Optimizing nickel-aluminium layered double hydroxides for supercapacitors: The role of 3D structural assembly.

Nickel-aluminium layered double hydroxides (NiAl-LDHs) have emerged as promising electrode materials for supercapacitors (SCs) due to their inherently high specific surface area and theoretical specific capacitance, which are primarily attributed to the rapid pseudocapacitive response at the surface. However, NiAl-LDHs typically form agglomerated nanosheets, leading to a significant reduction in specific surface area, which is crucial for enhancing the number of active sites and improving the capacitive properties of the materials. To overcome this limitation, 2D nanostructures were assembled into 3D architectures by synthesizing NiAl-LDHs with distinct morphologies in a one-step hydrothermal process using an alkaline agent (NH4F). This approach resulted in the formation of 3D NiAl-LDH/HN4F structures, which exhibit a larger contact area and a greater number of redox-active sites. Consequently, the 3D NiAl-LDH/HN4F electrodes demonstrated a significantly higher specific surface area, leading to remarkable improvements in specific capacitance (1219 ± 30F g-1) and energy density (61 ± 1 Wh kg-1) compared to their 2D counterparts. This structural enhancement increases both the surface area and active site density while providing a new framework for designing high-performance LDH-based electrodes.

Hollow dodecahedral Zn0.3Cd0.7S@NiCo-mixed metal oxide p-n heterojunction with high-efficiency photocatalytic hydrogen production activity.

The growing demand for clean and sustainable energy has driven extensive research into efficient photocatalysts for hydrogen production. However, many semiconductor photocatalysts in this field still face the challenges such as wide band gap, limited visible light absorption, and inefficient separation and transport of photoinduced charges. In this study, nickel-cobalt layered double hydroxide (NiCo-LDH) was synthesized using an "etch-and-grow" method with zeolitic imidazolate framework-67 (ZIF-67) as a sacrificial template, followed by high-temperature calcination to produce nickel-cobalt mixed metal oxide (NiCo-MMO). Zn0.3Cd0.7S quantum dots were used to modify NiCo-MMO resulting in a hollow dodecahedral Zn0.3Cd0.7S@NiCo-MMO composite photocatalyst. In hydrogen production performance test, the optimized Zn0.3Cd0.7S@NiCo-MMO exhibited excellent performance (8177.5 µmol·g-1·h-1) and demonstrated good cycling stability. The hollow dodecahedral structure of the Zn0.3Cd0.7S@NiCo-MMO enhanced the light trapping ability and provided large surface area. The p-n heterojunction formed within Zn0.3Cd0.7S@NiCo-MMO accelerated carrier separation and transfer, effectively inhibited the recombination of photogenerated electrons and holes, and significantly improved the hydrogen production activity.

Efficient chlorination reaction of Pt/RuO2/g-C3N4 under visible light irradiation for simultaneous removal of ammonia and bacteria from mariculture wastewater.

The removal of ammonia nitrogen (NH4+-N) and bacteria from aquaculture wastewater holds paramount ecological and production significance. In this study, Pt/RuO2/g-C3N4 photocatalysts were prepared by depositing Pt and RuO2 particles onto g-C3N4. The physicochemical properties of photocatalysts were explored by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV-vis diffuse reflectance spectrometer (UV-vis DRS). The photocatalysts were then applied to the removal of both NH4+-N and bacteria from simulated mariculture wastewater. The results clarified that the removals of both NH4+-N and bacteria were in the sequence of g-C3N4 < RuO2/g-C3N4 < Pt/g-C3N4 < Pt/RuO2/g-C3N4. This magnificent photocatalytic ability of Pt/RuO2/g-C3N4 can be interpreted by the transfer of holes from g-C3N4 to RuO2 to facilitate the in situ generation of HClO from Cl- in wastewater, while Pt extracts photogenerated electrons for H2 formation to enhance the reaction. The removal of NH4+-N and disinfection effect were more pronounced in simulated seawater than in pure water. The removal efficiency of NH4+-N increases with an increase in pH of wastewater, while the bactericidal effect was more significant under a lower pH in a pH range of 6-9. In actual seawater aquaculture wastewater, Pt/RuO2/g-C3N4 still exhibits effective removal efficiency of NH4+-N and bactericidal performance under sunlight. This study provides an alternative avenue for removement of NH4+-N and bacteria from saline waters under sunlight.

