20S-Ginsenoside Rh2, the major bioactive saponin in Panax notoginseng flowers, ameliorates cough by inhibition of NaV1.7 and TRPV1 channel currents and downregulation of TRPV1 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng flowers, which are the buds of the traditional Chinese medicinal herb Sanqi, are widely used in China for their cough-ameliorating properties, with demonstrated therapeutic effects in the treatment of both acute and chronic coughs. However, both the antitussive mechanism and active compound basis of P. notoginseng flowers remain poorly understood. AIM OF THE STUDY: We investigated the antitussive effects of P. notoginseng flowers, identified the bioactive constituents responsible for alleviating cough symptoms, and elucidated the underlying pharmacological mechanisms. MATERIALS AND METHODS: We analyzed the major chemical constituents of aqueous extracts of P. notoginseng flowers using liquid chromatography-mass spectrometry and quantitatively analyzed the key component, 20S-ginsenoside Rh2, using high-performance liquid chromatography. Using a cough reflex model in healthy mice and an ovalbumin-induced, highly sensitive guinea pig cough model, we verified the suppressive effects of P. notoginseng flowers and their saponin constituents on coughing. Furthermore, we explored the mechanisms of action of the key ion channels, NaV1.7 and TRPV1, using whole-cell patch-clamp techniques and molecular docking. Finally, the therapeutic mechanisms of P. notoginseng flowers on pathological cough were revealed using hematoxylin and eosin staining, immunohistochemistry, and western blotting. RESULTS: The active components of P. notoginseng flowers were primarily protopanaxadiol-type saponins, among which 20S-ginsenoside Rh2 had the highest content (51.46 mg/g). In the mouse model, P. notoginseng flowers exhibited antitussive effects comparable to those of pentoxyverine citrate. Although its main saponin component, 20S-ginsenoside Rh2, showed slightly weaker effects, it still demonstrated concentration-dependent inhibition of channel activity. The whole-cell patch-clamp technique and virtual molecular docking showed that Rh2 might exert its effects by directly binding to the NaV1.7 and TRPV1 channels. In the guinea pig model, P. notoginseng flowers and their saponin components not only reduced cough frequency and prolonged the latency period before cough onset, but also significantly inhibited tracheal and pulmonary inflammation and the overexpression of TRPV1. CONCLUSIONS: 20S-Ginsenoside Rh2, the major bioactive saponin in P. notoginseng flowers, exhibits potent antitussive effects. The potential mechanism of action of 20S-Ginsenoside Rh2 in the treatment of cough may involve inhibiting NaV1.7 and TRPV1 channel currents through direct binding to core protein active sites and downregulating TRPV1 expression.

Effect of surface species on the alcohol-acid adsorption from FTS wastewater on graphene: A structure-capacity study.

Fischer-Tropsch synthesis (FTS) wastewater retaining low-carbon alcohols and acids are organic pollutants as a limiting factor for FTS industrialization. In this work, the structure-capacity relationships between alcohol-acid adsorption and surface species on graphene were reported, shedding light into their intricate interactions. The graphene oxide (GO) and reduced graphene oxide (rGO) were synthesized via improved Hummers method with flake graphite (G). The physicochemical properties of samples were characterized via SEM, XRD, XPS, FT-IR, and Raman. The alcohol-acid adsorption behaviors and adsorption quantities on G, GO, and rGO were measured via theoretical and experimental method. It was revealed that the presence of COOH, C=O and CO species on graphene occupy the adsorption sites and increase the interactions of water with graphene, which are unfavorable for alcohol-acid adsorption. The equilibrium adsorption quantities of alcohols and acids grow in pace with carbon number. The monolayer adsorption occurs on graphene was verified via model fitting. rGO has the highest FTS modeling wastewater adsorption quantity (110 mg/g) due to the reduction of oxygen species. These novel findings provide a foundation for the alcohol-acid wastewater treatment, as well as the design and development of high-performance carbon-based adsorbent materials.

Research progress of exosomes from different sources in myocardial ischemia.

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.

Task-State Functional MRI of Brain Regions with Reduced Activation in Aphasia Patients: A Meta-analysis.

