bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering a mitochondria-related signature to supervise prognosis and immunotherapy in hepatocellular carcinoma
Authors: Shi Yanlong , Huang Guo , Jiang Fei , Zhu Jun , Xu Qiyang , Fang Hanlu , Lan Sheng , Pan Ziyuan , Jian Haokun , Li Li , Zhang Yewei
Published: December 2022

Background

Hepatocellular carcinoma (HCC) is a major public health problem in humans. The imbalance of mitochondrial function has been discovered to be closely related to the development of cancer recently. However, the role of mitochondrial-related genes in HCC remains unclear.

Methods

The RNA-sequencing profiles and patient information of 365 samples were derived from the Cancer Genome Atlas (TCGA) dataset. The mitochondria-related prognostic model was established by univariate Cox regression analysis and LASSO Cox regression analysis. We further determined the differences in immunity and drug sensitivity between low- and high-risk groups. Validation data were obtained from the International Cancer Genome Consortium (ICGC) dataset of patients with HCC. The protein and mRNA expression of six mitochondria-related genes in tissues and cell lines was verified by immunohistochemistry and qRT-PCR.

Results

The six mitochondria-related gene signature was constructed for better prognosis forecasting and immunity, based on which patients were divided into high-risk and low-risk groups. The ROC curve, nomogram, and calibration curve exhibited admirable clinical predictive performance of the model. The risk score was associated with clinicopathological characteristics and proved to be an independent prognostic factor in patients with HCC. The above results were verified in the ICGC validation cohort. Compared with normal tissues and cell lines, the protein and mRNA expression of six mitochondria-related genes was upregulated in HCC tissues and cell lines.

Conclusion

The signature could be an independent factor that supervises the immunotherapy response of HCC patients and possess vital guidance value for clinical diagnosis and treatment.
Overexpression of SMS in the tumor microenvironment is associated with immunosuppression in hepatocellular carcinoma
Authors: Xiang Lin , Piao Longhuan , Wang Dong , Qi Li-Feng-Rong
Published: December 2022

Disorders of polyamine metabolism may contribute to the development of hepatocellular carcinoma (HCC), but the precise mechanism remains unknown. This study reports that spermine synthase (SMS), an enzyme involved in polyamine biosynthesis, is overexpressed in HCC and not associated with hepatitis virus infection in HCC patients. The results of analyzing the clinical data of HCC patients showed that SMS level as a categorical dependent variable was related to clinicopathological features of poor prognosis. Furthermore, the Kaplan-Meier survival analysis and ROC curve indicated that increased SMS level is associated with poor survival rate in HCC and may be a potential biomarker to discriminate HCC tissues. However, SMS overexpression limited the therapeutic effect of immune checkpoint blockade (ICB), which seemed to be related to the immunosuppressive effect of the HCC immune microenvironment formed by higher mRNA transcript levels of immune checkpoints and higher infiltration levels of immunosuppressive cells. In samples with high and low SMS expression, functional enrichment analysis of the differentially expressed genes (DEGs) showed that SMS may be linked to the occurrence and development of HCC by affecting a variety of immune-related pathways, such as Intestinal immune network for IgA production, Fc gamma R-mediated phagocytosis, Antigen processing and presentation, Th1 and Th2 cell differentiation. Subsequently, analysis of the co-expression network of SMS in the liver hepatocellular carcinoma (LIHC) cohort revealed that SMS has a broad impact on multiple important immune- and metabolic-related processes in HCC. In summary, SMS is a promising biomarker to differentiate the prognosis, immune characteristics, and holds promise as a potential target for ICB therapy to improve HCC.
Identification of necroptosis-related subtypes, development of a novel signature, and characterization of immune infiltration in colorectal cancer
Authors: Sun Mengyu , Ji Xiaoyu , Xie Meng , Chen Xiaoping , Zhang Bixiang , Luo Xiangyuan , Feng Yangyang , Liu Danfei , Wang Yijun , Li Yiwei , Liu Bifeng , Xia Limin , Huang Wenjie
Published: December 2022

Introduction

Necroptosis, a type of programmed cell death, has recently been extensively studied as an important pathway regulating tumor development, metastasis, and immunity. However, the expression patterns of necroptosis-related genes (NRGs) in colorectal cancer (CRC) and their potential roles in the tumor microenvironment (TME) have not been elucidated.

Methods

We explored the expression patterns of NRGs in 1247 colorectal cancer samples from genetics and transcriptional perspective. Based on a consensus clustering algorithm, we identified NRG molecular subtypes and gene subtypes, respectively. Furthermore, we constructed a necroptosis-related signature for predicting overall survival time and verified the predictive ability of the model. Using the ESTIMATE, CIBERSORT, and ssGSEA algorithms, we assessed the association between the above subtypes, scores and immune infiltration.

Results

Most NRGs were differentially expressed between CRC tissues and normal tissues. We found that distinct subtypes exhibited different NRGs expression, patients’ prognosis, immune checkpoint gene expression, and immune infiltration characteristics. The scores calculated from the necroptosis-related signature can be used to classify patients into high-risk and low-risk groups, with the high-risk group corresponding to reduced immune cell infiltration and immune function, and a greater risk of immune dysfunction and immune escape.

