bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and validation of key molecules associated with humoral immune modulation in Parkinson’s disease based on bioinformatics
Authors: Xing Na , Dong Ziye , Wu Qiaoli , Kan Pengcheng , Han Yuan , Cheng Xiuli , Zhang Biao
Published: September 2022

Objective

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and immune-mediated mechanism is considered to be crucial to pathogenesis. Here, we investigated the role of humoral immune regulatory molecules in the pathogenesis of PD.

Methods

Firstly, we performed a series of bioinformatic analyses utilizing the expression profile of the peripheral blood mononuclear cell (PBMC) obtained from the GEO database (GSE100054, GSE49126, and GSE22491) to identify differentially expressed genes related to humoral immune regulatory mechanisms between PD and healthy controls. Subsequently, we verified the results using quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA) in clinical blood specimen. Lastly, receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic effects of verified molecules.

Results

We obtained 13 genes that were mainly associated with immune-related biological processes in PD using bioinformatic analysis. Then, we selected PPBP, PROS1, and LCN2 for further exploration. Fascinatingly, our experimental results don’t always coincide with the expression profile. PROS1 and LCN2 plasma levels were significantly higher in PD patients compared to controls (p < 0.01 and p < 0.0001). However, the PPBP plasma level and expression in the PBMC of PD patients was significantly decreased compared to controls (p < 0.01 and p < 0.01). We found that PPBP, PROS1, and LCN2 had an area under the curve (AUC) of 0.663 (95%CI: 0.551–0.776), 0.674 (95%CI: 0.569–0.780), and 0.885 (95%CI: 0.814–0.955). Furthermore, in the biological process analysis of gene ontology (GO), the three molecules were all involved in humoral immune response (GO:0006959).

Conclusions

In general, PPBP, PROS1, and LCN2 were identified and validated to be related to PD and PPBP, LCN2 may potentially be biomarkers or therapeutic targets for PD. Our findings also provide some new insights on the humoral immune modulation mechanisms in PD.
T cell receptor repertoire analysis in HTLV-1-associated diseases
Authors: Clauze Annaliese , Enose-Akahata Yoshimi , Jacobson Steven
Published: September 2022

Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 million people worldwide, although most infected individuals remain asymptomatic. HTLV-1 infected persons carry an estimated lifetime risk of approximately 5% of developing ATL, and between 0.25% and 1.8% of developing HAM/TSP. Most HTLV-1 infection is detected in CD4+T cellsin vivowhich causes the aggressive malignancy in ATL. In HAM/TSP, the increase of HTLV-1 provirus induces immune dysregulation to alter inflammatory milieu, such as expansion of HTLV-1-specific CD8+T cells, in the central nervous system of the infected subjects, which have been suggested to underlie the pathogenesis of HAM/TSP. Factors contributing to the conversion from asymptomatic carrier to disease state remain poorly understood. As such, the identification and tracking of HTLV-1-specific T cell biomarkers that may be used to monitor the progression from primary infection to immune dysfunction and disease are of great interest. T cell receptor (TCR) repertoires have been extensively investigated as a mechanism of monitoring adaptive T cell immune response to viruses and tumors. Breakthrough technologies such as single-cell RNA sequencing have increased the specificity with which T cell clones may be characterized and continue to improve our understanding of TCR signatures in viral infection, cancer, and associated treatments. In HTLV-1-associated disease, sequencing of TCR repertoires has been used to reveal repertoire patterns, diversity, and clonal expansions of HTLV-1-specific T cells capable of immune evasion and dysregulation in ATL as well as in HAM/TSP. Conserved sequence analysis has further been used to identify CDR3 motif sequences and exploit disease- or patient-specificity and commonality in HTLV-1-associated disease. In this article we review current research on TCR repertoires and HTLV-1-specific clonotypes in HTLV-1-associated diseases ATL and HAM/TSP and discuss the implications of TCR clonal expansions on HTLV-1-associated disease course and treatments.
COVID-19 patients exhibit unique transcriptional signatures indicative of disease severity
Authors: Daamen Andrea R. , Bachali Prathyusha , Bonham Catherine A. , Somerville Lindsay , Sturek Jeffrey M. , Grammer Amrie C. , Kadl Alexandra , Lipsky Peter E.
Published: September 2022

COVID-19 manifests a spectrum of respiratory symptoms, with the more severe often requiring hospitalization. To identify markers for disease progression, we analyzed longitudinal gene expression data from patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure (AHRF) as well as other ICU patients with or without AHRF and correlated results of gene set enrichment analysis with clinical features. The results were then compared with a second dataset of COVID-19 patients separated by disease stage and severity. Transcriptomic analysis revealed that enrichment of plasma cells (PCs) was characteristic of all COVID-19 patients whereas enrichment of interferon (IFN) and neutrophil gene signatures was specific to patients requiring hospitalization. Furthermore, gene expression results were used to divide AHRF COVID-19 patients into 2 groups with differences in immune profiles and clinical features indicative of severe disease. Thus, transcriptomic analysis reveals gene signatures unique to COVID-19 patients and provides opportunities for identification of the most at-risk individuals.
Food resources for Spoon-billed Sandpipers (Calidris pygmaea) in the mudflats of Leizhou Bay, southern China
Authors: Lu Xiuyuan , Yang Hongyan , Piersma Theunis , Sun Lili , Chen Qing , Jia Yifei , Lei Guangchun , Cheng Li , Rao Xinpeng
Published: September 2022

