Minocycline prevents photoreceptor degeneration in Retinitis pigmentosa through modulating mitochondrial homeostasis.

Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.

Integrative analysis of gene and microRNA expression profiles reveals candidate biomarkers and regulatory networks in psoriasis.

Psoriasis (PS) is a chronic inflammatory skin disease with a long course and tendency to recur, the pathogenesis of which is not fully understood. This article aims to identify the key differentially expressed genes (DEGs) and microRNA (miRNAs) of PS, construct the core miRNA-mRNA regulatory network, and investigate the underlying molecular mechanism through integrated bioinformatics approaches. Two gene expression profile datasets and 2 miRNA expression profile datasets were downloaded from the gene expression omnibus (GEO) database and analyzed by GEO2R. Intersection DEGs and intersection differentially expressed miRNAs (DEMs) were each screened. The Metascape database and R software were used to perform enrichment analysis of intersecting DEGs and study their functions. Target genes of DEMs were predicted from the online database miRNet. The protein-protein interaction files of the overlapping target genes were obtained from string and the miRNA-mRNA network was constructed by Cytoscape software. In addition, the online web tool CIBERSORT was used to analyze the immune infiltration of dataset GSE166388, and the relative abundance of 22 immune cells in the diseased and normal control tissues was calculated and assessed. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the relative expression of the screened miRNAs and mRNAs to assess the applicability of DEMs and DEGs as biomarkers in PS. A total of 205 mating DEGs and 6 mating DEMs were screened. 103 dysregulated crossover genes from 205 crossover DEGs and 7878 miRNA target genes were identified. The miRNA-mRNA regulatory network was constructed and the top 10 elements were obtained from CytoHubba, including hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2. QRT-PCR revealed significant differences in miRNA and gene expression between inflammatory and normal states. In this study, the miRNA-mRNA core regulator pairs hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2 may be involved in the course of PS. This study provides new insights to discover new potential targets and biomarkers to further investigate the molecular mechanism of PS.

Microcavity induced by a few-layer GaSe crystal on a silicon photonic crystal waveguide for efficient optical frequency conversion.

We demonstrate the post-induction of high-quality microcavities on a silicon photonic crystal (PC) waveguide by integrating a few-layer GaSe crystal, which promises efficient on-chip optical frequency conversions. The integration of GaSe shifts the dispersion bands of the PC waveguide mode into the bandgap, resulting in localized modes confined by the bare PC waveguides. Thanks to the small contrast of refractive index at the boundaries of the microcavity, it is reliable to obtain quality factors exceeding 104. With the enhanced light-GaSe interaction by the microcavity modes and GaSe's high second-order nonlinearity, remarkable second-harmonic generation (SHG) and sum-frequency generation (SFG) are achieved with continuous-wave (CW) lasers.

Synergy of Target-Induced Magnetic Network and Single-Drop Chromogenic System for Ultrasensitive "All-in-Tube" Detection of miRNA in Whole Blood.

The development of liquid biopsy methods for the accurate and reliable detection of miRNAs in whole blood is critical for the early diagnosis and monitoring of diseases. However, accurate quantification of miRNA expression levels remains challenging due to the complex matrix and low abundance of miRNAs in blood samples. Herein, we report a contactless signal output strategy with low background interference that ensures "zero-contact" between the reaction system and the colorimetry system. The designed target-induced magnetic ZnS/ZIF-90/ZnS network can serve as a unique signal amplifier and transducer. It releases hydrogen sulfide (H2S) gas in an acidic solution which can be concentrated in a droplet of only a few microliters in volume, etching the silver layer of Au@Ag nanostars (NSTs) in the droplet. This will lead to changes in the localized surface plasmon resonance signals of the NSTs. Finally, quantitative detection of let-7a is realized by measuring the offset value of the UV-vis absorption peak. Therefore, by virtue of the synergistic action of quadruple signal amplification methods, including catalytic hairpin assembly, ZnS/ZIF-90/ZnS, magnetic separation, and microextraction, the "All-in-Tube" ultrasensitive detection of low-abundance let-7a in whole blood is achieved with a detection limit as low as the aM level. In addition, the "zero-contact" signal output mode effectively solves the problem of complex matrix interference, demonstrating the great potential of this method for miRNA quantification in complex samples, such as whole blood.

