bluuebunny/crossref_metadata_2025 huggingface dataset:
Trained immunity: A “new” weapon in the fight against infectious diseases
Authors: Dagenais Amy , Villalba-Guerrero Carlos , Olivier Martin
Published: March 2023

Innate immune cells can potentiate the response to reinfection through an innate form of immunological memory known as trained immunity. The potential of this fast-acting, nonspecific memory compared to traditional adaptive immunological memory in prophylaxis and therapy has been a topic of great interest in many fields, including infectious diseases. Amidst the rise of antimicrobial resistance and climate change—two major threats to global health—, harnessing the advantages of trained immunity compared to traditional forms of prophylaxis and therapy could be game-changing. Here, we present recent works bridging trained immunity and infectious disease that raise important discoveries, questions, concerns, and novel avenues for the modulation of trained immunity in practice. By exploring the progress in bacterial, viral, fungal, and parasitic diseases, we equally highlight future directions with a focus on particularly problematic and/or understudied pathogens.
UcTCRdb: An unconventional T cell receptor sequence database with online analysis functions
Authors: Dou Yunsheng , Shan Shiwen , Zhang Jian
Published: March 2023

Unlike conventional major histocompatibility complex (MHC) class I and II molecules reactive T cells, the unconventional T cell subpopulations recognize various non-polymorphic antigen-presenting molecules and are typically characterized by simplified patterns of T cell receptors (TCRs), rapid effector responses and ‘public’ antigen specificities. Dissecting the recognition patterns of the non-MHC antigens by unconventional TCRs can help us further our understanding of the unconventional T cell immunity. The small size and irregularities of the released unconventional TCR sequences are far from high-quality to support systemic analysis of unconventional TCR repertoire. Here we present UcTCRdb, a database that contains 669,900 unconventional TCRs collected from 34 corresponding studies in humans, mice, and cattle. In UcTCRdb, users can interactively browse TCR features of different unconventional T cell subsets in different species, search and download sequences under different conditions. Additionally, basic and advanced online TCR analysis tools have been integrated into the database, which will facilitate the study of unconventional TCR patterns for users with different backgrounds. UcTCRdb is freely available at http://uctcrdb.cn/.
Effects of hypoxia on benthic eggs of calanoid copepods in the Southern Sea of Korea
Authors: Choi Seo Yeol , Soh Ho Young , Shin Kyoungsoon , Jung Seung Won , Jang Min-Chul
Published: March 2023

Global warming is affecting the composition, structure, and function of marine ecosystems. The increase in hypoxic regions due to stratification is a major environmental problem worldwide. Off the southern coast of Korea, hypoxia occurs frequently in summer, and the area of water affected is gradually expanding. In this study, we investigated the effects of hypoxia on the eggs of copepods in the order Calanoida. Data on the distribution and abundance of eggs in benthic sediments were collected from 17 stations, using a piston core sampler (64 mm internal diameter, 50 cm length), from August 1 to 7, 2012. Significant variations in the distribution of calanoid eggs and the occurrence of abnormalities in egg development were found between stations. The abundance of eggs found in the sediments ranged from 0.004 to 2.389 × 106 eggs·m−2, with higher abundances identified in hypoxic than in normoxic areas. The proportion of abnormal eggs ranged from 0 to 92.7%. In particular, there were significantly more abnormal than normal eggs in areas where hypoxia occurred (p < 0.01). These results show that hypoxia can have a lethal effect on calanoid eggs and further affect population and community dynamics.
Deletion of NADPH oxidase 2 attenuates cisplatin-induced acute kidney injury through reducing ROS-induced proximal tubular cell injury and inflammation
Authors: Chen Ho-Ching , Hou Hsin-Yu , Sung Junne-Ming , Shieh Chi-Chang
Published: March 2023

Backgrounds

Cisplatin is a commonly used chemotherapeutic agent in cancer treatment. However, its high nephrotoxicity limits its therapeutic application and efficacy. Cisplatin induces nephrotoxicity mainly through oxidative stress and inflammation. Reactive oxygen species (ROS) in the kidneys mainly arise from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 2 (NOX2), which is highly upregulated during ischemia-reperfusion injury and diabetes mellitus. However, its role in cisplatin-induced acute kidney injury (AKI) remains unknown.

Methods

A 8-10-week-old NOX2 gene-knockout and wild-type mice were injected with 25 mg/kg cisplatin intraperitoneally for experiments.

Results

We investigated the role of NOX2 in cisplatin-induced AKI and found that NOX2-mediated ROS production is a key inflammatory mediator of proximal tubular cell injury in cisplatin-induced AKI. NOX2 gene-knockout alleviated cisplatin-induced renal function decline, tubular injury score, kidney injury molecule-1(Kim-1) expression, and interleukin (IL)-6 and IL-1α levels with a reduction of ROS production. Moreover, in cisplatin-induced AKI, intercellular adhesion molecule 1 (ICAM-1) and the chemoattractant CXC ligand 1 (CXCL1) were highly expressed in association with neutrophil infiltration, which were all attenuated by deletion of NOX2.

Conclusion

These data indicate that NOX2 aggravates cisplatin nephrotoxicity by promoting ROS-mediated tissue injury and neutrophil infiltration. Thus, appropriate targeting of NOX2/ROS pathway may minimize the risk of cisplatin-induced kidney injury in patients receiving cancer therapy.
Changes in retinal circulation and choroidal thickness in patients with acute myeloid leukemia detected by optical coherence tomography angiography
Authors: Yang Ling , Chen Yanwei , Zhang Yunxiang , Shen Ting , Shen Xi
Published: March 2023

Purpose

To investigate changes in retinal circulation and the choroid in patients with acute myeloid leukemia (AML) in the acute and remission stages, to analyze the correlation between retinal circulation and laboratory parameters, and to assess risk factors associated with leukemic retinopathy.