Discussion

Our comprehensive analysis of NRGs in CRC demonstrated their potential role in clinicopathological features, prognosis, and immune infiltration in the TME. These findings help us deepen our understanding of NRGs and the tumor microenvironment landscape, and lay a foundation for effectively assessing patient outcomes and promoting more effective immunotherapy.
Characterizing the interfacial zones of fly ash based alkali activated adhesives to various substrates
Authors: Wisniewski Wolfgang , Ducman Vilma
Published: December 2022

Alkali Activated Materials (AAMs) are important potential substitutes for cement in many materials. The AAMs presented here are based on industrial ground granulated blast furnace slag (GGBFS) and fly ash (FA). They are tested for their suitability as adhesives for joining concrete, ceramic tiles, a wood-based geopolymer (WGP) and a high density geopolymer (HDGP). After mixing multiple batches and performing preliminary tests of the resulting shrinkage, bending-, compressive- and pull-of-strengths to standard ceramic tiles, selected mixtures are tested for their open time and applied to bond intended substrates. The interfacial zones (ITZ) of an AAM containing additional KOH and the most comparable KOH-free AAM to concrete, ceramic tiles, WPG and HDGP are subsequently characterized in detail using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDXS). Both mechanical interlocking and areas of probable chemical bonding are identified.
Spatial variation and metabolic diversity of microbial communities in the surface sediments of the Mariana Trench
Authors: Wang Fangzhou , Zhang Yue , Jing Hongmei , Liu Hao
Published: December 2022

Mariana Trench represents the deepest and one of least explored biosphere on Earth, and its carbon sources include euphotic sinking, lateral transportation and diffusion from underlying crust, etc. By far the spatial variation of microbial community with associated organic carbon degradation potential in the surface sediments of the Mariana Trench were still largely unknown. Based on the high-throughput 16S rRNA amplicon sequencing, significantly different microbial community structure was overserved between the shallow (<10,000 m) and deep stations (>10,000 m), which could be explained by spatial variation of Chloroflexi, Proteobacteria and Crenarchaeota, with sampling depth and total organic carbon (TOC) content as the environmental driving forces. During the 109-day incubation with Biolog EcoPlate™ microplate, polymers and carbohydrates were preferentially used, followed by amino acids and carboxylic acids, and microbial metabolic diversity was significantly different between the shallow and deep stations. The metabolic diversity of microorganisms at most shallow stations was significantly lower than that at deep stations. This could potentially be attributed the metabolic capabilities of different microbial groups with varied ecological niches, and reflected the initial preference of carbon source by the nature microbes as well. Our study obtained a rough assessment of physiological and taxonomic characteristics of the trench sediment microbial community with polyphasic approaches. Distinct microbial structure and potential carbon metabolic functions in different sampling depths might led to the differentiation of ecological niches, which enable various microorganisms to make full use of the limited resources in the deep sea, and provided a research basis for further exploration of the carbon cycle in different deep-sea regions.
A triton X-100 assisted PMAxx-qPCR assay for rapid assessment of infectious African swine fever virus
Authors: Liu Huan , Meng Fei , Nyaruaba Raphael , He Ping , Hong Wei , Jiang Mengwei , Liu Dongqing , Zhou Wenhao , Bai Dan , Yu Junping , Wei Hongping
Published: December 2022

Introduction

African Swine Fever (ASF) is a highly infectious disease of pigs, caused by African swine fever virus (ASFV). The lack of vaccines and drugs makes strict disinfection practices to be one of the main measurements to curb the transmission of ASF. Therefore, it is important to assess if all viruses are inactivated after disinfection or after long time exposure in their natural conditions. Currently, the infectivity of ASFV is determined by virus isolation and culture in a biosafety level 3 (BSL-3) laboratory. However, BSL-3 laboratories are not readily available, need skilled expertise and may be time consuming.

Methods

In this study, a Triton X-100 assisted PMAxx-qPCR method was developed for rapid assessment of infectious ASFV in samples. PMAxx, an improved version of propidium monoazide (PMA), can covalently cross-link with naked ASFV-DNA or DNA inside inactivated ASFV virions under assistance of 0.1% (v/v) TritonX-100, but not with ASFV-DNA inside live virions. Formation of PMAxx-DNA conjugates prevents PCR amplification, leaving only infectious virions to be detected. Under optimum conditions, the limit of detection of the PMAxx-qPCR assay was 2.32log10HAD50/mL of infectious ASFV. Testing different samples showed that the PMAxx-qPCR assay was effective to evaluate intact ASFV virions after treatment by heat or chemical disinfectants and in simulated samples such as swine tissue homogenate, swine saliva swabs, and environmental swabs. However, whole-blood and saliva need to be diluted before testing because they may inhibit the PCR reaction or the cross-linking of PMAxx with DNA.

Conclusion

The Triton X-100 assisted PMAxx-qPCR assay took less than 3 h from sample to result, offering an easier and faster way for assessing infectious ASFV in samples from places like pig farms and pork markets.
Effect of lactobacilli inoculation on protein and carbohydrate fractions, ensiling characteristics and bacterial community of alfalfa silage
Authors: Huo Wenjie , Zhang Yujuan , Zhang Luyao , Shen Chen , Chen Lei , Liu Qiang , Zhang Shuanlin , Wang Cong , Guo Gang
Published: December 2022

Introduction

Alfalfa (Medicago sativa L.) silage is one of the major forages with high protein for ruminants.

