bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of mesenchymal stromal cells and human recombinant Nerve Growth Factor delivered by bioengineered human corneal lenticule on an innovative model of diabetic retinopathy
Authors: Pelusi Letizia , Hurst Jose , Detta Nicola , Pipino Caterina , Lamolinara Alessia , Conte Gemma , Mastropasqua Rodolfo , Allegretti Marcello , Di Pietrantonio Nadia , Romeo Tiziana , El Zarif Mona , Nubile Mario , Guerricchio Laura , Bollini Sveva , Pandolfi Assunta , Schnichels Sven , Mandatori Domitilla
Published: October 2024

Introduction

Diabetic retinopathy (DR) is a microvascular complication of diabetes in which neurodegeneration has been recently identified as a driving force. In the last years, mesenchymal stromal cells (MSCs) and neurotrophins like Nerve Growth Factor (NGF), have garnered significant attention as innovative therapeutic approaches targeting DR-associated neurodegeneration. However, delivering neurotrophic factors directly in the eye remains a challenge. Hence, this study evaluated the effects of MSCs from human amniotic fluids (hAFSCs) and recombinant human NGF (rhNGF) delivered by human corneal lenticule (hCL) on a high glucose (HG) induced ex vivo model simulating the molecular mechanisms driving DR.

Methods

Porcine neuroretinal explants exposed to HG (25 mM for four days) were used to mimic DR ex vivo. hCLs collected from donors undergoing refractive surgery were decellularized using 0.1% sodium dodecyl sulfate and then bioengineered with hAFSCs, microparticles loaded with rhNGF (rhNGF-PLGA-MPs), or both simultaneously. Immunofluorescence (IF) and scanning electron microscopy (SEM) analyses were performed to confirm the hCLs bioengineering process. To assess the effects of hAFSCs and rhNGF, bioengineered hCLs were co-cultured with HG-treated neuroretinal explants and following four days RT-PCR and cytokine array experiments for inflammatory, oxidative, apoptotic, angiogenic and retinal cells markers were performed.

Results

Data revealed that HG-treated neuroretinal explants exhibit a characteristic DR-phenotype, including increased level of NF-kB, NOS2, NRF2 GFAP, VEGFA, Bax/Bcl2 ratio and decreased expression of TUBB3 and Rho. Then, the feasibility to bioengineer decellularized hCLs with hAFSCs and rhNGF was demonstrated. Interestingly, co-culturing hAFSCs- and rhNGF- bioengineered hCLs with HG-treated neuroretinal explants for four days significantly reduced the expression of inflammatory, oxidative, apoptotic, angiogenic and increased retinal markers.

Conclusion

Overall, we found for the first time that hAFSCs and rhNGF were able to modulate the molecular mechanisms involved in DR and that bioengineered hCLs represents a promising ocular drug delivery system of hAFSCs and rhNGF for eye diseases treatment. In addition, results demonstrated that porcine neuroretinal explants treated with HG is a useful model to reproduce ex vivo the DR pathophysiology.
Sleet damage to branches and crowns of street camphor trees (Cinnamomum camphora) in a central China mega-city: damage statistics, modelling, and implications
Authors: Liu Yichen , Zhang Junru , Rao Shanshan , Xu Kun
Published: October 2024

Introduction

Extreme weather becomes increasingly frequent and severe under climate change, causing unexpected damage to trees. Among them, sleet damage is particularly harmful to evergreen trees in subtropical area. Camphor trees (Cinnamomum camphora), as dominant street trees in central China, are prone to sleet damage, resulting in loss of valuable ecosystem functions.

Methods

By measuring tree size characteristics of 118 camphor trees before and after a record-breaking sleet event in Wuhan, a mega-city in central China, we built allometric equations between size and volume of broken branches and used the random forest regression to model sleet damage to camphor trees.

Results

We identified that larger trees with intermediate bole height suffered more than smaller trees with tall bole height from the sleet event. We estimated the volume of broken branches of a camphor tree with DBH at 35.0 cm as 106.4 dm3, equivalent to 55.3 kg biomass loss, from the sleet event.

Discussion

We suggest that pruning the branches instead of topping the main stems of small camphor trees would reduce the sleet hazard. To mitigate the negative impacts of climate change, regular pruning should be practiced on street camphor trees to protect them from future heavy sleet events.
Identification, function validation and haplotype analysis of salt-tolerant genes of lectin receptor kinase gene family in sorghum (Sorghum bicolor L.)
Authors: Mao Li , Huazhuan He , Haiyan Gao , Wangqi Huang , Qizhe Cai , Guiyun Yan , Qingjun Cheng , Yinpei Liang , Xiuhua Chen
Published: October 2024

Introduction

Salt stress is one of the significant challenges in sorghum production, greatly impacting the yield of S. bicolor. L-type lectin receptor kinases (LLRKs) are essential for plant stress tolerance, yet a comprehensive genome-level analysis in this species has not been conducted.