OBJECTIVE: Language is one of the most celebrated hallmarks of human cognition. With the continuous improvement of medical technology, functional MRI (fMRI) has been used in aphasia. Although many related studies have been carried out, most studies have not extensively focused on brain regions with reduced activation in aphasic patients. The aim of this study was to identify brain regions normally activated in healthy controls but with reduced activation in aphasic patients during fMRI language tasks. METHODS: We collected all previous task-state fMRI studies of secondary aphasia. The brain regions showed normal activation in healthy controls and reduced activation in aphasic patients were conducted activation likelihood estimation (ALE) meta-analysis to obtain the brain regions with consistently reduced activation in aphasic patients. RESULTS: The ALE meta-analysis revealed that the left inferior frontal gyrus, left middle temporal gyrus, left superior temporal gyrus, left fusiform gyrus, left lentiform nucleus and the culmen of the cerebellum were the brain regions with reduced activation in aphasic patients. DISCUSSION: These findings from the ALE meta-analysis have significant implications for understanding the language network and the potential for recovery of language functions in individuals with aphasia.

Temperature-Dependent Oxidation Behavior of Silicon Carbide Surface: Reactive Molecular Dynamics Simulations.

The high-temperature oxidation mechanism of silicon carbide (SiC) is crucial for designing thermal protection systems in aircraft. This study explored the oxidative chemical reaction processes and mechanism on SiC surface and interfaces within the temperature range of 300-2300 K by using reactive molecular dynamics simulation. The oxygen impact on the silica (SiOx) growth of the SiC surface was analyzed, which shows a progressive increase of silica thickness. The simulation results indicated that the oxidation process of SiC was a typical passive oxidation mechanism. With the environmental temperature rising and oxygen impact, the increase of oxidation thickness on the SiC surface undergoes three oxidizing reaction processes: little chemical adsorption of oxygen molecules on the initial surface, rapid oxidation of silicon and carbon, and dramatic oxidation of the interface between the oxidation layer and SiC. Additionally, this work studied the mechanism of oxidation thickness growth and chemical diffusion of oxygen. The oxidation rate is weakened according to the oxygen atom diffusion barrier effect of silica repulsion. Moreover, the kinetic parameters were statistically calculated by fitting the growth of Si-O bonds and their reaction rate constants. Subsequently, the activation energy and pre-exponential factors were derived by using the Arrhenius equation to model the chemical reaction kinetics of the thermal oxidation process. The chemical reaction behaviors of the two stages could be concluded as follows: (i) in stage I, the initial oxidation is reaction rate limiting; (ii) in stage II, SiC oxidation is limited by both the oxidation reaction rate and the oxygen diffusion coefficient of the oxidation layer. The activation energy of stage II increased compared with stage I due to the oxygen atoms diffusion barrier between the oxidation layers. This study on the oxidation and ablation mechanism of the SiC surface at the atomic scale would provide insight into understanding thermal oxidation behavior and the design of ceramic materials.

FT4 is a novel indicator for risk assessment of severe hypocalcemia following parathyroidectomy.

OBJECTIVE: To analyze the risk factors associated with the development of severe hypocalcemia (SH) in patients who have undergone parathyroidectomy (PTX). METHODS: This research involved patients with chronic kidney disease-secondary hyperparathyroidism who underwent PTX between June 1, 2021, and May 31, 2023. SH was characterized by a serum total calcium (tCa) level below 1.8 mmol/L. This study aimed to analyze differences in preoperative laboratory findings and clinical manifestations between patients with and without SH. Logistic regression analysis was used to identify potential risk factors associated with the development of SH. RESULTS: The incidence of SH was 23% (n = 176). Significant differences were observed in free thyroxine (FT4), free triiodothyronine, alanine aminotransferase, osteocalcin, tCa, alkaline phosphatase (ALP), C-terminal cross-linked telopeptide of type I collagen, and parathyroid hormone between the SH and non-SH groups. The three independent risk factors for SH were tCa [odds ratio (OR) 0.063, 95% confidence interval (95% CI) 0.006-0.663], ALP (OR 1.003, 95% CI 1.001-1.005), and FT4 (OR 0.439, 95%CI 0.310-0.621). The area under the curve, sensitivity, specificity, and overall accuracy of this model were 0.904 (95% CI 0.856-0.952), 46.3%(95% CI 32.0%-61.3%), 94.8% (95% CI 89.7%-97.5%), and 83.5% (95% CI 77.3%-88.3%), respectively. CONCLUSION: The preoperative level of FT4 plays a crucial role in predicting the risk of SH after PTX. The combined FT4-ALP-tCa model demonstrates the ability to predict SH risk, providing valuable insights for customizing calcium supplementation strategies and improving clinical decision-making.

