bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive oxygen species turnover, phenolics metabolism, and some key gene expressions modulate postharvest physiological deterioration in cassava tubers
Authors: Wahengbam Elizabeth Devi , Devi Chingakham Premabati , Sharma Susheel Kumar , Roy Subhra Saikat , Maibam Albert , Dasgupta Madhumita , Luikham Star , Chongtham Tania , Ningombam Arati , Bhupenchandra Ingudam , Singh Laishram Kanta , Devi Yumnam Prabhabati , Thokchom Sushmita , Khaba Chingakham Inao , Singh Nameirakpam Bunindro , Rajashekar Yallappa , Das Sudripta , Mohanty Sansuta , Sahoo Manas Ranjan
Published: March 2023

Rapid postharvest physiological deterioration (PPD) in cassava (Manihot esculentaCrantz) tuber is a significant concern during storage. The freshly harvested tubers start spoiling within 24 to 72 h. Accumulation of H2O2is one of the earliest biochemical events that occurred during PPD, which was detected using the 3,3 diaminobenzidine (DAB) in two contrast cassava genotypes, MNP Local A (29–57 μg g–1) and Sree Prakash (64–141 μg g–1). Accumulating the fluorescence hydroxycoumarin compounds emitted by the cassava tubers observed under an ultraviolet (UV) lamp showed significant variations at 0, 3, 6, 9, 12, and 15 days of storage. The total phenolics and carotenoids significantly and negatively correlated with PPD progression; however, the anthocyanin and flavonoids positively correlated with the PPD–anchored ROS accumulation. The primary compound, Phthalic acid, di(2–propylpentyl) ester, was identified in both the cassava tubers, Sree Prakash (57.21 and 35.21%), and MNP Local A (75.58 and 60.21%) at 0, and 72 h of PPD, respectively. The expression of PPD–associated genesAPX–2, APX–3, PAL, andAPwas higher at 6–12 days of PPD, which signified the synthesis of ROS turnover and phenylpropanoid biosynthesis. A significant, strong, and positive correlation was established between the secondary metabolites and PPD signaling gene expression, which was inversely correlated with hydroxycoumarin and H2O2accumulation. MNP Local A tubers exhibited longer storage life of 15 days with a low PPD score, higher metabolites synthesis, and gene expression. The PPD–resistant lines may be used to augment cassava breeding strategies for large–scale commercial and industrial use.
Morphology and phylogeny identify two new species and one new subspecies of Podoscypha from Yunnan Province, Southwest China
Authors: Si Jing , Zhang Yi-Zhe , Liang Jia-Qi , Li Hai-Jiao
Published: March 2023

In this study, Podoscypha was taxonomically and phylogenetically evaluated. In total, five specimens collected from the tropical areas of Yunnan Province in Southwest China were studied. In combination with morphological observations and phylogenetic analyses based on ITS and LSU loci, two new species and one new subspecies, Podoscypha subinvoluta, P. tropica, and P. petalodes subsp. cystidiata, respectively, were discovered. The illustrated descriptions of the new species and subspecies are provided. Moreover, the main morphological differences between related species are discussed.
Class 1 integrons and multiple mobile genetic elements in clinical isolates of the Klebsiella pneumoniae complex from a tertiary hospital in eastern China
Authors: Wang Lan , Zhu Mei , Yan Chunxia , Zhang Yanfang , He Xuying , Wu Lin , Xu Jiefeng , Lu Junwan , Bao Qiyu , Hu Yunliang , Xu Teng , Liang Jialei
Published: March 2023

Background

The emergence of highly drug-resistant K. pneumoniae, has become a major public health challenge. In this work, we aim to investigate the diversity of species and sequence types (STs) of clinical Klebsiella isolates and to characterize the prevalence and structure of class 1 integrons.

Methods

Based on the whole genome sequencing, species identification was performed by 16S rRNA gene homology and average nucleotide identity (ANI) analysis. STs were determined in accordance with the international MLST schemes for K. pneumoniae and K. variicola. Integron characterization and comparative genomic analysis were performed using various bioinformatic tools.

Results

Species identification showed that the 167 isolates belonged to four species: K. pneumoniae, K. variicola subsp. variicola, K. quasipneumoniae and K. aerogenes. Thirty-six known and 5 novel STs were identified in K. pneumoniae, and 10 novel STs were identified in K. variicola subsp. variicola. Class 1 integrons were found in 57.49% (96/167) of the isolates, and a total of 169 resistance gene cassettes encoding 19 types of resistance genes, including carbapenem resistance gene (blaIPM-4) and class D β-lactamases gene (blaOXA-1 and blaOXA-10), were identified. Among the 17 complete genomes, 29 class 1 integrons from 12 groups were found, only 1 group was encoded on chromosomes. Interestingly, one plasmid (pKP167-261) carrying two copies of approximately 19-kb IS26-Int1 complex resistance region that contains an integron and a multidrug resistance gene fragment.

