bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific myeloid signatures in peripheral blood differentiate active and rare clinical phenotypes of multiple sclerosis
Authors: Vakrakou Aigli G. , Paschalidis Nikolaos , Pavlos Eleftherios , Giannouli Christina , Karathanasis Dimitris , Tsipota Xristina , Velonakis Georgios , Stadelmann-Nessler Christine , Evangelopoulos Maria-Eleftheria , Stefanis Leonidas , Kilidireas Constantinos
Published: January 2023

Current understanding of Multiple Sclerosis (MS) pathophysiology implicates perturbations in adaptive cellular immune responses, predominantly T cells, in Relapsing-Remitting forms (RRMS). Nevertheless, from a clinical perspective MS is a heterogeneous disease reflecting the heterogeneity of involved biological systems. This complexity requires advanced analysis tools at the single-cell level to discover biomarkers for better patient-group stratification. We designed a novel 44-parameter mass cytometry panel to interrogate predominantly the role of effector and regulatory subpopulations of peripheral blood myeloid subsets along with B and T-cells (excluding granulocytes) in MS, assessing three different patient cohorts: RRMS, PPMS (Primary Progressive) and Tumefactive MS patients (TMS) (n=10, 8, 14 respectively). We further subgrouped our cohort into inactive or active disease stages to capture the early underlying events in disease pathophysiology. Peripheral blood analysis showed that TMS cases belonged to the spectrum of RRMS, whereas PPMS cases displayed different features. In particular, TMS patients during a relapse stage were characterized by a specific subset of CD11c+CD14+ CD33+, CD192+, CD172+-myeloid cells with an alternative phenotype of monocyte-derived macrophages (high arginase-1, CD38, HLA-DR-low and endogenous TNF-a production). Moreover, TMS patients in relapse displayed a selective CD4 T-cell lymphopenia of cells with a Th2-like polarised phenotype. PPMS patients did not display substantial differences from healthy controls, apart from a trend toward higher expansion of NK cell subsets. Importantly, we found that myeloid cell populations are reshaped under effective disease-modifying therapy predominantly with glatiramer acetate and to a lesser extent with anti-CD20, suggesting that the identified cell signature represents a specific therapeutic target in TMS. The expanded myeloid signature in TMS patients was also confirmed by flow cytometry. Serum neurofilament light-chain levels confirmed the correlation of this myeloid cell signature with indices of axonal injury. More in-depth analysis of myeloid subsets revealed an increase of a subset of highly cytolytic and terminally differentiated NK cells in PPMS patients with leptomeningeal enhancement (active-PPMS), compared to those without (inactive-PPMS). We have identified previously uncharacterized subsets of circulating myeloid cells and shown them to correlate with distinct disease forms of MS as well as with specific disease states (relapse/remission).
Recent advances in ocular graft-versus-host disease
Authors: Cheng Xianjing , Huang Ruihao , Huang Shiqin , Fan Wei , Yuan Rongdi , Wang Xiaoqi , Zhang Xi
Published: January 2023

Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals’ quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment.
A novel interleukin-2-based fusion molecule, HCW9302, differentially promotes regulatory T cell expansion to treat atherosclerosis in mice
Authors: Zhu Xiaoyun , Li Qiongzhen , George Varghese , Spanoudis Catherine , Gilkes Crystal , Shrestha Niraj , Liu Bai , Kong Lin , You Lijing , Echeverri Christian , Li Liying , Wang Zheng , Chaturvedi Pallavi , Muniz Gabriela J. , Egan Jack O. , Rhode Peter R. , Wong Hing C.
Published: January 2023

Atherosclerosis is a chronic inflammatory disease caused by deposition of oxidative low-density lipoprotein (LDL) in the arterial intima which triggers the innate immune response through myeloid cells such as macrophages. Regulatory T cells (Tregs) play an important role in controlling the progression or regression of atherosclerosis by resolving macrophage-mediated inflammatory functions. Interleukin-2 (IL-2) signaling is essential for homeostasis of Tregs. Since recombinant IL-2 has an unfavorable pharmacokinetic profile limiting its therapeutic use, we constructed a fusion protein, designated HCW9302, containing two IL-2 domains linked by an extracellular tissue factor domain. We found that HCW9302 exhibited a longer serum half-life with an approximately 1000-fold higher affinity for the IL-2Rα than IL-2. HCW9302 could be administered to mice at a dosing range that expanded and activated Tregs but not CD4+ effector T cells. In an ApoE-/- mouse model, HCW9302 treatment curtailed the progression of atherosclerosis through Treg activation and expansion, M2 macrophage polarization and myeloid-derived suppressor cell induction. HCW9302 treatment also lessened inflammatory responses in the aorta. Thus, HCW9302 is a potential therapeutic agent to expand and activate Tregs for treatment of inflammatory and autoimmune diseases.
Computing marine plankton connectivity under thermal constraints
Authors: Manral Darshika , Iovino Doroteaciro , Jaillon Olivier , Masina Simona , Sarmento Hugo , Iudicone Daniele , Amaral-Zettler Linda , van Sebille Erik
Published: January 2023

