bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital inclusive finance and the development of sports industry: An empirical study from the perspective of upgrading the living level of rural residents
Authors: Huang Hui , Zhang Yunxuan
Published: October 2022

With the development of science and technology, digital inclusive finance has been widely used in various fields and has promoted the development of industrial structures. The development of the sports industry is a realistic option for improving public health problems and sustainable economic development. In this study, we understand the impact of digital inclusion finance on the sports industry from the perspective of upgrading the living standards of rural residents. Using relevant data from some domestic provinces in China from 2015–2019 as a sample, we explore the relationship between digital inclusion finance and the sports industry and analyse whether the living standards of rural residents play a mediating role. The study finds that: firstly, digital inclusive finance has a facilitating effect on the development of the sports industry. Secondly, digital inclusive finance can create a scale effect by increasing rural per capita disposable income, which in turn promotes the development of the sports industry. Thirdly, digital inclusive finance will use its digital and precise characteristics to precisely improve the consumption structure of rural residents, thus promoting the development of the sports industry. The study enriches the research related to digital economy represented by digital inclusive finance, and has important practical guidance significance for the development of China’s sports industry.
Environmental fate of cefquinome: Adsorption and degradation
Authors: Qiu Jicheng , Yang Yuxin , Kong Jingyuan , Cao Yuying , Liu Yu , Sun Feifei , Cao Xingyuan
Published: October 2022

Cefquinome (CEQ), the fourth generation of cephalosporins, has been widely used in practice for the treatment of bacterial infections due to its broad antimicrobial spectrum, stability, and stronger antibacterial activity. However, the wide use of CEQ can cause an environmental risk via animal excretion. In the current study, the environmental fate of CEQ was investigated. The migration rate of CEQ from soil to the aquatic environment was approximately 60%. The half-life (T1/2) of CEQ degradation in the water ranged from 0.96 to 13.75 d. Our results showed that the temperature, illumination, and pH had an effect on the degradation rate, and the rate of CEQ degradation was significantly accelerated under high temperatures. CEQ was more stable in acidic environments than in alkaline. E-isomer of CEQ and △3-isomer of CEQ were the major degradation metabolites identified by UPLC-Q-Orbitrap MS. The product ion m/z 293.041 was the typical fragment ion for E-isomer of CEQ, and m/z 201.044 and m/z 152.016 were the typical fragment ion for △3-isomer of CEQ. The degradation metabolites exhibited lower antibacterial activity, simultaneously, the toxicity of the E-isomer of CEQ should pay more attention to.
Association of toll-like receptors polymorphisms with COPD risk in Chinese population
Authors: Sun Shulei , Shen Yuehao , Feng Jing
Published: October 2022

Background: Previous studies have reported that the Toll-like receptors (TLRs) are related with the progress of chronic obstructive pulmonary disease (COPD). We aimed to explore the association of TLRs single nucleotide polymorphisms (SNPs) and COPD risk.

Methods: 170 COPD patients and 181 healthy controls were enrolled in this case-control study. MassARRAY platform was used for genotyping seven tagging SNPs (TLR2: rs3804100, rs4696480, rs3804099; TLR3: rs3775290, rs3775291, rs5743305; TLR9: rs352140) of TLRs. The correlations between the SNPs and COPD risk were determined using logistic regression.

Results: We found that the rs3775291 of TLR3 significant decreased the risk of COPD (TT versus CC: non-adjusted OR = 0.329, 95% CI = 0.123–0.879, p = 0.027). In the genetic models analysis, the rs3775291 was associated with a decreased effect of COPD based on the recessive model (TT versus CC/CT: non-adjusted OR = 0.377, 95% CI = 0.144–0.988 p = 0.047). The rs4696480 of TLR2 gene was associated with a decreased risk of COPD after adjustment by age and gender (TA versus AA: adjusted OR = 0.606, 95% CI = 0.376–0.975, p = 0.039).

Conclusion: Our study showed that genetic variants in TLRs were associated with risk of COPD. The rs3775291 and rs4696480 may act as a potential biomarker for predicting the risk of COPD in Chinese population.
New insights into iNKT cells and their roles in liver diseases
Authors: Gu Xinyu , Chu Qingfei , Ma Xiao , Wang Jing , Chen Chao , Guan Jun , Ren Yanli , Wu Shanshan , Zhu Haihong
Published: October 2022

Natural killer T cells (NKTs) are an important part of the immune system. Since their discovery in the 1990s, researchers have gained deeper insights into the physiology and functions of these cells in many liver diseases. NKT cells are divided into two subsets, type I and type II. Type I NKT cells are also named iNKT cells as they express a semi-invariant T cell-receptor (TCR) α chain. As part of the innate immune system, hepatic iNKT cells interact with hepatocytes, macrophages (Kupffer cells), T cells, and dendritic cells through direct cell-to-cell contact and cytokine secretion, bridging the innate and adaptive immune systems. A better understanding of hepatic iNKT cells is necessary for finding new methods of treating liver disease including autoimmune liver diseases, alcoholic liver diseases (ALDs), non-alcoholic fatty liver diseases (NAFLDs), and liver tumors. Here we summarize how iNKT cells are activated, how they interact with other cells, and how they function in the presence of liver disease.
Functional identification of the zebrafish Interleukin-1 receptor in an embryonic model of Il-1β-induced systemic inflammation
Authors: Sebo Dylan J. , Fetsko Audrey R. , Phipps Kallie K. , Taylor Michael R.
Published: October 2022