Methods

The objective of this study was to investigate the effects of lactobacilli inoculants on protein and carbohydrate fractions, ensiling characteristics and bacterial community of alfalfa silage. Wilted alfalfa (35% dry matter) was inoculated without (control) or with Lactobacillus coryniformis, Lactobacillus casei, Lactobacillus plantarum, and Lactobacillus pentosus and ensiled for 7, 15, and 60 days.

Results and discussion

Silage inoculated with L. pentosus was superior to L. coryniformis, L. casei, L. plantarum in improving the fermentation quality of alfalfa silage, as indicated by the lowest ammonia nitrogen content and silage pH during ensiling. There was minor difference in water soluble carbohydrates content among all silages, but L. pentosus inoculants was more efficient at using xylose to produce lactic acid, with lower xylose content and higher lactic acid content than the other inoculants. Compared with the control, L. pentosus inoculants did not affect true protein content of silage, but increased the proportions of buffer soluble protein and acid detergent soluble protein. The L. pentosus inoculants reduced the bacterial diversity In alfalfa silage with lower Shannon, Chao1, and Ace indices, and promoted relative abundance of lactobacillus and decreased the relative abundance of Pediococcus compared with the control. As well as L. pentosus inoculants up-regulated amino acid, carbohydrate, energy, terpenoids, and polypeptides metabolism, and promoted lactic acid fermentation process. In summary, the fermentation quality and nutrient preservation of alfalfa silage were efficiently improved by inoculated with L. pentosus.
Efficient processing of natural scenes in visual cortex
Authors: Tesileanu Tiberiu , Piasini Eugenio , Balasubramanian Vijay
Published: December 2022

Neural circuits in the periphery of the visual, auditory, and olfactory systems are believed to use limited resources efficiently to represent sensory information by adapting to the statistical structure of the natural environment. This “efficient coding” principle has been used to explain many aspects of early visual circuits including the distribution of photoreceptors, the mosaic geometry and center-surround structure of retinal receptive fields, the excess OFF pathways relative to ON pathways, saccade statistics, and the structure of simple cell receptive fields in V1. We know less about the extent to which such adaptations may occur in deeper areas of cortex beyond V1. We thus review recent developments showing that the perception of visual textures, which depends on processing in V2 and beyond in mammals, is adapted in rats and humans to the multi-point statistics of luminance in natural scenes. These results suggest that central circuits in the visual brain are adapted for seeing key aspects of natural scenes. We conclude by discussing how adaptation to natural temporal statistics may aid in learning and representing visual objects, and propose two challenges for the future: (1) explaining the distribution of shape sensitivity in the ventral visual stream from the statistics of object shape in natural images, and (2) explaining cell types of the vertebrate retina in terms of feature detectors that are adapted to the spatio-temporal structures of natural stimuli. We also discuss how new methods based on machine learning may complement the normative, principles-based approach to theoretical neuroscience.
Spatial and temporal frequency band changes during infarct induction, infarct progression, and spreading depolarizations in the gyrencephalic brain
Authors: Kentar Modar , Díaz-Peregrino Roberto , Trenado Carlos , Sánchez-Porras Renán , San-Juan Daniel , Ramírez-Cuapio F. Leonardo , Holzwarth Niklas , Maier-Hein Lena , Woitzik Johannes , Santos Edgar
Published: December 2022

Aim

To describe the spatial and temporal electrocorticographic (ECoG) changes after middle cerebral artery occlusion (MCAo), including those caused by spreading depolarization (SD) in the pig brain.

Methods

The left middle cerebral arteries (MCAs) were clipped in six pigs. The clipping procedure lasted between 8 and 12 min, achieving a permanent occlusion (MCAo). Five-contact ECoG stripes were placed bilaterally over the frontoparietal cortices corresponding to the irrigation territory of the MCA and anterior cerebral artery (ACA). ECoG recordings were performed around 24 h: 1 h before and 23 h after the MCAo, and SDs were quantified. Five-minute ECoG signal segments were sampled before, 5 min, and 4, 8, and 12 h after cerebral artery occlusion and before, during, and after the negative direct current shift of the SDs. The power spectrum of the signals was decomposed into delta, theta, alpha, beta, and gamma bands. Descriptive statistics, Wilcoxon matched-pairs signed-rank tests, and Friedman tests were performed.

Results

Electrodes close to the MCAo showed instant decay in all frequency bands and SD onset during the first 5 h. Electrodes far from the MCAo exhibited immediate loss of fast frequencies and progressive decline of slow frequencies with an increased SD incidence between 6 and 14 h. After 8 h, the ACA electrode reported a secondary reduction of all frequency bands except gamma and high SD incidence within 12–17 h. During the SD, all electrodes showed a decline in all frequency bands. After SD passage, frequency band recovery was impaired only in MCA electrodes.

Conclusion

ECoG can identify infarct progression and secondary brain injury. Severe disturbances in all the frequency bands are generated in the cortices where the SDs are passing by.
The effect of blood pressure variability on the prognosis of patients with acute cerebral hemorrhage: Possible mechanism
Authors: Sun Xiangrong , Jv Xinyue , Mi Qi , Yang Qian , Chen Tao , Jiang Guohui
Published: December 2022

Background

Antihypertensive therapy in the acute phase of intracerebral hemorrhage (ICH) can reduce hematoma expansion. Numerous studies have demonstrated that blood pressure variability secondary to antihypertensive therapy has adverse effects on neurological outcomes, but the conclusions are diverse, and the mechanism of this occurrence is unknown. The aim of this research was to analyze the impact of blood pressure variability after antihypertensive treatment on the prognosis of patients with acute ICH, along with the possible mechanism.