Methods

Forty-eight patients (93 eyes) with AML were enrolled and divided into two groups according to fundus examination findings: the retinopathy and no retinopathy groups. Patients underwent eye measurements before treatment and after remission. Macular vessel density (VD), perfusion density (PD), foveal avascular zone (FAZ), and choroidal thickness (ChT) were measured using optical coherence tomography angiography. Patients with healthy eyes were recruited as control participants.

Results

Patients with leukemic retinopathy had higher measurements of white blood cells (WBCs), circulating blasts, fibrin degradation products, and cross-linked fibrin degradation products (D-dimer) and a lower hemoglobin (HB) count (p < 0.05). In the acute phase of the disease, the VD and PD were lower and the ChT was thicker in patients with AML than in controls (p < 0.05), irrespective of the presence of leukemic retinopathy; however, the patients were partially recovered in the remission stage. The VD was lower in patients with higher WBC (r = −0.217, p = 0.036), D-dimer (r = −0.279, p = 0.001), fasting blood glucose (FBG) (r = −0.298, p = 0.004) and triglyceride (r = −0.336, p = 0.001) levels. The FAZ area was negatively correlated with HB (r = −0.258, p = 0.012).

Conclusion

Patients with AML appear to have subclinical retinal perfusion loss and choroidal thickening in the acute phase of the disease, but this is reversible. Injury to bone marrow function may cause a decrease in retinal perfusion. Leukemic retinopathy is associated with abnormal hematologic parameters and coagulopathy.
Artificial intelligence-based 68Ga-DOTATOC PET denoising for optimizing 68Ge/68Ga generator use throughout its lifetime
Authors: Quak Elske , Weyts Kathleen , Jaudet Cyril , Prigent Anaïs , Foucras Gauthier , Lasnon Charline
Published: March 2023

Introduction

The yield per elution of a 68Ge/68Ga generator decreases during its lifespan. This affects the number of patients injected per elution or the injected dose per patient, thereby negatively affecting the cost of examinations and the quality of PET images due to increased image noise. We aimed to investigate whether AI-based PET denoising can offset this decrease in image quality parameters.

Methods

All patients addressed to our PET unit for a 68Ga-DOTATOC PET/CT from April 2020 to February 2021 were enrolled. Forty-four patients underwent their PET scans according to Protocol_FixedDose (150 MBq) and 32 according to Protocol_WeightDose (1.5 MBq/kg). Protocol_WeightDose examinations were processed using the Subtle PET software (Protocol_WeightDoseAI). Liver and vascular SUV mean were recorded as well as SUVmax, SUVmean and metabolic tumour volume (MTV) of the most intense tumoural lesion and its background SUVmean. Liver and vascular coefficients of variation (CV), tumour-to-background and tumour-to-liver ratios were calculated.

Results

The mean injected dose of 2.1 (0.4) MBq/kg per patient was significantly higher in the Protocol_FixedDose group as compared to 1.5 (0.1) MBq/kg for the Protocol_WeightDose group. Protocol_WeightDose led to noisier images than Protocol_FixedDose with higher CVs for liver (15.57% ± 4.32 vs. 13.04% ± 3.51, p = 0.018) and blood-pool (28.67% ± 8.65 vs. 22.25% ± 10.37, p = 0.0003). Protocol_WeightDoseAI led to less noisy images than Protocol_WeightDose with lower liver CVs (11.42% ± 3.05 vs. 15.57% ± 4.32, p < 0.0001) and vascular CVs (16.62% ± 6.40 vs. 28.67% ± 8.65, p < 0.0001). Tumour-to-background and tumour-to-liver ratios were lower for protocol_WeightDoseAI: 6.78 ± 3.49 vs. 7.57 ± 4.73 (p = 0.01) and 5.96 ± 5.43 vs. 6.77 ± 6.19 (p < 0.0001), respectively. MTVs were higher after denoising whereas tumour SUVmax were lower: the mean% differences in MTV and SUVmax were + 11.14% (95% CI = 4.84–17.43) and −3.92% (95% CI = −6.25 to −1.59).

Conclusion

The degradation of PET image quality due to a reduction in injected dose at the end of the 68Ge/68Ga generator lifespan can be effectively counterbalanced by using AI-based PET denoising.
Early diagnosis of neural impairment in seropositive leprosy household contacts: The experience of a reference center in Brazil
Authors: dos Santos Diogo Fernandes , Garcia Leonardo Peixoto , Borges Isabella Sabião , Oliveira Thales Junqueira , Antunes Douglas Eulálio , Luppi Andrea De Martino , Goulart Isabela Maria Bernardes
Published: March 2023

Introduction

Leprosy is an infectious disease that remains with a high number of new cases in developing countries. Household contacts have a higher risk for the development of the disease, but the neural impairment in this group is not well elucidated yet. Here, we measured the chance of occurrence of peripheral neural impairment in asymptomatic leprosy household.

Methods

Contacts who present anti-PGL-I IgM seropositivity, through electroneuromyography (ENMG) evaluation. We recruited 361 seropositive contacts (SPC) from 2017 to 2021, who were subjected to an extensive protocol that included clinical, molecular, and electroneuromyographic evaluations.