Interleukin-1β (IL-1β) is a potent proinflammatory cytokine that plays a vital role in the innate immune system. To observe the innate immune responsein vivo, several transgenic zebrafish lines have been developed to model IL-1β-induced inflammation and to visualize immune cell migration and proliferation in real time. However, our understanding of the IL-1β response in zebrafish is limited due to an incomplete genome annotation and a lack of functional data for the cytokine receptors involved in the inflammatory process. Here, we use a combination of database mining, genetic analyses, and functional assays to identify zebrafish Interleukin-1 receptor, type 1 (Il1r1). We identified putative zebrafishil1r1candidate genes that encode proteins with predicted structures similar to human IL1R1. To examine functionality of these candidates, we designed highly effective morpholinos to disrupt gene expression in a zebrafish model of embryonic Il-1β-induced systemic inflammation. In this double transgenic model,ubb:Gal4-EcR,uas:il1βmat, the zebrafishubiquitin b(ubb) promoter drives expression of the modified Gal4 transcription factor fused to the ecdysone receptor (EcR), which in turn drives the tightly-regulated expression and secretion of mature Il-1β only in the presence of the ecdysone analog tebufenozide (Teb). Application of Teb toubb:Gal4-EcR,uas:il1βmatembryos causes premature death, fin degradation, substantial neutrophil expansion, and generation of reactive oxygen species (ROS). To rescue these deleterious phenotypes, we injectedubb:Gal4-EcR,uas:il1βmatembryos with putativeil1r1morpholinos and found that knockdown of only one candidate gene prevented the adverse effects caused by Il-1β. Mosaic knockout ofil1r1using the CRISPR/Cas9 system phenocopied these results. Taken together, our study identifies the functional zebrafish Il1r1 utilizing a genetic model of Il-1β-induced inflammation and provides valuable new insights to study inflammatory conditions specifically driven by Il-1β or related to Il1r1 function in zebrafish.
Non-criteria antiphospholipid antibodies in antiphospholipid syndrome: Diagnostic value added
Authors: Liu Xiangjun , Zhu Lei , Liu Hongjiang , Cai Qingmeng , Yun Zelin , Sun Feng , Jia Yuan , Guo Jianping , Li Chun
Published: October 2022

Objective

Non-criteria antiphospholipid antibodies (aPLs) increase the diagnostic value for antiphospholipid syndrome (APS) and contribute to better recognition of seronegative APS (SNAPS). However, the clinical utility and the diagnostic value of non-criteria aPLs are inconsistent. This study aimed to investigate the prevalence and clinical significance of 7 non-criteria aPLs in a large APS cohort.

Methods

Seven non-criteria aPLs, including anti-phosphatidylserine/prothrombin (aPS/PT) antibodies IgG/IgA/IgM, anti-phosphatidylethanolamine antibodies (aPE) IgG/IgA/IgM, anti-Annexin V antibodies (aAnnexinV) IgG/IgA/IgM, anti-phosphatidylserine antibodies (aPS) IgM, aPS IgG, antibodies directed against a mixture of phospholipids (APhL) IgG, and APhL IgM were tested among 175 patients with APS, 122 patients with other autoimmune diseases (as disease controls), and 50 healthy controls.

Results

In the present study, the highest prevalence of non-criteria aPLs was seen in aAnnexinV (58.86%). APhL IgG and aPS IgM showed the highest specificity (95.35%) and aPS/PT showed the highest Youden index (0.3991) for the diagnostic value of APS. The aAnnexinV also showed the highest prevalence in SNAPS (43.3%), followed by APhL IgM (21.7%), aPE (16.7%) and aPS/PT (16.7%). APhL IgG, aPS/PT, and aPS IgG showed positive association with thrombotic events in APS patients [APhL IgG: odds ratio (OR) = 2.26, 95% confidence interval (CI) 1.18-4.34, p = 0.013; aPS/PT: OR = 2.48, 95% CI: 1.32-4.69, p = 0.004; aPS IgG: OR = 1.90, 95% CI 1.01-3.60, p = 0.046; respectively). The inclusion of the non-criteria aPLs increased the accuracy of APS diagnosis from 65.7% to 87.4%.

