bluuebunny/crossref_metadata_2025 huggingface dataset:
PCDH19-related epilepsy in mosaic males: The phenotypic implication of genotype and variant allele frequency
Authors: Chen Yi , Yang Xiaoxu , Chen Jiaoyang , Yang Xiaoling , Yang Ying , Liu Aijie , Zhang Xiaoli , Wu Wenjuan , Sun Dan , Yang Zhixian , Jiang Yuwu , Zhang Yuehua
Published: November 2022

Objective

To analyze the genotypes and phenotypes of mosaic male patients with PCDH19-related epilepsy (PCDH19-RE) and explore the correlation between genotype, variant allele frequency (VAF), and phenotypic severity.

Methods

Clinical data and peripheral blood samples of 11 male mosaic patients were collected and analyzed in our study. The VAF of the PCDH19 gene from peripheral blood was quantified using amplicon-based deep sequencing. Additional 20 mosaic male patients with PCDH19-RE were collected from the published literature, with 10 patients whose VAFs of the PCDH19 gene were available for analytic purposes.

Results

In our cohort of 11 patients, 10 variants were identified, and four were novel. The VAF of the PCDH19 gene from peripheral blood ranged from 27 to 90%. The median seizure onset age was 6 months (range: 4–9 months). Clinical manifestations included cluster seizures (100%), fever sensitivity (73%), focal seizures (91%), developmental delay/intellectual disability (DD/ID, 82%), and autistic features (45%). Thirty-one mosaic male patients collected from our cohort and the literature developed seizures mostly (87%) within one year of age. Variant types included missense variants (42%), truncating variants (52%), splice variants (3%), and whole PCDH19 deletion (3%). Among 21 patients with a definite VAF from our cohort and the literature, nine had a low VAF ( ≤ 50%) and 12 had a high VAF (> 50%). Seventy-five percent of variants from the high VAF group were missense, whereas 89% of those from the low VAF group were truncations. The median seizure onset age was 6 months in the low VAF group and 9 months in the high VAF group (p = 0.018). Forty-four percent (4/9) of patients from the low VAF group achieved seizure-free for ≥1 year, whereas none of the 12 patients from the high VAF group did (p = 0.021). DD/ID was present in 83% (10/12) of the high VAF group and 56% (5/9) of the low VAF group (p = 0.331).

Conclusion

The predominant variant types were truncating and missense variants. Missense variants tended to have higher VAFs. Patients with a high VAF were more likely to have a more severe epileptic phenotype. Our findings shed light on the phenotypic implications of VAF in mosaic males with PCDH19-RE.
High-precision neural stimulation by a highly efficient candle soot fiber optoacoustic emitter
Authors: Chen Guo , Shi Linli , Lan Lu , Wang Runyu , Li Yueming , Du Zhiyi , Hyman Mackenzie , Cheng Ji-Xin , Yang Chen
Published: November 2022

Highly precise neuromodulation with a high efficacy poses great importance in neuroscience. Here we developed a candle soot fiber optoacoustic emitter (CSFOE), capable of generating a high pressure of over 10 MPa with a central frequency of 12.8 MHz, enabling highly efficient neuromodulation in vitro. The design of the fiber optoacoustic emitter, including the choice of the material and the thickness of the layered structure, was optimized in both simulations and experiments. The optoacoustic conversion efficiency of the optimized CSFOE was found to be 10 times higher than the other carbon-based fiber optoacoustic emitters. Driven by a single laser, the CSFOE can perform dual-site optoacoustic activation of neurons, confirmed by calcium (Ca2+) imaging. Our work opens potential avenues for more complex and programmed control in neural circuits using a simple design for multisite neuromodulation in vivo.
Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy
Authors: Arai Takahide , Kanazawa Hideaki , Kimura Kensuke , Munakata Masahito , Yamakawa Hiroyuki , Shinmura Ken , Yuasa Shinsuke , Sano Motoaki , Fukuda Keiichi
Published: November 2022

Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC.
Analysis of postoperative effects of different semicircular canal surgical technique in patients with labyrinthine fistulas
Authors: Meng Wei , Cai Mingjing , Gao Yanhui , Ji Hongbo , Sun Chuan , Li Guangfei , Wei Yanyan , Chen Yan , Ni Hui , Yan Min , He Shuangba
Published: November 2022

Objective

Different semicircular canal surgery techniques have been used to treat patients with labyrinthine fistulas caused by middle ear cholesteatoma. This study evaluated postoperative hearing and vestibular function after various semicircular canal surgeries.

Materials and methods

In group 1, from January 2008 to December 2014, 29 patients with middle ear cholesteatoma complicated by labyrinthine fistulas were treated with surgery involving covering the fistulas with simple fascia. In group 2, from January 2015 to October 2021, 36 patients with middle ear cholesteatoma complicated by labyrinthine fistulas were included. Cholesteatomas on the surface of type I labyrinthine fistulas were cleaned using the “under water technique” and capped with a “sandwich” composed of fascia, bone meal, and fascia. Cholesteatomas on the surface of type II and III fistulas were cleaned using the “under water technique,” and the labyrinthine fistula was plugged with a “pie” composed of fascia, bone meal, and fascia, and then covered with bone wax.