Materials and methods

A total of 120 patients within 20 h of onset of ICH were divided into a good prognosis group (mRS ≤ 2 points) and a poor prognosis group (mRS ≥ 3 points) according to their 90-day mRS scores. The basic patient information, NIHSS score, GCS score, mRS score at 90 days after admission, head CT examination at admission and 24 h and CTP examination at 24 h were collected from some patients. The blood pressure values of patients were collected within 24 h, and multiple blood pressure variation (BPV) parameters within 1 and 24 h were calculated.

Results

(1) After excluding confounding factors such as age, whether the hematoma ruptured into the ventricle, confounding signs, amount of bleeding, edema around the hematoma, NIHSS on admission, operation or non-operation, and 24-h hematoma increment, the fourth quartile systolic blood pressure (SBP) maximum and minimum difference within 1 h [OR: 5.069, CI (1.036–24.813) P = 0.045] and coefficient of continuous variation (SV) within 24 h [OR: 2.912 CI (1.818–71.728) P = 0.009] were still independent factors affecting the 90-day mRS in ICH patients. (2) There was a negative correlation between SBP SV and CBF in terms of the difference between the contralateral side and the perihematomal region at 24 h (Rs = −0.692, P = 0.013).

Conclusion

Blood pressure variability after antihypertensive therapy in acute ICH is one of the influencing factors for 90-day mRS in patients. A 1-h dramatic drop in SBP and 24-h SBP SV may affect the long-term prognosis of patients by reducing whole cerebral perfusion.
Diverse organization of voltage-gated calcium channels at presynaptic active zones
Authors: Zhang Weijia , Jiang He-Hai , Luo Fujun
Published: December 2022

Synapses are highly organized but are also highly diverse in their organization and properties to allow for optimizing the computing power of brain circuits. Along these lines, voltage-gated calcium (CaV) channels at the presynaptic active zone are heterogeneously organized, which creates a variety of calcium dynamics profiles that can shape neurotransmitter release properties of individual synapses. Extensive studies have revealed striking diversity in the subtype, number, and distribution of CaV channels, as well as the nanoscale topographic relationships to docked synaptic vesicles. Further, multi-protein complexes including RIMs, RIM-binding proteins, CAST/ELKS, and neurexins are required for coordinating the diverse organization of CaV channels at the presynaptic active zone. In this review, we highlight major advances in the studies of the functional organization of presynaptic CaV channels and discuss their physiological implications for synaptic transmission and short-term plasticity.
Evaluating the effect of lactic acid bacteria fermentation on quality, aroma, and metabolites of chickpea milk
Authors: Zhang Panling , Tang Fengxian , Cai Wenchao , Zhao Xinxin , Shan Chunhui
Published: December 2022

Legumes are an attractive choice for developing new products since their health benefits. Fermentation can effectively improve the quality of soymilk. This study evaluated the impact of Lactobacillus plantarum fermentation on the physicochemical parameters, vitamins, organic acids, aroma substances, and metabolites of chickpea milk. The lactic acid bacteria (LAB) fermentation improved the color, antioxidant properties, total phenolic content, total flavonoid content, lactic acid content, and vitamin B6 content of raw juice. In total, 77 aroma substances were identified in chickpea milk by headspace solid-phase microextraction with gas chromatography/mass spectrometry (HS-SPME-GC-MS); 43 of the 77 aroma substances increased after the LAB fermentation with a significant decrease in beany flavor content (p < 0.05), improving the flavor of the soymilk product. Also, a total of 218 metabolites were determined in chickpea milk using non-targeted metabolomics techniques, including 51 differentially metabolites (28 up-regulated and 23 down-regulated; p < 0.05). These metabolites participated in multiple metabolic pathways during the LAB fermentation, ultimately improving the functional and antioxidant properties of fermented soymilk. Overall, LAB fermentation can improve the flavor, nutritional, and functional value of chickpea milk accelerating its consumer acceptance and development as an animal milk alternative.
Gut microbiota, behavior, and nutrition after type 1 diabetes diagnosis: A longitudinal study for supporting data in the metabolic control
Authors: Traversi Deborah , Scaioli Giacomo , Rabbone Ivana , Carletto Giulia , Ferro Arianna , Franchitti Elena , Carrera Deborah , Savastio Silvia , Cadario Francesco , Siliquini Roberta , Cerutti Franco , Durazzo Marilena
Published: December 2022

Introduction

Type 1 diabetes (T1D) risk involves genetic susceptibility but also epigenetics, environment, and behaviors. Appropriate metabolic control, especially quickly after the diagnosis, is crucial for the patient quality of life.

Methods

This study aimed to produce a quantitative comparison of the behavior, nutrition habits, and gut microbiota composition between the onset and the 1-year follow-up in 35 children with T1D.

