bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians
Authors: Ni Qi , Chen Xiang , Zhang Ping , Yang Lin , Lu Yulan , Xiao Feifan , Wu Bingbing , Wang Huijun , Zhou Wenhao , Dong Xinran
Published: March 2022

Background

Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but rarely reported in Chinese population. The prevalence and population-specific genetic spectrum of CF in China needs to be systematically estimated and compared with Caucasians.

Materials and methods

We reviewed 30,951 exome-sequencing samples, including 20,909 pediatric patient samples and 10,042 parent samples, from Chinese Children's Rare Disease Genetic Testing Clinical Collaboration System (CCGT). After the in-lab filtration process, 477 candidate variants of CFTR gene were left and 53 variants were manually curated as pathogenic/likely-pathogenic (P/LP). These P/LP variants were adopted to estimate CF prevalence in three methods: the carrier frequency method, the permutation-combinations method and the Bayesian framework method. Allele frequencies of the 477 CFTR variants were compared with non-Finland European (NFE) and East Asian (EAS) from gnomAD database. To investigate the haplotype structure difference of CFTR, another 2067 whole-genome-sequencing samples from CCGT and 195 NFE from 1000 genome project were analyzed by Shapeit4 software.

Result

With the 53 manually curated P/LP variants in CFTR gene, we excluded individuals identified or suspected with CF and their parents in our cohorts and estimated the Chinese CF prevalence is approximately 1/128,434. Only 21 (39.6%) of the 53 variants were included in Caucasian specific CF screening panels, resulting in significantly under-estimation of CF prevalence in our children cohort (1/143,171 vs. 1/1,387,395, P = 5e−24) and parent’s cohort (1/110,127 vs. 1/872,437, P = 7e−10). The allele frequencies of six pathogenic variants (G970D, D979A, M469V, G622D, L88X, 1898+5G->T) were significantly higher in our cohorts compared with gnomAD-NFE population (all P-value < 0.1). Haplotype analysis showed more haplotype diversity in Chinese compared to Caucasians. In addition, G970D and F508del were founder mutation of Chinese and Caucasians with two SNPs (rs213950-rs1042077) identified as related genotype in exon region.

Conclusions

Chinese population showed significantly different genetic spectrum pattern in CFTR gene compared with Caucasian population, and thus a Chinese-specific CF screening panel is needed.
Solving neurodegeneration: common mechanisms and strategies for new treatments
Authors: Wareham Lauren K. , Liddelow Shane A. , Temple Sally , Benowitz Larry I. , Di Polo Adriana , Wellington Cheryl , Goldberg Jeffrey L. , He Zhigang , Duan Xin , Bu Guojun , Davis Albert A. , Shekhar Karthik , Torre Anna La , Chan David C. , Canto-Soler M. Valeria , Flanagan John G. , Subramanian Preeti , Rossi Sharyn , Brunner Thomas , Bovenkamp Diane E. , Calkins David J.
Published: March 2022

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address these mechanisms and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus Foundation, and the Melza M. and Frank Theodore Barr Foundation collaborated to bring together key opinion leaders and experts in the field of neurodegenerative disease for a virtual meeting titled “Solving Neurodegeneration”. This “think-tank” style meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the world’s leading cause of irreversible blindness and the common interest of the three hosting foundations. Glaucoma, which causes vision loss through degeneration of the optic nerve, likely shares early cellular and molecular events with other neurodegenerative diseases of the central nervous system. Here we discuss major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions. We summarize important discussion points with emphasis on the research areas that are most innovative and promising in the treatment of neurodegeneration yet require further development. The research that is highlighted provides unique opportunities for collaboration that will lead to efforts in preventing neurodegeneration and ultimately vision loss.
Analyses of Kaposi Sarcoma trends among adults establishing initial outpatient HIV care in Nigeria: 2006–2017
Authors: Akanbi Maxwell O. , Bilaver Lucy A. , Achenbach Chad , Hirschhorn Lisa R. , Rivera Adovich S. , Silas Olugbenga A. , Agaba Patricia A. , Agbaji Oche , Shehu Nathan Y. , Sagay Solomon A. , Hou Lifang , Murphy Robert L.
Published: March 2022

Background

The incidence of Human Immunodeficiency Virus (HIV)-associated Kaposi Sarcoma (KS) in the pre-antiretroviral therapy (ART) population remains high in several countries in sub-Saharan Africa. We examined trends of KS prevalence in adults, establishing initial outpatient HIV care from 2006 to 2017 in Nigeria.

Methods

We analyzed data of 16,431 adults (age ≥ 18 years) enrolled for HIV care from January 1, 2006, to December 31, 2017, in a large clinic in Jos, Nigeria. KS at enrollment was defined as KS recorded in the electronic health record within 30 days of clinic enrollment. Time trends were compared among four periods: 2006–2008, 2009–2011, 2012–2014, and 2015–2017 using logistic regression models. Annual trends were analyzed using join point regression and restricted splines.

