bluuebunny/crossref_metadata_2025 huggingface dataset:
Collagen molecular organization preservation in human fascia lata and periosteum after tissue engineering
Authors: Vettese Julia , Manon Julie , Chretien Antoine , Evrard Robin , Fievé Lies , Schubert Thomas , Lengelé Benoît G. , Behets Catherine , Cornu Olivier
Published: April 2024

Large bone defect regeneration remains a major challenge for orthopedic surgeons. Tissue engineering approaches are therefore emerging in order to overcome this limitation. However, these processes can alter some of essential native tissue properties such as intermolecular crosslinks of collagen triple helices, which are known for their essential role in tissue structure and function. We assessed the persistence of extracellular matrix (ECM) properties in human fascia lata (HFL) and periosteum (HP) after tissue engineering processes such as decellularization and sterilization. Harvested from cadaveric donors (N = 3), samples from each HFL and HP were decellularized following five different chemical protocols with and without detergents (D1-D4 and D5, respectively). D1 to D4 consisted of different combinations of Triton, Sodium dodecyl sulfate and Deoxyribonuclease, while D5 is routinely used in the institutional tissue bank. Decellularized HFL tissues were further gamma-irradiated (minimum 25 kGy) in order to study the impact of sterilization on the ECM. Polarized light microscopy (PLM) was used to estimate the thickness and density of collagen fibers. Tissue hydration and content of hydroxyproline, enzymatic crosslinks, and non-enzymatic crosslinks (pentosidine) were semi-quantified with Raman spectroscopy. ELISA was also used to analyze the maintenance of the decorin (DCN), an important small leucine rich proteoglycan for fibrillogenesis. Among the decellularization protocols, detergent-free treatments tended to further disorganize HFL samples, as more thin fibers (+53.7%) and less thick ones (−32.6%) were recorded, as well as less collagen enzymatic crosslinks (−25.2%, p = 0.19) and a significant decrease of DCN (p = 0.036). GAG content was significantly reduced in both tissue types after all decellularization protocols. On the other hand, HP samples were more sensitive to the D1 detergent-based treatments, with more disrupted collagen organization and greater, though not significant loss of enzymatic crosslinks (−37.4%, p = 0.137). Irradiation of D5 HFL samples, led to a further and significant loss in the content of enzymatic crosslinks (−29.4%, p = 0.037) than what was observed with the decellularization process. Overall, the results suggest that the decellularization processes did not significantly alter the matrix. However, the addition of a gamma-irradiation is deleterious to the collagen structural integrity of the tissue.
Research progress on optimization of in vitro isolation, cultivation and preservation methods of dental pulp stem cells for clinical application
Authors: Wang Xinxin , Li Fenyao , Wu Shuting , Xing Wenbo , Fu Jiao , Wang Ruoxuan , He Yan
Published: April 2024

Due to high proliferative capacity, multipotent differentiation, immunomodulatory abilities, and lack of ethical concerns, dental pulp stem cells (DPSCs) are promising candidates for clinical application. Currently, clinical research on DPSCs is in its early stages. The reason for the failure to obtain clinically effective results may be problems with the production process of DPSCs. Due to the different preparation methods and reagent formulations of DPSCs, cell characteristics may be affected and lead to inconsistent experimental results. Preparation of clinical-grade DPSCs is far from ready. To achieve clinical application, it is essential to transit the manufacturing of stem cells from laboratory grade to clinical grade. This review compares and analyzes experimental data on optimizing the preparation methods of DPSCs from extraction to resuscitation, including research articles, invention patents and clinical trials. The advantages and disadvantages of various methods and potential clinical applications are discussed, and factors that could improve the quality of DPSCs for clinical application are proposed. The aim is to summarize the current manufacture of DPSCs in the establishment of a standardized, reliable, safe, and economic method for future preparation of clinical-grade cell products.
Revolutionizing construction safety: introducing a cutting-edge virtual reality interactive system for training US construction workers to mitigate fall hazards
Authors: Alzarrad Ammar , Miller Matthew , Durham Luke , Chowdhury Sudipta
Published: April 2024

