Plasma Aß level alterations after sleep deprivation correspond to brain structural remodeling in medical night shift workers.

The relationship between brain structure alteration and metabolic product clearance after night shift work with total sleep deprivation (SD) remains unclear. Twenty-two intensive care unit staff on regularly rotating shift work were implemented with structural and diffusion MRI under both rest wakefulness (RW) and SD conditions. Peripheral blood samples were collected for the measurement of cerebral metabolites. Voxel-based morphometry and diffusion tensor imaging analysis were used to investigate the alterations in the gray matter density (GMD) and mean diffusivity (MD) within the participants. Furthermore, correlation analysis was performed to investigate the relationship between the neuroimaging metrics and hematological parameters. A significant increase in the GMD values was observed in the anterior and peripheral areas of the brain under SD. In contrast, a decrease in the values was observed in the posterior regions, such as the bilateral cerebellum and thalamus. In addition, a significant reduction in the total cerebrospinal fluid volume was observed under SD. The Aß42/Aß40 levels in participants under SD were significantly lower than those under RW. The mean MD increment values extracted from the region of interest (ROI) of the anterior brain were negatively correlated with the increment of plasma Aß42/Aß40 levels (r = -0.658, P = 0.008). The mean GMD decrement values extracted from the posterior ROI were positively correlated with the increment of plasma Aß-40 levels (r = 0.601, P = 0.023). The findings of this study suggest that one night of shift work under SD induces extensive and direction-specific structural alterations of the brain, which are associated with aberrant brain metabolic waste clearance.

The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity.

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: ß = 0.251, P = 0.014; volume: ß = 0.237, P = 0.042; total iron burden: ß = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: ß = 0.325, P = 0.001; Evans's index: ß = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.

The incomplete circle of Willis is associated with vulnerable intracranial plaque features and acute ischemic stroke.

BACKGROUND: The circle of Willis (CoW) plays a significant role in intracranial atherosclerosis (ICAS). This study investigated the relationship between different types of CoW, atherosclerosis plaque features, and acute ischemic stroke (AIS). METHODS: We investigated 97 participants with AIS or transient ischemic attacks (TIA) underwent pre- and post-contrast 3T vessel wall cardiovascular magnetic resonance within 7 days of the onset of symptoms. The culprit plaque characteristics (including enhancement grade, enhancement ratio, high signal in T1, irregularity of plaque surface, and normalized wall index), and vessel remodeling (including arterial remodeling ratio and positive remodeling) for lesions were evaluated. The anatomic structures of the anterior and the posterior sections of the CoW (A-CoW and P-CoW) were also evaluated. The plaque features were compared among them. The plaque features were also compared between AIS and TIA patients. Finally, univariate and multivariate regression analysis was performed to evaluate the independent risk factors for AIS. RESULT: Patients with incomplete A-CoW showed a higher plaque enhancement ratio (P = 0.002), enhancement grade (P = 0.01), and normalized wall index (NWI) (P = 0.018) compared with the patients with complete A-CoW. A higher proportion of patients with incomplete symptomatic P-CoW demonstrated more culprit plaques with high T1 signals (HT1S) compared with those with complete P-CoW (P = 0.013). Incomplete A-CoW was associated with a higher enhancement grade of the culprit plaques [odds ratio (OR):3.84; 95% CI: 1.36-10.88, P = 0.011], after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Incomplete symptomatic P-CoW was associated with a higher probability of HT1S (OR:3.88; 95% CI: 1.12-13.47, P = 0.033), after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Furthermore, an irregularity of the plaque surface (OR: 6.24; 95% CI: 2.25-17.37, P < 0.001), and incomplete symptomatic P-CoW (OR: 8.03, 95% CI: 2.43-26.55, P = 0.001) were independently associated with AIS. CONCLUSIONS: This study demonstrated that incomplete A-CoW was associated with enhancement grade of the culprit plaque, and incomplete symptomatic side P-CoW was associated with the presence of HT1S of culprit plaque. Furthermore, an irregularity of plaque surface and incomplete symptomatic side P-CoW were associated with AIS.

