Oncolytic vaccinia virus harboring aphrocallistes vastus lectin exerts anti-tumor effects by directly oncolysis and inducing immune response through enhancing ROS in human ovarian cancer.

Aphrocallistes vastus lectin (AVL) is a Ca2+ dependent C-type lectin produced by sponges. Previous studies have demonstrated that oncolytic vaccinia virus harboring AVL (oncoVV-AVL) effectively triggers cell death in various tumors. However, the effects of oncoVV-AVL on human ovarian cancer (OV) remain unknown. This study aims to investigate the mechanism-of-action of oncoVV-AVL in human OV cell lines and in tumor-bearing nude mice. We found that oncoVV-AVL could directly induce apoptosis and autophagy in ovarian cancer cells. Additionally, our results showed that oncoVV-AVL increased the serum levels of mouse IFN-γ (mIFN-γ), leading to the activation of M1-polarized macrophages. Conversely, NADPH, a reducing agent by providing reducing equivalents, reduced the production of mIFN-γ, and suppressed M1-polarization of macrophage. Based on these findings, we propose that oncoVV-AVL not only contributes to direct cytolysis, but also enhances host immune response by promoting ROS levels.

Temporal Trends in Survival Outcomes for Patients with Esophageal Cancer Following Neoadjuvant Chemoradiotherapy: A 14-Year Analysis.

BACKGROUND: The prognosis for patients with esophageal cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery has shown improvement in recent years. We sought to identify the critical factors contributing to enhanced survival outcomes. PATIENTS AND METHODS: We retrospectively examined 427 patients with esophageal cancer treated with nCRT and esophagectomy across two periods: P1 (from 1 January 2004 to 31 December 2011) and P2 (from 1 January 2012 to 31 December 2017). The introduction of the CROSS regimen and total meso-esophagectomy in P2 prompted an evaluation of their effects on perioperative outcomes and overall survival (OS). RESULTS: During P2, the occurrence of recurrent laryngeal nerve palsy increased significantly from 3.9 to 16.8% (p < 0.001), while pneumonia and in-hospital mortality rates remained unchanged. The median OS improved from 19.2 to 29.2 months (p < 0.001) between P1 and P2. Multivariable analysis identified higher nodal yields and the achievement of major response as favorable prognostic factors. Conversely, an involved circumferential resection margin (CRM), an advanced ypN stage, and pneumonia were independently associated with poor outcomes. Patients treated during P2 had a lower prevalence of involved CRM (10% vs. 25.1%, p < 0.001), a higher rate of major response (52.7% vs. 34.8%, p < 0.01), and a greater nodal yield (27.8 vs. 10.9, p < 0.001). CONCLUSIONS: The clinical outcomes following nCRT and surgery have improved significantly over time. This progress can be attributed to multiple factors, with the primary drivers being the refinement of nCRT protocols and the application of radical surgery.

ROS Induced by Aphrocallistes vastus Lectin Enhance Oncolytic Vaccinia Virus Replication and Induce Apoptosis in Hepatocellular Carcinoma Cells.

Oncolytic virotherapy is expected to provide a new treatment strategy for cancer. Aphrocallistes vastus lectin (AVL) is a Ca2+-dependent lectin receptor containing the conserved domain of C-type lectin and the hydrophobic N-terminal region, which can bind to the bird's nest glycoprotein and D-galactose. Our previous studies suggested that the oncolytic vaccinia virus (oncoVV) armed with the AVL gene exerted remarkable replication and antitumor effects in vitro and in vivo. In this study, we found that oncoVV-AVL may reprogram the metabolism of hepatocellular carcinoma cells to promote ROS, and elevated ROS subsequently promoted viral replication and induced apoptosis. This study will provide a new theoretical basis for the application of oncoVV-AVL in liver cancer.

Using unsupervised learning to classify inlet water for more stable design of water reuse in industrial parks.

