Isolated anterior cerebral artery occlusion: an atypical form of moyamoya disease.

BACKGROUND: The relationship between anterior cerebral artery (ACA) occlusion and moyamoya disease (MMD) has rarely been studied. In this study, we focused on a special type of MMD: isolated ACA-occlusive MMD. We investigated clinical attributes, genotypes and progression risk factors in patients with ACA-occlusive MMD, providing initial insights into the relationship between ACA occlusion and MMD. METHODS: We retrospectively analysed digital subtraction angiography (DSA) from 2486 patients and diagnosed 139 patients with ACA-occlusive MMD. RNF213 p.R4810K (rs112735431) mutation analysis was performed. Patients were categorised into progression and non-progression groups based on whether they progressed to typical MMD. Differences in clinical characteristics, neuropsychological assessment, radiological findings and genotypes were evaluated. Logistic regression analyses identified risk factors for ACA-occlusive MMD progression. RESULTS: The median age of patients with ACA-occlusive MMD was 36 years, and the primary symptom was transient ischaemic attack (TIA). 72.3% of ACA-occlusive MMD patients had cognitive decline. Of 116 patients who underwent RNF213 gene mutation analysis, 90 patients (77.6%) carried the RNF213 p.R4810K GG allele and 26 (22.4%) carried the GA allele. Of 102 patients with follow-up DSA data, 40 patients (39.2%) progressed. Kaplan-Meier curve estimates indicated a higher incidence of ischaemic stroke in the progression group during follow-up (p=0.035). Younger age (p=0.041), RNF213 p.R4810K GA genotype (p=0.037) and poor collateral compensation from the middle cerebral artery (MCA) to ACA (p<0.001) were risk factors of ACA-occlusive MMD progression to typical MMD. CONCLUSIONS: Cognitive decline and TIA might be the main manifestations of ACA-occlusive MMD. Isolated ACA occlusion may be an early signal of MMD. The initial lesion site of MMD is not strictly confined to the terminal portion of the internal carotid artery. Younger patients, patients with RNF213 p.R4810K GA genotype or those with inadequate MCA-to-ACA compensation are more likely to develop typical MMD.

Effect of particle shape on mechanical behaviors of rocks: a numerical study using clumped particle model.

Since rocks are aggregates of mineral particles, the effect of mineral microstructure on macroscopic mechanical behaviors of rocks is inneglectable. Rock samples of four different particle shapes are established in this study based on clumped particle model, and a sphericity index is used to quantify particle shape. Model parameters for simulation in PFC are obtained by triaxial compression test of quartz sandstone, and simulation of triaxial compression test is then conducted on four rock samples with different particle shapes. It is seen from the results that stress thresholds of rock samples such as crack initiation stress, crack damage stress, and peak stress decrease with the increasing of the sphericity index. The increase of sphericity leads to a drop of elastic modulus and a rise in Poisson ratio, while the decreasing sphericity usually results in the increase of cohesion and internal friction angle. Based on volume change of rock samples during simulation of triaxial compression test, variation of dilation angle with plastic strain is also studied.

Combined analysis of transcriptomics and metabolomics on the cumulative effect of nano-titanium dioxide on mulberry seedlings.

