Nitrogen removal and carbon reduction of mature landfill leachate under extremely low dissolved oxygen conditions by simultaneous partial nitrification anammox and denitrification.

In this study, a SNAD-SBBR process was implemented to achieve ammonia removal and carbon reduction of mature landfill leachate under extremely low dissolved oxygen conditions (0.051 mg/L) for a continuous operation of 266 days. The process demonstrated excellent removal performance, with ammonia nitrogen removal efficiency reaching 100 %, total nitrogen removal efficiency reaching 87.56 %, and an average removal rate of 0.180 kg/(m3·d). The recalcitrant organic compound removal efficiency reached 34.96 %. Nitrogen mass balance analysis revealed that the Anammox process contributed to approximately 98.1 % of the nitrogen removal. Candidatus Kuenenia achieved a relative abundance of 1.49 % in the inner layer of the carrier. In the SNAD-SBBR system, the extremely low DO environment created by the highly efficient partial nitrification stage enabled the coexistence of AnAOB, denitrifying bacteria, and Nitrosomonas, synergistically achieving ammonia removal and carbon reduction. Overall, the SNAD-SBBR process exhibits low-cost and high-efficiency characteristics, holding tremendous potential for landfill leachate treatment.

Detoxifying bacterial genes for deoxynivalenol epimerization confer durable resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

Efficacy of cementless porous tantalum tibial components versus cemented tibial components in primary total knee arthroplasty: A meta-analysis.

BACKGROUND: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. METHODS: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms "(trabecular metal OR Porous tantalum)" AND "knee" up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. RESULTS: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (P < .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. CONCLUSION: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.

Achieving advanced nitrogen removal from mature landfill leachate in continuous flow system involving partial nitrification-anammox and denitrification.

Considering the challenges associated with nitrogen removal from mature landfill leachate, a novel combined continuous-flow process integrating denitrification and partial nitrification-Anammox (PN/A) was developed using an internal circulation (IC) system and a biological aerated filter (BAF) biofilm reactor (IBBR). In this study, IBBR successfully operated for 343 days, and when influent NH4+-N concentration of mature landfill leachate reached 1258.1 mg/L, an impressive total nitrogen removal efficiency (TNRE) of 93.3 % was achieved, along with a nitrogen removal rate (NRR) of 1.13 kg N/(m3·d). The analysis of the microbial community revealed that Candidatus Kuenenia, the dominant genus responsible for anammox, accounted for 1.7 % (day 265). Additionally, Nitrosomonas, Thauera and Truepera were identified as key contributors to the efficient removal of nitrogen from mature landfill. As a novel nitrogen removal strategy, the practical application of the IBBR system offers novel perspectives on addressing mature landfill leachate.

miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1α to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells.

Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting invasiveness, metastasis, and resistance to treatment under hypoxic conditions. MicroRNA (miRNA) research underscores the significance of these non-coding molecules in regulating cancer-related protein synthesis across diverse contexts. However, there is limited reporting on miRNA-mediated gene expression studies, especially with respect to epithelial-mesenchymal transition (EMT) and autophagy in the context of hypoxic breast cancer. Our study reveals decreased levels of miRNA-622 (miR-622) and miRNA-30a (miR-30a) in invasive breast cancer cells compared to their non-invasive counterparts. Inducing miR-622 suppresses HIF-1α protein expression, subsequently activating miR-30a transcription. This cascade results in reduced invasiveness and migration of breast cancer cells by inhibiting EMT markers, such as Snail, Slug, and vimentin. Furthermore, miR-30a negatively regulates beclin 1, ATG5, and LC3-II and inhibits Akt protein phosphorylation. Consequently, this improves the sensitivity of invasive MDA-MB-231 cells to docetaxel treatment. In conclusion, our study highlights the therapeutic potential of inducing miR-622 to promote miR-30a expression and thus disrupt HIF-1α-associated EMT and autophagy pathways. This innovative strategy presents a promising approach to the treatment of aggressive breast cancer.