Leizhou Bay in Guangdong Province is the most important wintering site in China for the critically endangered Spoon-billed Sandpipers (Calidris pygmaea). As food is usually a strong predictor of presence, in the winters of 2019-2022 we studied arthropod food resources and diet on the intertidal mudflats at the Tujiao and Hebei mudflats in Leizhou Bay. In December 2020, using a sampling device that encloses mobile epibenthic prey before the human sampler would disturb them in shallow pools, we visited 34 stations in their core foraging area at Tujiao. A total of 15 mobile benthic species were identified, including 13 arthropod and 2 fish species, with a total density of 106 animals/m2 (range= 0.2-48 animals/m2), with the lengths of the animals ranging from 1-19 mm. Two amphipod and one cumacean species contributed 85%. On the basis of photographs of foraging during low tide in 2019-2022, the visibly ingested prey items appeared to mainly consist of small shrimp, but also included crabs and fish. At 27 mm (compared with the 22 mm long bill of Spoon-billed Sandpipers) the average visibly ingested prey showed a strong size bias. Among the measured environmental covarying factors (sediment pH, salinity, TOC content, median particle size and distance from the seawall etc.) potentiually affecting the mobile epibenthic prey in shallow pools, only distance from the seawall was significantly and negatively correlated. Densities were higher within 1 km of the seawall (126 animals/m2) than further offshore (69 animals/m2). This may relate to the mangrove forests growing in abundance near the seawall providing released minerals, nutrients, bacterial production and diatoms for the benthic community in the adjacent mudflats. However, the potential negative impact of artificial mangrove expansion in Leizhou mudflats need to be carefully monitored and assessed to balance both mangrove and Spoon-billed Sandpipers conservation.
Environmental variability and fishing effects on artisanal flatfish fisheries along the Portuguese coast
Authors: Baptista Vânia , Blasco Ignacio Pérez , Bueno-Pardo Juan , Teodósio Maria Alexandra , Leitão Francisco
Published: September 2022

Assessing the effects of fishing activity and environmental variability on fishing species might help to understand their fluctuations and to manage them accordingly. However, despite the increasing number of studies linking fisheries and environmental data, few had a multi-species approach considering flatfish species and different age groups. Therefore, this study aims to determine the effects of environmental and fishing related variables on commercial flatfish species across different regions of the Portuguese coast. For that, sea surface temperature, North Atlantic Oscillation, upwelling index, wind components, river discharges and fishing effort were related to landings per unit effort (LPUE) of five commercial flatfish species (Pleuronectes platessa,Dicologlossa cuneata,Microchirusspp.,Solea lascaris, andSolea solea) fished by the artisanal fleet along different regions of Portuguese coast (Northwestern coast, Southwestern coast, and Southern coast), using a multi-model statistical approach from 1989 to 2009. The fishing effort had the same effect along the life cycle and was negatively related with LPUE trends for most of the species. Regarding to environmental variability, during early phases (larval to juvenile – age-group-0) the factors that affected the recruitment, in addition to being related to the physiological needs (e.g., sea surface temperature) of individuals that will trigger growth and survival, were related to larval transport and dispersion from offshore spawning areas to coastal nursery habitats beyond (e.g., wind components and upwelling). For juvenile and young-adult phases (age-groups I and II), the effects of environmental variability appeared to be linked to physiological needs important for growth and maturation (e.g., temperature). Concluding, different effects were observed depending on the region, species, and life-cycle phase. Therefore, these environmental-fishing relationships should be used when managing local fishing resources.
Insights into community assembly mechanisms, biogeography, and metabolic potential of particle-associated and free-living prokaryotes in tropical oligotrophic surface oceans
Authors: Ren Yanhu , Luo Zhenhao , Liu Qian , Wei Bin , Wu Yue-Hong , Shu Wen-Sheng , Xu Xue-Wei
Published: September 2022

Heterotrophic prokaryotes constitute the largest living biomass in the ocean and can be divided into particle-associated (PA) and free-living (FL) fractions. PA and FL prokaryotic communities play critical roles in the biogeochemical cycles of particulate and dissolved organic matter; however, their community assembly processes, biogeographical distribution patterns, and functional properties in oligotrophic surface water remain to be further elucidated. Based on 16S rRNA gene sequencing and shotgun metagenomics, we investigated the assembly mechanisms, biogeography, and functional potential of PA and FL prokaryotes in the surface waters of the West Pacific and Indian Oceans. FL prokaryotic communities were predominantly structured by deterministic processes, whereas their PA counterparts appeared to be shaped by the combined action of deterministic and stochastic processes. PA and FL prokaryotes in the tropical oligotrophic surface ocean exhibit markedly different community structures and functional potentials. Bacterial PA specialists such as Lentimonas, Alteromonas, and Pirellula as well as archaeal PA specialists Marine Group II and Marine Group III were significantly more abundant in PA assemblages, whereas lineages such as Prochlorococcus, SAR11 clade, and Candidatus Actinomarina were significantly more abundant in FL communities. The metabolic potential of the PA community was more abundant in pathways such as polyamine biosynthesis, carbohydrate metabolism, and glycosaminoglycan degradation. In contrast, the FL community was more enriched in functions related to amino acid metabolism, lipid biosynthesis, and aromatic degradation.
Reconstruction of ocean temperature and salinity profiles in the Northern South China Sea using satellite observations
Authors: Tang Bo , Zhao Dandan , Cui Chaoran , Zhao Xinhua
Published: September 2022

