bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of PARP inhibitors in prostate cancer: from specific to broader application
Authors: Zhang Zhenting , Diao Lei , Zhang Chao , Wang Feifei , Guan Xin , Yao Xin
Published: April 2023

Prostate cancer (PC) is one of the major health issues of elderly men in the word. It is showed that there were approximately 1.414 million patients with PC in 2020 worldwide, with a high mortality rate in metastatic cases. In the present choices of treatment in PC, androgen deprivation therapy has long been as a backbone of them. But the clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) were not ideal because of their poor prognosis, more effective therapeutic approaches are still necessary to further improve this problem. Poly (ADP-ribose) polymerase (PARP) inhibitors lead to the single-strand DNA breaks and/or double-strand DNA breaks, and result in synthetic lethality in cancer cells with impaired homologous recombination genes. It is estimated that approximately 20~25% of patients with mCRPC have a somatic or germinal DNA damage repair gene mutation. Furthermore, in “BRCAness” cases, which has been used to describe as tumors that have not arisen from a germline BRCA1 or BRCA2 mutation, there were also a number of studies sought to extend these promising results of PARP inhibitors. It is worth noting that an interaction between androgen receptor signaling and synthetic lethality with PARP inhibitors has been proposed. In this review, we discussed the mechanism of action and clinical research of PARP inhibitors, which may benefit population from “specific” to the “all-comer” in patients with PC when combined with novel hormonal therapies.
Energy trading support decision model of distributed energy resources aggregator in day-ahead market considering multi-stakeholder risk preference behaviors
Authors: Dong Jun , Dou Xihao , Liu Dongran , Bao Aruhan , Wang Dongxue , Zhang Yunzhou , Jiang Peng
Published: April 2023

In recent years, the power market and regional distributed energy systems (RDES) in China have experienced considerable growth. However, the critical issue of how multi-stakeholder parties within the distributed energy system evaluate risk preferences in order to develop scientifically sound trading strategies remains unclear. To address this problem, this study constructs a multi-agent assisted decision-making model that incorporates the critical features of a regional distributed energy system. By simulating various calculation scenarios using this model, the study aims to provide a better understanding of the system’s multi-agent interactions and decision-making processes. First, different types of stakeholders and risk preferences in RDES are delineated. Second, supply and demand fluctuations in RDRS are treated and the impact of wholesale market price volatility risk on distributed energy system aggregators (DERA) decisions is fully considered. Meanwhile, a multi-stakeholders DERA transaction decision-making model in the day-ahead market considering risk preference behaviors is constructed based on information gap decision theory (IGDT) and solved by the Opposition Learning Grey Wolf Optimizer (OLGWO). The mathematical analysis conducted in this study indicates that the approach proposed could provide an effective trading scheme and operational strategy for multi-interest entities participating in the market of RDES. Therefore, incorporating the proposed approach would be beneficial in enhancing the performance and effectiveness of such systems.
Heterogeneity of environmental protection law’s impact on firms’ pollutant discharge
Authors: Li Wenyu , Shan Wei , Gao Junguang
Published: April 2023

In 2015, China revised its Environmental Protection Law to strengthen regulations on firms’ pollution discharge. However, the efficacy of this law in protecting the environment remains unclear. Using panel data from China’s listed firms spanning from 2010 to 2020, this paper applies the continuous difference model to analyze the impact of the Environmental Protection Law on firms’ pollutant emissions. The results demonstrate a significant and consistent reduction in both total pollutant emissions and pollutant emissions per outcome for firms due to the implementation of the Environmental Protection Law. Additionally, the study indicates a significant reduction in pollutant emissions among firms that did not receive environmental protection subsidies, state-owned enterprises, and firms without prior environmental pollution behaviors. The findings also suggest a two-year lag for the Environmental Protection Law to impact firms’ pollution emissions per outcome. These results carry important practical implications for the government’s efforts to transform environmental protection policies and for firms seeking to enhance their environmental performance.
Identification of hub genes and biological mechanisms underlying the pathogenesis of asthenozoospermia and chronic epididymitis
Authors: Chen Yinwei , Sun Taotao , Gu Longjie , Ouyang Song , Liu Kang , Yuan Penghui , Liu Chang
Published: April 2023

Objective: Asthenozoospermia (AZS) is one of the most common causes of male fertility, affecting family wellbeing and population growth. Chronic epididymitis (CE) is a common and lingering inflammatory disease in the scrotum. Inflammation in the epididymis has a severe impact on sperm motility. This study aimed to explore the genetic profile and critical pathways involved in the pathological mechanisms of AZS and CE, and discover potential biomarkers.

Methods: Genomic datasets of AZS and CE were obtained from the Gene Expression Omnibus (GEO) database, and relevant differentially expressed genes (DEGs) were identified. GO and pathway enrichment analyses, construction of a protein-protein interaction network, and receiver operator characteristic curve analysis were conducted. The expression profile of hub genes was validated in immunohistochemical data and testicular cell data. Immune infiltration, miRNA-hub gene interactions, and gene-disease interactions were explored. The mRNA levels of hub genes were further measured by qRT-PCR.

