bluuebunny/crossref_metadata_2025 huggingface dataset:
T-CLEARE: a pilot community-driven tissue clearing protocol repository
Authors: Weiss Kurt R. , Huisken Jan , Khanjani Neda , Bakalov Vesselina , Engle Michelle L. , Krzyzanowski Michelle C. , Madden Tom , Maiese Deborah R. , Waterfield Justin R. , Williams David N. , Wood Lauren , Wu Xin , Hamilton Carol M. , Huggins Wayne
Published: September 2024

Selecting and implementing a tissue clearing protocol is challenging. Established more than 100 years ago, tissue clearing is still a rapidly evolving field of research. There are currently many published protocols to choose from, and each performs better or worse across a range of key evaluation factors (e.g., speed, cost, tissue stability, fluorescence quenching). Additionally, tissue clearing protocols are often optimized for specific experimental contexts, and applying an existing protocol to a new problem can require a lengthy period of adaptation by trial and error. Although the primary literature and review articles provide a useful starting point for optimization, there is growing recognition that results can vary dramatically with changes to tissue type or antibody used. To help address this issue, we have developed a novel, freely available repository of tissue clearing protocols named T-CLEARE (Tissue CLEAring protocol REpository; https://doryworkspace.org/doryviz). T-CLEARE incorporates community responses to an open survey designed to capture details not commonly found in the scientific literature, including modifications to published protocols required for specific use cases and instances when tissue clearing protocols did not perform well (negative results). The goal of T-CLEARE is to help the community share evaluations and modifications of tissue clearing protocols for various tissue types and potentially identify best-in-class methods for a given application.
GenoMine: a CRISPR-Cas9-based kill switch for biocontainment of Pseudomonas putida
Authors: Asin-Garcia Enrique , Martin-Pascual Maria , de Buck Claudia , Allewijn Max , Müller Alexandra , Martins dos Santos Vitor A. P.
Published: September 2024

Synthetic genetic circuits have revolutionised our capacity to control cell viability by conferring microorganisms with programmable functionalities to limit survival to specific environmental conditions. Here, we present the GenoMine safeguard, a CRISPR-Cas9-based kill switch for the biotechnological workhorse Pseudomonas putida that employs repetitive genomic elements as cleavage targets to unleash a highly genotoxic response. To regulate the system’s activation, we tested various circuit-based mechanisms including the digitalised version of an inducible expression system that operates at the transcriptional level and different options of post-transcriptional riboregulators. All of them were applied not only to directly control Cas9 and its lethal effects, but also to modulate the expression of two of its inhibitors: the AcrIIA4 anti-CRISPR protein and the transcriptional repressor TetR. Either upon direct induction of the endonuclease or under non-induced conditions of its inhibitors, the presence of Cas9 suppressed cell survival which could be exploited beyond biocontainment in situations where further CRISPR genome editing is undesirable.
Spatiotemporal regulation of MELK during mitosis
Authors: Majumdar Sreemita , Liu Song-Tao
Published: September 2024

Maternal Embryonic Leucine Zipper Kinase (MELK) has been studied intensively in recent years due to its overexpression in multiple cancers. However, the cell biology of MELK remains less characterized despite its well-documented association with mitosis. Here we report a distinctive pattern of human MELK that translocates from the cytoplasm to cell cortex within 3 min of anaphase onset. The cortex association lasts about 30 min till telophase. The spatiotemporal specific localization of MELK depends on the interaction between its Threonine-Proline (TP) rich domain and kinase associated 1 (KA1) domain, which is regulated by CDK1 kinase and PP4 protein phosphatase. KA1 domains are known to regulate kinase activities through various intramolecular interactions. Our results revealed a new role for KA1 domain to control subcellular localization of a protein kinase.
Catalytic revalorization of plastic waste phthalate plasticizers into simple aromatics and alkenes
Authors: Windels Simon , Seynaeve Nienke , Stuyck Wouter , De Vos Dirk E.
Published: September 2024

In order to deal with legacy additives in plastic waste streams, multiple extraction processes are being developed. For sustainability and economic reasons, these processes call for the parallel implementation of revalorisation routes for the extracted toxic compounds, especially when dealing with large volumes as in the case of phthalate plasticizers. On account of its intrinsic value, the recovery of the aromatic fragment from such end-of-life phthalate ester mixtures was prioritized in this work. To that end, a hydrolysis-decarboxylation process was designed using hydrophobic zeolites and heterogeneous Pt-catalysts, in water as a safe and environmentally benign solvent. By carefully tuning the reaction parameters, the selective formation of phthalic acid, benzoic acid or benzene can be achieved in near-quantitative yields, next to the recovery of alkene and alcohol side chain fragments (yields up to 99%).
Combination of aloe emodin, emodin, and rhein from Aloe with EDTA sensitizes the resistant Acinetobacter baumannii to polymyxins
Authors: Zhao Yue , Zhang Tingting , Liang Yinping , Xie Xiaoqing , Pan Hongwei , Cao Meng , Wang Shuhua , Wu Dalei , Wang Jing , Wang Chuandong , Hu Wei
Published: September 2024

Background

The continuous emergence and spread of polymyxin-resistant Acinetobacter baumannii pose a significant global health challenge, necessitating the development of novel therapeutic strategies. Aloe, with its long-standing history of medicinal use, has recently been the subject of substantial research for its efficacy against pathogenic infections.

