Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition: in vitro and in vivo study.

AIM: To provide the direct evidence for the crucial role of trimethylamine N-oxide (TMAO) in vascular permeability and endothelial cell dysfunction under diabetic condition. METHODS: The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells (HRMEC) under high glucose conditions was tested by a cell counting kit, wound healing, a transwell and a tube formation assay. The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction (RT-PCR). The expression of the cell junction was measured by Western blotting (WB) and immunofluorescence staining. In addition, two groups of rat models, diabetic and non-diabetic, were fed with normal or 0.1% TMAO for 16wk, and their plasma levels of TMAO, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested. The vascular permeability of rat retinas was measured using FITC-Dextran, and the expression of zonula occludens (ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining. RESULTS: TMAO administration significantly increased the cell proliferation, migration, and tube formation of primary HRMEC either in normal or high-glucose conditions. RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation, while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment. Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage, which were even higher in TMAO-feeding diabetic rats. Furthermore, TMAO administration increased the rat plasma levels of VEGF, IL-6 and TNF-α while decreasing the retinal expression levels of ZO-1 and claudin-5. CONCLUSION: TMAO enhances the proliferation, migration, and tube formation of HRMEC, as well as destroys their vascular integrity and tight connection. It also regulates the expression of VEGF, IL-6, and TNF-α.

Time trends and gender disparities of Chinese cataract burden and their predictions.

AIM: To evaluate the trends and changes in the number and rates of disability-adjusted life years (DALYs) and prevalence of cataract in China between 1990 and 2019, and to predict the trends of cataract burden from 2020 to 2030. METHODS: The Global Burden of Diseases (GBD) database was employed to collect the data on DALYs and the prevalence of cataract in China, which was distinguished by age and sex during the past three decades from 1990 to 2019, and then changes in the number and rates of cataract from 2020 to 2030 were predicted. All data were analyzed by the R program (version 4.2.2) and GraphPad Prism 9.0 statistics software. RESULTS: The number of DALYs of cataract increased from 449 322.84 in 1990 to 1 087 987.61 in 2019, number of cataract cases increased from 5 607 600.94 in 1990 to 18 142 568.96 in 2019. The age-standardized DALY rates (ASDR) generally increased slightly [estimated annual percentage change (EAPC=0.1; 95%CI: -0.24 to 0.45), age-standardized prevalence rates (ASPR) also increased (EAPC=0.88; 95%CI: 0.6 to 1.15). Cataract burden increased with age and female gender. Among the causes of cataract, air pollution was the most important, followed by smoking, high fasting plasma glucose, and high body mass index (BMI). The burden of cataract is predicted to grow persistently from 2020 to 2030, the number of DALYs and prevalence for cataract will rise to 2 336 431 and 43 698 620 respectively by 2030, the ASDR is predicted to be 85/100 000 and ASPR will be 1586/100 000 in 2030, females will still be at greater risk of suffering from cataract than males. CONCLUSION: The burden of cataract in China kept rising from 1990 to 2019. Increasing age and female gender are risk factors for cataract. Air pollution, smoking, high fasting plasma glucose, and high BMI are associated with cataract. The burden of cataract in China will gradually increase from 2020 to 2030, the elderly women in particular need attention. Our results may be of help for providing reference strategies to reduce cataract burden in the near future.

Application of dual-layer spectral detector computed tomography to evaluate the expression of Ki-67 in colorectal cancer.

BACKGROUND: Compared with traditional computed tomography (CT), dual-layer spectral detector CT (SDCT) shows significant improvement in imaging soft tissues of the digestive tract. This work aimed to explore the application of SDCT to evaluate the expression of the molecular marker Ki-67 in colorectal cancer. METHODS: We retrospectively analyzed the imaging data of the SDCT (IQon Spectral CT; Philips Healthcare) of 45 patients with colorectal cancer in our centre. We used Spearman's test for the imaging parameters (reconstruction of 40, 70, and 100 keV virtual monoenergetic images [VMIs] and the slope of the Hounsfield unit attenuation plot [VMI Slope] based on venous phase CT images, the arterial phase iodine concentration [AP-IC] and venous phase iodine concentration [VP-IC], and the effective atomic number [Z effect]) and correlation analysis for the Ki-67 index. Multivariate logistic regression was used to eliminate confounding factors. We evaluated the expression level of Ki-67 and drew the receiver operating characteristic curve. RESULTS: The 40-keV VMI, VMI Slope, and AP-IC were found to better reflect the Ki-67 index in patients with colorectal cancer with statistical significance. The 40-keV VMI (r = -0.612, p < 0.001) and VMI Slope (r = -0.523, p < 0.001) were negatively correlated with the Ki-67 index, and AP-IC (r = 0.378, p = 0.010) was positively correlated with the Ki-67 index. The other indexes (p > 0.05) were not statistically significant. The SDCT parameters demonstrated good performance, with area under curves of 0.785 for 40-keV VMI and 0.752 for AP-IC. CONCLUSION: The SDCT parameters 40-keV VMI and AP-IC can be used for preliminary evaluation of the Ki-67 index in colorectal cancer.

