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The prediction of future data using existing data is an effective tool for regional planning and watershed management. The back propagation neural network （BPNN） and convolutional neural network （CNN） were used to construct a prediction model based on the water quality index of Hengyang in Xiangjiang River Basin from April to May 2022 and the results of permanganate index prediction by different models were compared. The prediction results displayed by BPNN could predict the water quality； however, overfitting occurred during the prediction. BPNN modified by particle swarm optimization （PSO） could avoid overfitting, which improved the parameter selection method of the BPNN mode. The CNN model had a better prediction effect, which had a more complex structure and a more scientific fitting method to avoid the model falling into the local extreme value during the fitting process and improve the accuracy of the model prediction results. The evaluation parameters including root-mean-square error （RMSE）, coefficient of determination （ R 2 ）, and mean absolute error （MAE） were used to predict the accuracy of the network. Compared with that of the traditional BPNN model, PSO-BPNN reduced the RESM of the test set from 0.278 2 mg·L -1 to 0.210 9 mg·L -1 , reduced the MAE of the test set from 0.222 3 mg·L -1 to 0.153 7 mg·L -1 and increased the R 2 of the test set from 0.864 0 to 0.921 8, which indicated that PSO-BPNN had more stable fitting ability. RMSE, MAE, and R 2 of the test set in the CNN model were 0.122 0 mg·L -1 , 0.092 7 mg·L -1 , and 0.970 5, respectively, which showed that CNN had a better fitting and prediction effect than that of BPNN.

Chinese cordyceps (GL) is a traditional medicinal fungus, with Ophiocordyceps sinensis ( O. sinensis , BL) and Paecilomyces hepiali ( P. hepiali , JSB) being fungi isolated from wild Chinese cordyceps. These three species share similar chemical composition and pharmacological effects. Existing studies have primarily compared the metabolites of Chinese cordyceps and O. sinensis , overlooking the assessment of antioxidant capacity in Chinese cordyceps, P. hepiali , and O. sinensis . In this study, LC-MS/MS was employed to analyze metabolites in GL, JSB, and BL. Utilizing principal component analysis (PCA), supervised orthogonal partial least squares discriminant analysis (OPLS-DA), and hierarchical cluster analysis (HCA), it was observed that the majority of differential metabolites (DMs) primarily accumulated in organic acids and derivatives, lipids and lipid-like molecules, and organoheterocyclic compounds. Antioxidant activity analysis indicated that GL exhibited the higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability (DPPH•, scavenging rate is 81.87 ± 0.97%), hydroxyl free radical scavenging capacity (•OH, scavenging rate is 98.10 ± 0.60%), and superoxide anion radical scavenging capacity (O 2 •- , scavenging rate is 69.74 ± 4.36%), while JSB demonstrated the higher FRAP total antioxidant capacity of 8.26 μmol Trolox/g ( p < 0.05). Correlation analysis revealed a positive correlation between DMs (fatty acyls and amino acids) and DPPH•, FRAP, •OH, and O 2 •- ( p < 0.05). Additionally, glycerophospholipid DMs were found to be positively correlated with FRAP ( p < 0.05). Through KEGG pathway analysis, it was determined that the accumulation of DMs in pathways such as cutin, suberine and wax biosynthesis has a higher impact on influencing the antioxidant activity of the samples. These results shed light on the antioxidant capacity and metabolic characteristics of Chinese cordyceps and its substitutes and offer valuable insights into how different DMs impact the strength of antioxidant activity, aiding in the advancement and application of Chinese cordyceps and its substitutes.

