TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation.

A plethora of growth factors regulate keratinocyte proliferation and differentiation that control hair morphogenesis and skin barrier formation. Wavy hair phenotypes in mice result from naturally occurring loss-of-function mutations in the genes for TGF-alpha and EGFR. Conversely, excessive activities of TGF-alpha/EGFR result in hairless phenotypes and skin cancers. Unexpectedly, we found that mice lacking the Trpv3 gene also exhibit wavy hair coat and curly whiskers. Here we show that keratinocyte TRPV3, a member of the transient receptor potential (TRP) family of Ca(2+)-permeant channels, forms a signaling complex with TGF-alpha/EGFR. Activation of EGFR leads to increased TRPV3 channel activity, which in turn stimulates TGF-alpha release. TRPV3 is also required for the formation of the skin barrier by regulating the activities of transglutaminases, a family of Ca(2+)-dependent crosslinking enzymes essential for keratinocyte cornification. Our results show that a TRP channel plays a role in regulating growth factor signaling by direct complex formation.

Reconstructing Electrically Conductive Nanofiltration Membranes with an Aniline-Functionalized Carbon Nanotubes Interlayer for Highly Effective Toxic Organic Treatment.

Conductive nanofiltration (CNF) membranes hold great promise for removing small organic pollutants from water through enhanced Donnan exclusion and electrocatalytic degradation. However, current CNF membranes face limitations in conductivity, structural stability, and nanochannel control strategies. This work addresses these challenges by introducing aniline-functionalized carbon nanotubes (NH2-CNTs) as an interlayer. NH2-CNTs enhance the dispersibility and adhesion of pristine carbon nanotubes, leading to a more conductive and stable composite nanofiltration membrane. The redesigned NH2-CNTs interlayered conductive nanofiltration (NICNF) membrane exhibits a 10-fold increase in conductivity and a high response degree (80%) with excellent cyclic stability, surpassing existing CNF membranes. The synergistic effects of enhanced Donnan exclusion, voltage switching, and electrocatalysis enable the NICNF membrane to achieve selective recovery of mixed dyes, 98.97% removal of residual wastewater toxicity, and a 5.2-fold increase in permeance compared to the commercial NF270 membrane. This research paves the way for next-generation multifunctional membranes capable of the efficient recovery and degradation of toxic organic pollutants in wastewater.

Contribution of individual and cumulative social determinants of health underlying gender disparities in periodontitis in a representative US population: A cross-sectional NHANES study.

AIM: To examine the impact of both individual and cumulative social determinants of health (SDoH) on the likelihood of developing periodontitis, while also exploring any gender disparities in this relationship. MATERIALS AND METHODS: Data of self-reported SDoH domains and sub-items based on Healthy People 2030 were obtained from the U.S. National Health and Nutrition Examination Surveys between 1999 and 2014. Logistic regression models, weighted by survey responses, were used to examine the relationship between SDoH (including eight sub-items and the cumulative number of unfavourable SDoH) and periodontitis. The results were further analysed by gender. RESULTS: A total of 18,075 participants (8867 males and 9208 females) were included in the main analysis, of which 5814 (32.2%) had periodontitis. The study found that certain unfavourable SDoH were individually associated with higher odds of periodontitis, and the cumulative number of unfavourable SDoH was positively linked to the odds of developing periodontitis. Furthermore, males exposed to more unfavourable SDoH appeared to be more susceptible to developing periodontitis than females. CONCLUSIONS: The findings suggest that unfavourable SDoH, especially when they accumulate, are associated with an increased odds of periodontitis and contribute to gender disparities within the U.S.

Outdoor gardening activity with different frequency and duration may be associated with reduction of total and cause-specific mortality risk for general U.S. adults: Findings from the NHANES.

BACKGROUND AND AIMS: Engaging in recommended levels of physical activity (PA) is associated with reduced overall and cause-specific mortality rates. Our study aims to examine the relationship between gardening-specific PA and all-cause and cause-specific mortality based on representative U.S. adults. METHODS AND RESULTS: A total of 13,812 adults representing 663.5 million non-institutionalized U.S. adults were included in the National Health and Nutrition Examination Survey. Self-reported gardening activity (GA) was assessed by a validated questionnaire, and outcomes of interest were all-cause mortality and mortality specific to certain causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survey-multivariable Cox proportional hazards models. During a median follow-up period of 16.8 years (Interquartile range = 14.8-18.7), there were 3,476 deaths. After adjusting for potential covariates, we found that participants exposed to GA were more likely to have a lower risk of total mortality [HR (95% CI): 0.76 (0.68, 0.85), P-value < 0.001], cancer-specific mortality [HR (95% CI): 0.81 (0.67, 0.99), P-value < 0.05], cardiovascular disease mortality [HR (95% CI): 0.65 (0.53, 0.80), P-value < 0.001], and respiratory disease mortality [HR (95% CI): 0.66 (0.45, 0.98), P-value < 0.05], compared to those without GA exposure. Furthermore, engaging in GA more frequently and for longer durations was significantly associated with a lower total mortality risk. CONCLUSION: Our study provides evidence that engaging in GA is associated with a decreased risk of overall and cause-specific mortality. However, further longitudinal or interventional studies are needed to investigate the potential benefits of GA.