Degradation of thin-film lithium batteries characterised by improved potentiometric measurement of entropy change.

The degradation phenomena of thin-film solid state batteries caused by cycling at a high cut-off voltage and different temperatures were studied using an improved potentiometric measurement of entropy change combined with electrochemical impedance analysis and incremental capacity analysis. Entropy profiling is demonstrated as a viable non-destructive technique for solid state batteries that is sensitive to structural changes in electrodes during galvanostatic cycling, and is complementary to other techniques for studying degradation. The characteristic peaks and valleys in the entropy profile as a function of the state-of-charge could be closely correlated to theories of phase transitions in the cathode material. This technique is therefore a useful technique to help understand and diagnose the degradation mechanism, and specify the state-of-health in a promising new battery technology.

Enhancing Menaquinone-7 Production by Bacillus natto R127 Through the Nutritional Factors and Surfactant.

Bacillus natto is commonly used in industrial production of menaquinone-7, an important vitamin which plays a crucial role for blood clotting and may contribute to prevention of cardiovascular disease and osteoporosis. This study determined the optimal combination of key nutrients and established an effective use of surfactant in a coupling medium to enhance the yield of extracellular MK-7. MK-7 yield of 31.18 mg/L was achieved under optimal conditions containing 53.6 g/L glycerol, 100 g/L soy peptone, and 10 g/L K2HPO4. A maximal yield of 40.96 mg/L MK-7 and a secretion ratio of 61.1% were obtained when 20 g/L soybean oil was supplemented at the logarithmic phase. The non-ionic surfactant span 20 was the second most promising surfactant in improving product yield, whereas addition of 2 g/L betaine exerted a minimal effect on secretion ratio of MK-7 at 19.1%. The results collectively showed that the supplementation of surfactants was an effective strategy to regulate cytomembrane permeability. Graphical abstract ᅟ.

Potentiometric measurement of entropy change for lithium batteries.

Effective thermal management and tracking of battery degradation are two key challenges in the improved management of battery packs. Entropy change measurement is a non-destructive tool for characterizing both the thermal and structural properties of lithium batteries. However, conventional entropy measurements based on discontinuous potentiometric methods are too time-consuming for practical implementation in battery packs. We present a comprehensive review of potentiometric methods for the entropy change measurement of lithium batteries. We compare conventional and improved discontinuous methods as well as a fully continuous method. Entropy measurements were then made using all the techniques for a solid-state microbattery using a bespoke test system utilising Peltier elements for rapid temperature control. The trade-off between accuracy and speed for the different methods is discussed in detail. In conclusion, the improved discontinuous measurement with significantly reduced voltage relaxation time is recommended for the determination of entropy change during the lithiation/delithiation intercalation reaction in lithium batteries.

Intra- and Extramedullary Dumbbell-Shaped Schwannoma of the Medulla Oblongata: A Case Report and Review of the Literature.

BACKGROUND: Brainstem intramedullary schwannomas (ISs) are extremely rare. Various theories have been suggested to explain its origin. It was first speculated that ISs arise from the region where the nerve roots lose their sheaths on penetrating the pia mater. Later, it was further predicted that ISs would contain both intra- and extramedullary parts and would be shaped like a dumbbell. However, no cases reported previously can support this assumption adequately. CASE DESCRIPTION: A 40-year-old woman presented with constant cervical pain, accompanied by progressive weakness of upper extremities and glove distribution numbness. Magnetic resonance imaging of the brain revealed a rare intra- and extramedullary dumbbell-shaped lesion of the medulla oblongata, which was partially removed via a midline suboccipital craniectomy. Histologic and immunohistochemical examinations confirmed the diagnosis of schwannoma. Routine imaging performed 20 months after the initial resection revealed a regrowth of the intramedullary part, which was subsequently partially removed through a far-lateral approach, with symptoms alleviated. At 2-year follow-up, there continued to be no radiologic or clinical evidence of regrowth. CONCLUSIONS: To date and to our knowledge, there are only 16 reported cases of brainstem ISs, none of which contained both intra- and extramedullary components. We believe this is the first report of dumbbell schwannoma of the medulla oblongata with adequate radiologic evidence. The relevant literature is reviewed, and an assumption has been proposed that dumbbell or surfacing ISs arising near entry zones of sensory nerves, mixed cranial nerves, or ventral root may originate from the aberrant Schwann cells.