Based on historical temperature and salinity (T–S) profiles, the correlation between the sea surface temperature (SST) anomaly, sea surface dynamic height (SSH) anomaly, and temperature profile anomaly is constructed by regression analysis. A three-dimensional temperature field is reconstructed in the northern South China Sea by satellite SST and SSH, with daily temporal and 0.25°×0.25° spatial resolutions. The three-dimensional salinity field is also reconstructed based on the correlation between salinity and temperature. Compared with the observational T–S profiles, the reconstructed T–S field reflects the characteristics and structure and accurately describes the mesoscale variability of the ocean temperature field. The new expanded T–S field can be used as the initial field in numerical models and be assimilated into numerical reanalysis and prediction systems, improving their output.
Programmable metasurface RCS prediction under obstacles based on DNN
Authors: Jiang Yutong , Zhu Rongrong , Yang Bo , Lu Huan , Chen Tianhang , Zheng Bin
Published: September 2022

Programmable metasurfaces have attracted significant attention in various applications such as radar and 6G communications, owing to their ability freely shape the far-field pattern. However, complex calculations and simulations are always required when designing specific far-field patterns, especially when irregular obstacles are outside the metasurface. In this article, we propose a method using a four-layer artificial neural network to realize the far-field radar cross section (RCS) prediction of programmable metasurfaces in an environment with obstacles, and the prediction value agreed with the simulation data reasonably well. Results show that the proposed prediction model is characterized by better learning and generalization capacity. Our work has broad application prospects and value in complex environment signal transmission, metasurface inverse design, etc.
Case study of cervical cancer prevention in two sub-Saharan African countries: Rwanda and Sierra Leone
Authors: Bangura Mohamed S. , Zhao Yuqian , Gonzalez Mendez Maria Jose , Wang Yixuan , Didier Sama Salah , Xu Kunpeng , Ren Ran , Ma Li , Qiao You-Lin
Published: September 2022

Background

Cervical cancer is a public health issue of global concern. It is a preventable disease but continues to threaten the lives of women, especially in developing countries in sub-Saharan Africa.

Methods

We selected two African countries in sub-Saharan Africa (the Republic of Rwanda and the Republic of Sierra Leone) to show a good example of cervical cancer prevention and constrains hindering countries from effectively implementing cervical cancer programs. Secondary data were collected from the World Health Organization (WHO), the International Agency for Research on Cancer (IARC), the Global Burden of Cancer (GLOBOCAN), the United Nations Development Programme (UNDP), and the World Bank and from official websites of the selected countries. A descriptive analysis method was used to source data and compare variables such as the associated factors, disease burden, prevention programs, health workforce, success factors, and challenges.

Results

Rwanda achieved 93.3% human papillomavirus (HPV) vaccination of the three doses vaccinating girls in class 6, as a result of effective school-based platform delivery system and community partnership to identify girls who are out of school. Rwanda reduced the historical two-decade gap in vaccine introduction between high- and low-income countries. The country also introduced a nationwide cervical cancer screening and treatment program. An impressive decreased cervical cancer incidence rate in Rwanda in recent years was observed. Sierra Leone lags behind in terms of almost all cervical cancer prevention programs. Therefore, Sierra Leone needs more efforts to implement cervical cancer intervention programs at the national level, including HPV vaccination, and train and increase the number of health professionals, treatment, and palliative care services to accelerate cervical cancer activities.

Conclusion

The disease burden of cervical cancer for Rwanda and Sierra Leone is heavy. There remains huge room for improvement in preventing and controlling cervical cancer in these countries. The goal of cervical cancer elimination would not be feasible in countries without the awareness and will of the policymakers and the public, the compliance to fund cervical cancer programs, the prioritization of cervical cancer activities, the availability of resources, the adequate health workforce and infrastructure, the cross-sectional collaboration and planning, inter-sectorial, national, regional, and international partnerships.
Regional pleural strain measurements during mechanical ventilation using ultrasound elastography: A randomized, crossover, proof of concept physiologic study
Authors: Girard Martin , Roy Cardinal Marie-Hélène , Chassé Michaël , Garneau Sébastien , Cavayas Yiorgos Alexandros , Cloutier Guy , Denault André Y.
Published: September 2022

Background

Mechanical ventilation is a common therapy in operating rooms and intensive care units. When ill-adapted, it can lead to ventilator-induced lung injury (VILI), which is associated with poor outcomes. Excessive regional pulmonary strain is thought to be a major mechanism responsible for VILI. Scarce bedside methods exist to measure regional pulmonary strain. We propose a novel way to measure regional pleural strain using ultrasound elastography. The objective of this study was to assess the feasibility and reliability of pleural strain measurement by ultrasound elastography and to determine if elastography parameters would correlate with varying tidal volumes.