The construction industry is fraught with hazards, chief among them being the risk of falls from elevated positions, which are a leading cause of both fatalities and injuries among workers. Despite the prevalence of traditional safety training methods, their effectiveness in reducing fall risks remains limited. To solve this issue, this study proposes the adoption of interactive VR technologies to provide construction workers with immersive training experiences in the critical domain of fall safety. This approach not only ensures adherence to the Occupational Safety and Health Administration (OSHA) requirements but also leverages VR’s immersive capabilities to create a comprehensive and effective learning tool. To evaluate the proposed system’s efficacy, the researchers conducted an empirical assessment involving eighty-two construction workers from two small enterprises. Participants were divided into two groups: one receiving traditional training and the other undergoing VR-based instruction. Both groups underwent pre- and post-training evaluations comprising six targeted questions designed to measure the impact of each training method on their understanding and awareness of fall safety practices. The comparative analysis revealed no significant differences in baseline knowledge between the two groups prior to the training interventions. However, post-training evaluations demonstrated a notable improvement in the VR group, with a significant decrease in the number of incorrect responses, in stark contrast to the group subjected to traditional training methods. Statistical analysis further confirmed the superiority of VR training in enhancing participants’ knowledge. This was quantified by a p-value of 0.0016, indicating a high level of statistical significance well below the conventional threshold of 0.05. This study highlights the significant advantages of VR technology in construction safety training, demonstrating its superiority over traditional training methods in terms of knowledge retention and practical application. The results strongly support the wider adoption of VR in safety training, indicating its potential to enhance safety outcomes in the construction sector.
Swine influenza A virus: challenges and novel vaccine strategies
Authors: Petro-Turnquist Erika , Pekarek Matthew J. , Weaver Eric A.
Published: April 2024

Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination strategies are often not updated frequently enough to address the continuously evolving nature of IAV-S, fail to induce broadly cross-reactive responses, are susceptible to interference, may enhance respiratory disease, and can be expensive to produce. Here, we review the challenges and current status of universal IAV-S vaccine research. We also detail the current standard of licensed vaccines and their limitations in the field. Finally, we review recently described novel vaccines and vaccine platforms that may improve upon current methods of IAV-S control.
Regulation 2017/745 on medical devices, two major innovations: 1) the physiological action of devices consisting of natural materials such as vegetal matrices; 2) the chemical-physical-mechanical action of devices made of “substances”, which as such are artificial derivatives
Authors: Marletta Marcella
Published: April 2024

The Medical Device Regulation 2017/745 (MDR) enables the development of a wide range of innovative products. With respect to Directive 93/42, the MDR explicitly identifies the so-called “medical devices made of substances” (MDMS) through specific requirements. In addition, the MDR expands the definition of medical device (MD) by including the “modification of a physiological or pathological state” as a medical purpose specific to devices. This clarifies that materials interacting with the human body in such a way as to modify its “state” are medical devices. Natural materials, such as vegetal matrices, are characterized by the presence of both functional and structural interactions between their components; they can thus be described as “network/s" and interact with the human body in a coordinated, complex way. Since the “state” of the human body is a network of biological functions, the “network/s over a network” interaction between the natural material and the human body is likely to modify the “state” of the human body. Thus, therapeutic products consisting of natural materials, such as vegetal matrices, seem to fit perfectly into the definition of a medical device. Here we analyze the main characteristics of medicinal products, of medical devices made of substances and of medical devices consisting of natural materials. We see that medicinal products and medical devices made of substances have the common characteristic of being based on substances, either synthetic or derivatives of natural materials, but differ in their mechanism of action. On the other hand, medical devices constituted of natural materials relate to the general category of medical devices and cannot be characterized by any single component, identified as an active component. We also discuss how these characteristics relate to the mechanism of action of each type of product. This analysis should allow to identify the most appropriate path for each product, a necessary step to promote research and development of innovative therapies for a large number of unmet medical needs.
Geochemical characteristics of rare earth elements in late Palaeozoic coals from North China
Authors: Wen Long , Huang Wenhui , Zhang Yuanfu , Jiu Bo
Published: April 2024

Introduction: China is a large country of REE resources and production, supplying more than 90% of the world’s rare earth consumption market, China’s traditional REE resources, although rich, but reserves are also declining, in recent years, scholars have shown that the REEs in the specific geological conditions in the coals can be enriched, and even reach the industrial grade, the search for more REE mineral resources will be of great strategic significance.

Methods: The article has selected the Zibo, Taozao, Huainan, Datong, Huozhou, Jungar, and Weibei coalfields in North China as the research objects. Based on inductively coupled plasma mass spectrometry (ICP-MS) analyses, the study provides a detailed analysis of the enrichment rules and distribution patterns of rare earth elements (REEs) in coal under different geological conditions.

