bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of comparative genomics of Acetobacter species facilitates genome-scale metabolic reconstruction of the Acetobacter ghanensis LMG 23848T and Acetobacter senegalensis 108B cocoa strains
Authors: Pelicaen Rudy , Weckx Stefan , Gonze Didier , De Vuyst Luc
Published: November 2022

Acetobacter species play an import role during cocoa fermentation. However, Acetobacter ghanensis and Acetobacter senegalensis are outcompeted during fermentation of the cocoa pulp-bean mass, whereas Acetobacter pasteurianus prevails. In this paper, an in silico approach aimed at delivering some insights into the possible metabolic adaptations of A. ghanensis LMG 23848T and A. senegalensis 108B, two candidate starter culture strains for cocoa fermentation processes, by reconstructing genome-scale metabolic models (GEMs). Therefore, genome sequence data of a selection of strains of Acetobacter species were used to perform a comparative genomic analysis. Combining the predicted orthologous groups of protein-encoding genes from the Acetobacter genomes with gene-reaction rules of GEMs from two reference bacteria, namely a previously manually curated model of A. pasteurianus 386B (iAp386B454) and two manually curated models of Escherichia coli (EcoCyc and iJO1366), allowed to predict the set of reactions present in A. ghanensis LMG 23848T and A. senegalensis 108B. The predicted metabolic network was manually curated using genome re-annotation data, followed by the reconstruction of species-specific GEMs. This approach additionally revealed possible differences concerning the carbon core metabolism and redox metabolism among Acetobacter species, pointing to a hitherto unexplored metabolic diversity. More specifically, the presence or absence of reactions related to citrate catabolism and the glyoxylate cycle for assimilation of C2 compounds provided not only new insights into cocoa fermentation but also interesting guidelines for future research. In general, the A. ghanensis LMG 23848T and A. senegalensis 108B GEMs, reconstructed in a semi-automated way, provided a proof-of-concept toward accelerated formation of GEMs of candidate functional starter cultures for food fermentation processes.
The effects of elemene emulsion injection on rat fecal microbiota and metabolites: Evidence from metagenomic exploration and liquid chromatography-mass spectrometry
Authors: Gu Lei , Wu Hao , Zhang Yang , Wu Yousheng , Jin Yuan , Li Tian , Ma Litian , Zheng Jin
Published: November 2022

Objective

Elemene emulsion injection (EEI) has been approved for interventional and intracavitary chemotherapy in treating malignant ascites in China, but few studies have focused on the effects of EEI on gut microbiota and metabolites. In this study, we investigated the effects of EEI on the fecal microbiota and metabolites in healthy Sprague-Dawley (SD) rats.

Methods

We randomly assigned 18 male SD rats to three groups (n = 6 in each group): the sham group (group S), the low-concentration EEI group (L-EEI), and the high-concentration EEI group (H-EEI). The L-EEI and H-EEI rats were administered 14 days of consecutive EEI, 20 mg/kg, and 40 mg/kg intraperitoneally (IP). Group S rats were administered the same volume of normal saline. On day 14, each animal's feces were collected for metagenomic sequencing and metabolomic analysis, and the colonic contents were collected for 16S rRNA sequencing.

Results

EEI could alter the β-diversity but not the α-diversity of the fecal microbiota and induce structural changes in the fecal microbiota. Different concentrations of EEI affect the fecal microbiota differently. The effects of different EEI concentrations on the top 20 bacteria with significant differences at the species level among the three groups were roughly divided into three categories: (1) A positive or negative correlation with the different EEI concentrations. The abundance of Ileibacterium Valens increased as the EEI concentration increased, while the abundance of Firmicutes bacteria and Clostridium sp. CAC: 273 decreased. (2) The microbiota showed a tendency to increase first, then decrease or decrease first, and then increase as EEI concentration increased—the abundance of Prevotella sp. PCHR, Escherichia coli, and Candidatus Amulumruptor caecigallinarius tended to decrease with L-EEI but significantly increased with H-EEI. In contrast, L-EEI significantly increased Ruminococcus bromii and Dorea sp. 5–2 abundance, and Oscillibacter sp. 1–3 abundance tended to increase, while H-EEI significantly decreased them. (3) L-EEI and H-EEI decreased the abundance of bacteria (Ruminococcaceae bacterium, Romboutsia ilealis, and Staphylococcus xylosus). Fecal metabolites, like microbiota, were sensitive to different EEI concentrations and correlated with fecal microbiota and potential biomarkers.