Results

The study population had a mean age 35.1 (standard deviation, SD 9.5) years, and were 65.7% female (n = 10,788). The mean CD4 cell count was 220 (95% CI 117–223). The overall KS prevalence at entry was 0.59% (95% CI 0.48–0.72). Compared to 2006–2008, KS prevalence was significantly higher in 2009–2011 (adjusted odds ratio 5.07 (95% CI 3.12–8.24), p < 0.001), but remained unchanged in subsequent periods. Male sex and low CD4 T-cell count independently increased odds for KS.

Conclusions

Despite ART expansion, KS at enrollment showed no significant decline. The low CD4 cell count, across all periods, indicates delay in enrollment for HIV care, which increases KS risk. Interventions aimed at early HIV diagnosis and linkage to ART is critical to KS risk reduction in this population.
New insights regarding origin of monosomy occurrence in early developing embryos as demonstrated in preimplantation genetic testing
Authors: Samara N. , Peleg S. , Frumkin T. , Gold V. , Amir H. , Haikin Herzberger Einat , Reches A. , Kalma Y. , Ben Yosef Dalit , Azem F. , Malcov M.
Published: March 2022

Introduction

Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results.

Methods

For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used.

Results

We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases.

Conclusion

In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos.
mSRFR: a machine learning model using microalgal signature features for ncRNA classification
Authors: Anuntakarun Songtham , Lertampaiporn Supatcha , Laomettachit Teeraphan , Wattanapornprom Warin , Ruengjitchatchawalya Marasri
Published: March 2022

This work presents mSRFR (microalgae SMOTE Random Forest Relief model), a classification tool for noncoding RNAs (ncRNAs) in microalgae, including green algae, diatoms, golden algae, and cyanobacteria. First, the SMOTE technique was applied to address the challenge of imbalanced data due to the different numbers of microalgae ncRNAs from different species in the EBI RNA-central database. Then the top 20 significant features from a total of 106 features, including sequence-based, secondary structure, base-pair, and triplet sequence-structure features, were selected using the Relief feature selection method. Next, ten-fold cross-validation was applied to choose a classifier algorithm with the highest performance among Support Vector Machine, Random Forest, Decision Tree, Naïve Bayes, K-nearest Neighbor, and Neural Network, based on the receiver operating characteristic (ROC) area. The results showed that the Random Forest classifier achieved the highest ROC area of 0.992. Then, the Random Forest algorithm was selected and compared with other tools, including RNAcon, CPC, CPC2, CNCI, and CPPred. Our model achieved a high accuracy of about 97% and a low false-positive rate of about 2% in predicting the test dataset of microalgae. Furthermore, the top features from Relief revealed that the %GA dinucleotide is a signature feature of microalgal ncRNAs when compared to Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens.
Personalization of renal replacement therapy initiation: a secondary analysis of the AKIKI and IDEAL-ICU trials
Authors: Grolleau François , Porcher Raphaël , Barbar Saber , Hajage David , Bourredjem Abderrahmane , Quenot Jean-Pierre , Dreyfuss Didier , Gaudry Stéphane
Published: March 2022

Background

Trials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy.

Methods

We used data from the AKIKI, and IDEAL-ICU randomized controlled trials to develop a multivariable logistic regression model for renal replacement therapy initiation within 48 h after allocation to a delayed strategy. We then used an interaction with spline terms in a Cox model to estimate treatment effects across the predicted risks of RRT initiation.

Results

We analyzed data from 1107 patients (619 and 488 in the AKIKI and IDEAL-ICU trial respectively). In the pooled sample, we found evidence for heterogeneous treatment effects (P = 0.023). Patients at an intermediate-high risk of renal replacement therapy initiation within 48 h may have benefited from an early strategy (absolute risk difference, − 14%; 95% confidence interval, − 27% to − 1%). For other patients, we found no evidence of benefit from an early strategy of renal replacement therapy initiation but a trend for harm (absolute risk difference, 8%; 95% confidence interval, − 5% to 21% in patients at intermediate-low risk).

Conclusions

We have identified a clinically sound heterogeneity of treatment effect of an early vs a delayed strategy of renal replacement therapy initiation that may reflect varying degrees of kidney demand-capacity mismatch.
Effectiveness of a mobile app-based educational intervention to treat internet gaming disorder among Iranian adolescents: study protocol for a randomized controlled trial
Authors: Pakpour Amir H. , Fazeli Sara , Zeidi Isa Mohammadi , Alimoradi Zainab , Georgsson Mattias , Brostrom Anders , Potenza Marc N.
Published: March 2022

Background

The use of video games, a hobby for many teenagers in their leisure time, has brought with it a new potential for concerns. Internet gaming disorder (IGD) is a mental condition classified as a disorder due to addictive behaviors. It may include use of video games, both online and offline. Consequences of IGD may include introversion, social anxiety, mood swings, loneliness, sleep problems, behavioral problems, depression, low self-esteem, and increased violence. In order to design an app-based intervention for adolescents, a transtheoretical model (TTM) has been used. This widely used model in the field of behavioral change is also practical for health education programs. In addition, cognitive-behavioral therapy (CBT) has been used to make people more aware of their behaviors, feelings and thoughts and how to achieve behavioral change. The present study seeks to determine the effectiveness of this app-based intervention in in the treatment of IGD among adolescents.

