Enhancing diabetic wound healing through anti-bacterial and promoting angiogenesis using dual-functional slow-release microspheres-loaded dermal scaffolds.

Bacterial infections and the degeneration of the capillary network comprise the primary factors that contribute to the delayed healing of diabetic wounds. However, treatment modalities that cater to effective diabetic wounds healing in clinical settings are severely lacking. Herein, a dual-functional microsphere carrier was designed, which encapsulates polyhexamethylene biguanide (PHMB) or recombinant human vascular endothelial growth factor (rhVEGF) together. The in vitro release experiments demonstrated that the use of the microspheres ensured the sustained release of the drugs (PHMB or rhVEGF) over a period of 12 days. Additionally, the integration of these controlled-release microspheres into a dermal scaffold (DS-PLGA@PHMB/rhVEGF) imbued both antibacterial and angiogenic functions to the resulting material. Accordingly, the DS-PLGA@PHMB/rhVEGF scaffold exhibited potent antibacterial properties, effectively suppressing bacterial growth and providing a conducive environment for wound healing, thereby addressing the drawbacks associated with the susceptibility of rhVEGF to deactivation in inflammatory conditions. Additionally, the histological analysis revealed that the use of the DS-PLGA@PHMB/rhVEGF scaffold accelerated the process of wound healing by inhibiting inflammatory reactions, stimulating the production of collagen formation, and enhancing angiogenesis. This provides a novel solution for enhancing the antibacterial and vascularization capabilities of artificial dermal scaffolds, providing a beacon of hope for improving diabetic wound healing.

Exhaled VOC detection in lung cancer screening: a comprehensive meta-analysis.

BACKGROUND: Lung cancer (LC), characterized by high incidence and mortality rates, presents a significant challenge in oncology. Despite advancements in treatments, early detection remains crucial for improving patient outcomes. The accuracy of screening for LC by detecting volatile organic compounds (VOCs) in exhaled breath remains to be determined. METHODS: Our systematic review, following PRISMA guidelines and analyzing data from 25 studies up to October 1, 2023, evaluates the effectiveness of different techniques in detecting VOCs. We registered the review protocol with PROSPERO and performed a systematic search in PubMed, EMBASE and Web of Science. Reviewers screened the studies' titles/abstracts and full texts, and used QUADAS-2 tool for quality assessment. Then performed meta-analysis by adopting a bivariate model for sensitivity and specificity. RESULTS: This study explores the potential of VOCs in exhaled breath as biomarkers for LC screening, offering a non-invasive alternative to traditional methods. In all studies, exhaled VOCs discriminated LC from controls. The meta-analysis indicates an integrated sensitivity and specificity of 85% and 86%, respectively, with an AUC of 0.93 for VOC detection. We also conducted a systematic analysis of the source of the substance with the highest frequency of occurrence in the tested compounds. Despite the promising results, variability in study quality and methodological challenges highlight the need for further research. CONCLUSION: This review emphasizes the potential of VOC analysis as a cost-effective, non-invasive screening tool for early LC detection, which could significantly improve patient management and survival rates.

Association of weight-adjusted waist index with all-cause mortality among non-Asian individuals: a national population-based cohort study.

INTRODUCTION: The Weight-Adjusted Waist Index (WWI) is a new indicator of obesity that is associated with all-cause mortality in Asian populations. Our study aimed to investigate the linear and non-linear associations between WWI and all-cause mortality in non-Asian populations in the United States, and whether WWI was superior to traditional obesity indicators as a predictor of all-cause mortality. METHODS: We conducted a cohort study using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES), involving 18,592 participants. We utilized Cox proportional hazard models to assess the association between WWI, BMI, WC, and the risk of all-cause mortality, and performed subgroup analyses and interaction tests. We also employed a receiver operating characteristics (ROC) curve study to evaluate the effectiveness of WWI, BMI, and WC in predicting all-cause mortality. RESULTS: After adjusting for confounders, WWI, BMI, and WC were positively associated with all-cause mortality. The performance of WWI, BMI, and WC in predicting all-cause mortality yielded AUCs of 0.697, 0.524, and 0.562, respectively. The data also revealed a U-shaped relationship between WWI and all-cause mortality. Race and cancer modified the relationship between WWI and all-cause mortality, with the relationship being negatively correlated in African Americans and cancer patients. CONCLUSIONS: In non-Asian populations in the United States, there is a U-shaped relationship between WWI and all-cause mortality, and WWI outperforms BMI and WC as a predictor of all-cause mortality. These findings may contribute to a better understanding and prediction of the relationship between obesity and mortality, and provide support for effective obesity management strategies.