Conclusion

This study shows that intraperitoneal EEI modulates the composition of rat fecal microbiota and metabolites, particularly the gut microbiota's sensitivity to different concentrations of EEI. The impact of changes in the microbiota on human health remains unknown, particularly EEI's efficacy in treating tumors.
Phenomics in sport: Can emerging methodology drive advanced insights?
Authors: Kiefer Adam W. , Martin David T.
Published: November 2022

Methodologies in applied sport science have predominantly driven a reductionist grounding to component-specific mechanisms to drive athlete training and care. While linear mechanistic approaches provide useful insights, they have impeded progress in the development of more complex network physiology models that consider the temporal and spatial interactions of multiple factors within and across systems and subsystems. For this, a more sophisticated approach is needed and the development of such a methodological framework can be considered a Sport Grand Challenge. Specifically, a transdisciplinary phenomics-based scientific and modeling framework has merit. Phenomics is a relatively new area in human precision medicine, but it is also a developed area of research in the plant and evolutionary biology sciences. The convergence of innovative precision medicine, portable non-destructive measurement technologies, and advancements in modeling complex human behavior are central for the integration of phenomics into sport science. The approach enables application of concepts such as phenotypic fitness, plasticity, dose-response dynamics, critical windows, and multi-dimensional network models of behavior. In addition, profiles are grounded in indices of change, and models consider the athlete’s performance or recovery trajectory as a function of their dynamic environment. This new framework is introduced across several example sport science domains for potential integration. Specific factors of emphasis are provided as potential candidate fitness variables and example profiles provide a generalizable modeling approach for precision training and care. Finally, considerations for the future are discussed, including scaling from individual athletes to teams and additional factors necessary for the successful implementation of phenomics.
A family study of symbolic learning and synaptic plasticity in autism spectrum disorder
Authors: Granerud Guro , Elvsåshagen Torbjørn , Arntzen Erik , Juhasz Katalin , Emilsen Nina Merete , Sønderby Ida Elken , Nærland Terje , Malt Eva Albertsen
Published: November 2022

The current study presents a male with autism spectrum disorder (ASD) and a 3q29 deletion, and three healthy first-degree relatives. Our magnetic resonance imaging (MRI) dataset included a healthy control subset. We describe a comprehensive multimodal approach, including equivalence class formation, neurocognitive testing, MRI, and electroencephalography (EEG)-based cortical plasticity, which can provide new insights into socio-communicative and learning impairments and neural underpinnings in ASD. On neurocognitive testing, the proband showed reduced processing speed, attending behavior, and executive function. He required more training trials in equivalence class training compared with family members and exhibited impaired priming of words compared with priming with images. The proband had smaller intracranial volume and surface area and a larger visual evoked potential (VEP) C1 amplitude than family members and intact long-term potentiation (LTP)-like visual cortex plasticity. Together, these results suggest that 3q29 deletion-related ASD is associated with impaired problem-solving strategies in complex socio-communicative and learning tasks, smaller intracranial and surface area, altered VEP amplitude, and normal LTP-like visual cortex plasticity. Further studies are needed to clarify whether this multimodal approach can be used to identify ASD subgroups with distinct neurobiological alterations and to uncover mechanisms underlying socio-communicative and learning impairments.

Lay Summary: We studied learning, brain activity, and brain structure in a person with autism and a genetic aberration, and his close relatives. Compared with relatives, the person with autism required more training for learning, and visual learning was better than verbal learning. This person had some changes in the activity of the visual cortex, and the size and the surface area of the brain were reduced. Knowledge about learning and brain mechanisms is valuable for the development of training programs for individuals with autism.
Let the force guide you: a performance-based adaptive algorithm for postural training using haptic feedback
Authors: Agarwal Rakhi , Hussain Asif , SKM Varadhan , Campolo Domenico
Published: November 2022

Motor learning is an essential component of human behavior. Many different factors can influence the process of motor learning, such as the amount of practice and type of feedback. Changes in task difficulty during training can also considerably impact motor learning. Typical motor learning studies include a sequential variation of task difficulty, i.e., easy to challenging, irrespective of user performance. However, many studies have reported the importance of performance-based task difficulty variation for effective motor learning and skill transfer. A performance-based adaptive algorithm for task difficulty variation based on the challenge-point framework is proposed in this study. The algorithm is described for postural adaptation during simultaneous upper-limb training. Ten healthy participants (28 ± 2.44 years) were recruited to validate the algorithm. Participants adapted to a postural target of 20° in the anterior direction from the initial upright posture while performing a unimanual reaching task using a robotic device. Results suggest a significant decrease in postural error after training. The algorithm successfully adapted the task difficulty based on the performance of the user. The proposed algorithm could be modified for different motor skills and can be further evaluated for different applications in order to maximize the potential benefits of rehabilitation sessions.
Brain white matter hyperintensity lesion characterization in 3D T2 fluid-attenuated inversion recovery magnetic resonance images: Shape, texture, and their correlations with potential growth
Authors: Gwo Chih-Ying , Zhu David C. , Zhang Rong
Published: November 2022

