Construction of a nomogram with IrAE and clinic character to predict the survival of advanced G/GEJ adenocarcinoma patients undergoing anti-PD-1 treatment.

Objective: This study aimed to develop and validate a survival prediction model and nomogram to predict survival in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma undergoing treatment with anti-programmed cell death 1 receptor (PD-1). This model incorporates immune-related adverse events (irAEs) alongside common clinical characteristics as predictive factors. Method: A dataset comprising 255 adult patients diagnosed with advanced G/GEJ adenocarcinoma was assembled. The irAEs affecting overall survival (OS) to a significant degree were identified and integrated as a candidate variable, together with 12 other candidate variables. These included gender, age, Eastern cooperative oncology group performance status (ECOG PS) score, tumor stage, human epidermal growth factor receptor 2 (HER2) expression status, presence of peritoneal and liver metastases, year and line of anti-PD-1 treatment, neutrophil-to-lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and Charlson comorbidity index (CCI). To mitigate timing bias related to irAEs, landmark analysis was employed. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression to pinpoint significant predictors, and the variance inflation factor was applied to address multicollinearity. Subsequently, a Cox regression analysis utilizing the forward likelihood ratio method was conducted to develop a survival prediction model, excluding variables that failed to satisfy the proportional hazards (PH) assumption. The model was developed using the entire dataset, then internally validated through bootstrap resampling and externally validated with a cohort from another Hospital. Furthermore, a nomogram was created to delineate the predictive model. Results: After consolidating irAEs from the skin and endocrine systems into a single protective irAE category and applying landmark analysis, variable selection was conducted for the prognostic prediction model along with other candidate variables. The finalized model comprised seven variables: ECOG PS score, tumor stage, HER2 expression status in tumor tissue, first-line anti-PD-1 treatment, peritoneal metastasis, CONUT score, and protective irAE. The overall concordance index for the model was 0.66. Calibration analysis verified the model's accuracy in aligning predicted outcomes with actual results. Clinical decision curve analysis indicated that utilizing this model for treatment decisions could enhance the net benefit regarding 1- and 2-year survival rates for patients. Conclusion: This study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

DRAC 2022: A public benchmark for diabetic retinopathy analysis on ultra-wide optical coherence tomography angiography images.

We described a challenge named "DRAC - Diabetic Retinopathy Analysis Challenge" in conjunction with the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2022). Within this challenge, we provided the DRAC datset, an ultra-wide optical coherence tomography angiography (UW-OCTA) dataset (1,103 images), addressing three primary clinical tasks: diabetic retinopathy (DR) lesion segmentation, image quality assessment, and DR grading. The scientific community responded positively to the challenge, with 11, 12, and 13 teams submitting different solutions for these three tasks, respectively. This paper presents a concise summary and analysis of the top-performing solutions and results across all challenge tasks. These solutions could provide practical guidance for developing accurate classification and segmentation models for image quality assessment and DR diagnosis using UW-OCTA images, potentially improving the diagnostic capabilities of healthcare professionals. The dataset has been released to support the development of computer-aided diagnostic systems for DR evaluation.

Crizotinib loaded polydopamine-polylactide-TPGS nanoparticles in targeted therapy for non-small cell lung cancer.

To evaluate the effect and safety of crizotinib loaded polydopamine-polylactide-TPGS nanoparticles (CZT/pD-PT NPs) on non-small cell lung cancer (NSCLC). CZT/pD-PT NPs were synthesized and characterized, and their effects on PC-9 cell viability and apoptosis were determined. In vivo experiment was further performed to evaluate the anti-NSCLC efficacy of CZT/pD-PT NPs. TUNEL assay and Western blot were respectively applied for the determination of cell apoptosis and apoptosis-related protein expression, while liver function-related index expression detection and liver histopathological detection were used to evaluate the hepatotoxicity of CZT/pD-PT NPs. Compared with free CZT, CZT/pD-PT NPs had a sustained-release effect and promoted the cellular uptake of CZT. In addition, CZT/pD-PT NPs significantly inhibited PC-9 cell viability and promoted cell apoptosis both in vitro and in vivo, exhibiting superior cytotoxicity. At the same time, CZT/pD-PT NPs had no significant effect on liver tissue morphology and liver function-related indicators such as ALP, ALT, AST, and DBIL. CZT/pD-PT NPs have excellent anti-NSCLC effect with low hepatotoxicity, which can be served as a novel drug delivery system to improve the efficacy of chemotherapy for NSCLC.

Origin of Excellent Charge Storage Properties of Defective Tin Disulphide in Magnesium/Lithium-Ion Hybrid Batteries.

