Self-healing polyacrylates based on dynamic disulfide and quadruple hydrogen bonds.

Herein, a self-healing polyacrylate system was successfully prepared by introducing crosslinking agents containing disulfide bonds and monomers capable of forming quadruple hydrogen bonds through free radical copolymerization. This polymer material exhibited good toughness and self-healing properties through chemical and physical dual dynamic networks while maintaining excellent mechanical properties, which expanded the development path of self-healing acrylate materials. Compared to uncrosslinked and single dynamically crosslinked polymers, its elongation at break was as high as 437%, and its tensile strength was 5.48 MPa. Due to the presence of dual reversible dynamic bonds in the copolymer system, good self-healing was also achieved at 60 °C. In addition, differential scanning calorimetry and thermogravimetric analysis measurements confirmed that the thermal stability and glass transition temperature of the material were improved owing to the presence of physical and chemical cross-linking networks.

Metoprolol use is associated with improved outcomes in patients with sepsis-induced cardiomyopathy: an analysis of the MIMIC-IV database.

BACKGROUND: Metoprolol is commonly administered to critically ill patients; however, its effect on mortality in patients with sepsis-induced cardiomyopathy (SICM) remains uncertain. This study aimed to investigate the relationship between metoprolol use and mortality in patients with SICM. METHODS: Adults with SICM were identified from the MIMIC-IV database. The exposure of interest was metoprolol treatment. The outcomes assessed were 30-day mortality, 1-year mortality, and in-hospital mortality. Kaplan-Meier survival analysis evaluated the effect of metoprolol on these outcomes. Multivariable Cox proportional hazards and logistic regression analyses were performed to determine the correlation between metoprolol treatment and mortality in patients with SICM. RESULTS: 1163 patients with SICM were identified, with 882 receiving metoprolol treatment (MET group) and 281 not receiving metoprolol treatment (NOMET group). Overall, the 30-day, 1-year, and in-hospital mortality rates were 10.2%, 18.2%, and 8.9%, respectively. Significant differences in mortality existed between the groups. Multivariable Cox analysis revealed that patients in the NOMET group had a higher risk of 1-year mortality (adjusted hazard ratio [HR] 2.493; 95% confidence interval [CI] 1.800-3.451; P < 0.001) and 30-day mortality (adjusted HR 4.280; 95%CI 2.760-6.637; P < 0.001). Metoprolol treatment was associated with lower in-hospital mortality (odds ratio [OR] 5.076; 95% CI 2.848-9.047; P < 0.001). Subgroup analysis supported these findings. CONCLUSION: Metoprolol treatment is associated with reduced all-cause mortality in patients with SICM. Prospective studies are required to validate these findings.

Clinical characterization of EFHD2 (swiprosin-1) in Glioma-associated macrophages and its role in regulation of immunosuppression.

Glioblastoma has been extensively studied due to its high mortality and short survival. The evolution mechanism of tumor-associated macrophages (TAMs) to Glioma-associated microglia and macrophages (GAMs) in the tumor microenvironment (TME) remains to be elucidated. The tumor cell-to-cell interaction patterns have not been well defined yet. The EF-Hand Domain Family Member D2 (EFHD2) has been reported to be differentially expressed as an immunomodulatory molecule in a variety of cancers. But large-scale clinical data from multiple ethnic communities have not been used to investigate the role of EFHD2 in glioma. RNA-seq data from 313 or 657 glioma patients from the Chinese Glioma Genome Atlas (CGGA) database and 603 glioma patients from the Cancer Genome Atlas (TCGA) database were analyzed retrospectively. Cell localization was performed using single-cell sequencing data from the CGGA database and the GSE131928 dataset. Mouse glioma cell lines and primary macrophages isolated from Efhd2 knockout mice were co-cultured to validate the immunomodulatory effects of EFHD2 on macrophages and the remodeling of TME of glioblastoma. EFHD2 is enriched in high-grade gliomas, isocitrate dehydrogenase wild-type, and 1p/19q non-co-deficient gliomas. It is a potential biomarker of glioma-proneuronal subtypes and an independent prognostic factor for overall survival in patients with malignant glioblastoma. EFHD2 regulates the monocyte-macrophage system function and positively correlates with immunosuppressive checkpoints. Further experimental data demonstrates that Efhd2 influences the polarization state of GAMs and inhibits the secretion of TGF-ß1. In vitro experiments have revealed that macrophages lacking Efhd2 suppress the vitality of two glioma cell lines and decelerate the growth of glioma xenografts. In conclusion, EFHD2 promises to be a key target for TME-related immunotherapy.

circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNA, have been reported to be involved in the etiology of various malignancies. However, the underlying cellular mechanisms of circRNAs implicated in the pathogenesis of HCC remain unknown. In this study, we identified a functional RNA, hsa_circ_0000384 (circMRPS35), from public tumor databases using a set of computational analyses, and we further identified that circMRPS35 was highly expressed in 35 pairs of HCC from patients. Moreover, knockdown of the expression of circMRPS35 in Huh-7 and HCC-LM3 cells suppressed their proliferation, migration, invasion, clone formation, and cell cycle in vitro, and it suppressed tumor growth in vivo as well. Mechanically, circMRPS35 sponged microRNA-148a-3p (miR-148a), regulating the expression of Syntaxin 3 (STX3), which modulated the ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Unexpectedly, we detected a peptide encoded by circMRPS35 (circMRPS35-168aa), which was significantly induced by chemotherapeutic drugs and promoted cisplatin resistance in HCC. These results demonstrated that circMRPS35 might be a novel mediator in HCC progress, and they raise the potential of a new biomarker for HCC diagnosis and prognosis, as well as a novel therapeutic target for HCC patients.

Thuricin†Z: A Narrow-Spectrum Sactibiotic that Targets the Cell Membrane.

Sactionine-containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S-adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow-spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin-sectioning transmission electron microscopy, scanning electron microscopy, and large-unilamellar-vesicle-based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.

Strongly Asymmetric Spectroscopy in Plasmon-Exciton Hybrid Systems due to Interference-Induced Energy Repartitioning.

Recent intense effort has been devoted to exploring different manifestations of resonant excitations of strongly coupled plasmons and excitons, but so far such studies have been limited to situations where the Fano- or Rabi-type spectra are largely symmetric at zero detuning. Using a newly developed full quantum mechanical model, here we reveal the existence of a highly asymmetric spectroscopic regime for both the Rabi splitting and transparency dip. The asymmetric nature is inherently tied to the non-negligible exciton absorbance and is caused by substantial interference-induced energy repartitioning of the resonance peaks. This theoretical framework can be exploited to reveal the quantum behaviors of the two excitation entities with varying mutual coupling strengths in both linear and nonlinear regimes. We also use prototypical systems of rhodamine molecules strongly coupled with AuAg alloyed nanoparticles and well-devised control experiments to demonstrate the validity and tunability of the energy repartitioning and correlated electronic state occupations, as captured by the variations in the asymmetric spectroscopy and corresponding nonlinear absorption coefficient as a function of the Au:Ag ratio. The present study helps to substantially enrich our microscopic understanding of strongly coupled plasmon-exciton systems.

Acute and 28-day sub-acute oral toxicity evaluation of two dietary bamboo charcoal powders in Sprague-Dawley rats.

No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11.24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.

[Optimization of submerged culture conditions for Xylaria striata mycelium].

OBJECTIVE: To establish the optimum submerged culture condition of Xylaria striata mycelium. METHODS: One-factor-at-a-time method and orthogonal experiment design were applied and the dry weight of mycelium was tested for evaluation the biomass of the growth of Xylaria striata mycelium. RESULTS: The results from one-factor-at-a-time experiments showed that maltose, glucose or corn powder could be used as the best carbon source and the optimum nitrogen source was soybean powder. The best ratio of carbon source to nitrogen source was 5:1. In addition, the higher dry weight of mycelium was found at pH 6 when 2 mycelial discs were inoculated and fermented for 7 days. Otherwise, the growth of mycelium was observed to be promoted significantly by addition with K,Mg,P and VB1. The consequence of orthogonal experiment showed that the optimum carbon source and nitrogen source were maltose 4% and soybean powder 0.8%, respectively,and the highest mycelium biomass could be obtained at pH 7 and 25 °C shaking for 13 days. CONCLUSION: A large amount of mycelium will be obtained under the optimum condition of liquid culture for Xylaria striata.