An auxiliary diagnostic tool for common fundus diseases based on fundus color photography and light-weight classification models.

OBJECTIVE: To evaluate the performance of two lightweight neural network models in the diagnosis of common fundus diseases and make comparison to another two classical models. METHODS: A total of 16,000 color fundus photography were collected, including 2000 each of glaucoma, diabetic retinopathy (DR), high myopia, central retinal vein occlusion (CRVO), age-related macular degeneration (AMD), optic neuropathy, and central serous chorioretinopathy (CSC), in addition to 2000 normal fundus. Fundus photography was obtained from patients or physical examiners who visited the Ophthalmology Department of Beijing Tongren Hospital, Capital Medical University. Each fundus photography has been diagnosed and labeled by two professional ophthalmologists. Two classical classification models (ResNet152 and DenseNet121), and two lightweight classification models (MobileNetV3 and ShufflenetV2), were trained. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate the performance of the four models. RESULTS: Compared with the classical classification model, the total size and number of parameters of the two lightweight classification models were significantly reduced, and the classification speed was sharply improved. Compared with the DenseNet121 model, the ShufflenetV2 model took 50.7% less time to make a diagnosis on a fundus photography. The classical models performed better than lightweight classification models, and Densenet121 showed highest AUC in five out of the seven common fundus diseases. However, the performance of lightweight classification models is satisfying. The AUCs using MobileNetV3 model to diagnose AMD, diabetic retinopathy, glaucoma, CRVO, high myopia, optic atrophy, and CSC were 0.805, 0.892, 0.866, 0.812, 0.887, 0.868, and 0.803, respectively. For ShufflenetV2model, the AUCs for the above seven diseases were 0.856, 0.893, 0.855, 0.884, 0.891, 0.867, and 0.844, respectively. CONCLUSION: The training of light-weight neural network models based on color fundus photography for the diagnosis of common fundus diseases is not only fast but also has a significant reduction in storage size and parameter number compared with the classical classification model, and can achieve satisfactory accuracy.

Combined transcriptomic and metabolomic analysis of alginate oligosaccharides alleviating salt stress in rice seedlings.

BACKGROUND: Salt stress is one of the key factors limiting rice production. Alginate oligosaccharides (AOS) enhance plant stress resistance. However, the molecular mechanism underlying salt tolerance in rice induced by AOS remains unclear. FL478, which is a salt-tolerant indica recombinant inbred line and IR29, a salt-sensitive rice cultivar, were used to comprehensively analyze the effects of AOS sprayed on leaves in terms of transcriptomic and metabolite profiles of rice seedlings under salt stress. RESULTS: In this experiment, exogenous application of AOS increased SOD, CAT and APX activities, as well as GSH and ASA levels to reduce the damage to leaf membrane, increased rice stem diameter, the number of root tips, aboveground and subterranean biomass, and improved rice salt tolerance. Comparative transcriptomic analyses showed that the regulation of AOS combined with salt treatment induced the differential expression of 305 and 1030 genes in FL478 and IR29. The expressed genes enriched in KEGG pathway analysis were associated with antioxidant levels, photosynthesis, cell wall synthesis, and signal transduction. The genes associated with light-trapping proteins and RLCK receptor cytoplasmic kinases, including CBA, LHCB, and Lhcp genes, were fregulated in response to salt stress. Treatment with AOS combined with salt induced the differential expression of 22 and 50 metabolites in FL478 and IR29. These metabolites were mainly related to the metabolism of amino and nucleotide sugars, tryptophan, histidine, and ß -alanine. The abundance of metabolites associated with antioxidant activity, such as 6-hydroxymelatonin, wedelolactone and L-histidine increased significantly. Combined transcriptomic and metabolomic analyses revealed that dehydroascorbic acid in the glutathione and ascorbic acid cycles plays a vital role in salt tolerance mediated by AOS. CONCLUSION: AOS activate signal transduction, regulate photosynthesis, cell wall formation, and multiple antioxidant pathways in response to salt stress. This study provides a molecular basis for the alleviation of salt stress-induced damage by AOS in rice.

