Novel heterologously expressed protein, AjPSPLP-3, derived from Apostichopus japonicus exhibits cell proliferation and migration activities.

Developing more effective bioactive ingredients of natural origin is imperative for promoting wound healing. Sea cucumbers have long enjoyed a good reputation as both food delicacies and traditional medicines. In this study, we heterogeneously expressed a Apostichopus japonicus derived novel protein AjPSPLP-3, which exhibits a theoretical molecular weight of 13.034 kDa, through fusion with maltose binding protein (MBP). AjPSPLP-3 contains a strict CXXCXC motif, nine extremely conserved cysteine residues and two highly conserved cysteine residues. The predicted structure of AjPSPLP-3 consists of random coil and nine ß-sheets, Cys30-Cys67, Cys38-Cys58, Cys53-Cys90, Cys56-Cys66, and Cys81-Cys102 participating in the formation of five pairs of disulfide bonds. In vitro experiments conducted on HaCaT cells proved that AjPSPLP-3 and MBP-fused AjPSPLP-3 significantly contribute to HaCaT cells proliferation and migration without exhibiting hemolytic activity on murine erythrocytes. Specifically, treatment with 10 µmol/L MBP-fused AjPSPLP-3 protein increased the viability of HaCaT cells by 12.28 % (p < 0.001), while treatment with 10 µmol/L AjPSPLP-3 protein increased viability of HaCaT cells by 6.01 % (p < 0.01). Furthermore, wound closure of MBP-fused AjPSPLP-3 and AjPSPLP-3 were 22.51 % (p < 0.01) and 7.32 % (p < 0.05) higher than that of the control groups in HaCaT cells following 24 h of incubation.

Synthesis of flowerlike vanadium diselenide microspheres for efficient electromagnetic wave absorption.

The revelation of MoS2as an efficient electromagnetic wave (EMW) absorbing material has ratcheted up people's attention to other transition metal dichalcogenides (TMDs). To date, extensive studies have been conducted on the semiconducting VIB-Group TMDs while research into metallic VB-Group TMDs has been relatively rare. In this work, we successfully fabricated VB-Group VSe2microspheres through a facile one-step hydrothermal method and used them as EMW absorbers. The flowerlike VSe2microspheres based on VSe2nanosheets exhibited a minimum reflection loss of 46.58 dB with an effective absorption bandwidth of 4.86 GHz. The influence of material morphology, microstructure, and dielectric properties on the EMW absorption performance was systematically investigated. The hierarchically layered structure promoted dielectric loss and EMW absorption by means of multiple reflection, interfacial polarization and related relaxation, and enhanced attenuation ability. This work not only demonstrates that VSe2is potentially a high-efficiency single component EMW absorber, but also provides fresh insights into exploration on the EMW loss mechanisms of the metallic TMD-based absorbing materials.

Subslab ultra low velocity anomaly uncovered by and facilitating the largest deep earthquake.

It is enigmatic that M8+ earthquakes can take place at depth greater than 600 km inside the slab, where the P-T conditions generally do not favor seismic slip rate (~m/s) on faults. Here we provide fresh insights to the initial rupture and mechanism of the Mw 8.3 Sea of Okhotsk earthquake by analyzing high-frequency (up to 0.8 Hz) teleseismic array data. We determine the relative location and timing of two early subevents, and the geometry and velocity perturbation of a nearby structure anomaly. We found a small-scale (~30 × 60 × 60 km) ultralow (-18 ± 2%) P-wave velocity anomaly located beneath the Pacific slab around the 660 km discontinuity. The volatile-bearing highly melted nature of the anomaly provides significant buoyancy, stressing the slab dramatically closer to the critical condition for thermal runaway weakening that allows the rupture to propagate beyond the metastable olivine wedge, forming M8+ events. Enormous velocity reduction urges for further mineral physics and geodynamic investigations.

Effect of marinating with green tea extract on the safety and sensory profiles of oven-baked oyster.

