PDLIM3 knockdown promotes ferroptosis in endometriosis progression via inducing Gli1 degradation and blocking Hedgehog signaling pathway.

AIMS: Current evidence suggests that there is no completely effective method for endometriosis (EMS) without trauma due to diverse adverse effects. Reliable evidence illustrates that inhibiting ferroptosis is a potential strategy for EMS. We sufficiently verified that the expression of endogenous protein PDZ and LIM domain 3 (PDLIM3) was significantly increased in EMS. METHODS: PDLIM3 knockdown reduced primary ectopic endometrial stromal cells' (EESCs) viability and migration, and elevated ferroptosis signaling indicators including Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS) in EESCs. RESULTS: Mechanistic studies revealed that inhibition of PDLIM3 accelerated glioma-associated oncogene-1 (Gli1) degradation and further deactivated Hedgehog signaling. Gli1 inhibitor, GANT61, abrogated the impact of PDLIM3 deletion on EESC growth, migration, and ferroptosis. In vivo experiments suggested that PDLIM3 reduction repressed the growth of endometrial lesions. Likewise, repression of PDLIM3 promoted ferroptosis and attenuated Hedgehog signaling in endometrial lesions. CONCLUSIONS: Collectively, silencing of PDLIM3 facilitates ferroptosis in EMS by inducing Gli1 degradation and blocking Hedgehog signaling. It may provide an alternative strategy for developing therapeutic agents of EMS in the future.

Plasmon-Switched Kinetics for Formic Acid Dehydrogenation: Selective Adsorption Driven by Local Field and Hot Carriers.

Understanding illumination-mediated kinetics is essential for catalyst design in plasmon catalysis. Here we prepare Pd-based plasmonic catalysts with tunable electronic structures to reveal the underlying illumination-enhanced kinetic mechanisms for formic acid (HCOOH) dehydrogenation. We demonstrate a kinetic switch from a competitive Langmuir-Hinshelwood adsorption mode in dark to a non-competitive type under irradiation triggered by local field and hot carriers. Specifically, the electromagnetic field induces a spatial-temporal separation of dehydrogenation-favorable configurations of reactant molecule HCOOH and HCOO- due to their natural different polarities. Meanwhile, the generated energetic carriers can serve as active sites for selective molecular adsorption. The hot electrons act as adsorption sites for HCOOH, while holes prefer to adsorb HCOO- . Such unique non-competitive adsorption kinetics induced by plasmon effects serves as another typical characteristic of plasmonic catalysis that remarkably differs from thermocatalysis. This work unravels unique adsorption transformations and a kinetic switching driven by plasmon nonthermal effects.

Photo-enhanced dehydrogenation of formic acid on Pd-based hybrid plasmonic nanostructures.

Coupling visible light with Pd-based hybrid plasmonic nanostructures has effectively enhanced formic acid (FA) dehydrogenation at room temperature. Unlike conventional heating to achieve higher product yield, the plasmonic effect supplies a unique surface environment through the local electromagnetic field and hot charge carriers, avoiding unfavorable energy consumption and attenuated selectivity. In this minireview, we summarized the latest advances in plasmon-enhanced FA dehydrogenation, including geometry/size-dependent dehydrogenation activities, and further catalytic enhancement by coupling local surface plasmon resonance (LSPR) with Fermi level engineering or alloying effect. Furthermore, some representative cases were taken to interpret the mechanisms of hot charge carriers and the local electromagnetic field on molecular adsorption/activation. Finally, a summary of current limitations and future directions was outlined from the perspectives of mechanism and materials design for the field of plasmon-enhanced FA decomposition.

Destruction of a Copper Metal-Organic Framework to Induce CuPt Growth as a Heterojunction Catalyst for Hydrogen Peroxide Sensing.

Assembling bimetallic alloys (BAs) with metal-organic frameworks (MOFs) to form heterojunctions has emerged as a promising strategy for the construction of highly active electrocatalysts. However, the current approaches to prepare BA@MOF heterojunctions suffer from poor controllability. In this work, a fascinating method involving partial thermal reduction and galvanic replacement to induce CuPt growth on a CuHHTP MOF (HHTP=2,3,6,7,10,11-hexahydroxytriphenylene) is reported in order to construct a CuPt@CuHHTP heterojunction. The size of the CuPt nanoparticles can be effectively regulated by modifying the reduction temperature. The resultant CuPt NP@CuHHTP heterojunction nanoarrays exhibit high electrocatalytic activity and potential as an electrochemical H2 O2 sensor with a low detection limit (5 nM), high sensitivity (6.942 mA ⋅ mM-1 ⋅ cm-2 ), and outstanding selectivity. This in situ approach provides not only new insights into the preparation of BA@MOF-based heterojunctions but also an effective approach for the optimization of the catalytic performance of MOFs and related materials.

