Being thin-skinned can still reduce damage from dynamic puncture.

The integumentary system in animals serves as an important line of defence against physiological and mechanical external forces. Over time, integuments have evolved layered structures (scales, cuticle and skin) with high toughness and strength to resist damage and prevent wound expansion. While previous studies have examined their defensive performance under low-rate conditions, the failure response and damage resistance of these thin layers under dynamic biological puncture remain underexplored. Here, we utilize a novel experimental framework to investigate the mechanics of dynamic puncture in both bilayer structures of synthetic tissue-mimicking composite materials and natural skin tissues. Our findings reveal the remarkable efficiency of a thin outer skin layer in reducing the overall extent of dynamic puncture damage. This enhanced damage resistance is governed by interlayer properties through puncture energetics and diminishes in strength at higher puncture rates due to rate-dependent effects in silicone tissue simulants. In addition, natural skin tissues exhibit unique material properties and failure behaviours, leading to superior damage reduction capability compared with synthetic counterparts. These findings contribute to a deeper understanding of the inherent biomechanical complexity of biological puncture systems with layered composite material structures. They lay the groundwork for future comparative studies and bio-inspired applications.

[Implementation of Wearable Wireless Chest Patch Monitoring Terminal].

Objective: A wearable wireless chest patch monitoring terminal is designed to realize the acquisition, processing, and wireless transmission of ECG, respiration, and body temperature signals. Methods: The analog front-end ADS1292R, which integrates respiratory impedance and ECG front-end, is utilized to collect human ECG and respiratory signals. The body temperature is collected using a low-power, high-precision digital temperature sensor MAX30208. A filter algorithm for signal processing and wireless transmission is designed through a low-power nRF52840 Bluetooth SoC with an Arm Cortex-M4F kernel. Results: The experimental results show that the designed monitoring terminal can monitor the ECG, respiration, and body temperature parameters of the human body in real-time and send the monitoring results via Bluetooth, with a continuous working time of more than 13 hours. Conclusion: The wearable wireless chest patch monitoring terminal features good portability, long standby time, and high measurement accuracy, and it has promising application prospects in the fields of family health monitoring, mobile medical treatment, and smart healthcare.

Triterpenoids from the rhizomes and roots of Gentiana scabra Bge. And their cytotoxic activities.

Phytochemical investigation on the rhizomes and roots of Gentiana scabra (Gentianaceae) led to the isolation of five new triterpenoids (1-5), together with seven known ones (6-12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data interpretation, ECD calculation and X-ray crystallographic analysis. Noticeably, compound 4 was an uncommon 3,4-seco-pentacyclic triterpenoid in natural products. The in vitro cytotoxic activities of all isolates against human cancer cell lines (HepG2, Hep3B, HCT116, and U87) were measured using MTT assay. Among them, compounds 2-9, 11, and 12 exhibited anti-proliferative effects against these tumor cell lines.

Curving expectations: The minimal impact of structural curvature in biological puncture mechanics.

Living organisms have evolved various biological puncture tools, such as fangs, stingers, and claws, for prey capture, defense, and other critical biological functions. These tools exhibit diverse morphologies, including a wide range of structural curvatures, from straight cactus spines to crescent-shaped talons found in raptors. While the influence of such curvature on the strength of the tool has been explored, its biomechanical role in puncture performance remains untested. Here, we investigate the effect of curvature on puncture mechanics by integrating experiments with finite element simulations. Our findings reveal that within a wide biologically relevant range, structural curvature has a minimal impact on key metrics of damage initiation or the energies required for deep penetration in isotropic and homogeneous target materials. This unexpected result improves our understanding of the biomechanical pressures driving the morphological diversity of curved puncture tools and provides fundamental insights into the crucial roles of curvature in the biomechanical functions of living puncture systems.

Chemical profiling and quality evaluation of raw and vinegar-processing frankincense by multiple UPLC-MS/MS techniques.

