Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases.

Background: Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. Methods: In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. Results: Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P<0.05). Conclusion: The present study indicated that baseline plasma ET-1 levels were associated with the prognosis in prediabetic and diabetic patients with stable CAD, suggesting that ET-1 may be a valuable predictor in CAD patients with impaired glucose metabolism.

RemixFormer++: A Multi-modal Transformer Model for Precision Skin Tumor Differential Diagnosis with Memory-efficient Attention.

Diagnosing malignant skin tumors accurately at an early stage can be challenging due to ambiguous and even confusing visual characteristics displayed by various categories of skin tumors. To improve diagnosis precision, all available clinical data from multiple sources, particularly clinical images, dermoscopy images, and medical history, could be considered. Aligning with clinical practice, we propose a novel Transformer model, named Remix-Former++ that consists of a clinical image branch, a dermoscopy image branch, and a metadata branch. Given the unique characteristics inherent in clinical and dermoscopy images, specialized attention strategies are adopted for each type. Clinical images are processed through a top-down architecture, capturing both localized lesion details and global contextual information. Conversely, dermoscopy images undergo a bottom-up processing with two-level hierarchical encoders, designed to pinpoint fine-grained structural and textural features. A dedicated metadata branch seamlessly integrates non-visual information by encoding relevant patient data. Fusing features from three branches substantially boosts disease classification accuracy. RemixFormer++ demonstrates exceptional performance on four single-modality datasets (PAD-UFES-20, ISIC 2017/2018/2019). Compared with the previous best method using a public multi-modal Derm7pt dataset, we achieved an absolute 5.3% increase in averaged F1 and 1.2% in accuracy for the classification of five skin tumors. Furthermore, using a large-scale in-house dataset of 10,351 patients with the twelve most common skin tumors, our method obtained an overall classification accuracy of 92.6%. These promising results, on par or better with the performance of 191 dermatologists through a comprehensive reader study, evidently imply the potential clinical usability of our method.

The longitudinal changes in multiparametric MRI during neoadjuvant chemotherapy can predict treatment response early in patients with HER2-positive breast cancer.

PURPOSE: To investigate whether longitudinal changes in multiparametric MRI can predict early response to neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) and to further establish quantitative models based on these features. METHODS: A total of 164 HER2-positive BC patients from three centers were included. MRI was performed at baseline and after two cycles of NAC (early post-NAC). Clinicopathological characteristics were enrolled. MRI features were evaluated at baseline and early post-NAC, as well as longitudinal changes in multiparametric MRI, including changes in the largest diameter (LD) of the tumor (ΔLD), apparent diffusion coefficient (ADC) values (ΔADC), and time-signal intensity curve (TIC) (ΔTIC). The patients were divided into a training set (n = 95), an internal validation set (n = 31), and an independent external validation set (n = 38). Univariate and multivariate logistic regression analyses were used to identify the independent indicators of pCR, which were then used to establish the clinicopathologic model and combined model. The AUC was used to evaluate the predictive power of the different models and calibration curves were used to evaluate the consistency of the prediction of pCR in different models. Additionally, decision curve analysis (DCA) was employed to determine the clinical usefulness of the different models. RESULTS: Two models were enrolled in this study, including the clinicopathologic model and the combined model. The LD at early post-NAC (OR=0.913, 95 % CI=0.953-0.994 p = 0.026), ΔADC (OR=1.005, 95 % CI=1.005-1.008, p = 0.007), and ΔTIC (OR=3.974, 95 % CI=1.276-12.358, p = 0.017) were identified as the best predictors of NAC response. The combined model constructed by the combination of LD at early post-NAC, ΔADC, and ΔTIC showed good predictive performance in the training set (AUC=0.87), internal validation set (AUC=0.78), and external validation set (AUC=0.79), which performed better than the clinicopathologic model in all sets. CONCLUSIONS: The changes in multiparametric MRI can predict early treatment response for HER2-positive BC and may be helpful for individualized treatment planning.

Modified buried vertical mattress suture technique for excisional suturing of benign parotid tumors: A retrospective study.

