bluuebunny/crossref_metadata_2025 huggingface dataset:
A negative association between triglyceride glucose-body mass index and testosterone in adult males: a cross-sectional study
Authors: Wu Shenghao , Wu Yanhong , Fang Lizi , Zhao Junzhao , Cai Yaoyao , Xia Weiting
Published: June 2023

Background and objectives

Insulin resistance (IR) is closely related to the decline or deficiency of testosterone in males. Triglyceride glucose-body mass (TyG-BMI) is considered to be a novel indicator of IR. We conducted this analysis to investigate the association between TyG-BMI and male testosterone, and to explore whether its ability to predict testosterone deficiency is superior to HOMA-IR and TyG.

Methods

This was a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES, 2011–2016). The TyG-BMI index was calculated from serum triglyceride, fasting plasma glucose and BMI. The association of TyG-BMI with male testosterone was estimated by weighted multivariable regression.

Results

We included 3394 participants for the final analysis. After adjusting for confounders, TyG-BMI was found to show an independent negative association with testosterone (β=-1.12, 95%CI: -1.50, -0.75, P<0.0001). Multivariate-adjusted beta also showed testosterone levels were significantly lower in the two highest TyG-BMI group (Q3, Q4) compared to the lowest group (Q1). Similar results were seen in all of the subgroup populations by stratified analysis (all P-interaction >0.05). Furthermore, ROC curve analysis indicated that the area under the curve of TyG-BMI index (0.73, 95% CI: 0.71, 0.75) was larger than that of HOMA-IR index (0.71, 95% CI: 0.69, 0.73) and TyG index (0.66, 95% CI: 0.64, 0.68).

Conclusion

Our result suggested a negative association between TyG-BMI index and testosterone in adult males. The predictability of the TyG-BMI index for testosterone deficiency is better than that of HOMA-IR index and TyG index.
Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy
Authors: Wei Maoying , Liu Xingxing , Tan Zhijuan , Tian Xiaochan , Li Mingdi , Wei Junping
Published: June 2023

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. It has become a leading cause of death in patients with diabetes and end-stage renal disease. Ferroptosis is a newly discovered pattern of programmed cell death. Its main manifestation is the excessive accumulation of intracellular iron ion-dependent lipid peroxides. Recent studies have shown that ferroptosis is an important driving factor in the onset and development of DN. Ferroptosis is closely associated with renal intrinsic cell (including renal tubular epithelial cells, podocytes, and mesangial cells) damage in diabetes. Chinese herbal medicine is widely used in the treatment of DN, with a long history and definite curative effect. Accumulating evidence suggests that Chinese herbal medicine can modulate ferroptosis in renal intrinsic cells and show great potential for improving DN. In this review, we outline the key regulators and pathways of ferroptosis in DN and summarize the herbs, mainly monomers and extracts, that target the inhibition of ferroptosis.
Fencing affects movement patterns of two large carnivores in Southern Africa
Authors: Naha Dipanjan , Périquet Stéphanie , Kilian J. Werner , Kupferman Caitlin A. , Hoth-Hanssen Tammy , Beasley James C.
Published: June 2023

The erection of peripheral fences around protected areas has been shown to adversely affect the movement behavior, genetic connectivity and long-term viability of animal populations. However, fencing is also used extensively to reduce human encroachment, limit poaching activities, and mitigate human–wildlife conflicts. Limited information on the movement behavior of carnivores is available along the periphery of protected areas, particularly in semi-arid environments. To quantify the potential effects of the 824 km perimeter fence surrounding the Etosha National Park (Etosha, Namibia) on the movement and space use of carnivores, we collected GPS movement data from 36 lions (Panthera leo) and seven spotted hyenas (Crocuta crocuta) over a 14-year period. For these two apex carnivores, we measured the impact of the Etosha fence on their movements (step lengths and path straightness), calculated the likelihood of fence crossings, and evaluated the spatial–temporal characteristics of these crossings. Our results indicated that lions and hyenas moved faster (longer step lengths) when closer to the fence. Lions showed no variation in path straightness with respect to the fence but hyenas had straighter movement paths when closer to the fence. When moving within the vicinity of the fence, lions had a 9% likelihood of crossing the fence, while hyenas were much more likely (18%) to do so, which suggests that the Etosha fence was more permeable for hyenas than for lions. Fence crossings predominantly occurred at night for both species. Lions were more likely to cross the fence during the cold dry season (May–August) whereas hyenas crossed more often during the warm wet season (December–April). Female and adult lions had a higher probability of crossing the fence than males and subadults. These findings could be useful in the development of appropriate strategies to mitigate human–carnivore conflicts and thus promote the conservation of carnivores in multiple-use areas along the periphery of the park. Further research is needed to better elucidate the impact of perimeter fences on a broader suite of carnivores and other large mammals, including species-specific variation in the response to fences, as well as the economic benefits of fencing provided to local communities.
Investigating the unaccounted ones: insights on age-dependent reproductive loss in a viviparous fly
Authors: English Sinead , Barreaux Antoine M. G. , Leyland Robert , Lord Jennifer S. , Hargrove John W. , Vale Glyn A. , Haines Lee R.
Published: June 2023

