bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Observational Methods and the Detection of Seasonal and Atlantic Influence Upon Phytoplankton Communities in the Western Barents Sea
Authors: Orkney Andrew , Davidson Keith , Mitchell Elaine , Henley Sian F. , Bouman Heather A.
Published: May 2022

Phytoplankton community composition, and its dependency on environmental variation, are key to understanding marine primary production, processes of trophic transfer and the role of marine phytoplankton in global biogeochemical cycles. Understanding changes in phytoplankton community composition on Arctic shelves is important, because these productive environments are experiencing rapid change. Many different methods have been employed by researchers to quantify phytoplankton community composition. Previous studies have demonstrated that the way in which community composition is quantified can influence the interpretation of environmental dependencies. Researchers must consider both the suitability of the data they collect for monitoring marine ecosystems, as well as the research effort required to collect representative datasets. We therefore seek to understand how the representation of phytoplankton community structure in the western Barents Sea, a rapidly changing Arctic shelf sea, influences the interpretation of environmental dependencies. We compare datasets of cell counts, phytoplankton pigments and bio-optics (absorption spectra), relating them to a suite of environmental conditions with multivariate exploratory analyses. We show that, while cell counts reveal the greatest insight into environmental dependencies, pigment and absorption spectral datasets still provide useful information about seasonal succession and the influence of Atlantic water masses– two key subjects of great research interest in this region. As pigments and optical properties influence remotely-sensed ocean-colour, these findings hold implications for remote detection of phytoplankton community composition.
Characterization of Interface and Bulk Traps in Ultrathin Atomic Layer-Deposited Oxide Semiconductor MOS Capacitors With HfO2/In2O3 Gate Stack by C-V and Conductance Method
Authors: Wang Ziheng , Lin Zehao , Si Mengwei , Ye Peide D.
Published: May 2022

Oxide semiconductors have attracted revived interest for complementary metal–oxide–semiconductor (CMOS) back-end-of-line (BEOL) compatible devices for monolithic 3-dimensional (3D) integration. To obtain a high-quality oxide/semiconductor interface and bulk semiconductor, it is critical to enhance the performance of oxide semiconductor transistors. Atomic layer-deposited (ALD) indium oxide (In2O3) has been reported with superior performance such as high drive current, high mobility, steep subthreshold slope, and ultrathin channel. In this work, the interface and bulk traps in the MOS gate stack of ALD In2O3 transistors are systematically studied by using the C–V and conductance method. A low EOT of 0.93 nm is achieved directly from the accumulation capacitance in C–V measurement, indicating a high-quality gate oxide and oxide/semiconductor interface. Defects in bulk In2O3 with energy levels in the subgap are confirmed to be responsible for the conductance peak in GP/ω versus ω curves by TCAD simulation of C–V and G–V characteristics. A high n-type doping of 1×1020/cm3 is extracted from C–V measurement. A high subgap density of states (DOS) of 3.3×1020 cm−3 eV−1 is achieved using the conductance method, which contributes to the high n-type doping and high electron density. The high n-type doping further confirms the capability of channel thickness scaling because the charge neutrality level aligns deeply inside the conduction band.
A Qualitative Study of the Disorder Effect on the Phonon Transport in a Two-Dimensional Graphene/h-BN Heterostructure
Authors: Liu Yinong , Ren Weina , An Meng , Dong Lan , Gao Lei , Shai Xuxia , Wei Tingting , Nie Linru , Hu Shiqian , Zeng Chunhua
Published: May 2022

Recently, massive efforts have been made to control phonon transport via introducing disorder. Meanwhile, materials informatics, an advanced material-discovery technology that combines data-driven search algorithms and material property simulations, has made significant progress and shown accurate prediction ability in studying the target properties of new materials. However, with the introduction of disorder, the design space of random structures is greatly expanded. Global optimization for the entire domain is nearly impossible with the current computer resource even when materials informatics reduces the design space to a few percent. Toward the goal of reducing design space, we investigate the effect of different types of disorders on phonon transport in two-dimensional graphene/hexagonal boron nitride heterostructure using non-equilibrium molecular dynamics simulation. The simulation results show that when the hexagonal boron nitride is distributed disorderly in the coherent phonon-dominated structure, that is, the structure with a period length of 1.23 nm, the thermal conductivity is significantly reduced due to the appearance of coherent phonon localization. By qualitatively analyzing different types of disorder, we found that the introduction of disordered structure in the cross direction with a larger shift distance can further reduce the thermal conductivity. Further physical mechanism analysis revealed that the structures with lower thermal conductivity were caused by weak propagation and strong localization of phonon. Our findings have implications for accelerating machine learning in the search for structures with the lowest thermal conductivity, and provide some guidance for the future synthesis of 2D heterostructures with unique thermal properties.
Evaluation of the Presence of Bacterial and Viral Agents in the Semen of Infertile Men: A Systematic and Meta-Analysis Review Study
Authors: Gholami Mehrdad , Moosazadeh Mahmood , Haghshenash Mohammad Reza , Jafarpour Hamed , Mousavi Tahoora
Published: May 2022

Objectives

Infections in the male genitourinary system with bacterial and viral agents may play a significant role in male infertility. These agents usually infect the urethra, seminal vesicles, prostate, epididymis, vas deferens, and testes retrograde through the reproductive system. A meta-analysis review study was performed to evaluate the presence of bacterial and viral agents in the semen of infertile men and its correlation with infertility.

