bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic β-cells package double C2-like domain beta protein into extracellular vesicles via tandem C2 domains
Authors: Esparza Diana , Lima Carinna , Abuelreich Sarah , Ghaeli Ima , Hwang Jinhee , Oh Eunjin , Lenz Ayelet , Gu Angel , Jiang Nan , Kandeel Fouad , Thurmond Debbie C. , Jovanovic-Talisman Tijana
Published: October 2024

Introduction

Double C2-like domain beta (DOC2B) is a vesicle priming protein critical for glucose-stimulated insulin secretion in β-cells. Individuals with type 1 diabetes (T1D) have lower levels of DOC2B in their residual functional β-cell mass and platelets, a phenotype also observed in a mouse model of T1D. Thus, DOC2B levels could provide important information on β-cell dys(function).

Objective

Our objective was to evaluate the DOC2B secretome of β-cells. In addition to soluble extracellular protein, we assessed DOC2B localized within membrane-delimited nanoparticles – extracellular vesicles (EVs). Moreover, in rat clonal β-cells, we probed domains required for DOC2B sorting into EVs.

Method

Using Single Extracellular VEsicle Nanoscopy, we quantified EVs derived from clonal β-cells (human EndoC-βH1, rat INS-1 832/13, and mouse MIN6); two other cell types known to regulate glucose homeostasis and functionally utilize DOC2B (skeletal muscle rat myotube L6-GLUT4myc and human neuronal-like SH-SY5Y cells); and human islets sourced from individuals with no diabetes (ND). EVs derived from ND human plasma, ND human islets, and cell lines were isolated with either size exclusion chromatography or differential centrifugation. Isolated EVs were comprehensively characterized using dotblots, transmission electron microscopy, nanoparticle tracking analysis, and immunoblotting.

Results

DOC2B was present within EVs derived from ND human plasma, ND human islets, and INS-1 832/13 β-cells. Compared to neuronal-like SH-SY5Y cells and L6-GLUT4myc myotubes, clonal β-cells (EndoC-βH1, INS-1 832/13, and MIN6) produced significantly more EVs. DOC2B levels in EVs (over whole cell lysates) were higher in INS-1 832/13 β-cells compared to L6-GLUT4myc myotubes; SH-SY5Y neuronal-like cells did not release appreciable DOC2B. Mechanistically, we show that DOC2B was localized to the EV lumen; the tandem C2 domains were sufficient to confer sorting to INS-1 832/13 β-cell EVs.

Discussion

Clonal β-cells and ND human islets produce abundant EVs. In cell culture, appreciable DOC2B can be packaged into EVs, and a small fraction is excreted as a soluble protein. While DOC2B-laden EVs and soluble protein are present in ND plasma, further studies will be necessary to determine if DOC2B originating from β-cells significantly contributes to the plasma secretome.
Comparative assessment of pollution control measures for urban water bodies in urban small catchment by SWMM
Authors: Liu Jie , Zhang Xiang , Gui Haijiao
Published: October 2024

Under the current increasingly serious water pollution situation in urban, the comprehensive treatment and protecting measures in urban small catchment are the necessary step to the water pollution treatment, not only focus on the water bodies themself. In this paper, the Luojiagang river channel and its catchment in Wuhan, which has been heavily impacted by water pollution, are taken as an example for the comparative assessment of pollution control measures in order to explore the effective and sustainable schemes including the LID (Low Impact Development---LID) by using SWMM model (Storm Water Management Model---SWMM). Through the comparison of pollution treatment measures based on scenarios simulation with the baseline scenarios, it was found that the reduction effects of pollutant peak concentrations at the outlet node of Luojiagang River had the decreasing order of: the combined measures (COS) > LID control > the water diversion from Donghu Lake (WAD) > the sewage treatment (SET) > the sediment dredging (SED), and the reduction effects of total pollutant load had the decreasing order of: LID > COS > SET > SED > WAD. The results show that the control of non-point source pollution is the key for the improvement of water quality in Luojiagang River, and LID plays important role in the reduction of both pollutant peak concentrations and load. This study has the implication for the decision making of the water pollution controlling schemes in urban small catchment.
Stalk-eyed flies carrying a driving X chromosome compensate by increasing fight intensity
Authors: Paczolt Kimberly A. , Pritchard Macy E. , Welsh Gabrielle T. , Wilkinson Gerald S. , Reinhardt Josephine A.
Published: October 2024

Exaggerated ornaments provide opportunities to understand how selection can operate at different levels to shape the evolution of a trait. While these features aid their bearer in attracting mates or fending off competitors, they can also be costly and influenced by the environment and genetic variation. The eyestalks of the stalk-eyed fly, Teleopsis dalmanni, are of interest because eyestalk length is the target of both intra- and intersexual selection and is also reduced by loci on a highly-divergent sex ratio X chromosome (XSR), a meiotic driver accounting for up to 30% of wild X chromosomes. Male stalk-eyed flies fight to control access to females and over food using a combination of low-intensity displays and high-intensity physical fights. We staged, filmed, and scored contests between pairs of eyespan-matched males to evaluate whether X chromosome type impacts the behavior and outcome of aggressive interactions. While our results broadly match expectations from previous studies, we found that XSR males used more high-intensity behaviors than males carrying a non-driving, standard X chromosome (XST), particularly when their eyestalks were of similar size or smaller than their opponents. Additionally, we found that when XSR males use high-intensity behaviors, they win more bouts than when they use low-intensity behaviors. Taken together, these results suggest that XSR impacts male aggressive behavior to compensate for the shorter eyestalks of XSR males and may help to explain how this selfish chromosome is maintained.
Identification and validation of efferocytosis-related biomarkers for the diagnosis of metabolic dysfunction-associated steatohepatitis based on bioinformatics analysis and machine learning
Authors: Cao Chenghui , Liu Wenwu , Guo Xin , Weng Shuwei , Chen Yang , Luo Yonghong , Wang Shuai , Zhu Botao , Liu Yuxuan , Peng Daoquan
Published: October 2024