Materials and methods

Members of the SbLLRLK gene family were identified using bioinformatics methods. Gene structures, motifs, and phylogenetic relationships were analyzed. Subsequently, expression profiles under various stress conditions were examined using transcriptome data. Furthermore, functional validation was performed through homologous gene alignment and transgenic analysis, focusing on the gene SORBI_3004G304700.

Results

This study identified 49 SbLLRLK genes in Sorghum bicolor, categorized into four groups based on their lectin domain characteristics. Expression analyses revealed diverse patterns under salt, drought, and heat stresses. SORBI_3004G304700 was identified as a negative regulator of salt stress tolerance, with three unique haplotypes identified through haplotype analysis, suggesting a role in salt stress adaptation. Haplotype analysis of SORBI_3004G304700 revealed three unique haplotypes, with haplotype1 being the most prevalent, possibly due to selective advantages for salt stress tolerance.

Discussion

These findings offer valuable insights into the biological research on the role of the LLRLK gene family in Sorghum bicolor’s response to salt stress. The functional characterization of SORBI_3004G304700 and the identification of haplotypes associated with salt tolerance provide valuable insights for molecular breeding and genetic enhancement of sorghum.
Decoding mutational hotspots in human disease through the gene modules governing thymic regulatory T cells
Authors: Raposo Alexandre A. S. F. , Rosmaninho Pedro , Silva Susana L. , Paço Susana , Brazão Maria E. , Godinho-Santos Ana , Tokunaga-Mizoro Yumie , Nunes-Cabaço Helena , Serra-Caetano Ana , Almeida Afonso R. M. , Sousa Ana E.
Published: October 2024

Computational strategies to extract meaningful biological information from multiomics data are in great demand for effective clinical use, particularly in complex immune-mediated disorders. Regulatory T cells (Tregs) are essential for immune homeostasis and self-tolerance, controlling inflammatory and autoimmune processes in many diseases with a multigenic basis. Here, we quantify the Transcription Factor (TF) differential occupancy landscape to uncover the Gene Regulatory Modules governing lineage-committed Tregs in the human thymus, and show that it can be used as a tool to prioritise variants in complex diseases. We combined RNA-seq and ATAC-seq and generated a matrix of differential TF binding to genes differentially expressed in Tregs, in contrast to their counterpart conventional CD4 single-positive thymocytes. The gene loci of both established and novel genetic interactions uncovered by the Gene Regulatory Modules were significantly enriched in rare variants carried by patients with common variable immunodeficiency, here used as a model of polygenic-based disease with severe inflammatory and autoimmune manifestations. The Gene Regulatory Modules controlling the Treg signature can, therefore, be a valuable resource for variant classification, and to uncover new therapeutic targets. Overall, our strategy can also be applied in other biological processes of interest to decipher mutational hotspots in individual genomes.
Case report: The impact of dissociated response of immunotherapy on the treatment strategy of advanced head and neck cancer
Authors: Jiang Siqing , Li Xin , Li Jin
Published: October 2024

Some special therapeutic responses may appear during immunotherapy, such as hyperprogression, pseudoprogression and so on. Dissociated response of immunotherapy has been clinically reported in recent years mainly in lung cancer and kidney cancer. Since there were poor prognosis and simple treatment of advanced head and neck cancer, the application of immunotherapy in head and neck cancer has risen in recent years. But the dissociated response of immunotherapy in head and neck cancer is rarely reported. We reported two series of cases of advanced head and neck cancer that showed dissociated response after immunotherapy, tumor progression was assessed by imaging methods such as PET-CT, enhanced CT and enhanced MR, and reviewed the literature related to dissociated response in immunotherapy. We propose that the dissociated response of immunotherapy may affect the treatment strategy of advanced head and neck cancer, but more clinical analyses and researches are needed to confirm it.
Reinvesting the cellular properties of human amniotic epithelial cells and their therapeutic innovations
Authors: Yang Jing , Lu Yuefeng , Zhao Jinping , Luo Yi , Hao Wangping , Zhang Wencheng , He Zhiying
Published: October 2024

Human amniotic epithelial cells (hAECs) have shown promising therapeutic effects in numerous studies on various diseases due to their properties such as low immunogenicity, immunomodulation, paracrine effect, and no teratoma formation in vivo. Nevertheless, there are still many problems in archiving the large-scale clinical application of hAECs, ranging from the vague definition of cell properties to the lack of clarification of the motion of actions in cell therapies, additionally, to the gap between cell quantities with limited proliferation capacity. This review provides a detailed overview of hAECs in the aspects of the lineage development of amniotic epithelial cell, cell characteristics and functional roles, ex vivo cell cultivation and expansion systems, as well as their current status and limitations in clinical applications. This review also discusses the advantages, limitations and feasibility of hAECs, and anticipates their prospects as cell therapy products, with the aim of further promoting their clinical applications.
Modern developments in lasing with liquid crystals
Authors: Aljohani Omar , Dierking Ingo
Published: October 2024

