BANMF-S: a blockwise accelerated non-negative matrix factorization framework with structural network constraints for single cell imputation.

MOTIVATION: Single cell RNA sequencing (scRNA-seq) technique enables the transcriptome profiling of hundreds to ten thousands of cells at the unprecedented individual level and provides new insights to study cell heterogeneity. However, its advantages are hampered by dropout events. To address this problem, we propose a Blockwise Accelerated Non-negative Matrix Factorization framework with Structural network constraints (BANMF-S) to impute those technical zeros. RESULTS: BANMF-S constructs a gene-gene similarity network to integrate prior information from the external PPI network by the Triadic Closure Principle and a cell-cell similarity network to capture the neighborhood structure and temporal information through a Minimum-Spanning Tree. By collaboratively employing these two networks as regularizations, BANMF-S encourages the coherence of similar gene and cell pairs in the latent space, enhancing the potential to recover the underlying features. Besides, BANMF-S adopts a blocklization strategy to solve the traditional NMF problem through distributed Stochastic Gradient Descent method in a parallel way to accelerate the optimization. Numerical experiments on simulations and real datasets verify that BANMF-S can improve the accuracy of downstream clustering and pseudo-trajectory inference, and its performance is superior to seven state-of-the-art algorithms. AVAILABILITY: All data used in this work are downloaded from publicly available data sources, and their corresponding accession numbers or source URLs are provided in Supplementary File Section 5.1 Dataset Information. The source codes are publicly available in Github repository https://github.com/jiayingzhao/BANMF-S.

Unconditional cash transfers reduce homelessness.

Homelessness is an economic and social crisis. In a cluster-randomized controlled trial, we address a core cause of homelessness-lack of money-by providing a one-time unconditional cash transfer of CAD$7,500 to each of 50 individuals experiencing homelessness, with another 65 as controls in Vancouver, BC. Exploratory analyses showed that over 1 y, cash recipients spent fewer days homeless, increased savings and spending with no increase in temptation goods spending, and generated societal net savings of $777 per recipient via reduced time in shelters. Additional experiments revealed public mistrust toward the ability of homeless individuals to manage money and demonstrated interventions to increase public support for a cash transfer policy using counter-stereotypical or utilitarian messaging. Together, this research offers a new approach to address homelessness and provides insights into homelessness reduction policies.

NG-SEM: an effective non-Gaussian structural equation modeling framework for gene regulatory network inference from single-cell RNA-seq data.

Inference of gene regulatory network (GRN) from gene expression profiles has been a central problem in systems biology and bioinformatics in the past decades. The tremendous emergency of single-cell RNA sequencing (scRNA-seq) data brings new opportunities and challenges for GRN inference: the extensive dropouts and complicated noise structure may also degrade the performance of contemporary gene regulatory models. Thus, there is an urgent need to develop more accurate methods for gene regulatory network inference in single-cell data while considering the noise structure at the same time. In this paper, we extend the traditional structural equation modeling (SEM) framework by considering a flexible noise modeling strategy, namely we use the Gaussian mixtures to approximate the complex stochastic nature of a biological system, since the Gaussian mixture framework can be arguably served as a universal approximation for any continuous distributions. The proposed non-Gaussian SEM framework is called NG-SEM, which can be optimized by iteratively performing Expectation-Maximization algorithm and weighted least-squares method. Moreover, the Akaike Information Criteria is adopted to select the number of components of the Gaussian mixture. To probe the accuracy and stability of our proposed method, we design a comprehensive variate of control experiments to systematically investigate the performance of NG-SEM under various conditions, including simulations and real biological data sets. Results on synthetic data demonstrate that this strategy can improve the performance of traditional Gaussian SEM model and results on real biological data sets verify that NG-SEM outperforms other five state-of-the-art methods.

Fe Single-Atom Carbon Dots Nanozyme Collaborated with Nucleic Acid Exonuclease III-Driven DNA Walker Cascade Amplification Strategy for Circulating Tumor DNA Detection.