Background

Metabolic dysfunction-associated steatohepatitis (MASH) is a highly prevalent liver disease globally, with a significant risk of progressing to cirrhosis and even liver cancer. Efferocytosis, a process implicated in a broad spectrum of chronic inflammatory disorders, has been reported to be associated with the pathogenesis of MASH; however, its precise role remains obscure. Thus, we aimed to identify and validate efferocytosis linked signatures for detection of MASH.

Methods

We retrieved gene expression patterns of MASH from the GEO database and then focused on assessing the differential expression of efferocytosis-related genes (EFRGs) between MASH and control groups. This analysis was followed by a series of in-depth investigations, including protein–protein interaction (PPI), correlation analysis, and functional enrichment analysis, to uncover the molecular interactions and pathways at play. To screen for biomarkers for diagnosis, we applied machine learning algorithm to identify hub genes and constructed a clinical predictive model. Additionally, we conducted immune infiltration and single-cell transcriptome analyses in both MASH and control samples, providing insights into the immune cell landscape and cellular heterogeneity in these conditions.

Results

This research pinpointed 39 genes exhibiting a robust correlation with efferocytosis in MASH. Among these, five potential diagnostic biomarkers—TREM2, TIMD4, STAB1, C1QC, and DYNLT1—were screened using two distinct machine learning models. Subsequent external validation and animal experimentation validated the upregulation of TREM2 and downregulation of TIMD4 in MASH samples. Notably, both TREM2 and TIMD4 demonstrated area under the curve (AUC) values exceeding 0.9, underscoring their significant potential in facilitating the diagnosis of MASH.

Conclusion

Our study comprehensively elucidated the relationship between MASH and efferocytosis, constructing a favorable diagnostic model. Furthermore, we identified potential therapeutic targets for MASH treatment and offered novel insights into unraveling the underlying mechanisms of this disease.
Treatment and molecular analysis of bullous pemphigoid with tofacitinib: a case report and review of current literature
Authors: Li Xiang , Zhang Lian , Gu Hongzhi , He Wanzhen , Zhai Zhifang , Zhang Mingwang
Published: October 2024

Background

Bullous pemphigoid (BP) is a rare, life-threatening autoimmune blistering disease with pruritus and tension blisters/bullous as the main clinical manifestations. Glucocorticosteroids are the main therapeutic agents for it, but their efficacy is poor in some patients. Tofacitinib, a small molecule agent that inhibits JAK1/3, has shown incredible efficacy in a wide range of autoimmune diseases and maybe a new valuable treatment option for refractory BP.

Objective

To report a case of refractory BP successfully treated with tofacitinib, then explore the underlying mechanism behind the treatment, and finally review similarities to other cases reported in the literature.

Methods

Case report and literature review of published cases of successful BP treatment with JAK inhibitors. The case report describes a 73-year-old male with refractory BP that was successfully managed with the combination therapy of tofacitinib and low-dose glucocorticoids for 28 weeks. Immunohistochemistry and RNA sequencing were performed to analyze the underlying mechanism of tofacitinib therapy. A systematic literature search was conducted to identify other cases of treatment with JAK inhibitors.

Results

Throughout the 28-week treatment period, the patient experienced clinical, autoantibody and histologic resolution. Immunohistochemical analysis showed tofacitinib significantly decreased the pSTAT3 and pSTAT6 levels in the skin lesions of this patient. RNA sequencing and immunohistochemical testing of lesion samples from other BP patients identified activation of the JAK-STAT signaling pathway. Literature review revealed 17 previously reported cases of BP treated with four kinds of JAK inhibitors successfully, including tofacitinib (10), baricitinib (1), upadacitinib (3) and abrocitinib (3).

Conclusions

Our findings support the potential of tofacitinib as a safe and effective treatment option for BP. Larger studies are underway to better understand this efficacy and safety.
Immunoregulatory protein B7-H3 upregulated in bacterial and viral infection and its diagnostic potential in clinical settings
Authors: Tigabu Abiye
Published: October 2024

