Doping-Engineered Piezoelectric Ultrathin Nanosheets for Synergistically Piezo-Chemocatalytic Antitumor and Antibacterial Therapies Against Cutaneous Melanoma.

The post-surgical melanoma recurrence and wound infections have persistently troubled clinical management. Piezocatalytic therapy features high efficiency in generating reactive oxygen species (ROS) for tumor therapy, but it faces limitations in piezoelectricity and redox-active site availability. Herein, Fe-doped ultrathin Bi4Ti3O12 nanosheets (designated as Fe-UBTO NSs) with synergistically piezo-chemocatalytic activity are engineered for antitumor and antibacterial treatment against cutaneous melanoma. The doping-engineered strategy induces oxygen vacancies and lattice distortions in Fe-UBTO NSs, which narrows bandgap to enhance piezocatalytic 1O2 and H2O2 generation by improving the electron-hole pairs separation, hindering their recombination, and increasing oxygen adsorption. Moreover, Fe doping establishes a piezo-chemocatalytic system, in which the piezocatalysis enables the self-supply of H2O2 and expedites electron transfer in Fenton reactions, inducing increased ·OH production. Besides, the atomic-level thickness and expanded surface area enhance the sensitivity to ultrasound stimuli and expose more redox-active sites, augmenting the piezo-chemocatalytic efficiency, and ultimately leading to abundant ROS generation. The Fe-UBTO-mediated piezo-chemocatalytic therapy causes intracellular oxidative stress, triggering apoptosis and excessive autophagy of tumor cells. Moreover, this strategy accelerates wound healing by facilitating sterilization, angiogenesis, and collagen deposition. This work provides distinct options to develop doping-engineered ultrathin nanosheets with augmented piezo-chemocatalytic activity for postoperative management of cutaneous melanoma.

Engineering Photothermal Catalytic CO2 Nanoreactor for Osteomyelitis Treatment by In Situ CO Generation.

Photocatalytic carbon dioxide (CO2) reduction is an effective method for in vivo carbon monoxide (CO) generation for antibacterial use. However, the available strategies mainly focus on utilizing visible-light-responsive photocatalysts to achieve CO generation. The limited penetration capability of visible light hinders CO generation in deep-seated tissues. Herein, a photothermal CO2 catalyst (abbreviated as NNBCs) to achieve an efficient hyperthermic effect and in situ CO generation is rationally developed, to simultaneously suppress bacterial proliferation and relieve inflammatory responses. The NNBCs are modified with a special polyethylene glycol and further embellished by bicarbonate (BC) decoration via ferric ion-mediated coordination. Upon exposure to 1064 nm laser irradiation, the NNBCs facilitated efficient photothermal conversion and in situ CO generation through photothermal CO2 catalysis. Specifically, the photothermal effect accelerated the decomposition of BC to produce CO2 for photothermal catalytic CO production. Benefiting from the hyperthermic effect and in situ CO production, in vivo assessments using an osteomyelitis model confirmed that NNBCs can simultaneously inhibit bacterial proliferation and attenuate the photothermal effect-associated pro-inflammatory response. This study represents the first attempt to develop high-performance photothermal CO2 nanocatalysts to achieve in situ CO generation for the concurrent inhibition of bacterial growth and attenuation of inflammatory responses.

Rosmarinic acid nanomedicine for rheumatoid arthritis therapy: Targeted RONS scavenging and macrophage repolarization.

The infiltration of inflammatory cells, especially macrophages, integrated with the production of reactive oxygen and nitrogen species (RONS) and the release of inflammatory cytokines play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Synergistic combination of RONS scavenging and macrophage repolarization from pro-inflammatory M1 phenotype towards anti-inflammatory M2 phenotype, provides a promising strategy for efficient RA treatment. Herein, this study reported a unique self-assembly strategy to construct distinct rosmarinic acid nanoparticles (RNPs) for efficient RA treatment using the naturally occurring polyphenol-based compound, rosmarinic acid (RosA). The designed RNPs exhibited favorable capability in scavenging RONS and pro-inflammatory cytokines produced by macrophages. Attributing to the widened vascular endothelial-cell gap at inflammation sites, RNPs could target and accumulate at the inflammatory joints of collagen-induced arthritis (CIA) rats for guaranteeing therapeutic effect. In vivo investigation demonstrated that RNPs alleviated the symptoms of RA, including joint swelling, synovial hyperplasia, cartilage degradation, and bone erosion in CIA rats. Additionally, the designed RNPs promoted macrophage polarization from M1 phenotype towards M2 phenotype, resulting in the suppressed progression of RA. Therefore, this research represents the representative paradigm for RA therapy using antioxidative nanomedicine deriving from the natural polyphenol-based compound.

Ultrasound-Triggered Cascade Amplification of Nanotherapy.

Ultrasound (US)-triggered cascade amplification of nanotherapies has attracted considerable attention as an effective strategy for cancer treatment. With the remarkable advances in materials chemistry and nanotechnology, a large number of well-designed nanosystems have emerged that incorporate presupposed cascade amplification processes and can be activated to trigger therapies such as chemotherapy, immunotherapy, and ferroptosis, under exogenous US stimulation or specific substances generated by US actuation, to maximize antitumor efficacy and minimize detrimental effects. Therefore, summarizing the corresponding nanotherapies and applications based on US-triggered cascade amplification is essential. This review comprehensively summarizes and highlights the recent advances in the design of intelligent modalities, consisting of unique components, distinctive properties, and specific cascade processes. These ingenious strategies confer unparalleled potential to nanotherapies based on ultrasound-triggered cascade amplification and provide superior controllability, thus overcoming the unmet requirements of precision medicine and personalized treatment. Finally, the challenges and prospects of this emerging strategy are discussed and it is expected to encourage more innovative ideas and promote their further development.