Results: The REE distribution patterns in Late Palaeozoic coals in North China are characterized by enrichment of LREEs, deficit of HREEs with gentle changes, and obvious negative anomalies of Eu, the enrichment of REE in coal is controlled by provenance and volcanism, and is related to distance of transport terrigenous material and the sedimentary environment. The REEs concentrations in North China indicates that Late Palaeozoic coals in the mining areas of the north, northwest, and western parts of North China are significantly enriched in REEs. In addition, REEs in Late Palaeozoic coals in the southeastern mining areas are relatively enriched, and the central and eastern regions are significantly depleted.

Discussion: Large coal-type rare earth deposits are expected to be developed in North China, particularly the Datong coalfield, Jungar coal mine and the Weibei coal mine in the eastern margin of the Ordos Basin, and the Zibo coalfield.
Our responsibilities for future generations from a social-emotional learning perspective: revisiting mindfulness
Authors: Konishi Chiaki , Chowdhury Farhin , Tesolin Julia , Strouf Kendra
Published: April 2024

This article provides the readers with an opportunity to revisit the original purpose of mindfulness and to learn about some concerns and challenges raised in current understandings and practices of mindfulness, in order to make our mindfulness-based practices more effective and relevant, deriving in part from a perspective of social-emotional learning. Over the past several decades, mindfulness has gained increased attention within the clinical and educational settings, especially as intervention practices. The prevalence of mindfulness-based practice use has tripled between 2012 and 2017 among adults; the prevalence among children aged 4 to 17 years increased 9 times from 2012 to 2017, according to a recent national survey in the U.S. Given such a wide and steady rise in attention, our scientific interest in mindfulness has increased dramatically over the past two decades. However, we still have much work to do to translate appropriate knowledge and skills into effective practice.
Research on additional damping control strategy of flexible distribution transformer
Authors: Guo Guowei , Wang Jinfeng , Zhan Ximei , Liu Zhu , Gong Dehuang , Tang Aihong , Shang Yufei , Wang Zihan
Published: April 2024

Disturbances to the power system may lead to relative swing between synchronous generator rotors, causing low-frequency oscillation problems in the absence of damping. In this article, based on the single-machine infinity system containing flexible distribution transformer and synchronous generator, the linearized state equations of the system is deduced by the small-signal modeling. The mechanism of flexible distribution transformer on the rotor speed of synchronous generator is analyzed. The influence factors of flexible distribution transformer on the rotor speed of synchronous generator are analyzed. The equation of the additional damping provided by the flexible distribution transformer to this system is constructed. It was concluded that by controlling the output voltage of the regulating converter in the flexible distribution transformer, the rotor speed of the synchronous generator can be varied to increase the system damping. An additional damping control strategy for flexible distribution transformer is proposed. The simulation verifies that the proposed control strategy can effectively suppress the oscillation amplitude of each electrical quantity and shorten the oscillation duration when the system is subjected to large and small perturbations. The proposed additional damping control strategy of flexible distribution transformer can effectively improve the damping of the system and alleviate the problem of low frequency oscillation.
Boosting the immunogenicity of the CoronaVac SARS-CoV-2 inactivated vaccine with Huoxiang Suling Shuanghua Decoction: a randomized, double-blind, placebo-controlled study
Authors: Tang Ruying , Wang Linyuan , Zhang Jianjun , Fei Wenting , Zhang Rui , Liu Jinlian , Lv Meiyu , Wang Mengyao , Lv Ruilin , Nan Haipeng , Tao Ran , Chen Yawen , Chen Yan , Jiang Yanxin , Zhang Hui
Published: April 2024

Introduction

In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac’s CoronaVac SARS-CoV-2 (CVS) inactivated vaccine.

Methods

A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD.

Results

Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis.

Conclusion

Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.
C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration
Authors: Giralt Lena , Figueras-Roca Marc , Eguileor Beatriz De Luis , Romero Barbara , Zarranz-Ventura Javier , Alforja Socorro , Santiago Francisca , Bolaños Jennifer , Lozano Francisco , Dotti-Boada Marina , Sala-Puigdollers Anna , Dura Paula , Izquierdo-Serra Jordi , Valero Oliver , Adan Alfredo , Fonollosa Alex , Molins Blanca
Published: April 2024

Purpose

To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters.

Methods

Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters.

Results

Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023).