Chronic Pain and Obesity in Community-Dwelling Adults: Findings from the National Health and Nutrition Examination Survey.

Background: Chronic pain and obesity, together with their corresponding characteristics, are concerning health issues with high socioeconomic burden. The objective of this study is to ascertain the prevalence of chronic pain among individuals residing in the community and examine its association with obesity. Methods: The present study employed a cross-sectional design and analyzed data from three cycles of the National Health and Nutrition Examination Survey (NHANES). Univariate and multivariate logistic regression analysis were performed to examine the relationship between chronic pain and obesity. To evaluate the potential nonlinear association of chronic with body mass index (BMI), the restricted cubic spline (RCS) analysis was performed in multivariable-adjusted models. The researchers conducted subgroup analyses in order to investigate the potential influence of different confounding factors on the relationship between chronic pain and obesity. Results: Our final analysis included a sample size of 13,700 participants with higher prevalence of chronic pain with higher BMI, older age, female sex, lower educational level, smoking, and other pathologies. The prevalence of chronic pain in different BMI groups was 17.0% (underweight), 11.8% (normal weight), 12.9% (overweight), and 17.9% (obesity), respectively. In the fully adjusted model, obesity was associated with a 45% increase in the risk of chronic pain compared with the normal weight. The RCS analyses revealed a nonlinear and J-shaped positive association between BMI and chronic pain (OR 1.45, 95% CI 1.27-1.66, all P for nonlinearity < 0.05). The results of the subgroup analyses indicate that the presence of osteoporosis significantly influenced the relationship between obesity and chronic pain, as evidenced by a statistically significant interaction effect (OR 2.25, 95% CI 1.38-3.68, P for interaction = 0.019). Conclusion: The presence of obesity was found to be significantly correlated with an increased likelihood of experiencing chronic pain among adults living in the United States.

Association between waist circumference and sleep disorder in the elderly: Based on the NHANES 2005-2018.

The existing data do not consistently support the link between elderly adults' waist circumferences and sleep disorders. This study aimed to evaluate whether waist circumference was connected with sleep disorder in the elderly. This cross-sectional study utilized data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) regarding waist circumference, sleep disorders, and confounding factors. Included in the study were participants older than 60 who completed sleep questionnaires and waist circumference measurements. Using a multivariate logistic regression model and subgroup analyses, the relationship between waist circumference and sleep disorder was evaluated. To explore the non-linear relationship, restricted cubic spline (RCS) with three knots coupled with a logistic regression model to assess the dose-response relationship between waist circumference (continuous variables) and sleep disorder. A total of 2,545 (Weighted 14,682,916.3) elderly participants with complete information were included in the analysis and 312 (Weighted 1,777,137.8) subjects met the definition of sleep disorder. Compared with participants without sleep disorder, those with sleep disorder had a higher waist circumference (100.80 cm vs. 108.96 cm, P< 0.001). The results of the multivariable adjusted logistic regression model suggested that those in quartiles 4 (≥ 75th percentile) for their waist circumference had higher odds of sleep disorder [adjusted odds ratio (AOR) = 2.75, 95% confidence interval (CI) = 1.66-4.54, P < 0.001] compared with those in quartile 1. The RCS result showed that the OR of sleep disorder and waist circumference displayed a linear relationship (P <0.001, Non-linear P = 0.642). Age and gender subgroup analysis revealed comparable relationships between waist circumference and sleep disorder among elderly individuals. Waist circumference was associated with sleep disorders in the elderly. There was a dose-response relationship between waist circumference and the likelihood of sleep disorder. Those with a larger waist circumference were more likely to have a sleep disorder than those with a smaller waist circumference.

Nomogram for predicting major bleeding after off-pump coronary artery bypass grafting.

