bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative Analysis of Systems Pharmacology and Proteomics to Identify Key Targets and Pathways of Tuomin-Zhiti-Decoction for Allergic Rhinitis
Authors: Cheng Jinjun , Zhang Meiling , Zheng Yanfei , Wang Ji , Wang Qi 
Published: November 2021

Abstract
Background: Tuomin-Zhiti-Decoction (TZD) is a polyherbal medicine consisting of eleven different herbs and has a significant effect on Allergic rhinitis (AR), yet its underlying mechanism is still unknown. Methods: Mice were sensitized and intranasally challenged with ovalbumin (OVA), the nasal symptoms, Th1/Th2-related cytokines and histopathology were examinated after TZD treatments. Bio-active compounds, potential therapeutic targets and underlying mechanisms of TZD against AR were systematically elucidated by integrating systems pharmacology approach and proteomics analysis. Then we validated the binding affinity between key targets and their corresponding active compounds using molecular docking evaluation.Results: A total of 280 active ingredients, 240 targets of TZD and 643 AR-related targets were obtained. Furthermore, 74 overlapping targets were identified. TZD oral administrations inhibited allergic responses via reduction of OVA-specific immunoglobulin E (IgE) levels and histamine release. In nasal tissue, TZD not only decreased nasal rubbing and sneezing to AR mice, but also reduced AR-induced damage to nasal mucosa, accordingly, the nasal symptoms were also clearly ameliorated. Moreover, TZD modulated the balance of Th1/Th2/Th17. The proteomics analysis identified 41 differentially expressed proteins (DEPs), protein function analysis showed that the DEPs were mainly involved in PI3K-AKT, MAPK, EGFR tyrosine kinase inhibitor resistance, NF-kappa B signaling pathway. Our results indicate that TZD plays important roles by restoring DEPs, through the selection of key DEPs, IL-6 and CD40 may be potential protein targets of TZD in treatment of AR. Combining the systems pharmacology, quercetin and wogonin may play more effective roles in AR. Molecular docking confirmed that most active compounds of TZD could bind tightly to the key targets.Conclusion: TZD may have therapeutic potential for treating AR, integrating analysis of systems pharmacology and proteomics uncovered the underlying mechanism and targets of TZD, which provides a scientific method for the rational development of traditional Chinese medicine.
In situ Alphavirus Assembly and Budding Mechanism Revealed by Cellular CryoET
Authors: Chmielewski David , Schmid Michael , Simmons Graham , Jin Jing , Chiu Wah 
Published: November 2021

Abstract
Chikungunya virus (CHIKV) is a representative alphavirus causing debilitating arthritogenic disease in humans. Alphavirus particles assemble into two icosahedral protein layers: the glycoprotein spike shell embedded in a lipid envelope and the inner nucleocapsid (NC) core. In contrast to matrix-driven assembly of some enveloped viruses, the assembly/budding process of two-layered icosahedral particles remains poorly understood. Here we used cryogenic electron tomography (cryoET) to capture snapshots of the CHIKV assembly process in infected human cells. Subvolume classification of the snapshots revealed 12 intermediate structures, representing different stages of assembly/budding at the plasma membrane. Further subtomogram average structures ranging from subnanometer to nanometer resolutions show that immature, non-icosahedral NCs function as rough scaffolds to trigger icosahedral assembly of the glycoprotein spike lattice, which in turn progressively transforms the underlying NCs into icosahedral cores during budding. Here we resolve a long-standing mechanistic question about the role of spikes and NCs in assembly of two-layered icosahedral shells. Further, data of CHIKV-infected cells treated with budding-inhibiting antibodies shows that spacing spikes apart to prevent their lateral interactions prevents the plasma membrane bending around NC cores, thus blocking virus budding. These findings provide the molecular details of icosahedral enveloped virus formation and antibodies against assembly/budding.
Legacy Effects of Nitrogen Deposition and Increased Precipitation on Plant Productivity in a Semi-Arid Grassland
Authors: Meng Ya-ni , Li Tianpeng , Liu Heyong , Li Shao-peng , Xu Zhuwen , Jiang Yong 
Published: November 2021