AIM: The purpose of this retrospective patient chart review was to analyze the clinical data of 52 patients with benign parotid tumors who underwent modified buried vertical mattress sutures and to assess the postoperative complication rate and patient scarring. METHODS: A total of 52 patients with benign parotid tumors underwent total parotidectomy and modified buried vertical mattress suture. Variables included general characteristics (age, gender, tumor diameter, and pathologic type), surgical indicators (suture time, wound healing time, operative time, hospital stay, bleeding volume, and drainage volume), complication rates, and Sunnybrook facial neurological function score, visual scar scale (VSS) score and patient and observer scar assessment scale (POSAS) score. RESULTS: Most tumors were less than 3 cm in diameter, with pleomorphic adenomas being the most common. Suture time was 14.83 ± 1.61 min, operative time was 58.90 ± 15.76 min and hospital stay were 5.12 ± 0.96 days. Postoperatively, salivary fistulae developed in one patient, Frey's syndrome in two patients, temporary facial paralysis in six patients and temporary numbness in the incision area in six patients. At 6 months postoperatively, 86.5% of patients had a Sunnybrook score of more than 80, and VSS scores and POSAS scores were between one and two. CONCLUSION: The postoperative complication rate was 30.8%, and the scarring in the facial incision area was mild and close to normal skin at 3 years postoperatively.

CRISPR-Cas9 Mediated AGO2 Knockout inhibits tumorigenesis in human colorectal cancer cells.

AGO2 plays a vital role in small RNA-guided gene silencing, which has been implied in the tumorigenesis of different types of tumors. Fundamentally, increased expression of AGO2 protein is associated with cancer progression and metastasis. This study aims to investigate the molecular mechanism by which AGO2 promotes tumorigenesis in colorectal cancer (CRC). Databases were used to analyze the expression levels of AGO2 in CRC and confirmed by a quantitative reverse transcriptase-PCR (qRT-PCR) assay in CRC tissues and normal adjacent tissues collected from 25 CRC patients. CRISPR/Cas9-mediated genome editing was used to knockout the AGO2 in HCT116 cells as a model system for colorectal cancers. The cell proliferation, migration and invasion ability of HCT116 cells were detected by CCK-8 assay, Wound scratch assay and Transwell assay. Moreover, the quantities of miRNA binding with AGO2 were detected by RNA-Binding Protein Immunoprecipitation (RIP-Assay). We demonstrated that AGO2 was aberrantly high-expressed in 25 matched-tissue pairs of colorectal cancer and para-carcinoma tissue. The following functional experiments verified that knockout of AGO2 suppressed cell proliferation, migration and tumorigenesis to hamper the aggressiveness of CRC. Our study also suggests a possible link between AGO2 and miRNA in RISC. AGO2 was elevated in CRC and knockout of AGO2 suppressed proliferation and tumorigenicity of CRC cells. Moreover, RISC formation and the function of miRNAs are also subject to AGO2. AGO2 may be a meaningful target for CRC therapy.

Identification of hub genes and key pathways in arsenic-treated rice (Oryza sativa L.) based on 9 topological analysis methods of CytoHubba.