Circulating tumor DNA (ctDNA), as a next-generation tumor marker, enables early screening and monitoring of cancer through noninvasive testing. Exploring the development of new methods for ctDNA detection is an intriguing study. In this work, a unique electrochemical biosensor for the ctDNA detector was constructed in the first utilizing Fe single-atom nanozymes-carbon dots (SA Fe-CDs) as a signaling carrier in collaboration with a DNA walker cascade amplification strategy triggered by nucleic acid exonuclease III (Exo III). The electrochemical active surface area of AuNPs/rGO modified onto a glassy carbon electrode (AuNPs/rGO/GCE) was about 1.43 times that of a bare electrode (bare GCE), with good electrical conductivity alongside a high heterogeneous electron transfer rate (5.81 × 10-3 cm s-1), that is, as well as the ability to load more molecules. Sequentially, the DNA walker cascade amplification strategy driven by Exo III effectively converted the target ctDNA into an amplified biosignal, ensuring the sensitivity and specificity of ctDNA. Ultimately, the electrochemical signal was further amplified by introducing SA Fe-CDs nanozymes, which could serve as catalysts for 3,3',5,5'-tetramethylbenzidine (TMB) oxidation with facile responding (Vmax = 0.854 × 10-6 M s-1) and robust annexation (Km = 0.0069 mM). The integration of the triple signal amplification approach achieved detection limits as low as 1.26 aM (S/N = 3) for a linearity spanning from 5 aM to 50 nM. In this regard, our proposal for a biosensor with exceptional assay properties in complicated serum environments had great potential for early and timely diagnosis of cancer.

Effects of polyethylene, polylactic acid, and tire particles on the sediment microbiome and metabolome at high and low temperatures.

Global warming has led to a high incidence of extreme heat events, and the frequent occurrence of extreme heat events has had extensive and far-reaching impacts on wetland ecosystems. The widespread distribution of plastics in the environment, including polyethylene (PE), polylactic acid (PLA), and tire particles (TPs), has caused various environmental problems. Here, high-throughput sequencing techniques and metabolomics were used for the first time to investigate the effects of three popular microplastic types: PE, PLA, and TP, on the sediment microbiome and the metabolome at both temperatures. The microplastics were incorporated into the sediment at a concentration of 3% by weight of the dry sediment (wt/wt), to reflect environmentally relevant conditions. Sediment enzymatic activity and physicochemical properties were co-regulated by both temperatures and microplastics producing significant differences compared to controls. PE and PLA particles inhibited bacterial diversity at low temperatures and promoted bacterial diversity at high temperatures, and TP particles promoted both at both temperatures. For bacterial richness, only PLA showed inhibition at low temperature; all other treatments showed promotion. PE, PLA, and TP microplastics changed the community structure of sediment bacteria, forming two clusters at low and high temperatures. Furthermore, PE, PLA, and TP changed the sediment metabolic profiles, producing differential metabolites such as lipids and molecules, organic heterocyclic compounds, and organic acids and their derivatives, especially TP had the most significant effect. These findings contribute to a more comprehensive understanding of the potential impact of microplastic contamination.IMPORTANCEIn this study, we added 3% (wt/wt) microplastic particles, including polyethylene, polylactic acid, and tire particles, to natural sediments under simulated laboratory conditions. Subsequently, we simulated the sediment microbial and ecosystem responses under different temperature conditions by incubating them for 60 days at 15°C and 35°C, respectively. After synthesizing these results, our study strongly suggests that the presence of microplastics in sediment ecosystems and exposure under different temperature conditions may have profound effects on soil microbial communities, enzyme activities, and metabolite profiles. This is important for understanding the potential hazards of microplastic contamination on terrestrial ecosystems and for developing relevant environmental management strategies.

Audience segmentation approach to conservation messaging for transforming the exotic pet trade.