Results

Our data revealed a positivity of slit skin smear and skin biopsy qPCR of 35.5% (128/361) and 25.8% (93/361) respectively. The electroneuromyographic evaluation of the SPC showed neural impairment in 23.5% (85/361), with the predominance of a mononeuropathy pattern in 62.3% (53/85). Clinical neural thickening was observed in 17.5% (63/361) of seropositive contacts, but among the individuals with abnormal ENMG, only 25.9% (22/85) presented neural thickening in the clinical exam.

Discussion

Ours results corroborates the need to make the approach to asymptomatic contacts in endemic countries more timely. Since leprosy in its early stages can present an indolent and subclinical evolution, serological, molecular, and neurophysiological tools are essential to break the disease transmission chain.
Fluid-like cathode enhances valuable biomass production from brewery wastewater in purple phototrophic bacteria
Authors: Manchon Carlos , Asensio Yeray , Muniesa-Merino Fernando , Llorente María , Pun Álvaro , Esteve-Núñez Abraham
Published: March 2023

The climate crisis requires rethinking wastewater treatment to recover resources, such as nutrients and energy. In this scenario, purple phototrophic bacteria (PPB), the most versatile microorganisms on earth, are a promising alternative to transform the wastewater treatment plant concept into a biorefinery model by producing valuable protein-enriched biomass. PPB are capable of interacting with electrodes, exchanging electrons with electrically conductive materials. In this work, we have explored for mobile-bed (either stirred or fluidized) cathodes to maximize biomass production. For this purpose, stirred-electrode reactors were operated with low-reduced (3.5 e−/C) and high-reduced (5.9 e−/C) wastewater under cathodic polarization (−0.4 V and –0.8 V vs. Ag/AgCl). We observed that cathodic polarization and IR irradiation can play a key role in microbial and phenotypic selection, promoting (at –0.4 V) or minimizing (at –0.8 V) the presence of PPB. Then, we further study how cathodic polarization modulates PPB biomass production providing a fluid-like electrode as part of a so-called photo microbial electrochemical fluidized-bed reactor (photoME-FBR). Our results revealed the impact of reduction status of carbon source in wastewater to select the PPB photoheterotrophic community and how electrodes drive microbial population shifts depending on the reduction status of such carbon source.
A survey of neurophysiological differentiation across mouse visual brain areas and timescales
Authors: Gandhi Saurabh R. , Mayner William G. P. , Marshall William , Billeh Yazan N. , Bennett Corbett , Gale Samuel D. , Mochizuki Chris , Siegle Joshua H. , Olsen Shawn , Tononi Giulio , Koch Christof , Arkhipov Anton
Published: March 2023

Neurophysiological differentiation (ND), a measure of the number of distinct activity states that a neural population visits over a time interval, has been used as a correlate of meaningfulness or subjective perception of visual stimuli. ND has largely been studied in non-invasive human whole-brain recordings where spatial resolution is limited. However, it is likely that perception is supported by discrete neuronal populations rather than the whole brain. Therefore, here we use Neuropixels recordings from the mouse brain to characterize the ND metric across a wide range of temporal scales, within neural populations recorded at single-cell resolution in localized regions. Using the spiking activity of thousands of simultaneously recorded neurons spanning 6 visual cortical areas and the visual thalamus, we show that the ND of stimulus-evoked activity of the entire visual cortex is higher for naturalistic stimuli relative to artificial ones. This finding holds in most individual areas throughout the visual hierarchy. Moreover, for animals performing an image change detection task, ND of the entire visual cortex (though not individual areas) is higher for successful detection compared to failed trials, consistent with the assumed perception of the stimulus. Together, these results suggest that ND computed on cellular-level neural recordings is a useful tool highlighting cell populations that may be involved in subjective perception.
Association of smoking with the survival of patients with brain metastasis of lung cancer
Authors: Yu Jiayi , Zhang Yu , Liu Zheran , He Yan , Pei Yiyan , Zhang Renjie , Peng Xingchen , Fang Fang
Published: March 2023

Background

Smoking is associated with increased mortality in patients with cancer. However, there are limited data on the impact of smoking on the survival of patients with brain metastases. Therefore, this study aimed to evaluate whether smoking was associated with survival and whether smoking cessation was beneficial to these patients.

Methods

This study used lung cancer with a brain metastasis cohort of the West China Hospital of Sichuan University from 2013 to 2021. Patients were stratified according to smoking history; the distribution, clinical characteristics, and survival data of each group were estimated. Kaplan-Meier analysis and risk analysis were performed for the survival endpoint.

Results

Of the 2,647 patients included in the analysis, the median age was 57.8 years, and 55.4% were men. Among them, 67.1% had no smoking history, 18.9% still smoked, and 14% reported quitting smoking. Compared with never smokers, current smokers [HR, 1.51 (95% CI, 1.35-1.69), p < 0.01] and former smokers [HR, 1.32 (95% CI, 1.16-1.49), p<0.01] had an increased risk of death. However, quitting smoking was not associated with improved survival [HR, 0.90 (95% CI, 0.77-1.04), p = 0.16]. The overall survival increased with the increase of smoking cessation years.