Sexual reproduction in ascomycetes is controlled by the mating-type (MAT) locus. (Pseudo)homothallic reproduction has been hypothesized on the basis of genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis ). However, the differential occurrence and differential transcription of mating-type genes in the MAT1-1 and MAT1-2 idiomorphs were found in the genome and transcriptome assemblies of H. sinensis , and the introns of the MAT1-2-1 transcript were alternatively spliced with an unspliced intron I that contains stop codons. These findings reveal that O. sinensis reproduction is controlled at the genetic, transcriptional, and coupled transcriptional-translational levels. This study revealed that mutant mating proteins could potentially have various secondary structures. Differential occurrence and transcription of the a-/α-pheromone receptor genes were also found in H. sinensis . The data were inconsistent with self-fertilization under (pseudo)homothallism but suggest the self-sterility of H. sinensis and the requirement of mating partners to achieve O. sinensis sexual outcrossing under heterothallism or hybridization. Although consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis insect-fungi complexes, the mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in N-terminal or middle-truncated proteins with significantly altered overall hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction because of the co-occurrence of multiple genomically independent genotypes of O. sinensis and >90 fungal species in natural C. sinensis .

Background: Due to similar clinical manifestations and imaging signs, differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical practice., Aim: To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD., Methods: We collected contrast-enhanced computed tomography (CECT) and clinical data from 120 patients form center 1. A total of 944 features were extracted single-phase images of CECT scans. Using the last absolute shrinkage and selection operator model, the best predictive radiographic features and clinical indications were screened. Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model. The area under the receiver operating characteristic curve, accuracy, sensitivity and specificity were used for evaluation., Results: A total of five machine learning models were built to distinguish PIL from CD. Based on the results from the test group, most models performed well with a large area under the curve (AUC) (> 0.850) and high accuracy (> 0.900). The combined clinical and radiomics model (AUC = 1.000, accuracy = 1.000) was the best model among all models., Conclusion: Based on machine learning, a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Antrafenine is a drug initially designed for anti-inflammation uses. In this work we have synthesized a library of its structural analogs and tested the anti-influenza activities. These analogs belong to a group of 2-(quinolin-4-yl)amino benzamides or 2-(quinolin-4-yl)amino benzoate derivatives. Best performers were identified, namely 12, 34, 41, with IC 50 against A/WSN/33 (H1N1) of 5.53, 3.21 and 6.73 μM respectively. These chemicals were also effective against A/PR/8/34 (H1N1), A/HK/1/68 (H3N2) and B/Florida/04/2006 viruses. Time-of-addition study and minigenome luciferase reporter assay both supported that the compounds act on the ribonucleoprotein (RNP) components. Using 34 and 41 as representative compounds, we determined by microscale thermophoresis that this group of compounds bind to both PA C-terminal domain and the nucleoprotein (NP) which is the most abundant subunit of the RNP. Taken together, we have identified a new class of anti-influenza compounds with dual molecular targets and good potential to be further developed. IMPORTANCE: The influenza viruses, especially influenza A and B subtypes, cause many deaths each year. The high mutation rate of the virus renders available therapeutics less effective with time. In this work we identify a new class of compounds, structurally similar to the anti-inflammation drug antrafenine, with good potency against influenza A strains. The IC 50 of the best performers are within low micromolar range and thus have good potential for further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Optical limiters are greatly needed to protect eyes and sensitive optoelectronic devices such as photodetectors and sensors from laser damage, but they are currently plagued by low efficiency. In this work, we utilized Cu 3 VSe 4 nanocrystals (NCs) to enhance laser protection performance, and they exhibit higher saturation intensity and broader nonlinear spectral response extending into the near IR region than the C60 benchmark. A flexible optical limiter goggle prototype based on the NCs significantly attenuated the incident laser beam, with Z scan and I scan measurements demonstrating a giant nonlinear absorption coefficient β value of 1.0 × 10 -7 m W -1 , a large optical damage threshold of 3.5 J cm -2 , and a small starting threshold of 0.22 J cm -2 . Transient absorption spectroscopy disclosed that the origin of the excellent nonlinearity was associated with quasi-static dielectric resonance behavior and a large TPA cross-section of 3.3 × 10 6 GM was measured for Cu 3 VSe 4 NCs, suggesting the potential of intermediate bandgap (IB) semiconductors as alternatives to plasmonic noble metals for ultrafast photonics. Hence, optical limiters based on such semiconductors offer new avenues for laser protection in optoelectronic and defense fields.