Results: A total of 109 DEGs were identified between the AZS/CE and healthy control groups. Pathways of the immune system, neutrophil degranulation, and interleukin-4 and interleukin-13 signaling were enriched in AZS and CE. Five hub genes (CD300LB, CMKLR1, CCR4, B3GALT5, and CTSK) were selected, and their diagnostic values were validated in AZS, CE, and independent validation sets (area under the curve >0.7). Furthermore, the five-hub gene signature was well characterized in testicular immunohistochemical staining and testicular cells from healthy controls. Immune infiltration analysis showed that infiltration of CD8+ cells and T helper cells was significantly related to the expression level of five hub genes. In addition, a miRNA-hub gene network and interaction of other diseases were displayed. The mRNA levels of hub genes (CD300LB, CMKLR1, CCR4, and B3GALT5) were significantly elevated in the patient group. The mRNA level of CTSK also showed a similar trend.

Conclusion: Our study uncovered the genetic profile involved in AZS and CE, and elucidated enriched pathways and molecular associations between hub genes and immune infiltration. This finding provides novel insight into the common pathogenesis of both diseases as well as the potential biomarkers for CE-associated AZS.
Blood filtering system for COVID-19 management: novel modality of the cytokine storm therapeutics
Authors: Chavda Vivek P. , Raval Nidhi , Sheta Soham , Vora Lalitkumar K. , Elrashdy Fatma , Redwan Elrashdy M. , Uversky Vladimir N. , Ertas Yavuz Nuri
Published: April 2023

The newly emerged coronavirus (SARS-CoV-2) is virulent, contagious, and has rapidly gained many mutations, which makes it highly infectious and swiftly transmissible around the world. SARS-CoV-2 infects people of all ages and targets all body organs and their cellular compartments, starting from the respiratory system, where it shows many deleterious effects, to other tissues and organs. Systemic infection can lead to severe cases that require intensive intervention. Multiple approaches were elaborated, approved, and successfully used in the intervention of the SARS-CoV-2 infection. These approaches range from the utilization of single and/or mixed medications to specialized supportive devices. For critically ill COVID-19 patients with acute respiratory distress syndrome, both extracorporeal membrane oxygenation (ECMO) and hemadsorption are utilized in combination or individually to support and release the etiological factors responsible for the “cytokine storm” underlying this condition. The current report discusses hemadsorption devices that can be used as part of supportive treatment for the COVID-19-associated cytokine storm.
Differential expression of programmed death 1 (PD-1) on various immune cells and its role in human leprosy
Authors: Tarique Mohammad , Naz Huma , Suhail Mohd , Turan Ali , Saini Chaman , Muhammad Naoshad , Shankar Hari , Zughaibi Torki A. , Khan Tabish H. , Khanna Neena , Sharma Alpana
Published: April 2023

Leprosy is a chronic bacterial disease caused by Mycobacterium leprae. Leprosy patients have been found to have defects in T cells activation, which is critical to the clearance of the bacilli. Treg cell suppression is mediated by inhibitory cytokines such as IL10, IL-35 and TGF-β and its frequency is higher in leprosy patients. Activation and overexpression of programmed death 1 (PD-1) receptor is considered to one of the pathways to inhibit T-cell response in human leprosy. In the current study we address the effect of PD-1 on Tregs function and its immuno-suppressive function in leprosy patients. Flow cytometry was used to evaluate the expression of PD-1 and its ligands on various immune cells T cells, B cells, Tregs and monocytes. We observed higher expression of PD-1 on Tregs is associated with lower production of IL-10 in leprosy patients. PD-1 ligands on T cells, B cells, Tregs and monocytes found to be higher in the leprosy patients as compared to healthy controls. Furthermore, in vitro blocking of PD-1 restores the Tregs mediated suppression of Teff and increase secretion of immunosuppressive cytokine IL-10. Moreover, overexpression of PD-1 positively correlates with disease severity as well as Bacteriological Index (BI) among leprosy patients. Collectively, our data suggested that PD-1 overexpression on various immune cells is associated with disease severity in human leprosy. Manipulation and inhibition of PD-1 signaling pathway on Tregs alter and restore the Treg cell suppression activity in leprosy patients.
A novel multi-component protein vaccine ECP001 containing a protein polypeptide antigen nPstS1 riching in T-cell epitopes showed good immunogenicity and protection in mice
Authors: Yu Jinjie , Fan Xueting , Luan Xiuli , Wang Ruihuan , Cao Bin , Qian Chengyu , Li Guilian , Li Machao , Zhao Xiuqin , Liu Haican , Wan Kanglin , Yuan Xiuqin
Published: April 2023