OBJECTIVE: The purpose of this investigation is to develop a novel nomogram for predicting major bleeding following off-pump coronary artery bypass grafting (CABG). METHODS: Between January 2012 and December 2022, 541 patients who underwent off-pump isolated primary CABG were included in a retrospective analysis. The primary outcome measure after off-pump CABG was major bleeding. Based on the outcomes of a multivariate analysis, nomograms were constructed. Using receiver operating characteristic analysis and calibration, the predictive accuracy of the nomograms was assessed. Using decision curve analysis (DCA), the clinical benefit of the nomograms was determined. RESULTS: We categorized 399 and 142 patients in the "no major bleeding group" and "major bleeding group", respectively. Age (odds ratio (OR) 1.038; 95% confidence interval (CI) 1.009-1.068; p = 0.009), body mass index (OR 0.913; 95% CI 0.849-0.982; p = 0.014), hemoglobin (OR 0.958; 95% CI 0.945-0.971; p < 0.001), sodium (OR 0.873; 95% CI 0.807-0.945; p = 0.001), blood urea nitrogen (OR 1.198; 95% CI 1.073-1.338; p = 0.001), and operation time (OR 1.012; 95% CI 1.008-1.017; p < 0.001) were independent predictors for major bleeding after off-pump CABG. The model based on independent predictors exhibited excellent discrimination and calibration, with good agreement between actual and nomogram-estimated probabilities of generalization. DCA demonstrated that nomogram-assisted decisions have a greater positive benefit than treating all patients or none. CONCLUSIONS: The plotted nomogram accurately predicted major bleeding outcomes following off-pump CABG and may therefore contribute to clinical decision-making, patient treatment, and consultation services.

Association between haemoglobin-to-red blood cell distribution width ratio at admission and all-cause mortality in adult patients with sepsis in an intensive care unit: a secondary analysis of the MIMIC-IV database.

OBJECTIVE: The association between haemoglobin-to-red blood cell distribution width ratio (HRR) and all-cause mortality remains poorly understood. This study aimed to examine the influence of HRR at the time of admission mortality over 1 year and 30 days in patients with sepsis. DESIGN: This was a secondary analysis. SETTING: This study was conducted in intensive care units (ICUs). PARTICIPANTS: Adult patients with sepsis were identified and included from an intensive care database based on eligibility criteria. PRIMARY OUTCOME AND MEASURE: The primary outcome was the rate of death within 1 year. The secondary outcome was the death rate within 30 days. RESULTS: A total of 4233 patients with sepsis who met the inclusion criteria were analysed, excluding those ineligible. These participants were divided into quartiles based on their HRR at admission. The overall mortality rates at 1 year and 30 days were 42.9% and 25.5%, respectively. A significant inverse association was observed between HRR quartiles and all-cause mortality (p<0.001). Pairwise comparisons using Kaplan-Meier analysis showed significant differences in 1-year mortality rates across the quartiles. However, no significant difference was detected in 30-day mortality between the Q3 and Q4 groups (p=0.222). Multivariate Cox regression analysis demonstrated that a higher HRR at ICU admission was independently associated with reduced mortality at 1 year (HR, 0.935; 95% CI 0.913 to 0.958; p<0.001) and 30 days (HR, 0.969; 95% CI 0.939 to 0.999; p=0.043). Furthermore, restricted cubic spline models indicated a non-linear relationship between HRR and mortality at both 1 year and 30 days (p<0.001 for both). CONCLUSIONS: This retrospective analysis demonstrated that the HRR at the time of admission was a significant prognostic marker for long-term mortality in patients with sepsis.

Swiprosin-1 participates in the berberine-regulated AMPK/MLCK pathway to attenuate colitis-induced tight junction damage.