Prediction of metal recovery potential of end-of-life NEV batteries in China based on GRA-BiLSTM.

As Chinese new energy vehicle (NEV) sales continue to grow, end-of-life batteries have great potential for recycling in the future. In this study, a combined model based on Gray Relation Analysis and Bi-directional Long Short-Term Memory (GRA-BiLSTM) is proposed for predicting NEV sales, and the NEV battery life is modeled using the Weibull distribution. Then, the amount of end-of-life batteries, secondary utilization and metal recycling are calculated. The impact of end-of-life battery recycling on the supply and demand of key metals is studied. The results show that in 2040, the secondary utilization of end-of-life batteries in the Standard Growth Rate-Lithium Iron Phosphate Battery Dominated-High Secondary Utilization rate scenario (SGR-LFPH) is 391.76 GWh. The recycling volumes of lithium, nickel and cobalt are 45,900 tons, 92,900 tons and 22,100 tons, respectively. In the Standard Growth Rate-lithium nickel cobalt manganese oxide Battery Dominated-Low Secondary Utilization rate scenario (SGR-NCML), the recycling of lithium, nickel and cobalt is even greater, at 62,600 tons, 372,200 tons and 71,700 tons, respectively. End-of-life batteries recycling can reduce the demand for metals. However, as NEV sales continue to grow, the gap between metal supply and demand remains significant. The findings urge the Chinese government develop appropriate battery management strategies to increase the recycling rate of end-of-life batteries; and to encourage enterprises to research new types of batteries to resolve the conflict between supply and demand for metals.

Acute toxicity of salicylic acid and its derivatives on the diatom Phaeodactylum tricornutum: Physico-Biochemical and transcriptomic insights.

Salicylate pollutants (SAs) poses a serious threat to marine ecosystems as emerging contaminants. However, the toxic effects of SAs on marine phytoplankton, as well as the potential mechanisms and their ecological risks linked with them, are remain largely unknown. In this study, we aimed to evaluate the toxic effects of salicylic acid (SA) and its 5-substituted derivatives (5-sSA) on the marine diatom Phaeodactylum tricornutum, as well as the potential molecular mechanism involved in the toxicity. Physiological assays conducted on P. tricornutum revealed significant changes in photosynthetic pigments, chlorophyll fluorescence parameters, and antioxidant enzyme activities. The results showed that exposure of P. tricornutum to SAs caused a significant decline in chlorophyll contents and damage to the photosystem II (PSII) core resulting in the decline of photosynthesis. Although the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were enhanced, oxidative damage occurred. Transcriptome analysis showed that a large number of differentially expresses genes (DEGs) were significantly enriched in metabolic pathways such as porphyrin metabolism, terpenoid backbone biosynthesis, and carbon fixation in photosynthetic organisms after SA and 5-BrSA treatments. In addition, key genes in transcriptomic metabolic pathways were further analyzed and validated using weighted correlation network analysis (WGCNA) and real-time fluorescence quantitative PCR (qPCR). Considering the above results, SAs mainly inhibit the processes of photosynthesis by repressing the expression of genes involved in secondary metabolite synthesis and photosynthetic carbon sequestration pathways, thus exerting toxic effects on algal cells. The results of the study will provide key data for understanding the ecological risk and toxicity mechanisms of SA pollutants.

Correction: A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice.

Correction for 'A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice' by Tian Liu et al., Food Funct., 2024, 15, 5955-5971, https://doi.org/10.1039/D3FO05521C.

Hearing results following endoscopic type I tympanoplasty in medium and large perforations.