Bacterial and viral infections cause a huge burden to healthcare settings worldwide, and mortality rates associated with infectious microorganisms have remained high in recent decades. Despite tremendous efforts and resources worldwide to explore diagnostic biomarkers, rapid and easily assayed indicators for the diagnosis of bacterial and viral infections remain a challenge. B7 homolog 3 (B7-H3), a member of the B7 family of immunoregulatory proteins, is overexpressed in patients with septicemia, meningitis, pneumonia, and hepatitis. Therefore, B7-H3 could be used as a potential clinical indicator and therapeutic target for bacterial and viral infections caused by H. pylori, S. pneumoniae, M. pneumoniae, hepatitis B virus (HBV), viral hemorrhagic septicemia virus (VHSV), respiratory syncytial virus (RSV), and human immunodeficiency virus (HIV). Moreover, the interplay between infectious microorganisms and B7-H3 and exploration of the functional roles of the B7-H3 molecule could aid in the development of novel strategies for disease diagnosis and immunotherapy.
Combining the uncombinable: corporate memories, ethnobiological observations, oceanographic and ecological data to enhance climatic resilience in small-scale fisheries
Authors: Garibay-Toussaint Isabel , Olguín-Jacobson Carolina , Woodson C. Brock , Arafeh-Dalmau Nur , Torre Jorge , Fulton Stuart , Micheli Fiorenza , O’Connor Ryan , Précoma-de la Mora Magdalena , Hernández-Velasco Arturo , Narchi Nemer E.
Published: October 2024

The global food production system is increasingly strained by abrupt and unpredictable weather events, which hinder communities' ability to adapt to climate variations. Despite advances in meteorological predictions, many communities lack the academic knowledge or infrastructure to interpret these complex models. This gap highlights the need for solutions that make climate forecasts more accessible and actionable, especially for communities reliant on natural resources. This study explores the potential of enhancing seasonal climate forecasts by integrating local ecological knowledge (LEK) with scientific data. Specifically, we combined ethnobiological information gathered between 2022 and 2024 with existing oceanographic and ecological data to create an ethnobiological calendar for four fishing cooperatives. An ethnographic approach was used to understand the population's ethnobiological knowledge and their perceptions of marine heatwaves and climate change impacts. Coastal monitoring data was collected using moorings that recorded temperature over a 14-year period (2010–2024). To characterize giant kelp dynamics, we used an existing dataset of multispectral Landsat images, which estimates the surface canopy biomass of giant kelp forests. Ecological monitoring was conducted annually every summer from 2006 to 2023 to record the in situ abundance of ecologically and economically important invertebrate and fish species. Combining oceanographic, ecological, and ethnographic data, allowed for alligning fishers' observations with recorded marine heatwave events and ecological shifts. Our findings revealed that these observations closely matched documented marine heatwave data and corresponding ecological changes. The integration of LEK with scientific oceanographic data can significantly improved our understanding of dynamic climate regimes, offering contextually relevant information that enhances the reliability and utility of seasonal climate forecasts. By incorporating yearly data into an ethnobiological calendar, we promote more inclusive, community-based approaches to environmental management, advocating for the integration of LEK in climate adaptation efforts, emphasizing its crucial role in strengthening resilience strategies against climatic shocks.
Bacterial profiles and their antibiotic susceptibility patterns in neonatal sepsis at the University of Gondar Comprehensive Specialized Hospital, Ethiopia
Authors: Deress Teshiwal , Belay Gizeaddis , Ayenew Getahun , Ferede Worku , Worku Minichile , Feleke Tigist , Mulu Meseret , Belay Solomon , Getie Michael
Published: October 2024

Background

Neonatal sepsis is a major cause of morbidity and mortality worldwide. Understanding the bacterial profiles and antibiotic susceptibility patterns causing neonatal sepsis is crucial for guiding appropriate treatment, improving patient outcomes, and combating the emergence of antibiotic resistance. Despite its importance, data regarding neonatal sepsis in the study area is limited. Therefore, this study aimed to characterize the bacterial pathogens and identify associated factors among neonates with suspected sepsis at the University of Gondar Comprehensive Specialized Hospital, Ethiopia.

Methods

A cross-sectional study was conducted by reviewing laboratory records of neonates admitted for suspected sepsis from January 2019 to December 2021. Data were checked for completeness and encoded in a spreadsheet program. Then, data were exported to STATA version 17 for analysis. Descriptive statistics such as frequency and percentage were computed. The association between neonatal sepsis and potential risk factors was assessed using Pearson’s chi-square test. A p-value of < 0.05, was considered statistically significant.

Results

A total of 1,236 neonates were included. Of these, 96.2% (1,190/1,236) had a fever before admission. The prevalence of culture-confirmed sepsis was 25.4% (314/1,236). Bacterial pathogens accounted for 23% (284/1,236) of these isolates, with Gram-negative bacteria being more prevalent at 75.3% (214/284) than Gram-positive bacteria at 24.7% (70/284). The most frequently isolated bacterial pathogens were K. pneumoniae 38.7% (110/284) and S. aureus 13% (37/284). The isolates demonstrated a high resistance level to commonly used antibiotics, with 61.6% exhibiting multidrug resistance. K. pneumoniae showed the highest rate of multidrug resistance (90.9%). Neonatal sepsis was associated with several factors, including fever before and after admission, hypothermia, increased respiration, suspected pneumonia, and suspected meningitis.