Methods

A single-blind randomized crossover proof of concept study was conducted July to October 2017 at a tertiary care referral center. Ten patients requiring general anesthesia for elective surgery were recruited. After induction, patients received tidal volumes of 6, 8, 10, and 12 mL.kg–1 in random order, while pleural ultrasound cineloops were acquired at 4 standardized locations. Ultrasound radiofrequency speckle tracking allowed computing various pleural translation, strain and shear components. We screened 6 elastography parameters (lateral translation, lateral absolute translation, lateral strain, lateral absolute strain, lateral absolute shear and Von Mises Strain) to identify those with the best dose-response with tidal volumes using linear mixed effect models. Goodness-of-fit was assessed by the coefficient of determination. Intraobserver, interobserver and test-retest reliability were calculated using intraclass correlation coefficients.

Results

Analysis was possible in 90.7% of ultrasound cineloops. Lateral absolute shear, lateral absolute strain and Von Mises strain varied significantly with tidal volume and offered the best dose-responses and data modeling fits. Point estimates for intraobserver reliability measures were excellent for all 3 parameters (0.94, 0.94, and 0.93, respectively). Point estimates for interobserver (0.84, 0.83, and 0.77, respectively) and test-retest (0.85, 0.82, and 0.76, respectively) reliability measures were good.

Conclusion

Strain imaging is feasible and reproducible. Future studies will have to investigate the clinical relevance of this novel imaging modality.

Clinical trial registration

www.Clinicaltrials.gov, identifier NCT03092557.
Association of adenosine signaling gene signature with estrogen receptor-positive breast and prostate cancer bone metastasis
Authors: Shropshire Daniel Brian , Acosta Francisca M. , Fang Kun , Benavides Jaime , Sun Lu-Zhe , Jin Victor X. , Jiang Jean X.
Published: September 2022

Bone metastasis is a common and devastating consequence of several major cancer types, including breast and prostate. Osteocytes are the predominant bone cell, and through connexin (Cx) 43 hemichannels release ATP to the bone microenvironment that can be hydrolyzed to adenosine. Here, we investigated how genes related to ATP paracrine signaling are involved in two common bone-metastasizing malignancies, estrogen receptor positive (ER+) breast and prostate cancers. Compared to other sites, bone metastases of both cancer types expressed higher levels of ENTPD1 and NT5E, which encode CD39 and CD73, respectively, and hydrolyze ATP to adenosine. ADORA3, encoding the adenosine A3 receptor, had a similar expression pattern. In primary ER+ breast cancer, high levels of the triplet ENTPD1/NT5E/ADORA3 expression signature was correlated with lower overall, distant metastasis-free, and progression-free survival. In ER+ bone metastasis biopsies, this expression signature is associated with lower survival. This expression signature was also higher in bone-metastasizing primary prostate cancers than in those that caused other tumor events or did not lead to progressive disease. In 3D culture, a non-hydrolyzable ATP analog inhibited the growth of breast and prostate cancer cell lines more than ATP did. A3 inhibition also reduced spheroid growth. Large-scale screens by the Drug Repurposing Hub found ER+ breast cancer cell lines were uniquely sensitive to adenosine receptor antagonists. Together, these data suggest a vital role for extracellular ATP degradation and adenosine receptor signaling in cancer bone metastasis, and this study provides potential diagnostic means for bone metastasis and specific targets for treatment and prevention.
Spontaneous rupture of the uterus in the third trimester after high-intensity ultrasound ablation in adenomyosis: A case report
Authors: Wu Siyun , Liu Jun , Jiang Libin , Yang Lijun , Han Yanhua
Published: September 2022

Adenomyosis is a benign uterine disease. Due to the higher incidence of adenomyosis and patients' demands for fertility, high-intensity ultrasound ablation has been widely used in gynecological patients with uterine fibroids and adenomyosis. Ultrasound ablation of lesions can help alleviate symptoms in patients without increasing the incidence of obstetric complications in subsequent pregnancies. High-intensity ultrasound ablation is not considered a risk factor for uterine rupture. However, we describe a case of adenomyosis treated with high-intensity ultrasound ablation presenting with uterine rupture in the third trimester. The patient underwent an emergency cesarean section to deliver the baby successfully and underwent uterine repair surgery. When treating patients with adenomyosis, care should be taken to protect the myometrium, endometrium, and serous layer to reduce the risk of uterine rupture.
Predicting lymph node metastasis and recurrence in patients with early stage colorectal cancer
Authors: Chen Lei , Yang Funing , Qi Zhaoyan , Tai Jiandong
Published: September 2022

