Impact of baseline body composition on prognostic outcomes in urological malignancies treated with immunotherapy: a pooled analysis of 10 retrospective studies.

OBJECTIVE: Numerous epidemiological investigations have explored the impact of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in urological malignancies (UM) patients, yielding conflicting findings. As a result, our study aims to elucidate the influence of baseline body composition on the long-term prognosis of UM patients treated with ICIs. METHODS: We employed a rigorous systematic search across various databases, including PubMed, Embase, the Cochrane Library, and Google Scholar, to identify studies meeting our inclusion criteria. Our primary endpoints of interest encompassed overall survival (OS) and progression-free survival (PFS). RESULTS: This analysis included a total of 10 articles with a combined patient cohort of 707 individuals. Our findings revealed a noteworthy association between several body composition parameters and unfavorable OS outcomes, including low psoas muscle index (PMI; HR: 3.88, p < 0.001), low skeletal muscle index (SMI; HR: 1.63, p < 0.001), sarcopenia (HR: 1.88, p < 0.001), low visceral adipose index (VAI; HR: 1.38, p = 0.018) and low subcutaneous adipose index (SAI; HR: 1.37, p = 0.018). Furthermore, our analysis demonstrated that low PMI (HR: 2.05, p = 0.006), low SMI (HR: 1.89, p = 0.002), sarcopenia (HR: 1.80, p < 0.001), and low VAI (HR:1.59, p = 0.005) were significantly correlated with inferior PFS. Conversely, SAI did not manifest a pronounced association with PFS in UM patients treated with ICIs. CONCLUSION: Collectively, our study findings underscore a substantial relationship between baseline body composition and reduced clinical efficacy in UM patients undergoing ICI therapy.

Determination of cotinine and 3-hydroxynicotinine in human serum by liquid chromatography-tandem mass spectrometry and its application.

In this study, we developed a method for determining cotinine and 3-hydroxycotinine in human serum and established a methodology for an in-depth study of tobacco exposure and health. After the proteins in the human serum samples were precipitated with acetonitrile, they were separated on a ZORBAX SB-Phenyl column with a mobile phase of methanol encompassing 0.3% formic acid-water encompassing 0.15% formic acid. The measurement was performed on an API5500 triple quadrupole mass spectrometer in the multiple reaction monitoring mode. Cotinine, 3-hydroxycotinine, and cotinine-d3 isotope internal standards were held for 2.56 minutes, 1.58 minutes, and 2.56 minutes, respectively. In serum, the linear range was 0.05 to 500 ng·mL-1 for cotinine and 0.50 to 1250 ng·mL-1 for 3-hydroxycotinine. The lower limit of quantification (LLOQ) was 0.05 ng·mL-1 and 0.5 ng·mL-1 for cotinine and 3-hydroxycotinine, respectively. The intra-day and inter-day relative standard deviations were <11%, and the relative errors were within ±â€…7%. Moreover, the mean extraction recoveries of cotinine and 3-hydroxycotinine were 98.54% and 100.24%, respectively. This method is suitable for the rapid determination of cotinine and 3-hydroxycotinine in human serum because of its rapidity, sensitivity, strong specificity, and high reproducibility. The detection of cotinine levels in human serum allows for the identification of the cutoff value, providing a basis for differentiation between smoking and nonsmoking populations.

Unlocking Efficient Hydrogen Production: Nucleophilic Oxidation Reactions Coupled with Water Splitting.

