Real-time Realistic Volume Rendering of Consistently High Quality with Dynamic Illumination.

Direct Volume Rendering (DVR) plays an important role in scientific data visualization. To generate photo-realistic DVR results, the physical light transport throughout the volume is simulated by applying the Monte Carlo-based volumetric path tracing (VPT) approach. For real-time applications, due to the time constraint for rendering each frame, only a limited number of samples shall be taken for the computation per pixel. This can result in a significant amount of noise in the rendering results. This paper describes our optimized VPT sampling algorithm and a novel denoising technique to generate consistently high-quality realistic DVR results in real time. We develop a new shading model that can reduce estimation variance to enhance the quality of DVR results. Additionally, a hybrid acceleration structure is created by integrating both octree and macrocell to improve sampling efficiency. This allows the acquisition of sufficiently more shading samples while maintaining the desired interactive frame rate. To further eliminate remaining noise and improve temporal stability of DVR results, we develop a novel spatiotemporal denoising framework. Our denoiser decouples the estimated radiance into high-detail low-noise and low-detail high-noise components. Different denoising algorithms are separately applied to these components to reduce noise without introducing blurring artifacts. Our DVR system can consistently offer high rendering quality and good temporal stability across DVR result frames in real time. During fast user interactions and with rapid alterations of the illumination condition, our rendering method can still provide good visual comfort and representation accuracy without visible latency.

The effect of hyperuricemia and its interaction with hypertension towards chronic kidney disease in patients with type 2 diabetes: evidence from a cross- sectional study in Eastern China.

Objectives: This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes. Methods: This research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The correlation between serum uric acid levels and the risk of chronic kidney disease was assessed using a restricted cubic spline model. An unconditional multivariable logistic regression model, along with an interaction table, was utilized to explore the potential interaction effect of hyperuricemia and hypertension towards chronic kidney disease. Results: 1,756 patients with type 2 diabetes were included in this study, the prevalence of chronic kidney disease (CKD) was 27.62% in this population. A U-shaped non-linear pattern emerged correlating serum uric acid (SUA) levels and CKD risk, indicating that both low and high SUA levels were linked to an increased CKD risk. This risk achieved its lowest point (nadir) at SUA approximately equals to 285µmol/L (p for trend <0.05). Once adjustments for age, gender, education level, abnormal fasting plasma glucose (FPG), abnormal hemoglobin A1c (HbA1c), abnormal total cholesterol (TC), abnormal high-density lipoprotein cholesterol (HDL-C), alcohol consumption and duration of diabetes were factored in, it was found that patients with both hyperuricemia and hypertension demonstrated a 5.42-fold (95% CI: 3.72-7.90) increased CKD risk compared to the reference group. The additive interaction between hyperuricemia and hypertension was statistically significant, as manifested by the following values: a relative excess risk due to interaction (RERI) of 2.57 (95% CI: 0.71-4.71), an attributable proportion due to interaction (AP) of 0.47 (95% CI: 0.14-0.64), and a synergy index (SI) of 2.39 (95% CI: 1.24-4.58). In contrast, there was no significant interaction effect in multiplicative scale. Conclusion: Hyperuricemia and hypertension may contribute additively to CKD, beyond their isolated impacts. Evaluating the risk of CKD in type 2 diabetes patients necessitates considering this potential interaction.

The Relationship between Low-Sodium Salt Intake and Both Blood Pressure Level and Hypertension in Chinese Residents.

Compared to common salt, low-sodium salt can reduce blood pressure to varying degrees. However, the exact dosage relationship remains unclear. We aimed to investigate the dose-response relationships between low-sodium salt intake and systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the risk of hypertension, and to determine the optimal range for low-sodium salt intake. We investigated the basic characteristics and dietary profile of 350 individuals who consumed low-sodium salt. The samples were divided into three groups according to the 33.3rd and 66.6th percentiles of low-sodium salt intake in condiments (Q1: <4.72 g/d, Q2: ≥4.72 g/d, and <6.88 g/d, and Q3: ≥6.88 g/d). The restricted cubic spline results indicated that low-sodium salt intake decreased linearly with SBP and DBP, while low-sodium intake demonstrated a non-linear, L-shaped relationship with the risk of hypertension, with a safe range of 5.81 g to 7.66 g. The multiple linear regression analysis revealed that compared with group Q1, the DBP in group Q2 decreased by 2.843 mmHg (95%CI: -5.552, -0.133), and the SBP in group Q3 decreased by 4.997 mmHg (95%CI: -9.136, -0.858). Exploratory subgroup analyses indicated that low-sodium salt intake had a significant impact on reducing SBP in males, DBP in females, SBP in rural populations, and DBP in urban populations. The intake of low-sodium salt adheres to the principle of moderation, with 5.81-7.66 g potentially serving as a pivotal threshold.