Methods

This study investigates the potential application of anthraquinone components in aloe against polymyxin-resistant A. baumannii by liquid chromatography-mass spectrometry, in vitro activity assessment, and construction of animal infection models.

Results

The findings demonstrate that aloe emodin, emodin, rhein, and their mixtures in equal mass ratios (EAR) exhibit strain-specific antibacterial activities against polymyxin-resistant A. baumannii. Co-administration of EAR with EDTA synergistically and universally enhanced the antibacterial activity and bactericidal efficacy of polymyxins against polymyxin-resistant A. baumannii, while also reducing the frequency of polymyxin-resistant mutations in polymyxinssensitive A. baumannii. Following toxicity assessment on human hepatic and renal cell lines, the combination therapy was applied to skin wounds in mice infected with polymyxin-resistant A. baumannii. Compared to monotherapy, the combination therapy significantly accelerated wound healing and reduced bacterial burden.

Conclusions

The combination of EAR and EDTA with polymyxins offers a novel therapeutic approach for managing skin infections caused by polymyxinresistant A. baumannii.
Modes of production during the Inka Imperial Period (1420–1535 AD) and the Early Colonial Period (1535–1660 AD) in the Jujuy Valley, Argentina
Authors: Vaquer José María , Llapur Luciana , Stokes Freg
Published: September 2024

The transition between the Inka Imperial Period and the Early Colonial Period in the current territory of Argentina corresponds to the Spanish invasion and the impact it had on the native populations. The imposition of the early colonial mode of production, based on the exploitation of South American mineral resources and their export to Europe, in turn, gave rise to a series of subsidiary industries. Among them, cattle breeding, muleteering, and slaughtering to obtain dried beef occupied a prominent place since their destination was the sustenance of the mining workforce. In this work, based on historical sources and archaeological studies, we propose to interpret the relationships between landscapes, environments, territories, and human populations from the imposition of the early colonial mode of production, considering pre-Hispanic modes of production and anti-production. To do this, we focus on the different resistance strategies of the original populations and the advances and setbacks of the conquerors for the effective control of the territory, particularly the Jujuy Valley. The following pages do not aim to provide new data on the topic, but rather to offer a different analysis and approach to it.
Comprehensive study on the stability and failure mechanism of landslides under rainfall and earthquake in northwest mountainous areas
Authors: Yang Weixin , Zhang Yonggang , Zhang Lei , Bai Gexue , Wan Baofeng , An Ning
Published: September 2024

Landslides and geological disasters occur frequently in the mountainous areas of northwest China, seriously threatening people’s life and property of the region. In this study, we investigated the Lijie Beishan landslide as a typical case and combines the results of on-site geological surveys to conduct two-dimensional and three-dimensional numerical simulations of the landslide, evaluating its stability under self-weight, rainfall, and earthquake action. By analyzing the generalized shear strain, displacement, and stability coefficient of the landslide, it is determined that the stability of the landslide shows a decreasing trend under static, rainfall, and earthquake conditions. Landslides exhibit tension controlled failure modes under normal static and rainfall conditions, and translational failure modes under earthquake conditions. Compared with static and rainfall conditions, landslides have the largest volume and sliding distance under earthquake conditions. By combining the transfer coefficient method and the simplified Bishop method, a comparative analysis was conducted on the stability of the landslide. It was found that the stability coefficients under different working conditions were consistent with the simulation results, which verified the reliability of the simulation results. The research results of this paper will assist in clarifying the development mechanism of this type of landslides and provide valuable references for the stability evaluation of landslides in the northwest mountainous areas.
Association between serum iron status and the risk of five bone and joint-related diseases: a Mendelian randomization analysis
Authors: Wang Xiaolei , Qiu Linjing , Yang Zepei , Wu Changjiang , Xie Wenying , Zhang Jing , Li Wenhui , Li Wangyang , Gao Yanbin , Zhang Taojing
Published: September 2024

Background

According to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain.

Method

We obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis.

Result

Using the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process.

Conclusion

Our study demonstrated a significant correlation between iron status and bone and joint-related diseases.
Causality between sarcopenia and diabetic neuropathy
Authors: Fang Yi , Yuan Xiaoqing , Zhang Qing , Liu Juan , Yao Qing , Ye Xinhua
Published: September 2024

Background

Past studies have demonstrated that diabetic neuropathy is related to sarcopenia, but the further causal relation is still unclear. We sought to investigate the causal relationship by combining data from cross-sectional and Mendelian randomization (MR) studies.

