Unsupervised spectral reconstruction from RGB images under two lighting conditions.

Unsupervised spectral reconstruction (SR) aims to recover the hyperspectral image (HSI) from corresponding RGB images without annotations. Existing SR methods achieve it from a single RGB image, hindered by the significant spectral distortion. Although several deep learning-based methods increase the SR accuracy by adding RGB images, their networks are always designed for other image recovery tasks, leaving huge room for improvement. To overcome this problem, we propose a novel, to our knowledge, approach that reconstructs the HSI from a pair of RGB images captured under two illuminations, significantly improving reconstruction accuracy. Specifically, an SR iterative model based on two illuminations is constructed at first. By unfolding the proximal gradient algorithm solving this SR model, an interpretable unsupervised deep network is proposed. All the modules in the proposed network have precise physical meanings, which enable our network to have superior performance and good generalization capability. Experimental results on two public datasets and our real-world images show the proposed method significantly improves both visually and quantitatively as compared with state-of-the-art methods.

The Nrf2/ARE pathway as a potential target to ameliorate atrazine-induced endocrine disruption in granulosa cells.

Atrazine (ATR) is widely used worldwide as a commercial herbicide, Diaminochlorotriazine (DACT) is the main metabolite of ATR in the organism. Both of them disrupt the production of steroids and induce abnormal reproductive development. The granulosa cells (GCs) are important for growth and reproduction of animals. However, the toxicity of ATR on the GCs of birds is not well clarified. To evaluate the effect of the environmental pollutant ATR on bird GCs. The quail GCs were allotted into 7 groups, C (The medium of M199), A20 (20 µM ATR), A100 (100 µM ATR), A250 (250 µM ATR), D20 (20 µM DACT), D100 (100 µM DACT) and D200 (200 µM DACT). The results demonstrated that ATR reduced the viability of GCs, disrupted mitochondrial structure (including mitochondrial cristae fragmentation and the mitochondrial morphology disappearance) and decreased mitochondrial membrane potential. Meanwhile, ATR interfered with the expression of key factors in the steroid synthesis pathway, inducing the secretion of the sex hormones E2 and P in GCs. which in turn induced apoptosis. Furthermore, the Nrf2/ARE pathway as a potential target to ameliorate ATR-induced endocrine disruption in GCs for proper reproductive functions. Our research provides a new perspective for understanding the effects of ATR on reproductive functions in birds.

Phase-Dependent Magnetic Proximity Modulations on Valley Polarization and Splitting.

Proximate-induced magnetic interactions present a promising strategy for precise manipulation of valley degrees of freedom. Taking advantage of the splendid valleytronic platform of transition metal dichalcogenides, magnetic two-dimensional VSe2 with different phases are introduced to intervene in the spin of electrons and modulate their valleytronic properties. When constructing the heterostructures, 1T-VSe2/WX2 (X = S and Se) showcases significant improvement in the valley polarizations at room temperature, while 2H-VSe2/WX2 exhibits superior performance at low temperatures and demonstrates heightened sensitivity to the external magnetic field. Simultaneously, considerable valley splitting with a large geff factor up to -29.0 is observed in 2H-VSe2/WS2, while it is negligible in 1T-VSe2/WX2. First-principles calculations reveal a phase-dependent magnetic proximity mechanism on the valleytronic modulations, which is dominated by interfacial charge transfer in 1T-VSe2/WX2 and the proximity exchange field in 2H-VSe2/WX2 heterostructures. The effective control over valley degrees of freedom will bridge the valleytronic physics and devices, rendering enormous potential in the field of valley quantum applications.

Pathogenic gating pore current conducted by autism-related mutations in the NaV1.2 brain sodium channel.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment targeting the underlying molecular defects. ASD gating charge mutations in the KCNQ/KV7 potassium channel cause gating pore currents (Igp) and impair action potential (AP) firing of dopaminergic neurons in brain slices. Here, we investigated ASD gating charge mutations of the voltage-gated SCN2A/NaV1.2 brain sodium channel, which ranked high among the ion channel genes with mutations in individuals with ASD. Our results show that ASD mutations in the gating charges R2 in Domain-II (R853Q), and R1 (R1626Q) and R2 (R1629H) in Domain-IV of NaV1.2 caused Igp in the resting state of ~0.1% of the amplitude of central pore current. The R1626Q mutant also caused significant changes in the voltage dependence of fast inactivation, and the R1629H mutant conducted proton-selective Igp. These potentially pathogenic Igp were exacerbated by the absence of the extracellular Mg2+ and Ca2+. In silico simulation of the effects of these mutations in a conductance-based single-compartment cortical neuron model suggests that the inward Igp reduces the time to peak for the first AP in a train, increases AP rates during a train of stimuli, and reduces the interstimulus interval between consecutive APs, consistent with increased neural excitability and altered input/output relationships. Understanding this common pathophysiological mechanism among different voltage-gated ion channels at the circuit level will give insights into the underlying mechanisms of ASD.