Conclusion

Our data provide evidence that adding the non-criteria aPLs can improve the diagnostic accuracy in APS. APhL IgG, aPS/PT, and aPS IgG may be potential biomarkers to predict the risk of thrombosis in APS.
Integrating transcriptomics and network analysis-based multiplexed drug repurposing to screen drug candidates for M2 macrophage-associated castration-resistant prostate cancer bone metastases
Authors: Chang Jinyuan , Jiang Zhenglong , Ma Tianyu , Li Jie , Chen Jiayang , Ye Peizhi , Feng Li
Published: October 2022

Metastatic castration-resistant prostate cancer (CRPC) has long been considered to be associated with patient mortality. Among metastatic organs, bone is the most common metastatic site, with more than 90% of advanced patients developing bone metastases (BMs) before 24 months of death. Although patients were recommended to use bone-targeted drugs represented by bisphosphonates to treat BMs of CRPC, there was no significant improvement in patient survival. In addition, the use of immunotherapy and androgen deprivation therapy is limited due to the immunosuppressed state and resistance to antiandrogen agents in patients with bone metastases. Therefore, it is still essential to develop a safe and effective therapeutic schedule for CRPC patients with BMs. To this end, we propose a multiplex drug repurposing scheme targeting differences in patient immune cell composition. The identified drug candidates were ranked from the perspective of M2 macrophages by integrating transcriptome and network-based analysis. Meanwhile, computational chemistry and clinical trials were used to generate a comprehensive drug candidate list for the BMs of CRPC by drug redundancy structure filtering. In addition to docetaxel, which has been approved for clinical trials, the list includes norethindrone, testosterone, menthol and foretinib. This study provides a new scheme for BMs of CRPC from the perspective of M2 macrophages. It is undeniable that this multiplex drug repurposing scheme specifically for immune cell-related bone metastases can be used for drug screening of any immune-related disease, helping clinicians find promising therapeutic schedules more quickly, and providing reference information for drug R&D and clinical trials.
Microplastic particles are phagocytosed in gill cells of deep-sea and coastal mussels
Authors: Ikuta Tetsuro , Tame Akihiro , Takahashi Tomoko , Nomaki Hidetaka , Nakajima Ryota
Published: October 2022

It is becoming obvious that the abundance of microplastics is increasing in worldwide oceans, raising concerns about their impact on marine ecosystems. Tiny plastic particles enter the body of marine organisms not only via oral ingestion but also through the body surface (e.g., gills or epidermis), but the mechanism of internalization into cells is poorly understood. In this study, we conducted experiments using deep-sea chemosynthetic mussels with limited feeding by exposing their gills to fluorescently labeled microplastic beads. We identified the gill cell types that preferentially internalized the beads and demonstrated the inhibitory effect of phagocytosis inhibitors on bead uptake. Furthermore, using correlative light-electron microscopy, we microhistologically verified that beads were enclosed within membrane-bound vacuoles. Our results indicated that microplastic particles were internalized into gill cells of deep-sea and coastal mussels by phagocytosis. This study highlights the need for further research on plastic contamination via the body surface to conserve the highly endemic and vulnerable deep-sea fauna and mitigate human health risks from consuming coastal bivalves.
Drifting marine plastics as new ecological habitats for harmful eukaryotic microbial communities in Jeju Strait, Korea
Authors: Lee Bora , Park Myung Gil
Published: October 2022

Micro/macro plastics are ubiquitous and are emerging agents causing many ecological problems in marine environments. Plastics carry various fouling organisms, including harmful microorganisms, that could potentially have ecological impacts on the marine environment and eventually human health. In this study, marine micro/macro plastics drifting at multiple locations in the Jeju Strait and around Jeju Island, Korea, were collected and analyzed. DNA metabarcoding and scanning electron microscopy were used to characterize the species composition of the attached eukaryotic microbial communities, with a special emphasis on harmful or toxic dinoflagellates, fungi, and parasites. A total of 1,035 eukaryotic microbial operational taxonomic units (OTUs) were identified from plastics and surrounding seawater samples. Two types of samples shared half of the eukaryotic OTUs, and of which approximately 12% were unique to plastic samples. These included 68 Archaeplastida (54.0%), 45 Stramenopiles (35.7%), 12 Opisthokonta (9.5%), and 3 Alveolata (2.4%) OTUs. The harmful or toxic dinoflagellates observed on the plastic surface were Alexandrium, Coolia, Dinophysis, Heterocapsa, Karlodinium, Noctiluca, Ostreopsis, Prorocentrum, Scrippsiella, and Tripos. The most dominant parasite community of the plastisphere was represented by fungi (42% of all parasite OTUs), followed by Oomycota (33%), Stramenopiles (14%), and dinoflagellates (12%). Nonetheless, this study demonstrates that the eukaryotic communities are considerably shared between the plastisphere and seawater. This implies plastics serve as a new ecological habitat in the sea and could function as dispersal vectors that facilitate the spread of harmful eukaryotic species and parasites.
The use of habitat suitability modelling for seagrass: A review
Authors: Bertelli Chiara M. , Stokes Holly J. , Bull James C. , Unsworth Richard K. F.
Published: October 2022