Natural oxidase-mimicking copper-organic frameworks for targeted identification of ascorbate in sensitive sweat sensing.

Sweat sensors play a significant role in personalized healthcare by dynamically monitoring biochemical markers to detect individual physiological status. The specific response to the target biomolecules usually depends on natural oxidase, but it is susceptible to external interference. In this work, we report tryptophan- and histidine-treated copper metal-organic frameworks (Cu-MOFs). This amino-functionalized copper-organic framework shows highly selective activity for ascorbate oxidation and can serve as an efficient ascorbate oxidase-mimicking material in sensitive sweat sensors. Experiments and calculation results elucidate that the introduced tryptophan/histidine fundamentally regulates the adsorption behaviors of biomolecules, enabling ascorbate to be selectively captured from complex sweat and further efficiently electrooxidized. This work provides not only a paradigm for specifically sweat sensing but also a significant understanding of natural oxidase-inspired MOF nanoenzymes for sensing technologies and beyond.

Synergistic Combination of Fermi Level Equilibrium and Plasmonic Effect for Formic Acid Dehydrogenation.

Developing an efficient catalyst for formic acid (FA) dehydrogenation is a promising strategy for safe hydrogen storage and transportation. Herein, we successfully developed trimetallic NiAuPd heterogeneous catalysts through a galvanic replacement reaction and a subsequent chemical reduction process to boost hydrogen generation from FA decomposition at room temperature by coupling Fermi level engineering with plasmonic effect. We demonstrated that Ni worked as an electron reservoir to donate electrons to Au and Pd driven by Fermi level equilibrium whereas plasmonic Au served as an optical absorber to generate energetic hot electrons and a charge-redistribution mediator. Ni and Au worked cooperatively to promote the charge heterogeneity of surface-active Pd sites, leading to enhanced chemisorption of formate-related intermediates and eventually outstanding activity (342 mmol g-1 h-1 ) compared with bimetallic counterpart. This work offers excellent insight into the rational design of efficient catalysts for practical hydrogen energy exploitation.

In situ electrochemical reductive construction of metal oxide/metal-organic framework heterojunction nanoarrays for hydrogen peroxide sensing.

Transition metal oxide/metal-organic framework heterojunctions (TMO@MOF) that combine the large specific surface area of MOFs with TMOs' high catalytic activity and multifunctionality, show excellent performances in various catalytic reactions. Nevertheless, the present preparation approaches of TMO@MOF heterojunctions are too complex to control, stimulating interests in developing simple and highly controllable methods for preparing such heterojunction. In this study, we propose an in situ electrochemical reduction approach to fabricating Cu2O nanoparticle (NP)@CuHHTP heterojunction nanoarrays with a graphene-like conductive MOF CuHHTP (HHTP is 2,3,6,7,10,11-hexahydroxytriphenylene). We have discovered that size-controlled Cu2O nanoparticles could be in situ grown on CuHHTP by applying different electrochemical reduction potentials. Also, the obtained Cu2O NP@CuHHTP heterojunction nanoarrays show high H2O2 sensitivity of 8150.6 µA·mM-1·cm2 and satisfactory detection performances in application of measuring H2O2 concentrations in urine and serum samples. This study offers promising guidance for the synthesis of MOF-based heterojunctions for early cancer diagnosis.

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration.

Background: The current study aimed to investigate the interrelation between P2RY14 and the prognosis of patients suffering from lung adenocarcinoma (LUAD) following surgery. Methods: The differentially expressed gene (DEG) P2RY14 was screened by the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Immunology Database and Analysis Portal (ImmPort) databases. The relationship between P2RY14 and clinical data of LUAD was analyzed in TCGA and Kaplan-Meier (KM)-plotter databases. The association of P2RY14 with immune cells and immune-related expressed genes was analyzed in the Tumor Immune Estimation Resource (TIMER) database. A retrospective analysis of the 100 patients clinical data undergoing pulmonary adenocarcinoma surgery admitted to Nanjing Chest Hospital. Immunohistochemistry (IHC) analysis was carried out to evaluate the P2RY14 expression in lung cancer tissues, and quantitative reverse transcription PCR (RT-qPCR) was used to confirm the mRNA expression of this gene in LUAD tissues. And their survival was evaluated. KM method and the log-rank test were used for univariate survival analysis, and the Cox regression method was employed for multivariate survival analysis. Results: P2Y14 was the DEG identified by the database. P2Y14 expression was upregulated in para-cancer tissues in comparison to cancer tissues. Patients suffering from LUAD who have high P2RY14 expression had a better prognosis than those with low expression. P2RY14 expression was shown to be substantially linked with immune invasion in the TIMER database. Finally, the trial included 100 patients, of which 80 died and 20 survived with a mean overall survival (OS) of 48 months. Between the high and low expression groups of P2RY14, there were statistically significant variations in the clinical stage and differentiation degree (P<0.05). Cox regression analysis revealed that differentiation degree, smoking history, and P2RY14 expression were independent risk factors for the prognosis of LUAD patients (all P<0.05). Conclusions: P2RY14 can substantially prolong the OS of patients suffering from LUAD and can be utilized as a new LUAD predictive biomarker. P2RY14 may be related to LUAD immune invasion and have an essential role in inhibiting tumor cell immune escape within the LUAD microenvironment.

