High-efficient depletion and separation of histidine-rich proteins via Cu2+-chelated porous polymer microspheres.

Depletion and separation of histidine-rich proteins from complicated biosamples are crucial for various downstream applications in proteome research and clinical diagnosis. Herein, porous polymer microspheres coated with polyacrylic acid (SPSDVB-PAA) were fabricated through double emulsion interfacial polymerization technique and followed by immobilization of Cu2+ ions on the surface of SPSDVB-PAA. The as-prepared SPSDVB-PAA-Cu with uniform size and nanoscale pore structure enabled coordination interaction of Cu2+ with histidine residues in his-rich proteins, resulting in high-performance adsorption. As metal affinity adsorbent, the SPSDVB-PAA-Cu exhibited favorable selectivity for adsorbing hemoglobin (Hb) and human serum albumin (HSA) with the maximum adsorption capacities of 152.2 and 100.7 mg g-1. Furthermore, the polymer microspheres were used to isolate histidine-rich proteins from human whole blood and plasma, underscoring their effectiveness. The liquid chromatography tandem mass spectrometry (LC-MS/MS) results indicated that the content of 14 most abundant proteins in human plasma was depleted from 81.6 % to 30.7 % and low-abundance proteins were enriched from 18.4 % to 69.3 % after treatment with SPSDVB-PAA-Cu, illustrating potential application of SPSDVB-PAA-Cu in proteomic research.

Efficacy and Safety of Transarterial Chemoembolization and Repeated Partial Splenic Embolization for Hepatocellular Carcinoma with Hypersplenism and Thrombocytopenia.

Aim: Partial splenic embolization (PSE) combined with transarterial chemoembolization (TACE) has been reported in treatment of hepatocellular carcinoma (HCC) with cirrhotic hypersplenism and thrombocytopenia. However, efficacy and safety of repeated PSE when required are unclear. This study aims to investigate post-procedural changes in peripheral blood cell and hepatic function, progression-free survival (PFS), and safety of HCC patients with hypersplenism received TACE and repeated PSE compared to those received TACE alone. Methods: This retrospective study included 102 HCC patients with hypersplenism who received TACE (n = 73) or TACE+PSE (n = 29) from January 2014 to December 2021. Changes in peripheral blood cell and hepatic function were investigated at 1 week, 2, 6, 12, 18, and 24 months. TACE procedure sessions and adverse events were recorded. PFS and prognostic factors were analyzed. Results: Despite response to initial PSE being limited, repeated PSE increased platelet (PLT) again, which peaked at 18 months. It also continued to improve red blood cell (RBC) and hemoglobin, which showed significant differences in changes from baseline between two groups until 24 months, as well as Child-Pugh scores at 12 and 18 months. Mean TACE procedure sessions were significantly higher in TACE+PSE group than that in TACE alone group (4.55 vs 3.26, P = 0.019). TACE+PSE group had longer median PFS (19.4 vs 9.5 months, P = 0.023) than TACE alone group, where PSE was an independent protective factor (HR, 0.508; P = 0.014). Initial and repeated PSE showed no significant differences in safety. Conclusion: Repeated PSE is effective in increasing PLT again and improving RBC, hemoglobin and liver function. It contributed to performing serial TACE procedures thereafter. TACE combined with repeated PSE has significantly longer PFS than TACE alone, where PSE was an independent protective factor. Moreover, the safety of repeated PSE was comparable to initial PSE.

Restraint of Nonradiative Recombination via Modulation of n-Phase Distribution through Interfacial Lithium Salt Insertion for High-Performance Pure-Blue Perovskite LEDs.

Quasi-two-dimensional perovskite has been widely used in blue perovskite light-emitting diodes. However, the performance of these devices is still hampered by random phase distribution, nonradiative recombination, and imbalanced carrier transport. In this work, an effective strategy is proposed to mitigate these limitations by inserting lithium salts at the interfaces between the hole transport layer (HTL) and the perovskite layer. The perovskite film on the inserted Li2CO3 layer exhibits reasonable n-value redistribution, which leads to the repressive nonradiation recombination and enhanced carrier transport. Moreover, the inserted Li2CO3 layer also improves the electrical conductivity of PEDOT:PSS and hinders indium ion diffusion from the PEDOT:PSS layer to the perovskite film, which inhibits exciton quenching and nonradiative recombination loss at the HTL/perovskite interface. Taking advantage of these merits, we have successfully fabricated efficient pure-blue PeLEDs with an external quantum efficiency of 6.2% at 472 nm and a luminance of 726 cd cm-2. The restraint of nonradiative recombination at the interface offers a promising approach for efficient pure-blue PeLEDs.