Anticancer activity of oleanolic acid and its derivatives modified at A-ring and C-28 position.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

Synthesis, evaluation and mechanism exploration of 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors.

Thirteen 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids which were reported for the first time were designed and synthesized as novel urease inhibitors. Most of them showed higher potency than the positive control acetohydroxamic acid, with 2-(N-(3-nitrophenyl)-N-(4-bromophenylsulfonyl)aminoacetohydroxamic acid (d7) being the most active (IC50 = 0.13 ± 0.01 µM). Compound d7 reversibly inhibits urease with mixed mechanism showing excellent binding affinity to urease active site (KD = 0.34 nM, Ki=0.065 ± 0.003 µM andKi' = 1.20 ± 0.09 µM) and very low cytotoxicity against mammalian cells (cell viability of 91.4 % against HepG2 at 250 µg/mL). These positive results indicated that d7 may be used as the lead for further research to develop urease inhibitors with promising properties.

Diagnostic Value of Optical Coherence Tomography Angiography for Choroidal Neovascularization in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to evaluate the diagnostic value of optical coherence tomography angiography (OCTA) in detecting the choroidal neovascularization (CNV) in age-related macular degeneration (AMD). METHODS: A systematic review and meta-analysis was performed by searching Pubmed, Science Direct, Embase, and Web of Science. The pooled sensitivity and specificity with 95% confidence intervals (CIs), area under the summary receiver operator characteristic curve (sROC), and the total accurate classification rate were used to evaluate OCTA's diagnostic value of CNV in AMD patients. RESULTS: Seven studies involving 517 eyes were included in the analysis. The mean age of subjects in each study ranged from 58.5 years to 81.7 years. Fluorescein angiography was applied as the gold standard in 5 studies. There were 350 eyes diagnosed with CNV, OCTA detected 301 eyes correctly, while among the 167 eyes without CNV, OCTA identified 150 correctly. The total accurate classification rate was 87.23%. The Spearman's rank correlation coefficient was 0.5, indicating that there was no significant threshold effect in the current study (S = 8, p = 0.103). The pooled sensitivity and pooled specificity were 0.89 (95% CI: 0.82, 0.94) and 0.96 (95% CI: 0.85, 1.00), respectively. The area under sROC was up to 0.911. CONCLUSION: The specificity of OCTA for the detection of CNV in AMD patients is extremely high; however, the sensitivity still needs to be improved. In general, the meta-analysis revealed that OCTA had a high diagnostic value for the detection of CNV in AMD patients.

Precisely Patterned Nanostrand Surface of Cucurbituril[n]-Based Nanofiltration Membranes for Effective Alcohol-Water Condensation.

Low concentration alcohols produced by state-of-the-art biological fermentation restrict subsequent purification processes for chemical, pharmaceutical, biofuel, and other applications. Herein, a rarely reported cucurbituril[n] (n = 6, 8) is employed to pattern the thin-film composite membranes with controllable and quantifiable nanostrand structures through a host-guest strategy. The resulting nanofiltration membrane with such morphology is the first report that exhibits excellent separation performance for isopropyl alcohol (IPA) and water, condensing the initial 0.5 wt % IPA aqueous solution to 9.0 wt %. This not only provides a novel strategy for patterning nanostructural morphology but also makes nanofiltration membranes promising for alcohol condensation in the biological fermentation industry that may reduce energy consumption and postprocessing costs.

Primary malignant epithelioid and rhabdoid tumor of bone harboring ZNF532-NUTM1 fusion: the expanding NUT cancer family.