Methods

Relevant cross-sectional and/or case-control studies were found by an online review of national and international databases (Web of Science, PubMed, Scopus, Science Direct, and Google scholar), and suitable studies were selected. A checklist determined the qualities of all studies. Heterogeneity assay among the primary studies was evaluated by Cochran’s Q test and I2 index (significance level 50%). A statistical analysis was conducted using the Comprehensive Stata ver. 14 package (StataCorp, College Station, TX, United States).

Results

Seventy-two studies were included in this meta-analysis. Publication bias was compared with Egger’s test, and the impact of each research on overall estimate was evaluated by sensitivity analysis. In 56 studies, the rate of bacterial infections in the semen of infertile men was 12% [95% confidence interval (CI): 10–13]. Also, in 26 case-control studies, the association of infertility in men with bacterial infections was evaluated. The results show that the odds ratio of infertility in men exposed to bacterial infections is 3.31 times higher than that in non-infected men (95% CI: 2.60–4.23). Besides, in 9 studies that examined the prevalence of human papillomavirus (HPV), herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), and herpes simplex virus 1-2 (HSV1-2) in infertile men, the frequency of these viruses was 15% (95% CI: 9–21). In 6 case-control studies, the association between human cytomegalovirus (HCMV), Cytomegalovirus (CMV), and HPV and male infertility was evaluated. The chance of male infertility due to exposure to these viruses was 2.24 times higher than those without exposure to these viruses (CI 95%: 1.9–4.52). The results show that the chance of infertility in men exposed to bacteria was significantly higher than that in the uninfected population.

Conclusion

This meta-analysis showed that viral and bacterial infections are a risk factor and could impair male fertility potential. Moreover, our study supports the hypothesis that bacterial and viral infections of the genital tract correlate positively with impairment of sperm quality in the male population.
Anthropogenic Intensity-Determined Assembly and Network Stability of Bacterioplankton Communities in the Le’an River
Authors: Wu Bobo , Wang Peng , Devlin Adam Thomas , She Yuanyang , Zhao Jun , Xia Yang , Huang Yi , Chen Lu , Zhang Hua , Nie Minghua , Ding Mingjun
Published: May 2022

Bacterioplankton are essential components of riverine ecosystems. However, the mechanisms (deterministic or stochastic processes) and co-occurrence networks by which these communities respond to anthropogenic disturbances are not well understood. Here, we integrated niche-neutrality dynamic balancing and co-occurrence network analysis to investigate the dispersal dynamics of bacterioplankton communities along human activity intensity gradients. Results showed that the lower reaches (where intensity of human activity is high) had an increased composition of bacterioplankton communities which induced strong increases in bacterioplankton diversity. Human activity intensity changes influenced bacterioplankton community assembly via regulation of the deterministic-stochastic balance, with deterministic processes more important as human activity increases. Bacterioplankton molecular ecological network stability and robustness were higher on average in the upper reaches (where there is lower intensity of human activity), but a human activity intensity increase of about 10%/10% can reduce co-occurrence network stability of bacterioplankton communities by an average of 0.62%/0.42% in the dry and wet season, respectively. In addition, water chemistry (especially NO3–-N and Cl–) contributed more to explaining community assembly (especially the composition) than geographic distance and land use in the dry season, while the bacterioplankton community (especially the bacterioplankton network) was more influenced by distance (especially the length of rivers and dendritic streams) and land use (especially forest regions) in the wet season. Our research provides a new perspective of community assembly in rivers and important insights into future research on environmental monitoring and classified management of aquatic ecosystems under the influence of human activity.
Layer-by-Layer Coating of Single-Cell Lacticaseibacillus rhamnosus to Increase Viability Under Simulated Gastrointestinal Conditions and Use in Film Formation
Authors: Sbehat Maram , Altamimi Mohammad , Sabbah Mohammad , Mauriello Gianluigi
Published: May 2022

Probiotics and prebiotics are widely used as functional food ingredients. Viability of probiotics in the food matrix and further in the digestive system is still a challenge for the food industry. Different approaches were used to enhance the viability of probiotics including microencapsulation and layer-by-layer cell coating. The of aim of this study was to evaluate the viability of coated Lacticaseibacillus rhamnosus using a layer-by-layer (LbL) technique with black seed protein (BSP) extracted from Nigella sativa defatted seeds cakes (NsDSC), as a coating material, with alginate, inulin, or glucomannan, separately, and the final number of coating layers was 3. The viable cell counts of the plain and coated L. rhamnosus were determined under sequential simulated gastric fluid (SGF) for 120 min and simulated intestinal fluid (SIF) for 180 min. Additionally, the viability after exposure to 37, 45, and 55°C for 30 min was also determined. Generally, the survivability of coated L. rhamnosus showed significant (p ≤ 0.05) improvement (<4, 3, and 1.5 logs reduction for glucomannan, alginate and inulin, respectively) compared with plain cells (∼6.7 log reduction) under sequential exposure to SGF and SIF. Moreover, the cells coated with BSP and inulin showed the best protection for L. rhamnosus under high temperatures. Edible films prepared with pectin with LbL-coated cells showed significantly higher values in their tensile strength (TS) of 50% and elongation at the break (EB) of 32.5% than pectin without LbL-coated cells. The LbL technique showed a significant protection of probiotic cells and potential use in food application.
Double-Stranded RNA Viruses Are Released From Trichomonas vaginalis Inside Small Extracellular Vesicles and Modulate the Exosomal Cargo
Authors: Rada Petr , Hrdý Ivan , Zdrha Alois , Narayanasamy Ravi Kumar , Smutná Tamara , Horáčková Jana , Harant Karel , Beneš Vladimír , Ong Seow-Chin , Tsai Chih-Yu , Luo Hong-Wei , Chiu Cheng-Hsun , Tang Petrus , Tachezy Jan
Published: May 2022