Variations to plasma H2O2 levels and TAC in chronical medicated and treatment-resistant male schizophrenia patients: Correlations with psychopathology.

Accumulating evidence suggests that imbalanced oxidative stress (OS) may contribute to the mechanism of schizophrenia. The aim of the present study was to evaluate the associations of OS parameters with psychopathological symptoms in male chronically medicated schizophrenia (CMS) and treatment-resistant schizophrenia (TRS) patients. Levels of hydrogen peroxide (H2O2), hydroxyl radical (·OH), peroxidase (POD), α-tocopherol (α-toc), total antioxidant capacity (TAC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assayed in males with CMS and TRS, and matched healthy controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The results demonstrated significant differences in the variables H2O2 (F = 5.068, p = 0.008), ·OH (F = 31.856, p < 0.001), POD (F = 14.043, p < 0.001), α-toc (F = 3.711, p = 0.027), TAC (F = 24.098, p < 0.001), and MMP-9 (F = 3.219, p = 0.043) between TRS and CMS patients and healthy controls. For TRS patients, H2O2 levels were correlated to the PANSS positive subscale (r = 0.386, p = 0.032) and smoking (r = -0,412, p = 0.021), while TAC was significantly negatively correlated to the PANSS total score (r = -0.578, p = 0.001) and POD and TAC levels were positively correlated to body mass index (r = 0.412 and 0.357, p = 0.021 and 0.049, respectively). For patients with CMS, ·OH levels and TAC were positively correlated to the PANSS general subscale (r = 0.308, p = 0.031) and negatively correlated to the PANSS total score (r = -0.543, p < 0.001). Furthermore, H2O2, α-toc, and ·OH may be protective factors against TRS, and POD was a risk factor. Patients with CMS and TRS exhibit an imbalance in OS, thus warranting future investigations.

Variation in monthly and seasonal elevation use impacts behavioral and dietary flexibility in Rhinopithecus bieti.

Black-and-white snub-nosed monkeys (Rhinopithecus bieti) rely on behavioral and dietary flexibility to survive in temperate latitudes at high-elevation habitats characterized by climate and resource seasonality. However, little is known about how elevation influences their behavioral and dietary flexibility at monthly or seasonal scales. We studied an isolated R. bieti population at Mt. Lasha in the Yunling Provincial Nature Reserve, Yunnan, China, between May 2008 and August 2016 to assess the impacts of elevation on feeding behavior and diet. Across our sample, R. bieti occupied elevations between 3031 and 3637 m above mean sea level (amsl), with a 315.1 m amsl range across months and a 247.3 m amsl range across seasons. Contrary to expectations, individuals spent less time feeding when ranging across higher elevations. Lichen consumption correlated with elevation use across months and seasons, with individuals spending more time feeding on this important resource at higher elevations. Leaf consumption only correlated with elevation use during the spring. Our results suggest that R. bieti do not maximize their food intake at higher elevations and that monthly and seasonal changes in lichen and leaf consumption largely explain variation in elevation use. These findings shed light on the responses of R. bieti to environmental change and offer insight into strategies for conserving their habitats in the face of anthropogenic disturbance.

First Report of Paramyrothecium breviseta Causing Target Spot on Amorphophallus muelleri in Yunnan, China.