Cerebral blood flow regulates iron overload in the cerebral nuclei of hemodialysis patients with anemia.

Hemodialysis patients exhibit anemia-related cerebral hyperperfusion and iron deposition (ID). However, the mechanisms underlying the pathology of cerebral ID are not clear. We investigated the role of cerebral blood flow (CBF) in the pathophysiology of cerebral ID in hemodialysis patients with anemia. This study recruited 33 hemodialysis patients with anemia and thirty-three healthy controls (HCs). All the subjects underwent quantitative susceptibility mapping (QSM) and arterial spin labeling (ASL) to measure ID and CBF in the cerebral nuclei. Furthermore, we evaluated lacunar infarction (LI), cerebral microbleeds, and total white matter hyperintensity volume (TWMHV). Hemodialysis patients with anemia showed significantly higher ID and CBF in some nuclei compared to the HCs after adjusting for age, sex, and total intracranial volume (TIV) [P < 0.05, false discovery rate (FDR) corrected]. CBF showed a positive correlation with ID in both patients and HCs after adjustments for age, gender, and TIV (P < 0.05, FDR corrected). Serum phosphorus, calcium, TWMHV, hypertension, and dialysis duration were independently associated with ID (P < 0.05). Hemoglobin, serum phosphorus, and LI were independently associated with CBF (P < 0.05). Mediation analysis demonstrated that CBF mediated the effects between hemoglobin and ID. Our study demonstrated that CBF mediated aberrant cerebral ID in hemodialysis patients with anemia.

Formaldehyde gas sensor with extremely high response employing cobalt-doped SnO2 ultrafine nanoparticles.

Formaldehyde is a common carcinogen in daily life and harmful to health. The detection of formaldehyde by a metal oxide semiconductor gas sensor is an important research direction. In this work, cobalt-doped SnO2 nanoparticles (Co-SnO2 NPs) with typical zero-dimensional structure were synthesized by a simple hydrothermal method. At the optimal temperature, the selectivity and response of 0.5% Co-doped SnO2 to formaldehyde are excellent (for 30 ppm formaldehyde, R a/R g = 163 437). Furthermore, the actual minimum detectable concentration of 0.5%Co-SnO2 NPs is as low as 40 ppb, which exceeds the requirements for formaldehyde detection in the World Health Organization (WHO) guidelines. The significant improvement of 0.5%Co-SnO2 NPs gas performance can be attributed to the following aspects: firstly, cobalt doping effectively improves the resistance of SnO2 NPs in the air; moreover, doping creates more defects and oxygen vacancies, which is conducive to the adsorption and desorption of gases. In addition, the crystal size of SnO2 NPs is vastly small and has unique physical and chemical properties of zero-dimensional materials. At the same time, compared with other gases tested, formaldehyde has a strong reducibility, so that it can be selectively detected at a lower temperature.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

Subunit Vaccine ESAT-6:c-di-AMP Delivered by Intranasal Route Elicits Immune Responses and Protects Against Mycobacterium tuberculosis Infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains the most common cause of death from a single infectious disease. More safe and effective vaccines are necessary for preventing the prevalence of TB. In this study, a subunit vaccine of ESAT-6 formulated with c-di-AMP (ESAT-6:c-di-AMP) promoted mucosal and systemic immune responses in spleen and lung. ESAT-6:c-di-AMP inhibited the differentiations of CD8+ T cells as well as macrophages, but promoted the differentiations of ILCs in lung. The co-stimulation also enhanced inflammatory cytokines production in MH-S cells. It was first revealed that ESAT-6 and c-di-AMP regulated autophagy of macrophages in different stages, which together resulted in the inhibition of Mtb growth in macrophages during early infection. After Mtb infection, the level of ESAT-6-specific immune responses induced by ESAT-6:c-di-AMP dropped sharply. Finally, inoculation of ESAT-6:c-di-AMP led to significant reduction of bacterial burdens in lungs and spleens of immunized mice. Our results demonstrated that subunit vaccine ESAT-6:c-di-AMP could elicit innate and adaptive immune responses which provided protection against Mtb challenge, and c-di-AMP as a mucosal adjuvant could enhance immunogenicity of antigen, especially for innate immunity, which might be used for new mucosal vaccine against TB.

