Devastating the Supply Wagons: Multifaceted Liposomes Capable of Exhausting Tumor to Death via Triple Energy Depletion.

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.

Effects of toothpaste containing inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and dental plaque microbiota.

Plaque-induced gingivitis is an inflammatory response in gingival tissues resulting from bacterial plaque accumulation at the gingival margin. Postbiotics can promote the proliferation of beneficial bacteria and optimise the state of microbiota in the oral cavity. In this study, we investigated the effect of inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and the dental plaque microbiota. A total of 32 healthy gingival participants (Group N, using blank toothpaste for 3 months) and 60 patients with plaque-induced gingivitis (30 in Group F, using inactivated Probio-01 toothpaste for 3 months, and 30 in Group B, using blank toothpaste for 3 months, respectively) were recruited. Clinical indices, which included bleeding on probing (BOP), gingival index (GI), and plaque index (PI), were used to assess the severity of gingivitis. Furthermore, 16SrDNA amplicon sequencing was used to explore changes in the gingival state and dental plaque microbiota in patients with plaque-induced gingivitis. The results showed that inactivated Probio-01 significantly reduced clinical indices of gingivitis, including BOP, GI, and PI, in participants with plaque-induced gingivitis and effectively relieved gingival inflammation, compared with that observed in the control group (group B). Inactivated Probio-01 did not significantly influence the diversity of dental plaque microbiota, but increased the relative abundance of dental plaque core bacteria, such as Leptotrichia and Fusobacterium (P < 0.05). Strong correlations were observed between the indices and abundance of dental plaque microbiota. Overall, the inactivated Probio-01 significantly reduced the clinical indices of gingivitis and effectively improved gingival inflammation in patients with plaque-induced gingivitis. The activity of inactivated Probio-01 against plaque-induced gingivitis was possibly mediated by its ability to regulate the dental plaque microbiota, as indicated by the close correlation between the plaque microbiota and clinical indices of gingivitis.

Combined toxic effects of polyethylene microplastics and lambda-cyhalothrin on gut of zebrafish (Danio rerio).

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g-1 and 39.0 mg∙g-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Biodegradable polymeric nanoparticles increase risk of cardiovascular diseases by inducing endothelium dysfunction and inflammation.

Biodegradable polymers are expected to be an alternative to plastics. Because of its high biocompatibility, poly (lactic-co-glycolic acid) (PLGA) is widely used in medicine. It has been reported that micro-nano plastics can be accumulated in the circulatory system and cause tissue injury. With the increasing environmental exposure of degradable polymer nanoparticles (NPs), the impact of this risk factor on cardiovascular disease deserves attention. Thus, we aim to study the harmful effect of PLGA NPs on the process of vascular stenosis which is a typical pathological feature of cardiovascular diseases. We establish a mouse vascular stenosis model with intravenously injecting of PLGA NPs for 2 weeks. This model leads to a significant narrowing of the left common carotid artery which is characterized by the increasing intima area and focal stenosis. We observe that PLGA NPs accelerate stenosis progression by inducing inflammation and impairing vascular function. It promotes the proliferation of smooth muscle cells and causes abnormal collagen distribution. The combination of wall shear stress and PLGA NPs uptake speed up endothelial cell damage, decrease endothelial permeability and cell migration capacity. Our results suggest that PLGA NPs may pose a risk in cardiovascular stenosis which inspire us to concern the biodegradable polymeric materials in our living especially the clinic applications.

Advances in Stem Cell-Based Therapies in the Treatment of Osteoarthritis.

Osteoarthritis (OA) is a chronic, degenerative joint disease presenting a significant global health threat. While current therapeutic approaches primarily target symptom relief, their efficacy in repairing joint damage remains limited. Recent research has highlighted mesenchymal stem cells (MSCs) as potential contributors to cartilage repair, anti-inflammatory modulation, and immune regulation in OA patients. Notably, MSCs from different sources and their derivatives exhibit variations in their effectiveness in treating OA. Moreover, pretreatment and gene editing techniques of MSCs can enhance their therapeutic outcomes in OA. Additionally, the combination of novel biomaterials with MSCs has shown promise in facilitating the repair of damaged cartilage. This review summarizes recent studies on the role of MSCs in the treatment of OA, delving into their advantages and exploring potential directions for development, with the aim of providing fresh insights for future research in this critical field.

An Innovative Chiral UPLC-MS/MS Method for Enantioselective Determination and Dissipation in Soil of Fenpropidin Enantiomers.

