Assessment of in-situ monitoring and tracking the vertical migration of cyanobacterial blooms using LISST-HAB.

Cyanobacterial harmful algal blooms (cyanoHABs) are becoming increasingly common in aquatic ecosystems worldwide. However, their heterogeneous distributions make it difficult to accurately estimate the total algae biomass and forecast the occurrence of surface cyanoHABs by using traditional monitoring methods. Although various optical instruments and remote sensing methods have been employed to monitor the dynamics of cyanoHABs at the water surface (i.e., bloom area, chlorophyll a), there is no effective in-situ methodology to monitor the dynamic change of cell density and integrated biovolume of algae throughout the water column. In this study, we propose a quantitative protocol for simultaneously measurements of multiple indicators (i.e., biovolume concentration, size distribution, cell density, and column-integrated biovolume) of cyanoHABs in water bodies by using the laser in-situ scattering and transmissometry (LISST) instrument. The accuracy of measurements of the biovolume and colony size of algae was evaluated and exceeded 95% when the water bloom was dominated by cyanobacteria. Furthermore, the cell density of cyanobacteria was well estimated based on total biovolume and mean cell volume measured by the instrument. Therefore, this methodology has the potential to be used for broader applications, not only to monitor the spatial and temporal distribution of algal biovolume concentration but also monitor the vertical distribution of cell density, biomass and their relationship with size distribution patterns. This provides new technical means for the monitoring and analysis of algae migration and early warning of the formation of cyanoHABs in lakes and reservoirs.

Novel Insights into Alkyl Polyglucoside Biosurfactant Promoting Anaerobic Dark Fermentation for Hydrogen Production in Sludge.

Anaerobic fermentation of excess sludge (ES) for hydrogen production is a crucial strategy for resource utilization and environmentally friendly treatment. However, the low hydrolysis efficiency of ES and the depletion of produced hydrogen have become the limiting factors for low hydrogen yield. This study innovatively applied the bio-based surfactant alkyl polyglucoside (APG) to enhance the efficiency of dark fermentation for hydrogen production from ES. When the APG content was 100 mg/g (calculated based on total suspended solids), the maximum hydrogen production reached 17.8 mL/g VSS, approximately 3.7 times that in the control group. Mechanistic analysis revealed that APG promoted the release of organic matter from ES. APG also facilitated the release of soluble protein and soluble polysaccharide, increasing the organic matter reduction rate to 34.8%, significantly higher than other groups. APG enhanced the accumulation of volatile fatty acids and promoted the proportion of small molecular carboxylic acids. Enzyme activity analysis revealed that APG promoted the activity of hydrolytic enzymes but inhibited the activity of hydrogen-consuming enzymes. The research results provide a green and environmentally friendly strategy for the efficient resource utilization of ES.

Deciphering the Genomic Characterization of the GGP Gene Family and Expression Verification of CmGGP1 Modulating Ascorbic Acid Biosynthesis in Melon Plants.

Ascorbic acid (AsA), also known as vitamin C, is a well-known antioxidant found in living entities that plays an essential role in growth and development, as well as in defensive mechanisms. GDP-L-galactose phosphorylase (GGP) is a candidate gene regulating AsA biosynthesis at the translational and transcriptional levels in plants. In the current study, we conducted genome-wide bioinformatic analysis and pinpointed a single AsA synthesis rate-limiting enzyme gene in melon (CmGGP1). The protein prediction analysis depicted that the CmGGP1 protein does not have a signaling peptide or transmembrane structure and mainly functions in the chloroplast or nucleus. The constructed phylogenetic tree analysis in multispecies showed that the CmGGP1 protein has a highly conserved motif in cucurbit crops. The structural variation analysis of the CmGGP1 gene in different domesticated melon germplasms showed a single non-synonymous type-base mutation and indicated that this gene was selected by domestication during evolution. Wild-type (WT) and landrace (LDR) germplasms of melon depicted close relationships to each other, and improved-type (IMP) varieties showed modern domestication selection. The endogenous quantification of AsA content in both the young and old leaves of nine melon varieties exhibited the major differentiations for AsA synthesis and metabolism. The real-time quantitative polymerase chain reaction (qRT-PCR) analysis of gene co-expression showed that AsA biosynthesis in leaves was greater than AsA metabolic consumption, and four putative interactive genes (MELO3C025552.2, MELO3C007440.2, MELO3C023324.2, and MELO3C018576.2) associated with the CmGGP1 gene were revealed. Meanwhile, the CmGGP1 gene expression pattern was noticed to be up-regulated to varying degrees in different acclimated melons. We believe that the obtained results would provide useful insights for an in-depth genetic understanding of the AsA biosynthesis mechanism, aimed at the development of improving crop plants for melon.

