bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Patterns and Threshold of Chlorophyll-a in Lake Taihu Based on Microcystins
Authors: fu xuemei , Zheng Mingxia , Su Jing , Xi Beidou , Wu Daichun , Wang Xiaoli
Published: April 2021

Chlorophyll-a (Chl- a ) is considered an indicator of phytoplankton biomass dynamically reflecting the growth of algae. Therefore, determination of Chl- a threshold is of vital importance to the health of aquatic ecosystems and drinking water security. This research is aimed to investigate the spatial and temporal distributions of Chl- a and microcystin (MC) concentrations using Geographic Information System (GIS) and identify the Chl- a threshold in Lake Taihu based on available guideline values of MCs. Nearly the same characteristics of spatiotemporal variation of Chl- a and MCs were observed in Lake Taihu. Overall, the lakewide distributions of Chl- a and MCs were highly variable over time and space. The Chl- a concentration in the winter and spring was relatively low, and gradually increasing in summer and autumn, with the maximum concentration observed in August. But the maximum MCs concentration appeared in October, two months lagging behind the Chl- a . The highest annual average Chl- a and MCs concentrations were observed in Zhushan Bay, Meiliang Bay, Gonghu Bay in northwest of Lake Taihu, following by West Zone and Center Zone. Dongtaihu Bay, East Zone and South Zone always present good water quality. Referring to the guideline value of MCs, the Chl- a threshold was determined as 10-15 mg·m -3 based on the linear regression correlation between Chl- a and MCs. The establishment of Chl- a threshold is useful for eutrophication control, water quality management and drinking water utilities in developing water safety plans.
Safety and Efficacy of Pterygium Extended Removal Followed by Extended Conjunctival Transplant for Recurrent Pterygia
Authors: Allam Walid , Alagorie Ahmed Roshdy , Nasef Mohammed , El-Bakary Molham
Published: April 2021

Purpose
To study the safety and efficacy of pterygium extended removal followed by extended conjunctival transplant for recurrent pterygia.
Methods
Thirty-three eyes of 33 subjects with recurrent pterygia were enrolled in this prospective case series study. Pterygium extended removal followed by extended conjunctival transplantation was done for all subjects. One surgeon (WA) performed all surgeries. All subjects completed follow-up for at least 12 months and were evaluated for recurrence and complications.
Results
The mean age of the participants was 41.2 ± 10.3 years (range 22–60), 7 females (21.2%). The mean duration of follow-up was 25.64 ± 9.24 months (range 12–43). Corrected distance visual acuity (decimal notation) improved from 0.69 ± 0.22 (range 0.2–1.0) at presentation to a 1-year postoperative value of 0.83 ± 0.2 (range 0.3–1.0). No recurrence was reported in all subjects throughout the follow-up period. Transient graft swelling was recorded in 14 cases (42.4%) and resolved in all cases by the first week. All patients developed variable degrees of transient postoperative diplopia that resolved completely by the first 6 weeks. Donor site granuloma developed in 4 cases (12.1%). Spontaneous resolution was observed in 3 cases, while in one case, surgical excision was performed 2 months after the procedure.
Conclusions
In this study of eyes with recurrent pterygia, pterygium extended removal followed by extended conjunctival transplant was found safe and effective with no recurrence and minimal postoperative complications.
RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning
Authors: Kumar Gaurav , Chawla Prateek , Chadha Sanya , Sharma Sheetal , Sethi Kanupriya , Sharma Mahak , Tuli Amit
Published: April 2021

The whole-cell scale spatial organization of lysosomes is regulated by their bidirectional motility on microtubule tracks. Small GTP-binding (G) protein, Arl8b, stimulates the anterograde transport of lysosomes by recruiting adaptor protein SKIP (also known as PLEKHM2), which in turn couples the microtubule motor kinesin-1. Here, we have identified an Arl8b effector, RUN and FYVE domain-containing protein family member 3, RUFY3, which drives the retrograde transport of lysosomes. Artificial targeting of RUFY3 to the surface of mitochondria was sufficient to drive their perinuclear positioning. We find that RUFY3 interacts with the JIP4-Dynein-Dynactin complex and mediates Arl8b association with the retrograde motor complex. The mobile fraction of the total lysosomes per cell was significantly enhanced upon RUFY3 depletion, suggesting that RUFY3 maintains the lysosomes clustering within the perinuclear cloud. Expectedly, RUFY3 knockdown disrupted the perinuclear positioning of lysosomes upon nutrient starvation and/or serum depletion, although lysosome continued to undergo fusion with autophagosomes. Interestingly, lysosome fission events were more frequent in RUFY3-depleted cells and accordingly, there was a striking reduction in lysosome size, an effect that was also observed in dynein and JIP4 depleted cells. These findings indicate that the dynein-dependent “perinuclear cloud” arrangement of lysosomes also regulates the size of these proteolytic compartments and, likely, their cellular roles.
The staged treatment for tibial plateau fractures and the reconstruction of lateral column with autogenous iliac bone: an efficacy analysis report
Authors: Li Dong , Liang Xiao , Xi Kun , Zhao Bin , Hou Fushan
Published: April 2021