Conclusion

Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.
Case report: Treatment of psoriasiform dermatitis in patients with malignancy
Authors: Mao Jinzhu , Du Na , Jia Yuanyuan , Mao Qiuyu , Yang Jingyi , Zhang Yiwen , Li Yueyue , Cao Lei , Min Wei
Published: April 2024

Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain complex cases, the clinical and pathological features exhibit overlapping and atypical characteristics, making accurate clinical diagnosis and targeted treatment a challenge. Psoriasiform dermatitis is the term used to describe such cases. Moreover, when patients have a history of malignancy, the situation becomes even more intricate, resulting in limited treatment options. Biologic therapies have transformed the management of immune-mediated inflammatory diseases, including psoriasis and AD. Meanwhile, the safety of biologics in special populations, especially among patients with a history of malignancy, should be underlined. The selective Janus kinase 1 (JAK1) inhibitor abrocitinib has been approved for the treatment of AD and has showed satisfying efficacy and safety in the treatment of psoriasis in clinical trials. Although unreported, JAK1 inhibitors are thought to have the potential to increase the risk of potential tumors. Apremilast, an oral phosphodiesterase (PDE)-4 inhibitor, is approved for moderate to severe plaque psoriasis. It has been investigated for its efficacy in AD, and is not contraindicated in malignancy. This report presents three cases of psoriasiform dermatitis in patients with a history of malignancy, showcasing significant improvement following treatment with systemic glucocorticoid, abrocitinib, or apremilast.
Effects of dietary cecropin on growth performance, diarrhea rate and intestinal health of nursery Hainan pigs
Authors: Ouyang Kun , Chen Ting , Sun Ruiping , Xie Yali , Qi Qi , Li Xiang , Liu Jie , Liu Quanwei , Wei Limin
Published: April 2024

Antimicrobial peptides could inhibit the growth of harmful bacteria and promote the growth performance in weaned piglets. Here, we investigated the effects of dietary supplementation with cecropin antimicrobial peptides (CAP) on growth performance, diarrhea rate, intestinal health in nursery Hainan piglets. For this, 120 healthy nursery Hainan male piglets (13.29 ± 0.29 kg, 44 days old) were randomly divided into 5 groups—a control (CON) group (fed a basal diet), an antibiotic control (AC) group (fed a basal diet supplemented with 250 mg/kg colistin sulfate); and 3 experimental groups (provided the basal diet supplemented with 250, 500, or 1,000 mg/kg CAP). Pre-feeding lasted 7 days and the official period lasted 40 days. The results showed that compared with the CON group, dietary supplementation of 500 mg/kg CAP had significantly increased the average daily gain (ADG, p < 0.05), while the feed conversion ratio (FCR) and diarrhea rate were markedly reduced (p < 0.05), serum total protein (TP), albumin, IgA, IgM, and globulin concentrations were significantly increased (p < 0.05), where serum aspartate aminotransferase (AST) level was significantly reduced (p < 0.05), and it also increased the villus height and the villus height-to-crypt depth ratio in the jejunum, reduced the serum D-lactic acid concentrations and diamine oxidase activity, and increased the expression level of ZO-1 and occludin in the jejunum and ileum (p < 0.05), the relative abundance of Firmicutes, Lactobacillus, and Limoslactobacillus in the colon were increased (p < 0.05), whereas that of Streptococcus and Escherichia–Shigella were reduced (p < 0.05). These results indicated that dietary supplementation with 500 mg/kg CAP could improve the growth performance, reduce the diarrhea rate, improve the serum immunity, intestinal health of nursery pigs.
TGF-β mRNA levels in circulating extracellular vesicles are associated with response to anti-PD1 treatment in metastatic melanoma
Authors: Crucitta Stefania , Cucchiara Federico , Marconcini Riccardo , Bulleri Alessandra , Manacorda Simona , Capuano Annalisa , Cioni Dania , Nuzzo Amedeo , de Jonge Evert , Mathjissen Ron H. J. , Neri Emanuele , van Schaik Ron H. N. , Fogli Stefano , Danesi Romano , Del Re Marzia
Published: April 2024

Introduction: Immune checkpoint inhibitors (ICIs) represent the standard therapy for metastatic melanoma. However, a few patients do not respond to ICIs and reliable predictive biomarkers are needed.

Methods: This pilot study investigates the association between mRNA levels of programmed cell death-1 (PD-1) ligand 1 (PD-L1), interferon-gamma (IFN-γ), and transforming growth factor-β (TGF-β) in circulating extracellular vesicles (EVs) and survival in 30 patients with metastatic melanoma treated with first line anti-PD-1 antibodies. Blood samples were collected at baseline and RNA extracted from EVs; the RNA levels of PD-L1, IFN-γ, and TGF-β were analysed by digital droplet PCR (ddPCR). A biomarker-radiomic correlation analysis was performed in a subset of patients.