Analyses of age-related white matter hyperintensity (WMH) lesions manifested in T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance images (MRI) have been mostly on understanding the size and location of the WMH lesions and rarely on the morphological characterization of the lesions. This work extends our prior analyses of the morphological characteristics and texture of WMH from 2D to 3D based on 3D T2 FLAIR images. 3D Zernike transformation was used to characterize WMH shape; a fuzzy logic method was used to characterize the lesion texture. We then clustered 3D WMH lesions into groups based on their 3D shape and texture features. A potential growth index (PGI) to assess dynamic changes in WMH lesions was developed based on the image texture features of the WMH lesion penumbra. WMH lesions with various sizes were segmented from brain images of 32 cognitively normal older adults. The WMH lesions were divided into two groups based on their size. Analyses of Variance (ANOVAs) showed significant differences in PGI among WMH shape clusters (P = 1.57 × 10–3 for small lesions; P = 3.14 × 10–2 for large lesions). Significant differences in PGI were also found among WMH texture group clusters (P = 1.79 × 10–6). In conclusion, we presented a novel approach to characterize the morphology of 3D WMH lesions and explored the potential to assess the dynamic morphological changes of WMH lesions using PGI.
Diffusion kurtosis imaging and diffusion tensor imaging parameters applied to white matter and gray matter of patients with anti-N-methyl-D-aspartate receptor encephalitis
Authors: Liu Hanjing , Xiang Yayun , Liu Junhang , Feng Jinzhou , Du Silin , Luo Tianyou , Li Yongmei , Zeng Chun
Published: November 2022

Objectives

To compare parameters of diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) to evaluate which can better describe the microstructural changes of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients and to characterize the non-Gaussian diffusion patterns of the whole brain and their correlation with neuropsychological impairments in these patients.

Materials and methods

DTI and DKI parameters were measured in 57 patients with anti-NMDAR encephalitis and 42 healthy controls. Voxel-based analysis was used to evaluate group differences between white matter and gray matter separately. The modified Rankin Scale (mRS) was used to evaluate the severity of the neurofunctional recovery of patients, the Montreal Cognitive Assessment (MoCA) was used to assess global cognitive performance, and the Hamilton Depression Scale (HAMD) and fatigue severity scale (FSS) were used to evaluate depressive and fatigue states.

Results

Patients with anti-NMDAR encephalitis showed significantly decreased radial kurtosis (RK) in the right extranucleus in white matter (P < 0.001) and notably decreased kurtosis fractional anisotropy (KFA) in the right precuneus, the right superior parietal gyrus (SPG), the left precuneus, left middle occipital gyrus, and left superior occipital gyrus in gray matter (P < 0.001). Gray matter regions with decreased KFA overlapped with those with decreased RK in the left middle temporal gyrus, superior temporal gyrus (STG), supramarginal gyrus (SMG), postcentral gyrus (POCG), inferior parietal but supramarginal gyrus, angular gyrus (IPL) and angular gyrus (ANG) (P < 0.001). The KFA and RK in the left ANG, IPL and POCG correlated positively with MoCA scores. KFA and RK in the left ANG, IPL, POCG and SMG correlated negatively with mRS scores. KFA in the left precuneus and right SPG as well as RK in the left STG correlated negatively with mRS scores. No significant correlation between KFA and RK in the abnormal brain regions and HAMD and FSS scores was found.

Conclusion

The microstructural changes in gray matter were much more extensive than those in white matter in patients with anti-NMDAR encephalitis. The brain damage reflected by DKI parameters, which have higher sensitivity than parameters of DTI, correlated with cognitive impairment and the severity of the neurofunctional recovery.
Modulation of colonic function in irritable bowel syndrome rats by electroacupuncture at ST25 and the neurobiological links between ST25 and the colon
Authors: Zhang Lili , Yu Cheng , Chen Biwei , Chao Yuqiao , Zhang Haiyan , Zhao Qinyu , Yang Kaiwei , Zhang Yujiao , Chen Shaozong
Published: November 2022

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease characterized by abdominal pain and defecation disorders. Acupuncture therapy positively affects IBS, with ST25 being the main point. However, ST25 has mostly been used in conjunction with other acupoints. This study aimed to observe the therapeutic effect of electroacupuncture at ST25 alone in IBS and the neurobiological mechanism of ST25 associated with the colon. First, we observed the effect of electroacupuncture at ST25 on the visceral pain threshold and slow-wave discharge of the colon in IBS model rats. Second, we explored the neurobiological mechanism of ST25 associated with the colon using a neural tracer technique. The results showed that (1) electroacupuncture at ST25 alone can alleviate visceral hypersensitivity and restore normal slow-wave frequency and rhythm of the colon in IBS rats; (2) there is a close neuroanatomical connection between ST25 and the colon, i.e., in the dorsal root ganglion (DRG), ST25 is similar in innervation to the colon, mainly in the T8–L1 segment, while the presence of double-labeled positive neurons is present in a part of the DRG; retrogradely labeled motor neurons associated with ST25 were observed in the anterior horn of the spinal cord, and retrogradely labeled sympathetic postganglionic neurons associated with ST25 were observed in the sympathetic nerve chain. These findings suggested that the DRGs and the dorsal horn of the spinal cord are important targets for electroacupuncture at ST25 to reduce visceral hypersensitivity in IBS rats. The sympathetic ganglia may be an important site for ST25 to regulate intestinal motility. The neurobiological mechanism of ST25 action in IBS rats should be further investigated in the future by combining related techniques, such as pseudorabies virus, optogenetics, calcium imaging, and electrophysiology.
Bi-nasal sectors of ganglion cells complex and visual evoked potential amplitudes as biomarkers in pituitary macroadenoma management
Authors: Hernández-Echevarría Odelaisys , Cuétara-Lugo Elizabeth Bárbara , Pérez-Benítez Mario Jesús , González-Gómez Julio César , González-Diez Héctor Raúl , Mendoza-Santiesteban Carlos E.
Published: November 2022