A lightweight hybrid model for the automatic recognition of uterine fibroid ultrasound images based on deep learning.

PURPOSE: Uterine fibroids (UF) are the most frequent tumors in ladies and can pose an enormous threat to complications, such as miscarriage. The accuracy of prognosis may also be affected by way of doctor inexperience and fatigue, underscoring the want for automatic classification fashions that can analyze UF from a giant wide variety of images. METHODS: A hybrid model has been proposed that combines the MobileNetV2 community and deep convolutional generative adversarial networks (DCGAN) into useful resources for medical practitioners in figuring out UF and evaluating its characteristics. Real-time automated classification of UF can aid in diagnosing the circumstance and minimizing subjective errors. The DCGAN science is utilized for superior statistics augmentation to create first-rate UF images, which are labeled into UF and non-uterine-fibroid (NUF) classes. The MobileNetV2 model then precisely classifies the photos based totally on this data. RESULTS: The overall performance of the hybrid model contrasts with different models. The hybrid model achieves a real-time classification velocity of 40 frames per second (FPS), an accuracy of 97.45%, and an F1 rating of 0.9741. CONCLUSION: By using this deep learning hybrid approach, we address the shortcomings of the current classification methods of uterine fibroid.

Rapid flotation of Microcystis wesenbergii mediated by high light exposure: implications for surface scum formation and cyanobacterial species succession.

Increasing occurrences of Microcystis surface scum have been observed in the context of global climate change and the increase in anthropogenic pollution, causing deteriorating water quality in aquatic ecosystems. Previous studies on scum formation mainly focus on the buoyancy-driven floating process of larger Microcystis colonies, neglecting other potential mechanisms. To study the non-buoyancy-driven rapid flotation of Microcystis, we here investigate the floating processes of two strains of single-cell species (Microcystis aeruginosa and Microcystis wesenbergii), which are typically buoyant, under light conditions (150 µmol photons s-1 m-2). Our results showed that M. wesenbergii exhibited fast upward migration and formed surface scum within 4 hours, while M. aeruginosa did not form visible scum throughout the experiments. To further explore the underlying mechanism of these processes, we compared the dissolved oxygen (DO), extracellular polymeric substance (EPS) content, and colony size of Microcystis in different treatments. We found supersaturated DO and the formation of micro-bubbles (50-200 µm in diameter) in M. wesenbergii treatments. M. aeruginosa produces bubbles in small quantities and small sizes. Additionally, M. wesenbergii produced more EPS and tended to aggregate into larger colonies. M. wesenbergii had much more derived-soluble extracellular proteins and polysaccharides compared to M. aeruginosa. At the same time, M. wesenbergii contains abundant functional groups, which was beneficial to the formation of agglomerates. The surface scum observed in M. wesenbergii is likely due to micro-bubbles attaching to the surface of cell aggregates or becoming trapped within the colony. Our study reveals a species-specific mechanism for the rapid floatation of Microcystis, providing novel insights into surface scum formation as well as succession of cyanobacterial species.

MRI evaluation of cranial nerve abnormalities and extraocular muscle fibrosis in duane retraction syndrome and congenital extraocular muscle fibrosis.