A review of the recent developments in the field of lasing with liquid crystals (LCs) is presented. After an introduction into the principle of lasing the different relevant liquid crystal phases to the field are introduced, namely, the nematic and chiral nematic phase, Blue Phases, twist grain boundary and ferroelectric liquid crystals. The classic examples of liquid crystal lasing are shortly discussed, together with a variety of possibilities for tuning the lasing wavelength, before the modern trends in LC lasing are discussed in detail. These are particularly random lasers, where the effects of nanoparticles, quantum dots and solitons are highlighted, as well as localized surface plasmon resonance. Other modern laser systems that have attracted recent interest, white lasers, whispering gallery mode lasers and those with biological materials, for example, cellulose nanocrystals, are also introduced and the latest developments outlined.
Accuracy of intraoperative aberrometry versus preoperative biometry for intraocular lens power selection in short and long eyes
Authors: Tañá-Rivero Pedro , Orts-Vila Paz , Tañá-Sanz Pedro , Tañá-Sanz Santiago , Ruiz-Mesa Ramón , Montés-Micó Robert
Published: October 2024

Background

To compare the accuracy of intraoperative wavefront aberrometry using the ORA VLynk system with different biometry-based formulas in short and long eyes after cataract surgery.

Methods

This prospective study considered 48 eyes with axial lengths of <22.1 mm and 48 eyes with axial lengths of >25.0 mm. All eyes were implanted with the monofocal AcrySof IQ IOL, the power being determined using the ORA VLynk. The postoperative spherical equivalent (SE) at 3 months was compared to that predicted preoperatively using the SRK/T, Hoffer Q, Haigis, Holladay 2, Barrett Universal II, and Barrett True K formulas and intraoperatively using the ORA VLynk. Mean numerical and absolute errors and the percentage of eyes within ±0.50 D/1.00 D of their target were obtained.

Results

For long eyes, the mean absolute error values were 0.35, 0.52, 0.34, 0.30, 0.29, 0.27, and 0.24D for SRK/T, Hoffer Q, Haigis, Holladay 2, Barrett Universal II, Barrett True K, and ORA VLynk, respectively (p < 0.001). These values were 0.55, 0.45, 0.49, 0.40, 0.44, 0.44 and 0.50 D for short eyes, respectively (p < 0.001). The proportions of long eyes within ±0.50 D of the target were 77.08, 50, 75, 85.42, 83.33, 79.17, and 87.50%, respectively; and 50, 66.67, 60.42, 66.67, 60.42, 60.42, and 58.33%, respectively, for short eyes.

Conclusion

The ORA VLynk performs better than all biometry-based formulas in long eyes and, in short eyes, it is as effective as SRK/T, Haigis, Barrett Universal II, and Barrett true K, with the Hoffer Q and Holladay 2 being the most accurate; however, the differences between the calculation methods were small.

Clinical trial registration

Identifier DRKS000028106.
Association between central corneal thickness and systemic lupus erythematosus: a cross-sectional study protocol
Authors: Saldaña-Garrido Juan David , Cantó-Cerdán Mario , Gil-Guillén Vicente Francisco , Alfaro-Beltrá María Luisa , Sivera Francisca
Published: October 2024

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple systems and classified under connective tissue disorders. Ocular involvement occurs in up to 30% of SLE cases, with the cornea being particularly susceptible to thinning due to immune-complex deposits and its predominantly type I collagen composition. This corneal thinning is clinically significant in glaucoma, where patients with reduced central corneal thickness (CCT) may have up to a threefold increased risk of developing glaucoma, as well as in refractive surgery. However, existing studies on CCT in SLE are limited and marked by substantial heterogeneity in methodology, technology, criteria, and participant numbers, resulting in conflicting findings. Based in our hypothesis that SLE-related corneal lysis may result in decreased CCT, this study aims to determine and compare the mean CCT values between SLE patients and healthy controls to obtain a more precise understanding of the potential relationship.

Methods and analysis

A cross-sectional observational study will be conducted, enrolling SLE patients and age-and sex-matched healthy controls recruited from ophthalmology consultations. Exclusion criteria will be applied to rule out other corneal thinning risk factors. A pilot study estimated a minimum sample size of 34 participants per group. CCT measurements will be obtained using Zeiss HD Cirrus 5,000 optical coherence tomography (OCT) on a randomly selected eye, following concordance analysis using the Kappa index. Statistical analysis will include descriptive, bivariate, and multivariate methods. The study protocol was approved by the ethics committee.