Method

In this single-blinded, randomized, controlled trial, 206 high-school adolescents aged 13 to 18 years in Qazvin city will be recruited. Eligible adolescents will be randomly assigned into intervention and control groups. Eight consecutive sessions delivered over 2 months and based on the TTM and CBT will be delivered through the `app (named HAPPYTEEN) to the intervention group. The control group will receive a sleep hygiene intervention (8 consecutive sessions for 2 months) via the app. Data collection tools include the Internet Gaming Disorder Scale, Insomnia Severity Index, Depression, Anxiety, and Stress Scales, Stages of Change Questionnaire, Decision Balance, and Self-Efficacy. The study measures will be completed at baseline, post intervention, and 1 month and 3 months after the intervention.

Discussion

The results of this intervention could be used as adjunct therapy for adolescents with IGD.

Trial registration

Clinical Trial Registration Center of Iran (IRCT) IRCT20181226042140N1. Registered on June 9, 2020.
Chinese herbal formula Tongxie Yaofang for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized, multiple-blind, placebo-controlled trial
Authors: Liang Shi-Bing , Han Mei , Cheng Hong-Jie , Zhang Qiao-Yan , Zhang Nai-Wei , Jia Bo-Yi , Robinson Nicola , Liu Jian-Ping
Published: March 2022

Introduction

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a bowel disease with a high incidence. It significantly reduces the quality of life of patients and affects the patient's daily activities and mental health. No specific therapeutic medications for IBS-D have been found. Published clinical trials suggest that Chinese herbal formula Tongxie Yaofang (TXYF) for IBS-D may be effective. However, high-quality clinical evidence supporting its use in IBS-D is still lacking. This trial aims to evaluate the therapeutic effects and safety of TXYF for IBS-D in adults.

Methods/design

A randomized, multiple-blind, placebo-controlled trial will be conducted. It will consist of an 8-week intervention followed by a 3-month follow-up period.

The target sample size is 96 IBS-D patients aged 18 to 65 years. The eligible participants will be randomly allocated to either TXYF or placebo group in a ratio of 1:1. Participants in the experimental group will take TXYF granules, while participants in the control group will be given TXYF placebo granules. The primary outcome will be the degree of IBS symptom severity measured using the scale of IBS symptom severity score. The secondary outcomes include: (a) stool frequency, and (b) stool consistency measured using the Bristol stool scale, (c) quality of life measured using the scale of IBS-quality of life, (d) anxiety measured using the self-rating anxiety scale, (e) depression measured by the self-rating depression scale, and (f) the safety of using TXYF and placebo. Safety monitoring and assessment will be undertaken throughout treatment.

Discussion

Chinese herbal formula TXYF consists of four Chinese herbs: Atractylodes macrocephala Koidz., Paeonia lactiflora Pall., Citrus × aurantium L., and Radix saposhnikoviae. It has been used for diarrhea for hundreds of years and may have a potential benefit in treating adults with IBS-D, but due to lack of high-quality evidence, we designed a randomized, multiple-blind, placebo-controlled trial to evaluate its therapeutic effects and safety. This trial will provide important data to guide the clinical practice of TXYF for the treatment of IBS-D in adults.

Trial registration

ISRCTN registry ISRCTN12453166. Registered on 23 March 2021.
Experimental and theoretical study for removal of trimethoprim from wastewater using organically modified silica with pyrazole-3-carbaldehyde bridged to copper ions
Authors: Jodeh Shehdeh , Jaber Ahlam , Hanbali Ghadir , Massad Younes , Safi Zaki S. , Radi Smaail , Mehmeti Valbonë , Berisha Avni , Tighadouini Said , Dagdag Omar
Published: March 2022

Background

Human and veterinary antibiotics are typically discharged as parent chemicals in urine or feces and are known to be released into the environment via wastewater treatment plants (WWTPs). Several research investigations have recently been conducted on the removal and bioremediation of pharmaceutical and personal care products (PPCPs) disposed of in wastewater.