Microwave-assisted synthesis of porous and hollow α-Fe2O3/LaFeO3 nanostructures for acetone gas sensing as well as photocatalytic degradation of methylene blue.

To address the urgent issues of hazardous gas detection and the prevention of environmental pollution, various functional materials for gas sensing and catalytic reduction have been studied. Specifically, the p-type perovskite LaFeO3 has been studied widely because of its promising physicochemical properties. However, there remains several problems to develop a controllable synthesis of LaFeO3-based p-n heterojunctions. In this work, α-Fe2O3 was further compounded with LaFeO3 to form a porous and hollow α-Fe2O3/LaFeO3 heterojunction to improve its gas-sensing performance and photocatalytic efficiency via a microwave-assisted hydrothermal method. While evaluated as sensors of acetone gas, the optimized sample exhibits excellent performance, including a high response (48.3), excellent selectivity, good reversibility, fast response, and recovery ability. Furthermore, it is an efficient catalyst for the degradation of methylene blue. This can be attributed to the enhancement effect of its larger specific surface area, fast diffusion, enhanced surface activities, and p-n heterojunction. Additionally, this work provides a rapid and rational synthesis strategy to produce metal oxides with both enhanced gas-sensing performance and improved photocatalytic properties.

Ultrasensitive xylene gas sensor based on flower-like SnO2/Co3O4 nanorods composites prepared by facile two-step synthesis method.

Xylene is a volatile organic compound which is harmful to the human health and requires precise detection. The detection of xylene by an oxide semiconductor gas sensor is an important research direction. In this work, Co3O4 decorated flower-like SnO2 nanorods (SnO2/Co3O4 NRs) were synthesized by a simple and effective two-step method. The SnO2/Co3O4 NRs show high xylene response (R g/R a = 47.8 for 100 ppm) and selectivity at the operating temperature of 280 °C, and exhibit high stability in continuous testing. The resulting SnO2/Co3O4 NRs nanocomposites show superior sensing performance towards xylene in comparison with pure SnO2 nanorods. The remarkable enhancement in the gas-sensing properties of SnO2/Co3O4 NRs are attributed to larger specific surface area and the formation of p-n heterojunction between Co3O4 and SnO2. These results demonstrate that particular nanostructures and synergistic effect of SnO2 and Co3O4 enable gas sensors to selectively detect xylene.

Ag Nanoparticles Sensitized In2O3 Nanograin for the Ultrasensitive HCHO Detection at Room Temperature.

Formaldehyde (HCHO) is the main source of indoor air pollutant. HCHO sensors are therefore of paramount importance for timely detection in daily life. However, existing sensors do not meet the stringent performance targets, while deactivation due to sensing detection at room temperature, for example, at extremely low concentration of formaldehyde (especially lower than 0.08 ppm), is a widely unsolved problem. Herein, we present the Ag nanoparticles (Ag NPs) sensitized dispersed In2O3 nanograin via a low-fabrication-cost hydrothermal strategy, where the Ag NPs reduces the apparent activation energy for HCHO transporting into and out of the In2O3 nanoparticles, while low concentrations detection at low working temperature is realized. The pristine In2O3 exhibits a sluggish response (Ra/Rg = 4.14 to 10 ppm) with incomplete recovery to HCHO gas. After Ag functionalization, the 5%Ag-In2O3 sensor shows a dramatically enhanced response (135) with a short response time (102 s) and recovery time (157 s) to 1 ppm HCHO gas at 30 °C, which benefits from the Ag NPs that electronically and chemically sensitize the crystal In2O3 nanograin, greatly enhancing the selectivity and sensitivity.

