bluuebunny/crossref_metadata_2025 huggingface dataset:
Cadmium is acutely toxic for murine hepatocytes: effects on intracellular free Ca2+ homeostasis
Authors: Wang SS , Chen L , Xia SK
Published: August 2021

We studied cadmium toxicity in murine hepatocytes in vitro. Cadmium effects on intracellular free Ca(2+) concentration ([Ca(2+)](i)) were assayed, using a laser scanning confocal microscope with a fluorescent probe, Fluo-3/AM. The results showed that administration of cadmium chloride (CdCl(2), 5, 10, 25 microM) resulted in a dose-dependent decrease of hepatocyte viability and an elevated aspartate aminotransferase (AST) activity in the culture medium (p<0.05 for 25 microM CdCl(2) vs. control). Significant increases of lactate dehydrogenase (LDH) activities in 10 and 25 microM CdC1(2)-exposed groups were observed (p<0.05 and p<0.01, respectively). A greatly decreased albumin content and a more malondialdehyde (MDA) formation also occurred after CdC1(2) treatment. The Ca(2+) concentrations in the culture medium of CdCl(2)-exposed hepatocytes were significantly decreased, while [Ca(2+)](i) appeared to be significantly elevated (p<0.05 or p<0.01 vs. control). We found that in Ca(2+)-containing hydroxyethyl piperazine ethanesulfonic acid-buffered salt solution (HBSS) only, CdCl(2) elicited [Ca(2+)](i) increases, which comprised an initially slow ascent and a strong elevated phase. However, in Ca(2+)-containing HBSS with addition of 2-aminoethoxydiphenyl borane (2-APB), CdCl(2) caused a mild [Ca(2+)](i) elevation in the absence of an initial rise phase. Removal of extracellular Ca(2+) showed that CdCl(2) induced an initially slow [Ca(2+)](i) rise alone without being followed by a markedly elevated phase, but in a Ca(2+)-free HBSS with addition of 2-APB, CdCl(2) failed to elicit the [Ca(2+)](i) elevation. These results suggest that abnormal Ca(2+) homeostasis due to cadmium may be an important mechanism of the development of the toxic effect in murine hepatocytes. [Ca(2+)](i) elevation in acutely cadmium-exposed hepatocytes is closely related to the extracellular Ca(2+) entry and an excessive release of Ca(2+) from intracellular stores.
Pelatihan Akreditasi Jurnal Nasional Bagi Pengelola Jurnal Se-Indonesia di Universitas Pelita Bangsa, Cikarang, Bekasi
Authors: Syamruddin Syamruddin , Kusjono Gatot , Lubis Iman , Iqbal Khair Oki , Sopandi Andi
Published: August 2021

This Community Service (PkM) aims to share and share knowledge and enlightenment for journal managers in Indonesia on how to manage journals properly and correctly. Then provide tips on preparing for an accredited journal. Besides that, it also helps journal managers to achieve the National Journal Accreditation (Arjuna) SINTA. The methods used are in the form of orientation, lectures, workshops, journal reviews, and evaluations. The method consists of four stages, namely pre-training, training, post-training, and continuous PkM activities. The results obtained by the participants during the training were that they increasingly understood how to manage a good and correct journal. Participants know how to manage journals through open-access journals using open journal systems. Furthermore, after understanding the correct management of journals, participants are more confident in preparing their journals for national journal accreditation. The next stage, is ready to register the journal to be accredited by the National Research and Innovation Agency (BRIN).
Abstrak
Pengabdian kepada Masyarakat (PkM) ini bertujuan untuk sharing dan berbagi pengetahuan dan pencerahan bagi para pengelola jurnal di Indonesia bagaimana mengelola jurnal dengan baik dan benar. Kemudian memberikan tip-tip tentang persiapan menuju jurnal yang terakreditasi. Selain itu  mengantarkan para pengelola jurnal agar bisa meraih Akreditasi Jurnal Nasional (Arjuna) SINTA. Adapun metode yang dilakukan yaitu dalam bentuk orientasi, ceramah, workshop, bedah jurnal, dan evaluasi. Metode tersebut dalam empat tahap yakni pra pelatihan, pelatihan, paska pelatihan, dan kegiatan PkM berkelanjutan. Hasil yang diperoleh peserta selama pelatihan adalah semakin memahami bagaimana mengelola jurnal yang baik dan benar. Peserta mengetahui pengelolaan jurnal melalui open-access journal dengan cara open journal systems. Selanjutnya setelah memahami pengelolaan jurnal yang benar, peserta semakin yakin untuk mempersiapkan jurnalnya menuju akreditasi jurnal nasional. Tahap berikutnya, sudah siap untuk mendaftarkan jurnalnya untuk diakreditasi oleh Badan Riset dan Inovasi Nasional (BRIN).
Kata Kunci: pelatihan; akreditasi; jurnal; sistem jurnal terbuka
Drone Power: Conservation, Humanitarianism, Policing and War
Authors: Richardson Michael , Fish Adam
Published: August 2021