Tuberculosis (TB) is an infectious disease that seriously affects human health. Until now, the only anti-TB vaccine approved for use is the live attenuated Mycobacterium bovis (M. bovis) vaccine — BCG vaccine, but its protective efficacy is relatively low and does not provide satisfactory protection against TB in adults. Therefore, there is an urgent need for more effective vaccines to reduce the global TB epidemic. In this study, ESAT-6, CFP-10, two antigens full-length and the T-cell epitope polypeptide antigen of PstS1, named nPstS1, were selected to form one multi-component protein antigens, named ECP001, which include two types, one is a mixed protein antigen named ECP001m, the other is a fusion expression protein antigen named ECP001f, as candidates for protein subunit vaccines. were prepared by constructing one novel subunit vaccine by mixing or fusing the three proteins and combining them with aluminum hydroxide adjuvant, and the immunogenicity and protective properties of the vaccine was evaluated in mice. The results showed that ECP001 stimulated mice to produce high titre levels of IgG, IgG1 and IgG2a antibodies; meanwhile, high levels of IFN-γ and a broad range of specific cytokines were secreted by mouse splenocytes; in addition, ECP001 inhibited the proliferation of Mycobacterium tuberculosis in vitro with a capacity comparable to that of BCG. It can be concluded that ECP001 is a novel effective multicomponent subunit vaccine candidate with potential as BCG Initial Immunisation-ECP001 Booster Immunisation or therapeutic vaccine for M. tuberculosis infection.
Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques
Authors: Rahman Mohammad Arif , Becerra-Flores Manuel , Patskovsky Yury , Silva de Castro Isabela , Bissa Massimiliano , Basu Shraddha , Shen Xiaoying , Williams LaTonya D. , Sarkis Sarkis , N’guessan Kombo F. , LaBranche Celia , Tomaras Georgia D. , Aye Pyone Pyone , Veazey Ronald , Paquin-Proulx Dominic , Rao Mangala , Franchini Genoveffa , Cardozo Timothy
Published: April 2023

Introduction

An efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recurring challenge to determine the magnitude and protective effect of specific in vivo immune responses in isolation. We therefore designed a single, viral-spike-apical, epitope-focused V2 loop immunogen to reveal individual vaccine-elicited immune factors that contribute to protection against HIV/SIV.

Method

We generated a novel vaccine by incorporating the V2 loop B-cell epitope in the cholera toxin B (CTB) scaffold and compared two new immunization regimens to a historically protective ‘standard’ vaccine regimen (SVR) consisting of 2xDNA prime boosted with 2xALVAC-SIV and 1xΔV1gp120. We immunized a cohort of macaques with 5xCTB-V2c vaccine+alum intramuscularly simultaneously with topical intrarectal vaccination of CTB-V2c vaccine without alum (5xCTB-V2/alum). In a second group, we tested a modified version of the SVR consisting of 2xDNA prime and boosted with 1xALVAC-SIV and 2xALVAC-SIV+CTB-V2/alum, (DA/CTB-V2c/alum).

Results

In the absence of any other anti-viral antibodies, V2c epitope was highly immunogenic when incorporated in the CTB scaffold and generated highly functional anti-V2c antibodies in the vaccinated animals. 5xCTB-V2c/alum vaccination mediated non-neutralizing ADCC activity and efferocytosis, but produced low avidity, trogocytosis, and no neutralization of tier 1 virus. Furthermore, DA/CTB-V2c/alum vaccination also generated lower total ADCC activity, avidity, and neutralization compared to the SVR. These data suggest that the ΔV1gp120 boost in the SVR yielded more favorable immune responses than its CTB-V2c counterpart. Vaccination with the SVR generates CCR5- α4β7+CD4+ Th1, Th2, and Th17 cells, which are less likely to be infected by SIV/HIV and likely contributed to the protection afforded in this regimen. The 5xCTB-V2c/alum regimen likewise elicited higher circulating CCR5- α4β7+ CD4+ T cells and mucosal α4β7+ CD4+ T cells compared to the DA/CTB-V2c/alum regimen, whereas the first cell type was associated with reduced risk of viral acquisition.

Conclusion

Taken together, these data suggest that individual viral spike B-cell epitopes can be highly immunogenic and functional as isolated immunogens, although they might not be sufficient on their own to provide full protection against HIV/SIV infection.
Polysaccharide from aerial part of Chuanminshen violaceum alleviates oxidative stress and inflammatory response in aging mice through modulating intestinal microbiota
Authors: Zou Yuan-Feng , JiZe Xiao-Ping , Li Cen-Yu , Zhang Chao-Wen , Fu Yu-Ping , Yin Zhong-Qiong , Li Yang-Ping , Song Xu , Li Li-Xia , Zhao Xing-Hong , Feng Bin , Huang Chao , Ye Gang , Tang Hua-Qiao , Li Ning-Yuan , Chen Ji , Chen Xing-Fu , Tian Meng-Liang
Published: April 2023

Aging is a biological process of progressive deterioration of physiological functions, which poses a serious threat to individual health and a heavy burden on public health systems. As population aging continues, research into anti-aging drugs that prolong life and improve health is of particular importance. In this study, the polysaccharide from stems and leaves of Chuanminshen violaceum was obtained with water extraction and alcohol precipitation, and then separated and purified with DEAE anion exchange chromatography and gel filtration to obtain CVP-AP-I. We gavaged natural aging mice with CVP-AP-I and performed serum biochemical analysis, histological staining, quantitative real-time PCR (qRT-PCR) and ELISA kit assays to analyze inflammation and oxidative stress-related gene and protein expression in tissues, and 16SrRNA to analyze intestinal flora. We found that CVP-AP-I significantly improved oxidative stress and inflammatory responses of the intestine and liver, restored the intestinal immune barrier, and balanced the dysbiosis of intestinal flora. In addition, we revealed the potential mechanism behind CVP-AP-I to improve intestinal and liver function by regulating intestinal flora balance and repairing the intestinal immune barrier to regulate the intestinal-liver axis. Our results indicated that C. violaceum polysaccharides possessed favorable antioxidant, anti-inflammatory and potentially anti-aging effects in vivo.
The road to incorporating Scottish pelagic industry data in science for stock assessments
Authors: Mackinson Steven , Brigden Katie , Craig Jessica , Clarke Elizabeth D. , Angus Chevonne , Pert Campbell C.
Published: April 2023