Results

SiNP-Cu, a chelating matrix, was produced by delaying and slowing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel from functionalized with 3-aminopropyltrimethoxysilane. The prepared sorbent material was characterized using several techniques including BET surface area, FT-IR spectroscopy, Scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen adsorption–desorption isotherm. The pseudo-second-order model provided the best correlation due to the big match between the experimental and theoretical of different adsorption coefficients. The Langmuir and Freundlich adsorption models were used and the study showed a better match with the Freundlich model with a capacity of removal reached up to 420 mg g−1. The removal capacity was dependent on pH and increased by increasing pH. The removal percentage reached 91;5% at pH = 8. The adsorbent demonstrated a high percentage removal of TMP, reaching more than 94% when increased pH. The sample was simply regenerated by soaking it for a few minutes in 1 N HCl and drying it. The sorbent was repeated five times with no discernible decrease in removal capacity. The thermodynamic study also showed endothermic, increasing randomness and not spontaneous. The free energy was 2.71 kJ/mol at 320 K. The findings of the DFT B3LYP/6–31 + g (d, p) local reactivity descriptors revealed that nitrogen atoms and π-electrons of the benzene and pyrimidine rings in the TMP are responsible for the adsorption process with the SiNP surface. The negative values of the adsorption energies obtained by molecular dynamic simulation indicated the spontaneity of the adsorption process.

Conclusion

The global reactivity indices prove that TMP is stable and it can be removed from wastewater using SiNP surface. The results of the local reactivity indices concluded that the active centers for the adsorption process are the nitrogen atoms and the π-electrons of the pyrimidine and benzene rings. Furthermore, the positive value of the maximum charge transfer number (ΔN) proves that TMP has a great tendency to donate electrons to SiNP surface during the process of adsorption.
Development of two species of the Trypanosoma theileri complex in tabanids
Authors: Kostygov Alexei Yu. , Frolov Alexander O. , Malysheva Marina N. , Ganyukova Anna I. , Drachko Daria , Yurchenko Vyacheslav , Agasoi Vera V.
Published: March 2022

Background

Trypanosoma theileri species complex includes parasites of Bovidae (cattle, sheep, goat, etc.) and Cervidae (deer) transmitted mainly by Tabanidae (horse flies and deerflies) and keds (Hippoboscidae). While morphological discrimination of species is challenging, two big clades, TthI and TthII, each containing parasites isolated from bovids and cervids, have been identified phylogenetically. To date, the development in the vector has been studied in detail only for the ked-transmitted sheep parasite T. melophagium (TthII), while the fate of trypanosomes in tabanids was described only briefly by light microscopy.

Methods

We collected infected tabanids of various species and identified trypanosomes by molecular phylogenetic analysis. The morphology and development of trypanosomes was studied using the combination of statistical analyses as well as light and electron microscopy.

Results

Two trypanosome species belonging to both TthI and TthII clades of the T. theileri complex were identified. The phylogenetic position of these two trypanosomes suggests that they parasitize deer. Both species were indiscernible by morphology in the vector and showed the same development in its intestine. In contrast to the previously described development of T. melophagium, both trypanosomes of tabanids only transiently infected midgut and settled mainly in the ileum, while pylorus and rectum were neglected. Meanwhile, the flagellates developing in the tabanid ileum (pyriform epimastigotes and metacyclic trypomastigotes) showed similarities to the corresponding stages in T. melophagium by morphology, mode of attachment to the host cuticle and formation of the fibrillar matrix surrounding the mass of developing parasites. In addition, for the first time to our knowledge we documented extraintestinal stages in these trypanosomes, located in the space between the epithelium and circular muscles.

Conclusions

The development of different species of flagellates of the T. theileri complex in their insect vectors shows many similarities, which can be explained not only by their common origin, but also the same transmission mode, i.e. contamination of the oral mucosa with the gut content released after squashing the insect either by tongue or teeth. The observed differences (concerning primarily the distribution of developmental stages in the intestine) are associated rather with the identity of vectors than the phylogenetic position of parasites.

Graphical Abstract
Changing serotypes of hand, foot and mouth disease in Shanghai, 2017–2019
Authors: Hu Linjie , Maimaiti Hairenguli , Zhou Lu , Gao Jie , Lu Yihan
Published: March 2022

Background

Hand, foot, and mouth disease (HFMD) is a common reportable infectious disease that is highly contagious among children in China. This study aimed to characterize the epidemics of HFMD and the serotypes of enterovirus (EV) after the introduction of EV-A71 vaccines in Shanghai, a city in Eastern China.