NUTM1 gene rearrangement is the genetic hallmark of NUT carcinoma, an aggressive tumor that most commonly affects the thoracic and head and neck regions and often exhibits squamous differentiation. The most common fusion partner gene is BRD4, followed by BRD3 and NSD3. Recently, NUTM1 gene rearrangement has been identified in rare tumors from soft tissues, intracranial locations, and other visceral organs. These tumors often show high grade malignant epithelioid to round cell histomorphology and lack evidence of squamous and/or epithelial differentiation. Therefore, their relationship with classic NUT carcinoma is still uncertain. Here, we present a primary mandible bone tumor of a 21-year-old female exhibiting monotonous epithelioid and rhabdoid cytomorphology, vesicular chromatin, and prominent nucleoli. The initial immunohistochemical workup was non-specific, showing only CD34 positivity while being negative for cytokeratin (AE1/AE3), EMA, p63, etc. INI-1 expression was retained. RNA sequencing was performed and identified a rare ZNF532-NUTM1 gene fusion, which had only been reported in a single case of pulmonary NUT carcinoma. The fusion was confirmed by FISH for NUTM1 gene rearrangement and supported by diffuse and strong NUT immunoreactivity. MYC mRNA up-regulation and immunoreactivity, a common finding in NUT carcinoma, was also observed in this tumor, suggesting a possible common pathogenetic mechanism and potential treatment target. The patient presented with a non-metastatic disease status and received hemimandibulectomy, selective neck dissection (level Ib), and post-operative radiation therapy. She remained disease free 3.6 years after the initial diagnosis.

[The Impact of Demoralization on Spiritual Well-Being in Terminally Ill Patients].

BACKGROUND: Terminally ill patients often experience demoralization, which negatively impacts their spiritual well-being. However, studies on the relationship between demoralization and levels of spiritual well-being in Taiwan are still at an early stage. Thus, more research is required to verify and support the correlation between demoralization and spirituality and to establish methods to care for and treat demoralization. PURPOSE: The purposes of this study were to investigate the demoralization and spiritual-well-being status of terminally ill patients and to determine the value of demographic data, disease characteristics, demoralization in predicting spiritual well-being. METHODS: A cross-sectional research design was used to evaluate terminally ill patients who were currently receiving hospice care at a teaching hospital in southern Taiwan. Data were collected using a structured questionnaire that included a demographic datasheet and the Chinese demoralization and spiritual well-being scale. Pearson product-moment correlation and hierarchical multiple regression were performed to analyze the relationship between the target variables and spiritual well-being. RESULTS: Of the 82 participants surveyed, 81.7% had high levels of demoralization. The average spiritual well-being score for the participants was 31.7 (moderate). A significant and negative correlation was found between degree of demoralization and level of spiritual well-being (r = -.600, p < .01). Regression analysis showed that, after controlling for demographic characteristics, disease characteristics, and other variables, demoralization scores were shown to predict the spiritual-well-being score, explaining 12.7% of total variance (ß = -.41, p < .001). In other words, higher demoralization was associated with lower spiritual well-being. CONCLUSIONS: Demoralization is a common problem in people with terminal illnesses and is an important factor affecting spiritual well-being in this patient population. In clinical practice, early assessment and identification of demoralization in patients as well as establishing relevant models of care for demoralization are necessary to help patients attain spiritual well-being at the end of life.

Psychometric properties of the Chinese version of resilience scale specific to cancer: an item response theory analysis.

OBJECTIVE: Classic theory test has been used to develop and validate the 25-item Resilience Scale Specific to Cancer (RS-SC) in Chinese patients with cancer. This study was designed to provide additional information about the discriminative value of the individual items tested with an item response theory analysis. METHODS: A two-parameter graded response model was performed to examine whether any of the items of the RS-SC exhibited problems with the ordering and steps of thresholds, as well as the ability of items to discriminate patients with different resilience levels using item characteristic curves. RESULTS: A sample of 214 Chinese patients with cancer diagnosis was analyzed. The established three-dimension structure of the RS-SC was confirmed. Several items showed problematic thresholds or discrimination ability and require further revision. CONCLUSIONS: Some problematic items should be refined and a short-form of RS-SC maybe feasible in clinical settings in order to reduce burden on patients. However, the generalizability of these findings warrants further investigations.

Effect of a mentor-based, supportive-expressive program, Be Resilient to Breast Cancer, on survival in metastatic breast cancer: a randomised, controlled intervention trial.