A convergence of four genealogies reveals drone power. Environmentality describes the contradictory uses of drones in conservation. Humanitarianism articulates how control is enacted and challenged in human crises. Securitization examines drones in surveillance and counter-surveillance. Militarization, the use of drones in war, explains domination from above and resistance from below. While theories of governmentality dominate, an emergent materialism within drone studies emphasizes the diffusion of power and agency. A synthesis of drone governmentality and drone materialism exposes four flightways or elemental trajectories. The drone is an existential technology – a tool for enlivenment and senescence. As such, drone power migrates between biopolitics and resistance. In doing so, drone performativity generates assemblages of human and nonhuman actants entangled at material-discursive and onto-epistemological levels. Entrapment designates the consequences of increasing dependency on technologies in sociotechnical systems of life and death.
The Lack of Sex, Age, and Anthropometric Diversity in Neck Biomechanical Data
Authors: Booth Gabrielle R. , Cripton Peter A. , Siegmund Gunter P.
Published: August 2021

Female, elderly, and obese individuals are at greater risk than male, young, and non-obese individuals for neck injury in otherwise equivalent automotive collisions. The development of effective safety technologies to protect all occupants requires high quality data from a range of biomechanical test subjects representative of the population at risk. Here we sought to quantify the demographic characteristics of the volunteers and post-mortem human subjects (PMHSs) used to create the available biomechanical data for the human neck during automotive impacts. A systematic literature and database search was conducted to identify kinematic data that could be used to characterize the neck response to inertial loading or direct head/body impacts. We compiled the sex, age, height, weight, and body mass index (BMI) for 999 volunteers and 110 PMHSs exposed to 5,431 impacts extracted from 63 published studies and three databases, and then compared the distributions of these parameters to reference data drawn from the neck-injured, fatally-injured, and general populations. We found that the neck biomechanical data were biased toward males, the volunteer data were younger, and the PMHS data were older than the reference populations. Other smaller biases were also noted, particularly within female distributions, in the height, weight, and BMI distributions relative to the neck-injured populations. It is vital to increase the diversity of volunteer and cadaveric test subjects in future studies in order to fill the gaps in the current neck biomechanical data. This increased diversity will provide critical data to address existing inequities in automotive and other safety technologies.
Open Culture Ethanol-Based Chain Elongation to Form Medium Chain Branched Carboxylates and Alcohols
Authors: de Leeuw Kasper D. , Ahrens Theresa , Buisman Cees J. N. , Strik David P. B. T. B.
Published: August 2021

Chain elongation fermentation allows for the synthesis of biobased chemicals from complex organic residue streams. To expand the product spectrum of chain elongation technology and its application range we investigated 1) how to increase selectivity towards branched chain elongation and 2) whether alternative branched carboxylates such as branched valerates can be used as electron acceptors. Elongation of isobutyrate elongation towards 4-methyl-pentanoate was achieved with a selectivity of 27% (of total products, based on carbon atoms) in a continuous system that operated under CO2 and acetate limited conditions. Increasing the CO2 load led to more in situ acetate formation that increased overall chain elongation rate but decreased the selectivity of branched chain elongation. A part of this acetate formation was related to direct ethanol oxidation that seemed to be thermodynamically coupled to hydrogenotrophic carboxylate reduction to corresponding alcohols. Several alcohols including isobutanol and n-hexanol were formed. The microbiome from the continuous reactor was also able to form small amounts of 5-methyl-hexanoate likely from 3-methyl-butanoate and ethanol as substrate in batch experiments. The highest achieved concentration of isoheptanoate was 6.4 ± 0.9 mM Carbon, or 118 ± 17 mg/L, which contributed for 7% to the total amount of products (based on carbon atoms). The formation of isoheptanoate was dependent on the isoform of branched valerate. With 3-methyl-butanoate as substrate 5-methylhexanoate was formed, whereas a racemic mixture of L/D 2-methyl-butanoate did not lead to an elongated product. When isobutyrate and isovalerate were added simultaneously as substrates there was a large preference for elongation of isobutyrate over isovalerate. Overall, this work showed that chain elongation microbiomes can be further adapted with supplement of branched-electron acceptors towards the formation of iso-caproate and iso-heptanoate as well as that longer chain alcohol formation can be stimulated.
DNA Functional Nanomaterials for Controlled Delivery of Nucleic Acid-Based Drugs
Authors: Lv Zhaoyue , Zhu Yi , Li Feng
Published: August 2021

Nucleic acid-based drugs exhibited great potential in cancer therapeutics. However, the biological instability of nucleic acid-based drugs seriously hampered their clinical applications. Efficient in vivo delivery is the key to the clinical application of nucleic acid-based drugs. As a natural biological macromolecule, DNA has unique properties, such as excellent biocompatibility, molecular programmability, and precise assembly controllability. With the development of DNA nanotechnology, DNA nanomaterials have demonstrated significant advantages as delivery vectors of nucleic acid-based drugs by virtue of the inherent nucleic acid properties. In this study, the recent progress in the design of DNA-based nanomaterials for nucleic acid delivery is summarized. The DNA nanomaterials are categorized according to the components including pure DNA nanomaterials, DNA-inorganic hybrid nanomaterials, and DNA-organic hybrid nanomaterials. Representative applications of DNA nanomaterials in the controlled delivery of nucleic acid-based drugs are exemplified to show how DNA nanomaterials are rationally and exquisitely designed to address application issues in cancer therapy. At the end of this study, the challenges and future development of DNA nanomaterials are discussed.
A Novel ARL3 Gene Mutation Associated With Autosomal Dominant Retinal Degeneration
Authors: Ratnapriya Rinki , Jacobson Samuel G. , Cideciyan Artur V. , English Milton A. , Roman Alejandro J. , Sumaroka Alexander , Sheplock Rebecca , Swaroop Anand
Published: August 2021