Ocean currents are a key driver of plankton dispersal across the oceanic basins. However, species specific temperature constraints may limit the plankton dispersal. We propose a methodology to estimate the connectivity pathways and timescales for plankton species with given constraints on temperature tolerances, by combining Lagrangian modeling with network theory. We demonstrate application of two types of temperature constraints: thermal niche and adaptation potential and compare it to the surface water connectivity between sample stations in the Atlantic Ocean. We find that non-constrained passive particles representative of a plankton species can connect all the stations within three years at the surface with pathways mostly along the major ocean currents. However, under thermal constraints, only a subset of stations can establish connectivity. Connectivity time increases marginally under these constraints, suggesting that plankton can keep within their favorable thermal conditions by advecting via slightly longer paths. Effect of advection depth on connectivity is observed to be sensitive to the width of the thermal constraints, along with decreasing flow speeds with depth and possible changes in pathways.
Experimental study on the pullout characteristics of toothed warp knitted geogrid in different sand fillers
Authors: Yawei Fu , Wei Fang
Published: January 2023

In order to investigate the pullout characteristics of a toothed geogrid, a commercialized warp-knitted geogrid was combined with rigid angle aluminum to form a qualified toothed geogrid and used to perform pullout model tests in which four different gradations of fillers, three denti-strip heights, and three normal stress levels were adopted. The research shows that: 1) at the initial stage of the pullout test, pullout resistance rises rapidly and only the curves of the pullout force (T) and pullout displacement (△L) under lower normal stress reach the peak. The maximum pullout resistance is positively related to normal stress on the model, the denti-strip height, and the coarse particle content. 2) As the denti-strip’s height increases, the coefficient of the reinforcing effect, the quasi-shear strength parameters, and the quasi-frictional coefficient all show enhancements to some extent, as well as the drawing coefficient. When the normal stress rises, the quasi-shear strength parameters increase, while the quasi-frictional coefficients gradually decrease. The quasi-shear strength parameters and the quasi-frictional coefficient are positively correlated with the coarse particle content, while the drawing coefficient has a negative correlation with the coarse grain proportion. 3) It could be inferred that the denti-strip with a suitable height and coarser gradation of the filler would be beneficial to enhance the anti-pullout performance in reinforcement project entities, and the bearing resistance acting on the denti-strip is able to play a more dominant role in a low backfill condition. The research results can further enrich the relevant achievements in the field of spatial reinforcement and provide useful evidence for the design and construction of related projects, especially for low embankment filling.
Spatial patterns in sociodemographic factors explain to a large extent the prevalence of hypertension and diabetes in Aragon (Spain)
Authors: Bentué-Martínez Carmen , Mimbrero Marcos Rodrigues , Zúñiga-Antón María
Published: January 2023

Introduction

The global burden of multi-morbidity has become a major public health challenge due to the multi stakeholder action required to its prevention and control. The Social Determinants of Health approach is the basis for the establishment of health as a cross-cutting element of public policies toward enhanced and more efficient decision making for prevention and management.

Objective

To identify spatially varying relationships between the multi-morbidity of hypertension and diabetes and the sociodemographic settings (2015–2019) in Aragon (a mediterranean region of Northeastern Spain) from an ecological perspective.

Materials and methods

First, we compiled data on the prevalence of hypertension, diabetes, and sociodemographic variables to build a spatial geodatabase. Then, a Principal Component Analysis (PCA) was performed to derive regression variables, i.e., aggregating prevalence rates into a multi-morbidity component (stratified by sex) and sociodemographic covariate into a reduced but meaningful number of factors. Finally, we applied Geographically Weighted Regression (GWR) and cartographic design techniques to investigate the spatial variability of the relationships between multi-morbidity and sociodemographic variables.

Results

The GWR models revealed spatial explicit relationships with large heterogeneity. The sociodemographic environment participates in the explanation of the spatial behavior of multi-morbidity, reaching maximum local explained variance (R2) of 0.76 in men and 0.91 in women. The spatial gradient in the strength of the observed relationships was sharper in models addressing men’s prevalence, while women’s models attained more consistent and higher explanatory performance.

Conclusion

Modeling the prevalence of chronic diseases using GWR enables to identify specific areas in which the sociodemographic environment is explicitly manifested as a driving factor of multi-morbidity. This is step forward in supporting decision making as it highlights multi-scale contexts of vulnerability, hence allowing specific action suitable to the setting to be taken.
New prognostic scoring system for mortality in idiopathic pulmonary fibrosis by modifying the gender, age, and physiology model with desaturation during the six-minute walk test
Authors: Lee Jae Ha , Jang Ji Hoon , Jang Hang-Jea , Kim Song Yee , Chung Man Pyo , Yoo Hongseok , Jeong Sung Hwan , Song Jin Woo , Lee Hong Lyeol , Choi Sun Mi , Kim Young Whan , Kim Yong Hyun , Park Sung Woo , Park Jong Sun , Jegal Yangin , Lee Jongmin , Uh Soo-Taek , Kim Tae-Hyung , Kim Yee Hyung , Shin Beomsu , Lee Hyun-kyung , Yang Sei-Hoon , Lee Hyun , Kim Sang-Heon , Lee Eun-Joo , Choi Hye Sook , Kang Hyung Koo , Heo Eun Young , Lee Won-Yeon , Park Moo Suk
Published: January 2023

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry.