Conclusion

This study identified a high prevalence of culture-confirmed sepsis in neonates at UoGCSH, with Gram-negative bacteria, especially K. pneumoniae, dominating the isolated pathogens. The isolated bacteria exhibited alarming resistance to commonly used antibiotics, with a high proportion demonstrating multidrug resistance. Implementing effective antibiotic stewardship programs is crucial to optimize antibiotic use, reduce unnecessary prescriptions, and curb the spread of resistant strains.
Optimisation of Lactobacillus fermentation conditions and its application in the fermentation of salt-free sauerkraut
Authors: Wang Wenlun , Li Wenbing , Huang Yan , Yang Ying , Liu Hui , Yu Chaohang , Yuan Qing , He Lianmin , Hu Qianmin , Li Ye , Meng Taoyan , Chen Huanhuan , Liao Jiabi , Chen Ou , Yu Shirui , Zhang Feng
Published: October 2024

To identify what are the dominant lactic acid bacteria (LAB) involved in the fermentation of salt-free sauerkraut, and optimize its industrial culture conditions, we isolated and identified a strain of LAB, which is referred to as Lactobacillus sp. DF_001, with the preservation number CCTCC NO: M20232593, from five different regions in Guizhou Province. Industrial culture conditions were optimized using Plackett-Burman and Central Composite design experiments, and the potential role of this LAB in salt-free sauerkraut fermentation was validated. Bioproduction was optimal with a culture time of 66 h, starch/water ratio of 1.7% and inoculum of 0.02%, which gave approximately three-fold higher yield than the basal culture medium DeMan-Rogosa-Sharpe medium (MRS). The LAB was used in small-scale industrial experiments. The Dafang LAB significantly enhanced the sensory score of the salt-free sauerkraut products by about 32% compared to the control group. The total acid content increased by about 32% and the sugar and nitrite contents were reduced by 67.27 and 69.58%, respectively. The total number of bacterial colonies decreased by 37.5%. All other indicators complied with the national standard, providing overall the basis to improve salt-free sauerkraut fermentation.
Utility of syndromic surveillance for the surveillance of healthcare-associated infections in resource-limited settings: a narrative review
Authors: Mwanja Herman , Waswa J. P. , Kiggundu Reuben , Mackline Hope , Bulwadda Daniel , Byonanebye Dathan M. , Kambugu Andrew , Kakooza Francis
Published: October 2024

Globally, Healthcare-associated infections (HCAIs) pose a significant threat to patient safety and healthcare systems. In low- and middle-income countries (LMICs), the lack of adequate resources to manage HCAIs, as well as the weak healthcare system, further exacerbate the burden of these infections. Traditional surveillance methods that rely on laboratory tests are cost-intensive and impractical in these settings, leading to ineffective monitoring and delayed management of HCAIs. The rates of HCAIs in resource-limited settings have not been well established for most LMICs, despite their negative consequences. This is partly due to costs associated with surveillance systems. Syndromic surveillance, a part of active surveillance, focuses on clinical observations and symptoms rather than laboratory confirmation for HCAI detection. Its cost-effectiveness and efficiency make it a beneficial approach for monitoring HCAIs in LMICs. It provides for early warning capabilities, enabling timely identification and response to potential HCAI outbreaks. Syndromic surveillance is highly sensitive and this helps balance the challenge of low sensitivity of laboratory-based surveillance systems. If syndromic surveillance is used hand-in-hand with laboratory-based surveillance systems, it will greatly contribute to establishing the true burden of HAIs in resource-limited settings. Additionally, its flexibility allows for adaptation to different healthcare settings and integration into existing health information systems, facilitating data-driven decision-making and resource allocation. Such a system would augment the event-based surveillance system that is based on alerts and rumours for early detection of events of outbreak potential. If well streamlined and targeted, to monitor priority HCAIs such as surgical site infections, hospital-acquired pneumonia, diarrheal illnesses, the cost and burden of the effects from these infections could be reduced. This approach would offer early detection capabilities and could be expanded into nationwide HCAI surveillance networks with standardised data collection, healthcare worker training, real-time reporting mechanisms, stakeholder collaboration, and continuous monitoring and evaluation. Syndromic surveillance offers a promising strategy for combating HCAIs in LMICs. It provides early warning capabilities, conserves resources, and enhances patient safety. Effective implementation depends on strategic interventions, stakeholder collaboration, and ongoing monitoring and evaluation to ensure sustained effectiveness in HCAI detection and response.
Functions of p120-catenin in physiology and diseases
Authors: Jin Xin , Lin Ting , Wang Yunjuan , Li Xiaoqian , Yang Yanhong
Published: October 2024

p120-catenin (p120) plays a vital role in regulating cell-cell adhesion at adherens junctions, interacting with the juxtamembrane domain (JMD) core region of E-cadherin and regulates the stability of cadherin at the cell surface. Previous studies have shown significant functions of p120 in cell-cell adhesion, tumor progression and inflammation. In this review, we will discuss recent progress of p120 in physiological processes and diseases, and focus on the functions of p120 in the regulation of cancer and inflammation.
Nasal lymphatic obstruction of CSF drainage as a possible cause of Alzheimer’s disease and dementia
Authors: Phillips William Thomas , Schwartz Joyce Gensberg
Published: October 2024