DHTPY-Cu@ZOL-Enhanced Photodynamic Therapy: A Strategic Platform for Advanced Treatment of Drug-Resistant Bacterial Wound Infections.

Purpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation. Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections. Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.

Organophosphate esters (OPEs) in corals of the South China Sea: Occurrence, distribution, and bioaccumulation.

Organophosphate esters (OPEs) have garnered significant attention in recent years. In view of the enormous ecosystem services value and severe degradation of coral reefs in the South China Sea, this study investigated the occurrence, distribution, and bioaccumulation of 11 OPEs in five coral regions: Daya Bay (DY), Weizhou Island (WZ), Sanya Luhuitou (LHT), Xisha (XS) Islands, and Nansha (NS) Islands. Although OPEs were detected at a high rate, their concentration in South China Sea seawater (1.56 ± 0.89 ng L-1) remained relatively low compared to global levels. All OPEs were identified in coral tissues, with Luhuitou (575 ± 242 ng g-1 dw) showing the highest pollution levels, attributed to intense human activities. Coral mucus, acting as a defense against environmental stresses, accumulated higher ∑11OPEs (414 ± 461 ng g-1 dw) than coral tissues (412 ± 197 ng g-1 dw) (nonparametric test, p < 0.05), and their compositional characteristics varied greatly. In the case of harsh aquatic environments, corals increase mucus secretion and then accumulate organic pollutants. Tissue-mucus partitioning varied among coral species. Most OPEs were found to be bioaccumulative (BAFs >5000 L kg-1) in a few coral tissue samples besides Triphenyl phosphate (TPHP). Mucus' role in the bioaccumulation of OPEs in coral shouldn't be ignored.

Occurrence, distribution, and sources of organophosphate esters (OPEs) in the air of the Indo-China Peninsula Based on a Passive Air Monitoring Network.

Organophosphate esters (OPEs) are a class of emerging and ubiquitous contaminants that are attracting increasing attention, and their large-scale use as flame retardants and plasticizers has led to their pervasive presence in the environment, although their broader impacts remain unknown. In this study, 11 OPEs were measured in the atmosphere of Southeast Asia and Southwest China during 2016. The ∑11OPEs were higher in this region (78.0-1670 pg/m3, mean 458 pg/m3) than in many remote areas, lower than in developed regions, and comparable to levels in many developing country cities. Generally, the ∑11OPEs were higher in urban (105-1670 pg/m3, mean 538 pg/m3) than in suburban (78.0-1350 pg/m3, mean 388 pg/m3). Seasonal variations of OPEs in the air were more pronounced in Cambodia and Laos, especially for Triphenyl Phosphate (TPHP). Seasonal variations of ∑11OPEs in most regions correspond to changes in temperature and rainfall. Biomass burning may be also a factor in facilitating OPE emissions from biomass materials or soil into the atmosphere of Southeast Asia. The random forest analysis showed that among these, rainfall had the greatest effect on the seasonal variation of atmospheric OPE concentrations, followed by biomass burning and temperature. The inter-regional variation of ∑11OPEs in Southeast Asia was related to population and economic development in each region. Airflow trajectories indicated that the OPEs in this region were mainly from local sources. The health risk assessment revealed that the inhalation exposure risks of OPEs to the residents in the study areas were very low during the sampling period, but may be increasing.

Associations of ethylene oxide exposure and "Life's Essential 8".

Ethylene oxide (EtO) is a widely used industrial chemical with recognized health risks. While its carcinogenic properties have been extensively studied, emerging evidence suggests potential associations with cardiovascular diseases. Using the recently introduced Life's Essential 8 (LE8) score as a comprehensive cardiovascular health (CVH) measure, this study aimed to elucidate the relationship between EtO exposure and CVH. Data from the National Health and Nutrition Examination Survey (NHANES) encompassing 3748 adults was analyzed. CVH was assessed using the LE8 score, which incorporates diet, physical activity, tobacco/nicotine exposure, sleep duration, BMI, non-HDL cholesterol, blood glucose, and blood pressure. The association between EtO exposure, gauged by Hemoglobin adduct (HbEtO) levels, and CVH was examined using linear regression and Cox regression models. An inverse relationship between EtO exposure and the overall CVH score was identified. Specifically, for every 1-unit increase in ln-transformed HbEtO, a 3.69-point decrease in the total CVH score was observed. An inverted J-shaped association between ln-transformed HbEtO and CVH score emerged, with an inflection point at 3.15 pmol/g Hb. Elevated EtO exposure was not significantly linked to all-cause mortality but was robustly associated with increased cardiovascular mortality. Elevated EtO exposure is negatively associated with CVH, as outlined by the LE8 metrics. Beyond a certain threshold, this association underscores the cardiovascular risks of EtO exposure and highlights the importance of further research to determine underlying mechanisms and recommend preventive strategies.