BACKGROUND: Arsenic is a toxic metalloid that can cause acute and chronic adverse health problems. Unfortunately, rice, the primary staple food for more than half of the world's population, is generally regarded as a typical arsenic-accumulating crop plant. Evidence indicates that arsenic stress can influence the growth and development of the rice plant, and lead to high concentrations of arsenic in rice grain. But the underlying mechanisms remain unclear. METHODS: In the present research, the possible molecules and pathways involved in rice roots in response to arsenic stress were explored using bioinformatics methods. Datasets that involving arsenic-treated rice root and the "study type" that was restricted to "Expression profiling by array" were selected and downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between the arsenic-treated group and the control group were obtained using the online web tool GEO2R. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to investigate the functions of DEGs. The protein-protein interactions (PPI) network and the molecular complex detection algorithm (MCODE) of DEGs were analyzed using STRING and Cystoscope, respectively. Important nodes and hub genes in the PPI network were predicted and explored using the Cytoscape-cytoHubba plug-in. RESULTS: Two datasets, GSE25206 and GSE71492, were downloaded from Gene Expression Omnibus (GEO) database. Eighty common DEGs from the two datasets, including sixty-three up-regulated and seventeen down-regulated genes, were then selected. After functional enrichment analysis, these common DEGs were enriched mainly in 10 GO items, including glutathione transferase activity, glutathione metabolic process, toxin catabolic process, and 7 KEGG pathways related to metabolism. After PPI network and MCODE analysis, 49 nodes from the DEGs PPI network were identified, filtering two significant modules. Next, the Cytoscape-cytoHubba plug-in was used to predict important nodes and hub genes. Finally, five genes [Os01g0644000, PRDX6 (Os07g0638400), PRX112 (Os07g0677300), ENO1(Os06g0136600), LOGL9 (Os09g0547500)] were verified and could serve as the best candidates associated with rice root in response to arsenic stress. CONCLUSIONS: In summary, we elucidated the potential pathways and genes in rice root in response to arsenic stress through a comprehensive bioinformatics analysis.

Mini review on collagens in normal skin and pathological scars: current understanding and future perspective.

Pathological scar tissues are characterized by the presence of overabundant collagens whose structure and organization are also different from those in unwounded skin. This causes scar tissues to lose some functions performed by normal skin, and currently, there are no effective measures to prevent scar formation. Inflammation has been shown to modulate fibroblast proliferation, differentiation, and function, hence collagen production and organization. In this minireview, we provide an overview of the current understanding of collagen, specifically collagen type I and III which are main collagens in skin, structure and fibre formation and highlight their differences between normal skin and pathological scars. We discuss the role that cytokines play in modulating fibroblast function. We also identify some potential research directions which could help to further our understanding of the complex and dynamic wound healing and scar formation process.

Screening of the Lipid-Lowering Probiotic Lactiplantibacillus Plantarum SDJ09 and its Anti-Obesity Mechanism.

In this study, 39 strains of lactic acid bacteria were screened from several fermented foods. Based on the evaluation of functional and prebiotic properties, Lactiplantibacillus plantarum SDJ09 was selected as a promising candidate. It gave a 48.16% cholesterol reduction and 33.73% pancreatic lipase inhibition in cells; exhibited high resistance to acid, bile salts, and gastrointestinal fluid; and had strong antibacterial activity and high adhesion capabilities. More importantly, the lipid-lowering effect of L. plantarum SDJ09 was also investigated using 3T3-L1 mature adipocytes and HepG2 nonalcoholic fatty liver disease models. L. plantarum SDJ09 effectively decreased triglyceride accumulation by more than 50% in both cell models, in which the expression of PPARγ, C/EBPα, aP2, and LPL in 3T3-L1 cells was significantly downregulated by L. plantarum SDJ09. L. plantarum SDJ09 also improved lipid metabolism by downregulating the expression of HMGCR, SREBP-1c, ACC, and FAS and upregulating the expression of CYP7A1 in HepG2 nonalcoholic steatohepatitis cells. Therefore, L. plantarum SDJ09 has the potential to effectively decrease obesity and non-alcoholic fatty liver disease (NAFLD) by inhibiting lipid accumulation, providing a prospective probiotic agent for anti-obesity.

Tropism-shifted AAV-PHP.eB-mediated bFGF gene therapy promotes varied neurorestoration after ischemic stroke in mice.

ABSTRACT: AAV-PHP.eB is an artificial adeno-associated virus (AAV) that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically. While AAV-PHP.eB has been used in various disease models, its cellular tropism in cerebrovascular diseases remains unclear. In the present study, we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor (bFGF) gene therapy. Mice were injected intravenously with AAV-PHP.eB either 14 days prior to (pre-stroke) or 1 day following (post-stroke) transient middle cerebral artery occlusion. Notably, we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen (mNG). This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A (Ly6A). Furthermore, AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke. Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.