Results and discussion

At follow-up, with the metabolic control, many parameters improved significantly, with respect to the onset, such as glycated hemoglobin (−19%), body mass index (BMI), and also nutritional behaviors, such as normal calorie intake (+6%), carbohydrate intake (−12%), extra portion request (−4%), and meals distribution during the day. Moreover, glycated hemoglobin decrement correlated with both total and rapid absorption carbohydrate intake (Spearman's rho = 0.288, 95% CI 0.066–0.510, p = 0.013), showing as the nutritional behavior supported the insulin therapy efficiency. The next-generation sequencing (NGS) analysis of microbiota revealed abundance differences for Ruminococcus bromii and Prevotella copri (higher at onset, p < 0.001) and the genera Succinivibrio and Faecalibacterium (lower at onset, p < 0.001), as a consequence of nutritional behavior, but it was not the only changing driver. The qRT-PCR analysis showed significant variations, in particular for Bacteroidetes and Bifidobacterium spp. (+1.56 log gene copies/g stool at follow-up, p < 0.001). During the year, in 11% of the patients, severe clinical episodes occurred (hypoglycemic or ketoacidosis). The likelihood of a severe hypoglycemic episode was modulated when the Methanobrevibacter smithii amount increased (odds ratio 3.7, 95% CI 1.2–11.4, p = 0.026). Integrated evaluation, including nutritional behavior and microbiota composition, could be considered predictive of the metabolic control management for children cohort with a recent diagnosis of T1D.
Biparametric MRI-based radiomics classifiers for the detection of prostate cancer in patients with PSA serum levels of 4∼10 ng/mL
Authors: Lu Yangbai , Li Binfei , Huang Hongxing , Leng Qu , Wang Qiang , Zhong Rui , Huang Yaqiang , Li Canyong , Yuan Runqiang , Zhang Yongxin
Published: December 2022

Purpose

To investigate the predictive performance of the combined model by integrating clinical variables and radiomic features for the accurate detection of prostate cancer (PCa) in patients with prostate-specific antigen (PSA) serum levels of 4-10 ng/mL.

Methods

A retrospective study of 136 males (mean age, 67.3 ± 8.4 years) with Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 category ≤3 lesions and PSA serum levels of 4-10 ng/mL were performed. All patients underwent multiparametric MRI at 3.0T and transrectal ultrasound-guided systematic prostate biopsy in their clinical workup. Radiomic features were extracted from axial T2-weighted images (T2WI) and apparent diffusion coefficient (ADC) maps of each patient using PyRadiomics. Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were implemented to identify the most significant radiomic features. Independent clinic-radiological factors were identified via univariate and multivariate regression analyses. Seven machine-learning algorithms were compared to construct a single-layered radiomic score (ie, radscore) and multivariate regression analysis was applied to construct the fusion radscore. Finally, the radiomic nomogram was further developed by integrating useful clinic-radiological factors and fusion radscore using multivariate regression analysis. The discriminative power of the nomogram was evaluated by area under the curve (AUC), DeLong test, calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC).

Results

The transitional zone-specific antigen density was identified as the only independent clinic-radiological factor, which yielded an AUC of 0.592 (95% confidence interval [CI]: 0.527-0.657). The ADC radscore based on six features and Naive Bayes achieved an AUC of 0.779 (95%CI: 0.730-0.828); the T2WI radscore based on 13 features and Support Vector Machine yielded an AUC of 0.808 (95%CI: 0.761-0.855). The fusion radscore obtained an improved AUC of 0.844 (95%CI: 0.801-0.887), which was higher than the single-layered radscores (both P<0.05). The radiomic nomogram achieved the highest value among all models (all P<0.05), with an AUC of 0.872 (95%CI: 0.835-0.909). Calibration curve showed good agreement and DCA together with CIC confirmed the clinical benefits of the radiomic nomogram.

Conclusion

The radiomic nomogram holds the potential for accurate and noninvasive identification of PCa in patients with PI-RADS ≤3 lesions and PSA of 4-10 ng/mL, which could reduce unnecessary biopsy.
Multi-omics profiles refine L-dopa decarboxylase (DDC) as a reliable biomarker for prognosis and immune microenvironment of clear cell renal cell carcinoma
Authors: Chang Kun , Su Jiaqi , Li Chuanyu , Anwaier Aihetaimujiang , Liu Wangrui , Xu Wenhao , Qu Yuanyuan , Zhang Hailiang , Ye Dingwei
Published: December 2022

Background

Increasing evidence indicates that L-dopa decarboxylase (DDC), which mediates aberrant amino acid metabolism, is significantly associated with tumor progression. However, the impacts of DDC are not elucidated clearly in clear cell renal cell carcinoma (ccRCC). This study aimed to evaluate DDC prognostic value and potential mechanisms for ccRCC patients.

Methods

Transcriptomic and proteomic expressions of and clinical data including 532 patients with ccRCC (The Cancer Genome Atlas RNA-seq data), 226 ccRCC samples (Gene Expression Omnibus), 101 ccRCC patients from the E-MTAB-1980 cohort, and 232 patients with ccRCC with proteogenomic data (Fudan University Shanghai Cancer Center) were downloaded and analyzed to investigate the prognostic implications of DDC expression. Cox regression analyses were implemented to explore the effect of DDC expression on the prognosis of pan-cancer. The "limma" package identified the differentially expressed genes (DEGs) between high DDC subgroups and low DDC groups. Functional enrichments were performed based DEGs between DDC subgroups. The differences of immune cell infiltrations and immune checkpoint genes between DDC subgroups were analyzed to identify potential influence on immune microenvironment.