Alzheimer’s disease, the most common form of dementia among older adults, slowly destroys memory and thinking skills. In recent years, scientists have made tremendous progress in understanding Alzheimer’s disease, still, they do not yet fully understand what causes the disease. This article proposes a novel etiology for Alzheimer’s disease. Our hypothesis developed from a review of nuclear medicine scans, in which the authors observed a significant increase in nasal turbinate vasodilation and blood pooling in patients with hypertension, sleep apnea, diabetes and/or obesity, all risk factors for Alzheimer’s disease. The authors propose that nasal turbinate vasodilation and resultant blood pooling lead to the obstruction of normal nasal lymphatic clearance of cerebrospinal fluid and its waste products from the brain. The nasal turbinate vasodilation, due to increased parasympathetic activity, occurs alongside the well-established increased sympathetic activity of the cardiovascular system as seen in patients with hypertension. The increased parasympathetic activity is likely due to an autonomic imbalance secondary to the increase in worldwide consumption of highly processed food associated with dysregulation of the glucose regulatory system. The authors’ hypothesis offers a novel mechanism and a new paradigm for the etiology of Alzheimer’s disease and helps explain the rapid worldwide rise in the disease and other dementias which are expected to double in the next 20 years. This new paradigm provides compelling evidence for the modulation of the parasympathetic nervous system as a novel treatment strategy for Alzheimer’s disease and other degenerative brain diseases, specifically targeting nasal turbinate lymphatic flow.
Iron load in the normal aging brain measured with QSM and R2* at 7T: findings of the SENIOR cohort
Authors: Guevara Miguel , Roche Stéphane , Brochard Vincent , Cam Davy , Badagbon Jacques , Leprince Yann , Bottlaender Michel , Cointepas Yann , Mangin Jean-François , de Rochefort Ludovic , Vignaud Alexandre
Published: October 2024

Background

Iron accumulates in the brain during aging and is the focus of intensive research as an abnormal load, particularly in Deep Gray Matter (DGM), is related to neurodegeneration. Magnetic Resonance Imaging (MRI) metrics such as Quantitative Susceptibility Mapping (QSM) and apparent transverse relaxation rate R2* can be used to follow up iron in vivo. While the influence of age and sex on iron levels has already been reported, a careful consideration of neuronal risk factors, as well as for an enhanced sensitivity, is needed to define the normal evolution.

Methods

QSM and R2* at ultra-high field MRI are used to study iron in DGM using a carefully-characterized cohort of the healthy aging brain (SENIOR). Seventy-seven cognitively healthy elders (from 54 to 78 y/o) with clinical, biology, genetics, and cardiovascular risk factors careful evaluation. Differences linked with age, sex, cardiovascular risk factors and weight are studied.

Results

Age and sex have an influence on the brain iron deposition measured by QSM and R2* in a context of normal aging, without appearance of a pathological neurodegenerative process. Iron deposition shows higher values in the caudate and the putamen in older participants. Female participants present a higher level of iron in the amygdala, and males in the thalamus. Female participants also present differences in the accumbens, caudate and hippocampus when evaluating the joint age and sex effect. Participants with higher cardiovascular risk factors showed higher values of the iron, even without any impairment in their cognitive capability. An overweight is related with a higher iron load in the putamen for QSM and R2* in female participants. We controlled that these modifications of iron deposition are not related to a specific profile in the genotype of ApoE loci.

Conclusions

Establishing baseline values of QSM and R2* as iron probes in the context of aging is essential to determine differences in the process of neurodegeneration. Age and sex of participants are important factors that affect brain iron normal values. On the other hand, the presence of cardiovascular risk factors, which can be associated with age related diseases, can also potentially be linked with the iron deposition in the brain.
Ionising radiation exposure-induced regulation of selected biomarkers and their impact in cancer and treatment
Authors: Mzizi Yonwaba , Mbambara Saidon , Moetlhoa Boitumelo , Mahapane Johncy , Mdanda Sipho , Sathekge Mike , Kgatle Mankgopo
Published: October 2024

Ionising radiation (IR) is a form of energy that travels as electromagnetic waves or particles. While it is vital in medical and occupational health settings, IR can also damage DNA, leading to mutations, chromosomal aberrations, and transcriptional changes that disrupt the functions of certain cell regulators, genes, and transcription factors. These disruptions can alter functions critical for cancer development, progression, and treatment response. Additionally, IR can affect various cellular proteins and their regulators within different cell signalling pathways, resulting in physiological changes that may promote cancer development, progression, and resistance to treatment. Understanding these impacts is crucial for developing strategies to mitigate the harmful effects of IR exposure and improve cancer treatment outcomes. This review focuses on specific genes and protein biomarkers regulated in response to chronic IR exposure, and how their regulation impacts disease onset, progression, and treatment response.
The role of micronutrients and serum metabolites in intervertebral disk degeneration: insights from a Mendelian randomization study and mediation analysis
Authors: Jiang Nizhou , Wang Quanxiang , Jiang Jian , Li Lei
Published: October 2024

Background

Intervertebral disk degeneration (IVDD) is a complex degenerative skeletal condition, potentially influenced by micronutrients and serum metabolites in its etiology. However, the exact causal relationship between these factors and IVDD remains ambiguous.

Methods

The research employed a Two-Sample Mendelian Randomization (2SMR) analysis to thoroughly evaluate the causal relationship between 15 micronutrients (consisting of 7 minerals and 8 vitamins) as exposure variables, 1,091 blood metabolites, and 309 metabolite ratios as intermediary factors, and IVDD as the outcome. Additionally, reverse MR analysis and mediation analysis were carried out to validate the reliability of the results and explore the underlying mechanism by which micronutrients influence the risk of IVDD by regulating metabolites.