Blocking the TRAIL-DR5 Pathway Reduces Cardiac Ischemia-Reperfusion Injury by Decreasing Neutrophil Infiltration and Neutrophil Extracellular Traps Formation.

PURPOSE: Acute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release. METHODS: This study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice. RESULTS: NETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils. CONCLUSION: This work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study.

BACKGROUND: Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown anti-tumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. MATERIALS AND METHODS: This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and non-metformin groups, while competing risk regression was performed to assess cancer-specific death. RESULTS: Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with mean age 59.6 (10.3) years received metformin and 164 patients (139 male patients and 25 female patients) with mean age 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P<0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P<0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P<0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P=0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. CONCLUSION: Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.

Sorafenib plus transcatheter arterial chemoembolization with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma.

OBJECTIVES: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analysed 78 patients with intermediate or advanced HCC who were treated at our centres between January 2018 and December 2021. Twenty-six of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. RESULTS: The median OS (22 vs 10 months, P < .001) and median PFS (11 vs 6 months, P = .008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumour progression. For grade I and II AEs, the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the 2 groups (P > .05). CONCLUSION: Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. ADVANCES IN KNOWLEDGE: (1) Subgroup analysis demonstrated that TACE + sorafenib + camrelizumab could benefit HCC patients regardless of whether they had portal vein tumour thrombosis, Barcelona Clinic Liver Cancer B or C, or CHILD A or B; (2) We reported the immunotherapy-related AEs occurred with a significantly higher incidence in triple treatment, but all the AEs are tolerable.

Effect of Welding Gap of Thin Plate Butt Welds on Inherent Strain and Welding Deformation of a Large Complex Box Structure.

In this study, an effective numerical model was developed for the calculation of the deformation of laser-welded 3 mm 304L stainless steel plates with different gaps (0.2 mm, 0.5 mm, and 1.0 mm). The welding deformation would become larger when the welding gaps increased, and the largest deformation values along the Z direction, of 4 mm, were produced when the gap value was 1.0 mm. A larger plastic strain region was generated in the location near the weld seam, since higher plastic deformation had occurred. In addition, the tensile stress model was also applied at the plastic strain zone and demonstrated that a larger welding gap led to a wider residual stress area. Based on the above results, inherent deformations for butt and corner joints were calculated according to inherent strain theory, and the welding formation for the complex structure was calculated with different gaps. The numerical results demonstrated that a larger deformation was also produced with a larger welding gap and that it could reach the highest value of 10.1 mm. This proves that a smaller welding gap should be adopted during the laser welding of complex structures to avoid excessive welding deformation.

Two new withanolides from Physalis minima L.

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

Anti-neurofascin-155 antibody mediated a distinct phenotype of chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. METHODS: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. RESULTS: In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. CONCLUSION: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.

Inflammatory myofibroblastic tumor of the liver after adrenal neuroblastoma surgery: a case report.

A boy aged 55 months was diagnosed with stage IV Neuroblastoma (NB) of the right adrenal gland 2 years ago. Preoperative chemotherapy was given and he was then treated with retroperitoneal tumor resection and lymph node dissection. After surgery, the children were transferred to the Hemato-Oncology Department for chemotherapy according to the high-risk group NB, with outpatient follow-up every 6 months. In the second postoperative year, abdominal computed tomography (CT) scan revealed a rounded hypodense area in the upper part of the right posterior lobe of the liver, with marked inhomogeneous enhancement in the venous phase after enhancement, which was surgically resected, and postoperative pathology confirmed inflammatory myofibroblastic tumor (IMT) of liver. The patient was not given any special treatment after surgery. In this study, whole transcriptome sequencing was performed on the postoperative specimen of adrenal NB and the specimen of IMT of liver. This unusual case emphasizes the need for close monitoring of second tumor development in NB survivors even in the absence of known predisposing factors.

Direct Selective Epitaxy of 2D Sb2Te3 onto Monolayer WS2 for Vertical p-n Heterojunction Photodetectors.