Long non-coding HOXA-AS3 contributes to osteosarcoma progression through the miR-1286/TEAD1 axis.

Long non-coding RNA (lncRNA) HOXA cluster antisense RNA 3 (HOXA-AS3) regulates the progression of several types of human malignancy. However, the role and potential mechanism of HOXA-AS3 in osteosarcoma (OS) remain unknown. In this study, upregulation of HOXA-AS3 was observed in OS tissues and cell lines and associated with poor clinical outcomes. Silencing of HOXA-AS3 significantly inhibited the proliferation, migration and invasion of OS cells in vitro and suppressed the tumorigenesis of OS cells in vivo. Furthermore, knockdown of HOXA-AS3 inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and epithelial-to-mesenchymal transition (EMT) in OS. Further investigation of this mechanism revealed that HOXA-AS3 could directly upregulate the expression of TEAD1 via its competing endogenous RNA (ceRNA) activity on miR-1286. This study clarified the oncogenic roles of the HOXA-AS3/miR-1286/TEAD1 axis in OS progression, suggesting a novel therapeutic target for OS.

Hierarchical helical carbon nanotube fibre as a bone-integrating anterior cruciate ligament replacement.

High rates of ligament damage require replacements; however, current synthetic materials have issues with bone integration leading to implant failure. Here we introduce an artificial ligament that has the required mechanical properties and can integrate with the host bone and restore movement in animals. The ligament is assembled from aligned carbon nanotubes formed into hierarchical helical fibres bearing nanometre and micrometre channels. Osseointegration of the artificial ligament is observed in an anterior cruciate ligament replacement model where clinical polymer controls showed bone resorption. A higher pull-out force is found after a 13-week implantation in rabbit and ovine models, and animals can run and jump normally. The long-term safety of the artificial ligament is demonstrated, and the pathways involved in integration are studied.

UvATG6 Interacts with BAX Inhibitor 1 Proteins and Plays Critical Roles in Growth, Conidiation, and Virulence in Ustilaginoidea virens.

Autophagy and apoptosis are evolutionarily conserved catabolic processes involved in regulating development and cellular homeostasis. Bax inhibitor 1 (BI-1) and autophagy protein 6 (ATG6) perform essential functions in these roles, such as cellular differentiation and virulence in various filamentous fungi. However, the functions of ATG6 and BI-1 proteins in development and virulence in the rice false smut fungus Ustilaginoidea virens are still poorly understood. In this study, UvATG6 was characterized in U. virens. The deletion of UvATG6 almost abolished autophagy in U. virens and reduced growth, conidial production and germination, and virulence. Stress tolerance assays showed that UvATG6 mutants were sensitive to hyperosmotic, salt, and cell wall integrity stresses but were insensitive to oxidative stress. Furthermore, we found that UvATG6 interacted with UvBI-1 or UvBI-1b and suppressed Bax-induced cell death. We previously found that UvBI-1 could suppress Bax-induced cell death and was a negative regulator of mycelial growth and conidiation. Unlike UvBI-1, UvBI-1b could not suppress cell death. UvBI-1b-deleted mutants exhibited decreased growth and conidiation, while the UvBI-1 and UvBI-1b double deletion reduced the phenotype, indicating that UvBI-1 and UvBI-1b antagonistically regulate mycelial growth and conidiation. In addition, the UvBI-1b and double mutants exhibited decreased virulence. Our results provide evidence of the cross talk of autophagy and apoptosis in U. virens and give clues for studying other phytopathogenic fungi. IMPORTANCE Ustilaginoidea virens causes destructive panicle disease in rice, significantly threatening agricultural production. UvATG6 is required for autophagy and contributes to growth, conidiation, and virulence in U. virens. Additionally, it interacts with the Bax inhibitor 1 proteins UvBI-1 and UvBI-1b. UvBI-1 suppresses cell death induced by Bax, unlike UvBI-1b. UvBI-1 negatively regulates growth and conidiation, while UvBI-1b is required for these phenotypes. These results indicate that UvBI-1 and UvBI-1b may antagonistically regulate growth and conidiation. In addition, both of them contribute to virulence. Additionally, our results suggest cross talk between autophagy and apoptosis, contributing to the development, adaptability, and virulence of U. virens.