As a chiral piperidine fungicide, fenpropidin has been widely used to control plant diseases. However, there are rare studies that have investigated fenpropidin at the enantiomer level. In this study, the single-factor analysis combined with a Box-Behnken design was used to obtain the optimal enantio-separation parameters of the fenpropidin enantiomers on ultra-performance liquid chromatography-tandem mass spectrometry. The absolute configuration of two fenpropidin enantiomers was confirmed for the first time using electron circular dichroism and optical activity. On the Lux cellulose-3 column, S-(-)-fenpropidin flowed out before R-(+)-fenpropidin. The enantio-separation mechanism was revealed by molecular docking. A modified QuEChERS method was developed for the trace determination of the fenpropidin enantiomers in seven food and environmental substrates. The average recoveries were 71.5-106.1% with the intra-day and inter-day relative standard deviations of 0.3-8.9% and 0.5-8.0%. The method was successfully verified by enantioselective dissipation of fenpropidin in soil under the field. R-(+)-fenpropidin dissipated faster than S-(-)-fenpropidin, and the half-lives were 19.8 d and 22.4 d. This study established a brand-new effective chiral analysis method for the fenpropidin enantiomers, providing a basis for accurate residue monitoring and the risk assessment of fenpropidin.

Phagocytosis of polymeric nanoparticles aided activation of macrophages to increase atherosclerotic plaques in ApoE-/- mice.

The unique physiochemical properties of nanomaterials have been widely used in drug delivery systems and diagnostic contrast agents. The safety issues of biomaterials with exceptional biocompatibility and hemo-compatibility have also received extensive attention at the nanoscale, especially in cardiovascular disease. Therefore, we conducted a study of the effects of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) on the development of aortic atherosclerotic plaques in ApoE-/- mice. The particle size of PLGA NPs was 92.69 ± 3.1 nm and the zeta potential were - 31.6 ± 2.8 mV, with good blood compatibility. ApoE-/- mice were continuously injected with PLGA NPs intravenously for 4 and 12 weeks. Examination of oil red O stained aortic sinuses confirmed that the accumulation of PLGA NPs caused a significantly higher extension of atherosclerotic plaques and increasing the expression of associated inflammatory factors, such as TNF-α and IL-6. The combined exposure of ox-LDL and PLGA NPs accelerated the conversion of macrophages to foam cells. Our results highlight further understanding the interaction between PLGA NPs and the atherosclerotic plaques, which we should consider in future nanomaterial design and pay more attention to the process of using nano-medicines on cardiovascular diseases.

Oral health status of 12-year-old children in Lisu minority ethnic group in China: a cross-sectional study.

BACKGROUND: Lisu is an ethnic minority group and most of them are living in Yunnan, China. This study investigated the oral health status among 12-year-old Lisu children in Yunnan. METHOD: This survey employed a multistage sampling method to recruit 12-year-old Lisu children. Two calibrated dentists performed the oral examinations in the primary schools. They examined dental caries, gingival bleeding and dental fluorosis using the diagnosis criteria recommended by the World Health Organization. A self-administrated questionnaire was distributed to the children to collect their sociodemographic background information and oral health-related behaviours. A chi-square test, the Mann-Whitney U test, zero-inflated negative binomial (ZINB) regression and multivariate logistic regression were used for statistical analysis. RESULTS: This survey invited 512 children, and 482 children (48% boys) participated in the study (response rate: 94%). Their caries prevalence was 35% and their caries experience in mean (SD) DMFT scores was 0.63 (0.10). The mean (SD) DT score was 0.60 (1.10), consisting 95% of the mean DMFT scores. No dental fluorosis was observed; whereas 426 children (88%) had gingival bleeding. Results of ZINB model indicated sex and sugary-snacking habits were related to the dental caries experience (p < 0.05). The gingival-bleeding prevalence was associated with the mother's education level, the child's monthly-pocket money and daily toothbrushing frequency (p < 0.05). CONCLUSION: Dental caries and gingival bleeding were prevalent among 12-year-old Lisu children in the Yunnan province in China, and most of the decayed teeth were unrestored. Dental fluorosis was not observed in the children.

Magnetic-Field-Driven Extraction of Bioreceptors into Polymeric Membranes for Label-Free Potentiometric Biosensing.

