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Abstract Background Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. Methods DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. Results 1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. Conclusions The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.

Abstract Background Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease (DKD). This study explored the value of noninvasively measuring lens AGEs to diagnose and evaluate the severity of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM). Methodology A total of 134 T2DM patients admitted to the Fifth People's Hospital of Shanghai from March 2020 to May 2021 were selected randomly. Patients were divided into low-, medium-and high-risk groups according to the risk assessment criteria for DKD progression and into DKD and non-DKD (non-DKD) groups according to the Guidelines for the Prevention and Treatment of Diabetic Nephropathy in China. The concentrations of noninvasive AGEs in the lens in all the groups were retrospectively analyzed. Results The concentration of noninvasive lens AGEs in the high-risk patients, according to the 2012 guidelines of the Global Organization for Improving the Prognosis of Kidney Diseases, was significantly higher than that in the remaining groups. Regression analysis suggested the value of lens AGEs in diagnosing DKD and evaluating DKD severity. Cox regression analysis indicated that the noninvasive lens AGE concentration was positive correlated with the course of disease. Conclusion The receiver operating characteristic (ROC) curve suggested that using noninvasive lens AGE measurements has clinical value in the diagnosis of DKD (area under the curve 62.4%,95% confidence interval (CI) 52.4%–73.9%, p = 0.014) and in assessing the severity of DKD (area under the curve 83.2%, 95% CI 74.1%–92.3%, P

Abstract With the popularity of smart devices, people pay more attention to the experience of text input. The authors propose an in‐air digit input system, namely UltraDigit, which enables users to input digits in the air using acoustic signal via transfer learning. Different from other technologies, UltraDigit can obtain the finger movement through a speaker and a microphone built in the smartphone, which does not need the assistance of other hardware. In addition, the authors use the idea of transfer learning with a small amount of data to train classification model, which achieves good performance with low training cost (such as time cost and data cost). Experimental results show the average accuracy of digit recognition is 92.9%, which verifies the validity of the ultrasound signal‐based contactless digit input.

Abstract Objective Colorectal cancer (CRC) is a commonly diagnosed human malignancy worldwide. Both epithelial‐mesenchymal transition (EMT) and N6‐methyladenosine (m6A) modification play a crucial role in CRC development. This study aimed to construct a prognostic signature based on the genes related to EMT and m6A modification. Method Firstly, the mRNA expression profiling of CRC tissues was analyzed using TCGA and GEO databases. The prognostic hub genes related to EMT and m6A modification were selected using weighted correlation network and cox regression analysis. The prognostic signature was constructed based on hub genes, followed by validation in three external cohorts. Finally, the expression of the representative hub gene was detected in clinical samples, and its biological role was investigated using assays in vivo and in vitro. Results A prognostic signature was constructed using the following genes: YAP1, FAM3C, NUBPL, GLO1, JARID2, NFKB1, CDKN1B, HOOK1, and GIPC2. The signature effectively stratified the clinical outcome of CRC patients in the training cohort and two validation cohorts. The subgroup analysis demonstrated the signature could identify high‐risk population from CRC patients within stage I‐II or III‐IV, female, male and elder patients. The signature was correlated with the infiltration of some immune cells (such as macrophage and regulatory T cells) and gene mutation counts. Finally, the hub gene GIPC2 was found to be downregulated in CRC tissues and most CRC cells lines. GIPC2 overexpression inhibited the malignant characteristics of CRC cells in vitro and in vivo through upregulating E‐cadherin and downregulating N‐cadherin, Vimentin, and Snail, while the opposite results were observed for GIPC2 knockdown in CRC cells. Conclusion Our present study for the first time constructed a novel prognostic signature related to EMT, m6A modification, and immune infiltration for CRC risk stratification. In addition, GIPC2 is identified as a promising clinical biomarker or therapeutical target for CRC.