Photothermal and enhanced chemodynamic reinforced anti-tumor therapy based on PDA@POM nanocomposites.

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have both demonstrated considerable efficacy in the tumor treatment individually, owing to their non-invasive nature and excellent selectivity. However, due to the propensity of tumors for metastasis and recurrence, a singular therapeutic approach falls short of achieving optimal treatment outcomes. Polydopamine (PDA) has excellent photothermal conversion ability and polyoxometalates (POMs) possess diverse enzymatic activities. Here, we synthesized PDA@POM nanospheres comprising polydopamine-coated Tungsten-based polyoxometalate (W-POM). These nanospheres leverage dual enzymatic activities that synergistically enhance both chemodynamic and photothermal therapies for tumor treatment. The PDA-mediated PTT effect enables precise tumor cell destruction, while the W-POM nanozymes catalyzes the generation of highly toxic reactive oxygen species (ROS) from hydrogen peroxide within tumor cells through a Fenton-like reaction, which mitigates tumor hypoxia and induces tumor cell death. This synergistic photothermal catalytic therapy shows enhanced efficacy in tumor suppression, providing a promising new approach for tumor treatment.

Two-color fluorescence-guided surgery for head and neck cancer resections.

Significance: Head and neck squamous cell carcinoma (HNSCC) has the sixth highest incidence worldwide, with > 650,000 cases annually. Surgery is the primary treatment option for HNSCC, during which surgeons balance two main goals: (1) complete cancer resection and (2) preservation of normal tissues to ensure post-surgical quality of life. Unfortunately, these goals are not synergistic, where complete cancer resection is often limited by efforts to preserve normal tissues, particularly nerves, and reduce life-altering comorbidities. Aim: Currently, no clinically validated technology exists to enhance intraoperative cancer and nerve recognition. Fluorescence-guided surgery (FGS) has successfully integrated into clinical medicine, providing surgeons with real-time visualization of important tissues and complex anatomy, where FGS imaging systems operate almost exclusively in the near-infrared (NIR, 650 to 900 nm). Notably, this spectral range permits the detection of two NIR imaging channels for spectrally distinct detection. Approach: Herein, we evaluated the utility of spectrally distinct NIR nerve- and tumor-specific fluorophores for two-color FGS to guide HNSCC surgery. Using a human HNSCC xenograft murine model, we demonstrated that facial nerves and tumors could be readily differentiated using these nerve- and tumor-specific NIR fluorophores. Results: The selected nerve-specific fluorophore showed no significant difference in nerve specificity and off-target tissue fluorescence in the presence of xenograft head and neck tumors. Co-administration of two NIR fluorophores demonstrated successful tissue-specific labeling of nerves and tumors in spectrally distinct NIR imaging channels. Conclusions: We demonstrate a comprehensive FGS tool for cancer resection and nerve sparing during HNSCC procedures for future clinical translation.

Medicine and food homology substances: A review of bioactive ingredients, pharmacological effects and applications.

In recent years, the idea of medicine and food homology (MFH), which highlights the intimate relationship between food and medicine, has gained international recognition. Specifically, MFH substances have the ability to serve as both food and medicine. Many foods have been reported to have good nutritional and medical values, not only for satiety but also for nourishing the body and treating diseases pharmacologically. As modern scientific research has progressed, the concept of MFH has been emphasized and developed in a way that has never been seen before. Therefore, in this paper, we reviewed the development history of MFH substances, summarized some typical bioactive ingredients, and recognized pharmacological effects. In addition, we further discussed the application of MFH substances in the food field, with the goal of providing ideas and references for the research and development of MFH in the food industry as well as the progress of related industries.