Results: Patients with high TGF-β expression (cut-off fractional abundance [FA] >0.19) at baseline had longer median progression-free survival (8.4 vs. 1.8 months; p = 0.006) and overall survival (17.9 vs. 2.63 months; p = 0.0009). Moreover, radiomic analysis demonstrated that patients with high TGF-β expression at baseline had smaller lesions (2.41 ± 3.27 mL vs. 42.79 ± 101.08 mL, p < 0.001) and higher dissimilarity (12.01 ± 28.23 vs. 5.65 ± 8.4; p = 0.018).

Discussion: These results provide evidence that high TGF-β expression in EVs is associated with a better response to immunotherapy. Further investigation on a larger patient population is needed to validate the predictive power of this potential biomarker of response to ICIs.
Targeting shared pathways in tauopathies and age-related macular degeneration: implications for novel therapies
Authors: Rinaldi Michele , Pezone Antonio , Quadrini Gaia Italia , Abbadessa Gianmarco , Laezza Maria Paola , Passaro Maria Laura , Porcellini Antonio , Costagliola Ciro
Published: April 2024

The intricate parallels in structure and function between the human retina and the central nervous system designate the retina as a prospective avenue for understanding brain-related processes. This review extensively explores the shared physiopathological mechanisms connecting age-related macular degeneration (AMD) and proteinopathies, with a specific focus on tauopathies. The pivotal involvement of oxidative stress and cellular senescence emerges as key drivers of pathogenesis in both conditions. Uncovering these shared elements not only has the potential to enhance our understanding of intricate neurodegenerative diseases but also sets the stage for pioneering therapeutic approaches in AMD.
Astrocyte activation in hindlimb somatosensory cortex contributes to electroacupuncture analgesia in acid-induced pain
Authors: Ye Qing , Li Jie , Ren Wen-Jing , Zhang Ying , Wang Tao , Rubini Patrizia , Yin Hai-Yan , Illes Peter , Tang Yong
Published: April 2024

Background

Several studies have confirmed the direct relationship between extracellular acidification and the occurrence of pain. As an effective pain management approach, the mechanism of electroacupuncture (EA) treatment of acidification-induced pain is not fully understood. The purpose of this study was to assess the analgesic effect of EA in this type of pain and to explore the underlying mechanism(s).

Methods

We used plantar injection of the acidified phosphate-buffered saline (PBS; pH 6.0) to trigger thermal hyperalgesia in male Sprague–Dawley (SD) rats aged 6–8 weeks. The value of thermal withdrawal latency (TWL) was quantified after applying EA stimulation to the ST36 acupoint and/or chemogenetic control of astrocytes in the hindlimb somatosensory cortex.

Results

Both EA and chemogenetic astrocyte activation suppressed the acid-induced thermal hyperalgesia in the rat paw, whereas inhibition of astrocyte activation did not influence the hyperalgesia. At the same time, EA-induced analgesia was blocked by chemogenetic inhibition of astrocytes.

Conclusion

The present results suggest that EA-activated astrocytes in the hindlimb somatosensory cortex exert an analgesic effect on acid-induced pain, although these astrocytes might only moderately regulate acid-induced pain in the absence of EA. Our results imply a novel mode of action of astrocytes involved in EA analgesia.
Spatial anxiety contributes to the dizziness-related handicap of adults with peripheral vestibular disease
Authors: Jáuregui-Renaud Kathrine , García-Jacuinde Dulce Maria , Bárcenas-Olvera Simón Pedro , Gresty Michael A. , Gutiérrez-Márquez Aralia
Published: April 2024