The water reuse facilities of industrial parks face the challenge of managing a growing variety of wastewater sources as their inlet water. Typically, this clustering outcome is designed by engineers with extensive expertise. This paper presents an innovative application of unsupervised learning methods to classify inlet water in Chinese water reuse stations, aiming to reduce reliance on engineer experience. The concept of 'water quality distance' was incorporated into three unsupervised learning clustering algorithms (K-means, DBSCAN, and AGNES), which were validated through six case studies. Of the six cases, three were employed to illustrate the feasibility of the unsupervised learning clustering algorithm. The results indicated that the clustering algorithm exhibited greater stability and excellence compared to both artificial clustering and ChatGPT-based clustering. The remaining three cases were utilized to showcase the reliability of the three clustering algorithms. The findings revealed that the AGNES algorithm demonstrated superior potential application ability. The average purity in six cases of K-means, DBSCAN, and AGNES were 0.947, 0.852, and 0.955, respectively.

Exploring source-specific ecological risks of PAHs near oil platforms in the Yellow River Estuary, Bohai Sea.

The Yellow River Estuary (YRE) is one of highly remarkable regions profoundly impacted by human activities, with numerous oil platforms dispersed throughout. In this area, offshore oil exploitation may pose significant ecological risks. To comprehensively evaluate the quantitative impacts of oil field exploitation on the marine coastal ecosystem, this study investigated the occurrence, sources, and ecological risks associated with 16 polycyclic aromatic hydrocarbons (PAHs) in seawater and sediment near oil platforms in the YRE. We found that 1) The concentrations of PAHs decreased from the surface seawater to sediments; 2) The ecological risk level of PAHs in seawater exceeded that in sediments; 3) terrestrial sources (combustion), rather than offshore oil drilling activities, significantly influenced regional ecological risks through processes of atmospheric deposition and surface runoff. These findings provide essential data for future estuarine research efforts while supporting mitigation measures aimed at addressing marine environmental pollution related to oil production activities.

Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy.

In the field of innovative cancer treatment strategies, oncolytic vaccinia virus (VV)es have gained traction as promising vectors. In the current study, we inserted the human C-type lectin domain family 2 member A (CLEC2A) gene into VV, creating a replicating therapeutic, oncoVV-CLEC2A. The findings reveal that oncoVV-CLEC2A effectively suppresses colorectal proliferation of mouse xenografts and a range of human cancer cell lines by augmenting viral reproduction capabilities, including the lung cancer H460 cell line, colorectal cancer cell lines (HCT116 and SW620), and hepatocellular carcinoma HuH-7 cell line. Moreover, it is evident that oncoVV-CLEC2A can induce antitumor immunity by boosting cytokine production but not antivirus response, and enhancing calreticulin expression. Further investigation indicates that oncoVV-CLEC2A can enhance antitumor capabilities by activating natural killer cells to produce interferon-γ and induce M1-like macrophage polarization. These findings shed light on the antitumor mechanisms of oncoVV-CLEC2A, provide a theoretical basis for oncolytic therapies, and lay the groundwork for novel strategies for modifying VVs.

Governance pathway for coastal eutrophication based on regime shifts in diatom-dinoflagellate composition of the Bohai and Baltic Seas.

Regime shifts in the diatom-dinoflagellate composition have occurred in the Baltic Sea (BS) and Bohai Sea (BHS) under eutrophication and have affected the entire coastal ecosystem, damaging the regulatory, provisioning, cultural, and supporting service functions of marine ecosystems. Therefore, finding a solution to restore the balance of phytoplankton community composition and mitigate eutrophication is of utmost importance. In this study, the Driver (per capita gross domestic product)-Pressure (terrestrial inputs)-State (seawater environmental parameters)-Impact (proportions of diatoms and dinoflagellates)-Response (eutrophication governance projects) framework served as a guide for our analysis of the causal relationship among various environmental components in the coastal system. The relevant data in BS and BHS spanning from the 1950s to the 2010s were collected and used to construct a diatom-dinoflagellate composition single index, which allowed us to identify the shifts in regimes (mutation points and phases) of the diatom-dinoflagellate composition and environmental factors using sequential t-test analysis. We also identified key environmental factors that moderated the diatom-dinoflagellate composition using redundancy analysis and analyzed the partial effects of the main environmental factors on the diatom-dinoflagellate composition using a generalized additive model. Finally, the regulation of the eutrophication governance investment on diatom-dinoflagellate composition was investigated. We found that (1) BS is a "time machine," with coastal eutrophication governance and regime shift of diatom-dinoflagellate composition and environmental factors two decades earlier than that in BHS; (2) in BS, the key moderation factor of diatom proportion is SiO3-Si and those of dinoflagellates are sea surface salinity and N:P ratio; in BHS, the key moderation factors of diatom proportion are PO4-P and Si:N ratio and those of dinoflagellate are dissolved inorganic nitrogen and N:P and Si:P ratios; (3) it is projected that BHS will enter its recovery phase from eutrophication after mid-2020s. In summary, the N/P/Si stoichiometric relationships should be given greater consideration, with the exception of the "dose-response" relationship in both sea areas. Our results indicate an urgent need for an improved mechanistic understanding of how phytoplankton biodiversity changes in response to changes in nutrient load and how we should ultimately deal with the challenges that arise.

