Tumor microenvironment-modulated nanoparticles with cascade energy transfer as internal light sources for photodynamic therapy of deep-seated tumors.

Photodynamic therapy (PDT) is an appealing modality for cancer treatments. However, the limited tissue penetration depth of external-excitation light makes PDT impossible in treating deep-seated tumors. Meanwhile, tumor hypoxia and intracellular reductive microenvironment restrain the generation of reactive oxygen species (ROS). To overcome these limitations, a tumor-targeted self-illuminating supramolecular nanoparticle T-NPCe6-L-N is proposed by integrating photosensitizer Ce6 with luminol and nitric oxide (NO) for chemiluminescence resonance energy transfer (CRET)-activated PDT. The high H2O2 level in tumor can trigger chemiluminescence of luminol to realize CRET-activated PDT without exposure of external light. Meanwhile, the released NO significantly relieves tumor hypoxia via vascular normalization and reduces intracellular reductive GSH level, further enhancing ROS abundance. Importantly, due to the different ROS levels between cancer cells and normal cells, T-NPCe6-L-N can selectively trigger PDT in cancer cells while sparing normal cells, which ensured low side effect. The combination of CRET-based photosensitizer-activation and tumor microenvironment modulation overcomes the innate challenges of conventional PDT, demonstrating efficient inhibition of orthotopic and metastatic tumors on mice. It also provoked potent immunogenic cell death to ensure long-term suppression effects. The proof-of-concept research proved as a new strategy to solve the dilemma of PDT in treatment of deep-seated tumors.

Exploring near-infrared autofluorescence properties in parathyroid tissue: an analysis of fresh and paraffin-embedded thyroidectomy specimens.

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

SCKansformer: Fine-Grained Classification of Bone Marrow Cells via Kansformer Backbone and Hierarchical Attention Mechanisms.

The incidence and mortality rates of malignant tumors, such as acute leukemia, have risen significantly. Clinically, hospitals rely on cytological examination of peripheral blood and bone marrow smears to diagnose malignant tumors, with accurate blood cell counting being crucial. Existing automated methods face challenges such as low feature expression capability, poor interpretability, and redundant feature extraction when processing highdimensional microimage data. We propose a novel finegrained classification model, SCKansformer, for bone marrow blood cells, which addresses these challenges and enhances classification accuracy and efficiency. The model integrates the Kansformer Encoder, SCConv Encoder, and Global-Local Attention Encoder. The Kansformer Encoder replaces the traditional MLP layer with the KAN, improving nonlinear feature representation and interpretability. The SCConv Encoder, with its Spatial and Channel Reconstruction Units, enhances feature representation and reduces redundancy. The Global-Local Attention Encoder combines Multi-head Self-Attention with a Local Part module to capture both global and local features. We validated our model using the Bone Marrow Blood Cell FineGrained Classification Dataset (BMCD-FGCD), comprising over 10,000 samples and nearly 40 classifications, developed with a partner hospital. Comparative experiments on our private dataset, as well as the publicly available PBC and ALL-IDB datasets, demonstrate that SCKansformer outperforms both typical and advanced microcell classification methods across all datasets.

Potential protective role of chlorogenic acid against cyclophosphamide-induced reproductive damage in male mice.

Background: Cyclophosphamide (CP) is an anticancer drug; however, clinical utilization of CP is limited, resulting from its considerable toxicities. This research was performed to explore the protective effects of Chlorogenic acid (CGA) on reproductive damage induced by CP in mice. Methods: Blood samples were collected for analysis of hormone content subsequently; semen samples were evaluated for quality, and testis samples were used for histopathological evaluation and analysis of oxidative stress biomarkers, protein and gene expression levels of steroid regulatory factors, and steroid synthase. Results: The results noted that CGA increased serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) activity; increased SOD, GPx, and GSH oxidative stress levels in testis tissue; and decreased MDA content in testis tissue. Testicular cells in the CGA treatment group gradually returned to normal morphology, and CYP11A1 and CYP17A1 levels increased after CGA treatment. The mRNA levels of CYP11A1, CYP17A1, StAR, 3ß-HSD, and 17ß-HSD were significantly raised in the CGA dose group. In the test dose range, CGA can improve sperm quality, quantitative abnormality, and serum T synthesis disorder caused by CP. This mechanism may be correlated with the inhibition of oxidative stress and antioxidation levels. Conclusions: Therefore, CGA has a protective impact on testicular injuries arising from CP in mice.