Conclusion

The results of this work demonstrated that the species and STs of the clinical Klebsiella isolates were more complex by the whole genome sequence analysis than by the traditional laboratory methods. Finding of the new structure of MGEs related to the resistance genes indicates the great importance of deeply exploring the molecular mechanisms of bacterial multidrug resistance.
The advent of a pan-collagenous CLOVIS POINT for pathotropic targeting and cancer gene therapy, a retrospective
Authors: Gordon Erlinda M. , Hall Frederick L.
Published: March 2023

The ‘Clovis Point’—an enabling prehistoric gain-of-function in stone-age tool technologies which empowered the Paleoindian-Americans to hunt, to strike-deep, and to kill designated target megafauna more efficiently—was created biochemically by molecular-genetic bio-engineering. This Biomedical “Clovis Point” was crafted by adapting a broad-spectrum Pan-Collagen Binding Domain (Pan-Coll/CBD) found within the immature pre-pro-peptide segment of Von Willebrand Factor into a constructive series of advanced medical applications. Developed experimentally, preclinically, and clinically into a cutting-edge Biotechnology Platform, the Clovis Point is suitable for 1) solid-state binding of growth factors on collagenous scaffolds for improved orthopedic wound healing, 2) promoting regeneration of injured/diseased tissues; and 3) autologous stem cell capture, expansion, and gene-based therapies. Subsequent adaptations of the high-affinity Pan-Coll/CBD (exposed-collagen-seeking/surveillance function) for intravenous administration in humans, enabled the physiological delivery, aka Pathotropic Targeting to diseased tissuesviathe modified envelopes of gene vectors; enabling 4) precision tumor-targeting for cancer gene therapy and 5) adoptive/localized immunotherapies, demonstrating improved long-term survival value—thus pioneering a proximal and accessible cell cycle control point for cancer management—empowering modern medical oncologists to address persistent problems of chemotherapy resistance, recurrence, and occult progression of metastatic disease. Recent engineering adaptations have advanced the clinical utility to include the targeted delivery of small molecule APIs: including taxanes, mAbs, and RNA-based therapeutics.
Altered topological properties of functional brain networks in patients with first episode, late-life depression before and after antidepressant treatment
Authors: Liu Chaomeng , Li Li , Pan Weigang , Zhu Dandi , Lian Siyuan , Liu Yi , Ren Li , Mao Peixian , Ren Yanping , Ma Xin
Published: March 2023

Objectives

To preliminarily explore the functional activity and information integration of the brains under resting state based on graph theory in patients with first-episode, late-life depression (LLD) before and after antidepressant treatment.

Methods

A total of 50 patients with first-episode LLD and 40 non-depressed controls (NCs) were recruited for the present research. Participants underwent the RBANS test, the 17-item Hamilton depression rating scale (HAMD-17) test, and resting-state functional MRI scans (rs-fMRI). The RBANS test consists of 12 sub-tests that contribute to a total score and index scores across the five domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Escitalopram or sertraline was adopted for treating depression, and the dosage of the drug was adjusted by the experienced psychiatrists. Of the 50 LLD patients, 27 cases who completed 6-month follow-ups and 27 NCs matched with age, sex, and education level were included for the final statistical analysis.

Results

There were significant differences in RBANS total score, immediate memory, visuospatial/constructional, language, attention, and delayed memory between LLD baseline group and NCs group (P < 0.05). Considering the global attribute indicators, the clustering coefficient of global indicators was lower in the LLD baseline group than in the NCs group, and the small-world attribute of functional brain networks existed in all three groups. The degree centrality and node efficiency of some brains were lower in the LLD baseline group than in the NCs group. After 6 months of antidepressant therapy, the scores of HAMD-17, immediate memory, language, and delayed memory in the LLD follow-up group were higher than those in the LLD baseline group. Compared with the LLD baseline group, the degree centrality and node efficiency of some brains in the cognitive control network were decreased in the LLD follow-up group.

Conclusions

The ability to integrate and divide labor of functional brain networks declines in LLD patients and linked with the depression severity. After the relief of depressive symptoms, the small-world attribute of functional brain networks in LLD patients persists. However, the information transmission efficiency and centrality of some brain regions continue to decline over time, perhaps related to their progressive cognitive impairment.
Automatic adaptive emotion regulation is associated with lower emotion-related activation in the frontoparietal cortex and other cortical regions with multi-componential organization
Authors: Sugiura Motoaki , Katayori Yoko , Muratsubaki Tomohiko , Shiratori Miyuki , Hanawa Sugiko , Nejad Keyvan Kashkouli , Tamura Daisaku , Kawashima Ryuta , Fukudo Shin
Published: March 2023

