Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Advances in Synthesis and Applications of Single-Atom Catalysts for Metal Oxide-Based Gas Sensors.

As a stable, low-cost, environment-friendly, and gas-sensitive material, semiconductor metal oxides have been widely used for gas sensing. In the past few years, single-atom catalysts (SACs) have gained increasing attention in the field of gas sensing with the advantages of maximized atomic utilization and unique electronic and chemical properties and have successfully been applied to enhance the detection sensitivity and selectivity of metal oxide gas sensors. However, the application of SACs in gas sensors is still in its infancy. Herein, we critically review the recent advances and current status of single-atom catalysts in metal oxide gas sensors, providing some suggestions for the development of this field. The synthesis methods and characterization techniques of SAC-modified metal oxides are summarized. The interactions between SACs and metal oxides are crucial for the stable loading of single-atom catalysts and for improving gas-sensitive performance. Then, the current application progress of various SACs (Au, Pt, Cu, Ni, etc.) in metal oxide gas sensors is introduced. Finally, the challenges and perspectives of SACs in metal oxide gas sensors are presented.

NR2F6 is essential for brown adipocyte differentiation and systemic metabolic homeostasis.

OBJECTIVE: Brown adipose tissue (BAT) development and function are essential for maintaining energy balance. However, the key factors that specifically regulate brown adipogenesis require further identification. Here, we demonstrated that the nuclear receptor subfamily 2 group F member 6 (NR2F6) played a pivotal role in brown adipogenesis and energy homeostasis. METHODS: We examined the differentiation of immortalized brown adipocytes and primary brown adipocytes when NR2F6 were deleted, and explored the mechanism through which NR2F6 regulated adipogenesis using ChIP-qPCR in vitro. Male wild type (WT) and Pdgfra-Cre-mediated deletion of Nr2f6 in preadipocytes (NR2F6-PKO) mice were fed with high fat diet (HFD) for 12 weeks, and adiposity, glucose intolerance, insulin resistance and inflammation were assessed. RESULTS: NR2F6 exhibited abundant expression in BAT, while its expression was minimal in white adipose tissue (WAT). Within BAT, NR2F6 was highly expressed in preadipocytes, experienced a transient increase in the early stage of brown adipocyte differentiation, and significantly decreased in the mature adipocytes. Depletion of NR2F6 in preadipocytes inhibited brown adipogenesis, caused hypertrophy of brown adipocytes, and impaired thermogenic function of BAT, but without affecting WAT development. NR2F6 transcriptionally regulated PPARγ expression to promote adipogenic process in brown adipocytes. Loss of NR2F6 in preadipocytes led to increased susceptibility to diet-induced metabolic disorders. CONCLUSIONS: Our findings unveiled NR2F6 as a novel key regulator of brown adipogenesis, potentially opening up new avenues for maintaining metabolic homeostasis by targeting NR2F6.

Modulation of microglial polarization by sequential targeting surface-engineered exosomes improves therapy for ischemic stroke.

Microglia are important cells that act on regulating neuroinflammation and neurofunction after the induction of ischemic stroke (IS). Consequently, the efficient accumulation of drugs within ischemic regions, particularly in microglia, serves as a valuable approach for achieving effective therapy by attenuating microglia-mediated cerebral ischemic injury. In this study, we designed mannose (man)-conjugated luteolin (lut)-loaded platelet-derived exosomes (lut/man-pEXO) as surface engineered multifunctional cascade-delivery drug carriers to target ischemic blood vessels and subsequent microglia to enhance drug accumulation and induce neuroprotection of neurovascular unit (NVU) against IS. The results revealed that as platelets naturally gathered in pathological ischemic cerebral vessels, lut/man-pEXO could bind to platelets and efficiently target ischemic injury sites. Moreover, owing to the selective binding affinity of mannose present in lut/man-pEXO towards the mannose receptor expressed on microglia, lut/man-pEXO exhibited superior microglia-targeting properties, inducing the increased uptake of lut by microglia. As a result, lut/man-pEXO regulated microglia by inhibiting the activation of detrimental M1 and promoting the transition towards the anti-inflammatory type (M2), thus attenuating ischemic damage of NVU by reducing the infarct area, rescuing the damage of blood-brain barrier (BBB) and preventing inflammatory transformation of astrocytes.