A novel multi-omics data analysis of dose-dependent and temporal changes in regulatory pathways due to chemical perturbation: a case study on caffeine.

Comprehensive analysis of multi-omics data can reveal alterations in regulatory pathways induced by cellular exposure to chemicals by characterizing biological processes at the molecular level. Data-driven omics analysis, conducted in a dose-dependent or dynamic manner, can facilitate comprehending toxicity mechanisms. This study introduces a novel multi-omics data analysis designed to concurrently examine dose-dependent and temporal patterns of cellular responses to chemical perturbations. This analysis, encompassing preliminary exploration, pattern deconstruction, and network reconstruction of multi-omics data, provides a comprehensive perspective on the dynamic behaviors of cells exposed to varying levels of chemical stimuli. Importantly, this analysis is adaptable to any number of omics layers, including site-specific phosphoproteomics. We implemented this analysis on multi-omics data obtained from HepG2 cells exposed to a range of caffeine doses over varying durations and identified six response patterns, along with their associated biomolecules and pathways. Our study demonstrates the effectiveness of the proposed multi-omics data analysis in capturing multidimensional patterns of cellular response to chemical perturbation, enhancing understanding of pathway regulation for chemical risk assessment.

Multiplexed transcriptional profiling of Dermatophagoides house dust mites allergens in human epithelium cells.

Allergic asthma, a chronic disease characterized by airway inflammation, poses a significant public health concern. It is well-established that house dust mites (HDMs) are common inducers of allergic responses in individuals, particularly children. In central Taiwan, our research team observed that over 80% of allergic children exhibited sensitization to various HDMs species. This investigation aims to bridge the gap between these observations and a better understanding of the early fundamental mechanisms for preventing allergic diseases. Specifically, our study delves into the impact of crude extracts of HDMs on human epithelial BEAS-2B cells. Our findings, based on RNA sequencing (RNA-seq) analysis, shed light on how three major Dermatophagoides HDMs allergens activate a common Toll-like receptor signaling pathway in human epithelial cells within a 4-h treatment. During this process, the nuclear transcription factor NF-κB translocated into the cell nucleus within 30 min of allergen stimulation, triggering the expression of pro-inflammatory genes such as IL-6 and IL-8 over 4 h. Additionally, when the cells were treated with specific Dermatophagoides microceras (Der m) allergens, it resulted in the upregulation of genes that regulate type 1 diabetes mellitus (T1DM) signaling pathways. This led to the mediation of IL-12A inflammation. Furthermore, there was an increase in gene sets associated with cilia function and the microtubule cytoskeleton in human epithelial cells after treatment with a combination of Der m allergens and Dexamethasone. Additionally, OMICs analysis was conducted to examine the effects of HDMs allergenic stimulation on human epidermal cells. We aimed to improve our understanding of the molecular mechanisms within cells and identify potential targets and natural products in the treatment of asthma caused by HDMs allergens.

Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats.

Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury (CCI) in the rat spinal dorsal horn. Meanwhile, cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling was also activated with hyperalgesia. Silencing TAOK2 reversed hyperalgesia and suppressed the activation of cGAS-STING signaling induced by CCI, while pharmacological activation of TAOK2 induced pain hypersensitivity and upregulation of cGAS-STING signaling in naive rats. Furthermore, pharmacological inhibition or gene silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia. Taken together, these data demonstrate that the activation of spinal TAOK2 contributes to CCI-induced hyperalgesia via cGAS-STING signaling activation, providing new molecular targets for the treatment of neuropathic pain.

Delivering Biopsychosocial Health Care Within Routine Care: Spotlight-AQ Pivotal Multicenter Randomized Controlled Trial Results.