Although some researchers consider automatic adaptive emotion regulation to be an automatized strategy whereas others consider it to be implicit disengagement of deliberative process, to date, its neural correlates have been poorly investigated. In addition, the valence specificity of automatic adaptive emotion regulation and levels of activation relative to the neutral condition are controversial; the former is relevant to the attribution of resilient emotion regulation to positivity bias or emotional stability, and the latter to determining whether regulation is based on emotion-specific or emotion-non-specific processes. In this functional magnetic resonance imaging (fMRI) study, we presented positive and negative emotional pictures to healthy young participants and investigated the neural correlates of automatic adaptive emotion regulation in spontaneous emotional response. A significant negative trait effect (i.e., regression coefficient) on activation was identified both for positive and negative emotional responses in various cortical regions. A cluster analysis identified three clusters among these regions based on the valence specificity of the trait effect and level of activation relative to neutral stimuli. Cluster 1 included regions in the sensorimotor cortex characterized by negative emotion-specific decreases in activation relative to neutral stimuli in adaptive individuals. Cluster 2 included several cortical regions including the bilateral dorsal executive network, anterior cingulate, and inferior frontal gyrus, which were characterized by valence-independent decreases in activation in adaptive individuals. Cluster 3 included the bilateral ventrolateral and dorsomedial prefrontal cortices, right insula, and other posterior regions, which were characterized by increased activation for negative stimuli in non-adaptive individuals. These findings support the assumption that automatic adaptive emotion regulation involves the implicit disengagement of deliberative process and suggest the relevance of different cortical networks to the potential emotion- and valence-specificity of adaptive regulation.
Novel mutations in the ABCD1 gene caused adrenomyeloneuropathy in the Chinese population
Authors: He Raoli , Zhang Jian , Huang Tianwen , Cai Guoen , Zou Zhangyu , Ye Qinyong
Published: March 2023

Background

As a rare genetic disease, adrenomyeloneuropathy (AMN) is the most common adult phenotype of X-linked adrenoleukodystrophy (X-ALD). Mutations in the ABCD1 gene have been identified to cause AMN.

Methods

We applied clinical evaluation, laboratory tests, and neuroimaging on three patients with progressive spastic paraparesis. In genetic analysis, we investigated ABCD1 gene mutations by whole-exome sequencing and Sanger sequencing. Bioinformatics tools were used to predict the effects of identified ABCD1 mutations on the protein.

Results

All three patients were men with adult-onset disease, mainly characterized by progressive spastic paraparesis. Among them, two patients had peripheral neuropathy and one patient had signs of adrenal insufficiency. All three patients showed cerebral involvement on brain MRI, while two patients were found with diffuse cord atrophy on spinal MRI. High-VLCFA levels in plasma, as well as C24:0/C22:0 and C26:0/C22:0 ratios, were found in all three patients. In addition, three different ABCD1 mutations were identified in three unrelated Chinese families, including one known mutation (c.1415_1416delAG) and two novel mutations (c.217C>T and c.160_170delACGCAGGAGGC). Based on the clinical assessment, radiographic, biochemical, and genetic testing, the final diagnosis was AMN in these patients with spastic paraparesis.

Conclusion

This study reported three patients with AMN and identified two novel mutations in the ABCD1 in the Chinese population. Our finding emphasized that X-ALD is an important cause of adult-onset spastic paraplegia. Thus, neuroimaging, VLCFA testing, and especially the detection of the ABCD1 gene have important implications for the etiological diagnosis of adult patients with spastic paraplegia.
Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2
Authors: Sakuma Hiroshi , Takanashi Jun-ichi , Muramatsu Kazuhiro , Kondo Hidehito , Shiihara Takashi , Suzuki Motomasa , Okanari Kazuo , Kasai Mariko , Mitani Osamu , Nakazawa Tomoyuki , Omata Taku , Shimoda Konomi , Abe Yuichi , Maegaki Yoshihiro , Murayama Kei , Murofushi Yuka , Nagase Hiroaki , Okumura Akihisa , Sakai Yasunari , Tada Hiroko , Mizuguchi Masashi ,   Japanese Pediatric Neuro-COVID-19 Study Group
Published: March 2023

Background and objectives

To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes.

Methods

A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge.

Results

Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01).

Discussion

Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.
Questionnaires based on natural language processing elicit immersive ruminative thinking in ruminators: Evidence from behavioral responses and EEG data
Authors: Li Yulong , Li Chenxi , Zhang Tian , Wu Lin , Lin Xinxin , Li Yijun , Wang Lingling , Yang Huilin , Lu Diyan , Miao Danmin , Fang Peng
Published: March 2023

Rumination is closely related to mental disorders and can thus be used as a marker of their presence or a predictor of their development. The presence of masking and fabrication in psychological selection can lead to inaccurate detection of psychological disorders. Human language is considered crucial in eliciting specific conscious activities, and the use of natural language processing (NLP) in the development of questionnaires for psychological tests has the potential to elicit immersive ruminative thinking, leading to changes in neural activity. Electroencephalography (EEG) is commonly used to detect and record neural activity in the human brain and is sensitive to changes in brain activity. In this study, we used NLP to develop a questionnaire to induce ruminative thinking and then recorded the EEG signals in response to the questionnaire. The behavioral results revealed that ruminators exhibited higher arousal rates and longer reaction times, specifically in response to the ruminative items of the questionnaire. The EEG results showed no significant difference between the ruminators and the control group during the resting state; however, a significant alteration in the coherence of the entire brain of the ruminators existed while they were answering the ruminative items. No differences were found in the control participants while answering the two items. These behavioral and EEG results indicate that the questionnaire elicited immersive ruminative thinking, specifically in the ruminators. Therefore, the questionnaire designed using NLP is capable of eliciting ruminative thinking in ruminators, offering a promising approach for the early detection of mental disorders in psychological selection.
A mechanistic review of pharmacological activities of homeopathic medicine licorice against neural diseases
Authors: Zulfugarova Parvin , Zivari-Ghader Tayebeh , Maharramova Sevinj , Ahmadian Elham , Eftekhari Aziz , Khalilov Rovshan , Turksoy Vugar Ali , Rosić Gvozden , Selakovic Dragica
Published: March 2023