Low loading of Pt on MoB Constructed by microwave Quasi-solid approach with solvent Regulation for hydrogen evolution reaction.

The interaction between metal nanoclusters and the carrier can enhance the electron transfer rate to optimize the hydrogen evolution reaction (HER) performance, but the common synthesis approaches often lead to metal particle agglomeration, and then blocking active sites. Herein, highly-dispersed Pt nanoclusters supported onto molybdenum boride (MoB) is developed through microwave approach with various solvent to regulate the catalytic performance. The synthesized electrocatalyst with the addition of methanol (Pt/MoB-M) exhibits excellent electrocatalytic performance towards HER with low overpotential (13 mV at 10 mA cm-2), small Tafel slope (24 mV dec-1), and high mass activity (10.06 A/mgPt at 50 mV). This work presents a novel approach to prepare highly-efficient electrocatalysts for renewable energy-related applications of non-carbon supported low loading of precious metals.

Accumulation characteristics and fate modeling of phthalic acid esters in surface water from the Three Gorges Reservoir area, China.

Phthalic acid esters (PAEs) are a group of compounds widespread in the environment. To investigate the occurrence and accumulation characteristics of PAEs, surface water samples were collected from the Three Gorges Reservoir area, China. The total concentrations of 11 analyzed PAEs (∑11PAEs) in the collected water samples ranging from 197.7 to 1,409.3 ng/L (mean ± IQR: 583.1 ± 308.4 ng/L). While DEHP was the most frequently detected PAE, DnBP and DnNP were the most predominant PAEs in the analyzed water samples with a mean contribution of 63.3% of the ∑11PAEs. The concentrations of the ∑11PAEs in the water samples from the upper reaches of the Yangtze River were significantly higher than those from the middle reaches. To better understand the transport and fate of the PAEs, seven detected PAEs were modeled by Quantitative Water Air Sediment Interaction (QWASI). The simulated and measured values were close for most PAEs, and differences are within one order of magnitude even for the worst one. For all simulated PAEs, water and particle inflow were main sources in the reservoir, whereas water outflow and degradation in water were important removal pathways. The contribution ratios of different sources/losses varied from PAEs, depending on their properties. The calculated risk quotients of DnNP in the Three Gorges Reservoir area whether based on monitoring or simulating results were all far exceeded the safety threshold value, implying the occurrence of this PAE compound may cause potential adverse effects for the aquatic ecology of the Three Gorges Reservoir area.

Ag Atom Induces Microstrain Environment around Cd Sites to Construct Diatomic Sites for Almost 100% CO2-to-CO Electroreduction.

Deeply understanding how local microstrain environment around diatomic sites influences their electronic state and adsorption is crucial for improving electrochemical CO2 reduction (eCO2R) reaction; however, precise engineering of the atomic microstrain environment is challenging. Herein, we fabricate Ag-CdTMT electrocatalysts with AgN2S2-CdN2S2 diatomic sites by anchoring Ag to the nodes of CdTMT (TMT = 2,4,6-trimercaptotriazine anion) coordination polymers. The Ag-CdTMT catalysts achieve approximately 100% Faradaic efficiency for CO reduction with an industrial level current density (∼200 mA cm-2 in H-cell). The embedded Ag atoms induce the formation of Ag-Cd diatomic sites with local microstrain, stretching Cd-N/S bonds, and reinforcing electron localization at Cd sites. The microstrain engineering and adjacent Ag atoms synergistically reduced Cd 4d-C 2p antibonding orbital occupancy for intensifying *COOH adsorption as the rate-determining step. This study provides novel insights into customizing the electronic structure of diatomic sites through strain engineering.

Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy-a systematic review and meta-analysis.

