bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies
Authors: Zhou Guoyang , Wang Yongjie , Gao Shiqi , Fu Xiongjie , Cao Yang , Peng Yucong , Zhuang Jianfeng , Hu Junwen , Shao Anwen , Wang Lin
Published: April 2021

Ischemic stroke (IS) remains one of the major causes of death and disability due to the limited ability of central nervous system cells to regenerate and differentiate. Although several advances have been made in stroke therapies in the last decades, there are only a few approaches available to improve IS outcome. In the acute phase of IS, mechanical thrombectomy and the administration of tissue plasminogen activator have been widely used, while aspirin or clopidogrel represents the main therapy used in the subacute or chronic phase. However, in most cases, stroke patients fail to achieve satisfactory functional recovery under the treatments mentioned above. Recently, cell therapy, especially stem cell therapy, has been considered as a novel and potential therapeutic strategy to improve stroke outcome through mechanisms, including cell differentiation, cell replacement, immunomodulation, neural circuit reconstruction, and protective factor release. Different stem cell types, such as mesenchymal stem cells, marrow mononuclear cells, and neural stem cells, have also been considered for stroke therapy. In recent years, many clinical and preclinical studies on cell therapy have been carried out, and numerous results have shown that cell therapy has bright prospects in the treatment of stroke. However, some cell therapy issues are not yet fully understood, such as its optimal parameters including cell type choice, cell doses, and injection routes; therefore, a closer relationship between basic and clinical research is needed. In this review, the role of cell therapy in stroke treatment and its mechanisms was summarized, as well as the function of different stem cell types in stroke treatment and the clinical trials using stem cell therapy to cure stroke, to reveal future insights on stroke-related cell therapy, and to guide further studies.
Mitofusin-2: A New Mediator of Pathological Cell Proliferation
Authors: Xin Yanguo , Li Junli , Wu Wenchao , Liu Xiaojing
Published: April 2021

Cell proliferation is an important cellular process for physiological tissue homeostasis and remodeling. The mechanisms of cell proliferation in response to pathological stresses are not fully understood. Mitochondria are highly dynamic organelles whose shape, number, and biological functions are modulated by mitochondrial dynamics, including fusion and fission. Mitofusin-2 (Mfn-2) is an essential GTPase-related mitochondrial dynamics protein for maintaining mitochondrial network and bioenergetics. A growing body of evidence indicates that Mfn-2 has a potential role in regulating cell proliferation in various cell types. Here we review these new functions of Mfn-2, highlighting its crucial role in several signaling pathways during the process of pathological cell proliferation. We conclude that Mfn-2 could be a new mediator of pathological cell proliferation and a potential therapeutic target.
Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma
Authors: Bai Changsen , Wang Hailong , Dong Dong , Li Tong , Yu Zhi , Guo Junfei , Zhou Wei , Li Ding , Yan Ruochen , Wang Liyan , Wang Zhaosong , Li Yueguo , Ren Li
Published: April 2021

Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis.
Rearrangement Strategy for the Preparation of Polymers With π-Conjugated Structures
Authors: Tang Jian , Xie Tinghao , Geng Jieting , Hua Jing , Wang Zhaobo
Published: April 2021

π-Conjugated polymers are usually prepared by polymerization only. In this perspective article, typical synthesis methods of conjugated polymers are briefly summarized, and a novel strategy for preparing conjugated polymers by rearrangement is proposed. During the metalation process, many conjugated structures were generated in polybutadiene by double bond migration. The effects of reaction time, temperature, and catalyst dosage on the product structure were investigated. Moreover, the structure of the products was confirmed by FTIR, 1H NMR, and 2D HSQC NMR spectra. Thus, a possible reaction mechanism was proposed, in which polybutadiene generates allylic carbanions in the presence of n-butyllithium, and then the double bonds migrate through the carbanions rearrangement to generate many conjugated structures in the backbone chain. The method shows promise in facile and low-cost synthesis of conjugated polymers without the need for precious metal catalysts.
VscF in T3SS1 Helps to Translocate VPA0226 in Vibrio parahaemolyticus
Authors: Lian Lele , Xue Jiao , Li Wanjun , Ren Jianluan , Tang Fang , Liu Yongjie , Xue Feng , Dai Jianjun
Published: April 2021