Safety and efficacy of tract embolization using gelatin sponge particles in reducing pneumothorax after CT-guided percutaneous lung biopsy in patients with emphysema.

BACKGROUND: The incidence of pneumothorax is higher in patients with emphysema who undergo percutaneous lung biopsy. Needle embolization has been shown to reduce the incidence of pneumothorax in patients with emphysema. Existing studies have reported small sample sizes of patients with emphysema, or the degree of emphysema has not been graded. Therefore, the efficacy of biopsy embolization in the prevention of pneumothorax induced by percutaneous pulmonary biopsy in patients with emphysema remains to be determined. METHODS: In this retrospective, controlled study, patients with emphysema who underwent CT-guided PTLB were divided into two groups: group A (n = 523), without tract embolization, and Group B (n = 504), with tract embolization. Clinical and imaging features were collected from electronic medical records and Picture Archiving and Communication Systems. Univariate and multivariate analyses were performed to identify risk factors for pneumothorax and chest tube placement. RESULTS: The two groups did not differ significantly in terms of demographic characteristics and complications other than pneumothorax. The incidence of pneumothorax and chest tube placement in group B was significantly lower than in group A (20.36% vs. 46.12%, p < 0.001; 3.95% vs. 9.18%, p < 0.001, respectively). In logistic regression analyses, variables affecting the incidence of pneumothorax and chest tube placement were the length of puncture of the lung parenchyma (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.30, p = 0.001; OR = 1.55, 95% CI: 1.30-1.85, p < 0.001, respectively), tract embolization (OR = 0.31, 95% CI: 0.24-0.41, p < 0.001; OR = 0.39, 95% CI: 0.22-0.69, p = 0.001, respectively), and grade of emphysema. CONCLUSIONS: Tract embolization with gelatin sponge particles after CT-guided PTLB significantly reduced the incidence of pneumothorax and chest tube placement in patients with emphysema. Tract embolization, length of puncture of the lung parenchyma, and grade of emphysema were independent risk factors for pneumothorax and chest tube placement. TRIAL REGISTRATION: Retrospectively registered.

Application of metagenomic next-generation sequencing for rapid molecular identification in spinal infection diagnosis.

Objective: This study aimed to determine the sensitivity and specificity of metagenomic next-generation sequencing (mNGS) for detecting pathogens in spinal infections and to identify the differences in the diagnostic performance between mNGS and targeted next-generation sequencing (tNGS). Methods: A total of 76 consecutive patients with suspected spinal infections who underwent mNGS, culture, and histopathological examinations were retrospectively studied. The final diagnosis of the patient was determined by combining the clinical treatment results, pathological examinations, imaging changes and laboratory indicators. The sensitivity and specificity of mNGS and culture were determined. Results: The difference between the two detection rates was statistically significant (p < 0.001), with mNGS exhibiting a significantly higher detection rate (77.6% versus 18.4%). The average diagnosis time of mNGS was significantly shorter than that of bacterial culture (p < 0.001, 1.65 versus 3.07 days). The sensitivity and accuracy of mNGS were significantly higher than that of the culture group (p < 0.001, 82.3% versus 17.5%; 75% versus 27.6%), whereas the specificity of mNGS (42.9%) was lower than that of the culture group (p > 0.05, 42.9% versus 76.9%). The sensitivity, specificity, accuracy, and positive predictive value (PPV) of pus were higher than those of tissue samples for mNGS, whereas for culture, the sensitivity, specificity, accuracy, and PPV of tissue samples were higher than those of pus. tNGS demonstrated higher sensitivity and accuracy in diagnosing tuberculosis (TB) than mNGS (80% versus 50%; 87.5% versus 68.8%). Conclusion: mNGS for spinal infection demonstrated better diagnostic value in developing an antibiotic regimen earlier, and it is recommended to prioritize pus samples for testing through mNGS. Moreover, tNGS outperformed other methods for diagnosing spinal TB and identifying antibiotic-resistance genes in drug-resistant TB.

TAR RNA selective targeting ruthenium(II) complexes as HIV-1 reverse transcriptase inhibitors: On exploring structure-activity relationships of multiple positions.

HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R1 and R3 groups. The most potent and selective TAR RNA binder was a3 with R1 = OH, R2 = H and R3 = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules.

Sensitive and isotopic interference-free analysis of Sb using hydride generation-microwave plasma torch-mass spectrometry under ambient condition.

A sensitive and isotopic interference-free analysis method for Sb was developed based on hydride generation-microwave plasma torch-mass spectrometry (HG-MPT-MS). Compared to the conventional ICP-MS, MPT coupled to an ion trap mass spectrometer enabled much "softer" ionization of Sb under ambient condition, which provided multi-detection modes and various ion forms, such as Sb+, SbO+, SbO2-, SbO++H2O and so on. These ion formations can be easily regulated by tuning capillary voltage and tube lens voltage, which facilitated elimination of isotopic interference during analysis, for instance the interference of 123Te on 123Sb could be effectively excluded by optimizing parameters of capillary voltage and tube lens voltage. The potential application of HG-MPT-MS for Sb isotope ratio analysis was also demonstrated, which could be determined in different forms, e.g., 123Sb/121Sb or 123Sb16O/121Sb16O. The value of 123Sb/121Sb was determined to be 0.75110 ± 0.00038 (2σ, n > 50). In addition, the detection limit, linearity and spike recovery were also studied. Overall, HG-MPT-MS performed equally well on detection limit (0.05 µg/L) with ICP-MS or HG-AFS. The linearity (R2 = 0.998) was checked in the concentration range of 10-500 µg/L. Spike recovery were evaluated with two soil samples, and the obtained spike recovery ranged 90-100 %. In general, HG-MPT-MS was expected to be a versatile tool for study the biochemical or geochemical behaviors of Sb and other hydride forming elements under ambient condition in a much simpler and more efficient way.

Knockout of C1q/tumor necrosis factor-related protein-9 aggravates cardiac fibrosis in diabetic mice by regulating YAP-mediated autophagy.

Introduction: Diabetic cardiomyopathy (DCM) is predominantly distinguished by impairment in ventricular function and myocardial fibrosis. Previous studies revealed the cardioprotective properties of C1q/tumor necrosis factor-related protein 9 (CTRP9). However, whether CTRP9 affects diabetic myocardial fibrosis and its underlying mechanisms remains unclear. Methods: We developed a type 1 diabetes (T1DM) model in CTRP9-KO mice via streptozotocin (STZ) induction to examine cardiac function, histopathology, fibrosis extent, Yes-associated protein (YAP) expression, and the expression of markers for autophagy such LC3-II and p62. Additionally, we analyzed the direct impact of CTRP9 on high glucose (HG)-induced transdifferentiation, autophagic activity, and YAP protein levels in cardiac fibroblasts. Results: In diabetic mice, CTRP9 expression was decreased in the heart. The absence of CTRP9 aggravated cardiac dysfunction and fibrosis in mice with diabetes, alongside increased YAP expression and impaired autophagy. In vitro, HG induced the activation of myocardial fibroblasts, which demonstrated elevated cell proliferation, collagen production, and α-smooth muscle actin (α-SMA) expression. CTRP9 countered these adverse effects by restoring autophagy and reducing YAP protein levels in cardiac fibroblasts. Notably, the protective effects of CTRP9 were negated by the inhibition of autophagy with chloroquine (CQ) or by YAP overexpression through plasmid intervention. Notably, the protective effect of CTRP9 was negated by inhibition of autophagy caused by chloroquine (CQ) or plasmid intervention with YAP overexpression. Discussion: Our findings suggest that CTRP9 can enhance cardiac function and mitigate cardiac remodeling in DCM through the regulation of YAP-mediated autophagy. CTRP9 holds promise as a potential candidate for pharmacotherapy in managing diabetic cardiac fibrosis.

Probing scaffold size effects on multivalent lectin-glycan binding affinity, thermodynamics and antiviral properties using polyvalent glycan-gold nanoparticles.

