bluuebunny/crossref_metadata_2025 huggingface dataset:
High Levels of Multi Drug Resistant Escherichia coli Pathovars in Preharvest Environmental Samples: A Ticking Time Bomb for Fresh Produce Related Disease Outbreak
Authors: Iwu Chidozie Declan , Kayode Adeoye John , Igere Bright Esegbuyota , Okoh Anthony Ifeanyin
Published: March 2022

The preharvest environment provides a suitable platform for the emergence and dissemination of multidrug resistant pathogenic bacteria. This could be detrimental to public health and may lead to fresh produce related disease outbreaks when transferred to the food web. This study evaluated the occurrence and antibiogram fingerprints of the pathogenic strains of Escherichia coli (E. coli) recovered from irrigation water and agricultural soil samples in fresh produce farms in the Eastern Cape Province, South Africa. E. coli was isolated, pathotyped and screened for antibiogram fingerprints using standard cultural and molecular methods. An antibiogram-based K-means cluster analysis and neighbour-joining dendrogram was used to elucidate the relatedness of the isolates. Of the confirmed isolates, 37% harboured at least one of the screened virulence genes (VGs) that encode for intestinal and extraintestinal E. coli pathovars. The most prevalent pathovar/associated VG in all the samples was Enterohemorrhagic E. coli/stx2. Of all the antimicrobials tested, E. coli pathovars conferred the highest resistance against ampicillin with a median single antimicrobial resistance (AMR) index of 0.23 (IQR: 0.10–0.38, 95% CI: 0.16–0.27) for pathovars from irrigation water and 0.01 (IQR: 0.01–0.03, 95% CI: 0.01–0.03) for pathovars from agricultural soil. About 60 and 20% of the pathovars from irrigation water and agricultural soil were multi drug resistant with a median multiple AMR index of 0.41 (IQR: 0.25–0.52, 95% CI: 0.31–0.47) and 0.38 (IQR: 0.23–0.66, 95% CI: 0.19–0.69) respectively. The most prevalent resistance genes detected were sulI, catII, tetA and AmpC across all sample types. The blaTEM was the most prevalent extended-spectrum β-lactamase resistance gene detected. A positive correlation between the phenotypic and genotypic AMR profiles of the pathovars in irrigation water samples, r = 0.6, p ≤ 0.01 and agricultural soil samples, r = 0.8, p ≤ 0.01 was recorded. The antibiogram based dendrogram generated 11 and 7 clades from irrigation water and agricultural soil samples respectively, indicating that the isolates are highly diversified. The findings revealed the occurrence of highly diversified multidrug resistant E. coli pathovars in the preharvest environment, indicating potential public health threats.
Changes in Green Space Use During a COVID-19 Lockdown Are Associated With Both Individual and Green Space Characteristics
Authors: Berdejo-Espinola Violeta , Zahnow Renee , Suárez-Castro Andrés F. , Rhodes Jonathan R. , Fuller Richard A.
Published: March 2022

Mobility restrictions imposed during the COVID-19 pandemic present a useful study system for understanding the temporal and spatial patterns of green space use. Here, we examine green space characteristics and sociodemographic factors associated with change in frequency of green space use before and during a COVID-19 lockdown in Brisbane, Australia drawing on a survey of 372 individuals. Applying regression analysis, we found that individuals who visited a different green space during lockdown than before tended to decrease their frequency of visits. In contrast, individuals who continued visiting their usual green space during lockdown were more inclined to increase their number of visits. Changes in frequency of green space use were also associated with particular characteristics of their usually visited green space. The presence of blue spaces and accessibility (carparks/public transport) were associated with increased frequency of use while foliage height diversity was associated with reduced frequency of use. We found that females were more likely to change their green space visitation frequency during COVID-19 compared to men and they also reported greater importance of green spaces for social and family interactions and spiritual reasons during COVID-19 compared to before. Males showed greater increases than females in the importance of green space for nature interactions and mental health benefits during the COVID-19 lockdown compared to before. Our results provide key insights for future resilient urban planning and policy that can fulfil a wide range of physical and psychological needs during a time of crisis and beyond.
A Novel Necroptosis-Related lncRNA Signature Predicts the Prognosis of Lung Adenocarcinoma
Authors: Lu Yinliang , Luo XueHui , Wang Qi , Chen Jie , Zhang Xinyue , Li YueSen , Chen Yuetong , Li Xinyue , Han Suxia
Published: March 2022

Background: Necroptosis is closely related to the tumorigenesis and development of cancer. An increasing number of studies have demonstrated that targeting necroptosis could be a novel treatment strategy for cancer. However, the predictive potential of necroptosis-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) still needs to be clarified. This study aimed to construct a prognostic signature based on necroptosis-related lncRNAs to predict the prognosis of LUAD.

Methods: We downloaded RNA sequencing data from The Cancer Genome Atlas database. Co-expression network analysis, univariate Cox regression, and least absolute shrinkage and selection operator were adopted to identify necroptosis-related prognostic lncRNAs. We constructed the predictive signature by multivariate Cox regression. Kaplan–Meier analysis, time-dependent receiver operating characteristics, nomogram, and calibration curves were used to validate and evaluate the signature. Subsequently, we used gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between the predictive signature and tumor immune microenvironment of risk groups. Finally, the correlation between the predictive signature and immune checkpoint expression of LUAD patients was also analyzed.