The study aimed to evaluate the retinal ganglion cell structure using optical coherence tomography and the visual pathway function employing visual evoked potentials in the diagnosis and monitoring of patients with pituitary macroadenoma. A descriptive, cross-sectional, and longitudinal study (3 and 12 months follow-up) was conducted on forty-two patients. Thirty-five age-matched healthy controls were used in the cross-sectional one. Full neuro-ophthalmological evaluation (structural and functional) was carried out including global and segmented retinal nerve fiber layer/ganglion cell complex analysis and amplitude and latency of P100 component in the electrophysiology. Statistical data analysis was conducted with R version 3.6.3 and Python version 3.8. Associations were evaluated using Spearman’s correlations. Amplitude sensitivities were 0.999, and bi-nasal sectors of ganglion cell complex thickness specificities were 0.999. This structural parameter had the highest diagnostic value (area under curve = 0.923). Significant associations were found between bi-nasal sectors with amplitude at 12′ (rho > 0.7, p < 0.01) and median deviation of the visual field (rho > 0.5, p < 0.01) at 3 months. Pre-surgical values of bi-nasal sectors and amplitude can predict post-surgically median deviation and amplitude (Oz, 12′) at 3 months with r2 > 0.5. Bi-nasal sectors of ganglion cell complex and visual evoked potentials P100 amplitude are efficient biomarkers of visual pathway damage for pituitary macroadenoma patients’ management. Pre-surgical values of the bi-nasal sector and visual evoked potentials’ amplitude could help to predict the restoration of parvocellular pathway traffic after decompression.
Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity
Authors: Chatterjee Dipashree , Beaulieu Jean Martin
Published: November 2022

Inhibition of Glycogen synthase kinase 3 (GSK3) is a popular explanation for the effects of lithium ions on mood regulation in bipolar disorder and other mental illnesses, including major depression, cyclothymia, and schizophrenia. Contribution of GSK3 is supported by evidence obtained from animal and patient derived model systems. However, the two GSK3 enzymes, GSK3α and GSK3β, have more than 100 validated substrates. They are thus central hubs for major biological functions, such as dopamine-glutamate neurotransmission, synaptic plasticity (Hebbian and homeostatic), inflammation, circadian regulation, protein synthesis, metabolism, inflammation, and mitochondrial functions. The intricate contributions of GSK3 to several biological processes make it difficult to identify specific mechanisms of mood stabilization for therapeutic development. Identification of GSK3 substrates involved in lithium therapeutic action is thus critical. We provide an overview of GSK3 biological functions and substrates for which there is evidence for a contribution to lithium effects. A particular focus is given to four of these: the transcription factor cAMP response element-binding protein (CREB), the RNA-binding protein FXR1, kinesin subunits, and the cytoskeletal regulator CRMP2. An overview of how co-regulation of these substrates may result in shared outcomes is also presented. Better understanding of how inhibition of GSK3 contributes to the therapeutic effects of lithium should allow for identification of more specific targets for future drug development. It may also provide a framework for the understanding of how lithium effects overlap with those of other drugs such as ketamine and antipsychotics, which also inhibit brain GSK3.
The AMPylase FIC-1 modulates TGF-β signaling in Caenorhabditis elegans
Authors: Hernandez-Lima Mirella A. , Champion Margaret , Mattiola Zachary , Truttmann Matthias C.
Published: November 2022

Post-translational protein modifications are essential for the spatio-temporal regulation of protein function. In this study, we examine how the activity of the Caenorhabditis elegans AMPylase FIC-1 modulates physiological processes in vivo. We find that over-expression (OE) of the constitutive AMPylase FIC-1(E274G) impairs C. elegans development, fertility, and stress resilience. We also show that FIC-1(E274G) OE inhibits pathogen avoidance behavior by selectively suppressing production of the Transforming Growth Factor-β (TGF-β) ligands DAF-7 and DBL-1 in ASI sensory neurons. Finally, we demonstrate that FIC-1 contributes to the regulation of adult body growth, cholinergic neuron function, and larval entry into dauer stage; all processes controlled by TGF-β signaling. Together, our results suggest a role for FIC-1 in regulating TGF-β signaling in C. elegans.
Effects of high-pressure homogenization on physicochemical and functional properties of enzymatic hydrolyzed soybean protein concentrate
Authors: Liang Yaru , Guo Yanan , Zheng Yuxuan , Liu Sibo , Cheng Tianfu , Zhou Linyi , Guo Zengwang
Published: November 2022