Design of ultrasensitive Ag-LaFeO3 methanol gas sensor based on quasi molecular imprinting technology.

An ultrasensitive methanol gas sensing device based on the quasi-molecular imprinting technology (quasi-MIT) is studied in this work. We applied the sol-gel method (ALS denotes Ag-LaFeO3 prepared by the sol-gel method) and combustion synthesis (ALC denotes Ag-LaFeO3 prepared by combustion synthesis) to prepare Ag-LaFeO3 based sensors. The morphologies and structures of the Ag-LaFeO3 materials were examined via various detection techniques. The ALSM and ALCM sensor (ALSM and ALCM denotes the devices prepared by coating the ALS and ALC materials with methanol, respectively) fabricated using the sol-gel method and combustion synthesis combined with quasi-MIT exhibit good gas sensing properties to methanol, in contrast with the two devices (ALSW and ALCW denote the devices prepared for coating the ALS and ALC materials with water, respectively) without the use of quasi-MIT. The results show that quasi-MIT introduced the target gas in the fabrication process of the device, playing an important role in the design of the ultrasensitive methanol gas sensor. The sensing response and the optimum working temperature of ALSM and ALCM gas sensor are 52.29 and 155 °C and 34.89 and 155 °C, respectively, for 5 ppm methanol, and the highest response to other gases is 8. The ALSM and ALCM gas sensors reveal good selectivity and response for methanol.

Identification, Characterization and Expression of Methuselah-Like Genes in Dastarcus helophoroides (Coleoptera: Bothrideridae).

Dastarcus helophoroides, which has a relatively longer lifespan compared to other insects, is one of the most effective natural enemies of many large-body long-horned beetles. Methuselah (Mth) is associated with the lifespan, stress resistance, and reproduction in Drosophila melanogaster, but Mth is not present in non-drosophiline insects. A number of methuselah-like genes (mth-likes, mthls) have been identified in non-drosophiline insects, but it is still unknown whether they are present in Dastarcus helophoroides. We identified three novel mth-like genes in D. helophoroides: mth-like1, mth-like2, and mth-like5, and carried out bioinformatic analysis based on the full-length nucleic acid sequences and deduced amino acid sequences. Real-time quantitative polymerase chain reaction (RT-qPCR) showed variations in expression patterns of mth-like genes in different tissues (highly expressed in reproductive systems) and at different developmental stages, indicating that mth-likes were likely be involved in reproduction and development. The altered mRNA expression in aging adults and under oxidation, high temperature, and starvation stress, indicated that mth-like genes were likely to be involved in aging and the resistance of oxidation, high temperature, and starvation. These results characterize, for the first time, the basic properties of three mth-like genes from D. helophoroides that probably play important roles in development, aging, reproduction, and stress resistance.

A myrsinol diterpene isolated from a traditional herbal medicine, LANGDU reverses multidrug resistance in breast cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: LANGDU, a Chinese traditional herbal medicine, was the dried roots of Euphorbia prolifera Buch-Ham. The herbal medicine has been used as anti-cancer and anti-inflammatory drug in local folk medicine for several hundred years. AIM OF THE STUDY: P-glycoprotein (P-gp) is a transmembrane exporter, which can expel a variety of anti-cancer drugs. Over-expressed P-glycoprotein in cancer cells impairs the effect of cancer chemotherapy and results in multidrug resistance (MDR). To elucidate the effect of LANGDU on MDR cancer cells, the constituents of Euphorbia prolifera Buch-Ham were analyzed. We found that a myrsinol diterpene, J196-10-1 could reverse multidrug resistance. MATERIALS AND METHODS: Cytotoxicity assays were performed to measure reversal efficiency of J196-10-1. Efflux assay, ATPase assay, and real-time PCR were used to elucidate the mechanism of the chemical. RESULTS: J196-10-1 could reverse the resistance to daunorubicin, vincristine, and topotecan effectively. The diterpene inhibited P-gp mediated efflux and did not alter transcription of the target gene significantly. The compound stimulated ATP hydrolysis at a low concentration and inhibited it at a high concentration. CONCLUSIONS: J196-10-1 inhibits P-gp competitively and reverses P-gp induced MDR in breast cancer cells.