Fisheries data collection through industry-science partnerships have significant potential to support stock assessments and sustainable management, but few studies have described the steps taken en route to a successful partnership. This paper describes the development of the Scottish Pelagic Industry-Science Data Collection Programme; why and how it started, and what it has taken to develop a routine and consistent voluntary sampling regime of sufficient quality to become the main source of biological data on pelagic fish catches in Scotland. Using our experience, we emphasise the importance of establishing procedures that ensure the quality of methods and results, of working with institutions responsible for provision of national data, and of actively engaging with the International Council for the Exploration of the Sea (ICES) workshops and working groups on data quality, stock assessment and stakeholder engagement. The development of the programme has been, and remains to be, a mutual learning process which is reflected upon from our different institutional perspectives. The experience gained during this work has built knowledge useful for practitioners in other situations. Specifically, we identify five transferable design principles that we believe have been essential to success so far. Finally, we look at the steps ahead in our efforts toward continuous improvements.
Effect of dietary bile acids supplementation on growth performance, feed utilization, intestinal digestive enzyme activity and fatty acid transporters gene expression in juvenile leopard coral grouper (Plectropomus leopardus)
Authors: Gao Yujie , Yao Yifan , Huang Jie , Sun Yuejia , Wu Qingjun , Guo Dingqian , Wang Shengpeng
Published: April 2023

This study aimed to evaluate the effects of dietary bile acids on growth performance, feed utilization, body composition, digestive enzyme activity, and related gene expression in juvenile leopard coral grouper (Plectropomus leopardus). Five diets with varying levels of dietary bile acids (0, 0.15, 0.3, 0.45 and 0.6%) were formulated and each diet was fed to triplicate groups of 15 fish (13.14 ± 0.14 g) for ten weeks. Results showed that the significant enhancement in weight gain (WG) and specific growth rate (SGR) was observed in fish fed 0.3% bile acids (P < 0.05). Additionally, feed conversion ratio (FCR) was significantly improved with bile acids inclusion (P < 0.05). Higher feed intake was also recorded in bile acids inclusion groups, and significantly up-regulated gene expression of hypothalamus neuropeptide Y (NPY) was found in 0.3% group compared with the control group (P < 0.05). Dietary bile acids (0.3%) significantly decreased lipid deposition in the whole-body (P < 0.05), and lower hepatosomatic index (HSI) and viscerosomatic index (VSI) were also found in this group. Moreover, intestinal trypsin and lipase activities were significantly increased in 0.3% group (P < 0.05) to promote feed digestion. In addition, the relative expression levels of intestinal fatty acid binding protein 2 (FABP2) significantly up-regulated with inclusion of dietary bile acids, suggesting an enhancement of fatty acid transport (P < 0.05). In contrast, cholesterol transport related genes NPC1 like intracellular cholesterol transporter 1 (NPC1L1) and CD36 were notably down-regulated as bile acids inclusion (P < 0.05). This study provides valuable information for the formulation of diets for juvenile coral trout and indicates that dietary bile acids could potentially be used to improve growth performance and feed utilization.
The roles of autophagy and mitophagy in corneal pathology: current knowledge and future perspectives
Authors: Ayilam Ramachandran Rajalakshmy , Sanches Jose Marcos , Robertson Danielle M.
Published: April 2023

The cornea is the clear dome that covers the front portion of the globe. The primary functions of the cornea are to promote the refraction of light and to protect the eye from invading pathogens, both of which are essential for the preservation of vision. Homeostasis of each cellular layer of the cornea requires the orchestration of multiple processes, including the ability to respond to stress. One mechanism whereby cells respond to stress is autophagy, or the process of “self-eating.” Autophagy functions to clear damaged proteins and organelles. During nutrient deprivation, amino acids released from protein breakdown via autophagy are used as a fuel source. Mitophagy, a selective form of autophagy, functions to clear damaged mitochondria. Thus, autophagy and mitophagy are important intracellular degradative processes that sustain tissue homeostasis. Importantly, the inhibition or excessive activation of these processes result in deleterious effects on the cell. In the eye, impairment or inhibition of these mechanisms have been associated with corneal disease, degenerations, and dystrophies. This review summarizes the current body of knowledge on autophagy and mitophagy at all layers in the cornea in both non-infectious and infectious corneal disease, dystrophies, and degenerations. It further highlights the critical gaps in our understanding of mitochondrial dysfunction, with implications for novel therapeutics in clinical practice.
Rating and ranking preparedness characteristics important for veterinary workplace clinical training: a novel application of pairwise comparisons and the Elo algorithm
Authors: Routh Jennifer , Paramasivam Sharmini Julita , Cockcroft Peter , Wood Sarah , Remnant John , Westermann Cornélie , Reid Alison , Pawson Patricia , Warman Sheena , Nadarajah Vishna Devi , Jeevaratnam Kamalan
Published: April 2023