BACKGROUND: Annual national diabetes audit data consistently shows most people with diabetes do not consistently achieve blood glucose targets for optimal health, despite the large range of treatment options available. AIM: To explore the efficacy of a novel clinical intervention to address physical and mental health needs within routine diabetes consultations across health care settings. METHODS: A multicenter, parallel group, individually randomized trial comparing consultation duration in adults diagnosed with T1D or T2D for ≥6 months using the Spotlight-AQ platform versus usual care. Secondary outcomes were HbA1c, depression, diabetes distress, anxiety, functional health status, and healthcare professional burnout. Machine learning models were utilized to analyze the data collected from the Spotlight-AQ platform to validate the reliability of question-concern association; as well as to identify key features that distinguish people with type 1 and type 2 diabetes, as well as important features that distinguish different levels of HbA1c. RESULTS: n = 98 adults with T1D or T2D; any HbA1c and receiving any diabetes treatment participated (n = 49 intervention). Consultation duration for intervention participants was reduced in intervention consultations by 0.5 to 4.1 minutes (3%-14%) versus no change in the control group (-0.9 to +1.28 minutes). HbA1c improved in the intervention group by 6 mmol/mol (range 0-30) versus control group 3 mmol/mol (range 0-8). Moderate improvements in psychosocial outcomes were seen in the intervention group for functional health status; reduced anxiety, depression, and diabetes distress and improved well-being. None were statistically significant. HCPs reported improved communication and greater focus on patient priorities in consultations. Artificial Intelligence examination highlighted therapy and psychological burden were most important in predicting HbA1c levels. The Natural Language Processing semantic analysis confirmed the mapping relationship between questions and their corresponding concerns. Machine learning model revealed type 1 and type 2 patients have different concerns regarding psychological burden and knowledge. Moreover, the machine learning model emphasized that individuals with varying levels of HbA1c exhibit diverse levels of psychological burden and therapy-related concerns. CONCLUSION: Spotlight-AQ was associated with shorter, more useful consultations; with improved HbA1c and moderate benefits on psychosocial outcomes. Results reflect the importance of a biopsychosocial approach to routine care visits. Spotlight-AQ is viable across health care settings for improved outcomes.

Status and frontier analysis of indoor PM2.5-related health effects: a bibliometric analysis.

Epidemiological data indicate atmospheric particulate matter, especially fine particulate matter (PM2.5), has many negative effects on human health. Of note, people spend about 90% of their time indoors. More importantly, according to the World Health Organization (WHO) statistics, indoor air pollution causes nearly 1.6 million deaths each year, and it is considered as one of the major health risk factors. In order to obtain a deeper understanding of the harmful effects of indoor PM2.5 on human health, we used bibliometric software to summarize articles in this field. In conclusion, since 2000, the annual publication volume has increased year by year. America topped the list for the number of articles, and Professor Petros Koutrakis and Harvard University were the author and institution with the most published in this research area, respectively. Over the past decade, scholars gradually paid attention to molecular mechanisms, therefore, the toxicity can be better explored. Particularly, apart from timely intervention and treatment for adverse consequences, it is necessary to effectively reduce indoor PM2.5 through technologies. In addition, the trend and keywords analysis are favorable ways to find out future research hotspots. Hopefully, various countries and regions strengthen academic cooperation and integration of multi-disciplinary.

Comparative and Functional Analysis of miRNAs and mRNAs Involved in Muscle Fiber Hypertrophy of Juvenile and Adult Goats.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate several pathway intermediates and affect the skeletal muscle development in mice, pigs, sheep, and cattle. However, to date, only a small number of miRNAs have been reported in the muscle development of goats. In this report, the longissimus dorsi transcripts of one- and ten-month-old goats were analyzed by sequencing RNAs and miRNAs. The results showed that the ten-month-old Longlin goats had 327 up- and 419 down-regulated differentially expressed genes (DEGs) compared with the one-month-old. In addition, 20 co-up-regulated and 55 co-down-regulated miRNAs involved in the muscle fiber hypertrophy of goats were identified in ten-month-old Longlin and Nubian goats compared with one-month-old. Five miRNA-mRNA pairs (chi-let-7b-3p-MIRLET7A, chi-miR193b-3p-MMP14, chi-miR-355-5p-DGAT2, novel_128-LOC102178119, novel_140-SOD3) involved in the goat skeletal muscle development were identified by miRNA-mRNA negative correlation network analysis. Our results provided new insight into the functional roles of goat muscle-associated miRNAs, allowing a deeper understanding of the transformation of miRNA roles during mammalian muscle development.

