bluuebunny/crossref_metadata_2025 huggingface dataset:
The light chain of tetanus toxin bound to arginine-rich cell-penetrating peptide inhibits cortical reaction in mouse oocytes
Authors: Klinsky Omar G. , Wetten Paula A. , Zanni-Ruiz Emilia , Pavarotti Martín A. , Berberian María Victoria , Michaut Marcela A.
Published: November 2023

Introduction: Cortical reaction is a secretory process that occurs after a spermatozoon fuses with the oocyte, avoiding the fusion of additional sperm. During this exocytic event, the cortical granule membrane fuses with the oocyte plasma membrane. We have identified several molecular components involved in this process and confirmed that SNARE proteins regulate membrane fusion during cortical reaction in mouse oocytes. In those studies, we microinjected different nonpermeable reagents to demonstrate the participation of a specific protein in the cortical reaction. However, the microinjection technique has several limitations. In this work, we aimed to assess the potential of cell-penetrating peptides (CPP) as biotechnological tools for delivering molecules into oocytes, and to evaluate the functionality of the permeable tetanus toxin (bound to CPP sequence) during cortical reaction.

Methods: Arginine-rich cell-penetrating peptides have demonstrated the optimal internalization of small molecules in mammalian cells. Two arginine-rich CPP were used in the present study. One, labeled with 5-carboxyfluorescein, to characterize the factors that can modulate its internalization, and the other, the permeable light chain of tetanus toxin, that cleaves the SNAREs VAMP1 and VAMP3 expressed in mouse oocytes.

Results: Results showed that fluorescent CPP was internalized into the oocyte cytoplasm and that internalization was dependent on the concentration, time, temperature, and maturation stage of the oocyte. Using our functional assay to study cortical reaction, the light chain of tetanus toxin bound to arginine-rich cell-penetrating peptide inhibited cortical granules exocytosis.

Discussion: Results obtained from the use of permeable peptides demonstrate that this CPP is a promising biotechnological tool to study functional macromolecules in mouse oocytes.
A new candidate epitope-based vaccine against PspA PhtD of Streptococcus pneumoniae: a computational experimental approach
Authors: Shafaghi Mona , Bahadori Zohreh , Barzi Seyed Mahmoud , Afshari Elnaz , Madanchi Hamid , Mousavi Seyed Fazlollah , Shabani Ali Akbar
Published: November 2023

Introduction

Pneumococcus is an important respiratory pathogen that is associated with high rates of death in newborn children and the elderly. Given the disadvantages of current polysaccharide-based vaccines, the most promising alternative for developing improved vaccines may be to use protein antigens with different roles in pneumococcus virulence. PspA and PhtD, highly immunogenic surface proteins expressed by almost all pneumococcal strains, are capable of eliciting protective immunity against lethal infections.

Methods

In this study using immunoinformatics approaches, we constructed one fusion construct (called PAD) by fusing the immunodominant regions of PspA from families 1 & 2 (PA) to the immunodominant regions of PhtD (PD). The objective of this project was to test the immunogenicity of the fusion protein PAD and to compare its protective activity against S. pneumoniae infection with PA or PD alone and a combination of PA and PD. The prediction of physicochemical properties, antigenicity, allergenicity, toxicity, and 3D-structure of the constructs, as well as molecular docking with HLA receptor and immune simulation were performed using computational tools. Finally, mice were immunized and the serum levels of antibodies/cytokines and functionality of antibodies in vitro were evaluated after immunization. The mice survival rates and decrease of bacterial loads in the blood/spleen were examined following the challenge.

Results

The computational analyses indicated the proposed constructs could be antigenic, non-allergenic, non-toxic, soluble and able to elicit robust immune responses. The results of actual animal experiments revealed the candidate vaccines could induce the mice to produce high levels of antibodies and cytokines. The complement-mediated bactericidal activity of antibodies was confirmed and the antibodies provided favorable survival in immunized mice after bacterial challenge. In general, the experimental results verified the immunoinformatics studies.

Conclusion

For the first time this report presents novel peptide-based vaccine candidates consisting of immunodominant regions of PspA and PhtD antigens. The obtained findings confirmed that the fusion formulation could be relatively more efficient than the individual and combination formulations. The results propose that the fusion protein alone could be used as a serotype-independent pneumococcal vaccine or as an effective partner protein for a conjugate polysaccharide vaccine.
Extracellular vesicle storm during the course of Ebola virus infection in primates
Authors: Vucetic Andrea , Lafleur Andrea , Côté Marceline , Kobasa Darwyn , Chan Mable , Alvarez Fernando , Piccirillo Ciriaco , Dong George , Olivier Martin
Published: November 2023

Introduction

Ebola virus (EBOV) is an RNA virus of the Filoviridae family that is responsible for outbreaks of hemorrhagic fevers in primates with a lethality rate as high as 90%. EBOV primarily targets host macrophages leading to cell activation and systemic cytokine storm, and fatal infection is associated with an inhibited interferon response, and lymphopenia. The EBOV surface glycoprotein (GP) has been shown to directly induce T cell depletion and can be secreted outside the virion via extracellular vesicles (EVs), though most studies are limited to epithelial cells and underlying mechanisms remain poorly elucidated.