Quantitatively eliciting perspectives about a large number of similar entities (such as a list of competences) is a challenge for researchers in health professions education (HPE). Traditional survey methods may include using Likert items. However, a Likert item approach that generates absolute ratings of the entities may suffer from the “ceiling effect,” as ratings cluster at one end of the scale. This impacts on researchers’ ability to detect differences in ratings between the entities themselves and between respondent groups. This paper describes the use of pairwise comparison (this or that?) questions and a novel application of the Elo algorithm to generate relative ratings and rankings of a large number of entities, on a unidimensional scale. A study assessing the relative importance of 91 student “preparedness characteristics” for veterinary workplace clinical training (WCT) is presented as an example of this method in action. The Elo algorithm uses pairwise comparison responses to generate an importance rating for each preparedness characteristic on a scale from zero to one. This is continuous data with measurement variability which, by definition, spans an entire spectrum and is not susceptible to the ceiling effect. The output should allow for the detection of differences in perspectives between groups of survey respondents (such as students and workplace supervisors) which Likert ratings may be insensitive to. Additional advantages of the pairwise comparisons are their low susceptibility to systematic bias and measurement error, they can be quicker and arguably more engaging to complete than Likert items, and they should carry a low cognitive load for respondents. Methods for evaluating the validity and reliability of this survey design are also described. This paper presents a method that holds great potential for a diverse range of applications in HPE research. In the pursuit quantifying perspectives on survey items which are measured on a relative basis and a unidimensional scale (e.g., importance, priority, probability), this method is likely to be a valuable option.
Hypoxia-induced Wnt/β-catenin signaling activation in subchondral bone osteoblasts leads to an osteoarthritis-like phenotype of chondrocytes in articular cartilage
Authors: Li Fang , Tan Qizhao , Li Feng , Zhang Ke , Liu Zhongjun , Tian Yun , Zhu Tengjiao
Published: April 2023

Background: Osteoarthritis (OA) is a whole-joint disease and characterized by alterations in the articular cartilage, subchondral bone, ligaments, and synovial membrane. The crosstalk between cartilage and subchondral bone plays a crucial role in the pathogenesis and progression of OA. Hypoxia has been reported to play an important role in cartilage degradation and subchondral bone remodeling in OA. In this study, we aimed to identify the involvement of hypoxia in modifying the osteoblast phenotypes and determine whether these alterations could influence the metabolism of chondrocytes.

Methods: First, the levels of Hif-1α in subchondral bone of different compartments in patients with OA were assessed using immunohistochemistry (IHC). In in vitro, human primary osteoblasts were cultured under hypoxic and normoxic conditions, and the hypoxic or normoxic conditioned media (HCM and NCM) were used to culture human primary chondrocytes. Then, phenotypic changes in osteoblasts were assessed using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the expression of type II collagen (COL2A1), aggrecan (ACAN), SRY-related high-mobility group-box gene 9 (SOX9), matrix metalloproteinase 13 (MMP13), and matrix metalloproteinase 3 (MMP3) in chondrocytes was measured using RT-PCR. Finally, the serum levels of Wnt-related proteins were determined using ELISA.

Results: Hif-1α was significantly increased in severely sclerotic subchondral bone compared to less damaged subchondral bone. β-Catenin and SOST were identified as upregulated and downregulated in hypoxic osteoblasts, respectively. The hypoxia-induced results were confirmed by ELISA. Stimulating human primary chondrocytes with HCM significantly induced MMP13 and MMP3 and inhibited COL2A1, ACAN, and SOX9 mRNA expression. The serum levels of DKK-1 were significantly increased in human OA.

Conclusion: Together, these findings revealed that hypoxia in subchondral bone is a key factor in the crosstalk between chondrocytes and osteoblasts and facilitates the shift of chondrocytes toward an OA-like phenotype probably by activating the Wnt/β-catenin signaling pathway in osteoblasts.
A directionally selective collision-sensing visual neural network based on fractional-order differential operator
Authors: Wang Yusi , Li Haiyang , Zheng Yi , Peng Jigen
Published: April 2023

In this paper, we propose a directionally selective fractional-order lobular giant motion detector (LGMD) visual neural network. Unlike most collision-sensing network models based on LGMDs, our model can not only sense collision threats but also obtain the motion direction of the collision object. Firstly, this paper simulates the membrane potential response of neurons using the fractional-order differential operator to generate reliable collision response spikes. Then, a new correlation mechanism is proposed to obtain the motion direction of objects. Specifically, this paper performs correlation operation on the signals extracted from two pixels, utilizing the temporal delay of the signals to obtain their position relationship. In this way, the response characteristics of direction-selective neurons can be characterized. Finally, ON/OFF visual channels are introduced to encode increases and decreases in brightness, respectively, thereby modeling the bipolar response of special neurons. Extensive experimental results show that the proposed visual neural system conforms to the response characteristics of biological LGMD and direction-selective neurons, and that the performance of the system is stable and reliable.
Trimethylamine-N-oxide: a potential biomarker and therapeutic target in ischemic stroke
Authors: Liu Yuan , Qu Juan , Xu Junjie , Gu Aiming , Deng Dezhi , Jia Xiaodan , Wang Baoxiang
Published: April 2023