Baked oyster is a popular seafood dish around the world. The present study investigated the effect of various concentrations of a green-tea extract (GTE) marinade on the safety and sensory profiles of oysters baked for different durations. The results showed 10 g/L of GTE and 10-min baking time was the optimal combination, as supported by significantly attenuated lipid oxidation (35.29 %) and Nε-(carboxyethyl)lysine (CEL) content (48.51 %) without appreciable negative impact on the sensory or nutritional quality of the oysters. However, high concentrations of the marinade or prolonged baking promoted protein oxidation and Nε-(carboxymethyl)lysine (CML) formation likely through the pro-oxidative action of the GTE phytochemicals. Correlation analysis further revealed the main factors that affected CML, CEL, and fluorescent AGEs generation, respectively. These findings provide theoretical support for the protective effect and mechanism of GTE against quality deterioration of baked oysters and would help broaden the application of GTE in the food industry.

Insights into the effects of anilofos on direct-seeded rice production system through untargeted metabolomics.

Weed infestation is the major biological threat in direct-seeded rice production and can cause significant yield losses. The effective use of herbicides is particularly important in direct-seeded rice production. Anilofos, a pre-emergence herbicide, has been shown to be effective against the weed barnyardgrass. However, its impacts on crop yield and the direct-seeded rice production ecosystem remain underexplored. In this study, we conducted field trials and used untargeted metabolomics to investigate systemic effects of two different treatments (40 g/acre and 60 g/acre) on rice shoot and root as well as the rhizosphere soil during the critical tillering stage. Here, a total of 400 metabolites were determined in the crop and soil, with differential metabolites primarily comprising lipids and lipid-like molecules as well as phenylpropanoids and polyketides. Spearman correlation network analysis and a Zi-Pi plot revealed 7 key differential metabolites with significant topological roles, including succinic acid semialdehyde and riboflavin. KEGG pathway analysis showed that anilofos downregulated the amino acid metabolism while mainly promoted carbohydrate metabolism and secondary metabolites biosynthesis of the crop, which made minimal disruption on soil metabolism. Notably, we found 40 g/acre anilofos application could significantly improve the rice yield, potentially linked to the improved activity of flavonoid biosynthesis and starch and sucrose metabolism. This research provides a comprehensive evaluation of anilofos effects in the direct-seeded rice production system, offering new insights into optimizing herbicide use to improve agricultural sustainability and productivity.

Cell-Surface Binding of DNA Nanostructures for Enhanced Intracellular and Intranuclear Delivery.

DNA nanostructures (DNs) have found increasing use in biosensing, drug delivery, and therapeutics because of their customizable assembly, size and shape control, and facile functionalization. However, their limited cellular uptake and nuclear delivery have hindered their effectiveness in these applications. Here, we demonstrate the potential of applying cell-surface binding as a general strategy to enable rapid enhancement of intracellular and intranuclear delivery of DNs. By targeting the plasma membrane via cholesterol anchors or the cell-surface glycocalyx using click chemistry, we observe a significant 2 to 8-fold increase in the cellular uptake of three distinct types of DNs that include nanospheres, nanorods, and nanotiles, within a short time frame of half an hour. Several factors are found to play a critical role in modulating the uptake of DNs, including their geometries, the valency, positioning and spacing of binding moieties. Briefly, nanospheres are universally preferable for cell surface attachment and internalization. However, edge-decorated nanotiles compensate for their geometry deficiency and outperform nanospheres in both categories. In addition, we confirm the short-term structural stability of DNs by incubating them with cell medium and cell lysate. Further, we investigate the endocytic pathway of cell-surface bound DNs and reveal that it is an interdependent process involving multiple pathways, similar to those of unmodified DNs. Finally, we demonstrate that cell-surface attached DNs exhibit a substantial enhancement in the intranuclear delivery. Our findings present an application that leverages cell-surface binding to potentially overcome the limitations of low cellular uptake, which may strengthen and expand the toolbox for effective cellular and nuclear delivery of DNA nanostructure systems.

