bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliable and Scalable Identification and Prioritization of Putative Cellulolytic Anaerobes With Large Genome Data
Authors: Wang Yubo , Li Liguan , Xia Yu , Zhang Tong
Published: March 2022

In the era of high-throughput sequencing, genetic information that is inherently whispering hints of the microbes’ functional niches is becoming easily accessible; however, properly identifying and characterizing these genetic hints to infer the microbes’ functional niches remains a challenge. Regarding genome-centric interpretation on the specific functional niche of cellulose hydrolysis for anaerobes, often encountered in practice is a lack of confidence in predicting the anaerobes’ real cellulolytic competency based solely on abundances of the varying carbohydrate-active enzyme modules annotated or on their taxonomy affiliation. Recognition of the synergy machineries that include but not limited to the cellulosome gene clusters is equally important as the annotation of individual carbohydrate-active modules or genes. In the interpretation of complete genomes of 2,768 microbe strains whose phenotypes have been well documented, with the incorporation of an automatic recognition of synergy among the carbohydrate active elements annotated, an explicit genotype–phenotype correlation was evidenced to be feasible for cellulolytic anaerobes, and a bioinformatic pipeline was developed accordingly. This genome-centric pipeline would categorize putative cellulolytic anaerobes into six genotype groups based on differential cellulose-hydrolyzing capacity and varying synergy mechanisms. Suggested in this genotype–phenotype correlation analysis was a finer categorization of the cellulosome gene clusters: although cellulosome complexes, by their nature, could enable the assembly of a number of carbohydrate-active units, they do not certainly guarantee the formation of the cellulose–enzyme–microbe complex or the cellulose-hydrolyzing activity of the corresponding anaerobe strains, for example, the well-known Clostridium acetobutylicum strains. Also, recognized in this genotype-phenotype correlation analysis was the genetic foundation of a previously unrecognized machinery that may mediate the microbe–cellulose adhesion, to be specific, enzymes encoded by genes harboring both the surface layer homology and cellulose-binding CBM modules. Applicability of this pipeline on scalable annotation of large genome datasets was further tested with the annotation of 7,902 reference genomes downloaded from NCBI, from which 14 genomes of putative paradigm cellulose-hydrolyzing anaerobes were identified. We believe the pipeline developed in this study would be a good add as a bioinformatic tool for genome-centric interpretation of uncultivated anaerobes, specifically on their functional niche of cellulose hydrolysis.
Magnetic Nanoparticle-Mediated Orientation of Collagen Hydrogels for Engineering of Tendon-Mimetic Constructs
Authors: Wright Abigail L. , Righelli Lucrezia , Broomhall T. J. , Lamont Hannah C. , El Haj Alicia J.
Published: March 2022

Despite the high incidence of tendon injuries worldwide, an optimal treatment strategy has yet to be defined. A key challenge for tendon repair is the alignment of the repaired matrix into orientations which provide maximal mechanical strength. Using oriented implants for tissue growth combined with either exogenous or endogenous stem cells may provide a solution. Previous research has shown how oriented fiber-like structures within 3D scaffolds can provide a framework for organized extracellular matrix deposition. In this article, we present our data on the remote magnetic alignment of collagen hydrogels which facilitates long-term collagen orientation. Magnetic nanoparticles (MNPs) at varying concentrations can be contained within collagen hydrogels. Our data show how, in response to the magnetic field lines, MNPs align and form string-like structures orientating at 90 degrees from the applied magnetic field from our device. This can be visualized by light and fluorescence microscopy, and it persists for 21 days post-application of the magnetic field. Confocal microscopy demonstrates the anisotropic macroscale structure of MNP-laden collagen gels subjected to a magnetic field, compared to gels without MNP dosing. Matrix fibrillation was compared between non- and biofunctionalized MNP hydrogels, and different gels dosed with varying MNP concentrations. Human adipose stem cells (hASCs) seeded within the magnetically aligned gels were observed to align in parallel to MNP and collagen orientation 7 days post-application of the magnetic field. hASCs seeded in isotropic gels were randomly organized. Tenocyte-likeness of the cells 7 days post-seeding in collagen I scaffolds was confirmed by the positive expression of tenomodulin and scleraxis proteins. To summarize, we have developed a convenient, non-invasive protocol to control the collagen I hydrogel architecture. Through the presence or absence of MNP dosing and a magnetic field, collagen can be remotely aligned or randomly organized, respectively, in situ. Tendon-like cells were observed to organize in parallel to unidirectionally aligned collagen fibers and polydirectionally in non-aligned collagen constructs. In this way, we were able to engineer the constructs emulating a physiologically and pathologically relevant tendon niche. This can be considered as an innovative approach particularly useful in tissue engineering or organ-on-a-chip applications for remotely controlling collagen matrix organization to recapitulate the native tendon.
Rapamycin Promotes the Expansion of Myeloid Cells by Increasing G-CSF Expression in Mesenchymal Stem Cells
Authors: Li Minghao , Lan Yanjie , Gao Juan , Yuan Shengnan , Hou Shuaibing , Guo Tengxiao , Zhao Fei , Wang Yuxia , Yuan Weiping , Wang Xiaomin
Published: March 2022

