Noninvasive tests maintain high accuracy for advanced fibrosis in chronic hepatitis B patients with different nomenclatures of steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a new nomenclature proposed in 2023. We aimed to compare the diagnostic efficacy of noninvasive tests (NITs) for advanced fibrosis under different nomenclatures in patients with chronic hepatitis B (CHB). A total of 844 patients diagnosed with CHB and concurrent steatotic liver disease (SLD) by liver biopsy were retrospectively enrolled and divided into four groups. The performances of fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio index (GPRI), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared among the four groups. The four NITs showed similar diagnostic efficacy for nonalcoholic fatty liver disease (NAFLD), MASLD, and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with CHB with advanced fibrosis. LSM showed the most stable accuracy for NAFLD (AUC = 0.842), MASLD (AUC = 0.846), and MAFLD (AUC = 0.863) compared with other NITs (p < 0.05). Among the four NITs, APRI (AUC = 0.841) and GPRI (AUC = 0.844) performed best in patients with CHB & MetALD (p < 0.05). The cutoff value for GPRI in patients with CHB & MetALD was higher than that in the other three groups, while further comparisons of NITs at different fibrosis stages showed that the median GPRI of CHB & MetALD (1.113) at F3-4 was higher than that in the CHB & MASLD group (0.508) (p < 0.05). Current NITs perform adequately in patients with CHB and SLD; however, alterations in cutoff values for CHB & MetALD need to be noted.

Evaluation of the in vitro and in vivo antimicrobial activity of alkaloids prepared from Chelidonium majus L. using MRSA- infected C. elegans as a model host.

Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.

Minor envelope proteins from GP2a to GP4 contribute to the spread pattern and yield of type 2 PRRSV in MARC-145 cells.

In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.

A multidisciplinary collaborative diagnosis and rehabilitation program for dysphagia in general hospitals.

Dysphagia is a common complication of various clinical conditions, with an increased incidence as age advances. Complications such as aspiration, malnutrition, and aspiration pneumonia caused by dysphagia significantly affect the overall treatment outcomes of patients. Scholars both domestically and internationally are increasingly focusing on early rehabilitation for dysphagia. This article summarizes common conditions causing dysphagia, clinical manifestations, complications, screening assessment, diagnosis, rehabilitation, and nutritional support related to dysphagia. It emphasizes the arrival at a multidisciplinary collaborative diagnosis and formulation of a rehabilitation management plan for dysphagia in general hospitals in order to provide strategic suggestions for establishing a multidisciplinary collaborative model for swallowing disorder management in general hospitals.

Spatial continuous modeling of early Cenozoic carbon cycle and climate.

A real spatial continuous modeling of climate and carbon cycle is developed, and tested for early Cenozoic from 60 Ma to 40 Ma.

Pelagic Sargassum in the Gulf of Mexico driven by ocean currents and eddies.

Pelagic Sargassum in the Gulf of Mexico (GoM) plays an important role in ocean biology and ecology, yet our knowledge of its origins and transport pathways is limited. Here, using satellite observations of Sargassum areal density and ocean surface currents between 2000 and 2023, we show that large amounts of Sargassum in the GoM can either originate from the northwestern GoM or be a result of physical transport from the northwestern Caribbean Sea, both with specific transport pathways. Sargassum of the northwestern GoM can be transported to the eastern GoM by ocean currents and eddies, eventually entering the Sargasso Sea. Sargassum entering the GoM from the northwestern Caribbean Sea can be transported in three different directions, with the northward and eastward transports governed by the Loop Current System (LCS) and westward transport driven by the westward extension of the LCS, the propagation or relaying of ocean eddies, the wind-driven westward currents on the Campeche Bank with or without eddies, and the westward currents with/without currents associated with eddies in the northern/central GoM. Overall, the spatial distribution patterns of pelagic Sargassum in the GoM are strongly influenced by the LCS and relevant eddies.

