bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of carbon exchange characteristics to meteorological factors, phenology, and extreme events in a rubber plantation of Danzhou, Hainan: evidence based on multi-year data
Authors: Yang Siqi , Wu Zhixiang , Yang Chuan , Song Bo , Liu Junyi , Chen Bangqian , Lan Guoyu , Sun Rui , Zhang Jie
Published: June 2023

Introduction

On Hainan Island, a rubber plantation that occupies a large swath of land plays an important role in the regional carbon budget. However, the carbon exchange of the rubber plantation is poorly understood.

Methods

In this study, using the eddy covariance methods we measured carbon metrics in the rubber plantation for 13 years from 2010 to 2022.

Results

We clarified that the rubber plantation is a carbon sink and the annual net ecosystem exchange (NEE), ecosystem respiration, and gross primary production were −911.89 ± 135.37, 1,528.04 ± 253.50, and 2,439.93 ± 259.63 gC·m−2·a−1, respectively. Carbon fluxes differed between interannual years; specifically, rainy season fluxes were nearly double dry season fluxes. Radiation explained 46% of the variation for NEE in rainy season, and temperature explained 36% of the variation for NEE in the dry season. LAI explained the highest proportion of the monthly variation in NEE (R2 = 0.72, p < 0.001), indicating that when hydrothermal conditions are sufficient phenology may be the primary factor controlling carbon sequestration of rubber plantation. Due to climate change, there is an increasing probability of extreme climate events, such as typhoons, heat waves, and drought. Thus, we compared NEE before and after such events and results show extreme climate events reduce carbon uptake in the rubber plantation. We found that typhoons reduced NEE to varying degrees on different timescales. Heat waves generally decreased NEE during the day but recovered quickly and increased carbon uptake if there was sufficient precipitation. Drought reduced carbon uptake and continued to decrease even after precipitation.

Discussion

Estimating the carbon sink capacity of the rubber plantation and studying the response to regional environmental changes are important for both applied research (carbon sink research and market trading, sink enhancement, and emission reduction, etc.) and basic research (land use change, phenology change, etc.).
Sankofa Urbanism: retrieval, resilience, and cultural heritage in cities through time
Authors: Campbell Jacob , Bouman Mark , Crawford Arlene , Derby Lewis Abigail
Published: June 2023

One frequently cited principle that underlies the current move toward sustainability in urban planning and policy is, “long-term vision, incorporating awareness of the past and looking way into the future.” We name this “Sankofa Urbanism,” from the Ghanaian symbol and proverb that suggests, “it is not wrong to reach back for that which you have forgotten.” Planners and policy-makers have sought to build in cultural heritage as an important feature of “nature-based solutions” for cities. We argue that retrievals from the past in multiple forms can strengthen the integration of biodiversity preservation, community place-making and urban sustainability initiatives. We present a case for broader examination of how the past, along with diverse forms of ancestral environmental knowledge, is deployed to design and realize sustainability plans. We also call for deeper consideration of how urban planning leverages the evidence of archeology and history. The paper features a case study from our work in the Chicago region where heritage-based activities have been developed as solutions to contemporary urban environmental problems.
Implications of inflammatory cell death-related IFNG and co-expressed RNAs (AC006369.1 and CCR7) in breast carcinoma prognosis, and anti-tumor immunity
Authors: Deng Yongran , Li Zhenlong , Pan Mingmei , Wu Huayun , Ni Bingqiang , Han Xueqiong
Published: June 2023

Objective: Interferon-γ (IFN-γ) encoded by IFNG gene is a pleiotropic molecule linked with inflammatory cell death mechanisms. This work aimed to determine and characterize IFNG and co-expressed genes, and to define their implications in breast carcinoma (BRCA).

Methods: Transcriptome profiles of BRCA were retrospectively acquired from public datasets. Combination of differential expression analysis with WGCNA was conducted for selecting IFNG-co-expressed genes. A prognostic signature was generated through Cox regression approaches. The tumor microenvironment populations were inferred utilizing CIBERSORT. Epigenetic and epitranscriptomic mechanisms were also probed.

Results: IFNG was overexpressed in BRCA, and connected with prolonged overall survival and recurrence-free survival. Two IFNG-co-expressed RNAs (AC006369.1, and CCR7) constituted a prognostic model that acted as an independent risk factor. The nomogram composed of the model, TNM, stage, and new event owned the satisfying efficacy in BRCA prognostication. IFNG, AC006369.1, and CCR7 were closely linked with the tumor microenvironment components (e.g., macrophages, CD4/CD8 T cells, NK cells), and immune checkpoints (notably PD1/PD-L1). Somatic mutation frequencies were 6%, and 3% for CCR7, and IFNG, and high amplification potentially resulted in their overexpression in BRCA. Hypomethylated cg05224770 and cg07388018 were connected with IFNG and CCR7 upregulation, respectively. Additionally, transcription factors, RNA-binding proteins, and non-coding RNAs possibly regulated IFNG and co-expressed genes at the transcriptional and post-transcriptional levels.