Rapamycin, also known as sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), is a regulatory kinase responsible for multiple signal transduction pathways. Although rapamycin has been widely used in treating various hematologic diseases, the effects of rapamycin are still not fully understood. Here we found that both oral and intraperitoneal administration of rapamycin led to the expansion of myeloid lineage, while intraperitoneal administration of rapamycin impaired granulocyte differentiation in mice. Rapamycin induced bone marrow mesenchymal stem cells to produce more G-CSF in vitro and in vivo, and promoted the myeloid cells expansion. Our results thus demonstrated that intraperitoneal administration of rapamycin might promote the expansion of myeloid lineage while impair myeloid cell differentiation in vivo.
Identification of New m6A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients
Authors: Zheng Bin , Cheng Fajuan , Yao Zhongshun , Zhang Yiming , Cong Zixiang , Wang Jianwei , Niu Zhihong , He Wei
Published: March 2022

N6-methyladenosine (m6A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m6A modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between m6A modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct m6A modification patterns based on 23 m6A-related genes. Next, the correlation between m6A modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as m6A score, was established to evaluate m6A modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct m6A expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established m6A score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low m6A score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between m6A modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients.
Clemastine Induces an Impairment in Developmental Myelination
Authors: Palma Ana , Chara Juan Carlos , Montilla Alejandro , Otxoa-de-Amezaga Amaia , Ruíz-Jaén Francisca , Planas Anna M. , Matute Carlos , Pérez-Samartín Alberto , Domercq María
Published: March 2022

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promising drug with promyelinating properties. Clemastine penetrates the blood brain barrier efficiently and promotes remyelination in different animal models of neurodegeneration including multiple sclerosis, ischemia and Alzheimer’s disease. However, its role in myelination during development is unknown. We showed that clemastine treatment during development increased oligodendrocyte differentiation in both white and gray matter. However, despite the increase in the number of oligodendrocytes, conduction velocity of myelinated fibers of corpus callosum decreased in clemastine treated mice. Confocal and electron microscopy showed a reduction in the number of myelinated axons and nodes of Ranvier and a reduction of myelin thickness in corpus callosum. To understand the mechanisms leading to myelin formation impairment in the presence of an excess of myelinating oligodendrocytes, we focused on microglial cells that also express muscarinic M1 receptors. Importantly, the population of CD11c+ microglia cells, necessary for myelination, as well as the levels of insulin growth factor-1 decrease in clemastine-treated mice. Altogether, these data suggest that clemastine impact on myelin development is more complex than previously thought and could be dependent on microglia-oligodendrocyte crosstalk. Further studies are needed to clarify the role of microglia cells on developmental myelination.
Correlation Analysis of Vaginal Microbiome Changes and Bacterial Vaginosis Plus Vulvovaginal Candidiasis Mixed Vaginitis Prognosis
Authors: Xiao Bingbing , A Disi , Qin Hanyu , Mi Lan , Zhang Dai
Published: March 2022

Mixed vaginitis is the result of the simultaneous presence of different pathogenic processes mediated by at least two types of vaginal pathogens. Among the various types of mixed vaginitis presentations, bacterial vaginosis (BV) plus vulvovaginal candidiasis (VVC) presents to be the most prevalent form. Mixed vaginitis affects the health of women of all ages worldwide. However, few studies have focused on clinical manifestations, pathogenesis, diagnostic criteria, or therapy of mixed vaginitis. We recruited 48 symptomatic patients with clinical diagnoses of VVC complicated with BV, they were treated with oral metronidazole combined with local clotrimazole and followed to assess the drug efficacy and vaginal microbiome alterations before and after treatment. The vaginal microbiome in BV+VVC mixed vaginitis patients was altered significantly after the combined drug treatment within a unique form different from a simple overlay mode of BV and VVC, the key bacteria including Gardnerella and Atopobium, Lactobacillus. The combined drug therapy for the mixed vaginitis in this study was effective and enhanced treatment for BV may be more favorable because of more difficulty in dealing with BV according to the treatment outcome. The abundance of Lactobacillus in patients with mixed vaginitis affects the recovery of the vaginal microbiome as well as the prognosis, and the abundance should be actively restored. This is the first study to investigate the composition, diversity, and other characteristics of the vaginal microbiome in patients with BV+VVC mixed vaginitis before and after drug treatment, our results provide clues to improving the cure rate and reducing recurrences.
On the Frontiers of Software Science and Software Engineering
Authors: Wang Yingxu
Published: March 2022

Advances in software engineering, software science, computational intelligence, and intelligent mathematics have led to the establishment of Frontiers in Computer Science—Software (FCSS). FCSS aims to promote transdisciplinary research on software science and engineering (SSE), autonomous systems, and computational intelligence. FCSS covers not only classical empirical software engineering and industrial processes, but also contemporary topics of software science, intelligent programming languages, autonomous code generation, mathematical foundations of software, and programming knowledge bases. FCSS reports empirical studies and emerging topics in software engineering including tools, development platforms, industrial processes, management infrastructures, quality assurance schemes, big data systems, and software migrations across languages and platforms.
Reperfusion Strategy of ST-Elevation Myocardial Infarction: A Meta-Analysis of Primary Percutaneous Coronary Intervention and Pharmaco-Invasive Therapy
Authors: Li Kaiyin , Zhang Bin , Zheng Bo , Zhang Yan , Huo Yong
Published: March 2022

Background

Pharmaco-invasive therapy (PIT), combining thrombolysis and percutaneous coronary intervention, was a potential complement for primary percutaneous coronary intervention (pPCI), while bleeding risk was still a concern.