Results: We constructed a signature composed of 7 necroptosis-related lncRNAs (AC026355.2, AC099850.3, AF131215.5, UST-AS2, ARHGAP26-AS1, FAM83A-AS1, and AC010999.2). The signature could serve as an independent predictor for LUAD patients. Compared with clinicopathological variables, the necroptosis-related lncRNA signature has a higher diagnostic efficiency, with the area under the receiver operating characteristic curve being 0.723. Meanwhile, when patients were stratified according to different clinicopathological variables, the overall survival of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the low-risk group. ssGSEA further confirmed that the predictive signature was significantly related to the immune status of LUAD patients. The immune checkpoint analysis displayed that low-risk patients had a higher immune checkpoint expression, such as CTLA-4, HAVCR2, PD-1, and TIGIT. This suggested that immunological function is more active in the low-risk group LUAD patients who might benefit from checkpoint blockade immunotherapies.

Conclusion: The predictive signature can independently predict the prognosis of LUAD, helps elucidate the mechanism of necroptosis-related lncRNAs in LUAD, and provides immunotherapy guidance for patients with LUAD.
Body Appreciation, Depressive Symptoms, and Self-Esteem in Pregnant and Postpartum Brazilian Women
Authors: Meireles Juliana Fernandes Filgueiras , Neves Clara Mockdece , Amaral Ana Carolina Soares , Morgado Fabiane Frota da Rocha , Ferreira Maria Elisa Caputo
Published: March 2022

Background

During pregnancy and the postpartum period, women experience tremendous biopsychosocial changes in a short period of time. Poor body appreciation, depressive symptoms, and low self-esteem during the perinatal period may cause negative consequences for both the mother and the infant's physiological and psychological health. The aim of this study was to analyze the differences in body appreciation, depressive symptoms, and self-esteem between the three gestational trimesters and the postpartum period.

Methods

Participants (N = 1,423 pregnant and postpartum Brazilian women), aged between 18 and 42 years old (M = 29.22; SD = ±5.72), answered questionnaires on body appreciation, depressive symptoms, and self-esteem. BMI was self-reported. Descriptive and nonparametric covariance analysis were performed, comparing women who were in the first, second, and third trimesters and the postpartum period.

Results

Body appreciation was significantly higher among women in the third trimester compared to those in the first and second trimester. However, it was lower for women in all three gestational trimesters than for those in the postpartum. There was no difference in self-esteem during pregnancy, but it was significantly lower in the postpartum group. Similarly, depressive symptoms did not vary through pregnant groups but it was significantly higher in the postpartum group.

Conclusions

The results showed that the postpartum period can be a difficult experience for women. They presented poor body appreciation and lower self-esteem and higher depressive symptoms compared to the pregnancy period. Therefore, it is necessary for public health policies to support women in this period, preserving their mental health and making this experience more positive.
Global Proteomic Analyses Reveals Abnormal Immune Regulation in Patients With New Onset Ankylosing Spondylitis
Authors: Yu Zongchao , Hong Xiaoping , Zhang Xiaoli , Zheng Fengping , Liu Fanna , Xu Huixuan , Zhu Chengxin , Cai Wanxia , Liu Dongzhou , Yin Lianghong , Hu Bo , Tang Donge , Dai Yong
Published: March 2022

Background

Ankylosing spondylitis (AS) is a chronic inflammatory disease with serious consequences and a high rate of morbidity and mortality, In our previous work, we reveal the key features of proteins in new-onset ankylosing spondylitis patients.

Material and Methods

Ankylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine, and inflammation plays an essential role in AS pathogenesis. The inflammatory process in AS, however, is still poorly understood due to its intricacy. Systematic proteomic and phosphorylation analyses of peripheral blood mononuclear cells (PBMCs) were used to investigate potential pathways involved in AS pathogenesis.

Results

Liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was performed and discovered 782 differentially expressed proteins (DEPs) and 122 differentially phosphorylated proteins (DPPs) between 9 new-onset AS patients and 9 healthy controls. The DEPs were further verified using parallel reaction monitoring (PRM) analysis. PRM analysis verified that 3 proteins (HSP90AB1, HSP90AA1 and HSPA8) in the antigen processing and presentation pathway, 6 proteins (including ITPR1, MYLK and STIM1) in the platelet activation pathway and 10 proteins (including MYL12A, MYL9 and ROCK2) in the leukocyte transendothelial migration pathway were highly expressed in the PBMCs of AS patients.

Conclusion

The key proteins involved in antigen processing and presentation, platelet activation and leukocyte transendothelial migration revealed abnormal immune regulation in patients with new-onset AS. These proteins might be used as candidate markers for AS diagnosis and new therapeutic targets, as well as elucidating the pathophysiology of AS.
Roles of Insect Oenocytes in Physiology and Their Relevance to Human Metabolic Diseases
Authors: Huang Kerui , Liu Ying , Perrimon Norbert
Published: March 2022

Oenocytes are large secretory cells present in the abdomen of insects known to synthesize very-long-chain fatty acids to produce hydrocarbons and pheromones that mediate courtship behavior in adult flies. In recent years, oenocytes have been implicated in the regulation of energy metabolism. These hepatocyte-like cells accumulate lipid droplets under starvation and can non-autonomously regulate tracheal waterproofing and adipocyte lipid composition. Here, we summarize evidence, mostly from Drosophila, establishing that oenocytes perform liver-like functions. We also compare the functional differences in oenocytes and the fat body, another lipid storage tissue which also performs liver-like functions. Lastly, we examine signaling pathways that regulate oenocyte metabolism derived from other metabolic tissues, as well as oenocyte-derived signals that regulate energy homeostasis.
Spatiotemporal Modeling of Nursery Habitat Using Bayesian Inference: Environmental Drivers of Juvenile Blue Crab Abundance
Authors: Hyman A. Challen , Chiu Grace S. , Fabrizio Mary C. , Lipcius Romuald N.
Published: March 2022