The use of medicinal plants has grown in popularity in recent decades because, as natural ingredients, they have fewer adverse effects and are more effective than synthetic alternatives. As a small perennial herb, Glycyrrhiza glabra L. (Licorice) has been investigated for its therapeutic efficacy against neural disorders mainly ischemic stroke as well as the neurodegenerative diseases such as dementia and Alzheimer’s disease, and Parkinson’s disease which has been attributed to its HMGB inhibitory function, reactive oxygen scavenging and anti-inflammatory activity. The objective of current review is to review the evidence for the pharmacological effects of licorice and its vital active components on neurological disorders and the underlying signaling networks. We reviewed Papers published from 2000.1.1 up to 2 January 2023 in web of science, Google Scholar and PubMed data bases using key words including “Licorice,” “Glycyrrhiza glabra L.,” “Glycyrrhizic acid,” “brain,” “neurodegenerative disease,” “Alzheimer’s,” and “Parkinson” were used to search in title/abstracts. Licorice extract and/or its active components can be used safely in therapeutic doses for optimizing the management of a multiple neurodegenerative disorders, and hampering the extent of neural tissue injury and neurologic deficits subsequent to cerebrovascular accidents.
Triose-phosphate isomerase deficiency is associated with a dysregulation of synaptic vesicle recycling in Drosophila melanogaster
Authors: Stone Aelfwin , Cujic Oliver , Rowlett Angel , Aderhold Sophia , Savage Emma , Graham Bruce , Steinert Joern R.
Published: March 2023

Introduction

Numerous neurodegenerative diseases are associated with neuronal dysfunction caused by increased redox stress, often linked to aberrant production of redox-active molecules such as nitric oxide (NO) or oxygen free radicals. One such protein affected by redox-mediated changes is the glycolytic enzyme triose-phosphate isomerase (TPI), which has been shown to undergo 3-nitrotyrosination (a NO-mediated post-translational modification) rendering it inactive. The resulting neuronal changes caused by this modification are not well understood. However, associated glycation-induced cytotoxicity has been reported, thus potentially causing neuronal and synaptic dysfunction via compromising synaptic vesicle recycling.

Methods

This work uses Drosophila melanogaster to identify the impacts of altered TPI activity on neuronal physiology, linking aberrant TPI function and redox stress to neuronal defects. We used Drosophila mutants expressing a missense allele of the TPI protein, M81T, identified in a previous screen and resulting in an inactive mutant of the TPI protein (TPIM81T, wstd1). We assessed synaptic physiology at the glutamatergic Drosophila neuromuscular junction (NMJ), synapse morphology and behavioural phenotypes, as well as impacts on longevity.

Results

Electrophysiological recordings of evoked and spontaneous excitatory junctional currents, alongside high frequency train stimulations and recovery protocols, were applied to investigate synaptic depletion and subsequent recovery. Single synaptic currents were unaltered in the presence of the wstd1 mutation, but frequencies of spontaneous events were reduced. Wstd1 larvae also showed enhanced vesicle depletion rates at higher frequency stimulation, and subsequent recovery times for evoked synaptic responses were prolonged. A computational model showed that TPI mutant larvae exhibited a significant decline in activity-dependent vesicle recycling, which manifests itself as increased recovery times for the readily-releasable vesicle pool. Confocal images of NMJs showed no morphological or developmental differences between wild-type and wstd1 but TPI mutants exhibited learning impairments as assessed by olfactory associative learning assays.

Discussion

Our data suggests that the wstd1 phenotype is partially due to altered vesicle dynamics, involving a reduced vesicle pool replenishment, and altered endo/exocytosis processes. This may result in learning and memory impairments and neuronal dysfunction potentially also presenting a contributing factor to other reported neuronal phenotypes.
Bi-directional causal effect between vitamin B12 and non-alcoholic fatty liver disease: Inferring from large population data
Authors: Fu Liwan , Wang Yuquan , Hu Yue-Qing
Published: March 2023

Objectives

Many observational studies evaluate the association between vitamin B12 and non-alcoholic fatty liver disease (NAFLD). However, the causality of this association remains uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to explore the association between vitamin B12 and NAFLD.