Near-infrared Rhodols-based fluorescent probe with large Stokes shift for tracking of H2S in food spoilage and living cells.

Hydrogen sulfide (H2S), as a biomarker signaling gas, is not only susceptible to food spoilage, but also plays a key function in many biological processes. In this work, an activated near infrared (NIR) H2S fluorescent probe was designed and synthesized with quinoline-conjugated Rhodols dye as fluorophore skeleton and a dinitrophenyl group as the responsive moiety. Due to the quenching effect of dinitrophenyl group and the closed-loop structure of Rhodols fluorophore, probe itself has a very weak absorption and fluorescence background signal. After the H2S-induced thiolysis reaction, the probe exhibits a remarkable colormetric change and NIR fluorescent enhancement response at 716 nm with large Stokes shift (116 nm), and possesses high sensing selectivity and sensitivity with a low detection limits of 330 nM. The response mechanism is systematically characterized by 1H NMR, MS and DFT calculations. The colorimetric change allows the probe to be used as a test strips to detect H2S in food spoilage, while NIR fluorescent response helps the probe monitor intracellular H2S.

A novel red-to-near-infrared AIE fluorescent probe for detection of Hg2+ with large Stokes shift in plant and living cells.

Due to the highly toxic nature of mercury ions to living organisms, accurately detecting Hg2+ in water samples and biological systems is of great significance. In this study, we designed and synthesized a novel red-to-near-infrared Aggregation-Induced Emission (AIE) fluorescent probe (named as DS) based Fluorene derivatives on specifically for Hg2+ detection. Probe DS can visually identify Hg2+ through an red-to-near-infrared fluorescence enhancement change, characterized by a large Stokes shift (130 nm) and AIE feature. This probe offers a fast response, high selectivity and sensitivity. The Hg2+-induced deprotection reaction of the thioketal mechanism was thoroughly investigated using nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) calculation. Additionly, dynamic light scattering (DLS) results indicated that the aggregation states changes of the molecular play a crucial role in the AIE fluorescence response of probe DS toward Hg2+. The red-to-near-infrared response with AIE feature not only avoids the interference of auto-fluorescence signals in complex environments, but also reduces the fluorescence quenching caused by probe molecular aggregation. This makes probe DS highly suitable for high-quality imaging detection of Hg2+ in aqueous environments. Furthermore, probe DS demonstrates the capability for visual fluorescence detection of Hg2+ concentrations in water sample, plant roots and living cells.

Prognostic nutritional index (PNI) and risk of non-alcoholic fatty liver disease and advanced liver fibrosis in US adults: Evidence from NHANES 2017-2020.

