Carbon Free Radical (R⋠) Inactivates NF-κB for Radical Capping Therapy.

Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (R⋅) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive R⋅ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of R⋅. At a temperature of 43 °C, the generated R⋅ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied R⋅ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.

Ion Current Rectification Activity Induced by Boron Hydride Nanosheets to Enhance Magnesium Analgesia.

The low analgesic efficiency has limited magnesium used in analgesia. Here, we report boron hydride (BH) with ion current rectification activity can significantly improve the analgesic efficiency of magnesium, even higher than morphine. The synthesized injectable MgB2 composes of hexagonal boron sheets alternating with Mg2+. In pathological environment, while the intercalated Mg2+ will be exchanged by H+, the 2-dimensional borophene-analogue BH sheets will be formed to interact with the charged cations via the cation-pi interaction, synergistically leading to a sort of two-way dynamic modulation of sodium and potassium ion currents in neurons. By coordinating with the released Mg2+ to compete Ca2+, the threshold potential remarkably increases from the normal -35.9 mV to -5.9 mV, which significantly suppresses neuronal excitability, providing a potent analgesic effect. In three typical pain models , including CFA-induced inflammatory pain, PINP- or CCI-induced neuropathic pain, MgB2 demonstrates its analgesic efficiency approximately 2.23, 3.20, and 2.0 times higher than the clinical MgSO4, respectively. The development of MgB2 as analgesic drugs addresses the unmet medical need of pain relief without the risks of drug tolerance or addiction to opioids.

Three-Dimensional Neodymium Metal-Organic Framework for Catalyzing the Cyanosilylation of Aldehyde and the Synthesis of 2,3-Dihydroquinazolin-4(1H)-one Derivatives.

In this work, a novel 3D lanthanide metal-organic framework (Ln-MOF) Nd-cdip (H4cdip = 5,5'-carbonyldiisophthalic acid) was successfully synthesized, which could be used as an efficient heterogeneous catalyst for cyanosilylation and the synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives at room temperature based on the Lewis acid sites in the channels of the MOF. Moreover, Nd-cdip had an excellent turnover number (500) for catalyzing cyanosilylation in no solvent condition. Nd-cdip could be reused in both of the above-mentioned reactions at least five times without a significant decrease in yield. The possible mechanism of cyanosilylation catalyzed by Nd-cdip was studied by using the luminescence properties of Tb-cdip, which has the same structure and functions as Nd-cdip. Furthermore, both reactions catalyzed by Nd-cdip were fitted to zero-order dynamics.

Biomedicine Meets Fenton Chemistry.

Since the first connection between Fenton chemistry and biomedicine, numerous studies have been presented in this field. Comprehensive presentation of the guidance from Fenton chemistry and a summary of its representative applications in cancer therapy would help us understand and promote the further development of this field. This comprehensive review first supplies basic information regarding Fenton chemistry, including Fenton reactions and Fenton-like reactions. Subsequently, the current progress of Fenton chemistry is discussed, with some corresponding representative examples presented. Furthermore, the current strategies for further optimizing the performance of chemodynamic therapy guided by Fenton chemistry are highlighted. Most importantly, future perspectives on the combination of biomedicine with Fenton chemistry or a wider range of catalytic chemistry approaches are presented. We hope that this review will attract positive attention in the chemistry, materials science, and biomedicine fields and further tighten their connections.

A programmable ferrofluidic droplet robot.

Soft miniature robots have wide potential applications in lab-on-a-chip and biomedical sciences due to their deformability, safety, and remarkable controllability. However, current ferrofluidic droplet robots have some problems, such as easy broken, limited motion range and high energy consumption. Therefore, the objective of this study is to propose a programmable ferrofluidic flexible droplet robot (PFDR) with control strategies for elongation, splitting and merging behaviors by designing an actuation system consisting of a row of electromagnets and a robotic arm or a coordinate robot. The PFDR can not only deform actively to prevent itself from breaking, but also deform passively to fit the profile of channels or tubes to move efficiently. The actuation system can make PFDR have larger motion range as well as lower energy consumption. The design concept and the operating principle of PFDR are presented. The magnetic actuation system is developed. The lag of PFDR is analyzed in theoretical and experimental ways. The splitting and merging behaviors are investigated and other functionalities are studied as well.

[Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope].

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

[PK/PD model of Chuanxiong gel plaster in treatment of rheumatoid arthritis].

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1ß, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1ß was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.

A Forward Vision for Chemodynamic Therapy: Issues and Opportunities.

Since the insight to fuse Fenton chemistry and nanomedicine into cancer therapy, great signs of progress have been made in the field of chemodynamic therapy (CDT). However, the exact mechanism of CDT is obscured by the unique tumor chemical environment and inevitable nanoparticle-cell interactions, thus impeding further development. In this Scientific Perspective, the significance of CDT is clarified, the complex mechanism is deconstructed into primitive chemical and biological interactions, and the mechanism research directions based on the chemical kinetics and biological signaling pathways are discussed in detail. Moreover, beneficial outlooks are presented to enlighten the evolution of next-generation CDT. Hopefully, this Scientific Perspective can inspire new ideas and advances for CDT and provide a reference for breaking down the interdisciplinary barriers in the field of nanomedicine.

Synthesis of a Lanthanide Metal-Organic Framework and Its Fluorescent Detection for Phosphate Group-Based Molecules Such as Adenosine Triphosphate.

Adenosine triphosphate (ATP) is an important kind of metabolized biological molecule that is formed in organisms, especially in mitochondria, is used universally as energy, and is one of the most significant multifunctional biological molecules. Metal-organic frameworks (MOFs) have been widely used in many applications such as gas storage and separation, drug delivery, heterogeneous catalysis, chemical sensors, etc. Remarkably, lanthanide MOFs (Ln-MOFs), which display large pores, multiple dimensions, and unique lanthanide luminescence properties, are widely used as chemical sensors. A novel three-dimensional probe, Eu2(sbdc)3(H2O)3 (Eu-sbdc), was successfully self-assembled with Eu(NO3)3·6H2O and 5,5-dioxo-5H-dibenzo[b,d]thiophene-3,7-dicarboxylic acid (H2sbdc). The Ln-MOF Eu-sbdc can quickly and effectively optically detect ATP via a luminescent quenching mechanism. The Ksv value of Eu-sbdc is 1.02 × 104 M-1, and the lower detection limit of Eu-sbdc for ATP is 20 µM, which is more sensitive to ATP. Its mechanism of monitoring ATP might be a dynamic or static quenching process. Eu-sbdc could effectively and quickly recognize ATP with high sensitivity.

Constructing Electron Levers in Perovskite Nanocrystals to Regulate the Local Electron Density for Intensive Chemodynamic Therapy.

The local electron density of an atom is one key factor that determines its chemical properties. Regulating electron density can promote the atom's reactivity and so reduce the reaction activation energy, which is highly desired in many chemical applications. Herein, we report an intra-crystalline electron lever strategy, which can regulate the electron density of reaction centre atoms via manipulating ambient lattice states, for Fenton activity improvement. Typically, with the assistance of ultrasound, the Mn4+ -O-Fe3+ bond in BiFe0.97 Mn0.03 O3 perovskite nanocrystals can drive valence electrons and free electrons to accumulate on Fe atoms by a polarization electric field originated from the designed lattice strain. The increase of electron density significantly improves the catalytic activity of Fe, decreasing the activation energy of BiFe0.97 Mn0.03 O3 -mediated Fenton reaction by 52.55 %, and increasing the . OH yield by 9.21-fold. This study provides a new way to understand the sono-Fenton chemistry, and the increased . OH production enables a highly effective chemodynamic therapy.

ZIF-Based Nanoparticles Combine X-Ray-Induced Nitrosative Stress with Autophagy Management for Hypoxic Prostate Cancer Therapy.

Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors. Herein, X-ray triggered nitrite (NO2- ) is used for hypoxic prostate cancer therapy by inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazole framework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles, electrophilic ligands and Zn2+ are delivered into cancer cells. Electrophilic ligands can not only consume GSH under hypoxia but also capture low-energy electrons derived from X-rays to generate NO2- , which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn2+ specifically limits the migration and invasion of prostate cancer cells through ion interference. In vitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells. Overall, this nitrosative stress-mediated tumor therapy strategy provides a novel approach targeting hypoxic tumors.

Reversal of P-glycoprotein-mediated multidrug resistance by novel curcumin analogues in paclitaxel-resistant human breast cancer cells.

Multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy, and the main cause of MDR has been attributed to overexpression of P-glycoprotein (P-gp). In this present study, four P-gp modulators (E,E)-4,6-bis(styryl)-2-(substituted amino)-pyrimidines were evaluated for their activity in a breast cancer cell line overexpressing P-gp (LCC6MDR). The four modulators displayed significantly better P-gp modulating activity compared with the positive control verapamil (RF = 5.4), with a relative fold (RF) increase in activity ranging from 33.3 to 86.0. In contrast to compounds a and c that exhibited lower cytotoxicity, compounds b and d were nontoxic towards both cancer cells and normal cells, with IC50 values greater than 100 µmol/L. The qRT-PCR results demonstrated that after exposure to 2 µmol/L of compounds a, b, c, and d, the mRNA expression level of MDR1 in LCC6MDR cells decreased to 45%, 50%, 38%, and 51%, respectively. However, the Western-blot results indicated that compound c could reverse P-gp mediated MDR, but not via decreases in protein expression. DOX and Rh123 accumulation and efflux results further confirmed that the reversal of MDR activity happens via inhibition of P-gp efflux and increases in intracellular drug accumulation. These results demonstrated that compound c has low toxicity and is an efficient P-gp modulator, highlighting its potential as a promising candidate for P-gp-mediated reversal of MDR.

[Clinical and genetic analysis of two patients with congenital neutropenia caused by ELANE gene mutation].

OBJECTIVE: To explore the clinical characteristics of congenital neutropenia caused by ELANE gene mutations. METHODS: Clinical manifestations, absolute blood neutrophil count, high-throughput exome sequencing for mutation screening, suspected locus Sanger sequencing verification, processes of diagnosis and treatment of two patients with congenital neutropenia caused by ELANE gene mutation were retrospectively analyzed. RESULTS: High-throughput sequencing has found that proband 1 has carried a heterozygous c.170C>T (p.Ala57Val) missense mutation in exon 2 of the ELANE gene, which was known to be pathological, and a heterozygous c.251T>G (p.Leu84Arg) mutation in exon 3 of proband 2, which was unreported previously. Sanger sequencing confirmed that neither mutation was inherited from their parents. CONCLUSION: ELANE mutation is an important cause for congenital neutropenia. Detection of new pathogenic variants has enriched the mutation spectrum of the ELANE gene.

Redox Dyshomeostasis Strategy for Hypoxic Tumor Therapy Based on DNAzyme-Loaded Electrophilic ZIFs.

Redox homeostasis is one of the main reasons for reactive oxygen species (ROS) tolerance in hypoxic tumors, limiting ROS-mediated tumor therapy. Proposed herein is a redox dyshomeostasis (RDH) strategy based on a nanoplatform, FeCysPW@ZIF-82@CAT Dz, to disrupt redox homeostasis, and its application to improve ROS-mediated hypoxic tumor therapy. Once endocytosed by tumor cells, the catalase DNAzyme (CAT Dz) loaded zeolitic imidazole framework-82 (ZIF-82@CAT Dz) shell can be degraded into Zn2+ as cofactors for CAT Dz mediated CAT silencing and electrophilic ligands for glutathione (GSH) depletion under hypoxia, both of which lead to intracellular RDH and H2 O2 accumulation. These "disordered" cells show reduced resistance to ROS and are effectively killed by ferrous cysteine-phosphotungstate (FeCysPW) induced chemodynamic therapy (CDT). In vitro and in vivo data demonstrate that the pH/hypoxia/H2 O2 triple stimuli responsive nanocomposite can efficiently kill hypoxic tumors. Overall, the RDH strategy provides a new way of thinking about ROS-mediated treatment of hypoxic tumors.