Background: Complications in treating comminuted tibial plateau fractures with extensive soft tissue damage are common. In this study, we discussed the effect of staged treatment in the reconstruction of the lateral column with autogenous iliac bone using case follow-up. Methods: A retrospective analysis of 18 patients with comminuted tibial plateau fractures and extensive soft tissue damage from October 2016 to February 2020 who underwent staged treatment in our hospital. After the soft tissue damage repair, a large autologous iliac bone was used to reconstruct the lateral column of the tibial plateau.Results: All 18 patients were followed up over the course of 8-40 months, with an average of 23.44 months. All patients reported zero postoperative infection, skin and soft tissue necrosis, and loosening/breakage of the internal fixation. Regular postoperative review revealed that all patients achieved complete bony union, as evidenced by X-ray film, at 6 months after operation. Knee function (HSS) scores averaged 86.72 points at 1 year after operation; 15 people with 85 points or more, 2 people with 70-84 points, and one with 68 points. The excellent rate, according to HSS was 90%.Conclusions: Complex tibial plateau fractures with extensive soft tissue damage can be effectively remedied with a staged treatment, wherein a lateral column reconstruction is performed using a large iliac bone.
First Characterization of Congenital Myasthenic Syndrome Type 5 in North Africa
Authors: rochdi khaoula , Cerino Mathieu , Silva Nathalie Da , Delague Valerie , Nahili Halima , Kriouile Yamna , Gorokhova Svetlana , Bartoli Marc , Saile Rachid , Barakat Abdelhamid , Krahn Martin
Published: April 2021

Congenital myasthenic syndromes (CMS) are associated with defects in the structure and the function of neuromuscular junctions. These rare disorders can result from mutations in the collagenic tail of endplate acetylcholinesterase (COLQ) essentially associated with autosomal recessive inheritance.With the lowered cost of genetic testing and increased access to next-generation sequencing, many mutations have been reported to date. In this study we identified the first COLQ homozygous mutation c.1193T>A in the North African population. This study outlines the genetic and phenotypic features of a CMS patient in a Moroccan family. It also describes a novel COLQ missense mutation associated with CMS-5. COLQ mutations are probably underdiagnosed in these North African populations, this is an issue as CMS-5 may be treated with ephedrine, and albuterol. Indeed, patients can seriously benefit and even recover after the treatment that should be planned according to genetic tests and clinical findings.
Fragmented yet high economic costs of biological invasions in India
Authors: Bang Alok , Cuthbert Ross , Haubrock Phillip , Fernandez Romina , Moodley Desika , Diagne Christophe , Turbelin Anna , Banerjee Achyut Kumar , Renault David , Dalu Tatenda , Courchamp Franck
Published: April 2021

Biological invasions are one of the top drivers of the ongoing biodiversity crisis. An underestimated consequence of invasions is the enormity of their economic impacts. Knowledge gaps regarding economic costs produced by invasive alien species (IAS) are pervasive, particularly for emerging economies such as India — the fastest growing economy worldwide. To bridge this gap, we synthesised data on economic costs of IAS in India. Specifically, we examine how IAS costs are distributed spatially, environmentally, sectorally, taxonomically, temporally and across introduction pathways; and discuss globally how IAS costs vary with socioeconomic indicators. We found that IAS have cost the Indian economy between at least US$ 127.3 billion to 182.6 billion (Indian Rupees ₹ 8.3 trillion to 11.9 trillion) over 1960–2020, and these costs have increased with time. Most recorded costs were not assigned to specific regions, environments, sectors, cost types and causal IAS. When costs were specifically assigned, maximum costs were incurred in west, south and north India, by invasive alien insects in semi-aquatic ecosystems, incurred mainly by the public and social welfare sector, and were associated with damages and losses rather than management expenses. Our findings indicate that the reported economic costs grossly underestimate the actual costs, especially when considering the expected costs given India's population size and gross domestic product (GDP). This cost analysis improves our knowledge of the negative economic impacts associated with biological invasions in India and the burden they can represent for its development. We hope that this study motivates policymakers to address socio-ecological issues, especially since economic growth will be accompanied by greater impacts of global change.
The Mediterranean Diet and Dietary Approach to Stop Hypertension (DASH)-style Diet Are Differently Associated With Lipid Profile in a Large Sample of Iranian Adults: Shahedieh Cohort Study
Authors: Panbehkar-Jouybari Monireh , Mollahosseini Mehdi , Salehi-Abargouei Amin , Fallahzadeh Hossein , Mirzaei Masoud , Hosseinzadeh Mahdieh
Published: April 2021

Background: The association between the Mediterranean diet (MED) or dietary approach to stop hypertension (DASH) and cardiovascular disease (CVD) risk factors is well-documented. Nevertheless, a consistent relationship in the Middle East population has yet to be identified. Thus, we aimed to investigate the association between DASH/MED and blood lipids in Iranian adults.Methods: We followed 4740 participants 35-70 years (mean: 50.0) of the Shahedieh cohort study in Yazd, Iran. Participants provided dietary and blood lipid data through a validated semi-quantitative food frequency questionnaire, and blood samples were taken after a fasted state. We used binary logistic regression to examine the association between DASH/MED scores and blood lipids.Results: The DASH diet could reduce the level of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and LDL/HDL (high-density lipoprotein) ratio (P: 0.01; third vs. the first tertile). While the MED diet could increase the HDL level (P: 0.01). In Binary logistic regression, higher adherence to DASH diet shown 19% lower odds of high TC level (OR: 0.81; 95 %CI: 0.69–0.95) and 18% lower odds of high LDL/HDL ratio (OR: 0.82; 95 %CI: 0.70–0.96). Besides, high adherence to the MED diet was associated with lower odds of LDL/HDL ratio (OR: 0.85; 95 %CI: 0.72–0.99).Conclusion: Our findings suggest that the DASH diet and the MED diet respectively might have a protective effect on TC, TG, LDL, LDL/HDL ratio, and HDL, and the LDL/HDL ratio, subsequently on CVDs risk. Further epidemiological studies are needed to confirm our findings.
Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent inflammatory responses
Authors: Klenerman David , Meng Jonathan , Zhang Yu , Saman Dominik , De Suman , Sang Jason , Jiang Kun , Humphrey Jane , Julian Linda , Hidari Eric , Floto R. Andres , Lee Steven , Bryant Clare , Benesch Justin , Ye Yu
Published: April 2021