Results

We found significantly decreased DDC expression in ccRCC tissues compared with normal tissues from multiple independent cohorts based on multi-omics data. We also found that DDC expression was correlated with tumor grades and stages.The following findings revealed that lower DDC expression levels significantly correlated with shorter overall survival (P <0.001) of patients with ccRCC. Moreover, we found that DDC expression significantly correlated with an immunosuppressive tumor microenvironment, higher intra-tumoral heterogeneity, elevated expression of immune checkpoint CD274, and possibly mediated malignant behaviors of ccRCC cells via the PI3k/Akt signaling pathway.

Conclusion

The present study is the first to our knowledge to indicate that decreased DDC expression is significantly associated with poor survival and an immune-suppressive tumor microenvironment in ccRCC. These findings suggest that DDC could serve as a biomarker for guiding molecular diagnosis and facilitating the development of novel individual therapeutic strategies for patients with advanced ccRCC.
IgE-expressing long-lived plasma cells in persistent sensitization
Authors: Xiong Shiqiu , Jia Yang , Liu Chuanhe
Published: December 2022

Persistent allergies affect the quality of life of patients and increase economic burdens. Many clinical observations indicate the presence of IgE+ long-lived plasma cells (LLPCs), which account for the persistent secretion of specific IgE; however, the characteristics of the IgE+ LLPCs have yet to be identified clearly. In this review, we summarized the generation of IgE+ PCs, discussed the prosurvival factors in the microenvironment, and reviewed the unique IgE-BCR signaling, which may bring insights into understanding the survival mechanisms of IgE+ LLPCs.
When there is no air, the cradle will fall: A narrative review of tobacco-related content across infant safe sleep interventions
Authors: Jawed Aysha , Jassal Mandeep
Published: December 2022

Sudden Unexpected Infant Death (SUID) from sleep-related causes is a leading cause of infant mortality worldwide. Sudden Infant Death Syndrome (SIDS) is one of the primary causes of SUID attributed to one or more environmental or behavioral determinants surrounding safe sleep practices among infants. The focus of many interventions on mitigating sleep-related infant deaths have addressed visible determinants pertaining to bed sharing, safe sleep surfaces, and removal of blankets, toys and other choking or strangulation hazards. Tobacco reduction and cessation have not been at the heart of any infant safe sleep interventions although addressing tobacco exposure is one of the primary safe sleep recommendations of the American Academy of Pediatrics. To date, there has not been a comprehensive review published on tobacco-related components across safe sleep interventions to reduce the risk of SIDS and SUID as the basis to contribute towards decreasing the rate of infant mortality. This review synthesizes the best practices, strategies, education, and additional interventions centered on addressing tobacco exposure as a risk factor for sleep-related infant deaths. Ten peer-reviewed studies were identified between 1995 and 2021 and integrated into this narrative review. There were three cross-sectional studies, three campaigns, one multi-center case control study, two randomized controlled trials, and two group comparison studies. Strengths and limitations of each approach are delineated followed by recommendations for future campaign, research, program, and practice endeavors to account for the totality of pertinent modifiable risk factors that contribute towards heightened infant mortality from sleep-related causes.
Chaihu-Shugan-San ameliorates tumor growth in prostate cancer promoted by depression via modulating sphingolipid and glycerinphospholipid metabolism
Authors: Li Wei , Zhou Runze , Zheng Jie , Sun Bo , Jin Xin , Hong Min , Chen Ruini
Published: December 2022

Background: Psychologic depression is a pivotal pathological characteristic and has been shown to promote prostate cancer (PCa) progression. Chaihu-Shugan-San (CSS), a well-known Chinese herbal decoction, exhibits efficacy in the treatment of stress-accelerated PCa. However, the underlying mechanism of CSS in resisting PCa growth is still unknown, and further study is needed.

Objective: To evaluate the effects of CSS on stress-accelerated PCa in a BALB/C nude mice model and to investigate the underlying mechanisms.

Methods: PC-3 cells were implanted into BALB/C nude mice, and the stressed mice were exposed to chronic unpredictable mild stress (CUMS) to study the effects of CSS. The PCa growth were evaluated by tumor volume and tumor weight. Analyses of depression-like behaviors were evaluated by sucrose consumption test, tail suspension test and open field test. Network pharmacology was used to analyze the potential targets and signaling pathways of CSS against PCa. Untargeted lipidomics were used to analyze the serum lipid profiles and further elucidate the possible mechanism.

Results: In the CUMS stressed PCa mice, CSS can restrain tumor growth with reduced tumor volume and tumor weight, and depression-like behaviors with increased sucrose consumption, reduced immobility duration, and increased total distance and center distance. Network pharmacology suggested that the lipid metabolism-related pathways are the most likely potential targets of CSS against PCa. Using untargeted lipidomics analysis, 62 lipids were found to have significant changes in PCa mice under CUMS treatment. The levels of glycerophospholipids containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylglycerol (PG), except PC (18:0_22:6) and PC (18:0_20:4), were significantly increased. Likewise, the levels of all sphingolipids (including sphingomyelin (SM), ceramides (Cer) and hexosyl-1-ceramide (Hex1Cer)) and diglyceride (DG) (32:1e) were significantly increased. CSS water extract was found to contribute to restore 32 lipids including 6 sphingolipids, 25 glycerophospholipids and 1 glyceride.