Two-dimensional transition metal dichalcogenides (2D-TMDs) possess appropriate bandgaps and interact via van der Waals (vdW) forces between layers, effectively overcoming lattice compatibility challenges inherent in traditional heterojunctions. This property facilitates the creation of heterojunctions with customizable bandgap alignments. However, the prevailing method for creating heterojunctions with 2D-TMDs relies on the low-efficiency technique of mechanical exfoliation. Sb2Te3, recognized as a notable p-type semiconductor, emerges as a versatile component for constructing diverse vertical p-n heterostructures with 2D-TMDs. This study presents the successful large-scale deposition of 2D Sb2Te3 onto inert mica substrates, providing valuable insights into the integration of Sb2Te3 with 2D-TMDs to form heterostructures. Building upon this initial advancement, a precise epitaxial growth method for Sb2Te3 on pre-existing WS2 surfaces on SiO2/Si substrates is achieved through a two-step chemical vapor deposition process, resulting in the formation of Sb2Te3/WS2 heterojunctions. Finally, the development of 2D Sb2Te3/WS2 optoelectronic devices is accomplished, showing rapid response times, with a rise/decay time of 305 µs/503 µs, respectively.

PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-ß pathway.

BACKGROUND: Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients' average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits. METHODS: The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated. Cell counting kit-8, plate colony formation, flow cytometry and subcutaneous xenograft tumor model assays were employed to explore the effects of PDZK1 on ccRCC. Further research on the molecular mechanism was conducted through western blot, co-immunoprecipitation, immunofluorescence co-localization and immunohistochemical staining. RESULTS: We elucidated that PDZK1 is significantly downregulated in sunitinib-resistant ccRCC specimens, and PDZK1 negatively regulates the phosphorylation of PDGFR-ß and the activation of its downstream pathways through interaction with PDGFR-ß. The dysregulated low levels of PDZK1 contribute to inadequate inhibition of cell proliferation, tumor growth, and insensitivity to sunitinib treatment. Notably, our preclinical investigations showed that miR-15b antagomirs enhance sunitinib cytotoxic effects against ccRCC cells by upregulating PDZK1 levels, suggesting their potential in overcoming sunitinib resistance. CONCLUSIONS: Our findings establish the miR-15b/PDZK1/PDGFR-ß axis as a promising therapeutic target and a novel predictor for ccRCC patients' response to sunitinib treatment.

Gestational diabetes mellitus affects the differentiation of hematopoietic stem cells in neonatal umbilical cord blood.

PURPOSE: There are abundant hematopoietic stem cells (HSCs) in cord blood. It is known that HSCs continue to differentiate to CLP, CMP and erythroid progenitor cells (EPC), EPC ultimately differentiated to platelets and erythrocytes. It has been reported that the proportion of HSCs in cord blood was higher than that in healthy pregnant women, so as the incidence of neonatal polycythemia in gestational diabetes mellitus (GDM) patients. We aimed to investigate whether the hyperglycemic and/or hyperinsulin environment in GDM patients has effects on the differentiation of HSCs into erythrocytes in offspring cord blood. METHODS: In this study, we collected cord blood from 23 GDM patients and 52 healthy pregnant women at delivery. HSCs, CLP, CMP and EPCs in cord blood of the two groups were identified and quantified by flow cytometry. HSCs were sorted out and treated with glucose and insulin, respectively, and then, the changes of HSCs proliferation and differentiation were detected. RESULTS: Compared to healthy controls, HSCs, CMP and EPC numbers in cord blood from GDM group were significantly increased, while CLP cell number was decreased. The differentiation of HSCs into EPC was promoted after treatment with glucose or insulin. CONCLUSION: There were more HSCs in the cord blood of GDM group, and the differentiation of HSCs to EPCs was increased. These findings were probably caused by the high-glucose microenvironment and insulin medication in GDM patients, and the HSCs differentiation changes might be influencing factors of the high incidence of neonatal erythrocytosis in GDM patients.

Analysis of care-seeking and diagnosis delay among pulmonary tuberculosis patients in Beijing, China.