OBJECTIVES: To clarify the hearing outcomes after endoscopic type I tympanoplasty for medium and large perforations due to chronic otitis media. METHODS: We examined the clinical records of patients who underwent endoscopic type I tympanoplasty for medium and large perforations of the eardrum resulting from chronic otitis media between January 2019 and December 2021. We analyzed the changes in hearing pre- and post-operation in patients with healed eardrums and assessed the impact of tympanosclerosis on hearing. Patients with incomplete follow-up data, middle ear cholesteatoma, stapes fixation, severe lesions in the tympanic antrum and mastoid necessitating mastoidectomy and/or ossicular chain reconstruction were excluded. RESULTS: A total of 156 patients underwent analysis for audiological outcomes. Among them, 63 had medium tympanic membrane perforations, with 18 cases showing calcification of the tympanic membrane and 20 cases with calcification in the tympanic cavity. Additionally, 93 cases had large tympanic membrane perforations, with 25 cases showing tympanic membrane calcification and 32 cases with tympanic cavity calcification. Prior to surgery, the Air Conduction threshold (AC) in the large perforation group was higher than in the medium perforation group, particularly at low frequencies, measuring (47.4 ± 13.3 dB) and (41.2 ± 14.7 dB), respectively (p-value < 0.05). Following surgery, both groups experienced an improvement in AC, measuring (33.6 ± 13.9 dB) and (32.6 ± 12.8 dB), respectively, with no significant difference noted (p-value > 0.05). There was no significant change in Bone Conduction threshold (BC) before and after surgery in either the large or medium perforation groups (all p-values > 0.05). Except for 4000 Hz an increase, bone conduction did not increase post-surgery, instead showing further improved. Pre-surgery, the Air-Bone Gap (ABG) in the large and medium perforation groups was (27.7 ± 8.5 dB) and (21.8 ± 8.3 dB), respectively, mainly affecting low frequencies, with a statistically significant difference noted (p-value < 0.05). Following surgery, ABG in both groups improved to (16.3 ± 7.6 dB) and (15.7 ± 8.4 dB), respectively, with no significant difference observed (p-value > 0.05). There was no significant difference in hearing pre-surgery among the groups with No calcification (No), Tympanic Membrane Calcification (TM), and Tympanic Cavity Calcification (TC). However, TC significantly impacted low frequency (250-500 Hz) AC and ABG. The differences in AC and ABG pre-surgery between TC and No group, and TC and TM group (at 250-500 Hz) were statistically significant (all p-values < 0.05). Preoperative ABG in TM group was better than in No group and TC group, suggesting minimal impact of tympanic membrane calcification on hearing. No interaction was observed between tympanic membrane perforation size and tympanosclerosis on hearing. Post-surgery, both large and medium tympanic membrane perforation groups, regardless of tympanosclerosis presence, showed good AC and ABG, with no statistically significant difference in △ABG (all p-values > 0.05). CONCLUSION: Preoperative AC and ABG were increase in cases of large tympanic membrane perforations and medium tympanic membrane perforations with tympanic cavity calcification. Surgical intervention led to more significant hearing improvement in these patients. However, irrespective of tympanic membrane perforation size and the presence of tympanosclerosis, as long as the ossicular chain remains intact and functional, postoperative AC and ABG outcomes are satisfactory. Endoscopic type I tympanoplasty proves effective in achieving improved hearing outcomes for patients with medium to large tympanic membrane perforations and tympanosclerosis, provided there is no ossicle chain fixation. LEVEL OF EVIDENCE: Level 4.

A Review on Bi2WO6-Based Materials for Photocatalytic CO2 Reduction.

Photocatalytic reduction of CO2 (PCR) technology offers the capacity to transmute solar energy into chemical energy through an eco-friendly and efficacious process, concurrently facilitating energy storage and carbon diminution, this innovation harbors significant potential for mitigating energy shortages and ameliorating environmental degradation. Bismuth tungstate (Bi2WO6) is distinguished by its robust visible light absorption and distinctive perovskite-type crystal architecture, rendering it highly efficiency in PCR. In recent years, numerous systematic strategies have been investigated for the synthesis and modification of Bi2WO6 to enhance its photocatalytic performance, aiming to achieve superior applications. This review provides a comprehensive review of the latest research progress on Bi2WO6 based materials in the field of photocatalysis. Firstly, outlining the fundamental principles, associated reaction mechanisms and reduction pathways of PCR. Then, the synthesis strategy of Bi2WO6-based materials is introduced for the regulation of its photocatalytic properties. Furthermore, accentuating the extant applications in CO2 reduction, including metal-Bi2WO6, semiconductor-Bi2WO6 and carbon-based Bi2WO6 composites etc. while concludes with an examination of the future landscape and challenges faced. This review hopes to serve as an effective reference for the continuous improvement and implementation of Bi2WO6-based photocatalysts in PCR.