BackgroundPrognostic nutritional index (PNI) has been identified as a reliable prognostic factor for cancer adjuvant therapy. However, its prognostic value in lung cancer patients receiving immune checkpoint inhibitors (ICIs) remains inconclusive.MethodA systematic literature review and meta-analysis was performed based on online databases before March 1th 2023. The correlation of PNI with overall survival (OS) or progression-free survival (PFS) was determined using the hazard ratios (HRs) coupled with 95% confidence intervals (CIs). Then, a retrospective cohort enrolling 123 ICI-treated lung cancer patients from two hospitals was utilized for validation and further investigation.ResultsA total of 14 studies enrolling 1,260 lung cancer patients were included in the meta-analysis. The high PNI level was significantly correlated with better OS (HR = 2.56, 95% CI = 1.86–3.54) and PFS (HR = 1.91, 95% CI = 1.53–2.40) of the lung cancer patients. The subgroup analysis confirmed the results except for the PFS in patients receiving anti-PD-1 therapy (HR = 1.51, 95% CI = 0.86–2.65). In the retrospective study, the high PNI level was identified as a favorable factor for OS and PFS not only in the whole cohort but also in the subgroups stratified by non-small cell lung cancer and small cell lung cancer. The high PNI was also correlated with better anti-cancer therapy response and performed better than body mass index and serum albumin level in OS prediction. Finally, we established a novel prognostic nomogram based on PNI and other clinical parameters. The nomogram was found to perform well in predicting the 1-year OS of ICI-treated lung cancer patients.ConclusionBoth the meta-analysis and retrospective work demonstrate the PNI is a reliable prognostic factor for advanced lung cancer patients receiving ICI-based therapies. Our study further highlights the crucial role of nutrition assessment and intervention in cancer immunotherapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42023424146.

Abstract For the power generation system of wind, photovoltaic, hydro, thermal and out‐purchased electricity, taking the minimum economic cost of thermal power generation as the objective function, an optimal dispatching model including the complementary system of wind‐photovoltaic‐hydro‐thermal‐out purchased electricity is proposed. The power balance and renewable energy accommodation are prerequisites, thermal power unit maintenance plans and various constraints are considered. The improved multi‐objective cuckoo search algorithm was used for short‐term scheduling, and the proposed hybrid firefly and particle swarm optimization was used for mid‐long term scheduling. The results show that the two algorithms can be effectively applied to the short‐term and mid‐long term joint optimal scheduling problem of wind, photovoltaic, hydro, thermal and out‐purchased electricity. It makes the power grid arrange the unit output reasonably, ensure the security and stability operation. It can better absorb renewable energy, reduces coal consumption and pollution, and improves the overall benefit of the system.

Since the fingerprints of numerous crucial biologic materials can be identified by terahertz (THz) spectroscopy, THz sensing have become an important approach of biological and medical detections. Particularly, benefit from the excellent capability of metasurface, strong interactions between the metasurface and THz waves can be realized, thus the THz sensing with high sensitivity becomes reality. However, the common configuration of metasurface-based THz sensor is composed of metallic subwavelength structure. Due to the inherent resistive loss of metal, it is still a great challenge to further enhance the quality factor (Q-factor) of resonance and sensitivity of THz sensor. In this work, we designed an all-dielectric metasurface with high Q-factor for highly sensitive THz sensors. The metasurface is a windmill-like structure consisting of four cuboids, and every adjacent two cuboids are arranged alternately vertically and horizontally. The transmission spectrum of metasurface exhibits four polarization-independent and strong resonance peaks with high Q-factor in 0.1–2.5 THz, and all of them show high sensitivity related to ambient refractive index. The transmitted structure and polarization-independent resonances can relief the difficulty of measurement. We believe these studies will lay the theoretical and technical foundation for the design of high-sensitivity terahertz sensing.