Ischemic stroke is by far the most common cerebrovascular disease and a major burden to the global economy and public health. Trimethylamine-N-oxide (TMAO), a small molecule compound produced by the metabolism of intestinal microorganisms, is reportedly associated with the risk of stroke, as well as the severity and prognosis of stroke; however, this conclusion remains contentious. This article reviews the production of TMAO, TMAO’s relationship with different etiological types of ischemic stroke, and the possibility of reducing TMAO levels to improve the prognosis of ischemic stroke.
Isolating the speed factor is crucial in gait analysis for Parkinson’s disease
Authors: Patoz Aurélien , Malatesta Davide , Burtscher Johannes
Published: April 2023

Introduction

Parkinson’s disease (PD) is characterized by an alteration of the walking gait, frequently including a slower self-selected walking speed (SSWS). Although the reduction of walking speed is inherent to people with PD, such speed reduction also represents a potential confounding factor that might partly explain the observed gait differences between PD and control participants.

Methods

In this study, each participant walked along a 25 m level corridor during which vertical ground reaction force signals were recorded using shoes equipped with eight pressure sensors. Vertical ground reaction force signals (using statistical parametric mapping) and temporal and kinetic variables as well as their related variability and asymmetry (using Student’s t-test) were compared between PD (n = 54) and walking-speed-matched control subjects (n = 39).

Results

Statistical parametric mapping did not yield significant differences between PD and control groups for the vertical ground reaction force signal along the walking stance phase. Stride time and single support time (equivalent to swing time) were shorter and peak vertical ground reaction force was larger in PD patients compared to controls (p ≤ 0.05). However, the single support time was no longer different between people with PD and healthy subjects when expressed relatively to stride time (p = 0.07). While single support, double support, and stance times were significantly more variable and asymmetric for PD than for the control group (p ≤ 0.05), stride time was similar (p ≥ 0.07).

Discussion

These results indicate that at matched SSWS, PD patients adopt a higher cadence than control participants. Moreover, the temporal subdivision of the walking gait of people with PD is similar to healthy individuals but the coordination during the double support phase is different. Hence, this study indicates that isolating the speed factor is crucial in gait analysis for PD.
Calcium-binding properties, stability, and osteogenic ability of phosphorylated soy peptide-calcium chelate
Authors: Kong Xiao , Xiao Ziqun , Chen Yuhang , Du MengDi , Zhang Zihui , Wang Zhenhua , Xu Bo , Cheng Yongqiang , Yu Tianying , Gan Jing
Published: April 2023

Introduction

Bioactive peptides based on foodstuffs are of particular interest as carriers for calcium delivery due to their safety and high activity. The phosphorylated peptide has been shown to enhance calcium absorption and bone formation.

Method

A novel complex of peptide phosphorylation modification derived from soybean protein was introduced, and the mechanism, stability, and osteogenic differentiation bioactivity of the peptide with or without calcium were studied.

Result

The calcium-binding capacity of phosphorylated soy peptide (SPP) reached 50.24 ± 0.20 mg/g. The result of computer stimulation and vibration spectrum showed that SPP could chelate with calcium by the phosphoric acid group, carboxyl oxygen of C-terminal Glu, Asp, and Arg, and phosphoric acid group of Ser on the SPP at a stoichiometric ratio of 1:1, resulting in the formation of the complex of ligand and peptide. Thermal stability showed that chelation enhanced peptide stability compared with SPP alone. Additionally, in vitro results showed that SPP-Ca could facilitate osteogenic proliferation and differentiation ability.

Discussion

SPP may function as a promising alternative to current therapeutic agents for bone loss.
Potential therapeutic benefits of unconventional oils: assessment of the potential in vitro biological properties of some Rubiaceae, Cucurbitaceae, and Brassicaceae seed oils
Authors: Fratianni Florinda , Amato Giuseppe , De Feo Vincenzo , d'Acierno Antonio , Coppola Raffaele , Nazzaro Filomena
Published: April 2023

Introduction

Seed oils are versatile in the food sector and for pharmaceutical purposes. In recent years, their biological properties aroused the interest of the scientific world.

Materials and methods

We studied the composition of fatty acids (FAs) and some in vitro potential therapeutic benefits of five cold-pressed commercial oils obtained from broccoli, coffee, green coffee, pumpkin, and watermelon seeds. In particular, we assayed the antioxidant activity (using diphenyl-1-picrylhydrazyl (DPPH) and azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays). In addition, through the fatty acid composition, we calculated the atherogenicity index (AI) and thrombogenicity index (TI) to evaluate the potential impact of such oils on cardiovascular diseases. Furthermore, we assessed the in vitro anti-inflammatory capacity of the oils (evaluated through their effectiveness in preventing protein degradation, using bovine serum albumin as protein standard) and the ability of the oils to inhibit in vitro activity of three among the essential enzymes, cholinesterases and tyrosinase, involved in the Alzheimer's and Parkinson's neurodegenerative diseases. Finally, we evaluated the capacity of the oils to inhibit the biofilm of some pathogenic bacteria.

