Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P  < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P <  0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P  < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).

Glycoside hydrolases in the biodegradation of lignocellulosic biomass.

Lignocellulose is a plentiful and intricate biomass substance made up of cellulose, hemicellulose, and lignin. Cellulose and hemicellulose are polysaccharides characterized by different compositions and degrees of polymerization. As renewable resources, their applications are eco-friendly and can help reduce reliance on petrochemical resources. This review aims to illustrate cellulose, hemicellulose, and their structures and hydrolytic enzymes. To obtain desirable enzyme sources for the high hydrolysis of lignocellulose, highly stable, efficient and thermophilic enzyme sources, and new technologies, such as rational design and machine learning, have been introduced in detail. Generally, the efficient biodegradation of abundant natural biomass into fermentable sugars or other intermediates has great potential in practical applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03819-1.

Intuitionistic fuzzy-based entropy weight method-TOPSIS for multi-attribute group decision-making in drilling fluid waste treatment technology selection.

Drilling fluid waste is produced by oil and gas industry operations and can potentially cause serious environmental pollution and energy consumption if not properly treated. Currently, there are several treatment methods available for drilling fluid waste such as bioremediation, thermal treatment, solidification/stabilization treatment, electrochemical remediation, physiochemical treatment, and supercritical fluid treatment. However, selecting an adequate method to treat drilling fluid waste is a critical consideration. The objective of this work is to analyze the problem of drilling fluid waste pollution and treatment methods, establish a drilling fluid waste treatment decision index system that takes into account various factors, and apply the intuitionistic fuzzy-based entropy weight method (EWM)-technique for order of preference by similarity to ideal solution (TOPSIS) method to make a multi-attribute group decision on drilling fluid waste treatment methods. The method is then applied to the WBQ004-1-H1 drilling project as an example for comprehensive analysis. The final decision results show that A3 (0.566) > A1 (0.537) > A6 (0.526) > A5 (0.485) > A4 (0.478) > A2 (0.447), so the solidification/stabilization treatment is the most suitable method for this project, providing new insights into selecting drilling fluid waste treatment methods in actual projects.

[M8L4]8+-Type Squares Self-Assembled by Dipalladium Corners and Bridging Aromatic Dipyrazole Ligands for Iodine Capture.

Square-like metallamacrocyclic palladium(II) complexes [M8L4]8+ (1-7) were synthesized by reacting aromatic dipyrazole ligands (H2L1-H2L3 with pyromellitic arylimide-, 1,4,5,8-naphthalenetetracarboxylic arylimide-, and anthracene-based aromatic groups, respectively) with dipalladium corners ([(bpy)2Pd2(NO3)2](NO3)2, [(dmbpy)2Pd2(NO3)2](NO3)2, or [(phen)2Pd2(NO3)2](NO3)2, where bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine, and phen = 1,10-phenanthroline) in aqueous solutions via metal-directed self-assembly. Metallamacrocycles 1-7 were fully characterized by 1H and 13C nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry, and the square structure of 7·8NO3- was further confirmed via single crystal X-ray diffraction. These square-like metallamacrocycles exhibit effective performance for iodine adsorption.

The effect of regulating MCU expression on experimental ischemic brain injury.

Mitochondrial calcium uniporter (MCU) is a critical channel for Ca2+ influx into mitochondria. The present study aimed to determine if MCU knockdown has beneficial effects on ischemic brain injury and to explore the underlying mechanisms. The present study demonstrated that MCU knockdown but not total knockout (KO) attenuated ischemia infarction volume and primary cortical neuronal cells' ischemic damage. MCU knockdown maintained mitochondrial ultrastructure, alleviated calcium overload, and reduced mitochondrial apoptosis. Moreover, MCU knockdown regulated the changes of MICU1 and MICU2 after cerebral infarction, while no changes were observed in other mitochondrial calcium handling proteins. Based on metabolomics, MCU knockdown reversed middle cerebral artery occlusion (MCAO)-induced up-regulated phosphoenolpyruvate and down-regulated GDP to protect energy metabolism after cerebral infarction. Furthermore, a total of 87 and 245 differentially expressed genes (DEGs) were detected by transcriptome sequencing among WT mice, MCU KO mice and MCU knockdown mice in the MCAO model, respectively. Then, NR4A1 was identified as one of the DEGs in different MCU expressions in vivo ischemia stroke model via transcriptomic screening and genetic validation. Furthermore, MCU knockdown downregulated the ischemia-induced upregulation of NR4A1 expression. Together, this is the further evidence that the MCU knockdown exerts a protective role after cerebral infarction by promoting calcium homeostasis, inhibiting mitochondrial apoptosis and protecting energy metabolism.