Introduction: Titanium dioxide nanoparticles (TiO2 NPs) are among the most widely used inorganic nanomaterials in industry, medicine and food additives. There are increasing concerns regarding their potential risks to plants and the environment. Mulberry trees are widely grown in China due to their high survival rate and ability to aid ecological recovery. Methods: Herein, the effects of TiO2 NPs with different concentrations (100, 200, 400 and 800 mg/L) on the growth and physiology of the mulberry tree were systematically evaluated in aspects of physiology, transcriptomics and metabolomics. Results: Results showed that TiO2 NPs could be absorbed by the mulberry sapling root system and be transferred to the plant shoot. This results in the destruction of mulberry sapling root and leaf tissue. Furthermore, the number of chloroplasts and their pigment contents were reduced and the homeostasis of metal ions was disrupted. The toxic effects of TiO2 NPs attenuated the mulberry sapling's stress resistance, the contents of malondialdehyde in 100 mg/L, 200 mg/L 400 mg/L and 800 mg/L treatment groups increased by 87.70%, 91.36%, 96.57% and 192.19% respectively compared with the control group. The transcriptomic data showed that TiO2 NPs treatment mainly affected the expression of genes related to energy synthesis and transport, protein metabolism, and response to stress. Meanwhile, the results of metabolomics showed that 42 metabolites produced significant differences in mulberry, of which 26 differential metabolites were up-regulated in expression and 16 differential metabolites were down-regulated, mainly including metabolic pathways such as secondary metabolite biosynthesis, citric acid cycle, and tricarboxylic acid cycle, and was not conducive to the seed germination and or growth of the mulberry sapling. Discussion: This study enriches the understanding of the effects of TiO2 NPs on plants and provides a reference for the comprehensive scientific assessment of the potential risks of nanomaterials on plants.

Association of cognitive function and hypoperfusion in Moyamoya disease patients without stroke.

The influence of hypoperfusion on cognition in patients with Moyamoya disease (MMD) is unclear. This study investigated cognitive function changes in MMD patients without stroke and illustrated the relationship between cognitive impairment and hypoperfusion. We prospectively performed a structured battery of seven neurocognitive tests on 115 adult MMD patients without stroke and 82 healthy controls. Hemodynamic assessment was performed using dynamic susceptibility contrast-enhanced MRI. The best subset regression (BSR) strategy was used to identify risk factors. Global cognition (MoCA), speed of information processing (TMT-A), executive function (TMT-B), visuospatial function (CDT), and verbal memory (CAVLT) were significantly poorer in MMD patients without stroke than in healthy controls. The TMT-B score significantly correlated with cerebral blood flow (CBF) in the bilateral lateral frontal lobes, centrum semiovale, and temporal lobes. The TMT-A and CAVLT scores significantly correlated with CBF in the left centrum semiovale (L-CSO) and temporal lobes. According to the BSR results, age, education, white matter lesions, and hypoperfusion of the L-CSO were risk factors for cognitive impairment. Hypoperfusion leads to multiple cognitive impairments in MMD patients without stroke. The perfusion of particular areas may help evaluate the cognitive function of MMD patients and guide therapeutic strategies.

Wavelet Analysis of Cerebral Oxygenation Signal Measured by Near-Infrared Spectroscopy in Moyamoya Disease.

BACKGROUND: Spontaneous low-frequency oscillations (LFOs) have been widely studied in cerebrovascular disease, but little is known about their role in moyamoya disease (MMD). The objective of this study was to assess the value of spontaneous LFOs in MMD based on wavelet analysis of near-infrared spectroscopy signals. METHODS: Sixty-four consecutive idiopathic adult patients were prospectively enrolled. The regional tissue oxygenation index (TOI) obtained from continuous near-infrared spectroscopy signals. Five frequency intervals of spontaneous LFOs (I, 0.0095-0.02 Hz; II, 0.02-0.06 Hz; III, 0.06-0.15 Hz; IV, 0.15-0.40 Hz; and V, 0.40-2.00 Hz) were extracted based on wavelet analysis. The data were compared between the patients and healthy control groups. Clinical features, cognitive function, and disease progression of MMD were analyzed using TOI and frequency interval data. RESULTS: Compared with the healthy control group, patients with MMD had a higher cerebral TOI in both hemispheres. Based on wavelet analysis, the spontaneous LFO of TOI was found to be significantly lower for patients with MMD in frequency intervals II to IV than that for the controls. The spontaneous LFO of TOI is also related to the Suzuki stages in intervals II to IV, stroke in interval III, and cognitive impairment in intervals III to Ⅳ. CONCLUSIONS: There were significant differences in spontaneous LFO between patients with MMD and healthy controls. The change in spontaneous LFO in MMD is related to Suzuki stage, cerebral infarction, and cognitive impairment. This might be an effective method for evaluating the severity and monitoring the progression of MMD.