Background: Tuberculosis (TB) remains a significant public health challenge in China. Early detection and diagnosis of TB cases are crucial to interrupt disease transmission and prevent its progression. This study aims to describe the delay in seeking care and diagnosis among patients with pulmonary tuberculosis (PTB) and identify the influencing factors in two counties in Beijing. Methods: A retrospective analysis was carried out to investigate care-seeking and diagnosis delay in two counties in Beijing. Basic information of PTB patients from January 1 to December 31, 2021, was extracted from the Tuberculosis Information Management System of China (TBIMS), and all enrolled patients were interviewed via telephone using a standard questionnaire. Statistical description was performed using the median and interquartile range (IQR). Chi-square test and multivariate logistic regression model were used to analyze the influencing factors. Results: 537 patients were enrolled. The median duration of care-seeking and diagnosis delay was 11 (IQR: 5-26) days and 8 (IQR: 0-18) days, with 41.71 and 35.20% of patients experiencing delays (>14 days). The study found that being asymptomatic (OR = 2.791, 95%CI: 1.710-4.555) before seeking medical care and not attending work during treatment (OR = 2.990, 95%CI: 1.419-6.298) were identified as risk factors for care-seeking delay. Patients who were tracked (OR = 2.632, 95%CI: 1.062-6.521) and diagnosed at tuberculosis control and prevention institutions (OR = 1.843, 95%CI: 1.061-3.202) had higher odds of diagnostic delays. 44.69% of patients presented a total delay (>28 days), with a median duration of 25 (IQR: 13-39) days. A multivariate logistic regression analysis showed that healthy examination (OR = 0.136, 95%CI: 0.043-0.425) was a protective factor for total delay. Conclusion: Public interventions are necessary to improve the efficiency of PTB patients detection and treatment in Beijing. Medical services should focus on the target population and improve access to medical care to further reduce delays for PTB patients.

Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy.

BACKGROUND: Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. METHODS: Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. RESULTS: Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102- 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102- 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. CONCLUSION: HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr.

Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration.

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Gentisic acid prevents colorectal cancer metastasis via blocking GPR81-mediated DEPDC5 degradation.

BACKGROUND: Metastasis driven by epithelial-mesenchymal transition (EMT) remains a significant contributor to the poor prognosis of colorectal cancer (CRC), and requires more effective interventions. GPR81 signaling has been linked to tumor metastasis, while lacks an efficient specific inhibitor. PURPOSE: Our study aimed to investigate the effect and mechanism of Gentisic acid on colorectal cancer (CRC) metastasis. STUDY DESIGN: A lung metastasis mouse model induced by tail vein injection and a subcutaneous graft tumor model were used. Gentisic acid (GA) was administered by an intraperitoneal injection. HCT116 was treated with lactate to establish an in vitro model. METHODS: MC38 cells with mCherry fluorescent protein were injected into tail vein to investigate lung metastasis ability in vivo. GA was administered by intraperitoneal injection for 3 weeks. The therapeutic effect was evaluated by survival rates, histochemical analysis, RT-qPCR and live imaging. The mechanism was explored using small interfering RNA (siRNA), Western blotting, RT-qPCR and immunofluorescence. RESULTS: GA had a therapeutic effect on CRC metastasis and improved survival rates and pathological changes in dose-dependent manner. GA emerged as an GPR81 inhibitor, effectively suppressed EMT and mTOR signaling in CRC induced by lactate both in vivo and in vitro. Mechanistically, GA halted lactate-induce degradation of DEPDC5 through impeding the activation of Chaperone-mediated autophagy (CMA). CONCLUSION: CMA-mediated DEPDC5 degradation is crucial for lactate/GPR81-induced CRC metastasis, and GA may be a promising candidate for metastasis by inhibiting GPR81 signaling.

Gram-scale synthesis of small-sized PtM intermetallics as high-performance catalysts for the hydrogen evolution reaction.

Pt-based intermetallics exhibit excellent activity in electrocatalysis. However, their controlled syntheses remain difficult. Herein, carbon-supported PtM (M = Fe, Co, Ni, Zn and Mn) intermetallics with small size (3 nm) were prepared at the gramscale and applied as a highly effective electrocatalyst for the hydrogen evolution reaction.

Exploration and Application of a Muscle Fatigue Assessment Model Based on NMF for Multi-Muscle Synergistic Movements.

Muscle fatigue significantly impacts coordination, stability, and speed in daily activities. Accurate assessment of muscle fatigue is vital for effective exercise programs, injury prevention, and sports performance enhancement. Current methods mostly focus on individual muscles and strength evaluation, overlooking overall fatigue in multi-muscle movements. This study introduces a comprehensive muscle fatigue model using non-negative matrix factorization (NMF) weighting. NMF is employed to analyze the duration multi-muscle weight coefficient matrix (DMWCM) during synergistic movements, and four electromyographic (EMG) signal features in time, frequency, and complexity domains are selected. Particle Swarm Optimization (PSO) optimizes feature weights. The DMWCM and weighted features combine to calculate the Comprehensive Muscle Fatigue Index (CMFI) for multi-muscle synergistic movements. Experimental results show that CMFI correlates with perceived exertion (RPE) and Speed Dynamic Score (SDS), confirming its accuracy and real-time tracking in assessing multi-muscle synergistic movements. This model offers a more comprehensive approach to muscle fatigue assessment, with potential benefits for exercise training, injury prevention, and sports medicine.