Methods

The genome-wide association studies data were collected from the UK Biobank and the European Working Group on Sarcopenia to conduct a bi-directional two-sample MR study to explore the causality between diabetic neuropathy and relevant clinical traits of sarcopenia, including appendicular lean mass (ALM), walking speed and low hand grip strength. The inverse-variance weighted and various sensitivity analyses were used to obtain MR estimates. We also enrolled a total of 196 Type 2 diabetes patients from April 2021 to April 2024 and divided them into the Distal peripheral neuropathy (DPN) group (n=51) and non-DPN group (n=145) via vibration perception threshold (VPT) and neuropathy deficit score. Logistic regression and ROC curve analysis were used to investigate the relationship between DPN and relevant sarcopenia clinical features.

Results

According to a forward MR analysis, decreased walking speed (OR: 0.04, 95% confidence interval (CI): 0.01-0.16; P<0.001) and increased ALM (1.25 [1.05-1.50], P=0.012) had a causal effect on developing diabetic neuropathy. According to reverse MR results, developing diabetic neuropathy had a causal effect on decreased walking speed (0.99 [0.99-1.00], P=0.007) and low grip strength (1.05 [1.02-1.08], P<0.001). The cross-sectional study showed that 5-time stand time (P=0.002) and 6-meter walking speed (P=0.009) had an inverse association with DPN. Additionally, we discovered that ASMI (P=0.030) and 5-time stand time (P=0.013) were separate risk factors for DPN.

Conclusion

The MR study suggested that diabetic neuropathy may have a causality with relevant clinical traits of sarcopenia, and our cross-sectional study further proved that sarcopenia indexes are predictors of diabetic neuropathy.
Association between metabolic score for insulin resistance and cardiovascular disease mortality in patients with rheumatoid arthritis: evidence from the NHANES 1999-2018
Authors: Zhou Yan , Gao Jie
Published: September 2024

Aim

To explore the association between Metabolic Score for Insulin Resistance (METS-IR) and the risk of cardiovascular disease (CVD) death in patients with rheumatoid arthritis (RA).

Methods

This retrospective cohort study extracted data on 1,218 RA patients from the National Health and Nutrition Examination Survey. The weighted univariate and multivariate Cox regression model was established to explore the association between METS-IR and CVD mortality. Subgroup analysis was performed in terms of age, gender, body mass index, diabetes, and CVD. Hazard ratios (HRs) and 95% confidence levels (CIs) were presented.

Results

Increased METS-IR was associated with a significantly higher risk of CVD mortality (HR=4.59, 95%CI: 1.98-10.67), and METS-IR>2.48 was associated with higher odds of CVD mortality compared with METS-IR ≤ 2.25 (HR=3.57, 95%CI: 2.04-6.24). METS-IR was positively associated with the risk of CVD mortality (HR=3.83, 95%CI: 1.62-9.08), and METS-IR>2.48 was associated with a significantly higher risk of CVD mortality in contrast to METS-IR ≤ 2.25 (HR=3.38, 95%CI: 1.87-6.09).

Conclusion

Increased METS-IR was associated with a significantly higher risk of CVD mortality in RA patients. Clinicians could consider incorporating the METS-IR score into routine assessment of the prognosis of RA patients.
The HVDC commutation failure mechanism impacted by harmonics and its suppression method
Authors: Zhang Guojiang , Zhao Jingbo , Jia Yongyong , Zhou Qian , Xu Ke
Published: September 2024

Harmonics are an important cause of voltage distortion, and voltage reduction and voltage distortion are the main causes of commutation failure. But most of the current research studies on commutation failure are based on the drop in fundamental voltage after a fault, and there are few reports on the impact of voltage distortion on commutation failure. Aiming to solve the above problem, this article first analyzes the generation and transmission characteristics of harmonics in AC and DC systems, as well as the coupling degree of harmonics in DC systems. Then, starting from the mechanism of the commutation process, a commutation failure analysis method based on the harmonic voltage time area is proposed. This method can quantitatively analyze the impact of different harmonics on commutation failure. On this basis, the harmonic criteria for causing commutation failure are established, and the harmonic characteristics of AC voltage when harmonics cause subsequent commutation failure are quantitatively analyzed. Finally, a preventive controller is proposed to suppress commutation failure caused by different harmonics, where the above analysis is verified by the simulations.
Exhausted signature and regulatory network of NK cells in myasthenia gravis
Authors: Zhang Qing , Han Xingyu , Bi Zhuajin , Yang Mengge , Lin Jing , Li Zhijun , Zhang Min , Bu Bitao
Published: September 2024

Introduction

NK cells are dysfunctional in myasthenia gravis (MG), but the mechanism is unclear. This study aims to measure associations and underlying mechanisms between the NK cells and the development of MG.

Methods

Twenty healthy controls (HCs) and 53 MG patients who did not receive glucocorticoids and immunosuppressants were collected. According to the Myasthenia Gravis Foundation of America (MGFA) classification, MG patients were categorized into MGFA I group (n = 18) and MGFA II-IV group (n = 35). Flow cytometry, cell sorting, ELISA, mRNA-sequencing, RT-qPCR, western blot, and cell culture experiments were performed to evaluate the regulatory mechanism of exhausted NK cells.