Advancing transformative change for sustainability requires population-wide behavior change. Yet, many behavioral interventions tackling environmental problems only examine average effects on the aggregate, overlooking the heterogeneous effects in a population. We developed and preregistered a novel audience segmentation approach to test the diverse impact of conservation messaging on reducing demand for exotic pets (private action - i.e., desire to own exotic pets or visit wildlife entertainment places) and fostering citizen engagement for system-wide change (civic action - e.g., signing a petition or participating in a protest against the exotic pet trade). Through an online survey with US participants (n = 2953), we identified 4 population segments (early adopters, early majority, late majority, and laggards), representing varying levels of commitment to wildlife conservation and then randomly assigned each segment to one of 3 messaging conditions. Messages highlighting negative consequences of the exotic pet trade and the power of collective action for system change effectively promoted private action among all segments except early adopters (ηp 2 = 0.005). Among civic actions, only the collective action message motivated early adopters and the early majority to sign petitions (φC = 0.193 and φC = 0.097, respectively). Furthermore, the 4 segments showed distinct reasoning for action and inaction on wildlife conservation, with certain relational values, such as care, serving as both motivations and barriers to action. These findings highlight the need for targeted behavioral interventions across diverse populations.

Estrategia de segmentación del público en los mensajes de conservación para transformar el mercado de mascotas exóticas Resumen El progreso en el cambio transformativo para la sustentabilidad requiere de cambios conductuales a nivel poblacional. Sin embargo, muchas intervenciones conductuales que abordan los problemas ambientales sólo analizan los efectos promedio sobre el agregado, lo que ignora los efectos heterogéneos sobre la población. Desarrollamos y preinscribimos una estrategia novedosa de segmentación del público para evaluar los diversos impactos de los mensajes de conservación sobre la reducción de la demanda de mascotas exóticas (acción privada [es decir, el deseo de poseer mascotas exóticas o visitar sitios de entretenimiento con fauna] y promover la participación ciudadana para un cambio sistémico [por ejemplo, firmar una petición o participar en una protesta contra el mercado de mascotas exóticas]). Realizamos una encuesta en línea con participantes estadunidenses (n = 2953) para identificar cuatro segmentos de la población (adoptadores tempranos, mayoría temprana, mayoría tardía y rezagados), los cuales representan diferentes niveles de compromiso con la conservación de fauna, y después le asignamos aleatoriamente a cada segmento una de las siguientes condiciones de mensaje: las consecuencias negativas del mercado de mascotas exóticas, el poder de la acción colectiva para el cambio sistémico e información neutral como control. Los mensajes que resaltaban las consecuencias negativas del mercado de mascotas exóticas y el poder de la acción colectiva promovieron de forma eficiente la acción privada en todos los segmentos excepto los adoptadores tempranos (ηp 2 = 0.005). Entre las acciones cívicas, sólo el mensaje de acción colectiva motivó a los adoptadores tempranos y a la mayoría temprana a firmar peticiones (φC = 0.193 y φC = 0.097, respectivamente). Además, los cuatro segmentos mostraron un razonamiento distinto para la acción e inacción para la conservación de fauna, con ciertos valores de relación, como el cuidado, fungiendo como motivación o barreras para la acción. Estos resultados enfatizan la necesidad de tener intervenciones conductuales focalizadas entre las diferentes poblaciones.

Advances in understanding and mitigating Atrazine's environmental and health impact: A comprehensive review.

Atrazine is a widely used herbicide in agriculture, and it has garnered significant attention because of its potential risks to the environment and human health. The extensive utilization of atrazine, alongside its persistence in water and soil, underscores the critical need to develop safe and efficient removal strategies. This comprehensive review aims to spotlight atrazine's potential impact on ecosystems and public health, particularly its enduring presence in soil, water, and plants. As a known toxic endocrine disruptor, atrazine poses environmental and health risks. The review navigates through innovative removal techniques across soil and water environments, elucidating microbial degradation, phytoremediation, and advanced methodologies such as electrokinetic-assisted phytoremediation (EKPR) and photocatalysis. The review notably emphasizes the complex process of atrazine degradation and ongoing scientific efforts to address this, recognizing its potential risks to both the environment and human health.

Evaluating Patient Experience with Food in a Hospital-Wide Survey.