Conclusions

In lung cancer patients with brain metastases, smoking was associated with an increased risk of death, but quitting smoking was not associated with improved survival.
Comparison between audio-vestibular findings and contrast-enhanced MRI of inner ear in patients with unilateral Ménière’s disease
Authors: Leng Yangming , Fan Wenliang , Liu Yingzhao , Xia Kaijun , Zhou Renhong , Liu Jingjing , Wang Hongchang , Ma Hui , Liu Bo
Published: March 2023

Objective

The diagnosis of Ménière’s disease (MD), characterized by idiopathic endolymphatic hydrops (ELH), remains a clinical priority. Many ancillary methods, including the auditory and vestibular assessments, have been developed to identify ELH. The newly emerging delayed magnetic resonance imaging (MRI) of the inner ear after intratympanic gadolinium (Gd) has been used for identifying ELH in vivo. We aimed to investigate the concordance of audio-vestibular and radiological findings in patients with unilateral MD.

Methods

In this retrospective study, 70 patients with unilateral definite MD underwent three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences following intratympanic application of Gd. Audio-vestibular evaluations were performed, including pure tone audiometry, electrocochleogram (ECochG), glycerol test, caloric test, cervical and ocular vestibular evoked myogenic potentials (VEMPs), and video head impulse test (vHIT). The relationship between imaging signs of ELH and audio-vestibular results was investigated.

Results

The incidence of radiological ELH was higher than that of neurotological results, including the glycerol test, caloric test, VEMPs, and vHIT. Poor or slight agreement was observed between audio-vestibular findings and radiological ELH in cochlear and/or vestibular (kappa values <0.4). However, the pure tone average (PTA) in the affected side significantly correlated with the extent of both cochlear (r = 0.26795, p = 0.0249) and vestibular (r = 0.2728, p = 0.0223) hydrops. Furthermore, the degree of vestibular hydrops was also positively correlated with course duration (r = 0.2592, p = 0.0303) and glycerol test results (r = 0.3944, p = 0.0061) in the affected side.

Conclusion

In the diagnosis of MD, contrast-enhanced MRI of the inner ear is advantageous in detecting ELH over the conventional audio-vestibular evaluations, which estimates more than hydropic dilation of endolymphatic space.
Broad learning for early diagnosis of Alzheimer's disease using FDG-PET of the brain
Authors: Duan Junwei , Liu Yang , Wu Huanhua , Wang Jing , Chen Long , Chen C. L. Philip
Published: March 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and the development of AD is irreversible. However, preventive measures in the presymptomatic stage of AD can effectively slow down deterioration. Fluorodeoxyglucose positron emission tomography (FDG-PET) can detect the metabolism of glucose in patients' brains, which can help to identify changes related to AD before brain damage occurs. Machine learning is useful for early diagnosis of patients with AD using FDG-PET, but it requires a sufficiently large dataset, and it is easy for overfitting to occur in small datasets. Previous studies using machine learning for early diagnosis with FDG-PET have either involved the extraction of elaborately handcrafted features or validation on a small dataset, and few studies have explored the refined classification of early mild cognitive impairment (EMCI) and late mild cognitive impairment (LMCI). This article presents a broad network-based model for early diagnosis of AD (BLADNet) through PET imaging of the brain; this method employs a novel broad neural network to enhance the features of FDG-PET extracted via 2D CNN. BLADNet can search for information over a broad space through the addition of new BLS blocks without retraining of the whole network, thus improving the accuracy of AD classification. Experiments conducted on a dataset containing 2,298 FDG-PET images of 1,045 subjects from the ADNI database demonstrate that our methods are superior to those used in previous studies on early diagnosis of AD with FDG-PET. In particular, our methods achieved state-of-the-art results in EMCI and LMCI classification with FDG-PET.
An absolute approach to using whole exome DNA and RNA workflow for cancer biomarker testing
Authors: Malhotra Richa , Javle Vyomesh , Tanwar Nishtha , Gowda Pooja , Varghese Linu , K Anju , Madhusudhan Nandhitha , Jaiswal Nupur , K. S. Bhargavi , Chatterjee Manjima , Prabhash Kumar , Sreekanthreddy Peddagangannagari , Rishi Kshitij D. , Goswami Hitesh M. , Veldore Vidya H.
Published: March 2023

Introduction

The concept of personalized medicine in cancer has emerged rapidly with the advancement of genome sequencing and the identification of clinically relevant variants that contribute to disease prognosis and facilitates targeted therapy options. In this study, we propose to validate a whole exome-based tumor molecular profiling for DNA and RNA from formalin-fixed paraffin-embedded (FFPE) tumor tissue.

Methods

The study included 166 patients across 17 different cancer types. The scope of this study includes the identification of single-nucleotide variants (SNVs), insertions/deletions (INDELS), copy number alterations (CNAs), gene fusions, tumor mutational burden (TMB), and microsatellite instability (MSI). The assay yielded a mean read depth of 200×, with >80% of on-target reads and a mean uniformity of >90%. Clinical maturation of whole exome sequencing (WES) (DNA and RNA)- based assay was achieved by analytical and clinical validations for all the types of genomic alterations in multiple cancers. We here demonstrate a limit of detection (LOD) of 5% for SNVs and 10% for INDELS with 97.5% specificity, 100% sensitivity, and 100% reproducibility.

Results

The results were >98% concordant with other orthogonal techniques and appeared to be more robust and comprehensive in detecting all the clinically relevant alterations. Our study demonstrates the clinical utility of the exome-based approach of comprehensive genomic profiling (CGP) for cancer patients at diagnosis and disease progression.