Results

Peripheral NK cells in MGFA II-IV patients exhibit exhausted phenotypes than HCs, marked by the dramatic loss of total NK cells, CD56dimCD16− NK cells, elevated PD1 expression, reduced NKG2D expression, impaired cytotoxic activity (perforin, granzyme B, CD107a) and cytokine secretion (IFN-γ). Plasma IL-6 and IL-21 are elevated in MG patients and mainly derived from the aberrant expansion of monocytes and Tfh cells, respectively. IL-6/IL-21 cooperatively induced NK-cell exhausted signature via upregulating SOCS2 and inhibiting the phosphorylation of STAT5. SOCS2 siRNA and IL-2 supplement attenuated the IL-6/IL-21-mediated alteration of NK-cell phenotypes and function.

Discussion

Inhibition of IL-6/IL-21/SOCS2/STAT5 pathway and recovery of NK-cell ability to inhibit autoimmunity may be a new direction in the treatment of MG.
Supplementation with Lactobacillus helveticus NS8 alleviated behavioral, neural, endocrine, and microbiota abnormalities in an endogenous rat model of depression
Authors: Alatan Husile , Liang Shan , Shimodaira Yosuke , Wu Xiaoli , Hu Xu , Wang Tao , Luo Jia , Iijima Katsunori , Jin Feng
Published: September 2024

Introduction

Major depressive disorder is a condition involving microbiota–gut–brain axis dysfunction. Increasing research aims to improve depression through gut microbiota regulation, including interventions such as probiotics, prebiotics, and fecal microbiota transplants. However, most research focuses on exogenous depression induced by chronic stress or drugs, with less attention given to endogenous depression. Additionally, research on gut mycobiota in depression is significantly less than that on gut bacteria.

Methods

In the present study, Wistar–Kyoto rats were used as an endogenous depression and treatment-resistant depression model, while Wistar rats served as controls. Differences between the two rat strains in behavior, gut bacteria, gut mycobiota, nervous system, endocrine system, immune system, and gut barrier were evaluated. Additionally, the effects of Lactobacillus helveticus NS8 supplementation were investigated.

Results

Wistar–Kyoto rats demonstrated increased depressive-like behaviors in the forced swimming test, reduced sucrose preference in the sucrose preference test, and decreased locomotor activity in the open field test. They also exhibited abnormal gut bacteria and mycobiota, characterized by higher bacterial α-diversity but lower fungal α-diversity, along with increased butyrate, L-tyrosine, and L-phenylalanine biosynthesis from bacteria. Furthermore, these rats showed dysfunction in the microbiota–gut–brain axis, evidenced by a hypo-serotonergic system, hyper-noradrenergic system, defective hypothalamic–pituitary–adrenal axis, compromised gut barrier integrity, heightened serum inflammation, and diminished gut immunity. A 1-month L. helveticus NS8 intervention increased the fecal abundance of L. helveticus; reduced the abundance of Bilophila and Debaryomycetaceae; decreased immobility time but increased climbing time in the forced swimming test; reduced hippocampal corticotropin-releasing hormone levels; decreased hypothalamic norepinephrine levels; increased hippocampal glucocorticoid receptor, brain-derived neurotrophic factor dopamine, and 5-hydroxyindoleacetic acid content; and improved the gut microbiota, serotonergic, and noradrenergic system.

Conclusion

The depressive phenotype of Wistar–Kyoto rats is not only attributed to their genetic context but also closely related to their gut microbiota. Abnormal gut microbiota and a dysfunctional microbiota–gut–brain axis play important roles in endogenous depression, just as they do in exogenous depression. Supplementing with probiotics such as L. helveticus NS8 is likely a promising approach to improve endogenous depression and treatment-resistant depression.
Immune checkpoint pathways in glioblastoma: a diverse and evolving landscape
Authors: Inocencio Julio F. , Mitrasinovic Stefan , Asad Mohammad , Parney Ian F. , Zang Xingxing , Himes Benjamin T.
Published: September 2024

Immune checkpoint (IC) inhibition in glioblastoma (GBM) has not shown promising results in the last decade compared to other solid tumors. Several factors contributing to the lack of immunotherapy response include the profound immunosuppressive nature of GBM, highly redundant signaling pathways underlying immune checkpoints, and the negative immunogenic impact of current standard of care on the tumor microenvironment. In this review, we will discuss various ICs in the context of GBM, their interplay with the tumor immune microenvironment, relevant pre-clinical and clinical studies, and the impact of current treatment modalities on GBM IC blockade therapy. Understanding the molecular mechanisms that drive ICs, and how they contribute to an immunosuppressive tumor microenvironment is critical in advancing IC inhibition therapy in GBM. Furthermore, revisiting current treatment modalities and their impact on the immune landscape is instrumental in designing future combinatorial therapies that may overcome treatment resistance.
Association between dietary vitamin C intake and gout among American adults
Authors: Zou Yadan , Liu Yongyu , Li Shengguang
Published: September 2024

Introduction

Gout is a common type of inflammatory arthritis. Vitamin C is a potent antioxidant that neutralizes reactive oxygen species. However, the association between dietary vitamin C levels and gout remains unclear. This study evaluated the relationship between dietary vitamin C intake and gout.