Conclusion: Collectively, our work identifies IFNG and co-expressed genes as prognostic markers for BRCA, and as possible therapeutic targets for improving the efficacy of immunotherapy.
A current and future perspective on T cell receptor repertoire profiling
Authors: Shen Yiran , Voigt Alexandria , Leng Xuebing , Rodriguez Amy A. , Nguyen Cuong Q.
Published: June 2023

T cell receptors (TCR) play a vital role in the immune system’s ability to recognize and respond to foreign antigens, relying on the highly polymorphic rearrangement of TCR genes. The recognition of autologous peptides by adaptive immunity may lead to the development and progression of autoimmune diseases. Understanding the specific TCR involved in this process can provide insights into the autoimmune process. RNA-seq (RNA sequencing) is a valuable tool for studying TCR repertoires by providing a comprehensive and quantitative analysis of the RNA transcripts. With the development of RNA technology, transcriptomic data must provide valuable information to model and predict TCR and antigen interaction and, more importantly, identify or predict neoantigens. This review provides an overview of the application and development of bulk RNA-seq and single-cell (SC) RNA-seq to examine the TCR repertoires. Furthermore, discussed here are bioinformatic tools that can be applied to study the structural biology of peptide/TCR/MHC (major histocompatibility complex) and predict antigenic epitopes using advanced artificial intelligence tools.
Genotypic capacity of post-anthesis stem reserve mobilization in wheat for yield sustainability under drought and heat stress in the subtropical region
Authors: Gurumurthy S. , Arora A. , Krishna Hari , Chinnusamy V. , Hazra K. K.
Published: June 2023

Wheat productivity is severely affected by drought and heat stress conditions worldwide. Currently, stem reserve mobilization (SRM) is receiving increased attention as a trait that can sustain wheat yields under adverse environments. However, the significance of SRM in sustaining wheat yields under drought and heat stress conditions remains uncertain in the tropical climate of Indo-Gangetic Plain region. Therefore, this study aimed to investigate genotypic variations in SRM in wheat and their influence on yield sustainability under drought and heat stress environments. The experiment was designed in an alpha-lattice layout, accommodating 43 genotypes under four simulated environments [timely sown and well irrigated (non-stress); timely sown and water-deficit/drought stress; late-sown and well-irrigated crop facing terminally high temperature; and late-sown and water-deficit stress (both water-deficit and heat stress)]. The water-deficit stress significantly increased SRM (16%–68%, p < 0.01) compared to the non-stress environment, while the heat stress conditions reduced SRM (12%–18%). Both SRM and stem reserve mobilization efficiency exhibited positive correlations with grain weight (grain weight spike−1) under all three different stress treatments (p < 0.05). Strong positive correlations between stem weight (at 12 days after anthesis) and grain weight were observed across the environments (p < 0.001); however, a significant positive correlation between stem weight and SRM was observed only with stress treatments. Results revealed that the SRM trait could effectively alleviate the impacts of water-deficit stress on yields. However, the SRM-mediated yield protection was uncertain under heat stress and combined water-deficit and heat stress treatments, possibly due to sink inefficiencies caused by high temperature during the reproductive period. Defoliated plants exhibited higher SRM than non-defoliated plants, with the highest increment observed in the non-stress treatment compared to all the stress treatments. Results revealed that wider genetic variability exists for the SRM trait, which could be used to improve wheat yield under drought stress conditions.
Identification, characterization, and validation of NBS-encoding genes in grass pea
Authors: Alsamman Alsamman M. , Mousa Khaled H. , Nassar Ahmed E. , Faheem Mostafa M. , Radwan Khaled H. , Adly Monica H. , Hussein Ahmed , Istanbuli Tawffiq , Mokhtar Morad M. , Elakkad Tamer Ahmed , Kehel Zakaria , Hamwieh Aladdin , Abdelsattar Mohamed , El Allali Achraf
Published: June 2023

Grass pea is a promising crop with the potential to provide food and fodder, but its genomics has not been adequately explored. Identifying genes for desirable traits, such as drought tolerance and disease resistance, is critical for improving the plant. Grass pea currently lacks known R-genes, including the nucleotide-binding site-leucine-rich repeat (NBS-LRR) gene family, which plays a key role in protecting the plant from biotic and abiotic stresses. In our study, we used the recently published grass pea genome and available transcriptomic data to identify 274 NBS-LRR genes. The evolutionary relationships between the classified genes on the reported plants and LsNBS revealed that 124 genes have TNL domains, while 150 genes have CNL domains. All genes contained exons, ranging from 1 to 7. Ten conserved motifs with lengths ranging from 16 to 30 amino acids were identified. We found TIR-domain-containing genes in 132 LsNBSs, with 63 TIR-1 and 69 TIR-2, and RX-CCLike in 84 LsNBSs. We also identified several popular motifs, including P-loop, Uup, kinase-GTPase, ABC, ChvD, CDC6, Rnase_H, Smc, CDC48, and SpoVK. According to the gene enrichment analysis, the identified genes undergo several biological processes such as plant defense, innate immunity, hydrolase activity, and DNA binding. In the upstream regions, 103 transcription factors were identified that govern the transcription of nearby genes affecting the plant excretion of salicylic acid, methyl jasmonate, ethylene, and abscisic acid. According to RNA-Seq expression analysis, 85% of the encoded genes have high expression levels. Nine LsNBS genes were selected for qPCR under salt stress conditions. The majority of the genes showed upregulation at 50 and 200 μM NaCl. However, LsNBS-D18, LsNBS-D204, and LsNBS-D180 showed reduced or drastic downregulation compared to their respective expression levels, providing further insights into the potential functions of LsNBSs under salt stress conditions. They provide valuable insights into the potential functions of LsNBSs under salt stress conditions. Our findings also shed light on the evolution and classification of NBS-LRR genes in legumes, highlighting the potential of grass pea. Further research could focus on the functional analysis of these genes, and their potential use in breeding programs to improve the salinity, drought, and disease resistance of this important crop.
KL-6 levels in the connective tissue disease population: typical values and potential confounders–a retrospective, real-world study
Authors: Zhou Aiyuan , Tang Haiyun , Peng Wenzhong , Wang Yanan , Tang Xiaoping , Yang Hang , Lu Rongli , Pan Pinhua
Published: June 2023