Nursery grounds provide conditions favorable for growth and survival of juvenile fish and crustaceans through abundant food resources and refugia, and enhance secondary production of populations. While small-scale studies remain important tools to assess nursery value of structured habitats and environmental factors, targeted applications that unify survey data over large spatial and temporal scales are vital to generalize inference of nursery function, identify highly productive regions, and inform management strategies. Using 21 years of spatio-temporally indexed survey data (i.e., water chemistry, turbidity, blue crab, and predator abundance) and GIS information on potential nursery habitats (i.e., seagrass, salt marsh, and unvegetated shallow bottom), we constructed five Bayesian hierarchical models with varying spatial and temporal dependence structures to infer variation in nursery habitat value for young juveniles (20–40 mm carapace width) of the blue crabCallinectes sapiduswithin three tributaries (James, York and Rappahannock Rivers) in lower Chesapeake Bay. Out-of-sample predictions of juvenile blue crab counts from a model considering fully nonseparable spatiotemporal dependence outperformed predictions from simpler models. Salt marsh surface area and turbidity were the strongest determinants of crab abundance (positive association in both cases). Highest crab abundances occurred near the turbidity maximum where relative salt marsh area was greatest. Relative seagrass area, which has been emphasized as the most valuable nursery in studies conducted at small spatial scales, was not associated with high crab abundance within the three tributaries. Hence, salt marshes should be considered a key nursery habitat for the blue crab, even where extensive seagrass beds occur. The patterns between juvenile blue crab abundance and environmental variables also indicated that identification of nurseries should be based on investigations at broad spatial and temporal scales incorporating multiple potential nursery habitats, and based on statistical analyses that address spatial and temporal statistical dependence.
Saturation Approach to Determine Grazing Mortality in Picoeukaryote and Synechococcus Populations
Authors: Archer Stephen D. , Lubelczyk Laura C. , Kunes Moriah , McPhee Kathryn , Dawydiak Walter , Staiger Michael , Posman Kevin M. , Poulton Nicole J.
Published: March 2022

A substantial component of phytoplankton production in the oceans is channeled through protistan grazers but understanding what dictates the magnitude of this process on a regional and temporal basis is limited, in part, by a shortage of experimental options. A novel saturation approach based on the functional response of planktonic grazers to increasing prey abundance was developed using laboratory cultures of the predator-prey combination of Ochromonas danica and Micromonas pusilla and tested in the coastal waters of the Gulf of Maine. In incubation series, 2 μm polystyrene microspheres were used as surrogate prey to generate increasing levels of saturation of predator ingestion rates of natural prey, resulting in increased rates of apparent growth of the picophytoplankton populations. The relationship between level of addition of surrogate prey to apparent growth, consistently provided significant estimates of maximal growth in the absence of grazing and grazing mortality for populations of picoeukaryotes and Synechococcus. Estimates of gross growth and grazing mortality were comparable to results from dilution experiments carried out in the same waters. The saturation approach represents an additional tool to investigate predator-prey interactions in planktonic communities. Further investigations may show that it can be used to quantify group-specific grazing mortality and growth rates beyond coastal waters and in multiple size classes of prey.
Enhanced Magneto-Optical Effect in Heterostructures Composed of Epsilon-Near-Zero Materials and Truncated Photonic Crystals
Authors: Hu Shengyu , Guo Zhiwei , Dong Lijuan , Deng Fusheng , Jiang Haitao , Chen Hong
Published: March 2022

Optical non-reciprocal transmission plays an important role in many applications such as optical isolation, switching, and integrated photonic circuits. However, the non-reciprocity of natural magneto-optical (MO) materials is too weak to be widely used in the actual applications. Magnetized metamaterials enable the exploration of a new regime about the MO effect, including the enhanced non-reciprocal transmission and one-way surface waves. In this work, the Fano-type interference effect is studied in the heterostructure composed of a magnetized epsilon-near-zero material and a truncated photonic crystal. The inherent weak MO activity is significantly enhanced in the heterostructure because of the field intensity enhancement mechanism and Fano interference. The results provide a way to design novel optical non-reciprocal devices with excellent performance using metamaterials.
Artificial Ovary for Young Female Breast Cancer Patients
Authors: Chen Jing , Torres-de la Roche Luz Angela , Kahlert Ulf D. , Isachenko Vladimir , Huang Hui , Hennefründ Jörg , Yan Xiaohong , Chen Qionghua , Shi Wenjie , Li Youzhu
Published: March 2022

In recent decades, there has been increasing attention toward the quality of life of breast cancer (BC) survivors. Meeting the growing expectations of fertility preservation and the generation of biological offspring remains a great challenge for these patients. Conventional strategies for fertility preservation such as oocyte and embryo cryopreservation are not suitable for prepubertal cancer patients or in patients who need immediate cancer therapy. Ovarian tissue cryopreservation (OTC) before anticancer therapy and autotransplantation is an alternative option for these specific indications but has a risk of retransplantation malignant cells. An emerging strategy to resolve these issues is by constructing an artificial ovary combined with stem cells, which can support follicle proliferation and ensure sex hormone secretion. This promising technique can meet both demands of improving the quality of life and meanwhile fulfilling their expectation of biological offspring without the risk of cancer recurrence.
The Prevalence and Risk Factors for Severe Maternal Morbidities: A Systematic Review and Meta-Analysis
Authors: Nik Hazlina Nik Hussain , Norhayati Mohd Noor , Shaiful Bahari Ismail , Mohamed Kamil Halilul Rahman
Published: March 2022

Introduction

Maternal mortality and severe maternal morbidity remain major public health problems globally. Understanding their risk factors may result in better treatment solutions and preventive measures for maternal health. This review aims to identify the prevalence and risk factors of severe maternal morbidity (SMM) and maternal near miss (MNM).

Methods

A systematic review and meta-analysis was conducted to assess the prevalence and risk factors of SMM and MNM. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic search was performed in the MEDLINE (PubMed), CINAHL (EBSCOhost), and Science Direct databases for articles published between 2011 and 2020.

Results

Twenty-four of the 44 studies included were assessed as being of good quality and having a low risk of bias. The prevalence of SMM and MNM was 2.45% (95% CI: 2.03, 2.88) and 1.68% (95% CI: 1.42, 1.95), respectively. The risk factors for SMM included history of cesarean section (OR [95% CI]: 1.63 [1.43, 1.87]), young maternal age (OR [95% CI]: 0.71 [0.60, 0.83]), singleton pregnancy (OR [95% CI]: 0.42 [0.32, 0.55]), vaginal delivery (OR [95% CI]: 0.11 [0.02, 0.47]), coexisting medical conditions (OR [95% CI]: 1.51 [1.28, 1.78]), and preterm gestation (OR [95% CI]: 0.14 [0.08, 0.23]). The sole risk factor for MNM was a history of cesarean section (OR [95% CI]: 2.68 [1.41, 5.10]).

Conclusions

Maternal age, coexisting medical conditions, history of abortion and cesarean delivery, gestational age, parity, and mode of delivery are associated with SMM and MNM. This helps us better understand the risk factors and their strength of association with SMM and MNM. Thus, initiatives such as educational programs, campaigns, and early detection of risk factors are recommended. Proper follow-up is important to monitor the progression of maternal health during the antenatal and postnatal periods.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226137, identifier: CRD42021226137.
A Comprehensive Network Integrating Signature Microbes and Crucial Soil Properties During Early Biological Soil Crust Formation on Tropical Reef Islands
Authors: Wang Lin , Li Jie , Zhang Si
Published: March 2022

Biological soil crusts (BSCs/biocrusts), which are distributed across various climatic zones and well-studied in terrestrial drylands, harbor polyextremotolerant microbial topsoil communities and provide ecological service for local and global ecosystem. Here, we evaluated BSCs in the tropical reef islands of the South China Sea. Specifically, we collected 41 BSCs, subsurface, and bare soil samples from the Xisha and Nansha Archipelagos. High-throughput amplicon sequencing was performed to analyze the bacterial, fungal, and archaeal compositions of these samples. Physicochemical measurement and enzyme activity assays were conducted to characterize the soil properties. Advanced computational analysis revealed 47 biocrust-specific microbes and 10 biocrust-specific soil properties, as well as their correlations in BSC microbial community. We highlighted the previously underestimated impact of manganese on fungal community regulation and BSC formation. We provide comprehensive insight into BSC formation networks on tropical reef islands and established a foundation for BSC-directed environmental restoration.
Inflammasome Contribution to the Activation of Th1, Th2, and Th17 Immune Responses
Authors: Martynova Ekaterina , Rizvanov Albert , Urbanowicz Richard A. , Khaiboullina Svetlana
Published: March 2022

Inflammasomes are cytosolic polyprotein complexes formed in response to various external and internal stimuli, including viral and bacterial antigens. The main product of the inflammasome is active caspase 1 which proteolytically cleaves, releasing functional interleukin-1 beta (IL-1β) and interleukin-18 (IL-18). These cytokines play a central role in shaping immune response to pathogens. In this review, we will focus on the mechanisms of inflammasome activation, as well as their role in development of Th1, Th2, and Th17 lymphocytes. The contribution of cytokines IL-1β, IL-18, and IL-33, products of activated inflammasomes, are summarized. Additionally, the role of cytokines released from tissue cells in promoting differentiation of lymphocyte populations is discussed.
Molecular Genetic Characteristics of Plasmid-Borne mcr-9 in Salmonella enterica Serotype Typhimurium and Thompson in Zhejiang, China
Authors: Fan Jianzhong , Cai Heng , Fang Youhong , He Jintao , Zhang Linghong , Xu Qingye , Yang Yunxing , Leptihn Sebastian , Yu Yunsong , Zhao Dongdong , Hua Xiaoting
Published: March 2022

Salmonella enterica is a zoonotic food-borne pathogen threatening public health around the world. As is the case with many other pathogens, the spread of mobilized colistin resistance (mcr) alleles is of grave concern. In this study, totally 689 clinical Salmonella isolates were collected from a local hospital in Hangzhou, Zhejiang Province, China between 2009 and 2018. Resistance genes were screen by PCR. Two mcr-9-positive Salmonella strains S15 and S639 were identified which belong to serotype Typhimurium and Thompson, respectively. We observed that both mcr-9 genes were located on conjugative IncHI2 plasmids which encoded numerous resistance genes, likely facilitating the dissemination of mcr-9 by co-resistance mechanisms. The mcr-9 cassettes encoded on the two plasmids were not identical: downstream of the mcr-9 genes, we found IS1 on one plasmid (pS15), while the other had a WbuC-IS26 (pS639). Despite the presence of mcr-9 cassettes, the strains were not rendered colistin resistant. Yet, it is of epidemiological importance to implement surveillance to be able to observe and possibly control the spread of mcr-9 due to its potential to mediate resistance to the last-resort antibiotic colistin.
Golgi Phosphoprotein 3 Promotes Colon Cancer Cell Metastasis Through STAT3 and Integrin α3 Pathways
Authors: Huang Anpei , Wang Ruizhi , Cui Ji , Gao Ying , Yin Zheng , Chen Lianzhou , He Meifang , Li Wen
Published: March 2022

Background: Golgi phosphoprotein 3 (GOLPH3) overexpression was recently reported to be associated with a poor clinical outcome in patients with colorectal cancer (CRC). However, the underlying molecular mechanism through which GOLPH3 promotes CRC metastasis remains poorly understood.

Methods:In vitro genetic ablation of GOLPH3 was performed using siRNA transfection, and a stably overexpressed GOLPH3 colon cancer cell line was constructed using the lentivirus system. Cell invasion and migration assays were conducted with or without Matrigel. Immunoblotting, qRT-PCR, immunofluorescence and immunohistochemistry were utilized to study the expression level of GOLPH3, ZEB1, integrin α3 and phosphorylation level of STAT3, AKT/mTOR and Raf/MEK/ERK pathways. Co-immunoprecipitation was used to investigate the interaction between GOLPH3 and p-STAT3 (Tyr705) or total STAT3.

Results: Overexpression of GOLPH3 was found in CRC tissues and colon cancer cell lines. Knockdown of GOLPH3 using siRNAs significantly suppressed the invasion and migration of HCT116 and HCT8 cells. In contrast, the overexpression of GOLPH3 promoted the migratory and invasive ability of colon cancer cells. The phosphorylation level of STAT3 as well as the protein and mRNA levels of ZEB1 and integrin α3, were significantly decreased after GOLPH3 knockdown. Moreover, Integrin α3 expression was correlated with GOLPH3 expression in CRC tissues. Co-immunoprecipitation assay revealed that GOLPH3 interacted with pSTAT3 (Tyr705) and total STAT3. Our further experiments suggested that GOLPH3 facilitated IL-6 induced STAT3 activation and subsequently induced transcription of integrin α3 and ZEB1, which promoted the metastasis and progression of CRC.

Conclusion: Our current work demonstrates that GOLPH3 facilitates STAT3 activation and regulates the expression of EMT transcription factor ZEB1 and Integrin α3 in colon cancer cells. These findings indicate that GOLPH3 plays a critical role in CRC metastasis and might be a new therapeutic target for CRC treatment.
Linking Alzheimer’s Disease and Type 2 Diabetes: Characterization and Inhibition of Cytotoxic Aβ and IAPP Hetero-Aggregates
Authors: Al Adem Kenana , Shanti Aya , Srivastava Amit , Homouz Dirar , Thomas Sneha Ann , Khair Mostafa , Stefanini Cesare , Chan Vincent , Kim Tae-Yeon , Lee Sungmun
Published: March 2022

The cytotoxic self-aggregation of β-amyloid (Aβ) peptide and islet amyloid polypeptide (IAPP) is implicated in the pathogenesis of Alzheimer’s disease (AD) and Type 2 diabetes (T2D), respectively. Increasing evidence, particularly the co-deposition of Aβ and IAPP in both brain and pancreatic tissues, suggests that Aβ and IAPP cross-interaction may be responsible for a pathological link between AD and T2D. Here, we examined the nature of IAPP-Aβ40 co-aggregation and its inhibition by small molecules. In specific, we characterized the kinetic profiles, morphologies, secondary structures and toxicities of IAPP-Aβ40 hetero-assemblies and compared them to those formed by their homo-assemblies. We demonstrated that monomeric IAPP and Aβ40 form stable hetero-dimers and hetero-assemblies that further aggregate into β-sheet-rich hetero-aggregates that are toxic (cell viability <50%) to both PC-12 cells, a neuronal cell model, and RIN-m5F cells, a pancreatic cell model for β-cells. We then selected polyphenolic candidates to inhibit IAPP or Aβ40 self-aggregation and examined the inhibitory effect of the most potent candidate on IAPP-Aβ40 co-aggregation. We demonstrated that epigallocatechin gallate (EGCG) form inter-molecular hydrogen bonds with each of IAPP and Aβ40. We also showed that EGCG reduced hetero-aggregate formation and resulted in lower β-sheets content and higher unordered structures in IAPP-Aβ40-EGCG samples. Importantly, we showed that EGCG is highly effective in reducing the toxicity of IAPP-Aβ40 hetero-aggregates on both cell models, specifically at concentrations that are equivalent to or are 2.5-fold higher than the mixed peptide concentrations. To the best of our knowledge, this is the first study to report the inhibition of IAPP-Aβ40 co-aggregation by small molecules. We conclude that EGCG is a promising candidate to prevent co-aggregation and cytotoxicity of IAPP-Aβ40, which in turn, contribute to the pathological link between AD and T2D.
Metabolic Imaging of Deep Brain Stimulation in Meige Syndrome
Authors: Liu Jiayu , Li Lei , Li Yuan , Wang Qian , Liu Ruen , Ding Hu
Published: March 2022

Objectives

The subthalamic nucleus (STN) has been shown to be a safe and effective deep brain stimulation (DBS) surgical target for the treatment of Meige syndrome. The aim of this study was to compare changes in brain metabolism before and 6 months after STN-DBS surgery.

Methods

Twenty-five patients with primary Meige syndrome underwent motor function assessment, including the Burke–Fahn–Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability subscale (BFMDRS-D) and positron emission tomography with an 18[F]-fluorodeoxyglucose scan before and 6 months after STN-DBS surgery. For the voxelwise metabolic change assessment, the p-value was controlled for multiple comparisons using the familywise error rate.

Results

There was a significant decrease in BFMDRS-M scores 6 months after STN-DBS, from 10.02 ± 3.99 to 4.00 ± 2.69 (p < 0.001). The BFMDRS-D scores also decreased significantly from 4.52 ± 2.90 to 0.64 ± 1.29 (p < 0.001). In the left hemisphere, hypermetabolism was found in the occipital lobe, superior parietal gyrus, postcentral gyrus and thalamus. In the right hemisphere, hypermetabolism was found in the lentiform nucleus, precuneus and precentral gyrus in patients with Meige syndrome receiving DBS. In addition, the bilateral inferior temporal gyrus and middle frontal gyrus exhibited glucose hypermetabolism.

Conclusion

Our findings indicate that STN-DBS has a significant effect on metabolic level in the brain, which may be an important mechanism for the treatment of Meige syndrome using STN-DBS.
Involvement of the Rostromedial Prefrontal Cortex in Human-Robot Interaction: fNIRS Evidence From a Robot-Assisted Motor Task
Authors: Le Duc Trung , Watanabe Kazuki , Ogawa Hiroki , Matsushita Kojiro , Imada Naoki , Taki Shingo , Iwamoto Yuji , Imura Takeshi , Araki Hayato , Araki Osamu , Ono Taketoshi , Nishijo Hisao , Fujita Naoto , Urakawa Susumu
Published: March 2022

Assistive exoskeleton robots are being widely applied in neurorehabilitation to improve upper-limb motor and somatosensory functions. During robot-assisted exercises, the central nervous system appears to highly attend to external information-processing (IP) to efficiently interact with robotic assistance. However, the neural mechanisms underlying this process remain unclear. The rostromedial prefrontal cortex (rmPFC) may be the core of the executive resource allocation that generates biases in the allocation of processing resources toward an external IP according to current behavioral demands. Here, we used functional near-infrared spectroscopy to investigate the cortical activation associated with executive resource allocation during a robot-assisted motor task. During data acquisition, participants performed a right-arm motor task using elbow flexion-extension movements in three different loading conditions: robotic assistive loading (ROB), resistive loading (RES), and non-loading (NON). Participants were asked to strive for kinematic consistency in their movements. A one-way repeated measures analysis of variance and general linear model-based methods were employed to examine task-related activity. We demonstrated that hemodynamic responses in the ventral and dorsal rmPFC were higher during ROB than during NON. Moreover, greater hemodynamic responses in the ventral rmPFC were observed during ROB than during RES. Increased activation in ventral and dorsal rmPFC subregions may be involved in the executive resource allocation that prioritizes external IP during human-robot interactions. In conclusion, these findings provide novel insights regarding the involvement of executive control during a robot-assisted motor task.
Microglia: Key Players in Retinal Ageing and Neurodegeneration
Authors: Guo Li , Choi Soyoung , Bikkannavar Priyanka , Cordeiro M. Francesca
Published: March 2022

Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in maintaining the normal function of the retina and brain. During early development, microglia migrate into the retina, transform into a highly ramified phenotype, and scan their environment constantly. Microglia can be activated by any homeostatic disturbance that may endanger neurons and threaten tissue integrity. Once activated, the young microglia exhibit a high diversity in their phenotypes as well as their functions, which relate to either beneficial or harmful consequences. Microglial activation is associated with the release of cytokines, chemokines, and growth factors that can determine pathological outcomes. As the professional phagocytes in the retina, microglia are responsible for the clearance of pathogens, dead cells, and protein aggregates. However, their phenotypic diversity and phagocytic capacity is compromised with ageing. This may result in the accumulation of protein aggregates and myelin debris leading to retinal neuroinflammation and neurodegeneration. In this review, we describe microglial phenotypes and functions in the context of the young and ageing retina, and the mechanisms underlying changes in ageing. Additionally, we review microglia-mediated retinal neuroinflammation and discuss the mechanisms of microglial involvement in retinal neurodegenerative diseases.
Decoding the Brain's Surface to Track Deeper Activity
Authors: Tenzer Mark L. , Lisinski Jonathan M. , LaConte Stephen M.
Published: March 2022

Neural activity can be readily and non-invasively recorded from the scalp using electromagnetic and optical signals, but unfortunately all scalp-based techniques have depth-dependent sensitivities. We hypothesize, though, that the cortex's connectivity with the rest of the brain could serve to construct proxy signals of deeper brain activity. For example, functional magnetic resonance imaging (fMRI)-derived models that link surface connectivity to deeper regions could subsequently extend the depth capabilities of other modalities. Thus, as a first step toward this goal, this study examines whether or not surface-limited support vector regression of resting-state fMRI can indeed track deeper regions and distributed networks in independent data. Our results demonstrate that depth-limited fMRI signals can in fact be calibrated to report ongoing activity of deeper brain structures. Although much future work remains to be done, the present study suggests that scalp recordings have the potential to ultimately overcome their intrinsic physical limitations by utilizing the multivariate information exchanged between the surface and the rest of the brain.
Organization of Presynaptic Autophagy-Related Processes
Authors: Gundelfinger Eckart D. , Karpova Anna , Pielot Rainer , Garner Craig C. , Kreutz Michael R.
Published: March 2022

Brain synapses pose special challenges on the quality control of their protein machineries as they are far away from the neuronal soma, display a high potential for plastic adaptation and have a high energy demand to fulfill their physiological tasks. This applies in particular to the presynaptic part where neurotransmitter is released from synaptic vesicles, which in turn have to be recycled and refilled in a complex membrane trafficking cycle. Pathways to remove outdated and damaged proteins include the ubiquitin-proteasome system acting in the cytoplasm as well as membrane-associated endolysosomal and the autophagy systems. Here we focus on the latter systems and review what is known about the spatial organization of autophagy and endolysomal processes within the presynapse. We provide an inventory of which components of these degradative systems were found to be present in presynaptic boutons and where they might be anchored to the presynaptic apparatus. We identify three presynaptic structures reported to interact with known constituents of membrane-based protein-degradation pathways and therefore may serve as docking stations. These are (i) scaffolding proteins of the cytomatrix at the active zone, such as Bassoon or Clarinet, (ii) the endocytic machinery localized mainly at the peri-active zone, and (iii) synaptic vesicles. Finally, we sketch scenarios, how presynaptic autophagic cargos are tagged and recruited and which cellular mechanisms may govern membrane-associated protein turnover in the presynapse.
How a 7-Week Food Literacy Cooking Program Affects Cooking Confidence and Mental Health: Findings of a Quasi-Experimental Controlled Intervention Trial
Authors: Rees Joanna , Fu Shih Ching , Lo Johnny , Sambell Ros , Lewis Joshua R. , Christophersen Claus T. , Byrne Matthew F. , Newton Robert U. , Boyle Siobhan , Devine Amanda
Published: March 2022

Obesity and mental health disorders are rising simultaneously with shifting dietary behavior away from home cooking, toward typically nutrition-poor and energy-dense convenience meals. Food literacy strongly influences nutrition choices. Community-based cooking interventions target barriers to healthy eating and facilitate development of food literacy skills, thereby potentially increasing preparation of home-cooked meals and positively influencing health. This study of 657 healthy Australian adults explored the efficacy of a 7-week cooking program in improving cooking confidence, whether this transferred to behavior surrounding food, and/or affected mental health. Significant post-program improvements in cooking confidence and satisfaction (all p < 0.001, ηp2 1.12 large), ability to change eating habits (p < 0.001) and overcome lifestyle barriers (p = 0.005) were observed for the intervention group but not control. Participation also improved mental and general health (all p < 0.05, ηp2 0.02 small). No changes were observed for acquisition and consumption of food, or nutrition knowledge in either group. This 7-week cooking program built cooking confidence and improved general and mental health but did not change dietary behavior. To further improve nutrition related behaviors associated with better mental health, more effort is needed to recruit those with below-average nutrition knowledge and interest in cooking.
Effects of PEF-Assisted Freeze-Drying on Protein Quality, Microstructure, and Digestibility in Chilean Abalone “Loco” (Concholepas concholepas) Mollusk
Authors: Palma-Acevedo Anais , Pérez-Won Mario , Tabilo-Munizaga Gipsy , Ortiz-Viedma Jaime , Lemus-Mondaca Roberto
Published: March 2022

The purpose of this study was to apply different pulsed electric field (PEF) conditions as a pretreatment to the freeze-drying (FD) process of Chilean abalone and to assess its effects on protein quality, microstructure, and digestibility of the freeze-dried product. The treatments PEF (0.5, 1.0, and 2.0 kV cm−1) and cooking (CO) were applied at 100°C × 15 min. Then, their performances were subjected to a FD process. PEF + CO pretreated freeze-dried samples showed shorter process times than freeze-dried control samples without PEF + CO, where the treatment PEF at 2.0 kV cm−1 reached the shortest time. In addition, the abovementioned samples presented the best textural parameters but a low protein content. The thermal properties indicate a total denaturation of the proteins, where the amide I region presented greater mobility in the sample pretreated with an electric field of 2.0 kV cm−1. The assay for digestibility shows better hydrolysis for the 2.0 kV cm−1 PEF sample and has a higher Computer-Protein Efficiency Ratio (C-PER). Thereby, variations in thermal behavior and physicochemical parameters in comparison to combined PEF + CO pretreatments were observed. In addition, high protein quality and digestibility of pretreated freeze-dried Chilean abalones were maintained to the desired properties (texture and C-PER) and conditions (FD time).
Optimization of the Artemisia Polysaccharide Fermentation Process by Aspergillus niger
Authors: Tao Ali , Feng Xuehua , Sheng Yajing , Song Zurong
Published: March 2022

In order to investigate the fermentation process of Artemisia polysaccharides, this paper showcases an investigation into the effects of fermentation time, fermentation temperature, strain inoculum, Artemisia annua addition, and shaker speed on the polysaccharides production of Artemisia annua. The yield of Artemisia polysaccharides content was determined based on the optimization of single-factor test, and then a response surface test was conducted with temperature, inoculum, and time as response variables and the yield of Artemisia polysaccharides as response values. The fermentation process was then optimized and the antioxidant activity of Artemisia polysaccharides was monitored using DPPH, ABTS+, OH, and total reducing power. The optimum fermentation process was determined by the test to be 5% inoculum of Aspergillus niger, temperature 36°C, time 2 d, shaker speed 180 r/min, and 4% addition of Artemisia annua, and the extraction of Artemisia polysaccharides was up to 17.04% by this condition of fermentation. The polysaccharides from Artemisia annua fermented by Aspergillus Niger had scavenging effects on DPPH, ABTS, and OH free radicals.
Systematic Analysis of the Expression and Prognosis of Fcγ Receptors in Clear Cell Renal Cell Carcinoma
Authors: Nie Wenyuan , Yao Yong , Luo Benjun , Zhu Jiyin , Li Shaocheng , Yang Xiaoteng , Luo Tao , Liu Wei , Yan Shibing
Published: March 2022

Background

Clear cell renal cell carcinoma (ccRCC) remains a common malignancy in the urinary system. Although dramatic progress was made in multimodal therapies, the improvement of its prognosis continues to be unsatisfactory. The antibody-binding crystallizable fragment (Fc) γ receptors (FcγRs) are expressed on the surface of leukocytes, to mediate antibody-induced cell-mediated anti-tumor responses when tumor-reactive antibodies are present. FcγRs have been studied extensively in immune cells, but rarely in cancer cells.