Methods

To assess the role of GP on EBOV-induced dysregulation of host immunity, we first utilized EBOV virus-like particles (VLPs) expressing VP40 and NP either alone (Bald-VLP) or in conjunction with GP (VLP-GP) to investigate early inflammatory responses in THP-1 macrophages and in a murine model. We then sought to decipher the role of non-classical inflammatory mediators such as EVs over the course of EBOV infection in two EBOV-infected rhesus macaques by isolating and characterizing circulatory EVs throughout disease progression using size exclusion chromatography, nanoparticle tracking-analysis, and LC-MS/MS.

Results

While all VLPs could induce inflammatory mediators and recruit small peritoneal macrophages, pro-inflammatory cytokine and chemokine gene expression was exacerbated by the presence of GP. Further, quantification of EVs isolated from infected rhesus macaques revealed that the concentration of vesicles peaked in circulation at the terminal stage, at which time EBOV GP could be detected in host-derived exosomes. Moreover, comparative proteomics conducted across EV populations isolated from serum at various time points before and after infection revealed differences in host-derived protein content that were most significantly pronounced at the endpoint of infection, including significant expression of mediators of TLR4 signaling.

Discussion

These results suggest a dynamic role for EVs in the modification of disease states in the context of EBOV. Overall, our work highlights the importance of viral factors, such as the GP, and host derived EVs in the inflammatory cascade and pathogenesis of EBOV, which can be collectively further exploited for novel antiviral development.
Immunization with different recombinant West Nile virus envelope proteins induces varying levels of serological cross-reactivity and protection from infection
Authors: Weiß Rebecca , Issmail Leila , Rockstroh Alexandra , Grunwald Thomas , Fertey Jasmin , Ulbert Sebastian
Published: November 2023

Introduction

West Nile Virus (WNV) is a zoonotic flavivirus transmitted by mosquitoes. Especially in the elderly or in immunocompromised individuals an infection with WNV can lead to severe neurological symptoms. To date, no human vaccine against WNV is available. The Envelope (E) protein, located at the surface of flaviviruses, is involved in the invasion into host cells and is the major target for neutralizing antibodies and therefore central to vaccine development. Due to their close genetic and structural relationship, flaviviruses share highly conserved epitopes, such as the fusion loop domain (FL) in the E protein, that are recognized by cross-reactive antibodies. These antibodies can lead to enhancement of infection with heterologous flaviviruses, which is a major concern for potential vaccines in areas with co-circulation of different flaviviruses, e.g. Dengue or Zika viruses.

Material

To reduce the potential of inducing cross-reactive antibodies, we performed an immunization study in mice using WNV E proteins with either wild type sequence or a mutated FL, and WNV E domain III which does not contain the FL at all.

Results and discussion

Our data show that all antigens induce high levels of WNV-binding antibodies. However, the level of protection against WNV varied, with the wildtype E protein inducing full, the other antigens only partial protection. On the other hand, serological cross-reactivity to heterologous flaviviruses was significantly reduced after immunization with the mutated E protein or domain III as compared to the wild type version. These results have indications for choosing antigens with the optimal specificity and efficacy in WNV vaccine development.
Reality bites: highlighting the potential discrepancies between multisensory taste perception in extended and physical reality
Authors: Dawes Christopher , Beganovic Sabina , Schwalk Matti , Mai Michaela , Pawlizak Steve , Zhang Jingxin , Nelles Gabriele , Krasteva Nadejda , Obrist Marianna
Published: November 2023

Introduction

When we taste, we take in a variety of sensory information that can be completely independent from the properties of the food itself: the ambient lighting and environmental sounds can all influence our taste perception and affective responses. However, current multisensory research is mixed as to whether these In Real Life (IRL) findings also apply to Extended Reality (XR) environments. A potential reason for this may be the limited realism of some XR scenarios, which this study aimed to overcome through an immersive Virtual Reality experience (VR, chosen for its greater realism relative to other XR applications) whilst also expanding the scope to flavour perception.

Methods

A total of 34 participants rated food samples under neutral, red, and green ambient lighting in VR. Participants ate either lime flavoured, strawberry flavoured, or “Neutral” (no added flavour) samples.

Results

While participants were equally immersed in all three environments, they rated the red and green lighting environments as substantially less natural than the neutral lighting environment. Interestingly, while participants associated sweetness and sourness with red lighting and green lighting respectively, this minimally extended to their behavioural ratings, when sampling the stimuli in VR. Samples eaten under red lighting were rated as significantly sweeter than those eaten under neutral lighting. However, neither red nor green lighting affected sample sourness nor the intensity of strawberry or lime flavour.