Dietary fiber intake associated with risk of rheumatoid arthritis among U.S. adults: NHANES 2010-2020.

Rheumatoid arthritis (RA) is a prevalent inflammatory joint disease that imposes a significant medical burden and morbidity. Recent scientific evidence suggests that dietary components and patterns could be associated with RA risk. In this study, we aim to investigate the possible relationship between dietary fiber intake and RA risk. We included 15,114 participants from the 2010 to 2020 National Health and Nutrition Examination Survey database in our study. Participants aged 20 or above were categorized into those with and without RA. Univariate logistic regression analysis and multivariate regression models were used to test the association between dietary fiber intake, high-sensitivity C-reactive protein, and RA. Out of all the participants, 1053 were diagnosed with RA (6.97%). Multivariate logistic regression analysis indicated that fiber intake was negatively associated with high-sensitivity c-reactive protein (-0.09 [-0.18, -0.02]) and RA risk (0.99 [0.98, 0.99]). Furthermore, our sensitivity analysis suggested that individuals with higher fiber intake (>19.1 g/day) had a 25% lower risk of developing RA than those with lower fiber intake [0.75 (0.63, 0.88)]. Our findings suggest that higher dietary fiber intake is associated with a reduced risk of RA and may help reduce systemic inflammation, thereby potentially slowing down RA progression.

Superficial Circumflex Iliac Artery Perforator Flap with Bilobed Design for the Donor Defect after Wrap-Around Flap Transfer Reconstruction.

OBJECTIVE: The repair of great toe donor site defect after wrap-around flap transfer is still controversial. The bilobed superficial circumflex iliac artery perforator (SCIP) flap can improve the aesthetics of the great toe while maintaining its function. Thus, this study aimed to report our experience in the reconstruction of big toe donor site defects with the bilobed SCIP flap and describe the clinical outcomes. METHODS: This study was a retrospective trial. From May 2017 to May 2020, 13 patients with the great toe donor site defect after wrap-around flap transfer were included in this study. The average age of the patients was 44 years (range, 23-60 years). All patients received free bilobed SCIP flaps to reconstruct the donor site defect of the great toe. Relevant clinical features were recorded preoperatively. The thickness and design of the SCIP flap and the harvesting layer of the flap were measured during the operation. The survival rate of flaps and skin grafts and the incidence of infection were recorded after operation. At follow-up, donor site complications and postoperative outcomes were evaluated. RESULTS: In all cases, the SCIP flap covering the donor site of the great toe survived. All patients were followed up for 24-40 months (mean, 30.5 months). The average thickness of the SCIP flap was 0.38cm. All SCIP flaps were harvested from the superficial fascial layer except for three obese patients. The thin SCIP flap had a bilobed design with no further defatting procedures. Postoperatively, the great toe-nail flap donor site regained its original appearance without bloating or flap necrosis. There was a hidden linear scar in the groin donor site, which did not affect hip joint movement. All patients were satisfied with the aesthetics of the surgical site. CONCLUSION: The SCIP flap with bilobed design for repairing the donor defect of the great toe after wrap-around flap transfer is a kind of surgical method with excellent contour, meeting the requirements of function and aesthetics.

A Novel Bifunctional Nanoplatform with Aggregation-Induced Emission Property for Efficient Photodynamic Killing of Bacteria and Wound Healing.

