Expressions of Neuregulin 1β and ErbB4 in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by Chronic MK-801 Administration

Recent human genetic studies and postmortem brain examinations of schizophrenia patients strongly indicate that dysregulation of NRG1 and ErbB4 may be important pathogenic factors of schizophrenia. However, this hypothesis has not been validated and fully investigated in animal models of schizophrenia. In this study we quantitatively examined NRG1 and ErbB4 protein expressions by immunohistochemistry and Western blot in the brain of a rat schizophrenia model induced by chronic administration of MK-801 (a noncompetitive NMDA receptor antagonist). Our data showed that NRG1β and ErbB4 expressions were significantly increased in the rat prefrontal cortex and hippocampus but in different subregions. These findings suggest that altered expressions of NRG1 and ErbB4 might be attributed to the schizophrenia. Further study in the role and mechanism of NRG1 and ErbB4 may lead to better understanding of the pathophysiology for this disorder

AdaptivePose++: A Powerful Single-Stage Network for Multi-Person Pose Regression

Multi-person pose estimation generally follows top-down and bottom-up paradigms. Both of them use an extra stage ($\boldsymbol{e.g.,}$ human detection in top-down paradigm or grouping process in bottom-up paradigm) to build the relationship between the human instance and corresponding keypoints, thus leading to the high computation cost and redundant two-stage pipeline. To address the above issue, we propose to represent the human parts as adaptive points and introduce a fine-grained body representation method. The novel body representation is able to sufficiently encode the diverse pose information and effectively model the relationship between the human instance and corresponding keypoints in a single-forward pass. With the proposed body representation, we further deliver a compact single-stage multi-person pose regression network, termed as AdaptivePose. During inference, our proposed network only needs a single-step decode operation to form the multi-person pose without complex post-processes and refinements. We employ AdaptivePose for both 2D/3D multi-person pose estimation tasks to verify the effectiveness of AdaptivePose. Without any bells and whistles, we achieve the most competitive performance on MS COCO and CrowdPose in terms of accuracy and speed. Furthermore, the outstanding performance on MuCo-3DHP and MuPoTS-3D further demonstrates the effectiveness and generalizability on 3D scenes. Code is available at https://github.com/buptxyb666/AdaptivePose.Comment: Submit to IEEE TCSVT; 11 pages. arXiv admin note: text overlap with arXiv:2112.1363

7,8beta-dihydroponasterone A, a new phytoecdysteroid from the needles of the Japanese Yew, Taxus cuspidata

A new plant ecdysteroid 7,8beta-dihydroponasterone A, together with ponasterone A, were isolated from the methanol extract of the needles of the Japanese yew, Taxus cuspidata. Their structures were elucidated on the basis of spectroscopic analysis including ¹H NMR, 13C NMR, ¹H-¹H COSY, NOESY, HMQC and HMBC and confirmed by high-resolution FABMS data

Aplikasi Image Thresholding Untuk Segmentasi Objek

Salah satu operasi di dalam analisis citra adalah segmentasi citra, yaitu memisahkan objek dari latar belakangnya atau dari objek lain yang tidak menjadi perhatian. Metode sementasi yang sederhana adalah dengan operasi pengambangan (thresholding). Operasi pengambangan menghasilkan citra biner, yang dalam hal ini objek yang diacu di-set berwarna putih sedangkan latar belakangnya di-set berwarna hitam (atau sebaliknya bergantung kasusnya). Makalah ini mempresentasikan penggunaan operasi pengambangan untuk melakukan segmentasi objek. Eksperimen dilakukan dengan menggunakan kakas MATLAB. Hasil eksperimen memperlihatkan bahwa pemilihan nilai ambang (threshold) yang tepat sangat menentukan keberhasilan segmentasi

The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

<p>Abstract</p> <p>Background</p> <p>High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo.</p> <p>Methods</p> <p>1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed.</p> <p>Results</p> <p>The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min.</p> <p>Conclusions</p> <p>The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.</p

The correlation between the plasma concentration of gemcitabine and short-term efficacy and adverse reactions in patients with advanced squamous cell carcinoma of the lung using liquid chromatography-mass spectrometry