Discussion

This study found limited evidence of multisensory integration in XR, wherein taste expectations do not extend to taste experiences. We discuss these results in light of prior works on crossmodal associations and raise a reflection on why multisensory integration of taste may not apply to XR in our study. While there is much excitement about the opportunities XR can offer, we argue that we are only at the beginning of understanding the experiences on the reality-virtuality continuum and that we need to establish a richer understanding of participants' experiences, expectations, and taste/flavour perceptions between IRL and XR.
Adiabatic quantum computing impact on transport optimization in the last-mile scenario
Authors: Ariño Sales Juan Francisco , Palacios Araos Raúl Andrés
Published: November 2023

In the ever-evolving landscape of global trade and supply chain management, logistics optimization stands as a critical challenge. This study takes on the Vehicle Routing Problem (VRP), a variant of the Traveling Salesman Problem (TSP), by proposing a novel hybrid solution that seamlessly combines classical and quantum computing methodologies. Through a comprehensive analysis of our approach, including algorithm selection, data collection, and computational processes, we provide in-depth insights into the efficiency, and effectiveness of our hybrid solution compared to traditional methods. The results after analysis of 14 datasets highlight the advantages and limitations of this approach, demonstrating its potential to address NP-hard problems and contribute significantly to the field of optimization algorithms in logistics. This research offers promising contributions to the advancement of logistics optimization techniques and their potential implications for enhancing supply chain efficiency.
Distance learning and face-to-face learning in a pathophysiology problem-based learning course during a pandemic
Authors: Chen Fang-Hsu , Wu Po-Jen , Chi Chih-Hsien
Published: November 2023

Introduction

During the past 2 years of the COVID-19 pandemic, education methods adjusted from conventional in-person classes to distance learning. Most classes were lectures that could go well if the participants were familiar with the online operation and had a stable network connection. However, problem-based learning (PBL) classes, which rely on the ability to engage in discussions, still had communication and group development limitations.

Methods

Here, we surveyed the learning effects of face-to-face (FF) and distance learning (DL) in a medical PBL course for two classes. Tutors and students were requested to give grades for five key areas (participation, communication, preparation, critical thinking, and group skills).

Results and discussions

A questionnaire found reduced participation, communication, and group skills in DL classes in comparison to FF classes. The tutors’ perspective regarded participation and communication ability as reduced in DL. Nevertheless, one of the two classes showed no difference in group skills.

Conclusion

Our research shows the experience of a PBL class focusing on discussion and communication. In the post-pandemic era, whether FF or DL, classes should be appropriately adjusted to facilitate effective student communication.
Integrative bioinformatics analysis of biomarkers and pathways for exploring the mechanisms and molecular targets associated with pyroptosis in type 2 diabetes mellitus
Authors: Wang Wei , Wang Yao
Published: November 2023

Introduction

Research has shown that pyroptosis contributes greatly to the progression of diabetes and its complications. However, the exact relationship between this particular cell death process and the pathology of type 2 diabetes mellitus (T2DM) remains unclear. In this study, we used bioinformatic tools to identify the pyroptosis-related genes (PRGs) associated with T2DM and to analyze their roles in the disease pathology.

Methods

Two microarray datasets, GSE7014 and GSE25724, were obtained from the GEO database and assessed for differentially expressed genes (DEGs). The T2DM-associated DEGs that overlapped with differentially expressed PRGs were noted as T2DM-PRGs. Subsequently, 25 T2DM-PRGs were validated and subjected to functional enrichment analysis through Gene Ontology annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene set enrichment analysis (GSEA). The diagnostic and predictive value of the T2DM-PRGs was evaluated using receiver operating characteristic curves (ROC). Additionally, a single-sample GSEA algorithm was applied to study immune infiltration in T2DM and assess immune infiltration levels.

Results

We identified 25 T2DM-PRGs that were significantly enriched in the nuclear factor-kappa B signaling and prostate cancer pathways. The top five differentially expressed prognostic T2DM-PRGs targeted by miRNAs were PTEN, BRD4, HSP90AB1, VIM, and PKN2. The top five differentially expressed T2DM-PRGs associated with transcription factors were HSP90AB1, VIM, PLCG1, SCAF11, and PTEN. The genes PLCG1, PTEN, TP63, CHI3L1, SDHB, DPP8, BCL2, SERPINB1, ACE2, DRD2, DDX58, and BTK showed excellent diagnostic performance. The immune infiltration analysis revealed notable differences in immune cells between T2DM and normal tissues in both datasets. These findings suggest that T2DM-PRGs play a crucial role in the development and progression of T2DM and could be used as potential diagnostic biomarkers and therapeutic targets.

Discussion

Investigating the mechanisms and biomarkers associated with pyroptosis may offer valuable insights into the pathophysiology of T2DM and lead to novel therapeutic approaches to treat the disease.
A prediction model for high ovarian response in the GnRH antagonist protocol
Authors: Jiang Yilin , Cui Chenchen , Guo Jiayu , Wang Ting , Zhang Cuilian
Published: November 2023

Backgrounds

The present study was designed to establish and validate a prediction model for high ovarian response (HOR) in the GnRH antagonist protocol.

Methods

In this retrospective study, the data of 4160 cycles were analyzed following the in vitro fertilization (IVF) at our reproductive medical center from June 2018 to May 2022. The cycles were divided into a training cohort (n=3121) and a validation cohort (n=1039) using a random sampling method. Univariate and multivariate logistic regression analyses were used to screen out the risk factors for HOR, and the nomogram was established based on the regression coefficient of the relevant variables. The area under the receiver operating characteristic curve (AUC), the calibration curve, and the decision curve analysis were used to evaluate the performance of the prediction model.