Electrocatalytic water splitting driven by sustainable energy is a clean and promising water-chemical fuel conversion technology for the production of high-purity green hydrogen. However, the sluggish kinetics of anodic oxygen evolution reaction (OER) pose challenges for large-scale hydrogen production, limiting its efficiency and safety. Recently, the anodic OER has been replaced by a nucleophilic oxidation reaction (NOR) with biomass as the substrate and coupled with a hydrogen evolution reaction (HER), which has attracted great interest. Anode NOR offers faster kinetics, generates high-value products, and reduces energy consumption. By coupling NOR with hydrogen evolution reaction, hydrogen production efficiency can be enhanced while yielding high-value oxidation products or degrading pollutants. Therefore, NOR-coupled HER hydrogen production is another new green electrolytic hydrogen production strategy after electrolytic water hydrogen production, which is of great significance for realizing sustainable energy development and global decarbonization. This review explores the potential of nucleophilic oxidation reactions as an alternative to OER and delves into NOR mechanisms, guiding future research in NOR-coupled hydrogen production. It assesses different NOR-coupled production methods, analyzing reaction pathways and catalyst effects. Furthermore, it evaluates the role of electrolyzers in industrialized NOR-coupled hydrogen production and discusses future prospects and challenges. This comprehensive review aims to advance efficient and economical large-scale hydrogen production.

HTR+: a novel algorithm for identifying type and polycrystal of gas hydrates.

In this work, the hierarchical topology ring (HTR+) algorithm, an extension of the HTR algorithm, was developed for identifying gas hydrate types, cage structures, and grain boundaries (GBs) within polycrystalline structures. Utilizing molecular dynamics trajectories of polycrystalline hydrates, the accuracy of the HTR+ algorithm is validated in identifying sI, sII and sH hydrate types, hydrate grains, and GBs in multi-hydrate polycrystals, as well as clathrate cages at GBs. Additionally, during the hydrate nucleation and growth processes, clathrate cages, hydrate type, hydrate grains and ice structures are accurately recognized. Significantly, this algorithm demonstrates high efficiency, particularly for large hydrate systems. HTR+ algorithm emerges a powerful tool for identifying micro/mesoscopic structures of gas hydrates, enabling an in-depth understanding of the formation mechanisms and properties of gas hydrates.

The involvement of VEGF and VEGFR in bacterial recognition and regulation of antimicrobial peptides in Eriocheir sinensis.

Vascular endothelial growth factor (VEGF) and VEGF reporter (VEGFR) are essential molecules in VEGF signalling pathway. Although the functions of VEGF and VEGFR have been well reported in vertebrates, their functions are still poorly understood in invertebrates. In this study, the open reading frame sequences of EsVEGF1 and EsVEGFR4 were cloned from Eriocheir sinensis, and their corresponding proteins shared typical structure characteristics with their counterparts in other species. EsVEGF1 were predominantly expressed in hepatopancreas and muscle while EsVEGFR4 mainly expressed in hemocytes and intestine. The expression levels of EsVEGF1 in hemocytes were rapidly induced by Staphylococcus aureus and Vibrio parahaemolyticus, and it also increased rapidly in hepatopancreas after being challenged with V. parahaemolyticus. The expression levels of EsVEGFR4 only increased in hepatopancreas of crabs injected with S. aureus. The extracellular immunoglobulin domain of EsVEGFR4 could bind with Gram-negative and Gram-positive bacteria as well as lipopolysaccharide and peptidoglycan. EsVEGF1 could act as the ligand for EsVEGFR4 and Toll-like receptor and regulate the expression of crustins and lysozyme with a tissue-specific manner, while have no regulatory function on that of anti-lipopolysaccharide factors. This study will provide new insights into the immune defense mechanisms mediated by VEGF and VEGFR in crustaceans.

Observation of an acoustic topological Euler insulator with meronic waves.

Topological band theory has conventionally been concerned with the topology of bands around a single gap. Only recently non-Abelian topologies that thrive on involving multiple gaps were studied, unveiling a new horizon in topological physics beyond the conventional paradigm. Here, we report on the first experimental realization of a topological Euler insulator phase with unique meronic characterization in an acoustic metamaterial. We demonstrate that this topological phase has several nontrivial features: First, the system cannot be described by conventional topological band theory, but has a nontrivial Euler class that captures the unconventional geometry of the Bloch bands in the Brillouin zone. Second, we uncover in theory and probe in experiments a meronic configuration of the bulk Bloch states for the first time. Third, using a detailed symmetry analysis, we show that the topological Euler insulator evolves from a non-Abelian topological semimetal phase via. the annihilation of Dirac points in pairs in one of the band gaps. With these nontrivial properties, we establish concretely an unconventional bulk-edge correspondence which is confirmed by directly measuring the edge states via. pump-probe techniques. Our work thus unveils a nontrivial topological Euler insulator phase with a unique meronic pattern and paves the way as a platform for non-Abelian topological phenomena.