In Vibrio parahaemolyticus, type III secretion system 1 (T3SS1) is a major virulence factor that delivers effectors into the host eukaryotic cytoplasm; however, studies on its infection mechanism are currently limited. To determine the function of the vscF gene, we constructed the vscF deletion mutant ΔvscF and complementation strain CΔvscF. Compared with those of wild-type POR-1 and CΔvscF, the cytotoxic, adherent, and apoptotic abilities of ΔvscF in HeLa cells were significantly reduced (P < 0.01). Furthermore, in infected HeLa cells, the mutant strain reduced the translocation rates of VP1683 and VP1686 effectors compared to the wild-type and complementation strains. A BLAST search showed that vscF is homologous to the MixH needle protein of Shigella flexneri, indicating that the vscF gene encodes the needle protein of T3SS1 in V. parahaemolyticus. Additional translocation assays showed that VPA0226 translocated into the HeLa eukaryotic cytoplasm via T3SS1, secretion assays showed that VPA0226 can be secreted to supernatant by T3SS1, indicating that VPA0226 belongs to the unpublished class of T3SS1 effectors. In conclusion, our data indicate an essential role of vscF in V. parahaemolyticus T3SS1 and revealed that VPA0226 can be secreted into the host cell cytoplasm via T3SS1. This study provides insights into a previously unexplored aspect of T3SS1, which is expected to contribute to the understanding of its infection mechanism.
Aerobic Versus Resistance Training Effects on Ventricular-Arterial Coupling and Vascular Function in the STRRIDE-AT/RT Trial
Authors: Lekavich Carolyn L. , Allen Jason D. , Bensimhon Daniel R. , Bateman Lori A. , Slentz Cris A. , Samsa Gregory P. , Kenjale Aarti A. , Duscha Brian D. , Douglas Pamela S. , Kraus William E.
Published: April 2021

Background: The goal was studying the differential effects of aerobic training (AT) vs. resistance training (RT) on cardiac and peripheral arterial capacity on cardiopulmonary (CP) and peripheral vascular (PV) function in sedentary and obese adults.

Methods: In a prospective randomized controlled trial, we studied the effects of 6 months of AT vs. RT in 21 subjects. Testing included cardiac and vascular ultrasoundography and serial CP for ventricular-arterial coupling (Ees/Ea), strain-based variables, brachial artery flow-mediated dilation (BAFMD), and peak VO2 (pVO2; mL/kg/min) and peak O2-pulse (O2p; mL/beat).

Results: Within the AT group (n = 11), there were significant increases in rVO2 of 4.2 mL/kg/min (SD 0.93) (p = 0.001); O2p of 1.9 mL/beat (SD 1.3) (p = 0.008) and the brachial artery post-hyperemia peak diameter 0.18 mm (SD 0.08) (p = 0.05). Within the RT group (n = 10) there was a significant increase in left ventricular end diastolic volume 7.0 mL (SD 9.8; p = 0.05) and percent flow-mediated dilation (1.8%) (SD 0.47) (p = 0.004). Comparing the AT and RT groups, post exercise, rVO2 2.97, (SD 1.22), (p = 0.03), O2p 0.01 (SD 1.3), (p = 0.01), peak hyperemic blood flow volume (1.77 mL) (SD 140.69) (p = 0.009), were higher in AT, but LVEDP 115 mL (SD 7.0) (p = 0.05) and Ees/Ea 0.68 mmHg/ml (SD 0.60) p = 0.03 were higher in RT.

Discussion: The differential effects of AT and RT in this hypothesis generating study have important implications for exercise modality and clinical endpoints.
Non-HDL-C Is More Stable Than LDL-C in Assessing the Percent Attainment of Non-fasting Lipid for Coronary Heart Disease Patients
Authors: Guo Li-Ling , Chen Yan-qiao , Lin Qiu-zhen , Tian Feng , Xiang Qun-Yan , Zhu Li-yuan , Xu Jin , Wen Tie , Liu Ling
Published: April 2021

This study aimed to compare the percentage attainment of fasting and non-fasting LDL-C and non-HDL-C target levels in coronary heart disease (CHD) patients receiving short-term statin therapy. This study enrolled 397 inpatients with CHD. Of these, 197 patients took statins for <1 month (m) or did not take any statin before admission (CHD1 group), while 204 patients took statins for ≥1 m before admission (CHD2 group). Blood lipid levels were measured at 0, 2, and 4 h after a daily breakfast. Non-fasting LDL-C and non-HDL-C levels significantly decreased after a daily meal (P < 0.05). Both fasting and non-fasting LDL-C or non-HDL-C levels were significantly lower in the CHD2 group. The percentage attainment of LDL-C <1.4 mmol/L at 2 and 4 h after a daily breakfast was significantly higher than that during fasting (P < 0.05), but the percent attainment of non-fasting non-HDL-C <2.2 mmol/L was close to its fasting value (P > 0.05). Analysis of c-statistic showed that non-fasting cut-off points for LDL-C and non-HDL-C were 1.19 and 2.11 mmol/L, corresponding to their fasting goal levels of 1.4 and 2.2 mmol/L, respectively. When post-prandial LDL-C and non-HDL-C goal attainments were re-evaluated using non-fasting cut-off points, there were no significant differences in percentage attainment between fasting and non-fasting states. Non-HDL-C is more stable than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients. If we want to use LDL-C to assess the percent attainment of post-prandial blood lipids, we may need to determine a lower non-fasting cut-off point.
The Effects of Non-Nutritive Sweetener Consumption in the Pediatric Populations: What We Know, What We Don’t, and What We Need to Learn
Authors: Shum Betty , Georgia Senta
Published: April 2021