Methods

ONCOMINE, UALCAN, GEPIA, TIMER, TISIDB, Kaplan–Meier Plotter, SurvivalMeth, and STRING databases were utilized in this study.

Results

Transcriptional levels of FcγRs were upregulated in patients with ccRCC. There was a noticeable correlation between the over expressions of FCGR1A/B/C, FCGR2A, and clinical cancer stages/tumor grade in ccRCC patients. Besides, higher transcription levels of FcγRs were found to be associated with poor overall survival (OS) in ccRCC patients. Further, high DNA methylation levels of FcγRs were also observed in ccRCC patients, and higher DNA methylation levels of FcγRs were associated with shorter OS. Moreover, we also found that the expression of FcγRs was significantly correlated with immune infiltrates, namely, immune cells (NK, macrophages, Treg, cells) and immunoinhibitor (IL-10, TGFB1, and CTLA-4).

Conclusions

Our study demonstrated that high DNA methylation levels of FcγRs lead to their low mRNA, protein levels, and poor prognosis in ccRCC patients, which may provide new insights into the choice of immunotherapy targets and prognostic biomarkers.
Knockdown of Annexin A2 Enhances Radiosensitivity by Increasing G2/M-Phase Arrest, Apoptosis and Activating the p38 MAPK-HSP27 Pathway in Nasopharyngeal Carcinoma
Authors: He Huocong , Lin Keyu , Zou Changyan , Pan Jianru , Fu Wankai , Zhou Yan , Lin Huamei , Chen Chao , Su Ying
Published: March 2022

Annexin A2 (ANXA2) has been found to be involved in cancer proliferation, metastasis and prognosis; however, its exact role in nasopharyngeal carcinoma (NPC) radioresistance remains unknown. We found that ANXA2 expression was correlated with prognosis in NPC patients, and longer overall survival in NPC patients with low ANXA2 expression than those with high ANXA2 expression. ANXA2 knockdown increased the radiosensitivity in radioresistant NPC cells, and ANXA2 overexpression decreased the radiosensitivity in NPC cells. Knocking-down ANXA2 expression increased the irradiation-induced apoptosis of radioresistant NPC cells, and ANXA2 overexpression decreased the irradiation-induced apoptosis of NPC cells. ANXA2 knockdown induced G2/M phase arrest in NPC cells post-irradiation, and ANXA2 overexpression abrogated G2/M phase arrest in NPC cells post-irradiation. ANXA2 overexpression resulted in inhibition of the p38 MAPK-HSP27 pathway, while ANXA2 knockdown resulted in activation of the p38 MAPK-HSP27 pathway. In addition, ANXA2 knockdown increased the radiosensitivity of the xenografted tumors in nude mice. Our data demonstrate that knockdown of Annexin A2 enhanced radiosensitivity in NPC by increasing G2/M-phase arrest, apoptosis and activating the p38 MAPK-HSP27 pathway. ANXA2 may be a promising target used to overcome radioresistance in NPC.
Case Report: Guillain-Barré Syndrome as Primary Presentation of Systemic Lupus Erythematosus (SLE-GBS) in a Teenage Girl
Authors: Beshir Elham , Belt Ernestina , Chencheri Nidheesh , Saqib Aqdas , Pallavidino Marco , Terheggen Ulrich , Abdalla Abdalla , Herlitz Leal , Sharif Elsadeg , Bitzan Martin
Published: March 2022

Peripheral nervous system involvement accounts for fewer than 10% of SLE cases with neuropsychiatric manifestations. Guillain-Barré syndrome (GBS) as the presenting, major manifestation of pediatric SLE is extremely rare, and the best treatment approach is unknown. A 14-year-old, previously healthy female teenager developed classic features of GBS with ascending bilateral muscle weakness leading to respiratory insufficiency, associated with protein-cell dissociation in cerebro-spinal fluid, nerve root enhancement by MRI and reduction in compound muscle action potential amplitude. SLE was diagnosed serologically and histologically (lupus nephritis WHO class II). Despite immediate treatment with intravenous immunoglobulin (IVIg), methylprednisolone pulses and subsequently, rituximab, the patient required prolonged mechanical ventilation. She achieved full recovery following 14 PLEX treatments and two more rituximab infusions. Anti-dsDNA, C3, C4 and urinalysis normalized while anti-Smith and Sjögren antibodies persisted 15 months after disease onset, with no other lupus manifestations. Review of the literature revealed two pediatric cases of GBS at the onset of SLE and a third case with GBS 6 years after the diagnosis of SLE. Conventional GBS therapy may not be adequate to treat SLE-GBS. SLE should be included in the differential diagnosis of GBS. Importantly, treatment experiences and outcomes of such cases need be reported to inform future treatment recommendations.