We report here the concept of a magnetically controlled extraction of hydrophilic bioreceptors into polymeric membranes for bioassays. The potentiometric assay relies on the intrinsic charges of an antimicrobial peptide and its unique recognition abilities, which can eliminate the probe labeling and indicator addition. The target binding event could effectively prevent the extraction of the peptide into the polymeric membrane doped with an ion exchanger, thus resulting in a potential change. The potentiometric response properties of the peptide assembled on magnetic beads can be dynamically controlled and modulated by applying a magnetic field. Staphylococcus aureus, as a model of food-borne pathogens, was measured at levels down to 10 CFU mL-1 . Based on this sensing strategy, a potentiometric array was developed for the pattern recognition of bacteria. The proposed general platform can be used for potentiometric biosensing using other hydrophilic bioreceptors.

Water-Dispersible Candle Soot-Derived Carbon Nano-Onion Clusters for Imaging-Guided Photothermal Cancer Therapy.

Herein, water-dispersible carbon nano-onion clusters (CNOCs) with an average hydrodynamic size of ≈90 nm are prepared by simply sonicating candle soot in a mixture of oxidizing acid. The obtained CNOCs have high photothermal conversion efficiency (57.5%), excellent aqueous dispersibility (stable in water for more than a year without precipitation), and benign biocompatibility. After polyethylenimine (PEI) and poly(ethylene glycol) (PEG) modification, the resultant CNOCs-PEI-PEG have a high photothermal conversion efficiency (56.5%), and can realize after-wash photothermal cancer cell ablation due to their ultrahigh cellular uptake (21.3 pg/cell), which is highly beneficial for the selective ablation of cancer cells via light-triggered intracellular heat generation. More interestingly, the cellular uptake of CNOCs-PEI-PEG is so high that the internalized nanoagents can be directly observed under a microscope without fluorescent labeling. Besides, in vivo experiments reveal that CNOCs-PEI-PEG can be used for photothermal/photoacoustic dual-modal imaging-guided photothermal therapy after intravenous administration. Furthermore, CNOCs-PEI-PEG can be efficiently cleared from the mouse body within a week, ensuring their excellent long-term biosafety. To the best of the authors' knowledge, the first example of using candle soot as raw material to prepare water-dispersible onion-like carbon nanomaterials for cancer theranostics is represented herein.

Dental caries status of Lisu preschool children in Yunnan Province, China: a cross-sectional study.

BACKGROUND: Dental caries is still considered a major public health concern for human beings, especially minority groups and those living in disadvantaged communities. The Lisu is a minority group in China of more than 702,000 people located primarily in Yunnan Province. The present study was aimed at studying the status of dental caries status, as well as its risk factors, among Lisu children aged 5 years in Yunnan Province, China. METHODS: A multistage cluster sampling method was employed for participants' recruitment. Two calibrated dentists carried out the clinical examination with dental mirrors and CPI probes under an LED headlight. The dental caries experience was assessed by the dmft index. Oral hygiene status was evaluated using the visible plaque index (VPI). Information on the child's socio-demographic characteristics and oral health-related practices were collected using a parental questionnaire. A zero-inflated negative binomial regression (ZINB) was employed to analyse the associations between the dental caries status and the children's social-demographic status and their oral health-related behaviours. RESULTS: In all, 470 Lisu children aged 5 were invited, and 404 were examined. Their mean dmft (±SD) and caries prevalence were 5.6 ± 4.8 and 80%, respectively. Their mean VPI scores were 58% ± 21%. Lisu children who brushed their teeth at least once daily had higher dmft scores, and children from high-income families were more likely to have dental caries. CONCLUSION: The prevalence of dental caries among Lisu children aged 5 years in Yunnan, China was high, and their caries status was severe, with a majority of carious teeth untreated. The dental caries experience of Lisu children aged 5 was related to their brushing frequency and families' economic backgrounds.

High-throughput pyrosequencing used for the discovery of a novel cellulase from a thermophilic cellulose-degrading microbial consortium.

OBJECTIVES: To analyze the microbial diversity and gene content of a thermophilic cellulose-degrading consortium from hot springs in Xiamen, China using 454 pyrosequencing for discovering cellulolytic enzyme resources. RESULTS: A thermophilic cellulose-degrading consortium, XM70 that was isolated from a hot spring, used sugarcane bagasse as sole carbon and energy source. DNA sequencing of the XM70 sample resulted in 349,978 reads with an average read length of 380 bases, accounting for 133,896,867 bases of sequence information. The characterization of sequencing reads and assembled contigs revealed that most microbes were derived from four phyla: Geobacillus (Firmicutes), Thermus, Bacillus, and Anoxybacillus. Twenty-eight homologous genes belonging to 15 glycoside hydrolase families were detected, including several cellulase genes. A novel hot spring metagenome-derived thermophilic cellulase was expressed and characterized. CONCLUSIONS: The application value of thermostable sugarcane bagasse-degrading enzymes is shown for production of cellulosic biofuel. The practical power of using a short-read-based metagenomic approach for harvesting novel microbial genes is also demonstrated.