Unusual coexistence: branchial cleft cyst harboring papillary thyroid carcinoma with lymph node metastasis - a rare case report and clinical insights.

Background: The simultaneous occurrence of Branchial Cleft Cyst (BCC) and Papillary Thyroid Carcinoma (PTC) represents an unusual malignant tumor, with cases featuring associated lymph node metastasis being particularly rare. This combination underscores an increased potential for metastasis, and the assessment of neck masses, particularly on the lateral aspect, may inadvertently overlook the scrutiny of the thyroid. Therefore, healthcare providers should exercise vigilance, especially in patients over the age of 40, regarding the potential for neck masses to signify metastasis from thyroid malignancies. Currently, surgical intervention stands as the primary effective curative method, while the postoperative administration of radioactive iodine therapy remains a topic of ongoing debate. Case report: In the presented case, a 48-year-old male patient with a right neck mass underwent surgical intervention. The procedure included the excision of the right neck mass, unilateral thyroidectomy with isthmus resection, and functional neck lymph node dissection under tracheal intubation and general anesthesia. Postoperative pathology findings revealed the coexistence of a BCC with metastatic PTC in the right neck mass, as well as papillary carcinoma in the right thyroid lobe. Lymph node metastasis was observed in the central and levels III of the right neck. Conclusion: The rare amalgamation of a BCC with PTC and concurrent lymph node metastasis underscores the invasive nature of this malignancy. Healthcare professionals should be well-acquainted with its clinical presentation, pathological characteristics, and diagnostic criteria. A multidisciplinary approach is strongly recommended to enhance patient outcomes.

Angiosarcoma of the breast: A review.

Breast angiosarcoma is a rare and highly aggressive malignancy with a poor prognosis. It can occur spontaneously or be associated with factors such as radiation therapy or chronic lymphedema. The etiology and pathogenesis of this disease are still unclear, the clinical symptoms and imaging findings lack specificity, and the pathological morphology is diverse, which is easy to be confused with other diseases. There is no clear guideline for surgical treatment. Although the optimal surgical approach remains unclear, the ultimate goal is surgical excision with optimal margins, which remains the primary method of treatment. In clinical practice, the choice of the surgical approach should be made by considering the tumor size, pathological type, and patient preferences. In clinical practice, the selection of surgical methods should be carried out with comprehensive consideration of tumor size, pathological types and patients' wishes. There is no clear consensus on whether radiotherapy and chemotherapy should be carried out after surgery, and its optimal program and efficacy are uncertain. This article reviews the etiology, clinical manifestations, pathological features, imaging findings, treatment, prognosis and other aspects of breast angiosarcoma, so as to strengthen clinicians' overall understanding of this disease and avoid missed diagnosis and misdiagnosis.

Shape Self-Adaptive Liquid Embolic Agent for Ultrafast and Durable Vascular Embolization.

Minimally invasive embolization greatly decreases the mortality resulting from vascular injuries while still suffering from a high risk of recanalization and systematic thrombosis due to the intrinsic hydrophobicity and poor adhesion of the clinically used liquid embolic agent of Lipiodol. In this study, a shape self-adaptive liquid embolic agent was developed by mixing biocompatible poly(acrylic acid) (PAA), two-dimensional magnesium-aluminum layered double hydroxide (LDH), and poly(ethylene glycol)200 (PEG200). Upon contact with blood, the injectable PAA-LDH@PEG200 would quickly absorb water to form an adhesive and mechanically strong PAA-LDH thin hydrogel within 5 s, which could firmly adhere to the blood vessel wall for ultrafast and durable embolization. In addition, benefiting from the "positively charged nucleic center effect" of LDH nanosheets, the liquid PAA-LDH@PEG200 could avoid vascular distension by PAA overexpansion and possess high shock-resistant mechanical strength from the blood flow. Furthermore, both in vitro and in vivo embolization experiments demonstrated the complete embolic capacity of liquid PAA-LDH@PEG200 without the occurrence of recanalization for 28 days and also the great potential to act as a platform to couple with chemotherapeutic drugs for the minimized transcatheter arterial chemoembolization (TACE) treatment of VX2 tumors without recurrence for 18 days. Thus, liquid PAA-LDH@PEG200 developed here possesses great potential to act as a shape self-adaptive liquid embolic agent for ultrafast and durable vascular embolization.