Tumor targeted cancer membrane-camouflaged ultra-small Fe nanoparticles for enhanced collaborative apoptosis and ferroptosis in glioma.

Glioma is recognized as the most common and aggressive primary brain tumor in adults. Owing to the occurrence of drug resistance and the failure of drug to penetrate the blood-brain barrier (BBB), there is no effective strategy for the treatment of glioma. The main objective of this study was to develop a biomimetic glioma C6 cell membrane (C6M) derived nanovesicles (DOX-FN/C6M-NVs) loaded with doxorubicin (DOX) and ultra-small Fe nanoparticles (FN) for accomplishing the effective brain tumor-targeted delivery of DOX and improving anti-cancer efficacy via inducing collaborative apoptosis and ferroptosis. The findings revealed that employing C6M-NVs as a carrier significantly improved the therapeutic efficacy by enabling evasion of immune surveillance, facilitating targeted drug delivery to tumor sites, and minimizing cardiotoxicity and adverse effects associated with DOX. DOX-FN/C6M-NVs exhibited more potent anti-tumor effects as compared with free DOX by promoting DOX-mediated apoptosis and accelerating ferroptosis via the mediation of FN. This study suggested that DOX-FN/C6M-NVs as the potential inducer of ferroptosis and apoptosis conferred effective tumor suppression in the treatment of glioma.

CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes.

Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1ß, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.

Dual Improvement in Sensitivity and Humidity Tolerance of a NO2 Sensor Based on 3-Aminopropyltriethoxysilane Self-Assembled Monolayer-Functionalized SnSe2 for Explosive Photolysis Gas Detection.

Explosives can be analyzed for their content by detecting the photolytic gaseous byproducts. However, to prevent electrostatic sparking, explosives are frequently preserved in conditions with low temperatures and high humidity, impeding the performance of gas detection. Thus, it has become a research priority to develop gas sensors that operate at ambient temperature and high humidity levels in the realm of explosive breakdown gas-phase detection. In this work, 3-aminopropyltriethoxysilane (APTES) self-assembled monolayer-functionalized tin diselenide (APTES-SnSe2) nanosheets were synthesized via a facile solution stirring strategy, resulting in a room-temperature NO2 sensor with improved sensitivity and humidity tolerance. The APTES-SnSe2 sensor with moderate functionalization time outperforms the pure SnSe2 sensor in terms of the response value (317.51 vs 110.98%) and response deviation (3.11 vs 24.13%) under humidity interference to 500 ppb NO2. According to density functional theory simulations, the stronger adsorption of terminal amino groups of the APTES molecules to NO2 molecules and stable adsorption energy in the presence of H2O are the causes of the improved sensing capabilities. Practically, the APTES-SnSe2 sensor achieves accurate detection of photolysis gases from trace nitro explosives octogen, pentaerythritol tetranitrate, and trinitrotoluene at room temperature and various humidity levels. This study provides a potential strategy for the construction of gas sensors with high responsiveness and antihumidity capabilities to identify explosive content in harsh environments.

Preparation of Ultra-Small Copper Nanoparticles-Loaded Self-Healing Hydrogels with Antibacterial, Inflammation-Suppressing and Angiogenesis-Enhancing Properties for Promoting Diabetic Wound Healing.