Trichomonas vaginalis is a parasitic protist that infects the human urogenital tract. During the infection, trichomonads adhere to the host mucosa, acquire nutrients from the vaginal/prostate environment, and release small extracellular vesicles (sEVs) that contribute to the trichomonad adherence and modulate the host-parasite communication. Approximately 40–70% of T. vaginalis strains harbor a double-stranded RNA virus called Trichomonasvirus (TVV). Naked TVV particles have the potential to stimulate a proinflammatory response in human cells, however, the mode of TVV release from trichomonads to the environment is not clear. In this report, we showed for the first time that TVV particles are released from T. vaginalis cells within sEVs. The sEVs loaded with TVV stimulated a higher proinflammatory response of human HaCaT cells in comparison to sEVs from TVV negative parasites. Moreover, a comparison of T. vaginalis isogenic TVV plus and TVV minus clones revealed a significant impact of TVV infection on the sEV proteome and RNA cargo. Small EVs from TVV positive trichomonads contained 12 enriched and 8 unique proteins including membrane-associated BspA adhesine, and about a 2.5-fold increase in the content of small regulatory tsRNA. As T. vaginalis isolates are frequently infected with TVV, the release of TVV via sEVs to the environment represents an important factor with the potential to enhance inflammation-related pathogenesis during trichomoniasis.
Pathways Linking Nicotinamide Adenine Dinucleotide Phosphate Production to Endoplasmic Reticulum Protein Oxidation and Stress
Authors: Gansemer Erica R. , Rutkowski D. Thomas
Published: May 2022

The endoplasmic reticulum (ER) lumen is highly oxidizing compared to other subcellular compartments, and maintaining the appropriate levels of oxidizing and reducing equivalents is essential to ER function. Both protein oxidation itself and other essential ER processes, such as the degradation of misfolded proteins and the sequestration of cellular calcium, are tuned to the ER redox state. Simultaneously, nutrients are oxidized in the cytosol and mitochondria to power ATP generation, reductive biosynthesis, and defense against reactive oxygen species. These parallel needs for protein oxidation in the ER and nutrient oxidation in the cytosol and mitochondria raise the possibility that the two processes compete for electron acceptors, even though they occur in separate cellular compartments. A key molecule central to both processes is NADPH, which is produced by reduction of NADP+ during nutrient catabolism and which in turn drives the reduction of components such as glutathione and thioredoxin that influence the redox potential in the ER lumen. For this reason, NADPH might serve as a mediator linking metabolic activity to ER homeostasis and stress, and represent a novel form of mitochondria-to-ER communication. In this review, we discuss oxidative protein folding in the ER, NADPH generation by the major pathways that mediate it, and ER-localized systems that can link the two processes to connect ER function to metabolic activity.
Beneficial Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation for the Verbal Memory and Default Mode Network in Healthy Older Adults
Authors: Cui Dong , Jin Jingna , Cao Weifang , Wang He , Wang Xin , Li Ying , Liu Tianjun , Yin Tao , Liu Zhipeng
Published: May 2022

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is a non-invasive effective treatment for cognitive disorder, but its underlying mechanism of action remains unknown. The aim of this study was to explore the effect of a 2-week high-frequency (HF) active or sham 10 Hz rTMS on verbal memory in 40 healthy older adults. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to measure functional connectivity (FC) within the default mode network (DMN). Verbal memory performance was evaluated using an auditory verbal learning test (AVLT). Additionally, we evaluated the relationship between memory improvement and FC changes within the DMN. The results revealed that HF-rTMS can enhance immediate recall and delayed recall of verbal memory and increased the FC of the bilateral precuneus (PCUN) within the DMN. The positive correlations between the immediate recall memory and the FC of the left PCUN after a 2-week intervention of HF-rTMS were detected. In conclusion, HF-rTMS may have the potential to improve verbal memory performance in older adults, which relation to FC changes in the DMN. The current findings are useful for increasing the understanding of the mechanisms of HF-rTMS, as well as guiding HF-rTMS treatment of cognitive disorders.
Ursolic Acid Ameliorates Spinal Cord Injury in Mice by Regulating Gut Microbiota and Metabolic Changes
Authors: Rong Zi-Jie , Cai Hong-Hua , Wang Hao , Liu Gui-Hua , Zhang Zhi-Wen , Chen Min , Huang Yu-Liang
Published: May 2022

Background: Spinal cord injury (SCI) damages the autonomic nervous system and affects the homeostasis of gut microbiota. Ursolic acid (UA) is a candidate drug for treating nervous system injury due to its neuroprotective and antioxidant functions. The purpose of our study was to investigate the role of UA on SCI and its mechanism.

Methods: UA was administered to SCI mice and the solvent corn oil was used as control. The weight of the mice was recorded daily. Mice feces were collected 21 days after surgery for 16S rRNA-amplicon sequencing and untargeted metabolomics analysis. The expressions of NF-κB, IL-1β, and TNF-α in the spinal cord and colon tissues of mice were detected by Western blot and Enzyme-linked immunosorbent assay, respectively. Immunohistochemistry was used to analyze the expression of NeuN, NF-200, and synapsin in the spinal cord tissues.

Results: UA treatment increased body weight and soleus muscle weight of SCI mice. UA treatment inhibited inflammatory response and protected neuronal activity in SCI mice. UA improved the relative abundance of Muribaculaceae, Lachnospiraceae_NK4A136_group, and Alloprevotell genus in the gut tract of SCI mice. SCI destroyed the Glutamine_and_D-glutamate_metabolism, Nitrogen_metabolism, Aminoacyl-tRNA_biosynthesis, and Taurine_and_hypotaurine_metabolism in the gut of mice, which might be alleviated by UA.

Conclusions: UA treatment could inhibit SCI progression by improving the gut environment and metabolic changes, promoting synaptic regeneration and anti-inflammatory effects.
Rhino-Orbital Cerebral Mucormycosis in a Patient With Diabetic Ketoacidosis: A Case Report and Literature Review
Authors: Dong Nan , Jordan Ashly E. , Shen Xiaozhu , Wu Xuan , Guo Xianghong , Zhao Hongru , Wang Yajuan , Wang Dapeng , Fang Qi
Published: May 2022

Background

Rhino-orbital cerebral mucormycosis (ROCM) is a rare, invasive, and fatal fungal disease. Due to the lack of specific clinical manifestations and adequate auxiliary examinations, patients are easily misdiagnosed in the early stage. Early diagnosis and timely therapy are essential for successful treatment.

Case Report

We report a 68-year-old man with diabetic ketoacidosis, presented with orbital apex syndrome (OAS), fever, and pansinusitis, which progressively worsened to death only 4 days after admission. It was finally confirmed as a fungal Rhizopus arrhizus infection by metagenomics cell-free DNA next-generation sequencing (mNGS) testing.

Conclusion

Orbital apex syndrome could be the initial presentation for mucormycosis. Thus, it is necessary to evaluate the presence of mucormycosis in patients with OAS, especially in diabetic or immunosuppressed hosts, and mNGS testing and timely antifungal therapy should be strongly recommended in highly suspected cases.
Pre-processing of Sub-millimeter GE-BOLD fMRI Data for Laminar Applications
Authors: Pais-Roldán Patricia , Yun Seong Dae , Shah N. Jon
Published: May 2022

Over the past 30 years, brain function has primarily been evaluated non-invasively using functional magnetic resonance imaging (fMRI) with gradient-echo (GE) sequences to measure blood-oxygen-level-dependent (BOLD) signals. Despite the multiple advantages of GE sequences, e.g., higher signal-to-noise ratio, faster acquisitions, etc., their relatively inferior spatial localization compromises the routine use of GE-BOLD in laminar applications. Here, in an attempt to rescue the benefits of GE sequences, we evaluated the effect of existing pre-processing methods on the spatial localization of signals obtained with EPIK, a GE sequence that affords voxel volumes of 0.25 mm3 with near whole-brain coverage. The methods assessed here apply to both task and resting-state fMRI data assuming the availability of reconstructed magnitude and phase images.
Intraoperative Real-Time Near-Infrared Image-Guided Surgery to Identify Intracranial Meningiomas via Microscope
Authors: Muto Jun , Mine Yutaka , Nishiyama Yuya , Murayama Kazuhiro , Yamada Seiji , Kojima Daijiro , Hayakawa Motoharu , Adachi Kazuhide , Hasegawa Mitsuhiro , Lee John Y. K. , Hirose Yuichi
Published: May 2022

Meningiomas are a common pathology in the central nervous system requiring complete surgical resection. However, in cases of recurrence and post-irradiation, accurate identification of tumor remnants and a dural tail under bright light remains challenging. We aimed to perform real-time intraoperative visualization of the meningioma and dural tail using a delayed-window indocyanine green (ICG) technique with microscopy. Fifteen patients with intracranial meningioma received 0.5 mg/kg ICG a few hours before observation during the surgery. We used near-infrared (NIR) fluorescence to identify the tumor location. NIR fluorescence could visualize meningiomas in 12 out of 15 cases. Near-infrared visualization during the surgery ranged from 1 to 4 h after the administration of ICG. The mean signal-to-background ratio (SBR) of the intracranial meningioma in delayed-window ICG (DWIG) was 3.3 ± 2.6. The ratio of gadolinium-enhanced T1 tumor signal to the brain (T1BR) (2.5 ± 0.9) was significantly correlated with the tumor SBR (p = 0.016). Ktrans, indicating blood–brain barrier permeability, was significantly correlated with tumor SBR (p < 0.0001) and T1BR (p = 0.013) on dynamic contrast-enhanced magnetic resonance imaging (MRI). DWIG demonstrated a sensitivity of 94%, specificity of 38%, positive predictive value (PPV) of 76%, and negative predictive value (NPV) of 75% for meningiomas. This is the first pilot study in which DWIG fluorescence-guided surgery was used to visualize meningioma and dural tail intraoperatively with microscopy. DWIG is comparable with second-window ICG in terms of mean SBR. Gadolinium-enhanced T1 tumor signal may predict NIR fluorescence of the intracranial meningioma. Blood–brain barrier permeability as shown by Ktrans on dynamic contrast-enhanced MRI can contribute to gadolinium enhancement on MRI and to ICG retention and tumor fluorescence by NIR.
Parkinson’s Disease: Overview of Transcription Factor Regulation, Genetics, and Cellular and Animal Models
Authors: Xia Ninuo , Cabin Deborah E. , Fang Fang , Reijo Pera Renee A.
Published: May 2022

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, affecting nearly 7–10 million people worldwide. Over the last decade, there has been considerable progress in our understanding of the genetic basis of PD, in the development of stem cell-based and animal models of PD, and in management of some clinical features. However, there remains little ability to change the trajectory of PD and limited knowledge of the underlying etiology of PD. The role of genetics versus environment and the underlying physiology that determines the trajectory of the disease are still debated. Moreover, even though protein aggregates such as Lewy bodies and Lewy neurites may provide diagnostic value, their physiological role remains to be fully elucidated. Finally, limitations to the model systems for probing the genetics, etiology and biology of Parkinson’s disease have historically been a challenge. Here, we review highlights of the genetics of PD, advances in understanding molecular pathways and physiology, especially transcriptional factor (TF) regulators, and the development of model systems to probe etiology and potential therapeutic applications.
CACNA1A Mutations Associated With Epilepsies and Their Molecular Sub-Regional Implications
Authors: Li Xue-Lian , Li Zong-Jun , Liang Xiao-Yu , Liu De-Tian , Jiang Mi , Gao Liang-Di , Li Huan , Tang Xue-Qing , Shi Yi-Wu , Li Bing-Mei , He Na , Li Bin , Bian Wen-Jun , Yi Yong-Hong , Cheng Chuan-Fang , Wang Jie
Published: May 2022

Purpose

Previously, mutations in the voltage-gated calcium channel subunit alpha1 A (CACNA1A) gene have been reported to be associated with paroxysmal disorders, typically as episodic ataxia type 2. To determine the relationship between CACNA1A and epilepsies and the role of molecular sub-regional on the phenotypic heterogeneity.

Methods

Trio-based whole-exome sequencing was performed in 318 cases with partial epilepsy and 150 cases with generalized epilepsy. We then reviewed all previously reported CACNA1A mutations and analyzed the genotype-phenotype correlations with molecular sub-regional implications.

Results

We identified 12 CACNA1A mutations in ten unrelated cases of epilepsy, including four de novo null mutations (c.2963_2964insG/p.Gly989Argfs*78, c.3089 + 1G > A, c.4755 + 1G > T, and c.6340-1G > A), four de novo missense mutations (c.203G > T/p.Arg68Leu, c.3965G > A/p.Gly1322Glu, c.5032C > T/p.Arg1678Cys, and c.5393C > T/p.Ser1798Leu), and two pairs of compound heterozygous missense mutations (c.4891A > G/p.Ile1631Val& c.5978C > T/p.Pro1993Leu and c.3233C > T/p.Ser1078Leu&c.6061G > A/p.Glu2021Lys). The eight de novo mutations were evaluated as pathogenic or likely pathogenic mutations according to the criteria of American College of Medical Genetics and Genomics (ACMG). The frequencies of the compound heterozygous CACNA1A mutations identified in this cohort were significantly higher than that in the controls of East Asian and all populations (P = 7.30 × 10–4, P = 2.53 × 10–4). All of the ten cases were ultimately seizure-free after antiepileptic treatment, although frequent epileptic seizures were observed in four cases. Further analysis revealed that episodic ataxia type 2 (EA2) had a tendency of higher frequency of null mutations than epilepsies. The missense mutations in severe epileptic phenotypes were more frequently located in the pore region than those in milder epileptic phenotypes (P = 1.67 × 10–4); de novo mutations in the epilepsy with intellectual disability (ID) had a higher percentage than those in the epilepsy without ID (P = 1.92 × 10–3).

Conclusion

This study suggested that CACNA1A mutations were potentially associated with pure epilepsy and the spectrum of epileptic phenotypes potentially ranged from the mild form of epilepsies such as absence epilepsy or partial epilepsy, to the severe form of developmental epileptic encephalopathy. The clinical phenotypes variability is potentially associated with the molecular sub-regional of the mutations.
Comparison of DNA Methylation Changes Between the Gestation Period and the After-Delivery State: A Pilot Study of 10 Women
Authors: Lin Ming-Wei , Tsai Mong-Hsun , Shih Ching-Yu , Tai Yi-Yun , Lee Chien-Nan , Lin Shin-Yu
Published: May 2022

Background

Gestational adaptation occurs soon after fertilization and continues throughout pregnancy, whereas women return to a pre-pregnancy state after delivery and lactation. However, little is known about the role of DNA methylation in fine-tuning maternal physiology. Understanding the changes in DNA methylation during pregnancy is the first step in clarifying the association of diet, nutrition, and thromboembolism with the changes in DNA methylation. In this study, we investigated whether and how the DNA methylation pattern changes in the three trimesters and after delivery in ten uncomplicated pregnancies.

Results

DNA methylation was measured using a Human MethylationEPIC BeadChip. There were 14,018 cytosine-guanine dinucleotide (CpG) sites with statistically significant changes in DNA methylation over the four time periods (p <
0.001). Overall, DNA methylation after delivery was higher than that of the three trimesters (p < 0.001), with the protein ubiquitination pathway being the top canonical pathway involved. We classified the CpG sites into nine groups according to the changes in the three trimesters and found that 38.37% of CpG sites had DNA methylation changes during pregnancy, especially between the first and second trimesters.

Conclusion

DNA methylation pattern changes between trimesters, indicating possible involvement in maternal adaptation to pregnancy. Meanwhile, DNA methylation patterns during pregnancy and in the postpartum period were different, implying that puerperium repair may also function through DNA methylation mechanisms.
Signal Pathways Involved in the Interaction Between Tumor-Associated Macrophages/TAMs and Glioblastoma Cells
Authors: Liu Xiaojin , Liu Yuan , Qi Yiwei , Huang Yimin , Hu Feng , Dong Fangyong , Shu Kai , Lei Ting
Published: May 2022

It is commonly recognized, that glioblastoma is a large complex composed of neoplastic and non-neoplastic cells. Tumor-associated macrophages account for the majority of tumor bulk and play pivotal roles in tumor proliferation, migration, invasion, and survival. There are sophisticated interactions between malignant cells and tumor associated-macrophages. Tumor cells release a variety of chemokines, cytokines, and growth factors that subsequently lead to the recruitment of TAMs, which in return released a plethora of factors to construct an immunosuppressive and tumor-supportive microenvironment. In this article, we have reviewed the biological characteristics of glioblastoma-associated macrophages and microglia, highlighting the emerging molecular targets and related signal pathways involved in the interaction between TAMs and glioblastoma cells, as well as the potential TAMs-associated therapeutic targets for glioblastoma.
Can Natural Products be Used to Overcome the Limitations of Colorectal Cancer Immunotherapy?
Authors: Dong Jiahuan , Qian Yufan , Zhang Guangtao , Lu Lu , Zhang Shengan , Ji Guang , Zhao Aiguang , Xu Hanchen
Published: May 2022

Colorectal cancer (CRC) is a common cancer of the digestive system that endangers human health. Immunotherapy is widely used in the treatment of patients with cancer. Some patients with dMMR/MSI-H CRC benefit from treatments that use immune checkpoint inhibitors, but most CRC patients are not sensitive to immunotherapy. Furthermore, internal resistance and immune escape lead to a reduced immunotherapy response. Therefore, the development of an effective combination therapy to improve the response rate to immunotherapy is a goal of cancer research. Natural products are potential candidates for comprehensive cancer treatments due to their wide range of immunomodulatory effects through multifactorial underlying mechanisms. In this review, we summarize the challenges in the treatment of CRC and assess the immunomodulatory effects of natural products and their active components. Our work suggests that natural products represent potential options for combined CRC immunotherapy.
Burnout in Pediatric Nephrology Fellows and Faculty: Lessons From the Sustainable Pediatric Nephrology Workforce Project (SUPERPOWER)
Authors: Halbach Susan M. , Pillutla Kartik , Seo-Mayer Patricia , Schwartz Alan , Weidemann Darcy , Mahan John D.
Published: May 2022

Physician well-being is an important contributor to both job satisfaction and patient outcomes. Rates of burnout among physicians vary by specialty, ranging from 35 to 70%. Among pediatric residents, longitudinal data demonstrates consistent rates of burnout around 50-60%, although little is known about burnout among pediatric subspecialty fellows. Specifically, the degree of burnout among pediatric nephrologists remains unknown, as does the impact faculty burnout may have on trainee burnout. We sought to evaluate prevalence and predictors of burnout among US pediatric nephrology fellows and faculty, and assess for interactions between groups. In this multi-center pilot survey of all United States pediatric nephrology training programs from February to April 2020, burnout was assessed through abbreviated Maslach Burnout Inventory and predictors were explored through survey items devoted to demographic, personal characteristics, and job and career satisfaction questions. A total of 30/34 available fellows and 86/102 faculty from 11 institutions completed the survey (overall response rate 85%). The prevalence of burnout was 13% among fellows and 16% among faculty. Demographic (age, gender, year of training, faculty rank, marital status) and program factors (fellowship size, faculty size, current block/rotation, vacation or weekend off timing) were not significantly associated with burnout. Faculty and fellows with burnout reported significantly lower quality of life (5.3 vs. 7.9, p < 0.05), higher perceived stress (2.4 vs. 1.4, p < 0.05) and lower satisfaction with career choice (66 vs. 22%) and work life balance (28 vs. 0%), compared to those without burnout (p < 0.05 for all). Other important factors positively associated with burnout included lower institutional support for wellness programs and lower satisfaction with both colleague and faculty support. Larger studies are needed to explore if burnout is truly less prevalent among pediatric nephrology fellows and faculty compared to pediatric residents and graduate physicians. A larger sample size is also necessary to determine whether any interactions exist between the faculty and trainee roles in the developments of burnout. Future studies should also explore how to promote well-being through addressing key factors such as overall learning/working environment, stress reduction, and building personal resilience.
Pediatric Average Volume Assured Pressure Support
Authors: Saddi Vishal , Thambipillay Ganesh , Martin Bradley , Blecher Gregory , Teng Arthur
Published: May 2022

Average volume assured pressure support (AVAPS) is a modality of non-invasive ventilation that enables the machine to deliver a pre-set tidal volume by adjusting the inspiratory pressure support within a set range. Data on its use in the pediatric population are limited to case reports and single centre case series. This article reviews paediatric data on use of AVAPS and highlights the need for validation to help develop specific guidelines on use of AVAPS in children.
Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes
Authors: Piccialli Ilaria , Tedeschi Valentina , Caputo Lucia , D’Errico Stefano , Ciccone Roselia , De Feo Vincenzo , Secondo Agnese , Pannaccione Anna
Published: May 2022

Alzheimer’s disease (AD) is a chronic, complex neurodegenerative disorder mainly characterized by the irreversible loss of memory and cognitive functions. Different hypotheses have been proposed thus far to explain the etiology of this devastating disorder, including those centered on the Amyloid-β (Aβ) peptide aggregation, Tau hyperphosphorylation, neuroinflammation and oxidative stress. Nonetheless, the therapeutic strategies conceived thus far to treat AD neurodegeneration have proven unsuccessful, probably due to the use of single-target drugs unable to arrest the progressive deterioration of brain functions. For this reason, the theoretical description of the AD etiology has recently switched from over-emphasizing a single deleterious process to considering AD neurodegeneration as the result of different pathogenic mechanisms and their interplay. Moreover, much relevance has recently been conferred to several comorbidities inducing insulin resistance and brain energy hypometabolism, including diabetes and obesity. As consequence, much interest is currently accorded in AD treatment to a multi-target approach interfering with different pathways at the same time, and to life-style interventions aimed at preventing the modifiable risk-factors strictly associated with aging. In this context, phytochemical compounds are emerging as an enormous source to draw on in the search for multi-target agents completing or assisting the traditional pharmacological medicine. Intriguingly, many plant-derived compounds have proven their efficacy in counteracting several pathogenic processes such as the Aβ aggregation, neuroinflammation, oxidative stress and insulin resistance. Many strategies have also been conceived to overcome the limitations of some promising phytochemicals related to their poor pharmacokinetic profiles, including nanotechnology and synthetic routes. Considering the emerging therapeutic potential of natural medicine, the aim of the present review is therefore to highlight the most promising phytochemical compounds belonging to two major classes, polyphenols and monoterpenes, and to report the main findings about their mechanisms of action relating to the AD pathogenesis.
Peedanil Gold, Herbo-Mineral Formulation, Moderates Cytokine Levels and Attenuates Pathophysiology in Monosodium Iodoacetate Induced Osteoarthritis in SD Rat Model
Authors: Balkrishna Acharya , Sinha Sandeep , Karumuri Shadrak , Srivastava Jyotish , Haldar Swati , Varshney Anurag
Published: May 2022

The inflammatory cartilaginous degeneration of the articular joints, mostly those of knee, hips and hands, is osteoarthritis (OA). The available treatment strategies for osteoarthritis are designed for pain relief, molecular targeting, cartilage regeneration and surgical intervention. However, meta-analysis of clinical trials has shown these strategies to be sub-optimal, thereby, eliciting a need for investigating alternative options. The herbo-mineral formulation, Peedanil Gold (PN-G) has been used against joint pains and inflammation. In the current study, anti-osteoarthritic effects of PN-G were investigated in rat model of OA, induced by intra-articular injection of monosodium-iodoacetate. PN-G treatment improved the clinical and Kellgren & Lawrence scores; and rescued the osteoarthritic rats from hyperalgesia and allodynia. Besides, PN-G treatment ameliorated joint inflammation and abrogated in vivo osteoarthritic pathology through effective cartilage regeneration, measured radiologically and histopathologically. PN-G also reduced the levels of interleukin-6 (IL-6) and interleukin-1 beta (IL-1β), in a dose dependent manner, in inflamed human macrophagic THP-1 cells, thereby, reaffirming its anti-inflammatory property at cytosafe concentrations. Ultra High performance liquid chromatography (UHPLC) revealed the presence of several analgesic and anti-inflammatory phytocompounds, like ellagic acid, guggulsterone E, guggulsterone Z, 5-(hydroxymethyl) furfural, corilagin, cinnamic acid, ferulic acid, gallic acid and protocatechuic acid in PN-G. In conclusion, this study has succinctly demonstrated that PN-G is capable of relieving the clinical symptoms of osteoarthritis, which is measurable through the established osteoarthritic serum biomarker, Cartilage Oligomeric Matrix Protein (COMP).
Detection of Inhomogeneity After Mixing Solutions by Analyzing the Chemical Wave Pattern in the Belousov-Zhabotinsky Reaction
Authors: Okamoto Yasunao , Okita Erika , Yamamoto Daigo , Nakata Satoshi , Shioi Akihisa
Published: May 2022

The correlation between BZ reaction and mixing state has been studied for decades, and the researchers are trying to apply it to chemical engineering. We observed a chemical wave pattern in the Belouzov-Zhabotinsky (BZ) reaction based on the inhomogeneity after mixing BZ and ferroin solutions with a mixing method named the rotation-and-stop method. A one-dimensional chemical wave appeared for large inhomogeneity in mixing. The frequency and wavenumber decreased with decreasing degree of inhomogeneity. In an almost perfectly mixed state, the wavenumber significantly reduced and approached the global oscillation. The degree of mixing could be efficiently determined by this reported method. Perfect mixing has never been realized in natural and biological systems. The results of this study can be applied to estimate the degree of mixing in a solution that is not being stirred after the mixing process.
Controllable Phononic Low-Pass Filter via Optomechanical Interactions
Authors: Yang Cheng , Sheng Jiteng , Wu Haibin
Published: May 2022