Results

Some patients with labyrinthine fistulas in group 1 exhibited symptoms of vertigo after surgery. In group 2 Patients with type II labyrinthine fistulas experienced short-term vertigo after semicircular canal occlusion, but no cases of vertigo were reported during long-term follow-up. “sandwich.” In patients with type II labyrinthine fistulas, the semicircular canal occlusion influenced postoperative hearing improvement. However, postoperative patient hearing was still superior to preoperative hearing.

Conclusion

The surface of type I labyrinthine fistulas should be capped by a “sandwich” composed of fascia, bone meal, and fascia. Type II and III labyrinthine fistulas should be plugged with a “pie” composed of fascia, bone meal, and fascia, covered with bone wax.
Calcium imaging: A versatile tool to examine Huntington’s disease mechanisms and progression
Authors: Barry Joshua , Peng Allison , Levine Michael S. , Cepeda Carlos
Published: November 2022

Huntington’s disease (HD) is a fatal, hereditary neurodegenerative disorder that causes chorea, cognitive deficits, and psychiatric symptoms. It is characterized by accumulation of mutant Htt protein, which primarily impacts striatal medium-sized spiny neurons (MSNs), as well as cortical pyramidal neurons (CPNs), causing synapse loss and eventually cell death. Perturbed Ca2+ homeostasis is believed to play a major role in HD, as altered Ca2+ homeostasis often precedes striatal dysfunction and manifestation of HD symptoms. In addition, dysregulation of Ca2+ can cause morphological and functional changes in MSNs and CPNs. Therefore, Ca2+ imaging techniques have the potential of visualizing changes in Ca2+ dynamics and neuronal activity in HD animal models. This minireview focuses on studies using diverse Ca2+ imaging techniques, including two-photon microscopy, fiber photometry, and miniscopes, in combination of Ca2+ indicators to monitor activity of neurons in HD models as the disease progresses. We then discuss the future applications of Ca2+ imaging to visualize disease mechanisms and alterations associated with HD, as well as studies showing how, as a proof-of-concept, Ca2+imaging using miniscopes in freely-behaving animals can help elucidate the differential role of direct and indirect pathway MSNs in HD symptoms.
Teneurin paralogues are able to localise synaptic sites driven by the intracellular domain and have the potential to form cis-heterodimers
Authors: Cheung Angela , Schachermayer Greta , Biehler Aude , Wallis Amber , Missaire Mégane , Hindges Robert
Published: November 2022

Synaptic specificity during neurodevelopment is driven by combinatorial interactions between select cell adhesion molecules expressed at the synaptic membrane. These protein–protein interactions are important for instructing the correct connectivity and functionality of the nervous system. Teneurins are one family of synaptic adhesion molecules, highly conserved and widely expressed across interconnected areas during development. These type-II transmembrane glycoproteins are involved in regulating key neurodevelopmental processes during the establishment of neural connectivity. While four teneurin paralogues are found in vertebrates, their subcellular distribution within neurons and interaction between these different paralogues remains largely unexplored. Here we show, through fluorescently tagging teneurin paralogues, that true to their function as synaptic adhesion molecules, all four paralogues are found in a punctate manner and partially localised to synapses when overexpressed in neurons in vitro. Interestingly, each paralogue is differentially distributed across different pre- and post-synaptic sites. In organotypic cultures, Tenm3 is similarly localised to dendritic spines in CA1 neurons, particularly to spine attachment points. Furthermore, we show that the intracellular domain of teneurin plays an important role for synaptic localisation. Finally, while previous studies have shown that the extracellular domain of teneurins allows for active dimer formation and transsynaptic interactions, we find that all paralogues are able to form the full complement of homodimers and cis-heterodimers. This suggests that the combinatorial power to generate distinct molecular teneurin complexes underlying synaptic specificity is even higher than previously thought. The emerging link between teneurin with cancers and neurological disorders only serves to emphasise the importance of further elucidating the molecular mechanisms of teneurin function and their relation to human health and disease.
Comparison of dural puncture and dural incision in deep brain stimulation surgery: A simple but worthwhile technique modification
Authors: Fan Shiying , Zhang Quan , Meng Fangang , Fang Huaying , Yang Guang , Shi Zhongjie , Liu Huanguang , Zhang Hua , Yang Anchao , Zhang Jianguo , Shi Lin
Published: November 2022

Background

The accuracy of the deep brain stimulation (DBS) electrode placement is influenced by a myriad of factors, among which pneumocephalus and loss of cerebrospinal fluid that occurs with dural opening during the surgery are considered most important. This study aimed to describe an effective method for decreasing pneumocephalus by comparing its clinical efficacy between the two different methods of opening the dura.