Glacial lake outburst floods threaten China-Nepal connectivity: Synergistic study of remote sensing, GIS and hydrodynamic modeling with regional implications.

Holistic study of glacial lakes and glacial lake outburst floods (GLOFs) in the strategically important China-Nepal transportation corridors is imperative for regional connectivity and disaster risk reduction. This study focuses on four China-Nepal transportation corridors, namely Chentang-Kimathanka, Zhangmu-Kodari, Keyrung-Kathmandu and Taklakot-Hilsa from east to west in the Himalayan region. Within a remote integrated framework, we present the latest high-resolution inventory of glacial lakes, assess their decadal spatio-temporal changes (1992-2022), identify potentially dangerous glacial lakes, and apply hydrodynamic model to assess downstream impacts of possible GLOFs along the study area. The results show 2688 glacial lakes (≥0.001 km2) with a total area of 116.10 ± 8.53 km2 over the study area in 2022. Glacial lakes exhibited spatiotemporal heterogeneity in expansion, with overall expansion of 32 % during 30 years. Keyrung-Kathmandu corridor, among others, was assessed with high GLOF susceptibility. Furthermore, hydrodynamic modeling of four highly dangerous lakes in each transportation area reveals that GLOFs have cross-border effects, impacting ∼103 km of China-Nepal highway, 103 bridges, two major dry ports and 3301 buildings in both countries. Based on these findings, we emphasize the joint efforts of both countries for integrated disaster management for smooth connectivity between two countries and saving downstream population through joint cooperation from central to local government levels by initiating artificial lake lowering, developing cross-border early warning systems and cooperation. This study is valuable for presenting a synergistic study of glacial lakes and GLOF for informing decision- and policy-makers of both China and Nepal for a joint approach to disaster mitigation.

DOT1L/H3K79me2 represses HIV-1 reactivation via recruiting DCAF1.

DOT1L mediates the methylation of histone H3 at lysine 79 and, in turn, the transcriptional activation or repression in a context-dependent manner, yet the regulatory mechanisms and functions of DOT1L/H3K79me remain to be fully explored. Following peptide affinity purification and proteomic analysis, we identified that DCAF1-a component of the E3 ligase complex involved in HIV regulation-is associated with H3K79me2 and DOT1L. Interestingly, blocking the expression or catalytic activity of DOT1L or repressing the expression of DCAF1 significantly enhances the tumor necrosis factor alpha (TNF-α)/nuclear factor κB (NF-κB)-induced reactivation of the latent HIV-1 genome. Mechanistically, upon TNF-α/NF-κB activation, DCAF1 is recruited to the HIV-1 long terminal repeat (LTR) by DOT1L and H3K79me2. Recruited DCAF1 subsequently induces the ubiquitination of NF-κB and restricts its accumulation at the HIV-1 LTR. Altogether, our findings reveal a feedback modulation of HIV reactivation by DOT1L-mediated histone modification regulation and highlight the potential of targeting the DOT1L/DCAF1 axis as a therapeutic strategy for HIV treatment.

Nanoenzyme Hydrogel Film-Based Portable Point-of-Care Testing Platform for Double-Signal Visual Detection of PSA.