Background: More and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection. Methods: We conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria. Results: A total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75∼0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [<2-cm subgroup: HR = 0.72, 95% CI (0.5∼0.94), P = 0.01; ≥2-cm subgroup: HR = 0.79, 95% CI (0.65∼0.96), P = 0.02] and the margin status [R0 subgroup: HR = 0.83, 95% CI (0.77∼0.88), P < 0.00001; R2 subgroup: HR = 0.75, 95% CI (0.61∼0.92), P = 0.007]. AC also benefited the patients with a stage N0 [HR = 0.79, 95% CI (0.74~0.84), P < 0.00001], N1 [HR = 0.78, 95% CI (0.72∼0.85), P < 0.00001], or poorly/undifferentiated tumor [HR = 0.76, 95% CI (0.66∼0.87), P < 0.0001] in survival but not in patients with a stage N2 [HR = 0.69, 95% CI (0.43∼1.09), P = 0.11] or well/moderately differentiated tumor [HR = 0.97, 95% CI (0.66∼1.42), P = 0.87]. Conclusions: Although AC showed survival benefit for patients with PC undergoing radical pancreatectomy after NAT, we still need to consider the lymph node stage and the degree of differentiation of the tumor when we gave AC to a patient. High-quality prospective randomized controlled studies are required to well disclose the value of AC in patients with PC undergoing radical pancreatectomy after NAT. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023461365.

Molecular and genetic basis of plant architecture in soybean.

Plant architecture determines canopy coverage, photosynthetic efficiency, and ultimately productivity in soybean (Glycine max). Optimizing plant architecture is a major goal of breeders to develop high yield soybean varieties. Over the past few decades, the yield per unit area of soybean has not changed significantly; however, rice and wheat breeders have succeeded in achieving high yields by generating semi-dwarf varieties. Semi-dwarf crops have the potential to ensure yield stability in high-density planting environments because they can significantly improve responses to fertilizer input, lodging resistance, and enhance resistance to various abiotic and biotic stresses. Soybean has a unique plant architecture, with leaves, inflorescences, and pods growing at each node; internode number greatly affects the final yield. Therefore, producing high-yielding soybean plants with an ideal architecture requires the coordination of effective node formation, effective internode formation, and branching. Dozens of quantitative trait loci (QTLs) controlling plant architecture have been identified in soybean, but only a few genes that control this trait have been cloned and characterized. Here, we review recent progress in understanding the genetic basis of soybean plant architecture. We provide our views and perspectives on how to breed new high-yielding soybean varieties.

Ambient air pollution and risk of allergic respiratory diseases in European and East Asian populations: A Mendelian randomization study.

BACKGROUND: Ambient air pollution has become a challenging global health issue since industrialization, especially affecting respiratory diseases. However, the causal link between air pollution and allergic respiratory diseases (ARDs) remains unclear due to confounding factors in conventional epidemiological studies across different populations. Thus, we aimed to clarify the causal associations between air pollution and ARDs in European and East Asian populations using Mendelian randomization (MR). METHODS: MR utilizes genetic variants and provides a satisfactory level of causal evidence. Genetic data for exposures (PM2.5, PM2.5 absorbance, PM10, PMcoarse, NO2 and NOx) and outcomes (allergic rhinitis, chronic rhinosinusitis, asthma, and obesity related asthma) were obtained from genome-wide association studies. Instrumental variables were strictly filtered based on core assumptions. Two-sample MR and sensitivity analyses were conducted separately for European and East Asian populations. RESULTS: PMcoarse was causally associated with an increased risk of chronic rhinosinusitis (OR = 1.588 [1.002-2.518]; p = 0.049) and obesity related asthma (OR = 1.956 [1.012-3.780]; p = 0.046) in European population, and PM10 was associated with a decreased risk of allergic rhinitis in East Asian population (OR = 0.882 [0.798-0.974]; p = 0.013). No heterogeneity or pleiotropy was detected in any significant causal association. CONCLUSION: Our findings indicate that ambient air pollution has opposite impacts on the etiology of ARDs in European and East Asian populations, which provides evidence for decisions on public policies and suggests that different responses to environmental factors such as air pollution may contribute to racial heterogeneity of ARDs.