High expression of transcription factor EGR1 is associated with postoperative muscle atrophy in patients with knee osteoarthritis undergoing total knee arthroplasty.

BACKGROUND: Muscle atrophy is a typical affliction in patients affected by knee Osteoarthritis (KOA). This study aimed to examine the potential pathogenesis and biomarkers that coalesce to induce muscle atrophy, primarily through the utilization of bioinformatics analysis. METHODS: Two distinct public datasets of osteoarthritis and muscle atrophy (GSE82107 and GSE205431) were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA) to probe for common differentially expressed genes (DEGs) and conduct transcription factor (TF) enrichment analysis from such genes. Venn diagrams were used to identify the target TF, followed by the construction of a protein-protein interaction (PPI) network of the common DEGs governed by the target TF. Hub genes were determined through the CytoHubba plug-in whilst their biological functions were assessed using GSEA analysis in the GTEx database. To validate the study, reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry techniques were employed. RESULTS: A total of 138 common DEGs of osteoarthritis and muscle atrophy were identified, with 16 TFs exhibiting notable expression patterns in both datasets. Venn diagram analysis identified early growth response gene-1 (EGR1) as the target TF, enriched in critical pathways such as epithelial mesenchymal transition, tumor necrosis factor-alpha signaling NF-κB, and inflammatory response. PPI analysis revealed five hub genes, including EGR1, FOS, FOSB, KLF2, and JUNB. The reliability of EGR1 was confirmed by validation testing, corroborating bioinformatics analysis trends. CONCLUSIONS: EGR1, FOS, FOSB, KLF2, and JUNB are intricately involved in muscle atrophy development. High EGR1 expression directly regulated these hub genes, significantly influencing postoperative muscle atrophy progression in KOA patients.

Structure, antioxidant activity, and neuroprotective effect of black soybean (Glycine max (L.) merr.) protein hydrolysates.

The potential biological properties of protein hydrolysates have generated considerable research interest. This study was to hydrolyze black soybean protein (BSP) using five different commercial enzymes, and elucidate the influence of these enzymes on the structure and biological activities of the resulting hydrolysates. Enzymatic treatment changed secondary and tertiary structures of BSP, decreased particle size, α-helix and ß-sheet. Alcalase hydrolysate had the highest hydrolytic degree (29.84 %), absolute zeta potential (38.43 mV), the smallest particle (149.87 nm) and molecular weight (<3 kDa). In silico revealed alcalase hydrolysate had the strongest antioxidant potential. This finding was further validated through the lowest IC50 (mg/mL) in DPPH (2.67), ABTS (0.82), Fe2+ chelating (1.33) and·OH (1.12). Moreover, cellular antioxidant assays showed alcalase hydrolysate had the strongest cytoprotective effects on H2O2-induced PC12 cells. These results suggest BSPEHs, especially those prepared by alcalase, have potential as bioactive ingredients for nutrition, healthcare and food industry.

Clinicopathological characteristics and prognosis of combined hepatocellular cholangiocarcinoma.

There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles.

Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.

Real-world evidence of avatrombopag for the treatment of immune thrombocytopenia intolerant or ineffective to eltrombopag/hetrombopag.

Due to the limited real-world research on the application of avatrombopag (AVA) for immune thrombocytopenia (ITP) in China, we evaluated the effectiveness and safety of AVA in clinical practice. We included 121 adult ITP patients treated with AVA across three medical centres. Based on the reasons for choosing AVA, these patients were divided into eltrombopag (ELT)/hetrombopag (HET) intolerance group (IG), and ELT/HET unresponsive group (UG). Compared with UG, more patients in IG had a history of liver disease and received fewer treatments before AVA. Amongst all patients, 83% had platelet response (≥30 × 109/L) after AVA and 62% achieved complete response (≥100 × 109/L, CR). Sixty-two percent in IG and 56% in UG were able to discontinue more than one concomitant ITP medication. A total of 17 patients underwent multiple switches of thrombopoietin receptor agonists (TPO-RAs), resulting in an 88% platelet response rate. Sixty-three patients discontinued AVA, 27% were due to unaffordability. AVA was well tolerated in most patients. In the ITP population, AVA proved effective and safe, particularly in patients intolerant or unresponsive to ELT/HET. Patients benefited from TPO-RAs switches, particularly those undergoing multiple switches. However, many patients struggled with the long-term financial burden of AVA.