Amorphophallus muelleri is an Araceae plant with perennial tuber, widely used in food, pharmaceutical and chemical industry due to its richness in glucomannan. In April 2022, an outbreak of a target spot on A. muelleri plantlets was observed in a nursery in Ruili, Yunnan, China. The leafstalks of the diseased plantlets in the nursery turned brown and decayed (Fig.1 A-B), then gradually some water-soaked spots on the true leaves developed along the veins (Fig.1 A). Subquencely, the spots on the true leaves turned dark green to white-grayish in the center, which formed light to dark brown concentric rings with a target-like appearance surrounded by a yellow halo (Fig.1 C). When the temperature was 20-34℃ and the relatively humidity was 25-80%, dark-green to black sporodochia with white hypha appeared on the lower and upper leaf surfaces. Finally, 5-8% of the plants surveyed on 800 m2 of one-year-old plantlets in the nursery showed the symptoms and some plants with infected leafstalks would be death. Similar symptoms were also observed on about 10% of the transplanted plants surveyed on 12000 m2 (1.2 ha) of two-year-old plantlets in the field. Five diseased leaves from five distinct plantlets in the nursery were collected for pathogen isolation. Leaf pieces(5 x 5 mm) were cut from the edge of necrotic lesions, and surface-sterilized with 2.5% sodium hypochlorite for 1 min, 75% ethanol for 30 s, then rinsed 5 times by sterilized distilled water, finally put the leaf pieces on sterilized filter paper for 3-5 minutes to dry them and transferred onto potato dextrose agar (PDA) in petri dishes at 25℃ for three days. Five pure cultures identical to colony and conidial characteristics were isolated from five individual plants. The representative pure culture (M1) was grayish-white and circular colonies were 7.50 cm in diamter after 15 days at 25℃, with dark green concentric rings of sporodochia, the dorsal view of the colonies were yellowish. Conidia were aseptate, smooth, cylindrical, 5.00-6.25 (5.71) x 1.25-1.67 (1.63) µm (n = 20) rounded at both ends. A spore suspension (1 x 106 spores/ml) was prepared by harvesting spores from 15-day-old cultures grown in the dark at 25℃, then a thirty-ml of spore suspension was sprayed on the healthy leaves of 10 two-year-old plantlets. Thirty-ml of sterile water was sprayed on the healthy leaves of another 10 seedlings and used as the control. All seedlings were placed in a nursery at 20 to 34℃ and a relative humidity of 25 to 80%. Similar symptoms (Fig.1 D-F) to those observed in the nursery and field developed on all the 10 seedlings inoculated with M1 after two days, but not on the control leaves. The pathogenicity tests were repeated for three times. Fungal cultures reisolated from the infected leaves were identical to the original colonies and conidia, completing Koch's postulates. The internal transcribed spacer (ITS, primers ITS1 and ITS4) region of ribosomal DNA (OQ553785), calmodulin (cmdA, primers CAL-228F and CAL2Rd)(OQ559103), RNA polymerase II second largest subunit (rpb2, primers RPB2-5F2 and RPB2-7cR) (OQ559104) and ß-tubulin (tub2, primers Bt2a and Bt2b) (OQ559105) of M1 had 100%, 98.52%, 98.98% and 98.98% identity with the sequences of Paramyrothecium breviseta CBS544.75 (KU846289 for ITS, KU846262 for cmdA, KU846351 for rpb2, and KU846406 for tub2), respectively. In the phylogenic tree based on ITS, cmdA, rpb2 and tub2 gene sequences, the pure culture M1 clustered with P. breviseta CBS544.75, SDBR-CMU387, DRL4 and DRL3, which has been reported as the pathogen of leaf spot of Coffea arabica in China, C. canephora in China and Thailand (Wu et al. 2021; Withee et al. 2022). Molecular and morphological observations showed the pure culture M1 were P. breviseta (Withee et al. 2022), in addition the disease was named as target spot dueing to the typical target symptom on the leaves. To our knowledge, this is the first report of P. breviseta on A. muelleri from Yunnan, China, as well as worldwide. This disease can caused serious economic losses of A. muelleri dueing to that it can result 5-8% death of the plants in the nursery.

A Noncentrosymmetric Metal-Free Borophosphate: Achieving a Large Birefringence and Excellent Stability by Covalent-Linkage.

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C5H6N)2B2O(HPO4)2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO3(OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C5H6N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials.

Optimizing Transseptal Puncture Guided by Three-Dimensional Mapping: Role of Unipolar Electrogram on Needle Tip.