Materials and methods

This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model.

Results

Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38–3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60–4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality.

Conclusion

The GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.
Systematic analysis reveals novel insight into the molecular determinants of function, diversity and evolution of sweet taste receptors T1R2/T1R3 in primates
Authors: Wang Congrui , Liu Yi , Cui Meng , Liu Bo
Published: January 2023

Sweet taste is a primary sensation for the preference and adaption of primates to diet, which is crucial for their survival and fitness. It is clear now that the sweet perception is mediated by a G protein-coupled receptor (GPCR)-sweet taste receptor T1R2/T1R3, and many behavioral or physiological experiments have described the diverse sweet taste sensitivities in primates. However, the structure-function relationship of T1R2s/T1R3s in primates, especially the molecular basis for their species-dependent sweet taste, has not been well understood until now. In this study, we performed a comprehensive sequence, structural and functional analysis of sweet taste receptors in primates to elucidate the molecular determinants mediating their species-dependent sweet taste recognition. Our results reveal distinct taxonomic distribution and significant characteristics (interaction, coevolution and epistasis) of specific key function-related residues, which could partly account for the previously reported behavioral results of taste perception in primates. Moreover, the prosimians Lemuriformes species, which were reported to have no sensitivity to aspartame, could be proposed to be aspartame tasters based on the present analysis. Collectively, our study provides new insights and promotes a better understanding for the diversity, function and evolution of sweet taste receptors in primates.
Associations between reproductive history, hormone use, APOE ε4 genotype and cognition in middle- to older-aged women from the UK Biobank
Authors: Lindseth Linn R. S. , de Lange Ann-Marie G. , van der Meer Dennis , Agartz Ingrid , Westlye Lars T. , Tamnes Christian K. , Barth Claudia
Published: January 2023

Introduction

Relative to men, women are at a higher risk of developing age-related neurocognitive disorders including Alzheimer’s disease. While women’s health has historically been understudied, emerging evidence suggests that reproductive life events such as pregnancy and hormone use may influence women’s cognition later in life.

Methods

We investigated the associations between reproductive history, exogenous hormone use, apolipoprotein (APOE) ε4 genotype and cognition in 221,124 middle- to older-aged (mean age 56.2 ± 8.0 years) women from the UK Biobank. Performance on six cognitive tasks was assessed, covering four cognitive domains: episodic visual memory, numeric working memory, processing speed, and executive function.

Results

A longer reproductive span, older age at menopause, older age at first and last birth, and use of hormonal contraceptives were positively associated with cognitive performance later in life. Number of live births, hysterectomy without oophorectomy and use of hormone therapy showed mixed findings, with task-specific positive and negative associations. Effect sizes were generally small (Cohen’s d < 0.1). While APOE ε4 genotype was associated with reduced processing speed and executive functioning, in a dose-dependent manner, it did not influence the observed associations between female-specific factors and cognition.

Discussion

Our findings support previous evidence of associations between a broad range of female-specific factors and cognition. The positive association between a history of hormonal contraceptive use and cognition later in life showed the largest effect sizes (max. d = 0.1). More research targeting the long-term effects of female-specific factors on cognition and age-related neurocognitive disorders including Alzheimer’s disease is crucial for a better understanding of women’s brain health and to support women’s health care.
Opposite pattern of transcranial direct current stimulation effects in middle-aged and older adults: Behavioral and neurophysiological evidence
Authors: Bagattini Chiara , Cid-Fernández Susana , Bulgari Martina , Miniussi Carlo , Bortoletto Marta
Published: January 2023

Introduction

Episodic memory (EM) exhibits an age-related decline, with overall increased impairment after the age of 65. The application of transcranial direct current stimulation (tDCS) to ameliorate cognitive decline in ageing has been extensively investigated, but its efficacy has been reported with mixed results. In this study, we aimed to assess whether age contributes to interindividual variability in tDCS efficacy.

Methods

Thirty-eight healthy adults between 50 and 81 years old received anodal tDCS over the left prefrontal cortex during images encoding and then performed an EM recognition task while event-related potentials (ERPs) were recorded.

Results

Our results showed an opposite pattern of effect between middle-aged (50–64 years) and older (65–81 years) adults. Specifically, performance in the recognition task after tDCS was enhanced in older adults and was worsened in middle-aged adults. Moreover, ERPs acquired during the recognition task showed that two EM components related to familiarity and post-retrieval monitoring, i.e., Early Frontal and Late Frontal Old-New effects, respectively, were significantly reduced in middle-aged adults after anodal tDCS.

Discussion

These results support an age-dependent effect of prefrontal tDCS on EM processes and its underlying electrophysiological substrate, with opposing modulatory trajectories along the aging lifespan.
No genetic causal association between Alzheimer’s disease and osteoporosis: A bidirectional two-sample Mendelian randomization study
Authors: Hu Hongxin , Mei Jian , Cai Yuanqing , Ding Haiqi , Niu Susheng , Zhang Wenming , Fang Xinyu
Published: January 2023

Objective

Many observational studies have found an association between Alzheimer’s disease (AD) and osteoporosis. However, it is unclear whether there is causal genetic between osteoporosis and AD.