Results

Among the micronutrients examined, vitamin B12 exhibited a noteworthy negative correlation with the incidence of IVDD (OR: 0.752, 95% [CI]: 0.573–0.987, p = 0.040), indicating a potential reduction in IVDD risk with increased vitamin B12 consumption. Of the 1,091 blood metabolites and 309 metabolite ratios analyzed, 52 metabolites displayed significant associations with IVDD, primarily linked to amino acid, fatty acid, nucleotide, and sphingolipid metabolic pathways. Mediation analysis identified 4-acetaminophen sulfate as a potential mediator in the protective effect of vitamin B12 against IVDD.

Conclusion

This study has shown that vitamin B12 may reduce the risk of IVDD and has identified 52 serum metabolites that are associated with IVDD. Furthermore, it proposes that 4-acetaminophen sulfate could serve as a potential mechanism by which vitamin B12 exerts its inhibitory effects on IVDD.
Joint association of serum sodium and frailty with mild cognitive impairment among hospitalized older adults with chronic diseases: a cross-sectional study
Authors: Hui Zhaozhao , Wang Lina , Deng Jing , Liu Feng , Cheng Liping , Li Yajing , Tian Yuxin , Ma Le , Liu Xiaohong
Published: October 2024

Background

To examine the associations of serum sodium and frailty with the risk of mild cognitive impairment (MCI) among hospitalized older adults with chronic diseases.

Methods

A cross-sectional study was conducted in 403 hospitalized older adults with chronic diseases. Serum sodium concentration was assessed by the ion-selective electrode method, frailty status was evaluated by the FRAIL scale, and MCI was determined by the Montreal Cognitive Assessment (MoCA). Multiple logistic regression models were used to estimate the associations of serum sodium and frailty with MCI.

Results

Participants with the lowest tertile of serum sodium had a higher risk of MCI than those in the middle tertile group (OR = 1.75, 95% CI: 1.01–3.04). Below 143 mmol/L, the risk of MCI was 1.38 (95% CI: 1.03–1.84) for per 1 SD decrease in serum sodium. Compared with the robust group, frailty was significantly associated with an increased risk of MCI (OR = 3.94, 95% CI: 1.92–8.10). Moreover, in comparison with participants with the middle tertile of serum sodium and who were robust/prefrail, those with frailty and either the lowest (OR = 5.53, 95% CI: 2.08–14.67) or the highest tertile of serum sodium (OR = 3.48, 95% CI: 1.20–10.05) had higher risks of MCI.

Conclusion

Both lower and higher serum sodium impose a significantly higher risk for MCI in older adults with frailty. This could inform the design of clinical trials and the development of guidelines and recommendations for correcting serum sodium and frailty in hospitalized older adults with chronic diseases.
The potential role of next-generation sequencing in identifying MET amplification and disclosing resistance mechanisms in NSCLC patients with osimertinib resistance
Authors: Xiao Xiao , Xu Ren , Lu Jun , Xin Beibei , Wang Chenyang , Zhu Kexin , Zhang Hao , Chen Xinyu
Published: October 2024

Purposes

Osimertinib, one of the third-generation EGFR-tyrosine kinase inhibitors (TKIs) designed to target EGFR T790M mutation, significantly improves the prognosis of lung cancer. However, drug resistance still happens and MET amplification is responsible for one of the main causes. Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection, but fundamentally limited by observer subjectivity. Herein, we assessed the value of next-generation sequencing (NGS) method in MET amplification detection in non-small cell lung cancer (NSCLC), as well as revealed the mutation profiling of NSCLC patients with osimertinib resistance to provide some valuable clues to the mechanisms of resistance.

Methods

A total of 317 cancer tissue samples from 317 NSCLC patients at time of progression following osimertinib were submitted to NGS and only 96 tissues were tested by FISH simultaneously. With FISH results as gold standard, enumeration algorithm was applied to establish the optimal model for identifying MET amplification using gene copy number (GCN) data.

Results

The optimal model for identifying MET amplification was constructed based on the GCN of MET, BRAF, CDK6 and CYP3A4, which achieved a 74.0% overall agreement with FISH and performed well in identifying MET amplification except polysomy with a sensitivity of 85.7% and a specificity of 93.9%. The inconsistency between NGS and FISH occurred mainly in polysomy subtype, while MET GCN ≥ 5 could be reliably recognized by NGS. Moreover, the most frequently mutated genes in NSCLC patients with osimertinib resistance were EGFR (59.94%), followed by TP53 (43.85%), NRG1 (9.46%), PIK3CA (6.31%), and ATM (5.36%). The known resistance mechanisms, including MET amplification, EGFR (C797S, L718Q/R), TP53, CDK4, CDK6, CDKN2A, BRAF, KRAS, NRAS and PIK3CA mutations were also disclosed in our cohort.