Background: The anatomy of the right posterior portal vein (RPPV) plays an important role in planning hepatic resection, living transplantation and interventional radiological procedures, yet the incidence of variations of RPPV without a common trunk in Chinese persons is still unclear. Therefore, we conducted this study and discussed its clinical implications., Methods: A retrospective analysis of multidetector computed tomography (MDCT) scans was performed in 1,933 patients with various abdominal pathologies between September 28, 2018 through May 23, 2019. After excluding 930 patients, a total of 1,003 patients were included in this study. Variations of the RPPV without a common trunk were classified according to classification standards., Results: A total of 1,003 patients were included. RPPV without a common trunk was found in 216 (21.54%, 216/1,003) patients. Among them, we identified three variations of the origin from the right portal vein (RPV): first separate origin of P6, P7, or simultaneous separate origin of P6 and P7, and the incidences of these three variations were 1.50% (15/1,003), 6.58% (66/1,003) and 13.46% (135/1,003), respectively. Among 1,003 patients included in this study, 787 patients (78.46%, 787/1,003) showed that RPPV normally divided into P6 and P7 branches., Conclusions: Variations of the RPPV without a common trunk were not rare in Chinese population. Knowledge of this anatomic variation of the RPPV is extremely important for hepatic and transplant surgeons and interventional radiologists., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4837/coif). JSH reports funding from the National Key R&D Program of China (No. 2019YFE0190500). XLL reports funding from the Key Research and Development Program of Hunan Province, China (No. 2018SK2090). The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Ethnopharmacological Relevance: Danhong injection (DHI), which is a Chinese clinical prescription consists of Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese)(Plant names have been checked with http://www.theplantlist.org on March 1st, 2022), has been mainly used in the clinical therapy of cardiovascular diseases, including hypertension in China for many years., Aim of the Study: Cardiovascular diseases (CVDs) are the major causes of death all around the world. Due to the various stimulation, a series of vasoconstrictor substances are secreted to regulate the vasoconstriction function and then change blood pressure. The representative substances leading to abnormal vasoconstriction include renin-angiotensin system, endothelin, vasopressin and adrenaline, which act on the corresponding receptors on vascular smooth muscle to constrict blood vessels. Finally, blood pressure increases, followed by a series of cardiovascular diseases, including hypertension. However, little is known about Danhong injection's specific vasodilating mechanisms and active substances. The aims of the study were to determine the vasodilating substances of Danhong injection and explain its molecular mechanism of vasodilation., Materials and Methods: The effects of DHI and its active components on vascular tension were measured by myograph system in the aortic or mesenteric rings of mice. Based on this, the pharmacodynamic substances were analyzed and effective molecules were found. Combined with multiple types of vascular myograph experiments and network pharmacological analysis, the molecular pathway was preliminarily determined. With molecular biology experiments, it was verified that the relevant mechanisms were closely related to calcium-mediated vasoconstriction in smooth muscle cells., Results: DHI could relax endothelium-removed aortic rings pre-constricted with PE and 3 possible active vasodilator substances, including salvianolic acid A, salvianolic acid B and danshensu, were screened out by network pharmacology and vascular myograph experiments, among which the effects of salvianolic acid A were dominant. Meanwhile, salvianolic acid A could dilate mesenteric artery in a pressure-dependent manner. Interestingly, salvianolic acid A could still relax the vascular rings under the stimulation of KCl and Bayk8644, two agonists of L-type calcium channel. By contrast, inhibitors of Kir, Kv, Katp and BKCa channels did not block the effect of salvianolic acid A on vasodilation. Salvianolic acid A alleviated Ca 2+ transient, referring to changes of intracellular calcium, induced by PE, Bayk8644 and high K + in the VSMCs. Salvianolic acid A could partially restore the vasodilation function of vascular smooth muscle damaged by AngII and ET-1 induced hypertension situation., Conclusions: Our results indicate that salvianolic acid A is the major vasodilator substance in DHI and the vasorelaxation pharmacology mechanism involved in inhibiting the L-type calcium channel signaling in smooth muscle cell. Hence, there are potential therapeutic effects of taking salvianolic acid A preparation which may be beneficial to protect cardiovascular system and reduce blood pressure., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Efficient cathode interfacial layers (CILs) are becoming essential elements for organic solar cells (OSCs). However, the absorption of commonly used cathode interfacial materials (CIMs) is either too weak or overlaps too much with that of photoactive materials, hindering their contribution to the light absorption. In this work, we demonstrate the construction of highly efficient CIMs based on 2,7-di-tert-butyl-4,5,9,10-pyrene diimide (t-PyDI) framework. By introducing amino, amino N-oxide and quaternary ammonium bromide as functional groups, three novel self-doped CIMs named t-PyDIN, t-PyDINO and t-PyDINBr are synthesized. These CIMs are capable of boosting the device performances by broadening the absorption, forming ohmic contact at the interface of active layer and electrode, as well as facilitating electron collection. Notably, the device based on t-PyDIN achieved a power conversion efficiency of 18.25 %, which is among the top efficiencies reported to date in binary OSCs., (© 2022 Wiley-VCH GmbH.)