Discussion

The cornea’s vulnerability to thinning and lysis in SLE, which impacts CCT, is crucial for the accurate assessment of glaucoma, the leading cause of irreversible blindness worldwide and the second leading cause in Europe. Given that patients with reduced CCT are at a significantly higher risk of developing glaucoma, further research is necessary to understand the association between SLE and CCT. Our study aims to enhance methodological rigor compared to prior research by determining an appropriate sample size and exclusively enrolling SLE patients to increase participant homogeneity. If a significant difference in CCT between groups and an association between CCT and SLE are found, a prospective study will be considered.
Understory growth of Paris polyphylla accumulates a reservoir of secondary metabolites of plants
Authors: Yan Xinru , Wang Dong , Zhang Ao , Xia Jing , Jiao Jinlong , Ghanim Murad , Xiaokun Ou , He Xiahong , Shi Rui
Published: October 2024

Paris polyphylla is an important traditional medicinal plant of the Himalayan region. It is extensively used for the production of natural steroidal saponins and flavonoids. Although seed dormancy of wild plants can be broken to be artificially maintained and regenerated through micropropagation in the laboratory, the success of secondary metabolite production in higher quantities and the synthesis of superior plant metabolites have been very limited. In this study, we present differential metabolic profiling of P. polyphylla plants maintained for 8 years in natural and greenhouse conditions. Untargeted profiling of the metabolites through ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), followed by statistical analysis, identified secondary metabolites that were enriched in the naturally occurring plant roots compared with the greenhouse plant roots. A multivariate statistical analysis revealed the differential distribution of the compounds between the two groups. Overall, we identified 1,182 secondary metabolites, with 116 metabolites being differentially upregulated and 256 metabolites being downregulated. Moreover, 810 metabolites showed no significant variation under both growing conditions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the naturally forest-grown P. polyphylla plants were significantly enriched in steroidal saponins, lipids, vitamins, flavonoids, and flavonols. An analysis of the top 10 differentially upregulated secondary metabolites indicated a significantly enriched quantity of spirost-5-en-3,12-diol and kaempferol synthesis pathways, which are known to reduce the effect of free radicals scavengers inside the cell. In addition, veratramine alkaloids were also enriched under natural conditions. Our findings indicated that naturally maintained P. polyphylla plants are suitable for the extraction of medicinally important compounds. Our study established a causal relationship between the metabolic composition of the roots and their natural growth condition. This study highlighted the importance of environmental conditions in the biosynthesis of secondary metabolites of plants.
Diverse new plasmid structures and antimicrobial resistance in strains isolated from perianal abscess patients
Authors: Xu Zhen , Shi Lulu , Meng Tao , Luo Mei , Zhu Jiaming , Wang Mingyu , Shen Wenlong
Published: October 2024

Introduction

Plasmids, the most important and versatile bacterial extrachromosomal DNA Molecules, has have been a center central topic for bacterial genetics and biology. However, the inability of short-read high-throughput sequencing methods to reliably assemble plasmids makes it difficult to investigate the diversity of plasmid structures and functions.

Methods

In this work, we used the long-read Nanopore sequencing method to address this issue, by producing high quality whole genome sequences of 33 bacterial strains from 11 perianal abscess-suffering patients.

Results and discussion

Successful high quality assemblies were generated with this method, including 20 perfect assemblies out of 33 genomes. A total of 47 plasmids were identified from the bacterial strains, including 12 unique, newly identified, high quality circular plasmids. These plasmids were further subject to structural analysis, leading to the finding of significant diversification from previously known plasmids, suggesting the diversity of plasmid structure and function. Particularly, two mcr-10.1-harboring conjugative plasmids were found from Citrobacter portucalensis and Enterobacter kobei, which were not previously reported. This works shows the feasibility of using long-read sequencing to identify plasmids, and the high diversity of plasmid structure and function that awaits further surveillance.
Associations between maternal microbiome, metabolome and incidence of low-birth weight in Guatemalan participants from the Women First Trial
Authors: Ruebel Meghan L. , Gilley Stephanie P. , Yeruva Laxmi , Tang Minghua , Frank Daniel N. , Garcés Ana , Figueroa Lester , Lan Renny S. , Assress Hailemariam Abrha , Kemp Jennifer F. , Westcott Jamie L. E. , Hambidge K. Michael , Shankar Kartik , Krebs Nancy F.
Published: October 2024

Background

Low birth weight (LBW; <2,500 g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings.

Methods

This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 weeks were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine.

Results

No differences in β-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 weeks was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers (p < 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance.