Tumor budding (TB), a powerful, independent predictor of colorectal cancer (CRC), is important for making appropriate treatment decisions. Currently, TB is assessed only using the tumor bud count (TBC). In this study, we aimed to develop a novel prediction model, which includes different TB features, for lymph node metastasis (LNM) and local recurrence in patients with pT1 CRC. Enrolled patients (n = 354) were stratified into training and validation cohorts. Independent predictors of LNM and recurrence were identified to generate predictive nomograms that were assessed using the area under the receiver operating characteristic (AUROC) and decision curve analysis (DCA). Seven LNM predictors [gross type, histological grade, lymphovascular invasion (LVI), stroma type, TBC, TB mitosis, and TB CDX2 expression] were identified in the training cohort. LNM, histology grade, LVI, TBC, stroma type, and TB mitosis were independent predictors of recurrence. We constructed an LNM predictive nomogram with a high clinical application value using the DCA. Additionally, a nomogram predicting recurrence-free survival (RFS) was constructed. It presented an AUROC value of 0.944 for the training cohort. These models may assist surgeons in making treatment decisions. In the high-risk group, radical surgery with a postoperative adjuvant chemotherapy was associated with RFS. Postoperative chemotherapy can be better for high-risk patients with pT1 CRC. We showed that TB features besides TBC play important roles in CRC pathogenesis, and our study provides prognostic information to guide the clinical management of patients with early stage CRC.
Effect of NZ2114 against Streptococcus dysgalactiae biofilms and its application in murine mastitis model
Authors: Yang Na , Zhang Qingjuan , Mao Ruoyu , Hao Ya , Ma Xuanxuan , Teng Da , Fan Huan , Wang Jianhua
Published: September 2022

Bovine mastitis caused by Streptococcus dysgalactiae (S. dysgalactiae) is usually treated with antibiotics, which may potentially increase drug resistance as the abuse. NZ2114, a variant of fungal defensin plectasin, displayed a potent antibacterial activity against S. dysgalactiae. The inhibition/eradication effect of the antimicrobial peptide NZ2114 on the early/mature biofilm of S. dysgalactiae CVCC 3938 was evaluated, as well as the elimination of bacteria in mature biofilms. In this study, NZ2114 displayed potent antibacterial activity against S. dysgalactiae CVCC 3938 and three clinical isolated S. dysgalactiae strains (0.11-0.45 μM). The early biofilm inhibition of S. dysgalactiae CVCC 3938 was 55.5–85.9% after treatment with NZ2114 at concentrations of 1–16 × MIC, which was better than that of vancomycin at the same concentration. The mature biofilm eradication rate was up to 92.7–97.6% with the increasing concentration (2–16 × MIC) of NZ2114, and the eradication rate did not change significantly with further increase of NZ2114 concentration, while the biofilm eradication rate of vancomycin-treated group at the same concentration remained at 92.5%. NZ2114 reduced the number of persister bacteria in biofilm. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) further demonstrated that NZ2114 could effectively reduce the biofilm thickness and bacterial number of S. dysgalactiae CVCC 3938. In vivo therapeutic effect of NZ2114 on murine mastitis model showed that NZ2114 was better than vancomycin in alleviating mammary gland inflammation by regulating cytokines production, inhibiting bacterial proliferation, and reducing the number of mammary gland bacteria. These data suggested that NZ2114 is a potential peptide candidate for the treatment of mastitis.
Novel CRISPR-based detection of Leishmania species
Authors: Dueñas Eva , Nakamoto Jose A. , Cabrera-Sosa Luis , Huaihua Percy , Cruz María , Arévalo Jorge , Milón Pohl , Adaui Vanessa
Published: September 2022

Tegumentary leishmaniasis, a disease caused by protozoan parasites of the genus Leishmania, is a major public health problem in many regions of Latin America. Its diagnosis is difficult given other conditions resembling leishmaniasis lesions and co-occurring in the same endemic areas. A combination of parasitological and molecular methods leads to accurate diagnosis, with the latter being traditionally performed in centralized reference and research laboratories as they require specialized infrastructure and operators. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) systems have recently driven innovative tools for nucleic acid detection that combine high specificity, sensitivity and speed and are readily adaptable for point-of-care testing. Here, we harnessed the CRISPR-Cas12a system for molecular detection of Leishmania spp., emphasizing medically relevant parasite species circulating in Peru and other endemic areas in Latin America, with Leishmania (Viannia) braziliensis being the main etiologic agent of cutaneous and mucosal leishmaniasis. We developed two assays targeting multi-copy targets commonly used in the molecular diagnosis of leishmaniasis: the 18S ribosomal RNA gene (18S rDNA), highly conserved across Leishmania species, and a region of kinetoplast DNA (kDNA) minicircles conserved in the L. (Viannia) subgenus. Our CRISPR-based assays were capable of detecting down to 5 × 10−2 (kDNA) or 5 × 100 (18S rDNA) parasite genome equivalents/reaction with PCR preamplification. The 18S PCR/CRISPR assay achieved pan-Leishmania detection, whereas the kDNA PCR/CRISPR assay was specific for L. (Viannia) detection. No cross-reaction was observed with Trypanosoma cruzi strain Y or human DNA. We evaluated the performance of the assays using 49 clinical samples compared to a kDNA real-time PCR assay as the reference test. The kDNA PCR/CRISPR assay performed equally well as the reference test, with positive and negative percent agreement of 100%. The 18S PCR/CRISPR assay had high positive and negative percent agreement of 82.1% and 100%, respectively. The findings support the potential applicability of the newly developed CRISPR-based molecular tools for first-line diagnosis of Leishmania infections at the genus and L. (Viannia) subgenus levels.
Microbial interactions play an important role in regulating the effects of plant species on soil bacterial diversity
Authors: Wang Yajun , Ma Lan , Liu Ziyang , Chen Jingwei , Song Hongxian , Wang Jiajia , Cui Hanwen , Yang Zi , Xiao Sa , Liu Kun , An Lizhe , Chen Shuyan
Published: September 2022