PURPOSE: To investigate the alterations in extraocular muscles (EOMs) by magnetic resonance imaging (MRI) among patients diagnosed with Duane retraction yndrome (DRS) and congenital fibrosis of the extraocular muscles (CFEOM), who present with various cranial nerve anomalies in an attempt to enhance the clinical diagnostic process. METHODS: A case-control study was conducted to evaluate 27 patients with DRS and 14 patients with CFEOM. All patients underwent MRI scans of the brainstem and orbital examination. Neurodevelopmental assessments were conducted through MRI, and maximum cross-sectional area and volumes of EOMs were obtained. Three types of models were constructed using machine learning decision tree algorithms based on EOMs to predict disease diagnosis, cranial nerve abnormalities, and clinical subtypes. RESULTS: Patients with bilateral CN VI abnormalities had smaller volumes of LR, MR, and IR muscles compared to those with unilateral involvement (P < 0.05). Similarly, patients with CFEOM and unilateral third cranial nerve abnormalities had a smaller maximum cross-section of the affected eye's SR compared to the contralateral eye (P < 0.05). In patients with both CN III and CN VI abnormalities, the volume of SR was smaller than in patients with CN III abnormalities alone (P < 0.05). The prediction model using EOMs volume showed a diagnostic precision of 82.5% for clinical cases and 60.1% for predicting cranial nerve abnormalities. Nonetheless, the precision for identifying clinical subtypes was relatively modest, at only 41.7%. CONCLUSION: The distinctive volumetric alterations in EOMs among individuals exhibiting distinct cranial nerve anomalies associated with DRS or CFEOM provide valuable diagnostic insights into to Congenital Cranial Neurodevelopmental Disorders (CCDDs). MRI analysis of EOMs should thus be regarded as a crucial diagnostic modality.

Z-scheme heterojunction photocatalyst formed by MOF-derived C-TiO2 and Bi2WO6 for enhancing degradation of oxytetracycline: Mechanistic insights and toxicity evaluation in the presence of a single active species.

In the work, Bi2WO6/C-TiO2 photocatalyst was successfully synthesized for the first time by loading narrow bandgap semiconductor Bi2WO6 on MOF-derived carboxyl modified TiO2. The phase structure, morphology, photoelectric properties, surface chemical states and photocatalytic performance of the prepared photocatalysts were systematically investigated using various characterization tools. The degradation efficiency of oxytetracycline by 6BT Z-scheme heterojunction photocatalyst under visible light could reach 93.6 % within 100 min, which was related to the high light harvesting and effective separation and transfer of photo-generated carriers. Furthermore, the effects of various environmental factors in actual wastewater were further investigated, and the results showed that 6BT exhibited good adaptability, durability and resistance to interference. Unlike most works, the degradation system with a different single active species were designed and constructed based on their formation mechanism. In addition, for the first time, a positive study was conducted on the priority attack sites, intermediate products, and degradation pathways for the photocatalytic degradation of oxytetracycline by a single active species through HPLC-MS and Fukui index calculations. The toxicity changes of intermediate products produced in three different single active species oxidation systems were evaluated using toxicity assessment software tools (T.E.S.T.), Escherichia coli growth experiments, and wheat growth experiments. Among them, the intermediate products formed through O2- oxidation had the lowest toxicity and the main active sites it attacked were the 20C, 38O, 18C, 41O, and 55O atoms with high f+ values in the oxytetracycline molecular structure. This work provided the insight into the role of each active species in the degradation of antibiotics and offered new ideas for the design and synthesis of efficient and eco-friendly photocatalysts.

Recalled age of myopia onset may predict risk of high adult myopia in Chinese adults.

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

Effect of extracellular polymeric substances on the colony size and morphological changes of Microcystis.

