bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of preserved bowel and mesentery fixation in apple-peel intestinal atresia
Authors: han jinbao , Hao Zenghui , Wang Long , Yao Ting , Fan Wei , Zhao Zheng , huang liuming , xu zhilin
Published: May 2022

Objective
This study explored the feasibility of mesoplasty with end-to-side anastomosis in the treatment of different apple-peel mesenteric defects with high jejunal atresia.
Methods
A retrospective analysis was performed on 42 premature infants admitted to the hospital between 2014 and 2021. Prenatal ultrasound scans revealed bowel dilatation. The patients experienced vomiting after birth and produced white or no meconium. Plain radiography showed double or triple bubble signs and the patients underwent emergency laparotomies. High jejunal atresia with different apple-peel atresia appearance was discovered intraoperatively, involving mobilization of the ileocecal region. Patients received end-to-side anastomosis between the enlarged blind pouch and atresic bowel, as well as mesoplasty. A jejunal feeding tube was placed trans-nasally. Patients were discharged after achieving full enteral feeding.
Results
Three patients died and 39 survived. The discharged patients were followed up for 12 months, and none showed post-operative complications such as intestinal obstruction, malnutrition, or chronic diarrhea. All surviving patients reached the expected height and weight for children of the same age.
Conclusion
For cases of high jejunal atresia with apple-peel intestinal atresia, mesoplasty is a good option to avoid postoperative volvulus.
Evaluating the National System for Rare Diseases in China from the Point of Drug Access: Progress and Challenges
Authors: Qiao Luyao , Liu Xin , Shang Junmei , Zuo Wei , Xu Tingting , Qu Jinghan , Jiang Jiandong , Bo Zhang , Zhang Shuyang
Published: May 2022

Background: There are about 7000 rare diseases worldwide, of which only 5% of the diseases can be treated with medicines, showing that it’s important to improve patient access to orphan drugs. Recently, China has actively worked to set up a national system for rare diseases to improve the diagnosis and treatment capabilities and ensure the accessibility of drugs. However, the benefits of the system have yet not to be measured. This study aimed to provide an overview of orphan drug access based on the Compendium of China’s First List of Rare Diseases and National Network to Collaborate on Diagnosis and Treatment of Rare Diseases, expecting to map a blueprint for orphan drug access in China. Methods: Framework of China’s national system for rare diseases was summarized. We surveyed the availability and affordability of 79 approved orphan drugs based on the Compendium of China’s First List of Rare Diseases in 30 leading provincial institutions from 2017 to 2020. The availability was measured annually at 3 levels (market, hospital and drug), and affordability was reflected by comparing costs of daily defined dose with per capita income of urban and rural residents, with the National Basic Medical Insurance considered. Results: The market availability of orphan drugs in China showed an upward trend. As of 2020, the median hospital-level availability was 41.1% (increased by 1.5 times), highly available drugs increased by 16.5%. There were 64 / 74 orphan drugs that were affordable to rural/urban residents with the National Basic Medical Insurance considered (an increase of 14.1%), and the urban-rural gap of affordability ratio was narrowed (down by 6.0%). Comprehensive analysis showed the proportions of drugs with better availability and affordability in urban and rural areas by 2020 were 26.53% and 21.43%, respectively, which had increased but were still at a low level.Conclusions: China’s national system for rare diseases has made great progress in orphan drug access, indicating that it’s been functioning under the joint reformation of medical treatment, medical insurance and medicines supply. The list of rare diseases will be updated and collaboration in networks will be enhanced to further improve the system.
Introgression of the RppQ gene from field corn improves southern rust resistance in sweet corn
Authors: Zhang Nan , Qi Xitao , Li Xiaofeng , Li Guangyu , Li Gaoke , Hu Jianguang
Published: May 2022

Southern rust, one of the most destructive foliar diseases of sweet corn (Zea mays convar. saccharata var. rugosa), is caused by Puccinia polysora Underw. and leads to enormous yield losses and reduced quality of sweet corn in China. Utilization of resistance genes is an effective and environmentally friendly strategy for improving southern rust resistance of sweet corn. However, improvement is hampered by a lack of resistance genes in Chinese sweet corn germplasm. In this study, we used marker-assisted backcross breeding to introgress the southern rust resistance gene RppQ from Qi319, an inbred line of southern rust resistant field corn, into four elite sweet corn inbred lines, 1401, 1413, 1434, and 1445. These are parental inbred lines of the popular sweet corn varieties Yuetian 28, Yuetian 13, Yuetian 16, and Yuetian 27. We developed five RppQ-based markers, M0607, M0801, M0903, M3301, and M3402, and employed these for foreground selection; 92.3 to 97.9% of the recurrent parent genomes were recovered following three or four rounds of backcrossing. The four newly developed sweet corn lines all showed significant improvement of southern rust resistance compared with their respective parent lines. Meanwhile, there was no significant difference in phenotypic data for agronomic traits. In addition, reconstituted hybrids derived from the converted lines retained resistance to southern rust, while other agronomic traits and sugar content remained unchanged. Our study provides an example of successful development of southern rust resistant sweet corn using a resistance gene from field corn.
Theoretical calculation and experiment of the impact characteristics in the plane ultrasonic rolling
Authors: Lan Shuai-ling , Qi Meng , Liu Ming-xian , Bie Wen-bo
Published: May 2022

To achieve high machining efficiency in optimal surface integrity manufacturing, a relationship model between rolling depth and rolling force was established based on Hertz contact theory, and a theoretical model of impact characteristics was established according to the indentation geometry to evaluate the machining efficiency. Subsequently, the plane ultrasonic rolling experiment of 7075 aluminum alloy was carried out to verify the relationship between rolling depth and rolling force, meanwhile, the mapping between process parameters and surface characteristics, impact characteristics and surface morphology were studied, respectively. On this basis, the surface integrity prediction model was established by using nonlinear curve fitting method, and the optimal parameter solution was obtained by using quantum genetic algorithm (NSGA-Ⅱ). The results show that the rolling force increases linearly with the increase in rolling depth. The impact characteristics increase with the increase in static force and amplitude, and decreases with the increase in step and feed rate, and the impact characteristics is negatively correlated with the processing efficiency. The optimization results provide a reference for engineering applications.
Light orthodontic force with high-frequency vibration accelerates tooth movement with minimal root resorption in rats
Authors: Tangtanawat Porntip , Thammanichanon Peungchaleoy , Sutthapreyasri Srisurang , Leethanakul Chidchanok
Published: May 2022

Objectives
To determine and compare the effects of high-frequency mechanical vibration (HFV) with light force and optimal force on the tooth movement and root resorption in rat model.
Materials and Methods
Seventy-two sites in 36 male Wistar rats were randomly assigned using a split-mouth design to control (no force/no vibration) or experimental groups: HFV (125 Hz), light force (5 g), optimal force (10 g), light force with HFV, and optimal force with HFV for 14 and 21days. The amount of tooth movement, three-dimensional root volume and root resorption area were assessed by micro-computed tomography and histomorphometric analysis.
Results
Adjunction of HFV with light force significantly increased the amount of tooth movement by 1.8-fold (p = 0.01), 2.0-fold (p = 0.01) at days 14 and 21 respectively. The HFV combine with optimal force significantly increased the amount of tooth movement by 2.1-fold (p = 0.01), 2.2-fold (p = 0.01) at days 14 and 21 respectively. The root volume in control (distobuccal root (DB): 0.60 ± 0.19 mm3, distopalatal root (DPa): 0.60 ± 0.07 mm3) and HFV (DB: 0.60 ± 0.08 mm3, DPa: 0.59 ± 0.11 mm3) were not different from the other experimental group (range from 0.44 ± 0.05 mm3 to 0.60 ± 0.1 mm3) with the lowest volume in optimal force group.
Conclusions
Adjunction of HFV with orthodontic force significantly increased tooth movement without causing root resorption
Clinical Relevance
Using light force with HFV could help to identify alternative treatment option to reduce the risk of root resorption.
Triptolide-mediated Downregulation of FLIPs in Hepatoma Cells Occurs at the Post-transcriptional Level Independently of Proteasome-mediated Pathways
Authors: Liu Weixia , Yang Ying , Wang Jing , Wu Shanshan , Chen Zhi
Published: May 2022

Cellular c-FLIP prevents apoptosis mediated by death receptor through inhibiting activation of caspase-8. Therefore, when c-FLIP is downregulated or eliminated, caspase-8 activation is promoted, and death receptor ligand-induced apoptosis is activated. It was reported that triptolide (TPL) sensitized tumor cells to TNF-α-induced apoptosis by blocking TNF-α-induced activation of NF-κB and transcription of c-IAP1 and c-IAP2. However, the effect of TPL on basal c-FLIP expression was not understood. In this study, we found that the combination of TNF-α and TPL accelerated apoptosis in human hepatocellular carcinoma cells and TNF-α-induced elevated as well as basal level of FLIPs protein were downregulated. Additionally, we demonstrated that basal level of FLIPs in Huh7 cells was continuously downregulated following the incubation of TPL and downregulated more when dosage of TPL for treatment was increased. Subsequently, we showed that TPL reduced FLIPs level in a transcription- and degradation-independent mechanism. Our findings suggest that TPL induces loss of FLIPs at the post-transcriptional level independently of proteasome-mediated pathway, an additional mechanism of TPL sensitizing cancer cells to TNF-α-induced apoptosis.
A novel method to evaluate transverse pedicle angle of lower lumbar using digital radiography
Authors: Wu Shixun , Liu Shizhang , Ling Ming , Huang Minggang , Liu Zhe , Duan Xianglong
Published: May 2022

To investigate a novel approach of establishment for transverse pedicle angle (TPA) of lower lumbar spine using preoperative digital radiography(DR). CT dataset of the lower lumbar were reconstructed using MIMICS 17.0 software, then imported into the 3matic software for surgical simulation and anatomical parameters measurement. Mathematical algorithm of TPA based on Pythagorean theorem was established, all obtained data was analysised by SPSS software. CT dataset from 66 samples were reconstructed as digital model of lower lumbar vertebrate(L3-L5), AP length / estimated lateral length for L3 between right and left were significant statistically(P = 0.015, P = 0.005). AP length of right for L4 was smaller than that of left after Paired t-test was executed(P = 0.006). Both width of pedicle and length of pedicle (P2C1) are consistent with TPA(L3 < L4 < L5). No statistical differences in TAN-TPA and DR-TPA compared with real TPA. ICC for real TPA and DR-TPA within L3 is good reliability, ICC for real TPA and DR-TPA within both L4 and L5 are moderate reliability. Our novel approach can be well considered as a reliable way to determine the transverse pedicle angle from routine DR, width and length of pedicle within lumbar DR should be considered to determine the length and trajectory of screw during preoperation planning.
Hold tight or loosen up? Functional consequences of a shift in anther architecture depend substantially on bee body size
Authors: Wilkins Rachel V. , Mayberry Maggie M. , Vallejo-Marín Mario , Russell Avery Leigh
Published: May 2022

A fundamental question in pollination ecology is how pollinators affect the evolution of different floral forms. Yet functional effects of shifts in floral form for plant and pollinator are frequently unclear. For instance, flowers that conceal pollen within tube-like anthers that are spread apart and move freely (free architecture) or are tightly joined together (joined architecture) have evolved independently across diverse plant families and are geographically widespread. Surprisingly, how their bee pollinators affect the function of both architectures remains unknown. We hypothesized that bee body size would affect foraging success and pollination differently for free and joined anther architectures. We therefore modified the anther architecture of a single plant species (Solanum elaeagnifolium) and used a single species of generalist bumble bee (Bombus impatiens), which varies greatly in body size. We found that on free anther architecture, larger bees were better pollinators. More pollen on their bodies was available for pollination and they deposited more pollen on stigmas. Conversely, on joined anther architecture, smaller bees were better pollinators. They collected less pollen into their pollen baskets, had more pollen on their bodies available for pollination, and deposited more pollen on stigmas. While we also found modest evidence that plants benefit more from joined versus free anther architecture, further investigation will likely reveal this also depends on pollinator traits. We discuss potential mechanisms by which pollinator size and anther architecture interact and implications for floral evolution.
Seismic vulnerability of southern parts of South India in the context of the recent earth tremors (22 March 2022) occurred in Dindigul region, Tamil Nadu, India
Authors: Joshua R.Melwyn , R Rajaperumal , A Vijay , R Kathiravan , J Saravanavel , K Palanivel , CJ Kumanan
Published: May 2022

The seismicity witnessed on 22 March 2022 in parts of Dindigul, Tamilnadu again indicates the seismic alertness of the southern part of the Indian peninsula. So, an integrated study was carried out between the lineaments and the present episode and the historical seismicity of the region as well. It revealed the coincidence of the maximum seismic episodes of 54% − 88% with N15o-60oE / S15o-60oW oriented tectonic lineaments/faults and the lineaments/faults associated with geomorphic anomalies. Since, these are inferred to be the regional sinistral strike slip faults related to the ongoing post collision tectonic compression of the Indian plate, the lineaments in general and the lineaments of NE-SW group in particular warrant detailed study.
Lambda-vector: Modeling temporal and channel interactions for text-independent speaker verification
Authors: Wei Guangcun , Min Hang , Xu Yunfei , Zhang Yanna
Published: May 2022

Most of the current excellent models in speaker verification are ResNet-based deep models and attention-based models. These models have a general weakness, which is the large number of parameters and high hardware requirements have limited their application on small devices. On the other hand, many deep structures only generate embedding features from the features extracted by the last frame-level layer, which causes shallow features and channel-related features to be ignored. To solve these problems, this paper proposed a shallow speaker verification model based on Lambda-vector, its main structure is composed of three Lambda-SE modules. The module extracts long-distance dependencies between frame-level features and channel-related interaction information to enhance representation of features. Meanwhile, so that adequately mine the information in deep and shallow features, the model introduces multi-layer feature aggregation to fuse the features of different frame-level layers together. It can increase the detailed information in the deep features and improve the model's ability to represent complex information. The experimental results on the public datasets Voxceleb1 and Voxceleb2 show that the model has more stable training speed, fewer model parameters, and better identification performances than baseline models.
Effect of Intralymphatic Allergen-specific Immunotherapy on House Dust Mite in a Murine Model of Allergic Rhinitis
Authors: Jung Joo Hyun , Lee Sang Min , Cho Min Young , Cha Heung Eog , Kim Seon Tae
Published: May 2022

BackgroundIntralymphatic immunotherapy (ILIT) is a promising alternative for the treatment of patients with allergic rhinitis, providing similar therapeutic efficacy to conventional allergen-specific immunotherapy (AIT). However, the allergic mechanism of ILIT is not completely known. The aim of this study was to determine the efficacy of ILIT in a house dust mite (HDM) mouse model of allergic rhinitis.Methods Six-week-old female BALB/c mice were divided into four groups. Four groups were established: Group 1 (G1, n=10), control group without allergy; Group 2 (G2, n=10), allergy group sensitized with HDM without ILIT; Group 3 (G3, n=10), allergy group with ILIT (L1: starting with HDM 1.25 mg/mL); and Group 4 (G4, n=10), allergy group with ILIT (L2: starting with HDM 2.5 mg/mL) After the murine model of allergic rhinitis with HDM was established, mice were administered an intralymphatic injection through the inguinal lymph nodes with HDM once per week for 5 weeks. Thereafter, the levels of total serum IgE, interleukin IL-6, IL-13, IL-17A, IL-25, IL-33, and interferon (IFN)-γ in serum and spleen were measured using ELISA kits. Eosinophils in nasal mucosa were also evaluated via hematoxylin and eosin staining. Cytokine expression in nasal mucosa were determined using RT-PCR and the effects of ILIT on FoxP3(+) Treg cell in splenocytes were assessed using flow cytometry. ResultsILIT significantly decreased serum total IgE and eosinophil counts in nasal mucosa; IL-6 IL-17A, IL-25, and IFN-γ in serum (P< 0.05); and IL-17A and IL-33 in splenocyte supernatant (P< 0.05). ILIT also reduced the mRNA expression of IL-4, IL-6, IL-17A, and IL-33 cytokines in nasal mucosa. FoxP3(+) Treg cell expression was significantly decreased in the allergic group and significantly increased in the ILIT group (P< 0.05). ConclusionOur results suggest that ILIT regulates the specific immunotherapy immunologic mechanism by downregulating Th1, Th2, and Th17 cytokines and upregulating FoxP3(+) T reg cells in the HDM allergic mouse model.
Retrotransposon insertion as a novel mutational cause of spinal muscular atrophy
Authors: Vezain Myriam , Thauvin-Robinet Christel , Vial Yoann , Coutant Sophie , Drunat Séverine , Urtizberea Jon Andoni , Rolland Anne , Jacquin-Piques Agnès , Fehrenbach Séverine , Nicolas Gaël , Lecoquierre François , Saugier-Veber Pascale
Published: May 2022

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder resulting from biallelic alterations of the SMN1 gene: deletion, gene conversion or, in rare cases, intragenic variants. The disease severity is mainly influenced by the copy number of SMN2, a nearly identical gene, which produces only low amounts of full-length (FL) mRNA. Here we describe the first example of retrotransposon insertion as a pathogenic SMN1 mutational event. The 50-year-old patient is clinically affected by SMA type III with a diagnostic odyssey spanning nearly 30 years. Despite a mild disease course, he carries a single SMN2 copy. Using Exome Sequencing and Sanger sequencing, we characterized a SVA-F retrotransposon inserted in SMN1 intron 7. Using RT-PCR and RNASeq experiments on lymphoblastoid cell lines, we documented the dramatic decrease of FL transcript production in the patient compared to subjects with the same SMN1 and SMN2 copy number, thus validating the pathogenicity of this SVA insertion. We characterized the mutant FL-SMN1-SVA transcript and showed that it is subject to degradation by nonsense-mediated mRNA decay. The stability of the SMN-SVA protein may explain the mild course of the disease. This observation exemplifies the role of retrotransposons in human genetic disorders.
Mesenchymal stem cells improve liver fibrosis and protect hepatocytes by promoting microRNA-148a-5p mediated inhibition of Notch signaling pathway
Authors: Zhou Qing , Rong Chao , Gu Tengfei , Li Hongda , Wu Lei , Zhuansun Xuemei , Zhao Xin , Xiao Zuorun , Kuang Yuting , Xu Sanrong , Wang Shouli
Published: May 2022

Background
Mesenchymal stem cells (MSCs) are considered to be a potential therapeutic tool for liver fibrosis. Inhibiting the activation of hepatic stellate cells (HSCs) and protecting hepatocytes are important mechanisms for the anti-fibrotic effect of MSCs. However, how MSCs inhibit liver fibrosis by regulating the expression of microRNAs (miRNAs) has not been fully clarified.
Methods
Transforming growth factor-β1 (TGF-β1) activated HSCs LX-2 were single cultured or co-cultured with human umbilical cord mesenchymal stem cells (HUC-MSCs). High-throughput sequencing was used to evaluate the differentially expressed microRNAs (DEMs) between the two groups. Quantitative real-time PCR (qRT-PCR), Western blot, and transfection experiments were used to investigate and screen the most significantly up-regulated DEM. Bioinformatics analysis was used to predict the target mRNAs and the potential functions of the DEM. The possible mechanism of HUC-MSCs against liver fibrosis was analyzed by co-culture experiment of HUC MSCs with LX-2 cells, and HUC-MSCs treatment of Bile duct ligation (BDL) induced liver fibrosis in mice. Finally, the mechanism of the DEM regulating liver fibrosis was confirmed in human liver fibrosis specimens.
Results
MicroRNA-148a-5p (miR-148a-5p) was the most significantly up-regulated DEM in activated LX-2 cells co-cultured with HUC-MSCs compared with LX-2 cells single cultured. Up-regulation the expression of miR-148a-5p in activated LX-2 cells could significantly inhibit the expression of hepatic fibrosis markers α-SMA and Col1α1. Notch2 was one target gene of miR-148a-5p. Co-cultured with HUC-MSCs could inhibit the activation of LX-2 cells by inhibiting the expression of the Notch2 and the Notch signaling pathway. In addition, HUC-MSCs treatment could up-regulate the expression of miR-148a-5p in liver tissue and hepatocytes, promote the proliferation and avoid the apoptosis of hepatocytes, and reduce the degree of fibrosis by inhibiting expression of the Notch2 and the Notch signaling pathway in BDL-induced liver fibrosis mice. Moreover, miR-148a-5p was down-regulated and Notch2 was up-regulated in fibrotic human liver tissues compared with the normal livers.
Conclusions
HUC-MSCs treatment could inhibit HSCs activation, protect hepatocytes, and alleviate BDL-induced liver fibrosis in mice by up-regulating the expression of miR-148-5p and inhibiting the Notch signaling pathway. The down-regulation of miR-148-5p and up-regulation of Notch2 could be used as biomarkers to monitor the progression of liver fibrosis.
Weld morphology, microstructure evolution and mechanical properties of laser beam welding of wire arc additive manufactured Al-Cu substrate
Authors: Shi Bowen , Wang Leilei , Zhan Xiaohong , Lyu Feiyue , Gao Zhuanni , Shi Huizi
Published: May 2022

Additive manufacturing (AM) cannot meet the manufacturing requirements of specific large structures, so use the welding method to joint the small size parts of AM to solve the problem. In work, the laser weld 3mm thick samples cut from WAAM block under different laser powers and welding directions to explore the feasibility of technology. The properties evolution, and weldability of the laser-welded wire arc additive manufactured Al-Cu alloy joints are investigated. The results indicate that the wire arc additive manufactured Al-Cu alloy has excellent laser weldability without apparent detection. The microstructures of the laser-welded joints consist of columnar grains, dendrites and fine equiaxed grains. The 3500 W laser power joint has higher tensile strength and elongation than other laser powers, reaching 203.48 MPa, 4.13%. Compared with the different welding direction joints, “0°and 0°” has the higher tensile strength and elongation, reaching 180.77 MPa, 2.40%. The microstructures have a weak effect, but the anisotropy plays a significant role in the tensile properties. This study has demonstrated that it is possible to laser-welded WAAM samples, and provide solutions that AM technology difficultly produces large size parts.
Suxiao Jiuxin Pills, a Chinese herbal complex, block human potassium channel current hKv1.5 in CHO cells
Authors: Zhang Minzhou , Yu Juan , Qu Jiashin , Qi Jianyong
Published: May 2022

Kv1.5 channel plays key roles in cardiac action potential and atrial repolarization. Suxiao Jiuxin Pills (SXJ), an herbal remedy had been widely used in China in treating angina pectoris and atrial arrhythmia. However, whether SXJ regulates Kv1.5 channels is still unclear. The goal of the present study was to examine the effects of SXJ on cloned human potassium channels (hKv1.5) in Chinese hamster ovary (CHO) cells. The ionic and gating currents were detected; dose-dependent curve, current-voltage curve, steady-state activation curve (SSA), activation time constant (τact), deactivation (τdeact), and gating currents were compared between SXJ and control. Further, intracellular application of SXJ was implemented. Results showed that SXJ inhibited the hKv1.5 current in a time-, dose- and voltage-dependent manner with a half maximal inhibitive concentration (IC50) value of 38.85 milligram per liter. The voltage dependence was described by an equivalent electrical distance δ of 0.15, which suggested that at the binding site SXJ experienced 15% of the applied transmembrane electrical field. There were no significant different changes of SSA, τact, τdeact , ‘On’ gating current (on-Ig), and ‘off’ gating current (off-Ig) between SXJ and Control (P > 0.05). Intracellular application of SXJ could block the hKv1.5 current significantly (P < 0.05). In conclusion, SXJ produces a dose-, time-, and voltage-dependent block of hKv1.5, with interacting electrical distance δ of 0.15. SXJ did not influence the gating currents and deactivation time course. SXJ was an open-blocker, which provided the experimental research of SXJ in clinical treating atrial arrhythmia.
Integrated multi-omics reveals the beneficial roles of chlorogenic acid in improving the immune function of immunologically-stressed broilers
Authors: Liu Huawei , Li Xuemin , Zhang Kai , Lv Xiaoguo , Zhang Quanwei , Chen Peng , Wang Yang , Zhao Jinshan
Published: May 2022

Background:
Commercial broilers under intensive production are highly vulnerable to various stressors, especially immunologically. It has been reported that chlorogenic acid (CGA) could affect the intestinal microbiota and barrier function and elicit several health benefits, including improved immune function. Complex interrelations regulate the dynamic interplay among gut microbiota, host, and diverse health outcomes. The aim of the present study was to elucidate the immunoregulatory mechanisms of CGA using multi-omics approaches.
Results:
CGA supplementation significantly improved jejunal morphology, jejunal barrier function, and immune function in dexamethasone (DEX)-treated broilers. Moreover, in DEX-CGA-treated broilers, the increase in gut microbiome diversity was consistent with change in taxonomic composition, especially in the Clostridiales_vadinBB60_group. Additionally, the levels of short chain fatty acids increased remarkably after CGA supplementation, which was consistent with the results of Kyoto Encyclopedia of Genes and Genomes pathway analysis for different gut microbes. Moreover, through multiple reaction monitoring, significant enrichment was observed in the pyruvate fermentation and butanonate metabolism pathways in the DEX-CGA group. Proteomic and metabolomic analyses revealed that CGA treatment increased the expression of several health promoting proteins (TMSB4X and LGMN) and metabolites (2,4-dihydroxy benzoic acid and homogentisic acid), and regulated the peroxisome proliferator-activated receptor (PPAR) and mitogen-activated protein kinase (MAPK) pathways, which were supported by western blotting results. Pearson’s correlation analyses showed significant correlations between altered parameters of immune function, jejunal barrier function, and different microbiota, proteins, and metabolites.
Conclusions:
Overall, our data indicated that CGA treatment improved the performance and immunological functions of DEX-treated broilers by regulating gut microbiota, especially Clostridiales_vadinBB60_group, and PPAR and MAPK pathways. The result offer novel insights into CGA-mediated improvement in immune function and intestinal health.
Klotho alleviate contrast-induced acute kidney injury by suppressing oxidative stress, inflammation and NF-kappaB/NLRP3-mediated pyroptosis
Authors: Fu Yanbin , Wei Xuebiao , Cao Jianfeng , Ge Yanzhi , Su Zedazhong , Yu Danqing
Published: May 2022

Background
Contrast-induced acute kidney injury (CI-AKI) is a common complication following percutaneous coronary intervention in coronary artery disease (CAD) patients with more than 30% incidence. Klotho is a multifunctional protein that inhibits oxidative stress and inflammation, but its role in CI-AKI is poorly understood. The present study aimed to explore the effects of klohto in CI-AKI.
Methods
Six-week-old mice and HK-2 were divided into control group, contrast medium (CM) group, CM + klotho group, and klotho group. Kidney injury was evaluated by HE staining. And the renal function was shown by Scr and BUN. Cell viability and damage were determined by CCK-8 assay and lactate dehydrogenase (LDH) activity assay. Oxidative stress related indicators including intracellular reactive oxygen species (ROS), superoxidase dismutase (SOD), and malondialdehyde (MDA) were tested by fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and enzyme-linked immunosorbent assay (ELISA) assay. IL-6, TNF-α, IL-1β, and IL-18 in the cell supernatant were tested by ELISA assay and used to reflect inflammation responses. Propidium iodide (PI) staining showed the cell death of HK-2. The expression of NF-κB, phosphorylated NF-κB (p-NF-κB), and pyroptosis-related protein levels of NLRP3, caspase-1, GSDMD, and cleaved-GSDMD were detected by western blot.
Results
Exogenous Klotho administration reduced kidney histopathological alterations and improved renal function in vivo. In vitro, Klotho significantly inhibited CM-induced oxidative stress and productions of both IL-6 and TNF-α. Moreover, we found klotho inhibited the activation of p-NF-κB and down-regulated pyroptosis-related protein (NLRP3, caspase-1, GSDMD, and cleaved-GSDMD).
Conclusion
The findings suggested that klotho had a protective effect on CI-AKI via suppressing oxidative stress, inflammation and NF-κB/NLRP3-mediated pyroptosis, contributing to the potential therapy of CI-AKI.
Sleep and the Nigerian Environment: Understanding the True Markers of Sleep Quality
Authors: Ismaila Ismaila S.Olasukanmi , Odumosu Odumosu O.Odugbemi , Kuye Kuye S.I. , Folorunso Folorunso Olusegun
Published: May 2022

Sound sleep aids sound health and good ageing, unfortunately, people still wake up in the morning feeling tired, sleep at work, and sometimes unnecessarily aggressive. It is normal to experience sleeplessness once in a while, but it is not normal to regularly have problems getting to sleep at night and to wake up feeling exhausted. Poverty, socioeconomic instability, inadequate medicare etc. have continued to hamper the quality of sleep for the majority of the populace. Sleep helps the brain to function properly and not getting enough sleep or poor quality sleep has many consequences: behavioural problems in children, hypertension, fatigue, cardiovascular diseases, mental health problems etc. in adults. This study evaluated subjective sleep qualities (timing of sleep, environmental factors, health status, and socioeconomic status) on the sleep status of an average Nigerian adult in selected areas of South-West Nigeria. A descriptive analysis was used for the study as contained in the SPSS version 15.0 software on a total population of 207 adults. A self-developed questionnaire validated by experts in the field producing an Alpha reliability co-efficient of 0.735 was used for the study analysis. Findings from the study revealed no significant relationship between gender, religious affiliations and sleep quality, whereas, age, nature of work, health status, body height, marriage, the timing of sleep and hobbies have critical negative and positive significances with sleep qualities respectively. In all, the subjective sleep factors as indicated in the study could be depended upon in rating the sleep quality of an average Nigerian adult.
Prevalence of frailty and cognitive impairment in older transplant candidates. A preview to the Kidney Transplantation in Older People (KTOP): impact of frailty on outcomes study
Authors: Thind Amarpreet Kaur , Rule Annabel , Goodall Dawn , Levy Shuli , Brice Sarah , Dor Frank JMF , Evans Nicola , Ospalla David , Thomas Nicola , Wellsted David , Johannsson Lina , Willicombe Michelle , Brown Edwina A
Published: May 2022

BackgroundKidney transplantation in older people has increased, however older transplant recipients experience mixed outcomes that invariably impacts on their quality of life. The increased vulnerability of older end stage kidney disease patients to frailty and cognitive impairment may partially explain the differences in outcomes observed. The Kidney Transplantation in Older People (KTOP): impact of frailty on clinical outcomes study is an active clinical study aiming to explore the experience of older people waiting for and undergoing transplantation. In this manuscript we present the study protocol, the study cohort, and the prevalence of frailty and cognitive impairment identified at recruitment. MethodsThe KTOP study is a single centre, prospective, mixed methods, observational study. Recruitment began in October 2019. All patients aged 60 or above either active on the deceased donor waitlist or undergoing live donor transplantation were eligible for recruitment. Recruited participants completed a series of questionnaires assessing frailty, cognition, and quality of life, which are repeated at defined time points whilst on the waitlist and post-transplant. Clinical data was concurrently collected. Any participants identified as frail or vulnerable to frailty were also eligible for enrolment into the qualitative sub-study. Results208 participants have been recruited (age 60-78). Baseline Montreal Cognitive Assessments were available for 172 participants, with 72 (41.9%) participants identified as having scores below normal (score <26). Edmonton Frail Scale assessments were available for 184 participants, with 30 participants (16.3%) identified as frail (score ³8), and a further 37 participants (20.1%) identified as being vulnerable to frailty (score 6-7). ConclusionIn the KTOP study cohort we have identified a prevalence of 41.9% of participants with MoCA scores suggestive of cognitive impairment, and a prevalence of frailty of 16.3% at recruitment. A further 20.1% were vulnerable to frailty. As formal testing for cognition and frailty is not routinely incorporated into the work up of older people across many units, the presence and significance of these conditions is likely not known. Ultimately the KTOP study will report on how these parameters evolve over time and following a transplant, and describe their impact on quality of life and clinical outcomes.
Long-term prognostic implications of residual left ventricular hypertrophy and systolic dysfunction in aortic stenosis following transcatheter aortic valve replacement
Authors: Pedersen Anders Lehmann Dahl , Povlsen Jonas Agerlund , Rasmussen Vibeke Guldbrand , Frederiksen Christian Alcaraz , Christiansen Evald Høj , Terkelsen Christian Juhl , Vase Henrik , Poulsen Steen Hvitfeldt
Published: May 2022

Purpose: The impact of left ventricle (LV) hypertrophy (LVH) regression on contractility, the extent of residual cardiac dysfunction and prognostic implications after the initial remodeling process after transcatheter aortic valve replacement (TAVR) has not been investigated. We aimed to assess whether greater LV mass regression from pre-TAVR to 12-months after TAVR was associated with increased contractility and systolic function; and assess the long-term prognostic value of residual LVH, systolic function and contractility 12-months after TAVR.Methods: A total of 439 symptomatic patients were included and examined by echocardiography. LVH regression was assessed as percentage change in LV mass index (LVMi) from baseline to 12-months after TAVR. Midwall fractional shortening (mFS) and stress-corrected (SC-mFS) were used to assess contractility. Primary outcome was all-cause mortality.Results: SC-mFS increased from 0.94 (0.7) at baseline (BS) to 1.22 (0.7) (p<0.05) 12-months after TAVR for patients with the most LVH regression, compared to patients with no LV regression (BS 1.06 (0.7) to 1.04 (0.5), NS).At 12-months after TAVR, multivariate analysis showed independent prognostic value of LVEF<50% or GLS<15% (HR 1.59, p=0.049) and mFS <14% (HR 1.99, p=0.002) for future all cause death.Conclusions: LVH regression in AS after TAVR is associated with significant improvements of LV contractility in contrast to patients without LV regression. Residual LVH and subsequent LV systolic dysfunction is substantial 12 months after TAVR and are associated with reduced survival. Impaired mFS and the combination of abnormal LVEF or GLS independently predicted all-cause mortality beyond 12 months after TAVR.
Combining Bioinformatics and Experiments to Identify MAD2L2 as a Key Regulator in Ovarian Cancer
Authors: Xu Kejun , Zheng Xiaojiao , Shi Hongyan , Ou Jilan , Ding Huiqing
Published: May 2022

Ovarian cancer (OVCA) is a common gynecological malignant tumor and the fourth most common female tumor, following breast cancer, cervical cancer and endometrial cancer. Spindle Assembly checkpoint (SAC) can finely control the dynamic balance between kinetosomes and microtubules during mitosis. MAD2L2 is a chromatin binding protein and selective shear body of MAD2, one part of SAC. However, the expression and prognostic values of MAD2L2 in OVCA have not been clarified. GEPIA, UALCAN, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TIMER, Kaplan-Meier and in vito cell experiments were utilized in this study. MAD2L2 was over expression in OVCA patients and accompanied with poor survival time, especially in grade four patients. MAD2L2’s mRNA alteration way was amplification and ubiquitination was the mainly regulation way. Significant GO term analysis showed that MAD2L2 were located mainly in the organellar ribosome, where they participate primarily in NADH dehydrogenase activity. They also acted as structural constituents in mitochondrial translation elongation. KEGG pathway analysis showed enrichment in the sulfur relay system and ribosome. Four types of immune module were used and the results showed that MAD2L was relate to CD4, CD8, B cell, NK cell and Myeloid dendritic cell. At last, high level of MAD2L2 promoted cell proliferation and migration of OVCA and upregulation of MAD2L2 suppressing ferroptosis process and accompanied by mTOR signaling in OVCA cells. Therefore, suppressing MAD2L2 might be a next choice of treatment of OVCA patients. In addition to the common strategies, like chemotherapy, preventing mTOR signaling might also be a better treatment method in the future.
Characterization of Cutaneous Melanoma: Carcinogenesis Beyond Ultraviolet Light
Authors: Loss Lairane Bridi , Santi Juliana Casotti , Lima Sarah Aparecida Fernandes , Lorencini Mariana Santos , Ferri Sabrina Chaves Costa , Junior Rogério Pimentel Terra , Chiarelli-Neto Orlando
Published: May 2022

Melanoma is the most aggressive type of skin cancer due to its metastatic potential, and its incidence has increased considerably in recent decades. Sun exposure to ultraviolet A and B rays remains the main risk factor for the development of this type of cancer, however, other factors involved are family history, artificial tanning, melanocytic nevi, low phototype and melanin photosensitization by visible light (VL). Through early diagnostic detection of the malignant lesion, it is possible to initiate therapy in an early and curative way, increasing survival with a subsequent decrease in the overall mortality rate. Advances in immunotherapy and targeted therapy have changed treatment paradigms and improved the prognosis of late-stage disease. Due to the high prevalence of the disease worldwide, the objective was to review the main aspects described in the literature regarding the etiology, pathophysiology, clinic, diagnosis, and management of the pathology, with special emphasis on cutaneous melanoma upon VL exposure.
Neutrophilia during hospitalization predicts ARDS and risk of death in COVID-19 patients
Authors: Ghazi Bouchra , Azhary Khadija El , Kantri Aziza , ElGhanmi Adil , Bakkouri Jalila El , Aidaoui Karim El , Haoudar Amal , Dini Nezha , Naitlho Abdelhamid , Kettani Chafik El , Chamlal Hasna , Nejjari Chakib , Badou Abdallah
Published: May 2022

Background
Coronavirus disease 2019 (COVID-19), poses a threat to the global public health. Early identification of critical cases is crucial to providing timely treatment to patients. Here, we investigated whether white immune cell levels could predict respiratory decline, complications and mortality.
Methods
We performed a retrospective study including 119 patients presenting with COVID-19. We divided our cohort into two categories, using two different classifications. Comparison tests, prediction analysis and the logistic regression analysis were used in this study.
Results
The study revealed that a rise in neutrophils levels was associated with respiratory deterioration and intubation. In contrast, neutrophils levels plateaued in patients who remained stable. Neutrophils levels, during the first 5 days of hospitalization, positively correlated with the procalcitonin and C-reactive protein levels. Interestingly, neutrophils levels at day 5 proved to be a better predictor of intubation and acute respiratory distress syndrome than initial neutrophils counts, C-reactive protein or procalcitonin. Neutrophils counts at day 5 higher than 7,7 (109/l) (normal range: 1,4–7,7 (109/L) also effectively predicted patient mortality, independently of usual clinical classifications. Moreover, binary logistic regression with stratified revealed that neutrophils at day5 > 7,7 (109/l) was an independent risk factor of mortality and acute respiratory distress syndrome. Finally, neutrophils levels at day 5 and the proinflammatory cytokine IL-6 were correlated, which suggested a mechanistic link.
Conclusions
Our data showed that neutrophils count at day 5, rather than at admission, proved to be an excellent predictor of complications and mortality during hospitalization and could be used to improve COVID-19 patients’management.
Micellar Enhanced Spectrofluorimetric Determination of Diphenylpyraline HCl and Dual Detection Cyclodextrin Micellar Liquid Chromatographic Method for Simultaneous Determination of Diphenylpyraline HCl, Paracetamol and Caffeine in Dosage Form
Authors: Hammad Sherin F. , El-Malla Samah F. , El-Khateeb Basma Z.
Published: May 2022

Highly sensitive micellar spectrofluorimetric method (Method I) has been developed and validated for the determination of diphenylpyraline HCl in pharmaceutical tablets and in plasma. Sodium dodecyl sulfate at pH 5 enhances the fluorescence intensity of diphenylpyraline at 286 nm that allow its determination at nano-level in plasma with mean percent recovery ± S.D of 99.719 ± 0.338. In addition, Green cyclodextrin micellar liquid chromatographic method (Method II) has been developed and validated for simultaneous determination of diphenylpyraline, paracetamol and caffeine using cyclodextrin micellar mobile phase consisted of 30 mM Brij*35, 0.5 mM hydroxypropyl β-cyclodextrin and phosphate buffer pH 4: MeOH (95:5, %v/v) that allows their simultaneous determination with enhanced spectrofluorimetric detection of diphenylpyraline. Method II was successfully applied for the simultaneous determination of diphenylpyraline, paracetamol and caffeine in a ternary laboratory prepared mixture containing all possible excipients with mean percent recoveries ± S.D of 100.176 ± 1.008, 101.166 ± 0.415 and 100.708 ± 1.836, respectively. The methods are verified to have excellent greenness.
Automatic comprehensive radiological reports for clinical acute stroke MRIs
Authors: Liu Chin-Fu , Zhao Yi , Miller Michael , Hillis Argye , Faria Andreia
Published: May 2022

Background: Although artificial intelligence systems that diagnosis among different conditions from medical images are long term aims, specific goals for automation of human-labor, time-consuming tasks are not only feasible but equally important. Acute conditions that require quantitative metrics, such as acute ischemic strokes, can greatly benefit by the consistency, objectiveness, and accessibility of automated radiological reports.Methods: We used 1,878 annotated clinical brain MRIs from patients with acute ischemic strokes to generate a fully automated artificial intelligence based system that outputs radiological reports in addition to the infarct volume, 3D digital infarct mask, and the feature vector of anatomical regions affected by the acute infarct. Findings: The performance of our system was comparable to that of an expert evaluator. The weight of the components of the feature vectors that supported the prediction of the reports, as well as the prediction probabilities are outputted, making the pre-trained models behind our system interpretable. The system is publicly available, runs in real time, in local computers, with minimal computational requirements, and it is readily useful for non-expert users.Interpretation: Our system supports large-scale processing of new and legacy data, enabling clinical and translational research. The generation of reports indicates that our fully automated system is able to extract quantitative, objective, structured, and personalized information of potential clinical relevance from stroke MRIs.