Superoxide Photoproduction from Wetland Plant-Derived Dissolved Organic Matter: Implications for Biogeochemical Impacts of Plant Invasion.

Although the impacts of exotic wetland plant invasions on native biodiversity, landscape features, and carbon-nitrogen cycles are well appreciated, biogeochemical consequences posed by ecological competition, such as the heterogeneity of dissolved organic matter (DOM) from plant detritus and its impact on the formation of reactive oxygen species, are poorly understood. Thus, this study delves into O2•- photogeneration potential of DOM derived from three different parts (stem, leaf, and panicle) of invasive Spartina alterniflora (SA) and native Phragmites australis (PA). It is found that DOM from the leaves of SA and the panicles of PA has a superior ability to produce O2•-. With more stable aromatic structures and a higher proportion of sulfur-containing organic compounds, SA-derived DOM generally yields more O2•- than that derived from PA. UVA exposure enhances the leaching of diverse DOM molecules from plant detritus. Based on the reported monitoring data and our findings, the invasion of SA is estimated to approximately double the concentration of O2•- in the surrounding water bodies. This study can help to predict the underlying biogeochemical impacts from the perspective of aquatic photochemistry in future scenarios of plant invasion, seawater intrusion, wetland degradation, and elevated solar UV radiation.

Effect Modification of Heat-Related Mortality Risk by Air Pollutants in Shandong, China.

Although studies have reported the modification effect of air pollutants on heat-related health risk, little is known on the modification effect among various particulate matter with different particle size on mortality. We aimed to investigate whether the associations of hot temperatures with daily mortality were modified by different air pollutant levels in Shandong Province, China. Daily data of air pollutants, meteorological factors, and mortality of 1,822 subdistricts in Shandong province from 2013 to 2018 were collected. We used a time-stratified case-crossover model with an interaction term between the cross-basis term for ambient temperature and the linear function of particulate matter ≤1 µm (PM1), PM2.5, nitrogen dioxide (NO2), and ozone to obtain heat-mortality associations during the hot season. Results showed that the cumulative odds ratio of extreme heat on mortality over 0 to 10 days was 3.66 (95% CI: 3.10-4.31). The mortality risk during hot seasons was stronger at high air pollutant levels. The modification effect of particulate matters on heat-related mortality decreased by its aerodynamic diameter. Females and older adults over 75 years were more vulnerable to the modification effect of air pollutants, and significant differences were detected in the association between temperatures and mortality stratified by PM1 and PM2.5. Higher heat-related mortality risks were observed at high NO2 levels, especially for cardiorespiratory disease. The findings suggest that more consideration should be given to the combined effect of very fine particles and NO2 with ambient heat when developing healthcare strategies, and women and older adults should be given priority in health-related settings.

Association between spot urinary sodium-to-potassium ratio and blood pressure among Chinese adults aged 18-69 years: the SMASH study.