Methods

Two-sample Mendelian randomization study was conducted. Summary statistics for vitamin B12 were acquired from a genome-wide association studies (GWAS) meta-analysis including 45,576 subjects. Summary-level data for NAFLD was obtained from a GWAS meta-analysis of 8,434 cases and 770,180 non-cases and another GWAS meta-analysis of 1,483 cases and 17,781 non-cases. Summary-level data for 4 enzymes including alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GGT), was available from the UK Biobank. Inverse variance weighting (as main analysis), weighted median estimate, robust adjusted profile score, MR-Egger, and MR-PRESSO (sensitivity analyses) were performed to calculate causal estimates.

Results

Genetically predicted higher vitamin B12 concentrations were consistently associated with an increased NAFLD in two sources. The combined odds ratio (OR) of NAFLD was 1.30 (95% confidence interval (CI), 1.13 to 1.48; p < 0.001) per SD-increase in vitamin B12 concentrations. Genetic liability to NAFLD was also positively associated with vitamin B12 concentrations (Beta 0.08, 95%CI, 0.01 to 0.16; p = 0.034). Sensitivity analyses also revealed consistent results. Genetically predicted vitamin B12 concentrations showed no significant association with liver enzymes.

Conclusion

The present study indicates that increased serum vitamin B12 concentrations may play a role in NAFLD risk. NAFLD also has a causal impact on elevated vitamin B12 concentrations in the circulation. Notably, vitamin B12 concentrations imply the levels of vitamin B12 in the circulation, and higher intake of vitamin B12 may not directly lead to higher levels of serum vitamin B12, instead the higher levels of vitamin B12 in the circulation may be caused by the dysregulation of the metabolism of this vitamin in this study. There exist bidirectional causal effects between serum vitamin B12 concentrations and risk of NAFLD in European individuals.
Eater-oriented knowledge framework for reducing salt and dietary sodium intake (scoping review)
Authors: Endaltseva Alexandra , Coeurquetin Paul , Thomas-Danguin Thierry , Poulain Jean-Pierre , Tibère Laurence , Dupuy Anne
Published: March 2023

Salt and dietary sodium are ubiquitously present in daily food practices and, at the same time, reducing salt intake presents an important public health issue. Given such an ambivalent position of salt in human diet, we argue that public health guidelines toward dietary sodium reduction require an eater-oriented knowledge framework. In this article we are making the first steps toward a flexible interdisciplinary database which would include nutritional, socio-economic, cultural, material, and socio-psychological determinants of salt consumption for comprehensive public health campaigns. We employ an explorative scoping review of academic articles and reports, limiting our review to the original data on salt or sodium consumption published in English or French between 2000 and 2022. We describe salt consumption as research object, identifying its representation in different research fields, data sources, methodologies, samples, and links with nutritional recommendations. We synthesize existing approachesviafour eater-oriented categories: Socio-demographic and cultural descriptors of salt consumers; Knowledge, attitudes, and beliefs on nutritional norms; Salt practices associated with dietary or medical regimes; Salt materialities: interactions and contexts. In each category, we identify the dominant relational features, i.e., what kind of ‘eater-salt’ relation is being put forward. We thus build an interdisciplinary documentary base of dietary sodium consumption factors. We discuss the results, suggesting that comprehensive nutritional policies for global salt reduction require interdisciplinary eater-oriented data frameworks.
Metabolic classification of non-small cell lung cancer patient-derived xenografts by a digital pathology approach: A pilot study
Authors: Ferrarini Federica , Zulato Elisabetta , Moro Massimo , Del Bianco Paola , Borzi Cristina , Esposito Giovanni , Zanin Tiziana , Sozzi Gabriella , Indraccolo Stefano
Published: March 2023

Introduction

Genetically characterized patient-derived tumor xenografts (PDX) are a valuable resource to understand the biological complexity of cancer and to investigate new therapeutic approaches. Previous studies, however, lack information about metabolic features of PDXs, which may limit testing of metabolism targeting drugs.

Methods

In this pilot study, we investigated by immunohistochemistry (IHC) expression of five essential metabolism-associated markers in a set of lung adenocarcinoma PDX samples previously established and characterized. We exploited digital pathology to quantify expression of the markers and correlated results with tumor cell proliferation, angiogenesis and time of PDX growth in mice.

Results

Our results indicate that the majority of the analyzed PDX models rely on oxidative phosphorylation (OXPHOS) metabolism, either alone or in combination with glucose metabolism. Double IHC enabled us to describe spatial expression of the glycolysis-associated monocarboxylate transporter 4 (MCT4) marker and the OXPHOS-associated glutaminase (GLS) marker. GLS expression was associated with cell proliferation and with expression of liver-kinase B1 (LKB1), a tumor suppressor involved in the regulation of multiple metabolic pathways. Acetyl CoA carboxylase (ACC) was associated with the kinetics of PDX growth.