Purpose: Patient dissatisfaction with hospital food is an important driver of poor food intake in hospitals. The objective of this study was to examine patient satisfaction with current menu offerings and explore patient preferences and values, in order to inform a patient-centred menu redesign.Methods: Between July and September 2021, a cross-sectional survey was distributed to inpatients receiving a lunch tray at Vancouver General Hospital, a large tertiary care centre in Vancouver, Canada. The survey was based on the Acute Care Hospital Foodservice Patient Satisfaction Questionnaire, with additional questions on food experience, factors impacting preferences for hospital meals, interest in plant-rich diets, and demographics.Results: The response rate was 5.5%, with 271 patients completing at least part of the survey. On a 5-point Likert scale, (5 - highest score; 1 - lowest score) satisfaction with food quality (mean = 3.09, p < 0.001) and the overall experience (mean = 3.54, p < 0.001) was lower than industry benchmark of 4, and qualitative feedback was generally negative. Open-ended responses indicated patients were interested in expanded cultural diversity in food provision, more fresh produce and better flavours, and were generally open to trying plant-rich foods.Conclusions: A number of opportunities for improvement were identified in this survey, which will inform an upcoming menu redesign in this institution.

[Research progress on the neural mechanism of the regulation of social isolation on innate behaviors].

Innate behavior is mainly controlled by genetics, but is also regulated by social experiences such as social isolation. Studies in animal models such as Drosophila and mice have found that social isolation can regulate innate behaviors through the changes at the molecular level, such as hormone, neurotransmitter, neuropeptide level, and at the level of neural circuits. In this review, we summarized the research progress on the regulation of social isolation on various animal innate behaviors, such as sleep, reproduction and aggression by altering the expression of conserved neuropeptides and neurotransmitters, hoping to deepen the understanding of the key and conserved signal pathways that regulate innate behavior by social isolation.

Improving staff wellness via an after-hours healthy sustainable meals program: A general surgery residency pilot.

Healthcare worker wellness is foundational to delivering quality care. Yet, healthcare facilities often lack access to healthy and sustainable food overnight and on weekends. Healthy, low-carbon meals were provided free of charge after hours to on-call General Surgery residents at the University of British Columbia and the impact on resident well-being assessed using pre- and post-intervention surveys. Financial and time stress reduced significantly with the provision of meals (P's < .01), while emotional and physical stress levels did not change. Average meal expenses decreased from $33 to $10 (P < .001). Increasing food access on call is an impactful intervention to improve resident health and well-being.

Macrophage PTEN controls STING-induced inflammation and necroptosis through NICD/NRF2 signaling in APAP-induced liver injury.

BACKGROUND: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling has been known to play a critical role in maintaining cellular and tissue homeostasis, which also has an essential role in the inflammatory response. However, it remains unidentified whether and how the macrophage PTEN may govern the innate immune signaling stimulator of interferon genes (STING) mediated inflammation and hepatocyte necroptosis in APAP-induced liver injury (AILI). METHODS: Myeloid-specific PTEN knockout (PTENM-KO) and floxed PTEN (PTENFL/FL) mice were treated with APAP (400 mg/kg) or PBS. In a parallel in vitro study, bone marrow-derived macrophages (BMMs) were isolated from these conditional knockout mice and transfected with CRISPR/Cas9-mediated Notch1 knockout (KO) or CRISPR/Cas9-mediated STING activation vector followed by LPS (100 ng/ml) stimulation. RESULTS: Here, we report that myeloid-specific PTEN knockout (PTENM-KO) mice were resistant to oxidative stress-induced hepatocellular injury with reduced macrophage/neutrophil accumulation and proinflammatory mediators in AILI. PTENM-KO increased the interaction of nuclear Notch intracellular domain (NICD) and nuclear factor (erythroid-derived 2)-like 2 (NRF2) in the macrophage nucleus, reducing reactive oxygen species (ROS) generation. Mechanistically, it is worth noting that macrophage NICD and NRF2 co-localize within the nucleus under inflammatory conditions. Additionally, Notch1 promotes the interaction of immunoglobulin kappa J region (RBPjκ) with NRF2. Disruption of the Notch1 signal in PTEN deletion macrophages, reduced RBPjκ and NRF2 binding, and activated STING signaling. Moreover, PTENM-KO macrophages with STING activated led to ROS generation and TNF-α release, resulting in hepatocyte necroptosis upon co-culture with primary hepatocytes. CONCLUSIONS: Our findings demonstrate that the macrophage PTEN-NICD/NRF2-STING axis is critical to regulating oxidative stress-induced liver inflammation and necroptosis in AILI and implies the therapeutic potential for managing sterile liver inflammation. Video Abstract.