Background

Krebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation.

Methods

From the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD.

Results

Univariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the β were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P < 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients.

Conclusion

KL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account.
IL-15 promotes self-renewal of progenitor exhausted CD8 T cells during persistent antigenic stimulation
Authors: Lee Junghwa , Lee Kyungmin , Bae Hyeonjin , Lee Kunhee , Lee Solhwi , Ma Junhui , Jo Kyungjo , Kim Ijun , Jee ByulA , Kang Minyong , Im Se Jin
Published: June 2023

In chronic infections and cancer, exhausted CD8 T cells exhibit heterogeneous subpopulations. TCF1+PD-1+ progenitor exhausted CD8 T cells (Tpex) can self-renew and give rise to Tim-3+PD-1+ terminally differentiated CD8 T cells that retain their effector functions. Tpex cells are thus essential to maintaining a pool of antigen-specific CD8 T cells during persistent antigenic stimulation, and only they respond to PD-1-targeted therapy. Despite their potential as a crucial therapeutic target for immune interventions, the mechanisms controlling the maintenance of virus-specific Tpex cells remain to be determined. We observed approximately 10-fold fewer Tpex cells in the spleens of mice chronically infected with lymphocytic choriomeningitis virus (LCMV) one-year post-infection (p.i.) than at three months p.i. Similar to memory CD8 T cells, Tpex cells have been found to undergo self-renewal in the lymphoid organs, prominently the bone marrow, during chronic LCMV infection. Furthermore, ex vivo treatment with IL-15 preferentially induced the proliferation of Tpex cells rather than the terminally differentiated subsets. Interestingly, single-cell RNA sequencing analysis of LCMV-specific exhausted CD8 T cells after ex vivo IL-15 treatment compared with those before treatment revealed increased expression of ribosome-related genes and decreased expression of genes associated with the TCR signaling pathway and apoptosis in both Tpex and Ttex subsets. The exogenous administration of IL-15 to chronically LCMV-infected mice also significantly increased self-renewal of Tpex cells in the spleen and bone marrow. In addition, we assessed the responsiveness of CD8 tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma patients to IL-15. Similar to the data we obtained from chronic viral infection in mice, the expansion of the Tpex subset of PD-1+ CD8 TILs upon ex vivo IL-15 treatment was significantly higher than that of the terminally differentiated subset. These results show that IL-15 could promote self-renewal of Tpex cells, which has important therapeutic implications.
Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis
Authors: Cheng Wen , Liao Yang , Mou Ruiyu , Xiao Xian , Jia Yingjie
Published: June 2023

Background

Previous epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis.

Methods

We performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.

Results

Genetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn’s disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method.

Conclusions

This study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.
Imidazoquinolines with improved pharmacokinetic properties induce a high IFNα to TNFα ratio in vitro and in vivo
Authors: Keppler Manuel , Straß Simon , Geiger Sophia , Fischer Tina , Späth Nadja , Weinstein Thilo , Schwamborn Anna , Guezguez Jamil , Guse Jan-Hinrich , Laufer Stefan , Burnet Michael
Published: June 2023