We present an experimental demonstration of an optically controllable phononic low-pass filter in a multimode optomechanical system. By coupling two spatially separated nanomechanical resonators via optomechanical interactions, the phononic signal below a cutoff frequency can be transferred between mechanical resonators, while the signal above the cutoff frequency is attenuated, which resembles an electronic low-pass filter. Moreover, the cutoff frequency is controllable by tuning the optomechanical interaction via the intracavity field. Our results provide an essential element in phononic circuits and have potential applications for information processing in hybrid quantum systems.
Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology
Authors: Oliveira Thamires Siqueira , Santos Anderson Teixeira , Andrade Cherley Borba Vieira , Silva Johnatas Dutra , Blanco Natália , Rocha Nazareth de Novaes , Woyames Juliana , Silva Pedro Leme , Rocco Patricia Rieken Macedo , da-Silva Wagner Seixas , Ortiga-Carvalho Tânia Maria , Bloise Flavia Fonseca
Published: May 2022

Graphical Abstract

Septic diaphragm has impaired morphology and increased thickness that seems to be associated, at least in part, with decreased mitochondrial function related to reducing in Pgc1α expression, ATP production, mitochondrial number, and quality in the CLP mice compared with the control group.
Thickened Retinal Nerve Fiber Layers Associated With High-Altitude Headache
Authors: Yin Xianhong , Li Yi , Ma Yanyun , Xie Yuan , Wang Kun , Sun Dayan , Liu Xiaoyu , Hao Meng , Liang Meng , Zhang Shixuan , Guo Yuan , Jin Li , Wang Ningli , Wang Jiucun
Published: May 2022

Purpose: This study aimed to quantify the different quadrants of the optic nerve head (ONH) and macular parameters and their changes during exposure to high altitude, and to assess their correlation with high-altitude headache (HAH).

Methods: Spectral-domain optical coherence tomography (OCT) was used to quantify changes in the retinal structure in 109 healthy subjects during acute exposure to high altitude (3,700 m). Self-reported symptoms of HAH and acute mountain sickness AMS were assessed using Lake Louise Score (LLS), alongside measurements of physiological parameters (oxygen saturation [SpO2], heart rate [HR], hemoglobin level [Hb], and red blood cell [RBC] count). Measurements were taken before and after exposure to the high-altitude environment. The correlations of these parameters and changes at ONH were examined.

Results: With the exposure to high altitude, the incidence of AMS was 44.0% and the frequency of HAH was 67.0% (54.1% mild, 12.9% moderate-severe). As for systemic parameters measured at high altitude, the participants exhibited significantly lower SpO2, higher resting HR, higher Hb, and a higher RBC (all p < 0.05). Key stereometric parameters used to describe ONH [superior, inferior, nasal, temporal, and mean retinal nerve fiber layer (RNFL) thickness] and macula (macular thickness) increased at high altitude compared with baseline. Most parameters of ONH changed, especially superior, inferior, and mean RNFL thickness (p < 0.05). There was a significant correlation between the ratios of RNFL at ONH and HAH [mean thickness (r = 0.246, p = 0.01); inferior (r = 0.216, p = 0.02); nasal (r = 0.193, p = 0.04)]. No associations between parameters of ONH and AMS or LLS were observed.

Conclusion: The high-altitude environment can increase RNFL thickness at ONH. Furthermore, we found that the ratios of mean thickness, inferior area, and nasal area correlated positively with HAH, which provides new insights for understanding of the underlying pathological mechanisms of high-altitude retinopathy (HAR).
NtNAC053, A Novel NAC Transcription Factor, Confers Drought and Salt Tolerances in Tobacco
Authors: Li Xiaoxu , Wang Qi , Guo Cun , Sun Jinhao , Li Zhiyuan , Wang Yaofu , Yang Aiguo , Pu Wenxuan , Guo Yongfeng , Gao Junping , Wen Liuying
Published: May 2022

The NAC (NAM, ATAF1/2, and CUC2) family acts as one of the largest families of the transcription factor in the plant kingdom and was revealed to function as the important regulators in various environmental stresses. However, a few studies were reported about the biofunctions of the NAC transcription factor in tobacco. In the current study, we characterized a novel NAC transcription factor encoding the gene NtNAC053 in tobacco, which was significantly up-regulated when exposed to salt and drought treatments. The results of cis-acting elements analysis suggested that the promoter region of NtNAC053 gene possesses a number of stress-responsive elements, and this gene could be induced by exogenous abscisic acid (ABA) treatment. Moreover, the NtNAC053–GFP fusion protein was localized in the cell nucleus and possessed a transactivation domain in its C-terminal, implying that NtNAC053 may undertake as a transcriptional activator in tobacco. Notably, the overexpression of NtNAC053 in tobacco resulted in hypersensitivity to ABA treatment. Furthermore, these overexpression lines showed significantly enhanced tolerances to drought and salt stresses. Under salt and drought stresses, these overexpression lines possessed higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities. Interestingly, the expressions of putative stress-related genes, including NtCOR15A, NtRAB18, NtDREB1A, NtERF5, NtKAT2, and NtERD11, were up-regulated in these overexpression lines when subjected to salt and drought stresses. The clues provided in our study suggested that the NtNAC053 gene encodes a novel NAC transcription factor and could confer the drought and salt stress tolerances by inspiring the downstream stress-responsive genes and antioxidant system in tobacco.