The development of the Point-of-Care Testing (POCT) platform that combines convenience and cost-effectiveness is crucial for enabling the visual detection of disease biomarkers. In this work, a POCT platform for the sensitive in situ detection of prostate specific antigen (PSA) with dual-signal output was constructed by functionalizing the Eppendorf (EP) tube. This was achieved through the modification of aptamer hairpin probes (AHPs) on the lid of the EP tube and the assembly of a nanoenzyme hydrogel film on its inner wall. The target could trigger the release of Ag+ by AHP and subsequently activate Ag+-dependent DNAzyme (Ag-DNAzyme). This would initiate the cleavage of the DNA-Au/Pt NP hydrogel network, leading to the release of Au/Pt NPs. The released Au/Pt NPs exhibit both peroxidase (POD)-like and catalase (CAT)-like activity to produce a colorimetric response and induce liquid flow under pressure. Therefore, the target can be measured visually and quantitatively through colorimetric analysis and the measurement of total dissolved solids (TDS) using a pressure-triggered liquid flow device integrated into the platform. The designed platform is distinguished by its simplicity, specificity, cost-effectiveness, and remarkable sensitivity. It allows for the visual detection of PSA within concentration ranges of 0.5-100 ng/L (colorimetric) and 3-100 ng/L (TDS reading), boasting detection limits as low as 0.15 ng/L (colorimetric) and 0.57 ng/L (TDS reading). The strategy of target-triggered nanoenzyme release significantly enhances sensitivity and provides a guiding approach for visual biomarker detection.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Quercetin-loaded Human Umbilical cord Mesenchymal Stem Cell-derived sEVs for Spinal Cord Injury Recovery.

Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood-brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury.

Gastrointestinal Incomplete Degradation Exacerbates Neurotoxic Effects of PLA Microplastics via Oligomer Nanoplastics Formation.

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.

Factors associated with depressive symptoms among cancer patients: a nationwide cross-sectional study.

OBJECTIVE: Research on factors contributing to depressive symptoms in cancer patients at a national level, encompassing a comprehensive set of variables was limited. This study aimed to address this gap by identifying the factors associated with depressive symptoms among cancer patients through a nationwide cross-sectional analysis. METHODS: Various factors, including demographic, socioeconomic, behavioral patterns, general and self-rated health status, chronic conditions, dietary habits, and cancer-related factors, were examined. Data was from the National Health and Nutrition Examination Survey. Univariate and multivariate logistic regression analyses were performed to identify associated factors. The receiver-operating characteristic (ROC) curve was used to evaluate the performance of the logistic model. RESULTS: The findings showed that five sociodemographic factors, two behavioral styles, self-rated health status, comorbid arthritis, two dietary factors and two cancer-related factors were strongly associated with depressive symptoms. Compared with those aged 20-39 years, cancer individuals aged 40-59 years (OR = 0.48, P < 0.05) and those 60 years or older (OR = 0.18, P < 0.05) had lower odds of depression. Positive factors included being never married (OR = 1.98, P < 0.05), widowed, divorced or separated (OR = 1.75, P < 0.05), unemployment (OR = 1.87, P < 0.05), current smoking (OR = 1.84, P < 0.05), inadequate sleep (OR = 1.96, P < 0.05), comorbid arthritis (OR = 1.79, P < 0.05), and poor self-rated health status (OR = 3.53, P < 0.05). No significant association was identified between the Healthy Eating Index 2015 and the Dietary Inflammatory Index with depression (P > 0.05). Shorter cancer diagnosis duration was associated with reduced odds of depression (P < 0.05). The logistic model had an area under the curve of 0.870 (95% CI: 0.846-0.894, P < 0.05). CONCLUSIONS: Cancer patients should receive enhanced family and social support while cultivating a healthy lifestyle and diet. Incorporating plenty of fruits, greens, and beans is highly recommended, along with establishing a comprehensive health management framework.

Enhanced therapeutic efficacy for glioblastoma immunotherapy with an oncolytic herpes simplex virus armed with anti-PD-1 antibody and IL-12.