Background: Photodynamic antimicrobial therapy (PDAT) has been extensively studied because of its potential applications such as precise controllability, high spatiotemporal accuracy, and non-invasiveness. More importantly, it is difficult for bacteria to develop resistance to the aforementioned PDATs. However, the selectivity of traditional PDAT methods to bacteria is generally poor, so it has been proposed to introduce positively charged components such as quaternary ammonium salts to enhance the targeting of bacteria; however, they always possess high toxicity to normal cells. As a result, measures should be taken to enhance the targeting of bacteria and avoid side effects on normal cells. Methods and Results: In our work, we creatively design a nanoplatform with high anti-bacterial efficiency, low side effects and its size is approximately 121 nm. BSA, as a nanocarrier, encapsulates the photosensitizer (E)-4-(4-(diphenylamino)styryl)-1-methylpyridin-1-ium with AIE properties named as BSA-Tpy, which increases its circulation time in vivo and improves the biocompatibility. Under acidic conditions (pH = 5.0), the surface positive charge of the BSA-Tpy is increased to +18.8 mV due to protonation of amine residues to achieve the targeting effect on bacteria. Besides, under the irradiation of white light, the BSA-Tpy will produce ROS to kill bacteria efficiently about 99.99% for both Gram-positive and Gram-negative bacteria, which shows the potential application value for the treatment of infected wounds. Conclusion: We have developed a feasible method for photodynamic antibacterial therapy, possessing excellent biocompatibility and high antibacterial efficiency with good fluorescence imaging property.

The Relationship Between Ferroptosis and Diseases.

Ferroptosis is an iron-dependent mode of cell death. It can occur through two major pathways, exogenous (or transporter-dependent) and endogenous (or enzyme-regulated) pathways are activated by biological or chemical inducers, and glutathione peroxidase activity is inhibited, which causes intracellular iron accumulation and lipid Peroxidation. Ferroptosis is closely related to the pathological process of many diseases. How to intervene in the occurrence and development of related diseases by regulating ferroptosis has become a hot research topic. At present, studies have shown that ferroptosis is found in common diseases such as tumors, inflammatory diseases, bacterial infections, pulmonary fibrosis, hepatitis, inflammatory bowel disease, neurodegenerative diseases, kidney injury, ischemia-reperfusion injury and skeletal muscle injury. This article reviews the characteristics and mechanism of ferroptosis, and summarizes how ferroptosis participates in the pathophysiological process in various systemic diseases of the body, which may provide new references for the treatment of clinical diseases in the future.

Relationship between nonalcoholic fatty liver disease and bone mineral density in adolescents.

Liver metabolism is strongly linked to bone metabolism, and a significant correlation between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) in adults has been demonstrated. However, the current relationship between NAFLD and BMD in the adolescent population remains controversial. The purpose of this study was to investigate the specific relationship between NAFLD and BMD in adolescents aged 12 to 19 years in the United States. The quantitative relationship between NAFLD and total BMD was investigated using multivariate logistic regression and smoothed fitted curve curves based on multiperspective data from the National Health and Nutrition Examination Survey (NHANES). A total of 740 adolescents were included in this study after excluding unusable samples. The results showed that NAFLD was positively associated with total BMD in adolescents. The results of the subgroup analysis showed that this positive association was mainly found in boys, whites and blacks. The association was not significant in girls, Mexican Americans and other racial groups. Among US adolescents, there was a significant positive association between NAFLD and total BMD, and this relationship varied by gender and race.

Application of nanosonosensitizer materials in cancer sono-dynamic therapy.

Sonodynamic therapy (SDT) is a novel non-invasive treatment for cancer combining low-intensity ultrasound and sonosensitizers. SDT activates sonosensitizers through ultrasound, releasing energy and generating reactive oxygen species to kill tumor cells. Compared with traditional photodynamic therapy (PDT), SDT is a promising anti-cancer therapy with the advantages of better targeting, deeper tissue penetration, and higher focusing ability. With the development and broad application of nanomaterials, novel sonosensitizers with tumor-targeting specificity can deliver to deep tumors and enhance the tumor microenvironment. In this review, we first review the mechanisms of sonodynamic therapy. In addition, we also focus on the current types of sonosensitizers and the latest design strategies of nanomaterials in sonosensitizers. Finally, we summarize the combined strategy of sonodynamic therapy.

Saturation Effect of Body Mass Index on Bone Mineral Density in Adolescents of Different Ages: A Population-Based Study.