Conclusions

NGS assay can achieve a high concordance with FISH in MET amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion.
Gastrointestinal manifestations and pathogenesis in childhood immunoglobulin A vasculitis
Authors: Kato Seiichi , Gold Benjamin D. , Kato Ayumu
Published: October 2024

Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common form of systemic vasculitis in childhood. The primary organs involved are the skin, gastrointestinal (GI) tract, joints, and kidneys. The spectrum of GI involvement in IgAV ranges from being mild and self-limited to severe manifestations often requiring surgical intervention. Galactose-deficient IgA1 on the immunoglobulin hinge region and its immune complexes are thought to play a central pathogenetic role in IgAV, however, an association between such molecules and specific GI mucosal damage remains unclear. GI endoscopy (both upper and lower) shows a variety of mucosal findings, many of which are not specific for IgAV. In upper GI endoscopy, however, the mucosal features can be diagnostic when found localized in the more distal part of upper GI tract (second and/or third parts of the duodenum). Abdominal computed tomography and capsule endoscopy have demonstrated that the small intestine is most commonly involved in IgAV. The GI mucosal involvement when evaluated microscopically shows IgA deposition which is histologically diagnostic. Conversely, leukocytoclastic vasculitis is less useful. Since the 1960s, cases of duodenojejunitis, in which IgAV was suspected but evident purpura was not dermatologically present, have often been labeled as “idiopathic”. In a pediatric case series, IgA enteropathy, without dermatological manifestations (i.e., purpura), was reported to have similar symptoms, as well as endoscopic characteristics and immunohistological findings as in IgAV. Subsequently, several case reports provide additional supportive evidence that IgA enteropathy must be a variant of IgAV. Thus, the immunologically driven auto-immune vasculitis results in the symptom complex dependent on the organ system involved, and the subsequent clinical features which are manifested. Present classification criteria are useful and universally available for diagnosing IgAV. However, based upon current knowledge including IgA enteropathy, minor modification of the IgAV criteria is proposed in the review.
Proteomic study of medicinal mushroom extracts reveals antitumor mechanisms in an advanced colon cancer animal model via ribosomal biogenesis, translation, and metabolic pathways
Authors: Jakopovic Boris , Horvatić Anita , Baranasic Jurica , Car Iris , Oršolić Nada , Jakopovich Ivan , Sedić Mirela , Kraljević Pavelić Sandra
Published: October 2024

Introduction

Colorectal cancer ranks as the third most common cancer in both men and women, with approximately 35% of cases being stage IV metastatic at diagnosis. Even with treatment advancements, the survival rates for these patients remain suboptimal. There is a significant focus on developing multi-targeted therapies due to the common issue of drug resistance in standard and targeted cancer treatments. Medicinal mushrooms, both as single compounds and as complex extracts, have undergone extensive research. Numerous types of mushrooms have been shown to be safe, effective inhibitors of cancer pathways and strong enhancers of the immune system.

Methods

In this study, we performed both qualitative and quantitative proteomic analyses using tandem mass tags (TMT) on CT26 wild type (CT26. WT) colon cancer tissues from Balb/c mice, which were treated with a special blend of medicinal mushroom extracts, either alone or in combination with the chemotherapy drug 5-fluorouracil.

Results

The results showed a notable increase in survival rates and indicated that medicinal mushroom preparation Agarikon Plus, both alone and combined with 5-fluorouracil or another medicinal mushroom preparation Agarikon.1, impedes multiple key processes in colorectal cancer progression. The analysis of differentially expressed proteins in treated groups was done by use of bioinformatics tools and a decrease in ribosomal biogenesis (e.g., RPS3) and translation processes (e.g., RPL14) as well as an increase in unfolded protein response (e.g., DNAJC3), lipid metabolism (e.g., ACOT7), and the tricarboxylic acid cycle (e.g., FH) were observed.

Conclusion

The treatment induced various alterations of known biomarkers and protein clusters critical to the progression and prognosis of colorectal cancer, laying a promising foundation for further translational research on this treatment modality.
Near-infrared photoimmunotherapy in cancer treatment: a bibliometric and visual analysis
Authors: Tian Jinglin , Chen Chunbao , Du Xue , Wang Miao
Published: October 2024

Background

Near-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment technology that combines the advantages of optical technology and immunotherapy to provide a highly effective, precise, and low side-effect treatment approach. The aim of this study is to visualize the scientific results and research trends of NIR-PIT based on bibliometric analysis methods.

Methods

The Web of Science Core Collection (WoSCC) database was searched in August 2024 for relevant publications in the field of NIR-PIT. Data were analyzed using mainly CiteSpace and R software for bibliometric and visual analysis of the country/region, authors, journals, references and keywords of the publications in the field.

Results

A total of 245 publications were retrieved, including articles (n = 173, 70.61%) and reviews (n = 72, 29.39%). The annual and cumulative number of publications increased every year. The highest number of publications was from the United States (149, 60.82%), followed by Japan (70, 28.57%) and China (33, 13.47%). The research institution with the highest number of publications was National Institutes of Health (NIH)-USA (114, 46.53%). Kobayashi H (109) was involved in the highest number of publications, Mitsunaga M (211) was the most frequently cited in total. CANCERS (17) was the most frequently published journal, and NAT MED (220) was the most frequently co-cited journal. The top 10 keywords include near-infrared photoimmunotherapy (166), photodynamic therapy (61), monoclonal antibody (58), in vivo (50), cancer (46), expression (31), breast cancer (27), enhanced permeability (24), antibody (23), growth factor receptor (16). Cluster analysis based on the co-occurrence of keywords resulted in 13 clusters, which identified the current research hotspots and future trends of NIR-PIT in cancer treatment.