Objectives

This study aims to compare the efficacy and safety outcomes of PIT and pPCI.

Methods

A systematic search for randomized controlled trials (RCTs) and observational studies were conducted on Pubmed, Embase, Cochrane library, and Scopus. RCTs and observational studies were all collected and respectively analyzed, and combined pooled analysis was also presented. The primary efficacy outcome was short-term all-cause mortality within 30 days, including in-hospital period. The primary safety outcome was 30-day trial-defined major bleeding events.

Results

A total of 26,597 patients from 5 RCTs and 12 observational studies were included. There was no significant difference in short-term mortality [RCTs: risk ratio (RR): 1.14, 95% CI: 0.67–1.93, I2 = 0%, p = 0.64; combined results: odds ratio (OR): 1.09, 95% CI: 0.93–1.29, I2 = 0%, p = 0.30] and 30-day major bleeding events (RCTs: RR: 0.44, 95% CI: 0.07–2.93, I2 = 0%, p = 0.39; combined results: OR: 1.01, 95% CI: 0.53–1.92, I2 = 0%, p = 0.98). However, pPCI reduced risk of in-hospital major bleeding events, stroke and intracranial bleeding, but increased risk of in-hospital heart failure and 30-day heart failure in combined analysis of RCTs and observational studies, despite no significant difference in analysis of RCTs.

Conclusion

Pharmaco-invasive therapy could be an important complement for pPCI in real-world clinical practice under specific conditions, but studies aiming at optimizing thrombolysis and its combination of mandatory coronary angiography are also warranted.
Analysis of the Dose-Response Effects of Physical Activity on Cardiocerebrovascular and All-Cause Mortality in Hypertension
Authors: Xu Jun-Peng , Zeng Rui-Xiang , Lu Hai-Ning , Zhang Yu-Zhuo , Mai Xiao-Yi , Mao Shuai , Zhang Min-Zhou
Published: March 2022

Background

Leisure-time moderate-to-vigorous physical activity (MV-PA) has been consistently regarded as a protective factor to prevent and treat hypertension. However, the effect of different levels of MV-PA against cardiocerebrovascular and all-cause mortality in hypertension is still unclear. The aim of this study was to explore the dose relationships of MV-PA on these adverse outcomes in hypertension.

Methods

In the National Health and Nutritional Examination Survey (NHANES) from 1999 to 2006, participants with hypertension were enrolled and classified into inactive (0 MET-h/week), low-active (0 < to < 7.5 MET-h/week), and high-active (≥ 7.5 MET-h/week) groups. A multivariate Cox regression analysis was conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the association between different levels of MV-PA and adverse outcomes, Kaplan-Meier survival curves, subgroup analysis, and restricted cubic spline curves were performed.

Results

During a median 10.93-year follow-up, 1,510 and 347 patients had died from any causes and cardiocerebrovascular, respectively. The high-active group had the highest event-free survivals of all outcomes compared with low-active and inactive groups. A multivariate Cox regression analysis demonstrated that the high-active and low-active groups were associated with reduced risks of all-cause [HR: 0.70, 95% CI: 0.60–0.82; 0.76 (0.68–0.86), respectively] and cardiocerebrovascular mortality [0.56 (0.41–0.77); 0.63 (0.50–0.81), respectively] compared with the inactive group. Subgroup analysis and restricted cubic spline curves showed that MV-PA surpassing 15 MET-h/week could decrease the risks of cardiovascular and all-cause mortality with inverse relationships, which was not the case for cerebrovascular mortality, indicating a U-shaped association.

Conclusion

Our study suggests that highly active MV-PA of 7.5 to < 15 MET-h/week was associated with the lowest risks of cardiocerebrovascular and all-cause mortality in hypertension.
Using a Chatbot to Study Medication Overuse Among Patients Suffering From Headaches
Authors: Bézie Arthur , Morisseau Valentin , Rolland Romain , Guillemassé Arthur , Brouard Benoît , Chaix Benjamin
Published: March 2022