Most empirical and theoretical studies on reproductive senescence focus on observable attributes of offspring produced, such as size or postnatal survival. While harder to study, an important outcome of reproduction for a breeding individual is whether a viable offspring is produced at all. While prenatal mortality can sometimes be directly observed, this can also be indicated through an increase in the interval between offspring production. Both direct reproductive loss and presumed losses have been found to increase in older females across several species. Here, we study such reproductive loss (or “abortion”) in tsetse, a viviparous and relatively long-lived fly with high maternal allocation. We consider how age-dependent patterns of abortion depend on the developmental stage of offspring and find that, as per previous laboratory studies, older females have higher rates of abortion at the late-larval stage, while egg-stage abortions are high both for very young and older females. We track the reproductive output of individual females and find little evidence that experiencing an abortion is an adaptive strategy to improve future reproductive outcomes. After an abortion, females do not generally take less time to produce their next offspring, these offspring are not larger, and there is no sex bias towards females, the sex with presumed higher fitness returns (being slightly larger and longer-lived than males, and with high insemination rates). Abortion rates are higher for breeding females experiencing stress, measured as nutritional deprivation, which echoes previous work in tsetse and other viviparous species, i.e., humans and baboons. We discuss our results in the context of studies on reproductive loss across taxa and argue that this is an important yet often overlooked reproductive trait which can vary with maternal age and can also depend on environmental stressors.
Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations
Authors: Nardone Giuseppe Giovanni , Spedicati Beatrice , Concas Maria Pina , Santin Aurora , Morgan Anna , Mazzetto Lorenzo , Battaglia-Parodi Maurizio , Girotto Giorgia
Published: June 2023

Introduction: Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (OPN1LW, OPN1MW, OPN1SW) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms.

Materials and Methods: Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed.

Results: Concerning DP, three genes: PIWIL4 (FDR-p: 9.01*10–9), MBD2 (FDR-p: 4.97*10–8) and NTN1 (FDR-p: 4.98*10–8), stood out as promising candidates. PIWIL4 is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while MBD2 and NTN1 are both involved in visual signal transmission. With regards to TR, four genes: VPS54 (FDR-p: 4.09*10–9), IQGAP (FDR-p: 6,52*10–10), NMB (FDR-p: 8.34*10–11), and MC5R (FDR-p: 2.10*10–8), were considered promising candidates. VPS54 is reported to be associated with Retinitis pigmentosa; IQGAP1 is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; NMB is involved in RPE homeostasis regulation; MC5R is reported to regulate lacrimal gland function.

Discussion: Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities.
Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice
Authors: Burger Beatriz , Sagiorato Roberta Nicolli , Silva Jéssica Rondoni , Candreva Thamiris , Pacheco Mariana R. , White Daniel , Castelucci Bianca G. , Pral Laís P. , Fisk Helena L. , Rabelo Izadora L. A. , Elias-Oliveira Jefferson , Osório Wislei Riuper , Consonni Silvio Roberto , Farias Alessandro dos Santos , Vinolo Marco Aurélio Ramirez , Lameu Claudiana , Carlos Daniela , Fielding Barbara A. , Whyte Martin Brunel , Martinez Fernando O. , Calder Philip C. , Rodrigues Hosana Gomes
Published: June 2023

Delayed wound healing is a devastating complication of diabetes and supplementation with fish oil, a source of anti-inflammatory omega-3 (ω-3) fatty acids including eicosapentaenoic acid (EPA), seems an appealing treatment strategy. However, some studies have shown that ω-3 fatty acids may have a deleterious effect on skin repair and the effects of oral administration of EPA on wound healing in diabetes are unclear. We used streptozotocin-induced diabetes as a mouse model to investigate the effects of oral administration of an EPA-rich oil on wound closure and quality of new tissue formed. Gas chromatography analysis of serum and skin showed that EPA-rich oil increased the incorporation of ω-3 and decreased ω-6 fatty acids, resulting in reduction of the ω-6/ω-3 ratio. On the tenth day after wounding, EPA increased production of IL-10 by neutrophils in the wound, reduced collagen deposition, and ultimately delayed wound closure and impaired quality of the healed tissue. This effect was PPAR-γ-dependent. EPA and IL-10 reduced collagen production by fibroblasts in vitro. In vivo, topical PPAR-γ-blockade reversed the deleterious effects of EPA on wound closure and on collagen organization in diabetic mice. We also observed a reduction in IL-10 production by neutrophils in diabetic mice treated topically with the PPAR-γ blocker. These results show that oral supplementation with EPA-rich oil impairs skin wound healing in diabetes, acting on inflammatory and non-inflammatory cells.
Clinical and HLA genotype analysis of immune checkpoint inhibitor-associated diabetes mellitus: a single-center case series from China
Authors: Liu Yi-chen , Liu Hong , Zhao Shao-li , Chen Ke , Jin Ping
Published: June 2023

Objective

To investigate the clinical characteristics and HLA genotypes of patients with immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in China.