Plant species and microbial interactions have significant impacts on the diversity of bacterial communities. However, few studies have explored interactions among these factors, such the role of microbial interactions in regulating the effects of plant species on soil bacterial diversity. We assumed that plant species not only affect bacterial community diversity directly, but also influence bacterial community diversity indirectly through changing microbial interactions. Specifically, we collected soil samples associated with three different plant species, one evergreen shrub (Rhododendron simsii) and the other two deciduous shrubs (Dasiphora fruticosa and Salix oritrepha). Soil bacterial community composition and diversity were examined by high-throughput sequencing. Moreover, soil bacterial antagonistic interactions and soil edaphic characteristics were evaluated. We used structural equation modeling (SEM) to disentangle and compare the direct effect of different plant species on soil bacterial community diversity, and their indirect effects through influence on soil edaphic characteristics and microbial antagonistic interactions. The results showed that (1) Plant species effects on soil bacterial diversity were significant; (2) Plant species effects on soil microbial antagonistic interactions were significant; and (3) there was not only a significant direct plant species effect on bacterial diversity, but also a significant indirect effect on bacterial diversity through influence on microbial antagonistic interactions. Our study reveals the difference among plant species in their effects on soil microbial antagonistic interactions and highlights the vital role of microbial interactions on shaping soil microbial community diversity.
Tannin tolerance lactic acid bacteria screening and their effects on fermentation quality of stylo and soybean silages
Authors: Gao Lin , Guo Xiang , Wu Shuo , Chen Dandan , Ge Liangfa , Zhou Wei , Zhang Qing , Pian Ruiqi
Published: September 2022

Some excellent legume forages are difficult to ensile naturally due to their high buffering capacity and low water-soluble carbohydrate content. This may cause serious problems like proteolysis. In the present study, strains of lactic acid bacteria with high acid productivity and high tannin tolerance were screened from different silages and combined with tannic acid (TA) as an addition to ensiling. The screened strains were identified as Lactobacillus plantarum (LP), with four of these strains then selected for their high tannin tolerance. Stylosanthes guianensis and whole-plant soybean (WPS) were ensiled with 1 and 2% (fresh matter basis) TA, four LP strains alone (6 log10 colony forming units per gram of fresh matter), or TA combined with LP strains. Fermentation parameters and in vitro rumen fermentation characteristics were analyzed after 30 days of fermentation. The results showed that TA + LP can be used to reduce pH values (P < 0.01), non-protein nitrogen (P < 0.01), and ammonia-nitrogen (P < 0.01). The in vitro crude protein digestibility of WPS silage was also decreased with the addition of TA + LP (P < 0.01). These results indicate that the addition of TA combined with tannin tolerance LP strains may improve the fermentation quality of legume silage, especially for reducing proteolysis.
CAT-CPI: Combining CNN and transformer to learn compound image features for predicting compound-protein interactions
Authors: Qian Ying , Wu Jian , Zhang Qian
Published: September 2022

Compound-protein interaction (CPI) prediction is a foundational task for drug discovery, which process is time-consuming and costly. The effectiveness of CPI prediction can be greatly improved using deep learning methods to accelerate drug development. Large number of recent research results in the field of computer vision, especially in deep learning, have proved that the position, geometry, spatial structure and other features of objects in an image can be well characterized. We propose a novel molecular image-based model named CAT-CPI (combining CNN and transformer to predict CPI) for CPI task. We use Convolution Neural Network (CNN) to learn local features of molecular images and then use transformer encoder to capture the semantic relationships of these features. To extract protein sequence feature, we propose to use a k-gram based method and obtain the semantic relationships of sub-sequences by transformer encoder. In addition, we build a Feature Relearning (FR) module to learn interaction features of compounds and proteins. We evaluated CAT-CPI on three benchmark datasets—Human, Celegans, and Davis—and the experimental results demonstrate that CAT-CPI presents competitive performance against state-of-the-art predictors. In addition, we carry out Drug-Drug Interaction (DDI) experiments to verify the strong potential of the methods based on molecular images and FR module.
Hormone and implant osseointegration: Elaboration of the relationship among function, preclinical, and clinical practice
Authors: Yi Ming , Yin Ying , Sun Jiwei , Wang Zeying , Tang Qingming , Yang Cheng
Published: September 2022