Results

Multivariate logistic regression analysis revealed that age, body mass index (BMI), follicle-stimulating hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH) were independent risk factors for HOR (all P< 0.05). The prediction model for HOR was constructed based on these factors. The AUC of the training cohort was 0.884 (95% CI: 0.869–0.899), and the AUC of the validation cohort was 0.884 (95% CI:0.863–0.905).

Conclusion

The prediction model can predict the probability of high ovarian response prior to IVF treatment, enabling clinicians to better predict the risk of HOR and guide treatment strategies.
Gut microbiome and blood glucose control in type 1 diabetes: a systematic review
Authors: Abuqwider Jumana , Corrado Alessandra , Scidà Giuseppe , Lupoli Roberta , Costabile Giuseppina , Mauriello Gianluigi , Bozzetto Lutgarda
Published: November 2023

Objective

The risk of developing micro- and macrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gut microbial composition between healthy individuals and those with T1D. These changes in the gut ecosystem may lead to inflammation, modifications in intestinal permeability, and alterations in metabolites. Such effects can collectively impact the metabolic regulation system, thereby influencing blood glucose control. This review aims to explore the relationship between the gut microbiome, inflammation, and blood glucose parameters in patients with T1D.

Methods

Google Scholar, PubMed, and Web of Science were systematically searched from 2003 to 2023 using the following keywords: “gut microbiota,” “gut microbiome,” “bacteria,” “T1D,” “type 1 diabetes,” “autoimmune diabetes,” “glycemic control,” “glucose control,” “HbA1c,” “inflammation,” “inflammatory,” and “cytokine.” The examination has shown 18,680 articles with relevant keywords. After the exclusion of irrelevant articles, seven observational papers showed a distinct gut microbial signature in T1D patients.

Results

This review shows that, in T1D patients, HbA1c level was negatively correlated with abundance of Prevotella, Faecalibacterium, and Ruminococcaceae and positively correlated with abundance of Dorea formicigenerans, Bacteroidetes, Lactobacillales, and Bacteriodes. Instead, Bifidobacteria was negatively correlated with fasting blood glucose. In addition, there was a positive correlation between Clostridiaceae and time in range. Furthermore, a positive correlation between inflammatory parameters and gut dysbiosis was revealed in T1D patients.

Conclusion

We draw the conclusion that the gut microbiome profiles of T1D patients and healthy controls differ. Patients with T1D may experience leaky gut, bacterial translocation, inflammation, and poor glucose management due to microbiome dysbiosis. Direct manipulation of the gut microbiome in humans and its effects on gut permeability and glycemic control, however, have not been thoroughly investigated. Future research should therefore thoroughly examine other potential pathophysiological mechanisms in larger studies.
Is MG53 a potential therapeutic target for cancer?
Authors: Du Yunyu , Li Tieying , Yi Muqing
Published: November 2023

Cancer treatment still encounters challenges, such as side effects and drug resistance. The tripartite-motif (TRIM) protein family is widely involved in regulation of the occurrence, development, and drug resistance of tumors. MG53, a member of the TRIM protein family, shows strong potential in cancer therapy, primarily due to its E3 ubiquitin ligase properties. The classic membrane repair function and anti-inflammatory capacity of MG53 may also be beneficial for cancer prevention and treatment. However, MG53 appears to be a key regulatory factor in impaired glucose metabolism and a negative regulatory mechanism in muscle regeneration that may have a negative effect on cancer treatment. Developing MG53 mutants that balance the pros and cons may be the key to solving the problem. This article aims to summarize the role and mechanism of MG53 in the occurrence, progression, and invasion of cancer, focusing on the potential impact of the biological function of MG53 on cancer therapy.
Anomalies and major cluster-based grouping of electricity users for improving the forecasting performance of deep learning models
Authors: Aurangzeb Khursheed
Published: November 2023

Analyzing and understanding the electricity consumption of end users, especially the anomalies (outliers), are vital for the planning, operation, and management of the power grid. It will help separate the group of users with unpredictable consumption behavior and then develop and train specialized deep learning models for power load forecasting or regular and non-regular users. The aim of the current work is to divide electricity customers into numerous groups based on anomalies in consumption behavior and major clusters. Successful separation of such groups of customers will provide us with two advantages. One is the increase in the accuracy of load forecasting of other users or groups of users due to their predictable consumption behavior. The second is the opportunity to develop and train specialized deep learning models for customers with highly unpredictable behaviors. The novelty of the work is the segregation of anomalous electricity users from normal/regular users based on outliers in their past power consumption behavior over a period of 92 days. Results indicate that almost 85 percent of the users in the selected residential community attribute one major cluster in their consumption behavior over a period of 3 months of data (92 days). It is also evident from the results that only a small proportion of customers, i.e., 10 out of 69 customers (15 percent), have either more than one cluster or attribute no cluster (zero clusters), which is highly important and indicates that these are the possible users who cause higher variations in power consumption of the residential community.
2022 UK heatwave impacts on agrifood: implications for a climate-resilient food system
Authors: Davie Jemma C. S. , Falloon Pete D. , Pain Daniel L. A. , Sharp Tierney J. , Housden Maddie , Warne Thomas C. , Loosley Tom , Grant Erin , Swan Jess , Spincer James D. G. , Crocker Tom , Cottrell Andrew , Pope Edward C. D. , Griffiths Simon
Published: November 2023