Lithium-ion batteries (LIBs) are excellent electrochemical energy sources, albeit with existing challenges, including high costs and safety concerns. Magnesium-ion batteries (MIBs) are one of the potential alternatives. However, the performance of MIBs is poor due to their sluggish solid-state Mg2+ diffusion kinetics and severe electrode polarizability. Rechargeable magnesium-ion/lithium-ion (Mg2+/Li+) hybrid batteries (MLHBs) with Mg2+ and Li+ as the charge carriers create a synergy between LIBs and MIBs with significantly improved charge transport kinetics and reliable safety features. However, MLHBs are yet to reach a reasonable electrochemical performance as expected. This work reports a composite electrode material with highly defective two-dimensional (2D) tin sulphide nanosheets (SnSx) encapsulated in three-dimensional (3D) holey graphene foams (HGF) (SnSx/HGF), which exhibits a specific capacity as high as 600 mAh g-1 at 50 mA g-1 and a compelling specific energy density of ~ 330 Wh kg-1. The excellent electrochemical performance surpasses previously reported hybrid battery systems based on intercalation-type cathode materials under comparable conditions. The role played by the defects in the SnSx/HGF composite is studied to understand the origin of the observed excellent electrochemical performance. It is found that it is closely related to the defect structure in SnSx, which offers percolation pathways for efficient ion transport and increased internal surface area assessable to the charge carriers. The defective sites also absorb structural stress caused by Mg2+ and Li+ insertion. This work is an important step towards realizing high-capacity cathode materials with fast charge transport kinetics for hybrid batteries.

Improvement of O/W emulsion performance by adjusting the interaction between gelatin and bacterial cellulose nanofibrils.

This study was designed to improve the stability of medium internal phase emulsion by adjusting the electrostatic interaction between gelatin (GLT) and TEMPO-oxidized bacterial cellulose nanofibrils (TOBC). The influences of polysaccharide-protein ratio (1:10, 1:5, and 1:2.5) and pH (3.0, 4.7, 7.0, and 11.0) on the emulsion properties were investigated. The droplet size of TOBC/GLT-stabilized emulsion was increased with the TOBC proportion increasing at pH 3.0-11.0. Additionally, emulsion had a larger droplet size at pH 4.7 (the electrical equivalence point pH of mixtures). However, the addition of TOBC significantly improved the emulsion stability. The emulsions prepared with TOBC/GLT mixtures (mixing ratio of 1:2.5) at pH 3.0-7.0 were stable without creaming during the storage. It was because the formation of nanofibrils network impeded the droplet mobility, and the emulsion viscosity and viscoelastic modulus were increased with the addition of TOBC. These findings were meaningful to modulate the physical properties of emulsions.

Multicenter assessment of shotgun metagenomics for pathogen detection.

BACKGROUND: Shotgun metagenomics has been used clinically for diagnosing infectious diseases. However, most technical assessments have been limited to individual sets of reference standards, experimental workflows, and laboratories. METHODS: A reference panel and performance metrics were designed and used to examine the performance of shotgun metagenomics at 17 laboratories in a coordinated collaborative study. We comprehensively assessed the reliability, key performance determinants, reproducibility, and quantitative potential. FINDINGS: Assay performance varied significantly across sites and microbial classes, with a read depth of 20 millions as a generally cost-efficient assay setting. Results of mapped reads by shotgun metagenomics could indicate relative and intra-site (but not absolute or inter-site) microbial abundance. INTERPRETATION: Assay performance was significantly impacted by the microbial type, the host context, and read depth, which emphasizes the importance of these factors when designing reference reagents and benchmarking studies. Across sites, workflows and platforms, false positive reporting and considerable site/library effects were common challenges to the assay's accuracy and quantifiability. Our study also suggested that laboratory-developed shotgun metagenomics tests for pathogen detection should aim to detect microbes at 500 CFU/mL (or copies/mL) in a clinically relevant host context (10^5 human cells/mL) within a 24h turn-around time, and with an efficient read depth of 20M. FUNDING: This work was supported by National Science and Technology Major Project of China (2018ZX10102001).

Tannin foam immobilized with ferric ions for efficient removal of ciprofloxacin at low concentrations.