As clusters of peptides or steroids capable of high-efficiency information transmission, hormones have been substantiated to coordinate metabolism, growth, development, and other physiological processes, especially in bone physiology and repair metabolism. In recent years, the application of hormones for implant osseointegration has become a research hotspot. Herein, we provide a comprehensive overview of the relevant reports on endogenous hormones and their corresponding supplementary preparations to explore the association between hormones and the prognosis of implants. We also discuss the effects and mechanisms of insulin, parathyroid hormone, melatonin, vitamin D, and growth hormone on osseointegration at the molecular and body levels to provide a foothold and guide future research on the systemic conditions that affect the implantation process and expand the relative contraindications of the implant, and the pre-and post-operative precautions. This review shows that systemic hormones can regulate the osseointegration of oral implants through endogenous or exogenous drug-delivery methods.
Aberrant gray matter volume and functional connectivity in Parkinson’s disease with minor hallucination
Authors: Zhong Min , Li Chenglin , Lu Hongquan , Xue Donghui , Wang Yaxi , Jiang Yinyin , Zhu Sha , Gu Ruxin , Jiang Xu , Shen Bo , Zhu Jun , Zhang Wenbin , Pan Yang , Yan Jun , Zhang Li
Published: September 2022

Background

Minor hallucination (MH) is the most common psychotic symptom in Parkinson’s disease (PD); it can develop into well-structured visual hallucination (VH), suggesting that MH may be a staccato form of well-structured VH. However, it remains unclear whether the pathogenesis is the same. Therefore, the aim of this study was to investigate the altered gray matter volume (GMV) and functional connectivity (FC) of MH in PD to further understand the complex mechanisms.

Materials and methods

We included 67 PD patients who attended the outpatient clinic of Nanjing Medical University Affiliated Brain Hospital and recruited 31 healthy controls (HC). Demographic data and clinical characteristics of all subjects were recorded, and cranial structural magnetic resonance imaging (MRI) and resting-state functional MRI data were acquired. Patients were classified into the PD with MH (PD-MH) group and PD without hallucinations or delusions (PD-NH) group. Voxel-based morphometry was used to analyze the differences in GMV in the structural pattern. Seed-based FC was used to analyze the functional pattern. Gaussian random field correction was used, with voxel level P < 0.001 and cluster level P < 0.05 representing statistically significant differences. Finally, the correlation between FC values and scores on the clinical characteristics assessment scale was analyzed.

Results

In the GMV analysis, compared to the PD-NH group, the PD-MH group had reduced GMV in the medial superior frontal gyrus (SFGmed). In the FC analysis, the FC between the SFGmed and the left middle occipital gyrus and right calcarine sulcus decreased in the PD-MH group compared with the PD-NH group, while the FC between SFGmed and the left middle temporal gyrus increased. Correlation analysis revealed that the FC values of the SFGmed and right calcarine sulcus were correlated with the assessment scores for anxiety and sleep symptoms. The FC values of the SFGmed and left middle occipital gyrus were correlated with assessment scores for rapid eye movement disorder.

Conclusion

The aberrant structure and function of the default mode network and visual processing areas seems to facilitate the generation of MH in PD, as the alteration was previously found in well-structured VH, suggesting that the two hallucinations have similar pathophysiological mechanisms.
Blood pressure trajectories over 35 years and dementia risk: A retrospective study: The HUNT study
Authors: Selbaek Geir , Stuebs Josephine , Engedal Knut , Hachinski Vladimir , Hestad Knut , Trevino Cathrine Selnes , Skjellegrind Håvard , Wedatilake Yehani , Strand Bjørn Heine
Published: September 2022

High blood pressure is a well-established risk factor of dementia. However, the timing of the risk remains controversial. The aim of the present study was to compare trajectories of systolic blood pressure (SBP) over a 35-year follow-up period in the Health Survey in Trøndelag (HUNT) from study wave 1 to 4 in people with and without a dementia diagnosis at wave 4 (HUNT4). This is a retrospective cohort study of participants aged ≥ 70 years in HUNT4, where 9,720 participants were assessed for dementia. In the HUNT study all residents aged ≥ 20 years have been invited to four surveys: HUNT1 1984–86, HUNT2 1995–97, HUNT3 2006–08 and HUNT4 2017–19. The study sample was aged 70–102 years (mean 77.6, SD 6.0) at HUNT4, 54% were women and 15.5% had dementia, 8.8% had Alzheimer’s disease (AD), 1.6% had vascular dementia (VaD) and 5.1% had other types of dementia. Compared to those without dementia at HUNT4, those with dementia at HUNT4 had higher SBP at HUNT1 and HUNT2, but lower SBP at HUNT4. These differences at HUNT1 and 2 were especially pronounced among women. Results did not differ across birth cohorts. For dementia subtypes at HUNT4, the VaD group had a higher SBP than the AD group at HUNT2 and 3. Age trajectories in SBP showed that the dementia group experienced a steady increase in SBP until 65 years of age and a decrease from 70 to 90 years. SBP in the no- dementia group increased until 80 years before it leveled off from 80 to 90 years. The present study confirms findings of higher midlife SBP and lower late-life SBP in people with dementia. This pattern may have several explanations and it highlights the need for close monitoring of BP treatment in older adults, with frequent reappraisal of treatment needs.
Spatiotemporal patterns of gliosis and neuroinflammation in presenilin 1/2 conditional double knockout mice
Authors: Peng Wenjun , Xie Yuan , Liao Chongzheng , Bai Yunxia , Wang Huimin , Li Chunxia
Published: September 2022