Aquilaria sinensis is an important non-timber tree species for producing high-value agarwood, which is widely used as a traditional medicine and incense. Agarwood is the product of Aquilaria trees in response to injury and fungal infection. The APETALA2/ethylene responsive factor ( AP2/ERF ) transcription factors (TFs) play important roles in plant stress responses and metabolite biosynthesis. In this study, 119 AsAP2/ERF genes were identified from the A. sinensis genome and divided into ERF, AP2, RAV, and Soloist subfamilies. Their conserved motif, gene structure, chromosomal localization, and subcellular localization were characterized. A stress/defense-related ERF-associated amphiphilic repression (EAR) motif and an EDLL motif were identified. Moreover, 11 genes that were highly expressed in the agarwood layer in response to whole-tree agarwood induction technique (Agar-Wit) treatment were chosen, and their expression levels in response to methyl jasmonate (MeJA), salicylic acid (SA), or salt treatment were further analyzed using the quantitative real time PCR (qRT-PCR). Among the 11 genes, eight belonged to subgroup B-3. All 11 genes were significantly upregulated under salt treatment, while eight genes were significantly induced by both MeJA and SA. In addition, the gene clusters containing these upregulated genes on chromosomes were observed. The results obtained from this research not only provide useful information for understanding the functions of AP2/ERF genes in A. sinensis but also identify candidate genes and gene clusters to dissect their regulatory roles in agarwood formation for future research.

Peaking carbon emissions and achieving carbon neutrality have become the consensus goal of the international community to solve the environmental problems threatening mankind caused by accumulative greenhouse gases like CO 2 . Herein we proposed vacancy engineering of two-dimensional (2D) topological W 2 N 3 for efficient CO 2 hydrogenation into high value-added chemicals and fuels. Spherical aberration corrected scanning transmission electron microscopy (Cs-corrected STEM) confirmed a large amount of N vacancies on the catalyst surface, which significantly reduced the energy barrier for the formation of the essential intermediates of *CO and *CHO as revealed by density functional theory (DFT) calculations. Consequently, the highly stable catalyst exhibited efficient CO 2 hydrogenation superior to many previous reports with a maximum CO 2 conversion rate of 24% and a high selectivity of 23% for C 2+ hydrocarbons. This work provided not only insight into the vacancy-controlled CO 2 hydrogenation mechanism, but also fresh ammunition to bring the remaining potential of 2D topological transition metal nitrides in the field of catalysis.

