ATF5-regulated Mitochondrial Unfolded Protein Response Attenuates Neuronal Damage in Epileptic Rat by Reducing Endoplasmic Reticulum Stress Through Mitochondrial ROS.

Endoplasmic reticulum (ER) dysfunction caused by excessive ER stress is a crucial mechanism underlying seizures-induced neuronal injury. Studies have shown that mitochondrial reactive oxygen species (ROS) are closely related to ER stress, and our previous study showed that activating transcription factor 5 (ATF5)-regulated mitochondrial unfolded protein response (mtUPR) modulated mitochondrial ROS generation in a hippocampal neuronal culture model of seizures. However, the effects of ATF5-regulated mtUPR on ER stress and the underlying mechanisms remain uncertain in epilepsy. In this study, ATF5 upregulation by lentivirus infection attenuated seizures-induced neuronal damage and apoptosis in a rat model of pilocarpine-induced epilepsy, whereas ATF5 downregulation by lentivirus infection had the opposite effects. ATF5 upregulation potentiated mtUPR by increasing the expression of mitochondrial chaperone heat shock protein 60 (HSP60) and caseinolytic protease proteolytic subunit (ClpP) and reducing mitochondrial ROS generation in pilocarpine-induced seizures in rats. Additionally, upregulation of ATF5 reduced the expression of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), suggesting suppression of ER stress; Moreover, ATF5 upregulation attenuated apoptosis-related proteins such as B-cell lymphoma-2 (BCL2) downregulation, BCL2-associated X (BAX) and cleaved-caspase-3 upregulation. However, ATF5 downregulation exerted the opposite effects. Furthermore, pretreatment with the mitochondria-targeted antioxidant mito-TEMPO attenuated the harmful effects of ATF5 downregulation on ER stress and neuronal apoptosis by reducing mitochondrial ROS generation. Overall, our study suggested that ATF5-regulated mtUPR exerted neuroprotective effects against pilocarpine-induced seizures in rats and the underlying mechanisms might involve mitochondrial ROS-mediated ER stress.

Induction and Stabilization of Columnar Mesophases in Fluorinated Polycyclic Aromatic Hydrocarbons by Arene-Perfluoroarene Interactions.

The straightforward synthesis of several Fluorinated Polycyclic Aromatic Hydrocarbons by the efficient, transition-metal-free, arene fluorine nucleophilic substitution reaction is described, and the full investigation of their liquid crystalline and optical properties reported. The key precursors for this study, i. e. 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl derivatives, were obtained in two steps from the highly selective Scholl oxidative homo-coupling of 3,4-dialkoxy-1-bromobenzene, followed by quantitative double-lithiation. In situ room temperature nucleophilic annulation with either perfluorobenzene or perfluoronaphthalene leads to 1,2,3,4-tetrafluoro-6,7,10,11-tetraalkxoytriphenylenes and 9,10,11,12,13,14-hexafluoro-2,3,6,7-tetraalkoxybenzo[f]tetraphenes, respectively, in good yields. Exploiting the same strategy, subsequent double annulations resulted in the formation of 9,18-difluoro-2,3,6,7,11,12,15,16-octa(alkoxy)tribenzo[f,k,m]tetraphenes and 9,10,19,20-tetrafluoro-2,3,6,7,12,13,16,17-octakis(hexyloxy)tetrabenzo[a,c,j,l]tetracenes, respectively. Despite the presence of only four alkoxy chains, the polar "Janus" mesogens display a columnar hexagonal mesophase over broad temperature ranges, with higher mesophase stability than the archetypical 2,3,6,7,10,11-hexa(alkoxy)triphenylenes and their hydrogenated counterparts. The improvement or induction of mesomorphism is attributed to efficient antiparallel face-to-face π-stacking driven by the establishment of non-covalent perfluoroarene-arene intermolecular interactions. The larger lipophilic discotic π-extended compounds also exhibit columnar mesomorphism, over similar temperature ranges and stability than their hydrogenated homologs. Finally, these fluorinated molecules form stringy gels in various solvents, and show interesting solvatochromic emission properties in solution as well as strong emission in thin films and gels.

Metal-free sulfonylation of quinoxalinones to access 2-sulfonyl-oxylated quinoxalines via oxidative O-S cross coupling.