This paper investigates the effect on the physicochemical and functional properties of soybean protein concentrate (SPC) by using Alcalase protease and high-pressure homogenization (HPH) (0, 20, 40, 60, 80, and 100 MPa) for the combined modification. The results showed that the degree of hydrolysis of SPC was 4.1% and the antigen protein was degraded after Alcalase hydrolysis, when the homogenization pressure (HP) was 6 0Mpa, the particle size of the SPC was the smallest, the zate potential absolute value up to 33.45 mV, the secondary structure has the lowest β-sheet content, the highest random coil content, and the highest surface hydrophobicity (H0), the size of protein fragments on the microstructure surface is the smallest, the lowest denaturation temperature (Td) and enthalpy (△H) are 72.59°C and 1.35 J/g, the highest solubility is 80.54%, and the highest water and oil holding capacities are 7.73 g/g and 6.51 g/g, respectively. The best emulsifying activity and emulsifying stability were 43.46 m2/g and 190.35 min, the most even distribution of emulsion droplets. This indicates that the HPH treatment destroys the structure of enzymatic hydrolyzed SPC, changes its physicochemical properties, and improves its functional properties. In this study, SPC was modified by HPH and enzyme combined treatment, in order to improve the functionality and application range of SPC, and provide a theoretical basis for its high-value utilization in the food field.
Oncolytic virus: A catalyst for the treatment of gastric cancer
Authors: Wang Junqing , Du Linyong , Chen Xiangjian
Published: November 2022

Gastric cancer (GC) is a leading contributor to global cancer incidence and mortality. According to the GLOBOCAN 2020 estimates of incidence and mortality for 36 cancers in 185 countries produced by the International Agency for Research on Cancer (IARC), GC ranks fifth and fourth, respectively, and seriously threatens the survival and health of people all over the world. Therefore, how to effectively treat GC has become an urgent problem for medical personnel and scientific workers at this stage. Due to the unobvious early symptoms and the influence of some adverse factors such as tumor heterogeneity and low immunogenicity, patients with advanced gastric cancer (AGC) cannot benefit significantly from treatments such as radical surgical resection, radiotherapy, chemotherapy, and targeted therapy. As an emerging cancer immunotherapy, oncolytic virotherapies (OVTs) can not only selectively lyse cancer cells, but also induce a systemic antitumor immune response. This unique ability to turn unresponsive ‘cold’ tumors into responsive ‘hot’ tumors gives them great potential in GC therapy. This review integrates most experimental studies and clinical trials of various oncolytic viruses (OVs) in the diagnosis and treatment of GC. It also exhaustively introduces the concrete mechanism of invading GC cells and the viral genome composition of adenovirus and herpes simplex virus type 1 (HSV-1). At the end of the article, some prospects are put forward to determine the developmental directions of OVTs for GC in the future.
Understanding and harnessing triple-negative breast cancer-related microbiota in oncology
Authors: Devoy Ciaran , Flores Bueso Yensi , Tangney Mark
Published: November 2022

Bacterial inhabitants of the body have the potential to play a role in various stages of cancer initiation, progression, and treatment. These bacteria may be distal to the primary tumour, such as gut microbiota, or local to the tissue, before or after tumour growth. Breast cancer is well studied in this context. Amongst breast cancer types, Triple Negative Breast Cancer (TNBC) is more aggressive, has fewer treatment options than receptor-positive breast cancers, has an overall worse prognosis and higher rates of reoccurrence. Thus, an in-depth understanding of the bacterial influence on TNBC progression and treatment is of high value. In this regard, the Gut Microbiota (GM) can be involved in various stages of tumour progression. It may suppress or promote carcinogenesis through the release of carcinogenic metabolites, sustenance of proinflammatory environments and/or the promotion of epigenetic changes in our genome. It can also mediate metastasis and reoccurrence through interactions with the immune system and has been recently shown to influence chemo-, radio-, and immune-therapies. Furthermore, bacteria have also been found to reside in normal and malignant breast tissue. Several studies have now described the breast and breast tumour microbiome, with the tumour microbiota of TNBC having the least taxonomic diversity among all breast cancer types. Here, specific conditions of the tumour microenvironment (TME) - low O2, leaky vasculature and immune suppression - are supportive of tumour selective bacterial growth. This innate bacterial ability could enable their use as delivery agents for various therapeutics or as diagnostics. This review aims to examine the current knowledge on bacterial relevance to TNBC and potential uses while examining some of the remaining unanswered questions regarding mechanisms underpinning observed effects.
Circ_0007534 as new emerging target in cancer: Biological functions and molecular interactions
Authors: Liu Bowen , Dong Chengbin , Chen Quan , Fan Zhenhua , Zhang Yu , Wu Yifan , Cui Ting , Liu Fuquan
Published: November 2022

Circular RNA (circRNAs), an important member of the non-coding RNA (ncRNA) family, are widely expressed in a variety of biological cells. Owing to their stable structures, sequence conservations, and cell- or tissue-specific expressions, these RNA have become a popular subject of scientific research. With the development of sequencing methods, it has been revealed that circRNAs exert their biological function by sponging microRNAs (miRNAs), regulating transcription, or binding to proteins. Humans have historically been significantly impacted by various types of cancer. Studies have shown that circRNAs are abnormally expressed in various cancers and are involved in the occurrence and development of malignant tumors, such as tumor cell proliferation, migration, and invasion. As one of its star molecules, circ_0007534 is upregulated in colorectal, cervical, and pancreatic cancers; is closely related to the occurrence, development, and prognosis of tumors; and is expected to become a novel tumor marker and therapeutic target. This article briefly reviews the expression and mechanism of circ_0007534 in malignant tumors based on the domestic and foreign literature.
Comparative efficacy and toxicity of immune checkpoint inhibitors in combination with or without chemotherapy treatment for advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis
Authors: Ma Yue , Xin Yu , Su Dan , Zhou Yuxin , Li Hongxu , Zou Haoyi , Yu Xuefan , Yang Qing , Cui Jie , Wang Changsong , Zhang Yanqiao
Published: November 2022

Introduction

We did a systematic review and meta-analysis to assess the efficacy and safety of immune checkpoint inhibitors combined with or without chemotherapies in patients with esophageal squamous cell carcinoma.