Background: Bacterial invasion, protracted inflammation, and angiogenesis inhibition are hallmarks of chronic diabetic wounds, bringing about patient morbidity and rising healthcare costs. For such wounds, there are currently few efficient therapies available. Methods: We reported the development of carboxymethyl chitosan (CMCS)-based self-healing hydrogel loaded with ultra-small copper nanoparticles (Cunps) for local treatment of diabetic wound healing. The structure of Cunps was identified by XRD, TEM, XPS and other methods, and the characterization of the synthesized Cunps-loaded self-healing carboxymethyl chitosan (CMCS)-protocatechualdehyde (PCA) hydrogel (Cunps@CMCS-PCA hydrogel) was further investigated. The therapeutic effect of Cunps@CMCS-PCA hydrogel in diabetic wound healing was explored in vitro and in vivo. Results: The findings showed that a kind of ultra-small size copper nanoparticles with excellent biocompatibility was prepared. CMCS was chemically conjugated to PCA to form self-healing hydrogels via the formation of an amide bond followed by the loading of ultra-small copper nanoparticles. The obtained Cunps@CMCS-PCA hydrogel showed a typical three-dimensional interlinked network structure with self-healing ability and porosity. It exhibited good biocompatibility in diabetic wounds. Furthermore, Cunps@CMCS-PCA hydrogel group significantly prevented bacterial growth in the skin wound of diabetic rats as compared to model group and CMCS-PCA hydrogel-treated group. After 3 days, no visible bacterial proliferation was observed. It also increased angiogenesis through Cunps mediated activation of ATP7A to prevent induction of autophagy. Furthermore, Cunps@CMCS-PCA hydrogel mainly depended on PCA-induced inhibition on inflammation of macrophage via JAK2/STAT3 signaling pathway. As a result, compared with delayed wound healing process with lower wound healing rate valued at 68.6% within 7 days in the model group, Cunps@CMCS-PCA significantly accelerated wound healing recovery and increased wound healing rate to 86.5%, suggesting that Cunps@CMCS-PCA hydrogel effectively accelerated wound healing. Conclusion: Cunps@CMCS-PCA hydrogel offered a new therapeutic approach for quickening diabetic wound healing.

Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves' disease in children.

The aim of this study was to systematically evaluate the correlation between the rs231775 locus polymorphism in the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene and genetic susceptibility to Graves' disease (GD) in children. Some studies found that the CTLA-4 gene polymorphism was associated with GD in children. The data up to February 2022 were retrieved from the databases. Stata 15.0 software was used for meta-analysis. A total of seven studies were included in our research. The results of the meta-analysis showed that the rs231775 locus polymorphism in the CTLA-4 gene in general and Asian populations was correlated with children's susceptibility to GD (A vs G: OR = 0.75, 95% CI (0.660-0.86); GG vs AA: OR = 1.34, 95% CI (1.04-1.73); AG vs AA: OR = 1.32, 95% CI (1.02-1.10); AG + GG vs AA: OR = 3.81, 95% CI (2.17-6.70); GG vs AA + AG: OR = 1.23, 95% CI (1.05-1.45)). In summary, the rs231775 locus polymorphism in the CLTA-4 gene may be a risk factor for GD in Asian children. The G allele may be a susceptibility factor, while the allele A may be a protective factor against GD in Asian children. In the future, more large-scale studies may be needed to verify our results.

Biomimetic oxygen-boosted hybrid membrane nanovesicles as the treatment strategy for ischemic stroke with the concept of the neurovascular unit.

The pathogenesis of ischemic cerebrovascular disease has revealed that ischemic stroke often leads to deprivation of oxygen, blood-brain barrier (BBB) damage and enhanced inflammatory activation, eventually causing severe brain tissue damage. Herein, we prepared hybrid membrane nanovesicles (YC-1@[RBC-PL] NVs) composed of red blood cell (RBC) membrane and platelet (PL) membrane encapsulating hypoxia inducible factor-1α (HIF-1α) inhibitor YC-1 for contributing to the protection of the neurovascular unit (NVU) in ischemic stroke. YC-1@[RBC-PL] NVs targeted the ischemic brain by the thrombus targeting properties of PL membrane and relieved the hypoxia inside ischemic brain in the presence of YC-1 and catalase in YC-1@[RBC-PL] NVs. Finally, YC-1@[RBC-PL] NVs attenuated ischemic injury to NVU by reducing infarct volume, preserving BBB integrity, and blocking activation of astrocyte and microglia in a middle cerebral artery occlusion/reperfusion (MCAO/R) model.