Abstract
Nitrogen (N) deposition and increased precipitation induced by anthropogenic activities were widely reported to promote plant productivity in terrestrial ecosystems. However, few studies have explored the effects of historical resource supplement on plant communities although N deposition was predicted to decrease in the near future and the directional change of precipitation would shift among years. Here, we examined the legacy effects of N deposition and increased precipitation on plant productivity in a semi-arid steppe after cessation of a 13-year N and water addition experiment. We found historical N and water addition generally had positive effects on plant productivity even after the treatments were ceased. However, such legacy effects showed strong inter-annual variation, and the positive effect of N and water addition on productivity were stronger in a wet year (i.e., 2019) than an extremely drought year (i.e., 2018). Although N and water availability decreased rapidly, the independently positive effects of historical N and water input persisted after 2 years of cessation largely due to the stable community composition. The increased plant stature of dominant functional groups largely contributed to the increased current productivity after the historical N and water addition. Together, these findings will facilitate the projection of the primary productivity and carbon cycling under the scenarios of predicted reduce in N deposition and changeable precipitation.
Climate Change Effects On Height-Diameter Allometric Relationship Vary With Tree Species And Size For Larch Plantations In Northern And Northeastern China
Authors: Xu Qigang , Lei Xiangdong , Zang Hao , Zeng Weisheng 
Published: November 2021

Abstract
Background: Tree height-diameter relationship is very important in forest investigation, understanding forest ecosystem structure and estimating carbon storage. Climate change may modify the relationship. However, our understanding of the effects of climate change on height-diameter allometric growth is still limited at large scale.Methods: In this study, we explore how the climate change effects on height-diameter allometric relationship vary with tree species and size for larch plantations in northern and northeastern China. Based on the repeated measurement data of 535 plots from the 6th to 8th national forest inventory of China, climate-sensitive tree height-diameter models of Larix plantations in north and northeast China were developed by two-level nonlinear mixed effect (NLME) method. The final model was used to analyze the height-diameter relationship of different Larch species under RCP2.6, RCP 4.5, and RCP8.5 climate change scenarios from 2010 to 2100.Results: The values of B(adjusted coefficient of determination), MAE(mean absolute error) and RMSE(root mean squared error) of the NLME models for calibration data were 0.92, 0.76m and 1.06m, respectively. The inclusion of climate variables MAT (Mean annual temperature), CMD (Hargreaves climatic moisture deficit) with random effects was able to increase a by 19.5% and reduce the AIC (Akaike’s information criterion), MAE and RMSE by 22.2%, 44.5% and 41.8%, respectively. The climate sensitivity was ranked as L. gmelinii > the unidentified species group > L. pincipis-rupprechtii > L. kaempferi > L. olgensis under RCP4.5, but L. gmelinii > L. pincipis-rupprechtii > the unidentified species group > L. olgensis > L. kaempferi under RCP2.6 and RCP8.5. Conclusion: According to the climate sensitivity, tree species could be classified as group I(L. gmelinii, L. pincipis-rupprechtii and the unidentified species group) with large c (from -4.77% to 18.17%) and group II (L. kaempferi and L. olgensis) with small k (from -6.37% to 9.4%).Large trees were more sensitive to climate change than small trees.
Diurnal variations in the stratosphere of an ultrahot exoplanet
Authors: Mikal-Evans Thomas , Sing David , Barstow Joanna , Kataria Tiffany , Goyal Jayesh , Lewis Nikole , Taylor Jake , Mayne Nathan , Daylan Tansu , Wakeford Hannah , Marley Mark , Spake Jessica 
Published: November 2021