The presence of ciprofloxacin (CIP) in natural water may cause potential threats to the environment. Adsorption is a convenient and efficient method to remove CIP from aqueous solution. Bayberry tannin (BT), a natural polyphenol, has been utilized in the synthesis of tannin foam (TF) due to its abundant polyphenolic hydroxyls to chelate with metal ions. The obtained TF was subsequently immobilized with Fe3+ via a facile chelative adsorption to fabricate functional tannin foam (TF-Fe), which was highly porous, with a porosity of 78.93%. The Fe species in the TF-Fe featured good dispersity, which were active for chelative adsorption of CIP. The adsorption of CIP on the TF-Fe was a pH-dependent process. At the optimized pH of 7.0, the TF-Fe provided the adsorption capacity of 91.8 mg g-1. When applied in removal of CIP at the low concentration of 2.0 µg mL-1, a high removal efficiency of 96.60% was still obtained, which was superior to commercial activated carbon (28.78%). The adsorption kinetics were well fitted by the pseudo-second-order rate model while the adsorption isotherms were well described by the Langmuir model. The TF-Fe was capable of recycling, which still maintained a high removal efficiency of 92.25% in the 5th cycle.

Blood Pressure Variability during Angiography in Patients with Ischemic Stroke and Intracranial Artery Stenosis.

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge.

Oleogel Films Through the Pickering Effect of Bacterial Cellulose Nanofibrils Featuring Interfacial Network Stabilization.

As bio-based food packaging materials promise a more sustainable future, this work fabricated edible oleofilms by casting beeswax-in-water Pickering emulsions, which were formed by the physical hybrid particles of bacterial cellulose nanofibrils (BCNFs) and carboxymethyl chitosan (CCS) (BC/CCS). The emulsion droplet size was varied from 4 to 9 µm, and the emulsion index (EI) was all up to 100%. The obtained emulsions exhibited excellent long-term stability, and there was no change in the EI (100%) after the storage of the emulsion for 3 months. Moreover, the environmental temperature had almost no impact on the droplet size and EI of the emulsion. The mechanical properties of the oleofilms were significantly improved by enhancing the content of BC/CCS. There was also a visual reduction in the water vapor permeability (WVP) value, which was lower than 1.1 × 10-7 g·m-1·h-1·Pa-1. Furthermore, the obtained oleofilms exhibited a notable improvement in surface hydrophobicity, and surprisingly, it could be easily redispersed into water to recover back to the emulsion state without additional high energy mixing. This suggested that this edible oleofilm was prepared by a fully green method by casting Pickering emulsions stabilized by BC/CCS and could extend its application for the development of food-grade coating materials.

DNA Methylation Analysis Identifies Differentially Methylated Sites Associated with Early-Onset Intracranial Atherosclerotic Stenosis.

AIM: Studies have suggested that genetic and environmental factors do not account for all risks and mechanisms of intracranial atherosclerotic stenosis (ICAS). DNA methylation may play a role in the progression of ICAS. METHODS: DNA methylation profiles of peripheral blood leucocytes from 7 patients with early-onset ICAS and 7 perfectly matched controls were interrogated for the first time using the Illumina Infinium Human MethylationEPIC BeadChip. Afterward, functional analysis for differentially methylated genes was conducted. In addition, pyrosequencing verification was performed in an independent cohort comprising 21 patients with early-onset ICAS and 21 age- and gender-matched controls. RESULTS: A total of 318 cytosine-phosphate-guanine sites were found to be differentially methylated based on the established standards. Functional analysis annotated differentially methylated sites to atherosclerosis-related processes and pathways, such as the negative regulation of hydrolase activity (GO 0051346), type II diabetes mellitus (KEGG hsa04930), and the insulin signaling pathway (KEGG hsa04910). In addition, a differentially methylated site was also validated, cg22443212 in gene Rnf213, which showed significant hypermethylation in patients with early-onset ICAS compared with controls 59.56% (49.77%, 88.55%) vs. 44.65% (25.07%, 53.21%), respectively; P=0.010). Receiver operating characteristic curve analysis showed that the area under the curve value of cg22443212 was 0.744 (95% confidence interval, 0.586-0.866; P=0.002). CONCLUSIONS: We revealed that altered DNA methylation may play a role in the occurrence and development of ICAS. These results provided new epigenetic insights into ICAS.

Lack of Correlation Between Intracranial Carotid Artery Modified Woodcock Calcification Score and Prognosis of Patients With Acute Ischemic Stroke After Intravenous Thrombolysis.

There have been few studies about the association between intracranial carotid artery calcification (ICAC) and acute ischemic stroke (AIS) prognosis after intravenous thrombolysis (IVT). We aimed to analyze the association between ICAC and prognosis (including symptomatic intracranial hemorrhage (sICH), functional outcome and death) of AIS patients treated with IVT. In this retrospective study, we consecutively included 232 AIS patients treated with IVT between April 2012 and December 2018. ICAC was evaluated using the modified Woodcock calcification visual score on non-enhanced cranial computed tomography scans. Poor functional outcome was defined as a modified Rankin Scale score > 2 at 3 months. We found that the modified Woodcock calcification score was associated with ICH, poor outcome, and death in univariable analyses on the symptomatic side and/or bilaterally. However, after adjustment for other different covariates, the results showed no significant difference. We documented that the presence and severity of ICAC did not significantly modify the beneficial effects of rtPA treatment in AIS.