Childhood obesity is increasing at an alarming rate in the United States. This trend carries serious risk of children developing obesity-related diseases including Type 2 diabetes and cardiovascular disease. Non-nutritive sweeteners (NNS) are used as substitution for table sugar as a way to prevent weight gain. Their consumption is ubiquitous in adults and children; however the long-term health outcomes of chronic NNS consumption in children are unclear. Conflicting observational studies suggest that children consuming NNS are at risk of obesity and development of type 2 diabetes, while others concluded some benefits in weight reduction. Here, we review the physiological mechanisms that can contribute to the negative metabolic effects of NNS. We will focus on how NNS alters the sweet perception leading to increase caloric consumption, how NNs alters the gut microbiota, and how NNS may disrupt glucose homeostasis and initiate a vicious cycle of pancreatic endocrine dysfunction. Studies focused on the pediatric population are limited but necessary to determine whether the potential weight loss benefits outweigh the potential negative metabolic outcomes during this critical development period.
Everolimus Related Fulminant Hepatitis in Pancreatic Neuroendocrine Tumor With Liver Metastases: A Case Report and Literature Review
Authors: Chang Shih-Chun , Tsai Chun-Yi , Liu Keng-Hao , Wang Shang-yu , Hsu Jun-Te , Yeh Ta-Sen , Yeh Chun-Nan
Published: April 2021

Background

Everolimus, an immunosuppressant, is approved for the treatment of advanced renal cell carcinoma, metastatic hormone receptor-positive breast cancer, and pancreatic neuroendocrine tumors (P-NETs) but has been reported to be related to hepatitis B reactivation. Here, we present the first case of fatal fulminant hepatitis B reactivation in a man with P-NET accompanied by multiple liver metastases who received everolimus and octreotide long-acting repeatable (LAR).

Case Presentation

A 45-year-old male had a history of chronic hepatitis B infection. He was found to have a complicated liver cyst incidentally, and then he underwent biopsy, which disclosed a grade 2 neuroendocrine tumor (NET). Subsequent MRI of the abdomen and PET revealed a solid mass at the pancreatic tail with numerous liver tumors favoring metastases and peripancreatic lymph node metastases. Transarterial chemoembolization (TACE) of the right lobe of the liver was performed, and he started to take 5 mg everolimus twice a day and 20 mg octreotide LAR every month 8 days after the 1st TACE. No hepatitis B virus (HBV) prophylaxis treatment was administered. He then underwent laparoscopic distal pancreatectomy and splenectomy three and half months after the initial treatment of everolimus. He continued everolimus 5 mg twice a day and octreotide 20 mg every month after the operation. Three months later, hepatic failure occurred due to acute hepatitis B flare-up–related fulminant hepatic failure since other possible causes of hepatic failure were excluded. Five days after hepatic failure presented, hepatic failure was apparent, and pulseless ventricular tachycardia occurred. The patient expired after failed resuscitation.

Conclusion

A literature review of everolimus-related hepatitis B reactivation was conducted. In P-NET patients with chronic hepatitis B who will undergo everolimus treatment, HBV prophylaxis should be considered since fatal hepatitis B reactivation might occur under rare conditions.
The Impact of COVID-19 Pandemic Lockdown on the Incidence of New-Onset Type 1 Diabetes and Ketoacidosis Among Saudi Children
Authors: Alaqeel Aqeel , Aljuraibah Fahad , Alsuhaibani Mohammed , Huneif Mohammed , Alsaheel Abdulhameed , Dubayee Mohammad Al , Alsaedi Abdulaziz , Bakkar Ayman , Alnahari Ahmed , Taha Areej , Alharbi Khulood , Alanazi Yousef , Almadhi Samia , Khalifah Reem Al
Published: April 2021

Background

Overburdened healthcare systems during the coronavirus disease (COVID-19) pandemic led to suboptimal chronic disease management, including that of pediatric type 1 diabetes mellitus (T1DM). The pandemic also caused delayed detection of new-onset diabetes in children; this increased the risk and severity of diabetic ketoacidosis (DKA). We therefore investigated the frequency of new-onset pediatric T1DM and DKA in Saudi Arabia during the COVID-19 pandemic and compared it to the same period in 2019.

Methods

We conducted a multicenter retrospective cohort study, including patients aged 1–14 years admitted with new-onset T1DM or DKA during the COVID-19 pandemic (March–June 2020) and the same period in 2019. We assessed factors including age, sex, anthropometric measures, nationality, duration of diabetes, diabetes management, HbA1c levels, glycemic control, cause of admission, blood gas levels, etiology of DKA, DKA complications, length of hospital stay, and COVID-19 test status.

Result

During the lockdown, 106 children, compared with 154 in 2019, were admitted to 6 pediatric diabetes centers. Among the admissions, DKA was higher in 2020 than in 2019 (83% vs. 73%; P=0.05; risk ratio=1.15; 95% confidence interval, 1.04–1.26), after adjusting for age and sex. DKA frequency among new-onset T1DM and HbA1c levels at diagnosis were higher in 2020 than in 2019 (26% vs. 13.4% [P=<0.001] and 12.1 ± 0.2 vs. 10.8 ± 0.25 [P<0.001], respectively). Females and older patients had a higher risk of DKA.

Conclusion

The lockdown implemented in Saudi Arabia has significantly impacted children with T1DM and led to an increased DKA frequency, including children with new-onset T1DM, potentially owing to delayed presentation.
Can Chinese Families Achieve a Low-Carbon Lifestyle? An Empirical Test of China’s Low-Carbon Pilot Policy
Authors: Sun Xuetao , Wang Zhenhua
Published: April 2021

Global warming has caused concern among countries worldwide. Since 2010, the Chinese government has implemented low-carbon pilot policies (LCPPs) in some regions to control carbon emissions. To evaluate the implementation effects of the LCPPs, we matched China’s macro data with Chinese household financial survey data. Specifically, we used a OLS model for assessing the impact of LCPPs on China’s household carbon emissions and conducted heterogeneous analysis. Further, we evaluated the mechanism through which LCPPs affect the carbon emissions of Chinese households. The research results yielded three main findings. (1) LCPPs can promote a reduction in household carbon emissions; however, the impact of LCPPs on household carbon emissions exhibits a time lag. (2) LCPPs reduce household carbon emissions by promoting the upgradation of the household consumption structure. The LCPP enables households to reduce consumption of products involving high levels of carbon emissions, while increasing consumption of low-carbon emission products, thereby affecting total household carbon emissions. (3) An analysis of household heterogeneity revealed that LCPPs mainly affect household carbon emissions in the country’s eastern and central regions, especially urban households’ carbon emissions. This paper describes the implementation effects of LCPPs and suggests a viable path for the further implementation of LCPPs.
UAV to Inform Restoration: A Case Study From a California Tidal Marsh
Authors: Haskins John , Endris Charlie , Thomsen Alexandra S. , Gerbl Fuller , Fountain Monique C. , Wasson Kerstin
Published: April 2021

Monitoring of environmental restoration is essential to communicate progress and improve outcomes of current and future projects, but is typically done in a very limited capacity due to budget and personnel constraints. Unoccupied aerial vehicles (UAVs) have been used in a variety of natural and human-influenced environments and have been found to be time- and cost-efficient, but have not yet been widely applied to restoration contexts. In this study, we evaluated the utility of UAVs as an innovative tool for monitoring tidal marsh restoration. We first optimized methods for creating high-resolution orthomosaics and Structure from Motion digital elevation models from UAV imagery by conducting experiments to determine an optimal density of ground control points (GCPs) and flight altitude for UAV monitoring of topography and new vegetation. We used elevation models and raw and classified orthomosaics before, during, and after construction of the restoration site to communicate with various audiences and inform adaptive management. We found that we could achieve 1.1 cm vertical accuracy in our elevation models using 2.1 GCPs per hectare at a flight altitude of 50 m. A lower flight altitude of 30 m was more ideal for capturing patchy early plant cover while still being efficient enough to cover the entire 25-hectare site. UAV products were valuable for several monitoring applications, including calculating the volume of soil moved during construction, tracking whether elevation targets were achieved, quantifying and examining the patterns of vegetation development, and monitoring topographic change including subsidence, erosion, and creek development. We found UAV monitoring advantageous for the ability to survey areas difficult to access on foot, capture spatial variation, tailor timing of data collection to research needs, and collect a large amount of accurate data rapidly at relatively low cost, though with some compromise in detail compared with field monitoring. In summary, we found that UAV data informed the planning, implementation and monitoring phases of a major landscape restoration project and could be valuable for restoration in many habitats.
Long-Term Growth of Alfalfa Increased Soil Organic Matter Accumulation and Nutrient Mineralization in a Semi-Arid Environment
Authors: Song Xin , Fang Chao , Yuan Zi-Qiang , Li Feng-Min
Published: April 2021

Land use patterns and vegetation coverage in semi-arid areas of the Loess Plateau have undergone great changes due to the implementation of the “Grain for Green” project. The introduction of legume pasture species, such as alfalfa (Medicago sativa L.) and sweet clover (Melilotus officinalis L.), is one of the most efficient methods of vegetation restoration and reconstruction in this region. However, there is a need for an effective assessment of the root system distribution and its interaction with soil after long-term introduction. An experiment involving the introduction of alfalfa and sweet clover on abandoned farmlands was initiated in 2003 to assess the long-term effects. After 17 years, root and soil samples at depths of 0–20 and 20–60 cm were collected to characterize the root biomass, root carbon (C), nitrogen (N), and phosphorus (P), soil microbial biomass carbon (MBC) and nitrogen (MBN), soil organic carbon (SOC), and soil N and P. The results showed that the root biomass density of alfalfa in the 0–20 and 20–60 cm layers (63.72 and 12.27 kg m–3, respectively) were significantly higher than for sweet clover (37.43 and 8.97 kg m–3, respectively) and under natural abandonment (38.92 and 9.73 kg m–3, respectively). The SOC, total nitrogen (TN), total phosphorus (TP), available phosphorus (AP), nitrate-nitrogen (NO3–-N), MBC and MBN in the 0–20 and 20–60 cm layers were higher after alfalfa introduction compared with sweet clover introduction and natural abandonment, although the ammonia-nitrogen (NH4+-N) concentration in the 0–20 cm layer was lower. There were significantly positive correlations between root biomass density and both soil nutrients and microbial biomass, while there was a negative correlation between the soil NH4+-N and root biomass density. These results indicate that alfalfa root growth improved soil organic matter accumulation and nutrient mineralization. The accumulation and mineralization of soil nutrients also guaranteed root and microorganism growth. Therefore, it was concluded that alfalfa introduction will promote soil nutrients immobilization and mineralization and may enable sustainable land use in the semi-arid region of the Loess Plateau, China.
Untargeted Metabolomic Profiling of the Correlation Between Prognosis Differences and PD-1 Expression in Sepsis: A Preliminary Study
Authors: Bu Y. , Wang H. , Ma X. , Han C. , Jia X. , Zhang J. , Liu Y. , Peng Y. , Yang M. , Yu K. , Wang C.
Published: April 2021

Objectives: The mortality rate of sepsis remains very high. Metabolomic techniques are playing increasingly important roles in diagnosis and treatment in critical care medicine. The purpose of our research was to use untargeted metabolomics to identify and analyze the common differential metabolites among patients with sepsis with differences in their 7-day prognosis and blood PD-1 expression and analyze their correlations with environmental factors.

Methods: Plasma samples from 18 patients with sepsis were analyzed by untargeted LC-MS metabolomics. Based on the 7-day prognoses of the sepsis patients or their levels of PD-1 expression on the surface of CD4+ T cells in the blood, we divided the patients into two groups. We used a combination of multidimensional and monodimensional methods for statistical analysis. At the same time, the Spearman correlation analysis method was used to analyze the correlation between the differential metabolites and inflammatory factors.

Results: In the positive and negative ionization modes, 16 and 8 differential metabolites were obtained between the 7-day death and survival groups, respectively; 5 and 8 differential metabolites were obtained between the high PD-1 and low PD-1 groups, respectively. We identified three common differential metabolites from the two groups, namely, PC (P-18:0/14:0), 2-ethyl-2-hydroxybutyric acid and glyceraldehyde. Then, we analyzed the correlations between environmental factors and the common differences in metabolites. Among the identified metabolites, 2-ethyl-2-hydroxybutyric acid was positively correlated with the levels of IL-2 and lactic acid (Lac) (P < 0.01 and P < 0.05, respectively).

Conclusions: These three metabolites were identified as common differential metabolites between the 7-day prognosis groups and the PD-1 expression level groups of sepsis patients. They may be involved in regulating the expression of PD-1 on the surface of CD4+ T cells through the action of related environmental factors such as IL-2 or Lac, which in turn affects the 7-day prognosis of sepsis patients.
Tremella fuciformis Polysaccharides Inhibited Colonic Inflammation in Dextran Sulfate Sodium-Treated Mice via Foxp3+ T Cells, Gut Microbiota, and Bacterial Metabolites
Authors: Xu Yingyin , Xie Liyuan , Zhang Zhiyuan , Zhang Weiwei , Tang Jie , He Xiaolan , Zhou Jie , Peng Weihong
Published: April 2021

Tremella fuciformis is an edible medicinal mushroom, and its polysaccharide components are found to confer various health benefits. This study identified the protective effects of polysaccharides of Tremella fuciformis (TPs) against dextran sulfate sodium (DSS)-induced colitis in mice. High dose of TPs (HTPs) could prevent the colon from shortening, reduce activity of colonic myeloperoxidase and serum diamine oxidase (DAO), decrease the concentration of D-lactate, and alleviate the colonic tissue damage in colitic mice. HTPs treatment stimulated Foxp3+T cells, and promoted the production of anti-inflammatory cytokines whereas it reduced the production of pro-inflammatory and the portion of immunoglobulin A (IgA)-coated bacteria, which was related to modulation of immune responses. 16S rRNA sequencing analysis showed that TPs could significantly increase gut community diversity, and restore the relative abundances of Lactobacillus, Odoribacter, Helicobacter, Ruminococcaceae, and Marinifilaceae. According to metabolomic analysis, HTPs induced specific microbial metabolites akin to that in normal mice. Tyrosine biosynthesis, tryptophan metabolism, and bile acid metabolism were influenced in the HTPs group compared with those in the DSS group. HTPs could alleviate DSS-induced colitis by immunoregulation and restored the gut microbiota and microbial metabolites. The results indicated that HTPs have potential to be developed as a food supplement to ameliorate intestinal diseases.
Method for Reproducible Shipboard Segmented Flow Analysis Ammonium Measurement Using an In-House Reference Material for Quality Control
Authors: Rees Christine , Janssens Julie , Sherrin Kendall , Hughes Peter , Tibben Stephen , McMahon Merinda , McDonald Jack , Camac Alicia , Schwanger Cassie , Marouchos Andreas
Published: April 2021

Ammonium is a fundamental nutrient for phytoplankton growth in seawater and is a key component of the microbial loop. Ammonium measured in parallel with other nutrients is crucial in understanding the small temporal scale changes in oceanographic ecology. Despite the importance of measuring ammonium at sea, owing to its lability, there is no consensus on the best method. The lack of availability of certified reference materials for ammonium in seawater also makes it difficult to assess the accuracy and reproducibility of ammonium measurements. In this study we present a modified segmented flow analysis method using ortho-phthaldialdehyde (OPA) with fluorescence detection to measure ammonium at sea together with four other macro-nutrients (nitrate, nitrite, silicate and phosphate) in near real time. An in-house ammonium quality control (QC) material was produced to improve the accuracy and repeatability of the measurement at sea. The QC was prepared following two different methods and stored in two types of containers. The suitability of the in-house QC’s as a reference material were assessed onboard the RV Investigator in 2018 during two oceanographic voyages, including one on the repeat SR03 CLIVAR transect. This paper describes the production and assessment of the in-house QC for ammonium in seawater, providing groundwork for creating a short-term stable ammonium reference material for sea going voyages. The uncertainty of this method of ammonium measurement was found to be 0.10 μmol/L at ammonium concentration of 1.0 μmol/L. Results show that preparation of the QC inside a laminar flow cabinet and directly into 10 mL polypropylene sample tubes just prior to the commencement of the voyage improved its stability.
Pruning and Tending Immune Memories: Spacer Dynamics in the CRISPR Array
Authors: Garrett Sandra C.
Published: April 2021

CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated genes) is a type of prokaryotic immune system that is unique in its ability to provide sequence-specific adaptive protection, which can be updated in response to new threats. CRISPR-Cas does this by storing fragments of DNA from invading genetic elements in an array interspersed with short repeats. The CRISPR array can be continuously updated through integration of new DNA fragments (termed spacers) at one end, but over time existing spacers become obsolete. To optimize immunity, spacer uptake, residency, and loss must be regulated. This mini-review summarizes what is known about how spacers are organized, maintained, and lost from CRISPR arrays.
The Adjuvant Effects on Vaccine and the Immunomodulatory Mechanisms of Polysaccharides From Traditional Chinese Medicine
Authors: Wang Danyang , Liu Yonghui , Zhao Wei
Published: April 2021

Vaccination is still the most successful strategy to prevent and control the spread of infectious diseases by generating an adequate protective immune response. However, vaccines composed of antigens alone can only stimulate weak immunogenicity to prevent infection in many cases. Adjuvant can enhance the immunogenicity of the antigens. Therefore, adjuvant is urgently needed to strengthen the immune response of the vaccines. An ideal adjuvant should be safe, cheap, biodegradable and biologically inert. In addition to having a long shelf life, it can also promote cellular and humoral immune responses. Traditional Chinese medicine (TCM) has many different ingredients, such as glycosides, polysaccharides, acids, terpenes, polyphenols, flavonoids, alkaloids, and so on. TCM polysaccharides are one of the main types of biologically active substances. They have a large range of pharmacological activities, especially immunomodulatory. TCM polysaccharides can regulate the immune system of animals by binding to multiple receptors on the surface of immune cells and activating different signal pathways. This review focuses on a comprehensive summary of the most recent developments in vaccine adjuvant effects of polysaccharides from many important TCM, such asArtemisia rupestris L., Cistanche deserticola, Pinus massoniana, Chuanminshen violaceum, Astragalus,Ganoderma lucidum, Codonopsis pilosula, Lycium barbarum, Angelica, Epimedium, and Achyranthes bidentata.Moreover, this review also introduces their immunomodulatory effects and the molecular mechanisms of action on animal bodies, which showed that TCM polysaccharides can activate macrophages, the signal pathway of T/B lymphocytes, regulate the signal pathway of natural killer cells, activate the complement system, and so on.
Event-Related Potential Measures of the Passive Processing of Rapidly and Slowly Presented Auditory Stimuli in MCI
Authors: Kamal Farooq , Morrison Cassandra , Campbell Kenneth , Taler Vanessa
Published: April 2021

Much research effort is currently devoted to the development of a simple, low-cost method to determine early signs of Alzheimer’s disease (AD) pathology. The present study employs a simple paradigm in which event-related potentials (ERPs) were recorded to a single auditory stimulus that was presented rapidly or very slowly while the participant was engaged in a visual task. A multi-channel EEG was recorded in 20 healthy older adults and 20 people with mild cognitive impairment (MCI). In two different conditions, a single 80 dB sound pressure level (SPL) auditory stimulus was presented every 1.5 s (fast condition) or every 12.0 s (slow condition). Participants were instructed to watch a silent video and ignore the auditory stimuli. Auditory processing thus occurred passively. When the auditory stimuli were presented rapidly (every 1.5 s), N1 and P2 amplitudes did not differ between the two groups. When the stimuli were presented very slowly, the amplitude of N1 and P2 increased in both groups and their latencies were prolonged. The amplitude of N1 did not significantly differ between the two groups. However, the subsequent positivity was reduced in people with MCI compared to healthy older adults. This late positivity in the slow condition may reflect a delayed P2 or a summation of a composite P2 + P3a. In people with MCI, the priority of processing may not be switched from the visual task to the potentially much more relevant auditory input. ERPs offer promise as a means to identify the pathology underlying cognitive impairment associated with MCI.
Effects of Remote Immune Activation on Performance in the 5-Choice Serial Reaction Time Task Following Mild Traumatic Brain Injury in Adolescence
Authors: Kaukas Lola , Krieg Justin , Collins-Praino Lyndsey , Corrigan Frances
Published: April 2021

In adult pre-clinical models, traumatic brain injury (TBI) has been shown to prime microglia, exaggerating the central inflammatory response to an acute immune challenge, worsening depressive-like behavior, and enhancing cognitive deficits. Whether this phenomenon exists following mTBI during adolescence has yet to be explored, with age at injury potentially altering the inflammatory response. Furthermore, to date, studies have predominantly examined hippocampal-dependent learning domains, although pre-frontal cortex-driven functions, including attention, motivation, and impulsivity, are significantly affected by both adolescent TBI and acute inflammatory stimuli. As such, the current study examined the effects of a single acute peripheral dose of LPS (0.33 mg/kg) given in adulthood following mTBI in mid-adolescence in male Sprague–Dawley rats on performance in the 5-choice serial reaction time task (5-CSRTT). Only previously injured animals given LPS showed an increase in omissions and reward collection latency on the 5-CSRTT, with no effect noted in sham animals given LPS. This is suggestive of impaired motivation and a prolonged central inflammatory response to LPS administration in these animals. Indeed, morphological analysis of myeloid cells within the pre-frontal cortex, via IBA1 immunohistochemistry, found that injured animals administered LPS had an increase in complexity in IBA1+ve cells, an effect that was seen to a lesser extent in sham animals. These findings suggest that there may be ongoing alterations in the effects of acute inflammatory stimuli that are driven, in part by increased reactivity of microglial cells.
Non-invasive Urinary Biomarkers in Moyamoya Disease
Authors: Sesen Julie , Driscoll Jessica , Moses-Gardner Alexander , Orbach Darren B. , Zurakowski David , Smith Edward R.
Published: April 2021

Introduction:A major difficulty in treating moyamoya disease is the lack of effective methods to detect novel or progressive disease prior to the onset of disabling stroke. More importantly, a tool to better stratify operative candidates and quantify response to therapy could substantively complement existing methods. Here, we present proof-of-principle data supporting the use of urinary biomarkers as diagnostic adjuncts in pediatric moyamoya patients.

Methods:Urine and cerebrospinal fluid specimens were collected from pediatric patients with moyamoya disease and a cohort of age and sex-matched control patients. Clinical and radiographic data were paired with measurements of a previously validated panel of angiogenic proteins quantified by ELISA. Results were compared to age and sex-matched controls and subjected to statistical analyses.

Results:Evaluation of a specific panel of urinary and cerebrospinal fluid biomarkers by ELISA demonstrated significant elevations of angiogenic proteins in samples from moyamoya patients compared to matched controls. ROC curves for individual urinary biomarkers, including MMP-2, MMP-9, MMP-9/NGAL, and VEGF, showed excellent discrimination. The optimal urinary biomarker was MMP-2, providing a sensitivity of 88%, specificity of 100%, and overall accuracy of 91%. Biomarker levels changed in response to therapy and correlated with radiographic evidence of revascularization.

Conclusions:We report, for the first time, identification of a panel of urinary biomarkers that predicts the presence of moyamoya disease. These biomarkers correlate with presence of disease and can be tracked from the central nervous system to urine. These data support the hypothesis that urinary proteins are useful predictors of the presence of moyamoya disease and may provide a basis for a novel, non-invasive method to identify new disease and monitor known patients following treatment.
Secreted Amyloid Precursor Protein-Alpha Enhances LTP Through the Synthesis and Trafficking of Ca2+-Permeable AMPA Receptors
Authors: Livingstone Rhys W. , Elder Megan K. , Singh Anurag , Westlake Courteney M. , Tate Warren P. , Abraham Wickliffe C. , Williams Joanna M.
Published: April 2021