TLR Agonists have promising activity in preclinical models of viral infection and cancer. However, clinical use is only in topical application. Systemic uses of TLR-ligands such as Resiquimod, have failed due to adverse effects that limited dose and thus, efficacy. This issue could be related to pharmacokinetic properties that include fast elimination leading to low AUC with simultaneously high cmax at relevant doses. The high cmax is associated with a sharp, poorly tolerated cytokine pulse, suggesting that a compound with a higher AUC/cmax-ratio could provide a more sustained and tolerable immune activation. Our approach was to design TLR7/8-agonist Imidazoquinolines intended to partition to endosomes via acid trapping using a macrolide-carrier. This can potentially extend pharmacokinetics and simultaneously direct the compounds to the target compartment. The compounds have hTLR7/8-agonist activity (EC50 of the most active compound in cellular assays: 75-120 nM hTLR7, 2.8-3.1 µM hTLR8) and maximal hTLR7 activation between 40 and 80% of Resiquimod. The lead candidates induce secretion of IFNα from human Leukocytes in the same range as Resiquimod but induce at least 10-fold less TNFα in this system, consistent with a higher specificity for human TLR7. This pattern was reproduced in vivo in a murine system, where small molecules are thought not to activate TLR8. We found that Imidazoquinolines conjugated to a macrolide or, substances carrying an unlinked terminal secondary amine, had longer exposure compared with Resiquimod. The kinetics of pro-inflammatory cytokine release for these substances in vivo were slower and more extended (for comparable AUCs, approximately half-maximal plasma concentrations). Maximal IFNα plasma levels were reached 4 h post application. Resiquimod-treated groups had by then returned to baseline from a peak at 1 h. We propose that the characteristic cytokine profile is likely a consequence of altered pharmacokinetics and, potentially, enhanced endosomal tropism of the novel substances. In particular, our substances are designed to partition to cellular compartments where the target receptor and a distinct combination of signaling molecules relevant to IFNα-release are located. These properties could address the tolerability issues of TLR7/8 ligands and provide insight into approaches to fine-tune the outcomes of TLR7/8 activation by small molecules.
Nutrient-rich submarine groundwater discharge increases algal carbon uptake in a tropical reef ecosystem
Authors: La Valle Florybeth Flores , Jacobs Julian M. , Thomas Florence I. , Nelson Craig E.
Published: June 2023

Submarine groundwater discharge (SGD) in high volcanic islands can be an important source of freshwater and nutrients to coral reefs. High inorganic nutrient content is generally thought to augment primary production in coastal systems but when this is delivered via a freshwater vector as is the case with SGD in this study, the effects on productivity are unclear. In the current literature, there is limited evidence for a direct association between SGD and primary productivity of reefs. To elucidate the response of primary productivity to SGD, we conducted spatially and temporally explicit in situ benthic chamber experiments on a reef flat along a gradient of SGD. We found significant quadratic relationships between C-uptake and SGD for both phytoplankton and the most abundant macroalga, Gracilaria salicornia, with uptake maxima at SGD-derived salinities of ~21−22 (24.5−26.6 μmol NO3-L−1). These results suggest a physiological tradeoff between salinity tolerance and nutrient availability for reef primary producers. Spatially explicit modeling of reefs with SGD and without SGD indicate reef-scale G. salicornia and phytoplankton C-uptake decreased by 82% and 36% in the absence of SGD, respectively. Thus, nutrient-rich and low salinity SGD has significant effects on algal C-uptake in reef systems.
Molecular dynamics simulation of frictional properties of Pt cluster on graphite under load
Authors: Cörüt S. , İpek S.
Published: June 2023

Structural lubricity, characterized by nearly frictionless behavior at solid incommensurate interfaces with weak interactions, holds significant technological importance. However, various factors can lead to the breakdown of structural lubricity, such as spontaneous reorientation to a commensurate state, applied load, edge effects, deformations, and wear. To overcome these challenges, clusters can be employed at interfaces. With their high Young’s modulus and stiffness, clusters can withstand high loads and tolerate elastic deformations. Therefore, Pt cluster, which inherently possess incommensurate contact with graphite surface, are expected to exhibit structural superlubric behavior, even under high loads, as long as they can sustain incommensurate contact. Our molecular dynamics (MD) simulations, however, have revealed that a Pt cluster on graphite can undergo metastable transitions from the incommensurate state to a commensurate state, resulting in subsequent stick-slip behavior. In the absence of any external load, the Pt cluster has demonstrated the ability to maintain incommensurate contact with almost zero friction force, primarily attributed to its weak interaction with graphite. However, the presence of an applied load force leads to the loss of the initial incommensurate contact between the Pt cluster and graphite, resulting in the emergence of high friction forces and the breakdown of structural lubricity with a similar stick-slip behavior to that observed in the comparative simulations conducted for the commensurate state. It becomes evident that the maintenance of incommensurate contact is crucial for achieving superlubric behavior in Pt cluster-graphite systems, while the presence of an applied load force can disrupt this behavior and lead to higher friction forces.
Sentinel node mapping in thyroid cancer: an overview
Authors: Puccini Marco , Ambrosini Carlo Enrico , Rossi Leonardo , De Napoli Luigi , Materazzi Gabriele
Published: June 2023

In this paper we describe the current status of sentinel node mapping (SNM) in thyroid tumors and its potential perspectives. SNM in thyroid cancer has been tested since the end of the twentieth century, mainly in papillary thyroid cancer (PTC) and in medullary thyroid cancer (MTC). In PTC, it has been employed to find occult lymph node metastases in the central compartment of the neck as an alternative or indication for prophylactic dissection, by several methods. All of them have proven effective in spotting sentinel nodes, but the results have been somewhat diminished by uncertainty about the clinical significance of occult metastases in differentiated thyroid cancer. SNM in MTC has also been used to find occult lymph node metastases in the lateral compartments of the neck, also with excellent results hindered by a similar doubt about the real clinical significance of MTC micrometastases. Well designed, adequately sized randomized controlled trials are lacking, so SNM in thyroid tumors remains an interesting yet experimental methodology. New technology is emerging that could facilitate such studies, which could add solid information about the clinical significance of occult neck metastases in thyroid cancer.
Multisite transformation in Neisseria gonorrhoeae: insights on transformations mechanisms and new genetic modification protocols
Authors: Seow Vui Yin , Tsygelnytska Olga , Biais Nicolas
Published: June 2023