Increasing evidence indicates that neuroinflammation contributes to and exacerbates the pathogenesis of Alzheimer’s disease (AD). Neuroinflammation is thought to be primarily driven by glial cells (microglia and astrocytes) and escalates with neurodegenerative progression in AD. However, the spatiotemporal change patterns of glial reactivity and neuroinflammatory response during different stages of neurodegeneration, especially early in disease, remain unknown. Here we found that gliosis and the up-regulation of substantial neuroinflammatory genes were primarily initiated in the cortex of presenilin 1/2 conditional double knockout (cDKO) mice, rather than in the hippocampus. Specifically, astrocyte activation preceding microglial activation was found in the somatosensory cortex (SS) of cDKO mice at 6 weeks of age. Over time, both astrocyte and microglial activation were found in the whole cortex, and age-related increases in gliosis activation were more pronounced in the cortex compared to hippocampus. Moreover, the age-associated increase in glial activation was accompanied by a gradual increase in the expression of cell chemokines Ccl3 and Ccl4, complement related factors C1qb, C3 and C4, and lysosomal proteases cathepsin S and Z. These findings suggest that astrocyte and microglial activation with a concurrent increase in inflammatory mediators such as chemokines might be an early event and contribute to the pathogenesis of neurodegeneration due to presenilin deficiency.
Crosstalk of Alzheimer’s disease-phenotype, HPA axis, splenic oxidative stress and frailty in late-stages of dementia, with special concerns on the effects of social isolation: A translational neuroscience approach
Authors: Muntsant Aida , Giménez-Llort Lydia
Published: September 2022

Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer’s disease (AD), alterations in the innate immune system result in crosstalk between immune mediators and neuronal and endocrine functions. Besides, neuropsychiatric symptoms such as depression, anxiety, or agitation are observed in most patients. Here, we studied the psychophysiological response to intrinsic (AD-phenotype) and extrinsic (anxiogenic tests) stress factors and their relation to liver, kidneys, heart, and spleen oxidative status in 18-months-old female gold-standard C57BL/6 mice and 3xTg-AD mice model for AD. The emotional, cognitive, and motor phenotypes were assessed under three different anxiogenic conditions. Survival, frailty index, and immunoendocrine status (corticosterone levels and oxidative stress of peripheral organs) were evaluated. Genotype differences in neuropsychiatric-like profiles and cognitive disfunction in 3xTg-AD females that survived beyond advanced stages of the disease persisted despite losing other behavioral and hypothalamic–pituitary–adrenal (HPA) physiological differences. A secondary analysis studied the impact of social isolation, naturally occurring in 3xTg-AD mice due to the death of cage mates. One month of isolation modified hyperactivity and neophobia patterns and disrupt the obsessive-compulsive disorder-like digging ethogram. Frailty index correlated with spleen organometrics in all groups, whereas two AD-specific salient functional correlations were identified: (1) Levels of corticosterone with worse performance in the T-maze, (2) and with a lower splenic GPx antioxidant enzymatic activity, which may suppose a potent risk of morbidity and mortality in AD.
Pair-bonding and social experience modulate new neurons survival in adult male and female prairie voles (Microtus ochrogaster)
Authors: Castro Analía E. , Domínguez-Ordoñez Raymundo , Young Larry J. , Camacho Francisco J. , Ávila-González Daniela , Paredes Raúl G. , Díaz Nestor F. , Portillo Wendy
Published: September 2022

Prairie voles are a socially monogamous species that, after cohabitation with mating, form enduring pair bonds. The plastic mechanisms involved in this social behavior are not well-understood. Neurogenesis in adult rodents is a plastic neural process induced in specific brain areas like the olfactory bulbs (OB) and dentate gyrus (DG) of the hippocampus. However, it is unknown how cell survival is modulated by social or sexual experience in prairie voles. This study aimed to evaluate if cohabitation with mating and/or social exposure to a vole of the opposite sex increased the survival of the new cells in the main and accessory OB and DG. To identify the new cells and evaluate their survival, voles were injected with the DNA synthesis marker 5-bromo-2’-deoxyuridine (BrdU) and were randomly distributed into one of the following groups: (A) Control (C), voles that did not receive any sexual stimulation and were placed alone during the behavioral test. (B) Social exposure (SE), voles were individually placed in a cage equally divided into two compartments by an acrylic screen with small holes. One male and one female were placed in opposite compartments. (C) Social cohabitation with mating (SCM), animals mated freely. Our findings demonstrated that SCM females had increases in the number of new cells (BrdU-positive cells) in the main olfactory bulb and new mature neurons (BrdU/NeuN-positive cells) in the glomerular layer (GlL). In contrast, these new cells decrease in males in the SE and SCM conditions. In the granular cell layer (GrL), SCM females had more new cells and neurons than the SE group. In the accessory olfactory bulb, in the anterior GlL, SCM decreased the number of new cells and neurons in females. On the other hand, in the DG, SCM and SE increase the number of new cells in the suprapyramidal blade in female voles. Males from SCM express more new cells and neurons in the infrapyramidal blade compared with SE group. Comparison between male and females showed that new cells/neurons survival was sex dependent. These results suggest that social interaction and sexual behavior modulate cell survival and influence the neuronal fate in a sex-dependent manner, in the OB and DG. This study will contribute to understand neural mechanisms of complex social and pair bond behaviors in the prairie voles; supporting adult neurogenesis as a plastic mechanism potentially involved in social monogamous strategy.