Coastal ecosystems, including coral reefs, mangroves, and seagrass, are in global decline. Mitigation approaches include restoration and other managed recovery interventions. To maximise success, these should be guided by an understanding of the environmental niche and geographic limits of foundational species. However, the choices of data, variables, and modelling approaches can be bewildering when embarking on such an exercise, and the biases associated with such choices are often unknown. We reviewed the current available knowledge on methodological approaches and environmental variables used to model and map habitat suitability for coastal ecosystems. While our focus is on seagrass, we draw on information from all marine macrophyte studies for greater coverage of approaches at different scales around the world. We collated 75 publications, of which 35 included seagrasses. Out of all the publications, we found the most commonly used predictor variables were temperature (64%), bathymetry (61%), light availability (49%), and salinity (49%), respectively. The same predictor variables were also commonly used in the 35 seagrass Habitat Suitability Models (HSM) but in the following order: bathymetry (74%), salinity (57%), light availability (51%), and temperature (51%). The most popular method used in marine macrophyte HSMs was an ensemble of models (29%) followed by MaxEnt (17%). Cross-validation was the most commonly used selection procedure (24%), and threshold probability was the favoured model validation (33%). Most studies (87%) did not calculate or report uncertainty measures. The approach used to create an HSM was found to vary by location and scale of the study. Based upon previous studies, it can be suggested that the best approach for seagrass HSM would be to use an ensemble of models, including MaxEnt along with a selection procedure (Cross-validation) and threshold probability to validate the model with the use of uncertainty measures in the model process.
Effectiveness of the available early therapies in reducing severe COVID-19 in non-hospitalized patients with solid tumors on active treatment
Authors: Lasagna Angioletta , Cassaniti Irene , Lilleri Daniele , Quaccini Mattia , Ferrari Alessandra , Sacchi Paolo , Bruno Raffaele , Baldanti Fausto , Pedrazzoli Paolo
Published: October 2022

Emergency use authorization of drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by regulatory authorities has provided new options to treat high-risk outpatients with mild-to-moderate Coronavirus disease 2019 (COVID-19). We conducted an ambispective cohort study of patients with solid tumors on active treatment to examine the effectiveness of these drugs in preventing the progression to severe COVID-19. Sixty-nine patients with solid tumors (43 women, 26 men; median age 61, range 26–80) reported a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Forty-nine patients received early therapy. Only one patient (14.5%) required hospitalization for COVID-19. As for safety, two patients (5.9%) reported nausea during nirmatrelvir/ritonavir. The majority of treated patients showed a reduced time to negative sample (73 vs. 18%, p = 0.0011) and shorter symptoms’ duration (94 vs. 27%; p < 0.0001) compared to the patients not treated with the early COVID-19 therapies. Our data suggest that early therapies may reduce the morbidity of COVID-19 in patients with solid tumors.
Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome
Authors: Sato Mami , Arakaki Rieko , Tawara Hiroaki , Nagao Ruka , Tanaka Hidetaka , Tamura Kai , Kawahito Yuhki , Otsuka Kunihiro , Ushio Aya , Tsunematsu Takaaki , Ishimaru Naozumi
Published: October 2022

Objective

Innate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS.

Methods

Multiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared byin vitroexperiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice.

Results

The number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice.

Conclusion

The results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders.
Adipositas and metabolic bone disorder in a 16th century Upper Austrian infant crypt mummy—An interdisciplinary palaeopathological insight into historical aristocratic life
Authors: Nerlich Andreas G. , Panzer Stephanie , Wimmer Judith , Hamann Christian , Peschel Oliver K.
Published: October 2022

We describe here the results of a multidisciplinary study on an infant mummy from 16th century Upper Austria buried in the crypt of the family of the Counts of Starhemberg. The macroscopic-anthropological, radiological (whole-body CT scan), histological (skin tissue), and radiocarbon isotope investigations suggested a male infant of 10–18 months' age, most likely dying between 1550 and 1635 CE (probably Reichard Wilhelm, 1625–1626 CE), that presented with evidence of metabolic bone disease with significant bilateral flaring of costochondral joints resembling “rachitic rosary” of the ribs, along with straight long bones and lack of fractures or subperiosteal bleeding residues. Although incompletely developed, the osteopathology points toward rickets, without upper or lower extremities long bone deformation. The differential diagnosis is vitamin C deficiency (scurvy) (also with an incomplete presentation, although overlap between both disorders may be present). As additional pathology, there was significantly enlarged subcutaneous fat tissue (thickness more than 1 cm at the navel and thighs and longitudinal creases of the skin) along with a histologically enlarged subcutaneous fat layer consistent with infantile adipositas as a coincident disorder. Finally, remnants of lung tissue with pleural adhesion of the right lung indicate possibly lethal pneumonia, a disease with an increased prevalence in vitamin D deficient infants. Ultimately, the skull presented with extensive destruction of the bones of the base and dislocation of the bones of the skull squama. These changes, however, are most likely post-mortal pseudopathology, the result of a burial in a flat, narrow coffin because there were no bone fractures or residues of bleeding/tissue reaction that would have occurred whilst the patient was alive.
Molecular characterization and transcriptomic analysis of a novel polymycovirus in the fungus Talaromyces amestolkiae
Authors: Teng Li , Chen Sen , Hu Zuquan , Chen Jili , Liu Hongmei , Zhang Tingting
Published: October 2022