INTRODUCTION: Frankincense is used for analgesic, tumor-suppressive, and anti-inflammatory treatments in Traditional Chinese Medicine but poses toxicological concerns. Vinegar processing is a common technique used to reduce the toxicity of frankincense. OBJECTIVE: This study aimed to investigate the chemical composition and quality evaluation of raw and vinegar-processing frankincense by multiple UPLC-MS/MS techniques. Additionally, we purposed refining the vinegar processing technique and identifying potentially harmful ingredients in the raw frankincense. METHODOLOGY: Sub-chronic oral toxicity studies were conducted on raw and vinegar-processing frankincense in rats. The composition of frankincense was identified by UPLC-Q-TOF-MS/MS. Chemometrics were used to differentiate between raw and vinegar-processing frankincense. Potential chemical markers were identified by selecting differential components, which were further exactly determined by UPLC-QQQ-MS/MS. Moreover, the viability of the HepG2 cells of those components with reduced contents after vinegar processing was assessed. RESULTS: The toxicity of raw frankincense is attenuated by vinegar processing, among which vinegar-processing frankincense (R40) (herb weight: rice vinegar weight = 40:1) exhibited the lowest toxicity. A total of 83 components were identified from frankincense, including 40 triterpenoids, 37 diterpenoids, and 6 other types. The contents of six components decreased after vinegar-processing, with the lowest levels in R40. Three components, specifically 3α-acetoxy-11-keto-ß-boswellic acid (AKBA), 3α-acetoxy-α-boswellic acid (α-ABA), and 3α-acetoxy-ß-boswellic acid (ß-ABA), inhibited the viability of HepG2 cells. The processing of frankincense with vinegar at a ratio of 40:1 could be an effective method of reducing the toxicity in raw frankincense. CONCLUSION: Our research improves understanding of the toxic substance basis and facilitates future assessments of frankincense quality.

TMEM147: A Promising Cancer Biomarker Associated with Immune Cell Infiltration and Prognosis in LIHC-Insights from a Comprehensive Pan-Cancer Genomic Analysis.

Previous studies have demonstrated the regulatory roles of Transmembrane protein 147 (TMEM147) in various diseases, including cancer. However, systematic pan-cancer analyses investigating the role of TMEM147 in diagnosis, prognosis, and immunological prediction are lacking. An analysis of data from The Cancer Genome Atlas (TCGA) revealed differential TMEM147 expression across various types of cancer as well as within immune and molecular cancer subtypes. Moreover, high TMEM147 expression was associated with poor disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) across cancers, suggesting its potential as a prognostic biomarker. Our study further revealed a significant correlation between TMEM147 expression and T helper cell and Tcm cell infiltration in most cancer types. In the case of liver hepatocellular carcinoma (LIHC), the effect of TMEM147 on prognosis varied among different clinical subtypes. Additionally, functional enrichment analysis revealed an association between TMEM147 and metabolic pathways. Finally, experiments on the MIHA cell line and four LIHC cell lines confirmed the role of TMEM147 in promoting liver cancer cell proliferation, further confirming the clinical value of TMEM147 in liver cancer diagnosis. Our findings suggest that TMEM147 may serve as a diagnostic and prognostic biomarker across cancers while also playing a significant role in LIHC.

New cembranoid with potent anti-inflammatory effect isolated from Boswellia sacra by inactivating the NF-κB signaling pathway.

Boswellia sacra has the properties of activating blood circulation, fixing pain, subduing swelling and promoting muscle growth. However, the anti-inflammatory active ingredients and molecular mechanisms of Boswellia sacra are still not clearly explored. Boswellia sacra was grounded and extracted using 95% ethanol, the extracts were separated by column chromatography preparation to give compounds. Spectral analysis and quantum calculations confirmed the structures of compounds and identified compound 1 as a new compound. Compounds 1-3 showed potent inhibitory activities and their effects on inflammatory mediator NO and inflammatory cytokines were examined by ELISA assay. Furthermore, their modulatory mechanism on inflammatory signal pathways was explored.

Characterization of Sesquiterpene Dimers from the Flowers of Inula japonica and the Structural Revisions of Related Compounds.