BACKGROUND AND PURPOSE: Activation of AMP-activated protein kinase (AMPK) is essential in maintaining the epithelial tight junction (TJ) barrier. Berberine, a phytochemical AMPK agonist, has been widely reported to ameliorate colitis. Berberine or AMPK activation inhibits cytoskeletal contraction induced by myosin light chain kinase (MLCK), thereby ameliorating TJ barrier defects. We previously found that swiprosin-1, an actin-binding protein, affects MLCK expression. Here, we aimed to reveal the role of swiprosin-1 in the regulation of AMPK/MLCK by berberine. METHODS: Caco-2 monolayer transfected with AMPKα1 (or swiprosin-1) siRNA was treated with berberine after being stimulated with TNFα/IFNγ to assess the effect on the TJ barrier. Intestinal epithelial conditional knockout mice for AMPKα1 (or swiprosin-1) were treated with berberine after experimental colitis to evaluate the effect on the TJ barrier. TJ integrity was evaluated by immunoblotting and immunofluorescence for ZO-1 and Occludin. RESULTS: The protection of berberine against TJ barrier damage was blocked by AMPK inhibitor or knockout of AMPKα1 in epithelial cells. Swiprosin-1 was distributed in colonic epithelial cells and upregulated in colitis. Knockout of swiprosin-1 in intestinal epithelial cells ameliorated TJ barrier damage and abolished the protective effect of berberine. Impaired assembly of TJ caused by overexpression of swiprosin-1 was alleviated by MLCK inhibitor, and inhibition of the MLCK pathway by berberine also required the presence of swiprosin-1. In addition, berberine downregulated swiprosin-1 expression in an AMPK-dependent manner. CONCLUSION: Swiprosin-1 may be a key intermediate molecule in the regulation of the AMPK/MLCK pathway by berberine to attenuate colitis-induced TJ barrier damage.

Time-programmed release of curcumin and Zn2+ from multi-layered RSF coating modified PET graft for improvement of graft-host integration.

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn2+ on the surface of the PET grafts (Cur@Zn2+@PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn2+ from the Cur@Zn2+@PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1ß. Meanwhile, a significant release of Zn2+ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn2+@PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn2+@PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.

Inhibition of mitochondrial over-division by (+)-14,15-Dehydrovincamine attenuates cisplatin-induced acute kidney injury via the JNK/Mff pathway.

Cisplatin-induced acute kidney injury (AKI) is characterized by mitochondrial damage and apoptosis, and safe and effective therapeutic agents are urgently needed. Renal tubular epithelial cells, the main site of AKI, are enriched with a large number of mitochondria, which are crucial for the progression of AKI with an impaired energy supply. Vincamine has anti-inflammatory and antioxidant effects in mouse AKI models. As a natural compound derived from Tabernaemontana pandacaqui, (+)-14, 15-Dehydrovincamine and Vincamine differ in structure by only one double bond, and the role and exact mechanism of (+)-14, 15-Dehydrovincamine remains to be elucidated in AKI. The present study demonstrated that (+)-14,15-Dehydrovincamine significantly ameliorated mitochondrial dysfunction and maintained mitochondrial homeostasis in a cisplatin-induced AKI model. Furthermore, (+)-14,15-Dehydrovincamine ameliorates cytochrome C-dependent apoptosis in renal tubular epithelial cells. c-Jun NH2-terminal kinase (JNK) was identified as a potential target protein of (+)-14,15-Dehydrovincamine attenuating AKI by network pharmacological analysis. (+)-14,15-Dehydrovincamine inhibited cisplatin-induced JNK activation, mitochondrial fission factor (Mff) phosphorylation, and dynamin-related protein 1 (Drp1) translocation to the mitochondria in renal tubular epithelial cells. Meanwhile, the JNK activator anisomycin restored Mff phosphorylation and Drp1 translocation, counteracting the protective effect of (+)-14,15-Dehydrovincamine on mitochondrial dysfunction in cisplatin-induced TECs injury. In conclusion, (+)-14,15-Dehydrovincamine reduced mitochondrial fission, maintained mitochondrial homeostasis, and attenuated apoptosis by inhibiting the JNK/Mff/Drp1 pathway, which in turn ameliorated cisplatin-induced AKI.

Identification of antibacterial constituents from Rhododendron simsii Planch with an activity-guided method.

Bacterial infections and antibiotic resistance pose significant public health challenges globally. Natural products serve as valuable sources for discovering antimicrobial agents. Rhododendron simsii Planch, a folk medicine, is traditionally used to treat various inflammatory diseases. In this study, we investigated the antibacterial metabolites derived from R. simsii Planch. Rhodosimsiin A (1), bearing a 1,5-seco-1,6 and 3,6-epoxy grayanane diterpene skeleton, representing a novel 5/6/7/6/5 pentacyclic ring system, and 3ß,16α-dihydroxy-6ß-ethoxy-14ß-acetoxy-grayan-1(5)-ene-10-one (4), which represents the first example of the degradation of C-20 and carbonylation in C-10 diterpenoid, together with two new grayanane diterpenes (2-3), three new triterpenes (13-15), and known analogs (5-12, 16-30), were isolated from the leaves of R. simsii Planch by using the bioassay-guided method. Their structures were elucidated by comprehensive spectroscopic analyses, and absolute configurations were established by single-crystal X-ray diffraction and calculated ECD spectra. Compounds 14, 15, 18, 20, 27, 28, and 30 exhibited potent antibacterial activity with an MIC50 of 1.4-24.3 µg/mL against Staphylococcus aureus. The findings of this research indicate that secondary metabolites derived from R. simsii Planch are promising natural antimicrobial candidates.