[Variation Characteristics of Total Gaseous Mercury at Simian Mountain Background Station in Mid-subtropical Region].

Total gaseous mercury (TGM) was continuously monitored at the Simian Mountain Forest Nature Reserve in Chongqing, a representative of the mid-subtropical region, using high-resolution automatic atmospheric mercury vapor analyzer (Tekran 2537X) from March 2012 to February 2013. The results showed that the average concentration of TGM during the monitoring was (2.88 ± 1.54) ng · m⁻³, which was much higher than the background TGM on north hemisphere but lower than those at most of the other monitoring sites in China. These results suggested that the TGM level in Simian Mountain was still in the normal range on regional scale, but had an increasing tendency globally. The TGM level exhibited a distinct seasonal variation, following the order of winter (3.68 ± 2.43) ng · m⁻³ > summer (3.29 ± 0.79) ng · m⁻³ > spring (2.44 ± 0.69) ng · m⁻³ > autumn (2.13 ± 0.97) ng · m⁻³, and the TGM concentration varied to a greater extent in winter. The diurnal variation of TGM concentration characterized as being higher at the nighttime in spring, while higher during the daytime in other seasons. The concentration variation of TGM had a positive correlation to temperature and light intensity. The result of backward trajectory analysis using HYSPLIT showed that the main source of the TGM in Simian Mountain was the local coal combustion, and long distance transportation by the Indian monsoon might also play a role in the increasing TGM level.

Effect of Cu substitution on structures and electrochemical properties of Li[NiCo1-xCuxMn]1/3O2 as cathode materials for lithium ion batteries.

Copper ions are one of the major associated metal ions present in the precursors of the synthesis of Li[NiCoMn]1/3O2 from the recovery of spent Li-ion batteries by wet chemical processes. To evaluate the feasibility of reusing Cu(2+) as a favourable dopant in Li[NiCoMn]1/3O2 instead of as usual removing it as an undesirable impurity, the effect of Cu-doping on the electrochemical behaviour of Li[NiCoMn]1/3O2 is investigated in this work. Li[NiCo1-xCuxMn]1/3O2 (x = 0, 0.02, 0.04, 0.06 and 0.08) is synthesized through two steps, roasting the precursors obtained from carbonate co-precipitation, and their structures and electrochemical performances are systemically investigated. The results indicate that substitution of Co with Cu was successfully achieved without any detectable second phases. The initial discharge capacity of Li[NiCo1-xCuxMn]1/3O2 gradually dropped with an increase of x but the rate property and capacity retention were remarkably enhanced. In particular, the capacity retention of the Li[NiCo0.94Cu0.06Mn]1/3O2 sample reached 95.87% within 50 cycles at a current density of 160 mA g(-1). CV and EIS revealed that such improvements are ascribed to a higher Li(+) diffusion coefficient and lower charge-transfer resistance derived from Cu(2+) doping. The results suggest that Cu can be used as a beneficial dopant to partially substitute Co in synthesizing Li[NiCoMn]1/3O2 from spent LIBs instead of having to remove it as an impurity.

Clinical presentation and mutation analysis of VHL disease in a large Chinese family.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited neoplastic disorder characterized by marked phenotypic variability and age-dependent penetrance. This disease is caused by germline mutations in the VHL tumor suppressor gene. Systematic physical examinations, imaging assessments and molecular genetic tests for the VHL gene were performed in a large Chinese VHL family. The examined Chinese VHL family, which has 25 members from four generations, including 7 diagnosed VHL patients and 2 asymptomatic mutation carriers. The average ages of first onset for generations I, II, and III were 37, 30 and 16, respectively. The male:female ratio among VHL patients was 6:1. Molecular genetic investigations detected the c.433C>T [p.Q145X] nonsense mutation in the VHL gene. Molecular modeling of the VHL-ElonginC- ElonginB-HIF-1α complex predicted that the p.Q145X mutation markedly alters the L7 loop structure of the ß-domain of the VHL protein (pVHL), destabilizes the VHL-HIF-1αcomplex, and induces the truncation of pVHL. We speculate that the p.Q145X nonsense mutation leads to relatively obvious familial aggregation. This mutation causes the type I phenotype of VHL disease and is associated with a high risk of retinal and central nervous system (CNS) hemangioblastomas (HGBs) and visceral cysts, but a low risk of renal cell carcinoma. Moreover, within a VHL family, the average ages of first onset became younger in successive generations, and the CNS HGBs are more likely to occur in male patients.