SNAI2 as a Prognostic Biomarker Based on Cancer-Associated Fibroblasts in Patients With Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a common type of malignant tumor with therapeutic challenges. Cancer-associated fibroblasts (CAFs) promote LUAD growth and metastasis, regulate the tumor immune response, and influence tumor treatment responses and drug resistance. However, the molecular mechanisms through which CAFs control LUAD progression are largely unknown. In this study, we aimed to determine the correlations between CAF-related genes and overall survival (OS) in patients with LUAD. Methods: We acquired the gene expression data and clinical information of 522 patients with LUAD patients from The Cancer Genome Atlas (TCGA) and 442 patients with LUAD from the Gene Expression Omnibus (GEO) databases. CAF infiltration levels were assessed using the Microenvironment Cell Population (MCP) counter, the Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm, and Tumor Immune Dysfunction and Exclusion (TIDE) scores. A CAF-related gene network was constructed using the Weighted gene co-expression network analysis (WGCNA). Based on the CAF-related genes, univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to identify prognostic genes. Gene expression levels within the prognostic model were validated using the Cancer Cell Line Encyclopedia (CCLE) databases and Western blotting. Results: Our results demonstrated that high CAF scores were associated with lower survival rates in patients with LUAD. Gene modules that were highly correlated with high CAF scores were closely associated with tissue characteristics and extracellular matrix structures in LUAD. In addition, correlations between CAF scores and responses to immunotherapy and chemotherapy were observed. Finally, we found that SNAI2 expression was higher in lung cancer tissues than in normal tissues. Conclusion: Deepening our understanding of the influence of CAFs on tumor progression and treatment response at the molecular level can aid the development of more effective therapeutic strategies. This study provides important insights into the functional mechanisms of action of CAFs in LUAD and highlights their clinical implications.

Effect of concentration, temperature, and time on the stability of hepatitis C virus nucleic acid in serum.

To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 106-108 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant (P < 0.01). There was an interaction effect between concentration and time (P = 0.0448), and there was also an interaction effect between temperature and time (P < 0.01). There was no interaction effect between concentration and temperature (P = 0.11) or between concentration, temperature, and time (P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C. IMPORTANCE: Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control.

Detailed analysis of learning phases and outcomes in robotic and endoscopic thyroidectomy.

BACKGROUND: Thyroid surgery has undergone significant transformation with the introduction of minimally invasive techniques, particularly robotic and endoscopic thyroidectomy. These advancements offer improved precision and faster recovery but also present unique challenges. This study aims to compare the learning curves, operational efficiencies, and patient outcomes of robotic versus endoscopic thyroidectomy. METHODS: A retrospective cohort study was conducted, analyzing 258 robotic (da Vinci) and 214 endoscopic thyroidectomy cases. Key metrics such as operation duration, drainage volume, lymph node dissection outcomes, and hypoparathyroidism incidence were assessed to understand surgical learning curves and efficiency. RESULTS: Robotic thyroidectomy showed a longer learning curve with initially longer operation times and higher drainage volumes but superior lymph node dissection outcomes. Both techniques were safe, with no permanent hypoparathyroidism or recurrent laryngeal nerve damage reported. The study delineated four distinct stages in the robotic and endoscopic surgery learning curve, each marked by specific improvements in proficiency. Endoscopic thyroidectomy displayed a shorter learning curve, leading to quicker operational efficiency gains. CONCLUSION: Robotic and endoscopic thyroidectomies are viable minimally invasive approaches, each with its learning curves and efficiency metrics. Despite initial challenges and a longer learning period for robotic surgery, its benefits in complex dissections may justify specialized training. Structured training programs tailored to each technique are crucial for improving outcomes and efficiency. Future research should focus on optimizing training protocols and increasing accessibility to these technologies, enhancing patient care in thyroid surgery.

Quantitative Changes and Transformation Mechanisms of Saponin Components in Chinese Herbal Medicines during Storage and Processing: A Review.