Pre- and postnatal particulate matter exposure and blood pressure in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Early life is a susceptible period of air pollution-related adverse health effects. Hypertension in children might be life-threatening without prevention or treatment. Nevertheless, the causative association between environmental factors and childhood hypertension was limited. In the light of particulate matter (PM) as an environmental risk factor for cardiovascular diseases, this study investigated the association of pre- and postnatal PM exposure with blood pressure (BP) and hypertension among children and adolescents. METHOD: Four electronic databases were searched for related epidemiological studies published up to September 13, 2022. Stata 14.0 was applied to examine the heterogeneity among the studies and evaluate the combined effect sizes per 10 µg/m3 increase of PM by selecting the corresponding models. Besides, subgroup analysis, sensitivity analysis, and publication bias test were also conducted. RESULTS: Prenatal PM2.5 exposure was correlated with increased diastolic blood pressure (DBP) in offspring [1.14 mmHg (95% CI: 0.12, 2.17)]. For short-term postnatal exposure effects, PM2.5 (7-day average) was significantly associated with systolic blood pressure (SBP) [0.20 mmHg (95% CI: 0.16, 0.23)] and DBP [0.49 mmHg (95% CI: 0.45, 0.53)]; and also, PM10 (7-day average) was significantly associated with SBP [0.14 mmHg (95% CI: 0.12, 0.16)]. For long-term postnatal exposure effects, positive associations were manifested in SBP with PM2.5 [ß = 0.44, 95% CI: 0.40, 0.48] and PM10 [ß = 0.35, 95% CI: 0.19, 0.51]; DBP with PM1 [ß = 0.45, 95% CI: 0.42, 0.49], PM2.5 [ß = 0.31, 95% CI: 0.27, 0.35] and PM10 [ß = 0.32, 95% CI: 0.19, 0.45]; and hypertension with PM1 [OR = 1.43, 95% CI: 1.40, 1.46], PM2.5 [OR = 1.65, 95% CI: 1.29, 2.11] and PM10 [OR = 1.26, 95% CI: 1.09, 1.45]. CONCLUSION: Both prenatal and postnatal exposure to PM can increase BP, contributing to a higher prevalence of hypertension in children and adolescents.

Learning to Explore Distillability and Sparsability: A Joint Framework for Model Compression.

Deep learning shows excellent performance usually at the expense of heavy computation. Recently, model compression has become a popular way of reducing the computation. Compression can be achieved using knowledge distillation or filter pruning. Knowledge distillation improves the accuracy of a lightweight network, while filter pruning removes redundant architecture in a cumbersome network. They are two different ways of achieving model compression, but few methods simultaneously consider both of them. In this paper, we revisit model compression and define two attributes of a model: distillability and sparsability, which reflect how much useful knowledge can be distilled and how many pruned ratios can be obtained, respectively. Guided by our observations and considering both accuracy and model size, a dynamically distillability-and-sparsability learning framework (DDSL) is introduced for model compression. DDSL consists of teacher, student and dean. Knowledge is distilled from the teacher to guide the student. The dean controls the training process by dynamically adjusting the distillation supervision and the sparsity supervision in a meta-learning framework. An alternating direction method of multiplier (ADMM)-based knowledge distillation-with-pruning (KDP) joint optimization algorithm is proposed to train the model. Extensive experimental results show that DDSL outperforms 24 state-of-the-art methods, including both knowledge distillation and filter pruning methods.

Protein-DNA binding sites prediction based on pre-trained protein language model and contrastive learning.