Despite major progress in the discovery of causative genes, many individuals and families with inherited retinal degenerations (IRDs) remain without a molecular diagnosis. We applied whole exome sequencing to identify the genetic cause in a family with an autosomal dominant IRD. Eye examinations were performed and affected patients were studied with electroretinography and kinetic and chromatic static perimetry. Sequence variants were analyzed in genes (n = 271) associated with IRDs listed on the RetNet database. We applied a stepwise filtering process involving the allele frequency in the control population, in silico prediction tools for pathogenicity, and evolutionary conservation to prioritize the potential causal variant(s). Sanger sequencing and segregation analysis were performed on the proband and other family members. The IRD in this family is expressed as a widespread progressive retinal degeneration with maculopathy. A novel heterozygous variant (c.200A > T) was identified in the ARL3 gene, leading to the substitution of aspartic acid to valine at position 67. The Asp67 residue is evolutionary conserved, and the change p.Asp67Val is predicted to be pathogenic. This variant was segregated in affected members of the family and was absent from an unaffected individual. Two previous reports of a de novo missense mutation in the ARL3 gene, each describing a family with two affected generations, are the only examples to date of autosomal dominant IRD associated with this photoreceptor gene. Our results, identifying a novel pathogenic variant in ARL3 in a four-generation family with a dominant IRD, augment the evidence that the ARL3 gene is another cause of non-syndromic retinal degeneration.
Gate Alignment of Liquid Water Molecules in Electric Double Layer
Authors: Li Xiaoqun , Lin Xin , Li Ying , Liu Wei-Tao
Published: August 2021

The behavior of liquid water molecules near an electrified interface is important to many disciplines of science and engineering. In this study, we applied an external gate potential to the silica/water interface via an electrolyte-insulator-semiconductor (EIS) junction to control the surface charging state. Without varying the ionic composition in water, the electrical gating allowed an efficient tuning of the interfacial charge density and field. Using the sum-frequency vibrational spectroscopy, we found a drastic enhancement of interfacial OH vibrational signals at high potential in weakly acidic water, which exceeded that from conventional bulk-silica/water interfaces even in strong basic solutions. Analysis of the spectra indicated that it was due to the alignment of liquid water molecules through the electric double layer, where the screening was weak because of the low ion density. Such a combination of strong field and weak screening demonstrates the unique tuning capability of the EIS scheme, and would allow us to investigate a wealth of phenomena at charged oxide/water interfaces.
SmartFFR, a New Functional Index of Coronary Stenosis: Comparison With Invasive FFR Data
Authors: Siogkas Panagiotis K. , Lakkas Lampros , Sakellarios Antonis I. , Rigas George , Kyriakidis Savvas , Stefanou Kostas A. , Anagnostopoulos Constantinos D. , Clemente Alberto , Rocchiccioli Silvia , Pelosi Gualtiero , Parodi Oberdan , Papafaklis Michail I. , Naka Katerina K. , Michalis Lampros K. , Neglia Danilo , Fotiadis Dimitrios I.
Published: August 2021

Aims: In this study, we evaluate the efficacy of SmartFFR, a new functional index of coronary stenosis severity compared with gold standard invasive measurement of fractional flow reserve (FFR). We also assess the influence of the type of simulation employed on smartFFR (i.e. Fluid Structure Interaction vs. rigid wall assumption).

Methods and Results: In a dataset of 167 patients undergoing either computed tomography coronary angiography (CTCA) and invasive coronary angiography or only invasive coronary angiography (ICA), as well as invasive FFR measurement, SmartFFR was computed after the 3D reconstruction of the vessels of interest and the subsequent blood flow simulations. 202 vessels were analyzed with a mean total computational time of seven minutes. SmartFFR was used to process all models reconstructed by either method. The mean FFR value of the examined dataset was 0.846 ± 0.089 with 95% CI for the mean of 0.833–0.858, whereas the mean SmartFFR value was 0.853 ± 0.095 with 95% CI for the mean of 0.84–0.866. SmartFFR was significantly correlated with invasive FFR values (RCCTA = 0.86, pCCTA < 0.0001, RICA = 0.84, pICA < 0.0001, Roverall = 0.833, poverall < 0.0001), showing good agreement as depicted by the Bland-Altman method of analysis. The optimal SmartFFR threshold to diagnose ischemia was ≤0.83 for the overall dataset, ≤0.83 for the CTCA-derived dataset and ≤0.81 for the ICA-derived dataset, as defined by a ROC analysis (AUCoverall = 0.956, p < 0.001, AUCICA = 0.975, p < 0.001, AUCCCTA = 0.952, p < 0.001).