BACKGROUND AND AIMS: A three-dimensional electroanatomic mapping system-guided transseptal puncture (3D-TSP), without fluoroscopy or echocardiography, was insufficiently reported. Indications for 3D-TSP remain unclear. This study aimed to establish a precise technique and create a workflow for validating and selecting eligible patients for fluoroless 3D-TSP. METHODS AND RESULTS: We developed a new methodology for 3D-TSP based on the unipolar electrogram derived from transseptal needle tip (UEGM-tip) in 102 cases (the derivation cohort) with intracardiac echocardiography (ICE) from March 2018 to February 2019. The apparent current of injury (COI) was recorded at the muscular limbus of the foramen ovalis (FO) on UEGM-tip (sinus rhythm: 2.57 ± 0.95 mV, atrial fibrillation: 1.92 ± 0.77 mV), which then disappeared or significantly reduced at central FO. Changes in COI, serving as a major criterion to establish 3D-TSP workflow, proved to be the most valuable indicator for identifying FO in 99% (101/102) of patients compared to three previous techniques (3 minor criteria) of reduction in atrial unipolar or bipolar potential and FO protrusion.A total of 1042 patients in the validation cohort underwent successful 3D-TSP through the workflow from March 2019 to July 2023. ICE guidance was required for 6.6% (69/1042) of cases. All four criteria were met in 740 patients, resulting in a 100% pure fluoroless 3D-TSP success rate. CONCLUSION: Most cases successfully achieved fluoroless 3D-TSP using changes of COI on UEGM tip. Patients who met all four criteria were suitable for 3D-TSP, while those who met none required ICE guidance.

Ratiometric emission of Tb(III)-functionalized Cd-based layered MOFs for portable visual detection of trace amounts of diquat in apples, potatoes and corn.

Diquat (DQ) is a typical bipyridine herbicide widely used to control weeds in fields and orchards. The severe toxicity of diquat poses a serious threat to the environment and human health. Metal-organic frameworks (MOFs) have received widespread attention due to their unique physical and chemical properties and applications in the detection of toxic and harmful substances. In this work, a two-dimensional (2D) Tb(III) functionalized MOF Tb(III)@1 (1 = [Cd(HTATB)(bimb)]n·H2O (Cd-MOF), H3TATB = 4,4',4″-triazine-2,4,6-tribenzoicacid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene) has been prepared and characterized. Tb(III)@1 has excellent optical properties and high water and chemical stability. After the Tb(III) is fixed by the uncoordinated -COO- in the 1 framework, Tb(III)@1 emits the typical green fluorescence of the lanthanide ion Tb(III) through the "antenna effect". It is worth noting that Tb(III)@1 can be used as a dual emission fluorescence chemical sensor for the ratio fluorescence detection of pesticide DQ, exhibiting a relatively low detection limit of 0.06 nM and a wide detection range of 0-50 nM. After the addition of DQ, a rapid color change of Tb(III)@1 fluorescence from green to blue was observed due to the combined effects of IFE, FRET and dynamic quenching. Therefore, a simple test paper box has been designed for direct on-site determination of pesticide DQ. In addition, the developed sensor has been successfully applied to the detection of DQ in real samples (fruits a Yin-Xia Sun and Bo-Tao Ji contributed equally to this work and should be considered co-first authors.nd vegetables) with satisfactory results. The results indicate that the probe developed in this study has broad application prospects in both real sample detection and actual on-site testing.

Meta-learning-based Inductive logistic matrix completion for prediction of kinase inhibitors.