According to the World Health Organization, half the adult population around the world suffers from headaches. Even though this condition remains in most cases innocuous, it can have a major impact on the patient's quality of life but also on public health expenditure. Moreover, most patients manage their headaches on their own, without consulting a doctor. Therefore, self-medication can eventually lead to drug overuse, and consequently the emergence of a secondary disease called medication-overuse headache (MOH). The detection and follow-up of these unconventional patients represent a major challenge. Some of the latest technology advancements seem to be tailored and fitting for this context. The goal of this study is to investigate medication overuse in French patients suffering from headaches using the chatbot Vik Migraine. Data collection and analysis were assembled from answers to a questionnaire of 28 questions divided into three parts: socio-demographic profile, drug consumption, and medical follow-up. The study showed that medication overuse was often linked to increased headache frequency. Prescription drugs like triptans and opioids, were the most overused drugs among the cohort. This suggests that healthcare professionals could play a critical role in targeting these drugs in prevention of overuse.
Vesiculation of Rhyolitic Melts Under Oscillatory Pressure
Authors: Seropian Gilles , Kennedy Ben M. , Kendrick Jackie E. , Lavallée Yan , Nichols Alexander R. L. , von Aulock Felix W. , Dingwell Donald B. , Hess Kai-Uwe , Lamur Anthony , Schauroth Jenny , Vasseur Jérémie , Wadsworth Fabian B.
Published: March 2022

Magma ascending in the Earth’s crust can undergo oscillations in pressure, from ultra-low frequency changes associated with tectonics, to relatively higher frequency oscillations associated with seismicity. Seismic waves travelling through shallow magma bodies can lead to a range of unrest phenomena and potentially trigger volcanic eruptions. The mechanisms by which pressure oscillations can induce unrest or eruption remain debated. Here, we experimentally impose pressure oscillations on magma and study how they affect vesiculation processes. We use cylindrical samples (4.00 mm long, 4.85 mm diameter) of hydrous rhyolitic obsidian (0.11 ± 0.01 wt% H2O) placed in alumina (AL23) crucibles and vary pressure by the uniaxial loading of an alumina plunger in a thermo-mechanical analyzer. We monitor vesiculation at temperatures of 950–990°C and confining pressure of 177 kPa. We perform two types of experiment: 1) “static” experiments (at constant pressure) and 2) “oscillating” experiments in which we impose sinusoidal pressure oscillations of up to 71 kPa upon the static pressure (i.e., between 106 and 250 kPa). In both cases, we dilatometrically observe sample expansion driven by vesiculation. Post-experimental bubble textures reveal that bubbles formed preferentially at the sample margins. For the oscillating experiments, the sample expansion rate is lower than in the static experiments, and there are fewer vesicles at the sample margins. We examine the constituent processes of bubble formation (nucleation, growth, coalescence) and gas loss (diffusion, permeable flow) occurring during static experiments and with the added element of pressure oscillations. The most likely mechanism responsible for reduced sample expansion is that pressure oscillations drive the sample in and out of water saturation conditions and thus reduce the fraction of residence time over which bubble nucleation and/or growth are driven. Future work will be needed to confirm this hypothesis. These results are relevant to the study of earthquake-volcano interactions, where a magma body that sits close to volatile saturation is subject to pressure fluctuations.
Negative Impacts of Pandemic Induced At-Home Remote Learning Can Be Mitigated by Parental Involvement
Authors: Guillaume Mathieu , Toomarian Elizabeth Y. , Van Rinsveld Amandine , Baskin-Sommers Arielle , Dick Anthony Steven , Dowling Gayathri J. , Gonzalez Marybel Robledo , Hasak Lindsey , Lisdahl Krista M. , Marshall Andrew T. , Nguyen Quynh Trang H. , Pelham William E. , Pillai Cha Cha , Sheth Chandni , Wang Angie M. , Tapert Susan F. , McCandliss Bruce D.
Published: March 2022

Format changes in U.S. schooling in response to the COVID-19 pandemic varied by month and by school district, ranging from exclusively home-based to full in-person learning. The impact of these changes on adolescent schooling experiences, and the factors that mitigate such impact, have been challenging to quantify. To address these challenges we employed bi-monthly repeated surveys of youths (N = 6, 546, aged 13–14 years) in a longitudinal study, starting before the pandemic peak (October 2020) and continuing through one year after the pandemic was declared (March 2021). We investigated how school format (in-person vs. remote) impacted objective time spent on academic activities and the subjective experience of school, and how these were influenced by parental engagement. Periods of exclusive at-home remote schooling were pervasive—reported by more than 60% of youths—and linked to a reduction in school enjoyment and time spent on reading, math, and science. In contrast, such periods were linked to more time with parents or guardians helping with school activities, and the frequency of such parental involvement was associated with reductions in negative feelings about school. Results point to potential pathways to mitigate the negative consequences of future school disruptions.
Full Functional Sex Reversal Achieved Through Silencing of MroDmrt11E Gene in Macrobrachium rosenbergii: Production of All-Male Monosex Freshwater Prawn
Authors: Xu Hai-Jing , Chen Yi-Lai , Wang Yong-Mei , Luo Jing-Yu , Li Jian-Wen , Shen Shuai-Qi , Yang Jin-Shu , Ma Wen-Ming
Published: March 2022