Insights into the mechanical stability of tetrahydrofuran hydrates from experimental, machine learning, and molecular dynamics perspectives.

Natural gas hydrates (NGHs) hold immense potential as a future energy resource and for sustainable applications such as gas capture and storage. Due to the challenging formation conditions, however, their mechanical properties remain poorly understood. Herein, the mechanical characteristics of tetrahydrofuran (THF) hydrates, a proxy for methane hydrates, were investigated at different ice contents, strain rates, and temperatures using uniaxial compressive experiments. The results unveil a distinct behavior in the peak strength of THF hydrates with a varying ice content, strain rate and temperature, exhibiting an increase as the strain rate and temperature decrease, in contrast to the peak strength-strain rate relationship observed in polycrystalline ice. Based on the experimental data, four machine learning (ML) models including extreme gradient boosting (XGboost), multilayer perceptron (MLP), gradient boosting decision tree (GBDT) and decision tree (DT) were developed to predict the peak strength. The XGboost model demonstrates superior predictive performance, emphasizing the significant influence of ice content and temperature on the peak strength of hydrates. Furthermore, molecular dynamics (MD) simulations were employed to gain insights into the dissociation and formation processes of clathrate cages, as well as phase transitions and amorphization occurring at grain boundaries (GBs) involving diverse unconventional clathrate cages, including 51265, 4151062, 4151064, 425861 and 425862, with 425861 and 425862 cages being predominant. This study enhances our understanding of the mechanical properties and deformation mechanisms of hydrates and provides a ML-based predictive framework for estimating the compressive strength of hydrates under diverse coupling conditions. The findings have significant implications for stability assessments of NGHs and the exploitation of NGH resources.

Ligation of cervical lymphatic vessels decelerates blood clearance and worsens outcomes after experimental subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is characterized by the extravasation of blood into the subarachnoid space, in which erythrocyte lysis is the primary contributor to cell death and brain injuries. New evidence has indicated that meningeal lymphatic vessels (mLVs) are essential in guiding fluid and macromolecular waste from cerebrospinal fluid (CSF) into deep cervical lymph nodes (dCLNs). However, the role of mLVs in clearing erythrocytes after SAH has not been completely elucidated. Hence, we conducted a cross-species study. Autologous blood was injected into the subarachnoid space of rabbits and rats to induce SAH. Erythrocytes in the CSF were measured with/without deep cervical lymph vessels (dCLVs) ligation. Additionally, prior to inducing SAH, we administered rats with vascular endothelial growth factor C (VEGF-C), which is essential for meningeal lymphangiogenesis and maintaining integrity and survival of lymphatic vessels. The results showed that the blood clearance rate was significantly lower after dCLVs ligation in both the rat and rabbit models. DCLVs ligation aggravated neuroinflammation, neuronal damage, brain edema, and behavioral impairment after SAH. Conversely, the treatment of VEGF-C enhanced meningeal lymphatic drainage of erythrocytes and improved outcomes in SAH. In summary, our research highlights the indispensable role of the meningeal lymphatic pathway in the clearance of blood and mediating consequences after SAH.

PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway.