Natural transformation, or the uptake of naked DNA from the external milieu by bacteria, holds a unique place in the history of biology. This is both the beginning of the realization of the correct chemical nature of genes and the first technical step to the molecular biology revolution that sees us today able to modify genomes almost at will. Yet the mechanistic understanding of bacterial transformation still presents many blind spots and many bacterial systems lag behind power horse model systems like Escherichia coli in terms of ease of genetic modification. Using Neisseria gonorrhoeae as a model system and using transformation with multiple DNA molecules, we tackle in this paper both some aspects of the mechanistic nature of bacterial transformation and the presentation of new molecular biology techniques for this organism. We show that similarly to what has been demonstrated in other naturally competent bacteria, Neisseria gonorrhoeae can incorporate, at the same time, different DNA molecules modifying DNA at different loci within its genome. In particular, co-transformation of a DNA molecule bearing an antibiotic selection cassette and another non-selected DNA piece can lead to the integration of both molecules in the genome while selecting only through the selective cassette at percentages above 70%. We also show that successive selections with two selection markers at the same genetic locus can drastically reduce the number of genetic markers needed to do multisite genetic modifications in Neisseria gonorrhoeae. Despite public health interest heightened with the recent rise in antibiotic resistance, the causative agent of gonorrhea still does not possess a plethora of molecular techniques. This paper will extend the techniques available to the Neisseria community while providing some insights into the mechanisms behind bacterial transformation in Neisseria gonorrhoeae. We are providing a suite of new techniques to quickly obtain modifications of genes and genomes in the Neisserial naturally competent bacteria.
The association between physical activity and cognitive function in the elderly in rural areas of northern China
Authors: Wang Xueyan , Zhang Jiesong , Chen Chen , Lu Zhonghai , Zhang Dongfeng , Li Suyun
Published: June 2023

Background

Physical activity plays an important role in cognitive function in older adults, and the threshold effect and saturation effect between physical activity and cognitive function are unclear.

Objective

The purpose of this study was to explore the threshold effect and saturation effect between physical activity and cognitive function in the elderly.

Methods

The International Physical Activity Questionnaire (IPAQ) was used to measure moderate-intensity physical activity and vigorous-intensity physical activity and total physical activity in older adults. Cognitive function assessment uses the Beijing version of the Montreal Cognitive Assessment Scale (MoCA). The scale consists of seven parts: visual space, naming, attention, language, abstract ability, delayed recall and orientation, for a total of 30 points. The total score of the study participants < 26 was defined as the optimum cutoff point for a definition of mild cognitive impairment (MCI). The multivariable linear regression model was used to initially explore the relationship between physical activity and total cognitive function scores. The logistic regression model was used to assess the relationship between physical activity and cognitive function dimensions and MCI. The threshold effect and saturation effect between the total physical activity and the total cognitive function scores were investigated by smoothed curve fitting.

Results

This cross-sectional survey had a total of 647 participants aged 60 years and older (mean age: 73 years, female: 53.7%). Participants’ higher level of physical activity were associated with higher visual space, attention, language, abstract ability, and delayed recall scores (P < 0.05). Physical activity was not statistically associated with naming and orientation. Physical activity was a protective factor for MCI (P < 0.05). Physical activity was positively correlated with total cognitive function scores. There was a saturation effect between total physical activity and total cognitive function scores, and the saturation point was 6546 MET × min/wk.

Conclusion

This study showed a saturation effect between physical activity and cognitive function, and determined an optimal level of physical activity to protect cognitive function. This finding will help update physical activity guidelines based on cognitive function in the elderly.
Altered circadian behavior and light sensing in mouse models of Alzheimer’s disease
Authors: Weigel Thaddeus K. , Guo Cherry L. , Güler Ali D. , Ferris Heather A.
Published: June 2023