Conclusion: SmartFFR is a fast and accurate on-site index of hemodynamic significance of coronary stenosis both at single coronary segment and at two or more branches level simultaneously, which can be applied to all CTCA or ICA sequences of acceptable quality.
Positron Emission Tomography Techniques to Measure Active Inflammation, Fibrosis and Angiogenesis: Potential for Non-invasive Imaging of Hypertensive Heart Failure
Authors: Balogh Viktoria , MacAskill Mark G. , Hadoke Patrick W. F. , Gray Gillian A. , Tavares Adriana A. S.
Published: August 2021

Heart failure, which is responsible for a high number of deaths worldwide, can develop due to chronic hypertension. Heart failure can involve and progress through several different pathways, including: fibrosis, inflammation, and angiogenesis. Early and specific detection of changes in the myocardium during the transition to heart failure can be made via the use of molecular imaging techniques, including positron emission tomography (PET). Traditional cardiovascular PET techniques, such as myocardial perfusion imaging and sympathetic innervation imaging, have been established at the clinical level but are often lacking in pathway and target specificity that is important for assessment of heart failure. Therefore, there is a need to identify new PET imaging markers of inflammation, fibrosis and angiogenesis that could aid diagnosis, staging and treatment of hypertensive heart failure. This review will provide an overview of key mechanisms underlying hypertensive heart failure and will present the latest developments in PET probes for detection of cardiovascular inflammation, fibrosis and angiogenesis. Currently, selective PET probes for detection of angiogenesis remain elusive but promising PET probes for specific targeting of inflammation and fibrosis are rapidly progressing into clinical use.
Graves’ Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study
Authors: Wu Dide , Xian Wei , Hong Shubin , Liu Boyuan , Xiao Haipeng , Li Yanbing
Published: August 2021

Background

The frequent coexistence of Graves’ disease (GD) and rheumatoid arthritis (RA) has been cited and discussed in observational studies, but it remains a question as to whether there is a causal effect between the two diseases.

Methods

We retrieved genome-wide association study (GWAS) summary data of GD and RA from BioBank Japan (BBJ). Single nucleotide polymorphisms (SNPs) associated with diseases of interest were selected as instrumental variables (IVs) at a genome-wide significance level (P < 5.0 × 10−8). The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. The horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. The statistical power of our MR result was calculated according to Brion’s method.

Results

Our study discovered a bidirectional causal effect between GD and RA. The presence of RA may increase the risk of GD by 39% (OR 1.39, 95% CI 1.10–1.75, P = 0.007). Similarly, the existence of GD may increase the risk of RA by 30% (OR 1.30, 95% CI 0.94–1.80, P = 0.112). Our study provides 100% power to detect the causal effect of RA on GD risk, and vice versa.

Conclusions

We found a bidirectional causal effect between GD and RA in an Asian population. Our study supported the clinical need for screening GD in RA patients, and vice versa. The potential benefit of sound management of RA in GD patients (or GD in RA patients) merits excellent attention. Moreover, novel satisfactory medicine for RA may be applicable to GD and such potential is worthy of further investigation.
Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells
Authors: Jo Sugyeong , Fang Sungsoon
Published: August 2021

Increased incidence of type I and type II diabetes has been prevailed worldwide. Though the pathogenesis of molecular mechanisms remains still unclear, there are solid evidence that disturbed immune homeostasis leads to pancreatic β cell failure. Currently, autoimmunity and uncontrolled inflammatory signaling pathways have been considered the major factors in the pathogenesis of diabetes. Many components of immune system have been reported to implicate pancreatic β cell failure, including helper T cells, cytotoxic T cells, regulatory T cells and gut microbiota. Immune modulation of those components using small molecules and antibodies, and fecal microbiota transplantation are undergoing in many clinical trials for the treatment of type I and type II diabetes. In this review we will discuss the basis of molecular pathogenesis focusing on the disturbed immune homeostasis in type I and type II diabetes, leading to pancreatic β cell destruction. Finally, we will introduce current therapeutic strategies and clinical trials by modulation of immune system for the treatment of type I and type II diabetes patients.
The Advanced Multilevel Predictor-Corrector Quasi-Static Method for Pin-Resolved Neutron Kinetics Simulation
Authors: Kang Le , Hao Chen , Zhao Qiang , Xu Yunlin
Published: August 2021

The Advanced Multilevel Predictor-Corrector Quasi-static Method (AML-PCQM) is proposed in this work. The four computational levels, including transport, Multi-Group (MG) Coarse Mesh Finite Difference (CMFD), One-Group (1G) CMFD, and Exact Point-Kinetics Equation (EPKE), are coupled with a new dynamic iteration strategy. In each coupling algorithm, the original Transient Fixed Source Problem (TFSP) is solved in the predictor process using coarse time step, and then the flux distribution is factorized to the functions of amplitude and shape in the next corrector process. Finally, multiple fine time steps are used to adjust the predicted solution. Two heterogeneous single assembly problems with the prompt control rod withdrawal event are used to verify the AML-PCQM scheme’s accuracy and efficiency. The numerical results obtained by different cases are compared and analyzed. The final results indicate that the AML-PCQM performs the remarkable advantages of efficiency and accuracy with the reference cases.
Response of Iron and Cadmium on Yield and Yield Components of Rice and Translocation in Grain: Health Risk Estimation
Authors: Siddique Abu Bakkar , Rahman Mohammad Mahmudur , Islam Md. Rafiqul , Mondal Debapriya , Naidu Ravi
Published: August 2021