Human breast adipose-derived stem cells transfected with the stromal cell-derived factor-1 receptor CXCR4 exhibit enhanced viability in human autologous free fat grafts.

BACKGROUND: The main complication of autologous free fat tissue transplantation is fat resorption and calcification due to the ischemic necrosis of fat. The promotion of transplant neovascularization soon after autologous free fat grafts may reduce these outcomes. In adulthood, stromal cell-derived factor-1 (SDF-1) and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4) are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. We hypothesized that CXCR4 may improve the long-term survival of free fat tissue transplants by recruiting endothelial progenitor cells (EPCs) and may therefore improve graft revascularization. In this study, we aimed to determine the effect of human breast adipose-derived stem cells (HBASCs) transfected with the CXCR4 gene on the survival rate of human autologous free fat transplants in nude mice. METHODS: Human breast adipose-derived stem cells (HBASCs) were expanded ex vivo for 3 passages, labeled with green fluorescent protein (GFP) and transfected with CXCR4 or left untransfected. Autologous fat tissues were mixed with the GFP-labeled, CXCR4-transfected HBASCs (group A), GFP-labeled HBASCs (group B), the known vascularization-promoting agent VEGF (group C), or medium (group D) and then injected subcutaneously into 32 nude mice at 4 spots in a random fashion. Six months later, the transplanted tissue volume and histology were evaluated, and neo-vascularization was quantified by counting the capillaries. CXCR4 and SDF-1α mRNA expression in the transplants was determined using real-time quantitative PCR analysis (qPCR). RESULTS: The data revealed that the control (group D) transplant volume survival was 28.3 ± 4.5%. Mixing CXCR4-transfected (group A) and untransfected (group B) HBASCs significantly increased transplant volume survival (79.5 ± 8.3% and 67.2 ± 5.9%, respectively), whereas VEGF-transfected HBASCs (group C) were less effective (41.2 ± 5.1%). Histological analysis revealed that both types of HBASCs-treated transplants consisted predominantly of adipose tissue, unlike the control transplants, and also presented significantly less fat necrosis and fibrosis. The CXCR4-transfected HBASCs-treated transplants had a significantly higher capillary density than did the other transplants and showed GFP and CD31 double-positive cells (i.e., ASCs-derived endothelial cells). The mRNA expression of CXCR4 and SDF-1α was much higher in the CXCR4-transfected HBASCs transplants than in the other three transplants. CONCLUSIONS: Our data demonstrated that HBASCs can enhance the survival and quality of transplanted free fat tissues. Moreover, CXCR4 transfection of these HBASCs could augment this effect. Stimulation of angiogenesis and decreased fat cell apoptosis due to the recruitment of endothelial progenitor cells (EPCs) and an increase in graft revascularization are potential mechanisms underlying the improved long-term survival of free fat transplants following CXCR4-transfected HBASCs treatment.

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight.

Epigenetic and metabolic reprogramming alterations are two important features of tumors, and their reversible, spatial, and temporal regulation is a distinctive hallmark of carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, is a new entry point for tumor therapy. Moreover, metabolic reprogramming drives hepatocellular carcinoma (HCC) initiation and progression, highlighting the significance of metabolism in this disease. Exploring the inter-regulatory relationship between tumor metabolic reprogramming and epigenetic modification has become one of the hot directions in current tumor metabolism research. As viral etiologies have given way to metabolic dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it is urgent that complex molecular pathways linking them and hepatocarcinogenesis be explored. However, how aberrant crosstalk between epigenetic modifications and metabolic reprogramming affects MASLD-induced HCC lacks comprehensive understanding. A better understanding of their linkages is necessary and urgent to improve HCC treatment strategies. For this reason, this review examines the interwoven landscape of molecular carcinogenesis in the context of MASLD-induced HCC, focusing on mechanisms regulating aberrant epigenetic alterations and metabolic reprogramming in the development of MASLD-induced HCC and interactions between them while also updating the current advances in metabolism and epigenetic modification-based therapeutic drugs in HCC.