Conclusion

Albeit limited by the small number of samples and markers analyzed, metabolic classification of existing collections of PDX by this mini panel will be useful to inform pre-clinical testing of metabolism-targeting drugs.
Progression in immunotherapy for advanced prostate cancer
Authors: Liang Hao , Liu Yang , Guo Jiao , Dou Maoyang , Zhang Xiaoyi , Hu Liyong , Chen Jun
Published: March 2023

Prostate cancer is one of the most common malignant cancers of the male genitourinary system and has high morbidity and mortality. Currently, treatment modalities for localized prostate cancer focus mainly on radical prostatectomy or radical radiation therapy. Some patients still experience disease recurrence or progression after these treatments, while others are already at an advanced stage or have metastases at the time of diagnosis. With the continuous development and progress of medicine in recent years, immunotherapy has become a revolutionary cancer treatment, and has achieved remarkable accomplishments in the treatment of hematologic malignancies. A variety of immunotherapies have also appeared in the field of advanced prostate cancer treatment, including therapeutic vaccines and immune checkpoint therapies. Despite the discrepancy between the results of some immunotherapy studies, immunotherapy for prostate cancer has shown some initial success, especially in combination immunotherapies. Currently, immunotherapy is mainly used in advanced prostate cancer, especially in patients with metastatic castration-resistant prostate cancer. However, with the development of more clinical trials of immunotherapy, more evidence will be provided supporting the rational application of immunotherapy in the future.
Prognostic and immunological characteristics of CDK1 in lung adenocarcinoma: A systematic analysis
Authors: Du Qingwu , Liu Wenting , Mei Ting , Wang Jingya , Qin Tingting , Huang Dingzhi
Published: March 2023

Background

Cyclin-dependent kinases (CDKs) play a key role in cell proliferation in lung adenocarcinoma (LUAD). Comprehensive analysis of CDKs to elucidate their clinical significance and interactions with the tumor immune microenvironment is needed.

Methods

RNA expression, somatic mutation, copy number variation, and single-cell RNA sequencing data were downloaded from public datasets. First, we comprehensively evaluated the expression profile and prognostic characteristics of 26 CDKs in LUAD, and CDK1 was selected as a candidate for further analysis. Then, a systematic analysis was performed to explore the relationships of CDK1 with clinical characteristics and tumor immune microenvironment factors in LUAD.

Results

CDK1 was markedly upregulated at both the mRNA and protein level in LUAD. Moreover, overexpression of CDK1 was related to poor clinical outcomes. CDK1 coexpressed genes were mainly involved in the cell cycle, the DNA repair process, and the p53 signaling pathway. In addition, CDK1 expression was found to be correlated with the expression of multiple immunomodulators and chemokines, which participate in activating and suppressing the immune microenvironment. CDK1 expression was also correlated with increased infiltration of numerous immune cells, including CD4+ T cells and M1 macrophages. Patients with high CDK1 expression tended to have a poor response to immunotherapy but were sensitive to multiple chemotherapies and targeted drugs. The MDK-NCL and SPP1-CD44 ligand−receptor pairs were markedly activated in the intercellular communication network. CDK1 was an independent prognostic factor for LUAD and improved the ability to predict overall survival when combined with tumor stage.

Conclusion

CDK1 plays an essential role in reshaping the tumor immune microenvironment and might be a prognostic and treatment biomarker in LUAD.
Mapping trends and hotspot regarding testicular torsion: A bibliometric analysis of global research (2000–2022)
Authors: Hu Shaowen , Guo Mingjie , Xiao Yafei , Li Yang , Luo Qingyang , Li Zun , Zhu Chaoyang
Published: March 2023

Background

Testicular torsion is an acute scrotal disorder requiring immediate emergency treatment. Ischemic injury and reperfusion injury are important causes of oxidative stress and irreversible oxidative damage after testicular torsion. Although a large number of literatures have discussed the causes and treatment of testicular torsion, there is currently a lack of systematic exploration of the historical evolution of testicular torsion and the construction of a knowledge framework.

Method

The Web of Science Core Collection was searched for studies on testicular torsion published between 2000 and 2022. The basic data of the literature were analyzed by using Excel and CiteSpace software.

Result

A total of 1,007 publications on testicular torsion published were found in 64 countries between 2000 and 2022, with an increasing annual publication level. Early detection, early diagnosis and early treatment of testicular torsion had always been at the core of clinical practice, and the pathological cascade reaction of ischemic injury and ischemia-reperfusion injury after testicular torsion were also at the core of basic research. Emphasis had been placed on the development of protective drugs for ischemia and reperfusion after testicular torsion in various countries, regions and institutions.

Conclusion

Over the past 20 years, the research on testicular torsion had been widely concerned. Hot topics in testicular torsion in recent years were ischemia-reperfusion injury, oxidative stress, rat, doppler ultrasonography, diagnosis and orchiectomy. This article may provide a useful resource for clinicians and basic researchers regarding testicular torsion.
Detection of enterovirus in cerebrospinal fluids without pleocytosis in febrile infants under 3 months old reduces antibiotherapy duration
Authors: Blachez Marion , Boussier Jeremy , Mariani Patricia , Caula Caroline , Gaschignard Jean , Lefèvre-Utile Alain
Published: March 2023

Background

Infants under 3 months old with fever often receive empirical antibiotic treatment. Enterovirus is one of the leading causes of infection and aseptic meningitis but is not systematically screened. We aimed to evaluate enterovirus positive RT-PCR proportion in cerebrospinal fluid (CSF) with no pleocytosis and its impact on antibiotic treatment duration.