Coxsackievirus B3 Induces Autophagic Response in Cardiac Myocytes in vivo.

Viral myocarditis is a common disease that contributes to dilated cardiomyopathy or heart failure. Coxsackievirus B (CVB) is one of the major causative pathogens of viral myocarditis. Previous studies have shown that autophagy is exploited to promote CVB replication in cell lines. To study whether cardiac myocytes respond to CVB infection in a similar way, viral myocarditis was established by the inoculation of 3-week-old BALB/c mice with CVB3. Electron microscopic observation showed that autophagosome-like vesicles were induced in the cardiac myocytes of mice infected by CVB3 at 3, 5, and 7 days after viral infection. The lipidated microtubule-associated protein 1 light chain 3 (LC3), LC3-II, was also significantly increased in both myocardium and the cardiac myocytes extracted from the ventricles of mice infected with CVB3. The increased LC3-II coincided with high level of viral RNA and proteins in both myocardium and isolated cardiac myocytes. Moreover, viral protein synthesis was significantly decreased in primary cardiac myocytes by the treatment with 3-methyladenine, an inhibitor of autophagy. The expression and the phosphorylation of extracellular signal regulated kinase (ERK) were also increased in both myocardium and in the isolated cardiac myocytes of the virus-infected mice, while the interplay of ERK with autophagic response remains to be studied. This study demonstrated that cardiac myocytes respond to CVB3 infection by increased formation of autophagosomes in vivo, which might be exploited for viral replication.

The mitochondrial genome of Dastarcus helophoroides (Coleoptera: Bothrideridae) and related phylogenetic analyses.

The complete mitochondrial genome of Dastarcus helophoroides (Coleoptera: Bothrideridae) which consists of 13 PCGs, 22 tRNA genes, two rRNA genes and a non-coding region (D-loop), is sequenced for its nucleotide sequence of 15,878 bp (GenBank: KF811054.1). The genome has a typical gene order which is identical to other Coleoptera species. Except for COI gene generally starts with non-canonical initial codon, all protein-coding genes start with ATN codon and terminate with the stop codon TA(A) or TAG. The secondary structure of rrnL and rrnS consists of 48 helices (contains four newly proposed helices) and 35 helices (contains two newly proposed helices) respectively. All 22 tRNAs in D. helophoroides are predicted to fold into typical cloverleaf secondary structure, except trnS1 (AGN), in which the dihydrouracil arm (DHU arm) could not form stable stem-loop structure. Thirteen protein-coding genes (nucleotide dataset and nucleic acid dataset) of the available species (29 taxa) have been used to infer the phylogenetic relationships among these orders. Tenebrionoidea and Cucujoidea form a sister group, and D. helophoroides is classified into Cucujoidea (Bothrideridae). The study first research on the phylogenetic analyses involving to the D. helophoroides mitogenome, and the results strongly bolster the current morphology-based hypothesis.

TiCl4 promoted formal [3 + 3] cycloaddition of cyclopropane 1,1-diesters with azides: synthesis of highly functionalized triazinines and azetidines.

A TiCl4 promoted formal [3 + 3] cycloaddition of cyclopropane 1,1-diesters with azides has been developed for the synthesis of highly functionalized triazinines. Both stoichiometric and substoichiometric versions of this reaction were accomplished dependent on the choice of solvent. It is noteworthy that the corresponding products could be easily converted to biologically important azetidines by simple thermolysis.