Methods

Data related to the treatment of esophageal squamous cell carcinoma with immune checkpoint inhibitors therapy were retrieved from the database construction to August 2022. The risk of bias was assessed using the Cochrane Manual standard and RevMan 5.3 software for data synthesis. The outcome measures observed included overall survival, 12-month survival, disease control rate, objective response rate, treatment-related adverse events of grade 3 or higher, and progression-free survival. The adverse reactions included fatigue, diarrhea, hypothyroidism, rash, anemia, and anorexia.

Results

In this meta-analysis, a total of 17 randomized controlled trials were included. In first-line therapy, immune checkpoint inhibitors combined with or without chemotherapy in the treatment of esophageal squamous cell carcinoma was more effective than chemotherapy alone. Overall survival, 12-month survival rate, and objective response rate were statistically significant. Among second-line treatments, immune checkpoint inhibitors combined with or without chemotherapy in the treatment of esophageal squamous cell carcinoma had statistically significant overall survival, 12-month survival, objective response rate, treatment-related adverse events of grade 3 or higher, and progression-free survival compared with chemotherapy alone.

Conclusion

Both first- and second-line immune checkpoint inhibitors are effective for esophageal squamous cell carcinoma, and the adverse reactions are controllable and safe.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021282586.
Comparative metabolic profiling of wild Cordyceps species and their substituents by liquid chromatography-tandem mass spectrometry
Authors: Guo Shan , Lin Manting , Xie Di , Zhang Wenqing , Zhang Mi , Zhou Li , Li Sheng , Hu Hankun
Published: November 2022

Cordyceps is a genus of ascomycete fungi and used widely in fungal drugs. However, in-depth studies of the metabolites of wild Cordyceps species and their substituents are lacking. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics analysis was carried out to comprehensively profile the metabolites in wild Chinese Cordyceps species (Ophiocordyceps sinensis (Berk.) G.H. Sung, J.M. Sung, Hywel-Jones and Spatafora 2007) from Naqu (NCs) and Yushu (YCs) and their substituents including artificially cultivated Cordyceps species (CCs) and mycelia. A total of 901 metabolites were identified in these samples, including lipids, amino acids, nucleosides, carbohydrates, organic acids, coenzymes, vitamins, alkaloids and their derivatives. Univariate and multivariate statistical analyses revealed remarkable differences and significantly different metabolites among them. Seventy amino acid-relevant metabolites were analyzed quantitatively in four samples for the first time. The four samples contained abundant L-glutamic acid and oxidized glutathione as well as multiple unique amino acid-relevant metabolites (e.g., 3-chloro-L-tyrosine, 6-aminocaproic acid, L-theanine, anserine, γ-glutamyl-cysteine). Collectively, our study provides rich metabolic information of wild Cordyceps species and their substituents, which could facilitate their quality control and optimal utilization.
Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries
Authors: Bots Sophie H. , Riera-Arnau Judit , Belitser Svetlana V. , Messina Davide , Aragón Maria , Alsina Ema , Douglas Ian J. , Durán Carlos E. , García-Poza Patricia , Gini Rosa , Herings Ron M. C. , Huerta Consuelo , Sisay Malede Mequanent , Martín-Pérez Mar , Martin Ivonne , Overbeek Jetty A. , Paoletti Olga , Pallejà-Millán Meritxell , Schultze Anna , Souverein Patrick , Swart Karin M. A. , Villalobos Felipe , Klungel Olaf H. , Sturkenboom Miriam C. J. M.
Published: November 2022

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses.

Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis.

Findings: Over 35 million individuals (49·2% women, median age 39–49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination.

Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.
Thymoquinone protects the testes of hypothyroid rats by suppressing pro-inflammatory cytokines and oxidative stress and promoting SIRT1 testicular expression
Authors: Algaidi Sami A. , Faddladdeen Khadija A. , Alrefaei Ghadeer I. , Qahl Safa H. , Albadawi Emad A. , ALmohaimeed Hailah M. , Ayuob Nasra N.
Published: November 2022

Background: Hypothyroidism has been linked to many testicular structural and dysfunctional changes in males. Thymoquinone (TQ) has shown a potent testicular protective effect through its antioxidant, anti-inflammatory, antiapoptotic, fertility-enhancing, and endocrine modulatory activities.

Objectives: This study aimed to investigate the efficacy of TQ in preserving the testicular structure of a model of experimentally induced hypothyroidism in rats and identify the mechanism behind this effect.

