated and identified, and the effects of eight common antibiotics (cefotaxime, kanamycin, neomycin, ampicillin, streptomycin, tetracycline, chloramphenicol, and erythromycin) on the cell growth of symbiotic bacteria and C. sorokiniana FZU60 were investigated. Results showed that the main symbiotic bacteria were Bacillus (78.76%) and Methylobacterium (3.14%). Besides, 10 mg/L cefotaxime, 10 mg/L tetracycline, 100 mg/L kanamycin, and 100 mg/L erythromycin showed excellent inhibitory effect on these two symbiotic bacteria but no obvious effect on the cell growth of C. sorokiniana FZU60. Based on the above-mentioned results, the inhibition effect of different antibiotic combinations on symbiotic bacteria of C. sorokiniana FZU60 was further investigated. It was found that the heterotrophic axenic system could be successfully constructed by using the combination of 10 mg/L cefotaxime, 10 mg/L tetracycline, and 100 mg/L kanamycin. Moreover, C. sorokiniana FZU60 could maintain stable and axenic growth after three generations. The experimental results would provide theoretical reference and experimental basis for the preparation of axenic microalgal seed for high-cell-density heterotrophic cultivation of C. sorokiniana.

Abstract In addition to the classical role as a serum effector system of innate immunity, accumulating evidence suggests that intracellular complement components have indispensable functions in immune defense, T cell homeostasis, and tumor cell proliferation and metastasis. Here, we revealed that complement component 3 (C3) is remarkably upregulated in paclitaxel (PTX)-resistant non-small cell lung cancer (NSCLC) cells and that knockdown of C3 promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy. Ectopic C3 decreased PTX-induced apoptosis and induced resistance to PTX treatment in original NSCLC cells. Interestingly, C3b, the activated fragment of C3, was found to translocate into the nucleus and physically associate with the HDAC1/2-containing SIN3A complex to repress the expression of GADD45A, which plays an important role in cell growth inhibition and apoptosis induction. Importantly, C3 downregulated GADD45A by enhancing the binding of the SIN3A complex with the promoter of GADD45A, thus decreasing the H3Ac level to compress chromatin around the GADD45A locus. Subsequently, ectopic GADD45A promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy, and insufficiency of GADD45A in original cancer cells induced resistance to PTX treatment. These findings identify a previously unknown nucleus location and oncogenic property for C3 in chemotherapy and provide a potential therapeutic opportunity to overcome PTX resistance.

Microalgae are a group of microscopic eukaryotic organisms that can transform carbon dioxide into diverse bioactive compounds through photosynthesis using chlorophyll a. Over the past decade, biohybrid materials comprising live microalgae and other biocompatible components have exhibited tremendous potential in solving many medical challenges, such as oncotherapy, tissue reconstruction, and drug delivery. Microalgae immobilized within conventional biomaterials can maintain their photosynthetic activity for an extended period of time, thereby providing local oxygen and working as biocompatible interfacing materials for regulating cell activities. The motility of microalgae has also inspired the development of biohybrid microrobots, in which drug molecules can be bound to the surface of microalgae via noncovalent adsorption and delivered to the target area through precisely controlled locomotion. Moreover, the autofluorescence, phototaxis, and biomass production of microalgae can be integrated into the design of novel biohybrid materials with versatile functions. Furthermore, through appropriate genetic manipulation, engineered microalgae can endow biohybrid materials with novel properties, such as specific cell-targeting capability and the local release of recombinant proteins from algae cells—technologies that show promise for promoting and diversifying the clinical use of microalgae-based biohybrid materials (MBBMs) in several fields of biomedicine. Herein, we summarize the fabrication, physiology, and locomotion ability of MBBMs; we then review typical and recent reports on the use of MBBMs in the biomedical field; finally, we provide critical discussions on the challenges and future perspectives of MBBMs.