Materials and methods

We retrospectively compared two different methods of opening the dura in 108 patients who underwent bilateral DBS surgery in our center. The dural incision group comprised 125 hemispheres (58 bilateral and 9 unilateral) and the dural puncture group comprised 91 (41 bilateral and 9 unilateral). The volume of intracranial air, dural opening time, intraoperative microelectrode recordings (MERs), postoperative electrode displacement, clinical efficacy, and complications were examined. Spearman correlation analysis was employed to identify factors associated with the volume of intracranial air and postoperative electrode displacement.

Results

The volume of intracranial air was significantly lower (0.35 cm3 vs. 5.90 cm3) and dural opening time was significantly shorter (11s vs. 35s) in the dural puncture group. The volume of intracranial air positively correlated with dural opening time. During surgery, the sensorimotor area was longer (2.47 ± 1.36 mm vs. 1.92 ± 1.42 mm) and MERs were more stable (81.82% vs. 47.73%) in the dural puncture group. Length of the sensorimotor area correlated negatively with the volume of intracranial air. As intracranial air was absorbed after surgery, significant anterior, lateral, and ventral electrode displacement occurred; the differences between the two groups were significant (total electrode displacement, 1.0mm vs. 1.4mm). Electrode displacement correlated positively with the volume of intracranial air. Clinical efficacy was better in the dural puncture group than the dural incision group (52.37% ± 16.18% vs. 43.93% ± 24.50%), although the difference was not significant.

Conclusion

Our data support the hypothesis that opening the dura via puncture rather than incision when performing DBS surgery reduces pneumocephalus, shortens dural opening time, enables longer sensorimotor area and more stable MERs, minimizes postoperative electrode displacement, and may permit a better clinical efficacy.
Autism spectrum disorders pathogenesis: Toward a comprehensive model based on neuroanatomic and neurodevelopment considerations
Authors: Beopoulos Athanasios , Géa Manuel , Fasano Alessio , Iris François
Published: November 2022

Autism spectrum disorder (ASD) involves alterations in neural connectivity affecting cortical network organization and excitation to inhibition ratio. It is characterized by an early increase in brain volume mediated by abnormal cortical overgrowth patterns and by increases in size, spine density, and neuron population in the amygdala and surrounding nuclei. Neuronal expansion is followed by a rapid decline from adolescence to middle age. Since no known neurobiological mechanism in human postnatal life is capable of generating large excesses of frontocortical neurons, this likely occurs due to a dysregulation of layer formation and layer-specific neuronal migration during key early stages of prenatal cerebral cortex development. This leads to the dysregulation of post-natal synaptic pruning and results in a huge variety of forms and degrees of signal-over-noise discrimination losses, accounting for ASD clinical heterogeneities, including autonomic nervous system abnormalities and comorbidities. We postulate that sudden changes in environmental conditions linked to serotonin/kynurenine supply to the developing fetus, throughout the critical GW7 – GW20 (Gestational Week) developmental window, are likely to promote ASD pathogenesis during fetal brain development. This appears to be driven by discrete alterations in differentiation and patterning mechanisms arising from in utero RNA editing, favoring vulnerability outcomes over plasticity outcomes. This paper attempts to provide a comprehensive model of the pathogenesis and progression of ASD neurodevelopmental disorders.
Effects of essential oil extracted from Artemisia argyi leaf on lipid metabolism and gut microbiota in high-fat diet-fed mice
Authors: Wang Kaijun , Ma Jie , Li Yunxia , Han Qi , Yin Zhangzheng , Zhou Miao , Luo Minyi , Chen Jiayi , Xia Siting
Published: November 2022

Artemisia argyi leaf is a well-known species in traditional Chinese medicine, and its essential oil (AAEO) has been identified to exert various physiological activities. The aim of this study was to investigate the effects of AAEO on lipid metabolism and the potential microbial role in high-fat diet (HFD)-fed mice. A total of 50 male mice were assigned to five groups for feeding with a control diet (Con), a high-fat diet (HFD), and the HFD plus the low (LEO), medium (MEO), and high (HEO) doses of AAEO. The results demonstrated that dietary HFD markedly increased the body weight gain compared with the control mice (p < 0.05), while mice in the HEO group showed a lower body weight compared to the HFD group (p < 0.05). The weight of fatty tissues and serum lipid indexes (TBA, HDL, and LDL levels) were increased in response to dietary HFD, while there was no significant difference in AAEO-treated mice (p < 0.05). The jejunal villus height was dramatically decreased in HFD-fed mice compared with the control mice, while HEO resulted in a dramatically higher villus height than that in the HFD group (p < 0.05). Microbial α-diversity was not changed in this study, but β-diversity indicated that microbial compositions differed in control, HFD, and EO subjects. At the genus level, the relative abundance of Bacteroides was greater (p < 0.05) in the feces of the Con group when compared to the HFD and EO groups. On the contrary, the abundance of Muribaculum was lower in the Con group compared to the HFD and EO groups (p < 0.05). Although the Muribaculum in the EO group was lower than that in the HFD group, there was no statistically notable difference between the HFD and EO groups (p > 0.05). Simultaneously, the relative abundance of Alistipes (p < 0.05) and Rikenella (p < 0.05) was also dramatically higher in the Con group than in the HFD and EO groups. The abundance of norank_f__norank_o__Clostridia_UCG-014 was lower in the HFD or EO group than in the Con group (p < 0.05). In conclusion, the results suggested that HEO could affect body weight and lipid metabolism without gut microbes in ICR mice, and it was beneficial for the structure of the jejunal epithelial tissue.
Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease
Authors: Whittaker Daniel S. , Tamai T. Katherine , Bains Raj S. , Villanueva Sophia Anne Marie , Luk Shu Hon Christopher , Dell’Angelica Derek , Block Gene D. , Ghiani Cristina A. , Colwell Christopher S.
Published: November 2022

Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington’s disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would ameliorate the symptoms and delay disease progression in the BACHD mouse model of HD. Adult WT and BACHD male mice were fed a normal or a ketogenic diet (KD) for 3 months. The KD evoked a robust rhythm in serum levels of β-hydroxybutyrate and dramatic changes in the microbiome of male WT and BACHD mice. NanoString analysis revealed transcriptional changes driven by the KD in the striatum of both WT and BACHD mice. Disturbances in sleep/wake cycles have been reported in mouse models of HD and are common among HD patients. Having established that the KD had effects on both the WT and mutant mice, we examined its impact on sleep/wake cycles. KD increased daytime sleep and improved the timing of sleep onset, while other sleep parameters were not altered. In addition, KD improved activity rhythms, including rhythmic power, and reduced inappropriate daytime activity and onset variability. Importantly, KD improved motor performance on the rotarod and challenging beam tests. It is worth emphasizing that HD is a genetically caused disease with no known cure. Life-style changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of diet-based treatment strategies in a pre-clinical model of HD.
Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience
Authors: Di Lalla Vanessa , Elakshar Sara , Anidjar Maurice , Tolba Marwan , Hassan Toufic , Bahoric Boris , McPherson Victor , Probst Stephan , Niazi Tamim
Published: November 2022

Purpose/objectives

High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure.

Materials/methods

We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis.

Results

From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%.

Conclusions

To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.
DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway
Authors: Han Zhitao , Wang Lining , Wang Dongshuo , Zhang Luosheng , Bi Yifeng , Zheng Xinlei , Liu Weibo , Bai Guangjian , Wang Zhenhua , Wan Wei , Ma Yong , Cai Xiaopan , Liu Tielong , Jia Qi
Published: November 2022

Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.
GZ17-6.02 kills prostate cancer cells in vitro and in vivo
Authors: Booth Laurence , Roberts Jane L. , West Cameron , Dent Paul
Published: November 2022

GZ17-6.02 is undergoing clinical evaluation in solid tumors and lymphoma. We defined the biology of GZ17-6.02 in prostate cancer cells and determined whether it interacted with the PARP1 inhibitor olaparib to enhance tumor cell killing. GZ17-6.02 interacted in a greater than additive fashion with olaparib to kill prostate cancer cells, regardless of androgen receptor expression or loss of PTEN function. Mechanistically, GZ17-6.02 initially caused peri-nuclear activation of ataxia-telangiectasia mutated (ATM) that was followed after several hours by activation of nuclear ATM, and which at this time point was associated with increased levels of DNA damage. Directly downstream of ATM, GZ17-6.02 and olaparib cooperated to activate the AMP-dependent protein kinase (AMPK) which then activated the kinase ULK1, resulting in autophagosome formation that was followed by autophagic flux. Knock down of ATM, AMPKα or the autophagy-regulatory proteins Beclin1 or ATG5 significantly reduced tumor cell killing. GZ17-6.02 and olaparib cooperated to activate protein kinase R which phosphorylated and inactivated eIF2α, i.e., enhanced endoplasmic reticulum (ER) stress signaling. Knock down of eIF2α also significantly reduced autophagosome formation and tumor cell killing. We conclude that GZ17-6.02 and olaparib interact to kill prostate cancer cells in vitro by increasing autophagy and by enhancing ER stress signaling. In vivo, GZ17-6.02 as a single agent profoundly reduced tumor growth and significantly prolonged animal survival. GZ17-6.02 interacted with olaparib to further suppress the growth of LNCaP tumors without ultimately enhancing animal survival. Our data support the consideration of GZ17-6.02 as a possible therapeutic agent in patients with AR+ prostate cancer.
Establishment and validation of novel MRI radiomic feature-based prognostic models to predict progression-free survival in locally advanced rectal cancer
Authors: Xie Fei , Zhao Qin , Li Shuqi , Wu Shuangshuang , Li Jinli , Li Haojiang , Chen Shenghuan , Jiang Wu , Dong Annan , Wu Liqing , Liu Long , Huang Huabin , Xu Shuoyu , Shao Yuanzhi , Liu Lizhi , Li Li , Cai Peiqiang
Published: November 2022