Nonlocal photonic quantum gates over 7.0 km.

Quantum networks provide a prospective paradigm to connect separated quantum nodes, which relies on the distribution of long-distance entanglement and active feedforward control of qubits between remote nodes. Such approaches can be utilized to construct nonlocal quantum gates, forming building blocks for distributed quantum computing and other novel quantum applications. However, these gates have only been realized within single nodes or between nodes separated by a few tens of meters, limiting the ability to harness computing resources in large-scale quantum networks. Here, we demonstrate nonlocal photonic quantum gates between two nodes spatially separated by 7.0 km using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fibers. Furthermore, we illustrate quantum parallelism by implementing the Deutsch-Jozsa algorithm and the quantum phase estimation algorithm between the two remote nodes. These results represent a proof-of-principle demonstration of quantum gates over metropolitan-scale distances and lay the foundation for the construction of large-scale distributed quantum networks relying on existing fiber channels.

The association between serum S100ß levels and prognosis in acute stroke patients after intravenous thrombolysis: a multicenter prospective cohort study.

BACKGROUND: S100ß is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100ß and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. METHODS: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100ß levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. RESULTS: A total of 1072 patients were included in the analysis. The highest S100ß levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100ß level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: ß 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: ß 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100ß levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: ß 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: ß 0.326, 95% CI  - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100ß levels and HT was not significant in either stroke lateralization group. CONCLUSIONS: Serum S100ß levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100ß in judging the degree of disease and predicting prognosis.

Reposition: Focalizing ß-Alanine Metabolism and the Anti-Inflammatory Effects of Its Metabolite Based on Multi-Omics Datasets.

The incorporation of multi-omics data methodologies facilitates the concurrent examination of proteins, metabolites, and genes associated with inflammation, thereby leveraging multi-dimensional biological data to achieve a comprehensive understanding of the complexities involved in the progression of inflammation. Inspired by ensemble learning principles, we implemented ID normalization preprocessing, categorical sampling homogenization, and pathway enrichment across each sample matrix derived from multi-omics datasets available in the literature, directing our focus on inflammation-related targets within lipopolysaccharide (LPS)-stimulated RAW264.7 cells towards ß-alanine metabolism. Additionally, through the use of LPS-treated RAW264.7 cells, we tentatively validated the anti-inflammatory properties of the metabolite Ureidopropionic acid, originating from ß-alanine metabolism, by evaluating cell viability, nitric oxide production levels, and mRNA expression of inflammatory biomarkers. In conclusion, our research represents the first instance of an integrated analysis of multi-omics datasets pertaining to LPS-stimulated RAW264.7 cells as documented in the literature, underscoring the pivotal role of ß-alanine metabolism in cellular inflammation and successfully identifying Ureidopropionic acid as a novel anti-inflammatory compound. Moreover, the findings from database predictions and molecular docking studies indicated that the inflammatory-related pathways and proteins may serve as potential mechanistic targets for Ureidopropionic acid.

Reactivity of Polynuclear Niobium Oxynitride Cluster Anions Nb4N5-xOx- (x = 0-5) toward N2.

The activation of N2 under mild conditions remains a significant challenge in chemistry. Understanding how the composition of ligands modulates the reactivity of metal centers is pivotal for the rational design of efficient catalysts for nitrogen fixation. Herein, the reactions between polynuclear niobium oxynitride anions Nb4N5-xOx- (x = 0-5) and N2 were investigated by employing mass spectrometry, photoelectron imaging spectroscopy, and theoretical calculations. The rate constants of Nb4N5-xOx-/N2 gradually decrease for x = 0 to x = 4, and then increase again for x = 5. The sharp increase of the rate constants of Nb4O5-/N2 corresponds to a decrease in the electron detachment energy of the Nb4O5- cluster in the photoelectron spectroscopic experiment. Theoretical calculations suggest that the low-coordinated Nb-Nb site in Nb4N5-xOx- (x = 0-5) behaves as the active center to bind N2 in the side-on/end-on manner. Mechanistic analysis reveals that raising the O/N ratio leads to higher electron densities on the active Nb-Nb center and decreased positive charge on the metal atoms, which hinders the approach of N2 to the clusters. This finding discloses fundamental insights into the impact of N/O ratios in fine-tuning the reactivity of metal centers towards N2 adsorption in related catalytic processes.