Circadian symptoms have long been observed in Alzheimer’s disease (AD) and often appear before cognitive symptoms, but the mechanisms underlying circadian alterations in AD are poorly understood. We studied circadian re-entrainment in AD model mice using a “jet lag” paradigm, observing their behavior on a running wheel after a 6 h advance in the light:dark cycle. Female 3xTg mice, which carry mutations producing progressive amyloid beta and tau pathology, re-entrained following jet lag more rapidly than age-matched wild type controls at both 8 and 13 months of age. This re-entrainment phenotype has not been previously reported in a murine AD model. Because microglia are activated in AD and in AD models, and inflammation can affect circadian rhythms, we hypothesized that microglia contribute to this re-entrainment phenotype. To test this, we used the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX3397, which rapidly depletes microglia from the brain. Microglia depletion did not alter re-entrainment in either wild type or 3xTg mice, demonstrating that microglia activation is not acutely responsible for the re-entrainment phenotype. To test whether mutant tau pathology is necessary for this behavioral phenotype, we repeated the jet lag behavioral test with the 5xFAD mouse model, which develops amyloid plaques, but not neurofibrillary tangles. As with 3xTg mice, 7-month-old female 5xFAD mice re-entrained more rapidly than controls, demonstrating that mutant tau is not necessary for the re-entrainment phenotype. Because AD pathology affects the retina, we tested whether differences in light sensing may contribute to altered entrainment behavior. 3xTg mice demonstrated heightened negative masking, a circadian behavior measuring responses to different levels of light, and re-entrained dramatically faster than WT mice in a jet lag experiment performed in dim light. 3xTg mice show a heightened sensitivity to light as a circadian cue that may contribute to accelerated photic re-entrainment. Together, these experiments demonstrate novel circadian behavioral phenotypes with heightened responses to photic cues in AD model mice which are not dependent on tauopathy or microglia.
MLNet: a multi-level multimodal named entity recognition architecture
Authors: Zhai Hanming , Lv Xiaojun , Hou Zhiwen , Tong Xin , Bu Fanliang
Published: June 2023

In the field of human–computer interaction, accurate identification of talking objects can help robots to accomplish subsequent tasks such as decision-making or recommendation; therefore, object determination is of great interest as a pre-requisite task. Whether it is named entity recognition (NER) in natural language processing (NLP) work or object detection (OD) task in the computer vision (CV) field, the essence is to achieve object recognition. Currently, multimodal approaches are widely used in basic image recognition and natural language processing tasks. This multimodal architecture can perform entity recognition tasks more accurately, but when faced with short texts and images containing more noise, we find that there is still room for optimization in the image-text-based multimodal named entity recognition (MNER) architecture. In this study, we propose a new multi-level multimodal named entity recognition architecture, which is a network capable of extracting useful visual information for boosting semantic understanding and subsequently improving entity identification efficacy. Specifically, we first performed image and text encoding separately and then built a symmetric neural network architecture based on Transformer for multimodal feature fusion. We utilized a gating mechanism to filter visual information that is significantly related to the textual content, in order to enhance text understanding and achieve semantic disambiguation. Furthermore, we incorporated character-level vector encoding to reduce text noise. Finally, we employed Conditional Random Fields for label classification task. Experiments on the Twitter dataset show that our model works to increase the accuracy of the MNER task.
Synchronous multimode ultrasound for assessing right-to-left shunt: a prospective clinical study
Authors: Yao Qingyang , Xiong Huahua , Zhang Daxue , Ren Shuqun , Qi Wenwei , Zou Xia , Zhao Yingying , Huang Shanshan , Wang Jing , Cao Liming
Published: June 2023

Background

Right-to-left shunt (RLS) is associated with several conditions and causes morbidity. In this study, we aimed to evaluate the effectiveness of synchronous multimode ultrasonography in detecting RLS.

Methods

We prospectively enrolled 423 patients with high clinical suspicion of RLS and divided them into the contrast transcranial Doppler (cTCD) group and synchronous multimode ultrasound group, in which both cTCD and contrast transthoracic echocardiography (cTTE) were performed during the same process of contrast-enhanced ultrasound imaging. The simultaneous test results were compared with those of cTCD alone.

Results

The positive rates of grade II (22.0%:10.0%) and III (12.7%:10.8%) shunts and the total positive rate (82.1748%) in the synchronous multimode ultrasound group were higher than those in the cTCD alone group. Among patients with RLS grade I in the synchronous multimode ultrasound group, 23 had RLS grade I in cTCD but grade 0 in synchronous cTTE, whereas four had grade I in cTCD but grade 0 in synchronous cTTE. Among patients with RLS grade II in the synchronous multimode ultrasound group, 28 had RLS grade I in cTCD but grade II in synchronous cTTE. Among patients with RLS grade III in the synchronous multimode ultrasound group, four had RLS grade I in cTCD but grade III in synchronous cTTE. Synchronous multimode ultrasound had a sensitivity of 87.5% and specificity of 60.6% in the patent foramen ovale (PFO) diagnosis. Binary logistic regression analyses showed that age (odds ratio [OR] = 1.041) and risk of paradoxical embolism score ≥ 7 (OR = 7.798) were risk factors for stroke recurrence, whereas antiplatelets (OR = 0.590) and PFO closure with antiplatelets (OR = 0.109) were protective factors.

Conclusion

Synchronous multimodal ultrasound significantly improves the detection rate and test efficiency, quantifies RLS more accurately, and reduces testing risks and medical costs. We conclude that synchronous multimodal ultrasound has significant potential for clinical applications.
Diagnosis of post-neurosurgical bacterial meningitis in patients with aneurysmal subarachnoid hemorrhage based on the immunity-related proteomics signature of the cerebrospinal fluid
Authors: Zhao Liang , Li Pingping , Xu Ziao , Ji Xuefei , Guan Liao , Wang Xiaojian , Luo Jin , Cheng Hongwei , Ye Lei
Published: June 2023

Introduction

Post-neurosurgical bacterial meningitis (PNBM) is a serious complication for patients who receive neurosurgical treatment, but the diagnosis is difficult given the complicated microenvironment orchestrated by sterile brain injury and pathogenic infection. In this study, we explored potential diagnostic biomarkers and immunological features using a proteomics platform.