In subjects with peripheral vestibular disease and controls, we assessed: 1. The relationship between spatial anxiety and perceived stress, and 2. The combined contribution of spatial anxiety, spatial perspective-taking, and individual cofactors to dizziness-related handicap. 309 adults participated in the study (153 with and 156 without peripheral vestibular disease), including patients with bilateral vestibular deficiency, unilateral deficiency (evolution <3 or ≥3 months), Meniere’s disease, and Benign Paroxysmal Positional Vertigo. Assessments included: general health, personal habits, spatial anxiety (3-domains), perceived stress, spatial perspective-taking, dizziness-related handicap (3-domains), unsteadiness, sleep quality, motion sickness susceptibility, trait anxiety/depression, state anxiety, depersonalization/derealization. After bivariate analyses, analysis of covariance was performed (p ≤ 0.05). Spatial anxiety was related to unsteadiness and perceived stress, with an inverse relationship with trait anxiety (ANCoVA, adjusted R2 = 0.27–0.30, F = 17.945–20.086, p < 0.00001). Variability on perspective-taking was related to vestibular disease, trait and state anxiety, motion sickness susceptibility, and age (ANCoVA, adjusted R2 = 0.18, F = 5.834, p < 0.00001). All domains of spatial anxiety contributed to the Physical domain of dizziness-related handicap, while the Navigation domain contributed to the Functional domain of handicap. Handicap variability was also related to unsteadiness, spatial perspective-taking, quality of sleep, and trait anxiety/depression (ANCoVA, adjusted R2 = 0.66, F = 39.07, p < 0.00001). Spatial anxiety is related to perceived stress in adults both with and without vestibular disease, subjects with trait anxiety rated lower on spatial anxiety. State anxiety and acute stress could be helpful for recovery after peripheral vestibular lesion. Spatial anxiety and perspective-taking contribute to the Physical and Functional domains of dizziness-related handicap, possibly because it discourages behavior beneficial to adaptation.
Nano-pulling stimulates axon regeneration in dorsal root ganglia by inducing stabilization of axonal microtubules and activation of local translation
Authors: Falconieri Alessandro , Folino Pietro , Da Palmata Lorenzo , Raffa Vittoria
Published: April 2024

Introduction

Axonal plasticity is strongly related to neuronal development as well as regeneration. It was recently demonstrated that active mechanical tension, intended as an extrinsic factor, is a valid contribution to the modulation of axonal plasticity.

Methods

In previous publications, our team validated a the “nano-pulling” method used to apply mechanical forces to developing axons of isolated primary neurons using magnetic nanoparticles (MNP) actuated by static magnetic fields. This method was found to promote axon growth and synaptic maturation. Here, we explore the use of nano-pulling as an extrinsic factor to promote axon regeneration in a neuronal tissue explant.

Results

Whole dorsal root ganglia (DRG) were thus dissected from a mouse spinal cord, incubated with MNPs, and then stretched. We found that particles were able to penetrate the ganglion and thus become localised both in the somas and in sprouting axons. Our results highlight that nano-pulling doubles the regeneration rate, and this is accompanied by an increase in the arborizing capacity of axons, an accumulation of cellular organelles related to mass addition (endoplasmic reticulum and mitochondria) and pre-synaptic proteins with respect to spontaneous regeneration. In line with the previous results on isolated hippocampal neurons, we observed that this process is coupled to an increase in the density of stable microtubules and activation of local translation.

Discussion

Our data demonstrate that nano-pulling enhances axon regeneration in whole spinal ganglia exposed to MNPs and external magnetic fields. These preliminary data represent an encouraging starting point for proposing nano-pulling as a biophysical tool for the design of novel therapies based on the use of force as an extrinsic factor for promoting nerve regeneration.
Increased functional connectivity following ingestion of dried bonito soup
Authors: Satake Takatoshi , Taki Ai , Ouchi Kazuya , Kasahara Kazumi , Tsurugizawa Tomokazu
Published: April 2024

Soup, including dried bonito broth, is customarily consumed as an umami taste during meals in Japan. Previous functional magnetic resonance imaging (fMRI) studies have investigated neuronal activation following human exposure to carbohydrates and umami substances. However, neuronal activity following ingestion of dried bonito soup has not been investigated. Additionally, recent progress in fMRI has enabled us to investigate the functional connectivity between two anatomically separated regions, such as the default mode network. In this study, we first investigated the altered functional connectivity after ingesting dried bonito soup in healthy volunteers. Functional connectivity in several brain regions, including the connection between the vermis, part of the cerebellum, and bilateral central opercular cortex, was markedly increased after ingesting dried bonito soup, compared to the ingestion of hot water. Physiological scaling showed that satiety was substantially increased by ingesting hot water rather than dried bonito soup. These results indicate that increased functional connectivity reflects the post-ingestive information pathway of dried bonito soup.
Keap1-Nrf2 pathway: a key mechanism in the occurrence and development of cancer
Authors: Chen Feilong , Xiao Mei , Hu Shaofan , Wang Meng
Published: April 2024