In locally advanced rectal cancer (LARC), an improved ability to predict prognosis before and after treatment is needed for individualized treatment. We aimed to utilize pre- and post-treatment clinical predictors and baseline magnetic resonance imaging (MRI) radiomic features for establishing prognostic models to predict progression-free survival (PFS) in patients with LARC. Patients with LARC diagnosed between March 2014 and May 2016 were included in this retrospective study. A radiomic signature based on extracted MRI features and clinical prognostic models based on clinical features were constructed in the training cohort to predict 3-year PFS. C-indices were used to evaluate the predictive accuracies of the radiomic signature, clinical prognostic models, and integrated prognostic model (iPostM). In total, 166 consecutive patients were included (110 vs. 56 for training vs. validation). Eleven radiomic features were filtered out to construct the radiomic signature, which was significantly related to PFS. The MRI feature-derived radiomic signature exhibited better prognostic performance than the clinical prognostic models (P = 0.007 vs. 0.077). Then, we proposed an iPostM that combined the radiomic signature with tumor regression grade. The iPostM achieved the highest C-indices in the training and validation cohorts (0.942 and 0.752, respectively), outperforming other models in predicting PFS (all P < 0.05). Decision curve analysis and survival curves of the validation cohort verified that iPostM demonstrated the best performance and facilitated risk stratification. Therefore, iPostM provided the most reliable prognostic prediction for PFS in patients with LARC.
Therapeutic mechanism and clinical application of Chinese herbal medicine against diabetic kidney disease
Authors: Chen Dan-Qian , Wu Jun , Li Ping
Published: November 2022

Diabetic kidney disease (DKD) is the major complications of type 1 and 2 diabetes, and is the predominant cause of chronic kidney disease and end-stage renal disease. The treatment of DKD normally consists of controlling blood glucose and improving kidney function. The blockade of renin-angiotensin-aldosterone system and the inhibition of sodium glucose cotransporter 2 (SGLT2) have become the first-line therapy of DKD, but such treatments have been difficult to effectively block continuous kidney function decline, eventually resulting in kidney failure and cardiovascular comorbidities. The complex mechanism of DKD highlights the importance of multiple therapeutic targets in treatment. Chinese herbal medicine (active compound, extract and formula) synergistically improves metabolism regulation, suppresses oxidative stress and inflammation, inhibits mitochondrial dysfunction, and regulates gut microbiota and related metabolism via modulating GLP-receptor, SGLT2, Sirt1/AMPK, AGE/RAGE, NF-κB, Nrf2, NLRP3, PGC-1α, and PINK1/Parkin pathways. Clinical trials prove the reliable evidences for Chinese herbal medicine against DKD, but more efforts are still needed to ensure the efficacy and safety of Chinese herbal medicine. Additionally, the ideal combined therapy of Chinese herbal medicine and conventional medicine normally yields more favorable benefits on DKD treatment, laying the foundation for novel strategies to treat DKD.
Eupatilin attenuates the senescence of nucleus pulposus cells and mitigates intervertebral disc degeneration via inhibition of the MAPK/NF-κB signaling pathway
Authors: Yang Huan , Yang Xiao , Rong Kewei , Liang Jiarong , Wang Zhengting , Zhao Jie , Zhang Pu , Li Yijie , Wang Lihuan , Ma Hui , Ye Bin
Published: November 2022

Intervertebral disc degeneration (IDD) is the main cause of low back pain. An increasing number of studies have suggested that inflammatory response or the senescence of nucleus pulposus (NP) cells is strongly associated with the progress of IDD. Eupatilin, the main flavonoid extracted from Artemisia, was reported to be associated with the inhibition of the intracellular inflammatory response and the senescence of cells. However, the relationship between eupatilin and IDD is still unknown. In this study, we explored the role of eupatilin in tumor necrosis factor-α (TNF-α)-induced activation of inflammatory signaling pathways and NP cell senescence, in the anabolism and catabolism of NP cell extracellular matrix (ECM) and in the effect of the puncture-induced model of caudal IDD in the rat. In vitro, eupatilin significantly inhibited TNF-α-induced ECM degradation, downregulated the expression of related markers of NP cells (MMP3, MMP9, and MMP13), and upregulated the expression of SOX9 and COL2A1. Furthermore, eupatilin reduced TNF-α-induced cell senescence by inhibiting the expression of the senescence of NP cell-related markers (p21 and p53). Mechanistically, ECM degradation and cell senescence were reduced by eupatilin, which inhibited the activation of MAPK/NF-κB signaling pathways. Consistent with the in vitro data, eupatilin administration ameliorated the puncture-induced model of caudal IDD in the rat. In conclusion, eupatilin can inhibit the inflammatory response and the senescence of NP cells, which may be a novel treatment strategy for IDD.
Exploring robust computer-aided diagnosis of Parkinson’s disease based on various voice signals
Authors: Xie Jiu-Cheng , Gan Yanyan , Liang Ping , Lan Rushi , Gao Hao
Published: November 2022