The freshwater prawn Macrobrachium rosenbergii is one kind of important economic aquaculture species and displays remarkable sexual dimorphism. The molecular mechanism of sexual differentiation in M. rosenbergii has been primarily unraveled through the research efforts of the androgenic gland and its related genes. However, the understanding of conserved genes involved in the molecular mechanism underpinning sex determination and sexual differentiation of M. rosenbergii is still fragmentary. MroDmrt11E is a member of the doublesex and mab-3-related transcription factor (Dmrt) gene family and is prominently expressed in the testis. In the present study, in vivo knockdown of MroDmrt11E at the postlarva stage in male prawn induced a complete and functional sex reversal and achieved the production of an all-male monosex population. Furthermore, a great deal of new information of upregulated and downregulated transcriptions involved in sexual differentiation of MroDmrt11E knockdown was enriched by comparative transcriptomic analysis. The effects of RNAi-mediated gene knockdown of MroDmrt11E on the differentially expressed and sex-related candidate genes, such as transformer, fruitless, feminization, insulin-like androgenic gland gene, Dmrt gene family, were primarily focused on, and their possible molecular regulatory relationships in sexual differentiation were analyzed. Meanwhile, the response of primary Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways was investigated to expound the potential roles of MroDmrt11E in male sexual differentiation, which provided a deeper understanding of the molecular regulatory network underlying sexual differentiation of M. rosenbergii. The finding provided a novel sexual manipulation technique through silencing of Dmrt gene family for achieving a complete and functional sex reversal and offered a new insight regarding the mechanism of the Dmrt gene family in the sexual differentiation of crustaceans.
Androgen Excess Induced Mitochondrial Abnormality in Ovarian Granulosa Cells in a Rat Model of Polycystic Ovary Syndrome
Authors: Song Linyi , Yu Jin , Zhang Danying , Li Xi , Chen Lu , Cai Zailong , Yu Chaoqin
Published: March 2022

Background

Androgen excess could profoundly lead to follicular dysplasia or atresia, and finally result in polycystic ovary syndrome (PCOS); however, the exact mechanism remains to be fully elucidated.

Methods

PCOS model rats were induced by dehydroepiandrosterone, and their fertility was assessed. The ovarian granulosa cells (GCs) from matured follicles of PCOS model rats were collected and identified by immunofluorescence. The mitochondrial ultrastructure was observed by transmission electron microscope and the mitochondrial function was determined by detecting the adenosine triphosphate (ATP) content and mtDNA copy number. Besides, the expressions of respiratory chain complexes and ATP synthases in relation to mitochondrial function were analyzed.

Results

The PCOS model rats were successfully induced, and their reproductive outcomes were obviously adverse. The GCs layer of the ovarian was apparently cut down and the mitochondrial ultrastructure of ovarian GCs was distinctly destroyed. The ATP content and mtDNA copy number of ovarian GCs in PCOS model rats were greatly reduced, and the expressions of NDUFB8 and ATP5j were significantly down-regulated without obvious deletion of mtDNA 4834-bp.

Conclusions

Androgen excess could damage mitochondrial ultrastructure and function of GCs in rat ovary by down-regulating expression of NDUFB8 and ATP5j in PCOS.
Low Maternal Serum 25‐Hydroxyvitamin D Concentration Is Associated With Postpartum Hemorrhage: A Retrospective Observational Study
Authors: Li Wei-Jiun , Chen Kuo-Hu , Huang Lee-Wen , Tsai Yieh-Loong , Seow Kok-Min
Published: March 2022

Objective

The primary aim of this study is to investigate the relationship between vitamin D serum level and the incidence of postpartum hemorrhage (PPH). The secondary objective is to determine the relative risk of low vitamin D associated with PPH.

Methods

This was a retrospective observational study. A total of 600 women who had delivered their babies in a single tertiary teaching hospital were enrolled. Serum blood test for 25(OH)D was performed at 35 + 0 to 36 + 6 weeks of pregnancy to measure vitamin D. A 25(OH)D level < 20 ng/mL was defined as vitamin D deficient, and a level 21–29 ng/mL as insufficient.

Results

Vitamin D levels were deficient in 145 (24.1%) and insufficient in 254 (42.3%) of the women tested. Women with deficient and insufficient vitamin D levels were significantly younger than those with sufficient vitamin D levels (p < 0.001). The overall rates of PPH in the deficient and insufficient groups were 6.9% (10/145) and 6.7% (17/254), respectively, and were significantly higher than the rate of the normal vitamin D group (1.5%, p = 0.009). Women with sufficient vitamin D levels had significantly higher hemoglobin levels than those with low vitamin D levels. Higher vitamin D levels were associated with a significantly low risk of PPH (AOR: 0.93, CI: 0.89–0.98, p = 0.006).