Record-breaking high temperatures were experienced across the United Kingdom during summer 2022. The impacts of these extreme climatic conditions were felt across the food system, including increased energy costs for cold storage, the failure of refrigeration systems in numerous retail facilities, and impacts on livestock including heat stress. Future climate projections indicate an increased likelihood and duration of extreme high temperatures like those experienced in 2022. Learning from the impacts of the 2022 heatwave on the United Kingdom food system can help identify adaptations that build resilience to climate change. We explore the impacts through two case studies (United Kingdom poultry and wheat sectors), discuss potential adaptation options required for a climate-resilient, net-zero United Kingdom food system and consider future research needs. United Kingdom chicken meat production was 9% lower in July 2022 than July 2021; in contrast, energy costs increased for both production and refrigeration. Potential heatwave adaptation measures for poultry include transitioning to heat tolerant chicken breeds, lower stocking density, dehumidification cooling and misting systems, nutritional supplements, and improving retail refrigeration resilience and efficiency. United Kingdom wheat yields were 8% higher in 2022 than the 2017–2021 average. Increases were observed in every United Kingdom region but were least in the South and East where the heatwave intensity was strongest. Future adaptation measures to avoid negative impacts of summer heat stress on winter wheat could include earlier maturing and heat/drought tolerant varieties, earlier autumn sowing, targeted irrigation for drought around anthesis, and soil and water conservation measures.
Washed microbiota transplantation: a case report of clinical success with skin and gut microbiota improvement in an adolescent boy with atopic dermatitis
Authors: Deng Wan-Ying , Chen Wen-Jia , Zhong Hao-Jie , Wu Li-Hao , He Xing-Xiang
Published: November 2023

Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease characterized by itching. The gut microbiome can help maintain skin immune homeostasis by regulating innate and adaptive immunity. Here, we report a case of AD in a 15-year-old adolescent boy who benefited from washed microbiota transplantation (WMT). WMT was performed for three courses, with each course lasting for three consecutive days and an interval of one month between two courses. Clinical assessments were conducted at each WMT course, and skin, blood, and stool samples were collected for microbial analysis. After three months of WMT treatment, the boy’s itchiness was effectively controlled: his skin showed noticeable improvement, with reduced Staphylococcus aureus in the skin lesions. The scores of SCORAD (SCORing Atopic Dermatitis), EASI (Eczema Area and Severity Index), NRS (Numerical Rating Scale), and DLQI (Dermatology Life Quality Index) significantly decreased compared to the baseline. Serum levels of eosinophil ratio, tumor necrotic factor-α, and interleukin-6 also reduced to the normal levels. There was a significant decrease in S. aureus in the skin lesions. Additionally, the intestinal flora became more diverse, and the abundance of Bifidobacterium species, significantly increased after WMT. No adverse events were reported during the treatment and the 1-year follow-up period. This case report provides direct clinical evidence for WMT as a novel promising treatment strategy for AD, and preliminary experimental data suggests the existence of an intestinal-skin axis in terms of the gut microbiota and the skin immune homeostasis.
The GEM-handle as convenient labeling strategy for bimodal single-domain antibody-based tracers carrying 99mTc and a near-infrared fluorescent dye for intra-operative decision-making
Authors: Declerck Noemi B. , Huygen Celine , Mateusiak Lukasz , Stroet Marcus C. M. , Hernot Sophie
Published: November 2023

Intra-operative fluorescence imaging has demonstrated its ability to improve tumor lesion identification. However, the limited tissue penetration of the fluorescent signals hinders the detection of deep-lying or occult lesions. Integrating fluorescence imaging with SPECT and/or intra-operative gamma-probing synergistically combines the deep tissue penetration of gamma rays for tumor localization with the precision of fluorescence imaging for precise tumor resection. In this study, we detail the use of a genetically encoded multifunctional handle, henceforth referred to as a GEM-handle, for the development of fluorescent/radioactive bimodal single-domain antibody (sdAb)-based tracers. A sdAb that targets the urokinase plasminogen activator receptor (uPAR) was engineered to carry a GEM-handle containing a carboxy-terminal hexahistidine-tag and cysteine-tag. A two-step labeling strategy was optimized and applied to site-specifically label IRDye800CW and 99mTc to the sdAb. Bimodal labeling of the sdAbs proved straightforward and successful. 99mTc activity was however restricted to 18.5 MBq per nmol fluorescently-labeled sdAb to prevent radiobleaching of IRDye800CW without impeding SPECT/CT imaging. Subsequently, the in vivo biodistribution and tumor-targeting capacity of the bimodal tracer were evaluated in uPAR-positive tumor-bearing mice using SPECT/CT and fluorescence imaging. The bimodal sdAb showed expected renal background signals due to tracer clearance, along with slightly elevated non-specific liver signals. Four hours post-injection, both SPECT/CT and fluorescent images achieved satisfactory tumor uptake and contrast, with significantly higher values observed for the anti-uPAR bimodal sdAb compared to a control non-targeting sdAb. In conclusion, the GEM-handle is a convenient method for designing and producing bimodal sdAb-based tracers with adequate in vivo characteristics.
High population frequencies of MICA copy number variations originate from independent recombination events
Authors: Klussmeier Anja , Putke Kathrin , Klasberg Steffen , Kohler Maja , Sauter Jürgen , Schefzyk Daniel , Schöfl Gerhard , Massalski Carolin , Schäfer Gesine , Schmidt Alexander H. , Roers Axel , Lange Vinzenz
Published: November 2023