As the voice disorder is a typical early symptom of Parkinson, some researchers attempt to diagnose this disease based on voice data collected from suspected patients. Although existing methods can provide acceptable results, they just work in partial scenarios. In other words, they are not generable and robust enough. To this end, we present a Parkinson’s auxiliary diagnosis system based on human speech, which can adaptively build a suitable deep neural network based on sound features. The system includes two modules: hybrid features extraction and adaptive network construction. We extract kinds of information from the voice data to form a new compound feature. Furthermore, particle swarm optimization (PSO) algorithm is employed to build the corresponding 1D convolution network for features classification. Extensive experiments on two datasets consisting of English and Italian are conducted for evaluation purposes. Experimental results show that our method improves the accuracy of voice-based Parkinson’s disease detection to some extent.
Optimizing the spectrum of high power narrow linewidth fiber amplifier through the same complex degree of coherence
Authors: Lai Wenchang , Ma Pengfei , Song Jiaxin , Ren Shuai , Liu Wei , Zhou Pu
Published: November 2022

The spectra of narrow linewidth fiber amplifiers are closely related to both the stimulated Brillouin scattering (SBS) threshold in power scaling process and the combining efficiency in coherent beam combining (CBC) system. In this manuscript, the SBS thresholds of fiber amplifier with different spectral distributions (Gaussian, sinc2 and rectangular) have been compared under the same spectral complex degree of coherence (CDC), which could promise the same combining efficiency in CBC system. A SBS dynamic model is established to analyze the SBS process in fiber amplifier and a comparing experiment is also performed by measuring the SBS thresholds of different spectra that have the same CDC set to be 0.96. The FWHM linewidths of Gaussian, sinc2 and rectangular spectra are adjusted to be 1.1 GHz, 0.5 GHz and 1.06 GHz, respectively. The corresponding SBS thresholds are measured to be 108 W, 77 W, and 135 W. By contrast, the rectangular spectra could have most excellent capacity on improving SBS threshold in fiber amplifier under the same combining efficiency in CBC system. Overall, it could provide a feasible method on spectra designing in high power narrow linewidth fiber amplifiers used in CBC system.
Could cardiac autonomic modulation be an objective method to identify hypobaric hypoxia symptoms at 25.000ft among Brazilian military airmen?
Authors: Honorato Fernando Sousa , Deus Lysleine Alves de , Reis Andrea Lucena , Neves Rodrigo Vanerson Passos , Corrêa Hugo de Luca , Medeiros Ana Paola Brasil , Haberland Débora Fernanda , Medeiros Radamés Maciel Vitor , Prestes Jonato , Ferreira Carlos Ernesto Santos , Rosa Thiago Santos
Published: November 2022

Hypobaric hypoxia during a flight can cause accidents, resulting in deaths. Heart rate variability may be more sensitive than self-reported hypoxia symptoms to the effects of HH. The level of physical fitness can contribute to efficient cardiac autonomic modulation. However, no studies have examined the association between fitness, heart rate variability, and the time of onset of hypobaric hypoxia symptoms. To analyze the influence of hypobaric hypoxia on cardiac autonomic function at the time of onset of the first symptoms and its association with physical fitness. Male airmen trained and belonging to the staff of the Brazilian Air Force (n = 23; 30 ± 6.7 years) participated in a flight simulation in a 25.000 ft hypobaric chamber. Heart rate variability was recorded with a Polar® cardiac monitor. Data were analyzed in the time-domain method using Kubios software. We evaluated pulse oximetry with the Mindray PM-60 oximeter. Physical fitness assessment test results were collected from the archive. At moments rest vs. hypoxia revealed a decrease in heart rate variability indices iRR and RMSSD (p < 0.001). The individual analysis of hypoxia-rest variation showed that 100% of the airmen had a negative delta for both iRR and RMSSD indices. The time of onset of hypoxia symptoms was not associated with body composition, physical fitness, oxygen saturation, and HRV indices. Also, we suggest that cardiac autonomic modulation seems to be more sensitive to the effects of hypobaric hypoxia at 25.000 ft than the self-reported subjective perception of symptoms. Further devices that alert to a hypoxic condition during a flight should consider heart rate variability allowing more time and security to reestablish control of the flight.
A new player in circadian networks: Role of electrical synapses in regulating functions of the circadian clock
Authors: Iyer Aishwarya Ramakrishnan , Sheeba Vasu
Published: November 2022

Several studies have indicated that coherent circadian rhythms in behaviour can be manifested only when the underlying circadian oscillators function as a well-coupled network. The current literature suggests that circadian pacemaker neuronal networks rely heavily on communication mediated by chemical synapses comprising neuropeptides and neurotransmitters to regulate several behaviours and physiological processes. It has become increasingly clear that chemical synapses closely interact with electrical synapses and function together in the neuronal networks of most organisms. However, there are only a few studies which have examined the role of electrical synapses in circadian networks and here, we review our current understanding of gap junction proteins in circadian networks of various model systems. We describe the general mechanisms by which electrical synapses function in neural networks, their interactions with chemical neuromodulators and their contributions to the regulation of circadian rhythms. We also discuss the various methods available to characterize functional electrical synapses in these networks and the potential directions that remain to be explored to understand the roles of this relatively understudied mechanism of communication in modulating circadian behaviour.
The reliability of back-extrapolation in estimating V˙O2peak in different swimming performances at the severe-intensity domain
Authors: Massini Danilo Alexandre , Simionato Astor Reis , Almeida Tiago André Freire , Macedo Anderson Geremias , Espada Mário Cunha , Reis Joana Filipa , Besone Alves Francisco , Pessôa Filho Dalton Müller
Published: November 2022