[Terahertz time-domain spectroscopy of alpha endosulfan persistent organic pollutant].

Frequency-dependent absorption coefficient spectrum and refractive index spectrum of alpha endosulfan, a kind of persistent organic pollutants, are presented in the terahertz frequency region by terahertz (THz) time-domain spectroscopy (TDS). The spectral features in the THz region have a number of unique characteristic absorption peaks. The result demonstrates that THz-TDS is a promising method to identify materials. Then we adopted density functional calculation method to analyze theoretic absorption coefficients of single alpha endosulfan molecule within 0.2-2 THz. The results show that absorption peaks at 1.68, 1.91 THz in theoretical calculation correspond to 1.7, 1.88 THz in the experiment. Finally, vibrational modes and approximate assignments were discussed, showing that these matched peaks are caused by intramolecular vibrational modes of alpha endosulfan. Others might be related to intermolecular vibrational modes or combined vibrational modes.

[Spectral analysis of nitrofurantoin in the terahertz frequency range].

The present article measured the absorption coefficient spectra and refractive index spectra of nitrofurantoin original drug, which is one kind of nitrofuran drugs, in the terahertz frequency range from 0.2 to 1.8 THz using terahertz time-domain spectroscopy. The results showed that there exist a number of characteristic absorption peaks of nitrofurantoin with different intensity in the range and the absorption coefficient spectra can be used to identify nitrofurantoin. The article also simulated absorption coefficient spectra of nitrofurantoin molecule within 0.2 - 1.8 THz using density functional theory by Gaussian software, and vibrational modes of some peaks in the experimental absorption coefficient spectra were analyzed and identified. The results show that the experimental absorption peaks at 1.25 and 1.60 THz correspond with the theoretical peaks at 1.30 and 1.67 THz, and these experimental peaks were caused by intramolecular vibrational modes of nitrofurantoin.

[Terahertz time-domain spectroscopy of ractopamine hydrochloride].

The terahertz spectra of Ractopamine hydrochloride in the range of 0.2 to 2.2 THz was obtained by THz time-domain spectroscopy, and the absorption and refraction spectra of Ractopamine hydrochloride was got meanwhile. The structure and vibrational frequencies of Ractopamine molecule in the THz range were simulated by density functional theory. The difference between experimental and theoretical results was analyzed. And assisted by Gaussian View 3.09, the origin of the vibrational frequencies was recognized. The results show that besides the intramolecular vibrations, THz absorption of Ractopamine hydrochloride originated from the intermolecular hydrogen bond network and Van der Waals force between molecules. This study demonstrated the feasibility of time-domain terahertz spectroscopy for the identification of Ractopamine hydrochloride and provided a new way for the detection of Ractopamine hydrochloride.

[Terahertz time-domain spectroscopy of Clenbuterol hydrochloride].

The terahertz spectra of Clenbuterol hydrochloride in the range of 0.2 to 2.6 THz were obtained by THz time-domain spectroscopy, the absorption and refraction spectra of Clenbuterol hydrochloride was got meanwhile. The structure and vibrational frequencies of Clenbuterol molecule, Clenbuterol hydrochloride molecule and Clenbuterol hydrochloride crystal in the THz range were simulated. Based on the difference between experimental and theoretical results, the origin of the vibrational frequencies was analyzed. This study demonstrated the feasibility of time-domain terahertz spectroscopy for the identification of Clenbuterol hydrochloride and provides a new way for the detection of Clenbuterol hydrochloride.

[Terahertz spectroscopic investigation of elaidic acid].

The optical properties of elaidic acid in the THz band were investigated by using THz time-domain spectroscopy (THZ-TDS). The absorption and refractive index spectra in the frequency range from 0.5 to 2.5 THz were obtained at room temperature under nitrogen atmosphere, and the results show that elaidic acid had some characteristic absorption peaks, and the average refractive index of the sample was 1.43. The structure and vibrational frequencies of elaidic acid molecule in the THz range were simulated by the B3LYP algorithm of density functional theory, and the THz characteristic absorption peaks of elaidic acid molecule were identified by using Gaussian View software. The results show that the experimental and theoretical results agree in general, and the observed absorption peaks in the THz range were mainly caused by the intramolecular and intermolecular vibrations jointly. At the same time, the fingerprint spectra of elaidic acid in the THz band verify that the time-domain terahertz spectroscopy can be used to detect oleic acid, and this study provides a new experimental method for the detection of trans fatty acids in food.

METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukaemia.

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukaemia (AML) cells. MSCs from AML patients (AML-MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors. However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differs from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m6 A epigenetic changes in MSCs determined via RIP-qPCR and MeRIP-qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m6 A modification of AKT1-mRNA. Downregulated METTL3 expression in AML-MSCs induced an increase in AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance.

[Terahertz time-domain spectroscopy of L-ascorbic acid].

The present paper reports the theoretical and experimental vibrational frequencies of L-ascorbic acid in the frequency range from 0.2 to 2.4 THz respectively. The vibrational frequencies of L-ascorbic acid in the THz range were simulated by Becke-3-Lee-Yang-Parr (B3LYP) algorithm of density functional theory. Simultaneously, the absorption and refractive index spectra of L-ascorbic acid were obtained using terahertz time-domain spectroscopy (THz-TDS). Based on the results from density functional calculations, the observed vibrational peaks were assigned with the aid of Gaussian View 3.07. Finally, the tera-hertz absorption spectra of tablets of vitamin C were compared with those of L-ascorbic acid. It was found that L-ascorbic acid had some distinct fingerprint spectra in the THz region and the theoretical results were in good agreement with the experimental results. The observed vibrational peaks were induced jointly by the intramolecular and intermolecular vibrations. The absorption peaks of L-ascorbic acid could be observed in the absorption spectra of the tablets of vitamin C. Our research is helpful to understanding the role of L-ascorbic acid in biological reactions. Still, the research results show the potential of the application of THz-TDS in the quantification of L-ascorbic acid.

[Determination of pyrethroid pesticides in tea by accelerated solvent extraction and ultra-performance liquid chromatography-tandem mass spectrometry].

A method was developed for the determination of pyrethroid pesticides in tea by accelerated solvent extraction (ASE) combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The target compounds were extracted from tea using n-hexane and acetone (2:1, v/v) for 5 min at 10.34 MPa and 80℃ via a single cycle of accelerated solvent extraction. The extract was purified by GCB/NH2 and Florisil columns, analyzed by UPLC-MS/MS in positive electrospray ionization (ESI+) and multiple reaction monitoring (MRM) modes, and quantified by the external standard method. Regression analysis revealed that the linear relationships between mass concentration and peak area are significant for the 10 pyrethroid pesticides, and the correlation coefficients (r) are all not less than 0.9995. The limits of detection (LOD) of the 10 pyrethroid pesticides ranged from 0.5 µg/kg to 5.0 µg/kg and the limits of quantification (LOQ) ranged from 1.6 µg/kg to 16.6 µg/kg. The recoveries of all the pesticides ranged from 68.7% to 103.8% at the spiked levels of LOQ, 0.4 mg/kg and maximum residue limit (MRL) (added 1 mg/kg without MRL) with RSDs ranging from 0.8% to 13.2% (n=7). The proposed method is simple, rapid, sensitive, and accurate, and could be effective for trace analysis of pyrethroid pesticides in tea.

[Terahertz spectroscopic investigation of imidacloprid].

Terahertz radiation generated by ultra short laser pulses has a broad band width in the far-infrared range. Terahertz wave interacting with materials is a new research field. In this paper, we performed measurement of absorption coefficient and refractive index of imidacloprid in the frequency range 0.2-2.0 THz at room temperature by THz-TDS. The results indicate that imidacloprid has absorption fingerprints in this frequency range, and the absorption coefficient increases with the frequency. The average refractive index of imidacloprid is 1.65, and the refractive index of imidacloprid increases slightly with frequency. A semi-empirical theory was applied to obtain the structure and vibrational frequencies of the imidacloprid molecules in THz region. The calculated results agree well with the experimental data. The absorption features are caused by the collective vibrational and torsional modes, and different absorption peaks correspond to different vibrational modes. The comparison between experimental and theoretical study shows that far-infrared absorption features are highly sensitive to the structure and spatial arrangement of the molecules. THz-TDS is a potential tool to understand the collective vibrational modes and conformational structures of biomolecules.