Protein kinases become an important source of potential drug targets. Developing new, efficient, and safe small-molecule kinase inhibitors has become an important topic in the field of drug research and development. In contrast with traditional wet experiments which are time-consuming and expensive, machine learning-based approaches for predicting small molecule inhibitors for protein kinases are time-saving and cost-effective, which are highly desired for us. However, the issue of sample scarcity (known active and inactive compounds are usually limited for most kinases) poses a challenge to the research and development of machine learning-based kinase inhibitors' active prediction methods. To alleviate the data scarcity problem in the prediction of kinase inhibitors, in this study, we present a novel Meta-learning-based inductive logistic matrix completion method for the Prediction of Kinase Inhibitors (MetaILMC). MetaILMC adopts a meta-learning framework to learn a well-generalized model from tasks with sufficient samples, which can fast adapt to new tasks with limited samples. As MetaILMC allows the effective transfer of the prior knowledge learned from kinases with sufficient samples to kinases with a small number of samples, the proposed model can produce accurate predictions for kinases with limited data. Experimental results show that MetaILMC has excellent performance for prediction tasks of kinases with few-shot samples and is significantly superior to the state-of-the-art multi-task learning in terms of AUC, AUPR, etc., various performance metrics. Case studies also provided for two drugs to predict Kinase Inhibitory scores, further validating the proposed method's effectiveness and feasibility. SCIENTIFIC CONTRIBUTION: Considering the potential correlation between activity prediction tasks for different kinases, we propose a novel meta learning algorithm MetaILMC, which learns a prior of strong generalization capacity during meta-training from the tasks with sufficient training samples, such that it can be easily and quickly adapted to the new tasks of the kinase with scarce data during meta-testing. Thus, MetaILMC can effectively alleviate the data scarcity problem in the prediction of kinase inhibitors.

Stability and Bioaccessibility of Quercetin-Enriched Pickering Emulsion Gels Stabilized by Cellulose Nanocrystals Extracted from Rice Bran.

To investigate the optimal delivery system of quercetin, in this paper, cellulose nanocrystals (CNCs) extracted from rice bran were used to stabilize the Pickering emulsion and Pickering emulsion gels (PEGs) with quercetin. To compare the emulsion properties, stability, antioxidation activity, encapsulation rate, and bioaccessibility of the quercetin, four emulsions of CNC Pickering emulsion (C), CNC Pickering emulsion with quercetin (CQ), CNC Pickering gel emulsion (CG), and CNC Pickering gel emulsions with quercetin (CQG) were prepared. All four emulsions exhibited elastic gel network structure and good stability. The quercetin significantly reduced the particle size, increased the stability, and improved the antioxidant capacity of CQ and CQG. Compared to C and CG, the ABTS+ radical scavenging capacities of CQ and CQG were respectively enhanced by 46.92% and 3.59%. In addition, CQG had a higher encapsulation rate at 94.57% and higher bioaccessibility (16.17) compared to CQ. This study not only indicated that CNC from rice bran could be exploited as an excellent stabilization particle for Pickering emulsions, but also provided a highly stable and bioaccessible delivery system for water-insoluble functional active factors.

Stable Super-Resolution Imaging of Cell Membrane Nanoscale Subcompartment Dynamics with a Buffering Cyanine Dye.

Super-resolution fluorescence imaging is a crucial method for visualizing the dynamics of the cell membrane involved in various physiological and pathological processes. This requires bright fluorescent dyes with excellent photostability and labeling stability to enable long-term imaging. In this context, we introduce a buffering-strategy-based cyanine dye, SA-Cy5, designed to identify and label carbonic anhydrase IX (CA IX) located in the cell membrane. The unique feature of SA-Cy5 lies in its ability to overcome photobleaching. When the dye on the cell membrane undergoes photobleaching, it is rapidly replaced by an intact probe from the buffer pool outside the cell membrane. This dynamic replacement ensures that the fluorescence intensity on the cell membrane remains stable over time. Under the super-resolution structured illumination microscopy (SIM), the cell membrane can be continuously imaged for 60 min with a time resolution of 20 s. This extended imaging period allows for the observation of substructural dynamics of the cell membrane, including the growth and fusion of filamentous pseudopodia and the fusion of vesicles. Additionally, this buffering strategy introduces a novel approach to address the issue of poor photostability associated with the cyanine dyes.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Integrating transcriptomics and machine learning for immunotherapy assessment in colorectal cancer.