Cerebral ischemic stroke ranks the second leading cause of death and the third leading cause of disability in lifetime all around the world, urgently necessitating effective therapeutic interventions. Reactive oxygen species (ROS) have been implicated in stroke pathogenesis and peroxisome proliferator-activated receptors (PPARs) are prominent targets for ROS management. Although recent research has shown antioxidant effect of berberine (BBR), little is known regarding its effect upon ROS-PPARs signaling in stroke. The aim of this study is to explore whether BBR could target on ROS-PPARs pathway to ameliorate middle cerebral artery occlusion (MCAO)-induced stroke. Herein, we report that BBR is able to scavenge ROS in oxidation-damaged C17.2 neural stem cells and stroked mice. PPARδ, rather than PPARα or PPARγ, is involved in the anti-ROS effect of BBR, as evidenced by the siRNA transfection and specific antagonist treatment data. Further, we have found BBR could upregulate NF-E2 related factor-1/2 (NRF1/2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) following a PPARδ-dependent manner. Mechanistic study has revealed that BBR acts as a potent ligand (Kd = 290 ± 92 nM) to activate PPARδ and initiates the transcriptional regulation functions, thus promoting the expression of PPARδ, NRF1, NRF2 and NQO1. Collectively, our results indicate that BBR confers neuroprotective effects by activating PPARδ to scavenge ROS, providing a novel mechanistic insight for the antioxidant action of BBR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Photocathodic biosensor has great capability in anti-interference from reductive substances, however, the low signal intensity of photoactive species with inferior detection sensitivity restricts its wide application. In this work, the P3HT-PbS nanocomposites were synthesized as signal tags, by integrating with target-trigger generated hemin/G-quadruplex nanotail as bi-enhancer to significantly apmplify the photocurrent, an ultrasensitive photocathodic biosensor was proposed for detection of β2-microglobulin (β2-MG). Impressively, P3HT with cathode signal is an attractive polymer consisted of substantial thiophene groups with high absorption coefficient and mobility of photo-generated holes, which could anchor with the PbS dots as sensitizer, providing a high charge mobility and strong photosensitivity. More importantly, target-trigger generated hemin/G-quadruplexes could accept the electron from illuminated photoactive species through the conversion of Fe(III)/Fe(II) in hemin, effectively reducing charge recombination rate as well as accelerating the generation of electron acceptor O 2 in the assistant of H 2 O 2 . Moreover, hemin/G-quadruplexes inherited the HRP mimicking catalytic capability that further improved the produce of plentiful O 2 . As a result, PEC cathode signal was significantly enhanced for sensitive analysis of β2-MG protein with a good detection range of 0.1 pg/mL to 100 ng/mL. It would provide a path for establishing PEC platform with excellent anti-interference ability and extend the application of photoelectrochemical (PEC) biosensor in bioanalysis and early disease diagnosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Two novel nitrogen-doped, hexa-peri-hexabenzocoronene (HBC)-based nanographenes (NGs) 1 and 2 bearing an azepine and an azocine at the fjord region, respectively, were synthesized and characterized. Notably, structure 1 was synthesized by Diels-Alder reaction of cyclic alkene and tetrachlorothiophene-S,S-dioxide, followed by Suzuki-Miyaura cross-coupling and Scholl-type reactions, which represents a modified strategy to construct NGs. The azo-heptagon-embedded NG 1 leads to a saddle shape, and the azo-octagon-embedded NG 2 exhibits a distorted saddle-helix conformation with the largest torsion angle recorded so far in [5]helicenes. As a result, the different structural topographies for NGs 1 and 2 lead to significant changes in the optical properties including UV absorption and fluorescent emission. Additionally, the 8π-heterocycles azepine and azocine in the NGs 1 and 2 exhibited obvious antiaromatic properties., (© 2021 Wiley-VCH GmbH.)

Ribosome-inactivating proteins (RIPs) hydrolyze the N-glycosidic bond and depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. In this study, we have purified and characterized lyophyllin, an unconventional RIP from Lyophyllum shimeji , an edible mushroom. The protein resembles peptidase M35 domain of peptidyl-Lys metalloendopeptidases. Nevertheless, protein either from the mushroom or in recombinant form possessed N-glycosidase and protein synthesis inhibitory activities. A homology model of lyophyllin was constructed. It was found that the zinc binding pocket of this protein resembles the catalytic cleft of a classical RIP, with key amino acids that interact with the adenine substrate in the appropriate positions. Mutational studies showed that E122 may play a role in stabilizing the positively charged oxocarbenium ion and H121 for protonating N-3 of adenine. The tyrosine residues Y137 and Y104 may be used for stacking the target adenine ring. This work first shows a protein in the peptidase M35 superfamily based on conserved domain search possessing N-glycosidase activity.