Methods

Cross-sectional data from individuals aged > 20 years who participated in the National Health and Nutrition Examination Survey between 2013 and 2018 were collected. Details on gout, dietary vitamin C intake, and several other essential variables were recorded.

Results

There were 12589 participants, 5% (652/12589) of whom experienced gout. Compared with individuals with lower vitamin C consumption in the Q1 group (≤19.9 mg/day), the adjusted odds ratio(OR)values for dietary vitamin C intake and gout in the Q2 group (19.9–49.7 mg/day), Q3 group (49.7–110.375 mg/day), and Q4 group (≥110.375 mg/day) were 0.87 (95% confidence interval (CI): 0.69–1.1, P = 0.237), 0.81 (95% CI: 0.64–1.02, P = 0.076), and 0.77 (95% CI: 0.6–0.99, P= 0.042), respectively. Accordingly, the association between dietary vitamin C intake and gout exhibited an L-shaped curve (nonlinear, P = 0.245) in a restricted cubic spline. Subgroup analysis revealed significant interactions between vitamin C levels and gout according to sex (P < 0.05). When we used data on dietary vitamin C from the second survey, we observed a similar inverse association between vitamin C intake and gout. The vitamin C was also negatively associated with hyperuricemia (OR, 0.94; 95% CI, 0.9–0.98, P=0.005). Compared with Q1, the adjusted OR values for dietary vitamin C and hyperuricemia in Q2, Q3, and Q4 were 0.77 (95% CI: 0.69–0.86, P = 0.65), 0.81 (95% CI: 0.72–0.91, P = 0.014), and 0.72 (95% CI: 0.64–0.81, P < 0.001), respectively. No association was observed between vitamin C supplementation and gout.

Conclusion

The population-based data indicate that dietary vitamin C intake is inversely associated with gout. These findings support the potential role of vitamin C in preventing gout.
Multivalent MVA-vectored vaccine elicits EBV neutralizing antibodies in rhesus macaques that reduce EBV infection in humanized mice
Authors: Escalante Gabriela M. , Reidel Ivana G. , Mutsvunguma Lorraine Z. , Cua Simeon , Tello Brenda A. , Rodriguez Esther , Farelo Mafalda A. , Zimmerman Cloe , Muniraju Murali , Li He , Govindan Aparna N. , Axthelm Michael K. , Wong Scott W. , Ogembo Javier Gordon
Published: September 2024

Introduction

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus associated with ~350,000 cases of lymphoid and epithelial malignancies every year, and is etiologically linked to infectious mononucleosis and multiple sclerosis. Despite four decades of research, no EBV vaccine candidate has yet reached licensure. Most previous vaccine attempts focused on a single viral entry glycoprotein, gp350, but recent data from clinical and pre-clinical studies, and the elucidation of viral entry mechanisms, support the inclusion of multiple entry glycoproteins in EBV vaccine design.

Methods

Here we generated a modified vaccinia Ankara (MVA)-vectored EBV vaccine, MVA-EBV5-2, that targets five EBV entry glycoproteins, gp350, gB, and the gp42gHgL complex. We characterized the genetic and translational stability of the vaccine, followed by immunogenicity assessment in BALB/c mice and rhesus lymphocryptovirus-negative rhesus macaques as compared to a gp350-based MVA vaccine. Finally, we assessed the efficacy of MVA-EBV5-2-immune rhesus serum at preventing EBV infection in human CD34+ hematopoietic stem cell-reconstituted NSG mice, under two EBV challenge doses.

Results

The MVA-EBV5-2 vaccine was genetically and translationally stable over 10 viral passages as shown by genetic and protein expression analysis, and when administered to female and male BALB/c mice, elicited serum EBV-specific IgG of both IgG1 and IgG2a subtypes with neutralizing activity in vitro. In Raji B cells, this neutralizing activity outperformed that of serum from mice immunized with a monovalent MVA-vectored gp350 vaccine. Similarly, MVA-EBV5-2 elicited EBV-specific IgG in rhesus macaques that were detected in both serum and saliva of immunized animals, with serum antibodies demonstrating neutralizing activity in vitro that outperformed serum from MVA-gp350-immunized macaques. Finally, pre-treatment with serum from MVA-EBV5-2-immunized macaques resulted in fewer EBV-infected mice in the two challenge experiments than pretreatment with serum from pre-immune macaques or macaques immunized with the monovalent gp350-based vaccine.