Talaromyces amestolkiae is an important fungal species owing to its ubiquity in soils, plants, air, and food. In this study, we identified a novel six-segmented polymycovirus, Talaromyces amestolkiae polymycovirus 1 (TaPmV-1). Each of the double-stranded (ds) RNA segments of TaPmV-1 contained a single open reading frame, and the proteins encoded by dsRNA1, dsRNA2, dsRNA3, and dsRNA 5 shared significant amino acid identities of 56, 40, 47, and 43%, respectively, with the corresponding proteins of Aspergillus fumigatus polymycovirus-1(AfuPmV-1). DsRNA1, dsRNA3, and dsRNA5 of TaPmV-1 encoded an RNA-dependent RNA polymerase (RdRp), a viral methyltransferase, and a PAS-rich protein, respectively. The functions of the proteins encoded by dsRNA2, dsRNA4, and dsRNA6 have not been elucidated. Comparison of the virus-infected strain LSH3 with virus-cured strain LSHVF revealed that infection with TaPmV-l may reduce the production of red pigments and induce the clustering of fungal sclerotia. Furthermore, transcriptomic analyses demonstrated that infection with TaPmV-l downregulated the expression of transcripts related to metabolism, and may correlate with the reduced production of red pigments and clustering of sclerotia in T. amestolkiae. These results of this study provide novel insights into the mechanism of fungal gene regulation by polymycovirus infections at the transcriptome level, and this study is the first to report a novel polymycovirus of T. amestolkiae.
Bromo-protopine, a novel protopine derivative, alleviates tau pathology by activating chaperone-mediated autophagy for Alzheimer’s disease therapy
Authors: Sreenivasmurthy Sravan Gopalkrishnashetty , Iyaswamy Ashok , Krishnamoorthi Senthilkumar , Reddi Rambabu N. , Kammala Ananth Kumar , Vasudevan Karthick , Senapati Sanjib , Zhu Zhou , Su Cheng-Fu , Liu Jia , Guan Xin-Jie , Chua Ka-Kit , Cheung King-Ho , Chen Hubiao , Zhang Hong-Jie , Zhang Yuan , Song Ju-Xian , Kumar Durairajan Siva Sundara , Li Min
Published: October 2022

Emerging evidence from Alzheimer’s disease (AD) patients suggests that reducing tau pathology can restore cognitive and memory loss. To reduce tau pathology, it is critical to find brain-permeable tau-degrading small molecules that are safe and effective. HDAC6 inhibition has long been considered a safe and effective therapy for tau pathology. Recently, we identified protopine as a dibenzazecine alkaloid with anti-HDAC6 and anti-AD activities. In this study, we synthesized and tested novel protopine derivatives for their pharmacological action against AD. Among them, bromo-protopine (PRO-Br) demonstrated a two-fold increase in anti-HDAC6 activity and improved anti-tau activities compared to the parent compound in both in vitro and in vivo AD models. Furthermore, molecular docking results showed that PRO-Br binds to HDAC6, with a ∆G value of −8.4 kcal/mol and an IC50 value of 1.51 µM. In neuronal cell lines, PRO-Br reduced pathological tau by inducing chaperone-mediated autophagy (CMA). In 3xTg-AD and P301S tau mice models, PRO-Br specifically decreased the pathogenic hyperphosphorylated tau clumps and led to the restoration of memory functions. In addition, PRO-Br treatment promoted the clearance of pathogenic tau by enhancing the expression of molecular chaperones (HSC70) and lysosomal markers (LAMP2A) via CMA in AD models. Our data strongly suggest that administration of the brain-permeable protopine derivative PRO-Br, could be a viable anti-tau therapeutic strategy for AD.
The performance of deep generative models for learning joint embeddings of single-cell multi-omics data
Authors: Brombacher Eva , Hackenberg Maren , Kreutz Clemens , Binder Harald , Treppner Martin
Published: October 2022

Recent extensions of single-cell studies to multiple data modalities raise new questions regarding experimental design. For example, the challenge of sparsity in single-omics data might be partly resolved by compensating for missing information across modalities. In particular, deep learning approaches, such as deep generative models (DGMs), can potentially uncover complex patternsviaa joint embedding. Yet, this also raises the question of sample size requirements for identifying such patterns from single-cell multi-omics data. Here, we empirically examine the quality of DGM-based integrations for varying sample sizes. We first review the existing literature and give a short overview of deep learning methods for multi-omics integration. Next, we consider eight popular tools in more detail and examine their robustness to different cell numbers, covering two of the most common multi-omics types currently favored. Specifically, we use data featuring simultaneous gene expression measurements at the RNA level and protein abundance measurements for cell surface proteins (CITE-seq), as well as data where chromatin accessibility and RNA expression are measured in thousands of cells (10x Multiome). We examine the ability of the methods to learn joint embeddings based on biological and technical metrics. Finally, we provide recommendations for the design of multi-omics experiments and discuss potential future developments.
Oxidation and hydrogenation of monolayer MoS2 with compositing agent under environmental exposure: The ReaxFF Mo/Ti/Au/O/S/H force field development and applications
Authors: Mao Qian , Zhang Yuwei , Kowalik Malgorzata , Nayir Nadire , Chandross Michael , van Duin Adri C. T.
Published: October 2022