The C2 sulfonylation of quinoxalinones via a metal-free oxidative S-O cross-coupling strategy for synthesizing 2-sulfonyloxylated quinoxalines is established. It effectively solved the long-standing problems in the C2 transformation of quinoxalinones via a metal-free oxidative O-S coupling strategy. Compared with the traditional C2 transformed quinoxalinones-C2 chlorination method, this protocol is mild, facile, and environmentally friendly and exhibits good atomic economy and excellent functional group tolerance. Moreover, the utility of this methodology and the sulfonyloxyl handles was demonstrated through the synthesis of 2-substituted quinoxaline-based bioactive molecules.

Brazilin inhibits bladder cancer by promoting cell necroptosis.

Brazilin possesses anticancer effects, but the mechanisms are poorly understood. This study investigated the mechanisms of brazilin-induced cell death in the T24 human bladder cancer cell line. Low serum cell culture and the lactate dehydrogenase assay were used to confirm the antitumor effect of brazilin. Annexin V and propidium iodide double staining, transmission electron microscopy, fluo-3-AM assay for Ca2+ mobilization and caspase activity assay were performed to identify the type of cell death after brazilin treatment. Mitochondria membrane potentials were measured using JC-1. Quantitative real-time polymerase chain reaction and western blot analyses were performed to verify the expression of the necroptosis-related genes and proteins receptor interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain-like (MLKL). The results showed that brazilin induced necrosis in T24 cells and upregulated the mRNA and protein levels of RIP1, RIP3 and MLKL and Ca2+ influx. The necroptosis-mediated cell death was rescued by the necroptosis inhibitor necrostatin-1 (Nec-1), but not by the apoptosis inhibitor z-VAD-fmk. Brazilin repressed caspase 8 expression and decreased the mitochondrial membrane potentials; both effects were partially reversed by Nec-1. Brazilin induced physiological and morphological changes in T24 cells and RIP1/RIP3/MLKL-mediated necroptosis might be involved. In conclusion, the results confirm the involvement of necroptosis in brazilin-induced cell death and suggest that brazilin could be explored as an anticancer agent against bladder cancer.

Unravelling Species Diversity and Pathogenicity of Colletotrichum Associated with Anthracnose on Osmanthus fragrans in Quanjiao, China.

Osmanthus fragrans is a popular ornamental tree species known for its fragrant flowers and is widely cultivated in Asia, Europe, and North America. Anthracnose is a disastrous threat to the growth and development of O. fragrans and has caused significant economic losses. To reveal the potential pathogen diversity of anthracnose, 127 isolates of Colletotrichum were isolated from the symptomatic leaves. Morphological studies and multilocus phylogenetic analyses with the concatenated sequences of the internal transcribed spacer, glyceraldehyde-3-phosphate dehydrogenase, chitin synthase, actin, beta-tubulin, calmodulin, and the intergenic region between Apn2 and Mat1-2-1, as well as a pairwise homoplasy index, test placed the causal fungi as two new species, Colletotrichum anhuiense (two isolates) and C. osmanthicola (12 isolates), and three known taxa, C. fructicola (18 isolates), C. gloeosporioides (62 isolates), and C. karstii (33 isolates). Among them, C. gloeosporioides was the most dominant, and C. anhuiense was occasionally discovered from the host tissues. Pathogenicity tests in vivo on O. fragrans leaves revealed a significant difference in virulence among these species. Of them, C. gloeosporioides, C. osmanthicola, and C. anhuiense were significantly more virulent than C. fructicola and C. karstii, while C. karstii was the least virulent. To our knowledge, this study was the first to report the pathogen diversity of anthracnose on O. fragrans.

First report of leaf spot on Ilex verticillata caused by Alternaria alternata in China.