Glioblastoma is the most common and aggressive malignant brain tumor and has limited treatment options. Hence, innovative approaches are urgently needed. Oncolytic virus therapy is emerging as a promising modality for cancer treatment due to its tumor-specific targeting and immune-stimulatory properties. In this study, we developed a new generation of oncolytic herpes simplex virus C5252 by deletion of a 15-kb internal repeat region and both copies of γ34.5 genes. Additionally, C5252 was armed with anti-programmed cell death protein 1 antibody and interleukin-12 to enhance its therapeutic efficacy for glioblastoma immune-virotherapy. In vitro and in vivo experiments demonstrate that C5252 has a remarkable safety profile and potent anti-tumor activity against glioblastoma. Mechanistic studies demonstrated that C5252 specifically induces cell apoptosis by caspase-3/7 activation via downregulating ciliary neurotrophic factor receptor α. Furthermore, the enhanced anti-tumor therapeutic efficacy of C5252 in a subcutaneous glioblastoma model and an orthotopic glioblastoma model was confirmed. Moreover, syngeneic mouse models showed that the murine surrogate of C5252 has superior anti-tumor activity compared to the unarmed backbone virus, with enhanced immune activation. Taken together, our findings support C5252 as a promising therapeutic option for glioblastoma treatment, positioning it as a highly promising candidate for clinical translation.

Hyperspectral imaging combined with blood oxygen saturation for in vivo analysis of small intestinal necrosis tissue.

Acute mesenteric ischemia (AMI) is a clinically significant vascular and gastrointestinal condition, which is closely related to the blood supply of the small intestine. Unfortunately, it is still challenging to properly discriminate small intestinal tissues with different degrees of ischemia. In this study, hyperspectral imaging (HSI) was used to construct pseudo-color images of oxygen saturation about small intestinal tissues and to discriminate different degrees of ischemia. First, several small intestine tissue models of New Zealand white rabbits were prepared and collected their hyperspectral data. Then, a set of isosbestic points were used to linearly transform the measurement data twice to match the reference spectra of oxyhemoglobin and deoxyhemoglobin, respectively. The oxygen saturation was measured at the characteristic peak band of oxyhemoglobin (560 nm). Ultimately, using the oxygenated hemoglobin reflectance spectrum as the benchmark, we obtained the relative amount of median oxygen saturation in normal tissues was 70.0 %, the IQR was 10.1 %, the relative amount of median oxygen saturation in ischemic tissues was 49.6 %, and the IQR was 14.6 %. The results demonstrate that HSI combined with the oxygen saturation computation method can efficiently differentiate between normal and ischemic regions of the small intestinal tissues. This technique provides a powerful support for internist to discriminate small bowel tissues with different degrees of ischemia, and also provides a new way of thinking for the diagnosis of AMI.

Alignment-Based Adversarial Training (ABAT) for Improving the Robustness and Accuracy of EEG-Based BCIs.

Machine learning has achieved great success in electroencephalogram (EEG) based brain-computer interfaces (BCIs). Most existing BCI studies focused on improving the decoding accuracy, with only a few considering the adversarial security. Although many adversarial defense approaches have been proposed in other application domains such as computer vision, previous research showed that their direct extensions to BCIs degrade the classification accuracy on benign samples. This phenomenon greatly affects the applicability of adversarial defense approaches to EEG-based BCIs. To mitigate this problem, we propose alignment-based adversarial training (ABAT), which performs EEG data alignment before adversarial training. Data alignment aligns EEG trials from different domains to reduce their distribution discrepancies, and adversarial training further robustifies the classification boundary. The integration of data alignment and adversarial training can make the trained EEG classifiers simultaneously more accurate and more robust. Experiments on five EEG datasets from two different BCI paradigms (motor imagery classification, and event related potential recognition), three convolutional neural network classifiers (EEGNet, ShallowCNN and DeepCNN) and three different experimental settings (offline within-subject cross-block/-session classification, online cross-session classification, and pre-trained classifiers) demonstrated its effectiveness. It is very intriguing that adversarial attacks, which are usually used to damage BCI systems, can be used in ABAT to simultaneously improve the model accuracy and robustness.

Hydrogen Bonding-Induced Aggregation of Chiral Functionalized AuNS@Ag NPs for Photothermal Enantioanalysis.