Antibiotic resistance gene distribution in Shine Muscat grapes and health risk assessment of streptomycin residues in mice.

Antibiotic residues and antibiotic resistance genes (ARGs) in fruits and vegetables pose public health risks via the food chain, attracting increased attention. Antibiotics such as streptomycin, used directly on seedless grapes or introduced into vineyard soil through organic fertilizers. However, extensive data supporting the risk assessment of antibiotic residues and resistance in these produce remains lacking. Utilizing metagenomic sequencing, we characterized Shine Muscat grape antibiotic resistome and mobile genetic elements (MGEs). Abundant MGEs and ARGs were found in grapes, with 174 ARGs on the grape surface and 32 in the fruit. Furthermore, our data indicated that soil is not the primary source of these MGEs and ARGs. Escherichia was identified as an essential carrier and potential transmitter of ARGs. In our previous study, streptomycin residue was identified in grapes. Further short-term exposure experiments in mice revealed no severe physiological or histological damage at several environment-related concentrations. However, with increased exposure, some ARGs levels in mouse gut microbes increased, indicating a potential threat to animal health. Overall, this study provides comprehensive insights into the resistance genome and potential hosts in grapes, supporting the risk assessment of antibiotic resistance in fruits and vegetables.

Serum metabolites and hypercholesterolemia: insights from a two-sample Mendelian randomization study.

Background: Hypercholesterolemia, a critical contributor to cardiovascular disease, is not fully understood in terms of its relationship with serum metabolites and their role in disease pathogenesis. Methods: This study leveraged GWAS data to explore the relationship between serum metabolites and hypercholesterolemia, pinpointing significant metabolites via Mendelian Randomization (MR) and KEGG pathway enrichment analysis. Data on metabolites were sourced from a European population, with analysis focusing on individuals diagnosed with hypercholesterolemia. Results: Out of 486 metabolites analyzed, ten showed significant associations with hypercholesterolemia, categorized into those enhancing risk and those with protective effects. Specifically, 2-methoxyacetaminophen sulfate and 1-oleoylglycerol (1-monoolein) were identified as risk-enhancing, with odds ratios (OR) of 1.545 (95% CI: 1.230-1.939; P_FDR = 3E-04) and 1.462 (95% CI: 1.036-2.063; P_FDR = 0.037), respectively. On the protective side, 3-(cystein-S-yl)acetaminophen, hydroquinone sulfate, and 2-hydroxyacetaminophen sulfate demonstrated ORs of 0.793 (95% CI: 0.735-0.856; P_FDR = 6.18E-09), 0.641 (95% CI: 0.423-0.971; P_FDR = 0.042), and 0.607 (95% CI: 0.541-0.681; P_FDR = 5.39E-17), respectively. In addition, KEGG pathway enrichment analysis further revealed eight critical pathways, comprising "biosynthesis of valine, leucine, and isoleucine", "phenylalanine metabolism", and "pyruvate metabolism", emphasizing their significant role in the pathogenesis of hypercholesterolemia. Conclusion: This study underscores the potential causal links between particular serum metabolites and hypercholesterolemia, offering innovative viewpoints on the metabolic basis of the disease. The identified metabolites and pathways offer promising targets for therapeutic intervention and warrant further investigation.

Prediction of prognosis in patients with systemic sclerosis based on a machine-learning model.