Receptor-Interacting Protein 3/Calmodulin-Dependent Kinase II/Proline-Rich Tyrosine Kinase 2 Pathway is Involved in Programmed Cell Death in a Mouse Model of Brain Ischaemic Stroke.

Neuronal necroptosis and apoptosis are the most important pathways for programmed cell death after brain ischaemic stroke. Although apoptosis signalling pathways have been extensively studied, molecular mechanisms underlying necroptosis remain unclear. In this study, we found that receptor-interacting protein 3 (RIP3) deficiency reduced cerebral infarction volume, neurological deficits, and neuronal ultrastructural damage in a mouse model of brain ischaemic stroke by inhibiting programmed cell death. RIP3 deficiency inhibited the activation of both calmodulin-dependent kinase II (CaMKII) and proline-rich tyrosine kinase 2 (Pyk2) cascade, decreased the expression of classic necroptotic and apoptotic proteins, and ultimately decreased neuronal necroptosis and apoptosis. We further confirmed that RIP3 deficiency inhibited the decrease of mitochondrial membrane potential, the increase of calcium influx and reactive oxygen species (ROS) production. In addition, compared with WT primary cortical neurons, the decreased expression of CaMKII and Pyk2 was further verified in a Ripk3-/- primary cortical neurons underlying oxygen and glucose deprivation/reoxygenation (OGD/R) model. In conclusion, we first identified that the RIP3/CaMKII/Pyk2 pathway is involved in programmed cell death after brain ischaemic stroke, which suggests it is a promising therapeutic target in ischaemia-induced neuronal injury.

Effect of intracranial venous collaterals on neurological outcomes in cerebral venous thrombosis.

This study identifies predictors of favourable intracranial venous collaterals and the effect of intracranial venous collaterals on outcomes and recanalization in patients with cerebral venous thrombosis (CVT). Data of 61 patients with CVT were retrospectively reviewed. Venous collateralization was defined as expanded cortical vein formation through different drainage pathways. Recanalization grades were classified into complete or partial recanalization based on images obtained during hospitalisation and follow-up. Independent predictors of collateral formation and poor prognosis were investigated via univariate and binary logistic regression analyses. The effects of different intracranial venous collaterals on recanalization in patients with CVT were assessed. A risk prediction nomogram for prognosis was constructed. Age ≤ 35 years (odds ratio (OR) = 7.067; 95% confidence interval (CI) = 1.776-28.277; P = 0.006) and male sex (OR = 5.490; 95% CI = 1.205-25.004; P = 0.028) were independent predictors of favourable venous collaterals. Venous collaterals were associated with early recanalization (P = 0.017) and not with long-term recanalization (P = 0.252). Male sex (OR = 0.047; 95% CI = 0.003-0.651; P = 0.023), subacute onset (OR = 0.026; 95% CI = 0.002-0.367; P = 0.007), and good collateral grade (OR = 0.168; 95% CI = 0.029-0.985; P = 0.048) were independent factors of favourable neurological outcomes at discharge. Haemorrhage on computed tomography at admission (OR = 10.868; 95% CI = 2.082-56.733; P = 0.005) was inversely correlated with prognosis. These findings suggested that male patients under 35 years of age are more likely to have favourable venous collaterals and good outcomes. Venous collaterals are significantly associated with early recanalization. These findings highlight the importance of venous collateral evaluation in patients with CVT.

Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression.