Abstract Background Enhancer of zeste homolog 2 (EZH2), the key catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed and plays an oncogenic role in various cancers through catalysis-dependent or catalysis-independent pathways. However, the related mechanisms contributing to ovarian cancer (OC) are not well understood. Methods The levels of EZH2 and H3K27me3 were evaluated in 105 OC patients by immunohistochemistry (IHC) staining, and these patients were stratified based on these levels. Canonical and noncanonical binding sites of EZH2 were defined by chromatin immunoprecipitation sequencing (ChIP-Seq). The EZH2 solo targets were obtained by integrative analysis of ChIP-Seq and RNA sequencing data. In vitro and in vivo experiments were performed to determine the role of EZH2 in OC growth. Results We showed that a subgroup of OC patients with high EZH2 expression but low H3K27me3 exhibited the worst prognosis, with limited therapeutic options. We demonstrated that induction of EZH2 degradation but not catalytic inhibition profoundly blocked OC cell proliferation and tumorigenicity in vitro and in vivo. Integrative analysis of genome-wide chromatin and transcriptome profiles revealed extensive EZH2 occupancy not only at genomic loci marked by H3K27me3 but also at promoters independent of PRC2, indicating a noncanonical role of EZH2 in OC. Mechanistically, EZH2 transcriptionally upregulated IDH2 to potentiate metabolic rewiring by enhancing tricarboxylic acid cycle (TCA cycle) activity, which contributed to the growth of OC. Conclusions These data reveal a novel oncogenic role of EZH2 in OC and identify potential therapeutic strategies for OC by targeting the noncatalytic activity of EZH2.

Abstract Background Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy. Methods Melatonin and cardiac melatonin receptors in patients and rat models with lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated cardiac delivery of RORα/cationic microbubbles (CMBs) at 1, 3 and 5 days before CLP surgery. Echocardiography, histopathology and oxylipin metabolomics were assessed at 16–20 h after inducing fatal sepsis. Results We observed that patients with sepsis have lower serum melatonin than healthy controls, which was observed in the blood and hearts of Sprague–Dawley rat models with LPS- or CLP-induced sepsis. Notably, a mild dose (2.5 mg/kg) of intravenous melatonin did not substantially improve septic cardiomyopathy. We found decreased nuclear receptors RORα, not melatonin receptors MT1/2, under lethal sepsis that may weaken the potential benefits of a mild dose of melatonin treatment. In vivo, repeated UTMD-mediated cardiac delivery of RORα/CMBs exhibited favorable biosafety, efficiency and specificity, significantly strengthening the effects of a safe dose of melatonin on heart dysfunction and myocardial injury in septic rats. The cardiac delivery of RORα by UTMD technology and melatonin treatment improved mitochondrial dysfunction and oxylipin profiles, although there was no significant influence on systemic inflammation. Conclusions These findings provide new insights to explain the suboptimal effect of melatonin use in clinic and potential solutions to overcome the challenges. UTMD technology may be a promisingly interdisciplinary pattern against sepsis-induced cardiomyopathy.

Abstract The structure and functionality of biomacromolecules are often regulated by chemical bonds, however, the regulation process and underlying mechanisms have not been well understood. Here, by using in situ liquid-phase transmission electron microscopy (LP-TEM), we explored the function of disulfide bonds during the self-assembly and structural evolution of sulfhydryl single-stranded DNA (SH-ssDNA). Sulfhydryl groups could induce self-assembly of SH-ssDNA into circular DNA containing disulfide bonds (SS-cirDNA). In addition, the disulfide bond interaction triggered the aggregation of two SS-cirDNA macromolecules along with significant structural changes. This visualization strategy provided structure information at nanometer resolution in real time and space, which could benefit future biomacromolecules research.

Objective Lily is an essential ornamental flowering species worldwide. Drought stress is a major constraint affecting the morphology and physiology and lily leaves and flowers. Therefore, understanding the molecular mechanism underlying lily response to drought stress is important. Method Transcriptome and metabolome analysis were performed on Oriental Lily subjected to drought stress. Result Most transcription factors and metabolites yielded by the conjoint analysis displayed a downregulated expression pattern. Differential genes and metabolites mainly co-enriched in glycolic pathways related to sugars, such as galactose, and sucrose, glycolysis and gluconeogenesis, indicating that drought stress reduced the sugar metabolism level of Oriental Lily. Combined with transcriptome and metabolome data, nine pairs of differentially expressed metabolites and the genes (p < 0.05) were obtained. Interestingly, a gene named TRINITY_DN2608 (encoding a type of alpha-D-glucose) cloned and its overexpression lines in Arabidopsis thaliana was generated. Overexpression of TRINITY_DN2608 gene elevated the susceptibility to drought stress possibly by suppressing the glucose level. Conclusion The enrichment of sugar-related pathways advocates the potential role of glucose metabolism in drought stress. Our study provides theoretical information related to the glucose-mediated drought response and would be fruitful in future lily breeding programs.