Methods

We enrolled 23 patients with ICI-DM and 51 patients with type 1 diabetes (T1D). Clinical characteristics of the patients were collected. HLA-DRB1, HLA-DQA1, and HLA-DQB1 genotyping was conducted via next-generation sequencing.

Results

The ICI-DM patients had a male predominance (70.6%), a mean body mass index (BMI) of 21.2 ± 3.5 kg/m2, and a mean onset of ICI-DM in 5 (IQR, 3-9) cycles after ICI therapy. Most (78.3%) ICI-DM patients were treated with anti-PD-1, 78.3% presented with diabetic ketoacidosis, and all had low C-peptide levels and received multiple insulin injections. Compared to T1D patients, ICI-DM patients were significantly older (57.2 ± 12.4 vs 34.1 ± 15.7 years) and had higher blood glucose but lower HbA1c levels (P<0.05). Only two (8.7%) ICI-DM patients were positive for islet autoantibodies, which was lower than that in T1D patients (66.7%, P<0.001). A total of 59.1% (13/22) of ICI-DM patients were heterozygous for an HLA T1D risk haplotype, and DRB1*0901-DQA1*03-DQB1*0303 (DR9) and DRB1*0405-DQA1*03-DQB1*0401 were the major susceptible haplotypes. Compared to T1D, the susceptible DR3-DQA1*0501-DQB1*0201 (DR3) and DR9 haplotypes were less frequent (17.7% vs 2.3%; P=0.011 and 34.4% vs 15.9%; P=0.025), whereas the protective haplotypes (DRB1*1101-DQA1*05-DQB1*0301 and DRB1*1202-DQA1*0601-DQB1*0301) were more frequent in ICI-DM patients (2.1% vs 13.6%; P=0.006 and 4.2% vs 15.9%; P=0.017). None of the ICI-DM patients had T1D-associated high-risk genotypes DR3/DR3, DR3/DR9, and DR9/DR9. Among the 23 ICI-DM patients, 7 (30.4%) presented with ICI-associated fulminant type 1 diabetes (IFD), and 16 (69.6%) presented with ICI-associated type 1 diabetes (IT1D). Compared to IT1D patients, IFD patients exhibited marked hyperglycemia and low C-peptide and HbA1c levels (P<0.05). Up to 66.7% (4/6) of IFD patients were heterozygous for reported fulminant type 1 diabetes susceptibility HLA haplotypes (DRB1*0405-DQB1*0401 or DRB1*0901-DQB1*0303).

Conclusion

ICI-DM shares similar clinical features with T1D, such as acute onset, poor islet function and insulin dependence. However, the lack of islet autoantibodies, the low frequencies of T1D susceptibility and high frequencies of protective HLA haplotypes indicate that ICI-DM represents a new model distinct from classical T1D.
Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma
Authors: Guo Yangyang , Wu Zhixuan , Cen Kenan , Bai Yongheng , Dai Ying , Mai Yifeng , Hong Kai , Qu Liangchen
Published: June 2023

Background

Patients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients’ prognoses.

Methods

The URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO) regression analysis of data from TCGA-PAAD. Verification analyses were conducted across TCGA-PAAD, GSE57495 and ICGC-PACA-AU to show the robustness of the signature. RT-qPCR was used to verify the expression of risk genes. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.

Results

The URGs signature, comprised of three genes, was developed and was shown to be highly correlated with the prognoses of PAAD patients. The nomogram was established by combining the URGs signature with clinicopathological characteristics. We discovered that the URGs signature was remarkably superior than other individual predictors (age, grade, T stage, et al). Also, the immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, and StromalScores were elevated in the low-risk group. The immune cells that infiltrated the tissues were different between the two groups, as did the expression of immune-related genes.

Conclusion

The URGs signature could act as the biomarker of prognosis and selecting appropriate therapeutic drugs for PDAC patients.
The biological roles of CD24 in ovarian cancer: old story, but new tales
Authors: Gu Yuanyuan , Zhou Guannan , Tang Xue , Shen Fang , Ding Jingxin , Hua Keqin
Published: June 2023

CD24 is a glycosylphosphatidylinositol linked molecular which expressed in diverse malignant tumor cells, particular in ovarian carcinoma cells and ovarian carcinoma stem cells. The CD24 expression is associated with increased metastatic potential and poor prognosis of malignancies. CD24 on the surface of tumor cells could interact with Siglec-10 on the surface of immune cells, to mediate the immune escape of tumor cells. Nowadays, CD24 has been identified as a promising focus for targeting therapy of ovarian cancer. However, the roles of CD24 in tumorigenesis, metastasis, and immune escape are still not clearly demonstrated systematically. In this review, we i) summarized the existing studies on CD24 in diverse cancers including ovarian cancer, ii) illustrated the role of CD24-siglec10 signaling pathway in immune escape, iii) reviewed the existing immunotherapeutic strategies (targeting the CD24 to restore the phagocytic effect of Siglec-10 expressing immune cells) based on the above mechanisms and evaluated the priorities in the future research. These results might provide support for guiding the CD24 immunotherapy as the intervention upon solid tumors.
It takes two to tango: the role of tumor-associated macrophages in T cell-directed immune checkpoint blockade therapy
Authors: Sheban Fadi
Published: June 2023