[Functionalized exosome-loaded ginsenoside Rg1 for the treatment of ischemic stroke].

The aim of this study was to investigate the therapeutic effects and potential mechanism of c(RGDyK) peptide modified mesenchymal stem cell exosomes loaded with ginsenoside Rg1 (G-Rg1) on ischemic stroke. Thread-tying method was used to establish SD rats transient middle cerebral occlusion model (tMCAO). The model rats were randomly divided into tMCAO group, Exo group, free G-Rg1 group, Exo-Rg1 group and cRGD-Exo-Rg1 group, and sham group was used as control. The infarct volume was measured by 2, 3, 5-triphenyltetrachloride (TTC) staining, the changes of neuron and endothelium were observed by immunofluorescence, and the expression of related proteins was detected by Western blotting. The results showed that cRGD-Exo-Rg1 up-regulated the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIF-1α) by activating PI3K/AKT pathway, thus promoting angiogenesis and neurogenesis, effectively reducing the volume of cerebral infarction and improving neural function. In addition, the delivery of cRGD-Exo-Rg1 to ischemic brain tissue up-regulated the expression of occludin and claudin-5, and reduced the injury of blood-brain barrier. Taken together, cRGD-Exo-Rg1 was effective in the treatment of ischemic stroke by promoting angiogenesis and neurogenesis, which provided experimental evidence for the potential clinical benefits of other neuroprotective therapies.

Clusterbody Enables Flow Sorting-Assisted Single-Cell Mass Spectrometry Analysis for Identifying Reversal Agent of Chemoresistance.

Identifying effective reversal agents overcoming multidrug resistance with causal mechanisms from an efflux pump protein is of vital importance for enhanced tumor chemotherapy in clinic. To achieve this end, we construct a metal cluster-based probe, named clusterbody, to develop flow sorting-assisted single-cell mass spectrometry analysis. This clusterbody synthesized by biomimetic mineralization possesses an antibody-like property to selectively recognize an efflux pump protein. The intrinsic red fluorescence emission of the clusterbody facilitates fluorescence-activated high-throughput cell sorting of subpopulations with different multidrug resistance levels. Furthermore, based on the accurate formula of the clusterbody, the corresponding protein abundance at the single-cell level is determined through detecting gold content via precise signal amplification by laser ablation inductively coupled plasma mass spectrometry. Therefore, the effect of reversal agent treatment overcoming multidrug resistance is evaluated in a quantitative manner. This work opens a new avenue to identify reversal agents, shedding light on developing combined or synergetic tumor therapy.

Ratiometric detection of polymyxin B based on the disaggregation of pyrenyl nanoassemblies in 100% aqueous media.

Polymyxin B (PMB) was an antibiotic with highly effective antibacterial effect but narrow safety interval, and its residues in food had attracted widespread attention. It was important to develop an accurate method for the rapid detection of PMB in animal foods. In this work, we had established a ratiometric sensing system based on the formation of supramolecular assemblies of pyrenyl probes, which were driven by the synergy of noncovalent forces such as multiple-electrostatic and π-π stacking interactions. Compared with the traditional fluorescence detection based on the single wavelength change, the present approach showing two-wavelength fluorescence response could reduce the interference of other factors making the experimental results more accurate. The sensor exhibited high sensitivity and selectivity with a low detection limit (28.3 nM). This method could be used to realize visual detection and had a visual detection limit of 1 µM. As we had learned yet, this was the first ratiometric sensor for PMB detection in aqueous solution. We believed all our preliminary would not only provide a complementary strategy for the detection of PMB, but also develop some new ideas for the construction of sensors for rapid antibiotic detection.