Abstract
The temperature profile of a planetary atmosphere is a key diagnostic of radiative and dynamical processes governing the absorption, redistribution, and emission of energy. Observations have revealed dayside stratospheres that either cool [1,2] or warm [3,4] with altitude for a small number of gas giant exoplanets, while others are consistent with constant temperatures [5,6,7,8]. Here we report spectroscopic phase curve measurements for the gas giant WASP-121b,[9] which constrain stratospheric temperatures throughout the diurnal cycle. Variations measured for a water vapor spectral feature reveal a temperature profile that transitions from warming with altitude on the dayside hemisphere to cooling with altitude on the nightside hemisphere. The data are well explained by models assuming chemical equilibrium, with water molecules thermally dissociating at low pressures on the dayside and recombining on the nightside [10,11]. Nightside temperatures are low enough for perovskite (CaTiO3) to condense, which could deplete titanium from the gas phase [12,13] and explain recent non-detections at the day-night terminator [14,15,16,17]. Nightside temperatures are also low enough for refractory species, such as magnesium, iron, and vanadium, to condense. Detections [16,17,18,19] of these metals at the day-night terminator suggest, however, that if they do form nightside clouds, cold trapping is not as effective at removing them from the upper atmosphere.

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Clinicopathologic Features and Lymph Node Metastasis Pattern of the Cervical MiNEN
Authors: Xu Huihui , Zhao Zehua , Zhu Yanmei 
Published: November 2021

Abstract
Purpose: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare type of cervical tumor. Its clinicopathological features, lymph node(LN) metastatic patterns and outcomes are still unclear. Methods: We have analyzed the clinicopathological information of 26 patients with cervical MiNEN.Results: The median age of onset for cervical MiNEN was 48 years. Macroscopically, polyps and nodules were the main types. The neuroendocrine components included small cell neuroendocrine carcinoma (SCNEC) (14/26 cases), large cell neuroendocrine carcinoma (LCNEC) (10/26 cases), and typical carcinoid (2/26 cases). Non-neuroendocrine components included adenocarcinoma (AC) (12/26, including one case of AC in situ) and squamous cell carcinoma (SC) (10/26) and adeno-squamous cell carcinoma (ASC) (4/26). Of the 16 AC cases, 15 were human papilloma virus (HPV) -associated AC and onewasHPV-independent AC. Except for the case of MiNEN with HPV-independent AC, all cases were diffusely and strongly positive for p16 protein. The lympho-vascular space invasion (LVSI) was seen in 17/26 cases, and the components that invade lymphatic vessels were mainly neuroendocrine carcinomas (NECs) (15/17), followed by SC (1/17) and AC (1/17). Ten patients developed LN metastases, including six in combined SCNECs (6/14) and four in combined LCNECs (4/10); the metastatic component was pure NEC in eight cases (8/10) and SC or AC in two cases (2/10) .Conclusions: NEC component is the key factor that determines the clinical behavior and prognosis of cervical MiNEN.
Cinnamomi Ramulus Inhibits the Growth of Colon Cancer Cells Via Akt/ERK Signaling Pathways
Authors: Pan Boyu , Xia Yafei , Gao Zilu , Zhao Gang , Wang Liangjiao , Fang Senbiao , Liu Liren , Yan Shu 
Published: November 2021

Abstract
Background
Colon cancer (CC) has the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancers has recently received increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism of against CC still needs to be fully evaluated.
Methods
TCMSP and China National Knowledge Infrastructure database were obtained to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. Then, we evaluated the therapeutic effect of CR on CC by oral administration in CC-bearing mice and performed in vitro cellular functional verifications. Next, the potential CC-related targets were further identified by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis results were validated by a series of cellular functional and molecular biological assays.
Results
In this study, we first found that CR has potential therapeutic effects on cancers. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, and it could inhibit the viability and motility of CC cells. Meanwhile, we further obtained 111 potential core therapeutic targets, and enrichment analyses showed that CR could induce the apoptosis and cell cycle arrest in CC cells by blocking the Akt/ERK signaling pathways. The above virtual results were further verified. Next, we used ultraperformance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) to identify 5 key components from the crude extract of CR. Molecular docking analysis revealed that taxifolin is mostly likely to be a potential key active ingredient.
Conclusions
In summary, our results indicate that CR has good prospects in the treatment of CC.
The prediction model of fatty liver was established by blood biochemical indexes
Authors: xu yan , LIU Rong 
Published: November 2021