Conclusion: This study is the first to delineate the lipid profile of stressed PCa BALB/C nude mice using untargeted lipidomics analysis. CSS restrained tumor growth and ameliorated depression-like behaviors by reprogramming lipid metabolism. Intervention of lipid metabolism could be a preventive and therapeutic approach for PCa patients with depression.
Decrementally cost-effective health technologies in non-inferiority studies: A systematic review
Authors: Darlington Meryl , Scarica Raffaele , Chavez-Pacheco Xyomara , Blamplain Segar Laeticia , Durand-Zaleski Isabelle
Published: December 2022

Background: HTA guidance has generally been driven by situations where innovative and usually more expensive technologies are compared to the prevailing standards of care. Cheaper and less efficacious interventions have received scarce attention, although strategies with minimal individual efficacy losses might produce collective health gains when savings are redistributed.

Purpose: This systematic review of health economic evaluations identified interventions that are both cost and outcome reducing to procure a list of candidate decrementally cost-effective technologies.

Data Sources: English language searches were performed in PubMed, EMBASE and ClinicalTrials.gov covering 2005 to September 2021.

Study Selection: Full economic evaluations reporting in English decrementally cost-effective health technologies based on RCT data, modelling or mixed methods.

Data Synthesis: After filtering 4,975 studies found through the systematic database search, 107 decrementally cost-effective health technologies (HTs) were identified. Nearly a third were services (n = 29) and similarly for drugs (n = 31). For over half of the studies (n = 54) health outcomes were measured in QALYs and the cost-utility ratios varied from €140 to €5 million saved per QALY lost, albeit with time horizons varying from 4 days of follow-up to lifetime extrapolations. Less than a quarter of the studies were carried out from the societal perspective.

Limitations: Despite including ClinicalTrials.gov as data source, unpublished studies may have been missed.

Conclusions: Our results show a growth in recent years in the number of economic publications demonstrating decrementally cost-effective HTs. Economic tools are needed to facilitate the adoption of such HTs by policy-makers at the national level to maximise health outcomes at the population level.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=95504, identifier CRD42018095504.
Effects of CYP3A4*22 and CYP3A5 on clinical outcome in patients treated with ticagrelor for ST-segment elevation myocardial infarction: POPular Genetics sub-study
Authors: Azzahhafi Jaouad , Bergmeijer Thomas O. , van den Broek Wout W. A. , Chan Pin Yin Dean R. P. P. , Rayhi Senna , Peper Joyce , Bor Willem L. , Claassens Daniel M. F. , van Schaik Ron H. N. , ten Berg Jurriën M.
Published: December 2022

Aims: To determine the clinical efficacy, adverse events and side-effect dyspnea of CYP3A4*22 and CYP3A5 expressor status in ticagrelor treated patients.

Methods and results: Ticagrelor treated patients from the POPular Genetics randomized controlled trial were genotyped for CYP3A4*22 and CYP3A5*3 alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included. CYP3A4*22 carriers (n = 152) versus CYP3A4*22 non-carrier status (n = 1,129) were not found to have a significant correlation with the primary thrombotic endpoint: cardiovascular death, myocardial infarction, definite stent thrombosis and stroke [1.3% vs. 2.5%, adjusted hazard ratio 1.81 (0.43–7.62) p = 0.42], or the primary bleeding endpoint: PLATO major and minor bleeding [13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58–1.50) p = 0.77]. Among the CYP3A4*1/*1 patients, CYP3A5 expressors (n = 196) versus non-expressors (n = 926) did not show a significant difference for the primary thrombotic [2.6% vs. 2.5%, adjusted hazard ratio 1.03 (0.39–2.71) p = 0.95], or the primary bleeding endpoint [12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73–1.76) p = 0.58]. With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers [44.0% vs. 45.0%, odds ratio 1.04 (0.45–2.42) p = 0.93], or in the CYP3A4*1/*1 group, CYP3A5 expressors versus CYP3A5 non-expressors [35.3% vs. 47.8%, odds ratio 0.60 (0.27–1.30) p = 0.20].

Conclusion: In STEMI patients treated with ticagrelor, neither the CYP3A4*22 carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea.

Clinical Trial Registration:ClinicalTrials.gov, identifier NCT01761786.
Early and accurate detection of melanoma skin cancer using hybrid level set approach
Authors: Ragab Mahmoud , Choudhry Hani , Al-Rabia Mohammed W. , Binyamin Sami Saeed , Aldarmahi Ahmed A. , Mansour Romany F.
Published: December 2022

Digital dermoscopy is used to identify cancer in skin lesions, and sun exposure is one of the leading causes of melanoma. It is crucial to distinguish between healthy skin and malignant lesions when using computerised lesion detection and classification. Lesion segmentation influences categorization accuracy and precision. This study introduces a novel way of classifying lesions. Hair filters, gel, bubbles, and specular reflection are all options. An improved levelling method is employed in an innovative method for detecting and removing cancerous hairs. The lesion is distinguished from the surrounding skin by the adaptive sigmoidal function; this function considers the severity of localised lesions. An improved technique for identifying a lesion from surrounding tissue is proposed in the article, followed by a classifier and available features that resulted in 94.40% accuracy and 93% success. According to research, the best method for selecting features and classifications can produce more accurate predictions before and during treatment. When the recommended strategy is put to the test using the Melanoma Skin Cancer Dataset, the recommended technique outperforms the alternative.
Metabolic engineering of cucurbitacins in Cucurbita pepo hairy roots
Authors: Almeida Aldo , Dong Lemeng , Thorsen Theis H. , Raadam Morten H. , Khakimov Bekzod , Carreno-Quintero Natalia , Kampranis Sotirios C. , Bak Søren
Published: December 2022