Conclusion

Our results suggest that a low vitamin D level is a risk factor for PPH. Low vitamin D also related to high risk of low hemoglobin before delivery. Thus, antepartum care should include vitamin D supplements for all women if possible.
Advancing Microbial Electrolysis Technology via Impedance Spectroscopy and Multi-Variate Analysis
Authors: Timmerman Lucas R. , Raghavan Sankar , Borole Abhijeet P.
Published: March 2022

In this study, EIS data collected from three electrode half-cell configurations was used to qualitatively identify and quantitatively determine the responses of ohmic, kinetic, and mass transfer impedances to buffer concentration, flow rate, and applied potential in an MEC consisting of a bioanode and an abiotic nickel-mesh cathode separated by a microporous membrane. EIS measurements were collected during startup and growth (including an abiotic run) at closed circuit and open circuit conditions to accurately match portions of the EIS spectra with the corresponding physical processes and to quantify kinetic changes as the biofilm matured. Once the MEC reached a target current density of 10 A/m2, a multifactorial experimental design formulated as a Taguchi array was executed to assess the impact of flow rate, buffer concentration, and applied voltage on EIS and performance response variables. Multivariate analysis was conducted to ascertain the relative importance of the independent variables and identify any correlations between process conditions and system response. The liquid flow through the anode was found to be strongly correlated with the impedance parameters and the MEC performance, while applied voltage influenced them to a lesser degree. The results are important from an industrial application perspective and provide insights into parameters important for process optimization.
The Influence of the North Atlantic Oscillation and East Atlantic Pattern on Drought in British Catchments
Authors: West Harry , Quinn Nevil , Horswell Michael
Published: March 2022

Drought events are influenced by a combination of both climatic and local catchment characteristics. In Great Britain the North Atlantic Oscillation (NAO) has long been recognised as the leading mode of climate variability, and studies have also noted the role of the East Atlantic Pattern (EA) as a secondary mode. This study aimed to develop an understanding of the combined influence of the NAO and EA on rainfall distribution and magnitude and the variable nature of meteorological to hydrological drought propagation. Initially, this study explores correlations between teleconnection indices and standardised precipitation and streamflow indices for 291 catchments across Great Britain, before focusing on nine case study catchments for further analysis. For each case study catchment, we use quantile regression and an analysis of drought frequency to explore the combined influence of the NAO and EA on drought conditions. Through a convergence of evidence from these analyses we make three observations. Firstly, in the winter months both the NAO and EA exert an influence on drought conditions, however there is spatial variability in the relative influence of the NAO and EA; the NAO has a stronger influence in the north-west, whilst the EA has a stronger influence in the southern and central regions. Secondly, in the summer months, less distinctive spatial differences were found, with higher probability of drought conditions under NAO+ phases, which however can be enhanced or moderated by the EA. Finally, as a result of catchment characteristics there is spatio-temporal variability in the propagation of meteorological to hydrological drought. Our findings suggest that by considering the NAO and EA in combination, we can better describe climate and drought variability. We conclude by noting the potential implications our study has on the role of monthly teleconnection forecasts in water management decision making in Great Britain, and acknowledge the current limitations associated with incorporating such understanding.
Post-exercise Hypothermia Varies Between High- and Low-Altitude Populations in the Asiatic Toad (Bufo gargarizans)
Authors: Yao Zhongyi , Huang Kun , Qi Yin
Published: March 2022

Whether and how poikilothermic animals change their thermal performance to cope with global warming are crucial questions to predict the future of biodiversity. Intraspecific comparison among populations that occur in different climatic zones can provide insight into how poikilotherms may alter their thermal performance under a particular climatic event. We compared populations of the Asiatic toad (Bufo gargarizans) from two altitudinal zones (3239 and 926 m above sea level) to explore variations of post-exercise hypothermia, which can lead to lower temperature preference than normal conditions. Common garden experiment was also employed to test plasticity of hypothermic performance in adult toads. As results, exhaustive exercise induced measurable reduction in body temperature for both populations. Furthermore, high-altitude population experienced larger reduction in body temperature than low-altitude conspecifics in both original habitat and common garden conditions. Therefore, low-altitude toads may to enhance their hypothermic reaction if they shift their ranges to higher altitudes to survive warming climate; However, the relatively limited plasticity of hypothermic performance may constraint their adaptative process.
Diversity and Distribution of Traditional Home Gardens Along Different Disturbances in a Dry Tropical Region, India
Authors: Patel Sanoj Kumar , Sharma Anil , Singh Rinku , Tiwari Amit Kumar , Singh Gopal Shankar
Published: March 2022

Home gardening is an indigenous practice of cultivation that has effectively adapted to local ecological conditions over generations. This study examined the effects of disturbance and garden size on biodiversity to develop a better understanding of vegetation cover and its role in livelihood and provision of forest management in the Vindhyan highlands. Data were collected from 60 gardens which were classified into large (> 650 m2), medium (400–650 m2), and small (< 400 m2), based on size and disturbance gradients viz., high, medium, and low. A total of 133 species from 50 families were recorded, in which trees (47.4%) were dominant followed by shrubs (18%) and herbs (16.5%). With respect to disturbance, the highest number of tree species (39) were found at low disturbance (LD) followed by 33 species in medium disturbance (MD) and 32 species in high disturbhance (HD). The total mean richness of species was greater at LD (20.3 ± 2.3) and lowest at HD (18.5 ± 2.2). Tree density was significantly (P≤ 0.05) higher at LD (293.75 ± 16.1 individual ha–1) as compared to MD (221 ± 11.5 individual ha–1) and HD (210 ± 10.3 individual ha–1). However, the results for shrubs and herbs density were considerably different, where shrubs density was highest at HD (70 ± 6.9 individual per 1,000 m2) and lowest at LD (62.5 ± 5.8 individual per 1,000 m2), while the maximum density of herbs was recorded at MD (466.25 ± 29.8 individual per 100 m2) and minimum at LD (370 ± 21.4 individual per 100 m2). The summed dominance ratio indicated frequent use of garden plants in bio-fencing, vegetables, ornamental, and ethnomedicine. Diversity (P< 0.01) and species richness (P< 0.05) showed a significant positive correlation with garden size. The Principal Component Analysis (PCA) showed that the first component (PC1) accounted for 28.6% of variance, whereas the second explained 21.9% of variance in both disturbance and garden size with a cumulative variance of 50.5%. These components depicted the positive association with HD (14.34), SDiv (13.91), TCD (12.47), and HDiv (12.09). We concluded that the diversity of home gardens changed with disturbance, which crucially served as a refuge for native tree species in a degraded landscape. This pattern highlighted the importance of home gardens for plant biodiversity conservation and local livelihood, which must be a viable option for regeneration of deforested dry tropics, while also reducing the burden on dry tropical forest regions.
Comprehensive Analysis of the Transcriptome-Wide m6A Methylation in Mouse Pachytene Spermatocytes and Round Spermatids
Authors: Hong Shihao , Shen Xiaozhong , Cheng Jinmei , Tang Hanyu , Sun Fei
Published: March 2022

Spermatogenesis, an efficient and complex system in male germline development, requires a series of elaborately regulated genetic events in which diploid spermatogonia differentiate into haploid spermatozoa. N6-methyladenosine (m6A) is an important epigenetic RNA modification that occurs during spermatogenesis. ALKBH5 is an m6A eraser and knocking outAlkbh5increases the level of total m6A methylation and causes male infertility. In this study, comprehensive analyses of MeRIP-seq and RNA-seq data revealed differences between wild-type (WT) andAlkbh5knockout (KO) mice. In pachytene spermatocytes (PA), 8,151 m6A peaks associated with 9,959 genes were tested from WT and 10,856 m6A peaks associated with 10,016 genes were tested from KO mice. In the round spermatids (RO), 10,271 m6A peaks associated with 10,109 genes were tested from WT mice and 9,559 m6A peaks associated with 10,138 genes were tested from KO mice. The peaks were mainly concentrated in the coding region and the stop codon of the GGAC motif. In addition, enrichment analysis showed significant m6A methylation genes in related pathways in spermatogenesis. Furthermore, we conducted joint analyses of the m6A methylome and RNA transcription, suggesting an m6A regulatory mechanism of gene expression. Finally, seven differentially expressed mRNAs from RNA-seq data in both PA and RO were verified using qPCR. Overall, our study provides new information on m6A modification changes between WT and KO in PA and RO, and may provide new insights into the molecular mechanisms of m6A modification in germ cell development and spermatogenesis.
An Integrated Algorithm for Designing Oligodeoxynucleotides for Gene Synthesis
Authors: Fang Gang , Liang Hanjie
Published: March 2022

The design and construction of large synthetic genes can be a slow, difficult, and confusing process, especially in the key step of oligodeoxynucleotide design. Herein we present an integrated algorithm to design oligonucleotide sets for gene synthesis by both ligase chain reaction and polymerase chain reaction. It offers much flexibility with no constraints on the gene to be synthesized. Firstly, it divides the long-input DNA sequence by a greedy algorithm based on the length of the oligodeoxynucleotide overlap region. Secondly, it tunes the length of the overlap region iteratively in an attempt to minimize the melting temperature variance of overlap. Thirdly, dynamic programming algorithm is used to achieve the uniform melting temperature of the oligodeoxynucleotide overlaps. Finally, the oligodeoxynucleotides with homologous melting temperature necessary for ligase chain reaction-based or two-step assembly PCR-based synthesis of the desired gene are outputted.
Methods to Analyze the Non-Coding RNA Interactome—Recent Advances and Challenges
Authors: Cao Huifen , Kapranov Philipp
Published: March 2022

Most of the human genome is transcribed to generate a multitude of non-coding RNAs. However, while these transcripts have generated an immense amount of scientific interest, their biological function remains a subject of an intense debate. Understanding mechanisms of action of non-coding RNAs is a key to addressing the issue of biological relevance of these transcripts. Based on some well-understood non-coding RNAs that function inside the cell by interacting with other molecules, it is generally believed many other non-coding transcripts could also function in a similar fashion. Therefore, development of methods that can map RNA interactome is the key to understanding functionality of the extensive cellular non-coding transcriptome. Here, we review the vast progress that has been made in the past decade in technologies that can map RNA interactions with different sites in DNA, proteins or other RNA molecules; the general approaches used to validate the existence of novel interactions; and the challenges posed by interpreting the data obtained using the interactome mapping methods.
Autophagy and Exosome Coordinately Enhance Macrophage M1 Polarization and Recruitment in Influenza A Virus Infection
Authors: Xia Chengjie , Xu Weiming , Ai Xin , Zhu Yingqi , Geng Ping , Niu Yijun , Zhu Haiyan , Zhou Wei , Huang Hai , Shi Xunlong
Published: March 2022

Background

Influenza A virus infection results in viral pneumonia, which is often accompanied by the infiltration and recruitment of macrophages, overactivation of inflammatory responses, and obvious cell autophagy and exosome production. However, little is known about the roles of autophagy and exosome production in these inflammatory responses.