MICA is a stress-induced ligand of the NKG2D receptor that stimulates NK and T cell responses and was identified as a key determinant of anti-tumor immunity. The MICA gene is located inside the MHC complex and is in strong linkage disequilibrium with HLA-B. While an HLA-B*48-linked MICA deletion-haplotype was previously described in Asian populations, little is known about other MICA copy number variations. Here, we report the genotyping of more than two million individuals revealing high frequencies of MICA duplications (1%) and MICA deletions (0.4%). Their prevalence differs between ethnic groups and can rise to 2.8% (Croatia) and 9.2% (Mexico), respectively. Targeted sequencing of more than 70 samples indicates that these copy number variations originate from independent nonallelic homologous recombination events between segmental duplications upstream of MICA and MICB. Overall, our data warrant further investigation of disease associations and consideration of MICA copy number data in oncological study protocols.
Numerical study of double-chambered perforated caisson with a top cover based on SPH method
Authors: Tang Xiaocheng , Liu Huayu , Mei Lili , Fu Pengshuai , Song Dongrui , Chen Hongzhou
Published: November 2023

The Smoothed Particle Hydrodynamics (SPH) method modified by Corrective Smoothed Particle Method (CSPM) and Riemann solution is employed to simulate the interaction between double-chambered perforated caissons and waves. The accuracy and applicability of the numerical method are verified by the theoretical values and experimental data through comparisons. The effects of the top cover height s, the width of the wave dissipation chamber B and the perforated rate μ on the wave surface η or wave pressure p of the caisson are numerically analysis. The results show that under the calculated wave conditions, the top cover height s and perforated rate μ are significant factors affecting the wave dissipation performance of the caisson, while the width of the wave dissipation chamber B has little effect on the wave surface η. In the meanwhile, with the increase of the top cover height s, the wave pressure p on the front perforated plate and the back wall at the static water level gradually decreases, and the wave pressure p on the back perforated plate first decreases and then increases. In addition, the modified SPH method is also used to explore the changes of the pressure field and the velocity field of water particles, tracing the instantaneous velocity of water particles at different positions at different time, and describe the motion state of water particles, which provides effective facilitates for investigating the interaction between double-chambered perforated caissons and waves.
Experimental study on the nozzle-shape effect on liquid jet characteristics in gaseous crossflow
Authors: Jalili B. , Jalili P. , Ommi F. , Ganji D. D.
Published: November 2023

This study presents experimental findings on the crossflow injection of a liquid jet into a gaseous flow. Crossflow injection is favored over co-axial trajectory injection because of its potential to enhance atomization, promote the formation of smaller droplets, and improve injection parameters, mainly due to the differing trajectory of fuel injection within the transverse airflow. The study’s experiments use two circular and four elliptical nozzles with varying aspect ratios. The research investigates the influential factors that affect the trajectory and breakup of the liquid jet, specifically analyzing the impact of the nozzle geometry, Weber number, and momentum ratio of the liquid jet to the air crossflow. Additionally, equations are derived to describe the trajectory for both elliptical and circular nozzles. The relationship between breakup height and length is explored, with the observation that breakup length remains constant for both nozzle shapes. Furthermore, the study investigates the analysis of breakup regimes and establishes a direct correlation between the Weber number and the breakup regime. Column, bag, and multimode breakup are observed at Weber numbers 4, 38, and 82, respectively. The experimental error for the liquid jet trajectory obtained is approximately 2%. Importantly, the experimental results align with previously published experimental and numerical data, confirming the validity and reliability of the findings.
Deep learning-based denoising streamed from mobile phones improves speech-in-noise understanding for hearing aid users
Authors: Diehl Peter Udo , Zilly Hannes , Sattler Felix , Singer Yosef , Kepp Kevin , Berry Mark , Hasemann Henning , Zippel Marlene , Kaya Müge , Meyer-Rachner Paul , Pudszuhn Annett , Hofmann Veit M. , Vormann Matthias , Sprengel Elias
Published: November 2023