Discussion

The assay provides a consolidated picture of tumor heterogeneity and prognostic and predictive biomarkers, thus helping in precision oncology practice. The primary intended use of WES (DNA+RNA) assay would be for patients with rare cancers as well as for patients with unknown primary tumors, and this category constitutes nearly 20–30% of all cancers. The WES approach may also help us understand the clonal evolution during disease progression to precisely plan the treatment in advanced stage disease.
Heterogeneity of tumour mutational burden in metastatic NSCLC demonstrated by endobronchial ultrasound sampling
Authors: Leong Tracy L. , Aloe Christian , Aujla Savreet , Wang Hao , Gayevskiy Velimir , Asselin-Labat Marie-Liesse , Gray Lesley-Ann , Steinfort Daniel , Bozinovski Steven
Published: March 2023

Introduction

Tumour mutational burden (TMB) is an important emerging biomarker for immune checkpoint inhibitors (ICI). The stability of TMB values across distinct EBUS tumour regions is not well defined in advanced lung cancer patients.

Methods

This study included a whole-genome sequencing cohort (n=11, LxG cohort) and a targeted Oncomine TML panel cohort (n=10, SxD cohort), where paired primary and metastatic samples were obtained by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA).

Results

The LxG cohort displayed a strong correlation between the paired primary and metastatic sites, with a median TMB score of 7.70 ± 5.39 and 8.31 ± 5.88 respectively. Evaluation of the SxD cohort demonstrated greater inter-tumoural TMB heterogeneity, where Spearman correlation between the primary and metastatic sites fell short of significance. Whilst median TMB scores were not significantly different between the two sites, 3 out of 10 paired samples were discordant when using a TMB cut-off of 10 mutations per Mb. In addition, PD-L1 copy number and KRAS mutations were assessed, demonstrating the feasibility of performing multiple molecular tests relevant to ICI treatment using a single EBUS sample. We also observed good consistency in PD-L1 copy number and KRAS mutation, where cut-off estimates were consistent across the primary and metastatic sites.

Conclusions

Assessment of TMB acquired by EBUS from multiple sites is highly feasible and has the potential to improve accuracy of TMB panels as a companion diagnostic test. We demonstrate similar TMB values across primary and metastatic sites, however 3 out of 10 samples displayed inter-tumoural heterogeneity that would alter clinical management.
A giant teratoma in the anterior mediastinum found prenatally: A case report
Authors: Su Yuntian , Alifu Ailixiati , Wang Haifan , Lin Shibin , Su Xiaoman , Wei Yong , Wan Ying , Chen Renwei
Published: March 2023

Prenatal anterior mediastinal teratomas are rare. Anterior mediastinal teratomas can cause edema during the perinatal period. Color Doppler ultrasonography and chest computed tomography (CT) are of great value in diagnosing neonatal anterior mediastinal teratomas. Here, we report a case of prenatally diagnosed neonatal anterior mediastinal teratoma. After birth, transthoracic echocardiography and chest enhanced CT showed a large solid mass in the pericardial cavity. Owing to compression of the heart, the tumor was completely removed 1 day after birth, and cardiopulmonary bypass was performed. Pathology results indicated an immature teratoma (Grade I). At 9-month follow-up, the patient remained in good overall condition without observed recurrences.
Role of posttranslational modifications in memory and cognitive impairments caused by neonatal sevoflurane exposure
Authors: Jiang Yongliang , Zhou Yue , Tan Siwen , Xu Chongxi , Ma Junpeng
Published: March 2023

With the advancement of technology, increasingly many newborns are receiving general anesthesia at a young age for surgery, other interventions, or clinical assessment. Anesthetics cause neurotoxicity and apoptosis of nerve cells, leading to memory and cognitive impairments. The most frequently used anesthetic in infants is sevoflurane; however, it has the potential to be neurotoxic. A single, short bout of sevoflurane exposure has little impact on cognitive function, but prolonged or recurrent exposure to general anesthetics can impair memory and cognitive function. However, the mechanisms underlying this association remain unknown. Posttranslational modifications (PTMs), which can be described roughly as the regulation of gene expression, protein activity, and protein function, have sparked enormous interest in neuroscience. Posttranslational modifications are a critical mechanism mediating anesthesia-induced long-term modifications in gene transcription and protein functional deficits in memory and cognition in children, according to a growing body of studies in recent years. Based on these recent findings, our paper reviews the effects of sevoflurane on memory loss and cognitive impairment, discusses how posttranslational modifications mechanisms can contribute to sevoflurane-induced neurotoxicity, and provides new insights into the prevention of sevoflurane-induced memory and cognitive impairments.
The mechanism of action of paeoniae radix rubra–angelicae sinensis radix drug pair in the treatment of rheumatoid arthritis through PI3K/AKT/NF-κB signaling pathway
Authors: Li Jia , Zhang Xiaofei , Guo Dongyan , Shi Yajun , Zhang Shihao , Yang Ruiying , Cheng Jiangxue
Published: March 2023

Objective: To investigate the effects and mechanisms of Paeoniae radix rubra–Angelicae sinensis radix (P-A) drug pair in the treatment of rheumatoid arthritis (RA).

Methods: Mass spectrometry was employed to accurately characterize the main components of the P-A drug pair. Network pharmacology was used to analyze the main components and pathways of the P-A drug pair in the treatment of RA, and Discovery Studio software was used to molecularly dock the key proteins on the pathway with their corresponding compounds. The levels of serum TNF-a, IL-1β, and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). The histopathology of the ankle joint was observed by hematoxylin-eosin (HE) staining, and the positive expression of p-PI3K, p-IKK, p-NF-κB, and p-AKT in the synovial tissue of the ankle joint was detected by immunohistochemical analysis. Finally, the expression of PI3K, IKK, and AKT and their phosphorylation levels were determined by western blot in each group of rats.