Rice consumption is a major dietary source of Cd and poses a potential threat to human health. The aims of this study were to examine the influence of Fe and Cd application on yield and yield components, dynamics of Cd in pore water, translocation factors, daily dietary intake, and estimation of human health risks. A pot experiment was performed under glasshouse conditions where rice cultivars (Langi and Quest) were cultivated in two dissimilar soils under different levels of Cd (0, 1.0, and 3.0 mg kg−1) and Fe (0, 1.0, and 2.0 g kg−1). The results showed that variation in two rice cultivars in terms of yield and yield-related components was dose dependent. Cadmium concentration in soil pore water was decreased over time and increased with increasing Cd levels but decreased with Fe application. Translocation factors (TFs) from root to straw (TFroot-straw) or straw to husk (TFstraw-husk) were higher than root to grain (TFroot-grain) or straw to grain (TFstraw-grain). The Quest cultivar had 20% lower Cd than the Langi cultivar. Application of Fe at the rate of 1 and 2 g kg−1 soil reduced Cd by 23 and 46%, respectively. Average daily intake (ADI) of Cd exceeded the permissible limit (5.8 × 10−3 mg −1 kg−1 bw per week) when rice plant subjected 1 and 3 mg kg−1 Cd stress with or without Fe application. Results also indicated that ADI value was lower in the Quest cultivar as compared to the Langi cultivar. Estimation of human health risk revealed that the non-carcinogenic risks (HQ > 1) and carcinogenic risks (CR > 1.0 × 10−4) increased with increasing Cd levels in the soil. The application of Fe decreased the human health risks from rice consumption which is more pronounced in Fe 2.0 than in Fe1.0 treatments. The rice cultivar grown in soil-1 (pH 4.6) showed the highest health risks as compared to soil-2 (pH 6.6) and the Quest cultivar had lower health risks than the Langi cultivar.
An Evaluation of First-Come, First-Served Scheduling in a Geometrically-Constrained Wet Bulk Terminal
Authors: Eisen Heleen E. , Van der Lei Joachim E. , Zuidema Joost , Koch Thomas , Dugundji Elenna R.
Published: August 2021

In 2022, a new sea lock at IJmuiden is expected to open, permitting an increase in marine traffic of larger ships from the sea to the port. In the interest of facilitating operations, we evaluate the impact of the current first-come, first-served (FCFS) admittance policy in the context of berth allocation for a wet bulk terminal in the port. Four model types are constructed: optimal FCFS; no FCFS with fixed arrival times; 48-h arrival time relaxation; and complete arrival time relaxation. Comparison of the model types is done by means of a rolling time window: of each day within the time frame, a schedule was created for the following 2 weeks, after which the objective value was calculated. When comparing the average of all objective values, it was found that the optimal FCFS model already shows an improvement compared to the historical situation. Between the FCFS and the no FCFS model, there are no considerable differences, because the vessels are constrained to be scheduled on/after their arrival time at the port. When relaxation is allowed, a considerable efficiency gain is possible, especially if larger ships arrive at the port.
Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients
Authors: Izati Aziz Farah , Mohd Shukri Nur Diyana , Wan Ghazali Wan Syamimee , Che Hussin Che Maraina , Wong Kah Keng
Published: August 2021

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.
Crucial Mutations of Spike Protein on SARS-CoV-2 Evolved to Variant Strains Escaping Neutralization of Convalescent Plasmas and RBD-Specific Monoclonal Antibodies
Authors: Ding Chengchao , He Jun , Zhang Xiangyu , Jiang Chengcheng , Sun Yong , Zhang Yuqing , Chen Qingqing , He Hongliang , Li Wenting , Xie Jiajia , Liu Zhirong , Gao Yong
Published: August 2021

Small number of SARS-CoV-2 epidemic lineages did not efficiently exhibit a neutralization profile, while single amino acid mutation in the spike protein has not been confirmed in altering viral antigenicity resulting in immune escape. To identify crucial mutations in spike protein that escape humoral immune response, we evaluated the cross-neutralization of convalescent plasmas and RBD-specific monoclonal antibodies (mAbs) against various spike protein-based pseudoviruses. Three of 24 SARS-CoV-2 pseudoviruses containing different mutations in spike protein, including D614G, A475V, and E484Q, consistently showed an altered sensitivity to neutralization by convalescent plasmas. A475V and E484Q mutants are highly resistant to neutralization by mAb B38 and 2-4, suggesting that some crucial mutations in spike protein might evolve SARS-CoV-2 variants capable of escaping humoral immune response.
IL-6 and IL-10 Levels, Rather Than Viral Load and Neutralizing Antibody Titers, Determine the Fate of Patients With Severe Fever With Thrombocytopenia Syndrome Virus Infection in South Korea
Authors: Yoo Jeong Rae , Kim Tae-Jin , Heo Sang Taek , Hwang Kyung-Ah , Oh Hyunjoo , Ha TaeHong , Ko Hye Kyung , Baek Seungjae , Kim Ju Eun , Kim Jun Hyeong , Lee Jiin , Kang Min Ji , Yoo Mi Soo , Kim Jung Mogg , Lee Kyung-Mi , Lee Keun Hwa
Published: August 2021

Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne viral disease, and most SFTS virus (SFTSV) infections occur via bites from the tick Haemaphysalis longicornis; however, SFTSV transmission can also occur through close contact with an infected patient. SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzyme levels, gastrointestinal symptoms, and multiorgan failure and has a 16.2 to 30% mortality rate. In this study, we found that age, dyspnea rates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, multiorgan dysfunction score (MODS), viral load, IL-6 levels, and IL-10 levels were higher in patients with fatal disease than in patients with nonfatal disease during the initial clinical course of SFTS. In addition, we found that IL-6 and IL-10 levels, rather than viral load and neutralizing antibody titers, in patients with an SFTSV infection strongly correlated with outcomes (for severe disease with an ultimate outcome of recovery or death).
Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease
Authors: Ren Pingping , Lu Luying , Cai Shasha , Chen Jianghua , Lin Weiqiang , Han Fei
Published: August 2021

Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them.
Targeting the Microtubule-Network Rescues CTL Killing Efficiency in Dense 3D Matrices
Authors: Zhao Renping , Zhou Xiangda , Khan Essak S. , Alansary Dalia , Friedmann Kim S. , Yang Wenjuan , Schwarz Eva C. , del Campo Aránzazu , Hoth Markus , Qu Bin
Published: August 2021

Efficacy of cytotoxic T lymphocyte (CTL)-based immunotherapy is still unsatisfactory against solid tumors, which are frequently characterized by condensed extracellular matrix. Here, using a unique 3D killing assay, we identify that the killing efficiency of primary human CTLs is substantially impaired in dense collagen matrices. Although the expression of cytotoxic proteins in CTLs remained intact in dense collagen, CTL motility was largely compromised. Using light-sheet microscopy, we found that persistence and velocity of CTL migration was influenced by the stiffness and porosity of the 3D matrix. Notably, 3D CTL velocity was strongly correlated with their nuclear deformability, which was enhanced by disruption of the microtubule network especially in dense matrices. Concomitantly, CTL migration, search efficiency, and killing efficiency in dense collagen were significantly increased in microtubule-perturbed CTLs. In addition, the chemotherapeutically used microtubule inhibitor vinblastine drastically enhanced CTL killing efficiency in dense collagen. Together, our findings suggest targeting the microtubule network as a promising strategy to enhance efficacy of CTL-based immunotherapy against solid tumors, especially stiff solid tumors.
The Role of Stokes Drift in the Dispersal of North Atlantic Surface Marine Debris
Authors: Bosi Sofia , Broström Göran , Roquet Fabien
Published: August 2021

Understanding the physical mechanisms behind the transport and accumulation of floating objects in the ocean is crucial to efficiently tackle the issue of marine pollution. The main sinks of marine plastic are the coast and the bottom sediment. This study focuses on the former, investigating the timescales of dispersal from the ocean surface and onto coastal accumulation areas through a process called “beaching.” Previous studies found that the Stokes drift can reach the same magnitude as the Eulerian current speed and that it has a long-term effect on the trajectories of floating objects. Two particle tracking models (PTMs) are carried out and then compared, one with and one without Stokes drift, named PTM-SD and PTM-REF, respectively. Eulerian velocity and Stokes drift data from global reanalysis datasets are used for particle advection. Particles in the PTM-SD model are found to beach at a yearly rate that is double the rate observed in PTM-REF. The main coastal attractors are consistent with the direction of large-scale atmospheric circulation (Westerlies and Trade Winds). After 12 years (at the end of the run), the amount of beached particles is 20% larger in PTM-SD than in PTM-REF. Long-term predictions carried out with the aid of adjacency matrices found that after 100 years all particles have beached in PTM-SD, while 8% of the all seeded particles are still floating in PTM-REF. The results confirm the need to accurately represent the Stokes drift in particle models attempting to predict the behaviour of marine debris, in order to avoid overestimation of its residence time in the ocean and effectively guide policies toward prevention and removal.
Dynamic Performance Detection of CFRP Composite Pipes based on Quasi-Distributed Optical Fiber Sensing Techniques
Authors: Wang Hua-Ping , Feng Si-Yuan , Gong Xiang-Shu , Guo Yan-Xin , Xiang Ping , Fang Yu , Li Qi-Ming
Published: August 2021