Conclusion

Collectively, the findings indicate that alterations in the maternal microbiome and metabolome were associated with LBW. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight.
New insights into the spatial variability of microbial diversity and density in peatlands exposed to various electron acceptors with an emphasis on methanogenesis and CO2 fluxes
Authors: Shabbir Sadaf , Qian Chang , Faheem Muhammad , Zhou Fengwu , Yu Zhi-Guo
Published: October 2024

Peatlands are vital in the global carbon cycle, acting as significant sinks for carbon and releasing methane (CH4) and carbon dioxide (CO2) into the atmosphere. However, the complex interactions between environmental factors and the microbial communities responsible for these greenhouse gas emissions remain insufficiently understood. To address this knowledge gap, a pilot-scale mesocosm study was conducted to assess the impact of different terminal electron acceptors (TEAs), including sulfate (SO42−), humic acid (HA), and goethite, on CH4 and CO2 emissions and microbial community structures in peatlands. Our results revealed that the addition of TEAs significantly altered the CH4 and CO2 emissions. Specifically, the addition of SO42− nearly doubled CO2 production while substantially inhibiting CH4 emissions. The combined addition of SO42− and HA, as well as HA alone, followed a similar pattern, albeit with less pronounced effects on CH4. Goethite addition resulted in the highest inhibition of CH4 among all treatments but did not significantly increase CO2 production. Community composition and network analysis indicated that TEAs primarily determined the structure of microbial communities, with each treatment exhibiting distinct taxa networks. Proteobacteria, Acidobacteria, Chloroflexi, and Bacteroidetes were the most abundant phyla across all mesocosms. The presence of methanotrophs, including Methylomirabilales and Methylococcales, was linked to the inhibition of CH4 emissions in these mesocosms. This study provides novel insights into the spatial variability of microbial diversity and density in peatlands under various TEAs, emphasizing the role of methanogenesis and CO2 fluxes in carbon cycling. Our findings enhance the understanding of carbon cycling in microbe-rich environments exposed to TEAs and highlight the potential for future studies to investigate the long-term effects of TEAs on microbial communities, enzymes, and carbon storage.
At home e-based physical exercise programs in patients with multiple sclerosis: a scoping review
Authors: Adnan Rafl , Roikjaer Stine Gundtoft , Samadzadeh Sara , Richter Camilla Josefine , Weinshenker Brian G. , Paul Friedemann , Skou Søren Thorgaard , Dalgas Ulrik , Asgari Nasrin
Published: October 2024

Introduction

Physical exercise (PE) improves symptoms and quality of life in people with multiple sclerosis (pwMS). However, incorporating PE into daily lives of pwMS pose difficulties. As an alternative to in-person PE, e-based PE has been proposed because of its advantages in terms of accessibility and convenience.

Objective

To synthesize existing evidence on e-based PE at home in adults MS and discuss study designs, rehabilitation programs, intervention effects and possible knowledge gaps.

Methods

In this scoping review, a systematic search in electronic databases including Embase, Medline, CINAHL and Cochrane Library was conducted following the PRISMA guidelines. Peer-reviewed articles in English on e-based PE interventional studies at home involving adult pwMS, published from 2008 until April 2023, were identified and exported to Covidence. Data from the included studies were extracted and synthesized. This scoping review identified different types of e-based PE interventions used in pwMS across different study designs, but when evaluating intervention effects, this review focused solely on randomized controlled trials (RCTs).

Results

A total of 3,006 studies were retrieved and 179 studies were screened in full text, resulting in the inclusion of 54 studies with a total of 2,359 pwMS. Of those, 33 were RCTs and three were qualitative studies. The studies reported on various e-based interventions including video-based programs, telerehabilitation, and web-based programs. The interventions evaluated muscle strength, cardiorespiratory fitness, walking speed, endurance, balance, and fatigue, as well as symptoms of depression and cognitive dysfunction. E-based PE interventions at home in RCTs demonstrated improvement of depressive symptoms and anxiety, while inconsistent results were reported for fatigue, walking speed and balance. No significant benefits were observed regarding dexterity. Results were generally heterogeneous and were limited by small sample sizes. Several limitations were identified, such as lack of physical activity assessment prior to the intervention and poor reporting of duration, intensity, frequency and adherence to e-based PE interventions.

Conclusion

E-based PE interventions in pwMS may improve MS-related symptoms, but the study quality is generally low, and findings are often inconsistent. Several important limitations of the existing literature have been identified in the present review, which can guide future research.
Perceptual representations in L1 and L2 spatial and abstract language processing: applying an innovative sentence-diagram verification paradigm
Authors: Wang Menghan , Zhao Helen
Published: October 2024

Introduction

Perceptual representations in language comprehension were examined using sentence-picture verification tasks. However, concerns have been raised regarding the suitability of concrete pictures for representing abstract concepts compared to image-schematic diagrams. To assess the perceptual representations of spatial and abstract domains in both first language (L1) and second language (L2) processing, the study tests bilingual speakers’ mental imagery on the basis of the simulation-based L1 comprehension model and proposes a simulation-based L2 comprehension model, supported by empirical evidence from an innovative sentence-diagram verification paradigm.