Abstract Background Chlorella sorokiniana FZU60 is a promising lutein producing microalga. A mixotrophy/photoautotrophy two-stage strategy can achieve high biomass concentration at stage 1 and high lutein content at stage 2, leading to excellent lutein production efficiency in C. sorokiniana FZU60. However, the underlying molecular mechanisms are still unclear, restraining the further improvement of lutein production. Results In this study, physiological and biochemical analysis revealed that photochemical parameters (Fv/Fm and NPQ) and photosynthetic pigments contents increased during the shift from mixotrophy to photoautotrophy, indicating that photosynthesis and photoprotection enhanced. Furthermore, transcriptomic analysis revealed that the glyoxylate cycle and TCA cycle were suppressed after the shift to photoautotrophy, leading to a decreased cell growth rate. However, the gene expression levels of photosynthesis, CO2 fixation, autophagy, and lutein biosynthesis were upregulated at the photoautotrophy stage, demonstrating that microalgal cells could obtain more precursor to synthesize lutein for enhancing photosynthesis and reducing reactive oxygen species. Conclusions The findings help to elucidate the molecular mechanisms for high lutein production efficiency of C. sorokiniana FZU60 under the mixotrophy/photoautotrophy strategy, identify key functional genes responsible for lutein biosynthesis, and shed light on further improvement of lutein production by genetic or metabolic engineering in future studies.

In the study of atmospheric wind fields from the upper troposphere to the stratosphere (10 km to 50 km), direct detection wind LiDAR is considered a promising method that offers high-precision atmospheric wind field data. In 2020, Xie et al. of the Anhui Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, developed an innovative rotating Rayleigh Doppler wind LiDAR (RRDWL). The system aims to achieve single-LiDAR detection of atmospheric wind fields by rotating the entire device cabin. In 2022, the feasibility of the system was successfully validated in laboratory conditions, and field deployment was completed. Due to the structural differences between this system and traditional direct-detection wind LiDAR, performance tests were conducted to evaluate its continuous detection capability in outdoor environments. Subsequently, based on the test results and error analysis, further analysis was carried out to identify the main factors affecting the system’s detection performance. Finally, the error analysis and traceability of the detection results were conducted, and corresponding measures were discussed to provide a theoretical foundation for optimizing the performance of RRDWL.

Conventional human-involved maintenance methods for asphalt pavement pose significant challenges when applied to high-traffic road sections, often leading to congestion and safety risks, as well as reduced maintenance efficiency. In recent years, explorations into unmanned construction technology for newly constructed expressways have yielded beneficial and encouraging results. However, its application in road maintenance in more complex environments still needs to be expanded. In this study, an intelligent unmanned maintenance technology for asphalt pavement was applied to the Lilong Highway in Zhejiang Province, China, and the compactability, thickness, surface smoothness, permeability coefficient, and constructure depth of maintenance road sections were measured. Then, based on fuzzy comprehensive mathematics and the analytic hierarchy process, a comprehensive evaluation was performed on the intelligent unmanned maintenance technology, considering the aspects of road quality, safety, application, and socio-economic benefits. The results show that the road quality of intelligent unmanned maintenance technology can meet the road specification requirements. In addition, the membership degree of unmanned maintenance technology in the excellent grade is the highest, reaching 0.805, and the quantified value for the overall evaluation of the application effectiveness of unmanned maintenance technology is 92.10. This means that the final comprehensive evaluation result of unmanned maintenance technology is rated as excellent. The research findings provide decision-makers with valuable insights into the unmanned automation maintenance challenges faced by asphalt pavement, enabling them to implement appropriate measures to elevate the maintenance standards of road transportation.

The Fabry–Perot interferometer (FPI) plays a crucial role as the frequency discriminator in the incoherent Doppler wind lidar. However, in the practical receiver system, reflections occurring between optical elements introduce non-normal incident components in the light beams passing through the FPI. This phenomenon results in the deformation of the FPI transmission spectral lines. Based on that, a theoretical model has been developed to describe the transmission spectrum of the FPI when subjected to obliquely incident light beams with a divergence angle. By appropriately adjusting the model parameters, the simulated transmission spectrum of the FPI edge channels can coincide with the experimentally measured FPI spectral line. Subsequently, the impact of deformations in the transmission spectrum of the two edge channels on wind measurements is evaluated. The first implication is a systematic shift of 30.7 m/s in line-of-sight (LOS) wind velocities. This shift is based on the assumption that the lidar echo is solely backscattered from atmospheric molecules. The second consequence is the inconsistency in the response sensitivities of Doppler frequency shift between Rayleigh signals and Mie signals. As a result, the lidar system fails to fully achieve its initial design objectives, particularly in effectively suppressing interference from Mie signals. The presence of aerosols can introduce a significant error of several meters per second in the measurement of LOS wind velocity.