Acute lung injury (ALI) is a common clinical syndrome, which often results in pulmonary edema and respiratory distress. It has been recently reported that phosphatidylethanolamine binding protein 4 (PEBP4), a basic cytoplasmic protein, has anti-inflammatory and hepatoprotective effects, but its relationship with ALI remains undefined so far. In this study, we generated PEBP4 knockout (KO) mice to investigate the potential function of PEBP4, as well as to evaluate the capacity of alveolar fluid clearance (AFC) and the activity of phosphatidylinositide 3-kinases (PI3K)/serine-theronine protein kinase B (PKB, also known as AKT) signaling pathway in lipopolysaccharide (LPS)-induced ALI mice models. We found that PEBP4 deficiency exacerbated lung pathological damage and edema, and increased the wet/dry weight ratio and total protein concentration of bronchoalveolar lavage fluid (BALF) in LPS-treated mice. Meanwhile, PEBP4 KO promoted an LPS-induced rise in the pulmonary myeloperoxidase (MPO) activity, serum interleuin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels, and pulmonary cyclooxygenase-2 (COX-2) expression. Mechanically, PEBP4 deletion further reduced the protein expression of Na+ transport markers, including epithelial sodium channel (ENaC)-α, ENaC-γ, Na,K-ATPase α1, and Na,K-ATPase ß1, and strengthened the inhibition of PI3K/AKT signaling in LPS-challenged mice. Furthermore, we demonstrated that selective activation of PI3K/AKT with 740YP or SC79 partially reversed all of the above effects caused by PEBP4 KO in LPS-treated mice. Altogether, our results indicated the PEBP4 deletion has a deterioration effect on LPS-induced ALI by impairing the capacity of AFC, which may be achieved through modulating the PI3K/AKT pathway.

Observation of D-class topology in an acoustic metamaterial.

Topological materials and metamaterials opened new paradigms to create and manipulate phases of matter with unconventional properties. Topological D-class phases (TDPs) are archetypes of the ten-fold classification of topological phases with particle-hole symmetry. In two dimensions, TDPs support propagating topological edge modes that simulate the elusive Majorana elementary particles. Furthermore, a piercing of π-flux Dirac-solenoids in TDPs stabilizes localized Majorana excitations that can be braided for the purpose of topological quantum computation. Such two-dimensional (2D) TDPs have been a focus in the research frontier, but their experimental realizations are still under debate. Here, with a novel design scheme, we realize 2D TDPs in an acoustic crystal by synthesizing both the particle-hole and fermion-like time reversal symmetries for a wide range of frequencies. The design scheme leverages an enriched unit cell structure with real-valued couplings that emulate the targeted Hamiltonian of TDPs with complex hoppings: A technique that could unlock the realization of all topological classes with passive metamaterials. In our experiments, we realize a pair of TDPs with opposite Chern numbers in two independent sectors that are connected by an intrinsic fermion-like time-reversal symmetry built in the system. We measure the acoustic Majorana-like helical edge modes and visualize their robust topological transport, thus revealing the unprecedented D and DIII class topologies with direct evidence. Our study opens up a new pathway for the experimental realization of two fundamental classes of topological phases and may offer new insights in fundamental physics, materials science, and phononic information processing.

Role of clinical pharmacists in multidisciplinary collaborative management of blood glucose in COVID-19 patients with hyperglycemia.

BACKGROUND: During the ongoing global pandemic of COVID-19, the association between hyperglycemia and COVID-19 infection has emerged as a notable concern. Therefore, finding effective methods to manage hyperglycemia in patients with COVID-19 is crucial. OBJECTIVE: To introduce the clinical pharmacists participating in multidisciplinary collaborative whole hospital blood glucose management mode, and to explore its effect on blood glucose control in patients with coronavirus disease 2019 infection and complicated with hyperglycemia. METHODS: Patients with COVID-19 treated at Nanjing Drum Tower Hospital from December 2022 to January 2023 were assigned to routine diagnosis and treatment group and whole hospital blood glucose management group according to the blood glucose management plan received by patients. The groups were compared in regards to their adherence to management advice, blood glucose levels, fluctuation, inflammation-related indicators, medical service-related indicators, and incidence of hypoglycemia and adverse events. RESULTS: After 5 days of glucose management, both groups showed a decrease in fasting and postprandial blood glucose. Postprandial blood glucose in the whole hospital glucose management group was significantly lower than the routine group (P < 0.05). The whole hospital glucose management group showed a significant increase in compliance rate, improved inflammation-related indicators, and higher detection rates for hemoglobin and islet function (P < 0.05). Implementation rates for medical orders and treatment plans were also higher in the whole hospital group (P < 0.05). There was no significant difference in incidence of adverse events. CONCLUSIONS: Multidisciplinary blood glucose management is highly recommended for patients with COVID-19 who have hyperglycemia due to its effectiveness, standardization, safety, and improvement of inflammation indicators.