Methods

During the enterovirus endemic season, from 2015 to 2018, we retrospectively studied infants under 3 months old, consulting for fever without cause, with normal CSF analysis, and receiving empirical antibiotic treatment. Clinical and biological data were analyzed, notably enterovirus RT-PCR results. The primary outcome was the duration of antibiotic therapy.

Results

92 patients were recruited. When tested, 41% of infants were positive for enterovirus, median antibiotic duration was reduced in enterovirus positive in comparison to negative patients with respectively 1.9 [interquartile range (IQR), 1.7–2] vs. 4.1 [IQR, 2–6], p < 0.001. No clinical nor biological features differed according to the enterovirus status.

Conclusion

In this population, enterovirus positive CSF are frequent despite the absence of pleocytosis. However, its research was not guided by clinical or biological presentations. Systematic and routine use of enterovirus RT-PCR during enterovirus season, regardless of CSF cell count, could reduce the prescription of antibiotics in febrile infants under 3 months old without clinical orientation.
The efficacy and safety of Chinese herbal medicine in the treatment of painful diabetic neuropathy: A systematic review and meta-analysis
Authors: Song Min , Huai Baogeng , Shi Zhenpeng , Li Wenyi , Xi Yutan , Liu Zhenguo , Zhang Jihang , Zhou Junyu , Qiao Yun , Liu Deshan
Published: March 2023

Objective: The objective of this systematic review and meta-analysis is to assess the effectiveness and security of Chinese herbal medicine (CHM) in the therapy of painful diabetic neuropathy (PDN).

Methods: We searched databases for randomized controlled trials (RCTs) of CHM in the treatment of PDN. Outcome indicators included nerve conduction velocity, clinical efficiency, pain score, TCM syndrome score, and adverse events. Stata 16.0 was used to carry out the Meta-analysis.

Results: A total of 21 RCTs with 1,737 participants were included. This meta-analysis found that using CHM as adjuvant treatment or as monotherapy for PDN can improve SCV of median nerve [mean difference (MD) = 3.56, 95% Confidence interval (CI) (2.19, 4.92) ], MCV of median nerve [ MD = 3.82, 95% CI (2.51, 5.12) ], SCV of common peroneal nerve [ MD = 4.16, 95% CI (1.62, 6.70) ], MCV of common peroneal nerve [ MD = 4.37, 95% CI (1.82, 6.93) ], SCV of gastrocnemius nerve [ MD = 4.95, 95% CI (3.52, 6.37) ], SCV of tibial nerve [ MD = 3.17, 95% CI (−2.64, 8.99) ], MCV of tibial nerve [MD = 6.30, 95%CI (5.00, 7.60)] and clinical effective rate [ odds ratio (OR) = 4.00, 95% CI (2.89, 5.52) ] and reduce pain score [standardized mean difference (SMD) = -2.23, 95% CI (-3.04, -1.41) ], TCM syndrome score [ MD = -4.70, 95% CI (-6.61, -2.80) ]. In addition, compared to the control group, adverse events of Chinese medicine intervention occurred less.

Conclusion: CHM as adjuvant therapy or single treatment has a good curative effect and is safe for patients with PDN, which is worthy of clinical promotion and use, however; higher quality clinical studies are still needed to prove.

Systematic Review Registration:https://www.crd.york.ac.uk/, identifier CRD42022327967
Current landscape and tailored management of immune-related adverse events
Authors: Liu Wenhui , Luo Zhiying , Liu Yiping , Sun Bao
Published: March 2023

Unprecedented advances have been made in immune checkpoint inhibitors (ICIs) in the treatment of cancer. However, the overall benefits from ICIs are impaired by the increasing incidence of immune-related adverse events (irAEs). Although several factors and mechanisms have been proposed in the development of irAEs, there is still incomprehensive understanding of irAEs. Therefore, it is urgent to identify certain risk factors and biomarkers that predict the development of irAEs, as well as to understand the underlying mechanisms of these adverse events. Herein, we comprehensively summarize the state-of-the-art knowledge about clinical features and the related risk factors of irAEs. Particularly, we also discuss relevant mechanisms of irAEs and address the mechanism-based strategies, aiming to develop a tailored management approach for irAEs.
Ethyl-acetate fraction from a cinnamon-cortex extract protects pancreatic β-cells from oxidative stress damage
Authors: Li Weiling , Qiao Jialu , Lin Kuan , Sun Ping , Wang Yuansong , Peng Qian , Ye Xiansheng , Liu Wei , Sun Binlian
Published: March 2023

Background: The pathogenesis of diabetes mellitus is mediated mainly by oxidative stress produced by damaged pancreatic β-cells. We identified that an ethyl-acetate fraction (EA) from a cinnamon-cortex extract (CCE) is rich in flavonoid, and showed no toxicity to β cells.

Objective: In this study, we evaluated the pharmacologic activities of EA on pancreatic β cells using a model of oxidative stress induced by H2O2 or alloxan.