Results

A total of 2271 HFMD cases were recruited in this study from May 2017 through October 2020. Among these cases, a male-to-female ratio of 1.6:1 was observed, and the cases were mainly in 1–4 years old (63.1%). Children of all ages had a relatively similar time span between the onset of HFMD and the initial medical visit (P = 0.5192). The cases were reported year-round with peaks in the summer (2018 and 2019) and fall (2017), which was consistent with previous epidemics of the reported HFMD cases in the Shanghai municipality. Among the specimens that tested positive for EV (n = 1855), CV-A6 was predominantly detected (71.1%), followed by CV-A16 (14.2%) and EV-A71 (7.0%). Notably, the number of HFMD cases infected with EV-A71 increased in 2019. Furthermore, 9.2% of the cases had comorbidities, mostly convulsion, bronchopneumonia, and pneumonia; however, they were not correlated with the EV serotypes. In addition, 31.2% (709/2271) of the cases were vaccinated with EV-A71 vaccines. The time span differed significantly between the time of vaccination and the onset of the disease across the groups based on whether the onset was before or after vaccination (P < 0.001).

Conclusions

CV-A6 is the predominant EV serotype in the epidemic of HFMD in Shanghai; in addition, CV-A16 and EV-A71 may be moderately prevalent. The changing trends in the presence of EV serotypes contributes to the periodicity of the HFMD epidemic. In addition, the minority of HFMD cases may have comorbidities, regardless of the EV serotype. The use of the EV-A71 vaccine has affected the HFMD epidemic. And serotype-specific protection by the EV-A71 vaccine may promote vaccination in children infected with EV-A71 compared to those infected with non-EV-A71 serotypes, which would further change the epidemic scenario of HFMD.
The impact of COVID-19 restrictions on Australians' frequency and duration of participation in different types of sport and physical activity
Authors: Eime Rochelle , Harvey Jack , Charity Melanie , Pankowiak Aurelie , Westerbeek Hans
Published: March 2022

Background

Sports management and public health physical activity stakeholders need to understand changing patterns of participation to inform the development of sport and physical activity opportunities and strategies. This study investigated changes in the frequency and duration of participation in sport and physical activity in Australia from pre-COVID-19 to during-COVID-19, broken down by the specific type of activity and by gender, age and region.

Methods

During the first pandemic restrictions and lockdowns in Australia in May–June 2020, 6140 survey respondents provided information about the types, frequency and duration of the sport and physical activity they participated in prior to and during COVID-19 restrictions. Differences between mean values were analyzed.

Results

The greatest decline in participation during COVID-19 was in team sports, and the decline was greater for men than for women.

Conclusion

How will sport respond to getting these men back in the game, and women back from home-based yoga and Pilates?
Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes
Authors: Xue Jing , Gao Jieqing , Gu Yulin , Wang Aihong , Yu Songyan , Li Bing , Yin Yaqi , Wang Jie , Su Wanlu , Zhang Haixia , Ren Weizheng , Gu Weijun , Lv Zhaohui , Mu Yiming , Cheng Yu
Published: March 2022

Background

Previous research has demonstrated that the spleen plays an important role in mesenchymal stem cell (MSC)-mediated alleviation of acute inflammation, as MSC infusion increases the spleen-derived anti-inflammatory cytokine interleukin 10 (IL-10) levels. However, studies on splenic involvement in MSC-induced protection against chronic inflammatory diseases are limited. Obesity is characterized by chronic low-grade inflammation, a key driver of insulin resistance. This study aims to evaluate the effects of MSCs on obesity-related insulin resistance and explore the underlying mechanism, particularly regarding splenic involvement.

Methods

We induced obesity in mice by feeding them high-fat diets for 20 weeks. Human umbilical cord-derived MSCs (UC-MSCs) were systemically infused into the obese mice once per week for 6 weeks. Systemic glucose metabolic homeostasis and insulin sensitivity in epididymal adipose tissue (EAT) were evaluated. Then, we conducted in vivo blockade of IL-10 during UC-MSC infusion by intraperitoneally administrating an IL-10-neutralizing antibody twice per week. We also investigated the therapeutic effects of UC-MSCs on obese mice after removal of the spleen by splenectomy.

Results

UC-MSC infusions improved systemic metabolic homeostasis and alleviated insulin resistance in EAT but elicited no change in weight. Despite rare engraftment of UC-MSCs in EAT, UC-MSC infusions attenuated insulin resistance in EAT by polarizing macrophages into the M2 phenotype, coupled with elevated serum IL-10 levels. In vivo blockade of IL-10 blunted the effects of UC-MSCs on obese mice. Furthermore, UC-MSCs overwhelmingly homed to the spleen, and the ability of UC-MSCs to elevate serum IL-10 levels and alleviate insulin resistance was impaired in the absence of the spleen. Further in vivo and in vitro studies revealed that UC-MSCs promoted the capacity of regulatory T cells (Treg cells) to produce IL-10 in the spleen.