The hearing loss of almost half a billion people is commonly treated with hearing aids. However, current hearing aids often do not work well in real-world noisy environments. We present a deep learning based denoising system that runs in real time on iPhone 7 and Samsung Galaxy S10 (25 ms algorithmic latency). The denoised audio is streamed to the hearing aid, resulting in a total delay of around 65–75 ms, depending on the phone. In tests with hearing aid users having moderate to severe hearing loss, our denoising system improves audio across three tests: 1) listening for subjective audio ratings, 2) listening for objective speech intelligibility, and 3) live conversations in a noisy environment for subjective ratings. Subjective ratings increase by more than 40%, for both the listening test and the live conversation compared to a fitted hearing aid as a baseline. Speech reception thresholds, measuring speech understanding in noise, improve by 1.6 dB SRT. Ours is the first denoising system that is implemented on a mobile device, streamed directly to users’ hearing aids using only a single channel as audio input while improving user satisfaction on all tested aspects, including speech intelligibility. This includes overall preference of the denoised and streamed signal over the hearing aid, thereby accepting the higher latency for the significant improvement in speech understanding.
Responses of gut microbiota in crocodile lizards (Shinisaurus crocodilurus) to changes in temperature
Authors: Lin Zhengzhong , He Mingxian , Zhong Chunying , Li Yuhui , Tang Sanqi , Kang Xindan , Wu Zhengjun
Published: November 2023

The gut microbiota plays an essential role in maintaining the health and fitness of the host organism. As a critical environmental variable, temperature exerts significant effects on animal survival and reproduction. Elevated temperatures can influence the composition and function of the animal gut microbiota, which may have potentially detrimental effects on the host. The crocodile lizard (Shinisaurus crocodilurus) is an ancient and currently endangered reptile species due to human hunting and habitat destruction. Given the predicted shifts in global temperatures in the next century, it is important to understand how warming affects the gut microbiota of these vulnerable lizards, which remains unclear. To determine how the microbial communities change in crocodile lizards in response to warming, we analyzed the gut microbiota under five temperature conditions (22°C, 24°C, 26°C, 28°C, and 30°C) using 16S rRNA high-throughput sequencing. Results showed that the dominant phyla, Proteobacteria and Bacteroidetes, in gut microbiota were not significantly affected by temperature variations, but increasing temperature altered the structure and increased the community richness of the gut microbiota. In addition, warming changed the abundance of Pseudomonas aeruginosa and Actinobacteria, which may have negative effects on the physiological health of the crocodile lizards. Functional prediction analysis demonstrated that the functional pathways enriched in crocodile lizards were mainly related to metabolism, with no significant differences observed in these pathways at KEGG pathway level 1 after warming. These results provide valuable insights into the ecological adaptations and regulatory mechanisms employed by crocodile lizards in response to warming, which may be of benefit for their conservation.
Gut microbiome, metabolome and alopecia areata
Authors: Liu Zhiyu , Liu Xiaoyan
Published: November 2023

Alopecia areata (AA) is a type of dermatological disease characterized by rapid and non-scarring hair loss of the scalp or body skin that may be related to genetic, immunological and physiological factors. It is now believed that AA is associated with oxidative stress, autoimmune disease, neuropsychological factors, pathogens, immune checkpoint inhibitors and microecological imbalance under the premise of host genetic susceptibility. In recent years, studies have revealed the significant role of the gut microbiome or metabolome in many aspects of human health. Diverse studies have revealed that the gut microbiome and metabolome have an important influence on skin conditions. This review highlights the relationship between AA and the gut microbiome or metabolome to provide novel directions for the prevention, clinical diagnosis and treatment of AA.
Inhibitory mechanism of quercetin on Alicyclobacillus acidoterrestris
Authors: Liang Xinhong , Tu Cunjian , Li Yongchao , Sun Junliang , Zhao Ruixiang , Ran Junjian , Jiao Lingxia , Huang Junchao , Li Junrui
Published: November 2023

In this the antibacterial of quercetin against Alicyclobacillus acidoterrestris was evaluated by measuring the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Subsequently, the effect of quercetin on A. acidoterrestris cell membrane was evaluated through scanning electron microscopy (SEM), surface hydrophobicity determination, diacetate fluorescein staining and propidium iodide (PI) staining. Additionally, the effects of quercetin on intracellular macromolecules and cell metabolism were explored by measuring the culture medium protein, bacterial protein and intracellular sodium and potassium adenosine triphosphate (ATP) enzyme activity. The results revealed that quercetin exhibited the MIC and MBC values of 100 ug/mL and 400 ug/mL, respectively, against A. acidoterrestris. The SEM results revealed that quercetin could induce irreversible damage to the cell membrane effectively. Moreover, quercetin could enhance the surface hydrophobicity of A. acidoterrestris. The results of flow cytometry and fluorescence microscopy analyses revealed that quercetin could promote cell damage by altering the cell membrane permeability of A. acidoterrestris, inducing the release of nucleic acid substances from the cells. Furthermore, the determination of protein content in the culture medium, bacterial protein content, and the Na(+)/K(+)-ATPase activity demonstrated that quercetin could reduce the intracellular protein content and impedes protein expression and ATPase synthesis effectively, leading to apoptosis.
iTRAQ-based quantitative proteomic analysis of the antibacterial mechanism of silver nanoparticles against multidrug-resistant Streptococcus suis
Authors: Liu Baoling , Liu Dingyu , Chen Tianbao , Wang Xiaohu , Xiang Hua , Wang Gang , Cai Rujian
Published: November 2023

Background

The increase in antibiotic resistance of bacteria has become a major concern in clinical treatment. Silver nanoparticles (AgNPs) have significant antibacterial effects against Streptococcus suis. Therefore, this study aimed to investigate the antibacterial activity and mechanism of action of AgNPs against multidrug-resistant S. suis.