BACKGROUND: Because of medical advances, metastatic breast cancer (MBC) is now viewed as a chronic disease, rather than an imminent death sentence. Helping women live with this disease requires more than a medical approach to symptoms. Thus, a mentor-based and supportive-expressive program 'Be Resilient to Breast Cancer' (BRBC) was designed to help Chinese women with MBC enhance their resilience levels, biopsychosocial functions, and potentially extend their life span. METHODS: A total of 226 women with MBC were randomly assigned, in a 1 : 1 ratio, to an intervention group (IG) that participated in BRBC or to a control group (CG) that received no intervention. Be Resilient to Breast Cancer was conducted for 120 min once a week. Primary outcomes were cancer-specific survival and secondary outcomes were resilience, Allostatic Load Index (ALI), anxiety, depression, and quality of life (QoL). The Cox proportional-hazards model was used for survival analysis and growth mixture models were performed for secondary outcomes. RESULTS: Be Resilient to Breast Cancer did not significantly prolong 3- or 5-year survival (median survival, 36.7 months in IG and 31.5 months in CG). The hazard ratio for death was 0.736 (95% CI, 0.525-1.133, P=0.076; univariate Cox model) and 0.837 (95% CI, 0.578-1.211, P=0.345; multivariate Cox analysis). The IG improved in anxiety (ES=0.85, P<0.001), depression (ES=0.95, P<0.001), QoL (ES=0.55, P<0.001), resilience (ES=0.67, P<0.001), and ALI (ES=0.90, P<0.001) compared to CG. CONCLUSIONS: BRBC does not improve survival of women with MBC in this study, though longer follow up is warranted. It positively impacts resilience, QoL, ALI, and emotional distress.

Effect of a multidiscipline mentor-based program, Be Resilient to Breast Cancer (BRBC), on female breast cancer survivors in mainland China-A randomized, controlled, theoretically-derived intervention trial.

To reduce the risk of adjustment problems for breast cancer patients in mainland China, we examined the efficacy of a multidiscipline mentor-based program, Be Resilient to Breast Cancer (BRBC), delivered after breast surgery to (a) increase protective factors of social support, hope for the future, etc.; (b) decrease risk factors of Physical and Emotional Distress; and (c) increase outcomes of Resilience, Transcendence and Quality of Life (QOL). A multisite randomized controlled trial was conducted at 6 specialist cancer hospitals. 101 and 103 breast cancer patients were allocated to intervention group (IG) and control group (CG), respectively, and 112 general females (without breast cancer) were allocated to the norm group (NG). Participants completed measures that were related to latent variables derived from the Resilience Model for Breast Cancer (RM-BC) at baseline (T1), 2 months (T2), 6 months (T3), and 12 months (T4) after intervention. At T2, the IG reported significantly lower Depression (ES = 0.65,P = 0.0019) and Illness Uncertainty (ES = 0.57, P = 0.004), better Hope (ES = 0.81, P < 0.001) and QOL (ES = 0.60, P = 0.002) than did the CG. At T3, the IG reported significantly lower Anxiety (ES = 0.74, P < 0.001), better Social Support (ES = 0.51,P = 0.009), Transcendence (ES = 0.87, P < 0.001), and Resilience (ES = 0.83, P < 0.001) compared with the CG. At T4, the IG reported better Resilience though not significant (P = 0.085) and better Transcendence (P = 0.0243) than did the NG. The BRBC intervention improves the positive health outcomes and decreases the risk factors of illness-related distress of breast cancer patients during the high-risk cancer treatment.

Severe disturbance of glucose metabolism in peripheral blood mononuclear cells of schizophrenia patients: a targeted metabolomic study.

BACKGROUND: Schizophrenia is a widespread and debilitating mental disorder. However, the underlying molecular mechanism of schizophrenia remains largely unknown and no objective laboratory tests are available to diagnose this disorder. The aim of the present study was to characterize the alternations of glucose metabolites and identify potential diagnostic biomarkers for schizophrenia. METHODS: Gas chromatography/mass spectrometry based targeted metabolomic method was used to quantify the levels of 13 glucose metabolites in peripheral blood mononuclear cells (PBMCs) derived from healthy controls, schizophrenia and major depression subjects (n = 55 for each group). RESULTS: The majority (84.6%) of glucose metabolites were significantly disturbed in schizophrenia subjects, while only two (15.4%) glucose metabolites were differently expressed in depression subjects relative to healthy controls in both training set (n = 35/group) and test set (n = 20/group). Antipsychotics had only a subtle effect on glucose metabolism pathway. Moreover, ribose 5-phosphate in PBMCs showed a high diagnostic performance for first-episode drug-naïve schizophrenia subjects. CONCLUSION: These findings suggested disturbance of glucose metabolism may be implicated in onset of schizophrenia and could aid in development of diagnostic tool for this disorder.

Secular trends in the prevalence of meeting 24-hour movement guidelines among U.S. adolescents: evidence from NHANES 2007-2016.