The Keap1-Nrf2 signaling pathway is a major regulator of the cytoprotective response, participating in endogenous and exogenous stress caused by ROS (reactive oxygen species). Nrf2 is the core of this pathway. We summarized the literature on Keap1-Nrf2 signaling pathway and summarized the following three aspects: structure, function pathway, and cancer and clinical application status. This signaling pathway is similar to a double-edged sword: on the one hand, Nrf2 activity can protect cells from oxidative and electrophilic stress; on the other hand, increasing Nrf2 activity can enhance the survival and proliferation of cancer cells. Notably, oxidative stress is also considered a marker of cancer in humans. Keap1-Nrf2 signaling pathway, as a typical antioxidant stress pathway, is abnormal in a variety of human malignant tumor diseases (such as lung cancer, liver cancer, and thyroid cancer). In recent years, research on the Keap1-Nrf2 signaling pathway has become increasingly in-depth and detailed. Therefore, it is of great significance for cancer prevention and treatment to explore the molecular mechanism of the occurrence and development of this pathway.
Case Report: A developmental and epileptic encephalopathy 45 due to de novo variant of GABRB1
Authors: Wang Lu , Xu Haiquan , Shu Jianbo , Yan Dandan , Li Dong , Cai Chunquan
Published: April 2024

Background

The gamma-aminobutyric acid (GABA) variant causes developmental and epileptic encephalopathy 45 (DEE45), an autosomal dominant disorder that results in oculocortical visual impairment, reduced muscle tone, psychomotor retardation, and epilepsy. Analysis of the clinical features and genetics of DEE45 may be helpful in complementing genotype-phenotype studies.

Case presentation

We collected peripheral blood samples from the affected children and parents and extracted genomic DNA. Whole exome sequencing (WES) was utilized to identify the underlying disease-causing variant. WES showed that the prior carried a heterozygous variant c.686C > T p.(Ala229Val) in exon 7 of the GABRB1 (NM_000812.4), and no variant was detected in either parental sample. The child has DEE45.

Conclusion

The variant c.686C > T of the GABRB1 is a possible cause of DEE45. Gene variant analysis of the relevant family lines using WES provides effective genetic counseling for developing and regressing such patients in the clinic. However, further studies are needed to verify the pathogenic mechanism.
Chinese herbal medicines for the treatment of depression: a systematic review and network meta-analysis
Authors: Dang Chun , Wang Qinxuan , Li Qian , Xiong Ying , Lu Yaoheng
Published: April 2024

Objectives: Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions.

Methods: Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals.

Results: A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly Guipiwan, Ease Pill, and Chaihu Jia Longgu Muli Decoction; the top three treatments on the reduction of HAMD scores were Chai Hu Shu Gan San, Xingnao Jieyu Decoction, and Xiaoyao Powder; and the top three treatments with the lowest adverse effects rates were Xiaoyao Powder, Alprazolam, and Xingnao Jieyu Decoction. Interestingly, commonly used synthetic drugs such as Fluoxetine, Escitalopram, Amitriptyline, Sertraline, Flupentixol and Melitracen, and Venlafaxine, not only appeared to be less effective than specific Chinese herbal medicines (Gan Mai Da Zao Decoction, Chaihu Jia Longgu Muli Decoction, Chai Hu Shu Gan San, Danzhi-Xiaoyao-San, and Xingnao Jieyu Decoction), but they were also related to substantially higher risk of adverse events.

Conclusion: Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings.

Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.
Adenylyl cyclase isoforms 5 and 6 in the cardiovascular system: complex regulation and divergent roles
Authors: Maghsoudi Saeid , Shuaib Rabia , Van Bastelaere Ben , Dakshinamurti Shyamala
Published: April 2024