SYSTEMATIC SKILL PRACTICE IN WOMEN's FLOOR EXERCISE / Prática sistemática de habilidades no exercício de solo feminino / Práctica sistemática de habilidades en el ejercicio de suelo femenino

ABSTRACT Introduction Ground exercise is a high-level event of Chinese women's gymnastics. Maintaining the dominant strength of women's floor exercise in China has become one of the issues that coaches, athletes and gymnastics researchers should actively discuss. A research analysis on athletes' competition in the National Games can better reflect and illustrate the fundamental level of athletes and their overall developmental status. Objective To verify the relationship between women's floor exercise skills and competition performance. Methods The analysis and study of 65 female athletes participating in floor exercises at the National Games was carried out. In this paper, the on-the-spot statistical method is used to perform statistics on the skills and the athletes' completion in the four games. Movement training and choreography experts were consulted. Results The performance of women's floor drills in the National Games was discussed from three aspects: the difficulty and arrangement of movements, the initial score and bonus points, and the completion of movements. Conclusion Most athletes can adapt to the changes in the new rules and master many complex movements. This also gets them a higher score. However, the choreography of the athletes' complete movements is relatively simple and lacks features. Strength training in the lower limbs should be the key to improving the athletes' ability in floor exercise. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O exercício no solo é um evento de alto nível da ginástica feminina chinesa. Manter a força dominante do exercício físico feminino na China tornou-se uma das questões que treinadores, atletas e pesquisadores de ginástica devem discutir ativamente. Uma análise de pesquisa sobre a competição dos atletas nos Jogos Nacionais pode refletir e ilustrar melhor o nível fundamental dos atletas e seu status geral de desenvolvimento. Objetivo Verificar a relação entre as habilidades de exercício do solo feminino e o desempenho na competição. Métodos Foi efetuada a análise e estudo de 65 atletas femininas que participam de exercícios de solo nos Jogos Nacionais. Neste trabalho, o método estatístico no local é utilizado para realizar estatísticas sobre as habilidades e a conclusão dos atletas nos quatro jogos. Foram consultados especialistas em treino de movimento e coreografia. Resultados Discutiu-se o desempenho dos exercícios de piso feminino nos Jogos Nacionais a partir de três aspectos: a dificuldade e a disposição dos movimentos, a pontuação inicial e os pontos de bônus, e a conclusão dos movimentos. Conclusão A maioria dos atletas pode se adaptar às mudanças nas novas regras e dominar muitos movimentos complexos. Isto também obtém uma pontuação mais alta. Entretanto, a coreografia dos movimentos completos dos atletas é relativamente simples e carece de características. O treinamento da força nos membros inferiores deve ser a chave para melhorar a habilidade das atletas no exercício do solo. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El ejercicio en el suelo es una prueba de alto nivel de la gimnasia femenina china. Mantener la fuerza dominante del ejercicio de suelo femenino en China se ha convertido en una de las cuestiones que entrenadores, atletas e investigadores de la gimnasia deben debatir activamente. Un análisis de la investigación sobre la competición de los atletas en los Juegos Nacionales puede reflejar e ilustrar mejor el nivel fundamental de los atletas y su estado de desarrollo general. Objetivo Verificar la relación entre las habilidades del ejercicio de suelo de las mujeres y el rendimiento en la competición. Métodos Se llevó a cabo el análisis y estudio de 65 atletas femeninas que participaron en ejercicios de suelo en los Juegos Nacionales. En este trabajo se utiliza el método estadístico in situ para realizar estadísticas sobre las habilidades y la realización de los atletas en los cuatro partidos. Se consultó a expertos en formación del movimiento y coreografía. Resultados El rendimiento de los ejercicios de suelo de las mujeres en los Juegos Nacionales se analizó desde tres aspectos: la dificultad y la disposición de los movimientos, la puntuación inicial y los puntos de bonificación, y la finalización de los movimientos. Conclusión La mayoría de los atletas pueden adaptarse a los cambios de las nuevas reglas y dominar muchos movimientos complejos. Esto también obtiene una mayor puntuación. Sin embargo, la coreografía de los movimientos completos de los atletas es relativamente simple y carece de características. El entrenamiento de la fuerza en los miembros inferiores debe ser la clave para mejorar la capacidad de los atletas en el ejercicio de suelo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

M1 Microglia Induced Neuronal Injury on Ischemic Stroke via Mitochondrial Crosstalk between Microglia and Neurons.