For the high strength, corrosion resistance, and good stability, carbon fiber–reinforced polymer (CFRP) composites have been made into pipes to transfer gasses and oils in subsea environment. Structural performance of CFRP composite pipes is particularly important to sustain the regular operation of the delivery system. To obtain the in-field behavior of the CFRP composite pipes, quasi-distributed optical fiber sensing techniques are developed based on the multiple configuration of fiber Bragg grating (FBG) sensing elements. Theoretical investigation on the dynamic response of the pipes is performed. Experiments on cantilever CFRP pipes with surface-attached FBGs in series and packaged FBG sensors have been conducted to check the feasibility and effectiveness of the proposed sensing technique. Results validate the good measurement performance of the proposed sensors and the accuracy of the vibration analysis. The study can be adopted to instruct the establishment of the structural health monitoring system of CFRP composite pipes and assess the safety operation state of the pipe systems.
Probiotic Properties of Bacillus proteolyticus Isolated From Tibetan Yaks, China
Authors: Zeng Zhibo , He Xiaoling , Li Feiran , Zhang Yan , Huang Zonghao , Wang Yaping , Li Kun , Bao Yuhua , Iqbal Mudassar , Fakhar-e-Alam Kulyar Muhammad , Li Jiakui
Published: August 2021

Yaks (Bos grunniens) live primarily in high-altitude hypoxic conditions and have a unique intestinal micro-ecosystem, remarkable adaptability, and strong climatic resistance. Accumulating evidence revealed the importance of probiotics in host metabolism, gut microbiota, growth performance, and health. The goal of this study was to screen out probiotics with excellent probiotic potential for clinical application. In this study, four strains of Bacillus, i.e., Bacillus proteolyticus (named Z1 and Z2), Bacillus amyloliquefaciens (named J), and Bacillus subtilis (named K), were isolated and identified. Afterward, their probiotic potential was evaluated. Antioxidant activity tests revealed that Z1 had the highest DPPH and hydroxyl radical scavenging activity, whereas Z2 had higher reducing power and inhibited lipid peroxidation. Additionally, the antibacterial testing revealed that all strains were antagonistic to three indicator pathogens, Escherichia coli C83902, Staphylococcus aureus BNCC186335, and Salmonella enteritidis NTNC13349. These isolates also had a higher hydrophobicity, autoaggregation, and acid and bile tolerance, all of which helped to survive and keep dangerous bacteria out of the host intestine. Importantly, all strains could be considered safe in terms of antibiotic susceptibility and lack of hemolysis. In conclusion, this is the first study to show that B. proteolyticus and B. amyloliquefaciens isolated from yaks have probiotic potential, providing a better foundation for future clinical use.
Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan
Authors: Abidi Syed Hani , Nduva George Makau , Siddiqui Dilsha , Rafaqat Wardah , Mahmood Syed Faisal , Siddiqui Amna Rehana , Nathwani Apsara Ali , Hotwani Aneeta , Shah Sharaf Ali , Memon Sikander , Sheikh Saqib Ali , Khan Palwasha , Esbjörnsson Joakim , Ferrand Rashida Abbas , Mir Fatima
Published: August 2021

Introduction

In April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children. It was assumed that the outbreak originated from a single source, namely a doctor at a private health facility. In this study, we performed subtype distribution, phylogenetic and drug-resistance analysis of HIV-1 sequences from 2019 outbreak in Larkana, Pakistan.

Methods

A total of 401 blood samples were collected between April–June 2019, from children infected with HIV-1 aged 0–15 years recruited into a case-control study to investigate the risk factors for HIV-1 transmission. Partial HIV-1 pol sequences were generated from 344 blood plasma samples to determine HIV-1 subtype and drug resistance mutations (DRM). Maximum-likelihood phylogenetics based on outbreak and reference sequences was used to identify transmission clusters and assess the relationship between outbreak and key population sequences between and within the determined clusters. Bayesian analysis was employed to identify the time to the most recent common recent ancestor (tMRCA) of the main Pakistani clusters.

Results

The HIV-1 circulating recombinant form (CRF) 02_AG and subtype A1 were most common among the outbreak sequences. Of the treatment-naïve participants, the two most common mutations were RT: E138A (8%) and RT: K219Q (8%). Four supported clusters within the outbreak were identified, and the median tMRCAs of the Larkana outbreak sequences were estimated to 2016 for both the CRF02_AG and the subtype A1 clusters. Furthermore, outbreak sequences exhibited no phylogenetic mixing with sequences from other high-risk groups of Pakistan.

Conclusion

The presence of multiple clusters indicated a multi-source outbreak, rather than a single source outbreak from a single health practitioner as previously suggested. The multiple introductions were likely a consequence of ongoing transmission within the high-risk groups of Larkana, and it is possible that the so-called Larkana strain was introduced into the general population through poor infection prevention control practices in healthcare settings. The study highlights the need to scale up HIV-1 prevention programmes among key population groups and improving infection prevention control in Pakistan.
Variations of Soybean Meal and Corn Mixed Substrates in Physicochemical Characteristics and Microbiota During Two-Stage Solid-State Fermentation
Authors: Su Weifa , Jiang Zipeng , Hao Lihong , Li Wentao , Gong Tao , Zhang Yu , Du Shuai , Wang Cheng , Lu Zeqing , Jin Mingliang , Wang Yizhen
Published: August 2021