Regulation of AMPA receptor expression by neuronal activity and neuromodulators is critical to the expression of both long-term potentiation (LTP) and memory. In particular, Ca2+-permeable AMPARs (CP-AMPAR) play a unique role in these processes due to their transient, activity-regulated expression at synapses. Secreted amyloid precursor protein-alpha (sAPPα), a metabolite of the parent amyloid precursor protein (APP) has been previously shown to enhance hippocampal LTP as well as memory formation in both normal animals and in Alzheimer’s disease models. In earlier work we showed that sAPPα promotes trafficking of GluA1-containing AMPARs to the cell surface and specifically enhances synthesis of GluA1. To date it is not known whetherde novosynthesized GluA1 form CP-AMPARs or how they contribute to sAPPα-mediated plasticity. Here, using fluorescent non-canonical amino acid tagging–proximity ligation assay (FUNCAT-PLA), we show that brief treatment of primary rat hippocampal neurons with sAPPα (1 nM, 30 min) rapidly enhanced the cell-surface expression ofde novoGluA1 homomers and reduced levels ofde novoGluA2, as well as extant GluA2/3-AMPARs. Thede novoGluA1-containing AMPARs were localized to extrasynaptic sites and later internalized by sAPPα-driven expression of the activity-regulated cytoskeletal-associated protein, Arc. Interestingly, longer exposure to sAPPα increased synaptic levels of GluA1/2 AMPARs. Moreover, the sAPPα-mediated enhancement of LTP in area CA1 of acute hippocampal slices was dependent on CP-AMPARs. Together, these findings show that sAPPα engages mechanisms which specifically enhance the synthesis and cell-surface expression of GluA1 homomers, underpinning the sAPPα-driven enhancement of synaptic plasticity in the hippocampus.
Strategies for Dodging the Obstacles in CAR T Cell Therapy
Authors: Safarzadeh Kozani Pooria , Safarzadeh Kozani Pouya , Rahbarizadeh Fatemeh , Khoshtinat Nikkhoi Shahryar
Published: April 2021

Chimeric antigen receptor (CAR) T cell therapy has offered cancer patients a new alternative therapeutic choice in recent years. This novel type of therapy holds tremendous promise for the treatment of various hematologic malignancies including B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. However, CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. Adverse events such as cytokine release syndrome (CRS), neurotoxicity, graft rejection, on-target off-tumor toxicities, and tumor relapse have tied the rescuing hands of CAR T cell therapies. Moreover, in the case of solid tumor treatment, CAR T cell therapies have not yielded encouraging results mainly due to challenges such as the formidable network of the tumor microenvironments (TME) that operates in a suppressive fashion resulting in CAR T cell dysfunction. In this review, we tend to shine a light on emerging strategies and solutions for addressing the mentioned barriers. These solutions might dramatically help shorten the gap between a successful clinical outcome and the hope for it.
Exosomal MicroRNAs Mediating Crosstalk Between Cancer Cells With Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in the Tumor Microenvironment
Authors: Su Tong , Zhang Panpan , Zhao Fujun , Zhang Shu
Published: April 2021

Exosomes are small extracellular vesicles containing diverse bioactive molecules. They play essential roles in mediating bidirectional interplay between cancer and stromal cells. Specific elements are selected into different types of exosomes via various mechanisms, including microRNAs (miRNAs), a subset of non-coding RNA that could epigenetically reprogram cells and modulate their activities. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are two major types of stromal cells inhibiting immune response and facilitating tumor progression. Notably, accumulated studies provided critical evidence regarding the significance of exosomal miRNA–mediated intercellular crosstalk between cancer cells with TAMs and CAFs for tumor progression. This review aimed to summarize the current knowledge of cell–cell interactions between stromal and cancer cells conveyed by exosome-derived miRNAs. The findings might help find effective therapeutic targets of cancer.
Integrative Analysis of Methylation and Copy Number Variations of Prostate Adenocarcinoma Based on Weighted Gene Co-expression Network Analysis
Authors: Hou Yaxin , Hu Junyi , Zhou Lijie , Liu Lilong , Chen Ke , Yang Xiong
Published: April 2021

Prostate adenocarcinoma (PRAD) is the most pervasive carcinoma diagnosed in men with over 170,000 new cases every year in the United States and is the second leading cause of death from cancer in men despite its indolent clinical course. Prostate-specific antigen testing, which is the most commonly used non-invasive diagnostic method for PRAD, has improved early detection rates in the past decade, but its effectiveness for monitoring disease progression and predicting prognosis is controversial. To identify novel biomarkers for these purposes, we carried out weighted gene co-expression network analysis of the top 10,000 variant genes in PRAD from The Cancer Genome Atlas in order to identify gene modules associated with clinical outcomes. Methylation and copy number variation analysis were performed to screen aberrantly expressed genes, and the Kaplan–Meier survival and gene set enrichment analyses were conducted to evaluate the prognostic value and potential mechanisms of the identified genes. Cyclin E2 (CCNE2), rhophilin Rho GTPase-binding protein (RHPN1), enhancer of zeste homolog 2 (EZH2), tonsoku-like DNA repair protein (TONSL), epoxide hydrolase 2 (EPHX2), fibromodulin (FMOD), and solute carrier family 7 member (SLC7A4) were identified as potential prognostic indicators and possible therapeutic targets as well. These findings can improve diagnosis and disease monitoring to achieve better clinical outcomes in PRAD.
Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression
Authors: Li Huili , Wang Jiliang , Huang Kun , Zhang Tao , Gao Lu , Yang Sai , Yi Wangyang , Niu Yanfeng , Liu Hongli , Wang Zheng , Wang Guobin , Tao Kaixiong , Wang Lin , Cai Kailin
Published: April 2021

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene,in vitroandin vivotumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1expression.