Methods

41 adult L1 Mandarin Chinese speakers participated in the study. 21 participants completed the Chinese sentence-diagram verification task (Experiment 1), while 20 participants completed the translation-equivalent version in L2 English (Experiment 2). Participants read a sentence [e.g., A diligent worker walked into the office (spatial sense); A strong team headed into the final (abstract sense)] at their self-paced speed, followed by a congruent (e.g., into diagram) or incongruent diagram (e.g., out-of diagram), and made binary judgments to verify spatial configurations between the sentence and diagram. Semantic rating tasks in both Chinese and English were also conducted to validate congruency between diagrams and sentences in both languages.

Results and discussion

Results from Experiment 1 indicate overall compatibility effects on L1 Chinese processing, unaffected by directional verbs or abstractness of sense. Results from Experiment 2 reveal interference effects on L2 English processing, with interference observed only after reading sentences encoding spatial senses, not abstract senses. Aligning with previous findings using sentence-picture verification tasks, the current findings confirm the weaker mental simulation effects in L2 processing compared to L1 processing. These findings extend the existing simulation-based L1 comprehension model, provide empirical support for the proposed simulation-based L2 comprehension model, and validate the innovative sentence-diagram verification paradigm for examining image-schematic representations in spatial and abstract language processing among Chinese-English bilinguals. The paradigm holds significant potential for research on perceptual representations in processing a broader range of grammatical and semantic properties during both online and offline L1 and L2 comprehension.
Using genetic variations to reveal the complex relationships between vegetarianism and well-being, depressive symptoms and neuroticism
Authors: Chen Ke , Wen Yuan , Shu Zhendi
Published: October 2024

Background

The relationship between vegetarianism and mental well-being remains a debated topic in traditional observational studies. Recent studies have revealed the genetic factors in vegetarianism. We aimed to use genetic variations to explore the potential causal relationships between vegetarianism and mental well-being, offering insights from a new perspective.

Methods

We conducted the inverse variance weighted approach as the primary analysis to explore the bidirectional genetic associations between vegetarianism (N = 442,589) and depressive symptoms (N = 180,866), neuroticism (N = 170,910), and subjective well-being (N = 298,420). The analysis used the summary data from the largest genome-wide association studies (GWAS). We also performed sensitivity analyses to ensure the robustness of the findings, accounting for potential heterogeneity and pleiotropy.

Results

Genetically predicted vegetarianism showed positive causal relationships with depressive symptoms (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.03–10.31; p = 0.044) and neuroticism (OR, 6.72; 95% CI, 2.29–19.74; p = 5.31 × 10−4), as well as a negative causal relationship with subjective well-being (OR, 0.20; 95% CI, 0.05–0.77; p = 0.019). Additionally, depressive symptoms were found to have a causal influence on vegetarianism (OR, 1.01; 95% CI, 1.00–1.02; p = 6.87 × 10−3). No significant heterogeneity or pleiotropy was detected.

Conclusion

Vegetarianism is causally correlated with negative mental well-being, reflected in an increased risk of depressive symptoms and neuroticism, as well as lower subjective well-being. Further research should explore the underlying mechanisms in broader populations.
Integration of host gene regulation and oral microbiome reveals the influences of smoking during the development of oral squamous cell carcinoma
Authors: Liang Dan , Ma Xuemeng , Zhong Xiaoyi , Zhou Yinghua , Chen Wenxia , He Xuan
Published: October 2024

Objective

This study aims to investigate the regulation of host gene transcription and microbial changes during the development of oral squamous cell carcinoma (OSCC) associated with smoking.

Methods

The OSCC mouse model and smoking mouse model were established using 200 μg/mL 4-nitroquinoline-1-oxide (4NQO) in drinking water and exposure to cigarette smoke (four cigarettes per session, once a day, 5 days a week). Tongue tissues were harvested at 4 weeks and 16 weeks. Histopathological changes were evaluated using hematoxylin and eosin staining and Ki67 staining. RNA sequencing was performed on the mouse tongue tissues to identify differentially expressed genes (DEGs), and the results were validated by RT-PCR and immunohistochemistry. 16S rDNA sequencing was used to analyze changes in the oral microbiota during the early development of OSCC, identifying differentially abundant taxa associated with smoking. Finally, associations between the relative abundances of the oral microbiome and host gene expression were modeled using the Origin software.

Results

DEGs associated with smoking during the development of OSCC were identified. There were 12 upregulated genes, including NR4A3 and PPP1R3C, and 23 downregulated genes, including CD74 and ANKRD1. These genes were enriched in functions related to the signal transduction of cellular processes such as inflammation, differentiation, immunity, and PI3K/AKT, NF-κB signaling pathways. 4NQO and smoking treatment decreased oral microbial diversity and reduced the abundance of Bacteroidetes, Proteobacteria, and Lactobacillus but increased the abundance of Staphylococcus. Integrative analysis showed that the expression of CD74 was positively correlated with the relative abundance of Lactobacillus, while PPP1R3C was negatively correlated with Bacteroidota.