Soluble aggregates of the microtubule-associated protein tau have been challenging to assemble and characterize, despite their important role in the development of tauopathies. We found that sequential hyperphosphorylation by PKA in conjugation with either GSK3-β or SAPK4 enabled recombinant wild-type (WT) tau of isoform 0N4R to spontaneously polymerize into small amorphous aggregates in vitro. We employed tandem mass spectrometry to determine the phosphorylation sites and the degree of phosphorylation, and super-resolution microscopy and electron microscopy to characterize the morphology of aggregates formed. Functionally, in comparison with the unmodified aggregates, which require heparin induction to assemble, these self-assembled hyperphosphorylated tau aggregates more efficiently disrupt membrane bilayers and induce Toll-like receptor 4 (TLR4)-dependent inflammatory responses. Together, our results demonstrate that tau hyperphosphorylation is potentially damaging to cells, providing a mechanistic model of how hyperphosphorylation of tau aggregates drives neuroinflammation in tauopathies.
Combined Foliar and Soil Selenium Fertilizer Improves Selenium Transport in Oats and the Diversity of the Bacterial Community in Rhizosphere Soil
Authors: Li Junhui , Yang Wenping , Guo Anna , Yang Sheng , Chen Jie , Qiao Yuejing , Anwar Sumera , Wang Kai , Yang Zhenping , Gao Zhiqiang , Wang Jianwu
Published: April 2021

Reasonable application of selenium (Se) fertilizer is beneficial for improving Se contents in grains and can affect soil ecology. No study has compared Se fertilizer application methods on biofortification, yield, and soil bacterial community. This study investigated the effects of topsoil (T), foliar (S), and soil+foliar (TS) application of Se fertilizer on oats. TS treatment significantly increased oat yield compared with the control and S. The Se content in grains was increased in the order of TS > S > T. T and TS increased the nutrients, soil organic matter, activities of urease, alkaline phosphatase, and sucrose, as well as the diversity and abundance of soil bacterial communities. According to PCA analysis, TS and T increased the relative abundance of bacteria involved in the decomposition of organic matter, such as Proteobacteria, Chloroflexi, and Bacteroidetes, while reduced Granulicella, Bacillus, Raoultella, Lactococcus, Klebsiella, and Pseudomonas. Furthermore, TS significantly increased the relative abundance of Aciditeromonas, Gemmatimonas, Geobacter, and Thiobacter. While, T significantly increased the abundance of Lysobacter, Holophaga, Candidatus-Koribacter, Povalibacter, and Pyrinomonas. S did not significantly change the bacterial communities. The redundancy analysis revealed that soil nutrients and enzyme activities were positively correlated with the abundance of Actinobacteria, Acidobacteria, Gemmatimonadetes, Bacteroidetes, Planctomycetes, and Chloroflexi, but negatively correlated with the abundance of Proteobacteria and Firmicutes. Thus, a combined application of foliar and soil Se proved most conducive for achieving higher yield, grain Se content, and improving bacterial community structure and functional gene expression in rhizosphere soil.
Ultra-robust stretchable electrode for e-skin: in situ assembly using a nanofiber scaffold and liquid metal to mimic water-to-net interaction
Authors: Cao Jin Wei , Liang Fei , Li Hua Yang , Li Xin , Fan You Jun , Yin Yiming , Li Fali , Xu Jin , Feng Hanfang , Xu Dan , Yang Huali , Liu Yiwei , Li Run-Wei , Zhu Guang
Published: April 2021

The development of stretchable electronics will thrive on the novel interface structure to solve the stretchability-conductivity dilemma, which is still a great challenge. Herein, we report a nano-liquid metal (LM)-based high-robust stretchable electrode (NHSE) with a self-adaptable interface that mimics water-to-net interaction. Based on in situ assembly of electrospun elastic nanofibers scaffold and electrosprayed LM nanoparticles, the NHSE exhibits an extremely low sheet resistance of 52 mΩ/□. It is not only insensitive to a large degree of mechanical stretching (i.e., 350% electrical resistance change upon 570% elongation), but also immune to cyclic deformation (i.e., 5% electrical resistance increase after 100,000 stretching cycles with 100% elongation). These key properties are far more superior to the state-of-the-art reports. Its robustness and stability are verified under diverse circumstances, including long-term exposure in air (420 days), cyclic washing (30,000 times), and resilience against mechanical damages. The combination of conductivity, stretchability and durability makes the NHSE a promising conductor/electrode solution to flexible/stretchable electronics for applications such as wearable on-body physiological signal detection.
Mortality and Clinical Characteristics of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 in critically ill patients: an observational multicenter study (MISCO STUDY)
Authors: Acevedo Lorena , Piñeres-Olave Byron Enrique , Niño-Serna Laura Fernanda , Mazillo-Vega Liliana , Gómez Ivan Jose Ardila , Chacón Shayl , Jaramillo-Bustamante Juan Camilo , Mulett-Hoyos Hernando , González-Pardo Otto Mauricio , Zemanate Eliana , Izquierdo Ledys , Mejía Jaime Piracoca , González Jose Luis Junco , Durán Beatriz Giraldo , Bonilla Carolina , Preciado Helen , Marín Rafael Orozco , Alvarez Martha , Giraldo Carolina , Rojas Jorge , Salazar-Uribe Juan Carlos , Anaya Juan-Manuel , Fernández-Sarmiento Jaime
Published: April 2021