Immunotherapy has revolutionized cancer care in the past decade. Treatment with immune checkpoint inhibitors has demonstrated promising clinical activity against tumors. However, only a subset of patients responds to these treatments, limiting their potential benefit. Efforts to understand, predict, and overcome the lack of response in patients, have thus far focused mainly on the tumor immunogenicity and the quantity and characteristics of tumor-infiltrating T cells, since these cells are the main effectors of immunotherapies. However, recent comprehensive analyses of the tumor microenvironment (TME) in the context of immune checkpoint blockade (ICB) therapy have revealed critical functions of other immune cells in the effective anti-tumor response, highlighting the need to account for complex cell-cell interaction and communication underlying clinical outputs. In this perspective, I discuss the current understanding of the crucial roles of tumor-associated macrophages (TAMs) in the success of T cell-directed immune checkpoint blockade therapies, as well as the present, and the future of clinical trials on combinatorial therapies targeting both cell types.
Immunization with a mucosal, post-fusion F/G protein-based polyanhydride nanovaccine protects neonatal calves against BRSV infection
Authors: Maina Teresia W. , Grego Elizabeth A. , Broderick Scott , Sacco Randy E. , Narasimhan Balaji , McGill Jodi L.
Published: June 2023

Human respiratory syncytial virus (HRSV) is a leading cause of death in young children and there are no FDA approved vaccines. Bovine RSV (BRSV) is antigenically similar to HRSV, and the neonatal calf model is useful for evaluation of HRSV vaccines. Here, we determined the efficacy of a polyanhydride-based nanovaccine encapsulating the BRSV post-fusion F and G glycoproteins and CpG, delivered prime-boost via heterologous (intranasal/subcutaneous) or homologous (intranasal/intranasal) immunization in the calf model. We compared the performance of the nanovaccine regimens to a modified-live BRSV vaccine, and to non-vaccinated calves. Calves receiving nanovaccine via either prime-boost regimen exhibited clinical and virological protection compared to non-vaccinated calves. The heterologous nanovaccine regimen induced both virus-specific cellular immunity and mucosal IgA, and induced similar clinical, virological and pathological protection as the commercial modified-live vaccine. Principal component analysis identified BRSV-specific humoral and cellular responses as important correlates of protection. The BRSV-F/G CpG nanovaccine is a promising candidate vaccine to reduce RSV disease burden in humans and animals.
Bioinformatic analysis of hub markers and immune cell infiltration characteristics of gastric cancer
Authors: Li Chao , Yang Tan , Yuan Yu , Wen Rou , Yu Huan
Published: June 2023

Background

Gastric cancer (GC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Due to the lack of specific markers, the early diagnosis of gastric cancer is very low, and most patients with gastric cancer are diagnosed at advanced stages. The aim of this study was to identify key biomarkers of GC and to elucidate GC-associated immune cell infiltration and related pathways.

Methods

Gene microarray data associated with GC were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were analyzed using Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia, Gene Set Enrichment Analysis (GSEA) and Protein−Protein Interaction (PPI) networks. Weighted gene coexpression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to identify pivotal genes for GC and to assess the diagnostic accuracy of GC hub markers using the subjects’ working characteristic curves. In addition, the infiltration levels of 28 immune cells in GC and their interrelationship with hub markers were analyzed using ssGSEA. And further validated by RT-qPCR.

Results

A total of 133 DEGs were identified. The biological functions and signaling pathways closely associated with GC were inflammatory and immune processes. Nine expression modules were obtained by WGCNA, with the pink module having the highest correlation with GC; 13 crossover genes were obtained by combining DEGs. Subsequently, the LASSO algorithm and validation set verification analysis were used to finally identify three hub genes as potential biomarkers of GC. In the immune cell infiltration analysis, infiltration of activated CD4 T cell, macrophages, regulatory T cells and plasmacytoid dendritic cells was more significant in GC. The validation part demonstrated that three hub genes were expressed at lower levels in the gastric cancer cells.

Conclusion

The use of WGCNA combined with the LASSO algorithm to identify hub biomarkers closely related to GC can help to elucidate the molecular mechanism of GC development and is important for finding new immunotherapeutic targets and disease prevention.
Mapping marine ecosystem services in a multifunctional seascape: the case of Grande Vasière (Bay of Biscay)
Authors: Lavialle Gaël , Boussarie Germain , Kopp Dorothée , Morfin Marie , Mouchet Maud A.
Published: June 2023

Introduction

Coastal and continental shelf ecosystems are among the most productive, yet exploited, ecosystems. The Grande Vasière (GV) covers most part of the French Northern part of the Bay of Biscay, a crucial fishing ground for metropolitan France. It is the place of numerous uses, especially fishing, and will soon shelter sand extraction activities and offshore windfarms. All these activities may compete for space and resources and put pressure on habitats, biodiversity and subsequent ecosystem services (ES). Current management strategies integrate these activities and biodiversity conservation schemes but no ES.