The amount of anerobic energy released during exercise might modify the initial phase of oxygen recovery (fast-O2debt) post-exercise. Therefore, the present study aimed to analyze the reliability of peak oxygen uptake (V˙O2peak) estimate by back-extrapolation (BE−V˙O2peak) under different swimming conditions in the severe-intensity domain, verifying how the alterations of the V˙O2 recovery profile and anerobic energy demand might affect BE−V˙O2peak values. Twenty swimmers (16.7 ± 2.4 years, 173.5 ± 10.2 cm, and 66.4 ± 10.6 kg) performed an incremental intermittent step protocol (IIST: 6 × 250 plus 1 × 200 m, IIST_v200m) for the assessment of V˙O2peak. The V˙O2 off-kinetics used a bi-exponential model to discriminate primary amplitude, time delay, and time constant (A1off, TD1off, and τoff) for assessment of fast-O2debt post IIST_v200m, 200-m single-trial (v200 m), and rest-to-work transition at 90% delta (v90%Δ) tests. The linear regression estimated BE−V˙O2peak and the rate of V˙O2 recovery (BE-slope) post each swimming performance. The ANOVA (Sidak as post hoc) compared V˙O2peak to the estimates of BE−V˙O2peak in v200 m, IIST_v200 m, and v90%Δ, and the coefficient of dispersion (R2) analyzed the association between tests. The values of V˙O2peak during IIST did not differ from BE−V˙O2peak in v200 m, IIST_v200 m, and v90%Δ (55.7 ± 7.1 vs. 53.7 ± 8.2 vs. 56.3 ± 8.2 vs. 54.1 ± 9.1 ml kg−1 min−1, p > 0.05, respectively). However, the V˙O2peak variance is moderately explained by BE−V˙O2peak only in IIST_v200 m and v90%Δ (RAdj2 = 0.44 and RAdj2 = 0.43, p < 0.01). The TD1off and τoff responses post IIST_v200 m were considerably lower than those in both v200 m (6.1 ± 3.8 and 33.0 ± 9.5 s vs. 10.9 ± 3.5 and 47.7 ± 7.9 s; p < 0.05) and v90%Δ ( 10.1 ± 3.8 and 44.3 ± 6.3 s, p < 0.05). The BE-slope post IIST_v200m was faster than in v200 m and v90%Δ (-47.9 ± 14.6 vs. -33.0 ± 10.4 vs. -33.6 ± 13.8 ml kg−1, p < 0.01), and the total anerobic (AnaerTotal) demand was lower in IIST_v200 m (37.4 ± 9.4 ml kg−1) than in 200 m and 90%Δ (51.4 ± 9.4 and 46.2 ± 7.7 ml kg−1, p < 0.01). Finally, the τ1off was related to AnaerTotal in IIST_v200m, v200 m, and v90%Δ (r = 0.64, r = 0.61, and r = 0.64, p < 0.01). The initial phase of the V˙O2 recovery profile provided different (although reliable) conditions for the estimate of V˙O2peak with BE procedures, which accounted for the moderate effect of anerobic release on V˙O2 off-kinetics, but compromised exceptionally the V˙O2peak estimate in the 200-m single trial.
Experimental duration determines the effect of arbuscular mycorrhizal fungi on plant biomass in pot experiments: A meta-analysis
Authors: Qin Mingsen , Li Lei , Miranda Jean‐Pascal , Tang Yun , Song Bo , Oosthuizen Maria Kathleen , Wei Wangrong
Published: November 2022

Arbuscular mycorrhizal fungi (AMF) play various important roles in promoting plant growth. Numerous environmental and evolutionary factors influence the response of plants to AMF. However, the importance of the individual factors on the effects of AMF on plant biomass is not clearly understood. In this study, a meta-analysis using 1,640 observations from 639 published articles related to the influence of AMF on the plant shoot, root, and total biomass was performed; 13 different experimental setting factors that had an impact on the influence of AMF and their importance were quantitatively synthesized. The meta-analysis showed that AMF had positive effects on the plant shoot, root, and total biomass; moreover, the experimental duration, plant root-to-shoot ratio (R/S), AMF root length colonization, plant family, pot size, soil texture, and the soil pH all influenced the effects of AMF on the shoot, root, and total biomass. In addition, the plant root system and plant functional type had impacts on the effect of AMF on shoot biomass; AMF guild also impacted the effect of AMF on root biomass. Of these factors, the experimental duration, plant R/S, and pot size were the three most important predicting the effects of AMF on the plant shoot, root, and total biomass. This study comprehensively assessed the importance of the different factors that influenced the response of plants to AMF, highlighting that the experimental duration, plant R/S, and pot size should be taken into consideration in pot experiments in studies of the functions of AMF. Multiple unfavorable factors that may obscure or confound the observed functions of AMF should be excluded.
CEO birth order and corporate social responsibility behaviors: The moderating effect of female sibling and age gap
Authors: Zheng Minna , Ren Guangqian , Wu Sihong , Jiang Zezhen
Published: November 2022