Previous chronic symptomatic and asymptomatic cerebral hemorrhage in patients with acute ischemic stroke.

PURPOSE: Identifying previous chronic cerebral hemorrhage (PCH), especially asymptomatic cases in patients with ischemic stroke, is essential for proper antithrombotic management. The study aimed to further clarify the prevalence of PCH and the associated factors in patients with acute ischemic stroke using multi-modal neuroimaging including susceptibility-weighted MR imaging (SWI). METHODS: This was a retrospective cross-sectional study of 382 patients with acute ischemic stroke. All patients underwent 3.0-T MRI for cranial SWI, 1.5-T or 3.0-T conventional cranial MRI, and cranial CT. Patients found with PCH were matched 1:4 with patients without PCH. Clinical manifestation, computed tomography, conventional cranial MRI, and cranial SWI were used to determine PCH. Clinical and neuroimaging findings between the patients with symptomatic vs. asymptomatic PCH were compared. RESULTS: Thirty-six patients (36/382, 9.4%) were determined to have had a PCH. Of these 36 patients, 17 (17/36, 47.2%, or 17/382, 4.5%) had asymptomatic PCH. Multivariable analysis showed that serum total cholesterol (OR = 0.510, 95%CI 0.312-0.832, P = 0.007), cerebral microbleeds (OR = 6.251, 95%CI 2.220-17.601, P = 0.001), and antithrombotic drugs history (OR = 3.213, 95%CI 1.018-10.145, P = 0.047) were independently associated with PCH. Asymptomatic PCH had similar clinical and neuroimaging characteristics with symptomatic PCH. CONCLUSION: PCH is not uncommon in acute ischemic stroke patients. Total serum cholesterol, cerebral microbleeds on SWI, and history of antithrombotic drugs were independently associated with PCH in patients with acute ischemic stroke. Asymptomatic PCH, which is easier to be missed and has similar characteristics with symptomatic PCH, should draw much attention.

Brain functional changes in patients with botulism after illegal cosmetic injections of botulinum toxin: A resting-state fMRI study.

BACKGROUND: Botulinum toxin type A (BoNT-A) is generally considered safe and is widely used to treat a variety of clinical conditions involving muscle hyperactivity and for cosmetic purposes. However, the effects of BoNT-A poisoning (botulism) on brain function are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we investigated brain functions in 9 patients who received illegal cosmetic injections of botulinum and 18 matched controls by combining the analysis methods of regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI. Compared with the controls, the patients with botulism exhibited significantly reduced ReHo values in the left posterior lobe of the cerebellum extending to the right anterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum extending to the parahippocampal gyrus and right posterior lobe of the cerebellum. The patients with botulism also showed weakened ALFF values in the right anterior lobe of the cerebellum extending to the left anterior lobe of the cerebellum and right posterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum. CONCLUSIONS/SIGNIFICANCE: The results indicate that BoNT-A may modulate cerebral activation in specific areas, which may play roles in both the adverse effects of botulism and the mechanism underlying clinical treatment with BoNT-A.

Insight into resistance mechanism of anaplastic lymphoma kinase to alectinib and JH-VIII-157-02 caused by G1202R solvent front mutation.

BACKGROUND: Mutated anaplastic lymphoma kinase (ALK) drives the development of advanced non-small cell lung cancer (NSCLC). Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02), which demonstrated potent effects against the G1202R mutation. METHODS: Molecular docking, conventional molecular dynamics (MD) simulations, free energy calculations, and umbrella sampling (US) simulations were carried out to make clear the principles of the binding preferences of alectinib and JH-VIII-157-02 toward ALKWT and the ALK G1202R (ALKG1202R) mutation. RESULTS: JH-VIII-157-02 has similar binding affinities to both ALKWT and ALKG1202R whereas it has has a much lower binding affinity for alectinib to ALKG1202R. Analysis of individual energy terms indicate the major variation involves the van der Waals and entropy terms. Structural analysis reveals that the conformational change of the ATP-binding glycine-rich loop was primarily responsible for the alectinib resistance, not JH-VIII-157-02. In addition, US simulations prove JH-VIII-157-02 has similar dissociative processes from both ALKWT and ALKG1202R, while alectinib is more easily dissociated from ALKG1202R than from ALKWT, thus indicating lesser residence time. CONCLUSION: Both the binding affinity and the drug residence time should be emphasized in rational drug design to overcome the G1202R solvent front mutation in ALK resistance.