Conclusion

In addition to characterizing host gene expression and the oral microbiome, our study explored the potential role of host–microbiome interactions in the development of OSCC. These findings enhance our understanding of smoking-related OSCC occurrence and development, providing new insights for its prevention.
Evaluating pain in non-verbal critical care patients: a narrative review of the critical care pain observation tool and Its clinical applications
Authors: Afenigus Abebe Dilie
Published: October 2024

Background

Assessing pain in critically ill patients who cannot communicate verbally poses significant challenges. Traditional self-report measures are ineffective for these patients, making the need for reliable observational tools crucial.

Objective

To evaluate the effectiveness, reliability, and clinical applicability of the Critical Care Pain Observation Tool (CPOT) in various intensive care unit (ICU) settings and to explore potential innovations for improving its use and integration into clinical practice.

Methods

A narrative review evaluated the Critical Care Pain Observation Tool (CPOT) for non-communicative ICU patients, comparing it to the Behavioral Pain Scale (BPS) and the FLACC scale. The review assessed CPOT's effectiveness across different ICU settings, identified limitations and challenges, and explored potential enhancements such as electronic scoring, additional physiological indicators, and improved training protocols.

Results

The CPOT has been validated as an effective pain assessment tool for non-verbal ICU patients. It evaluates pain through facial expressions, body movements, muscle tension, and ventilator compliance. The CPOT shows superior sensitivity at 76.5% compared to 62.7% for the BPS and offers a more comprehensive assessment of pain indicators like muscle tension and ventilator compliance than the FLACC scale. Despite its strengths, the CPOT has limitations, including inter-rater variability and challenges in certain patient populations. Barriers to implementation include resource constraints and the need for extensive training.

Conclusion

The Critical Care Pain Observation Tool (CPOT) is a highly effective instrument for assessing pain in non-verbal ICU patients, demonstrating superior accuracy and reliability compared to other tools like the Behavioral Pain Scale (BPS) and FLACC scale. Its detailed approach, covering facial expressions, body movements, muscle tension, and ventilator compliance, offers a detailed measure of pain. However, challenges such as inter-rater variability and limitations in specific patient populations highlight the need for ongoing refinement and research.
Willingness to pay and price elasticity of demand for long-acting injectable cabotegravir among men who have sex with men in Guangxi, China
Authors: Chen Shiwen , Ruan Yuhua , Liu Lu , Pei Hengyan , Jiang Yu , Huang Tengda , Wei Yuxia , Qin Litai , Dai Xuebin , Liu Yu , Liu Junhui , Xie Yihong
Published: October 2024

Objectives

There is still no study focused on willingness to pay for long-acting injectable cabotegravir (CAB-LA) after it was available on the market in the United States in 2021. Here, we explored the willingness to pay for CAB-LA and associated factors and price elasticity of demand (PED) of CAB-LA among men who have sex with men (MSM) in Guangxi, China.

Methods

A cross-sectional study was conducted. Univariate and multivariate ordinal logistic regression analyses were performed to explore the associated factors of willingness to pay for CAB-LA. PED was used to measure the change in the number of participants willing to pay to a change in price.

Results

A total of 1,006 MSM were recruited, among which 84.1% were aged between 18 and 39 years old. The median (interquartile) of the maximum amount of willing to pay for CAB-LA was 200 (100–500) Chinese yuan (CNY) per month. Most (84.2%) were willing to pay less than 600 CNY per month. The number of participants willing to pay for CAB-LA significantly increased with decrease in the price. When the price (CNY per month) decreased from 600 to 500, 500 to 400, 400 to 300, and 300 to 200, PED was 3.13, 1.64, 1.33, and 1.17, respectively. The maximum amount of willing to pay for CAB-LA was positively associated with younger age (vs. ≥40 years group, 18–24 years group, aOR: 1.94, 95% CI: 1.32–2.85; 25–39 year group, aOR: 1.70, 95% CI: 1.20–2.42), being high educated (vs. middle school or lower group, high school or college group, aOR: 1.61, 95% CI: 1.06–2.48; bachelor’s degree or above group, aOR: 2.21, 95% CI: 1.41–3.49), monthly income ≥6000 CNY (vs. <3000 CNY, aOR: 1.46, 95% CI: 1.02–2.09), being bisexual/unsure sexual orientation (vs. gay, aOR: 1.73, 95% CI: 1.24–2.43), and heard of PrEP and used (vs. never heard of PrEP, aOR: 1.76, 95% CI: 1.11–2.77).