Methods

A two-sample Mendelian randomization (MR) study was used to investigate whether there is a causal relationship between osteoporosis and AD. Genes for osteoporosis and AD were obtained from published the genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) with significant genome-wide differences (p < 5 × 10−8) and independent (r2 < 0.001) were selected, and SNPs with F ≥ 10 were further analyzed. Inverse variance weighted (IVW) was used to assess causality, and the results were reported as odds ratios (ORs). Subsequently, heterogeneity was tested using Cochran’s Q test, pleiotropy was tested using the MR–Egger intercept, and leave-one-out sensitivity analysis was performed to assess the robustness of the results.

Results

Using the IVW method, MR Egger method, and median-weighted method, we found that the results showed no significant causal effect of osteoporosis at different sites and at different ages on AD, regardless of the removal of potentially pleiotropic SNPs. The results were similar for the opposite direction of causality. These results were confirmed to be reliable and stable by sensitivity analysis.

Conclusion

This study found that there is no bidirectional causal relationship between osteoporosis and AD. However, they share similar pathogenesis and pathways.
Fault-tolerance in metric dimension of boron nanotubes lattices
Authors: Hussain Zafar , Munir Muhammad Mobeen
Published: January 2023

The concept of resolving set and metric basis has been very successful because of multi-purpose applications both in computer and mathematical sciences. A system in which failure of any single unit, another chain of units not containing the faulty unit can replace the originally used chain is called a fault-tolerant self-stable system. Recent research studies reveal that the problem of finding metric dimension is NP-hard for general graphs and the problem of computing the exact values of fault-tolerant metric dimension seems to be even harder although some bounds can be computed rather easily. In this article, we compute closed formulas for the fault-tolerant metric dimension of lattices of two types of boron nanotubes, namely triangular and alpha boron. These lattices are formed by cutting the tubes vertically. We conclude that both tubes have constant fault tolerance metric dimension 4.
Rescue intracranial stenting for acute ischemic stroke after the failure of mechanical thrombectomy: A systematic review, meta-analysis, and trial sequential analysis
Authors: Cai Junxiu , Xu Hai , Xiao Rongzhou , Hu Liping , Xu Ping , Guo Xianbin , Xie Yu , Pan Min , Tang Jie , Gong Qingtao , Liu Yan , Su Rong , Deng Jiahua , Wang Li
Published: January 2023

Background

Intracranial rescue stenting (RS) might be an option for acute ischemic stroke after the failure of mechanical thrombectomy (MT). However, the findings were not consistent in previous systematic reviews, and whether the conclusion was supported by sufficient statistical power is unknown.

Aim

To examine the effect of RS on acute ischemic stroke after the failure of MT with a systematic review, meta-analysis, and trial sequential analysis (TSA).

Methods

We searched Ovid Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 15 June 2022, without any language restriction. Studies assessing the effect of RS for acute ischemia stroke after MT failure were included. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the quality of the included studies through the New Ottawa Scale (NOS). The primary outcome was the recanalization rate after RS. Secondary outcomes included modified Rankin Scale (mRS) at 3 months after stroke, symptomatic intracranial hemorrhage (sICH), and mortality rate. We synthesized the data through a random-effects model and performed a TSA analysis.

Results

We included 15 studies (containing 1,595 participants) after screening 3,934 records. The pooled recanalization rate for rescue stenting was 82% (95% CI 77–87%). Compared with non-stenting, rescue stenting was associated with a higher proportion of patients with 0–2 mRS score (OR 3.96, 95% CI 2.69–5.84, p < 0.001) and a lower 90-day mortality rate (OR 0.46, 95% CI 0.32–0.65, p < 0.001), and stenting did not increase sICH rate (OR 0.63, 95% CI 0.39–1.04, p = 0.075). The TSA analysis showed that the meta-analysis of the mRS score had a sufficient sample size and statistical power.

Conclusions

Our study showed that rescue stenting was effective and safe for patients with acute ischemia stroke who also had a failed MT, and this result was confirmed in a TSA analysis.
Association between intensity or accumulating pattern of physical activity and executive function in community-dwelling older adults: A cross-sectional study with compositional data analysis
Authors: Hyodo Kazuki , Kitano Naruki , Ueno Aiko , Yamaguchi Daisuke , Watanabe Yuya , Noda Takayuki , Nishida Sumiyo , Kai Yuko , Arao Takashi
Published: January 2023

Objective

Previous studies have suggested a positive association between physical activity (PA) and executive function in older adults. However, they did not adequately consider the compositional nature of daily time use and accumulated PA patterns. Therefore, this study aimed to examine the association between intensity or accumulated PA patterns and executive functions (inhibitory control, working memory, and cognitive flexibility) in community-dwelling older adults, considering the interaction of daily time spent in PA, sedentary behavior (SB), and sleep.