Electroacupuncture at Baliao point alleviates post-operative pain and anal distension after procedure for prolapse and hemorrhoids (stapled hemorrhoidopexy): a prospective randomized clinical trial.

PURPOSE: The purpose of this study was to explore the effect of electroacupuncture (EA) at Baliao point on short-term complications, such as anal pain and swelling, after procedure for prolapse and hemorrhoids (PPH) in patients with mixed hemorrhoids. METHODS: A total of 124 eligible patients undergoing PPH surgery were included in this study and randomly divided into a control group (n = 67) and an EA group (n = 57), with patients in the control group receiving only PPH surgery and patients in the EA group receiving PPH surgery and EA at Baliao point. RESULTS: The visual analogue scale (VAS) scores of EA group at 8, 24, 48, and 72 h after operation were significantly lower than those of control group. The anal distension scores at 8, 48, and 72 h after operation were also significantly lower than those of control group. The number of postoperative analgesic drug administration per patient was also significantly lower in the EA group. The incidence of urinary retention and tenesmus in EA group was significantly lower than that in control group within the first day after surgery. CONCLUSION: EA treatment at the Baliao point can alleviate short-term anal pain and anal swelling after the procedure for prolapse and hemorrhoids, reduce the incidence of urinary retention, and decrease the use of postoperative analgesic drugs. TRIAL REGISTRATION: This study was approved and registered by the Chinese Clinical Trial Center, Registration number: ChiCTR2100043519, Registration time: February 21, 2021 ( https://www.chictr.org.cn/ ).

Associated Risk Factors and Diagnostic Value of Fiberoptic Bronchoscopy for Protracted Bacterial Bronchitis in Children.

Objective: Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease. However, clinical diagnostic criteria are currently nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and the risk factors associated with PBB. Methods: Children with chronic cough at The First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n = 141) or a non-PBB (n = 206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. Results: All 347 children had a chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB (P < 0.05). Dermatophagoides (odds ratio (OR), 2.642; 95% CI, 1.283-5.369), milk protein (OR, 2.452; 95% CI, 1.243-4.836) allergies, and eczema (OR, 1.763; 95% CI, 1.011-3.075) were risk factors significantly associated with PBB. Conclusion: Dermatophagoides, milk protein, and eczema were associated with an increased risk of PBB. Sputum distribution and tracheal wall changes observed through FOB may distinguish PBB and assist in its diagnosis.

The associations between prenatal phthalate exposure and childhood glycolipid metabolism and blood pressure: An updated systematic review and a pilot meta-analysis of prospective cohort studies.

This is the first pilot meta-analysis on the association of prenatal phthalate exposure with childhood cardiometabolic risks. A systematic literature search was performed in MEDLINE, Web of Science and CNKI (Chinese National Knowledge Infrastructure) until June 5, 2023. A total of seven studies with 5746 children (2646 girls and 3100 boys) were finally included. Four, three and two studies investigated the effects of maternal phthalate exposure on childhood blood pressure (BP), blood lipids and blood glucose profiles, respectively. The pilot meta-analysis suggested that di-2-ethylhexyl phthalate (DEHP) metabolite exposure was associated with a decrease in childhood z-systolic BP (SBP, ß = -0.169, 95% CI = -0.338-0.001). Furthermore, the pooled results showed negative relationships of prenatal ∑DEHP exposure with z-SBP (ß = -0.109, 95% CI = -0.163 to -0.055) and z-diastolic BP (DBP, ß = -0.126, 95% CI = -0.182 to -0.069) in girls. In addition, MEP exposure was associated with z-SBP in girls (ß = -0.227, 95% CI = -0.387 to -0.066). The pooled result showed a positive relationship between prenatal ∑DEHP exposure and triglycerides (ß = 0.103, 95% CI = 0.028-0.178). The overall results revealed that exposure to ∑DEHP throughout gestation was associated with a decrease in insulin (ß = -0.074, 95% CI = -0.144 to -0.004) and glucose (ß = -0.129, 95% CI = -0.199 to -0.058) in boys. Interestingly, there was an inverse relationship of prenatal mono- 3 -carboxypropyl phthalate (MCPP) exposure with glucose in pubertal boys (ß = -3.749, 95% CIs = -6.758 to -0.741) but not found in postpubertal children. In conclusion, prenatal phthalate exposure interfered with cardiovascular risk in children with gender-specific differences and was influenced by puberty. Overall, prenatal ∑DEHP was negatively associated with systolic blood pressure in girls and with insulin and glucose in boys but increased the level of triglycerides.