Objective: This study explored the potential association between the Prognostic Nutritional Index (PNI) and the incidence of non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF) in the adult population of the United States. Methods: Information on 6409 participants ≥18 years old was downloaded from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Multivariate analysis was combined with demographic factors to assess the relationships between PNI, NAFLD, and AF. A restricted cubic spline (RCS) was used to characterise the nonlinear association between the PNI and NAFLD and AF. Results: Patients without NAFLD had substantially lower mean values for parameters such as age, lymphocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), total cholesterol, triglycerides, HbA1c, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) than patients with NAFLD. Interestingly, non-NAFLD patients showed a pronounced increase in serum albumin levels compared to their NAFLD counterparts. In the subset without AF, there were discernibly lower measures of NLR, age, AST, ALT, γ-glutamyl transferase, triglycerides, neutrophil count, and body mass index (BMI) than in patients with AF. It was evident that those without AF had markedly elevated mean albumin and PNI levels in comparison to AF-affected individuals. In the comprehensive multivariable framework, a direct correlation was observed between PNI and NAFLD (adjusted odds ratio[aOR] = 1.07, 95% confidence interval [CI]: 1.05-1.09; p < 0.001), whereas PNI and AF were inversely correlated (aOR = 0.92; 95% CI: 0.88-0.96; p < 0.001). Within the RCS model, a swift ascendancy was noted in the relationship between the PNI and NAFLD, peaking at approximately 52. Conversely, a non-linear inverse association was observed between PNI and AF. Conclusion: Our analytical results indicate that elevated PNI levels are positively associated with an increased risk of NAFLD, but inversely related to the risk of AF. For robust validation of these observations, further research is required.

NLRP3 knockout in mice provided protection against Serratia marcescens-induced acute pneumonia by decreasing PD-L1 and PD-1 expression in macrophages.

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1ß secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO+ alveolar macrophages. The frequency of MARCO+ alveolar macrophages, PD-1 expression, particularly PD-1+ interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1ß levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia.

Unveiling the common laws of extracellular polymeric substances (EPS) properties on short-chain fatty acids production from sludge by EPS disintegration pretreatment.

The production of short-chain fatty acids (SCFAs) from sludge is promising, but the efficiency and product quality often vary because of extracellular polymeric substances (EPS) characteristics and pretreatment principles. This study adopted specific EPS disintegration pretreatment to treat different types of sludge. By correlation coefficient matrix analysis and correlation dynamics change resolution, the intrinsic relationships between the nature of EPS and the production of SCFAs from sludge was unveiled. We demonstrate that tight-bound EPS (TB-EPS) is a principal carbon reservoir, positively impacting SCFAs yields, in the fermentation system with EPS as the main fermentation substrate, it can contribute about 29.2 % for SCFAs growth during fermentation. Conversely, TB-EPS exhibits a negative correlation during fermentation due to EPS-SCFAs interconversion, while loosely bound EPS (LB-EPS) correlates positively. Proteins and polysaccharides in TB-EPS, especially proteins, significantly enhance individual SCFAs yields, predominantly acetic, propionic, and isovaleric acids. The findings would provide a theoretical basis for developing pretreatments and process-control technologies aimed at improving SCFAs production efficiency and quality.

Land use/cover drive functional patterns of bacterial communities in sediments of a subtropical river, China.

The bacterial community in sediment serves as an important indicator for assessing the environmental health of river ecosystems. However, the response of bacterial community structure and function in river basin sediment to different land use/cover changes has not been widely studied. To characterize changes in the structure, composition, and function of bacterial communities under different types of land use/cover, we studied the bacterial communities and physicochemical properties of the surface sediments of rivers. Surface sediment in cropland and built-up areas was moderately polluted with cadmium and had high nitrogen and phosphorus levels, which disrupted the stability of bacterial communities. Significant differences in the α-diversity of bacterial communities were observed among different types of land use/cover. Bacterial α-diversity and energy sources were greater in woodlands than in cropland and built-up areas. The functional patterns of bacterial communities were shown that phosphorus levels and abundances of pathogenic bacteria and parasites were higher in cropland than in the other land use/cover types; Urban activities have resulted in the loss of the denitrification function and the accumulation of nitrogen in built-up areas, and bacteria in forested and agricultural areas play an important role in nitrogen degradation. Differences in heavy metal and nutrient inputs driven by land use/cover result in variation in the composition, structure, and function of bacterial communities.

Population genetics of Aedes albopictus in the port cities of Hainan Island and Leizhou Peninsula, China.