Discussion

These results support the inclusion of multiple entry glycoproteins in EBV vaccine design and position our vaccine as a strong candidate for clinical translation.
Bayesian network analysis enhancing alternative design schemes of large-scale offshore systems
Authors: Li Jianing , Wang Gaoshuai , Liu Chao , Guo Yong , Chen Gang
Published: September 2024

The design for large-scale offshore systems like renewable energy systems as well as ship structures represents the key factor for the investigation and application of such devices. The existing guide for design schemes of offshore systems cannot cover novel large-scale design demand for recent offshore systems, as a result of the fast-growing scale of offshore systems but the late update of guides. To this end, this paper proposes a novel risk estimation approach of alternative design schemes for large-scale offshore systems as a basis to support the design scheme determinations. Initially, the risks of design schemes are analyzed by fault tree analysis. Subsequently, Bayesian networks and fuzzy sets are employed to calculate the reliability of alternative designs that comply with, or deviate from, the existing guides. The risk level of alternative designs is assessed to ensure the better performance of alternative design schemes in terms of safety. The Bayesian network approach proposed also accretions the weak links in the alternative designs. The results of this paper contribute to enhancing the survivability of offshore systems, such as renewable energy systems as well as ship structures.
Current and emerging approaches for eliminating Borrelia burgdorferi and alleviating persistent Lyme disease symptoms
Authors: Zafar Kashaf , Azuama Onyedikachi C. , Parveen Nikhat
Published: September 2024

Lyme disease is the most prevalent tick-borne infection caused by Borrelia burgdorferi bacteria in North America. Other Borrelia species are predominately the cause of this disease in Eurasia with some distinct and various overlapping manifestations. Consequently, caution must be exercised when comparing the disease and its manifestations and treatment regimens in North America and Europe. Diagnosis of the early Lyme disease remains difficult using the currently FDA approved serological tests in the absence of a reported tick bite or of erythema migrans in many individuals, non-specific initial symptoms, and the absence of detectable anti-Borrelia antibodies in the prepatent period of infection. Furthermore, it is difficult to distinguish persistence of infection and disease versus reinfection in the endemic regions of Lyme disease by serological assays. If early infection remains untreated, spirochetes can disseminate and could affect various organs in the body with a variety of disease manifestations including arthralgias and musculoskeletal pain, neurologic symptoms and anomalies, and acrodermatitis chronicum atrophicans (ACA) in Europe. Although most patients recover after antibiotic treatment, an estimated ∼10–20% patients in the United States show persistence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). The causes and biomarkers of PTLDS are not well-defined; however, several contributing factors with inconsistent degree of supporting evidence have been suggested. These include antigenic debris, dysregulation of immunological response, bacterial persisters, or combination of these features. This review highlights currently employed treatment approaches describing different antimicrobials used, and vaccine candidates tried to prevent B. burgdorferi infection.
Oral microbiome diversity shapes the association between sleep duration and depression
Authors: Liu Yan , Zhang Ling , Yang Can , Zhi Liping , Steven Xu Xu , Yuan Min
Published: September 2024

Background

Emerging research suggests the relationship between the oral microbiome and sleep duration with depression, however, the precise mechanisms by which oral microbial diversity influences the sleep-depression nexus remain to be elucidated.

Methods

We analyzed data from 4,692 participants in the National Health and Nutrition Examination Survey (NHANES), incorporating key demographic variables, oral microbiome diversity metrics, sleep duration, and depression assessment variables. Classical multidimensional scaling facilitated dimensionality reduction, while unsupervised clustering divided participants into groups based on β-diversity dissimilarity matrices. We examined the moderating effects of oral microbiome diversity on the sleep-depression relationship by incorporating interaction terms sleep-oral microbiome diversity into multiple linear regression models.

Results

Our analysis revealed a U-shaped relationship between sleep duration and depression. Specifically, α-diversity was a significant moderator, with reduced diversity linked to an increased depression risk in participants with insufficient sleep. Regarding β-diversity, using both Bray-Curtis and UniFrac distance measures, Cluster 2 exhibited the strongest associations in sleep-deprived individuals (Bray-Curtis: β = 1.02, p < 0.001; Weighted UniFrac: β = 0.91, p < 0.001). In contrast, Cluster 1 displayed notable effects in individuals with excessive sleep (Bray-Curtis: β = 0.63, p = 0.008). Additionally, Cluster 3 was prominently associated with depression in sleep-deprived participants using unweighted UniFrac distance (β = 0.93, p < 0.001), and Cluster 2 was significant among those with excessive sleep across both unweighted (β = 0.80, p = 0.0004) and weighted UniFrac distances (β = 0.60, p = 0.001).

Conclusion

This study highlights the crucial role of oral microbiome diversity in moderating the U-shaped relationship between sleep duration and depression risk.
Enhancement of laryngeal contrasts in non-native English clear speech: a comparison between L2-immersed sequential bilinguals and L1-immersed speakers
Authors: Jung Ye Jee , Dmitrieva Olga
Published: September 2024