Low dimensional tellurium is currently of great interest for potential electronic applications due to the experimentally observed Weyl fermions and the excellent carrier mobility, on/off ratios and current-carrying capacity in devices. However, the optical properties of Te nanostructures are not well explored, especially in the field of nonlinear optics. Here, we prepared a series of Te nanostructures by electrochemical exfoliation and liquid phase exfoliation methods, including one-dimensional (1D) Te nanowires (NWs), quasi-1D Te nanorods (NRs), zero-dimensional (0D) Te nanodots (NDs) and two-dimensional (2D) Te nanosheets (NSs). Femtosecond Z-scan measurements reveal unique dimension-dependent nonlinear optical (NLO) properties. 1D Te NWs and quasi-1D Te NRs exhibited higher saturable absorption behavior than 0D Te nanostructures, while the 2D Te NSs are a high performance optical limiting material. Ultrafast transient absorption spectroscopy revealed the dimension-dependent exciton dynamics. The reverse saturable absorption of 2D Te NSs is derived from faster exciton relaxation and stronger excited state absorption. This work paves the way for the design of saturable absorbers with high performance and broadens the application of 2D Te in the field of laser protection and other novel ultrafast photonics.

The rats were exposed to chronic unpredictable mild stress(CUMS) and kept in separate cages for inducing depressive disorder, which was judged by behavioral indicators. The number and morphology of neurons in hippocampal CA3 area and prefrontal cortex were observed by hematoxylin-eosin(HE) staining. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), norepinephrine(NE), glutamic acid(GLU), interleukin-1β(IL-1β), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(RT-PCR) and Western blot were conducted to determine the mRNA and protein expression levels of related molecules in NLRP3 pathway. The results showed that compared with the model group, acidic polysaccharides from Poria at the low-, medium-, and high-doses(0.1, 0.3 and 0.5 g·kg~(-1)·d~(-1)) all improved the depression-like behavior of rats, increased the number of neurons and the levels of BDNF, 5-HT, 5-HIAA, DA, and NE in the hippocampus, and reduced GLU and serum IL-1β, IL-18, and TNF-α levels. The mRNA expression levels of ASC, caspase-1, IL-1β, and IL-18 and the protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in each medication group were down-regulated, whereas the protein expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18 were up-regulated. All these have indicated that acidic polysaccharides from Poria exerted the antidepressant effect possibly by regulating neurotransmitters and NLRP3 inflammasome signaling pathway.

The mechanism of the deactivation and regeneration of PtSn intermetallic compound nanoparticle (iNP) catalysts was studied by in situ TEM investigation. Our study reveals the reversible dynamic structural transition of the iNPs during deactivation and regeneration, which provides a direct correlation between the atomic structure and the catalytic activity of the iNPs.

Background: Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war, during which patients are exposed to prolonged periods of hypobaric hypoxia; however, the effects of such exposure on burn injuries, particularly on burn-induced lung injuries, are largely unexplored. This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model., Methods: A total of 40 male Wistar rats were randomly divided into four groups (10 in each group): sham burn (SB) group, burn in normoxia condition (BN) group, burn in hypoxia condition (BH) group, and burn in hypoxia condition with treatment intervention (BHD) group. Rats with 30% total body surface area burns were exposed to hypobaric hypoxia (2000 m altitude simulation) or normoxia conditions for 4 h. Deoxyribonuclease I (DNase I) was administered systemically as a treatment intervention. Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid (mtDNA) levels were determined. A histopathological evaluation was performed and the acute lung injury (ALI) score was determined. Malonaldehyde (MDA) content, myeloperoxidase (MPO) activity, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome level were determined in lung tissues. Data among groups were compared using analysis of variance followed by Tukey's test post hoc analysis., Results: Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release, which was further heightened by hypobaric hypoxia exposure (P < 0.01). Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, MDA content, and MPO activity in the lung (P < 0.05 or P < 0.01). Burn-induced lung injuries were exacerbated, as shown by the histopathological evaluation and ALI score (P < 0.01). Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production. Furthermore, the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated (P < 0.01)., Conclusions: Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury. DNase I reduced the release of mtDNA, limited mtDNA-induced systemic inflammation, and ameliorated burn-induced ALI. The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.

