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.

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.

Newborn Screening of 6 Lysosomal Storage Disorders by Tandem Mass Spectrometry.

This study was designed to screen 6 lysosomal storage diseases (LSDs) in neonates using tandem mass spectrometry (MS/MS), and establish cutoff values for these LSDs with 3000 dried blood spots (DBS) samples. Cutoff values for α-L-iduronidase (IDUA), α-galactosidase (GLA), acid beta glucosidase (ABG), ß-galactocerebrosidase (GALC), acid sphingomyelinase (ASM), and acid alpha glucosidase (GAA) were as follows: GLA, > 2.06 µmol/L·h; ABG, > 1.78 µmol/L·h; ASM, > 0.99 µmol/L·h; IDUA, > 1.33 µmol/L·h; GALC, > 0.84 µmol/L·h; and GAA, > 2.06 µmol/L·h. There were 30 positives in initial MS/MS screening test, and 15 samples were still positive with repeat testing. Their parents/guardians were recontacted and DBS samples were collected again for test. Only 1 child showed abnormal GAA enzyme activity after recontacting process, and was diagnosed with Pompe disease after genetic screening. Eventually, cutoff values of 6 specific enzyme activities were established and MS/MS is effective for early LSDs screening.

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.

Biochemical and molecular features of tetrahydrobiopterin deficiency in Fujian Province, southeastern China.

The estimated prevalence of tetrahydrobiopterin deficiency (BH4D) and the mutational spectrum of the causal 6-pyruvoyl-tetrahydropterin synthase (PTS) gene vary widely according to race and region. This study assessed the prevalence and genetic characteristics of BH4D in Fujian Province, southeastern China. A total of 3,204,067 newborns were screened between 2012 and 2022 based on the phenylalanine level and the phenylalanine/tyrosine ratio in dried blood spots. Differential diagnosis was determined by the urine purine spectrum, dihydropteridine reductase activity in red blood cells, and genetic testing. The PTS mutation spectrum and genotypes were determined by next-generation sequencing. A total of 189 newborns were diagnosed with hyperphenylalaninemia (HPA) over the study period, including 159 with phenylalanine hydroxylase deficiency and 30 with BH4D. Therefore, the prevalence of BH4D in Fujian was 9.36 per 1,000,000 live births (30/3,204,067) and the proportion of BH4D among patients with HPA was 15.87% (30/189). A total of 58 PTS alleles were identified in the 29 patients with PTS deficiency (PTPSD), and those alleles were composed of 10 different variants, including eight missense variants and two splice-site variants. The most prevalent variants were c.155A>G, p.Asn52Ser (44.83%); c.259C>T, p.Pro87Ser (39.66%); and c.84-291A>G, p.Tyr27Argfs*8 (3.45%). The predominant genotype was c [155A>G]; [259C>T] (11/29, 37.93%). The prevalence of BH4D and the spectrum of associated PTS mutations were successfully determined for the first time in Fujian Province, southeastern China. Since the mutation spectrum of PTS is region-specific, such data will facilitate molecular diagnosis and genetic counseling in PTPSD cases.

Millirobot Based on a Phase-Transformable Magnetorheological Liquid Metal.

Droplet robots have attracted much attention in recent years due to their large-scale deformability and flexible mobility in confined spaces. However, droplet robots are always difficult to maintain rigid shapes, making them difficult to manipulate objects with large inertia. Moreover, their low conductivity makes them unable to complete tasks such as circuit repair. Herein, a millirobot made from magnetorheological liquid metal is proposed to address the problems. Specifically, the magnetorheological liquid metal (MLM) robot is made by engulfing iron particles into gallium-indium alloy, and the mass fraction of the MLM robot is determined by microscopic observation and rheological test. The MLM robot possesses both solid and liquid properties, enabling the robot with plasticity, large-scale deformability, good conductivity, motion flexibility, and good object manipulation. The MLM robot can achieve almost all of the functions of existing droplet robots, including splitting, merging, navigating in narrow channels, and pushing objects. In addition, it can also accomplish some other tasks that are difficult for existing droplet robots, such as pulling large objects, repairing damaged circuits selectively and reversibly, and repairing suspended circuits through plasticity. The demos show that MLM robots can traverse narrow spaces and repair circuit damage selectively and reversibly. It is believed that MLM robots can enrich diverse functionalities in the future.

Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China.

BACKGROUND: Glutaric acidemia type 1 (GA1) is a rare autosomal recessive inherited metabolic disorder caused by variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). The estimated prevalence of GA1 and the mutational spectrum of the GCDH gene vary widely according to race and region. The aim of this study was to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 in Fujian Province, southeastern China. RESULTS: From January 2014 to December 2022, a total of 1,151,069 newborns (631,016 males and 520,053 females) were screened using MS/MS in six newborn screening (NBS) centers in Fujian Province and recruited for this study. Through NBS, 18 newborns (13 females and 5 males) were diagnosed with GA1. Thus, the estimated incidence of GA1 was 1 in 63,948 newborns in Fujian province. In addition, 17 patients with GA1 were recruited after clinical diagnosis. All but one patient with GA1 had a remarkable increase in glutarylcarnitine (C5DC) concentrations. The results of urinary organic acid analyses in 33 patients showed that the concentration of glutaric acid (GA) increased in all patients. The levels of C5DC and GA in patients identified via NBS were higher than those in patients identified via clinical diagnosis (P < 0.05). A total of 71 variants of 70 alleles were detected in patients with GA1, with 19 different pathogenic variants identified. The three most prevalent variants represented 73.23% of the total and were c.1244-2 A > C, p.(?) (63.38%), c.1261G > A, p.Ala421Thr (5.63%), and c.406G > T, p.Gly136Cys (4.22%). The most abundant genotype observed was c.[1244-2 A > C]; [1244-2 A > C] (18/35, 52.43%) and its phenotype corresponded to high excretors (HE, GA > 100 mmol/mol Cr). CONCLUSIONS: In conclusion, we investigated the biochemical and molecular features of 35 unrelated patients with GA1. C5DC concentrations in dried blood spots and urinary GA are effective indicators for a GA1 diagnosis. Our study also identified a GCDH variant spectrum in patients with GA1 from Fujian Province, southeastern China. Correlation analysis between genotypes and phenotypes provides preliminary and valuable information for genetic counseling and management.

MnS Nanocapsule Mediates Mitochondrial Membrane Permeability Transition for Tumor Ion-Interference Therapy.

"Structure subserves function" is one fundamental biological maxim, and so the biological membrane that delimits the regions primarily serves as the margin between life and death for individual cells. Here, an Oswald ripening mechanism-guided solvothermal method was proposed for the synthesis of uniform MnS nanocapsules assembled with metastable γ-MnS nanocrystals. Through designing the physicochemical properties, MnS nanocapsules would disaggregate into small γ-MnS nanocrystals in a tumor acidic environment, with the surface potential switched from negative to positive, thus showing conspicuous delivery performance. More significantly, the specific accumulation of Mn2+ in mitochondria was promoted due to the downregulation of mitochondrial calcium uptake 1 (MICU1) by the formed H2S, thus leading to serious mitochondrial Mn-poisoning for membrane permeability increase and then tumor apoptosis. This study provides a synthesis strategy of metal sulfide nanocapsules and encourages multidisciplinary researchers to focus on ion-cancer crosstalk for the development of an antitumor strategy.

[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.

Magnetic Liquid Metal Droplet Robot with Multifunction and High Output Force in Milli-Newton.