Conclusion

This study systematically investigated the research hotspots and development trends of NIR-PIT in cancer treatment through bibliometric and visual analysis. As an emerging strategy, the research on the application of NIR-PIT in cancer treatment has significantly increased in recent years, mainly focusing on the targeting, immune activation mechanism, and treatment efficacy in solid tumors has received extensive attention. Future studies may focus on improving the efficacy and safety of NIR-PIT in cancer treatment, as well as developing novel photosensitizers and combination therapeutic regimens, and exploring the efficacy of its application in a wide range of solid tumors, which will provide an important reference and guidance for the application of NIR-PIT in clinical translation.
Tailored biosynthesis of diosmin through reconstitution of the flavonoid pathway in Nicotiana benthamiana
Authors: Lee Hyo , Park Sangkyu , Lee Saet Buyl , Song Jaeeun , Kim Tae-Hwan , Kim Beom-Gi
Published: October 2024

The flavonoid diosmin (diosmetin 7-O-rutinoside) is used as a therapeutic agent for disorders of the blood vessels such as hemorrhoids and varicose veins. Diosmin is commercially produced using semi-synthetic methods involving the oxidation of hesperidin, the most abundant flavonoid in citrus fruits. However, this method produces byproducts that are toxic to the environment, and new sustainable methods to produce diosmin are required. Here, we used a synthetic biology approach to produce diosmin without generating toxic byproducts through reconstitution of the diosmin biosynthetic pathway in Nicotiana benthamiana. We first established that N. benthamiana leaves co-infiltrated with all seven genes in the flavonoid biosynthesis pathway produced high levels of luteolin, a precursor of diosmetin. We then compared the activity of modification enzymes such as methyltransferases, glucosyltransferases, and rhamnosyltransferases in Escherichia coli and in planta and selected genes encoding enzymes with the highest activity for producing diosmetin, diosmetin 7-O-glucoside, and diosmin, respectively. Finally, we reconstructed the entire diosmin biosynthetic pathway using three constructs containing ten genes encoding enzymes in this pathway, from phenylalanine ammonia lyase to rhamnosyltransferase. N. benthamiana leaves transiently co-expressing all these genes yielded 37.7 µg diosmin per gram fresh weight. To our knowledge, this is the first report of diosmin production in a heterologous plant system without the supply of a precursor. Successful production of diosmin in N. benthamiana opens new avenues for producing other commercially important flavonoids using similar platforms.
A scoping review of the impact of eco-distress and coping with distress on the mental health experiences of climate scientists
Authors: Calabria Luis , Marks Elizabeth
Published: October 2024

Introduction

In the face of a future predicted to be one defined by an increase in the Earth’s surface temperature, and the associated extreme weather events, distressing emotional responses are understandable. Climate scientists comprise a unique group, in that they are deeply and consistently faced with the current reality, and consequences of, climate change. ‘Ecological distress’, a term to describe climate-related emotional experiences, can include feelings of grief, anxiety, and hopelessness proportionate to the existential threat of climate change.

Methods

This review sought to scope the current literature into how ecological distress is experienced by this population, factors that mitigate or exacerbate these experiences, and the coping strategies that are used. This review used Interpretive Content Analysis to code the data and employed a narrative synthesis of the findings.

Results

This paper demonstrates the significant emotional impacts associated with working as a climate scientist, along with an associated set of coping strategies. Climate scientists share experiences of emotional distress, involving both intra- and interpersonal processes, highlighting how people working in this profession may be vulnerable to unique pressures and psychological burdens related to their work.

Discussion

Climate scientists have an essential role to play in helping society and policy makers understand the implications of climate change and identifying the most useful responses. As such, it is integral that the psychological wellbeing of this group is understood and cared for. This review is the first step in synthesising current knowledge, in preparation for developing helpful methods and strategies for keeping our climate scientists well, motivated, and engaged.
The impact of stress on sleep quality: a mediation analysis based on longitudinal data
Authors: Zhang Jun , Xiang Shungui , Li Xiaowen , Tang Yin , Hu Qun
Published: October 2024

Objective

This study evaluates the potential mechanisms through which stress affects sleep quality and examines the mediating roles of rumination, social anxiety, emotion-focused coping strategies, and smartphone dependence in the relationship between stress and sleep quality.

Methods

From October 2023 to April 2024, we conducted three surveys with 426 university students and utilized structural equation modeling to explore the mechanisms by which stress impacts sleep quality.

Results

Stress not only significantly predicts sleep quality but also significantly affects sleep quality through rumination, emotion-focused coping strategies, and smartphone dependence as independent mediators. Additionally, stress influences sleep quality through both dual-mediation and triple-mediation paths.

Conclusion

Stress has a significant direct and indirect impact on sleep quality. This study reveals the complex mechanisms through which stress affects sleep quality. Improving individuals’ sleep quality requires not only considering the influence of real-life stressors but also examining the intersecting effects between stress and factors such as ruminative thinking, social anxiety, smartphone dependency, and emotion-focused coping strategies. The intense social competition in Chinese society exacerbates the decline in sleep quality, highlighting the need for the government to implement more policies aimed at maintaining the physical and mental health of the population to alleviate the increasingly severe sleep issues and mental health crisis.