Multivalent lectin-glycan interactions (MLGIs) are pivotal for viral infections and immune regulation. Their structural and biophysical data are thus highly valuable, not only for understanding their basic mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information for some important MGLIs remains poorly understood, greatly limiting research progress. We have recently developed densely glycosylated nanoparticles, e.g., ∼4 nm quantum dots (QDs) or ∼5 nm gold nanoparticles (GNPs), as mechanistic probes for MLGIs. Using two important model lectin viral receptors, DC-SIGN and DC-SIGNR, we have shown that these probes can not only offer sensitive fluorescence assays for quantifying MLGI affinities, but also reveal key structural information (e.g., binding site orientation and binding mode) useful for MLGI targeting. However, the small sizes of the previous scaffolds may not be optimal for maximising MLGI affinity and targeting specificity. Herein, using α-manno-α-1,2-biose (DiMan) functionalised GNP (GNP-DiMan) probes, we have systematically studied how GNP scaffold size (e.g., 5, 13, and 27 nm) and glycan density (e.g., 100, 75, 50 and 25%) determine their MLGI affinities, thermodynamics, and antiviral properties. We have developed a new GNP fluorescence quenching assay format to minimise the possible interference of GNP's strong inner filter effect in MLGI affinity quantification, revealing that increasing the GNP size is highly beneficial for enhancing MLGI affinity. We have further determined the MLGI thermodynamics by combining temperature-dependent affinity and Van't Hoff analyses, revealing that GNP-DiMan-DC-SIGN/R binding is enthalpy driven with favourable binding Gibbs free energy changes (ΔG°) being enhanced with increasing GNP size. Finally, we show that increasing the GNP size significantly enhances their antiviral potency. Notably, the DiMan coated 27 nm GNP potently and robustly blocks both DC-SIGN and DC-SIGNR mediated pseudo-Ebola virus cellular entry with an EC50 of ∼23 and ∼49 pM, respectively, making it the most potent glycoconjugate inhibitor against DC-SIGN/R-mediated Ebola cellular infections. Our results have established GNP-glycans as a new tool for quantifying MLGI biophysical parameters and revealed that increasing the GNP scaffold size significantly enhances their MLGI affinities and antiviral potencies.

Preferred crystal plane electrodeposition of aluminum anode with high lattice-matching for long-life aluminum batteries.

Aluminum batteries have become the most attractive next-generation energy storage battery due to their advantages of high safety, high abundance, and low cost. However, the dendrite problem associated with inhomogeneous electrodeposition during cycling leads to low Coulombic efficiency and rapid short-circuit failure of the aluminum metal anode, which severely hampers the cycling stability of aluminum battery. Here we show an aluminum anode material that achieves high lattice matching between the substrate and the deposit, allowing the aluminum deposits to maintain preferred crystal plane growth on the substrate surface. It not only reduces the nucleation barrier of aluminum and decreases electrode polarization, but also enables uniform deposition of aluminum, improving the cycling stability of aluminum batteries. Aluminum anode with (111) preferred crystal plane can stably 25000 cycles at the current density of 5 A·g-1, with a capacity retention rate of over 80%.

Deciphering the role of micro/nano-hydroxyapatite in aerobic granular sludge system: Effects on treatment performance and enhancement mechanism.