Corporate social responsibility (CSR) is one of the most important business strategies which helps enterprises obtain competitive advantage and improve performance. Scholars have conducted many beneficial studies on the driving factors of CSR behaviors from the perspective of CEO traits, but rarely focus on the impact of the CEO's early family experiences. This study aims to fill this research gap by investigating the influence of CEO birth order on firms' CSR behaviors, and further exploring the possible moderating effects of the presence of a female sibling and the age gap between the CEO and the closest sibling. This study takes Chinese non-financial private listed companies from 2010 to 2017 as the research samples, and empirically tests the relationship between CEO birth order and a firm's CSR behaviors. The empirical results show that CEO birth order negatively influences corporate social responsibility behaviors, and this relationship would be weakened when the CEO has a female sibling or the age gap between CEO and the closest sibling is larger. This paper extends the research on personal family factors from the field of social psychology to the business field and finds a new driving factor of corporate social responsibility behavior from the perspective of the CEOs' early family factors.
Mindfulness mediates the relationship between positive parenting and aggression, depression, and suicidal ideation: A longitudinal study in middle school students
Authors: Su Yanhua , Sun Wenyan , Gan Yiqun , Zhu Qian , Liu Guoyan , Hui Linhu , Tang Hui , Liu Zhijun
Published: November 2022

Previous research has indicated that parenting factors affect the risk of maladaptive psychological outcomes (e.g., aggression, depression, or suicidal ideation), and that positive parenting is a prospective risk factor for maladaptive psychological outcomes. However, the mechanisms underlying the relationships between positive parenting, mindfulness, and maladaptive psychological outcomes remain unknown, as do the processes that mediate the effect of positive parenting on maladaptive psychological outcomes in adolescents. The objective of the present study was to investigate the longitudinal relationship between positive parenting, mindfulness, and maladaptive psychological outcomes in middle school students, as well as the mediating effect of mindfulness in the relationships between positive parenting and depression, aggression, and suicidal ideation. In this study, 386 middle school children (aged 12–16) were tested three times over a period of 6 months. Positive parenting was assessed at Time 1, mindfulness at Time 2, and depression, aggression, and suicidal ideation at Time 3. Using structural equation modeling, positive parenting was revealed to be longitudinally associated with mindfulness and negatively associated with maladaptive psychological outcomes. More crucially, mindfulness mediated the relationship between positive parenting and maladaptive psychological outcomes. This research provides important insights into how to effectively decrease adolescent maladaptive psychological outcomes and highlights the importance of teaching mindfulness to youths.
Farmers’ trust in government and participation intention toward rural tourism through TAM: The moderation effect of perceived risk
Authors: Yu Xia
Published: November 2022

At present, there are almost 700 million rural population in China, and the farm and farmers in China are highly associated with the steadiness and development of the country and even the world. Farmers are the main subjects in rural development and play a vital role in the reception, management, and benefit distribution in rural tourism activities during the development of rural tourism. Farmers’ perception and participation intention in rural tourism development are directly related to the sustainable development of rural tourism and the realization of rural revitalization goals. The decision-making process of participation in the rural tourism development fits the application conditions of the technology acceptance model (TAM). Therefore, in order to explore the influencing factors of farmers’ decision-making process in participating in the rural tourism, this study employs the technology acceptance model to predict and judge individual farmers’ willingness and behavior to participate in the rural tourism. The government trust and perceived risk in the real problem of low participation of farmers in the rural tourism development are considered. Then, an extended technology acceptance model was established by taking 409 farm households as research samples. The influence of government trust on farmers’ participation intention in the rural tourism was empirically analyzed based on the PLS-SEM model. The results show that farmers’ perceived usefulness and perceived ease of use in rural tourism affect their participation intention. Farmers’ judgments on whether governments can assume public responsibilities and achieve public interests through rural tourism development affects their trust in government, while the government trust can positively affect farmers’ participation intention via perceived usefulness and perceived ease of use. This indicates that government trust is an important antecedent variable influencing farmers’ participation in the rural tourism. The perceived risk affects farmers’ perceived usefulness and participation intention in the rural tourism, and plays a moderating role in the relationship between government trust and perceived usefulness. Finally, this study recommends to highlight the utility and convenience of rural tourism participation during the promotion of farmers’ participation in rural tourism development, enhance the ability of farmers to participate in rural tourism development, and choose multiple channels to increase government trust to reduce farmers’ risk concerns.