Methods

To fill that gap, we quantified and mapped nine indicators of ecosystem processes (EP), used as proxies of four ES (i.e. sea food provisioning, biological control, regulation of environmental conditions and life cycle maintenance). Due to the complexity of ES, we investigated several EP by ES. Then we identified hotspots and coldspots of supply and spatial overlap among EP and other uses (conservation, fishing, offshore windfarms and sand extraction).

Results

EP mapping suggests a higher capacity of supply of the chosen ES in the Northern part of the GV. We found a strong spatial heterogeneity among the EP related to the same ES, underlining a point of vigilance when designing management measures to sustain ES supply. Northern EP hotspots overlap with high amounts of bottom trawl fishing effort. Higher levels of commercial species diversity and sole spawning grounds in the South overlap with higher amounts of gillnet fishing effort. Areas of sand extraction prospection and offshore windfarms under construction should not overlap with hotspots of EP, at the exception of the sole spawning ground and the commercial species diversity hotspots. Finally, we highlight an overlap of more than 20% of four EP hotspots with Natura 2000 areas, while the Marine Natural Park in the South covers more EP coldspots (i.e. hake nursery, encounter rate, trophic links diversity) than hotspots.

Discussion

Incorporating such a multifunctional spatial approach with hotspots and coldspots opens new perspective for marine spatial planning, pointing out the potential strengths and weaknesses of areas currently defined or prioritized for future uses like conservation, sand extraction or emerging activities like offshore windfarms.
Sedimentary ancient DNA: a new paleogenomic tool for reconstructing the history of marine ecosystems
Authors: Nguyen Ngoc-Loi , Devendra Dhanushka , Szymańska Natalia , Greco Mattia , Angeles Inès Barrenechea , Weiner Agnes K. M. , Ray Jessica Louise , Cordier Tristan , De Schepper Stijn , Pawłowski Jan , Pawłowska Joanna
Published: June 2023

Sedimentary ancient DNA (sedaDNA) offers a novel retrospective approach to reconstructing the history of marine ecosystems over geological timescales. Until now, the biological proxies used to reconstruct paleoceanographic and paleoecological conditions were limited to organisms whose remains are preserved in the fossil record. The development of ancient DNA analysis techniques substantially expands the range of studied taxa, providing a holistic overview of past biodiversity. Future development of marine sedaDNA research is expected to dramatically improve our understanding of how the marine biota responded to changing environmental conditions. However, as an emerging approach, marine sedaDNA holds many challenges, and its ability to recover reliable past biodiversity information needs to be carefully assessed. This review aims to highlight current advances in marine sedaDNA research and to discuss potential methodological pitfalls and limitations.
Investigation of fluid flow pattern in a 3D meandering tube
Authors: Ibrahim Syed , Khan Marwat Dil Nawaz , Ullah Naeem , Nisar Kottakkaran Sooppy
Published: June 2023

Several types of meandering channels and their mathematical simulation have been proposed and discussed widely in the open literature. In the present study, the impact of a novel meandering tube geometry on streamwise vortices and pressure losses have been determined. Using a simplified Poiseuille flow simulation approach with a sinusoidal wavy meandering tube of non-uniform radius, the onset flow separation, vertex formation, and the impact of Reynolds number on field variables and stream function has been analyzed. Moreover, the linear stability theory has been implemented to trace the vertex formation. A decrease in wavelength leads to flow separation near the tube’s surface, but the flow becomes rectilinear with a sudden disturbance caused by the meander, becoming independent of vertex generating centrifugal forces. Novel insights are provided on the impact of meandering tube geometry on fluid flow and potential applications for enhancing flow conditions are suggested.
Influence of the fracture on the seepage stability of loess slopes
Authors: Li Hongru , Yang Min , Dang Tong
Published: June 2023