Sesquiterpene dimers are mainly found in the Asteraceae family. However, conflicting reports on the structures of these compounds can be found in the literature. Herein, we describe ten sesquiterpene dimers isolated from the flowers of Inula japonica, including configurational revisions of japonicone H (1-1), japonicone D (2-1), inulanolide A (4-1), japonicone X (5-1), and inulanolide F (5-2) to compounds 1, 2, 4, and 5, respectively. Five new related metabolites (3 and 6-9) are also described. Application of GIAO NMR/DP4+ analyses and ECD/OR calculations enabled us to revise the absolute configurations of an additional 13 sesquiterpene dimers isolated from plants of the genus Inula. Compounds 1, 2, 4, and 6 exhibited inhibition of nitric oxide production in lipopolysaccharide activated RAW264.7 macrophages with IC50 values of 4.07-10.00 µM.

Benzoate glycosides from Gentiana scabra Bge. and their lipid-lowering activity.

Seven undescribed benzoate glycosides (1-7) and five known ones (8-12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 µM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents.

Discovery of natural AMPK activator from the fruits of Xanthium sibiricum Patr.: Xanthiumine A, protoberberine alkaloid with unique C28 skeleton.

Two protoberberine alkaloids with a unique C28 skeleton, named xanthiumines A (1) and B (2), respectively, were isolated from the fruits of Xanthium sibiricum Patr. Their structures including absolute configurations were unequivocally established by the comprehensive NMR and MS spectroscopic data analysis together with gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are the first examples of natural protoberberine alkaloid with a phenolic acid group at C-13a. Their plausible biosynthetic pathway was proposed on the basis of the coexisting alkaloid monomer as the precursor. Furthermore, the effects and related molecular mechanism of compound 1 on hepatic lipid accumulation were also investigated in oleic acid (OA)-treated HepG2 cells.

Role of protein arginine methyltransferase 1 in obesity-related metabolic disorders: Research progress and implications.

Obesity has become a major global problem that significantly confers an increased risk of developing life-threatening complications, including type 2 diabetes mellitus, fatty liver disease and cardiovascular diseases. Protein arginine methyltransferases (PRMTs) are enzymes that catalyse the methylation of target proteins. They are ubiquitous in eukaryotes and regulate transcription, splicing, cell metabolism and RNA biology. As a key, epigenetically modified enzyme, protein arginine methyltransferase 1 (PRMT1) is involved in obesity-related metabolic processes, such as lipid metabolism, the insulin signalling pathway, energy balance and inflammation, and plays an important role in the pathology of obesity-related metabolic disorders. This review summarizes recent research on the role of PRMT1 in obesity-related metabolic disorders. The primary objective was to comprehensively elucidate the functional role and regulatory mechanisms of PRMT1. Moreover, this study attempts to review the pathogenesis of PRMT1-mediated obesity-related metabolic disorders, thereby offering pivotal information for further studies and clinical treatment.

The regulatory role of m6A methylation modification in metabolic syndrome pathogenesis and progression.

Metabolic syndromes are characterized by various complications caused by disrupted glucose and lipid metabolism, which are major factors affecting the health of a population. However, existing diagnostic and treatment strategies have limitations, such as the lack of early diagnostic and therapeutic approaches, variability in patient responses to treatment, and cost-effectiveness. Therefore, developing alternative solutions for metabolic syndromes is crucial. N6-methyladenosine (m6A) is one of the most abundant modifications that determine the fate of RNA. m6A modifications are closely associated with metabolic syndrome development and present novel prospects for clinical applications. Aberrant m6A modifications have been detected during inflammatory infiltration, apoptosis, autophagy, iron sagging, necrosis, and scorching during metabolic syndrome pathogenesis and progression. However, few reviews have systematically described the correlation between m6A modifications and these factors concerning metabolic syndrome pathogenesis and progression. This study summarizes the m6A methylation regulators and their roles in metabolic syndrome development, highlighting the potential of m6A modification as a biomarker in metabolic disorders.

