Modeling the global ocean distribution of dissolved cadmium based on machine learning-SHAP algorithm.

Cadmium (Cd) is a bio-essential trace metal in the ocean that can be toxic at high concentrations, significantly impacting the marine environment and phytoplankton growth. Its distribution pattern is closely proportional to that of phosphate (PO), although the mechanism is not fully understood. At low concentrations, evidence indicates Cd is able to act as an enzyme cofactor in biological processes.

Copper homeostasis and Cuprotosis: Exploring novel therapeutic strategies for connective tissue diseases.

Copper is an indispensable element for human health, with its balance being critical to prevent the onset of diseases, particularly those affecting connective tissues. Imbalances in copper levels can lead to pathological alterations. Research indicates that copper supplements and chelators hold promise for the treatment of certain conditions, yet the precise mechanisms by which copper imbalances and the cell death mechanism known as cuprotosis contribute to connective tissue diseases remain elusive.

The value of amide proton transfer imaging in assessing brain damage in patients with obstructive sleep apnea.

Objective: To investigate the application value of amide proton transfer (APT) magnetic resonance imaging in evaluating brain damage in patients with obstructive sleep apnea (OSA).

Materials And Methods: 49 OSA patients and 25 healthy individuals matched for age and sex were included as case and control groups. All study participants underwent conventional 3D T1WI and APT imaging of the head.

Theoretical investigation on the oxidation mechanism of methylglyoxal in the aqueous phase.

The oxidation mechanism of methylglyoxal (CHCOCHO) in the aqueous phase plays a crucial role in the formation of secondary organic aerosols (SOA). To date, the investigations of reaction mechanisms of MG in the aqueous phase still needs to be refined, and the oxidation mechanisms of MG in the existence of various oxidants (e.g.

EGB761 ameliorates mild cognitive impairment by inhibiting the pyroptosis and apoptosis in both in vivo and in vitro experiments.

Mild cognitive impairment (MCI) is a neurodegenerative condition that is clinically prevalent among the elderly. EGB761 is widely recognized for its promising therapeutic properties in both the prevention and treatment of neurodegenerative disorders. The aim of this study was to investigate the effects of EGB761 in MCI and the underlying molecular mechanism.

Methyltransferase-Like 3-Driven N6-Methyladenosine Modification of Recombination Signal Binding Protein for Immunoglobulin Kappa J Region Promotes Vascular Remodeling in Pulmonary Hypertension.

The dysregulation of N6-methyladenosine (m6A) RNA modification is widely recognized for its crucial roles in various diseases, including pulmonary hypertension (PH). Prior studies have highlighted the significant role of methyltransferase-like 3 (METTL3) in the pathogenesis of PH. Nevertheless, the potential and underlying mechanisms of METTL3 and its inhibitors as targets for PH treatment require further elucidation.

Short-term sedimentary evidence for increasing diatoms in Arctic fjords in a warming world.

Arctic fjords are hotspots of marine carbon burial, with diatoms playing an essential role in the biological carbon pump. Under the background of global warming, the proportion of diatoms in total phytoplankton communities has been declining in many high-latitude fjords due to increased turbidity and oligotrophication resulting from glacier melting. However, due to the habitat heterogeneity among Svalbard fjords, diatom responses to glacier melting are also expected to be complex, which will further lead to changes in the biological carbon pumping and carbon sequestration.

MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions.

The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key component of the innate immune system that triggers inflammation and pyroptosis and contributes to the development of several diseases. Therefore, blocking the activation of the NLRP3 inflammasome has therapeutic potential for the treatment of these diseases. MCC950, a selective small molecule inhibitor, has emerged as a promising candidate for blocking NLRP3 inflammasome activation.

Electrochemical stability of biodegradable Zn-Cu alloys through machine-learning accelerated high-throughput discovery.

Zn-Cu alloys have attracted great attention as biodegradable alloys owing to their excellent mechanical properties and biocompatibility, with corrosion characteristics being crucial for their suitability for biomedical applications. However, the unresolved identification of intermetallic compounds in Zn-Cu alloys affecting corrosion and the complexity of the application environment hamper the understanding of their electrochemical behavior. Utilizing high-throughput first-principles calculations and machine-learning accelerated evolutionary algorithms for screening the most stable compounds in Zn-Cu systems, a dataset encompassing the formation energy of 2033 compounds is generated.

(±)-Hypernumqulins A-H: Eight pairs of unexpected [2+2] cycloaddition sesquiterpenoid alkaloid with 6/6/6/4/10 ring system from Hypericum monogynum L.

(±)-Hypernumqulins A-H (1-8), eight pairs of enantiomeric quinoline alkaloids fused with an isopentenyl and a germacrane-type sesquiterpenoid, featuring an unprecedented skeleton with 6/6/6/4/10 ring system, were isolated from Hypericum monogynum L. under the guidance of molecular networking strategy. Their structures including absolute configuration were elucidated by NMR spectroscopy analysis, X-ray crystallography and quantum chemical calculation.

Tumour-microenvironment-responsive NaSO nanocrystals encapsulated in hollow organosilica-metal-phenolic networks for cycling persistent tumour-dynamic therapy.