Integrated systems are facing complex and changing environments with the wide application of atmospheric LiDAR in civil, aerospace, and military fields. Traditional analysis methods employ optical software to evaluate the optical performance of integrated systems, and cannot comprehensively consider the influence of optical and mechanical coupling on the optical performance of the integrated system, resulting in the unsatisfactory accuracy of the analysis results. Optical–mechanical integration technology provides a promising solution to this problem. A small-field-of-view LiDAR system with high repetition frequency, low energy, and single-photon detection technology was taken as an example in this study, and the Zernike polynomial fitting algorithm was programmed to enable transmission between optical and mechanical data. Optical–mechanical integration technology was employed to obtain the optical parameters of the integrated system under a gravity load in the process of designing the optical–mechanical structure of the integrated system. The experimental validation results revealed that the optical–mechanical integration analysis of the divergence angle of the transmission unit resulted in an error of 2.586%. The focal length of the telescope increased by 89 μm, its field of view was 244 μrad, and the error of the detector target surface spot was 4.196%. The continuous day/night detection results showed that the system could accurately detect the temporal and spatial variations in clouds and aerosols. The inverted optical depths were experimentally compared with those obtained using a solar photometer. The average optical depth was 0.314, as detected using LiDAR, and 0.329, as detected by the sun photometer, with an average detection error of 4.559%. Therefore, optical–mechanical integration analysis can effectively improve the stability of the structure of highly integrated and complex optical systems.

Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood. α-Hydroxybutyrate (α-HB), a byproduct metabolite increased in diabetes and cancer, including colorectal cancer (CRC), triggers lactate dehydrogenase A (LDHA) nuclear translocation. Nuclear LDHA markedly extends NF-κB nuclear retention by interacting with phosphorylated p65, leading to an increase in TNF-α production, impaired insulin secretion and the exacerbation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC and high-fat diet (HFD)-induced type 2 diabetes. Furthermore, metformin interrupted this process by inhibiting the transcription of FOXM1 and c-MYC, the resultant downregulation of LDHA expression and α-HB-induced LDHA nuclear translocation. Thus, the results reveal the elevated α-HB level could be a novel shared risk factor of linking CRC, diabetes and the use of metformin treatment, as well as highlight the importance of preventing NF-κB activation for protecting against cancer and diabetes.

Abstract Natural killer/T‐cell lymphoma (NKTL) is an uncommon malignancy with poor prognosis and limited therapeutic options. Activating mutations of signal transducer and activator of transcription 3 (STAT3) are frequently found in patients with NKTL, suggesting that targeted inhibition of STAT3 is a potential therapeutic option for this disease. Here, we have developed a small molecule drug WB737 as a novel and potent STAT3 inhibitor that directly binds to the STAT3‐Src homology 2 domain with high affinity. In addition, the binding affinity of WB737 to STAT3 is 250‐fold higher than STAT1 and STAT2. Interestingly, WB737 is more selective for NKTL with STAT3‐activating mutations in terms of growth inhibition and apoptotic induction when compared with Stattic. Mechanistically, WB737 inhibits both canonical and noncanonical STAT3 signaling via suppression of STAT3 phosphorylation at Tyr705 and Ser727, respectively, thereby inhibiting the expression of c‐Myc and mitochondria‐related genes. Moreover, WB737 inhibited STAT3 more potently than Stattic, resulting in a significant antitumor effect with undetectable toxicity, followed by almost complete tumor regression in an NKTL xenograft model harboring a STAT3‐activating mutation. Taken together, these findings provide preclinical proof‐of‐concept for WB737 as a novel therapeutic strategy for the treatment of NKTL patients with STAT3‐activating mutations.