Structure of the exopolyphosphatase (PPX) from Zymomonas mobilis reveals a two-magnesium-ions PPX.

Rapid adaptation of metabolic capabilities is crucial for bacterial survival in habitats with fluctuating nutrient availability. In such conditions, the bacterial stringent response is a central regulatory mechanism activated by nutrient starvation or other stressors. This response is primarily controlled by exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) enzymes. To gain further insight into these enzymes, the high-resolution crystal structure of PPX from Zymomonas mobilis (ZmPPX) was determined at 1.8 Å. The phosphatase activity of PPX was strictly dependent on the presence of divalent metal cations. Notably, the structure of ZmPPX revealed the presence of two magnesium ions in the active site center, which is atypical compared to other PPX structures where only one divalent ion is observed. ZmPPX exists as a dimer in solution and belongs to the "long" PPX group consisting of four domains. Remarkably, the dimer configuration exhibits a substantial and deep aqueduct with positive potential along its interface. This aqueduct appears to extend towards the active site region, suggesting that this positively charged aqueduct could potentially serve as a binding site for polyP.

The development of droplet-based microfluidic virus detection technology for human infectious diseases.

Virus-based human infectious diseases have a significant negative impact on people's health and social development. The need for quick, accurate, and early viral infection detection in preventive medicine is expanding. A microfluidic control is particularly suitable for point-of-care-testing virus diagnosis due to its advantages of low sample consumption, quick detection speed, simple operation, multi-functional integration, small size, and easy portability. It is also thought to have significant development potential and a wide range of application prospects in the research on virus detection technology. In an effort to aid researchers in creating novel microfluidic tools for virus detection, this review highlights recent developments of droplet-based microfluidics in virus detection research and also discusses the challenges and opportunities for rapid virus detection.

Undescribed sesquiterpenoids with NO production inhibitory activity from oleo-gum resin of Commiphora myrrha.

Six undescribed cadinane sesquiterpenoids (1-6), two undescribed guaiane sesquiterpenoids (7-8), and an undescribed germacrane sesquiterpenoid (9) were isolated from the oleo-gum resin of Commiphora myrrha. Their structures were determined by the analysis of 1D/2D NMR and HRESIMS data, as well as quantum chemical ECD and NMR calculations. All the sesquiterpenoids were evaluated for their NO production inhibitory activity in LPS-stimulated RAW 264.7 mouse monocyte-macrophages. The results revealed that commiphone A (1) and commipholide D (7) exhibited significant inhibitory effect on NO generation with IC50 values of 18.6 ± 2.0 and 37.5 ± 1.5 µM, respectively. Furthermore, 1 and 7 dose-dependently inhibited the mRNA expression of inflammatory cytokines IL-1ß, IL-6 and TNF-α induced by LPS in the RAW264.7 cells, indicating that 1 and 7 possess potent anti-inflammatory activity in vitro.

New depside and rosmarinic acid derivatives from Perilla frutescens and their anti-inflammatory activity.

Two new depside derivatives 1 and 2 as well as a new pair of rosmarinic acid enantiomers 3a/b were isolated from the leaves of Perilla frutescens (L.) britt. The chemical structures of these compounds were identified based on detailed spectroscopic and physicochemical analyses (HR-ESI-MS, NMR) and comparison of literature data. Compounds 3a/b were obtained by chiral separation, and their absolute configurations were determined by comparison of experimental and calculated ECD spectra. Compounds 3a/b exhibited potential inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells with IC50 values of 15.92 ± 3.32 µM and 48.72 ± 4.12 µM.

Development of Cas13a-based therapy for cancer treatment.

Gene therapy has become a major focus of current biomedical research. CRISPR (Clustered Regularly Inter spaced Short Palindromic Repeats) systems have been extensively researched for disease treatment applications through genome editing specificity. Compared with Cas9 (CRISPR-associated proteins, Cas), a commonly used tool enzyme for genome editing, Cas13a exhibits RNA-dependent endonuclease activity, including collateral cleavage without obvious potential genetic risks. With its high specificity, Cas13a has significantly improved the sensitivity of viral diagnosis and shown potential to eliminate viruses. However, its efficacy in tumor therapy has not been determined. This review introduces the mechanism and research developments associated with the CRISPR-Cas13a system in tumor treatments and its potential to be used as a new tool for gene therapy. We hope more research would apply Cas13a-based therapy in cancer treatment in the future.