Saponins are an important class of active components in Chinese herbal medicines (CHMs), which are present in large quantities in Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, Polygonati Rhizoma, etc., and have immune regulation, anti-tumor, anti-inflammatory, anti-cardiovascular disease, and hypoglycemic activities. Storage and processing are essential processes in the production process of CHMs which affect the stability of saponin components and then reduce the medicinal and economic value. Therefore, it is of great importance to investigate the effects of storage and processing conditions on the content of saponin components in CHMs. In this paper, the effects of various storage and processing factors, including temperature, pH, enzymes, meta lions, extraction methods, etc., on the saponin content of CHMs are investigated and the underlying mechanisms for the quantitative changes of saponin are summarized. These findings may provide technical guidance for the production and processing of saponin-rich CHMs.

Immunocompatible elastomer with increased resistance to the foreign body response.

Polymeric elastomers are extensively employed to fabricate implantable medical devices. However, implantation of the elastomers can induce a strong immune rejection known as the foreign body response (FBR), diminishing their efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE). EVADE materials effectively suppress the inflammation and capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane. We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting the local immune responses.

Aerobic Copper-Catalyzed Oxysulfonylation of Vinylarenes with Sodium Sulfinates under Mild Conditions: A Modular Synthesis of ß-Ketosulfones.

An aerobic copper-catalyzed oxysulfonylation of vinylarenes with sodium sulfinates is described. This protocol features mild reaction conditions, convenient operation, and broad substrate scope with respect to vinylarenes and sodium sulfinates. Notably, the protocol demonstrates excellent tolerance of functional groups such as chloro, bromo, ester, cyano, and nitro groups. Mechanistic investigations indicated that the reaction should undergo radical cascades involving a sulfonyl radical generated from sodium sulfinate with air as the terminal oxidant, addition across alkene to deliver a benzylic radical, and subsequent cross-coupling with air.

Defining correlates of protection for mammalian livestock vaccines against high-priority viral diseases.

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, and food security. Vaccination is fundamental to the control and prevention of exotic and endemic high-priority infectious livestock diseases. Successful implementation of vaccination in a biosecurity plan is underpinned by a strong understanding of correlates of protection-those elements of the immune response that can reliably predict the level of protection from viral challenge. While correlates of protection have been successfully characterized for many human viral vaccines, for many high-priority livestock viral diseases, including African swine fever and foot and mouth disease, they remain largely uncharacterized. Current literature provides insights into potential correlates of protection that should be assessed during vaccine development for these high-priority mammalian livestock viral diseases. Establishment of correlates of protection for biosecurity purposes enables immune surveillance, rationale for vaccine development, and successful implementation of livestock vaccines as part of a biosecurity strategy.

[Spatiotemporal Variation Characteristics and Driving Factors of Cultivated Land NPP in the Shandong Area Around the Bohai Sea].

The Bohai Rim Plain is an important grain-producing area in China. The cultivated land resources have great potential for production, but there are many influencing factors. Understanding the spatiotemporal change characteristics and driving factors of the net primary productivity （NPP） of cultivated land vegetation in this region is of great significance to improve the regional cultivated land production conditions, excavate and enhance the production capacity of cultivated land, and ensure national food security. In this study, Theil-Sen Median trend analysis, Mann-Kendall significance test, Hurst index, and other methods were used to explore the spatiotemporal change characteristics, stability, and sustainability of regional cultivated land NPP. The influence of driving factors on the spatial heterogeneity of cultivated land NPP was analyzed by using optical parameters-based geographical detectors. The results showed that： ① From 2001 to 2019, due to the expansion of construction land during industrialization and urbanization, the cumulative decrease in the area of cultivated land in the Shandong area around the Bohai Sea was 2 004.51 km2. ② During the selected research period, the interannual variation of average cultivated land NPP showed a fluctuating and increasing trend. In terms of spatial distribution, the NPP of cultivated land was bounded by the Dongying District, with the spatial heterogeneity in the north being significantly lower than that in the south. ③ The area with increasing NPP of cultivated land accounted for 88.06% of the total area of cultivated land, mainly with low and medium fluctuations. The NPP of cultivated land will maintain an overall sustained trend of increase across the region in the future. ④ The average annual relative humidity study area had the strongest explanatory power for the spatial variability of NPP in cropland, with a q-value of 0.26, followed by surface soil salinity and subsoil salinity, with q-values greater than 0.2. The interactions between the different drivers all showed either nonlinear enhancement or bifactorial enhancement. The results of this study will help to reveal the characteristics of the changes in cultivated land production capacity and its driving forces in the Bohai Sea region and also provide a theoretical basis for the ecological protection and sustainable development of the region.

Removable Photocatalysis Microneedle Reactor for Carbon Monoxide Delivery to Enhance Chemosensitization.