Results

The unsaturated fatty acids greatly predominated in broccoli seed oil (84.3%), with erucic acid as the main constituent (33.1%). Other unsaturated fatty acids were linolenic (20.6%) and linoleic (16.1%) acids. The saturated fatty acids fraction comprised the palmitic (6.8%) and stearic acids (0.2%). Broccoli seed oil showed the best AI (0.080) and TI (0.16) indexes. The oils expressed a good antioxidant ability. Except for the watermelon seed oil, the oils exhibited a generally good in vitro anti-inflammatory activity, with IC50 values not exceeding 8.73 micrograms. Broccoli seed oil and green coffee seed oil showed the best acetylcholinesterase inhibitory activity; coffee seed oil and broccoli seed oil were the most effective in inhibiting butyrylcholinesterase (IC50 = 15.7 μg and 20.7 μg, respectively). Pumpkin and green coffee seed oil showed the best inhibitory activity against tyrosinase (IC50 = 2 μg and 2.77 μg, respectively). In several cases, the seed oils inhibited the biofilm formation and the mature biofilm of some gram-positive and gram-negative bacteria, with Staphylococcus aureus resulting in the most sensitive strain. Such activity seemed related only in some cases to the capacity of the oils to act on the sessile bacterial cells' metabolism, as indicated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method.
The short-term efficacy and safety of induction chemotherapy combined with PD-1 inhibitor or anti-EGFR in locoregionally advanced nasopharyngeal carcinoma
Authors: Xiang Xiaoyong , Chen Peng , Lan Fengming , Ma Li , Jin Jing , Zhang Ye
Published: April 2023

Purpose

This study aimed to investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with PD-1 inhibitor or anti-EGFR in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC).

Methods and materials

We retrospectively reviewed the clinical data of 206 patients with LA-NPC, including IC combined with anti-PD-1 (57 patients), IC combined with anti-EGFR (28 patients), and IC alone (121 patients). The short-term efficacy was assessed at the end of IC and one month after overall treatment. According to the RECIST v1.1, the short-term efficacy of cervical lymph nodes and primary nasopharynx foci was divided into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). The overall response (ORR) was defined as the sum of CR and PR. Acute toxicities were graded according to the CTCAE v5.0. One-way analysis of variance (ANOVA) was used to compare differences in the numerical variables among groups. Fisher Freeman-Halton test or Pearson Chi-square test was used to compare classified variables.

Results

The ORR rates of primary nasopharynx foci in IC, anti-EGFR, and anti-PD-1 group were 68.60%, 67.9%, and 94.7%, respectively, and the corresponding rates of ORR in cervical lymph nodes were 78.5%, 71.4%, and 93.0%, respectively. There was a statistical difference in the ORR between the three groups. Further analysis showed that after IC or overall treatment, the CR rate of primary nasopharynx foci in the anti-PD-1 group was significantly higher than the other two groups. The most common adverse effects were hematotoxicity, gastrointestinal toxicity, and transaminase elevation. However, there were no statistical differences in the frequency of any common adverse effects between the three groups.

Conclusions

The addition of anti-PD-1 based on IC significantly improved the short-term efficacy of LA-NPC and toxicities were tolerable.
The effect of triple reuptake inhibitor toludesvenlafaxine on neurological function in cerebral ischemic rats
Authors: Sun Xiaohui , Wang Tian , Zhou Lin , Zhang Ce , Fu Fenghua
Published: April 2023

Purpose: The aim is to investigate the effect of toludesvenlafaxine (Tdv), a reuptake inhibitor of serotonin, norepinephrine, and dopamine, on the neurological function in cerebral ischemic rats and the underlying mechanisms.

Material and Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) model was induced in rats and the neuroprotective effects of Tdv were evaluated by infarct size, Garcia test, and beam walking test. Neuronal apoptosis in the peri-infarct area was observed by TUNEL staining. And the apoptosis-related proteins were evaluated with Western blotting. The role of CREB pathway in effect of Tdv was also investigated using Western blotting and immunofluorescence.

Results: In the MCAO/R model, administration of Tdv reduced the infarct size, promoted neural functional recovery, decreased the expression of Bax and Caspase-3, and increased the expression of Bcl-2 and BDNF. In addition, Tdv reduced neuronal apoptosis in the peri-infarct area. Tdv increased the expression of phosphorylated CREB. The application of the specific CREB inhibitor, compound 666-15, could reverse the anti-ischemic cerebral injury of Tdv in MCAO/R rats.

Conclusion: Tdv ameliorated cerebral ischemic injury through reducing neuronal apoptosis and increasing the expression of BDNF via the activation of CREB pathway.
Immunomodulatory biomaterials on chemokine signaling in wound healing
Authors: Apte Anisha , Liechty Kenneth W. , Zgheib Carlos
Published: April 2023