METTL3 exacerbates insulin resistance in hepatocytes by regulating m6A modification of cytochrome P450 2B6.

BACKGROUND: Insulin resistance (IR) in hepatocytes endangers human health, and frequently results in the development of non-alcoholic fatty liver disease (NAFLD). Research on m6A methylation of RNA molecules has gained popularity in recent years; however, the molecular mechanisms regulating the processes of m6A modification and IR are not known. The cytochrome P450 (CYP450) enzyme system, which is mainly found in the liver, is associated with the pathogenesis of NAFLD. However, few studies have been conducted on CYP450 related m6A methylation. Here, we investigated the role of the methyltransferase METTL3 in exacerbating IR in hepatocytes, mainly focusing on the regulation of m6A modifications in CYP2B6. METHODS AND RESULTS: Analysis using dot blot and epitranscriptomic chips revealed that the m6A modification pattern of the transcriptome in high-fat diet (HFD)-induced fatty liver and free fatty acid (FFA)-induced fatty hepatocytes showed significant changes. CYP450 family members, especially Cyp2b10, whose homolog in humans is CYP2B6, led to a noticeable increase in m6A levels in HFD-induced mice livers. Application of the METTL3 methyltransferase inhibitor, STM2457, increased the level of insulin sensitivity in hepatocytes. We then analyzed the role of METTL3 in regulating m6A modification of CYP2B6 in hepatocytes. METTL3 regulated the m6A modification of CYP2B6, and a positive correlation was found between the levels of CYP2B6 translation and m6A modifications. Furthermore, interference with METTL3 expression and exposure to STM2457 inhibited METTL3 activity, which in turn interfered with the phosphorylated insulin receptor substrate (pIRS)-glucose transporter 2 (GLUT2) insulin signaling pathway; overexpression of CYP2B6 hindered IRS phosphorylation and translocation of GLUT2 to membranes, which ultimately exacerbated IR. CONCLUSION: These findings offer unique insights into the role that METTL3-mediated m6A modifications of CYP2B6 play in regulating insulin sensitivity in hepatocytes and provide key information for the development of strategies to induce m6A modifications for the clinical treatment of NAFLD.

Investigation of the rate-mediated form-function relationship in biological puncture.

Puncture is a vital mechanism for survival in a wide range of organisms across phyla, serving biological functions such as prey capture, defense, and reproduction. Understanding how the shape of the puncture tool affects its functional performance is crucial to uncovering the mechanics underlying the diversity and evolution of puncture-based systems. However, such form-function relationships are often complicated by the dynamic nature of living systems. Puncture systems in particular operate over a wide range of speeds to penetrate biological tissues. Current studies on puncture biomechanics lack systematic characterization of the complex, rate-mediated, interaction between tool and material across this dynamic range. To fill this knowledge gap, we establish a highly controlled experimental framework for dynamic puncture to investigate the relationship between the puncture performance (characterized by the depth of puncture) and the tool sharpness (characterized by the cusp angle) across a wide range of bio-relevant puncture speeds (from quasi-static to [Formula: see text] 50 m/s). Our results show that the sensitivity of puncture performance to variations in tool sharpness reduces at higher puncture speeds. This trend is likely due to rate-based viscoelastic and inertial effects arising from how materials respond to dynamic loads. The rate-dependent form-function relationship has important biological implications: While passive/low-speed puncture organisms likely rely heavily on sharp puncture tools to successfully penetrate and maintain functionalities, higher-speed puncture systems may allow for greater variability in puncture tool shape due to the relatively geometric-insensitive puncture performance, allowing for higher adaptability during the evolutionary process to other mechanical factors.