An atomistic modeling tool is essential to an in-depth understanding upon surface reactions of transition metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS2), with the presence of compositing agents, including Ti and Au, under different environmental exposures. We report a new ReaxFF reactive force field parameter set for Mo, Ti, Au, O, S, and H interactions. We apply the force field in a series of molecular dynamics (MD) simulations to unravel the impact of the Ti dopant on the oxidation/hydrogenation behaviors of MoS2 surface. The simulation results reveal that, in the absence of Ti clusters, the MoS2 surface is ruptured and oxidized at elevated temperatures through a process of adsorption followed by dissociation of the O2 molecules on the MoS2 surface during the temperature ramp. When the MoS2 surface is exposed to H2O molecules, surface hydrogenation is most favored, followed by oxidation, then hydroxylation. The introduction of Ti clusters to the systems mitigates the oxidation/hydrogenation of MoS2 at a low or intermediate temperature by capturing the O2/H2O molecules and locking the O/H-related radicals inside the clusters. However, OH− and H3O+ are emitted from the Ti clusters in the H2O environment as temperature rises, and the accelerating hydrogenation of MoS2 is consequently observed at an ultra-high temperature. These findings indicate an important but complex role of Ti dopants in mitigating the oxidation and hydrogenation of MoS2 under different environmental exposures. The possible mechanisms of oxidation and hydrogenation revealed by MD simulations can give an insight to the design of oxidation resistant TMDs and can be useful to the optical, electronic, magnetic, catalytic, and energy harvesting industries.
Influence of proprioceptive training based on ankle-foot robot on improving lower limbs function in patients after a stroke
Authors: Mao Yajun , Gao Zhenzhen , Yang Hang , Song Caiping
Published: October 2022

Background

Proprioception is important for our everyday activity, as it indicates the position, movement, and force on the body. This is important not only for ambulation but also for patients who are diagnosed with stroke.

Objective

This study aimed to evaluate the influence of proprioceptive training on lower limb function in patients after a stroke using an ankle-foot robot.

Method

In total, 60 adult participants who met the criteria were randomly divided into a control group and an experimental group. The control group (RG) was given regular physical activity, and the sensory training group (SG) was given proprioceptive training based on an ankle-foot robot, the rest being the same as RG. Measurements for 10-meter walking time (10MWT), the Berg Balance Scale (BBS), the Fugl-Meyer assessment of lower extremity (FMA-LE), and active range of motion (AROM), passive range of motion (PROM), and ankle joint sensitivity before and after 6 weeks of treatment (30 sessions; five times per week) were assessed.

Results

There was a significant decrease in both 10MWT and ankle joint sensitivity in both groups (p < 0.05), while there was a significant increase in BBS, FMA-LE, AROM, and PROM in both groups (p < 0.05). A significant relationship was identified between the two groups, the SG group had greater degrees of improvement compared to the RG group.

Conclusion

The proprioceptive training based on an ankle-foot robot could improve proprioception and effectively improve the motor function and walking ability in patients after a stroke. Proprioceptive strength training is recommended to be emphasized in the regular rehabilitation of patients after a stroke.
Glial cells and neurologic autoimmune disorders
Authors: Li Zhao-Qing , Li Tong-Xin , Tian Miao , Ren Ze-Sheng , Yuan Chen-Yi , Yang Rui-Kun , Shi Su-Juan , Li Hui , Kou Zhen-Zhen
Published: October 2022

Neurologic autoimmune disorders affect people’s physical and mental health seriously. Glial cells, as an important part of the nervous system, play a vital role in the occurrence of neurologic autoimmune disorders. Glial cells can be hyperactivated in the presence of autoantibodies or pathological changes, to influence neurologic autoimmune disorders. This review is mainly focused on the roles of glial cells in neurologic autoimmune disorders and the influence of autoantibodies produced by autoimmune disorders on glial cells. We speculate that the possibility of glial cells might be a novel way for the investigation and therapy of neurologic autoimmune disorders.
Synaptic plasticity in two cell types of central amygdala for regulation of emotion and pain
Authors: Ge Jianlong , Cai Youqing , Pan Zhizhong Z.
Published: October 2022

The amygdala is a critical brain site for regulation of emotion-associated behaviors such as pain and anxiety. Recent studies suggest that differential cell types and synaptic circuits within the amygdala complex mediate interacting and opposing effects on emotion and pain. However, the underlying cellular and circuit mechanisms are poorly understood at present. Here we used optogenetics combined with electrophysiological analysis of synaptic inputs to investigate pain-induced synaptic plasticity within the amygdala circuits in rats. We found that 50% of the cell population in the lateral division of the central nucleus of the amygdala (CeAl) received glutamate inputs from both basolateral amygdala (BLA) and from the parabrachial nucleus (PBN), and 39% of the remaining CeAl cells received glutamate inputs only from PBN. Inflammatory pain lasting 3 days, which induced anxiety, produced sensitization in synaptic activities of the BLA–CeAl–medial division of CeA (CeAm) pathway primarily through a postsynaptic mechanism. Moreover, in CeAl cells receiving only PBN inputs, pain significantly augmented the synaptic strength of the PBN inputs. In contrast, in CeAl cells receiving both BLA and PBN inputs, pain selectively increased the synaptic strength of BLA inputs, but not the PBN inputs. Electrophysiological analysis of synaptic currents showed that the increased synaptic strength in both cases involved a postsynaptic mechanism. These findings reveal two main populations of CeAl cells that have differential profiles of synaptic inputs and show distinct plasticity in their inputs in response to anxiety-associated pain, suggesting that the specific input plasticity in the two populations of CeAl cells may encode a different role in amygdala regulation of pain and emotion.
Social determinants and chronic kidney disease of undetermined origin in childhood: Its communication and understanding described by families in Lake Chapala, Mexico
Authors: Ruiz-Velazco Norma Guadalupe , Lozano-Kasten Felipe de Jesús , Guzman-Torres Horacio , Mejía-Sanchez Aaron Ismael
Published: October 2022