Ilex verticillata (L.) A. Gray (Winter Red) is a deciduous shrub and native to North America with high ornamental value, which was introduced into China in 2006. In Oct. 2020, leaf spots occurred on I. verticillata at the nursery of Baima Base for Teaching and Scientific Research of Nanjing Forestry University (31°36'51"N, 119°11'8"E). In the early stage, there were small black spots occurred on the leaves. Then, these spots enlarged and coalesced into regular or irregular gray necrotic lesions with dark margins (Fig. S1A). The incidence of this disease was ca. 93%. Infected leaves were collected and surface-sterilized with 75% ethanol. Pieces cut from the margin of the lesions of ca. 5×5 mm were placed on potato dextrose agar (PDA) Petri plates and incubated at 25±2°C for 7 days. Ten Alternaria fungal isolates were single-spore isolated. Since these isolates shared similar morphological characters, isolates 9-1 and 15-2-2 were randomly chosen for further experiments. 2-yr-old potted I. verticillata were used for pathogenicity test in vivo. Leaves were surface-sterilized using 75% ethanol and wounded using a sterilized needle and inoculated with mycelial plugs or 10 µL of conidial suspensions (105 spores mL-1), respectively. The inoculated plants were kept in a growth chamber at 25°C and 85% RH under a 12-h photoperiod. PDA plugs without fungus or sterilized H2O were used as controls, respectively. The experiment was repeated 2 times. Each treatment had 3 replicates. By day 7, necrotic lesions were observed on the leaves inoculated with the fungal isolates 9-1 or 15-2-2. No lesions were found on the plants inoculated with PDA discs or dH2O (Fig. S1). To complete Koch's postulates, the pathogen was re-isolated from the infected leaves and shared similar morphological characteristics of colonies and conidia with the original inoculated isolates. Conidiophores of the 2 isolates were pale brown, erect or curved, (20.1-)21.4-29.9(-39.9) × (8.4-)10.6-14.9(-18.3) µm, (n = 30). Conidia were dictyospores, nearly ovoid or clubbed, brown or grayish brown, (25.2-)27.5-42.8(-47.9) × (5.7-)6-7.7(-8.7) µm, (n = 30), in branched or unbranched chains (Fig. S1). These morphological characteristics matched A. alternata (Woudenberg et al. 2013). The internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH), endopolygalacturonase gene (endoPG), anonymous noncoding region (OPA10-2), small subunit gene (SSU), and large subunit gene (LSU) of isolates 9-1 and 15-2-2 were amplified using primer sets of Woudenberg et al. (2013). The SSU (OK428540, OK428541), LSU (OK428538, OK428539), ITS (OK316966, OK316967), GAPDH (OK428542, OK428543), endoPG (OK428544, OK428545), and OPA10-2 (OK428536, OK428537) of isolates 9-1 and 15-2-2 showed 99, 99, 99, 99, 100, and 100% similarity to the sequences of A. alternata ex-type CBS 916.96, respectively. Phylogenetic analyses using concatenated sequences of ITS, GAPDH, OPA10-2, LSU, SSU, and endOPG also showed that the isolates of 9-1 and 15-2-2 clustered with A. alternata ex-type and was supported with a 100% bootstrap value (Fig. S2). Based on the morphological and phylogenetic results, these fungal isolates were identified as A. alternata. A. alternata was reported as the pathogen of leaf spot and other diseases on more than 380 hosts (Farr & Rossman, 2022). To our knowledge, this was the first report of A. alternata causing leaf spot on I. verticillata in China. This report is important because the discovery is related to the management strategies of the new pathogen on I. verticillata. The monitoring and control of the disease needs to be emphasized in the future.

A Reinforcement Learning Handover Parameter Adaptation Method Based on LSTM-Aided Digital Twin for UDN.

Adaptation of handover parameters in ultra-dense networks has always been one of the key issues in optimizing network performance. Aiming at the optimization goal of effective handover ratio, this paper proposes a deep Q-learning (DQN) method that dynamically selects handover parameters according to wireless signal fading conditions. This approach seeks good backward compatibility. In order to enhance the efficiency and performance of the DQN method, Long Short Term Memory (LSTM) is used to build a digital twin and assist the DQN algorithm to achieve a more efficient search. Simulation experiments prove that the enhanced method has a faster convergence speed than the ordinary DQN method, and at the same time, achieves an average effective handover ratio increase of 2.7%. Moreover, in different wireless signal fading intervals, the method proposed in this paper has achieved better performance.

Facile Synthesis of 2D/2D Ti2C3/ZnIn2S4 Heterostructure for Enhanced Photocatalytic Hydrogen Generation.

ZnIn2S4, a novel two-dimensional visible light-responsive photocatalyst, has attracted much attention in the photocatalytic evolution of H2 under visible light irradiation due to its attractive intrinsic photoelectric properties and geometric configuration. However, ZnIn2S4 still has severe charge recombination, which results in moderate photocatalytic performance. Herein, we report the successful synthesis of 2D/2D ZnIn2S4/Ti3C2 nanocomposites by a facile one-step hydrothermal method. The efficiency of the nanocomposites in photocatalytic hydrogen evolution under visible light irradiation was also evaluated for different ratios of Ti3C2, and the optimal photocatalytic activity was achieved at 5% Ti3C2. Importantly, the activity was significantly higher than that of pure ZnIn2S4, ZnIn2S4/Pt, and ZnIn2S4/graphene. The enhanced photocatalytic activity is mainly due to the close interfacial contact between Ti3C2 and ZnIn2S4 nanosheets, which amplifies the transport of photogenerated electrons and enhances the separation of photogenerated carriers. This research describes a novel approach for the synthesis of 2D MXenes for photocatalytic hydrogen production and expands the utility of MXene composite materials in the fields of energy storage and conversion.