Background: Adolescence is a critical period for bone development, and peak bone mass may be reached in late adolescence. Boosting bone accumulation at this time can help preserve adult bone health and avoid osteoporosis later in life. Body mass index (BMI) has been found to have a favorable impact on bone mineral density (BMD) in previous research. However, excessive obesity is harmful to health and may lead to various systemic diseases. Therefore, finding an appropriate BMI to maintain a balance between obesity and BMD is critical for adolescents. Methods: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between BMI and BMD. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Subgroup analyses were then conducted based on gender and age. Results: This population-based study included a total of 6,143 adolescents aged 8-19 years. In a multivariate linear regression analysis, a good association between BMI and total BMD was shown [0.014 (0.013, 0.014)]. This positive association was maintained in all subgroup analyses grouped by sex and age. Furthermore, the association between BMI and BMD was nonlinear with a saturation point present, as evidenced by smoothed curve fitting. According to the threshold effect study, with an age group of two years, adolescents of different ages had different BMI saturation values with respect to BMD. Conclusions: Our study showed a significant positive and saturated association between BMI and BMD in adolescents aged 8-19 years. Maintaining BMI at saturation values may reduce other adverse effects while achieving optimal BMD.

Myocardin suppression increases lipid retention and atherosclerosis via downregulation of ABCA1 in vascular smooth muscle cells.

Myocardin (MYOCD) plays an important role in cardiovascular disease. However, its underlying impact on atherosclerosis remains to be elucidated. ATP binding cassette transporter A1 (ABCA1), a key membrane-associated lipid transporter which maintains intracellular lipid homeostasis, has a protective function in atherosclerosis progress. The purpose of this study was to investigate whether and how the effect of MYOCD on atherosclerosis is associated with ABCA1 in vascular smooth muscle cells (VSMCs). We found both MYOCD and ABCA1 expression were dramatically decreased in atherosclerotic patient aortas compared to control. MYOCD knockdown inhibited ABCA1 expression in human aortic vascular smooth muscle cells (HAVSMCs), leading to reduced cholesterol efflux and increased intracellular cholesterol contents. MYOCD overexpression exerted the opposite effect. Mechanistically, MYOCD regulates ABCA1 expression in an SRF-dependent manner. Consistently, apolipoprotein E-deficient mice treated with MYOCD shRNA developed more plaques in the aortic sinus, which is associated with reduced ABCA1 expression, increased cholesterol retention in the aorta, and decreased high-density lipoprotein cholesterol levels in the plasma. Our data suggest that MYOCD deficiency exacerbates atherosclerosis by downregulating ABCA1 dependent cholesterol efflux from VSMCs, thereby providing a novel strategy for the therapeutic treatment of atherosclerotic cardiovascular disease.

A fiber-shaped neural probe with alterable elastic moduli for direct implantation and stable electronic-brain interfaces.

Researchers developing implantable neural probes face a dilemma. Rigid neural probes facilitate direct implantation, but the brain tissue suffers from a vulnerable interface and a strong neuroinflammatory response due to mechanical mismatch between the probe and the brain tissue. Flexible neural probes offer stable interfaces and eliminate neuroinflammatory responses but require auxiliary implantation. Here, we have created a new kind of micro fiber-shaped neural probe with alterable elastic moduli before and after implantation. Carbon nanotube fibers and calcium crosslinked sodium alginate functioned as the core electrode and sheath layer, respectively. The response of calcium crosslinked sodium alginate to water will alter the probe elastic moduli from ∼10 GPa to ∼10 kPa post implantation, which is close to the elastic modulus of brain tissue. The micro fiber probes were directly implanted into mouse brains without any additional materials. After implantation, they became soft and offered dynamically adaptable interfaces with a reduced inflammatory response, benefiting long-term monitoring of neuron signals. Continuous four week monitoring of neuron signals was achieved. The simplicity of the strategy makes it suitable for versatile neuron techniques in neuron recording and modulation.

Functionalized helical fibre bundles of carbon nanotubes as electrochemical sensors for long-term in vivo monitoring of multiple disease biomarkers.

Mechanical mismatches between implanted electronics and biological tissues can lead to inaccurate readings and long-term tissue damage. Here, we show that functionalized multi-walled carbon nanotubes twisted into helical fibre bundles that mimic the hierarchical structure of muscle can monitor multiple disease biomarkers in vivo. The flexible fibre bundles are injectable, have a low bending stiffness and display ultralow stress under compression. As proof-of-concept evidence of the sensing capabilities of these fibre bundles, we show that the fibre bundles enable the spatially resolved and real-time monitoring of H2O2 when implanted in tumours in mice, and that they can be integrated with a wireless transmission system on an adhesive skin patch to monitor calcium ions and glucose in the venous blood of cats for 28 d. The versatility of the helical fibre bundles as chemically functionalized electrochemical sensors makes them suitable for multiple sensing applications in biomedicine and healthcare.