BACKGROUND: Transcriptomics, such as that of non-coding RNA (ncRNA), which include microRNA (miRNA), circular RNA, and the transfer RNA (tRNA)-derived fragments (tiRNA and tRF) in Alzheimer's disease (AD) have attracted much attention recently. The tiRNA and tRFs are produced when the tRNA splits at specific sites. The expression change and related function of tiRNA and tRFs in AD has not been fully investigated. METHODS: In our study, APP/PS1 transgenic mice (AD mice model) and healthy control mice were used to discover the differentially expressed tiRNA and tRFs with high-throughput sequencing. Among the differentially expressed tiRNA and tRFs, we chose two tRFs (tRF-Thr-CGT-003 and tRF-Leu-CAA-004) and predicted the target messenger RNAs (mRNAs) with miRanda and Target Scan. The target mRNAs of tRF-related function and pathways were analyzed, then we performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot to validate the related target mRNAs and pathways. RESULTS: A total of 27 significantly different tiRNA and tRFs were detected between wild type (WT) and APP/PS1 groups, including 14 up-regulated and 13 down-regulated. Through analyzing the target mRNAs of all differentially expressed tiRNA and tRFs with GO enrichment, we found the target mRNAs could take part in the learning and memory biological process, synapse organization, cognition biological process, synaptic transmission, amyloid-ß (Aß) metabolic process, and so on. We then chose three differentially expressed tRFs for further qPCR validation and passed two tRFs: tRF-Thr-CGT-003 and tRF-Leu-CAA-004, that were found to regulate the calcium regulation-related proteins (the voltage-gated calcium channel γ2 subunit and the RYR1 endoplasmic reticulum calcium released protein) and the retinol metabolism-related proteins (retinoic acid metabolic enzymes CYP2S1, CYP2C68, CYP2S1). CONCLUSIONS: The APP expression and presenilin mutation in APP/PS1 mice could cause tiRNA and tRFs expression change. Among the differentially expressed tiRNA and tRFs, we found some tRFs took part in the voltage-gated calcium channel γ2 subunit expression and regulation, influencing the neuron calcium homeostasis. Moreover, we also found the tRFs may participate in the regulation of retinol metabolism. Our findings suggest that the dysregulated tiRNA and tRFs may be beneficially exploited as potential diagnostic biomarkers and/or therapeutic targets of AD.

Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis.

Objective: Multiple mechanisms including vascular endothelial cell damage have a critical role in the formation and development of atherosclerosis (AS), but the specific molecular mechanisms are not exactly clarified. This study aims to determine the possible roles of proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway in AS mouse model and H2O2-induced endothelial cell damage model and explore its possible mechanisms. Approach and Results: The AS mouse model was established using apolipoprotein E-knockout (ApoE-/-) mice that were fed with a high-fat diet. It was very interesting to find that Pyk2/MCU expression was significantly increased in the artery wall of atherosclerotic mice and human umbilical vein endothelial cells (HUVECs) attacked by hydrogen peroxide (H2O2). In addition, down-regulation of Pyk2 by short hairpin RNA (shRNA) protected HUVECs from H2O2 insult. Furthermore, treatment with rosuvastatin on AS mouse model and H2O2-induced HUVEC injury model showed a protective effect against AS by inhibiting the Pyk2/MCU pathway, which maintained calcium balance, prevented the mitochondrial damage and reactive oxygen species production, and eventually inhibited cell apoptosis. Conclusion: Our results provide important insight into the initiation of the Pyk2/MCU pathway involved in AS-related endothelial cell damage, which may be a new promising target for atherosclerosis intervention.

Rapid qualitative profiling and quantitative analysis of phenolics in Ribes meyeri leaves and their antioxidant and antidiabetic activities by HPLC-QTOF-MS/MS and UHPLC-MS/MS.

Ribes meyeri leaves are used as traditional Kazakh medicine in China. However, no study on the characterization of the phenolic compounds in R. meyeri leaves has been reported, resulting in the lack of quality control measures and poor standardization. This study was conducted to identify the phenolic compounds in R. meyeri leaves and evaluate their antioxidant and antidiabetic activities. A total of 77 phenolics were tentatively identified by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry was applied to simultaneously quantify 12 phenolics in R. meyeri leaves. Rutin, epigallocatechin, isoquercitrin, epicatechin, protocatechuic acid, and kaempferol-3-O-rutinoside were abundant in the R. meyeri leaves. The methanol extract and four different extracts enhanced the glucose uptake in 3T3-L1 adipocytes. The ethyl acetate extracts showed a total phenolic content of 966.89 ± 3.59 mg gallic acid equivalents/g, a total flavonoid content of 263.58 ± 17.09 mg catechin equivalents/g, and good protein-tyrosine phosphatase-1B inhibitory activities (IC50 : 0.60 ± 0.03 µg/mL). To our knowledge, this work is the first to identify and quantify the major phenolics in R. meyeri leaves.

Subtypes of anterior circulation large artery occlusions with acute brain ischemic stroke.