Clear speech, a speaking style used to mitigate communicative circumstances affecting the transmission or decoding of speech signal, often involves the enhancement of language-specific phonological contrasts, including laryngeal contrasts. This study investigates the role of language dominance in the implementation of language-specific laryngeal contrasts in L2 clear speech. Two groups of Korean-English speakers (L1 Korean) were tested: a relatively less Korean-dominant L2-immersed group of sequential bilinguals (N = 30) and a strongly Korean-dominant L1-immersed group (N = 30), with dominance assessed based on the results of the Bilingual Language Profile. Participants read a set of English minimal pairs differing in the voicing of word-initial stops (e.g., tab vs. dab), and their acoustic enhancement strategies were compared with those of native English speakers (N = 20). As correlates of the English laryngeal contrast, voice onset time (VOT) and onset f0 were measured. Results showed that both bilingual groups enhanced English laryngeal contrast in clear speech via voiceless VOT lengthening, similarly to native English speakers, but to a smaller extent than native speakers. Both bilingual groups also implemented a greater degree of onset f0 difference between voiced and voiced English stops than native English speakers did, although no enhancement of this parameter was observed in their clear speech. Surprisingly, no significant differences were found between L2- and L1-immersed speakers, suggesting a lack of language immersion effect on the acoustic enhancement strategies in L2 clear speech. We discuss possible explanations for this finding and propose directions for future research.
Exposure to biodiesel exhaust is less harmful than exposure to mineral diesel exhaust on blood-brain barrier integrity in a murine model
Authors: Nesbit Michael , Ko Colleen Kah Ling , Mamo John C. L. , Lam Virginie , Landwehr Katherine R. , Larcombe Alexander N. , Takechi Ryu
Published: September 2024

Emerging data suggest that air pollution is a persistent source of neuroinflammation, reactive oxygen species (ROS), and neuropathology that contributes to central nervous system (CNS) disorders. Previous research using animal models has shown that exposure to diesel exhaust causes considerable disruption of the blood-brain barrier (BBB), leading to marked neuroinflammation. However, the effects of biodiesel exhaust on cerebrovascular integrity and neuroinflammation have not been explored previously. Therefore, in this study, 8-week-old BALB/c mice were exposed to biodiesel exhaust (derived from canola biodiesel or tallow biodiesel) and compared with control mice that were exposed to air or mineral diesel exhaust. Consistently with previous findings, the integrity of the BBB was significantly disrupted by exposure to mineral diesel exhaust. Tallow and canola biodiesel exhaust exposure resulted in no BBB disruption. Moreover, both tallow and canola biodiesels significantly attenuated oxidative stress in the brain. The data collectively suggest that biodiesel exhaust may exert significantly less detrimental effects on brain function, compared to mineral diesel.
Transcutaneous spinal cord stimulation modulates quiet standing in healthy adults: stimulation site and cognitive style matter
Authors: Shamantseva Natalia , Timofeeva Olga , Semenova Varvara , Andreeva Irina , Moshonkina Tatiana
Published: September 2024

The study explored the effects of transcutaneous electrical spinal cord stimulation (tES) on postural control. Subjects were divided into field-dependent (FD) and field-independent (FI) groups according to their cognitive style. FD subjects use an exteroceptive afferent stream for spatial orientation, while FI subjects use an interoceptive stream. In darkness, vertical posture is maintained by head-trunk stabilization in FD subjects and by independent movements of body segments in FI subjects. Previously, we showed that tES at the L1-L2 vertebral level decreased postural stability in FD subjects. Now, stimulation was applied at the T11-T12 vertebral level (midline, above the left or right dorsal roots). Quiet standing was assessed using stabilometry in 18 FD and FI participants. Participants stood on a force platform in soundproof chamber with eyes closed during tES. Midline and left tES significantly improved postural stability by up to 28% in FD participants, while posture did not change significantly in FI participants. Pronounced differences between the effects of T11-T12 and L1-L2 stimulation are associated with selective topographical activation of proximal and distal leg muscles during tES of the lumbar enlargement. This study highlights the importance of considering cognitive style in postural control research.
Dietary vitamin K intake is associated with decreased neurofilament light chain among middle-aged and older adults from the NHANES
Authors: Luo Jing , Lin Song
Published: September 2024

Purpose

Neurofilament-light chain (NfL) is associated with neurodegenerative diseases, which are increasingly prevalent with aging. Vitamin K has been shown a neuroprotective effect. Therefore, we aimed to explore the potential relationship between dietary vitamin K intake and serum NfL.

Methods

This study was conducted on the 2013–2014 cycles of the National Health and Nutrition Examination Survey, a multi-site population-based study of the US general population. Serum NfL level was measured using a highly sensitive immunoassay. Dietary vitamin K intake was estimated from two-day dietary recall interviews, and its relationship with NfL was determined using linear regression models.

Results

The study included a total of 1,533 participants with a median age of 46 years, comprising 801 women (52.2%) and 732 men (47.8%). The median dietary intake of vitamin K was 81.6 μg/d, and the median serum NfL was 12 pg./mL. After adjusting for potential confounding factors in the full model, individuals with higher dietary vitamin K intake had lower serum NfL levels (Q4 vs. Q1, β = −4.92, 95%CI: −7.66, −2.19, p = 0.002). A non-linear negative dose–response association is found between dietary vitamin K intake and serum NfL levels (P for non-linearity = 0.008); this association reaches a plateau when the dietary vitamin K intake is higher than 200 μg/d. According to the results of stratified analysis, the relationship between dietary vitamin K intake and serum NfL levels was stronger in the population of middle-aged and older adults.