Among the middle-aged and senile populations, ischemic stroke (IS) is a frequently occurring acute condition of the cerebrovascular system. Traditionally, it is recognized that when stroke occurs, microglia are activated into M1 phenotype and release cytotoxic cytokines, reactive oxygen species, proteases, and other factors, thus exacerbating the injury by further destroying or killing nearby neurons. In the latest research, the crucial role of the intercellular mitochondrial crosstalk on the stroke management has been demonstrated. Therefore, we tried to clarify mitochondrial crosstalk between microglia and neurons, and evaluated M1 microglial mitochondria-mediated neurological performance in transient middle cerebral artery occlusion (tMCAO) rats. We found that when microglia was activated into the proinflammatory M1 type after stroke, mitochondrial fission process was accelerated, and damaged mitochondria were released, further transferred to neurons and fused with neuronal mitochondria. As a result, the function of neuronal mitochondria was damaged by decreasing adenosine triphosphate (ATP), mitochondria membrane potential, and increasing excessive reactive oxygen species (ROS), thus inducing mitochondria-mediated neuronal death and finally aggravating ischemia injury. Taken together, it provides a novel neuroglial crosstalk mechanism at the mitochondrial level.

Synergistic Effect of Reactive Oxygen Species in Photothermocatalytic Removal of VOCs from Cooking Oil Fumes over Pt/CeO2/TiO2.

The volatile organic compounds (VOCs) from cooking oil fumes are very complex and do harm to humans and the environment. Herein, we develop the high-efficiency and energy-saving synergistic photothermocatalytic oxidation approach to eliminate the mixture of heptane and hexanal, the representative VOCs with high concentrations in cooking oil fumes. The Pt/CeO2/TiO2 catalyst with nanosized Pt particles was prepared by the simple hydrothermal and impregnation methods, and the physicochemical properties of the catalyst were measured using numerous techniques. The Pt/CeO2/TiO2 catalyst eliminated the VOC mixture at low light intensity (100 mW cm-2) and low temperature (200 °C). In addition, it showed 25 h of catalytic stability and water resistance (water concentration up to 20 vol %) at 140 or 190 °C. It is concluded that O2 picked up the electrons from Pt to generate the •O2- species, which were transformed to the O22- and O- species after the rise in temperature. In the presence of water, the •OH species induced by light irradiation on the catalyst surface and the •OOH species formed via the thermal reaction were both supplementary oxygen species for VOC oxidation. The synergistic interaction of photo- and thermocatalysis was generated by the reactive oxygen species.

Bioengineered microglia-targeted exosomes facilitate Aß clearance via enhancing activity of microglial lysosome for promoting cognitive recovery in Alzheimer's disease.

Aggregation of amyloid in the form of senile plaques is currently considered to be one of the main mechanisms driving the development of Alzheimer's disease (AD). Therefore, targeting amyloid homeostasis is an important treatment strategy for AD. Microglia, as the main immune cells, contribute to endocytosis and clearance of amyloid beta (Aß) via lysosome mediated degradation. As abnormal lysosomal function in microglia is associated with inefficient clearance of Aß in AD, we designed bioengineered microglia-targeting exosomes to promote the targeted delivery of gemfibrozil (Gem) and restore the lysosomal activity of microglia in clearing Aß aggregation. Our results suggested that mannose-modified exosomes laden with Gem (MExo-Gem) can not only bind with Aß but also specifically target microglia through the interaction between Exo-delivered mannose and mannose receptors expressed in microglia, thus promoting Aß entry into microglia. Exosomal Gem activated lysosomal activity and accelerated lysosome-mediated clearance of Aß in microglia. Finally, MExo-Gem improved the learning and memory ability of AD model mice.