Surface blooms of colony-forming Microcystis are increasingly occurring in aquatic ecosystems on a global scale. Recent studies have found that the Microcystis colonial morphology is a crucial factor in the occurrence, persistence, and dominance of Microcystis blooms, yet the mechanism driving its morphological dynamics has remained unknown. This study conducted a laboratory experiment to test the effect of extracellular polymeric substances on the morphological dynamics of Microcystis. Ultrasound was used to disaggregate colonies, isolating the cells and of the Microcystis suspension. The single cells were then re-cultured under three homologous EPS concentrations: group CK, group Low, and group High. The size, morphology, and EPS [including tightly bound EPS (TB-EPS), loosely bound EPS (LB-EPS), bound polysaccharides (B-polysaccharides), and bound proteins (B-proteins)] changes of colonies were closely monitored over a period of 2 months. It was observed that colonies were rapidly formed in group CK, with median colony size (D50) reaching 183 µm on day 12. The proportion of colonies with a size of 150-500 µm increased from 1% to more than 50%. Colony formation was also observed in both groups Low and High, but their D50 increased at a slower rate and remained around 130 µm after day 17. Colonies with a size of 50-150 µm account for more than 50%. Groups CK and Low successively recovered the initial Microcystis morphology, which is a ring structure formed of several small colonies with a D50 of 130 µm. During the recovery of the colony morphology, the EPS per cell increased and then decreased, with TB-EPS and B-polysaccharides constituting the primary components. The results suggest that colony formation transitioned from adhesion driven to being division driven over time. It is suggested that the homologous EPS released into the ambient environment due to the disaggregation of the colony is a chemical cue that can affect the formation of a colony. This plays an important but largely ignored role in the dynamics of Microcystis and surface blooms.

Upcycling of Carbon Fiber/Thermoset Composites into High-Performance Elastomers and Repurposed Carbon Fibers.

Recycling of carbon fiber-reinforced polymer composites (CFRCs) based on thermosetting plastics is difficult. In the present study, high-performance CFRCs are fabricated through complexation of aromatic pinacol-cross-linked polyurethane (PU-AP) thermosets with carbon fiber (CF) cloths. PU-AP thermosets exhibit a breaking strength of 95.5 MPa and toughness of 473.6 MJ m-3 and contain abundant hydrogen-bonding groups, which can have strong adhesion with CFs. Because of the high interfacial adhesion between CF cloths and PU-AP thermosets and high toughness of PU-AP thermosets, CF/PU-AP composites possess a high tensile strength of >870 MPa. Upon heating in N,N-dimethylacetamide (DMAc) at 100 °C, the aromatic pinacols in the CF/PU-AP composites can be cleaved, generating non-destructive CF cloths and linear polymers that can be converted to high-performance elastomers. The elastomers are mechanically robust, healable, reprocessable, and damage-resistant with an extremely high tensile strength of 74.2 MPa and fracture energy of 149.6 kJ m-2. As a result, dissociation of CF/PU-AP composites enables the recovery of reusable CF cloths and high-performance elastomers, thus realizing the upcycling of CF/PU-AP composites.

Efficacy and Safety of Huachansu as an Adjuvant Therapy for Non-Small Cell Lung Cancer: An Overview of Systematic Reviews and Meta-Analyses.

OBJECTIVE: The purpose of this overview is to assess systematic reviews (SRs)/ meta-analyses (MAs) of Huachansu (HCS) combination chemotherapy for treating non-small cell lung cancer (NSCLC) and provide summarized evidence for clinical decision making. METHODS: From the creation of the database to JUNE 2023, 8 databases in English and Chinese were searched. SRs/MAs that met the inclusion and exclusion criteria were included. Two reviewers independently screened research, extracted data and assessed methodological quality, risk of bias, report quality and evidence quality by using relevant criteria from AMSTAR-2, ROBIS scale, PRISMA, and GRADE system. RESULTS: The short-term effect, long-term effect, quality of life improvement, safety and pain relief effect in 8 included SRs/MAs were assessed in this overview according to quantitative synthesis. Results assessed by AMSTAR-2, PRISMA, and ROBIS were generally unsatisfactory, with the results of the AMSTAR-2 assessment showing that all of them were of low or critically low quality; the number of items in the included research that were fully reported (compliance was 100%) by the PRISMA checklist was only 50%, while there were 38.10% of the research reporting less than 60% completeness; the ROBIS assessment showed a small number of systems to be low risk of bias. In addition, 26 items were rated as moderate quality, while 50.94% of items were rated as low or critically low quality by GRADE. CONCLUSION: HCS may be a promising adjuvant therapy for NSCLC. However, high-quality SRs/MAs and randomized control trials (RCTs) should be conducted to provide sufficient evidence so as to draw a definitive conclusion.

Wide Response Range Photoelectrochemical UV Detector Based on Anodized TiO2-Nanotubes@Ti@quartz Structure.