OBJECTIVE: The clinical manifestations of systemic sclerosis (SSc) are highly variable, resulting in varied outcomes and complications. Diverse fibrosis of the skin and internal organs, vasculopathy, and dysregulated immune system lead to poor and varied prognoses in patients with SSc subtypes. Therefore, this study aimed to develop a personalized tool for predicting the prognosis of patients with SSc. METHODS: A cohort of 517 patients with SSc were recruited between January 2009 and November 2021 at Xijing Hospital in China, and 266 patients completed the follow-up and performed in the survival analysis. Risk factors for death were identified using Cox survival analysis and random survival forest-based machine-learning methods separately. The consistency index, area under the curve (AUC), and integrated Brier scores were used to compare the predictive performance of the different prognostic models. RESULTS: The results of Cox-based multivariate regression analysis suggested that pulmonary arterial hypertension, digital ulcer, and Modified Rodnan Skin Score (mRSS) were independent risk factors for poor prognosis in patients with SSc and significant risk factors in random survival forest (RSF) surveys. A nomogram was plotted to evaluate the prognostic risk to facilitate clinical assessment; the RSF model had better predictive performance than the Cox model, with 3- and 5-year AUCs of 0.74 and 0.78, respectively. CONCLUSION: Machine-learning models can help us better understand the prognosis of patients with SSc and comprehensively evaluate the clinical characteristics of each individual. The early identification of the characteristics of high-risk patients can improve the prognosis of those with SSc. Key Points • Regarding predictive performance, the random survival forest model was more effective than the Cox model and had unique advantages in analyzing nonlinear effects and variable importance. • Machine learning using the simple clinical features of patients with systemic sclerosis (SSc) to predict mortality can guide attending physicians, and the early identification of high-risk patients with SSc and referral to experts will assist rheumatologists in monitoring and management planning.

The feasibility and clinical significance of lateral approach thyroidectomy.

BACKGROUND: By comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized. METHODS: From January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed. RESULTS: There were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group. CONCLUSION: The lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

"Age" of tea: The impact of long-term storage on the aroma of Tuo tea and age prediction.

This study investigates the dynamic changes in the aroma profile of Tuo tea during long-term storage, a process not well understood yet critical to the formation of aged tea's unique characteristics. Aroma profiling of Tuo tea samples stored for 2 to 25 years was conducted using sensory evaluation and the HS-SPME/GC × GC-QTOFMS technique, revealing a progressive transition from fresh, fruity, and floral scents to more stale, woody, and herbal notes. Among 275 identified volatiles, 55 were correlated with storage duration (|r| > 0.8, p < 0.05), and 49 differential compounds (VIP > 1, FC > 1.2, FC < 0.833, p < 0.05) were identified across three storage stages (2-4, 5-10, and 13-25 years). Furthermore, theaspirane, eucalyptol, o-xylene, and 1-ethylidene-1H-indene were selected as potential markers of Tuo tea aging, incorporating the implementation of a Random Forest (RF) model. Additionally, our model exhibited high accuracy in predicting the age of Tuo tea within a prediction error range of -2.51 to 2.84 years. This research contributes to a comprehensive understanding of the impact of storage time on tea aroma and aids in the precise identification of tea age.

A phylogenetic approach identifies patterns of beta diversity and floristic subregions of the Qinghai-Tibet Plateau.

Patterns of taxonomic and phylogenetic beta diversity and their relationships with environmental correlates can help reveal the origin and evolutionary history of regional biota. The Qinghai-Tibet Plateau (QTP) harbors an exceptionally diverse flora, however, a phylogenetic perspective has rarely been used to investigate its beta diversity and floristic regions. In this study, we used a phylogenetic approach to identify patterns of beta diversity and quantitatively delimit floristic regions on the Qinghai-Tibet Plateau. We also examined the relationships between multifaceted beta diversity, geographical distance, and climatic difference, and evaluated the relative importance of various factors (i.e., climate, topography and history) in shaping patterns of beta diversity. Sørensen dissimilarity indices indicated that patterns of species turnover among sites dominated the QTP. We also found that patterns of both taxonomic and phylogenetic beta diversity were significantly related to geographical distance and climatic difference. The environmental factors that contributed most to these patterns of beta diversity include annual precipitation, mean annual temperature, climatic gradients and climatic instability. Hierarchical dendrograms of dissimilarity and non-metric multidimensional scaling ordination based on phylogenetic beta diversity data identified ten floristic subregions in the QTP. Our results suggest that the contemporary environment and historical climate changes have filtered species composition among sites and eventually determined beta diversity patterns of plants in the QTP.