Methods

A total of 31 patients with aneurysmal subarachnoid hemorrhage (aSAH) who received neurosurgical treatment were recruited for this study. Among them, 15 were diagnosed with PNBM. The remaining 16 patients were categorized into the non-PNBM group. Proteomics analysis of the cerebrospinal fluid (CSF) was conducted on the Olink platform, which contained 92 immunity-related molecules.

Results

We found that the expressions of 27 CSF proteins were significantly different between the PNBM and non-PNBM groups. Of those 27 proteins, 15 proteins were upregulated and 12 were downregulated in the CSF of the PNBM group. The receiver operating characteristic curve analysis indicated that three proteins (pleiotrophin, CD27, and angiopoietin 1) had high diagnostic accuracy for PNBM. Furthermore, we also performed bioinformatics analysis to explore potential pathways and the subcellular localization of the proteins.

Conclusion

In summary, we found a cohort of immunity-related molecules that can serve as potential diagnostic biomarkers for PNBM in patients with aSAH. These molecules also provide an immunological profile of PNBM.
Preclinical models of middle cerebral artery occlusion: new imaging approaches to a classic technique
Authors: Sokolowski Jennifer D. , Soldozy Sauson , Sharifi Khadijeh A. , Norat Pedro , Kearns Kathryn N. , Liu Lei , Williams Ashley M. , Yağmurlu Kaan , Mastorakos Panagiotis , Miller G. Wilson , Kalani M. Yashar S. , Park Min S. , Kellogg Ryan T. , Tvrdik Petr
Published: June 2023

Stroke remains a major burden on patients, families, and healthcare professionals, despite major advances in prevention, acute treatment, and rehabilitation. Preclinical basic research can help to better define mechanisms contributing to stroke pathology, and identify therapeutic interventions that can decrease ischemic injury and improve outcomes. Animal models play an essential role in this process, and mouse models are particularly well-suited due to their genetic accessibility and relatively low cost. Here, we review the focal cerebral ischemia models with an emphasis on the middle cerebral artery occlusion technique, a “gold standard” in surgical ischemic stroke models. Also, we highlight several histologic, genetic, and in vivo imaging approaches, including mouse stroke MRI techniques, that have the potential to enhance the rigor of preclinical stroke evaluation. Together, these efforts will pave the way for clinical interventions that can mitigate the negative impact of this devastating disease.
Hyperbaric air mobilizes stem cells in humans; a new perspective on the hormetic dose curve
Authors: MacLaughlin Kent J. , Barton Gregory P. , Braun Rudolf K. , MacLaughlin Julia E. , Lamers Jacob J. , Marcou Matthew D. , Eldridge Marlowe W.
Published: June 2023

Introduction

Hyperbaric air (HBA) was first used pharmaceutically in 1662 to treat lung disease. Extensive use in Europe and North America followed throughout the 19th century to treat pulmonary and neurological disorders. HBA reached its zenith in the early 20th century when cyanotic, moribund “Spanish flu pandemic” patients turned normal color and regained consciousness within minutes after HBA treatment. Since that time the 78% Nitrogen fraction in HBA has been completely displaced by 100% oxygen to create the modern pharmaceutical hyperbaric oxygen therapy (HBOT), a powerful treatment that is FDA approved for multiple indications. Current belief purports oxygen as the active element mobilizing stem progenitor cells (SPCs) in HBOT, but hyperbaric air, which increases tensions of both oxygen and nitrogen, has been untested until now. In this study we test HBA for SPC mobilization, cytokine and chemokine expression, and complete blood count.

Methods

Ten 34–35-year-old healthy volunteers were exposed to 1.27ATA (4 psig/965 mmHg) room air for 90 min, M-F, for 10 exposures over 2-weeks. Venous blood samples were taken: (1) prior to the first exposure (served as the control for each subject), (2) directly after the first exposure (to measure the acute effect), (3) immediately prior to the ninth exposure (to measure the chronic effect), and (4) 3 days after the completion of tenth/final exposure (to assess durability). SPCs were gated by blinded scientists using Flow Cytometry.

Results

SPCs (CD45dim/CD34+/CD133-) were mobilized by nearly two-fold following 9 exposures (p = 0.02) increasing to three-fold 72-h post completion of the final (10th) exposure (p = 0.008) confirming durability.

Discussion

This research demonstrates that SPCs are mobilized, and cytokines are modulated by hyperbaric air. HBA likely is a therapeutic treatment. Previously published research using HBA placebos should be re-evaluated to reflect a dose treatment finding rather than finding a placebo effect. Our findings of SPC mobilization by HBA support further investigation into hyperbaric air as a pharmaceutical/therapy.
Clinical efficacy and safety of rimegepant in the treatment of migraine: a meta-analysis of randomized controlled trials
Authors: Wang Qinghui , Wang Shuangmei , Zhu Yi , Lin Fei
Published: June 2023

Background

This study aims to evaluate the clinical efficacy and safety of rimegepant for the treatment of migraine in adult patients using a meta-analysis.