Background: The 24-Hour Movement Guidelines (24-HMG) recommend a balanced combination of physical activity (PA), sedentary behavior (SB) and sleep (SLP) for optimal health. However, there is limited understanding of how well U.S. adolescents adhere to these guidelines. This study aims to analyze the prevalence trends of meeting the 24-HMG among a nationally representative sample of U.S. general adolescents. Methods: The study included 2,273 adolescents (55.3% boys) aged 16-19 who participated in the National Health and Nutrition Examination Surveys (NHANES) from 2007 to 2016. The researchers categorized the adolescents based on whether they met various PA, SB, and SLP recommendations, as well as different combinations of these recommendations, separately for boys and girls. The prevalence rate, weighted by survey data, was calculated along with a 95% confidence interval (CI) to assess the changes in meeting the 24-HMG among U.S. adolescents across different survey years and sociodemographic subgroups. Results: In the 2015-2016 cycle, approximately 6.3% of adolescents did not meet any of the three recommendations, while only 19.2% of adolescents achieved all three guidelines. Compliance with PA and SB recommendations among adolescents has decreased over time, from 72.5% (65.9% to 79.2%) to 64.2% (57.4% to 70.9%) for PA, and from 59.0% (49.6% to 68.4%) to 46.6% (37.8% to 55.5%) for SB, respectively, from 2007-2008 cycle to 2015-2016 cycle. Boys exhibited more favorable patterns in meeting different sets of recommendations compared to girls (p-value <0.001). This includes meeting both PA and SB guidelines (15.5% for boys and 11.1% for girls) and meeting both PA and SLP guidelines (19.5% for boys and 15.7% for girls). The level of parental education was found to have effect on meeting all three guidelines (Ptrend < 0.05). Conclusion: We analyzed ten consecutive years of representative NHANES data to evaluate the prevalence meeting 24-HMG and found that the proportion of adolescents aged 16-19 in the U.S. who adhered to all three movement guidelines simultaneously has consistently remained low throughout each survey cycle. Notably, there has been a significant decline in the proportion of adolescents meeting the SB guideline.

Circular DNAzyme-Switched CRISPR/Cas12a Assay for Electrochemiluminescent Response of Demethylase Activity.

DNA nanostructure provides powerful tools for DNA demethylase activity detection, but its stability has been significantly challenged. By virtue of circular DNA with resistance to exonuclease degradation, herein, the circular DNAzyme duplex with artificial methylated modification was constructed to identify the target and output the DNA activators to drive the CRISPR/Cas12a, constructing an "on-off-on" electrochemiluminescence (ECL) biosensor for monitoring the activity of the O6-methylguanine-DNA methyltransferase (MGMT). Specifically, the circular DNAzyme duplex consisted of the chimeric RNA-DNA substrate ring with double activator sequences and two single-stranded DNAzymes, whose catalytic domains were premodified with the methyl groups. When the MGMT was present, the methylated DNAzymes were repaired and restored the catalytic activity to cleave the chimeric RNA-DNA substrates, followed by the output of DNA activators to initiate the CRISPR/Cas12a. Subsequently, the ECL signals of silver nanoparticle-modified SnO2 nanospheres (Ag@SnO2) were recovered by releasing the ferrocene-labeled quenching probes (Fc-DNA) from the electrode surface because of the trans-cleavage activity of CRISPR/Cas12a, thus achieving the specific and sensitive ECL detection of MGMT from 2.5 × 10-4 to 2.5 × 102 ng/mL with a low limit (9.69 × 10-5 ng/mL). This strategy affords novel ideas and insights into research on how to project stable nucleic acid probes to detect DNA demethylases beyond traditional methods.

Microporous membrane with ionized sub-nanochannels enabling highly selective monovalent and divalent anion separation.

Membranes tailored for selective ion transport represent a promising avenue toward enhancing sustainability across various fields including water treatment, resource recovery, and energy conversion and storage. While nanochannels formed by polymers of intrinsic microporosity (PIM) offer a compelling solution with their uniform and durable nanometer-sized pores, their effectiveness is hindered by limited interactions between ions and nanochannel. Herein, we introduce the randomly twisted V-shaped structure of Tröger's Base unit and quaternary ammonium groups to construct ionized sub-nanochannel with a window size of 5.89-6.54 Å between anion hydration and Stokes diameter, which enhanced the dehydrated monovalent ion transport. Combining the size sieving and electrostatic interaction effects, sub-nanochannel membranes achieved exceptional ion selectivity of 106 for Cl-/CO32- and 82 for Cl-/SO42-, significantly surpassing the state-of-the-art membranes. This work provides an efficient template for creating functionalized sub-nanometer channels in PIM membranes, and paves the way for the development of precise ion separation applications.