Methods

The effect of AgNPs on the morphology of multidrug-resistant S. suis was observed using scanning electron microscopy (SEM). Differentially expressed proteins were analyzed by iTRAQ quantitative proteomics, and the production of reactive oxygen species (ROS) was assayed by H2DCF-DA staining.

Results

SEM showed that AgNPs disrupted the normal morphology of multidrug-resistant S. suis and the integrity of the biofilm structure. Quantitative proteomic analysis revealed that a large number of cell wall synthesis-related proteins, such as penicillin-binding protein and some cell cycle proteins, such as the cell division protein FtsZ and chromosomal replication initiator protein DnaA, were downregulated after treatment with 25 μg/mL AgNPs. Significant changes were also observed in the expression of the antioxidant enzymes glutathione reductase, alkyl hydroperoxides-like protein, α/β superfamily hydrolases/acyltransferases, and glutathione disulfide reductases. ROS production in S. suis positively correlated with AgNP concentration.

Conclusion

The potential antibacterial mechanism of AgNPs may involve disrupting the normal morphology of bacteria by inhibiting the synthesis of cell wall peptidoglycans and inhibiting the growth of bacteria by inhibiting the cell division protein FtsZ and Chromosomal replication initiator protein DnaA. High oxidative stress may be a significant cause of bacterial death. The potential mechanism by which AgNPs inhibit S. suis biofilm formation may involve affecting bacterial adhesion and interfering with the quorum sensing system.
Comparison of Lactiplantibacillus plantarum isolates from the gut of mice supplemented with different types of nutrients: a genomic and metabolomic study
Authors: Wang Ziyan , Zhang Zhixuan , Shi Qiuyue , Liu Songyi , Wu Qiaoli , Wang Ze , Saiding Emilaguli , Han Jiaojiao , Zhou Jun , Wang Rixin , Su Xiurong
Published: November 2023

Many studies have focused on the influence of dietary supplements on gut microbiota composition, but limited research have reported their effects on specific bacterial species in the gut. Lactiplantibacillus plantarum is one of the most widely studied probiotics, with a wide range of sources and good environmental adaptability. In this study, in order to elucidate the adaptation strategies of L. plantarum to the gut of mice supplemented with carbohydrates, peptides and minerals, whole genome resequencing and intracellular metabolites detection were performed, and high-frequency mutant genes and differential metabolites were screened. The results suggested different types of dietary supplements do have different effects on L. plantarum from the gut of mice. Additionally, KEGG annotation unveiled that the effects of these dietary supplements on the gene level of L. plantarum primarily pertained to environmental information processing, while the differential metabolites were predominantly associated with metabolism. This study provided new perspectives on the adaptive mechanism of L. plantarum in response to the host’s gut environment, suggesting that the diversity of the genome and metabolome of L. plantarum was correlated with dietary supplements. Furthermore, this study offered useful guidance in the effective utilization of dietary supplements.
Upregulation of LRRK2 following traumatic brain injury does not directly phosphorylate Thr175 tau
Authors: Donison Neil , Hintermayer Matthew , Subramaniam Maegha , Santandrea Erin , Volkening Kathryn , Strong Michael J.
Published: November 2023

Phosphorylated microtubule-associated protein tau (tau) aggregates are a pathological hallmark of various neurodegenerative diseases, including chronic traumatic encephalopathy and amyotrophic lateral sclerosis with cognitive impairment. While there are many residues phosphorylated on tau, phosphorylation of threonine 175 (pThr175 tau) has been shown to initiate fibril formation in vitro and is present in pathological tau aggregates in vivo. Given this, preventing Thr175 tau phosphorylation presents a potential approach to reduce fibril formation; however, the kinase(s) acting on Thr175 are not yet fully defined. Using a single controlled cortical impact rodent model of traumatic brain injury (TBI), which rapidly induces Thr175 tau phosphorylation, we observed an upregulation and alteration in subcellular localization of leucine-rich repeat kinase 2 (LRRK2), a kinase that has been implicated in tau phosphorylation. LRRK2 upregulation was evident by one-day post-injury and persisted to day 10. The most notable changes were observed in microglia at the site of injury in the cortex. To determine if the appearance of pThr175 tau was causally related to the upregulation of LRRK2 expression, we examined the ability of LRRK2 to phosphorylate Thr175in vitro by co-transfecting 2N4R human WT-tau with either LRRK2-WT, constitutively-active LRRK2-G2019S or inactive LRRK2-3XKD. We found no significant difference in the level of pThr175 tau between the overexpression of LRRK2-WT, -G2019S or -3XKD, suggesting LRRK2 does not phosphorylate tau at Thr175. Further, downstream events known to follow Thr175 phosphorylation and known to be associated with pathological tau fibril formation (pSer9-GSK3β and pThr231 tau induction) also remained unchanged. We conclude that while LRRK2 expression is altered in TBI, it does not contribute directly to pThr175 tau generation.