CdS Nanoparticles Supported by Cobalt@Carbon-Derived MOFs for the Improved Adsorption and Photodegradation of Ciprofloxacin.

The design and synthesis of efficient photocatalysts that promote the degradation of organic pollutants in water have attracted extensive attention in recent years. In this work, CdS nanoparticles are grown in situ on Co@C derived from metal-organic frameworks. The resulting hierarchical CdS/Co@C nanostructures are evaluated in terms of their adsorption and photocatalytic ciprofloxacin degradation efficiency under visible-light irradiation. The results show that, apart from offering a large surface area (55.69 m2·g-1), the prepared material can effectively suppress the self-agglomeration of CdS and enhance the absorption of visible light. The CdS/Co@C-7 composite containing 7% wt Co@C has the highest photodegradation rate, and its activity is approximately 4.4 times greater than that of CdS alone. Moreover, this composite exhibits remarkable stability after three successive cycles of photocatalysis. The enhanced photocatalytic performance is largely ascribed to the rapid separation of electron-hole pairs and the effective electron transfer between CdS and Co@C, which is confirmed via electrochemical experiments and photoluminescence spectra. The active substance capture experiment and the electron spin resonance technique show that h+ is the main active entity implicated in the degradation of CIP, and accordingly, a possible mechanism of CIP photocatalytic degradation over CdS/Co@C is proposed. In general, this work presents a new perspective on designing novel photocatalysts that promote the degradation of organic pollutants in water.

Designing Nonconventional Luminescent Materials with Efficient Emission in Dilute Solutions via Modulation of Dynamic Hydrogen Bonds.

Nonconventional luminescent materials (NLMs) which do not contain traditional aromatic chromophores are of great interest due to their unique chemical structures, optical properties, and their potential applications in various areas, such as cellular imaging and chemical sensing. However, most reported NLMs show weak or no emission in dilute solutions, which severely limits their applications. In this work, dynamic hydrogen bonds were utilized to design NLMs with efficient emission in dilute solutions. To further validate the results, polymers P1 and P2 were successfully prepared and investigated. It was found that the luminescence quantum efficiency of P1 and P2 at a concentration of 0.1 mg/mL in water solution was 8.9 and 0.6%, respectively. The high efficiency can be attributed to the fact that polymer P1 has more intra- or intermolecular dynamic hydrogen bonds and other short interactions than P2 in dilute solutions, allowing P1 to achieve the through-space conjugation effect to increase the degree of system conjugation, restrict molecular motion, and decrease nonradiative transitions, which can effectively improve luminescence. In addition, polymer P2 exhibits the characteristics of clustering-triggered emission, excitation wavelength-dependent and concentration-dependent fluorescence properties, excellent photobleaching resistance, low cytotoxicity, and selective recognition of Fe3+. The present study investigates the manipulation of luminescence properties of NLMs in dilute solutions through the modulation of dynamic hydrogen bonds. This approach can serve as a semi-empirical technique for designing and building innovative NLMs in the times ahead.

Total Structure, Electronic Structure and Catalytic Hydrogenation Activity of Metal-Deficient Chiral Polyhydride Cu57 Nanoclusters.

Accurate identifying and in-depth understanding of the defect sites in a working nanomaterial could hinge on establishing specific defect-activity relationships. Yet, atomically precise coinage-metal nanoclusters (NCs) possessing surface vacancy defects are scarce primarily owing to challenges in the synthesis and isolation of such defective NCs. Herein we report a mixed-ligand strategy to synthesizing an intrinsically chiral and metal-deficient copper hydride-rich NC [Cu57 H20 (PET)36 (TPP)4 ]+ (Cu57 H20 ). Its total structure (including hydrides) and electronic structure are well established by combined experimental and computational results. Crystal structure reveals Cu57 H20 features a cube-like Cu8 kernel embedded in a corner-missing metal-ligand shell of Cu49 (PET)36 (TPP)4 . Single Cu vacancy defect site occurs at one corner of the shell, evocative of mono-lacunary polyoxometalates. Theoretical calculations demonstrate that the above-mentioned point vacancy causes one surface hydride exposed as an interfacial capping µ3 -H- , which is accessible in chemical reaction, as proved by deuterated experiment. Moreover, Cu57 H20 shows catalytic activity in the hydrogenation of nitroarene. The success of this work opens the way for the research on well-defined chiral metal-deficient Cu and other metal NCs, including exploring their application in asymmetrical catalysis.