Method

This cross-sectional study used baseline data from a randomized controlled trial on the effect of exercise on cognitive function conducted between 2021 and 2022. Data from 76 community-dwelling older adults were used in the analysis. The time spent in PA and SB was assessed using an accelerometer, and sleep duration was self-reported. The Stroop task (inhibitory control), N-back task (working memory), and task-switching task (cognitive flexibility) were conducted to evaluate the subcomponents of executive function. Considering various potential confounders, compositional multiple linear regression analysis and compositional isotemporal substitution were performed to examine the association of PA with executive function and to estimate predicted changes in executive function in response to the hypothetical time-reallocation of movement behaviors, respectively.

Results

A longer time spent in light-intensity PA (LPA), relative to remaining behaviors, was associated with better Stroop task performance. Moreover, this association was stronger in LPA lasting longer than 10 min than in sporadic LPA. Additionally, theoretical 30 min/day time reallocation from SB or sleep to LPA was associated with better Stroop task performance (corresponding to approximately a 5%−10% increase). On the other hand, no significant associations of time spent in moderate- to vigorous-intensity PA with any subcomponents of executive function were observed.

Conclusion

LPA was positively associated with inhibitory control, and this association was stronger in bouts of LPA than in sporadic LPA. Moreover, reducing the time spent in SB or sleep and increasing the time spent in LPA, especially long-bout LPA, could be important measures for managing inhibitory control in late life. Future large longitudinal and intervention studies are needed to confirm these associations and reveal the causality and underlying mechanisms.
Proteomic profiling reveals the potential mechanisms and regulatory targets of sirtuin 4 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s mouse model
Authors: Weng Huidan , Song Wenjing , Fu Kangyue , Guan Yunqian , Cai Guoen , Huang En , Chen Xiaochun , Zou Haiqiang , Ye Qinyong
Published: January 2023

Introduction

Parkinson’s disease (PD), as a common neurodegenerative disease, currently has no effective therapeutic approaches to delay or stop its progression. There is an urgent need to further define its pathogenesis and develop new therapeutic targets. An increasing number of studies have shown that members of the sirtuin (SIRT) family are differentially involved in neurodegenerative diseases, indicating their potential to serve as targets in therapeutic strategies. Mitochondrial SIRT4 possesses multiple enzymatic activities, such as deacetylase, ADP ribosyltransferase, lipoamidase, and deacylase activities, and exhibits different enzymatic activities and target substrates in different tissues and cells; thus, mitochondrial SIRT4 plays an integral role in regulating metabolism. However, the role and mechanism of SIRT4 in PD are not fully understood. This study aimed to investigate the potential mechanism and possible regulatory targets of SIRT4 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice.

Methods

The expression of the SIRT4 protein in the MPTP-induced PD mouse mice or key familial Parkinson disease protein 7 knockout (DJ-1 KO) rat was compared against the control group by western blot assay. Afterwards, quantitative proteomics and bioinformatics analyses were performed to identify altered proteins in the vitro model and reveal the possible functional role of SIRT4. The most promising molecular target of SIRT4 were screened and validated by viral transfection, western blot assay and reverse transcription quantitative PCR (RT-qPCR) assays.

Results

The expression of the SIRT4 protein was found to be altered both in the MPTP-induced PD mouse mice and DJ-1KO rats. Following the viral transfection of SIRT4, a quantitative proteomics analysis identified 5,094 altered proteins in the vitro model, including 213 significantly upregulated proteins and 222 significantly downregulated proteins. The results from bioinformatics analyses indicated that SIRT4 mainly affected the ribosomal pathway, propionate metabolism pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway and peroxisome pathway in cells, and we screened 25 potential molecular targets. Finally, only fatty acid binding protein 4 (FABP4) in the PPAR signaling pathway was regulated by SIRT4 among the 25 molecules. Importantly, the alterations in FABP4 and PPARγ were verified in the MPTP-induced PD mouse model.

Discussion

Our results indicated that FABP4 in the PPAR signaling pathway is the most promising molecular target of SIRT4 in an MPTP-induced mouse model and revealed the possible functional role of SIRT4. This study provides a reference for future drug development and mechanism research with SIRT4 as a target or biomarker.
Electroacupuncture alleviates perioperative hypothalamus-pituitary-adrenal axis dysfunction via circRNA-miRNA-mRNA networks
Authors: Wang Yu , Hu Wei , Han Jing , Zheng Jiayuan , Jiang Ning , Feng Yi , Tian Zhanzhuang
Published: January 2023

Electroacupuncture (EA) has long been used to alleviate surgery-induced hypothalamic–pituitary–adrenal axis dysfunction. However, its downstream gene targets in the brain remain unclear. The aim of the present study was to clarify the potential targets of EA based on RNA sequencing techniques (RNA-seq). Rats were divided into normal control (NC), hepatectomy surgery (HT), HT + EA, and HT + sham EA groups followed by RNA-seq of two representative nuclei in the hypothalamus and amygdala. Weighted Gene Co-expression Network Analysis and Gene Set Enrichment Analysis identified six gene modules associated with neuroendocrine transmitters and neural remodeling in the hypothalamus. Furthermore, circRNA-miRNA-mRNA interaction networks revealed EA-related candidate miRNAs and circRNAs, of which opioid receptor mu 1 might be an EA-specific target, and showed regulation by competing endogenous RNA. We identified the neuroendocrine circRNA-miRNA-mRNA networks through which EA has an effect on HPA axis dysfunction, thus providing potential targets and future research directions for EA treatment.
A randomized controlled trial evaluating the effects of transversus abdominis plane block with compound lidocaine hydrochloride injection on postoperative pain and opioid consumption and gastrointestinal motility in patients undergoing gynecological laparotomy
Authors: Zhang Linlin , Jia Zhen , Gao Tianyu , Wang Yigang , Zhao Yuying , Li Jing , Yu Yonghao , Li Qing , Wang Guolin
Published: January 2023