The development of fractures in loess slopes often has a great influence on the stability of slopes. In this paper, taking the homogeneous slope model as an example, fractures with different distances and depths from the slope top angle are provided at the top of the slope. Firstly, the influence of single fracture location and depth on slope stability is analyzed, and after the most unfavorable location and depth of the fractures are determined, the influence of the slope top fractures on the slope seepage field and slope stability under the conditions with and without rainfall is studied secondly. The results show that with the increase of the distance from the fracture to the top angle of the slope, the safety coefficient of the slope shows the change law of decreasing first and then increasing. The critical fracture depth corresponding to the fractures at different locations is different, and when the critical fracture depth is exceeded, the slope safety factor tends to be stable. At the end of the rainfall moment through 1-1 section to analyze, it is found that at this time the pore water pressure and volume water content of the soil at the bottom of the fracture at different depths are greater than those of the upper soil, and the shallow fracture has less influence on the seepage field of the slope, and through 2-2 section it is found that the pore water pressure and volume water content in the soil far from the fracture are greater than those of the soil near the location of the fracture. When 288 h after the end of rainfall, the pore water pressure and volumetric water content of the soil around the fracture in section 2-2 were greater than those far from the fracture location. With the passage of time, the pore water pressure at the location of the fracture gradually dissipated and the corresponding volumetric water content gradually decreased, indicating that the fracture had an obvious influence on the characteristics of the seepage field in the soil at different times of rainfall. Under the condition of no rainfall, there exists a critical depth of fractures affecting slope safety stability, while under the condition of rainfall, the slope safety coefficient continuously decreases with the increase of fracture depth, and there is no critical fracture depth. The research results promote the understanding of the safety and stability of loess fracture slopes and provide a reference for slope management.
Identification and characterization of pathogens causing saffron corm rot in China
Authors: Ren Tingdan , Dai Dejiang , Yu Miao , Li Tao , Zhang Chuanqing
Published: June 2023

Corm rot is the most important disease of saffron, for which fungi from several genus such as Fusarium spp. Penicillium spp. and Botrytis spp., have been previously reported to be the pathogens. In this research, we used a combination of amplicon sequencing and traditional isolation methods to identify the causal agents, main infection source. The diversity of microbial communities in diseased saffron corms and soil decreased significantly compared with healthy corms and soil. The contents of Penicillium and Botrytis in healthy and diseased corms were similarly high, indicating that them were not directly related to the occurrence of corm rot. But the relative abundance of Fusarium, Cadophora and Fusicolla were significantly higher in the diseased corms than healthy ones. The abundance of Fusarium increased, while the abundance of Oidiodendron, Paraphaeosphaeria and the endophytic beneficial bacteria Pseudomonas decreased, which may relate to the occurrence of the disease. The co-occurrence network diagram showed that the correlation between fungal and bacterial communities was mainly positive. Plant pathogens were relatively abundant in the diseased soil, according to functional gene prediction. At the same time, we also collected 100 diseased corms from the fields in Jiande, where is known as the “hometown of saffron.” All isolated pathogenic strains were identified as Fusarium oxysporum through morphological observation and phylogenetic tree analysis of ITS, Tef-1α and β-tubulin. To better clarify the biological characteristics of F. oxysporum, we cultured the isolates at different temperatures and pH values. The optimum temperature for mycelial growth and sporulation was 25°C, pH 6，carbon sources sorbitol and nitrogen sources, peptone. In short, our results suggests that F. oxysporum was the pathogen causing corm rot in Jiande and corms other than soils are the main primary infection source. These new understanding of saffron corm rot will provide the theoretical basis for its better and efficiently management.
A targeted liquid cultivation method for previously uncultured non-colony forming microbes
Authors: Seo Eun-Young , Jung Dawoon , Epstein Slava S. , Zhang Weiyan , Owen Jeffrey S. , Baba Hiroaki , Yamamoto Akina , Harada Mifuyu , Nakashimada Yutaka , Kato Setsu , Aoi Yoshiteru , He Shan
Published: June 2023

A large number of microbes are not able to form colonies using agar-plating methods, which is one of the reasons that cultivation based on solid media leaves the majority of microbial diversity in the environment inaccessible. We developed a new Non-Colony-Forming Liquid Cultivation method (NCFLC) that can selectively isolate non-colony-forming microbes that exclusively grow in liquid culture. The NCFLC method involves physically separating cells using dilution-to-extinction (DTE) cultivation and then selecting those that could not grow on a solid medium. The NCFLC was applied to marine samples from a coastal intertidal zone and soil samples from a forest area, and the results were compared with those from the standard direct plating method (SDP). The NCFLC yielded fastidious bacteria from marine samples such as Acidobacteriota, Epsilonproteobacteria, Oligoflexia, and Verrucomicrobiota. Furthermore, 62% of the isolated strains were potential new species, whereas only 10% were novel species from SDP. From soil samples, isolates belonging to Acidobacteriota and Armatimonadota (which are known as rare species among identified isolates) were exclusively isolated by NCFLC. Colony formation capabilities of isolates cultivated by NCFLC were tested using solid agar plates, among which approximately one-third of the isolates were non-colony-forming, approximately half-formed micro-colonies, and only a minority could form ordinary size colonies. This indicates that the majority of the strains cultivated by NCFLC were previously uncultured microbial species unavailable using the SDP method. The NCFCL method described here can serve as a new approach to accessing the hidden microbial dark matter.
The lactate dehydrogenase gene is involved in the growth and metabolism of Lacticaseibacillus paracasei and the production of fermented milk flavor substances
Authors: Fang Sichang , Song Xin , Cui Liru , Bai Jinping , Lu Han , Wang Shijie
Published: June 2023

Objective

Lactate dehydrogenase (ldh) in lactic acid bacteria is an important enzyme that is involved in the process of milk fermentation. This study aimed to explore the changes and effects of fermented milk metabolites in mutant strains after knocking out the ldh gene of Lacticaseibacillus paracasei.