We discovered that the survival and growth of many primary acute myeloid leukemia (AML) samples and cell lines, but not normal CD34+ cells, are dependent on SIRT5, a lysine deacylase implicated in regulating multiple metabolic pathways. Dependence on SIRT5 is genotype-agnostic and extends to RAS- and p53-mutated AML. Results were comparable between SIRT5 knockdown and SIRT5 inhibition using NRD167, a potent and selective SIRT5 inhibitor. Apoptosis induced by SIRT5 disruption is preceded by reductions in oxidative phosphorylation and glutamine utilization, and an increase in mitochondrial superoxide that is attenuated by ectopic superoxide dismutase 2. These data indicate that SIRT5 controls and coordinates several key metabolic pathways in AML and implicate SIRT5 as a vulnerability in AML., Competing Interests: COMPETING INTERESTS STATEMENT Michael W. Deininger reports research funding and paid advisory board membership for the following companies: Blueprint, Pfizer, Novartis, Takeda, Incyte, Fusion Pharma, Medscape and Ascentage Pharma. None of these relationships pose any conflict of interest with the present manuscript. The other authors report no competing interests.

Background: Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections., Case Presentation: We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole., Conclusion: To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.

Betulin (BT) has been identified to exhibit potential benefits for treating hepatocellular carcinoma (HCC). The results of the present study demonstrated that a new semisynthetic derivative of BT, 3,28-di-(2-nitroxy-acetyl)-oxy-BT, may effectively decrease the viability of Huh7 cells. Mechanistic studies revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT inhibited the transition between G 2 and M phase of the cell cycle by regulating cell cycle regulatory proteins. Additional study revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may trigger Huh7 cells to undergo caspase-dependent apoptosis as an increased proportion of cells were identified in the sub-G 1 phase, which may be a result of poly(ADP-ribose) polymerase cleavage and caspase activation. Furthermore, 3,28-di-(2-nitroxy-acetyl)-oxy-BT-induced apoptosis was mitochondrion-mediated. The results of the present study demonstrated that Bcl-2-associated X protein translocated to the mitochondria from the cytosol following 3,28-di-(2-nitroxy-acetyl)-oxy-BT treatment. Notably, the phosphoinositide 3-kinase/protein kinase B signaling pathway was involved in 3,28-di-(2-nitroxy-acetyl)-oxy-BT-treated Huh7 cells. Therefore, the results of the present study demonstrated that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may inhibit HCC, which may be a possible application to treat HCC.

Background: Isolated distal deep venous thrombosis (IDDVT) is a common complication after ischemic stroke. However, there is a paucity of evidence regarding the clinical features and risk factors of IDDVT in patients with acute ischemic stroke. This study aimed to establish and validate a clinical prediction scale of IDDVT at an early stage of ischemic stroke development., Methods: We retrospectively studied consecutive patients with stroke admitted to our neurology department between January and December 2016. Selected clinical variables were assessed by multivariable logistic regression to determine the independent risk factors for IDDVT. A prediction scale was developed and verified by the receiver operating characteristic curve., Results: A total of 671 patients with ischemic stroke were included in the study, with 450 patients allocated into the derivation group and 221 patients into the validation group. A substantial proportion (22.1%) of patients developed IDDVT. A 16-point prediction scale (female gender = 2, older age [≥60 years] = 3, atrial fibrillation = 2, acute infection = 2, active cancer = 5, and higher [≥2.6 mmol/L] level of low-density lipoprotein = 2) derived from a multivariable logistic regression model was highly predictive of 10-day risk of IDDVT in both the validation group (c statistic = .70, 95% confidence interval [CI], .63-0.78, P < .0001) and the derivation group (c statistic = .68, 95% CI, .63-0.74, P < .0001)., Conclusions: This prediction scale may help to identify patients with ischemic stroke who are at a higher risk of developing IDDVT., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Autophagy is a highly conserved cellular self-digestion pathway, by which intracellular damaged proteins or organelles are delivered to lysosomes for degradation, so as to protect from various dangerous stimuli and maintain cellular homeostasis. Inflammation is a defensive response to injury or pathogens, through which various inflammatory mediators coordinate host defense and repair. However, uncontrolled inflammatory responses can lead to secondary damage and pathogenesis of inflammatory disease. Recent studies indicate that autophagy pathway and related proteins may play important roles in regulating immune response and controlling excessive inflammation. This review introduced research progress in the role of autophagy in regulating excessive inflammation and possible mechanisms.