Magnetically actuated miniature robots have immeasurable potential in lab-on-a-chip and biomedical due to their ability to navigate in constrained space. However, current soft robots made by elastomers have limited functionalities and are prevented from very narrow environments such as channel much smaller than their size because of their non- or limited deformability. In this study, a soft and multifunctional robot based on liquid metal (magnetic liquid-metal droplet robot [MLDR]) with high output force is reported. It is fabricated by engulfing iron particles into a Galinstan droplet. By changing the shape and motion of permanent magnets, the MLDR can be reshaped and moved. The MLDR can also be split in batches and merged efficiently. It shows good softness and flexibility when navigating freely in a narrow channel, and thus can pass through a confined space smaller than its size easily. Furthermore, the MLDR can also push and spread the accumulated liquid in a desired path, and manipulate the motions of small objects well. Benefiting from the solidification-like phenomenon, an MLDR can output milli-Newton-level force much higher than the output force of ferrofluid droplet robots in micro-Newton level. The demonstrated capabilities of the MLDR are promising for the applications in lab-on-a-chip or biomedical devices.

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.

Targeted metabolomics reveals serum changes of amino acids in mild to moderate ischemic stroke and stroke mimics.

Background: The pathophysiological processes linked to an acute ischemic stroke (IS) can be reflected in the circulating metabolome. Amino acids (AAs) have been demonstrated to be one of the most significant metabolites that can undergo significant alteration after a stroke. Methods: We sought to identify the potential biomarkers for the early detection of IS using an extensive targeted technique for reliable quantification of 27 different AAs based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A cohort with 216 participants was enrolled, including 70 mild to moderate ischemic stroke patients (National Institutes of Health Stroke Scale < 15, MB group), 76 stroke mimics (MM group) and 70 healthy controls (NC group). Results: It was found that upon comparing MB and MM to control patients, AAs shifts were detected via partial least squares discrimination analysis (PLS-DA) and pathway analysis. Interestingly, MB and MM exhibited similar AAs pattern. Moreover, ornithine, asparagine, valine, citrulline, and cysteine were identified for inclusion in a biomarker panel for early-stage stroke detection based upon an AUC of 0.968 (95% CI 0.924-0.998). Levels of ornithine were positively associated with infract volume, 3 months mRS score, and National Institutes of Health Stroke Scale (NIHSS) score in MB. In addition, a metabolites biomarker panel, including ornithine, taurine, phenylalanine, citrulline, cysteine, yielded an AUC of 0.99 (95% CI 0.966-1) which can be employed to effectively discriminate MM patients from control. Conclusion: Overall, alternations in serum AAs are characteristic metabolic features of MB and MM. AAs could serve as promising biomarkers for the early diagnosis of MB patients since mild to moderate IS patients were enrolled in the study. The metabolism of AAs can be considered as a key indicator for both the prevention and treatment of IS.

Blocking Spatiotemporal Crosstalk between Subcellular Organelles for Enhancing Anticancer Therapy with Nanointercepters.

The spatiotemporal characterization of signaling crosstalk between subcellular organelles is crucial for the therapeutic effect of malignant tumors. Blocking interactive crosstalk in this fashion is significant but challenging. Herein, a communication interception strategy is reported, which blocks spatiotemporal crosstalk between subcellular organelles for cancer therapy with underlying molecular mechanisms. Briefly, amorphous-core@crystalline-shell Fe@Fe3 O4 nanoparticles (ACFeNPs) are fabricated to specifically block the crosstalk between lysosomes and endoplasmic reticulum (ER) by hydroxyl radicals generated along with their trajectory through heterogeneous Fenton reaction. ACFeNPs initially enter lysosomes and trigger autophagy, then continuous lysosomal damage blocks the generation of functional autolysosomes, which mediates ER-lysosome crosstalk, thus the autophagy is paralyzed. Thereafter, released ACFeNPs from lysosomes induce ER stress. Without the alleviation by autophagy, the ER-stress-associated apoptotic pathway is fully activated, resulting in a remarkable therapeutic effect. This strategy provides a wide venue for nanomedicine to exert biological advantages and confers new perspective for the design of novel anticancer drugs.

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.

[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.

α-Synuclein fibril-specific nanobody reduces prion-like α-synuclein spreading in mice.