Adenylyl cyclases (ACs) are crucial effector enzymes that transduce divergent signals from upstream receptor pathways and are responsible for catalyzing the conversion of ATP to cAMP. The ten AC isoforms are categorized into four main groups; the class III or calcium-inhibited family of ACs comprises AC5 and AC6. These enzymes are very closely related in structure and have a paucity of selective activators or inhibitors, making it difficult to distinguish them experimentally. AC5 and AC6 are highly expressed in the heart and vasculature, as well as the spinal cord and brain; AC6 is also abundant in the lungs, kidney, and liver. However, while AC5 and AC6 have similar expression patterns with some redundant functions, they have distinct physiological roles due to differing regulation and cAMP signaling compartmentation. AC5 is critical in cardiac and vascular function; AC6 is a key effector of vasodilatory pathways in vascular myocytes and is enriched in fetal/neonatal tissues. Expression of both AC5 and AC6 decreases in heart failure; however, AC5 disruption is cardio-protective, while overexpression of AC6 rescues cardiac function in cardiac injury. This is a comprehensive review of the complex regulation of AC5 and AC6 in the cardiovascular system, highlighting overexpression and knockout studies as well as transgenic models illuminating each enzyme and focusing on post-translational modifications that regulate their cellular localization and biological functions. We also describe pharmacological challenges in the design of isoform-selective activators or inhibitors for AC5 and AC6, which may be relevant to developing new therapeutic approaches for several cardiovascular diseases.
Disease resistance features of the executor R gene Xa7 reveal novel insights into the interaction between rice and Xanthomonas oryzae pv. oryzae
Authors: He Lumei , Liu Pengcheng , Mei Le , Luo Huichao , Ban Tingxuan , Chen Xifeng , Ma Bojun
Published: April 2024

Bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), is a widespread and destructive disease in rice production. Previously, we cloned an executor R gene, Xa7, which confers durable and broad-spectrum resistance to BB. Here, we further confirmed that the transcription activator-like effector (TALE) AvrXa7 in Xoo strains could directly bind to the effector-binding element (EBE) in the promoter of the Xa7 gene. Other executor R genes (Xa7, Xa10, Xa23, and Xa27) driven by the promoter of the Xa7 gene could be activated by AvrXa7 and trigger the hypersensitive response (HR) in tobacco leaves. When the expression of the Xa23 gene was driven by the Xa7 promoter, the transgenic rice plants displayed a similar resistance spectrum as the Xa7 gene, demonstrating that the disease resistance characteristics of executor R genes are mainly determined by their induction patterns. Xa7 gene is induced locally by Xoo in the infected leaves, and its induction not only inhibited the growth of incompatible strains but also enhanced the resistance of rice plants to compatible strains, which overcame the shortcomings of its race-specific resistance. Transcriptome analysis of the Xa7 gene constitutive expression in rice plants displayed that Xa7-mediated disease resistance was related to the biosynthesis of lignin and thus enhanced resistance to Xoo. Overall, our results provided novel insights and important resources for further clarifying the molecular mechanisms of the executor R genes.
Silicon nanoparticles vs trace elements toxicity: Modus operandi and its omics bases
Authors: Mukarram Mohammad , Ahmad Bilal , Choudhary Sadaf , Konôpková Alena Sliacka , Kurjak Daniel , Khan M. Masroor A. , Lux Alexander
Published: April 2024

Phytotoxicity of trace elements (commonly misunderstood as ‘heavy metals’) includes impairment of functional groups of enzymes, photo-assembly, redox homeostasis, and nutrient status in higher plants. Silicon nanoparticles (SiNPs) can ameliorate trace element toxicity. We discuss SiNPs response against several essential (such as Cu, Ni, Mn, Mo, and Zn) and non-essential (including Cd, Pb, Hg, Al, Cr, Sb, Se, and As) trace elements. SiNPs hinder root uptake and transport of trace elements as the first line of defence. SiNPs charge plant antioxidant defence against trace elements-induced oxidative stress. The enrolment of SiNPs in gene expressions was also noticed on many occasions. These genes are associated with several anatomical and physiological phenomena, such as cell wall composition, photosynthesis, and metal uptake and transport. On this note, we dedicate the later sections of this review to support an enhanced understanding of SiNPs influence on the metabolomic, proteomic, and genomic profile of plants under trace elements toxicity.
Examination of medical student and physician attitudes towards suicide reveals need for required training
Authors: Schulz Paulyna , Zapata Isain , Huzij Teodor
Published: April 2024

The attitudes of healthcare providers towards suicidal patients are known to influence their motivation to treat patients during a suicidal crisis. Patients who attempted suicide are more likely to have recently visited a primary care provider who is not necessarily sufficiently trained in managing a suicidal patient rather than a mental health provider who is trained to do so. For those reasons, documenting medical students and physicians’ attitudes towards suicide can help in the development of effective intervention training to prepare them to manage these types of patients. In this mini review, attitudes towards suicidal patients, the effectiveness of training on changing their attitudes are discussed. In summary, primary care providers are recognized as a top area where improvements can prevent suicides; providing proper suicide prevention training can effectively improve attitudes and quality of care for suicidal patients.