Protein-DNA interaction is critical for life activities such as replication, transcription and splicing. Identifying protein-DNA binding residues is essential for modeling their interaction and downstream studies. However, developing accurate and efficient computational methods for this task remains challenging. Improvements in this area have the potential to drive novel applications in biotechnology and drug design. In this study, we propose a novel approach called Contrastive Learning And Pre-trained Encoder (CLAPE), which combines a pre-trained protein language model and the contrastive learning method to predict DNA binding residues. We trained the CLAPE-DB model on the protein-DNA binding sites dataset and evaluated the model performance and generalization ability through various experiments. The results showed that the area under ROC curve values of the CLAPE-DB model on the two benchmark datasets reached 0.871 and 0.881, respectively, indicating superior performance compared to other existing models. CLAPE-DB showed better generalization ability and was specific to DNA-binding sites. In addition, we trained CLAPE on different protein-ligand binding sites datasets, demonstrating that CLAPE is a general framework for binding sites prediction. To facilitate the scientific community, the benchmark datasets and codes are freely available at https://github.com/YAndrewL/clape.

PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B.

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.

Radiosensitization effect by HDAC inhibition improves NKG2D-dependent natural killer cytotoxicity in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Radiotherapy (RT) controls HCC unsatisfactorily and temporarily. Histone deacetylase inhibitor (HDACi) is a heterogeneous group of epigenetic therapeutics with promising anticancer effects and synergism in combination with RT. HDACi modulates natural killer (NK) cell ligand expression on tumor cells, and leads to immune evasion of cancer cells. Expressions of NK group 2D (NKG2D) ligands on cancer cells determine the cytotoxic effect by interacting with NKG2D receptor on NK cells. However, the role of NKG2D signaling in HCC upon combined RT and HDACi remains unclear. Method: In vitro co-culture system with NK cells was tested for human and murine HCC cell lines. Pan-HDACi (panobinostat) and specific HDAC4 knockdown (HDAC4-KD) were used for HDAC inhibition. Clonogenic assay and flow cytometry examined HCC cell survival and NKG2D ligand expression, respectively. Syngeneic mouse model was used to validate the radiosensitizing effect in vivo. Results: Combined RT and HDACi/HDAC4-KD significantly enhanced NK cell-related cytotoxicity and increased NKG2D ligands, MICA/MICB expressions in human and RAE-1/H60 expressions in murine HCC cells. Delayed tumor growth in vivo by the combinational treatment of RT and HDACi/HDAC4-KD was shown with the associated NKG2D ligand expressions. However, NKG2D receptor did not significantly change among tumors. Conclusion: Radiosensitizing effect with combined RT and HDAC inhibition increased the expression of NKG2D ligands in HCC cells and enhanced their susceptibility to NK cell-mediated cytotoxicity. These findings imply the potential use of combined RT/HDACi and NK cell-directed immunotherapy.

Metabolomics Markers of COVID-19 Are Dependent on Collection Wave.

The effect of COVID-19 infection on the human metabolome has been widely reported, but to date all such studies have focused on a single wave of infection. COVID-19 has generated numerous waves of disease with different clinical presentations, and therefore it is pertinent to explore whether metabolic disturbance changes accordingly, to gain a better understanding of its impact on host metabolism and enable better treatments. This work used a targeted metabolomics platform (Biocrates Life Sciences) to analyze the serum of 164 hospitalized patients, 123 with confirmed positive COVID-19 RT-PCR tests and 41 providing negative tests, across two waves of infection. Seven COVID-19-positive patients also provided longitudinal samples 2-7 months after infection. Changes to metabolites and lipids between positive and negative patients were found to be dependent on collection wave. A machine learning model identified six metabolites that were robust in diagnosing positive patients across both waves of infection: TG (22:1_32:5), TG (18:0_36:3), glutamic acid (Glu), glycolithocholic acid (GLCA), aspartic acid (Asp) and methionine sulfoxide (Met-SO), with an accuracy of 91%. Although some metabolites (TG (18:0_36:3) and Asp) returned to normal after infection, glutamic acid was still dysregulated in the longitudinal samples. This work demonstrates, for the first time, that metabolic dysregulation has partially changed over the course of the pandemic, reflecting changes in variants, clinical presentation and treatment regimes. It also shows that some metabolic changes are robust across waves, and these can differentiate COVID-19-positive individuals from controls in a hospital setting. This research also supports the hypothesis that some metabolic pathways are disrupted several months after COVID-19 infection.