Results: Network pharmacology combined with molecular docking analysis revealed that the pharmacodynamic mechanism of the P-A drug pair for the treatment of RA may be related to the contents of caffeic acid, quercetin, paeoniflorin, and baicalein in the regulation of the expression of the PI3K/AKT/NF-κB signaling pathway and the targets of PIK3CA, PIK3R1, AKT1, HSP90AA1 and IKBKB in the pathway. Compared with the model group, the P-A drug pair significantly improved the pathological changes of the synovial tissue and reduced feet swelling in RA model rats. Moreover, it regulated the levels of TNF-α, IL-1β, and IL-6 in serum (p < 0.05). The results of the immunohistochemical analysis and western blot showed that the expression of PI3K, IKK, NF-κB, and AKT decreased after phosphorylation in the synovial tissue (p < 0.05).

Conclusion: The P-A drug pair exhibited an inhibitory effect on the hyperactivation of the PI3K/AKT/NF-κB signaling pathway in the synovial membrane of RA rats. The mechanism may be related to the downregulation of the phosphorylation levels PI3K, IKK, NF-κB, and AKT, which in turn decreased inflammatory cell infiltration and synovial membrane proliferation.
ALDH2 attenuates myocardial pyroptosis through breaking down Mitochondrion-NLRP3 inflammasome pathway in septic shock
Authors: Zhang Ying , Lv Ying , Zhang Qingju , Wang Xingfang , Han Qi , Liang Yan , He Simeng , Yuan Qiuhuan , Zheng Jiaqi , Xu Changchang , Zhang Xiangxin , Wang Zichen , Yu Huaxiang , Xue Li , Wang Jiali , Xu Feng , Pang Jiaojiao , Chen Yuguo
Published: March 2023

Cell survival or death is critical for cardiac function. Myocardial pyroptosis, as a newly recognized programmed cell death, remains poorly understood in sepsis. In this study, we evaluated the effect of aldehyde dehydrogenase (ALDH2) on myocardial pyroptosis and revealed the underlying mechanisms in sepsis. We established a septic shock mice model by intraperitoneal injection of Lipopolysaccharide (LPS, 15 mg/kg) 12 h before sacrifice. It was found that aldehyde dehydrogenase significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation and Caspase-1/GSDMD-dependent pyroptosis, which remarkably improved survival rate and septic shock-induced cardiac dysfunction, relative to the control group. While aldehyde dehydrogenase knockout or knockdown significantly aggravated these phenomena. Intriguingly, we found that aldehyde dehydrogenase inhibited LPS-induced deacetylation of Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex α subunit (HADHA) by suppressing the translocation of Histone deacetylase 3 (HDAC3) from nuclei to mitochondria. Acetylated HADHA is essential for mitochondrial fatty acid β-oxidation, and its interruption can result in accumulation of toxic lipids, induce mROS and cause mtDNA and ox-mtDNA release. Our results confirmed the role of Histone deacetylase 3 and HADHA in NOD-like receptor protein 3 inflammasome activation. Hdac3 knockdown remarkedly suppressed NOD-like receptor protein 3 inflammasome and pyroptosis, but Hadha knockdown eliminated the effect. aldehyde dehydrogenase inhibited the translocation of Histone deacetylase 3, protected ac-HADHA from deacetylation, and significantly reduced the accumulation of toxic aldehyde, and inhibited mROS and ox-mtDNA, thereby avoided NOD-like receptor protein 3 inflammasome activation and pyroptosis. This study provided a novel mechanism of myocardial pyroptosis through mitochondrial Histone deacetylase 3/HADHA- NOD-like receptor protein 3 inflammasome pathway and demonstrated a significant role of aldehyde dehydrogenase as a therapeutic target for myocardial pyroptosis in sepsis.
Association between endometrial blood and clinical outcome in frozen single blastocyst transfer cycles
Authors: Zhang Qian , Wang Xiaolong , Li Zhishu , Wang Yinghua , Lu Hai’Ou , Xiao Yuhong , Yu Yuexin
Published: March 2023

Background: The success of embryo transfer cycle depends mainly on the quality of embryo and endometrial receptivity. Ultrasound examination is still the most widely used non-invasive evaluation method for its advantages of convenience, non-invasiveness and repeatability. Ultrasound-measured endometrial blood flow is one of the important evaluation indicators of morphology.

Aims: To investigate the effect of the number of endometrial blood flow branches on pregnancy outcome of frozen-thawed embryo transfer cycles which have undergoing hormone replacement therapy (HRT-FET).

Material and methods: A retrospective cohort study was performed looking at a total of 1390 HRT-FET cycles from our reproductive medicine center between January 2017 to December 2021, which transferred one blastocyst frozen on day 5 with good quality in morphology. Associations between endometrial blood flow branches and pregnancy outcomes were evaluated with multivariable linear regression analysis.

Results: The number of endometrial blood flow branches was independently associated with clinical pregnancy (OR 1.10; 95% CI 1.02–1.20). After adjusting for potential confounders, the effect size (odds ratio) was 1.09 (95% CI 1.00–1.19), and the results showed that the clinical pregnancy rate and live birth rate of T2 and T3 groups were significantly higher than those in group T1 (p < 0.05). Subgroup analysis showed that a consistent association between the endometrial blood flow branches and clinical pregnancy in all subgroups.