Methods

In this study, multiple methods, such as flow cytometry, real-time quantitative reverse transcription-polymerase chain reaction, immune–fluorescence technology, and western blot, were applied to explore the possible effects of autophagy and exosome production by H1N1-infected host cells.

Results

It was observed that a high number of polarized macrophages (CD11b+/F4/80+/CD86+) were recruited to the lung tissues of infected mice, which could be mimicked by tracking the movement of macrophages to H1N1-infected cells in vitro (transwell assays). Furthermore, there was some coordinated upregulation of M1 polarization signs (iNOS/Arg-1 bias) as well as autophagy (LC3) and exosome (CD63) biomarkers in the infected macrophages and epithelial cells. Moreover, exosomes extracted from the supernatant of virus-infected cells were shown to promote the recruitment and polarization of more peritoneal macrophages than the normal group. The fluorescence colocalization of LC3-CD63 and the inhibition of autophagy and exosome signaling pathway further revealed that H1N1 infection seemed to sequentially activate the M1 polarization and recruitment of macrophages via autophagy–exosome dependent pathway.

Conclusion

Autophagy and exosome production coordinately enhance the M1 polarization and recruitment of macrophages in influenza virus infection, which also provides potential therapeutic targets.
How Does Immunomodulatory Nanoceria Work? ROS and Immunometabolism
Authors: Ernst Lena M. , Puntes Victor
Published: March 2022

Dysregulation of the immune system is associated with an overproduction of metabolic reactive oxygen species (ROS) and consequent oxidative stress. By buffering excess ROS, cerium oxide (CeO2) nanoparticles (NPs) (nanoceria) not only protect from oxidative stress consequence of inflammation but also modulate the immune response towards inflammation resolution. Immunomodulation is the modulation (regulatory adjustment) of the immune system. It has natural and human-induced forms, and it is part of immunotherapy, in which immune responses are induced, amplified, attenuated, or prevented according to therapeutic goals. For decades, it has been observed that immune cells transform from relative metabolic quiescence to a highly active metabolic state during activation(1). These changes in metabolism affect fate and function over a broad range of timescales and cell types, always correlated to metabolic changes closely associated with mitochondria number and morphology. The question is how to control the immunochemical potential, thereby regulating the immune response, by administering cellular power supply. In this regard, immune cells show different general catabolic modes relative to their activation status, linked to their specific functions (maintenance, scavenging, defense, resolution, and repair) that can be correlated to different ROS requirements and production. Properly formulated, nanoceria is highly soluble, safe, and potentially biodegradable, and it may overcome current antioxidant substances limitations and thus open a new era for human health management.
Improving Assignments for Therapeutic and Prophylactic Treatment Within TB Households. A Potential for Immuno-Diagnosis?
Authors: Sivakumaran Dhanasekaran , Jenum Synne , Ritz Christian , Vaz Mario , Doherty Timothy Mark , Grewal Harleen M. S.
Published: March 2022

Delays in diagnosis and treatment of pulmonary tuberculosis (TB) can lead to more severe disease and increased transmission. Contact investigation among household contacts (HHCs) of TB patients is crucial to ensure optimal outcomes. In the context of a prospective cohort study in Palamaner, Southern India, this study attempted to assess the potential of 27 different soluble immune markers to accurately assign HHCs for appropriate treatment. A multiplex bead assay was applied on QuantiFERON (QFT)-nil supernatants collected from 89 HHCs grouped by longitudinal QFT status;M. tuberculosis(Mtb) infected (QFT positive at baseline and follow-up, n = 30), recent QFT converters (QFT-negative at baseline, n = 27) and converted to QFT-positivity within 6 months of exposure (at follow-up, n = 24) and QFT consistent negatives (n = 32). The 29 TB index cases represented Active TB. Active TB cases and HHCs withMtbinfection produced significantly different levels of both pro-inflammatory (IFNγ, IL17, IL8, IP10, MIP-1α, MIP1β, and VEGF) and anti-inflammatory (IL9 and IL1RA) cytokines. We identified a 4-protein signature (bFGF, IFNγ, IL9, and IP10) that correctly classified HHCs withMtbinfection vs. Active TB with a specificity of 92.6%, suggesting that this 4-protein signature has the potential to assign HHCs for either full-length TB treatment or preventive TB treatment. We further identified a 4-protein signature (bFGF, GCSF, IFNγ, and IL1RA) that differentiated HHCs withMtbinfection from QFT consistent negatives with a specificity of 62.5%, but not satisfactory to safely assign HHCs to no preventive TB treatment. QFT conversion, reflecting newMtbinfection, induced an elevated median concentration in nearly two-thirds (19/27) of the analyzed soluble markers compared to the levels measured at baseline. Validation in other studies is warranted in order to establish the potential of the immune biosignatures for optimized TB case detection and assignment to therapeutic and preventive treatment ofMtbinfected individuals.