Assessing the nonlinear impact of green space exposure on psychological stress perception using machine learning and street view images.

Introduction: Urban green space (GS) exposure is recognized as a nature-based strategy for addressing urban challenges. However, the stress relieving effects and mechanisms of GS exposure are yet to be fully explored. The development of machine learning and street view images offers a method for large-scale measurement and precise empirical analysis. Methods: This study focuses on the central area of Shanghai, examining the complex effects of GS exposure on psychological stress perception. By constructing a multidimensional psychological stress perception scale and integrating machine learning algorithms with extensive street view images data, we successfully developed a framework for measuring urban stress perception. Using the scores from the psychological stress perception scale provided by volunteers as labeled data, we predicted the psychological stress perception in Shanghai's central urban area through the Support Vector Machine (SVM) algorithm. Additionally, this study employed the interpretable machine learning model eXtreme Gradient Boosting (XGBoost) algorithm to reveal the nonlinear relationship between GS exposure and residents' psychological stress. Results: Results indicate that the GS exposure in central Shanghai is generally low, with significant spatial heterogeneity. GS exposure has a positive impact on reducing residents' psychological stress. However, this effect has a threshold; when GS exposure exceeds 0.35, its impact on stress perception gradually diminishes. Discussion: We recommend combining the threshold of stress perception with GS exposure to identify urban spaces, thereby guiding precise strategies for enhancing GS. This research not only demonstrates the complex mitigating effect of GS exposure on psychological stress perception but also emphasizes the importance of considering the "dose-effect" of it in urban planning and construction. Based on open-source data, the framework and methods developed in this study have the potential to be applied in different urban environments, thus providing more comprehensive support for future urban planning.

Excessive autophagy-inducing and highly penetrable biomineralized bacteria for multimodal imaging-guided and mild hyperthermia-enhanced immunogenic cell death.

The tumor microenvironment, characterized by hypoxia, supports the efficacy of anaerobic bacteria like attenuated S. typhimurium in cancer therapies. These bacteria target and penetrate deep tumor regions, significantly reducing tumor size but often lead to tumor regrowth due to limited long-term efficacy. To enhance the therapeutic impact, a novel biohybrid system, S@UIL, has been developed by coating S. typhimurium with a zirconium-based nanoscale metal-organic framework (UiO-66-NH2) loaded with indocyanine green (ICG) and luteolin (LUT). This system maintains the bacteria's tumor-targeting ability while increasing the penetration and therapeutic effectiveness through excessive autophagy and mild hyperthermia. In a subcutaneous colon cancer model, the integration of LUT and ICG promotes autophagic cell death and photothermal sensitization, leading to the release of damage-associated molecular patterns (DAMPs). These DAMPs activate immune responses through dendritic cells and T-cells, enhancing immunogenic cell death (ICD) and potentially reducing immune evasion by tumors. This single-administration approach also integrates multimodal imaging capabilities, providing a promising strategy for improved tumor ICD induction and cancer progression inhibition.

MRI-based endplate bone quality score independently predicts cage subsidence after anterior cervical corpectomy fusion.