Background: The role of Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) in tumorigenesis and development has been extensively studied. As we previously demonstrated, PinX1 plays an important role in modulating epithelial-mesenchymal transition (EMT), stemness, cell proliferation, and apoptosis in nasopharyngeal carcinoma (NPC). However, the relationship between PinX1, autophagy, and cell function in NPC remains unclear. This study aimed to investigate the mechanisms by which PinX1 regulates autophagy in NPC, and to explore its biological role and clinical significance in disease progression. Methods: The proliferative capacity of NPC cells was assessed by MTT and xenograft tumorigenicity assays. Autophagic flux was monitored using a tandem monomeric DAPI–FITC–LC3 reporter assay. The rates of apoptosis and the cell cycle in NPC cells were analyzed using flow cytometry. The activation of autophagy and the signaling status of the AKT/mTOR and NF-κB/p65 pathways were evaluated by Western blot analysis. Results: In addition to promoting autophagy and apoptosis, PinX1 overexpression suppressed proliferation, migration, invasion, and decelerated cell-cycle progression in NPC cells. These effects were reversed by inhibiting autophagy with 3-methyladenine. Mechanistic investigations clarified that PinX1 overexpression significantly reduced the expression of p-AKT, p-mTOR, p65, and p-p65. Chloroquine treatment in PinX1-overexpressing cells did not significantly alter p-AKT and p-mTOR levels, whereas 3-MA treatment in PinX1-overexpressing cells resulted in increased p65 and p-p65 expression, relative to untreated PinX1-overexpressing cells. Conclusions: It appears that PinX1 promotes autophagy by inhibiting the AKT/mTOR signaling pathway, which then inhibits NF-κB/p65 pathways, and consequently inhibiting cell proliferation and causing cell apoptosis in NPC cells.

Immune dysfunction caused by environmental factors plays an important role in the development of Graves’ disease (GD), and environmental factors are closely related to the intestinal flora. Our previous study showed significant changes in the intestinal flora in GD patients compared with healthy volunteers. This study analyzed the relationships between changes in the intestinal flora, thyroid function and relevant thyroid antibodies in GD patients before and after methimazole treatment. The subjects were divided into the UGD group (18 newly diagnosed GD patients), the TGD group (10 GD patients with normal or approximately normal thyroid function after methimazole treatment) and the NC group (11 healthy volunteers). Their fresh stool samples were sent for 16S rRNA gene amplification and Illumina platform sequencing. The correlations of the relative abundance of Bifidobacterium with the levels of TRAb, TgAb and TPOAb in the NC group and the UGD group were analyzed. A total of 1,562,445 high-quality sequences were obtained. In the UGD group, the abundances of Bifidobacterium and Collinsella were higher than that in the NC group; Bacteroides abundance in the TGD group was higher than that in the NC group, while Prevotella and Dialister abundances were lower than that in the NC group; Prevotella and Collinsella abundances in the UGD group were higher than that in the TGD group. The predominant abundance distribution of Bifidobacteriaceae in the UGD group at the family level was superior to that in the NC group. The abundance of Bifidobacterium was positively correlated with the levels of TRAb, TgAb, and TPOAb. The biological diversity of the intestinal flora was reduced in GD patients. After methimazole treatment, the composition of the intestinal flora was significantly altered. The change in Bifidobacterium abundance was positively correlated with TRAb, TgAb and TPOAb, suggesting that it might be related to the immune mechanism of GD. The results of this study may deepen our understanding of the pathogenesis of GD and provide a new idea for the treatment of GD.

Abstract Background Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial–mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression. Methods Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133+ cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133+ CSCs. Results We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133+ cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133+ CSCs. Conclusions Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200b-regulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.

BackgroundAlthough immune checkpoint inhibitors (ICIs) have revolutionized the current anticancer therapies, a considerable proportion of patients are found to hardly benefit from these drugs. Accumulating studies have demonstrated that concomitant proton pump inhibitor (PPI) use may affect the clinical efficacy of ICIs; however, their results are inconsistent. In this study, based on updated evidence, we aimed to perform a meta-analysis to clarify the prognostic significance of PPI use in advanced solid cancer patients receiving ICI therapy.MethodsEligible literature was searched using PubMed, Cochrane Library, Web of Science, EMBASE, and other network resources before July 2021. Clinical outcome was evaluated using overall survival (OS) and progression-free survival (PFS). The correlation of PPI use with OS or PFS was determined based on hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsA total of 17 studies enrolling 9,978 ICI-treated cancer patients were included in our meta-analysis. The global analysis demonstrated that PPI use was significantly correlated with worse OS [HR = 1.29 (1.10–1.50)] instead of PFS [HR = 1.19 (0.98–1.44)] in solid cancer patients receiving ICI therapy. In a subgroup analysis, the negative correlation of PPI use with ICI efficacy was significant in patients with non-small cell lung cancer [PFS, HR = 1.27 (1.10–1.47)] and urothelial carcinoma [OS, HR = 1.55 (1.31–1.84), PFS, HR = 1.52 (1.13–2.06)] and mixed cohorts containing multiple cancer types [OS, HR = 1.40 (1.16–1.69)], while an opposite result was observed in the PFS of patients with melanoma [HR = 0.48 (0.25–0.90)]. Moreover, the unfavorable prognostic impact of PPI use was also significant in patients over 65 years old [OS, HR = 1.28 (1.05–1.55), PFS, HR = 1.32 (1.12–1.56)] or those receiving anti-PD-1 [OS, HR = 1.37 (1.04–1.79)] or anti-PD-L1 therapies (OS, HR = 1.49 (1.30–1.69), PFS, HR = 1.34 (1.20–1.50). Finally, PPI use was significantly correlated with a worse prognosis in patients receiving PPIs 30 days before and/or after ICI initiation (OS, HR = 1.38 (1.18–1.62), PFS, HR = 1.23 (1.06–1.43)).ConclusionAlthough our global analysis revealed PPI use was not correlated with the PFS of ICI-treated patients, considering the results of our subgroup analysis, PPIs should be still cautiously used shortly before or during ICI therapy. Furthermore, more clinical validations and related mechanism investigations are of great necessity to clarify the clinical correlation of PPI use with ICI efficacy.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], PROSPERO [No. CRD42021243707].