Introduction

Incorporation of transversus abdominis plane (TAP) block into multimodal analgesia has been emphasized in Enhanced Recovery protocols (ERPs). However, benefit is limited in clinical practice. A potential explanation is the short duration of analgesia of standard local anesthetics. Herein, this randomized, double-blind, controlled trial evaluated whether TAPB with long-acting compound lidocaine hydrochloride injection reduces postoperative pain.

Methods

164 patients undergoing elective gynecological laparotomy under sevoflurane anesthesia randomly received ultrasound-guided TAP block with either saline, or ropivacaine, or compound lidocaine before anesthesia induction. The postoperative pain intensity (primary outcome) was evaluated by pain 11-point numerical rating scale. We also recorded sufentanil consumptions, time to first flatus, side-effects and hospital stay after surgery.

Results

We reported that pain scores at rest at postoperative 3h in group 0.375% ropivacaine was lower than that in group saline [mean 2.4 (SD 1.2) vs. 3.0 (1.0), p = 0.036]. Compared with saline, 0.4% and 0.6% compound lidocaine caused lower pain scores at rest at postoperative 12h [2.8 (0.9) vs. 2.1 (0.9) and 2.0 (0.9), p = 0.016 and p = 0.006]. Sufentanil usage for the first postoperative 48h was lower in group 0.6% compound lidocaine than group saline [24.2 (5.4) vs. 45.6 (7.5) µg, p  < 0.001]. Time to first flatus and hospital stay after surgery was shortest and the incidence of postoperative nausea was lowest in patients receiving 0.6% compound lidocaine.

Conclusion

TAP block with 0.6% compound lidocaine hydrochloride injection attenuates postoperative pain, reduces opioid consumption, accelerates gastrointestinal function recovery, and shortens length of hospital stay in patients after gynecological laparotomy.

Trial registration

ClinicalTrials.gov, identifier: NCT04938882.
Variations in volatile flavour compounds in Crataegi fructus roasting revealed by E-nose and HS-GC-MS
Authors: Fei Chenghao , Xue Qianqian , Li Wenjing , Xu Yan , Mou Liyan , Li Weidong , Lu Tulin , Yin Wu , Li Lin , Yin Fangzhou
Published: January 2023

Introduction

Crataegi fructus (CF) is an edible and medicinal functional food used worldwide that enhances digestion if consumed in the roasted form. The odour of CF, as a measure of processing degree during roasting, significantly changes. However, the changes remain unclear, but are worth exploring.

Methods

Herein, the variations in volatile flavour compounds due to CF roasting were investigated using an electronic nose (E-nose) and headspace gas chromatography–mass spectrometry (HS-GC-MS).

Results

A total of 54 components were identified by GC-MS. Aldehydes, ketones, esters, and furans showed the most significant changes. The Maillard reaction, Strecker degradation, and fatty acid oxidation and degradation are the main reactions that occur during roasting. The results of grey relational analysis (GRA) showed that 25 volatile compounds were closely related to odour (r > 0.9). Finally, 9 volatile components [relative odour activity value, (ROAV) ≥ 1] were confirmed as key substances causing odour changes.

Discussion

This study not only achieves the objectification of odour evaluation during food processing, but also verifies the applicability and similarity of the E-nose and HS-GC-MS.
Antioxidant activity and interactions between whey protein and polysaccharides from different parts of Houttuynia cordata
Authors: Liu Xiaocui , Tian Jin , Zhou Zhiran , Pan Yinzhen , Li Zhongqiao
Published: January 2023

Houttuynia cordata polysaccharides (PSY) are known to exhibit a variety of beneficial activities, but these are currently not specifically utilized in food. Hence, using the two edible parts of Houttuynia cordata, a herbaceous plant native to Southeast Asia, this study developed polysaccharides of a stem (HCPS)-whey protein concentrate (WPC) complex and a leaf (HCPL)-WPC complex, and studied their stability, structure and antioxidant activity. The results showed that stability differed in complexes with different proportions, exhibiting only relative stability in the two complexes in which the ratio of HCPS-WPC and HCPL-WPC was 1:4, but increased stability in the HCPL-WPC complex (ζ-potential of HCPL-WPC: | -21.87 mv| >ζ-potential of HCPS-WPC: | -21.70 mv|). Structural characterization showed that there was electrostatic interaction between HCPS and WPC and between HCPL and WPC. The HCPL-WPC was found to have better antioxidant activity. The findings of this study, thus, provide a reference for the development of Houttuynia cordata polysaccharide applications in food.
Excess selenium intake is associated with microalbuminuria in female but not in male among adults with obesity: Results from NHANES 2009–2018
Authors: Zhang Jia-wei , Lin Yi , Liu Yue-min , Wang Min-min , Gong Jian-guang , Shen Xiao-gang , Shen Quan-quan , Lin Bo , Su Wei-er , Gao Yuan-cheng , Yuan Chen-yi , Pan Zhi-hui , Zhu Bin
Published: January 2023