BACKGROUND: To reduce the amount of radiation that patients receive during surgery, surgeons can evaluate the quality of the bone prior to surgery using computed tomography (CT) or dual-energy X-ray absorptiometry. Recently, lumbar spine vertebral bone quality has been evaluated using an MRI-based scoring system. However, few studies have investigated the connection between cage subsidence in patients following cervical interbody fusion and site-specific MRI bone evaluation. It is unknown how cage subsidence following anterior cervical corpectomy decompression and fusion is related to MRI-based endplate bone quality assessment. PURPOSE: To create a similar MRI-based cervical spine scoring system (C-EBQ) and to investigate the predictive value of the MRI cervical endplate bone quality (C-EBQ) score for cage subsidence after ACCF. METHODS: The patients' demographic, surgical, and radiological data were collected. Cage subsidence was defined as fusion segment height loss ≥ 3 mm. Multivariate logistic regression models were developed to determine correlations between potential risk factors and subsidence, and simple linear regression analyses of statistically significant indicators were performed. RESULTS: Among the patients who underwent single-level ACCF, 72 met the requirements for inclusion. The C-VBQ scores also improved from 2.28 ± 0.12, indicating no subsidence, to 3.27 ± 0.35, which indicated subsidence, and the C-EBQ scores improved in both the nonsubsidence group (1.95 ± 0.80) and the subsidence group (2.38 ± 0.54). There was a statistically significant difference (p < 0.05) among the groups. Higher C-EBQ scores were strongly correlated with subsidence in the multivariate analysis (odds ratio [OR] = 17.249, 95% CI = 2.269 to 7.537, P < 0.001), and the C-VBQ score was the major independent predictor of subsidence following ACCF ([OR] = 4.752, 95% CI = 3.824 to 8.781, P < 0.05). The C-EBQ score outperformed the C-VBQ score (75.6%) in terms of predictive accuracy, with a ROC curve indicating an 89.4% score. CONCLUSIONS: After ACCF, cage subsidence was strongly correlated with higher C-EBQ scores on preoperative MRI. Assessing C-EBQ before ACCF may be a useful way to estimate the likelihood of postoperative subsidence.

Bifunctional fluorine doped Ru/RuO2 clusters with dynamic electron modification and strong metal-support interaction boost proton exchange membrane water electrolyzer.

The sluggish kinetics and inherent instability over the Ru/RuO2 clusters are still enormous challenges in proton exchange membrane (PEM) water electrolyzer. Herein, we innovatively report synergistic modulation of dynamic electron modification and strong metal-support interaction (SMSI) to activate and stabilize bifunctional fluorine doped Ru/RuO2 clusters anchored on carbon nanotube (CNT), thus achieving efficient and stable acidic overall water splitting. Theoretical and experimental studies found that surface metal-fluorine modification layer could dynamically regulate the interfacial electronic environment to stabilize and activate multiple active Ru species; and the SMSI between Ru/RuO2 cluster and CNT maintains stable electronic environment for dynamic electron modification and avoids migrating or shedding of active species in acidic environment. Therefore, the PEM electrolyzer assembled with optimal F5.5-Ru/RuO2@CNT can operate stably for 100 h at a high current density of 100 mA cm-2, which is the first time that bifunctional Ru-based nanocatalysts applied to PEM device at a high current density.

Phage-liposome nanoconjugates for orthopedic biofilm eradication.

Infection by multidrug-resistant (MDR) bacteria has become one of the biggest threats to public health worldwide. One reason for the difficulty in treatment is the lack of proper delivery strategies into MDR bacterial biofilms, where the thick extracellular polymeric substance (EPS) layer impedes the penetration of antibiotics and nanoparticles. Here, we propose a novel bioactive nanoconjugate of drug-loaded liposomes and bacteriophages for targeted eradication of the MDR biofilms in orthopedic infections. Phage Sb-1, which has the ability to degrade EPS, was conjugated with antibiotic-loaded liposomes. Upon encountering the biofilm, phage Sb-1 degrades the EPS structure, thereby increasing the sensitivity of bacteria to antibiotics and allowing the antibiotics to penetrate deeply into the biofilm. As a result, effective removal of MDR bacterial biofilm was achieved with low dose of antibiotics, which was proved in this study by both in vitro and in vivo investigations. Notably, in the rat prosthetic joint infection (PJI) model, we found that the liposome-phage nanoconjugates could effectively decrease the bacterial load in the infected area and significantly promote osteomyelitis recovery. It is therefore believed that the conjugation of bacteriophage and liposomes could open new possibilities for the treatment of orthopedic infections, possibly other infections in the deep tissues.