Global, regional and national burden of retinopathy of prematurity among childhood and adolescent: a spatiotemporal analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: This study aimed to provide a comprehensive assessment of burden estimates and the secular trend of vision loss due to retinopathy of prematurity (ROP) among people younger than 20 years, at the global, regional and national levels. METHODS: Data were obtained from the Global Burden of Disease Study 2019 database. The average annual percentage change (AAPC) was calculated to quantify the temporal trends in the measures of vision loss. RESULTS: In 2019, the global age-standardised rates (ASRs) of prevalence per 100 000 population was 86.4 for vision loss, specifically, 35 for moderate vision loss, 19.9 for severe vision loss, 31.6 for blindness due to ROP among people younger than 20 years. Moreover, the ASR of years lived with disability per 100 000 was 10.6 for vision loss, specifically, 1.1 for moderate vision loss, 3.6 for severe vision loss, 5.9 for blindness, respectively. From 1990 to 2019, the ASR of prevalence of blindness and vision loss due to ROP significantly increased, while its burden slightly decreased. Males showed higher ASR of prevalence than females in 2019, whereas females have larger increasing trend than males from 1990 to 2019. The global highest ASR of disease burden was observed in South Asia and Southern sub-Saharan Africa, as well as low sociodemographic index (SDI) regions in 2019. CONCLUSIONS: Globally, although the burden decreased, the prevalence of childhood and adulthood vision loss due to ROP continues to increase. Reasonable resource allocation and advanced intervention are recommended to prevent and control the vision loss due to ROP.

First principles molecular dynamics simulation and thermal decomposition kinetics study of CL-20.

CONTEXT: 2,4,6,8,10, 12-hexanitro-2,4,6,8,10, 12-hexazepane (CL-20) is a new energetic material with high performance and low sensitivity. In-depth study of the thermal decomposition mechanism of CL-20 is a necessary condition to improve its performance, ensure its safety, and optimize its application. On the basis of a large number of empirical force fields used in molecular dynamics simulation in the past, the machine learning augmented first-principles molecular dynamics method was used for the first time to simulate the thermal decomposition reaction of CL-20 at 2200 K, 2500 K, 2800 K, and 3000 K isothermal temperature. The main stable resulting compounds are N2, CO2, CO, H2O, andH2, where CO2 and H2O continue to decompose at higher temperatures. The initial decomposition pathways are denitration by N-N fracture, ring-opening by C-N bond fracture, and redox reaction involving NO2 and CL-20. After ring opening, two main compounds, fused tricyclic pyrazine and azadicyclic, were formed, which were decomposed continuously to form monocyclic pyrazine and pyrazole ring structures. The most common fragments formed during decomposition are those containing two, three, four, and six carbons. The formation rule and quantity of main small molecule intermediates and resulting stable products under different simulated temperatures were analyzed. METHODS: Based on ab initio Bayesian active learning algorithm, efficient and accurate prediction of CL-20 is made using the dynamic machine learning function of Vienna Ab-Initio Simulation Package (VASP), which constructs the energy potential surface by learning a large number of data based on AIMD calculations. The result is a machine learning force field (MLFF). Then the molecular dynamics of CL-20 was simulated using the trained MLFF model. PAW pseudopotentials and generalized gradient approximation (GGA), namely, Perdew-Burke-Ernzerhof (PBE) functional, are used in the calculation. The plane wave truncation energy (ENCUT) is set to 550 eV, and using the Gaussian broadening, the thermal broadening size of the single-electron orbital is 0.05 eV. A van der Waals revision of the system with Grimme Version 3. The energy convergence accuracy (EDIFF) of electron self-consistent iteration is set to 1E-5 eV and 1E-6 eV, respectively. The two-step structure optimization is carried out using 1'1'1 k point grid and conjugate gradient method. The ENCUT was changed to 500 eV and EDIFF to 1E-5 eV, and NVT integration (ISIF = 2) of Langevin thermostat was used for machine learning force field training and AIMD simulation of the system.