Influence of dextrans on the textural, rheological, and microstructural properties of acid-induced faba bean protein gels.

Dextrans (DXs) are a group of natural polysaccharides with different branching patterns. Previous studies examining the effects of DXs on plant protein gels have only focused on α-(1 â†’ 3)-branched DXs. Here, we compared the effects of α-(1 â†’ 3)-branched DX L12 with those of two α-(1 â†’ 2)-branched DXs on the properties of glucono-δ-lactone-induced faba bean protein isolate (FPI) gels. DX L12 showed stronger effects in decreasing gel hardness and enhancing gel viscoelasticity than the other two DXs. Moreover, DX L12 decreased the water-holding capacity of FPI gels, whereas the other DXs enhanced it. Microstructural analysis revealed that DX addition promoted phase separation during gel formation. However, FPI/L12 gels exhibited greater phase separation than the other two gels and contained larger void spaces. These differences could be attributed to the varying water adsorption and self-association properties of the DXs. These findings could guide the application of DX in the tailored preparation of plant protein gels.

Expression characteristics and inhibitory activity of a leucine-rich repeat (LRR)-only protein in the Chinese mitten crab, Eriocheir sinensis.

The leucine-rich repeat (LRR) domain is a crucial structure in a variety of immune related proteins and displays multiple immune functions. In this study, the open reading frame (ORF) of an LRR-only protein was cloned from the Chinese mitten crab, Eriocheir sinensis (EsLRRop1). The protein sequence of EsLRRop1 contained seven LRR motifs, three LRR-TYP motifs and an LRRCT motif. Tissue distribution exhibited that EsLRRop1 mainly expressed in nervous tissues including thoracic ganglion, eyestalk and brain while showed relatively lower transcriptional level in hemocyte. Based on the above expression characteristics, the responses of EsLRRop1 to the challenge of Vibrio parahaemolyticus and Staphylococcus aureus were tested. The result showed that the transcript of EsLRRop1 in thoracic ganglion and eyestalk up-regulated after being challenged with S. aureus, while it decreased post injection with V. parahaemolyticus. The transcript of EsLRRop1 in hemocytes up-regulated sharply at 3 h and decreased at 12 h and 24 h after being challenged with V. parahaemolyticus, while it decreased at 12 h and 24 h post injection with S. aureus. The recombinant protein of EsLRRop1 (His-EsLRRop1) displayed binding activities to V. alginolyticus, V. harveyi, V. parahaemolyticus, S. aureus, Corynebacterium glutamicum and Micrococcus lysodeikticus as well as lipopolysaccharide (LPS) and peptidoglycan (PGN). Moreover, the His-EsLRRop1 exhibited inhibitory activity against V. parahaemolyticus and V. harveyi with minimum inhibitory concentration (MIC) of 3.57-7.14 µM and 7.14-14.28 µM, respectively. These results provide theoretical basis for the application of EsLRRop1 in inhibiting bacteria in aquaculture practice.

Effects of Dextran on the Gel Properties of Faba Bean Protein Isolates Prepared Using Different Processes.

The properties of faba bean (Vicia faba L.) protein isolate (FPI) gels depend on their starting protein material and can be modulated by the addition of polysaccharides. In order to investigate the interplay between these two factors, commercial FPI (FPI1) and FPI prepared in-house (FPI2) were used to fabricate glucono-delta-lactone-induced gels, with or without dextran (DX) addition. FPI1 exhibited lower solubility in water and a larger mean particle size, likely because it experienced extensive degradation due to the intense conditions involved in its preparation. The FPI1 gel showed a similar water-holding capacity as the FPI2 gel; however, its hardness was lower and viscoelasticity was higher. After DX addition, the hardness of both FPI gels decreased, while their water-holding capacity increased. Interestingly, DX addition decreased the viscoelasticity of the FPI1 gel but enhanced the viscoelasticity of the FPI2 gel. The microstructural analysis demonstrated that the density of the aggregation network decreased in the FPI1 gel after DX addition but increased in the FPI2 gel. This was consistent with the changes observed in the dominant protein interaction forces in these gels after DX addition. Overall, these findings have the potential to guide ingredient selection for the tailored preparation of FPI gels.