Conventional sandwich structure photoelectrochemical UV detectors cannot detect UV light below 300 nm due to UV filtering problems. In this work, we propose to place the electron collector inside the active material, thus avoiding the effect of electrodes on light absorption. We obtained a TiO2-nanotubes@Ti@quartz photoanode structure by precise treatment of a commercial Ti mesh by anodic oxidation. The structure can absorb any light in the near-UV band and has superior stability to other metal electrodes. The final encapsulated photoelectrochemical UV detectors exhibit good switching characteristics with a response time below 100 ms. The mechanism of the oxidation conditions on the photovoltaic performance of the device was investigated by the electrochemical impedance method, and we obtained the optimal synthesis conditions. Response tests under continuous spectroscopy confirm that the response range of the device is extended from 300-400 nm to 240-400 nm. This idea of a built-in collector is an effective way to extend the response range of a photoelectrochemical detector.

Cultivation of microalgae-bacteria consortium by waste gas-waste water to achieve CO2 fixation, wastewater purification and bioproducts production.

The cultivation of microalgae and microalgae-bacteria consortia provide a potential efficient strategy to fix CO2 from waste gas, treat wastewater and produce value-added products subsequently. This paper reviews recent developments in CO2 fixation and wastewater treatment by single microalgae, mixed microalgae and microalgae-bacteria consortia, as well as compares and summarizes the differences in utilizing different microorganisms from different aspects. Compared to monoculture of microalgae, a mixed microalgae and microalgae-bacteria consortium may mitigate environmental risk, obtain high biomass, and improve the efficiency of nutrient removal. The applied microalgae include Chlorella sp., Scenedesmus sp., Pediastrum sp., and Phormidium sp. among others, and most strains belong to Chlorophyta and Cyanophyta. The bacteria in microalgae-bacteria consortia are mainly from activated sludge and specific sewage sources. Bioengineer in CBB cycle in microalgae cells provide effective strategy to achieve improvement of CO2 fixation or a high yield of high-value products. The mechanisms of CO2 fixation and nutrient removal by different microbial systems are also explored and concluded, the importance of microalgae in the technology is proven. After cultivation, microalgae biomass can be harvested through physical, chemical, biological and magnetic separation methods and used to produce high-value by-products, such as biofuel, feed, food, biochar, fertilizer, and pharmaceutical bio-compounds. Although this technology has brought many benefits, some challenging obstacles and limitation remain for industrialization and commercializing.

Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model.

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Soft-Hard Janus Nanoparticles Triggered Hierarchical Conductors with Large Stretchability, High Sensitivity, and Superior Mechanical Properties.

There is a long-standing conflict between the large stretchability and high sensitivity for strain sensors, a strategy of decoupling the mechanical/electrical module by constructing the hierarchical conductor has been developed in this study. The hierarchical conductor, consisting of a mechanically stretchable layer, a conductive network layer, and a strongly bonded interface, can be produced in a simple one-step process with the aid of soft-hard Janus nanoparticles (JNPs). The introduction of JNPs in the stretchable layer can evenly distribute stress and dissipate energy due to forming the rigid-flexible homogeneous networks. Specifically, JNPs can drive graphene nanosheets (GNS) to fold or curl, creating the unique JNPs-GNS building block that can further construct the conductive network. Due to its excellent deformability to hinder crack propagation, the flexible conductive network could be stretched continuously and the local conductive pathways could be reconstructed. Consequently, the hierarchical conductor could detect both subtle strain of 0-2% and large strain of up to 370%, with a gauge factor (GF) from 66.37 to 971.70, demonstrating outstanding stretchability and sensitivity. And it also owns large tensile strength (5.28 MPa) and high deformation stability. This hierarchical design will give graphene-based sensors a major boost in emerging applications.

Identifying BMI-associated genes via a genome-wide multi-omics integrative approach using summary data.