Recurrent headache and visual symptoms in a young man: a rare neuronal intranuclear inclusion disease case report.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease. Patients with NIID may present with heterogeneous clinical symptoms, including episodic encephalopathy, dementia, limb weakness, cerebellar ataxia, and autonomic dysfunction. Among the NIID cases reported in China, patients often have complicated and severe manifestations. Therefore, many clinicians do not consider the disease when the patient presents with relatively minor complaints. CASE PRESENTATION: We present the case of a 39-year-old man showing migraine-aura-like symptoms for the past 3 years. Brain magnetic resonance imaging (MRI) revealed hyperintense signals in the splenium of the corpus callosum and corticomedullary junction on diffusion-weighted imaging (DWI) over time. In addition, brain atrophy that was not concomitant with the patient's age was detected while retrospectively reviewing the patient's imaging results. Genetic analysis and skin biopsy confirmed a diagnosis of NIID. The patient was treated with sibelium, and the symptoms did not recur. DISCUSSION AND CONCLUSIONS: Migraine-aura-like symptoms may be the predominant clinical presentation in young patients with NIID. Persistent high-intensity signals on DWI in the brain and early-onset brain atrophy might be clues for the diagnosis of NIID.

Infrared Spectroscopic Study of Methane Ice, Pure and in Mixtures with Polar (H2O) and Nonpolar (N2) Molecules.

Mid-infrared studies of fundamental modes of ices of pure CH4 and its mixtures with polar (H2O) and nonpolar (e.g., N2) molecules are essential in order to learn the state of aggregation and thermal history of ices present in the interstellar medium and outer solar system bodies. Such data will be useful in the interpretation of observational data from the James Webb Space Telescope. Using an ultrahigh vacuum apparatus, we conducted reflection-absorption infrared spectroscopy measurements in the mid-IR range of pure methane ice and methane-containing ice mixtures of interest to interstellar and solar system ice chemistry, e.g., with H2O and N2 molecules. We found that nuclear spin conversion (NSC) in solid methane and its crystalline structures is affected─in different ways─by the presence of H2O and N2. Specifically, we found a relationship between the thickness and the solid-state ordering transformation in methane thin films. This new study of the NSC of pure CH4 ice and of the CH4:H2O ice mixture at 7 K is carried out in relation to the segregation of H2O using the ν1 and ν2 IR inactive modes of methane. The diffusion of N2 and CH4 in the CH4:N2 ice mixture with temperature cycling has been studied to obtain the relationship between IR features and the state of aggregation of the ice.

First report of leaf spot on Elaeagnus pungens caused by Neopestalotiopsis clavispora in China.