Conclusions

Our results demonstrated that UC-MSCs elevated serum IL-10 levels and subsequently promoted macrophage polarization, leading to alleviation of insulin resistance in EAT. The underlying mechanism was that UC-MSCs improved the capacity of Treg cells to produce IL-10 in the spleen. Our findings indicated that the spleen played a critical role in amplifying MSC-mediated immunomodulatory effects, which may contribute to maximizing MSC efficacy in clinical applications in the future.
Profiling and functional analysis of differentially expressed circular RNAs identified in foot-and-mouth disease virus infected PK-15 cells
Authors: Yang JinKe , Yang Bo , Wang Yong , Zhang Ting , Hao Yu , Cui HuiMei , Zhao DengShuai , Yuan XingGuo , Chen XueHui , Shen ChaoChao , Yan WenQian , Zheng HaiXue , Zhang KeShan , Liu Xiangtao
Published: March 2022

Circular RNAs (circRNAs) are a new type of endogenous noncoding RNA that exhibit a variety of biological functions. However, it is not clear whether they are involved in foot-and-mouth disease virus (FMDV) infection and host response. In this study, we established circRNA expression profiles in FMDV-infected PK-15 cells using RNA-seq (RNA-sequencing) technology analysis. The biological function of the differentially expressed circRNAs was determined by protein interaction network, Gene Ontology (GO), and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment. We found 1100 differentially expressed circRNAs (675 downregulated and 425 upregulated) which were involved in various biological processes such as protein ubiquitination modification, cell cycle regulation, RNA transport, and autophagy. We also found that circRNAs identified after FMDV infection may be involved in the host cell immune response. RNA-Seq results were validated by circRNAs qRT-PCR. In this study, we analyzed for the first time circRNAs expression profile and the biological function of these genes after FMDV infection of host cells. The results provide new insights into the interactions between FMDV and host cells.
Polysaccharides from the leaves of Polygonatum sibiricum Red. regulate the gut microbiota and affect the production of short-chain fatty acids in mice
Authors: Luo Yu , Fang Qi , Lai Yong , Lei Hui , Zhang Dan , Niu Hong , Wang Rui , Song Can
Published: March 2022

Polysaccharides from the rhizome of Polygonatum sibiricum display a variety of biological activities, including the regulation of intestinal microbiota, but the polysaccharides from the leaves of P. sibiricum have not been studied extensively. Here, we extracted crude polysaccharides from the leaves of P. sibiricum and further separated and purified them to study the effects of P. sibiricum polysaccharides (PsPs) on intestinal microbes and short-chain fatty acids (SCFAs). The PsPs had a total sugar content of 97.48% and a monosaccharide composition comprising mannose, rhamnose, galacturonic acid, glucose, xylose, and arabinose, with molar ratios of 6.6:15.4:4.5:8.8:40.7:24, respectively. The effects of PsPs on intestinal microflora in mice were also studied, with 16S sequencing results showing an increase in the relative abundance of Firmicutes and a decrease in Bacteroidetes at the phylum level. The abundance of Lactobacillus increased, while those of Lachnospiraceae and Bacteroides reduced (at the genus level) by PsPs treatment. The composition of microbes changed. Levels of SCFAs in the PsPs group were significantly increased compared with control mice, including acetic acid, propionic acid, and butyric acid. These results suggest that PsPs can act as prebiotics, regulating the intestinal tract probiotics.
Flow-based method for biofilm microbiota enrichment and exploration of metagenomes
Authors: Hageskal Gunhild , Heggeset Tonje Marita Bjerkan , Nguyen Giang-Son , Haugen Tone , Jønsson Malene , Egas Conceição , Hidalgo Aurelio , Wentzel Alexander , Lewin Anna Sofia
Published: March 2022

Most bacteria live in biofilms in their natural habitat rather than the planktonic cell stage that dominates during traditional laboratory cultivation and enrichment schemes. The present study describes the establishment of a flow-based enrichment method based on multispecies biofilm communities for directing biofilm functionality using an environmental inoculum. By controlling flow conditions and physio-chemical properties, the set-up aims to simulate natural conditions ex situ for biofilm formation. The functionality of the method was demonstrated by enrichment of biofilm microbiomes using consortia from a warm compost pile and industrial waste materials as growth substrate, and further exploring the metagenomes by biotechnological tools. The 16S rRNA gene sequencing results revealed a difference in consortium composition and especially in genus abundance, in flow experiments compared to traditional liquid-shake experiments after enrichment, indicating good biofilm development and increased abundance of biofilm-forming taxa. The shotgun sequence mining demonstrated that different enzymes classes can be targeted by enriching biofilms on different substrates such as oat husk, pine saw dust, and lignin. The flow-based biofilm method is effective in reducing bacterial consortia complexity and in selecting biofilm-forming bacteria, and it is possible to enrich the biofilm community in various directions based on the choice of sample material, environmental conditions, and nutritional preferences, targeting enzymes or enzyme classes of industrial interest.
High performance and resource efficient FFT processor based on CORDIC algorithm
Authors: Zhao Yupu , Lv Hong , Li Jun , Zhu Lulu
Published: March 2022