AbstractBackground: Worldwide, non-small cell lung cancers have the highest incidence and mortality rates of all cancers. Gemcitabine (2’,2’-difluoro-2’-deoxycytidine or dFdC, C9H11F2N304) is widely used as the first-line chemo-reagent for lung cancer patients whose tumors have been diagnosed to be at an advanced stage and are therefore unresectable. Objective: The objective of this systematic study was to establish the correlation between the plasma concentration of gemcitabine and short-term clinical efficacy and adverse reactions in patients with advanced squamous cell carcinoma of the lung using liquid chromatography-mass spectrometry. Material and methods: In total, 53 patients were given the chemotherapy medications, gemcitabine and cisplatin, every 3 weeks. Plasma concentrations of gemcitabine were determined using liquid chromatography-mass spectrometry. A modified methodology of the liquid chromatography-mass spectrometry system was verified and performed to detect plasma concentrations of gemcitabine. The clinical endpoints – short-term clinical efficacy and adverse reactions – were evaluated after two cycles. Results: The plasma concentration range of gemcitabine in 53 patients was 1.58-28.70μg/ml (mean 14.37±8.63μg/ml), with 28 patients in the &gt;15μg/ml group (mean 21.76±3.45μg/ml), and 25 patients in the ≤15μg/ml group (mean 6.09±3.57μg/ml). The clinical benefit rate (CBR) of the &gt;15μg/ml group was significantly higher than that of the 15μg/ml group (p&lt;0.05). The incidences of leukopenia and neutropenia, thrombocytopenia and grade III-IV gastrointestinal reactions in the &gt;15μg/ml group were significantly higher than in the ≤15μg/ml group (p&lt;0.05). There was no statistical difference between the two groups in terms of the incidences of reduced hemoglobin, liver and kidney function damage, allergic reaction and rash (p&gt;0.05). The analysis of the plasma concentration of gemcitabine and the percentage of reduction in neutrophil count (NEUT) (r2 = 0.3212; p&lt;0.05) and platelet (PLT) (r2 = 0.6439; p&lt;0.05) showed a significant positive correlation. Conclusions: In patients with advanced non-small cell lung cancer, a high plasma concentration of gemcitabine can improve the short-term clinical efficacy of treatment, but increase the incidence of grade III-IV adverse reactions. [Ethiop. J. Health Dev. 2021; 35(1):72-82] Key words: Non-small cell lung cancer, gemcitabine, plasma concentration, short-term efficacy, adverse reaction

Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models.

Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis. Vitamin D receptor (VDR) is highly expressed in the ileum of the small intestine, which prompted us to test a hypothesis that vitamin D signaling may determine the enterotype of gut microbiota through regulating the intestinal interface. Here, we demonstrate that high-fat-diet feeding (HFD) is necessary but not sufficient, while additional vitamin D deficiency (VDD) as a second hit is needed, to induce robust insulin resistance and fatty liver. Under the two hits (HFD+VDD), the Paneth cell-specific alpha-defensins including α-defensin 5 (DEFA5), MMP7 which activates the pro-defensins, as well as tight junction genes, and MUC2 are all suppressed in the ileum, resulting in mucosal collapse, increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D deficient high fat feeding (HFD+VDD), Helicobacter hepaticus, a known murine hepatic-pathogen, is substantially amplified in the ileum, while Akkermansia muciniphila, a beneficial symbiotic, is diminished. Likewise, the VD receptor (VDR) knockout mice exhibit similar phenotypes, showing down regulation of alpha-defensins and MMP7 in the ileum, increased Helicobacter hepaticus and suppressed Akkermansia muciniphila. Remarkably, oral administration of DEFA5 restored eubiosys, showing suppression of Helicobacter hepaticus and increase of Akkermansia muciniphila in association with resolving metabolic disorders and fatty liver in the HFD+VDD mice. An in vitro analysis showed that DEFA5 peptide could directly suppress Helicobacter hepaticus. Thus, the results of this study reveal critical roles of a vitamin D/VDR axis in optimal expression of defensins and tight junction genes in support of intestinal integrity and eubiosis to suppress NAFLD and metabolic disorders

Mitochondrial DNA Copy Number, but Not Haplogroup, Confers a Genetic Susceptibility to Leprosy in Han Chinese from Southwest China

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. The high level of inactivation of gene function in M. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. We hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to M. leprae and the onset of clinical leprosy, and this may be reflected by mitochondrial DNA (mtDNA) background and mtDNA copy number. METHODS: We analyzed the mtDNA sequence variation of 534 leprosy patients and 850 matched controls from Yunnan Province and classified each subject by haplogroup. mtDNA copy number, taken to be proportional to mtDNA content, was measured in a subset of these subjects (296 patients and 231 controls) and 12 leprosy patients upon diagnosis. RESULTS: Comparison of matrilineal components of the case and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that lepromatous leprosy patients had a significantly higher mtDNA content than controls (P = 0.008). Past medical treatments had no effect on the alteration of mtDNA copy number. CONCLUSIONS: Our results suggested that mtDNA content, but not haplogroup, affects leprosy and this influence is limited to the clinical subtype of lepromatous leprosy

Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis