bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung cancer in never smokers: Tumor immunology and challenges for immunotherapy
Authors: de Alencar Viviane Teixeira L. , Figueiredo Amanda B. , Corassa Marcelo , Gollob Kenneth J. , Cordeiro de Lima Vladmir C.
Published: August 2022

Lung cancer is the second most common and the most lethal malignancy worldwide. It is estimated that lung cancer in never smokers (LCINS) accounts for 10-25% of cases, and its incidence is increasing according to recent data, although the reasons remain unclear. If considered alone, LCINS is the 7th most common cause of cancer death. These tumors occur more commonly in younger patients and females. LCINS tend to have a better prognosis, possibly due to a higher chance of bearing an actionable driver mutation, making them amenable to targeted therapy. Notwithstanding, these tumors respond poorly to immune checkpoint inhibitors (ICI). There are several putative explanations for the poor response to immunotherapy: low immunogenicity due to low tumor mutation burden and hence low MANA (mutation-associated neo-antigen) load, constitutive PD-L1 expression in response to driver mutated protein signaling, high expression of immunosuppressive factors by tumors cells (like CD39 and TGF-beta), non-permissive immune TME (tumor microenvironment), abnormal metabolism of amino acids and glucose, and impaired TLS (Tertiary Lymphoid Structures) organization. Finally, there is an increasing concern of offering ICI as first line therapy to these patients owing to several reports of severe toxicity when TKIs (tyrosine kinase inhibitors) are administered sequentially after ICI. Understanding the biology behind the immune response against these tumors is crucial to the development of better therapeutic strategies.
All-inclusive coral reef restoration: How the tourism sector can boost restoration efforts in the caribbean
Authors: Blanco-Pimentel Macarena , Evensen Nicolas R. , Cortés-Useche Camilo , Calle-Triviño Johanna , Barshis Daniel J. , Galván Victor , Harms Erika , Morikawa Megan K.
Published: August 2022

Following a strong decline in the health of Caribbean coral reefs in the 1970s, disease outbreaks, overfishing, and warming events have continued to push these reefs towards a point of no return. As such, researchers and stakeholders have turned their attention to restoration practices to overcome coral recovery bottlenecks on Caribbean reefs. However, successful restoration faces many challenges, including economical and logistical feasibility, long-term stability, and biological and ecological factors yet to fully understand. The tourism sector has the potential to enhance and scale restoration efforts in the Caribbean, beyond simple financial contributions. Its strengths include long-term presence in several locations, logistical and human resources, and a business case focused on preserving the ecosystem services on which it depends. Here, we present the restoration program of Iberostar Hotels and Resorts which includes a scientific team that incorporates science-based solutions into resort operations to promote reef resilience in the face of climate change. We exemplify the potential of our program to scale up science-based reef restoration in collaboration with academia, local community, and government by presenting the first utilization of the Coral Bleaching Automated Stress System (CBASS) in Latin America and the Latin American Caribbean, with the aim of applying findings on coral thermotolerance directly to Iberostar’s reef restoration program across the Caribbean. This program presents a new model for tourism involvement in coral restoration and illustrates its capacity to scale up existing restoration practices by utilizing the strengths of the sector while maintaining science-based decision making.
Research advancement of Apostichopus japonicus from 2000 to 2021
Authors: Chen Jiting , Lv Zhimeng , Guo Ming
Published: August 2022

This study aims to establish a quantitative and qualitative evaluation model of sea cucumber Apostichopus japonicus research. Data from 2000 to 2021 were obtained from the Web of Science Core Collection (WoSCC) of Thomson Reuters. Bibliometrics and CiteSpace software were used to analyze authors, exporting countries, journals, influential articles, research areas, institutions, research hot spots, and trends. A total of 1,358 research papers on A. japonicus research were identified from 2000 to 2021. The number of papers published in this field is rapidly increasing, and the research phase can be divided into initial, developmental, and stabilization phases. Research on A. japonicus is mostly conducted in China, followed by Japan and the United States. Hongsheng Yang, Chenghua Li, and Shuanglin Dong are the lead authors. Research activities are focused on genetics and breeding, growth and development, immunology and disease, aestivation, regeneration, and food processing. Gut microbiota, activation, and collagen are potential research hot spots. The project highlights differences in the level of research between countries and teams, and regions with more developed industries or richer resources need further support. Governments or organizations are encouraged to 1) promote the development of the A. japonicus industry through the development or implementation of policies; 2) further participate in the research, production, and processing of A. japonicus; and 3) strengthen international exchange and cooperation to bring economic benefits to farmers in suitable breeding areas through technology sharing.
Sensitive time-resolved fluoroimmunoassay for the quantitative detection of okadaic acid
Authors: Qin Yuan , Li Jiayu , Kuang Jiani , Shen Sicheng , Jiang Jingwen , Zhang Zhi , Zhao Chenhao , Zhou Xiumei , Huang Biao , Han Bingnan
Published: August 2022

Okadaic acid (OA) is a biotoxin from marine microalgae and widely present in shellfish, which severely affects the seafood safety. Therefore, it is essential to establish a highly sensitive OA analysis and detection method. In this study, a new type of immunoassay technology was established on the basis of the competition method using time-resolved fluoroimmunoassay (TRFIA). OA-bovine serum albumin (OA-BSA) coated on a 96-well plate competes with OA standard or samples to bind OA antibodies. A rare-earth ion-labeled secondary antibody, which fluoresces strongly under the effect of the enhancement solution, was then added as a tracer for detection. The established linear range of OA detected by TRFIA was 2.49 × 10-3 – 50 ng/ml, and the limit of detection was 2.49 × 10-3 ng/ml. The average coefficients of variation from intra-assay and inter-assay batches were 3.34% and 5.87%, respectively, and the recovery rate was 93.04%–111.66%. The OA in shellfish samples was determined by TRFIA and high-performance liquid chromatography (HPLC), and the results showed a good correlation. This study established a TRFIA to detect OA, which has the characteristics of simplicity, sensitivity, precision, and high accuracy, far exceeding the EU or the US standards for the detection of shellfish toxins. It is expected to make proper contribution in marine biotoxin detection.
Metabarcoding survey of meroplankton communities in the South China Sea and Philippine Sea: Shedding light on inter-basin biogeography in the West Pacific
Authors: Qihang Li , Yuanming Chai , Qianwen Shao , Zaiming Wang , Wei Xie , Yadong Zhou , Dong Sun , Xiaohui Xie , Dongsheng Zhang
Published: August 2022

Planktonic larvae (meroplankton) plays an important role in both benthic and pelagic ecosystems. The meroplankton study of South China Sea (SCS) and Philippine Sea (PS) may be particularly important, where they could serve as vectors for the influx of Pacific species into the East Indies Triangle (global marine biodiversity center). Here, we employed a metabarcoding method to investigate the geographical distribution pattern of meroplankton among SCS and PS. Different primers and reference databases were tested, for a better and more reliable interpretation of the current results and improvement of the method. In this study, metabarcoding was efficient for meroplankton study with high taxonomic resolution and good accuracy. COI against NCBI NT database showed the best taxonomy annotation efficiency, followed by 18S V1-V2, then 18S V4. The SILVA database showed similar performance to the NCBI NT database for the two 18S primers. The meroplankton diversity of SCS is higher than that of PS, and both communities are dominated by Polychaeta, Mollusca, Arthropoda and Echinodermata. Meroplankton geographical patterns are significantly different between the two basins, possibly due to the different distribution of their benthic adult, as well as the influence of five key environmental factors (IC, SCM, SST, SSS and DO). Our results suggest that the unidirectional Kuroshio Current intrusion may play an important role in shaping the biogeographical pattern in the west Pacific, by facilitating planktonic-larvae flowing into the northern SCS from the Pacific, on the contrary, limiting planktonic-larvae spreading out.
Contact mechanics analysis of a soft robotic fingerpad
Authors: Achilli Gabriele Maria , Logozzo Silvia , Malvezzi Monica , Valigi Maria Cristina
Published: August 2022

The precision grasping capabilities of robotic hands is a key feature which is more and more required in the manipulation of objects in several unstructured fields, as for instance industrial, medical, agriculture and food industry. For this purpose, the realization of soft robotic fingers is crucial to reproduce the human finger skills. From this point of view the fingerpad is the part which is mostly involved in the contact. Particular attention must be paid to the knowledge of the mechanical contact behavior of soft artificial fingerpads. In this paper, artificial silicone fingerpads are applied to the last phalanx of robotic fingers actuated by tendons. The mechanical interaction between the fingerpad and a flat surface is analyzed in terms of deformations, contact areas and indentations. A reliable model of fingertip deformation properties provides important information for understanding robotic hand performance, that can be useful both in the design phase and for defining control strategies. The approach is based on theoretical, experimental, and numerical methods. The results will be exploited for the design of more effective robotic fingers for precision grasping of soft or fragile objects avoiding damages.
Cervical cancer screening, treatment and prophylaxis in Brazil: Current and future perspectives for cervical cancer elimination
Authors: Corrêa Flávia M. , Migowski Arn , de Almeida Liz M. , Soares Marcelo A.
Published: August 2022

As a middle-income country, Brazil has one of the largest public health systems worldwide, which deals with free and universal access to health care. Regarding cervical cancer, the country possesses a large infrastructure for the screening of premalignant and malignant lesions, but yet based on old technology, having Papanicolaou as the major screening method, followed by colposcopy and treatment. Also, large disparities in access are present, which makes effectiveness of screening and treatment in different regions of the country highly unequal. In this review, we describe and evaluate the current screening, treatment and prophylactic (HPV vaccination) strategies to combat cervical cancer in Brazil, and discuss potential incorporation of more recent technologies in these areas in the country to pave its way toward cervical cancer elimination.
Emergence of a novel hybrid mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain of clinical origin
Authors: Xia Shuang , Wang Wei , Cheng Jing , Zhang Tingting , Xia Ziwei , Zhao Xiaoyu , Han Yungang , Li Yonghong , Shi Xiufang , Qin Shangshang
Published: August 2022

Colistin is considered as an antibiotic of ‘last resort’ for the treatment of lethal infections caused by carbapenem-resistant Enterobacterales (CRE), dissemination of plasmid-borne colistin resistance gene mcr-1, particularly into CRE, resulting in the emergence of strains that approach pan-resistance. A wide variety of plasmid types have been reported for carrying mcr-1. Among which, large IncHI2-type plasmids were multidrug-resistant (MDR) plasmids harbored multiple resistance determinants in addition to mcr-1. Herein, we characterized a novel hybrid IncHI2-like mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain EC15-50 of clinical origin. Antimicrobial susceptibility testing showed E. coli EC15-50 exhibited an extensively drug-resistant (XDR) profile that only susceptible to amikacin and tigecycline. S1-PFGE, Southern hybridization and Whole-genome Sequencing (WGS) analysis identified a 46,161 bp blaNDM-7-harboring IncX3 plasmid pEC50-NDM7 and a 350,179 bp mcr-1-bearing IncHI2/HI2A/N/FII/FIA plasmid pEC15-MCR-50 in E. coli EC15-50. Sequence detail analysis revealed the type IV coupling protein (T4CP) gene was absent on pEC15-MCR-50, explaining that pEC15-MCR-50 was a non-conjugative plasmid. Comparative genetic analysis indicated the hybrid plasmid pEC15-MCR-50 was probably originated from pXGE1mcr-like IncHI2/HI2A/N plasmid and pSJ_94-like IncFII/FIA plasmid, and generated as a result of a replicative transposition process mediated by IS26. Currently, the prevalent mcr-1-carrying IncHI2 plasmids were rarely reported to be fused with other plasmids. The identification of the novel hybrid plasmid pEC15-MCR-50 in this study highlighted the importance of close surveillance for the emergence and dissemination of such fusion MDR plasmids, particularly in NDM-producing Enterobacterales.
Revealing the pharmacological effect and mechanism of darutoside on gouty arthritis by liquid chromatography/mass spectrometry and metabolomics
Authors: Wang Jing , Sun Yan-Chun
Published: August 2022

Darutoside is a diterpenoids compound with significant anti-inflammatory activity, however the pharmacological action and mechanism are still unclear. Metabolomics strategy was used to uncovering the pharmacological action and effective mechanism of darutoside against acute gouty arthritis rats. Liquid chromatography coupled with mass spectrometry technique was performed to explore the serum metabolites and potential pathways. We found that darutoside can up-regulate the level of glutamate, alanine, chenodeoxycholic acid, 1-methyladenosine, aspartic acid, citric acid, and down-regulate the level of valine, isoleucine, glutamine, alanyl-threonine, pyruvic acid, gamma-aminobutyric acid, uric acid. Metabolic pathway analysis showed that the therapeutic effect of darutoside was involved in amino acid metabolism, sugar metabolism, fatty acid metabolism, energy metabolism, purine metabolism and butanoate metabolism. It indicated that darutoside protect against acute gouty arthritis by regulating the expression of the key protein targets. It revealed that the mechanism of darutoside on acute gouty arthritis, which may be leading to the changes of serum metabolites, metabolic pathways and key protein targets to improve immune system response, inhibit oxidative stress and inflammatory response. It provides a novel method for molecular mechanisms of natural product in the disease treatment.
Busyness, mental engagement, and stress: Relationships to neurocognitive aging and behavior
Authors: Festini Sara B.
Published: August 2022

Considerable research identifies benefits of sustaining mental engagement in older adulthood. Frequent social, mental, and physical activities (e.g., exercise) and lifestyle factors that bolster cognitive reserve (i.e., education, occupation complexity) have been associated with cognitive benefits and delayed onset of dementia. Nevertheless, the relationship between general daily levels of busyness and cognition has been relatively understudied. Open questions remain about whether a causal link exists between a busy lifestyle and mental prowess, the relationship between busyness and stress, and methodological approaches to measure and track busyness levels. Here, the existing evidence is considered, along with future directions for research aimed at characterizing the effects of a busy lifestyle on neurocognitive aging and behavior.
Modified fischer-tropsch synthesis: A review of highly selective catalysts for yielding olefins and higher hydrocarbons
Authors: Tavares Marlon , Westphalen Gisele , Araujo Ribeiro de Almeida João Monnerat , Romano Pedro Nothaft , Sousa-Aguiar Eduardo Falabella
Published: August 2022

Global warming, fossil fuel depletion, climate change, as well as a sudden increase in fuel price have motivated scientists to search for methods of storage and reduction of greenhouse gases, especially CO2. Therefore, the conversion of CO2 by hydrogenation into higher hydrocarbons through the modified Fischer–Tropsch Synthesis (FTS) has become an important topic of current research and will be discussed in this review. In this process, CO2 is converted into carbon monoxide by the reverse water-gas-shift reaction, which subsequently follows the regular FTS pathway for hydrocarbon formation. Generally, the nature of the catalyst is the main factor significantly influencing product selectivity and activity. Thus, a detailed discussion will focus on recent developments in Fe-based, Co-based, and bimetallic catalysts in this review. Moreover, the effects of adding promoters such as K, Na, or Mn on the performance of catalysts concerning the selectivity of olefins and higher hydrocarbons are assessed.
Developmental differences in amygdala projection neuron activation associated with isolation-driven changes in social preference
Authors: Ferrara Nicole C. , Trask Sydney , Ritger Alexandra , Padival Mallika , Rosenkranz J. Amiel
Published: August 2022

Adolescence is a developmental period characterized by brain maturation and changes in social engagement. Changes in the social environment influence social behaviors. Memories of social events, including remembering familiar individuals, require social engagement during encoding. Therefore, existing differences in adult and adolescent social repertoires and environmentally-driven changes in social behavior may impact novel partner preference, associated with social recognition. Several amygdala subregions are sensitive to the social environment and can influence social behavior, which is crucial for novelty preference. Amygdala neurons project to the septum and nucleus accumbens (NAc), which are linked to social engagement. Here, we investigated how the social environment impacts age-specific social behaviors during social encoding and its subsequent impact on partner preference. We then examined changes in amygdala-septal and -NAc circuits that accompany these changes. Brief isolation can drive social behavior in both adults and adolescents and was used to increase social engagement during encoding. We found that brief isolation facilitates social interaction in adolescents and adults, and analysis across time revealed that partner discrimination was intact in all groups, but there was a shift in preference within isolated and non-isolated groups. We found that this same isolation preferentially increases basal amygdala (BA) activity relative to other amygdala subregions in adults, but activity among amygdala subregions was similar in adolescents, even when considering conditions (no isolation, isolation). Further, we identify isolation-driven increases in BA-NAc and BA-septal circuits in both adults and adolescents. Together, these results provide evidence for changes in neuronal populations within amygdala subregions and their projections that are sensitive to the social environment that may influence the pattern of social interaction within briefly isolated groups during development.
Associations of chronic diarrheal symptoms and inflammatory bowel disease with sleep quality: A secondary analysis of NHANES 2005–2010
Authors: Zhang Jingyun , Yu Senhai , Zhao Gang , Jiang Xiaoyan , Zhu Yimin , Liu Zuyun
Published: August 2022

Objective

Poor sleep quality is highly prevalent in patients with chronic diarrheal symptoms or inflammatory bowel disease (IBD). This study aimed to evaluate the associations of chronic diarrheal symptoms and IBD with sleep quality in the general US population.

Methods

14,696 adults (≥20 years) from the National Health and Nutrition Examination Survey (2005–2010) were included in the study. Chronic diarrheal symptoms and IBD were defined by self-reports. Sleep quality was assessed by sleep disorder, sleep trouble, and sleep duration. Multivariable logistic regression models were used to examine the associations.

Results

After adjustment of a series of covariates, we found that participants with chronic diarrheal symptoms or IBD had higher odds of sleep disorder [chronic diarrheal symptoms: odds ratio (OR) = 1.20, 95% confidence interval (CI) = 1.04–1.38; IBD: OR = 3.86, 95% CI = 1.92–7.77] and sleep trouble (chronic diarrheal symptoms: OR = 1.19, 95% CI = 1.09–1.30; IBD: OR = 2.32, 95% CI = 1.30–4.14), respectively. Sleep duration for participants with IBD was significantly shorter than that for those without IBD (β = −0.39, 95% CI = −0.78 to 0.01, P = 0.045). Subgroup analyses revealed that the associations of chronic diarrheal symptoms and IBD with sleep disorder and sleep trouble were more pronounced among women.

Conclusions

In this large sample of US adults, we found that chronic diarrheal symptoms and IBD were significantly associated with sleep quality, particularly in women. The findings highlight the importance of managing bowel health to promote high quality of sleep; and thus, improve quality of life in this subpopulation.
Platelet reactivity after clopidogrel loading in patients with acute ischemic stroke
Authors: Enomoto Yukiko , Shoda Kenji , Mizutani Daisuke , Matsubara Hirofumi , Egashira Yusuke , Iwama Toru
Published: August 2022

Objective

It remains unclear when sufficient antiplatelet effect is achieved after administration of a loading dose of clopidogrel in patients with acute ischemic stroke (AIS). This study aimed to evaluate the clopidogrel response in patients with AIS identified by the platelet function test (PFT).

Methods

P2Y12 reaction unit (PRU) values measured using VerifyNow at baseline and at 6, 24, and 72 h after administration of a loading dose (300 mg) of clopidogrel were compared between patients with AIS and those of other cerebrovascular diseases (CVD). The prevalence of clopidogrel abnormal response and its associated factors were examined.

Results

The PRU value was significantly reduced with time in the other CVD group (p < 0.0001), and also in the AIS group (p = 0.0073). The PRU values were significantly higher in the AIS group than in the other CVD group (p < 0.0001 between the groups, baseline: 314 ± 53 vs. 284 ± 62, p = 0.35; 6 h: 290 ± 66 vs. 214 ± 71, p = 0.016; 24 h: 270 ± 75 vs. 190 ± 70, p < 0.0001; and 72 h: 231 ± 76 vs. 163 ± 93, p = 0.105). The prevalence of clopidogrel hypo-responder (PRU > 240 at 24 h after administration) was higher in the AIS group (79 vs. 33%, p < 0.0001) and associated with the baseline PRU value but not with the cytochrome P450 2C19 genotype or clinical ischemic events.

Conclusions

Residual platelet reactivity at 24 h after clopidogrel loading was substantially higher in patients with AIS than in patients with other CVD. In addition, most patients with AIS were judged to be hypo-responders on PFT. This should be carefully interpreted in patients with AIS because of poor specificity for predicting clinical ischemic events.
Changes of brain function in patients with type 2 diabetes mellitus measured by different analysis methods: A new coordinate-based meta-analysis of neuroimaging
Authors: Li Ze-Yang , Ma Teng , Yu Ying , Hu Bo , Han Yu , Xie Hao , Ni Min-Hua , Chen Zhu-Hong , Zhang Yang-Ming , Huang Yu-Xiang , Li Wen-Hua , Wang Wen , Yan Lin-Feng , Cui Guang-Bin
Published: August 2022

Objective

Neuroimaging meta-analysis identified abnormal neural activity alterations in patients with type 2 diabetes mellitus (T2DM), but there was no consistency or heterogeneity analysis between different brain imaging processing strategies. The aim of this meta-analysis was to determine consistent changes of regional brain functions in T2DM via the indicators obtained by using different post-processing methods.

Methods

Since the indicators obtained using varied post-processing methods reflect different neurophysiological and pathological characteristics, we further conducted a coordinate-based meta-analysis (CBMA) of the two categories of neuroimaging literature, which were grouped according to similar data processing methods: one group included regional homogeneity (ReHo), independent component analysis (ICA), and degree centrality (DC) studies, while the other group summarized the literature on amplitude of low-frequency fluctuation (ALFF) and cerebral blood flow (CBF).

Results

The final meta-analysis included 23 eligible trials with 27 data sets. Compared with the healthy control group, when neuroimaging studies were combined with ReHo, ICA, and DC measurements, the brain activity of the right Rolandic operculum, right supramarginal gyrus, and right superior temporal gyrus in T2DM patients decreased significantly. When neuroimaging studies were combined with ALFF and CBF measurements, there was no clear evidence of differences in the brain function between T2DM and HCs.

Conclusion

T2DM patients have a series of spontaneous abnormal brain activities, mainly involving brain regions related to learning, memory, and emotion, which provide early biomarkers for clarifying the mechanism of cognitive impairment and neuropsychiatric disorders in diabetes.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=247071, PROSPERO [CRD42021247071].
Independent predictors and risk score for intraprocedural rupture during endovascular treatment of small ruptured intracranial aneurysms (<5 mm)
Authors: Peng Fei , Feng Xin , He Xiaoxin , Niu Hao , Zhang Hong , Tong Xin , Zhang Baorui , Xia Jiaxiang , Chen Xuge , Xu Boya , Qi Peng , Lu Jun , Wang Daming , Liu Aihua
Published: August 2022

Background and purpose

Intraprocedural rupture (IPR) is a devastating complication of endovascular treatment (EVT). Small-sized and ruptured aneurysms are independent predictors of IPR, which presents a technical challenge during EVT. We aimed to develop a score to quantify the individual patient risk of IPR in the EVT of small (<5 mm) ruptured aneurysms (SRAs).

Methods

A retrospective review was conducted to interrogate databases prospectively maintained at two academic institutions in China from January 2009 to October 2016. We collected intraoperative angiograms and medical records to identify independent predictors of IPR using univariate and multivariable analyses. A risk score for IPR was derived using multivariable logistic regression analyses.

Results

Of the 290 enrolled patients, IPR occurred in 16 patients (5.5%). The univariate analysis showed that the rate of IPR was significantly higher in patients having aneurysms with a small basal outpouching (SBO), in patients having aneurysms concomitant with adjacent moderate atherosclerotic stenosis (ACAMAS), and in former or current smokers. Multivariate analyses showed that SBO [odds ratio (OR): 3.573; 95% confidence interval (CI): 1.078–11.840; p = 0.037], vascular eloquence (VE; OR: 3.780; 95% CI: 1.080–13.224; p = 0.037), and ACAMAS (OR: 6.086; 95% CI: 1.768–20.955; p = 0.004) were significantly and independently associated with IPR. A three-point risk score (S-V-A) was derived to predict IPR [SBO (yes = 1), VE (yes = 1), and ACAMAS (yes = 1)].

Conclusions

Intraprocedural rupture occurred in 5.5% of the patients during EVT of SRA. SBO, VE, and ACAMAS were independent risk factors of IPR in the EVT of SRA. Based on these variables, the S-V-A score may be useful in predicting IPR daily, but more confirmation studies are required.
Effect of electroacupuncture on cyclic adenosine monophosphate-protein kinase A-vanillic acid receptor subtype 1 of the transient receptor potential/PLK-protein kinase C-vanillic acid receptor subtype 1 of the transient receptor potential pathway based on RNA-seq analysis in prostate tissue in rats with chronic prostatitis/chronic pelvic pain syndrome
Authors: Wu Xiao-Ling , Cheng Kai , Xu Chang , Chai Ye-Mao , Yap Tai-Heng , Yang Zhi-Wen , Sun Qian-Hui , Tan Yan , Zhang Jia-Ni , Chen Wei , Qiu Xing-Hua , Yang Xing-Yue , Li Na
Published: August 2022

Objective

To investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods

Thirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 μL of complete Freund’s adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR.

Results

The RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRT-PCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01).

Conclusion

The analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway.
Estimating the causal effect of frailty index on vestibular disorders: A two-sample Mendelian randomization
Authors: Xiao Gui , Wang Hu , Hu Jiaji , Liu Li , Zhang Tingting , Zhou Mengjia , Li Xingxing , Qin Chunxiang
Published: August 2022

Background

Frailty index and vestibular disorders appear to be associated in observational studies, but causality of the association remains unclear.

Methods

A two-sample Mendelian randomization (MR) study was implemented to explore the causal relationship between the frailty index and vestibular disorders in individuals of European descent. A genome-wide association study (GWAS) of frailty index was used as the exposure (n = 175, 226), whereas the GWAS of vestibular disorders was the outcome (n = 462,933). MR Steiger filtering method was conducted to investigate the causal effect of the frailty index on vestibular disorders. An inverse variance weighted (IVW) approach was used as the essential approach to examine the causality. Additionally, the MR-Egger methods, the simple mode analysis, the weighted median analysis, and the weighted mode analysis were used as supplementary methods. The MR-PRESSO analysis, the MR-Egger intercept analysis, and Cochran's Q statistical analysis also were used to detect the possible heterogeneity as well as directional pleiotropy. To evaluate this association, the odds ratio (OR) with 95% confidence intervals (CIs) was used. All statistical analyses were performed in R. The STROBE-MR checklist for the reporting of MR studies was used in this study.

Results

In total, 14 single nucleotide polymorphisms (SNPs) were identified as effective instrumental variables (IVs) in the two sample MR analyses. The significant causal effect of the frailty index on vestibular disorders was demonstrated by IVW method [OR 1.008 (95% CI 1.003, 1.013), p = 0.001]. Results from the various sensitivity analysis were consistent. The “leave-one-out” analysis indicated that our results were robust even without a single SNP. According to the MR-Egger intercept test [intercept = −0.000151, SE = 0.011, p = 0.544], genetic pleiotropy did not affect the results. No heterogeneity was detected by Cochran's Q test. Results of MR Steiger directionality test indicated the accuracy of our estimate of the potential causal direction (Steiger p < 0.001).

Conclusion

The MR study suggested that genetically predicted frailty index may be associated with an increased risk of vestibular disorders. Notably, considering the limitations of this study, the causal effects between frailty index and vestibular disorders need further investigation. These results support the importance of effectively managing frailty which may minimize vestibular disorders and improve the quality of life for those with vestibular disorders.
Chronic early-life lead exposure sensitizes adolescent rats to cocaine: Role of the dopaminergic system
Authors: Albores-Garcia Damaris , Stansfield Kirstie H. , McGlothan Jennifer L. , Bursac Zoran , Guilarte Tomás R.
Published: August 2022

Exposure to heavy metals has been associated with psychiatric disorders and recent studies suggest an association between childhood lead (Pb2+) intoxication and schizophrenia (SZ). In animal models, Pb2+ exposure recapitulates key neuropathological and dopaminergic system alterations present in SZ. Given the high comorbidity of mental disorders such as SZ and substance abuse, coupled with evidence showing that Pb2+ exposure affects addiction circuits, we hypothesized that early life Pb2+ exposure could sensitize neuronal systems relevant to SZ and substance abuse. To this goal, we examined the effects of chronic developmental Pb2+ exposure on the acute locomotor response to cocaine (0, 5, and 15 mg kg–1) and behavioral sensitization. We also examined the role of the dopaminergic system in the psychostimulant effects of cocaine, and measured D1-dopamine receptor (D1R) levels in the rat brain using [3H]-SCH23390 quantitative receptor autoradiography, as well as the ability of the D1R antagonist SCH23390 to block the cocaine effects on locomotor activation. These studies were performed in male and female rats at different developmental ages consisting of juveniles (postnatal, PN14), early-adolescent (PN28), late adolescent (PN50), and adults (PN120). Our results show that chronic developmental Pb2+ exposure increases the acute locomotor response to the higher dose of cocaine in Pb2+-exposed male adolescent (PN28 and PN50) rats, and to the lower dose of cocaine in adolescent female rats. No changes in the locomotor activity were detected in adult rats. Behavioral sensitization experiments showed a sustained sensitization in early adolescent Pb2+-exposed male but not female rats. The cocaine-induced effects on locomotor activity were abrogated by injection of a D1R antagonist suggesting the involvement of this dopamine receptor subtype. Furthermore, Pb2+-induced increases D1R levels in several brain regions were prominent in juveniles and early adolescence but not in late adolescence or in adults. In summary, early chronic developmental Pb2+ exposure results in age and sex-dependent effect on the locomotor response to cocaine, suggesting differential susceptibilities to the neurotoxic effects of Pb2+ exposure. Our data provides further support to the notion that Pb2+ exposure is an environmental risk factor for psychiatric disorders and substance abuse.
Automatic detection and delineation of pediatric gliomas on combined [18F]FET PET and MRI
Authors: Ladefoged Claes Nøhr , Henriksen Otto Mølby , Mathiasen René , Schmiegelow Kjeld , Andersen Flemming Littrup , Højgaard Liselotte , Borgwardt Lise , Law Ian , Marner Lisbeth
Published: August 2022

Introduction

Brain and central nervous system (CNS) tumors are the second most common cancer type in children and adolescents. Positron emission tomography (PET) imaging with radiolabeled amino acids visualizes the amino acid uptake in brain tumor cells compared with the healthy brain tissue, which provides additional information over magnetic resonance imaging (MRI) for differential diagnosis, treatment planning, and the differentiation of tumor relapse from treatment-related changes. However, tumor delineation is a time-consuming task subject to inter-rater variability. We propose a deep learning method for the automatic delineation of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET PET) pediatric CNS tumors.