Introduction

Selenium is a critical trace element with antioxidant activities that has been related to the preservation of kidney function. Few studies, however, have looked at the effects of excess selenium on kidneys. The purpose of the present study was performed to investigate the relationship between dietary selenium intake and the prevalence of microalbuminuria in American adults with obesity.

Methods

A total of 8,547 participants with obesity in the National Health and Nutrition Examination Survey (NHANES) with the age of 19 years or older were included in the present study. Multivariable regression and subgroup analyses were performed to examine the association between dietary selenium and microalbuminuria in the two genders, separately. A selenium intake above the median was defined as high selenium intake.

Results

Dietary selenium intake was significantly higher in men compared to women (139.49 μg/day vs. 101.06 μg/day; P < 0.0001). Among female participants, the prevalence of microalbuminuria was significantly higher in participants with a high selenium intake compared with those without a high selenium intake (13.82 vs. 9.96%; P = 0.008), whereas this difference did not exist in male participants (10.79 vs. 11.97%; P = 0.40). Dietary selenium is not significantly correlated with microalbuminuria (P = 0.68) in the male population, whereas each 1 μg/day of increase in selenium consumption was independently associated with a 6h higher risk of microalbuminuria (OR = 1.006; 95% CI, 1.001–1.011, P = 0.01) in females.

Conclusion

According to our research, excessive selenium consumption is positively correlated with microalbuminuria in females with obesity, but not in males with obesity.
Predictors of weight loss in patients with obesity treated with a Very Low-Calorie Ketogenic Diet
Authors: Ernesti Ilaria , Baratta Francesco , Watanabe Mikiko , Risi Renata , Camajani Elisabetta , Persichetti Agnese , Tuccinardi Dario , Mariani Stefania , Lubrano Carla , Genco Alfredo , Spera Giovanni , Gnessi Lucio , Basciani Sabrina
Published: January 2023

Introduction

The Very Low-Calorie Ketogenic Diet (VLCKD) has emerged as a safe and effective intervention for the management of metabolic disease. Studies examining weight loss predictors are scarce and none has investigated such factors upon VLCKD treatment. Among the molecules involved in energy homeostasis and, more specifically, in metabolic changes induced by ketogenic diets, Fibroblast Growth Factor 21 (FGF21) is a hepatokine with physiology that is still unclear.

Methods

We evaluated the impact of a VLCKD on weight loss and metabolic parameters and assessed weight loss predictors, including FGF21. VLCKD is a severely restricted diet (<800 Kcal/die), characterized by a very low carbohydrate intake (<50 g/day), 1.2–1.5 g protein/kg of ideal body weight and 15–30 g of fat/day. We treated 34 patients with obesity with a VLCKD for 45 days. Anthropometric parameters, body composition, and blood and urine chemistry were measured before and after treatment.

Results

We found a significant improvement in body weight and composition and most metabolic parameters. Circulating FGF21 decreased significantly after the VLCKD [194.0 (137.6–284.6) to 167.8 (90.9–281.5) p < 0.001] and greater weight loss was predicted by lower baseline FGF21 (Beta = −0.410; p = 0.012), male sex (Beta = 0.472; p = 0.011), and central obesity (Beta = 0.481; p = 0.005).

Discussion

VLCKD is a safe and effective treatment for obesity and obesity related metabolic derangements. Men with central obesity and lower circulating FGF21 may benefit more than others in terms of weight loss obtained following this diet. Further studies investigating whether this is specific to this diet or to any caloric restriction are warranted.
Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy
Authors: Arna Ananna Bhadra , Patel Hardikkumar , Singh Ravi Shankar , Vizeacoumar Frederick S. , Kusalik Anthony , Freywald Andrew , Vizeacoumar Franco J. , Wu Yuliang
Published: January 2023

DEAD/H-box helicases are implicated in virtually every aspect of RNA metabolism, including transcription, pre-mRNA splicing, ribosomes biogenesis, nuclear export, translation initiation, RNA degradation, and mRNA editing. Most of these helicases are upregulated in various cancers and mutations in some of them are associated with several malignancies. Lately, synthetic lethality (SL) and synthetic dosage lethality (SDL) approaches, where genetic interactions of cancer-related genes are exploited as therapeutic targets, are emerging as a leading area of cancer research. Several DEAD/H-box helicases, including DDX3, DDX9 (Dbp9), DDX10 (Dbp4), DDX11 (ChlR1), and DDX41 (Sacy-1), have been subjected to SL analyses in humans and different model organisms. It remains to be explored whether SDL can be utilized to identity druggable targets in DEAD/H-box helicase overexpressing cancers. In this review, we analyze gene expression data of a subset of DEAD/H-box helicases in multiple cancer types and discuss how their SL/SDL interactions can be used for therapeutic purposes. We also summarize the latest developments in clinical applications, apart from discussing some of the challenges in drug discovery in the context of targeting DEAD/H-box helicases.
Exosomes as drug delivery system in gastrointestinal cancer
Authors: Xie Fangyuan , Huang Yueying , Zhan Yangyang , Bao Leilei
Published: January 2023