Normal wound healing occurs through a careful orchestration of cytokine and chemokine signaling in response to injury. Chemokines are a small family of chemotactic cytokines that are secreted by immune cells in response to injury and are primarily responsible for recruiting appropriate immune cell types to injured tissue at the appropriate time. Dysregulation of chemokine signaling is suspected to contribute to delayed wound healing and chronic wounds in diseased states. Various biomaterials are being used in the development of new therapeutics for wound healing and our understanding of their effects on chemokine signaling is limited. It has been shown that modifications to the physiochemical properties of biomaterials can affect the body’s immune reaction. Studying these effects on chemokine expression by various tissues and cell type can help us develop novel biomaterial therapies. In this review, we summarize the current research available on both natural and synthetic biomaterials and their effects on chemokine signaling in wound healing. In our investigation, we conclude that our knowledge of chemokines is still limited and that many in fact share both pro-inflammatory and anti-inflammatory properties. The predominance of either a pro-inflammatory or anti-inflammatory profile is mostly likely dependent on timing after injury and exposure to the biomaterial. More research is needed to better understand the interaction and contribution of biomaterials to chemokine activity in wound healing and their immunomodulatory effects.
Efficacy and safety of apatinib versus sorafenib/placebo in first-line treatment for intermediate and advanced primary liver cancer: A systematic review and meta-analysis
Authors: Peng Dan , Cai Yongqing , Chen Geng , Hou Min , Luo Xiaofeng , Dongzhi Zhuoma , Xie Hongjun , Liu Yao
Published: April 2023

Background: Apatinib is a novel tyrosine kinase inhibitor used in the treatment of advanced hepatocellular carcinoma (HCC). For decades, sorafenib has been a classic first-line treatment option for patients with HCC. This meta-analysis aimed to assess the efficacy and safety of apatinib versus sorafenib/placebo as first-line treatment for intermediate and advanced primary liver cancer (PLC).

Methods: A literature search was performed via PubMed, Web of Science, CENTRAL, Embase, CNKI, VIP, and CBM. Data extraction from databases of other languages is not restricted. The Cochrane risk of bias tool, modified Jadad scale, Newcastle–Ottawa scale (NOS), and non-randomized studies of interventions (ROBINS-I) tool were employed to evaluate methodological qualities in original studies. Influence analysis was applied to assess the reliability of pooled results. Publication bias was evaluated using the funnel plot with Begg’s test and Egger’s test.

Results: Seven studies were included in the systematic review and meta-analysis. Four randomized controlled trials (RCTs) and one clinical controlled trial (CCT) were used for comparing apatinib with placebo, and two retrospective clinical studies (RCSs) were used for comparing apatinib with sorafenib. Apatinib led to higher overall effects in objective response rate (ORR), disease control rate (DCR), and mean survival time (MST) over placebo (RR = 2.03, 95% CI = 1.46–2.81, p < 0.0001, I2 = 0%; RR = 1.17, 95% CI = 1.04–1.33, p = 0.009, I2 = 45.8%; SMD = 2.63; 95% CI = 1.47–3.78, p < 0.0001, I2 = 92.7%, respectively). Compared to sorafenib, apatinib showed no superiority in ORR and DCR but was inferior in the 6-month and 1-year survival rate (RR = 1.99, 95% CI = 0.85–4.65, p = 0.111, I2 = 68.3%; RR = 1.04, 95% CI = 0.73–1.47, p = 0.840, I2 = 0.0%; RR = 0.63, 95% CI = 0.42–0.97, p = 0.036, I2 = 0.0%; RR = 0.47, 95% CI = 0.29–0.79, p < 0.0001, I2 = 0.0%, respectively). Apatinib had similar adverse effects over placebo but possessed a greater incidence rate of proteinuria and hypertension over sorafenib.

Conclusion: In the first-line setting, apatinib might be an alternative treatment approach for patients with intermediate and advanced PLC. Sorafenib alone showed a better survival rate within 1 year and a lower incidence rate in hypertension and proteinuria than apatinib monotherapy.
Biological evaluation and in silico studies of novel compounds as potent TAAR1 agonists that could be used in schizophrenia treatment
Authors: Wang Yunjie , Liu Zhaofeng , Lu Jing , Wang Wenyan , Wang Lin , Yang Yifei , Wang Hongbo , Ye Liang , Zhang Jianzhao , Tian Jingwei
Published: April 2023

Introduction: Schizophrenia is a serious mental illness that requires effective treatment with minimal adverse effects. As preclinical and clinical research progresses, trace amine-associated receptor 1 (TAAR1) is becoming a potential new target for the treatment of schizophrenia.

Methods: We used molecular docking and molecular dynamics (MD) simulations to discover TAAR1 agonists. The agonistic or inhibitory effects of compounds on TAAR1, 5-HT1A, 5-HT2A, and dopamine D2-like receptors were determined. We used an MK801-induced schizophrenia-like behavior model to assess the potential antipsychotic effects of compounds. We also performed a catalepsy assay to detect the adverse effects. To evaluate the druggability of the compounds, we conducted evaluations of permeability and transporter substrates, liver microsomal stability in vitro, human ether-à-go-go-related gene (hERG), pharmacokinetics, and tissue distribution.

Results: We discovered two TAAR1 agonists: compounds 50A and 50B. The latter had high TAAR1 agonistic activity but no agonistic effect on dopamine D2-like receptors and demonstrated superior inhibition of MK801-induced schizophrenia-like behavior in mice. Interestingly, 50B had favorable druggability and the ability to penetrate the blood-brain barrier (BBB) without causing extrapyramidal symptoms (EPS), such as catalepsy in mice.

Conclusion: These results demonstrate the potential beneficial role of TAAR1 agonists in the treatment of schizophrenia. The discovery of a structurally novel TAAR1 agonist (50B) may provide valuable assistance in the development of new treatments for schizophrenia.