Rosavin extends lifespan via the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.

Rosavin, a phenylpropanoid glycoside, is the specific index component and one of the main active components of Rhodiola rosea. Currently, there are few studies describing the antiaging effect of rosavin, and most of them are mainly based on in vitro antioxidant research. Our study aimed to investigate the antiaging activities and mechanisms of rosavin in Caenorhabditis elegans. Using Caenorhabditis elegans as the model, the lifespan of Caenorhabditis elegans under various stressors (heat and juglone) and normal conditions was studied, and the antioxidant activities of rosavin were discussed. To discover the underlying mechanisms, we analyzed daf-16 nuclear localization, the expression of the sod-3p::GFP fusion protein, mRNA levels, and loss-of-function mutants of IIS-associated genes. The results showed that rosavin significantly improved the lifespan of Caenorhabditis elegans under stress and normal conditions. Rosavin can increase the expression and activity of antioxidant enzymes and suppress the generation of malondialdehyde and ROS in nematodes. Additionally, it promotes the nuclear localization of daf-16 and improves the expression of the sod-3 gene in Caenorhabditis elegans. The data revealed that rosavin activated the insulin/IGF-1 signaling pathway by downregulating the upstream components daf-2 and age-1. In summary, these results verify that rosavin could increase the lifespan of Caenorhabditis elegans through the insulin/IGF-1 signaling pathway.

A tracer model nowcast/forecast study of the Tampa Bay, Piney Point effluent plume: Rapid response to an environmental hazard.

An emergency discharge of nutrient-rich effluent from the defunct Piney Point fertilizer stack into Tampa Bay at Port Manatee occurred from 30 March-8 April 2021. This resulted in a pollutant plume that evolved over time and space across the entire bay, including its environmentally sensitive marine preserves, and out onto the adjacent continental shelf. As a rapid response to environmental concerns, the plume evolution was simulated using the high resolution, unstructured grid, Tampa Bay Coastal Ocean Model (TBCOM) nowcast/forecast system, with an embedded tracer module that included realistic point discharge rates. Normalized tracer distributions were automatically updated each day, providing 1-day hindcasts and 3.5-day forecasts. Due to mixing and advection, tracer concentration was quickly reduced by two or more orders of magnitude as the plume spread out. Highest tracer concentrations hugged the southeastern Tampa Bay shoreline during the first week. Lower tracer concentrations were gradually advected to the western side of Tampa Bay, and the tracer was slowly flushed out of the bay to be transported primarily northward along the coast. The modeled plume evolution served as principal guidance for coordinating environmental monitoring by state, local and academic personnel. The model results also provide a basis for future multidisciplinary studies.

Ultrafast Axial Freezing in a Liquid-Filled Capillary Tube.

Liquid-filled capillary tubes are a kind of standard component in life science (e.g., blood vessels, interstitial pores, and plant vessels) and engineering (e.g., MEMS microchannel resonators, heat pipe wicks, and water-saturated soils). Under sufficiently low temperatures, the liquid in a capillary tube undergoes phase transition, forming an ice nucleus randomly on its inner wall. However, how an ice layer forms from the nucleus and then expands, either axially or radially to the tube inner wall, remains obscure. We demonstrated, both experimentally and theoretically, that axial freezing along the inner wall of a water-filled capillary tube occurs way ahead of radial freezing, at a nearly constant velocity 3 orders in magnitude faster than the latter. Rapid release of latent heat during axial freezing was identified as the determining factor for the short duration of recalescence, resulting in an exponential rise of the supercooling temperature from ice nucleation via axial freezing to radial freezing. The profile of the ice-water interface is strongly dependent upon the length-to-radius ratio of the capillary tube and the supercooling degree at ice nucleation. The results obtained in this study bridge the knowledge gap between the classical nucleation theory and the Stefan solution of phase transition.