Reshaping Membrane Polymorphism of Polymer Vesicles through Dynamic Gas Exchange.

The quest for a universal method to shape the vesicular morphology in dynamic and diversified manners is a challenging topic of cell mimicry. Here we present a simple gas exchange strategy that can direct the deformation movements of polymer vesicles. Such vesicles are assembled by a class of gas-based dynamic polymers, where CO2 connects between the frustrated Lewis pair via dynamic gas-bridged bonds. Use of other competitive gases (N2O, SO2, or C2H4) to in situ exchange the CO2 linkages can change the polymer structure and drive the membrane to proceed with three fundamental movements, including membrane stretching, membrane incurvation, and membrane protrusion, thus remolding the shapes of polymersomes. The choices of gas types, concentrations, and combinations are crucial to adjusting the vesicle evolution, local change of membrane curvature, and anisotropic geometrical transformation. This will become a generalized strategy to control the vesicular polymorphism and deformable behavior.

Targeting Cis-Regulatory Elements for Rice Grain Quality Improvement.

Rice is the most important source of food worldwide, providing energy, and nutrition for more than half of the population worldwide. Rice grain quality is a complex trait that is affected by several factors, such as the genotype and environment, and is a major target for rice breeders. Cis-regulatory elements (CREs) are the regions of non-coding DNA, which play a critical role in gene expression regulation. Compared with gene knockout, CRE modifications can fine-tune the expression levels of target genes. Genome editing has provided opportunities to modify the genomes of organisms in a precise and predictable way. Recently, the promoter modifications of coding genes using genome editing technologies in plant improvement have become popular. In this study, we reviewed the results of recent studies on the identification, characterization, and application of CREs involved in rice grain quality. We proposed CREs as preferred potential targets to create allelic diversity and to improve quality traits via genome editing strategies in rice. We also discussed potential challenges and experimental considerations for the improvement in grain quality in crop plants.

Outcomes and safety of concomitant topiramate or metformin for antipsychotics-induced obesity: a randomized-controlled trial.

BACKGROUND: Although there are some existing data describing the usage of topiramate in patients with antipsychotic-induced obesity, study on its comparison with metformin is limited. This study aimed to explore the effectiveness and safety of concomitant topiramate on antipsychotic-induced obesity as well as its comparison with metformin. METHODS: 62 stabilized outpatients with antipsychotic-induced obesity were randomized into the topiramate group and the metformin group with 16-week treatment. The patients' weight, body mass index (BMI), waist-hip ratio, and their side effects were assessed and compared. Intention-to-treat and completer analyses were performed. Meanwhile, covariance analysis was conducted to control the impact of the significant difference in BMI between the two groups. RESULTS: The two groups had comparable characteristics, though their difference in baseline BMI was significant. (1) Intention-to-treat analyses: the random missing values were replaced using the last observation carried forward method when intention-to-treat analyses were conducted. Compared with the baseline, the weight, BMI, and waist-hip ratio in the topiramate group markedly decreased at each follow-up, whereas, in the metformin group, only waist-hip ratio significantly decreased at 4 weeks after treatment. Compared with the metformin, only weight and BMI in the topiramate group were significantly decreased at week 4 after treatment, and at week 8-16, weight, BMI and waist-hip ratio were remarkably declined. (2) Completer analyses: compared with the baseline, the weight, BMI, and waist-hip ratio in the topiramate group at week 4-16 were markedly decreased, whereas only waist-hip ratio with metformin was significantly decreased at week 4. Compared with the metformin, all BMI with topiramate were markedly decreased at week 4-16. Moreover, its weight and waist-hip ratio also were notably lowered at week 8. No significant differences in adverse events were found between the two groups. CONCLUSIONS: Topiramate, similar to metformin in reducing obesity as previously reported, also significantly reduced body weight, BMI, and waist-hip ratio in patients with antipsychotic-induced obesity and demonstrated well tolerance in psychiatric patients. Trial registration The trial was registered at http://www.chictr.org.cn , and the number was ChiCTR-IPR-17013122.

Structural variation of transition metal-organic frameworks using deep eutectic solvents with different hydrogen bond donors.