Conclusion: Our study provided evidence for the influence of endometrial blood flow on pregnancy outcomes. There may be an independent association between the number of endometrial blood flow branches and pregnancy outcomes in frozen-thawed single blastocyst transfer cycles.
An in vivo study of isotropic and anisotropic wall stress in a hyperelastic holzapfel-gasser-ogden model in the human abdominal aorta: Effects of age and sex
Authors: Karlsson Jerker , Stålhand Jonas , Carlhäll Carl-Johan , Länne Toste , Engvall Jan
Published: March 2023

Background: Wall stress of the abdominal aorta (AA) appears to be an important factor in the assessment of risk for rupture based on the relationship between blood pressure and aortic diameter. We therefore investigated peak wall stress as well as isotropic and anisotropic wall stress of AA.

Methods: Thirty healthy adults (male = 15) were included. Pulsatile diameter changes were determined non-invasively by an echo-tracking system, and intra-aortic pressure was measured simultaneously. A computer based mechanical model was used to compute the isotropic and anisotropic components of circumferential and longitudinal stresses.

Results: Elderly males had higher total wall stress and a higher isotropic stress component in the circumferential direction and higher total longitudinal wall stress than elderly females. The isotropic component increased with age in males but not in females, whereas the anisotropic component decreased with age in both sexes.

Conclusion: We found that isotropic and anisotropic properties of the abdominal aortic wall differ between young and elderly participants and between the sexes. A possible explanation could relate to chemical alterations (e.g., due to sex hormones) and changes over time in the physical distribution of fibers. Modeling of wall stress components of the human AA may contribute to a better understanding of elastin-collagen interactions during remodeling of the aortic wall.
Genomic methylation patterns in pre-meiotic gynoecia of wild-type and RdDM mutants of Arabidopsis
Authors: Ortiz-Vasquez Quetzely , León-Martínez Gloria , Barragán-Rosillo Carlos , González-Orozco Eduardo , Deans Samuel , Aldridge Billy , Vickers Martin , Feng Xiaoqi , Vielle-Calzada Jean-Philippe
Published: March 2023

Introduction

Although DNA methylation patterns are generally considered to be faithfully inherited in Arabidopsis thaliana (Arabidopsis), there is evidence of reprogramming during both male and female gametogenesis. The gynoecium is the floral reproductive organ from which the ovules develop and generate meiotically derived cells that give rise to the female gametophyte. It is not known whether the gynoecium can condition genomic methylation in the ovule or the developing female gametophyte.

Methods

We performed whole genome bisulfite sequencing to characterize the methylation patterns that prevail in the genomic DNA of pre-meiotic gynoecia of wild-type and three mutants defective in genes of the RNA-directed DNA methylation pathway (RdDM): ARGONAUTE4 (AGO4), ARGONAUTE9 (AGO9), and RNA-DEPENDENT RNA POLYMERASE6 (RDR6).

Results

By globally analyzing transposable elements (TEs) and genes located across the Arabidopsis genome, we show that DNA methylation levels are similar to those of gametophytic cells rather than those of sporophytic organs such as seedlings and rosette leaves. We show that none of the mutations completely abolishes RdDM, suggesting strong redundancy within the methylation pathways. Among all, ago4 mutation has the strongest effect on RdDM, causing more CHH hypomethylation than ago9 and rdr6. We identify 22 genes whose DNA methylation is significantly reduced in ago4, ago9 and rdr6 mutants, revealing potential targets regulated by the RdDM pathway in premeiotic gyneocia.

Discussion

Our results indicate that drastic changes in methylation levels in all three contexts occur in female reproductive organs at the sporophytic level, prior to the alternation of generations within the ovule primordium, offering a possibility to start identifying the function of specific genes acting in the establishment of the female gametophytic phase of the Arabidopsis life cycle.
Widely targeted metabolome profiling of different plateau raspberries and berry parts provides innovative insight into their antioxidant activities
Authors: Ren Xiaoli , Wang Shulin , Wang Jinying , Xu Dan , Ye Ying , Song Yangbo
Published: March 2023

Raspberries are highly nutritious and have powerful antioxidant properties, making them functional berries with positive effects on physiological functioning. However, there is limited information available on the diversity and variability of metabolites in raspberry and its parts, especially in plateau raspberries. To address this, commercial raspberries and their pulp and seeds from two plateaus in China were subjected to LC-MS/MS-based metabolomics analysis and evaluated for antioxidant activity using four assays. A metabolite-metabolite correlation network was established based on antioxidant activity and correlation analysis. The results showed that 1661 metabolites were identified and classified into 12 categories, with significant variations in composition between the whole berry and its parts from different plateaus. Flavonoids, amino acids and their derivatives, and phenolic acids were found to be up-regulated in Qinghai’s raspberry compared to Yunnan’s raspberry. The main differently regulated pathways were related to flavonoid, amino acid, and anthocyanin biosynthesis. The antioxidant activity of Qinghai’s raspberry was stronger than Yunnan’s raspberry, and the order of antioxidant capacity was seed > pulp > berry. The highest FRAP (420.31 µM TE/g DW) values was found in the seed of Qinghai’s raspberry. Overall, these findings suggest that the environment in which the berries grow can affect their chemical composition, and comprehensive exploitation and cultivation of whole raspberry and its parts from different plateaus can lead to new opportunities for phytochemical compositions and antioxidant activity.
Workplace loneliness mediates the relationship between perceived organizational support and job performance: Differing by extraversion
Authors: Tian Guomei , Liu Tingting , Yang Ruo
Published: March 2023