A hierarchical three-dimensional NiCo2O4 nanowire array/carbon cloth as an air electrode for nonaqueous Li-air batteries.

A 3D NiCo2O4 nanowire array/carbon cloth (NCONW/CC) was employed as the cathode for Li-air batteries with a non-aqueous electrolyte. After its discharge, novel porous ball-like Li2O2 was found to be deposited on the tip of NiCo2O4 nanowires. The special structure of Li2O2 and active sites of catalysts are also discussed.

[Therapeutic strategy for intrasellar cystic lesions].

OBJECTIVE: To make a clear distinction of intrasellar cystic lesions: craniopharyngioma (CR), Rathke's cleft cyst (RCC), cystic pituitary adenoma (PA) and intrasellar arachnoid cyst (AC). METHODS: A total of 72 adult patients underwent transsphenoidal approach for the removal of intrasellar cystic lesions. The authors conducted a study to (1) investigate preoperative clinical, biochemical and radiographic features of patients with CR, RCC, PA and AC; (2) identify clinicopathological features of independently predicting recurrence in CR, PA and RCC in adults. These adult patients included CR (n = 10), RCC (n = 27), cystic PA (n = 32) and 1 patient with AC (n = 1). RESULTS: The CR patients presented with hypopituitarism in 80% of cases. According to the biochemical criteria, the percentage of patients with a slight prolactin increase happened in PA (55.6%) and RCC (44.4%). Cystic PA had post-contrasting enhancement in cyst wall because of tumor tissue. Calcification detectable on computed tomographic scanning was present in 70% of CR patients. It was a significantly greater proportion compared to other diseases. Typical RCC was located between anterior and posterior pituitary and the contents in RCC were variable. Mass effects vanished post-operatively in all kinds of lesions. Long-term hormone replacement therapy was administered more in CR patients (60%) and diabetes insipidus than other lesions. One PA patient and 2 CR patients had recurrence during a follow-up of 12 - 52 months (mean: 34). RCC and AC had no recurrence. CONCLUSION: Craniopharyngioma, Rathke's cleft cyst, cystic pituitary adenoma and intrasellar arachnoid cyst are a spectrum of diseases with different therapeutic strategies. An accurate diagnosis of these lesions is essential so as to determine the type of treatment to improve outcome.

Antioxidant and immunity activity of water extract and crude polysaccharide from Ficus carica L. fruit.

The antioxidative activities of water extract (WE) and crude hot-water soluble polysaccharide (PS) from Ficus carica L. fruit were investigated using various assays in vitro, including scavenging abilities on DPPH, superoxide and hydroxyl radicals and reducing power. The immunity activities of PS were evaluated using the carbon clearance test and serum hemolysin analysis in mice. In addition, total phenolics and flavonoids contents were also determined. Both WE and PS have notable scavenging activities on DPPH with the EC(50) values of 0.72 and 0.61 mg/ml, respectively. The PS showed higher scavenging activity than WE on superoxide radical (EC(50), 0.95 mg/ml) and hydroxyl anion radical (scavenging rate 43.4% at concentration of 4 mg/ml). The PS (500 mg/kg) also has a significant increase in the clearance rate of carbon particles and serum hemolysin level of normal mice. The results indicate that both WE and PS might be applicable in healthy medicine and food industry.

Clinical and pathological changes in cerebral arteriovenous malformations after stereotactic radiosurgery failure.