This work is based on the recognition of the existence of a complex relationship between social and environmental determinants and infants with chronic kidney disease of non-traditional etiology (CKDnT). The aim is to understand how the Social and Environmental Determinants are settled and its influence to the CKDnT in childhood, through knowledge built from the population that has lived the experience of this disease. This research was carried out with a narrative-conversational design. The experience of CKDnT was organized in stories focused on the experience of families in the social and environmental context where they live, get sick, suffer, and die from the disease. In the dialogue emerges the intersection of the social determinants of the disease, the different ways of life, and the relationship with the health services that attend them.
Effect of pinch types on pinch force sense in healthy adults
Authors: Li Lin , Li YanXia , Jia Peng , Wang Shuyan , Wang Wanpeng , Liu Yuxiang
Published: October 2022

Pinch force sense plays an important role in the performance of daily finger movements, including tip, key, palmar pinch. The present study investigated the roles of pinch type in the sensation of pinch force among healthy participants in the ipsilateral force reproduction trial. This study instructed forty healthy adult subjects (20 women and 20 men) in producing reference forces at different levels [10, 30, 50% maximal voluntary isometric contraction (MVIC)] by adopting 3 pinch types (tip, key, and palmar pinches) and in reproducing the above force levels with the identical hand. Our study revealed that subjects are significantly more sensitive detecting alterations of pinching forces with tip pinch but not key or palmar pinch under high forces (30 and 50% MVIC) but not at lower force levels (10% MVIC).
Missing pieces in decoding the brain oxytocin puzzle: Functional insights from mouse brain wiring diagrams
Authors: Manjila Steffy B. , Betty Rebecca , Kim Yongsoo
Published: October 2022

The hypothalamic neuropeptide, oxytocin (Oxt), has been the focus of research for decades due to its effects on body physiology, neural circuits, and various behaviors. Oxt elicits a multitude of actions mainly through its receptor, the Oxt receptor (OxtR). Despite past research to understand the central projections of Oxt neurons and OxtR- coupled signaling pathways in different brain areas, it remains unclear how this nonapeptide exhibits such pleiotropic effects while integrating external and internal information. Most reviews in the field either focus on neuroanatomy of the Oxt-OxtR system, or on the functional effects of Oxt in specific brain areas. Here, we provide a review by integrating brain wide connectivity of Oxt neurons and their downstream circuits with OxtR expression in mice. We categorize Oxt connected brain regions into three functional modules that regulate the internal state, somatic visceral, and cognitive response. Each module contains three neural circuits that process distinct behavioral effects. Broad innervations on functional circuits (e.g., basal ganglia for motor behavior) enable Oxt signaling to exert coordinated modulation in functionally inter-connected circuits. Moreover, Oxt acts as a neuromodulator of neuromodulations to broadly control the overall state of the brain. Lastly, we discuss the mismatch between Oxt projections and OxtR expression across various regions of the mouse brain. In summary, this review brings forth functional circuit-based analysis of Oxt connectivity across the whole brain in light of Oxt release and OxtR expression and provides a perspective guide to future studies.
Ligand-gated ion channel P2X7 regulates hypoxia-induced factor-1α mediated pain induced by dental pulpitis in the medullary dorsal horn
Authors: Zhang Jing , Si Jialin , Liang Rongrong , Lu Yuxin , Shang Hongwei , Li Xinwei , Sun Shukai , Wu Li-an
Published: October 2022

Dental pulpitis often induces severe pain, and the molecular immune response is remarkable in both peripheral and central nervous system. Accumulating evidence indicates that activated microglia in the medullary dorsal horn (MDH) contribute to dental pulpitis induced pain. The P2X7 receptor plays an important role in driving pain and inflammatory processes, and its downstream target hypoxia-induced factor-1α (HIF-1α) has a crucial role in maintaining inflammation. However, the relationship between P2X7 and HIF-1α in dental inflammatory pain remains unclear. This study demonstrated that the degree of inflammation in the dental pulp tissue became more severe in a time-dependent manner by establishing a rat dental pulpitis modelviapulp exposure. Meanwhile, the expression of P2X7, HIF-1α, IL-1β, and IL-18 in the MDH increased most on the seventh day when the pain threshold was the lowest in the dental pulpitis model. Furthermore, lipopolysaccharides (LPS) increased P2X7-mediated HIF-1α expression in microglia. Notably, the suppression of P2X7 caused less IL-1β and IL-18 release and lower HIF-1α expression, and P2X7 antagonist Brilliant Blue G (BBG) could alleviate pain behaviors of the dental pulpitis rats. In conclusion, our results provide further evidence that P2X7 is a key molecule, which regulates HIF-1α expression and inflammation in dental pulpitis-induced pain.
Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases
Authors: Zhou Kai , Han Jinming , Wang Yafeng , Zhang Yaodong , Zhu Changlian
Published: October 2022