Objectives: The pathogenesis of Graves’ disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China. Design and methods: Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis and partial least squares-discriminant analysis (PLS-DA). Results: The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P < 0.05). Conclusions: The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.

Chemerin is an adipocytokine that participates in glycolipid metabolism; however, its association with type 2 diabetes (T2DM) with lower extremity macroangiopathy (T2DM-V) has rarely been reported. This study explored the association of chemerin and inflammatory factors with body fat parameters, glucolipid metabolism, and insulin resistance (IR) in T2DM and T2DM-V. Patients were classified into normal glucose regulation (NGR), T2DM, and T2DM-V groups. Serum chemerin, glucolipid metabolic parameters, transforming growth factor (TGF)-β, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and fasting insulin levels were measured along with HOMA-IR, body mass index (BMI), and waist-to-stature ratio (WSR). Serum chemerin, TGF-β, IL-6, and MCP-1 levels were significantly higher in T2DM groups than in NGR group, and BMI, WSR, fasting plasma glucose (FPG), 2hPG, glycated hemoglobin (HbA1c), triglycerides (TG), and HOMA-IR were higher in T2DM-V subgroups with moderate or severe lower extremity macroangiopathy than in NGR group, simple T2DM group, and T2DM-V subgroup with mild macroangiopathy. FPG, 2hPG, HbA1c, TG, and HOMA-IR were higher in T2DM-V subgroup with severe macroangiopathy than in T2DM-V with moderate macroangiopathy (p < 0.05). In all groups, serum chemerin levels were positively correlated with BMI, WSR, FPG, 2hPG, HbA1c, fasting insulin, aspartate transaminase, TG, TGF-β, IL-6, and HOMA-IR (p < 0.05) and negatively correlated with high-density lipoprotein cholesterol [HDL-c] (p < 0.05). Multiple stepwise regression analysis showed that 2hPG, HbA1c, and HDL-c were independent predictors of serum chemerin levels (β = -0.768, -0.122, -0.115, and 3.261, respectively; p < 0.01). Collectively, chemerin, factors associated with obesity, pathological and physiological changes in glucolipid metabolism, and inflammatory factors may promote the development of T2DM macroangiopathy.

The correlation between serum 25-hydroxy vitamin D (25(OH)D) levels and lower extremity atherosclerotic disease and the predictive value of 25(OH)D for early-stage lower extremity atherosclerotic disease in patients with type 2 diabetes mellitus (T2DM) were explored. In total, 620 subjects (590 T2DM patients and 30 healthy subjects) completed a questionnaire. All subjects were divided into four groups according to serum 25(OH)D concentration quartile: Q1 (31.97 ng/ml). Participants were also divided into four groups based on the degree of lower extremity arteriostenosis: A1 (T2DM), A2 (T2DM with mild lower extremity vascular lesions (LEVL)), A3 (T2DM with moderate LEVL), and A4 (T2DM with severe LEVL). The incidence of lower extremity artery plaque was significantly higher in groups Q1 and Q2 than in group Q4 (both P

ABSTRACT Axonal transport of mitochondria is critical for neuronal survival and function. Automatically quantifying and analyzing mitochondrial movement in a large quantity remain challenging. Here, we report an efficient method for imaging and quantifying axonal mitochondrial transport using microfluidic-chamber-cultured neurons together with a newly developed analysis package named “MitoQuant”. This tool-kit consists of an automated program for tracking mitochondrial movement inside live neuronal axons and a transient-velocity analysis program for analyzing dynamic movement patterns of mitochondria. Using this method, we examined axonal mitochondrial movement both in cultured mammalian neurons and in motor neuron axons of Drosophila in vivo. In 3 different paradigms (temperature changes, drug treatment and genetic manipulation) that affect mitochondria, we have shown that this new method is highly efficient and sensitive for detecting changes in mitochondrial movement. The method significantly enhanced our ability to quantitatively analyze axonal mitochondrial movement and allowed us to detect dynamic changes in axonal mitochondrial transport that were not detected by traditional kymographic analyses.

Carney complex (CNC) is a rare genetic disease. Here, we report a case of CNC and explore clinical manifestations and gene mutation studies of CNC. A male patient with CNC at the age of 16 yr was admitted to Affiliated Hospital of Zunyi Medical University in July, 2015. Although the patient had typical signs of Cushing's syndrome, he also presented with certain rare signs of Cushing's syndrome, such as "freckle-like" scattered spots of pigmentation on the face and around the lips. In addition, concomitant severe osteoporosis led to flattened vertebrae and the compression of corresponding levels of the spinal cord. Radiographic findings revealed adrenal nodular hyperplasia. Based on sequencing, 2 novel heterozygous mutations of the PRKAR1A gene were found. CNC was eventually diagnosed via pathologic biopsy. After 1 year of follow-up, the patient exhibited weight loss, relief of low back pain, normal blood biochemical indicators and cortisol levels at the lower limit of the normal range.

Endocrine-disrupting chemical (EDC) has been thought to play a role in non-alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol (NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated. This study aimed to investigate whether exposure to NP could induce NAFDL, a promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects caused by NP was evaluated. Fourth eight male rats were assigned to four groups and each group was treated with a specific testing sample: normal-diet (ND) control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high-sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group (NP-HSHFD). At the age of 80 day, sonogram presents diffusely increased hepatic echogenicity in the NP-HSHFD group. The oblique diameter of liver in the NP-HSHFD group was significantly bigger than that in both the C-ND and NP-ND groups. At the age of 90 day, exposure to NP-HSHFD and NP-ND caused a significant increase in NP concentration in liver as compared to the C-ND group. The rats in the groups treated with NP+ND, HSHFD and NP+HSHFD produced significant increases in the body weight, fat weight and FMI, respectively, when compared to the C-ND group. The liver weight and hepatosomatic indexes (HIS) of rats in the NP-HSHFD group are higher than those in the C-HSHFD group. Exposure to NP-HSHFD induced the increases in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) as compared to the C-ND group. Morphological examination of liver tissue from rats exposed to NP+HSHFD shown steatosis with marked accumulation of lipid droplets, hepatocellular ballooning degeneration and inflammatory cell infiltration. Chronic exposure to NP might induce NAFLD in male rats. The high-sucrose-high-fat diet accelerates and exacerbates the development of NAFLD caused by NP exposure.

Published methods for imaging and quantitatively analyzing morphological changes in neuronal axons have serious limitations because of their small sample sizes, and their time-consuming and nonobjective nature. Here we present an improved microfluidic chamber design suitable for fast and high-throughput imaging of neuronal axons. We developed the AxonQuant algorithm, which is suitable for automatic processing of axonal imaging data. This microfluidic chamber-coupled algorithm allows calculation of an ‘axonal continuity index' that quantitatively measures axonal health status in a manner independent of neuronal or axonal density. This method allows quantitative analysis of axonal morphology in an automatic and nonbiased manner. Our method will facilitate large-scale high-throughput screening for genes or therapeutic compounds for neurodegenerative diseases involving axonal damage. When combined with imaging technologies utilizing different gene markers, this method will provide new insights into the mechanistic basis for axon degeneration. Our microfluidic chamber culture-coupled AxonQuant algorithm will be widely useful for studying axonal biology and neurodegenerative disorders. © 2014 S. Karger AG, Basel