Carbon monoxide (CO) has emerged as a promising therapeutic agent, yet ensuring safe and precise CO delivery remains challenging. Here, we report a removable hydrogel-forming microneedle (MN) reactor for CO delivery via photocatalysis, with an emphasis on chemosensitization. Upon application, body fluids absorbed by the MNs dissolve the effervescent agents, leading to the generation of carbon dioxide (CO2) and triggering the release of the chemotherapeutics cisplatin. Meanwhile, the photocatalysts (PCs) trapped within MNs convert CO2 to CO under 660 nm light irradiation. These PCs can be removed by hydrogel-forming MNs, thereby mitigating potential biological risks associated with residual PCs. Both in vitro and in vivo experiments showed that MN-mediated CO delivery significantly improved tumor sensitivity to cisplatin by suppressing DNA repair, using an A375/CDDP melanoma model. This removable photocatalysis MN reactor offers safe and precise local delivery of CO, potentially creating new opportunities for CO or its combination therapies.

An elastomer with in situ generated pure zwitterionic surfaces for fibrosis-resistant implants.

Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.

Decreased ENSO post-2100 in response to formation of a permanent El Niño-like state under greenhouse warming.

Under transient greenhouse warming, El Niño-Southern Oscillation (ENSO) is projected to increase pre-2100, accompanied by an easier establishment of atmospheric convection in the equatorial eastern Pacific, where sea surface temperature (SST) warms faster than surrounding regions. After 2100, how ENSO variability may change remains unknown. Here we find that under a high emission scenario, ENSO variability post-2100 reverses from the initial increase to an amplitude far smaller than that of the 20th century. The fast eastern warming persists and shrinks the equatorial Pacific non-convective area, such that establishing convection in the non-convective area, as during an El Niño, requires smaller convective anomaly, inducing weaker wind anomalies leading to reduced ENSO SST variability. The nonlinear ENSO response is thus a symptom of the persistent El Niño-like warming pattern. Therefore, the oscillatory ENSO impact could be replaced by that from the permanent El Niño-like mean condition with cumulative influences on affected regions.

Inhibition of Monilinia fructicola sporulation and pathogenicity through eucalyptol-mediated targeting of MfCat2 by Streptomyces lincolnensis strain JCP1-7.

Peach brown rot, attributed to Monilinia fructicola, presents a significant threat to postharvest peach cultivation, causing losses of up to 80%. With an increasing number of countries, spearheaded by the European Union, imposing bans on chemical agents in fruit production, there is a growing interest in mining highly active antibacterial compounds from biological control strains for postharvest disease management. In this study, we highlight the unique ability of Streptomyces lincolnensis strain JCP1-7 to inhibit M. fructicola sporulation, despite its limited antimicrobial efficacy. Through GC-MS analysis, eucalyptol was identified as the key compound. Fumigation of diseased fruits with eucalyptol at a concentration of 0.0335 µg cm-3 demonstrated an in vivo inhibition rate against M. fructicola of 93.13%, completely suppressing spore formation. Transcriptome analysis revealed the impact of eucalyptol on multiple pathogenesis-related pathways, particularly through the inhibition of catalase 2 (Cat2) expression. Experiments with a MfCat2 knockout strain (ΔMfCat2) showed reduced pathogenicity and sensitivity to JCP1-7 and eucalyptol, suggesting MfCat2 as a potential target of JCP1-7 and eucalyptol against M. fructicola. Our findings elucidate that eucalyptol produced by S. lincolnensis JCP1-7 inhibits M. fructicola sporulation by regulating MfCat2, thereby effectively reducing postharvest peach brown rot occurrence. The use of fumigation of eucalyptol offers insights into peach brown rot management on a large scale, thus making a significant contribution to agricultural research.

Genomic epidemiology of Mycobacterium abscessus at an adult cystic fibrosis programme reveals low potential for healthcare-associated transmission.