Gene therapy is a powerful tool to treat various central nervous system (CNS) diseases ranging from monogenetic diseases to neurodegenerative disorders. Adeno-associated viruses (AAVs) have been widely used as the delivery vehicles for CNS gene therapies due to their safety, CNS tropism, and long-term therapeutic effect. However, several factors, including their ability to cross the blood–brain barrier, the efficiency of transduction, their immunotoxicity, loading capacity, the choice of serotype, and peripheral off-target effects should be carefully considered when designing an optimal AAV delivery strategy for a specific disease. In addition, distinct routes of administration may affect the efficiency and safety of AAV-delivered gene therapies. In this review, we summarize different administration routes of gene therapies delivered by AAVs to the brain in mice and rats. Updated knowledge regarding AAV-delivered gene therapies may facilitate the selection from various administration routes for specific disease models in future research.
Effects of exercise on the sleep microarchitecture in the aging brain: A study on a sedentary sample
Authors: Cassim Tuan Z. , McGregor Keith M. , Nocera Joe R. , García Violet V. , Sinon Christopher G. , Kreuzer Matthias , García Paul S.
Published: October 2022

Having a healthy sleep pattern plays a vital role in one’s overall health. Sleep in the elderly is characterized by decreased slow-wave sleep and an increase of REM sleep. Furthermore, quantitative electroencephalographic (qEEG) studies have shown an age-related attenuation of total EEG power in sleep. However, exercise has been shown to improve sleep across all age groups. In this study, we used the Sleep Profiler™ EEG Sleep Monitor to observe EEG changes occurring during sleep following an aerobic exercise intervention. This study was done on older adults (N = 18, with only five subjects containing both pre- and post-data of sufficient quality for analysis) with an age range 60–85 years. The aerobics regimen was performed three times weekly for 12-weeks commencing with 20-min sessions. The time of each session progressed by 1–2 min/session as needed to a maximum time of 45 min per session. The macro-architecture (sleep stages) and microarchitecture (EEG) results were analyzed using MATLAB. For the microarchitecture, our results showed more deep sleep following the aerobic exercise regimen. Furthermore, for the microarchitecture, out results shows an increase in total EEG power post-exercise in both light (N1 and L1) and deep sleep (N2 and N3). These preliminary changes in sleep the microarchitecture suggest that non-pharmacologic methods might mitigate age-related EEG changes with potential implications for neurocognitive health.
Hybrid parallel strategies for the neutron transport code PANDAS-MOC
Authors: Tao Shunjiang , Xu Yunlin
Published: October 2022

PANDAS-MOC (Purdue Advanced Neutronics Design and Analysis System with Methods of Characteristics) is being developed to find high fidelity 3D solutions for steady state and transient neutron transport analysis. However, solving such transport problems in a large reactor core could be extremely computationally intensive and memory demanding. Because parallel computing is capable of improving computing efficiency and decreasing memory requirements, three parallel models of PANDAS-MOC are designed using the distributed memory and share memory architectures in this article: a pure message passing interface (MPI) parallel model (PMPI), a segment OpenMP threading hybrid model (SGP), and a whole-code OpenMP threading hybrid model (WCP). Their parallel performances are examined by the C5G7 3D core. For the measured speedup, PMPI model > WCP model > SGP model. The memory consumed by the WCP model is about 60% of that consumed by the PMPI model. This study also demonstrated that the performance of WCP parallelism is limited by the hybrid reduction in the CMFD calculation and omp atomic clause in the MOC sweep. Once they are optimized, the WCP model can outperform the PMPI model.
Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies
Authors: Izuegbuna Ogochukwu O.
Published: October 2022

Polyphenols are one of the largest plant-derived natural product and they play an important role in plants’ defense as well as in human health and disease. A number of them are pleiotropic molecules and have been shown to regulate signaling pathways, immune response and cell growth and proliferation which all play a role in cancer development. Hematological malignancies on the other hand, are cancers of the blood. While current therapies are efficacious, they are usually expensive and with unwanted side effects. Thus, the search for newer less toxic agents. Polyphenols have been reported to possess antineoplastic properties which include cell cycle arrest, and apoptosis via multiple mechanisms. They also have immunomodulatory activities where they enhance T cell activation and suppress regulatory T cells. They carry out these actions through such pathways as PI3K/Akt/mTOR and the kynurenine. They can also reverse cancer resistance to chemotherapy agents. In this review, i look at some of the molecular mechanism of action of polyphenols and their potential roles as therapeutic agents in hematological malignancies. Here i discuss their anti-proliferative and anti-neoplastic activities especially their abilities modulate signaling pathways as well as immune response in hematological malignancies. I also looked at clinical studies done mainly in the last 10–15 years on various polyphenol combination and how they enhance synergism. I recommend that further preclinical and clinical studies be carried out to ensure safety and efficacy before polyphenol therapies be officially moved to the clinics.