Silica nanoparticles perturbed mitochondrial dynamics and induced myocardial apoptosis via PKA-DRP1-mitochondrial fission signaling.

Silica nanoparticles (SiNPs) are among the most abundantly produced nanosized particles in the global market, and their potential toxicity has aroused a great concern. Increasing epidemiological investigations and experimental evidence revealed the threaten of SiNPs exposure to cardiovascular system. The myocardial toxicity caused by SiNPs was gradually demonstrated, nevertheless, the underlying mechanisms remain unclear. In view of mitochondria serving as the centrality in the prominent of cardiovascular disease, we investigated the role of mitochondria and related mechanisms in SiNPs-induced adverse effects on cardiomyocytes. As a result, SiNPs were found in cytoplasm, accompanied with morphological alterations in mitochondria, such as cristae fracture or disappearance, vacuolation. The induction of mitochondrial dysfunction by SiNPs was confirmed, as indicated by the excessive reactive oxygen species (ROS) formation, and blockage of cellular respiratory and ATP production. Concomitantly, SiNPs activated mitochondria-mediated apoptotic signaling in view of the up-regulated BAX, increased Caspase-9 cleavage and declined Bcl-2, ultimately resulting in myocardial apoptosis. It was noteworthy that SiNPs disturbed mitochondrial dynamics toward fission phenotype, which was supported by the dysregulated fission/fusion regulators. Especially, DRP1 and its phosphorylated level at s616 (p-DRP1s616) were up-regulated, whilst its phosphorylated level at s637 (p-DRP1s637) and PKA phosphorylation were down-regulated in SiNPs-treated cardiomyocytes in a dose-dependent manner. More importantly, the mechanistic investigations revealed PKA-DRP1-mediated mitochondrial fission was responsible for SiNPs-induced cardiomyocyte apoptosis through the mitochondria-mediated apoptotic way. This study firstly demonstrated the disturbance of mitochondrial dynamics played a crucial role in cardiomyocyte apoptosis caused by SiNPs, attributing to PKA-DRP1-mitochondrial fission signaling.

Novel SLIPS based on the photo-thermal MOFs with enhanced anti-icing/de-icing properties.

A photo-thermal anti-icing/de-icing SLIPS coating is designed based on porous light-responsive MOFs. Due to the strong light absorption and high light-thermal conversion, the as-synthetic SCMOFs exhibited prolonged freezing delay time and depressed water crystallization point under light irradiation. Meantime, the SCMOFs exhibit good deicing properties. With the irradiation, the half-melted ice slips off quickly.

Integrated OMICs Approach for the Group 1 Protease Mite-Allergen of House Dust Mite Dermatophagoides microceras.

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras (Der m), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component (Der m 1). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal component analysis (PCA) of mice cytokines revealed that the cytokine profiles of the allergen-sensitized mice model with combined Der m 1 and 2 were similar to those with Der m 2 alone but differed from those with Der m 1 alone. Regarding the possible sensitizing roles of Der m 1 in the cells, the fibrinogen cleavage products (FCPs) derived from combined Der m 1 and Der m 2 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelium cells. Der m 1 biologically functions as a cysteine protease and contributes to the α chain of fibrinogen digestion in vitro. The combination of Der m 1 and 2 could induce similar cytokines expression patterns to Der m 2 in mice, and the FCPs derived from Der m 1 has a synergistic effect with Der m 2 to induce the expression of pro-inflammatory cytokines in human bronchial epithelium cells.