Hydroxyapatite (HAP), a mineral nucleus identified within aerobic granular sludge (AGS), plays a vital role in enhancing the AGS systems. However, the microscopic mechanism underlying their roles remains largely unexplored. Herein, a systematic investigation was carried out to elucidate the impact and enhanced mechanisms associated with HAP of different sizes, i.e. micro-HAP (mHAP) and nano-HAP (nHAP), on the aerobic granulation, nutrient removal and microbial diversity of AGS. Results showed that the presence of nHAP and mHAP significantly shortened the granulation process to 15 and 20 days, respectively. This might be ascribed to the fact that the large specific surface area of nHAP aggregates was conducive to microbial adhesion, biomass accumulation and sludge granulation. Compared with mHAP, the granules with nHAP showed better settlement performance, mechanical strength and larger diameter. The X-ray diffraction (XRD) and Raman spectrometer analysis confirmed the presence of HAP within the granules, which was found to stimulate the secretion of extracellular polymeric substance, improve the compactness of granule structure and suppress the growth of filamentous bacteria, thereby contributing to a stable AGS system. The presence of HAP, especially nHAP, effectively enriched the functional microorganisms, such as nitrifying and denitrifying bacteria (e.g. Candidatus_Competibacter) and phosphorus accumulating organisms (e.g. Flavobacterium), leading to the improved nutrient removal efficiencies (COD > 96%, TN > 76%, and TP > 74%). Further analysis revealed the up-regulation of functional enzymes (e.g. nitrite oxidoreductase and polyphosphate kinase) involved in nutrient metabolism, underlying the inherent mechanisms for the excellent nutrient removal. This study deepens the understanding of granulation mechanisms from the perspective of mineral cores, and proposes an economically feasible strategy for rapid initiation and stabilization of AGS reactors.

Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma.

BACKGROUND: The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC. AIM: To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment. METHODS: Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry. RESULTS: Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC. CONCLUSION: TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.

A Senomorphlytic Three-Drug Combination Discovered in Salsola collina for Delaying Aging Phenotypes and Extending Healthspan.

The pursuit of pharmacological interventions in aging aims focuses on maximizing safety and efficacy, prompting an exploration of natural products endowed with inherent medicinal properties. Subsequently, this work establishes a unique library of plant extracts sourced from Yunnan Province, China. Screening of this herbal library herein revealed that Salsola collina (JM10001) notably enhances both lifespan and healthspan in C. elegans. Further analysis via network pharmacology indicates that the p53 signaling pathway plays a crucial role in mediating the anti-aging effects of JM10001. Additionally, this work identifies that a composition, designated as JM10101 and comprising three chemical constituents of JM10001, preserves the original lifespan-extending activity in C. elegans. Both JM10001 and JM10101 mitigate aging symptoms in senescence-accelerated mice treated with doxorubicin and in naturally aged mice. Notably, JM10101 exhibits a more sophisticated senomorphlytic role encompassing both senomorphic and senolytic functions than JM10001 in the modulation of senescent cells, offering a promising strategy for the discovery of combination drugs in the rational development of anti-aging therapies.

Dynamic changes and improvement paths of China's emergency logistics response capabilities under public emergencies-research based on the entropy weight TOPSIS method.

Introduction: Due to global industrialization and urbanization, natural disasters, accidents, and public health emergencies happen frequently. These events cause significant loss of life and property damage to countries worldwide. In the context of frequent public emergencies, enhancing emergency logistics response capabilities is crucial, ensuring rapid supply of rescue materials and support for rescue personnel, thereby saving lives and reducing economic losses. Methods: In order to identify the changes and enhancement paths of the emergency logistics response capability of Chinese regions under the shocks of public emergencies, this paper innovatively constructs emergency logistics response capability measurement indicators. This paper uses the entropy weight TOPSIS method and panel quantile regression model to quantify the change and enhancement paths of China's regional emergency logistics response capability under different events. Results: It is found that: (1) The gap in emergency logistics response capability among Chinese regions is widening, with the internal difference in the eastern region higher than that in the west, while the difference in the central region is relatively low. (2) China's emergency management department can effectively transform social logistics into emergency logistics, thereby promoting the improvement of emergency logistics response capabilities. (3) Sudden geological disasters break through the limits of social logistics resources when they cross lower scales, resulting in the failure of emergency logistics response capabilities. Discussion: This paper expands research on assessing emergency logistics capabilities, addressing issues in existing assessments such as reliance on single indicators and subjective measurement methods. Additionally, it quantifies the dynamic changes in China's regional emergency logistics response capabilities under public emergencies by extending the study of event content, types, and impacts. This enhances discussions on the effects of public emergencies. Finally, from an empirical perspective, the paper explores pathways to enhance regional emergency logistics response capabilities in China. In practice, this paper assists countries worldwide in assessing whether different regions of China can effectively provide emergency support for various resources in direct investments, thus providing a scientific basis for investment decisions.