Methods

A total of 109 [18F]FET PET and MRI scans from 66 pediatric patients with manually delineated reference were included. We trained an artificial neural network (ANN) for automatic delineation and compared its performance against the manual reference on delineation accuracy and subsequent clinical metric accuracy. For clinical metrics, we extracted the biological tumor volume (BTV) and tumor-to-background mean and max (TBRmean and TBRmax).

Results

The ANN produced high tumor overlap (median dice-similarity coefficient [DSC] of 0.93). The clinical metrics extracted with the manual reference and the ANN were highly correlated (r ≥ 0.99). The spatial location of TBRmax was identical in almost all cases (96%). The ANN and the manual reference produced similar changes in the clinical metrics between baseline and follow-up scans.

Conclusion

The proposed ANN achieved high concordance with the manual reference and may be an important tool for decision aid, limiting inter-reader variance and improving longitudinal evaluation in clinical routine, and for future multicenter studies of pediatric CNS tumors.
Gypenosides ameliorate high-fat diet-induced non-alcoholic steatohepatitis via farnesoid X receptor activation
Authors: Li Hongshan , Xi Yingfei , Liu Hongliang , Xin Xin
Published: August 2022

Background

Gypenosides (Gyps), the major botanical component of Gynostemma pentaphyllum, was found to up-regulate the farnesoid X receptor (FXR) in a mouse model of non-alcoholic steatohepatitis (NASH). However, the exact role of FXR and underlying mechanisms in Gyps-mediated effects on NASH remain to be elucidated.

Purpose

This study investigated whether Gyps attenuates NASH through directly activating FXR in high-fat diet (HFD)-induced NASH, and delineated the molecular pathways involved.

Study design

A mouse model of HFD-induced NSAH was used to examine effects of Gyps on NASH with obeticholic acid (OCA) as a positive control, and the role of FXR in its mechanism of action was investigated in wild-type (WT) and FXR knockout (KO) mice.

Methods

WT or FXR KO mice were randomly assigned into four groups: normal diet (ND) group as negative control, HFD group, HFD + Gyps group, or HFD + OCA group.

Results

Treatment with Gyps and OCA significantly improved liver histopathological abnormalities in HFD-induced NASH, reduced the non-alcoholic fatty liver disease (NAFLD) activity score (NAS), and lowered hepatic triglyceride (TG) content compared with the HFD group. In agreement with these liver tissue changes, biochemical tests of blood samples revealed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and fasting insulin (FINS) levels were significantly lower in the HFD + Gyps vs. HFD group. Furthermore, Gyps and OCA treatment significantly up-regulated hepatic FXR, small heterodimer partner (SHP), carnitine palmitoyltransferase 1A (CPT1A), and lipoprotein lipase (LPL) expression, and significantly down-regulated sterol-regulatory element binding protein 1 (SREBP1), fatty acid synthetase (FASN), and stearoyl-CoA desaturase 1 (SCD1) protein levels compared with the HFD group in WT mice but not in FXR KO mice. Notably, Gyps- and OCA-mediated pharmacological effects were significantly abrogated by depletion of the FXR gene in FXR KO mice.

Conclusion

Gyps ameliorated HFD-induced NASH through the direct activation of FXR and FXR-dependent signaling pathways.
Changes of volatile substance composition during processing of nine-processed tangerine peel (Jiuzhi Chenpi) determined by gas chromatography-ion mobility spectrometry
Authors: Fu Manqin , Wang Yuehan , Yu Yuanshan , Wen Jing , Cheong Meng Sam , Cheang Wai San , Wu Jijun
Published: August 2022

Nine-processed tangerine peel (Jiuzhi Chenpi in Chinese) is a famous Chinese traditional snack. The composition and contents of volatile substances during its processing is unclear. Gas chromatography combined with ion mobility spectrometry (GC-IMS) was applied to determine the characteristic changes of volatile components throughout the production process. Four stages such as untreated dry tangerine peel (raw material), debittered tangerine peel, pickled tangerine peel, and final product were examined. A total of 110 flavor compounds including terpenes, alcohols, aldehydes, ketones, esters, acids, and two others were successfully detected in tangerine peel samples across the various production stages. There were abundant amounts of terpenes contributing to the flavor, including limonene, gamma-terpinene, alpha-pinene, myrcene, beta-pinene, and alpha-thujene which were reduced at the later stage of production. Large amounts of esters and alcohols such as methyl acetate, furfuryl acetate, ethyl acetate, benzyl propionate, 2-hexanol, linalool, and isopulegol, were diminished at the early stage of processing, i.e., soaking for debittering. One the other hand, the final product contained increased amount of aldehydes and ketones including pentanal, hexanal, 2-hexenal, 2-heptenal (E), 2-pentenal (E), 1-penten-3-one, 6-methyl-5-hepten-2-one, 2-methyl-2-propenal, and 2-cyclohexen-1-one, and very high level of acetic acid. Present findings help to understand the formation of the unique flavor of nine-processed tangerine peel and provide a scientific basis for the optimization of processing methods and quality control.
Suppressor of fused associates with dissemination patterns in patients with glioma
Authors: Peris-Celda María , Carrión-Navarro Josefa , Palacín-Aliana Irina , Sánchez-Gómez Pilar , Acín Ricardo Prat , Garcia-Romero Noemi , Ayuso-Sacido Angel
Published: August 2022

Gliomas are the most common brain tumors, which present poor prognosis, due, in part, to tumor cell migration and infiltration into distant brain areas. However, the underlying mechanisms causing such effects are unknown. Hedgehog (HH)–Gli axis is one of the signaling pathways involved, with a high number of molecular mediators. In this study, we investigated the association between HH-Gli intermediates and clinical parameters. We found that high levels of SuFu are associated with high dissemination patterns in patients with glioma. Therefore, we analyzed SuFu expression data in three glioma cohorts of surgical samples (N =1,759) and modified its expression in Glioblastoma Cancer Stem Cells (GB CSC) in vitro models. Our data reveal that SuFu overexpression increases cancer stemness properties together with a migratory phenotype. This work identifies SuFu as a new molecular player in glioma cell migration and a promising target to develop blocking agents to decrease GB dissemination.
The SREBP-dependent regulation of cyclin D1 coordinates cell proliferation and lipid synthesis
Authors: Aldaalis Arwa , Bengoechea-Alonso Maria T. , Ericsson Johan
Published: August 2022

The sterol regulatory-element binding protein (SREBP) family of transcription factors regulates cholesterol, fatty acid, and triglyceride synthesis and metabolism. However, they are also targeted by the ubiquitin ligase Fbw7, a major tumor suppressor, suggesting that they could regulate cell growth. Indeed, enhanced lipid synthesis is a hallmark of many human tumors. Thus, the SREBP pathway has recently emerged as a potential target for cancer therapy. We have previously demonstrated that one of these transcription factors, SREBP1, is stabilized and remains associated with target promoters during mitosis, suggesting that the expression of these target genes could be important as cells enter G1 and transcription is restored. Activation of cyclin D-cdk4/6 complexes is critical for the phosphorylation and inactivation of the retinoblastoma protein (Rb) family of transcriptional repressors and progression through the G1 phase of the cell cycle. Importantly, the cyclin D-cdk4/6-Rb regulatory axis is frequently dysregulated in human cancer. In the current manuscript, we demonstrate that SREBP1 activates the expression of cyclin D1, a coactivator of cdk4 and cdk6, by binding to an E-box in the cyclin D1 promoter. Consequently, inactivation of SREBP1 in human liver and breast cancer cell lines reduces the expression of cyclin D1 and attenuates Rb phosphorylation. Rb phosphorylation in these cells can be rescued by restoring cyclin D1 expression. On the other hand, expression of active SREBP1 induced the expression of cyclin D1 and increased the phosphorylation of Rb in a manner dependent on cyclin D1 and cdk4/6 activity. Inactivation of SREBP1 resulted in reduced expression of cyclin D1, attenuated phosphorylation of Rb, and reduced proliferation. Inactivation of SREBP1 also reduced the insulin-dependent regulation of the cyclin D1 gene. At the same time, SREBP1 is known to play an important role in supporting lipid synthesis in cancer cells. Thus, we propose that the SREBP1-dependent regulation of cyclin D1 coordinates cell proliferation with the enhanced lipid synthesis required to support cell growth.
Case Report: Resolution of radiation pneumonitis with androgens and growth hormone
Authors: Yen Allen , Westover Kenneth D.
Published: August 2022

Radiation pneumonitis (RP) occurs in some patients treated with thoracic radiation therapy. RP often self-resolves, but when severe it is most commonly treated with corticosteroids because of their anti-inflammatory properties. Androgens and human growth hormone (HGH) also have anti-inflammatory and healing properties in the lung, but have not been studied as a remedy for RP. Here we present a case of corticosteroid-refractory RP that resolved with androgen and HGH-based therapy.

Case Presentation

A 62 year old male body builder with excellent performance status presented with locally advanced non-small cell lung cancer characterized by a 7 cm mass in the right lower lobe and associated right hilar and subcarinal lymph node involvement. He was treated with chemoradiation and an excellent tumor response was observed. However, 2 months post-treatment he developed severe shortness of breath and imaging was consistent with RP. His RP was refractory to prednisone and antibiotic therapy, despite various regimens over a 9 month period. The patient self-treated with an androgen and HGH-based regimen and the RP promptly resolved.

Conclusion

The anti-inflammatory properties of androgens and HGH have prompted an exploration of their potential role in therapeutic strategies to treat pro-inflammatory conditions such as sepsis, infections and interstitial lung disease. This case study suggests a potential role for the use of androgens for the treatment of steroid-refractory RP after radiation therapy. However, the applicability of this strategy to general populations should be weighed carefully against secondary effects of these agents, especially in the setting of cancer survivorship.