Deep eutectic solvents (DESs) have attracted extensive attention in the field of material synthesis as green solvents. They have similar physical and chemical properties to the traditional ionic liquids (ILs) while being much cheaper and more environmentally friendly. Herein, seven transition metal-organic frameworks, namely [NH4][Zn(BTC)(NH3)2]·H2O (1), [Cu(PDC)(NH3)] (2), [Co(H2BTC)2(e-urea)2]·(e-urea)·1/4H2O (3), K0.63(NH4)0.37[Mn(PZDC)] (4), [NH4][Mn(BTC)(H2O)] (5), [CH3NH3][Mn3(HBTC)2(BTC)·3H2O (6), and [Co3(BTC)2(urea)2]·2H2O (7), were synthesized in deep eutectic solvents of choline chloride and urea/e-urea/m-urea (H3BTC = 1,3,5-benzenetricarboxylic acid; H2PDC = 2,6-pyridinedicarboxylic acid; H2PZDC = 3,5-pyrazoledicarboxylic acid; e-urea = ethylene urea; m-urea = N,N-dimethylurea). Of particular interest is the fact that the utilization of different hydrogen bond donors in DES mixtures can lead to the formation of different frameworks. The multiple roles of hydrogen bond donors in the reactions were discussed. Furthermore, compound 7 exhibited catalytic activity for the oxidation of styrene, and thus it can be used as a heterogeneous catalyst due to its good stability. These results promote the understanding of the application of DESs in synthesizing novel transition metal-organic frameworks.

Initiation of Targeted Nanodrug Delivery in Vivo by a Multifunctional Magnetic Implant.

Implant-mediated targeted drug delivery without an external magnetic field is very challenging. In this work, we report targeted nanodrug delivery initiated by a Fe3O4/poly(lactic-co-glycolic acid) implant scaffold with high magnetism. The implant scaffold is biocompatible and durable. It effectively attracts nanodrugs to its surface, thus killing cancer cells. These findings provide a proof of concept for the magnetic implant-directed nanodrug targeting without the need for an external magnetic field. This approach may further facilitate more precise medical treatments.

The efficacy, acceptability, and safety of five atypical antipsychotics in patients with first-episode drug-naïve schizophrenia: a randomized comparative trial.

BACKGROUND: Differences in effectiveness and tolerability between different atypical antipsychotics may affect schizophrenic patients' treatment adherence or prognosis. However, which kind of antipsychotic was more effective and safe in the treatment of schizophrenia is still being debated. This study attempted to understand whether there are any differences in efficacy, acceptability, and safety between the five atypical antipsychotics in patients with first-episode schizophrenia. METHODS: Two hundred cases of inpatients with first-episode drug-naïve schizophrenia were randomly assigned to 6-8 weeks of treatment with either of aripiprazole, risperidone, quetiapine, olanzapine, or ziprasidone from October 2012 to November 2014. The efficacy, acceptability, and safety measurement after 6-8 weeks of treatment of the five kinds of antipsychotics were evaluated by the deduction rate of Brief Psychiatric Rating Scale (BPRS) total score, the proportion of treatment discontinuation, and adverse events, respectively. Whether the treatment discontinuation or combination therapy for baseline antipsychotics after titration mainly depended on ineffective or less effective on an initial-assigned antipsychotic during the study period. RESULTS: BPRS total scores in each antipsychotic group were significantly decreased at the end of the study (P < 0.01), and only the deduction rate of BPRS total scores in the risperidone group was markedly higher than those in the groups of aripiprazole (P < 0.01) and olanzapine (P < 0.05) after controlling the impact of the differences of age of onset. There were significant differences between quetiapine (χ2 = 5.46, P = 0.019), olanzapine (χ2 = 5.6, P = 0.018), and ziprasidone regarding the proportion of maintaining on initially allocated therapy. In addition, the difference in treatment discontinuation between male and female patients was also significant (χ2 = 9.897, P = 0.002), and odds ratio of treatment discontinuation in male and female patients was 0.37 (95% CI 0.198-0.693); however, no difference in treatment discontinuation was found between five antipsychotics. Extrapyramidal symptoms in the groups of quetiapine and olanzapine were notably less than the other three kinds of antipsychotics (P < 0.05), but there were no significant differences in other adverse events between the five antipsychotic groups. CONCLUSIONS: Risperidone was more effective than aripiprazole and olanzapine in treating first-episode schizophrenia. The present study revealed the superiority of quetiapine and olanzapine over ziprasidone with remarkably less severe extrapyramidal adverse effects, especially with lower drop-out and treatment discontinuation. There were no differences in terms of other adverse events although the risk of treatment discontinuation was higher in female patients. Trial registration 2012-3-88. Registered 20 July 2012.