Background: Excessive sodium and low potassium intake are involved in the development of hypertension. Growing evidence showed that the sodium-to-potassium ratio (Na/K) was significantly associated with blood pressure (BP). However, studies on the dose-response relationship of spot urinary Na/K ratio with hypertension and BP in the general population are scarce, especially in the Chinese population. Materials and methods: Data from the post-intervention survey of the Shandong Ministry of Health Action on Salt and Hypertension (SMASH) project was analyzed. Associations between Na/K molar ratio and hypertension prevalence and between Na/K molar ratio and BP indices were analyzed using multivariable logistic and linear regression, respectively, followed by subgroup analysis and interaction analysis. The restricted cubic spline model was used to explore the dose-response relationship. Informed by existing literature, we adjusted for potential confounding factors, including temperature and renal function, to assess the association and dose-response relationship. Results: There was a non-linear positive association between Na/K and hypertension (OR:1.09, 95%CI: 1.08-1.11) and a linear positive association between Na/K and systolic BP, diastolic BP, and mean arterial pressure (ß 0.53, 95%CI: 0.45-0.60; ß 0.36, 95%CI: 0.31-0.41; and ß 0.42, 95%CI: 0.36-0.47, respectively). The association was stronger in individuals with hypertension, female patients, those in the 50-59-year age group, and those who were obese. Environmental temperatures had little impact on associations. Conclusion: Our findings provide further evidence that the spot urinary Na/K ratio is a simple, useful, and convenient indicator for monitoring salt reduction and potassium increase, which could be used in clinical and public health practices.

Phosphate-mediated degradation of organic pollutants in water with peroxymonosulfate revisited: Radical or non-radical oxidation?

Whilst it is generally recognized that phosphate enables to promote the removal of some organic pollutants with peroxymonosulfate (PMS) oxidation, however, there is an ongoing debate as to whether free radicals are involved. By integrating different methodologies, here we provide new insights into the reaction mechanism of the binary mixture of phosphates (i.e., NaH2PO4, Na2HPO3, and NaH2PO2) with peroxymonosulfate (PMS) or hydrogen peroxide (H2O2). Enhanced degradation of organic pollutants and observation of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) adducts (i.e. DMPOOH and 5,5-dimethyl-2-oxopyrroline-1-oxyl (DMPOX)) with electron paramagnetic resonance (EPR) in most phosphates/PMS system seemly support a radical-dominant mechanism. However, fluorescence probe experiments confirm that no significant amount of hydroxyl radicals (•OH) are produced in such reaction systems. PMS in the phosphate solutions (without any organics) remains relatively stable, but is only consumed while organic substrates are present, which is distinct from a typical radical-dominant Co2+/PMS system where PMS is continuously decomposed. Through density functional theory (DFT) calculation, the energy barriers of the phosphates/PMS reaction processes are greatly decreased when non-radical mechanism dominates. Complementary evidence suggests that the reactive intermediates of PMS-phosphate complex, rather than the free radicals, are capable of oxidizing electron-rich substrates such as DMPO and organic pollutants. Taking the case of phosphate/PMS system as an example, this study demonstrates the necessity of acquisition of lines of evidence for resolving paradoxes in identifying EPR adducts.

Development of a c-MET x CD137 bispecific antibody for targeted immune agonism in cancer immunotherapy.

BACKGROUND: Targeting the costimulatory receptor CD137 has shown promise as a therapeutic approach for cancer immunotherapy, resulting in anti-tumor efficacy demonstrated in clinical trials. However, the initial CD137 agonistic antibodies, urelumab and utomilumab, faced challenges in clinical trials due to the liver toxicity or lack of efficacy, respectively. Concurrently, c-MET has been identified as a highly expressed tumor-associated antigen (TAA) in various solid and soft tumors. METHODS: In this study, we aimed to develop a bispecific antibody (BsAb) that targets both c-MET and CD137, optimizing the BsAb format and CD137 binder for efficient delivery of the CD137 agonist to the tumor microenvironment (TME). We employed a monovalent c-MET motif and a trimeric CD137 Variable Heavy domain of Heavy chain (VHH) for the BsAb design. RESULTS: Our results demonstrate that the c-MET x CD137 BsAb provides co-stimulation to T cells through cross-linking by c-MET-expressing tumor cells. Functional immune assays confirmed the enhanced efficacy and potency of the c-MET x CD137 BsAb, as indicated by activation of CD137 signaling, target cell killing, and cytokine release in various tumor cell lines. Furthermore, the combination of c-MET x CD137 BsAb with Pembrolizumab showed a dose-dependent enhancement of target-induced T cell cytokine release. CONCLUSION: Overall, the c-MET x CD137 BsAb exhibits a promising developability profile as a tumor-targeted immune agonist by minimizing off-target effects while effectively delivering immune agonism. It has the potential to overcome resistance to anti-PD-(L)1 therapies.