Rivaroxaban does not influence hemorrhagic transformation in a diabetes ischemic stroke and endovascular thrombectomy model.

Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.

LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR-193a/MCL1 pathway.

Although dexamethasone (DEX) remains a first-line agent for multiple myeloma (MM) therapy, the development of DEX resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to DEX. This study demonstrated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) was highly expressed in DEX-resistant myeloma cell lines, and upregulation of NEAT1 was tightly linked to poor prognosis. The in-depth study revealed that during the development of DEX resistance in these cells, the miR-193a levels were decreased, which resulted in the increased expression of the target gene myeloid cell leukemia-1 (MCL1). We also found knockdown of NEAT1, the DEX-induced sensitivity was enhanced in the resistant cells. Meanwhile, overexpression of NEAT1 increased the DEX-induced resistance in the sensitive cells. In conclusion, the NEAT1/miR-193a/MCL1 pathway is closely associated with the development of DEX resistance in myeloma cells, and knockdown of NEAT1 can significantly improve DEX sensitivity in MM.

The Posterior Insula Shows Disrupted Brain Functional Connectivity in Female Migraineurs Without Aura Based on Brainnetome Atlas.

Long-term headache attacks may cause human brain network reorganization in patients with migraine. In the current study, we calculated the topologic properties of functional networks based on the Brainnetome atlas using graph theory analysis in 29 female migraineurs without aura (MWoA) and in 29 female age-matched healthy controls. Compared with controls, female MWoA exhibited that the network properties altered, and the nodal centralities decreased/increased in some brain areas. In particular, the right posterior insula and the left medial superior occipital gyrus of patients exhibited significantly decreased nodal centrality compared with healthy controls. Furthermore, female MWoA exhibited a disrupted functional network, and notably, the two sub-regions of the right posterior insula exhibited decreased functional connectivity with many other brain regions. The topological metrics of functional networks in female MWoA included alterations in the nodal centrality of brain regions and disrupted connections between pair regions primarily involved in the discrimination of sensory features of pain, pain modulation or processing and sensory integration processing. In addition, the posterior insula decreased the nodal centrality, and exhibited disrupted connectivity with many other brain areas in female migraineurs, which suggests that the posterior insula plays an important role in female migraine pathology.

Overexpressing key component genes of the secretion pathway for enhanced secretion of an Aspergillus niger glucose oxidase in Trichoderma reesei.

Vast interest exists in developing T. reesei for production of heterologous proteins. Although rich genomic and transcriptomic information has been uncovered for the T. reesei secretion pathway, little is known about whether engineering its key components could enhance expression of a heterologous gene. In this study, snc1, a v-SNARE gene, was first selected for overexpression in T. reesei. In engineered T. reesei with additional copies of snc1, the Aspergillus niger glucose oxidase (AnGOD) was produced to a significantly higher level (2.2-fold of the parental strain). hac1 and bip1, two more component genes in the secretion pathway, were further tested for overexpression and found to be also beneficial for AnGOD secretion. The overexpression of one component gene more or less affected the expression of the other two genes, suggesting a complex regulating mechanism. Our study demonstrates the potential of engineering the secretion pathway for enhancing heterologous gene production in T. reesei.

Assessment of gray and white matter structural alterations in migraineurs without aura.

BACKGROUND: Migraine constitute a disorder characterized by recurrent headaches, and have a high prevalence, a high socio-economic burden and severe effects on quality of life. Our previous fMRI study demonstrated that some brain regions are functional alterations in migraineurs. As the function of the human brain is related to its structure, we further investigated white and gray matter structural alterations in migraineurs. METHODS: In current study, we used surface-based morphometry, voxel-based morphometry and diffusion tensor imaging analyses to detect structural alterations of the white matter and gray matter in 32 migraineurs without aura compared with 32 age- and gender-matched healthy controls. RESULTS: We found that migraineurs without aura exhibited significantly increased gray matter volume in the bilateral cerebellar culmen, increased cortical thickness in the lateral occipital-temporal cortex, decreased cortical thickness in the right insula, increased gyrification index in left postcentral gyrus, superior parietal lobule and right lateral occipital cortex, and decreased gyrification index in the left rostral middle frontal gyrus compared with controls. No significant change in white matter microstructure was found in DTI analyses. CONCLUSION: The significantly altered gray matter brain regions were known to be associated with sensory discrimination of pain, multi-sensory integration and nociceptive information processing and were consistent with our previous fMRI study, and may be involved in the pathological mechanism of migraine without aura.