Oral microbial community typing of caries and pigment in primary dentition.

BACKGROUND: Black extrinsic discoloration in primary dentition is a common clinical and aesthetic problem that can co-occur with dental caries, the most common oral diseases in childhood. Although the role of bacteria in the formation of pigment and caries in primary dentition is important, their basic features still remain a further mystery. METHODS: Using targeted sequencing of the V1-V3 hypervariable regions of bacterial 16S ribosomal RNA (rRNA) genes, we obtained a dataset consisting of 831,381 sequences from 111 saliva samples and 110 supragingival plaque samples from 40 patients with pigment (black extrinsic stain), 20 with caries (obvious decay), and 25 with both pigment and caries and from 26 healthy individuals. We applied a Dirichlet multinomial mixture (DMM)-based community typing approach to investigate oral microbial community types. RESULTS: Our results revealed significant structural segregation of microbial communities, as indicated by the identification of two plaque community types (A and B) and three saliva community types (C-E). We found that the independent occurrence of the two plaque community types, A and B, was potentially associated with our oral diseases of interest. For type A, three co-occurring bacterial genus pairs could separately play a potential role in the formation of pigment (Leptotrichia and Fusobacterium), caries (unclassified Gemellales and Granulicatella), and mixed caries and pigment (Streptococcus and Mogibacterium). For type B, three co-occurring bacterial genera (unclassified Clostridiaceae, Peptostreptococcus, and Clostridium) were related to mixed pigment and caries. Three dominant bacterial genera (Selenomonas, Gemella, and Streptobacillus) were linked to the presence of caries. CONCLUSIONS: Our study demonstrates that plaque-associated oral microbial communities could majorly contribute to the formation of pigment and caries in primary dentition and suggests potential clinical applications of monitoring oral microbiota as an indicator for disease diagnosis and prognosis.

Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese steelworks firm sample.

OBJECTIVES: Noise-induced hearing loss is one of the most serious occupational diseases worldwide. It is caused by interactions between environmental and genetic factors. The purpose of this study was to examine the association between the genetic susceptibility of the eye absent homolog 4 (EYA4) gene and the risk of developing noise-induced hearing loss in China. METHODS: A case-control association study was carried out with 326 hearing loss cases and 326 controls matched with age and duration of noise exposure, drawn from a cohort of steel workers. Five single nucleotide polymorphisms (SNPs) in the EYA4 were selected and genotyped. Logistic regression was performed to analyse the main effect of genotypes and interactions between genotypes and individual/environmental factors adjusted for confounding factors. Moreover, generalised multiple dimensionality reduction was applied to further detect interaction among the 5 selected SNPs. RESULTS: Analysis revealed that locus polymorphism of rs3813346 was associated with the risk of developing noise-induced hearing loss in the dominance model, the codominance model and the addictive model (p=0.004, 0.009 and 0.003, respectively). A significant interaction between rs9321402 and cumulative noise exposure was found (p=0.002). A significant main effect p value (p=0.006) was obtained in the high-level exposure group (cumulative noise exposure ≥98 dB(A)). Generalised multiple dimensionality reduction indicated that the combined interaction of the 2 loci-rs3813346 and rs9493627-significantly affected the incidence of noise-induced hearing loss. CONCLUSIONS: The research suggests that EYA4 genetic variant and its interaction with noise levels may modify the susceptibility to develop noise-induced hearing loss in Chinese population.

[Prevalence and influence factors of hypertension among the workers exposed to noise in steel making and steel rolling workshop of an iron and steel plant].