Elaeagnus pungens Thunb. is a common traditional Chinese herbal medicine. It has high medicinal, edible, and ornamental value. In Sep. 2020, a leaf spot disease was found on E. pungens in the campus of Nanjing Forestry University, China (31°36'51"N, 119°11'8"E). The incidence rate was ca. 77%. The disease primarily appeared as small brown spots on the leaves. Then, the spots enlarged and coalesced into regular or irregular gray necrotic lesions with dark margins. At the late stage of symptom development, black spots (acervulus) appeared on the necrotic lesions (Fig. S2A-C). Eight symptomatic leaves were collected and surface-sterilized using 75% ethanol for 30 s followed by 1% NaClO for 1 min, and then washed three times in sterile distilled water. Cuttings (ca. 5×5 mm) were made from the margins of the lesions and placed on 2% of potato dextrose agar (PDA) in Petri plates and incubated at 25 ± 2 °C for 5 days. The isolation frequency of pathogens from diseased tissues was ca. 100%. A total of four fungal isolates 3-3-1, 3-3-2, 3-3-3, and 3-3-4 were obtained using the monosporic isolation method and stored in the Forest Pathology Laboratory at Nanjing Forestry University. For molecular identification, the internal transcribed spacer (ITS), partial translation elongation factor 1-alpha (TEF1-α), and partial ß-tubulin (TUB2) were amplified from the isolate 3-3-1, 3-3-2, 3-3-3 and 3-3-4, with the corresponding primer sets published in Maharachchikumbura et al. (2014). The amplicons of ITS (ON510047, ON510048, ON510070, and ON510069), TEF1-α (ON808445, ON808446, ON808447, and ON808448), and TUB2 (ON808449, ON808450, ON808451, and ON808452) generated from the isolate 3-3-1, 3-3-2, 3-3-3, and 3-3-4 were sequenced and deposited in GenBank. The ITS, TEF1-α, and TUB2 of the isolate 3-3-1 shared the same nucleotide sequences with the corresponding sequences of the isolate 3-3-2, 3-3-3, and 3-3-4. The ITS, TEF1-α, and TUB2 sequences showed 100%, 97%, and 99% similarity to Neopestalotiopsis clavispora MFLUCC12-0281 (ex-type), respectively. Phylogenetic analysis using concatenated sequences of ITS, TEF1-α, and TUB2 also showed that isolate 3-3-1, 3-3-2, 3-3-3, and 3-3-4 clustered monophyletically with N. clavispora, and supported with a high bootstrap value (80%) (Fig. S1). Since these four isolates were same species based on phylogenetic analysis, isolate 3-3-4 was randomly chosen for the pathogenicity test and morphological analysis. Colonies of the isolate 3-3-4 grown on PDA were white, cottony, and flocculent, contained undulate edges with dense aerial mycelium on the surface, and averaged 12.2 mm d-1 growth at 25 °C (Fig. S2F). Black conidiomata formed superficially, scattered over the PDA at two weeks post incubation, 170.15-1820.32 × 90.33-1230.12 µm (n = 109), and contained slimy black conidial mass (Fig. S2G). Conidiogenous cells were pear-shaped to cylindrical, transparent, and colorless to pale yellow with smooth cell walls (Fig. S2H). Conidia were spindle shaped, five cells, four septa, 18.46-25.9 × 5.3-9.37 µm, (av ± SD = 23.31 ± 1.81 × 7.33 ± 1.07 µm, n = 34) (Fig. S2I). Apical and basal cells were lighter in color, mostly hyaline, and the middle three cells were darker in color, mostly brown. The apical cell showed two to three colorless, transparent unbranched accessory filaments, 9.68-30.59 µm in length, (av ± SD = 20.57 ± 4.52 µm, n = 95), whereas the basal cell only a single appendage, 3.52-9.4 µm in length, (av ± SD = 5.32 ± 1.29 µm, n = 34) (Fig. S2I). These morphological characteristics were similar to N. clavispora described by Daengsuwan et al. (2021). Based on phylogenetic analysis and morphological characteristics, isolate 3-3-1, 3-3-2, 3-3-3, and 3-3-4 were identified as N. clavispora. Healthy potted seedlings of E. pungens (63-85 cm in height, 0.7-1.6 cm in diameter) were selected for the pathogenicity test in vivo. The surface-sterilized leaves were wounded with sterilized needles (1 mm in dia.) and inoculated with mycelial plugs and conidial suspensions, respectively. One part of the leaves were inoculated with mycelial plugs (5 mm in dia.) of isolate 3-3-4. The other part of the leaves were inoculated with 10 µL of conidial suspensions (1×106 spores mL-1). The inoculated plants were kept in a growth chamber at ca. 25 ± 2 °C and ca. 90% RH under a 12-h photoperiod. PDA discs without fungi and sterilized dH2O were used as controls, respectively. All experiments were repeated twice, and each treatment had six replicates at least. After 10 and 12 days post-inoculation, the necrotic lesions appeared on the leaves inoculated with the mycelial plugs and conidial suspensions of the isolate 3-3-4, respectively (Fig. S2D and E). However, no lesions were found on the plants inoculated with PDA discs and dH2O (Fig. S2D and E). Fungal isolates were re-isolated from the infected leaves and shared similar morphological characteristics of colonies and conidia with the original one. Thus, Koch's postulates were fulfilled. Neopestalotiopsis clavispora was determined as the pathogens of a variety of plant diseases such as leaf spot on Taxus chinensis, gray blight on Camellia sinensis, and root and crown rot on strawberry (Kirschbaum et al., 2018; Wang et al., 2019a, b). To our knowledge, this is the first report of leaf spot caused by N. clavispora on E. pungens worldwide. The discovery will be helpful for monitoring and control of this disease in the future.

DAD-Net: Classification of Alzheimer's Disease Using ADASYN Oversampling Technique and Optimized Neural Network.