Background The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 is widespread and presents a very low mortality rate in highincome countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries compared to described series in high-income countries along with the factors associated with mortality and worse outcomes. Methods An observational cohort study was conducted in 14 PICUs in Colombia between April 01, 2020 and January 31, 2021. Patient´s age ranged between one month and 18 years and they met the requirements set forth by WHO for MIS-C. Results There were seventy-eight children in this study. The median age was seven years (IQR 1- 11), 18% (14/78) were under one year old, and 56% were male. Thirty-five percent (29/78) were obese or overweight. The PICU stay was six days (IQR 4-7), and 100% had a fever on admission lasting five days (IQR 3.7-6). Seventy percent (55/78) had diarrhea, and 87% (68/78) had shock or myocardial dysfunction (78%). Compared to the United Kingdom (UK) study, there were more children under the age of five (37% vs. 10%; p=0.004), and there was a higher frequency of obesity (29.5% vs. 10%; p=0.008). With regard to the US study, there was more lymphadenopathy (23% vs. 13%; p=0.02), diarrhea (70.5% vs. 53%; p=0.001), lymphopenia (64% vs. 35%; p=0.001), shock (87% vs. 35%; p=0.001), elevated troponin (51% vs. 31%; p=0.006) and elevated proBNP (82% vs 43%; p=0.001), as well as greater mortality (9% vs 1.8%; p=0.001). The group that did not survive had a longer duration of the disease until admission to the PICU (6 days vs. 5 days; p = 0.003), more frequency of ferritin above 500 ngr/mL (100% vs. 45%; p = 0.012) and more cardiovascular complications (100% vs. 54%; p = 0.019) compared to the group that survived. Conclusions Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. It was observed inflammatory response, and cardiovascular involvement were conditions that, added to the difficulties in accessing healthcare systems in countries with limited resources, may explain the higher mortality seen in these children.
Trajectories of loneliness and objective social isolation and associations between persistent loneliness and self- reported personal recovery in a cohort of secondary mental health service users in the UK
Authors: Ma Ruimin , Wang Jingyi , Lloyd-Evans Brynmor , Marston Louise , Johnson Sonia
Published: April 2021

Background: Loneliness is a frequent and distressing experience among people with mental health problems. However, few longitudinal studies have so far investigated the trajectories of loneliness and objective social isolation, and the extent to which both issues may impact mental health outcomes among mental health service users. Therefore, this study aims to describe the trajectories of loneliness and objective social isolation and their associations with self-rated personal recovery among people leaving crisis resolution teams (CRTs). Methods: A total of 224 participants receiving care from CRTs (recruited for a large multi-site randomised controlled trial) were included in this longitudinal cohort study. They completed the eight-item University of California at Los Angeles Loneliness Scale (ULS-8), Lubben-Social Network Scale (LNSN-6), and the Questionnaire about the Process of Recovery (QPR) (primary outcome) at baseline, 4- and 18-month follow-up, as well as baseline sociodemographic and clinical variables. Results: We compared groups who were persistently lonely (at all time points), intermittently lonely (at one or two time points) and never lonely. After adjusting for all potential confounders and baseline predictive variables, persistent severe loneliness was associated with worse personal recovery at 18-month follow-up compared with the never lonely (reference group) (coef. = -12.8, 95% CI -11.8, -3.8, p<.001), as was being intermittently lonely (coef. = -7.8, 95% CI -18.8, -6.8, p<.001). The persistently objectively social isolated group (coef. = -9.8, 95% CI -15.7, -3.8, p=.001) also had poorer self-rated recovery at 18-month follow-up than those who were not socially isolated at any timepoint (i.e., reference category). Conclusion: Results suggest that both persistent loneliness and objective social isolation are associated with poorer self-rated recovery following a crisis, compatible with a causal relationship. These findings suggest a potential role for interventions aimed at alleviating loneliness and objective social isolation in improving recovery outcomes for people with mental health symptoms. Increased awareness of both issues among health practitioners is also warranted.
Effects of gallic acid and Zn, Cu, and Ni on antioxidant enzyme activities of Hyphantria cunea larvae infected with Bacillus thuringiensis
Authors: Topkara Elif Fatma , Yanar Oğuzhan , Solmaz Fatma Gönül
Published: April 2021