OBJECTIVE: To investigate the prevalence and influence factors of hypertension among the workers exposed to noise in steel making and steel rolling workshop of an iron and steel plant. METHODS: Using cluster sampling method, 3 150 workers exposed to noise participated in this study. According to do questionnaire survey and blood pressure measurement, 2 924 workers were tested, among which 1 313 workers were from steel making workshop and 1 611 workers were from steel rolling workshop. The relationships between different demographic characteristics, different habits, and different cumulative noise exposures of workers exposed to noise and hypertension were analyzed. RESULTS: For the hypertension prevalence rate, the total prevalence rate was 27.43% (802/2 924), the male was higher than the female (29.88 % (753/2 520) vs 12.13% (49/404), χ² = 55.13, P < 0.001), married ones were higher than the unmarried (29.84% (718/2 406) vs 16.22% (84/518), χ² = 39.76, P < 0.001), the smoking subjects were higher than the no smoking (30.31% (438/1 445) vs 24.61% (364/1 479), χ² = 11.93, P = 0.001), drinking ones were higher than the no drinking (31.53% (541/1 716) vs 21.61% (261/1 208), χ² = 35.05, P < 0.001). The hypertension prevalence rates among the subjects with education background in junior high school and below, high school (secondary) and university and above were separately 44.96%(125/278), 29.95%(455/1 519) and 19.70%(222/1 127) (χ² = 81.65, P < 0.001), among cumulative exposure groups 77-89, 90-94, 95-99, 100-104 and 105-113 were separately 8.43% (14/166), 14.48% (53/366), 24.28% (297/1 223), 36.65% (335/914) and 40.39%(103/255) (χ² = 127.58, P < 0.001). Multivariate logistic regression analysis showed that workers who exposed to cumulative noise in 95-99, 100-104 and 105-113 dB(A) ·year had the higher risk of hypertension, the OR (95%CI) were 1.84 (95% CI: 1.35-2.51), 1.74 (95% CI: 1.24-2.45) and 1.68 (95% CI: 1.09-2.58). Drinking (OR = 1.60, 95% CI: 1.32-1.95) and BMI ≥ 24.0 kg/m² (OR = 1.26, 95% CI: 1.22-1.30) were the risk factors for hypertension as well. CONCLUSION: Cumulative noise exposure, alcohol consumption and above normal BMI may affect the hypertension prevalence rate of the workers exposed to noise.

Membrane nanotubes induced by aqueous phase separation and stabilized by spontaneous curvature.

Tubular membrane structures are widespread in eukaryotic cells, but the mechanisms underlying their formation and stability are not well understood. Previous work has focused on tube extrusion from cells and model membranes under the application of external forces. Here, we present novel membrane/polymer systems, where stable tubes form in the absence of externally applied forces. Solutions of two water-soluble polymers, polyethylene glycol and dextran, were encapsulated in giant lipid vesicles, cell-size model systems. Hypertonic deflation induced phase separation of the enclosed solution. The excess membrane area created during the deflation process was stored in a large number of membrane nanotubes inside the vesicle. The tubes had a diameter below optical resolution and became visible only when fluorescently labeled. The tubes were rather stable: In the absence of external forces, they existed for several days. A theoretical analysis of the shapes of the deflated vesicles reveals that these shapes would be unstable if the membranes had no spontaneous curvature. Using the large separation of length scales between the tube diameter and the overall size of the vesicles, the spontaneous curvature can be calculated and is found to be about -1/(240 nm) for a certain range of polymer concentrations. The nanotubes could also be retracted back into the mother vesicle by increasing the membrane tension via micropipette aspiration of the vesicle. Membrane tubes, which can form and be retracted easily, should be relevant for lipid storage in cells.

Long-circulating liposomal daptomycin enhances protection against systemic methicillin-resistant Staphylococcus aureus infection with improved therapeutic potential.

In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.

The antinociceptive and anti-alpha-glucosidase effects of glucosides from Hemiphragma heterophyllum Wall.

Hemiphragma heterophyllum Wall. is commonly used in traditional Yi herbal medicine for treating bellyache and toothache. In the current study, an unreported monoterpene glucoside, (S)-thymoquinol O-(6-O-oleuropeoyl)-ß-d-glucopyranoside (1), together with 11 known glucosides were obtained from the whole herb of H. heterophyllum. Their structures were determined based on a detailed analysis of spectroscopic data and acid hydrolysis and methanolysis reactions. Bioassay results showed that compounds 1 and 10 at 40 mg/kg exhibited significant antinociceptive activity in the acetic acid-induced writhing model, with inhibitions of 59.80% and 64.07%, respectively. Moreover, five of the isolates showed moderate anti-α-glucosidase activities with IC50 values ranging from 5.67 to 46.16 µM.

Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification.

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

A ferroptosis-reinforced nanocatalyst enhances chemodynamic therapy through dual H2O2 production and oxidative stress amplification.

The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H2O2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), ß-lapachone (a DNA topoisomerase inhibitor with H2O2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H2O2). HBGL can achieve rapid, continuous, and massive H2O2 and •OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment.