bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifunctional Rural Transition Along China’s Yangtze River Transect: Spatial differentiation and Economic Relevance
Authors: Jiang Tianhe , Shi Guoqing , Zhang Yingnan
Published: February 2021

To understand rural sustainability, it is necessary to scrutinize the relationship between rural transition and economic growth. The article uses rural multifunctionality as an analytical lens through which to view the processes of the development of rural occupancy. There is a pressing need to ascertain how to quantify rural multifunctionality and reveal its spatial differentiation, as well as garner and investigate how multifunctional rural transition (MRT) responds to economic growth. This paper employed the concept of Transect to compensate for data deficiencies in a long temporal series and established the indicator system from three different aspects- “living function, production function, and ecological function”, to measure MRT along China’s Yangtze River Transect. Our analysis showed that living function and production function display an increasing trend from underdeveloped western regions to eastern economically prosperous regions, and represent a high degree surrounding urban agglomerations, while economic growth only leads to a statistically insignificant decreasing trend in ecological function. The MRT resulting from multiple factors is much diverse, complex, sophisticated, therefore, it should be understood within a framework incorporating both endogenous and exogenous factors. According to the results, it is thus important to formulate differentiated managerial countermeasures corresponding to the economic development level rather than the uniform regulations.
Transforming Growth Factor -β Level Might Be An Independent Factor Related to Occurrence of Chronic Hepatitis B
Authors: Li Ming-hui , Lu Yao , Sun Fang-fang , Chen Qi-qi , Zhang Lu , Lu Hui-hui , Zeng Zhan , Yi Wei , Xie Yao
Published: February 2021

To investigate association between immune cell-related cytokines and development of chronic hepatitis B (CHB). Patients with chronic hepatitis B virus (HBV) infection in immune tolerance (IT, n=30) and hepatitis B envelope antigen (HBeAg) positive CHB (n=250) were enrolled in the study. HBV virus, serological indicators, and plasma cytokine levels were detected at the time of enrollment. The results showed that there were significant differences in median age of patients (27 vs. 31y), alanine aminotransferase level (ALT, 29.85 vs 234.70 U/L), alanine aminotransferase level (AST, 23.40 vs. 114.90 U/L), HBsAg level (4.79 vs. 3.88 log10 IU/ml), HBeAg (1606.36 vs. 862.47 S/CO) and HBV DNA load (8.17 vs 6.71 log10 IU/ml) between IT and CHB groups (all P<0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-γ (IFN-γ), interleukin- 17A (IL-17A) and transforming growth factor- beta (TGF-β1) in IT group were significantly higher than those in CHB group (FLT3-L: 41.62 vs. 27.47 pg/ml; IFN-γ: 42.48 vs. 33.18 pg/ml; IL-17A: 15.66 vs. 8.90 pg/ml; TGF-β1: 4921.50 vs. 2234 pg/ml. All P<0.01). The median values of IFN-a2, TGF-β3 and IL-10 levels in IT group were significantly lower than those in CHB group (IFN-α2: 15.24 vs. 35.78 pg/ml, P=0.000; TGF-β3: 131.69 vs. 162.61 pg/ml, P=0.025; IL-10: 5.02 vs. 7.9 pg/ml, P=0.012). The multivariate logistic regression analysis indicated that TGF-β 1 (OR=0.999, 95% CI 0.999-1.000, P<0.001) and TGF-β2 levels (OR=1.008, 95%CI 1.004-1.012, P <0.001) were significantly associated with the incidence of CHB. The results suggest that TGF-β level might be an independent factor related to the occurrence of CHB.
WITHDRAWN: Low-Intensity Pulsed Ultrasound-Generated Singlet Oxygen Induces Telomere Damage Leading to Glioma Stem Cell Awakening From Quiescence
Authors: Song Sirong , Ma Dongbin , Xu Lixia , Wang Qiong , Liu Lanxiang , Tong Xiaoguang , Yan Hua
Published: February 2021

Background: Cancer stem cells, quiescent and drug-resistant, have become a therapeutic target. Low-intensity pulsed ultrasound (LIPUS), a new noninvasive physical device, promotes pluripotent stem cell differentiation and is mainly applied in tissue engineering but rarely in oncotherapy. We explored the effect and mechanism of LIPUS on glioma stem cell (GSC) expulsion from quiescence.Methods: Immunofluorescence staining and flow cytometry were used to detect changes of stem hallmarkers. RT-PCR results showed the gene expression levels of stem-related transcription factors. Brud and RNA-seq were performed for cell cycle analysis. Western blotting showed different expressions of key point proteins. Telomeres damage was found by FISH and IF-FISH. Fluorescence detection was used for mitochondrial membrane potential assay and singlet oxygen detection. Tumor xenograft and immunohistochemical staining were performed to confirm the role of low intensity pulsed ultrasound.Results: We found that LIPUS led to attenuated expression of GSC hallmarks, promoted GSC escape from G0 quiescence, and significantly weakened the stemness-related Wnt and Hh pathways. Next, Interestingly, LIPUS transferred sonomechanical energy into recombinant cytochrome C and B5 proteins in vitro, which converted oxygen molecules into singlet oxygen, triggering a telomere crisis. The results in vivo and in vitro confirmed that LIPUS enhanced GSC sensitivity to temozolomide.Conclusion: These results demonstrated that LIPUS “wakes up” GSCs to improve chemotherapy by transferring energy to cyt families and leading to telomere crisis.
Symptomatic Metastases have Poorer Prognosis in Breast Cancer Patients Under Intensive Surveillance
Authors: Jung Sung Mi , Ryu Jai Min , Chae Byung Joo , Yu Jonghan , Lee Jeong Eon , Kim Seok Won , Nam Seok Jin , Lee Se Kyung
Published: February 2021

Purpose The purpose of this study was to investigate risk factors for post-metastasis overall survival (PMOS), and to analyze the effect of early detection of distant metastases before symptoms occur on survival in breast cancer patients under intensive surveillance.Methods A total of 7,840 patients underwent surgery for breast cancer from January 2010 to December 2014 at Samsung Medical Center; of these, we retrospectively studied 316 metastatic breast cancer patients. The patients were divided into two groups based on method of metastases detection, routine surveillance without symptoms (asymptomatic group) or follow-up for new-onset symptoms (symptomatic group).Results Multivariate analysis of PMOS showed that the patients with multiple metastases had a 1.872 fold risk of PMOS (p = 0.011) compared to the patients with bone metastasis only. The hazard ratio for the symptomatic group was higher than that for the asymptomatic group (p < 0.001). When patients were stratified by tumor subtype, patients who were HR-positive and asymptomatic on diagnosis of distant metastasis had a better prognosis than those who were HR-positive and symptomatic on diagnosis. However, patients who were HER2-positive showed no significant survival difference between two groups.Conclusion Breast cancer patients who were diagnosed with distant metastasis after symptoms occurred had a poorer prognosis than patients who were diagnosed before symptoms had developed. It is important to follow up patients regularly for symptoms related to distant metastases. Our findings validate the need for intensive surveillance, suggesting reconsideration of the guidelines for metastases screening in breast cancer patients.
High Resolution Time-to-digital Conversion Circuit for HgCdTe APD Detector at 77K
Authors: wen zhang qi , Honglei Chen , Ruijun Ding
Published: February 2021

HgCdTe avalanche photodiode (APD) is a frontier research on infrared focal plane technology, High-precision time stamp readout circuit is the basis of the APD focal plane at 77 K, which directly affects APD infrared focal plane performance. Time-to-digital conversion circuit (TDC) is one of the methods to achieve high-precision time stamping. Based on the analysis of MOSFET at low temperature, our design a vernier TDC circuit, which uses a synchronous counter to quantize an integer multiple of the period to achieve a coarse count of 6 bits; The on-chip PLL multiplied high-frequency clock has high-precision and high PVT characteristics, using it to quantify the part that is less than one clock cycle to achieve a fine-count of 6 bits output. The circuit adopts standard CMOS process tape out, our circuit works at a master-frequency of 120 MHz. At 77 K, the circuit test can distinguish the time resolution of 236.280 ps. The DNL is within -0.54~0.71 LSB, and INL is within -1.32~1.21 LSB.
Hydro-geochemical evaluation of groundwater for irrigation in the Ganges river basin areas of Bangladesh
Authors: Islam Md Shajedul , Mostafa Md. Golam
Published: February 2021

Groundwater is a vital source of irrigation water, and it provides over 80% of the irrigated water supply in Bangladesh. The study aimed to assess the status of irrigation water of the Ganges river basin areas in the middle-west part of Bangladesh through the hydrogeochemical characterization and classification of groundwater. The study parameters were pH, EC, TDS, Ca2+, Mg2+, total hardness, Na+, K+, B, Cl−, HCO3 −, SO 42−, NO3 −, and PO43− along with irrigation water quality index (IWQindex), Na%, soluble sodium percentage, sodium adsorption ratio, residual sodium bicarbonate, magnesium adsorption ratio, permeability index, and Kelley’s ratio. The results showed that most of the water samples were acidic in the pre-monsoon and alkaline in the post-monsoon seasons, and the water type was Ca-HCO3. The significant geochemical process in the area determined was calcite and dolomite mineral dissolution, and there was no active cation exchange, and silicate weathering occurred. The statistical analyses showed that both the geogenic and anthropogenic sources were controlling the chemistry of the groundwater aquifers. Concerning irrigation water quality, the results revealed that all the quality parameters and IWQindex (32.04 to 45.39) were within the safety ranges, except for the EC and total hardness. The study results would be useful for future groundwater monitoring and management of the Ganges basin areas of Bangladesh part.
WITHDRAWN: Forecasting Daily Global Solar Radiation in Hot Semi-Arid Climate Using a Novel Hybrid Machine Learning Paradigm
Authors: jamei Mehdi , Ahmadianfar Iman , Jamei Mozhdeh , Karbasi Masoud , Heidari Ali Asghar , Chen Huling
Published: February 2021

Solar energy is one of the most important renewable energy sources. Assessing the solar potential of area needs analyzed information about the dataset of the measured global solar radiation (GSR). Recently, researches detected the high potential of state-of-the-art artificial intelligence (AI) methods in estimating the GSR successfully. In this study, a novel hybrid AI-based tool consisting of least square support vector machine (LSSVM) integrated with improved simulated annealing (ISA) is proposed to predict the GSR over the Ahvaz synoptic station located in the South-West of Iran. The potential of the proposed hybrid paradigm so-called LSSVM-ISA was evaluated by using multivariate adaptive regression spline (MARS), generalization regression neural network (GRNN), and multivariate linear regression with interactions (MLRI). For precise assessment of efficiency of the AI models, various statistical metrics and validation methods were used to assess the precision of the developed models. A comparison of the obtained results indicated that the LSSVM-ISA method performed better than the MARS, GRNN, and MLRI models. The achieved RMSE values of the MARS, GRNN, and MLRI models were decreased by 9%, 16%, and 30% using the LSSVM-ISA model. Finally, the results demonstrated that the LSSVM-ISA model could be successfully employed for accurately predicting GSR.
Lamivudine-Induced Recurrent Drug Eruption in HIV: A Curious Case of Its Treatment
Authors: Wang Hong , Li Hongbo , Sui Jian'e , Zhao Juan , Ma Saisai , Chen Peng , Xu Guangyong
Published: February 2021

Background: Drug eruption may occur when HIV patients receive antiviral treatment. However, Lamivudine-induced repeated drug eruption has rarely been reported among the antiretrovirals.Case presentation: We report a rare case of repeated drug eruption caused by Lamivudine. The treatment history of this patient was interesting. Patients developed repeated drug eruption regardless of treatment TDF+3TC+EFV or TDF+3TC+LPV/r. The viral load of the patient in 2016 and 2017 was 58 copies/ml and < 50 copies/ml respectively by TDF+LPV/r with no drug eruption, but antiviral failure was found in 2018. This patient was successfully treated with TDF+LPV/r+DTG in 2019 and 2020.Conclusions: Through repeated drug eruption of the patient, we found that the allergenic drug is Lamivudine. The viral load of the patient can be effectively controlled by TDF+LPV/r+DTG.
Enlightening the Taxonomy Darkness of Human Gut Microbiomes With a Cultured Biobank
Authors: Liu Chang , Du Mengxuan , Abuduaini Rexiding , Yu Hai-Ying , Li Dan-Hua , Wang Yu-Jing , Zhou Nan , Jiang Min-Zhi , Niu Peng-Xia , Han Shan-Shan , Chen Hong-He , Shi Wen-Yu , Wu Linhuan , Xin Yu-Hua , Ma Juncai , Zhou Yuguang , Jiang Cheng-Ying , Liu Hong-wei , Liu Shuang-Jiang
Published: February 2021

BackgroundThe cultivated gut microbial resource plays essential roles in gut microbiome studies such as unraveling gut microbial functions and host-microbe interactions. Though several major studies have been performed to understand the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species remain uncultivated. Large-scale gut microbial isolation and identification and their access to public are imperative for gut microbial studies and further understanding of the human gut microbial functions.ResultsHere, we report the construction of a human Gut Microbial Biobank (hGMB) (homepage: hgmb.nmdc.cn) by cultivation of 10,558 isolates from 239 feces samples of healthy Chinese volunteers, and deposited 1,170 strains representing 400 different species in culture collections of International Depository Authority for long-term preservation and public access worldwide. The hGMB enriched the existing cultivable gut microbial repository and represented over 80% of the common and dominant human gut microbial genera and species of global human gut 16S rRNA gene amplicon data (n=11,647).Moreover, 102 new species were characterized and denominated and 28 new genera and 3 new families were proposed, following the rules of International Code of Nomenclature of Prokaryotes. The hGMB uncovered 24 “most-wanted” and “medium priority” taxa proposed by the Human Microbiome Project, while the novel-taxon genomes represented 22 previously-uncultured species in Unified Human Gastrointestinal Genome (UHGG) and contributed 24 potentially “dark-taxon” representatives that were not discovered by UHGG. The 115 newly-sequenced hGMB genomes covered over 50% of the known genes (KEGG Orthologs) in the global human gut gene catalogs and over 10% of the “most-wanted” functionally unknown proteins in FUnkFams database.ConclusionsA publicly accessible human Gut Microbial Biobank (hGMB) is established and contains 1,170 strains and represents 400 human gut microbial species. The hGMB expands gut microbial resources and genomic repository by adding 102 novel species, 28 new genera and 3 new families, and 115 new genomes of human gut microbes.
Two New Species of Russula Subsect. Virescentinae From Southern China
Authors: Chen Bin , Song Jie , Liang Jun Feng , Li Yang Kun
Published: February 2021

Two new species from southern China, Russula subpunicea and R. albolutea, were described and illustrated. Russula subpunicea is characterized by a pinkish to dark pink pileus with striations at the margin, white lamellae without lamellulae, subglobose to broadly ellipsoid to ellipsoid basidiospores with warts and spines sometimes joined to form a reticulum, hymenial cystidia that are mainly clavate, a suprapellis mainly composed of chains of short inflated cells with attenuated terminal cells and pileocystidia that are mainly clavate and turn reddish in sulfovanillin. Russula albolutea is recognized by a yellowish white pileus with long striations at the margin, a white stipe with a yellowish tinge, subglobose to broadly ellipsoid to ellipsoid basidiospores, hymenial cystidia that are mainly clavate and apically often obtuse and turn mauve in sulfovanillin, and a suprapellis mainly consisting of chains of short inflated cells with attenuated terminal cells. In this study, we performed phylogenetic analysis based on the ITS-nrLSU-RPB2-mtSSU dataset. By combining detailed morphological features with multigene phylogenetic evidence, we assigned the new taxa to Russula subsect. Virescentinae.
State-Level Partisanship Strongly Correlates With Health Outcomes for Us Children
Authors: Paul Megan , Zhang Ruya , Liu Bian , Saadai Payam , Coakley Brian A.
Published: February 2021

Introduction:The Cook Partisan Voting Index (PVI) determines how strongly a state leans toward the Democratic or Republican Party in presidential elections compared to the nation. We set out to determine the correlation between childhood health outcomes and state-level partisanship using PVI.Materials and Methods:16 measures of childhood health were obtained from the CDC, U.S. Census Bureau, and U.S. Bureau of Labor Statistics for 2012-2016. PVI was averaged for every state for the same time period. Pearson's rho determined the correlation between PVI and each health outcome, using a Bonferroni adjustment of 0.003. Multiple regression was also conducted, adjusting for children without health insurance, primary care physicians, childhood poverty, and % non-white. We also compared childhood health in moderately Democratic and Republican states (5%-9.9% more Democratic/Republican than the national mean) and, similarly, for extremely Democratic and Republican states (10% or more Democratic/Republican than the national mean), using Kruskal-Wallis tests. Results:Democratic-leaning states had better outcomes for 7 of 16 health measures (all p<0.003, table 1). In the adjusted model, Democratic-leaning states had better outcomes for 9 of the 16 variables (all p<0.003, table 1). Among moderately-partisan states, no outcomes were statistically better in one group of states but extremely-Democratic states had superior outcomes for 5 variables (all p<0.003, table 2). No health outcomes were found to be significantly better in Republican-leaning states.Conclusions:Multiple childhood health measures were statistically better in Democratic-leaning states compared to Republican counterparts. Future research should identify which state-level policies have led to such disparate health outcomes.
Structural, Electrical and Ferroelectric Properties of Lead-free Bi(Fe0.85dy0.15)o3 Electroceramic Compound
Authors: Thansanga L. , Shukla Alok , Kumar Nitin , Choudhary R.N.P.
Published: February 2021

This paper mainly reports detailed studies of structural, dielectric, impedance and ferroelectric properties of Bi(Fe0.85Dy0.15)O3­ (termed as BFDO15), fabricated via solid state reaction (SSR) method. Analysis of X-ray diffraction (XRD) data confirm the crystal symmetry changes from rhombohedral to orthorhombic symmetry. The scanning electron micrograph collected through field emission scanning electron microscopy (FE-SEM) shows a regular distribution of grains over the sample surface. The elemental composition of the sample was examined by using energy dispersive X-ray micro-analysis (EDXMA) and this confirms the existence of constituent elements of the sample. The electrical measurement was carried out using a computer-controlled phase sensitive multimeter (PSM) in a frequency range of 1 kHz - 1000 kHz and temperature range of 25 ºC – 500 ºC. Study of dielectric properties shows high dielectric permittivity and small value of dielectric loss in the sample. The frequency dependent impedance and electrical modulus analysis reveals the presence of a semiconducting nature and non-Debye type relaxation process. Analysis of ac-conductivity with respect to frequency obeys the universal Jonscher’s power law. The electric polarization study shows enhancement in ferroelectric property of the material. Hence, based on the significant enhancement found in the structural, electrical and ferroelectric properties of BFDO15 material, it could be a promising candidate for modern device applications.
Single-Port Endoscopic Sentinel Lymph Node Biopsy Combined with Indocyanine Green and Carbon Nanoparticles in Breast Cancer: A Retrospective Cohort Study
Authors: Wang Zi-Han , Gang Tian-Ran , Wu Shan-Shan , Lu Can , Xuan-Gao Guo , Xu Wei , Ding Guo-Qian , Qu Xiang , Zhang Zhong-Tao
Published: February 2021

PurposeIndocyanine green (ICG) is an efficient tracer method used in sentinel lymph node biopsy (SLNB). The application of single-port endoscopic-assisted technology in the field of breast cancer is widely accepted. In order to explore the surgical safety of single-port endoscopic-SLNB (SPE-SLNB) and the reliability of axillary staging, we combined it with ICG that was excited by near-infrared fluorescence endoscopy and carbon nanoparticles (CN) as a tracer and compared this method to conventional open SLNB (C-SLNB).MethodsSixty patients with early breast cancer were recruited and divided into three groups. Twenty patients who underwent SPE-SLNB combined with ICG and CNs were placed in group A. Twenty patients who underwent SPE-SLNB with CNs only were placed in group B. Twenty patients who underwent C-SLNB with ICG and CNs were placed in group C.ResultsThe detection rate of SLNs was 100% in group A, 100% in group B, and 95% in group C. In total, 97 SLNs were detected in group A, 65 SLNs were detected in group B, and 98 SLNs were detected in group C . ConclusionThe novel technique of combining ICG and CNs with SPE-SLNB and the utilization of the endoscopic fluorescence imaging system achieved the same detection rate and mean number of SLNs as C-SLNB. Therefore, for patients who meet the indications, SPE-SLNB is as safe and reliable as C-SLNB.
The Use of Robinia Pseudoacania L Fruit Extract as a Natural Corrosion Inhibitor in the Protection of Historical Bronze Objects
Authors: Pourzarghan Vahid , Fazeli-Nasab Bahman
Published: February 2021

Background: The phenomenon of bronze disease is considered as the most important factor in the destruction of bronze objects. Different methods have been proposed to deal with it. The most important inhibitors used in this regard are BTA and AMT. While these inhibitors control the corrosion, they are toxic and cancerous. In ideal conditions, these inhibitors are able to slow down the activity of chlorine ion, but leave some side effects after a period of treatment. Today, plant extracts are used for this purpose. In this study, Robinia pseudoacania L extract was selected for this purpose.Material and methods: The acacia fruit extract (200ppm to 1800 ppm) was used to the prevention of corrosion inhibition of bronze alloy in corrosive sodium chloride solution 0.5 M. The Bronze alloy used in this research, was made based on the same percentage as the ancient alloys (Cu-10Sn). This alloy was used for the effect of corrosion inhibitors in the potentiostat device, the weight loss method. The experiment was conducted in split plot desgin in time based on the randomized complete design in four replications.Results: Mean comparison showed that the highest rate of corrosion inhibition (93.5%) was obtained at a concentration of 1800 ppm and with increasing the concentration of the extract, corrosion inhibition also increased. EDX analysis of the control sample matrix showed that the amount of chlorine, which is the most important factor in the destruction of bronze disease, was 8.47%wt while in the presence of corrosive sodium chloride solution, after 4 weeks, the amount of chlorine detected was 3.20%wt. According to the morphology (needle and rhombus) of these corrosion products based on the SEM image, it can be said that they are of the type of atacamite and paratacamite that have caused bronze disease in historical bronze works. At higher concentrations of acacia extract, the presence and growth of fungi has been observed, which can cause poor performance of acacia extract in the long run.Conclusion: the natural inhibitor of acacia fruit aqueous extract can play an effective role in inhibiting corrosion of bronze, but at higher concentrations, it became fungal, which can reduce the role of acacia fruit aqueous extract and even ineffective. Because natural inhibitors can play an effective role in preventing the corrosion of bronze works. But to get better performance of these inhibitors, more tests need to be done to improve and optimize.
Progranulin Deficiency in Iba-1+ Myeloid Cells Exacerbates Choroidal Neovascularization by Perturbation of Lysosomal Function and Abnormal Inflammation
Authors: Takahashi Kei , Nakamura Shinsuke , Otsu Wataru , Shimazawa Masamitsu , Hara Hideaki
Published: February 2021

BackgroundAge-related macular degeneration (AMD) is the principal cause of permanent blindness among elderly individuals worldwide. Chronic inflammation in the subretinal space is associated with a progression of exudative AMD. Progranulin (PGRN) is a growth factor secreted from myeloid cells and plays an important role in controlling the lysosomal function. A deficiency of PGRN leads to inflammation of the neurons in the central nervous system. The purpose of this study was to investigate the role played by PGRN in the size of the choroidal neovascularization (CNV) in laser-induced CNV mice.MethodsCNVs were induced in C57BL/6J mice by laser photocoagulation of the retina. The expression of PGRN and the accumulation of Iba-1+ cells around the sites of the CNVs were determined. Grn−/−, Grn+/-, and Grn+/+ mice with laser-induced CNVs were also studied. To evaluate the effect of macrophages on the inflammation, we used a macrophage cell line (RAW264.7) in which the expression of PGRN was knocked down by RNA interference. These cells were incubated under hypoxic conditions (1% O2) for 12 hours.ResultsIba-1+ myeloid cells migrated and accumulated in the photocoagulation-induced CNV areas, and the CNV lesions secreted high levels of PGRN in Grn+/+ mice. The size of the CNVs was larger in Grn-/- mice than in Grn+/- and Grn+/+ mice. In Grn-/- mice, the number of ocular-infiltrating Iba-1+ cells around the CNV was higher, and these cells produced more VEGF-A than the cells in the Grn+/+ mice. PGRN-silencing of RAW264.7 cells led to an abnormal activation of the cells. In addition, hypoxic conditions promoted the production of pro-angiogenic and pro-inflammatory cytokines from PGRN-silenced macrophages. Interestingly, the expression level of lysosome-associated proteins and the number of activated lysosomes increased in siGrn-treated macrophages. ConclusionsThese findings indicate that PGRN deficiency in Iba-1+ cells activates the lysosomal function that then leads to abnormal inflammation. The aberrant activation of PGRN deficient Iba-1+ myeloid cells might promote the progression of the CNV.
A Network Pharmacology Study on the Qiju Dihuang Pills for Treatment of Dry Eye Disease
Authors: Song Qiuyi , Yang Jiawei , Zhang Mingxu , Zhu Siquan
Published: February 2021

BackgroundDry eye disease(DED) is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. DED has a higher incidence in old age and is seen predominantly in females worldwide. Treatments that replenish deficient tears include artificial tears, gels and ointments in mild to moderate disease. Qiju Dihuang Pills is a typical herb decoction applied to the treatment of ocular disease. This study is to identify potentially active compounds and the underlying mechanisms of Qiju Dihuang Pills in the treatment of DED.MethodCompounds in Qiju Dihuang Pills were collected from Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP) online databases and then screened by bioavailability and drug likeness parameters. Related targets of DED obtained from GeneCards database, thereby obtaining the targets of Qiju Dihuang Pills against DED. DED-related genes were conducted for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein-protein interaction (PPI) networks of the genes were constructed using Cytoscape software.ResultIn total, 121compounds from Qiju Dihuang Pills were screened out with 219 putative target genes. Hence, 219 potential target genes of Qiju Dihuang Pills were selected for further study. After overlap analysis of the 219 genes of Qiju Dihuang Pills and 3533 DED-associated genes, we finally achieved 162 Qiju Dihuang Pills-DED target genes. Network analysis indicated that main targets of main active components of Qiju Dihuang Pills were target genes such as Proline-rich AKT1 substrate 1 (AKT1), interleukin 6(IL-6), Mitogen-activated protein kinase 3(MAPK3), Vascular endothelial growth factor A(VEGFA), and Caspase-3(CASP3), which are involved in the regulation of cancer pathway, Tumor necrosis factor(TNF) signal pathway, hepatitis B pathway, The interleukin 17(IL-17) signaling pathway and so forth. ConclusionOur data provide deep understanding of the pharmacological mechanisms of Qiju Dihuang Pills in attenuating dry eye syndrome. The discovery shed new light on the development of active compounds of Qiju Dihuang Pills for the treatment of DED. Qiju Dihuang Pills alleviated dry eye disease through multi-component, and multi-pathway.
Dendrobium Mixture Improved Diabetic Nephropathy in db/db Mice by Regulating TGF-β1/Smads Signal Transduction
Authors: Chen Yong , Lin Xiaohui , Zheng Yanfang , Yu Wenzhen , Lin Fan , Zhang Jieping
Published: February 2021

BackgroundDendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. MethodsTwenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed using a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect mRNA expression of TGF-β1 and alpha-smooth muscle actin (α-SMA) genes and proteins, respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. ResultsDMix significantly reduced FBG level, BW, KW, and blood lipid level, and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced protein and mRNA expression of TGF-β1 and α-SMA, and inhibited Smad2 and Smad3 phosphorylation. ConclusionsThe findings suggest that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway. Key words: Diabetic nephropathy, Dendrobium mixture, TGF-β1/Smads signaling pathway
Detection of Chikungunya Virus in Saliva and Urine Samples of Patients from Rio de Janeiro, Brazil. A Minimally Invasive Tool for Surveillance
Authors: Salles Tiago Souza , Sá-Guimarães Thayane Encarnação , Guimarães-Ribeiro Victor , Melo Ana Claudia Amaral , Ferreira Davis Fernandes , Moreira Monica Ferreira
Published: February 2021

In this study, we collected saliva and urine samples from individuals in the metropolitan region of Rio de Janeiro, Brazil, during the years of 2017 through 2019 and we were able to detect the presence of Chikungunya virus genome in these samples. Our findings reinforce the possibility to monitor Chikungunya virus circulation by analyzing saliva and urine from individuals during inter-epidemic periods.
Challenges to Engaging Patients in Healthcare Implementation and Promising Solutions: An Environmental Scan
Authors: Woodward Eva , Castillo Andrea Isabel Melgar , True Gala , Willging Cathleen , Kirchner JoAnn
Published: February 2021

Background: Inequities exist in delivery of helpful, effective healthcare interventions. One emerging paradigm to address these inequities is to engage consumers of healthcare (e.g., patients, families, caregivers) in the implementation process. There are not enough examples or standards of successful consumer engagement in implementation, which limits clarity on processes other implementers could be using. Implementation scientists need a clear foundation from which to build processes or strategies with more specificity to engage consumers in healthcare settings. Methods: We conducted an environmental scan of three data sources: archived webinars, literature review articles, and interviews/observations with implementers who engaged consumers in efforts to introduce new programs and practices in healthcare settings. We described examples of consumer engagement in implementation efforts, categorized recurring challenges, and identified promising solutions to those challenges. We extracted and categorized data using a coding template informed by frameworks from implementation science and stakeholder engagement literature.Results: We found 26 examples of consumer engagement in implementation of healthcare service delivery (through research or clinical practice), mostly in the United States. Most implementers engaged consumers using a medium level of intensity. These projects described nine recurring challenges; the three most frequently identified were: 1) recruiting consumers representative of actual patients served in the healthcare system; 2) ensuring processes that allow for equitable communication among all stakeholders; and 3) retaining consumers in implementation efforts. We also matched promising solutions described by implementers to recurring challenges in consumer engagement in implementation.Conclusion: We clarified the foundation of who, how, and where a sample of implementers are engaging consumers in healthcare implementation initiatives. A notable finding is implementers rarely specified if they were targeting a patient population experiencing healthcare inequities.
Stability Analysis of Slope Considering the Energy Evolution of Locked Segment
Authors: Yin Xiangjie , Lin Hang , Chen Yifan , Tang Yi , Wang Yixian , Zhao Yanlin , Yong Weixun
Published: February 2021

Researches on the energy evolution of the key blocks is helpful to reveal the failure process of locked-segment type slope, whose stability is governed by the locking section along the potential slip surface. In order to study the failure mechanism of the locked segment in the process of slope progressive failure due to strength attenuation, a series of stability analysis on the numerical models of locked-segment type slope were implemented to record the relationship curve between energy and strength reduction coefficient. Then, according to the variation law and characteristic of energy evolution, the failure process of the locked segment was divided into four stages: elastic stage, initial damage stage, extensive damage stage and failure stage. And the reduction coefficient corresponding to the peak of the energy evolution curve was employed to achieve landslide warning. In addition, the method to determine the safety factor of locked-segment type slope was given, and its reliability was verified by comparing with other traditional methods. Finally, the formula for calculating the initial sliding velocity was presented based on the residual strain energy which is defined as the elastic strain energy of the locked segment when the slope is unstable.
Emergence of a Novel Recombinant of CV-A5 in HFMD Epidemics in Xiangyang, China
Authors: Yu Yuting , Luo Zhiyu , Jin Weiping , Mai Jianyi , Lu Jia , Meng Shengli , Wang Zejun , Guan Xuhua , Shen Shuo , Tong Yeqing
Published: February 2021

Hand, foot and mouth disease (HFMD) is caused by a variety of enterovirus serotypes and the etiological spectrum worldwide has been changing since a large scale of outbreaks occurred in 1997. A large number of clinical specimens of HFMD patients were collected in Xiangyang and genotyping was performed by qRT-PCR, conventional PCR amplification and sequencing. Among the146 CV-A5 cases detected, the complete genome sequences of representative strains were determined for genotyping and for recombination analysis. It was found that CV-A5 was one of the six major serotypes that caused the epidemic from October 2016 to December 2017. Phylogenetic analyses based on the VP1 sequences showed that these CV-A5 belong to the genotype D which dominantly circulates in China. Recombination occurred between the CV-A5 and CV-A2 strains with a breakpoint at the nt position 3,791 in the 2A region. The result may explain the emergence of CV-A5 as one of the major pathogens of HFMD.
Identification of a Frameshift Mutation in SON Gene via Whole Exome Sequencing in a Patient With ZTTK Syndrome
Authors: Peng Fujun , Zhu Lina , Hou Yu , Gu Ruijie , Wang Yongxia , Wen Xiufang , Jiang Taijiao , Ma Xiuwei
Published: February 2021

Backgrounds: Since the association between SON gene and Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM 617140) is formally recognized, the purpose of this study is to detailed report a Chinese girl with clinical features and SON variant. The other aim is to review the previously published papers of ZTTK syndromes to summarize the clinical and genetic characteristics to provide guidance for the ZTTK diagnosis.Case presentations: We report a Chinese girl with typically clinical features of ZTTK syndrome: intellectual disability, developmental delay, cerebral cortex’s aberrations, epilepsy, vision problems, musculoskeletal abnormalities and congenital malformations. Then, the whole exome sequencing (WES) analysis showed that the child had a heterozygous mutation c.5753_5756delTTAG (p. Val1918Glufs*87) in exon 3 of SON gene, which was verified by Sanger sequence, lead to the loss of function of SON protein. Conclusions: We predicted that the heterozygous mutation c.5753_5756delTTAG (p. Val1918Glufs*87) in exon 3 of SON gene caused the ZTTK syndrome, and also was a very hot-spot mutation of SON gene. Further, the summary of all the patients with ZTTK syndromes in clinical, neuroimaging and genetics characteristics could provide guidance for the ZTTK syndrome’s diagnosis.
Who has nature during the pandemic? COVID-19 cases track widespread inequity in nature access across the United States
Authors: Spotswood Erica , Benjamin Matthew , Stoneburner Lauren , Wheeler Megan , Beller Erin , Balk Deborah , McPhearson Timon , Kuo Ming , McDonald Robert
Published: February 2021

Urban nature can alleviate distress and provide space for safe recreation during the COVID-19 pandemic. However, nature is often less available in low-income and communities of color—the same communities hardest hit by COVID-19. We quantified nature inequality across all urbanized areas in the US and linked nature access to COVID-19 case rates for ZIP Codes in 17 states. Areas with majority persons of color had both higher case rates and less greenness. Furthermore, when controlling for socio-demographic variables, an increase of 0.1 in Normalized Difference Vegetation Index (NDVI) was associated with a 4.1% decrease in COVID-19 incidence rates (95% confidence interval: 0.9-6.8%). Across the US, block groups with lower-income and majority persons of color are less green and have fewer parks. Thus, communities most impacted by COVID-19 also have the least nature nearby. Given urban nature is associated with both human health and biodiversity, these results have far-reaching implications both during and beyond the pandemic.
A Transition Towards Localizing the Value Chain of Photovoltaic Energy in Saudi Arabia
Authors: Almarshoud A F , Adam Elfadil
Published: February 2021

The present paper draws attention to the importance of localizing the value chain of photovoltaic solar energy in Saudi Arabia based on the country’s vision for 2030 to meet the expected increase in energy demand. This paper describes various obstacles and enablers and shows the critical factors that restrain the development of the value chain of photovoltaic solar energy. In this paper, different phases of upstream and downstream activities of the photovoltaic industry value chain related to the current situation in Saudi Arabia were examined and analyzed. This paper further examines the capabilities of the local content of photovoltaic solar energy to determine the scenarios that can be adopted to enhance the photovoltaic solar energy industry. This paper analyzes the expected significant positive impact of localizing the value chain of the photovoltaic solar energy industry on the socioeconomic development, job creation, and technology transfer in Saudi Arabia. The paper concludes with recommendations to facilitate the expansion of the photovoltaic solar industry in Saudi Arabia.
Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation
Authors: Jiang Jianjun , Shi Yining , Cao Jiyu , Lu Youjin , Sun Gengyun , Yang Jin
Published: February 2021

Background: This study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms.Methods: Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1β and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content.Results: Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1β, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-κB (NF-κB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-κB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression.Conclusion: This study demonstrated that the ASM/Cer/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-κB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.
Implementation and effectiveness of continuous kangaroo mother care: a participatory action research protocol
Authors: Mohammadi Marzieh , Bergh Anne Marie , Heidarzadeh Mohammad , Hosseini Mohammad Baghr , Sattarzadeh Niloufar , Valizadeh Leila , Sarvaran Behzad , Hakimi Sevil
Published: February 2021

Background The efficacy of continuous kangaroo mother care (C-KMC) in reducing neonatal mortality and morbidity among low birth weight and premature infants has been confirmed. Despite the recommendations of the World Health Organization, UNICEF, and the Ministry of Health of Iran to use C-KMC for eligible hospitalized neonates, this type of care is not performed due to implementation problems. This protocol aims to describe the design, implementation, and assessment of C-KMC in one tertiary hospital by means of participatory action research.Methods The objective of this study is to design and implement a C-KMC program for neonates that will be performed in two phases using a stages-of-change model. The first phase will be conducted in three consecutive activities of designing, implementing, and assessing the introduction of C-KMC. The second phase of the study has a before-and-after design to assess the effectiveness of C-KMC by comparing the length of preterm neonates’ stay in hospital and exclusive breastfeeding at discharge before and after implementing C-KMC.Discussion KMC is an important component of neonatal developmental care as part of family-centered care. Applying this type of care requires creating appropriate strategies, budget allocation, and clear and coordinated planning at different levels of the health system. The stages-of-change model is one of the appropriate approaches to the implementation of C-KMC.
Thousands of previously unknown phages discovered in whole-community human gut metagenomes
Authors: Benler Sean , Yutin Natalya , Antipov Dmitry , Raykov Mikhail , Shmakov Sergey , Gussow Ayal B , Pevzner Pavel A , Koonin Eugene
Published: February 2021

Background: Double-stranded DNA bacteriophages (dsDNA phages) play pivotal roles in structuring human gut microbiomes; yet, the gut virome is far from being fully characterized, and additional groups of phages, including highly abundant ones, continue to be discovered by metagenome mining. A multilevel framework for taxonomic classification of viruses was recently adopted, facilitating the classification of phages into evolutionary informative taxonomic units based on hallmark genes. Together with advanced approaches for sequence assembly and powerful methods of sequence analysis, this revised framework offers the opportunity to discover and classify unknown phage taxa in the human gut.Results: A search of human gut metagenomes for circular contigs encoding phage hallmark genes resulted in the identification of 3,738 apparently complete phage genomes that represent 451 putative genera. Several of these phage genera are only distantly related to previously identified phages and are likely to found new families. Two of the candidate families, “Flandersviridae” and “Quimbyviridae”, include some of the most common and abundant members of the human gut virome that infect Bacteroides, Parabacteroides and Prevotella. The third proposed family, “Gratiaviridae”, consists of less abundant phages that are distantly related to the families Autographiviridae, Drexlerviridae and Chaseviridae. Analysis of CRISPR spacers indicates that phages of all three putative families infect bacteria of the phylum Bacteroidetes. Comparative genomic analysis of the three candidate phage families revealed features without precedent in phage genomes. Some “Quimbyviridae” phages possess Diversity-Generating Retroelements (DGRs) that generate hypervariable target genes nested within defense-related genes, whereas the previously known targets of phage-encoded DGRs are structural genes. Several “Flandersviridae” phages encode enzymes of the isoprenoid pathway, a lipid biosynthesis pathway that so far has not been known to be manipulated by phages. The “Gratiaviridae” phages encode a HipA-family protein kinase and glycosyltransferase, suggesting these phages modify the host cell wall, preventing superinfection by other phages. Hundreds of phages in these three and other families are shown to encode catalases and iron-sequestering enzymes that can be predicted to enhance cellular tolerance to reactive oxygen species.Conclusions: Analysis of phage genomes identified in whole-community human gut metagenomes resulted in the delineation of at least three new candidate families of Caudovirales and revealed diverse putative mechanisms underlying phage-host interactions in the human gut. Addition of these phylogenetically classified, diverse and distinct phages to public databases will facilitate taxonomic decomposition and functional characterization of human gut viromes.