Modified Unit-Mediated Strand Displacement Reactions for Direct Detection of Single Nucleotide Variants in Active Double-Stranded DNA.

Accurate identification of single nucleotide variants (SNVs) in key driver genes holds a significant value for disease diagnosis and treatment. Fluorescent probes exhibit tremendous potential in specific, high-resolution, and rapid detection of SNVs. However, additional steps are required in most post-PCR assays to convert double-stranded DNA (dsDNA) products into single-stranded DNA (ssDNA), enabling them to possess hybridization activity to trigger subsequent reactions. This process not only prolongs the complexity of the experiment but also introduces the risk of losing target information. In this study, we proposed two strategies for enriching active double-stranded DNA, involving PCR based on obstructive groups and cleavable units. Building upon this, we explored the impact of modified units on the strand displacement reaction (SDR) and assessed their discriminatory efficacy for mutations. The results showed that detection of low variant allele frequencies (VAF) as low as 0.1% can be achieved. The proposed strategy allowed orthogonal identification of 45 clinical colorectal cancer tissue samples with 100% specificity, and the results were generally consistent with sequencing results. Compared to existing methods for enriching active targets, our approach offers a more diverse set of enrichment strategies, characterized by the advantage of being simple and fast and preserving original information to the maximum extent. The objective of this study is to offer an effective solution for the swift and facile acquisition of active double-stranded DNA. We anticipate that our work will facilitate the practical applications of SDR based on dsDNA.

Slow rupture in a fluid-rich fault zone initiated the 2024 Mw 7.5 Noto earthquake.

The 2024 moment magnitude 7.5 Noto Peninsula (Japan) earthquake caused devastation to communities and was generated by a complex rupture process. Using space geodetic and seismic observations, we have shown that the event deformed the peninsula with a peak uplift reaching 5 meters at the west coast. Shallow slip exceeded 10 meters on an offshore fault. Peak stress drop was greater than 10 megapascals. This devastating event began with a slow rupture propagation lasting 15 to 20 seconds near its hypocenter, where seismic swarms had surged since 2020 because of lower-crust fluid supply. The slow start was accompanied by intense high-frequency seismic radiation. These observations suggest a distinct coseismic slip mode reflecting high heterogeneity in fault properties within a fluid-rich fault zone.

Development of Antibacterial Peptides with Membrane Disruption and Folate Pathway Inhibitory Activities against Methicillin-Resistant Staphylococcus aureus.

Antimicrobial peptides (AMPs) offer an opportunity to overcome multidrug resistance. Here, novel peptides were designed based on AMP fragments derived from sea cucumber hemolytic lectin to enhance anti-methicillin-resistant Staphylococcus aureus (MRSA) activity with less side effects. Two designed peptides, CGS19 (LARVARRVIRFIRRAW-NH2) and CGS20 (RRRLARRLIFFIRRAW-NH2), exhibited strong antibacterial activities against clinically isolated MRSA with MICs of 3-6 µM, but no obvious cytotoxicity was observed. Consistently, CGS19 and CGS20 exerted rapid bactericidal activity and effectively induced 5.9 and 5.8 log reduction of MRSA counts in mouse subeschar, respectively. Further, CGS19 and CGS20 kill bacteria not only through disturbing membrane integrity but also by binding formate-tetrahydrofolate ligase, a key enzyme in the folate metabolism pathway, thereby inhibiting the folate pathway of MRSA. CGS19 and CGS20 are promising lead candidates for drug development against MRSA infection. The dual mechanisms on the identical peptide sequence or scaffold might be an underappreciated manner of treating life-threatening pathogens.