Alterations of oral microbiota are associated with the development and severity of acute pancreatitis.

Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe acute pancreatitis (SAP), increasing morbidity and mortality. The microbiome's impact on AP pathophysiology has received increasing attention. Hence, to explore changes in oral microbial composition in acute pancreatitis, we collected clinical information and oral saliva samples from 136 adult participants: 47 healthy controls, 43 acute mild AP (MAP), 29 moderate AP (MSAP), and 17 severe AP (SAP). Using 16S rRNA gene sequencing, 663,175 high-quality sequences were identified. The relative abundance and diversity of oral microorganisms in AP patients increased, with decreased beneficial bacteria such as Streptococcus, Neisseria, and Gemella, and increased Prevotella, Veillonella, Granulicatella, Actinomyces, and Peptostreptococcus in the AP group. Further changes in microbial composition occurred with increasing disease severity, including a decreased abundance of beneficial bacteria such as Neisseria, Haemophilus, and Gemella in MSAP and SAP compared to MAP. Moreover, the Lefse analysis showed that Prevotella, Peptostreptococcus, Actinomyces, and Porphyromonas were better microbial markers for AP. Therefore, oral microbiome changes could distinguish AP from healthy individuals and serve as an early novel predictor of disease severity in AP patients.

Thermal conductivity of fivefold twinned silicon-germanium heteronanowires.

The thermal transport properties of five-fold twinned (5FT) germanium-silicon (Ge-Si) heteronanowires (h-NWs) with varying cross-sectional areas, germanium (Ge) domain ratios and heterostructural patterns are investigated using homogeneous nonequilibrium molecular dynamics (HNEMD) simulations. The results demonstrate a distinctive behavior in the thermal conductivity (κ) of 5FT-NWs, characterized by a "flipped" trend at a critical cross-sectional area. This behavior is attributed to the hydrodynamic phonon flow, arising from the normal three-phonon scattering process in the low-frequency region. In addition, the composition ratio of 5FT-NWs has a significant impact on reducing the κ of 5FT-NWs and suppressing the hydrodynamic effect. Intriguingly, as the homogeneous element domains are separated, stronger phonon hydrodynamic flows are observed in comparison to the adjacent homogeneous element domains. By analyzing various phonon properties, including phonon dispersion, three-phonon scattering rate, and phonon mean free path, critical insights into the origin of the differential κ in different 5FT-NW structures are provided. The findings deepen the understanding of the thermal transport properties of nanomaterials and hold implications for the design and development of nanoelectronics and thermoelectric devices.

Predicting mechanical properties of CO2hydrates: machine learning insights from molecular dynamics simulations.

Understanding the mechanical properties of CO2hydrate is crucial for its diverse sustainable applications such as CO2geostorage and natural gas hydrate mining. In this work, classic molecular dynamics (MD) simulations are employed to explore the mechanical characteristics of CO2hydrate with varying occupancy rates and occupancy distributions of guest molecules. It is revealed that the mechanical properties, including maximum stress, critical strain, and Young's modulus, are not only affected by the cage occupancy rate in both large 51262and small 512cages, but also by the distribution of guest molecules within the cages. Specifically, the presence of vacancies in the 51262large cages significantly impacts the overall mechanical stability compared to 512small cages. Furthermore, four distinct machine learning (ML) models trained using MD results are developed to predict the mechanical properties of CO2hydrate with different cage occupancy rates and cage occupancy distributions. Through analyzing ML results, as-developed ML models highlight the importance of the distribution of guest molecules within the cages, as crucial contributor to the overall mechanical stability of CO2hydrate. This study contributes new knowledge to the field by providing insights into the mechanical properties of CO2hydrates and their dependence on cage occupancy rates and cage occupancy distributions. The findings have implications for the sustainable applications of CO2hydrate, and as-developed ML models offer a practical framework for predicting the mechanical properties of CO2hydrate in different scenarios.