Alzheimer's Disease (AD) is a neurological brain disorder that causes dementia and neurological dysfunction, affecting memory, behavior, and cognition. Deep Learning (DL), a kind of Artificial Intelligence (AI), has paved the way for new AD detection and automation methods. The DL model's prediction accuracy depends on the dataset's size. The DL models lose their accuracy when the dataset has an imbalanced class problem. This study aims to use the deep Convolutional Neural Network (CNN) to develop a reliable and efficient method for identifying Alzheimer's disease using MRI. In this study, we offer a new CNN architecture for diagnosing Alzheimer's disease with a modest number of parameters, making it perfect for training a smaller dataset. This proposed model correctly separates the early stages of Alzheimer's disease and displays class activation patterns on the brain as a heat map. The proposed Detection of Alzheimer's Disease Network (DAD-Net) is developed from scratch to correctly classify the phases of Alzheimer's disease while reducing parameters and computation costs. The Kaggle MRI image dataset has a severe problem with class imbalance. Therefore, we used a synthetic oversampling technique to distribute the image throughout the classes and avoid the problem. Precision, recall, F1-score, Area Under the Curve (AUC), and loss are all used to compare the proposed DAD-Net against DEMENET and CNN Model. For accuracy, AUC, F1-score, precision, and recall, the DAD-Net achieved the following values for evaluation metrics: 99.22%, 99.91%, 99.19%, 99.30%, and 99.14%, respectively. The presented DAD-Net outperforms other state-of-the-art models in all evaluation metrics, according to the simulation results.

A caring leadership model in nursing: A grounded theory approach.

AIM: This study aimed to develop a theoretical model of caring leadership in nursing. BACKGROUND: Nurse leader's role plays an integral part in complex health care institutions. As a common feature of leaders, leaders' caring leadership can positively influence the stakeholders in health care institutions. Still, little is known about caring leadership in nursing, especially in the Chinese cultural background. METHODS: Grounded theory was used to develop the theoretical model of caring leadership. Both semi-structured interviews and open-ended questionnaire surveys were used to collect data for constructing the theory model. Ten nurse leaders and 11 nurse staff were recruited for an interview, and 168 nurse leaders and 286 nurses were recruited for an open-ended questionnaire survey. RESULTS: A theoretical model of caring leadership was developed using five core attributions: benevolent to others, appreciate the uniqueness, facilitate self-actualization, maintain mutual benefit and motivate with charisma. Caring leadership in nurse leaders works through the caring and leading process, resulting in nurses' well-being, patients' healing and organisational excellence. CONCLUSION: A caring leadership model was developed through grounded theory, revealing Chinese nurses' perspectives on caring leadership in Chinese cultural background. According to the model, the concept of caring leadership has been further explained, and it makes contributions to the measurement and leaders' practice in health care institutions. IMPLICATIONS FOR NURSING MANAGEMENT: This caring leadership model developed in our study provides a new perspective and understanding of caring and leadership for nurse leaders. Nurse leaders need to strengthen their responsibilities and personal qualities while caring for nurse staff to improve leadership efficacy based on the theoretical model. And caring leadership can help nurse leaders to balance the interests of stakeholders, leading to positive consequences for nurse staff, patients and health care organisations.

Infrared Spectroscopic Study of Solid Methane: Nuclear Spin Conversion of Stable and Metastable Phases.

Infrared spectroscopy was employed to study thin films of solid methane at low temperatures. We report new measurements of temporal changes of infrared spectra of methane ice in the ν3 and ν4 bands due to nuclear spin conversion upon rapid cooling from 30 to 6.0-11.0 K. The relaxation rates of the nuclear spin were found to be a function of temperature. The activation energy associated with the relaxation has been determined over an extended temperature range. We also found a new metastable phase of methane ice upon deposition at T < 7 K. After the deposition at 6 K and annealed to a higher temperature, a phase transition from the metastable phase to a stable crystalline phase takes place. We found that the relaxation has different activation energies below and above 8.5 K. From a quantitative analysis of the ν3 and ν4 IR bands, we suggest that the metastable phase is a crystalline phase with a degree of orientational disorder between the two known stable solid phases.

Myoglobin Mediates Autophagy of NRK-52E in Rat Renal Tubular Epithelial Cells Via the Pink1/Parkin Signaling Pathway.