BACKGROUND: Aedes albopictus is an important vector of arboviral diseases, transmitting yellow fever, dengue fever, chikungunya and Zika. Monitoring its population genetic diversity and genetic differentiation has become essential for the control of infectious disease epidemics, especially in the functional areas of ports of entry. Population genetic monitoring of Ae. albopictus in the port area can help in the monitoring of port mosquito invasions and establishing port sanitary and quarantine measures to prevent the introduction and transmission of vector-borne diseases. METHODS: Seventeen populations of Ae. albopictus were collected from five port cities on Hainan Island and the Leizhou Peninsula, 8 populations were collected from port areas, 4 from urban areas and 5 from rural areas. Nine microsatellite loci and the mitochondrial COI gene were used to study the population genetic diversity, population genetic structure and interpopulation gene flow of Ae. albopictus. RESULTS: The nine microsatellite loci used were highly polymorphic, with an average PIC value of 0.768. The UPGMA genetic tree, STRUCTURE barplot and PCoA analyses showed that the 17 Ae. albopictus populations could be divided into three genetic groups. All 17 populations showed high haplotype diversity (Hd = 0.8069-0.9678) and formed 133 distinct haplotypes. These haplotypes can be divided into four genetic clades, but they are not associated with the geographical distribution of Ae. albopictus. Fst and Nm showed strong gene flow and little differentiation among populations. CONCLUSION: Ae. albopictus in port areas are not significantly different from urban and rural populations due to strong gene flow, which prevents differentiation and increases the genetic diversity of the populations. High genetic diversity facilitates mosquito adaptation to complex environmental changes, which is a challenge for vector-borne disease control in port areas.

Identification of Novel, Selective Ataxia-Telangiectasia Mutated Kinase Inhibitors with the Ability to Penetrate the Blood-Brain Barrier: The Discovery of AZD1390.

The inhibition of ataxia-telangiectasia mutated (ATM) has been shown to chemo- and radio-sensitize human glioma cells in vitro and therefore might provide an exciting new paradigm in the treatment of glioblastoma multiforme (GBM). The effective treatment of GBM will likely require a compound with the potential to efficiently cross the blood-brain barrier (BBB). Starting from clinical candidate AZD0156, 4, we investigated the imidazoquinolin-2-one scaffold with the goal of improving likely CNS exposure in humans. Strategies aimed at reducing hydrogen bonding, basicity, and flexibility of the molecule were explored alongside modulating lipophilicity. These studies identified compound 24 (AZD1390) as an exceptionally potent and selective inhibitor of ATM with a good preclinical pharmacokinetic profile. 24 showed an absence of human transporter efflux in MDCKII-MDR1-BCRP studies (efflux ratio <2), significant BBB penetrance in nonhuman primate PET studies (Kp,uu 0.33) and was deemed suitable for development as a clinical candidate to explore the radiosensitizing effects of ATM in intracranial malignancies.

[Oral health and hygiene behavior in chronic renal failure patients].

PURPOSE: To investigate the oral health and hygiene behavior of chronic renal failure(CRF) patients in Shenzhen, so as to provide basis for formulating education for them. METHODS: The history of renal failure, oral health status and oral health care behavior of 336 patients with chronic renal failure(CRF) in the hemodialysis center of Shenzhen Second People's Hospital were investigated by questionnaire and oral examinations. RESULTS: At an average, dialysis was required for 3.2 years. The main cause of renal failure was glomerulonephritis in 49.11% of patients, hypertensive kidney lesion in 19.35% and diabetic nephropathy in 15.77% of patients; 77.8% of them kept brushing teeth two or more than two times every day; 72.9% patients suffered from oral problems such as toothache in recent 12 months. The rate of visiting a dentist when having complaints was 21.7%. CONCLUSIONS: The state of oral health of CRF is worse than the general population of comparable age in China, while their hygiene behavior is better than the corresponding reference general population. However, their consciousness of dental treatment is poor. Therefore, health education for CRF patients should include knowledge about oral diseases complicated with CRF and correct medical philosophy.