Methods

The PubMed, EMBASE, and Cochrane Library were searched up to March 2022. Only randomized controlled trials (RCTs) that evaluated migraine and other comparator treatments in adult patients were included. The clinical response at the post-treatment evaluation, including acute pain free and relief effect, whereas the secondary outcomes were the risk of adverse events (AEs).

Results

A total of 4 RCTs involving 4,230 patients with episodic migraine were included. Outcome indicators for the number of pain free and relief patients at 2 h, 2–24 h, 2–48 h post-dose showed that rimegepant had better effects relative to the placebo [free at 2 h: OR = 1.84, 95% CI (1.55, 2.18), P < 0.00001; relief at 2 h: OR = 1.80, 95% CI (1.59, 2.04), P < 0.00001]. And there was no significant difference between the occurrence of adverse events in the experimental and control groups [OR = 1.29, 95% CI (0.99, 1.67), P = 0.06].

Conclusion

Rimegepant has better therapeutic effects compared to placebo and no significant difference in adverse events.
Investigation of the efficacy and safety of retinal inactivation as a treatment for amblyopia in cats
Authors: Hogan Mairin , DiCostanzo Nadia R. , Crowder Nathan A. , Fong Ming-fai , Duffy Kevin R.
Published: June 2023

Introduction

Deprivation of normal vision early in postnatal development elicits modifications of neural circuitry within the primary visual pathway that can cause a severe and intractable vision impairment (amblyopia). In cats, amblyopia is often modeled with monocular deprivation (MD), a procedure that involves temporarily closing the lids of one eye. Following long-term MD, brief inactivation of the dominant eye’s retina can promote recovery from the anatomical and physiological effects of MD. In consideration of retinal inactivation as a viable treatment for amblyopia it is imperative to compare its efficacy against conventional therapy, as well as assess the safety of its administration.

Methods

In the current study we compared the respective efficacies of retinal inactivation and occlusion of the dominant eye (reverse occlusion) to elicit physiological recovery from a prior long-term MD in cats. Because deprivation of form vision has been associated with development of myopia, we also examined whether ocular axial length or refractive error were altered by a period of retinal inactivation.

Results

The results of this study demonstrate that after a period of MD, inactivation of the dominant eye for up to 10 days elicited significant recovery of visually-evoked potentials that was superior to the recovery measured after a comparable duration of reverse occlusion. After monocular retinal inactivation, measurements of ocular axial length and refractive error were not significantly altered from their pre-inactivation values. The rate of body weight gain also was not changed during the period of inactivation, indicating that general well-being was not affected.

Discussion

These results provide evidence that inactivation of the dominant eye after a period of amblyogenic rearing promotes better recovery than eye occlusion, and this recovery was achieved without development of form-deprivation myopia.
Innate immune activation and aberrant function in the R6/2 mouse model and Huntington’s disease iPSC-derived microglia
Authors: Gasser Julien , Gillet Gaelle , Valadas Jorge S. , Rouvière Laura , Kotian Apoorva , Fan Wenqiang , Keaney James , Kadiu Irena
Published: June 2023

Huntington’s disease (HD) is an inherited autosomal dominant neurodegenerative disease caused by CAG repeats in exon 1 of the HTT gene. A hallmark of HD along with other psychiatric and neurodegenerative diseases is alteration in the neuronal circuitry and synaptic loss. Microglia and peripheral innate immune activation have been reported in pre-symptomatic HD patients; however, what “activation” signifies for microglial and immune function in HD and how it impacts synaptic health remains unclear. In this study we sought to fill these gaps by capturing immune phenotypes and functional activation states of microglia and peripheral immunity in the R6/2 model of HD at pre-symptomatic, symptomatic and end stages of disease. These included characterizations of microglial phenotypes at single cell resolution, morphology, aberrant functions such as surveillance and phagocytosis and their impact on synaptic loss in vitro and ex vivo in R6/2 mouse brain tissue slices. To further understand how relevant the observed aberrant microglial behaviors are to human disease, transcriptomic analysis was performed using HD patient nuclear sequencing data and functional assessments were conducted using induced pluripotent stem cell (iPSC)-derived microglia. Our results show temporal changes in brain infiltration of peripheral lymphoid and myeloid cells, increases in microglial activation markers and phagocytic functions at the pre-symptomatic stages of disease. Increases in microglial surveillance and synaptic uptake parallel significant reduction of spine density in R6/2 mice. These findings were mirrored by an upregulation of gene signatures in the endocytic and migratory pathways in disease-associated microglial subsets in human HD brains, as well as increased phagocytic and migratory functions of iPSC-derived HD microglia. These results collectively suggest that targeting key and specific microglial functions related to synaptic surveillance and pruning may be therapeutically beneficial in attenuating cognitive decline and psychiatric aspects of HD.