A multifunctional antibacterial and self-healing hydrogel laden with bone marrow mesenchymal stem cell-derived exosomes for accelerating diabetic wound healing.

Chronic diabetic wound injury is a serious syndrome of diabetes, and the treatment of this syndrome is of great significance. Owing to metabolic abnormalities, diabetic wounds are difficult to heal due to chronic inflammation, immune dysfunction, impaired angiogenesis and bacterial reproduction. However, most traditional treatments can only play a limited role in dealing with unhealed wounds, and the overall healing effect is not ideal. We designed a novel bone marrow mesenchymal stem cell-derived exosome (MSC-Exo)-loaded carboxyethyl chitosan (CEC)-dialdehyde carboxymethyl cellulose (DCMC) hydrogel (MSC-Exos@CEC-DCMC HG) for chronic diabetic wound healing. The results demonstrated that CEC can be cross-linked with DCMC through Schiff base reactions to form antibacterial and self-healing hydrogels. The inherent MSC-Exos not only promoted angiogenesis but also enhanced the transformation of M1-type macrophages to the M2 type to reduce inflammatory effects. Finally, MSC-Exos@CEC-DCMC HG, as an effective therapeutic agent, synergistically adjusted the wound inflammation microenvironment, promoted neovascularization, and accelerated wound healing in type 1 diabetic rats.

Brain-targeted heptapeptide-loaded exosomes attenuated ischemia-reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons.

BACKGROUND: The exchange of mitochondria reportedly plays an important role in cell-cell communication in the central nervous system (CNS). The transfer of fragmented and dysfunctional astrocytic mitochondria into neurons and subsequent mitochondrial fusion often cause serious neuronal damage and cerebral ischaemic injury. METHODS: In this study, we prepared macrophage-derived exosomes laden with heptapeptide (Hep) as a dynamin-related protein-1 (Drp1)-fission 1 (Fis1) peptide inhibitor P110 to alleviate cerebral ischemia-reperfusion injury by reducing mitochondrial Drp1/Fis1 interaction-mediated astrocytic mitochondrial disorder and promoting the transfer of astrocyte-derived healthy mitochondria into neurons. RESULTS: The results demonstrated that Hep-loaded macrophage-derived exosomes (EXO-Hep) reduced mitochondrial damage in astrocytes by inhibiting the Drp1/Fis1 interaction after ischemia-reperfusion, ensuring the release of heathy astrocytic mitochondria and their subsequent transmission to neurons, alleviating mitochondria-mediated neuronal damage. CONCLUSION: EXO-Hep significantly mitigated ischemic injury in a model of transient middle cerebral artery occlusion (tMCAO) by reducing the infarct area and improving neurological performance during the process of cerebral ischemia-reperfusion.

DoSGuard: Mitigating Denial-of-Service Attacks in Software-Defined Networks.

Software-defined networking (SDN) is a new networking paradigm that realizes the fast management and optimal configuration of network resources by decoupling control logic and forwarding functions. However, centralized network architecture brings new security problems, and denial-of-service (DoS) attacks are among the most critical threats. Due to the lack of an effective message-verification mechanism in SDN, attackers can easily launch a DoS attack by faking the source address information. This paper presents DoSGuard, an efficient and protocol-independent defense framework for SDN networks to detect and mitigate such attacks. DoSGuard is a lightweight extension module on SDN controllers that mainly consists of three key components: a monitor, a detector, and a mitigator. The monitor maintains the information between the switches and the hosts for anomaly detection. The detector utilizes OpenFlow message and flow features to detect the attack. The mitigator protects networks by filtering malicious packets. We implement a prototype of DoSGuard in the floodlight controller and evaluate its effectiveness in a simulation environment. Experimental results show the DoSGuard achieves 98.72% detecion precision, and the average CPU utilization of the controller is only around 8%. The results demonstrate that DoSGuard can effectively mitigate DoS attacks against SDN with limited overhead.