Corn germ meal (CGM) and corn gluten feed (CGF) are the two main corn byproducts (CBs) obtained from corn starch extraction. Due to their high fiber content, low protein content, and severe imbalance of amino acid, CBs are unable to be fully utilized by animals. In this study, the effect of microorganism, proteases, temperature, solid–liquid ratio, and time on nutritional properties of CB mixture feed (CMF) was investigated with the single-factor method and the response surface method to improve the nutritional quality and utilization of CBs. Fermentation with Pichia kudriavzevii, Lactobacillus plantarum, and neutral protease notably improved the nutritional properties of CMF under the fermentation conditions of 37°C, solid–liquid ratio (1.2:1 g/ml), and 72 h. After two-stage solid-stage fermentation, the crude protein (CP) and trichloroacetic acid-soluble protein (TCA-SP) in fermented CMF (FCMF) were increased (p < 0.05) by 14.28% and 25.53%, respectively. The in vitro digestibility of CP and total amino acids of FCMF were significantly improved to 78.53% and 74.94%, respectively. In addition, fermentation degraded fiber and provided more organic acids in the CMF. Multiple physicochemical analyses combined with high-throughput sequencing were performed to reveal the dynamic changes that occur during a two-stage solid-state fermentation process. Generally, Ascomycota became the predominant members of the community of the first-stage of fermentation, and after 36 h of anaerobic fermentation, Paenibacillus spp., Pantoea spp., and Lactobacillales were predominant. All of these processes increased the bacterial abundance and lactic acid content (p < 0.00). Our results suggest that two-stage solid-state fermentation with Pichia kudriavzevii, Lactobacillus plantarum, and protease can efficiently improve protein quality and nutrient utilization of CMF.
Significant Difference of Immune Cell Fractions and Their Correlations With Differential Expression Genes in Parkinson’s Disease
Authors: Huang Yilin , Liu Huisheng , Hu Jiaqi , Han Chongyin , Zhong Zhenggang , Luo Wei , Zhang Yuhu , Ling Fei
Published: August 2021

Parkinson’s disease (PD) is the second most neurodegenerative disease in the world. T cell infiltration in the central nervous system (CNS) has provided insights that the peripheral immune cells participate in the pathogenesis of PD. However, the association between the peripheral immune system and CNS remains to be elucidated. In this study, we analyzed incorporative substantia nigra (SN) expression data and blood expression data using the CIBERSORT to obtain the 22 immune cell fractions and then explored the molecular function to identify the potential key immune cell types and genes of PD. We observed that the proportions of naïve CD4 T cells, gamma delta T cells, resting natural killer (NK) cells, neutrophils in the blood, and regulatory T cells (Tregs) in the SN were significantly different between patients with PD and healthy controls (HCs). We identified p53-induced death domain protein 1 (PIDD1) as the hub gene of a PD-related module. The enrichment score of the neuron-specific gene set was significantly different between PD and HC, and genes in the neuron-related module were enriched in the biological process about mitochondria and synapses. These results suggested that the fractions of naïve CD4 T cells, gamma delta T cells, resting NK cells, and neutrophils may be used as a combined diagnostic marker in the blood, and Tregs in SN may be a potential therapeutic design target for PD.
Severe Brain Atrophy Predicts Poor Clinical Outcome After Endovascular Treatment of Acute Basilar Artery Occlusion: An Automated Volumetric Analysis of a Nationwide Registry
Authors: Liu Chang , Liu Hansheng , Wu Deping , Zhou Zhiming , Huang WenGuo , Wu Zhilin , Zi Wenjie , Yang Qingwu
Published: August 2021

Background:Brain atrophy globally reflects the effects of preexisting risk factors and biological aging on brain structures and normally predicts poor outcomes in anterior circulation stroke. However, comparing with these patients, acute basilar artery occlusion (ABAO) impairs infratentorial regions frequently and might benefit from brain atrophy due to the resulting residual space to reduce tissue compression and thus improve prognosis, which raises doubts that current understandings for prognostic roles of brain atrophy are also applicable for ABAO. Therefore, this study aims to evaluate brain atrophy automatically from CT images and investigates its impact on outcomes of ABAO following endovascular treatment (EVT).

Methods:A total of 231 ABAO who underwent EVT from the BASILAR registry were enrolled. Brain atrophy was quantified as the ratio of brain parenchymal volume to cerebrospinal fluid volume on baseline CT. The primary outcome was the modified Rankin Scale (mRS) score at 3 months.

Results:The frequency of favorable outcomes (90-day mRS ≤ 3) was significantly lower in the severe atrophy group (P= 0.014). Adjusted logistic models revealed that severe brain atrophy was significantly negatively associated with favorable outcome incidence (P= 0.006), with no relationship with either in-hospital or 90-day overall mortality (allP> 0.05). Adding a severe atrophy index into the baseline model obviously enhanced its discriminatory ability in predicting the outcome by obviously increasing areas under the receiver operating characteristic curve, net reclassification improvement algorithm, and integrated discrimination improvement algorithm values (allP< 0.05).

Conclusion:Severe brain atrophy did not improve in-hospital or overall mortality but impaired the long-term recovery after EVT. This objective and automated marker has the potential to be incorporated into decision-support methods for treating ABAO.