In this paper we show that metabolic engineering in Cucurbita pepo hairy roots can be used to both effectively increase and modify cucurbitacins. Cucurbitacins are highly-oxygenated triterpenoids originally described in the Cucurbitaceae family, but have since been found in 15 taxonomically distant plant families. Cucurbitacin B, D, E and I are the most widespread amongst the Cucurbitaceae and they have both important biological and pharmacological activities. In this study C. pepo hairy roots were used as a platform to boost production and alter the structures of the afore mentioned cucurbitacins by metabolic engineering to potentially provide new or more desirable bioactivities. We report that the ability to induce cucurbitacin biosynthesis by basic Helix-Loop-Helix transcription factors is partially conserved within the Cucurbitaceae and therefore can potentially be used as a biotechnological tool to increase cucurbitacins in several genera of this family. Additionally, overexpression of a novel acyltransferase from cucurbitacin producing Iberis amara generates a hitherto undescribed acetylation at the C3-hydroxyl group of the cucurbitadienol backbone. While overexpression of the cytochromes P450 CsCYP88L2 and McCYP88L7 from Cucumis sativus and Momordica charantia (respectively), results in accumulation of new spectral feature as revealed by High resolution liquid chromatography mass spectroscopy analysis; the m/z of the new peak supports it might be a cucurbitacin hydroxylated at the C19 position in C. pepo hairy roots. Finally, this paper is a case study of how hairy roots can be used to metabolically engineer and introduce novel modifications in metabolic pathways that have not been fully elucidated.
Association study of SNP locus for color related traits in herbaceous peony (Paeonia lactiflora Pall.) using SLAF-seq
Authors: Liu Genzhong , Li Ying , Sun Xia , Guo Xianfeng , Jiang Nannan , Fang Yifu , Chen Junqiang , Bao Zhilong , Ma Fangfang
Published: December 2022

Paeonia lactiflora Pall. (P. lactiflora) is a famous ornamental plant with showy and colorful flowers that has been domesticated in China for 4,000 years. However, the genetic basis of phenotypic variation and genealogical relationships in P. lactiflora population is poorly understood due to limited genetic information, which brings about bottlenecks in the application of effective and efficient breeding strategies. Understanding the genetic basis of color-related traits is essential for improving flower color by marker-assisted selection (MAS). In this study, a high throughput sequencing of 99 diploid P. lactiflora accessions via specific-locus amplified fragment sequencing (SLAF-seq) technology was performed. In total, 4,383,645 SLAF tags were developed from 99 P. lactiflora accessions with an average sequencing depth of 20.81 for each SLAF tag. A total of 2,954,574 single nucleotide polymorphisms (SNPs) were identified from all SLAF tags. The population structure and phylogenetic analysis showed that P. lactiflora population used in this study could be divided into six divergent groups. Through association study using Mixed linear model (MLM), we further identified 40 SNPs that were significantly positively associated with petal color. Moreover, a derived cleaved amplified polymorphism (dCAPS) marker that was designed based on the SLAF tag 270512F co-segregated with flower colors in P. lactiflora population. Taken together, our results provide valuable insights into the application of MAS in P. lactiflora breeding programs.
Proteome-wide analysis of hydrogen peroxide-induced protein carbonylation in Arabidopsis thaliana
Authors: Fangue-Yapseu Georges Yannick , Tola Adesola Julius , Missihoun Tagnon D.
Published: December 2022

Introduction

Protein carbonylation is a non-enzymatic and irreversible post-translational modification that occurs naturally in living organisms under the direct or indirect effect of reactive oxygen species (ROS). In animals, signaling pathways involving numerous carbonylated proteins have been identified, highlighting the dual role of these molecules in ROS signal transduction. In plants, studies on phytohormone signaling (auxin, methyl jasmonate, abscisic acid) have shown that reactive carbonyl species (RCS: acrolein, malondialdehyde, 4-hydroxynonenal, etc.), derived from the action of ROS on lipids, play important roles in secondary root formation and stomatal closure. However, the carbonylated proteins involved in these signaling pathways remain to be identified.

Methods

In this study, we analyzed proteins responsive to carbonylation by exogenous hydrogen peroxide (H2O2) by profiling the carbonyl proteome extracted from Arabidopsis thaliana leaves after H2O2 treatment. Carbonylated proteins were enriched at the peptide level and analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).

Results and discussion

We identified 35 and 39 uniquely carbonylated proteins in the untreated and the H2O2-treated plant samples, respectively. In comparison to the control treatment, gene ontology enrichment analysis revealed that most of the carbonylated proteins identified in the H2O2-treated plant samples are related to sulfate adenylyl transferases and amidophosphoribosyl transferases involved in the immune system response, defense response, and external stimulus-response. These results indicated that exogenous H2O2 caused a change in the pattern of protein carbonylation in A. thaliana leaves. Protein carbonylation may thus influence the plant transcriptome and metabolism in response to H2O2 and ROS-triggering external stimuli.