Electroacupuncture Ameliorates Cognitive Impairment by Regulating γ-Amino Butyric Acidergic Interneurons in the Hippocampus of 5 Familial Alzheimer's Disease Mice.

OBJECTIVES: γ-amino butyric acid (GABA)-ergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer's disease (AD). Inhibitory interneurons play an important role in the regulation of E/I balance, synaptic transmission, and network oscillation through manipulation of GABAergic functions, showing positive outcomes in AD animal models. Mice expressing 5 familial AD mutation (5xFAD) exhibited a series of AD-like pathology and learning and memory deficits with age. Because electroacupuncture (EA) treatment has been used for a complementary alternative medicine therapy in patients with AD, we aimed to examine any usefulness of EA therapy in GABA interneuron function and its associated synaptic proteins, to determine whether EA could effectively improve inhibitory transmission and network oscillation and eventually alleviate cognitive impairments in 5xFAD mice, and to further elucidate the GABAergic system function underlying the antidementia response of EA. MATERIALS AND METHODS: 5xFAD mice were used to evaluate the potential neuroprotective effect of electroacupuncture at Baihui (DU 20) and Dazhui (DU 14) through behavioral testing, immunofluorescence staining, electrophysiology recording, and molecular biology analysis. RESULTS: First, we observed that EA improved memory deficits and inhibitory synaptic protein expression. Second, EA treatment alleviated the decrease of somatostatin-positive interneurons in the dorsal hippocampus. Third, EA attenuated E/I imbalance in 5xFAD mice. Last, EA treatment enhanced theta and gamma oscillation in the hippocampus of 5xFAD mice. CONCLUSIONS: EA stimulation at DU20 and DU14 acupoints may be a potential alternative therapy to ameliorate cognitive deficits in AD through the regulation of the function of the GABAergic interneuron.

i-Frame interventions enhance s-frame interventions.

We argue that i-frame interventions can and do increase support for systemic reforms, and s-frame interventions should be pursued in parallel to address key societal issues. Without accompanying i-frame interventions, s-frame interventions can fail. We offer an operant conditioning framework to generate positive spillover effects. Behavioral scientists should develop i-frame interventions that enhance, rather than compete with, s-frame interventions.

Catalytic Hairpin Assembly-Driven Ratiometric Dual-Signal Electrochemical Biosensor for Ultrasensitive Detection of MicroRNA Based on the Ratios of Fe-MOFs and MB-GA-UiO-66-NH2.

In this work, a novel ratio electrochemical biosensing platform based on catalytic hairpin assembly target recovery to trigger dual-signal output was developed for ultrasensitive detection of microRNA (miRNA). To achieve the ratiometric dual-signal strategy, methylene blue (MB), an electrochemical indicator, was ingeniously loaded into the pores of graphene aerogel (GA) and metal-organic framework (MOF) composites with high porosity and large specific surface area, and another electrochemical indicator Fe-MOFs with distinct separation of redox potential was selected as a signal probe. Concretely, with the presence of the target miRNA, the CHA process was initiated and the signal probe was introduced to the electrode surface, producing abundant double-stranded H1-H2@Fe-MOFs-NH2. Then, the measurement and analysis of the prepared ratiometric electrochemical biosensor by differential pulse voltammetry (DPV) showed that the introduction of the target miRNA led to an increase in the oxidation peak signal of Fe-MOFs (+0.8 V) and a decrease in the oxidation peak signal of MB (-0.23 V). Therefore, the peak current ratio of IFe-MOFs/IMB could be employed to accurately reflect the actual concentration of miRNA. Under optimal conditions, the detection limit of the proposed biosensor was down to 50 aM. It was worth noting that the proposed biosensor exhibited excellent detection performance in a complex serum environment and tumor cell lysates, showing great potential in biosensing and clinical diagnosis.

The histone deacetylase inhibitor belinostat ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting TLR2/MyD88 and HDAC3/ NF-κB p65-mediated neuroinflammation.