Materials and methods: Propylthiouracil (PTU) was used to induce hypothyroidism in adult male Wistar rats, who were then treated with TQ (50 mg/kg/body weight) for 4 weeks and compared to the untreated rats. Thyroid hormonal profile, oxidants/antioxidants profile, and serum testosterone levels were assessed. Gene expression and immune expression of SIRT1 and pro-inflammatory cytokines TNF-α and NF-κB were also assessed in the testicular tissue.

Results: TQ administration successfully improved PTU-induced disturbance in the thyroid hormonal profile (T3, T4, and TSH), serum testosterone level, and pancreatic antioxidants compared to the untreated hypothyroid group. TQ significantly downregulated (p = 0.001, p ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated (p = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased (p = 0.002, p = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased (p ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased (p ˂ 0.001) in the testes of TQ-treated hypothyroid rats.

Conclusion: Thymoquinone could limit the hypothyroidism-induced structural changes in the testis, mostly through the upregulation of SIRT1 expression, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects that were evident in this study. Therefore, TQ is recommended as an adjuvant safe supplement in managing hypothyroidism, especially in males.
Adverse event profiles of adjuvant treatment with opicapone in Parkinson’s disease: A systematic review and meta-analysis
Authors: Xie Luwen , Qi Xiaoyi , Wang Xuan , He Bing , Wang Yu , Zhang Wei , Yu Zehui , Deng Mingming , Liang Sicheng , Lü Muhan
Published: November 2022

Background: Opicapone, a novel third-generation catechol-O-methyltransferase inhibitor, has demonstrated efficacy in Parkinson’s Disease (PD) patients with end-of-dose motor fluctuations.

Objective: This study aimed to compare the short-term (<6 months) and long-term (≥6 months) tolerability of opicapone adjuvant treatment in PD patients.

Method: Electronic databases including PubMed, Embase, Web of Science and Cochrane library were searched for randomized controlled trials (RCTs) and observational studies. The end points included any treatment-related adverse events (TEAEs), serious TEAEs (SAEs) and treatment discontinuation. A random-effects model was used to generate overall incidences of TEAE.

Results: Three RCTs, three RCT extension studies and three open-label studies involving 2177 PD patients were evaluated. In the short-term studies, there were reports of TEAEs with an incidence of ≥5% in individuals treated with opicapone 50 mg, including dyskinesia (14.1%), elevated blood creatine phosphokinase levels (8.0%) and urinary tract infection (6.0%). Any TEAEs, SAEs and treatment discontinuation all occurred at rates of 62.9%, 4.8% and 9.3%, respectively. TEAEs with opicapone 50 mg that were reported by more than 5% of patients in long-term studies included dyskinesia (16.1%), dry mouth (12.1%), medication effect decreased (12.1%), PD exacerbated (7.8%), blood creatine phosphokinase level raised (7.4%), nausea (6.1%) and insomnia (5.1%). The incidence of any TEAEs, SAEs and treatment discontinuation were, correspondingly, 73.2%, 8.7% and 8.4%.

Conclusion: These studies demonstrated that opicapone was generally well-tolerated and had a low risk of adverse events, suggesting that it could be a valuable therapeutic choice for people with PD.
Evaluation and manipulation of tissue and cellular distribution of cardiac progenitor cell-derived extracellular vesicles
Authors: Roefs Marieke T. , Heusermann Wolf , Brans Maike A. D. , Snijders Blok Christian , Lei Zhiyong , Vader Pieter , Sluijter Joost P. G.
Published: November 2022

Cardiac progenitor cell-derived extracellular vesicles (CPC-EVs) have been successfully applied via different delivery routes for treating post-myocardial infarction injury in several preclinical models. Hence, understanding the in vivo fate of CPC-EVs after systemic or local, i.e. myocardial, delivery is of utmost importance for the further therapeutic application of CPC-EVs in cardiac repair. Here, we studied the tissue- and cell distribution and retention of CPC-EVs after intramyocardial and intravenous injection in mice by employing different EV labeling and imaging techniques. In contrast to progenitor cells, CPC-EVs demonstrated no immediate flush-out from the heart upon intramyocardial injection and displayed limited distribution to other organs over time, as determined by near-infrared imaging in living animals. By employing CUBIC tissue clearing and light-sheet fluorescent microscopy, we observed CPC-EV migration in the interstitial space of the myocardium shortly after EV injection. Moreover, we demonstrated co-localization with cTnI and CD31-positive cells, suggesting their interaction with various cell types present in the heart. On the contrary, after intravenous injection, most EVs accumulated in the liver. To potentiate such a potential systemic cardiac delivery route, targeting the cardiac endothelium could provide openings for directed CPC-EV therapy. We therefore evaluated whether decorating EVs with targeting peptides (TPs) RGD-4C or CRPPR connected to Lamp2b could enhance EV delivery to endothelial cells. Expression of both TPs enhanced CPC-EV uptake under in vitro continuous flow, but did not affect uptake under static cell culture conditions. Together, these data demonstrate that the route of administration influences CPC-EV biodistribution pattern and suggest that specific TPs could be used to target CPC-EVs to the cardiac endothelium. These insights might lead to a better application of CPC-EV therapeutics in the heart.
Cone-beam computed tomography study of the incidence and characteristics of the second mesiobuccal canal in maxillary permanent molars
Authors: Xu Yuan-Qing , Lin Jie-Qi , Guan Wei-Qun
Published: November 2022

Objective: This study aimed to review the characteristics of the second mesiobuccal canal (MB2) in the maxillary first and second permanent molars of 500 patients to analyze the incidence of MB2 and its connection with gender, age, tooth position, and mesiobuccal (MB) root length. The study also aimed to investigate the distribution of the root canal orifice on the pulp chamber floor to obtain an imaging reference for clinical practices related to maxillary molars in Fujian, China.