Methods

The ldh mutant ΔAF91_07315 was obtained from L. paracasei using clustered regularly interspaced short palindromic repeats technology, and we determined fermented milk pH, titratable acidity, viable count, and differential metabolites in the different stages of milk fermentation that were identified using metabolomic analysis.

Results

The results showed that the growth rate and acidification ability of the mutant strain were lower than those of the wild-type strain before the end of fermentation, and analysis of the differential metabolites showed that lactate, L-cysteine, proline, and intermediate metabolites of phenylalanine, tryptophan, and methionine were downregulated (P < 0.05), which affected the growth initiation rate and acidification ability of the strain. At the end of fermentation (pH 4.5), the fermentation time of the mutant strain was prolonged and all differential metabolites were upregulated (P < 0.05), including amino acids and precursors, acetyl coenzyme A, and other metabolites involved in amino acid and fatty acid synthesis, which are associated with the regulation of fermented milk flavors. In addition, riboflavin was upregulated to promote the growth of the strain and compensate for the growth defects caused by the mutation.

Conclusion

Our data established a link between the AF91_07315 gene and strain growth and metabolism and provided a target for the regulation of fermented milk flavor substances.
Advancements in understanding the molecular and immune mechanisms of Bartonella pathogenicity
Authors: Jin Xiaoxia , Gou Yuze , Xin Yuxian , Li Jingwei , Sun Jingrong , Li Tingting , Feng Jie
Published: June 2023

Bartonellae are considered to be emerging opportunistic pathogens. The bacteria are transmitted by blood-sucking arthropods, and their hosts are a wide range of mammals including humans. After a protective barrier breach in mammals, Bartonella colonizes endothelial cells (ECs), enters the bloodstream, and infects erythrocytes. Current research primarily focuses on investigating the interaction between Bartonella and ECs and erythrocytes, with recent attention also paid to immune-related aspects. Various molecules related to Bartonella’s pathogenicity have been identified. The present review aims to provide a comprehensive overview of the newly described molecular and immune responses associated with Bartonella’s pathogenicity.
Pooled analysis of frontal lobe transcriptomic data identifies key mitophagy gene changes in Alzheimer's disease brain
Authors: Mei Taoyu , Li Yuan , Orduña Dolado Anna , Li Zhiquan , Andersson Robin , Berliocchi Laura , Rasmussen Lene Juel
Published: June 2023

Background

The growing prevalence of Alzheimer's disease (AD) is becoming a global health challenge without effective treatments. Defective mitochondrial function and mitophagy have recently been suggested as etiological factors in AD, in association with abnormalities in components of the autophagic machinery like lysosomes and phagosomes. Several large transcriptomic studies have been performed on different brain regions from AD and healthy patients, and their data represent a vast source of important information that can be utilized to understand this condition. However, large integration analyses of these publicly available data, such as AD RNA-Seq data, are still missing. In addition, large-scale focused analysis on mitophagy, which seems to be relevant for the aetiology of the disease, has not yet been performed.

Methods

In this study, publicly available raw RNA-Seq data generated from healthy control and sporadic AD post-mortem human samples of the brain frontal lobe were collected and integrated. Sex-specific differential expression analysis was performed on the combined data set after batch effect correction. From the resulting set of differentially expressed genes, candidate mitophagy-related genes were identified based on their known functional roles in mitophagy, the lysosome, or the phagosome, followed by Protein-Protein Interaction (PPI) and microRNA-mRNA network analysis. The expression changes of candidate genes were further validated in human skin fibroblast and induced pluripotent stem cells (iPSCs)-derived cortical neurons from AD patients and matching healthy controls.

Results

From a large dataset (AD: 589; control: 246) based on three different datasets (i.e., ROSMAP, MSBB, & GSE110731), we identified 299 candidate mitophagy-related differentially expressed genes (DEG) in sporadic AD patients (male: 195, female: 188). Among these, the AAA ATPase VCP, the GTPase ARF1, the autophagic vesicle forming protein GABARAPL1 and the cytoskeleton protein actin beta ACTB were selected based on network degrees and existing literature. Changes in their expression were further validated in AD-relevant human in vitro models, which confirmed their down-regulation in AD conditions.