Traditional tumour-dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono-catalytic reaction. To fight against these issues, we skilfully develop a tumour-microenvironment-driven yolk-shell nanoreactor to realize the high-efficiency persistent dynamic therapy via cascade-responsive dual cycling amplification of •SO /•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the NaSO nanocrystals into hollow tetra-sulphide-introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)-Fe(II) cross-linking.

Structural Insight into the Binding Pattern and Interaction Mechanism of Antagonist MCC950 and Agonist BMS986299 with NLRP3 by Molecular Dynamics Simulation.

Objective: The NLRP3 inflammasome mediates a range of inflammatory responses that are associated with an increasing number of pathological mechanisms. Over-activation of NLRP3 can exacerbate many diseases. However, NLRP3 antagonists have significant therapeutic potential.

Ptehosides A-I: Nine undescribed iridoids with in vitro cytotoxicity from the whole plant of Pterocephalus hookeri (C.B. Clarke) Höeck.

Nine previously undescribed iridoids, ptehosides A-I (1-9), together with 12 known ones (10-21), were isolated from Pterocephalus hookeri (C.B. Clarke) Höeck.

Differential expression and analysis of extrachromosomal circular DNAs as serum biomarkers in pulmonary arterial hypertension.

Background: Extrachromosomal circular DNAs (eccDNAs) have been reported to play a key role in the occurrence and development of various diseases. However, the characterization and role of eccDNAs in pulmonary arterial hypertension (PAH) remain unclear.

Methods: In the discovery cohort, we first explored eccDNA expression profiles by Circle-sequencing analysis.

Typhoon- and pollution-driven enhancement of reactive bromine in the mid-latitude marine boundary layer.

Tropospheric reactive bromine is important for atmospheric chemistry, regional air pollution, and global climate. Previous studies have reported measurements of atmospheric reactive bromine species in different environments, and proposed their main sources, e.g.

Widefield functional speckle-correlation optical scattering mesoscopy toward hemodynamic imaging.

Speckle-correlation optical scattering imaging (SCOSI) has shown the potential for non-invasive biomedical diagnostic applications, which directly utilizes the scattering patterns to reconstruct the deep and non-line-of-sight objects. However, the course of the translation of this technique to preclinical biomedical imaging applications has been postponed by the following two facts: 1) the field of view of SCOSI was significantly limited by the optical memory effect, and 2) the molecular-tagged functional imaging of the biological tissues remains largely unexplored. In this work, a proof-of-concept design of the first-generation widefield functional SCOSI (WF-SCOSI) system was presented for simultaneously achieving mesoscopic mapping of fluid morphology and flow rate, which was realized by implementing the concepts of scanning synthesis and fluorescence scattering flowmetry.

Design, Synthesis, Antitumor Activity Evaluation, and Molecular Dynamics Simulation of Some 2-Aminopyrazine Derivatives.

Objective: Cancer poses a great threat to human health, and effective drugs to treat it are always needed. Several compounds containing a 2-aminopyrazine framework have been identified as antitumor agents with SHP2 inhibition activities. This current work aimed to search for more potent novel compounds possessing a 2-aminopyrazine moiety with antitumor activities.

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment.

Fulminant myocarditis induced by SARS-CoV-2 infection without severe lung involvement: insights into COVID-19 pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often leads to pulmonary complications. Cardiovascular sequelae, including myocarditis and heart failure, have also been reported. Here, the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury, as determined by imaging examinations.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

Background: While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited.

Hypothesis: This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes.

Methods: A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag.

Manganese disrupts the maturation and degradation of axonal autophagosome leading to hippocampal synaptic toxicity in mice via the activation of LRRK2 on phosphorylation of Rab10.

Manganese (Mn) overexposure induces hippocampal synaptotoxicity by the accumulation of dysfunctional synaptic vesicles (SVs). Leucine-rich repeat kinase 2 (LRRK2) kinase activity is involved in regulating axonal transport (autophagosomal maturation) and lysosomal function. Nevertheless, it remains unclear whether Mn-induced synaptotoxicity is associated with the LRRK2-mediated disruption of autophagosomal maturation in axonal transport and the impairment of lysosomes in hippocampal neurons.

The predictive value of systemic immune-inflammatory markers before and after treatment for pathological complete response in patients undergoing neoadjuvant therapy for breast cancer: a retrospective study of 1994 patients.

Purpose: Systemic immune-inflammatory markers have a certain predictive role in pathological complete response (pCR) after neoadjuvant treatment (NAT) in breast cancer. However, there is a lack of research exploring the predictive value of markers after treatment.

Methods: This retrospective study collected data from 1994 breast cancer patients who underwent NAT.

Diagnostic and prognostic value of the gut microbiota and its metabolite butyrate in children with biliary atresia.

Purpose: To determine the prevalent microbiological profile of biliary atresia (BA) patients at the time of its occurrence by studying their intestinal flora.

Methods: A total of 118 gut microbiota samples from three groups of 43 BA patients, 33 disease controls (DC) with other cholestatic diseases and 42 healthy controls (HC), were analyzed by deep mining of public data. Subsequently, a total of 23 fecal samples from three groups of clinically collected patients (11 BA, 6 DC and 6 HC) were sequenced for 16S rRNA gene amplification and analyzed for serum butyrate (BU) level by liquid chromatography.