BACKGROUND: Stereotactic radiosurgery is an alternative to resection of intracranial cerebral arteriovenous malformations (AVMs), while it will fail in some cases. This study aimed to evaluate the changes after stereotactic radiosurgery for AVMs. METHODS: Nineteen cases with cerebral AVMs had failure after stereotactic radiosurgery therapy. The symptoms and angiography were assessed. All patients underwent microsurgery. Pathologic examination was performed for all cases and electron microscopic examination was carried out in 6 patients. RESULTS: Seven cases had hemorrhage from 12 to 98 months after stereotactic radiosurgery, 5 had headache, 4 had refractory encephalon edema, 2 had epilepsy as a new symptom and 1 had a pressure cyst 5 years after radiosurgery. Angiography in 18 cases, 8 - 98 months after radiation therapy, demonstrated no significant changes in 5 cases, slight reduction in 9, near complete obliteration in 1 and complete obliteration in 3. An abnormal vessel was found on pathologic examination in 17 cases, even one case had obliterated in angiography. Electron microscopy examination showed vessel wall weakness, but the vessels remained open and blood circulated. One case died because of a moribund state before surgery. The other 18 cases had no new neurological deficiencies, seizure control and no hemorrhage occurred after microsurgery at an average follow-up of 3 years. CONCLUSION: Stereotactic radiotherapy for AVMs should have a long period follow-up. If serious complications occur, microsurgery can be performed as salvage treatment.

No association evidence between schizophrenia and dystrobrevin-binding protein 1 (DTNBP1) in Taiwanese families.

Several linkage studies have shown significant linkage of schizophrenia to chromosome 6p region, which includes the positional candidate genes, Dystrobrevin-binding protein 1 (DTNBP1). The aim was to examine the association evidence of the candidate gene in 693 Taiwanese families with at least two affected siblings of schizophrenia. We genotyped nine SNPs of this gene with average intermarker distance of 17 kb. Intermarker linkage disequilibrium was calculated with GOLD. Single locus and haplotype association analyses were performed with TRANSMIT program. We found no significant association between schizophrenia and DTNBP1 either through single locus or haplotype analyses. We failed to replicate the association evidence between DTNBP1 and schizophrenia and this gene may not play a major role in the etiology of schizophrenia in this Taiwanese family sample.

Genome scan of Han Chinese schizophrenia families from Taiwan: confirmation of linkage to 10q22.3.

OBJECTIVE: Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes, but given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. To address this issue, the authors ascertained 606 Han Chinese families comprising 1,234 affected members. METHOD: Probands with schizophrenia were recruited from six data collection field research centers in Taiwan. Each proband underwent a diagnostic screen with supplemental medical records and a semistructured interview. Following this screen, the authors administered the Mandarin Chinese version of the Diagnostic Interview for Genetic Studies. Best-estimate final diagnoses were made by two board-certified psychiatrists. The genotyping was conducted by the Center for Inherited Disease Research, with 386 markers spaced at an average of 9-centimorgan (cM) intervals. Empirical simulations were generated to determine genome-wide significance. RESULTS: The authors found five regions with nonparametric linkage z scores 2.0 or greater. These were the following: 2.08 was reached for D1S551 (113.7) cM at 1p31.1 and 2.31 for D2S410 (125.2 cM) at 2q14.1; 2.00 was reached for D4S2361 (93.5 cM) at 4q21.23, and 2.07 for D15S1012 (36 cM) at 15q14, the largest nonparametric linkage z score was 2.88 for D10S2327 (100.92 cM) at 10q22.3. CONCLUSIONS: Our 10q22.3 finding at 100.9 cM is consistent with a previously reported nonparametric linkage score of 4.27 at 107.2 cM on chromosome 10, although it did not attain genome-wide significance in this study.

[Study on fertillizer application techniques of annual Dioscoreae zingiberensis].

The experiment N,P and K fertilizer on Dioscorea zingiberensis were studied by setting fied parameter tests with rotational design. The selecton value of three agronomic factors were put forward by establishing regression mathematics models in the production and net value.

Evaluation of RGS4 as a candidate gene for schizophrenia.

Several studies have suggested that the regulator of G-protein signaling 4 (RGS4) may be a positional and functional candidate gene for schizophrenia. Three single nucleotide polymorphisms (SNP) located at the promoter region (SNP4 and SNP7) and the intron 1 (SNP18) of RGS4 have been verified in different ethnic groups. Positive results have been reported in these SNPs with different numbers of SNP combinatory haplotypes. In this study, these three SNP markers were genotyped in 218 schizophrenia pedigrees of Taiwan (864 individuals) for association analysis. Among these three SNPs, neither SNP4, SNP7, SNP18 has shown significant association with schizophrenia in single locus association analysis, nor any compositions of the three SNP haplotypes has shown significantly associations with the DSM-IV diagnosed schizophrenia. Our results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated from these three SNP markers.