The effects of copper, nickel, and zinc and the potent antioxidant gallic acid on the antioxidant enzyme activities of Hyphantria cunea larvae infected with Bacillus thuringiensis subsp. kurstaki have been identified in this study. With metal exposure, all the enzyme activities have increased. Antagonistic effects were observed in the combination of gallic acid with all three metals on the activities of superoxide dismutase and catalase. In glutathione peroxidase activity, an antagonistic effect was observed in gallic acid plus nickel group, while there was a synergistic effect for gallic acid plus zinc and gallic acid plus copper. Activities of these enzymes in larvae exposed only to the metals increased in the infected groups; while exposure to gallic acid alone elicited a decrease. As a consequence, it was found that enzyme activities were affected by both metals and gallic acid and infection.
Comprehensive Analysis of Lysine Crotonylation Modification in Patients with Chronic Renal Failure
Authors: Huang Jiahuang , Tang Donge , Zheng Fengping , Xu Huixuan , Dai Yong
Published: April 2021

Background： Post-translational modifications (PTMs) are at the heart of many cellular signaling events, which changes the function of protein. Crotonylation, one of the most important and common PTMs, plays a key role in the regulation of various biological processes. However, no study has evaluated the role of lysine crotonylation modification and chronic renal failure patients. Methods: Here, we comparatively evaluated the crotonylation proteome of normal controls and chronic renal failure patients using liquid chromatography tandem mass spectrometry (LC-MS/MS) coupled with highly sensitive immune-affinity purification.Results: A total of 1109 lysine modification sites were identified, of which 772 sites were up-regulated and 69 sites were down-regulated; this suggests that crotonylation modification maintains high levels in the patients’ kidneys with chronic renal failure. Gene ontology enrichment analysis showed that the crotonylated proteins were significantly enriched in the platelet alpha granule lumen, platelet degradulation, and cell adhesion molecule binding. In addition, KEGG-based gene and genomic functional enrichment analysis in Kyoto encyclopedia showed that battoacyl protein was enriched in CD36, which has an important relationship with renal failure.Conclusion: This is the first report on the global crotonylation proteome of chronic renal failure patients. crotonylation of histone and non-histone may play an important role in delaying the continuous deterioration of renal function in patients with chronic renal failure.
A Novel Redox Indicator based on Relative Abundances of C31 And C32 Homohopanes in the Eocene Lacustrine Dongying Depression, East China
Authors: Jiang Chong , Huang Haiping , Li Zheng , Zhang Hong , Zhai Zheng
Published: April 2021

A suite of oils and bitumens from the Eocene Shahejie Formation (Es) in the Dongying Depression, East China was geochemically characterized to illustrate the impact of source input and redox conditions on the distributions of pentacyclic terpanes. The fourth member (Es4) developed under highly reducing, sulfidic hypersaline conditions, while the third member (Es3) formed under dysoxic, brackish to freshwater conditions. Oils derived from Es4 are enriched in C32 homohopanes (C32H), while those from Es3 are prominently enriched in C31 homohopanes (C31H). The C32H/C31H ratio shows positive correlation with homohopane index (HHI), gammacerane index (G/C30H), and negative correlation with pristane/phytane (Pr/Ph) ratio, and can be used to evaluate oxic/anoxic conditions during deposition and diagenesis. High C32H/C31H ratio (> 0.8) is an important characteristic of oils derived from sulfidic, hypersaline anoxic environments, while low values (< 0.8) indicate non-sulfidic, dysoxic conditions. Extremely low C32H/C31H ratios (< 0.4) indicate strong oxic conditions of coal depsoition. Advantages to use C32H/C31H ratio as redox condition proxy compared to the HHI and gammacerane indexes are wider valid maturity range, less sensitive to biodegradation influence and better differentiation of reducing from oxic environments. Preferential cracking of C35-homohopanes leads HHI to be valid in a narrow maturity range before peak oil generation. No C35 homohopane can be reliably detected in the Es4 bitumens when vitrinite reflectance is > 0.75%, which explains the rare occurrence of high HHI values in Es4 source rocks. Gammacerane is thermally more stable and biologically more refractory than C30 hopane, leading G/C30H ratio more sensitive to maturation and biodegradation than C32H/C31H ratio. Meanwhile, both HHI and gammacerane index cannot differentiate level of oxidation. The C32H/C31H ratio can be applied globally as a novel redox proxy in addition to the Dongying Depression.
rAAV9‐mediated supplementation of miR-29b improve Angiotensin-II induced Renal Fibrosis in mice
Authors: Zhang Ju Hong , Li Jing , Ye Yang , Yu Wang Qi
Published: April 2021