The complete mitochondrial genome of the Basidiomycete edible fungus Hypsizygus marmoreus.

The complete mitochondrial genome of the edible fungus Hypsizygus marmoreus was published in this paper. It was determined using Pacbio and Illumina sequencing. The complete mitochondrial DNA (mtDNA) is 106,417 bp in length with a GC content of 31.74%, which was the fourth large mitogenome in Agaricales. The circular mitogenome encoded 67 protein-coding genes and one ribosomal RNAs (rns). Among these genes, 13 conserved protein-coding genes were determined in the genome, including 6 subunits of NAD dehydrogenase (nad1-4, 4L and 6), three cytochrome oxidases (cox1-3), one apocytochrome b (cob) and three ATP synthases (atp6, apt 8 and apt 9). The phylogenic analysis confirmed that H. marmoreus (Lyophyllaceae) clustered together with Tricholoma matsutake (Tricholomataceae).

Advances in pharmacotherapy for post-transplant diabetes mellitus / 解放军医学杂志

Post-transplant diabetes mellitus (PTDM) often occurs after solid organ transplantation, and treatment of PTDM is different from that of type 2 diabetes mellitus, the current research in this field is increasing gradually. The present paper summarizes the characteristics of blood glucose change in PTDM, risk assessment, the safety of hypoglycemic drugs, and the effect of immunosuppressive drugs on blood glucose in PTDM patients, and focuses on the efficacy and safety of new hypoglycemic drugs in PTDM patients, as well as the clinical research evidence such as the type of immunosuppressant used and the formula of administration has been summarized, so as to select a more optimized PTDM treatment options.

Preclinical transplantation and safety of HS/PCs expanded from human umbilical cord blood.

AIM: To expand hematopoietic/progenitor stem cells (HS/PCs) from umbilical cord blood (UCB) and prepare the HS/PC product, and analyze preclinical transplantation and safety of HS/PC product. METHODS: Human bone marrow-derived mesenchymal stem cells (MSCs) were used as feeder cells to expand HS/PCs from UCB in a serum-free culture system. The proliferation potential of HS/PCs was analyzed. The expanded HS/PCs were suspended in the L-15 medium to prepare the HS/PC product. The contamination of bacteria, fungi and mycoplasmas, the infection of exogenous virus, the concentration of bacterial endotoxin, and the SCF residual in HS/PC product were determined. Finally, cells from the HS/PC product with or without bone marrow-derived mesenchymal stem cells (BM-MSCs) were transplanted into the irradiated NOD/SCID mice to determine the in vivo engraftment potential. RESULTS: After co-culture for 10 d, the total nuclear cells (TNCs) increased 125-fold, and CD34(+) cells increased 43-fold. The granulocyte-macrophage colony- forming cells (GM-CFCs) and erythroid colony-forming cells (E-CFCs) increased 3.3- and 4.7-fold respectively. The expanded cells were collected and prepared as the expanded product of HS/PCs by re-suspending cells in L-15 medium. For preclinical safety, the HS/PC product was analysed for contamination by bacteria, fungi and mycoplasmas, the bacterial endotoxin concentration and the SCF content. The results showed that the HS/PC product contained no bacteria, fungi or mycoplasmas. The bacterial endotoxin concentration was less than the detection limit of 6 EU/mL, and residual SCF was 75 pg/mL. Based on clinical safety, the HS/PC product was qualified for clinical transplantation. Finally, the HS/PC product was transplanted the irradiated mice where it resulted in rapid engraftment of hematopoietic cells. CONCLUSION: HSPC product prepared from UCB in the serum-free culture system with hMSCs as feeder cells should be clinically safe and effective for clinical transplantation.