Objective: This study aimed to assess the efficacy of individual-donation nucleic acid testing (ID-NAT) in detecting occult hepatitis B virus infection (OBI) among anti-HBc positive blood donors, compared to minipool nucleic acid testing (MP-NAT). Methods: The present study analyzed data from the Shandong Blood Center in China during the period from January 2018 to June 2022, where HBsAg-negative blood donors were screened using the 6-sample minipool nucleic acid testing (6-sample MP NAT) method. NAT-positive samples underwent subsequent anti-HBc and anti-HBs testing. Approximately 5000 samples that passed the nucleic acid mixing test were randomly selected for anti-HBc testing, and over 100 anti-HBc positive samples underwent individual donor nucleic acid testing (ID-NAT). Any HBV DNA positive samples detected by ID-NAT were subsequently confirmed using alternative nucleic acid testing methods. Results: Among 220,445 HBsAg-negative blood donors, the positivity rate of HBV DNA detection using the 6-sample minipool nucleic acid testing (MP NAT) method was found to be 0.031% (69/220,445). Of the 67 HBV DNA positive samples, 55 (82.09%) and 25 (37.31%) were found to be positive for anti-HBc and anti-HBs, respectively, using the supplementary chemiluminescent microparticle immunoassay (CMIA). Among the 4797 HBsAg-negative/MP NAT-negative samples, 909 (18.95%) tested positive for anti-HBc. Further NAT testing was performed on 164 arbitrarily selected anti-HBc-positive/MP HBV DNA-negative samples, revealing a HBV DNA positivity rate of 1.22% (2/164). Conclusion: Using individual donation nucleic acid testing can significantly increase the detection rate of occult hepatitis B virus infection in anti-HBc-positive blood donors, resulting in a detection rate of 0.22% (1.22 × 0.1895). This rate is 8.10 times higher than the detection rate achieved by mixed testing methods (0.031%) [calculated as (0.22 + 0.031)/0.031]. Therefore, it is recommended to perform single HBV DNA testing on anti-HBc-positive blood donors, discard plasma with weakly positive or negative anti-HBs but positive anti-HBc, or avoid transfusing anti-HBc-positive plasma to recipients with weakly positive or negative anti-HBs to prevent HBV infection.

Deep learning-based methods for hyperspectral image super-resolution (HISR) have recently achieved remarkable success. However, the contextual correlation and intrinsic properties of adjacent bands in hyperspectral images have not been fully exploited in previous works. Therefore, this article proposes a network framework (TC-HISRNet) that leverages the local feature extraction capability of convolutional neural networks (CNNs) in tandem with the global feature extraction ability of transformer, to thoroughly investigate the role of contextual information in HISR. TC-HISRNet is comprised of a two-stage feature encoding network, which combines a two-channel CNN and a transformer encoder. Within the CNN encoder, the joint utilization of the real-time attention fusion module and two/three-dimensional convolutions enables the preservation of spectral correlation between bands while facilitating the extraction of local features from hyperspectral images. On the other hand, the developed transformer encoder leverages joint adjacent band contextual information to capture long-range dependencies and interdependencies among the combined features. Extensive evaluation and comparison of three public datasets demonstrated that the proposed method outperformed the state-of-the-art super-resolution method, resulting in superior reconstruction of hyperspectral images.

A rechargeable unmanned aerial vehicle (UAV) aided wireless sensor network was considered, which consists of multiple ground terminals with a large amount of time-sensitive data to be collected.Due to the limited battery capacity, the UAV cannot collect the data from all terminals through a single flight mission, and it needs to return to the charging pile to replenish its flight energy several times during the whole mission.The optimization of the terminal scheduling, trajectory, flight speed and transmission rate for the UAV was studied to maximize the number of terminals whose data had been collected within the data lifetime limit.Due to the variable coupling and the existence of discrete binary scheduling variables, the considered optimization problem is difficult to solve.To tackle such a difficulty, an efficient algorithm was proposed based on the stochastic optimization and the feature engineering.Specifically, the flight hover communication protocol was introduced to simplify the UAV flight process.And then a terminal scheduling algorithm was innovatively proposed with the influence factor and the stochastic preference, which extracted the features that affect the service time of the UAV, optimized the weights of the features, and further simplified the optimization problem into multiple subproblems.The subproblems were then solved by using the block coordinate descent and successive convex approximation techniques.Simulation results show that the proposed optimization algorithm achieves significant performance gains over several benchmark schemes in the scenarios with different data lifetime requirements and different numbers of ground terminals.

Summary: Dynamic regulation of integrin activation and inactivation is critical for precisely controlled cell adhesion and migration in physiological and pathological processes. The molecular basis for integrin activation has been intensively studied; however, the understanding of integrin inactivation is still limited. Here, we identify LRP12 as an endogenous transmembrane inhibitor for α4 integrin activation. The LRP12 cytoplasmic domain directly binds to the integrin α4 cytoplasmic tail and inhibits talin binding to the β subunit, thus keeping integrin inactive. In migrating cells, LRP12-α4 interaction induces nascent adhesion (NA) turnover at the leading-edge protrusion. Knockdown of LRP12 leads to increased NAs and enhanced cell migration. Consistently, LRP12-deficient T cells show an enhanced homing capability in mice and lead to aggravated chronic colitis in a T cell-transfer colitis model. Altogether, LRP12 is a transmembrane inactivator for integrins that inhibits α4 integrin activation and controls cell migration by maintaining balanced NA dynamics.