Conclusion

The present study suggested a negative association between dietary vitamin K intake and serum NfL levels in the general US population, especially in middle-aged and older adults. This study might offer a novel nutritional idea for the primary prevention and mechanism exploration of neurodegenerative diseases.
Exploring the causal links between cigarette smoking, alcohol consumption, and aneurysmal subarachnoid hemorrhage: a two-sample Mendelian randomization analysis
Authors: Lin Heng , Yin Yanqing , Li Jie , Liu Siwei , Long Xiaoao , Liao Zhuangbin
Published: September 2024

Background

Aneurysmal subarachnoid hemorrhage (aSAH) represents a critical health concern characterized by elevated mortality and morbidity rates. Although both genetic predisposition and lifestyle choices influence aSAH susceptibility, understanding the causative associations between cigarette smoking, alcohol consumption, and aSAH risk remains imperative. Mendelian randomization (MR) offers a robust methodological framework for dissecting these associations, leveraging genetic variants as instrumental variables.

Objective

In this study, a two-sample Mendelian randomization (TSMR) approach was employed to elucidate the causal connections between genetically determined cigarette smoking, alcohol consumption, and aSAH risk.

Methods

Genetic instruments associated with cigarette smoking and alcohol consumption were sourced from the genome-wide association study (GWAS) and Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Using a genome-wide association study (GWAS) dataset that encompassed aSAH cases and controls of European ancestry, TSMR, which utilized the inverse variance weighting (IVW) method, was employed to estimate the causal effects. Rigorous criteria were applied for selecting instrumental variables to ensure a robust Mendelian randomization analysis.

Results

A significant causal association was found between genetically determined cigarette smoking and an increased risk of aSAH, with a 1-standard deviation (SD) increase in cigarette use genetically linked to a 96% relative risk elevation [OR-IVW = 1.96, 95% confidence interval (CI) = 1.28–3.01, p = 0.0021]. However, genetically determined alcohol consumption did not exhibit a statistically significant association with aSAH risk (OR-IVW = 1.22, 95% CI = 0.61–2.45, p = 0.578).

Conclusion

The Mendelian randomization analysis revealed a causal nexus between cigarette smoking and an increased risk of aSAH, advocating for targeted smoking cessation interventions within genetically predisposed cohorts. The results regarding the relationship between alcohol consumption and aSAH were affected by insufficient statistical power. A prudent interpretation of the findings highlights the limitations of Mendelian randomization in elucidating intricate genetic epidemiological relationships. Ongoing research involving larger cohort sizes and advanced methodological approaches is essential for comprehending the genetic underpinnings of aSAH.
Chitosan and its derivatives regulate lactic acid synthesis during milk fermentation
Authors: Kurchenko Vladimir , Halavach Tatsiana , Yantsevich Alexey , Shramko Mariya , Alieva Lyudmila , Evdokimov Ivan , Lodygin Alexey , Tikhonov Vladimir , Nagdalian Andrey , Ali Zainy Faten M. , AL-Farga Ammar , ALFaris Nora Abdullah , Shariati Mohammad Ali
Published: September 2024

Introduction

The influence of chitosan's physicochemical characteristics on the functionality of lactic acid bacteria and the production of lactic acid remains very obscure and contradictory to date. While some studies have shown a stimulatory effect of oligochitosans on the growth of Lactobacillus spp, other studies declare a bactericidal effect of chitosan. The lack and contradiction of knowledge prompted us to study the effect of chitosan on the growth and productivity of L. bulgaricus in the presence of chitosan and its derivatives.

Methods

We used high molecular weight chitosan (350 kDa) and oligochitosans (25.4 and 45.3 kDa). The experiment was carried out with commercial strain of L. bulgaricus and the low fat skim cow milk powder reconstituted with sterile distilled water. After fermentation, dynamic viscosity, titratable acidity, pH, content of lactic acid, colony forming units, chitosan and oligochitosans radii were measured in the samples. Fermented dairy products were also examined using sodium dodecyl sulfate electrophoretic analysis, gas chromatography-mass spectrometry and light microscopy.

Results and discussion

The results of the study showed that when L. bulgaricus was cultured in the presence of 25.4 kDa oligochitosans at concentrations of 0.0025%, 0.005%, 0.0075% and 0.01%, the average rate of LA synthesis over 24 hours was 11.0 × 10−3 mol/L/h, 8.7 × 10−3 mol/L/h, 6.8 × 10−3 mol/L/h, 5.8 × 10−3 mol/L/h, respectively. The 45.3 kDa oligochitosans had a similar effect, while the average rate of lactic acid synthesis in the control sample was only 3.5 × 10−3 mol/L/h. Notably, 350 kDa chitosan did not affect the rate of lactic acid synthesis compared with the control sample. Interestingly, interaction of chitosan with L. bulgaricus led to a slowdown in the synthesis of propanol, an increase in the content of unsaturated and saturated fatty acids, and a change in the composition and content of other secondary metabolites. The quantity of L. bulgaricus in a sample with 0.01% chitosan exceeded their content in the control sample by more than 1,700 times. At the same chitosan concentration, the fermentation process was slowed down, increasing the shelf life of the fermented milk product from 5 to 17 days while maintaining a high content of L. bulgaricus (6.34 × 106 CFU/g).