Rationale: Nontuberculous mycobacteria (NTM) has been reported to be transmitted between people with cystic fibrosis (CF) attending CF centres. A suspected Mycobacterium abscessus outbreak was investigated at the University of Texas Southwestern (UTSW) Adult CF Program using a combination of pathogen genomic sequencing and epidemiologic methods. The objectives of the present study were to apply the Healthcare-Associated Links in Transmission of NTM (HALT NTM) study to investigate the occurrence of potential healthcare-associated transmission and/or acquisition of NTM among people with CF infected with genetically similar NTM isolates. Methods: Whole-genome sequencing of respiratory M. abscessus isolates from 50 people with CF receiving care at UTSW was performed to identify genetically similar isolates. Epidemiologic investigation, comparison of respiratory and environmental isolates, and home residence watershed mapping were studied. Measurements and main results: Whole-genome sequencing analysis demonstrated seven clusters of genetically similar M. abscessus (four ssp. abscessus and three ssp. massiliense). Epidemiologic investigation revealed potential opportunities for healthcare-associated transmission within three of these clusters. Healthcare environmental sampling did not recover M. abscessus, but did recover four human disease-causing species of NTM. No subjects having clustered infections lived in the same home residence watershed. Some subjects were infected with more than one M. abscessus genotype, both within and outside of the dominant circulating clones. Conclusions: Healthcare-associated person-to-person transmission of M. abscessus appears to be rare at this centre. However, polyclonal infections of M. abscessus species and subspecies, not originating from the endemic hospital environment, suggest multiple shared modes of acquisition outside the healthcare setting.

[Spatial Prediction and Influencing Factors Analysis of Soil Salinization in Coastal Area Based on MGWR].

Quantitative analysis of the spatial non-stationary characteristics of soil salinization influencing factors and the prediction of its spatial distribution are of great significance for the rational use of coastal saline soil resources and the formulation of local prevention and control measures. In this study, the Hekou District of Dongying City, Shandong Province, was used as the study area, and the descriptive statistics of soil salinization status were conducted using classical statistical methods. Spatial autocorrelation theory was used to explore the characteristics of global and local spatial structure of soil salinization in the study area. Influential factors related to soil salinity were selected, and multivariate linear regression （MLR）, geographically weighted regression （GWR）, and multi-scale geographically weighted regression （MGWR） methods were used to model and predict the spatial distribution of soil salinity in the study area and to analyze the spatial heterogeneity of the effects of different influencing factors on soil salinity. The results showed that： ① The mean value of soil salinity in the study area was 5.84 g·kg-1, indicating severe salinization, with a global Moran's I index of 0.19 （P<0.00） and obvious spatial aggregation characteristics. ② Among the three models, the MGWR model had the highest modeling accuracy. Compared with that of the MLR model, the Radj2 of GWR and MGWR improved by 0.05 and 0.07, respectively, and the RSS decreased by 210.13 and 179.95, respectively. ③ The results of MGWR regression showed that the spatial distribution of soil salinity appeared to be mainly affected by the middle soil salinity, soil clay content, and vegetation cover from the mean values of standardized regression coefficients of different influencing factors. Different influencing factors had significant spatial non-stationary characteristics on soil salinization. ④ The results of the spatial distribution prediction of soil salinity in MGWR showed that the areas of high soil salinity （≥6 g·kg-1） were mainly distributed in the northern part of the study area, with an overall spatial trend of decreasing from the coast to the interior. The results of the study can be used as a reference for the analysis and predictive mapping of factors affecting soil salinization in the county and on a larger scale using MGWR.

Oncolytic Activity of Sindbis Virus with the Help of GM-CSF in Hepatocellular Carcinoma.

Hepatocellular carcinoma is a refractory tumor with poor prognosis and high mortality. Many oncolytic viruses are currently being investigated for the treatment of hepatocellular carcinoma. Based on previous studies, we constructed a recombinant GM-CSF-carrying Sindbis virus, named SINV-GM-CSF, which contains a mutation (G to S) at amino acid 285 in the nsp1 protein of the viral vector. The potential of this mutated vector for liver cancer therapy was verified at the cellular level and in vivo, respectively, and the changes in the tumor microenvironment after treatment were also described. The results showed that the Sindbis virus could effectively infect hepatocellular carcinoma cell lines and induce cell death. Furthermore, the addition of GM-CSF enhanced the tumor-killing effect of the Sindbis virus and increased the number of immune cells in the intra-tumor microenvironment during the treatment. In particular, SINV-GM-CSF was able to efficiently kill tumors in a mouse tumor model of hepatocellular carcinoma by regulating the elevation of M1-type macrophages (which have a tumor-resistant ability) and the decrease in M2-type macrophages (which have a tumor-promoting capacity). Overall, SINV-GM-CSF is an attractive vector platform with clinical potential for use as a safe and effective oncolytic virus.