Gastrointestinal cancer is one of the most common malignancies with relatively high morbidity and mortality. Exosomes are nanosized extracellular vesicles derived from most cells and widely distributed in body fluids. They are natural endogenous nanocarriers with low immunogenicity, high biocompatibility, and natural targeting, and can transport lipids, proteins, DNA, and RNA. Exosomes contain DNA, RNA, proteins, lipids, and other bioactive components, which can play a role in information transmission and regulation of cellular physiological and pathological processes during the progression of gastrointestinal cancer. In this paper, the role of exosomes in gastrointestinal cancers is briefly reviewed, with emphasis on the application of exosomes as drug delivery systems for gastrointestinal cancers. Finally, the challenges faced by exosome-based drug delivery systems are discussed.
New nomogram for predicting lymph node positivity in pancreatic head cancer
Authors: Guo Xingren , Song Xiangyang , Long Xiaoyin , Liu Yahui , Xie Yixin , Xie Cheng , Ji Bai
Published: January 2023

Background

Pancreatic cancer is one of the most malignant cancers worldwide, and it mostly occurs in the head of the pancreas. Existing laparoscopic pancreaticoduodenectomy (LPD) surgical techniques have has undergone a learning curve, a wide variety of approaches for the treatment of pancreatic cancer have been proposed, and the operation has matured. At present, pancreatic head cancer has been gradually changing from “surgeons’ evaluation of anatomical resection” to “biologically inappropriate resection”. In this study, the risk of lymph node metastasis in pancreatic head cancer was predicted using common preoperative clinical indicators.

Methods

The preoperative clinical data of 191 patients with pancreatic head cancer who received LPD in the First Affiliated Hospital of Jilin University from May 2016 to December 2021 were obtained. A univariate regression analysis study was conducted, and the indicators with a significance level of P<0.05 were included in the univariate logistic regression analysis into multivariate. Lastly, a nomogram was built based on age, tumor size, leucocyte,albumin(ALB), and lymphocytes/monocytes(LMR). The model with the highest resolution was selected by obtaining the area under a curve. The clinical net benefit of the prediction model was examined using decision curve analyses.Risk stratification was performed by combining preoperative CT scan with existing models.

Results

Multivariate logistic regression analysis found age, tumor size, WBC, ALB, and LMR as five independent factors. A nomogram model was constructed based on the above indicators. The model was calibrated by validating the calibration curve within 1000 bootstrap resamples. The ROC curve achieved an AUC of 0.745(confidence interval of 95%: 0.673-0.816), thus indicating that the model had excellent discriminative skills. DCA suggested that the predictive model achieved a high net benefit in the nearly entire threshold probability range.

Conclusions

This study has been the first to investigate a nomogram for preoperative prediction of lymphatic metastasis in pancreatic head cancer. The result suggests that age, ALB, tumor size, WBC, and LMR are independent risk factors for lymph node metastasis in pancreatic head cancer. This study may provide a novel perspective for the selection of appropriate continuous treatment regimens, the increase of the survival rate of patients with pancreatic head cancer, and the selection of appropriate neoadjuvant therapy patients.
Ileal adenocarcinoma in a young pregnant woman: A rare case report
Authors: Xiao Chao , Cheng Qijun , Cao Chengjian , Xiao Xue , Zhang Yutao
Published: January 2023

Primary intestinal malignancies account for only 1%–3% of all malignant gastrointestinal tumors. Adenocarcinomas are uncommonly located in the ileum. Ileal adenocarcinoma (IA) is rare and difficult to diagnose because of its location. IA is common in older men and rare in young pregnant women. A 23-year-old pregnant woman was hospitalized several times for repeated vomiting and abdominal pain. Her symptoms were relieved after symptomatic treatment. She exhibited no typical manifestations of intestinal obstruction, such as abdominal distension, difficulty passing gas and defecation. Unfortunately, she was misdiagnosed with acute gastroenteritis. On the second day after delivery, the patient stopped passing gas and computed tomography (CT) revealed an intestinal obstruction. She was treated as paralytic ileus. However, in view of failed conservative management, she was decided for an exploratory laparotomy. A malignant ileal tumor 5cm from the ileocecal valve was found incidentally and was surgically excised accompanied with End-to-side anastomosis of ileal and transverse colon. The operation lasted 195 minutes. Pathological examination revealed an IA. Pregnant woman who experience symptoms of intestinal obstruction should be alert to the possibility of malignancy in the small intestine. IA is an insidious tumor in pregnant women. An “IA triad” can be defined as refractory vomiting, vague abdominal pain, and weight loss (or inadequate weight gain in pregnant women). Pregnant women with an IA triad should undergo investigation with endoscopy or, if necessary, magnetic resonance imaging (MRI).