Background Renin-angiotensin-aldosterone system activation is the critical factor in renal remodeling and dysfunction. Our previous study suggested that miR-29b might attenuate angiotensin II-induced renal intestinal fibrosis in vitro. In the present study, we aim to determine that recombinant adeno-associated virus mediated miR-29b delivery can protect AngII-induced renal fibrosis and dysfunction. Method Mice were treated with AngII via osmotic mini-pumps or PBS. Recombinant adeno-associated virus serotype 9 vectors were produced with the rBac-based system in SF9 cells. rAAV9-miR-29b or rAAV9-control-miR were injected into the kidney of a mouse model of AngII infusion. Role of miR-29b in renal fibrosis were assessed by Q-PCR, Western blot and histological examination. Results In AngII-induced fibrotic kidney, miR-29b expression was down-regulated. rAAV9-miR-29b delivery significantly reversed renal dysfunction as indicated by decreased blood serum creatinine in AngII-infused mice. As far to organ remodeling, tubulointerstitial fibrosis and deposition of extracellular matrix deposition such as Collagen type I and type III were significantly decreased in kidney tissue of rAAV9-miR-29b delivered mouse. Conclusion Our results show the great potential of rAAV9 as an applicable vector for miR-29b delivery for antifibrogenic factors in the treatment of renal dysfunction caused by tubulointerstitial fibrosis.
Structural insights into Rift Valley fever virus replication machinery
Authors: Chen Zhongzhou , Wang Hong-Wei , Wang Xue , Hu Cuixia , Wang Jia , Dong Xiaofei , Xu Jie , Li Xiaorong , Zhang Manfeng , Lu Hongyun , Ye Wei , Zhang Fanglin , Wu Wei
Published: April 2021

Rift Valley fever virus (RVFV) belongs to the order Bunyavirales and is the type species of genus Phlebovirus, which accounts for over 50% of family Phenuiviridae species. RNA-dependent RNA polymerase (L protein) is responsible for facilitating the replication and transcription of the virus. We report two cryo-EM RVFV L protein structures at 3.6 Å and 3.8 Å resolution in the presence and absence of RNA, respectively. In this first L protein structure of genus Phlebovirus, viral RNA induces considerable conformational changes of the polymerase. The RVFV L protein priming loop is distinctly different from those of other L proteins and undergoes large movements related to its replication elongation role. Structural and biochemical analyses indicate that a single template can initiate RNA replication, which is notably enhanced by 5’ viral RNA. These findings advance our understanding of RNA synthesis mechanism and provide a basis for antiviral inhibitor development.
Propensity-Score Matched Analysis of the Efficacy of Maintenance/Continuous Therapy in Newly Diagnosed Patients With Multiple Myeloma: A Multicenter Retrospective Collaborative Study of the Japanese Society of Myeloma
Authors: Ozaki Shuji , Handa Hiroshi , Koiso Hiromi , Saitoh Takayuki , Sunami Kazutaka , Ishida Tadao , Suzuki Kenshi , Narita Tomoko , Iida Shinsuke , Nakamura Yuichi , Suzuki Kazuhito , Nishimura Noriko , Murakami Hirokazu , Shimizu Kazuyuki
Published: April 2021

Maintenance/continuous therapy is considered a standard of care for both transplant-eligible and -ineligible patients with multiple myeloma (MM). However, long-term benefits of such therapy have not yet been clarified in the context of clinical practice. We retrospectively analyzed the efficacy of maintenance/continuous therapy in newly diagnosed MM patients using the cohort data by propensity-score matching based on age, gender, revised International Staging System (R-ISS) stage, and implementation of transplantation to reduce the bias due to confounding variables. Among 720 patients, 161 were identified for each of the maintenance and no maintenance groups. Maintenance/continuous therapy employed immunomodulatory drugs (n = 83), proteasome inhibitors (n = 48), combination of both (n = 29), or dexamethasone alone (n = 1). Progression-free survival (PFS) was significantly prolonged in the maintenance group compared with the no maintenance group (median, 37.7 and 21.9 months, p = 0.0002, respectively). Prolongation of PFS was observed in both transplanted and non-transplanted patients (p = 0.017 and p = 0.0008, respectively), with standard risk (p < 0.00001), R-ISS stage I (p = 0.037) and stage II (p = 0.00094), and those without obtaining complete response (p = 0.0018). There was no significant difference in overall survival (p = 0.19), but it appeared to be better in non-transplanted patients by continuous therapy. These results support the usefulness of maintenance/continuous therapy in the management of MM.
Development and validation of a gas chromatography method for the determination of β -caryophyllene in clove extract and its application
Authors: Park Mi Hee , Kim Chul Jin , Lee Jin Young , Kim In Seon , Kim Sung-kyu
Published: April 2021

The purpose of this study is to check the effectiveness of the analysis method that separates and quantifies β-caryophyllene among clove extracts and validate according to current ICH guidelines. The beta caryophyllene was active constituent of clove buds. The developed method gave a good detection response. In the specificity test, the standard solution was detected at about 17.316 minutes, and the test solution was detected at 17.317 minutes. The linearity of β-caryophyllen was confirmed, and at this time, the correlation coefficient (R 2 ) of the calibration curve showed a high linearity of 0.999 or more in the concentration range. The levels of LOD and LOQ were 1.28 ug/mL and 3.89 ug/mL, respectively. The accuracy was confirmed to be 101.6 ~ 102.2% and RSD 0.95 ~ 1.31%. As a result of checking the repeatability and inter-tester reproducibility to confirm the precision, the RSD was found to be 1.34 ~ 2.69%. This validated GC method was successfully applied to a soft capsule containing clove extract and other materials for clinical trials. Therefore, this method can be used as an analytical tool for quality control of various samples including clove extracts and their products for food and pharmaceutical uses.
Funneliformis Mosseae Application Under Water Deficit Stress Improves The Drug Yield And Phytochemical Characteristics of Thyme (Thymus vulgaris L.) in Intercropping With Soybean (Glycine Max L.)
Authors: Machiani Mostafa Amani , Javanmard Abdollah , Morshedloo Mohammad Reza , Aghaee Ahmad , Maggi Filippo
Published: April 2021