OBJECTIVE: This study aims to identify BMI-associated genes by integrating aggregated summary information from different omics data. METHODS: We conducted a meta-analysis to leverage information from a genome-wide association study (n = 339 224), a transcriptome-wide association study (n = 5619), and an epigenome-wide association study (n = 3743). We prioritized the significant genes with a machine learning-based method, netWAS, which borrows information from adipose tissue-specific interaction networks. We also used the brain-specific network in netWAS to investigate genes potentially involved in brain-adipose interaction. RESULTS: We identified 195 genes that were significantly associated with BMI through meta-analysis. The netWAS analysis narrowed down the list to 21 genes in adipose tissue. Among these 21 genes, six genes, including FUS, STX4, CCNT2, FUBP1, NDUFS3, and RAPSN, were not reported to be BMI-associated in PubMed or GWAS Catalog. We also identified 11 genes that were significantly associated with BMI in both adipose and whole brain tissues. CONCLUSION: This study integrated three types of omics data and identified a group of genes that have not previously been reported to be associated with BMI. This strategy could provide new insights for future studies to identify molecular mechanisms contributing to BMI regulation.

Combining TIGIT blockade with IL-15 stimulation is a promising immunotherapy strategy for lung adenocarcinoma.

BACKGROUND: T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immune checkpoint molecule that suppresses CD8+ T-cell function in cancer. However, the expression profile and functional significance of TIGIT in the immune microenvironment of lung adenocarcinoma (LUAD) remain elusive. Interleukin (IL)-15 has emerged as a promising candidate for enhancing CD8+ T-cell mediated tumour eradication. Exploring therapeutic strategies that combine IL-15 with TIGIT blockade in LUAD is warranted. METHODS: We investigated the regulatory network involving coinhibitory TIGIT and CD96, as well as costimulatory CD226 in LUAD using clinical samples. The potential role of TIGIT in regulating the pathogenesis of LUAD was addressed through a murine model with transplanted tumours constructed in Tigit-/- mice. The therapeutic strategy that combines TIGIT blockade with IL-15 stimulation was verified using a transplanted tumour murine model and a patient-derived organoid (PDO) model. RESULTS: The frequency of TIGIT+ CD8+ T cells was significantly increased in LUAD. Increased TIGIT expression indicated poorer prognosis in LUAD patients. Furthermore, the effector function of TIGIT+ CD8+ tumour-infiltrating lymphocytes (TILs) was impaired in LUAD patients and TIGIT inhibited antitumour immune response of CD8+ TILs in tumour-bearing mice. Mechanistically, IL-15 enhanced the effector function of CD8+ TILs but stimulated the expression of TIGIT on CD8+ TILs concomitantly. The application of IL-15 combined with TIGIT blockade showed additive effects in enhancing the cytotoxicity of CD8+ TILs and thus further increased the antitumour immune response in LUAD. CONCLUSIONS: Our findings identified TIGIT as a promising therapeutic target for LUAD. LUAD could benefit more from the combined therapy of IL-15 stimulation and TIGIT blockade.

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy.

Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

Zipper-Confined DNA Nanoframe for High-Efficient and High-Contrast Imaging of Heterogeneous Tumor Cell.

Current study in the heterogeneity and physiological behavior of tumor cells is limited by the fluorescence in situ hybridization technology in terms of probe assembly efficiency, background suppression capability, and target compatibility. In a typically well-designed assay, hybridization probes are constructed in a confined nanostructure to achieve a rapid assembly for efficient signal response, while the excessively high local concentration between different probes inevitably leads to nonspecific background leakage. Inspired by the fabric zipper, we propose a novel confinement reaction pattern in a zipper-confined DNA nanoframe (ZCDN), where two kinds of hairpin probes are independently anchored respective tracks. The metastable states of the dual tracks can well avoid signal leakage caused by the nonspecific probe configuration change. Biomarker-mediated proximity ligation reduces the local distance of dual tracks, kinetically triggering an efficient allosteric chain reaction between the hairpin probes. This method circumvents nonspecific background leakage while maintaining a high efficiency in responding to targets. ZCDN is employed to track different cancer biomarkers located in both the cytoplasm and cytomembrane, of which the expression level and oligomerization behavior can provide crucial information regarding intratumoral heterogeneity. ZCDN exhibits high target response efficiency and strong background suppression capabilities and is compatible with various types of biological targets, thus providing a desirable tool for advanced molecular diagnostics.

An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.