Abstract
Background

The main cause of chronic liver disease is fatty liver, which includes alcoholic fatty liver and non-alcoholic fatty liver disease. This study is aimed to establish the prediction model of fatty liver, and provide help for the prevention and treatment of fatty liver, especially NAFLD in the future.
Methods

Datasets from 2017 to March 2020 NHANES required for the analysis were downloaded from the NHANES web site and R 4.1.1. Software was used for data analysis. A total of 3762 subjects were enrolled in this study, which were divided into model construction group and model validation group in a 2:1 ratio.
Results

The study selected 6 indicators to build the prediction model, which are as follows: ALT, Platelet count, Creatinine, LDH, HS C-Reactive Protein, Glucose. Then the prediction model was constructed. The area under ROC curve of the model was 0.7471. In the validation population, the area under the ROC curve of the model was 0.7816.
Conclusions

F score has a good predictive effect on fatty liver, which can be used as an important means for the prevention and treatment of fatty liver, especially NAFLD in the future.
Discrepant Results of Hepatitis B Virus Genotype Determination by PCR and DNA Sequencing
Authors: Xiao Yihan , Ni Lan , Cui Zhigang , Sun Long , Zhou Xiaojun , Chen Xinjun , Li Lihua , Tang Chuanning , Yin Feifei , Du Jiang , Liu Lina , Lu Gang , Cui Xiuji , Quan Yunfan 
Published: November 2021

Abstract
Currently, multiplex-PCR with genotype-specific primers is widely used for preliminary screening of hepatitis B virus (HBV) genotyping, despite its relatively lower accuracy compared with whole genome sequencing. Here, we present the discrepant results of HBV genotyping by PCR and full-length sequencing. HBV DNA was isolated from chronic hepatitis B serum and the HBV genotype was detected by PCR using genotype-specific primers and full-length genome sequencing. As a result, the determination of genotype B by the PCR method was consistent with the DNA sequencing results; however, PCR revealed that genotype C exhibited a mixed genotype of B and C in the current study. In conclusion, the PCR-based genotyping method may not provide accurate information of the HBV genotype and whole genome sequencing remains the “gold standard” method for HBV genotyping.
Lactobacillus Paracasei BEJ01 Protects Against Fumonisin B1-Induced Intestinal Toxicity in Balb/c Mice
Authors: EZDINI Khawla , Salah-Abbès Jalila Ben , Belgacem Hela , Chaieb Kamel , Abbès Samir 
Published: November 2021

Abstract
Fumonisin B1 (FB1) is a carcinogenic (Class 2B) mycotoxin produced by Fusarium fungi and is responsible for several types of mycotoxicoses in animals and humans. Lactobacillus paracasei (LP), as a probiotic, is known to impart a wide range of advantageous effects on host health. The objective of the current study was to evaluate if LP (type BEJ01) isolated from Tunisian artisanal butter, could potentially help protect a host against intestinal alterations caused by exposure to FB1. Here, adult male Balb/c mice were randomly assigned to four groups, i.e., control (vehicle only), treated with FB1 (100 µg/kg BW), LP (2 × 109 CFU/ml [≈ 2 mg/kg BW]) and FB1 (100 µg/kg BW) + LP (2 × 109 CFU/ml) and treated per os daily for 10 days. At 24 hr after the final treatment, mice were euthanized and their jejunum harvested for examination of intestinal alterations induced by the FB1. The data showed that a variety of negative effects in jejunal tissue were induced by the FB1, including DNA fragmentation, oxidative stress, apoptotic cell death, and histopathological alterations. The results also showed that co-treatment of LP with FB1 was able to mitigate the harmful FB1 effects. LP alone imparted no damage to jejunal tissues. These results show that apart from potential use as a bio-preservative for extending the shelf-life of food and feeds, LP may also provide a benefit of helping prevent untoward effects from a potent mycotoxin like FB1.
Patients’ Attitudes Towards Involvement of Medical Students in Their Care at Three Selected University Teaching Hospitals in Uganda: A Cross Sectional Study
Authors: Ibingira Charles BENSTONS , Mwaka Amos Deogratius , Taremwa Seti , Adoch Winnie , Achan Jennifer , Ainembabazi Peruth , Walego Grace , Ntayi Moses Levi , Bongomin Felix 
Published: November 2021