This study investigated the mediating role of workplace loneliness relating perceived organizational support to job performance, as well as the moderating role of extraversion in such relationship. 332 full-time Chinese employees from various enterprises voluntarily participated in the two-wave surveys via either paper-and-pencil or online survey conducted at Credamo and Tencent Questionnaire website. Hierarchical regression and bootstrapping analyses were employed to examine the hypotheses. Results indicated that workplace loneliness partially mediates the linkage between perceived organizational support and job performance; extraversion serves as a moderator in the relationship between workplace loneliness and job performance, as well as the mediating role of workplace loneliness linking perceived organizational support to job performance, such that the relationship is stronger when extraversion is high. Supplementary analyses revealed that social companionship, but not emotional deprivation, serves as a mediator in the relationship between perceived organizational support and job performance; extraversion enhanced the direct influence of social companionship on job performance, as well as the indirect influence of perceived organizational support on job performance via social companionship. Theoretical and practical implications are discussed.
The relationship between grammatical knowledge and reading comprehension: A meta-analysis
Authors: Zheng Haoyuan , Miao Xuecong , Dong Yang , Yuan Daniel-Chongbo
Published: March 2023

The study aimed to examine the cohesive tie effect on reading comprehension through the grammatical knowledge cognition process. The present meta-analysis examined the correlation between grammatical knowledge and reading comprehension based on empirical results published between 1998 and 2021. This study selected 86 studies with a total of 14,852 readers whose grades were grouped from primary school to university. The results showed that the overall correlation effect size between grammatical knowledge and reading comprehension was large, and the significant interaction effect of the grade group was confirmed through moderator analysis. The results suggested that the grammatical knowledge’s function of the cohesive tie has a transfer effect across different text comprehension scripts.
The effect of perceived stress on depression in college students: The role of emotion regulation and positive psychological capital
Authors: Liu Yafei , Yu Haibo , Shi Yaohui , Ma Chao
Published: March 2023

Introduction

College students have become a high prevalence group and vulnerable group of depression. The present study aims to explore the effect of perceived stress on depression in a sample of Chinese college students and proposes that both emotion regulation and positive psychological capital play a moderating role between the two, so as to provide rational intervention for the prevention of potential depression among college students.

Method

In this study, 1,267 college students (46.4% female) from a university in western China were selected for the study using a whole-group convenience sampling method.

Results

After controlling for gender, this study found that both cognitive reappraisal and positive psychological capital positively moderated the relationship between perceived stress and depression, and both significantly inhibited depression in high and low stress perceivers, and the inhibitory effect was more pronounced in high stress perceivers, but expression inhibition did not moderate the relationship between perceived stress and depression.

Discussion

The results suggest that college students can be helped to cope with the negative effects of perceived stress on depression by increasing the frequency of their use of cognitive reappraisal strategies and encouraging the accumulation of positive psychological capital. This study provides theoretical and practical implications for rational interventions for depression among college students.
Risk factors for developmental quotients in ASD children: A cross-sectional study
Authors: Dong Han-Yu , Miao Chun-Yue , Zhang Yu , Shan Ling , Feng Jun-Yan , Jia Fei-Yong , Du Lin
Published: March 2023

Objective

To analyze the risk factors for developmental quotients (DQs) of children with autism spectrum disorder (ASD) and to better understand the effects of screen time on neurodevelopment in children with ASD.

Methods

We retrospectively analyzed the data of 382 children with ASD, including demographic profiles; socioeconomic status; score on the Chinese parent–child interaction scale (CPCIS); screen time questionnaire; ASD symptom rating scales, including the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Autism Diagnostic Observation Schedule Second Edition (ADOS-2); and DQs using Griffiths Development Scales–Chinese Edition. Univariate analysis was carried out to analyze the factors related to the DQs of children with ASD, and then the linear regression model was used to identify the independent influencing factors of the DQs of children with ASD.

Results

Vitamin D (β = 0.180, p = 0.002), age (β = −0.283, p = 0.000) and CARS score (β = −0.347, p = 0.000) are risk factors related to DQ of locomotor in children with ASD. Vitamin D (β = 0.108, p = 0.034), CARS score (β =  −0.503, p = 0.000), ADOS-2 severity score (β =  −0.109, p = 0.045) and CPCIS score (β = 0.198, p = 0.000) are risk factors related to DQ of personal social skill in children with ASD. Vitamin D (β = 0.130, p = 0.018), CARS score (β =  −0.469, p = 0.000), and CPCIS score (β = 0.133, p = 0.022) are risk factors related to DQ of hearing-speech in children with ASD. Vitamin D (β = 0.163, p = 0.003) and CARS score (β =  −0.471, p = 0.000) are risk factors related to DQ of eye-hand coordination in children with ASD. Age (β =  −0.140, p = 0.020), CARS score (β =  −0.342, p = 0.000), ADOS-2 severity score (β = −0.133, p = 0.034) and CPCIS score (β = 0.193, p = 0.002) are risk factors related to DQ of performance in children with ASD. Vitamin D (β = 0.801, p = 0.000) and CPCIS score (β = 0.394, p = 0.019) are risk factors related to DQ of practical reasoning in children with ASD.

Conclusion

Vitamin D status, the severity of autistic symptoms and parent-child interaction are risk factors for developmental quotients in children with ASD. Screen exposure time is negatively associated with DQs in children with ASD but is not an independent risk factor for DQs.