Fast Fourier Transform is widely used in communication and signal processing. I propose an improved multipath delay commutator pipelining architecture based on the radix-2 time decimation algorithm. By optimizing the intermediate data processing process and the first stage of pipelining, the architecture improves the system's computing speed and reduces the use of registers. I propose a multiplication scheme based on CORDIC and binary decomposition coding to realize complex number multiplication and constant multiplication and to eliminate the use of a multiplier. Experimental results suggest that proposed implementation has less latency and hardware utilization as compared to recently proposed implementations.
Rare earth element geochemistry in soils along arid and semiarid grasslands in northern China
Authors: Cao Yi-Wen , Liu Xiao-Ming , Wang Chao , Bai Edith , Wu Nanping
Published: March 2022

Background

Rare earth elements (REE) are a group of trace elements that behave geochemically coherently. REE fractionation patterns normalized to reference materials provide a powerful tool for documenting pedogenesis. In-soil processes are particularly difficult to illustrate with respect to contemporary and past climate conditions. In this study, we characterize the rare earth element (REE) contents in bulk soils and respective geochemical fractions (e.g., exchangeable, carbonate-bound, reducible, and oxidizable fractions) and to decipher the relationships between REE geochemistry components and climatic factors across a large-scale northern China transect (NCT).

Results

Across the NCT, bulk REE concentrations ranged from 55.2 to 241.1 μg g−1 with a main portion in the residual fraction (49–79%), followed by oxidizable fraction (2–40%), reducible fraction (3–22%), carbonate-bound fraction (0.1–16%), and negligible exchangeable fraction. The REE contents of geochemical components (carbonate-bound, reducible, and oxidizable) in topsoils correlated to climate factors (mean annual precipitation, mean annual temperature, potential evaporation, and aridity index (AI)). The normalized abundances to the upper continental crust (UCC) composition show that the middle REE was generally enriched than the light REE and heavy REE in topsoils along the transect. The overall UCC-normalized bulk REE patterns in topsoils and subsoils were similar, characterized by weak negative Ce anomalies and positive Eu anomalies.

Conclusions

Our data in topsoils and depth profiles collectively suggest that cycling of REE was primarily regulated by abiotic processes in area with AI < 0.2, while the biological effect on REE circulation in soil played a more effective role in area with AI > 0.3. The similar UCC normalized patterns in topsoils suggest that the REE was originated from a common source with limited influences from other sources (e.g., atmospheric dusts and anthropogenic contributions). Our results to some extent provide evidence for climatic influence REE distribution patterns both in topsoils and subsoils across the continental-scale transect. Our investigation gives insights into future studies on vertical REE mobility and its associated biogeochemical pathways.
Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system
Authors: Lopes Douglas M. , Llewellyn Sophie K. , Harrison Ian F.
Published: March 2022

Many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are characterised by the accumulation of misfolded protein deposits in the brain, leading to a progressive destabilisation of the neuronal network and neuronal death. Among the proteins that can abnormally accumulate are tau and α-synuclein, which can propagate in a prion-like manner and which upon aggregation, represent the most common intracellular proteinaceous lesions associated with neurodegeneration. For years it was thought that these intracellular proteins and their accumulation had no immediate relationship with extracellular homeostasis pathways such as the glymphatic clearance system; however, mounting evidence has now suggested that this is not the case. The involvement of the glymphatic system in neurodegenerative disease is yet to be fully defined; however, it is becoming increasingly clear that this pathway contributes to parenchymal solute clearance. Importantly, recent data show that proteins prone to intracellular accumulation are subject to glymphatic clearance, suggesting that this system plays a key role in many neurological disorders. In this review, we provide a background on the biology of tau and α-synuclein and discuss the latest findings on the cell-to-cell propagation mechanisms of these proteins. Importantly, we discuss recent data demonstrating that manipulation of the glymphatic system may have the potential to alleviate and reduce pathogenic accumulation of propagation-prone intracellular cytotoxic proteins. Furthermore, we will allude to the latest potential therapeutic opportunities targeting the glymphatic system that might have an impact as disease modifiers in neurodegenerative diseases.
Casein phosphopeptide amorphous calcium phosphate and universal adhesive resin as a complementary approach for management of white spot lesions: an in-vitro study
Authors: Aref Neven S. , Alrasheed Maha Kh.
Published: March 2022

Background

White spot lesion (WSL) is the most common consequence during and after orthodontic treatment. This study was conducted to investigate the ability of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) coupled with universal adhesive resin to treat white spot lesions.