Pathogenic α-synuclein (α-syn) is a prion-like protein that drives the pathogenesis of Lewy Body Dementia (LBD) and Parkinson's Disease (PD). To target pathogenic α-syn preformed fibrils (PFF), here we designed extracellular disulfide bond-free synthetic nanobody libraries in yeast. Following selection, we identified a nanobody, PFFNB2, that can specifically recognize α-syn PFF over α-syn monomers. PFFNB2 cannot inhibit the aggregation of α-syn monomer, but can significantly dissociate α-syn fibrils. Furthermore, adeno-associated virus (AAV)-encoding EGFP fused to PFFNB2 (AAV-EGFP-PFFNB2) can inhibit PFF-induced α-syn serine 129 phosphorylation (pS129) in mouse primary cortical neurons, and prevent α-syn pathology spreading to the cortex in the transgenic mice expressing human wild type (WT) α-syn by intrastriatal-PFF injection. The pS129 immunoreactivity is negatively correlated with the expression of AAV-EGFP-PFFNB2. In conclusion, PFFNB2 holds a promise for mechanistic exploration and therapeutic development in α-syn-related pathogenesis.

Chemical Factory-Guaranteed Enhanced Chemodynamic Therapy for Orthotopic Liver Cancer.

In the field of nanomedicine, there is a tendency of matching designed nanomaterials with a suitable type of orthotopic cancer model, not just a casual subcutaneous one. Under this condition, knowing the specific features of the chosen cancer model is the priority, then introducing a proper therapy strategy using designed nanomaterials. Here, the Fenton chemistry is combined with zinc peroxide nanoparticles in the treatment of orthotopic liver cancer which has a "chemical factory" including that liver is the main place for iron storage, metabolism, and also the main metabolic sites for the majority of ingested substances, guaranteeing customized and enhanced chemodynamic therapy and normal liver cells protection as well. The good results in vitro and in vivo can set an inspiring example for exploring and utilizing suitable nanomaterials in corresponding cancer models, ensuring well-fitness of nanomaterials for disease and satisfactory therapeutic effect.

Electron Transfer Strategies to Regulate Carriers' Separation for Intensive Pyroelectric Dynamic Therapy With Simultaneous Photothermal Therapy.

Endogenic heat shock proteins and uneven local heat distribution are two main problems in traditional tumor hyperthermia therapy strategies. Aiming at solving these problems, we designed Au-SnSe-PVP nanomaterials (ASNPs) by modifying Au nanoparticles (Au-NPs) and biocompatible PVP on SnSe nanorods via a new reactive oxygen species production strategy. The ASNPs with excellent photothermal conversion performance can produce thermoelectric effects in response to temperature differences during photothermal conversion. The modification of Au-NPs can attract free electron (e-) to accumulate and promote the separation of e- and holes (h+) in the thermoelectric process, thereby further promoting e--rich Au-NPs-induced H2O2 homolysis and h+-H2O half-reaction to generate hydroxyl radicals, realizing the synergistic application of photothermal therapy and pyroelectric dynamic therapy in tumor treatment.

Blocking Cancer-Nerve Crosstalk for Treatment of Metastatic Bone Cancer Pain.

The tumor microenvironment is a complex milieu where neurons constitute an important non-neoplastic cell type. From "cancer neuroscience," the crosstalk between tumors and neurons favors the rapid growth of both, making the cancer-nerve interaction a reciprocally beneficial process. Thus, cancer-nerve crosstalk may provide new targets for therapeutic intervention against cancer and cancer-related symptoms. We proposed a nerve-cancer crosstalk blocking strategy for metastatic bone cancer pain treatment, achieved by Mg/Al layered-double-hydroxide nanoshells (Mg/Al-LDH) with AZ-23 loaded inside and alendronate decorated outside. The pain-causing H+ is rapidly eliminated by the LDH, with neurogenesis inhibited by the antagonist AZ-23. As positive feedback, the decreased pain reverses the nerve-to-cancer Ca2+ crosstalk-related cell cycle, dramatically inhibiting tumor growth. All experiments confirm the improved pain threshold and enhanced tumor inhibition. The study may inspire multidisciplinary researchers to focus on cancer-nerve crosstalk for treating cancer and accompanied neuropathic diseases.

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.