Screening primary carnitine deficiency in 10 million Chinese newborns: a systematic review and meta-analysis.

BACKGROUND: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants. METHODS: PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns. RESULTS: After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05‰ [95%CI, (0.04‰, 0.06‰)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07‰, 95%CI, (0.05‰, 0.08‰)] than in northern China [0.02‰, 95%CI, (0.02‰, 0.03‰)] (P < 0.001). Furthermore, the result of the meta-analysis showed that the frequency of the variant with c.1400C > G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79‰, 95%CI, (47‰, 135‰)] (P < 0.05). CONCLUSIONS: This study systematically analyzed PCD prevalence and identified common SLC22A5 gene variants in the Chinese population. The findings provide valuable epidemiological insights and guidance for future PCD screening effects in newborns.

Ultrasound-Driven Non-Metallic Fenton-Active Center Construction for Extensive Chemodynamic Therapy.

Chemodynamic therapy (CDT) is an emerging tumor microenvironment-responsive cancer therapeutic strategy based on Fenton/Fenton-like reactions. However, the effectiveness of CDT is subject to the slow kinetic rate and non-homogeneous distribution of H2 O2 . In this study, a conceptual non-metallic "Fenton-active" center construction strategy is proposed to enhance CDT efficiency using Bi0.44 Ba0.06 Na0.5 TiO2.97 (BNBT-6) nanocrystals. The separated charge carriers under a piezoelectric-induced electric field synchronize the oxidation of H2 O and reduction of H2 O2 , which consequently increases hydroxyl radical (·OH) yield even under low H2 O2 levels. Moreover, acceptor doping induces electron-rich oxygen vacancies to facilitate the dissociation of H2 O2 and H2 O and further promote ·OH generation. In vitro and in vivo experiments demonstrate that BNBT-6 induces extensive intracellular oxidative stress and enhances cell-killing efficiency by activating necroptosis in addition to the conventional apoptotic pathway. This study proposes a novel design approach for nanomaterials used in CDT and presents a new treatment strategy for apoptosis-resistant tumors.

Nutrient-delivery and metabolism reactivation therapy for melanoma.

To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways.

Autologous platelet-rich plasma promotes neurogenic differentiation of human adipose-derived stem cells in vitro.

Nervous system injury causes severe medical and social problems worldwide, and doctors have not found any ultimate solutions to it until now. The regenerative medicine using stem cells is a promising technology to conquer this challenge. In this study, we explored the influence of platelet-rich plasma (PRP) on neural differentiation of adipose-derived stem cells (ASCs). Human ASCs (hASCs) were harvested and isolated from lipoaspirates of liposuction operations. They were cultured to the third passage and characterized by specific cell markers and multilineage differentiation capacities. Autologous PRP was isolated and prepared from venous blood of the same patient underwent liposuction. The cultured hASCs were treated with either neural inductive conditioned medium plus 10% PRP (experimental group) or neural inductive conditioned medium alone (control group). The supplement of autologous PRP into culture medium obviously promoted proliferation of hASCs. After two weeks of neurogenic induction, the hASCs treated with PRP displayed higher level of neuron-specific enolase and membrane-associated protein-2 compared with the control group. Gene expression level of growth associated protein-43 (GAP-43), neural cell adhesion molecule (NCAM), and synapsin 1 (SYN-1) in the PRP group was also higher than in the control group. These results indicate PRP is capable of promoting cell proliferation and neurogenic differentiation of hASCs in vitro. Addition of autologous PRP could facilitate the potential use of hASCs in nerve regeneration.