Anterior circulation large artery occlusion (AC-LAO) related acute ischemic stroke (AIS) is particularly common in clinics in China. We retrospectively analyzed 787 consecutively hospitalized AIS patients with AC-LAO in Hebei Province, China. AC-LAO was defined as a complete occlusion of at least one intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) based on computed tomography or magnetic resonance angiography. Among eight subtypes of AC-LAO, unilateral MCA occlusion is the most common one (49.8%, n = 392), while bilateral ICA/unilateral MCA occlusion is the least (0.3%, n = 2). Compared with unilateral MCA and unilateral ICA occlusion, patients with tandem ICA/MCA and bilateral ICA/MCA occlusion had poor outcomes after suffering AIS. Age (OR 1.022; 95%CI, 1.007 to 1.036) was an independent risk factor for single artery progressed to multiple artery occlusion, while ApoA1 (OR 0.453; 95% CI, 0.235 to 0.953) was a protective factor. Patients with unilateral MCA occlusion were prone to artery-to-artery embolism infarction subtype, unilateral ICA occlusion group were the most vulnerable to hypoperfusion/impaired emboli clearance subtype. Our results suggested various AC-LAO subtypes have different clinical characteristics and prognosis and were prone to different subtypes of infarction. Customized preventive measures based on AC-LAO subtypes may be more targeted preventions of stroke recurrences for AIS patients and could improve their prognoses.

Fast inflows as the adjacent fuel of supermassive black hole accretion disks in quasars.

Quasars, which are exceptionally bright objects at the centres (or nuclei) of galaxies, are thought to be produced through the accretion of gas into disks surrounding supermassive black holes1-3. There is observational evidence at galactic and circumnuclear scales4 that gas flows inwards towards accretion disks around black holes, and such an inflow has been measured at the scale of the dusty torus that surrounds the central accretion disk5. At even smaller scales, inflows close to an accretion disk have been suggested to explain the results of recent modelling of the response of gaseous broad emission lines to continuum variations6,7. However, unambiguous observations of inflows that actually reach accretion disks have been elusive. Here we report the detection of redshifted broad absorption lines of hydrogen and helium atoms in a sample of quasars. The lines show broad ranges of Doppler velocities that extend continuously from zero to redshifts as high as about 5,000 kilometres per second. We interpret this as the inward motion of gases at velocities comparable to freefall speeds close to the black hole, constraining the fastest infalling gas to within 10,000 gravitational radii of the black hole (the gravitational radius being the gravitational constant multiplied by the object mass, divided by the speed of light squared). Extensive photoionization modelling yields a characteristic radial distance of the inflow of approximately 1,000 gravitational radii, possibly overlapping with the outer accretion disk.

Crystal recombination control by using Ce doped in mesoporous TiO2 for efficient perovskite solar cells.

Efficient electron transport layers (ETLs) are the crucial issue for electron transport and hole blocking in organic-inorganic hybrid perovskite solar cells (PSCs). To date, most of the reported effective ETLs have comprised TiO2, which exhibits limited electron mobility and numerous defect states and restricts the enhancement of the performance of PSCs. Hence, the investigation of effective tactics for improving the electronic properties of TiO2 is critical for the fabrication of high-efficiency devices. In this study, a cerium doping method was adopted in mesoporous TiO2, which was prepared via a traditional one-step hydrothermal process, to improve its electron transport properties by recombining nanocrystals and optimizing the negative flat band potential of TiO2. Continuous, aligned and regulated recombined crystals of mesoporous TiO2 were obtained with optimized pathways of electron transport from the ETL to the FTO layer. Moreover, a small amount of Ti4+ ions was replaced by Ce4+ ions in the TiO2 lattice, which led to deformation of the TiO2 lattice and influenced the growth process of TiO2 grains. With an optimized mole proportion of Ce element in the TiO2 precursor, the power conversion efficiency (PCE) of perovskite solar cells was typically boosted to 17.75% in comparison with 15.92% in the case of undoped TiO2.

Programmable Self-Assembly of Heterometallic Palladium(II)-Copper(II) 1D Grid-Chain using Dinuclear Palladium(II) Corners with Pyrazole-Carboxylic Acid Ligands.

A novel heterometallic diPdII -diCuII grid-chain, {[(bpy)4 Pd4 Cu2 L4 ](NO3 )4 }n (2; bpy=2,2'-bipyridine), was synthesized through a programmable self-assembly approach from the molecular corners [(bpy)2 Pd2 (HL)(L)](NO3 ) (1) as linkers with CuII nitrate by using the bifunctional H2 L ligand featuring primary (pyrazole) and secondary (benzoic acid) groups. Structural analysis revealed that 1D structure 2 consists of one [Cu2 (O2 CPh)4 ]n unit as a bridge and two [(bpy)2 Pd2 L2 ]n corners. Additionally, the catalytic effect of the heterometallic synergy on the Suzuki coupling reaction by using 2 was further explored.