BACKGROUND The aim of this study was to investigate whether myoglobin mediates the autophagy of NRK-52E via the Pink1/Parkin signaling pathway. MATERIAL AND METHODS Differentially-expressed genes were selected by PCR chip analysis of the autophagy signaling pathway. RT-PCR and Western blot analyses were used to detect the expressions of Pink1/Parkin and autophagy-related proteins in myoglobin-treated NRK-52E. LC3 double-labeled lentivirus was used to infect NRK-52E for observing autophagy. The role of myoglobin mediates autophagy was evaluated through Pink1-siRNA inhibition of the Pink1/Parkin signaling pathway. RESULTS Myoglobin acted on NRK-52E, caused differential expressions of Pink1, Parkin, and Beclin 1, increased apoptosis, and decreased cell viability. myoglobin increased the levels of Pink1, Beclin 1 and ATG5, decreased the levels of P62 and Parkin. The level of LC3II/LC3I showed significant elevation in NRK-52E cells at after incubated with 100 µmol/L myoglobin. Inhibiting Pink1/Parkin signaling pathway through Pink1-siRNA could alleviate myoglobin induced apoptosis, decrease the levels of Pink, Beclin1, ATG5, LC3II/LC3I, and elevate the levels of Parkin and P62. Moreover, the autophagy spots were reduced after silencing Pink1 in myoglobin-treated NRK-52E. CONCLUSIONS Myoglobin mediates the autophagy of NRK-52E in rat renal tubular epithelial cells via the Pink1/Parkin signaling pathway.

Protective Effects of Total Alkaloids from Menispermum dauricum against Airway Inflammation in Asthmatic Mice.

Menispermum dauricum is widely used to treat respiratory inflammation, including laryngopharyngitis, tonsillitis, tracheitis, and bronchitis. Total alkaloids isolated from M. dauricum have shown a variety of beneficial bioactivities. However, available data on the effects of M. dauricum total alkaloids against allergic asthma has not been reported. In present study, the protective effect of M. dauricum total alkaloids was evaluated by using an ovalbumin-induced in vivo model of asthma. The asthma model was prepared by sensitizing and challenging mice with ovalbumin, and M. dauricum total alkaloids (100, 200, and 400 mg/kg) were administrated to asthmatic mice by gavage. Histopathological analysis of pulmonary changes was detected by hematoxylin and eosin, and periodic acid-schiff staining. Inflammatory cell counts were determined in bronchoalveolar lavage fluid. Total immunoglobulin E and ovalbumin-specific immunoglobulin E levels in serum, and T-helper 2 cytokines and chemokine levels in bronchoalveolar lavage fluid were detected by an ELISA. Histological results demonstrated that M. dauricum total alkaloids significantly attenuated pulmonary inflammation in asthmatic mice. M. dauricum total alkaloid treatment exhibited marked effects on asthmatic mice in reducing inflammatory cell counts, decreasing interleukin-4, interleukin-5, and interleukin-13 concentrations, and downregulating TNF-α and eotaxin levels in bronchoalveolar lavage fluid. In addition, M. dauricum total alkaloids could also inhibit the elevated serum levels of total immunoglobulin E and ovalbumin-specific immunoglobulin E. These findings confirmed that M. dauricum total alkaloids could suppress airway inflammation in ovalbumin-induced asthma through regulating the T-helper 2 response and chemokine level. M. dauricum total alkaloids may be a potential ethnopharmacological agent for asthmatic patients.

Comparative analysis reveals the Genomic Islands in Pasteurella multocida population genetics: on Symbiosis and adaptability.

BACKGROUND: Pasteurella multocida (P. multocida) is a widespread opportunistic pathogen that infects human and various animals. Genomic Islands (GIs) are one of the most important mobile components that quickly help bacteria acquire large fragments of foreign genes. However, the effects of GIs on P. multocida are unknown in the evolution of bacterial populations. RESULTS: Ten avian-sourced P. multocida obtained through high-throughput sequencing together with 104 publicly available P. multocida genomes were used to analyse their population genetics, thus constructed a pan-genome containing 3948 protein-coding genes. Through the pan-genome, the open evolutionary pattern of P. multocida was revealed, and the functional components of 944 core genes, 2439 accessory genes and 565 unique genes were analysed. In addition, a total of 280 GIs were predicted in all strains. Combined with the pan-genome of P. multocida, the GIs accounted for 5.8% of the core genes in the pan-genome, mainly related to functional metabolic activities; the accessory genes accounted for 42.3%, mainly for the enrichment of adaptive genes; and the unique genes accounted for 35.4%, containing some defence mechanism-related genes. CONCLUSIONS: The effects of GIs on the population genetics of P. multocida evolution and adaptation to the environment are reflected by the proportion and function of the pan-genome acquired from GIs, and the large quantities of GI data will aid in additional population genetics studies.