Abstract
BackgroundThe acceptance of medical students by patients during care is important and promotes appropriate clinical reasoning, competence and skills development among students. The attitudes and comfort of patients attending care at the medical and obstetrics/gynecology specialties was studied in teaching hospitals of three public universities in Uganda.MethodsThis was cross sectional study conducted among patients getting care at teaching hospitals for three public universities; of Mbarara University of Science and Technology (MUST), Makerere and Gulu Universities. Logistical regression was used to determine the magnitude of associations between independent and dependent variables. Two-sided p<0.05 was considered statistically significant.Results855 patients participated in the study. Majority (54%, n=460) were aged 18 — 39 years, female (81%, n=696) and married (67%, n=567). Seventy percent (n=599) of participants could recognize and differentiate medical students from qualified physicians, and had ever had involvement of medical students (65%, n=554) during earlier consultations. Regarding attitudes of patients towards presence of medical students during their consultations, most participants (96%; n=818) considered their involvement in patients’ care as an essential ingredient of training of future doctors/ health professionals. Most participants prefer the training of medical students to take place in the tertiary public hospitals (80%; n=683). Participants who were single/never married were 68% less likely to recognize and differentiate medical students (aOR = 0.32, 95%CI: 0.22 — 0.53) from other members of the healthcare team ,compared to married participants. Participants with university education had 55% lower odds of being comfortable with presence of medical students during consultation compared to those with primary education (aOR= 0.45, 95%CI: 0.21 — 0.94). Participants from MUST teaching hospital had 2-fold higher odds of being comfortable with presence of medical students compared to participants from Mak teaching hospitals (aOR = 2.01; 95%CI: 1.20 — 3.39).ConclusionPatients are generally comfortable with medical students’ involvement in their care; they prefer to seek care in hospitals where medical students contribute to their care. There is a need for disseminating clear messages to the public regarding the presence and roles of medical students in the university teaching hospitals in order to promote and inform patients’ autonomy and informed decisions.
Atypical parathyroid adenomas as a rare cause of primary hyperparathyroidism - in an academic institution experience
Authors: Kowalski Grzegorz , Buła Grzegorz , Bednarczyk Adam , Gawrychowska Agata , Gawrychowski Jacek 
Published: November 2021

Abstract
BACKGROUND

Primary hyperparathyroidism (PHPT) is caused by benign and malignant conditions. Most commonly by typical adenoma/single gland disease (PA) - this is 80-85% cases of PHPT. Parathyroid hyperplasia or multiple gland disease accounts for 10-15% of cases of PHPT. Atypical parathyroid adenoma (APA) and carcinoma (PC) - very rare conditions - are both responsible for PHPT in approximately 0,5 - 1,5% of cases.
OBJECTIVES

To estimate occurrence of atypical parathyroid adenoma, parathyroid carcinoma and parathyroid hyperplasia along with characterize them based on their etiology, clinical presentation, diagnosis and treatment
METHODS

We performed a retrospective study and enrolled 1,019 patients with primary hyperparathyroidism undergoing parathyroidectomy at academic Department of General and Endocrine Surgery between 1983 and 2018.
RESULTS

Out of 1,019 cases of primary hyperparathyroidism, 850 (83.4%) cases were due to typical parathyroid adenoma (PA), 135 (13.2%) cases were due to parathyroid hyperplasia, 29 (2.8%) cases were due to parathyroid carcinoma (PC), and 5 (0.5%) cases were due to atypical parathyroid adenoma (APA).