Methods: In accordance with the enrollment criteria, cone-beam computed tomography images of the maxillofacial area were collected from 500 patients, including 1,000 maxillary first molars and 1,000 maxillary second molars. The patients were grouped according to gender and tooth position. The incidence of MB2 was observed, and the MB root length and distribution angle of the mesiobuccal-palatal-distobuccal root canal orifices were measured for statistical analysis.

Results: The overall incidence of MB2 in maxillary first and second molars was 51.1% and 32.9%, respectively. The incidence of MB2 in maxillary molars was 50% in male patients and 35.45% in female patients, with a significant difference (p < 0.05). The incidence of MB2 in maxillary molars was significantly higher in subjects aged below 50 (especially in male patients) than those aged 50 and above. The MB root length of maxillary first and second molars with MB2 was longer than that without MB2, and the difference was statistically significant. An association was identified between the incidences of MB2 in contralateral molars of the same type and in ipsilateral adjacent molars. When MB2 occurred in the MB root of maxillary molars, the root canals were mostly classified as type IV, followed by type II. The angle formed by the MB-P-DB orifices on the pulp chamber floor in the maxillary first and second molars was (25.23 ± 5.20) and (20.17 ± 10.88)°respectively.

Conclusion: The incidence of MB2 in maxillary molars is high in Fujian, China. The occurrence of MB2 is affected by gender, age, and length of MB root, and it occurs symmetrically in adjacent molars and in contralateral molars of the same type. In addition, the distribution law of the main root canal orifice at the pulp chamber floor is conducive to locating MB2, thereby guiding clinical operations.
Confinement induces oxidative damage and synaptic dysfunction in mice
Authors: Li Nuomin , Wang Hao , Xin Shuchen , Min Rui , Zhang Yongqian , Deng Yulin
Published: November 2022

A confined environment is an enclosed area where entry or exit is highly restricted, which is a risk factor for a work crew’s mental health. Previous studies have shown that a crew is more susceptible to developing anxiety or depression in a confined environment. However, the underlying mechanism by which negative emotion is induced by confinement is not fully understood. Hence, in this study, mice were retained in a tube to simulate short-term confinement. The mice exhibited depressive-like behavior. Additionally, the levels of H2O2 and malondialdehyde in the prefrontal cortex were significantly increased in the confinement group. Furthermore, a label-free quantitative proteomic strategy was applied to analyze the abundance of proteins in the prefrontal cortex of mice. A total of 71 proteins were considered differentially abundant proteins among 3,023 identified proteins. Two differentially abundant proteins, superoxide dismutase [Mn] and syntaxin-1A, were also validated by a parallel reaction monitoring assay. Strikingly, the differentially abundant proteins were highly enriched in the respiratory chain, oxidative phosphorylation, and the synaptic vesicle cycle, which might lead to oxidative damage and synaptic dysfunction. The results of this study provide valuable information to better understand the mechanisms of depressive-like behavior induced by confined environments.
Brassinolide improves the tolerance of Malus hupehensis to alkaline stress
Authors: Sun Zhijuan , Zou Yawen , Xie Cheng , Han Lei , Zheng Xiaodong , Tian Yike , Ma Changqing , Liu Xiaoli , Wang Caihong
Published: November 2022

Malus hupehensis is one of the most widely used apple rootstocks in china but is severely damaged by alkaline soil. Alkaline stress can cause more serious harmful effects on apple plants than salt stress because it also induces high pH stress except for ion toxicity, osmotic stress, and oxidative damage. Brassinolide (BL) plays important roles in plant responses to salt stress. However, its role and function mechanism in apple plants in response to alkaline stress has never been reported. This study showed that applying exogenous 0.2 mg/L BL significantly enhanced the resistance of M. hupehensis seedlings to alkaline stress. The main functional mechanisms were also explored. First, exogenous BL could decrease the rhizosphere pH and promote Ca2+ and Mg2+ absorption by regulating malic acid and citric acid contents and increasing H+ excretion. Second, exogenous BL could alleviate ion toxicity caused by alkaline stress through enhancing Na+ efflux and inhibiting K+ expel and vacuole compartmentalization. Last, exogenous BL could balance osmotic stress by accumulating proline and reduce oxidative damage through increasing the activities of antioxidant enzymes and antioxidants contents. This study provides an important theoretical basis for further analyzing the mechanism of exogenous BL in improving alkaline tolerance of apple plants.