Conclusion

The maximum amount of willing to pay for CAB-LA was low in Guangxi, China. PED of CAB-LA is relatively elastic. The waived patent protection should be considered for the wide promotion of CAB-LA, and the health education should be strengthened to improve the recognition of CAB-LA.
Rapid identification of chemical profiles in vitro and in vivo of Huan Shao Dan and potential anti-aging metabolites by high-resolution mass spectrometry, sequential metabolism, and deep learning model
Authors: Li Xueyan , Pan Fulu , Wang Lin , Zhang Jing , Wang Xinyu , Qi Dongying , Chai Xiaoyu , Wang Qianqian , Yi Zirong , Ma Yuming , Pan Yanli , Liu Yang , Wang Guopeng
Published: October 2024

Background

Aging is marked by the gradual deterioration of cells, tissues, and organs and is a major risk factor for many chronic diseases. Considering the complex mechanisms of aging, traditional Chinese medicine (TCM) could offer distinct advantages. However, due to the complexity and variability of metabolites in TCM, the comprehensive screening of metabolites associated with pharmacology remains a significant issue.

Methods

A reliable and integrated identification method based on UPLC-Q Exactive-Orbitrap HRMS was established to identify the chemical profiles of Huan Shao Dan (HSD). Then, based on the theory of sequential metabolism, the metabolic sites of HSD in vivo were further investigated. Finally, a deep learning model and a bioactivity assessment assay were applied to screen potential anti-aging metabolites.

Results

This study identified 366 metabolites in HSD. Based on the results of sequential metabolism, 135 metabolites were then absorbed into plasma. A total of 178 peaks were identified from the sample after incubation with artificial gastric juice. In addition, 102 and 91 peaks were identified from the fecal and urine samples, respectively. Finally, based on the results of the deep learning model and bioactivity assay, ginsenoside Rg1, Rg2, and Rc, pseudoginsenoside F11, and jionoside B1 were selected as potential anti-aging metabolites.

Conclusion

This study provides a valuable reference for future research on the material basis of HSD by describing the chemical profiles both in vivo and in vitro. Moreover, the proposed screening approach may serve as a rapid tool for identifying potential anti-aging metabolites in TCM.
Computational identification of Vernonia cinerea-derived phytochemicals as potential inhibitors of nonstructural protein 1 (NSP1) in dengue virus serotype-2
Authors: Hossain Md. Shohel , Hasnat Soharth , Akter Shilpy , Mim Maria Mulla , Tahcin Anika , Hoque Majedul , Sutradhar Durjoy , Keya Mst. Alifa Akter , Sium Namin Rouf , Hossain Sophia , Masuma Runa , Rakib Sakhawat Hossen , Islam Md. Aminul , Islam Tofazzal , Bhattacharya Prosun , Hoque M. Nazmul
Published: October 2024

Background

Dengue virus (DENV) infection, spread by Aedes aegypti mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2.

Objective

This study aimed to identify inhibitory phytocompounds in silico in Vernonia cinerea (V. cinerea), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses.

Methods

The chemical structures of 17 compounds from V. cinerea were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses.

Results

Among these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski’s “rule of 5”, showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin.

Conclusion

Taken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections.
The single-strand DNA-binding protein SSB1 is involved in the expression of salivary gland radiation injury repair
Authors: Wang Xian , Wang Yuetong , Zeng Xianglin , Lu Haoyu , Mo Dongqin , Li Yuetao , Liu Zhiqing , Huang Yude , Yu Kun , Wang Daiyou
Published: October 2024

Objectives

Single-strand DNA-binding protein 1 (SSB1) plays a crucial role in the cellular response to DNA damage. This study aimed to explore the expression and regulation of SSB1 in normal rat salivary gland tissues and tissues following radiation, with a specific emphasis on its involvement in the repair of salivary gland injury.

Methods

A total of 45 adult SD rats were randomly assigned to one control group or eight experimental groups. In the control group, five rats were euthanized without irradiation, and their parotid gland tissues were collected for analysis. The experimental groups received a dose of 6 Gy of radiation targeting the head and neck region; subsequently, five rats from each group were euthanized hly to collect parotid gland tissue samples, resulting in a total of eight experimental groups. The expression levels of SSB1, γ-H2AX, and PARP1 in the parotid gland tissues were assessed via immunohistochemistry, while changes in SSB1 gene expression were quantified via RT-qPCR.

Results

No significant morphological differences were observed between the two groups following HE staining. In the immunohistochemistry (IHC) analysis, notable tissue-specific variation in SSB1 expression was identified, with higher levels detected in the ducts than in the acini and connective tissue. The expression of SSB1 gene initially increased post-radiation before subsequently decreasing, ultimately returning to baseline levels, as corroborated by the RT-qPCR results. In contrast, γ-H2AX and PARP1 exhibited minimal expression in the control group; however, their expression peaked at 1 h in the experimental group before gradually declining to levels comparable to those of the control group.

Conclusion

Radiation induces time-dependent upregulation of SSB1 expression in rat salivary glands, indicating that SSB1 may play a role in radiation-induced repair processes.