Multiple sclerosis (MS) is a Th cell-mediated inflammatory demyelinating autoimmune disease. MS cannot be cured, and long-term drug treatment is still needed for MS patients. In this study, we examined the effect of belinostat, a pan-histone deacetylase inhibitor (HDACi), on experimental autoimmune encephalomyelitis (EAE) and elucidated its mechanism of action. We found that belinostat alleviates the clinical symptoms, histopathological central nervous system (CNS) inflammation and demyelination outcomes in EAE mice. Compared to the MS oral drug dimethyl fumarate (DMF) (100 mg/kg), belinostat (30 mg/kg) treatment exhibited better efficacy in improving the clinical symptoms of EAE mice. Belinostat treatment significantly suppressed the activation of M1 microglia and the proinflammatory cytokine expression; but it had no effects on the M2 microglial polarization. Belinostat also decreased both NO and iNOS levels in LPS-stimulated BV2 microglia. Accordingly, belinostat treatment of EAE mice significantly inhibited activation of the TLR2/MyD88 signaling pathway and downregulated the expression of HDAC3 while upregulating the acetylated NF-κB p65 levels. Taken together, these data demonstrate for the first time that belinostat ameliorates EAE in mice through inhibiting neuroinflammation via suppressing M1 microglial polarization, and implicating belinostat as a potential candidate for the treatment of multiple sclerosis.

The MLR, NLR, PLR and D-dimer are associated with clinical outcome in lung cancer patients treated with surgery.

OBJECTIVE: The study objective was to investigate the use of peripheral blood biomarkers as predictors of patient survival. The aim of this study was to identify the baseline peripheral blood biomarkers associated with clinical outcome in patients with early lung cancer (stage I-II) treated with surgery. METHODS: We included and analysed data from 376 patients with early-stage lung cancer who underwent a standard lobectomy. Univariate and multivariate Cox regression analyses were performed on all patients to assess the relationships between progression-free survival (PFS) and overall survival (OS) and the peripheral blood biomarker metrics measured before surgical treatment. The peripheral blood parameters included monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and dimeric fibrin fragment D (D-dimer). RESULTS: After univariate Cox regression analysis, low MLR, low NLR, low PLR and low D-dimer values were significantly associated with both better OS and PFS (all p < 0.05). In multivariate Cox regression analysis, a low MLR was significantly and independently associated with both better overall survival and better progression-free survival (both p <0.05). A low D-dimer level was significantly and independently associated with better overall survival (p <0.05). Furthermore, the categorization of patients according to the number of factors with favourable results revealed that those without favourable results had significantly worse outcomes than that of those patients with at least one. CONCLUSION: A baseline signature of low MLR, low NLR, low PLR, and low D-dimer values was associated with a better survival outcome for patients treated with surgery. Patients with more favourable results had better survival outcomes.

A test strip electrochemical disposable by 3D MXA/AuNPs DNA-circuit for the detection of miRNAs.

The simple and reliable detection of microRNAs is of great significance for studying the biological functions, molecular diagnosis, disease treatment and targeted drug therapy of microRNA. In this study, we introduced a novel Ti3C2Tx (MXene) aerogels (denoted as MXA) composite gold nano-particles (AuNPs)-modified disposable carbon fiber paper (CFP) electrode for the label-free and sensitive detection of miRNA-155. Firstly, in the presence of MXene, graphene oxide (GO) and ethylenediamine (EDA), the 3D MXene hydrogel was formed by self-assembly method, and then adding the freeze-dried 3D MXA dropwise to CFP. Subsequently, electrodepositing AuNPs on the CFP/MXA was done to construct a 3D disposable DNA-circuit test strip with excellent interface. Under the optimum experimental conditions, the detection limit of 3D disposable DNA circuit strip for miRNA-155 was 136 aM (S/N = 3). The CFP/MXA/AuNPs (CMA) electrode also has a wide dynamic range (20 fM to 0.4 µM), with a span of 4 orders of magnitude. Notably, we also tested the practicality of the sensor in 8 clinical samples. The technological innovations in the detection and quantification of microRNA in this work may be helpful to the study new aspects of microRNA biology and the development of diagnosis.