Todays, there is a considerable demand in the global herbal market for thyme (Thymus vulgaris L.) and its related products such as extracts and essential oil (EO). In order to comply with this objective, an improvement of its cultivation area under water scarcity conditions is required. On this basis, a 2-year field experiment was performed with 18 treatments and three replications. Three irrigation levels, including i) irrigation after depletion of 20% (I20), 50% (I50) and 80 (I80) available water were applied as the first factor. The Second factor was different cropping patterns including thyme sole culture (Ts), soybean–thyme intercropping (in proportion of 50:50 and 66:34) and the third factor was non-usage (control) and usage of arbuscular mycorrhizal fungi (AMF) as bio-fertilizer. According to our results, the thyme dry yield under moderate (I50) and severe water deficit stress (I80) decreased by 35 and 44% in the first year, and by 27 and 40% in the second year compared with non-stressed (I20) plants, respectively. Also, the macro- and micro-nutrients of thyme leaves increased significantly in intercropping patterns after application of AMF. The maximum EO percentage of thyme was achieved in 50:50 intercropping ratio and moderate water deficit (I50). The major constituents of thyme EO were thymol, γ-terpinene, p-cymene, camphene, 1,8-cineole, camphor, (E)-caryophyllene, carvacrol and myrcene. Interestingly, as the water deficit stress was intensified the content of thymol, γ-terpinene and p-cymene increased significantly. Generally, AMF application in intercropping ratio of 50:50 (soybean: thyme) may be proposed to farmers as an eco-friendly approach to achieve desirable EO quality and quantity in thyme under water deficit stress conditions.
Evolution of the vertebrate head is revealed by the rosette mesoderm
Authors: Onai Takayuki , Sugahara Fumiaki , Adachi Noritaka
Published: April 2021

The vertebrate head comprises characteristic combinations of the cranium, brain, cranial nerves and head muscles. However, there have long been arguments about the developmental and evolutionary origins and the possible segmental nature of the head muscles, particularly those anterior to the otic vesicle. In gnathostomes, the presence of pre-otic segments (trunk somite homologs) has been denied by anti-segmentalists, but championed by segmentalists, who have focused on marginally detectable somitomeres or on more obvious head cavities. This metameric ideology has generated various definitions of segments, causing great controversy1,2, and the evaluation of such arguments has been impeded by the relative paucity of relevant work on the head mesoderm of cyclostomes (hagfishes and lampreys). Here, we demonstrate the presence of rosettes (which are reminiscent of somites) in the head mesoderm of lamprey (Lethenteron camtschaticum) embryos using confocal laser scanning and transmission electron microscopy. These transient rosettes, which were not segmented by acellular fissures and were genetically distinct from trunk somites, emerged several times during character individualization of the head muscles. This specialty of the rosette dynamics suggests that the lamprey head mesoderm evolved de novo, rather than from somites, and molecular comparison among deuterostomes supported this perspective.
Ascertaining The Prevalence of Heart Malformations in Neonates: A Novel Clinically Approved Solution
Authors: Bordbar Arash , Kashaki Mandana , Vafapour Maryam , Sepehri Amir A. , Partovi Elaheh
Published: April 2021

Background: Screening of all congenital heart malformations (CHD & CCHD) , as early as possible, is essentials to save children’s lives and, vanishing undetected CHD before becoming adult congenital heart disease (ACHD). As it is known, over 50% of neonates with heart malformations are not recognized at birth. Accurate screening of congenital heart malformations can be accomplished by a certified and patented passive intelligent machine known as Pouya Heart. The objective of this study is 2-fold: to evaluate true prevalence of neonates heart malformations and to evaluate screening of critical congenital heart diseases (CCHD) by the intelligent machine.Methods: 840 neonates with a median age of 31.16 hours and a median weight of 3.11 Kg from the well-baby nursery have been screened by the passive intelligent machine. 20 seconds of heart sounds are recorded into the intelligent machine from two thoracic sites. Each neonate is then classified as normal or abnormal. Echocardiography diagnosis is carried out for verification of each abnormal case.Results: The prevalence of heart malformations (CHD & CCHD), in our well-baby nursery, is 5%. Where, 44% of the heart malformations have not been recognized at birth through the standard medical examination routine.Conclusions: Screening of congenital heart malformations, in all neonates, can be accomplished accurately and cost-effectively by using the Pouya Heart. It detects even CCHD in which it has not been detected through standard medical routine. The innocent murmurs are interpreted as healthy heart sounds.
Multiple Output Analysis for Advanced Waveform and Controlled Short-circuit MIG/MAG Variants
Authors: Silva Régis Henrique Gonçalves e , Galeazzi Daniel , Rocha Pedro Correa Jaeger , Viviani Alberto Bonamigo , Bernardi Rafael Albino
Published: April 2021