A review of nanomaterials for biosensing applications.

A biosensor is a device that reacts with the analyte to be analyzed, detects its concentration, and generates readable information, which plays an important role in medical diagnosis, detection of physiological indicators, and disease prevention. Nanomaterials have received increasing attention in the fabrication and improvement of biosensors due to their unique physicochemical and optical properties. In this paper, the properties of nanomaterials such as the size effect, optical and electrical properties, and their advantages in the field of biosensing are briefly summarized, and the application of nanomaterials can effectively improve the sensitivity and reduce the detection limit of biosensors. The advantages of commonly used nanomaterials such as gold nanoparticles (AuNPs), carbon nanotubes (CNTs), quantum dots (QDs), graphene, and magnetic nanobeads for biosensor applications are also reviewed. Besides, the two main types of biosensors using nanomaterials involved in their construction and their working principles are described, and the toxicity and biocompatibility of nanomaterials and the future direction of nanomaterial biosensors are discussed.

Fully integrated wearable microneedle biosensing platform for wide-range and real-time continuous glucose monitoring.

Wearable microneedle sensors for continuous glucose monitoring (CGM) have great potential for clinical impact by allowing access to large data sets to provide individualized treatment plans. To date, their development has been challenged by the accurate wide linear range tracking of interstitial fluid (ISF) glucose (Glu) levels. Here, we present a CGM platform consisting of a three-electrode microneedle electrochemical biosensor and a fully integrated radio-chemical analysis system. The long-term performance of the robust CGM on diabetic rats was achieved by electrodepositing Prussian blue (PB), and crosslinking glucose oxidase (GOx) and chitosan to form a 3D network using glutaraldehyde (GA). After redox by GOx, PB rapidly decomposes hydrogen peroxide and mediates charge transfer, while the 3D network and graphite powder provide enrichment and release sites for Glu and catalytic products, enabling a sensing range of 0.25-35 mM. Microneedle CGM has high sensitivity, good stability, and anti-interference ability. In diabetic rats, CGM can accurately monitor Glu levels in the ISF in real-time, which are highly consistent with levels measured by commercial Glu meters. These results indicate the feasibility and application prospects of the PB-based CGM for the clinical management of diabetes. STATEMENT OF SIGNIFICANCE: This study addresses the challenge of continuous glucose monitoring system design where the narrow linear range of sensing due to the miniaturization of sensors fails to meet the monitoring needs of clinical diabetic patients. This was achieved by utilizing a three-dimensional network of glutaraldehyde cross-linked glucose oxidase and chitosan. The unique topology of the 3D network provides a large number of sites for glucose enrichment and anchors the enzyme to the sensing medium and the conductive substrate through covalent bonding, successfully blocking the escape of the enzyme and the sensing medium and shortening the electron transfer and transmission path.

Aculeaquamides B and C, two new paraherquamides from the co-culture of Aspergillus aculeatinus WHUF0198 and Penicillium sp. DM27.

Two new paraherquamides (PHQs) namely aculeaquamides B and C (1 and 2), along with four known PHQs (3-6), were isolated from the co-culture of marine fungus Aspergillus aculeatinus WHUF0198 and mangrove-associated fungus Penicillium sp. DM27. Compound 1 represents the first PHQ derivative featuring an uncommon 7/6/5/5/6/5 hexacyclic system. The structures of the isolated compounds were elucidated based on exhaustive NMR spectroscopy measurement and HRESIMS data. The absolute configurations of new compounds were determined by TDDFT-ECD calculations. Compound 3 demonstrated suppression of AngII-induced cardiac hypertrophy while exhibiting relatively low cardiomyocyte toxicity.

Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases.

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.