Colorectal cancer (CRC) is a highly prevalent and lethal malignancy worldwide. Although immunotherapy has substantially improved CRC outcomes, intolerance remains a major concern among most patients. Considering the pivotal role of the tumor microenvironment (TME) in tumor progression and treatment outcomes, profiling the TME at the transcriptomic level can provide novel insights for developing CRC treatment strategies. Seventy-seven TME-associated signatures were acquired from previous studies. To elucidate variations in prognosis, clinical features, genomic alterations, and responses to immunotherapy in CRC, we employed a non-negative matrix factorization algorithm to categorize 2595 CRC samples of 27 microarrays from the Gene Expression Omnibus database. Three machine learning techniques were employed to identify a signature specific to immunotherapy. Subsequently, the mechanisms by which this signature interacts with TME subtypes and immunotherapy were investigated. Our findings revealed five distinct TME subtypes (TMESs; TMES1-TMES5) in CRC, each exhibiting a unique pattern of immunotherapy response. TMES1, TMES4, and TMES5 had relatively inferior outcomes, TMES2 was associated with the poorest prognosis, and TMES3 had a superior outcome. Subsequent investigations revealed that activated dendritic cells could enhance the immunotherapy response rate, with their augmentation effect closely associated with the activation of CD8+T cells. We successfully classified CRC into five TMESs, each demonstrating varying response rates to immunotherapy. Notably, the application of machine learning to identify activated dendritic cells helped elucidate the underlying mechanisms contributing to these differences. We posit that these TMESs hold promising clinical implications for prognostic evaluation and guidance of immunotherapy strategies, thereby providing valuable insights to inform clinical decision-making.

Deferiprone-resveratrol hybrid attenuates iron accumulation, oxidative stress, and antioxidant defenses in iron-loaded human Huh7 hepatic cells.

Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to diminish harmful reactive oxygen species (ROS), purposing to ameliorate oxidative liver damage and dysfunctions. The deferiprone-resveratrol hybrid (DFP-RVT) is a synthetic iron chelator possessing anti-ß-amyloid peptide aggregation, anti-malarial activity, and hepatoprotection in plasmodium-infected mice. The study focuses on investigating the antioxidant, cytotoxicity, iron-chelating, anti-lipid peroxidation, and antioxidant defense properties of DFP-RVT in iron-loaded human hepatocellular carcinoma (Huh7) cells. In the findings, DFP-RVT dose dependently bound Fe(II) and Fe(III) and exerted stronger ABTS•- and DPPH•-scavenging (IC50 = 8.0 and 164 µM, respectively) and anti-RBC hemolytic activities (IC50 = 640 µM) than DFP but weaker than RVT (p < 0.01). DFP-RVT was neither toxic to Huh7 cells nor PBMCs. In addition, DFP-RVT diminished the level of redox-active iron (p < 0.01) and decreased the non-heme iron content (p < 0.01) in iron-loaded Huh7 cells effectively when compared without treatment in the order of DFP-RVT > RVT ∼ DFP treatments (50 µM each). Moreover, the compound decreased levels of hepatic ROS in a dose-dependent manner and the level of malondialdehyde, which was stronger than DFP but weaker than RVT. Furthermore, DFP-RVT restored the decrease in the GSH content and GPX and SOD activities (p < 0.01) in iron-loaded Huh7 cells in the dose-dependent manner, consistently in the order of RVT > DFP-RVT > DFP. Thus, the DFP-RVT hybrid possesses potent iron chelation, antioxidation, anti-lipid peroxidation, and antioxidant defense against oxidative liver damage under iron overload.

Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Rubellicoccus peritrichatus gen. nov., sp. nov., isolated from crustose coralline algae in a coral aquarium.

A Gram-stain-negative, motile, aerobic, non-spore-forming coccus, designated strain CR14T, was isolated from crustose coralline algae. Cells grew at 20-30 °C (optimum, 25 °C), at pH 6-9 (optimum, pH 7.6) and with NaCl concentrations of 0.5-9 % (w/v; optimum, 2-4 %). Global alignment based on 16S rRNA gene sequences indicated strain CR14T is closest to Ruficoccus amylovorans JCM 31066T with an identity of 92 %. The average nucleotide identity and average amino acid identity values between CR14T and R. amylovorans JCM 31066T were 68.4 and 59.9 %, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CR14T forms an independent branch within the family Cerasicoccaeae, which was consistent with the phylogenomic results. The sole isoprenoid quinone was MK-7. The major fatty acids were C14 : 0, C18 : 1 ω9c, C19 : 0 cyc 9,10 DMA, C16 : 0, and C18 : 2 ω6c. The major cellular polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and two unidentified lipids. The genome DNA G+C content was 48.7 mol%. Based on morphological, physiological and chemotaxonomic characteristics, strain CR14T is suggested to represent a novel species in a new genus, for which the name Rubellicoccus peritrichatus gen. nov., sp. nov. is proposed. The type strain is CR14T (=MCCC 1K03845T=KCTC 72139T).

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.