Function and inhibition of P38 MAP kinase signaling: Targeting multiple inflammation diseases.

Inflammation is a natural host defense mechanism that protects the body from pathogenic microorganisms. A growing body of research suggests that inflammation is a key factor in triggering other diseases (lung injury, rheumatoid arthritis, etc.). However, there is no consensus on the complex mechanism of inflammatory response, which may include enzyme activation, mediator release, and tissue repair. In recent years, p38 MAPK, a member of the MAPKs family, has attracted much attention as a central target for the treatment of inflammatory diseases. However, many p38 MAPK inhibitors attempting to obtain marketing approval have failed at the clinical trial stage due to selectivity and/or toxicity issues. In this paper, we discuss the mechanism of p38 MAPK in regulating inflammatory response and its key role in major inflammatory diseases and summarize the synthetic or natural products targeting p38 MAPK to improve the inflammatory response in the last five years, which will provide ideas for the development of novel clinical anti-inflammatory drugs based on p38 MAPK inhibitors.

Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study.

Background: In the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations. Methods: We enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results: After PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups. Conclusions: In real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Effect of Proinflammatory S100A9 Protein on Migration and Proliferation of Microglial Cells.

Alzheimer's disease (AD) is a multifactorial disease affecting aging population worldwide. Neuroinflammation became a focus of research as one of the major pathologic processes relating to the disease onset and progression. Proinflammatory S100A9 is the central culprit in the amyloid-neuroinflammatory cascade implicated in AD and other neurodegenerative diseases. We studied the effect of S100A9 on microglial BV-2 cell proliferation and migration. The responses of BV-2 cells to S100A9 stimulation were monitored in real-time using live cell microscopy, transcriptome sequencing, immunofluorescence staining, western blot analysis, and ELISA. We observed that a low dose of S100A9 promotes migration and proliferation of BV-2 cells. However, acute inflammatory condition (i.e., high S100A9 doses) causes diminished cell viability; it is uncovered that S100A9 activates TLR-4 and TLR-7 signaling pathways, leading to TNF-α and IL-6 expression, which affect BV-2 cell migration and proliferation in a concentration-dependent manner. Interestingly, the effects of S100A9 are not only inhibited by TNF-α and IL-6 antibodies. The addition of amyloid-ß (Aß) 1-40 peptide resumes the capacities of BV-2 cells to the level of low S100A9 concentrations. Based on these results, we conclude that in contrast to the beneficial effects of low S100A9 dose, high S100A9 concentration leads to impaired mobility and proliferation of immune cells, reflecting neurotoxicity at acute inflammatory conditions. However, the formation of Aß plaques may be a natural mechanism that rescues cells from the proinflammatory and cytotoxic effects of S100A9, especially considering that inflammation is one of the primary causes of AD.

Efficient Quantum Dot Light-Emitting Diode Enabled by a Thick Inorganic CdS Interfacial Modification Layer.

Ultrathin (∼10 nm) insulating polymer films are commonly employed as an interfacial modification layer (IML) to improve charge balance and suppress interfacial exciton quenching in quantum dot light-emitting diodes (QLEDs). However, because the thickness is smaller than the energy transfer distance, interfacial exciton quenching is only partially suppressed, leading to the degrading of device performance. In this work, a thick (35 nm) inorganic CdS film is developed to serve as the IML of CdSe quantum-dot-based QLED. Benefiting from relatively low electron mobility and well-matched energy level, the CdS IML can effectively improve charge balance. In addition, because the thickness is larger than the energy transfer distance, interfacial exciton quenching can be completely blocked. As a result, the QLEDs with CdS IML exhibit a maximum EQE of 21.2% and a peak current efficiency of 24.2 cd A-1, which are about 1.32- and 1.4-fold higher than 16.1% and 17.3 cd A-1 of the devices without CdS IML, respectively. Our work offers an efficient method to completely block interfacial exciton quenching, which may open a new avenue for developing higher-performance QLEDs.