Toward the challenges of signaling transduction amplified in enantioselective recognition, we herein devised an innovative strategy for highly selective recognition of amino acids and their derivatives, leveraging photothermal effects. In this approach, bifunctional l-ascorbic acid is employed to reduce silver ions in situ on Au nanostars. Simultaneously, its oxidate (l-dehydroascorbic acid) is bonded to the silver shell as a chiral selector to prepare chiral nanoparticles (C-AuNS@Ag NPs) with the ability to recognize stereoisomers and sensitively modulate the photothermal effect. l-Dehydroascorbic acid can selectively capture one of the enantiomers of the two forms through hydrogen bonding and drive aggregation of the nanoparticles, which sharply enhances the photothermal effect. Consequently, the two forms of the system exhibit a significant temperature difference, which enables the discrimination and quantification of enantiomers. Our strategy verifies that six chiral amino acids and their derivatives can be discriminated with enantioselective response values of up to 79. Additionally, the chiral recognition mechanism was revealed through density functional theory (DFT) calculations, providing a paradigm shift in the development of enantiomeric recognition strategies.

Identification of near-infrared characteristic bands of small bowel necrosis based on cellwise detection algorithm.

The near-infrared spectroscopy is often used to distinguish small bowel necrosis due to necrotizing enterocolitis (NEC). The characteristic bands of small bowel necrosis, as an important basis for evaluating the confidence of the differentiation results, are challenging to identify quickly. In this study, we proposed to identify characteristic bands of lesion samples based on hyperspectral imaging (HSI) and cellwise outlier detection. Rabbits were used as an animal model to simulate the clinical symptoms of NEC. The rabbits were detected at intervals of 10, 30, 60, and 90 min. The characteristic bands were identified within the same rabbit, between different rabbits and at different times. The result showed the bands near 763 nm, corresponding to the absorption peak of deoxyhemoglobin, were the characteristic bands separating samples with NEC. The identification result was plausible because hypoxia was the main cause of NEC. The method was easy to perform.

A novel laccase-like Cu-MOF for colorimetric differentiation and detection of phenolic compounds.

The development of convenient, fast, and cost-effective methods for differentiating and detecting common organic pollutant phenols has become increasingly important for environmental and food safety. In this study, a copper metal-organic framework (Cu-MOF) with flower-like morphology was synthesized using 2-methylimidazole (2-MI) as ligands. The Cu-MOF was designed to mimic the natural laccase active site and proved demonstrated excellent mimicry of enzyme-like activity. Leveraging the superior properties of the constructed Cu-MOF, a colorimetric method was developed for analyzing phenolic compounds. This method exhibited a wide linear range from 0.1 to 100 µM with a low limit of detection (LOD) of 0.068 µM. Besides, by employing principal component analysis (PCA), nine kinds of phenols was successfully distinguished and identified. Moreover, the combination of smartphones with RGB profiling enabled real-time, quantitative, and high-throughput detection of phenols. Therefore, this work presents a paradigm and offers guidance for the differentiation and detection of phenolic pollutants in the environment.

The Role of Grain Boundaries on Ion Migration and Charge Recombination in Halide Perovskites.

Grain boundaries (GBs) have a significant role in polycrystalline perovskite solar cells (PSCs). However, there is ongoing debate regarding the impact of GBs on the performance and long-term stability of PSCs. Employing the first-principles molecular dynamics for perovskites, the iodine vacancy defect migrations both in bulk and at GBs are investigated. i) The positive iodine vacancy (VI +) is found that have both lower formation energy (1.4 eV) and activation energy (0.18 eV) than those of neutral iodine vacancy (VI), statistically. It indicated the VI + acts as the dominant migrated iodine vacancy rather than VI; ii) the iodine vacancy at GBs has ≈0.48 eV higher activation energy than those in bulk, which leads to the accumulation of iodine vacancy at GBs; iii) the presence of VI + result in a 3-fold increase in charge recombination ratio at GBs, compared to pristine PSCs. Based on quantum molecular dynamics statistical results, which are consistent with experimental measurements, insights into iodine vacancy migration both at GBs and in the bulk are gained. This understanding can be valuable for defects engineering related to ion migration, in order to improve the long-term stability and promote the performance of PSCs.