Biogeochemical behavior and pollution control of arsenic in mining areas: A review.

Arsenic (As) is one of the most toxic metalloids that possess many forms. As is constantly migrating from abandoned mining area to the surrounding environment in both oxidation and reducing conditions, threatening human health and ecological safety. The biogeochemical reaction of As included oxidation, reduction, methylation, and demethylation, which is closely associated with microbial metabolisms. The study of the geochemical behavior of arsenic in mining areas and the microbial remediation of arsenic pollution have great potential and are hot spots for the prevention and remediation of arsenic pollution. In this study, we review the distribution and migration of arsenic in the mining area, focus on the geochemical cycle of arsenic under the action of microorganisms, and summarize the factors influencing the biogeochemical cycle of arsenic, and strategies for arsenic pollution in mining areas are also discussed. Finally, the problems of the risk control strategies and the future development direction are prospected.

Research progress of oral allergy syndrome / 中华预防医学杂志

Oral allergy syndrome (OAS) is an IgE-mediated hypersensitivity. Patients with pollen allergy will experience oropharyngeal allergy after eating fresh fruits or vegetables containing homologous pathogenesis-related allergen, occasionally accompanied by systemic symptoms, it is a special type of food hypersensitivity in which respiratory allergens and food allergens are similar structurally and lead to the cross-reactivity. At present, there is little research and attention to it in China. To master the definition, epidemiological characteristics, pathological mechanism, diagnosis, prevention and treatment of OAS is very important to the prevention and control of OAS. This article reviews the research progress of OAS, providing reference and prevention basis for clinicians to improve the diagnosis and differential diagnosis of OAS.

Sequential Ultrasound-Triggered and Hypoxia-Sensitive Nanoprodrug for Cascade Amplification of Sonochemotherapy.

Hypoxia, the typical and conspicuous characteristic of most solid tumors, worsens the tumor invasiveness and metastasis. Here, we engineered a sequential ultrasound (US)/hypoxia-sensitive sonochemotherapeutic nanoprodrug by initially synthesizing the hypoxia-activated azo bond-containing camptothecin (CPT) prodrug (CPT2-Azo) and then immobilizing it into the mesopores of sonosensitizer-integrated metal organic frameworks (MOF NPs). Upon entering the hypoxic tumor microenvironment (TME), the structure of CPT2-Azo immobilized MOFs (denoted as MCA) was ruptured and the loaded nontoxic CPT2-Azo prodrug was released from the MOF NPs. Under US actuation, this sonochemotherapeutic nanoprodrug not only promoted sonosensitizer-mediated sonodynamic therapy (SDT) via the conversion of oxygen into cytotoxic reactive oxygen species (ROS) but also aggravated hypoxia in the TME by elevating oxygen consumption. The exacerbated hypoxia in turn served as a positive amplifier to boost the activation of CPT2-Azo, and the controllable release of toxic chemotherapeutic drug (CPT), and compensated the insufficient treatment efficacy of SDT. In vitro and in vivo evaluations confirmed that sequential SDT and tumor hypoxia-activated sonochemotherapy promoted the utmost of tumor hypoxia and thereby contributed to the augmented antitumor efficacy, resulting in conspicuous apoptotic cell death and noteworthy tumor suppression in vivo. Our work provides a distinctive insight into the exploitation of the hypoxia-activated sonochemotherapeutic nanoprodrug that utilizes the hypoxic condition in TME, a side effect of SDT, to initiate chemotherapy, thus causing a significantly augmented treatment outcome compared to conventional SDT.

Engineering Oxygen-Irrelevant Radical Nanogenerator for Hypoxia-Independent Magnetothermodynamic Tumor Nanotherapy.

Tumor hypoxia substantially lowers the treatment efficacy of oxygen-relevant therapeutic modalities because the production of reactive oxygen species in oxygen-relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen-irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer-cell apoptosis in vitro and tumor suppression in vivo. Free-radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co-doped nanoparticles (MnFe2 O4 @CoFe2 O4 , denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation. Upon exposure to an exogenous AMF, the magnetic hyperthermia effect of superparamagnetic core lead to the rapid decomposition of the loaded/delivered initiators (AIPH) to produce oxygen-irrelevant free radicals. Both the magnetothermal effect and generation of toxic free radicals under AMF actuation are synergistically effective in promoting cancer-cell death and tumor suppression in the hypoxic tumor microenvironment. The prominent therapeutic efficacy of this radical nanogenerator represents an intriguing paradigm of oxygen-irrelevant nanoplatform for AMF-initiated synergistic cancer treatment.

Detection of EDA gene mutation and phenotypic analysis in patients with hypohidrotic ectodermal dysplasia / 北京大学学报(医学版)

OBJECTIVE@#To detect the ectodysplasin A (EDA) gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with EDA gene mutation.@*METHODS@#Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the EDA gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of EDA gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each EDA gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with EDA gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared.@*RESULTS@#Eight out of twelve HED families were identified to carry EDA gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with EDA gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (P>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence.@*CONCLUSION@#This study detected novel EDA gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of EDA gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.