Design of Twin Builder-Based Digital Twin Online Monitoring System for Crane Girders.

The crossbeam is frequently subjected to alternating loads during work as an essential load-bearing part of the crane. However, due to the large volume and the limitations of detection technology, it is impossible to realize online monitoring of the mechanical state. The ongoing advancement of ROMing and digital twin technology plays a pivotal role in facilitating the resolution of this particular issue. In this paper, we take the crane beam as the physical entity and combine the Twin Builder reduced-order technology and Deployer digital twin deployment technology to establish a digital twin of the beam. The load recognition model within the twin system exhibits a prediction error rate of ±5%. Furthermore, the accuracy of the ROM surpasses that of conventional machine learning models by a factor of 25. Upon deployment on the web platform, the results are delivered within 0.5 s, representing a substantial improvement as it is merely 1/15 of the time required for traditional 3D displays. The digital twin online monitoring system has the advantages of high accuracy and low requirements for monitoring equipment, which can be widely used in engineering practice to solve the problem that the mechanical state of large parts cannot be accurately monitored online.

ATG9A modulated by miR-195-5p can boost the malignant progression of cervical cancer cells.

Cervical cancer (CC) is a major public health problem, and its molecular mechanism requires further investigation. The goal of this study was to determine the role of miR-195-5p and the autophagy-related protein ATG9A in tumour metastasis, epithelial - mesenchymal transition (EMT), apoptosis, and autophagy of CC cells. Using bioinformatics analysis, we predicted ATG9A as a downstream target gene of miR-195-5p, an integral membrane protein required for autophagosome formation and involved in tumorigenesis. Next, western blotting and Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) showed that upregulation of miR-195-5p decreased protein and mRNA expression of ATG9A, and downregulation of miR-195-5p promoted ATG9A protein and mRNA expression. In addition, detection of the dual luciferase reporter gene further indicated ATG9A is a direct downstream target gene of miR-195-5p. Finally, the effects of miR-195-5p and ATG9A on CC cell proliferation, migration, invasion, EMT, autophagy, and apoptosis were evaluated in vitro. Our results showed that upregulation of miR-195-5p not only inhibits proliferation, migration, and the EMT of CC cells, but also induces apoptosis and autophagy. Conversely, downregulation of miR-195-5p increased malignant metastasis and the EMT of CC cells, and inhibited apoptosis as well as autophagy. In addition, miR-195-5p targeted and negatively regulated ATG9A, and rescue experiments suggested that overexpression of ATG9A could partially abolish miR-195-5p-mediated suppression of CC cells. Our findings improve our understanding of the mechanism of action of miR-195-5p in the malignant behaviour of CC. miR-195-5p is likely to be a promising cancer suppressor gene, which provides clinical evidence for targeted therapy of CC.

Recombinant human brain natriuretic peptide attenuates ischemic brain injury in mice by inhibiting oxidative stress and cell apoptosis via activation of PI3K/AKT/Nrf2/HO-1 pathway.