Results: The results showed that EA could significantly reduce reactive oxygen (ROS) accumulation to improve the survival of cells. Western blot showed that EA treatment upregulated expression of nuclear factor erythroid 2 related factor 2, heme oxygenase-1, and gamma glutamylcysteine synthetase. The same model study found that EA also can protect β cells against the apoptosis induced by oxidative stress. Furthermore, EA can enhance insulin secretion in rat and mouse β cell lines treated or not with alloxan or H2O2. The expression of the insulin transcription factor PDX-1 increased in an EA concentration-dependent manner. At last, the major functional compounds of EA analysis showed that three compounds, cinnamyl alcohol, coumarin, and cinnamic acid, had similar effects as EA.

Conclusions: In sum, our data suggested that EA fraction from CCE can protect β cells from oxidative stress, and increase insulin secretion to improve the function of β cells. This function might be due to these three compounds found in EA. Our findings provide a theoretical basis and functional molecules for the use of CCE against diabetes mellitus.
A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip
Authors: Sengupta Arunima , Dorn Aurélien , Jamshidi Mohammad , Schwob Magali , Hassan Widad , De Maddalena Lea Lara , Hugi Andreas , Stucki Andreas O. , Dorn Patrick , Marti Thomas M. , Wisser Oliver , Stucki Janick D. , Krebs Tobias , Hobi Nina , Guenat Olivier T.
Published: March 2023

Prolonged exposure to environmental respirable toxicants can lead to the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and fibrosis. The limited number of FDA-approved inhaled drugs for these serious lung conditions has led to a shift from in vivo towards the use of alternative in vitro human-relevant models to better predict the toxicity of inhaled particles in preclinical research. While there are several inhalation exposure models for the upper airways, the fragile and dynamic nature of the alveolar microenvironment has limited the development of reproducible exposure models for the distal lung. Here, we present a mechanistic approach using a new generation of exposure systems, the Cloud α AX12. This novel in vitro inhalation tool consists of a cloud-based exposure chamber (VITROCELL) that integrates the breathing AXLung-on-chip system (AlveoliX). The ultrathin and porous membrane of the AX12 plate was used to create a complex multicellular model that enables key physiological culture conditions: the air-liquid interface (ALI) and the three-dimensional cyclic stretch (CS). Human-relevant cellular models were established for a) the distal alveolar-capillary interface using primary cell-derived immortalized alveolar epithelial cells (AXiAECs), macrophages (THP-1) and endothelial (HLMVEC) cells, and b) the upper-airways using Calu3 cells. Primary human alveolar epithelial cells (AXhAEpCs) were used to validate the toxicity results obtained from the immortalized cell lines. To mimic in vivo relevant aerosol exposures with the Cloud α AX12, three different models were established using: a) titanium dioxide (TiO2) and zinc oxide nanoparticles b) polyhexamethylene guanidine a toxic chemical and c) an anti-inflammatory inhaled corticosteroid, fluticasone propionate (FL). Our results suggest an important synergistic effect on the air-blood barrier sensitivity, cytotoxicity and inflammation, when air-liquid interface and cyclic stretch culture conditions are combined. To the best of our knowledge, this is the first time that an in vitro inhalation exposure system for the distal lung has been described with a breathing lung-on-chip technology. The Cloud α AX12 model thus represents a state-of-the-art pre-clinical tool to study inhalation toxicity risks, drug safety and efficacy.
A new molecular subclassification and in silico predictions for diagnosis and prognosis of papillary thyroid cancer by alternative splicing profile
Authors: Li Haiyan , Lan Hao , Li Menglong , Pu Xuemei , Guo Yanzhi
Published: March 2023

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. However, different PTC variants reveal high heterogeneity at histological, cytological, molecular and clinicopathological levels, which complicates the precise diagnosis and management of PTC. Alternative splicing (AS) has been reported to be potential cancer biomarkers and therapeutic targets.

Method: Here, we aim to find a more sophisticated molecular subclassification and characterization for PTC by integrating AS profiling. Based on six differentially expressed alternative splicing (DEAS) events, a new molecular subclassification was proposed to reclassify PTC into three new groups named as Cluster0, Cluster1 and Cluster2 respectively.

Results: An in silico prediction was performed for accurate recognition of new groups with the average accuracy of 91.2%. Moreover, series of analyses were implemented to explore the differences of clinicopathology, molecular and immune characteristics across them. It suggests that there are remarkable differences among them, but Cluster2 was characterized by poor prognosis, higher immune heterogeneity and more sensitive to anti-PD1 therapy. The splicing correlation networks proved the complicated regulation relationships between AS events and splicing factors (SFs). An independent prognostic indicator for PTC overall survival (OS) was established. Finally, three compounds (orantinib, tyrphostin-AG-1295 and AG-370) were discovered to be the potential therapeutic agents.

Discussion: Overall, the six DEAS events are not only potential biomarkers for precise diagnosis of PTC, but also the probable prognostic predictors. This research would be expected to highlight the effect of AS events on PTC characterization and also provide new insights into refining precise subclassification and improving medical therapy for PTC patients.