De novo protein design with a denoising diffusion network independent of pretrained structure prediction models.

The recent success of RFdiffusion, a method for protein structure design with a denoising diffusion probabilistic model, has relied on fine-tuning the RoseTTAFold structure prediction network for protein backbone denoising. Here, we introduce SCUBA-diffusion (SCUBA-D), a protein backbone denoising diffusion probabilistic model freshly trained by considering co-diffusion of sequence representation to enhance model regularization and adversarial losses to minimize data-out-of-distribution errors. While matching the performance of the pretrained RoseTTAFold-based RFdiffusion in generating experimentally realizable protein structures, SCUBA-D readily generates protein structures with not-yet-observed overall folds that are different from those predictable with RoseTTAFold. The accuracy of SCUBA-D was confirmed by the X-ray structures of 16 designed proteins and a protein complex, and by experiments validating designed heme-binding proteins and Ras-binding proteins. Our work shows that deep generative models of images or texts can be fruitfully extended to complex physical objects like protein structures by addressing outstanding issues such as the data-out-of-distribution errors.

Link Between Obstructive Sleep Apnea and Kidney Stones: NHANES 2015-2018 and Mendelian Randomization.

Purpose: The prevalence of Obstructive Sleep Apnea (OSA) is high, and there are many complications. Few studies have reported the relationship between OSA and kidney stones. The purpose of this study is to explore whether people at risk of OSA will increase the risk of kidney stones. Methods: This was a cross-sectional study, and information was collected through the National Health and Nutrition Examination Survey conducted from 2015 to 2018. Multiple logistic regression analyses were employed to calculate the odds ratios (ORs) and their 95% confidence intervals (CIs) for the link between obstructive sleep apnea and the presence of kidney stones. Additionally, to assess causality and reduce observational biases, five distinct two-sample Mendelian randomization techniques were applied. Results: Following the adjustment for relevant confounders, findings indicated a statistically significant correlation between obstructive sleep apnea (OSA) and higher prevalence of kidney stones (OR = 1.29; 95% CI: 1.00-1.66). Additionally, using the inverse-variance weighted approach in Mendelian randomization, results suggested a genetic predisposition to OSA might be causally linked to an elevated risk of developing kidney stones (OR: 1.00221, 95% CI 1.00056-1.00387). Conclusion: OSA promotes the formation of kidney stones, and the treatment and management of OSA can improve or mitigate the occurrence of kidney stones.

VEGFB promotes adipose tissue thermogenesis by inhibiting norepinephrine clearance in macrophages.

Adipokines play key roles in adaptive thermogenesis of beige adipocytes, though its detailed regulatory mechanisms are not fully understood. In the present study, we identify a critical function of vascular endothelial growth factor B (VEGFB)/vascular endothelial growth factor receptor 1 (VEGFR1) signaling in improving thermogenesis in white adipose tissue (WAT). In mouse subcutaneous WAT (scWAT), thermogenesis activation leads to the up-regulation of VEGFB in adipocytes and its receptor VEGFR1 in macrophages. Ablation of adipocyte VEGFB results in deficiency in murine WAT browning. Meanwhile, supplementation of VEGFB promotes WAT thermogenesis, but this effect is blocked by knockout of macrophage VEGFR1. Mechanistic studies show that the VEGFB-activated VEGFR1 inhibits p38 MAPK signaling through its dissociation with receptor for activated C kinase 1, thereby preventing norepinephrine transporter (solute carrier family 6 member 2) and norepinephrine-degrative monoamine oxidase a mediated norepinephrine clearance in macrophages. Our findings demonstrate that VEGFB/VEGFR1 circuit contributes to the WAT thermogenesis.