Ischemic stroke followed by cerebral artery occlusion is a main cause of chronic disability worldwide. Recombinant human brain natriuretic peptide (rhBNP) has been reported to alleviate sepsis-induced cognitive dysfunction and brain I/R injury. However, the function and molecular mechanisms of rhBNP in ischemic brain injury have not been clarified. For establishment of an animal model of ischemic brain injury, C57BL/6 mice were treated with middle cerebral artery occlusion (MCAO) surgery for 1 h and reperfusion for 24 h. After subcutaneous injection of rhBNP into model mice, neurologic deficits were assessed by evaluating behavior of mice according to Longa scoring system, and TTC staining was utilized to determine the brain infarct size of mice. The levels of oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA), were detected in hippocampal tissues of mice by corresponding kits. Cell apoptosis in hippocampus tissues was examined by TUNEL staining. Protein levels of antioxidant enzymes (HO-1 and NQO1) in cerebral cortex, apoptotic markers (Bax, Bcl-2, and cleaved caspase), and PI3K/AKT pathway-associated factors in hippocampus were tested by western blot analysis. The results revealed that injection of rhBNP decreased neurologic deficit scores, the percent of brain water content, and infarct volume. Additionally, rhBNP downregulated MDA level, upregulated the levels of SOD, CAT, and GSH in hippocampus of mice, and increased protein levels of HO-1 and NQO1 in the cortex. Cell apoptosis in hippocampus tissues of model mice was inhibited by rhBNP which was shown as the reduced TUNEL-positive cells, the decreased Bax, cleaved caspase-3, and cleaved caspase-9 protein levels, and the enhanced Bcl-2 protein level. In addition, rhBNP treatment activated the PI3K/AKT signaling pathway and upregulated the protein levels of HO-1 and NRF2. Overall, rhBNP activates the PI3K/AKT/HO-1/NRF2 pathway to attenuate ischemic brain injury in mice after MCAO by suppression of cell apoptosis and oxidative stress.

Synthesis, structure anatomy, and catalytic properties of Ag14Cu2 nanoclusters co-protected by alkynyl and phosphine ligands.

We report the synthesis, structure anatomy, and catalytic properties of Ag14Cu2(CCArF)14(PPh3)4 (CCArF: 3,5-bis(trifluoromethyl)phenylacetylene) nanoclusters, denoted as Ag14Cu2. Ag14Cu2 has a robust electronic structure with two free valence electrons, and it has a distinctive absorbance feature. Single-crystal X-ray diffraction (SC-XRD) disclosed that Ag14Cu2 possesses an octahedral Ag6 metal kernel capped by two Ag4Cu1(CCArF)7(PPh3)2 metal-ligand units. Remarkably, it exhibits excellent bifunctional catalytic performance for 4-nitrophenol reduction and the electrochemical CO2 reduction reaction (eCO2RR). In 4-nitrophenol reduction, it adopts first-order reaction kinetics with a rate constant of 0.137 min-1, while in the eCO2RR, it shows a CO faradaic efficiency (FECO) of 83.71% and a high current density of 92.65 mA cm-2 at -1.6 V vs. RHE. Moreover, Ag14Cu2 showed robust long-term stability with no significant decay in current density and FECO over 10 h of continuous operation in the eCO2RR. This study not only enriches the potpourri of alkynyl-protected bimetallic AgCu nanoclusters, but also demonstrates the great potential of employing metal nanoclusters for bifunctional catalytic applications.

Reaction kinetics of chitosan nanogels crosslinked by genipin.

Crosslinking of chitosan chains in dilute solution by natural crosslinker genipin leads to biocompatible nanogels. Here we investigated the reaction kinetics between chitosan and genipin in a 200 mM acetate buffer at 37 °C, and the structural and conformational evolutions of the nanogels during the crosslinking reaction by multi detection asymmetric flow field-flow fractionation (AF4). Upon crosslinking by genipin, the z-average hydrodynamic radius Rhz of the chitosan chains increased from 26 nm to 130 nm, while the weight average molar mass Mw increased from 2.0 × 105 g/mol to 1.8 × 107 g/mol. The crosslinking reaction appeared to be first-order and size-dependent. In particular, the intrachain crosslinking reaction was preferentially for nanogels having the larger size, leading to formation of branched chains/nanogels having a wide range of molar masses between 106 and 108 g/mol but a similar radius of gyration Rg ∼ 40 nm. For the largest nanogel fractions with M > 2.0 × 108 g/mol, both Rg and Rh showed a scaling relation with exponent 1/3 and a structure parameter Rg/Rh = 0.74, as expected for the hard sphere particle. The reaction was accompanied by a reduction of charge density and an increase in hydrophobicity of chitosan nanogels, which plays a key role in the formation of uniform size nanogels with chain density ρ(Rh) up to 0.45 g/cm3.