A new quinoline-based fluorescent probe for Cd(2+) and Hg(2+) with an opposite response in a 100% aqueous environment and live cell imaging.

A new quinoline-based fluorescent probe was synthesized and characterized. Probe showed opposite fluorescence responses toward Cd(2+) (turn-on) and Hg(2+) (turn-off) in a 100% aqueous environment. X-ray crystallography analysis and TD-DFT calculations showed the different mechanisms of CHEF-based for -Cd(2+) and PET-based for -Hg(2+) caused by different binding modes and different electronic transfer patterns. The detection limits for the analysis of Cd(2+) and Hg(2+) ions were found to be 3.9 × 10(-8) M and 9.8 × 10(-7) M, respectively. Its in vivo sensitivities to Cd(2+) and Hg(2+) were demonstrated in the EC9706 cell line with the use of a laser scanning fluorescence microscope.

A dual functional probe for "turn-on" fluorescence response of Pb(2+) and colorimetric detection of Cu(2+) based on a rhodamine derivative in aqueous media.

A dual functional probe L based on rhodamine was devised and synthesized. Probe L can sense Pb(2+) and Cu(2+) in aqueous solution through two approaches: a significant fluorescence enhancement caused by Pb(2+) and a visible color change from colorless to orchid induced by Cu(2+). Competitive experiments showed that probe L had high fluorescence sensitivity for Pb(2+) and excellent colorimetric selectivity for Cu(2+) over many environmentally relevant ions. The mechanisms of L for sensing Pb(2+) and Cu(2+) have been well demonstrated by ESI-MS, (1)H NMR titration, IR, the crystal structure of L-Pb(2+) and density functional theory calculation of L-Cu(2+). In addition, fluorescence image detection of Pb(2+) in living cells displayed an enhanced fluorescence effect.

Ionic liquid directed syntheses of water-stable Eu- and Tb-organic-frameworks for aqueous-phase detection of nitroaromatic explosives.

Reactions of lanthanide nitrate, 1,3,5-benzenetrisbenzoic acid (H3BTB) and [RMI]Br ionic liquids (RMI = 1-alkyl-3-methylimidazolium; R = ethyl, propyl, butyl, amyl, or hexyl), gave rise to two novel lanthanide metal-organic frameworks (Ln-MOFs) [Ln(BTB)H2O], where Ln = Eu , Tb . In addition to helping solubilise the starting materials under the reaction conditions there is evidence that [RMI]Br itself can play a structure directing role and is intimately involved in template ordering in [Ln(BTB)H2O], even though neither the [RMI](+) cation nor the Br(-) anion is occluded into the ultimate structure. and are isostructural and consist of infinite rod-shaped lanthanide-carboxylate building units which are further bridged by trigonal-planar BTB ligands to give noninterpenetrated open 3D frameworks featuring a (6,6)-connected topology with the point symbol (4(4)·6(7)·8(4))(4(8)·6(7)). Importantly, the strong emission of and dispersed in water prompted us to explore their application for detection of different nitroaromatics in an aquatic system. and show similar selectivity and sensitivity towards the presence of trace amounts of nitroaromatic analytes in the aqueous phase, showing potential as explosive sensors.

Self-assembly of an unprecedented polyoxomolybdate anion [Mo20O66]12- in a giant peanut-like 62-core silver-thiolate nanocluster.

A polyoxometalate-templated silver thiolate nanocluster, [Ag62(S(t)Bu)40(Mo20O66)(Mo6O19)3(CH3CN)2]·(CF3SO3)4 (1), has been isolated, in which a giant peanut-like silver(i)-thiolate cluster [Ag62(S(t)Bu)40](22+) encapsulates an unprecedented [Mo20O66](12-) polyoxoanion core. It opens a new approach for the synthesis of both elusive polyoxometalates and high-nuclearity silver(i)-thiolate nanoclusters.

A highly sensitive C3-symmetric Schiff-base fluorescent probe for Cd2+.

A new C3-symmetric Schiff-base fluorescent probe (L) based on 8-hydroxy-2-methylquinoline has been developed. As expected, the probe L can display high fluorescent selectivity for Cd(2+) over Zn(2+) and most other common ions in neutral ethanol aqueous medium. Moreover, the mechanism of the L-Cd(2+) complex has been confirmed by X-ray crystallography and density functional theory calculation results. More importantly, L could be used to image Cd(2+) within living cells.