The latest advancements of MIG/MAG welding technologies have experienced a steep evolution in functionality, reliability and ever-growing process and weld controllability, within widely interdisciplinary approaches and driven by demanding trends of Advanced Manufacturing (Industry 4.0). Technologic development can be optimized through basic research, which focuses on understanding the physical phenomena involved in metal transfer, weld pool behavior and bead geometric formation and their correlation with each other and with the process´s variables. In this context, the objective of this work is to compare different waveforms of the short-circuiting MIG / MAG process with current control, namely CCC and SOFT, with the conventional process version, evaluating the influence of the electrical parameters on process stability and the general morphology of the weld beads. Analysis of metal transfer by means of high-speed filming and thermal analysis by infrared thermography supported conventional oscillogaphic monitoring for process characterization. Spatter emission assessment by means of image analysis was performed as well. The process´s versions with current control resulted in better operational weldability, geometric control of the bead and lower spatter emission.
New level of regulation of MITF activity by direct interaction with RAF proteins
Authors: Estrada Charlène , Mirabal-Ortega Liliana , Dingli Florent , Besse Laetitia , Messaoudi Cedric , Loew Damarys , Pouponnot Celio , Bertolotto Corine , Eychene Alain , Druillennec Sabine
Published: April 2021

The MITF transcription factor and the RAS/RAF/MEK/ERK pathway are two interconnected main players in melanoma. Understanding how MITF activity is regulated represents a key question since its dynamic modulation is involved in the phenotypic plasticity of melanoma cells and their resistance to therapy. By investigating the role of ARAF in NRAS-driven melanoma through mass spectrometry experiments followed by a functional siRNA-based screen, we unexpectedly identified MITF as a direct ARAF partner. Interestingly, this interaction is conserved among the RAF protein kinase family since the formation of BRAF/MITF and CRAF/MITF complexes was also observed in the cytosol of NRAS-mutated melanoma cells. The interaction occurs through the kinase domain of RAF proteins and is correlated with their kinase activity level. RAF/MITF complexes modulate MITF nuclear localization by inducing an accumulation of MITF in the cytoplasm, thus negatively controlling its transcriptional activity. Taken together, our study highlights a new level of regulation between two major mediators of melanoma progression, MITF and the MAPK/ERK pathway, which appears more complex than previously anticipated.
Itaconate as a Promising Therapy for Neuropathic Pain and Inflammatory Pain
Authors: Ren Jinxuan , Yu Lina , Lin Jiaqi , Ma Longfei , Gao Dave Schwinn , Sun Na , Liu Ying , Fang Lili , Cheng Zhenzhen , Sun Kai , Yan Min
Published: April 2021

Background: Chronic pain is a complex experience that often leads to multiple complications. Neuroinflammation in the immune system as well as in the peripheral and central nervous system contributes to the development and persistence of chronic pain. The metabolite itaconate, recently emerged as a regulator of immune cell functions, has features of anti-inflammation and immunomodulation via the activation of Nrf2. However, its effect on chronic pain is unclear. Methods: Chronic C57BL/6 neuropathic pain and inflammatory pain were induced followed by dimethyl itaconate (DI) treatment, an itaconate derivative. We evaluated the effect of DI on the changes of pain behaviors induced by chronic pain model. The effect of DI on inflammatory cytokine release, glial cells activation, ERK1/2 phosphorylation, inflammatory cell infiltration and Nrf2 expression in the DRGs, spinal cord and hind paw tissues was determined using the histochemistry, RT-PCR and western blot. Microglia was cultured to study the effect of DI on microglial inflammatory response and Nrf2 level.Results: DI reduced the secretion of inflammatory cytokines in DRGs, spinal cord and hind paw tissues, suppressed the activation of glial cells (like microglia and astrocytes) in spina dorsal horn and infiltration of inflammatory cells in the hind paw tissues, and decreased the phosphorylation of ERK1/2, but boosted Nrf2 levels in the DRGs and spinal dorsal horn. Similarly, administration of DI potently reversed the LPS-induced inflammatory effect in the microglia. Reduction of endogenous itaconate pretreated with irg1 siRNA prevented the expression of Nrf2, which did not exert the analgesic and anti-inflammatory effects in vitro experiment. Conclusions: Our findings verify for the first time that DI alleviates painful behaviors and suppresses neuroinflammation in neuropathic pain and inflammatory pain models through molecular mechanisms, suggesting that DI elicits sustained chronic pain relief, which will be regarded as a novel therapeutic agent for chronic pain treatment.
Ferrostatin-1 Alleviates White Matter Injury via Decreasing Ferroptosis Following Spinal Cord Injury
Authors: Ge Hongfei , Xue Xingsen , Xian Jishu , Yuan Linbo , Wang Long , Zou Yongjie , Zhong Jun , Jiang Zhouyang , Shi Jiantao , Chen Tunan , Su Hong , Feng Hua , Hu Shengli
Published: April 2021

Spinal cord injury (SCI), a devastating neurological impairment, ubiquitously imposes a long-term psychological stress and high socioeconomic burden for the suffers and their family. To date, recent researchers have paid arousing attention to white matter injury and uncovering the underlying mechanism post-SCI. Ferroptosis, to our knowledge, has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. However, its role in white matter damage after SCI remains unclear. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improve functional recovery after traumatic brain injury (TBI). But whether it inhibits white matter injury post-SCI is still unknown. Here, our results indicated that ferroptosis played an important role in the secondary white matter injury following SCI and ferrostatin-1 could reduce iron and reactive oxygen species (ROS) accumulation, downregulate the ferroptosis-related genes and its products of IREB2 and PTGS2 to further inhibit ferroptosis in oligodendrocyte progenitor cells (OPCs), finally reducing white matter injury and promoting functional recovery following SCI in rats, which enlarges the therapeutic scope for ferrostatin-1 and deciphers the potential mechanism of white matter damage after SCI.