Material and methods

Forty-five extracted premolars were sectioned to create 90 specimens. Seventy-five specimens were demineralized to generate artificially created WSLs. Different strategies have been applied for the management of the artificially created WSLs. Six experimental groups were employed: Group I: sound enamel (control), Group II: demineralized enamel (artificially-created WSLs), Group III: ICON resin-treated WSLs, Group IV: CPP-ACP-treated WSLs, Group V: universal adhesive resin-treated WSLs, and Group VI: CPP-ACP followed by universal adhesive resin-treated WSLs. Assessment of color stability using a spectrophotometer, surface microhardness using a Vickers tester, and surface roughness using a profilometer was done. The surface topography of representative specimens from each experimental group was inspected using a scanning electron microscope. Collected data were analyzed using one-way ANOVA followed by Tukey’s post hoc test atp ≤ 0.05.

Results

White spot lesions treated with CPP-ACP and subsequently coated with universal adhesive resin (Group VI) exhibited a significantly lower ΔEthan both CPP-ACP (Group IV) and universal adhesive resin-treated (Group V) groups (p ≤ 0.05), but it was not significantly different from the ICON resin-treated group (Group III). For surface microhardness, WSLs treated with CPP-ACP and consequently coated with universal adhesive resin (Group VI) recorded the highest mean that was significantly different from both ICON resin (Group III) and universal adhesive resin-treated (Group V) groups (p ≤ 0.05). All the tested strategies (ICON resin, CPP-ACP, universal adhesive resin, and CPP-ACP followed by universal adhesive resin) significantly lowered the surface roughness of the WSLs (p ≤ 0.05), while no significant difference was detected among them.

Conclusions

Combining a considerable caries remineralizing program using CPP-ACP with subsequent universal adhesive resin infiltration could be a promising approach to manage WSLs efficiently through increasing surface microhardness and restoring esthetic while developing a smoother surface.
Petrophysical characterization of the Los Humeros geothermal field (Mexico): from outcrop to parametrization of a 3D geological model
Authors: Weydt Leandra M. , Bär Kristian , Sass Ingo
Published: March 2022

The Los Humeros Volcanic Complex has been characterized as a suitable target for developing a super-hot geothermal system (> 350 °C). For the interpretation of geophysical data, the development and parametrization of numerical geological models, an extensive outcrop analogue study was performed to characterize all relevant key units from the basement to the cap rock regarding their petrophysical properties, mineralogy, and geochemistry. In total, 226 samples were collected and analyzed for petrophysical and thermophysical properties as well as sonic wave velocities and magnetic susceptibility. An extensive rock property database was created and more than 20 lithostratigraphic units and subunits with distinct properties were defined. Thereby, the basement rocks feature low matrix porosities (< 5%) and permeabilities (< 10–17 m2), but high thermal conductivities (2–5 W m−1 K−1) and diffusivities (≤ 4·10–6 m2s−1) as well as high sonic wave velocities (≥ 5800 m s−1). Basaltic to dacitic lavas feature matrix porosities and permeabilities in the range of < 2–30% and 10–18–10–14 m2, respectively, as well as intermediate to low thermal properties and sonic wave velocities. The pyroclastic rocks show the highest variability with respect to bulk density, matrix porosity (~ 4– > 60%) and permeability (10–18–10–13 m2), but feature overall very low thermal conductivities (< 0.5 W m−1 K−1) and sonic wave velocities (~ 1500–2400 m s−1). Specific heat capacity shows comparatively small variations throughout the dataset (~ 700–880 J kg−1 K−1), while magnetic susceptibility varies over more than four orders of magnitude showing formation-related trends (10–6–10–1 SI). By applying empirical correction functions, this study provides a full physiochemical characterization of the Los Humeros geothermal field and improves the understanding of the hydraulic and thermomechanical behavior of target formations in super-hot geothermal systems related to volcanic settings, the relationships between different rock properties, and their probability, whose understanding is crucial for the parametrization of 3D geological models.
University students’ satisfaction and future outlook towards forced remote learning during a global pandemic
Authors: Abdullah Siti Intan Nurdiana Wong , Arokiyasamy Klara , Goh Sock Leng , Culas Andrea Joveena , Manaf Nor Masheera Abdul
Published: March 2022

Technology has enabled the higher education ecosystem to tailor to the students who have diverse needs and to engage with them remotely, especially when face-to-face interaction is not possible. This research contributes knowledge in forced remote learning during the unprecedented global pandemic situation of Covid-19. Using a cross-sectional quantitative method, a total of 480 respondents among undergraduate students from five private universities in Malaysia participated in this study. The data was analysed using structural equation modelling and results indicated that online feedback, online future relevance, online interaction, online teaching effectiveness, and personal well-being were statistically significant in influencing students’ satisfaction. Moreover, online learning satisfaction directly predicted 68.3% of the students’ continuous usage intention while their usage intention was heightened with higher levels of proficiency in online learning. Students’ satisfaction was found to be a significant mediator between all the factors towards usage intention except online assessment, online support, and personal well-being. This study provides the higher education institutions with insights to continuously improve their online delivery strategies and bridge the gap with their students during the pandemic crisis.