Stroke is caused by vascular dysfunction and currently there are no effective therapeutics to stroke induced brain damage. In contrast to an intense emphasis on neuroprotection, relatively few studies have addressed means of vascular protection in cerebral ischemia. Here we discovered that the ligand to immidazolin receptor, 2-BFI, not only provided potent neuroprotection during middle cerebral artery occlusion in rat, which confirmed our previous reports, but also protected the integrity of the cerebral vasculature. Treatment with 2-BFI twice daily after the occlusion of the middle cerebral artery for 14 d significantly improved the neurological deficits, reduced brain infarction, and importantly, protected the cerebral vasculature as evidenced by the increased expression of an endothelial marker, von Willebrand factor, and better preservation of the cerebral vasculature, as viewed under a confocal microscope on rat brain perfused with FITC-labeled dextran. These results indicated that 2-BFI contributes to protection of neurovasculature. Understanding the molecular mechanisms could eventually lead to development of more effective therapies for stroke., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to determine whether 2-(2-benzofuranyl)-2-imidazoline, an imidazoline I(2) receptor ligand, could protect against cell death from brain injury and improve the functional outcome after focal cerebral ischemia in rats., Methods: Transient focal ischemia was induced by suture occlusion of the middle cerebral artery. Rats were intraperitoneally treated with a vehicle, 2-(2-benzofuranyl)-2-imidazoline or idazoxan immediately after focal ischemia. Infarct volume was assessed by 2,3,5-triphenyltrazolium chloride staining and neurobehavioral deficits were monitored. The volume of cell death in the penumbra after ischemia was determined by immunostaining using anti-cleaved caspase-3 antibody and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL)., Results: Both 2-(2-benzofuranyl)-2-imidazoline and idazoxan significantly improved the neurological score compared with the vehicle at 24 hours after focal ischemia. Treatment with 2-(2-benzofuranyl)-2-imidazoline or idazoxan also significantly reduced infarct volume and the number of both caspase-3- and TUNEL-positive cells in the penumbra compared with vehicle-treated rats (p<0.01 and p<0.05, respectively)., Conclusion: The results suggest the neuroprotective role of 2-(2-benzofuranyl)-2-imidazoline and idazoxan in focal cerebral ischemia, and may therefore represent useful targets for developing new treatments for stroke.

Adult neuronal stem cells (NSCs) hold great promise for brain repair because of their unique location within the central nervous system, their potential to proliferate and to differentiate into all major neural lineages, and their ability to functionally incorporate into existing neuronal circuitry after stroke. Nevertheless, the ability to exploit these cells for therapeutic purposes is hampered by the lack of knowledge about the signals that control the generation of a functional neuron from adult NSCs after stroke, particularly in the aged brain. Therefore, to further define the regulatory mechanisms that underlie neurogenesis after stroke, it is critically important to develop future NSC-based repair strategies. Notch signaling defines a fundamental pathway controlling cell fate acquisition. Studies have shown that Notch signaling pathways play critical roles during the maintenance, proliferation, and differentiation of NSCs in the developing brain. Recent evidence shows that Notch1 signaling is conserved in the regulation of adult neurogenesis. Here we summarize current knowledge about the role of Notch signaling in the regulation of neurogenesis in the normal and stroke brain.