Conclusion

Through the joint analysis of multiple publicly available data sets, we identify four differentially expressed key mitophagy-related genes potentially relevant for the pathogenesis of sporadic AD. Changes in expression of these four genes were validated using two AD-relevant human in vitro models, primary human fibroblasts and iPSC-derived neurons. Our results provide foundation for further investigation of these genes as potential biomarkers or disease-modifying pharmacological targets.
Distinct and shared neuropsychiatric phenotypes in FTLD-tauopathies
Authors: Keszycki Rachel , Kawles Allegra , Minogue Grace , Zouridakis Antonia , Macomber Alyssa , Gill Nathan , Vu My , Zhang Hui , Coventry Christina , Rogalski Emily , Weintraub Sandra , Mesulam M-Marsel , Geula Changiz , Gefen Tamar
Published: June 2023

Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy. Participants completed annual research visits at the Northwestern University Alzheimer’s Disease Research Center. All participants had an initial Global Clinical Dementia Rating (CDR) Scale score ≤ 2, and neuropsychiatric symptoms were evaluated via the Neuropsychiatric Inventory-Questionnaire (NPI-Q). We assessed the frequency of neuropsychiatric symptoms across all participants at their initial and final visits and performed logistic regression to determine whether symptoms predicted a specific FTLD-tau pathologic diagnosis. Across the FTLD-tau cohort, irritability and apathy were most frequently endorsed at initial and final visits, respectively, whereas psychosis was highly uncommon at both timepoints. Irritability at initial visit predicted greater odds of a 4-repeat compared to a 3-repeat tauopathy (OR = 3.95, 95% CI = 1.10–15.83, p < 0.05). Initial sleep disturbance predicted greater odds of progressive supranuclear palsy (PSP) compared to other FTLD-tau subtypes (OR = 10.68, 95% CI = 2.05–72.40, p < 0.01). Appetite disturbance at final evaluation predicted lower odds of PSP (OR = 0.15, 95% CI = 0.02–0.74, p < 0.05). Our findings suggest that characterization of neuropsychiatric symptoms can aid in the prediction of underlying FTLD-tauopathies. Given considerable pathologic heterogeneity underlying dementias, neuropsychiatric symptoms may be useful for differential diagnosis and treatment planning.
Unraveling molecular characteristic of fluoride neurotoxicity on U87 glial-like cells: insights from transcriptomic and proteomic approach
Authors: Puty Bruna , Bittencourt Leonardo Oliveira , Lima Leidiane Alencar Oliveira , Plaça Jéssica Rodrigues , Dionizio Aline , Buzalaf Marília Afonso Rabelo , Gomes Bruno Duarte , de Oliveira Edivaldo Herculano Correa , Lima Rafael Rodrigues
Published: June 2023

The potential of fluoride (F) as a neurotoxicant in humans is still controversial in the literature. However, recent studies have raised the debate by showing different mechanism of F-induced neurotoxicity, as oxidative stress, energy metabolism and inflammation in the central nervous system (CNS). In the present study, we investigated the mechanistic action of two F concentration (0.095 and 0.22 μg/ml) on gene and protein profile network using a human glial cell in vitro model over 10 days of exposure. A total of 823 genes and 2,084 genes were modulated after exposure to 0.095 and 0.22 μg/ml F, respectively. Among them, 168 were found to be modulated by both concentrations. The number of changes in protein expression induced by F were 20 and 10, respectively. Gene ontology annotations showed that the main terms were related to cellular metabolism, protein modification and cell death regulation pathways, such as the MAP kinase (MAPK) cascade, in a concentration independent manner. Proteomics confirmed the changes in energy metabolism and also provided evidence of F-induced changes in cytoskeleton components of glial cells. Our results not only reveal that F has the potential to modulate gene and protein profiles in human U87 glial-like cells overexposed to F, but also identify a possible role of this ion in cytoskeleton disorganization.
Prediction of subjective cognitive decline after corpus callosum infarction by an interpretable machine learning-derived early warning strategy
Authors: Xu Yawen , Sun Xu , Liu Yanqun , Huang Yuxin , Liang Meng , Sun Rui , Yin Ge , Song Chenrui , Ding Qichao , Du Bingying , Bi Xiaoying
Published: June 2023

Background and purpose

Corpus callosum (CC) infarction is an extremely rare subtype of cerebral ischemic stroke, however, the symptoms of cognitive impairment often fail to attract early attention of patients, which seriously affects the long-term prognosis, such as high mortality, personality changes, mood disorders, psychotic reactions, financial burden and so on. This study seeks to develop and validate models for early predicting the risk of subjective cognitive decline (SCD) after CC infarction by machine learning (ML) algorithms.

Methods

This is a prospective study that enrolled 213 (only 3.7%) CC infarction patients from a nine-year cohort comprising 8,555 patients with acute ischemic stroke. Telephone follow-up surveys were carried out for the patients with definite diagnosis of CC infarction one-year after disease onset, and SCD was identified by Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. Based on the significant features selected by the least absolute shrinkage and selection operator (LASSO), seven ML models including Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost), Gaussian Naïve Bayes (GNB), Complement Naïve Bayes (CNB), and Support vector machine (SVM) were established and their predictive performances were compared by different metrics. Importantly, the SHapley Additive exPlanations (SHAP) was also utilized to examine internal behavior of the highest-performance ML classifier.

Results

The Logistic Regression (LR)-model performed better than other six ML-models in SCD predictability after the CC infarction, with the area under the receiver characteristic operator curve (AUC) of 77.1% in the validation set. Using LASSO and SHAP analysis, we found that infarction subregions of CC infarction, female, 3-month modified Rankin Scale (mRS) score, age, homocysteine, location of angiostenosis, neutrophil to lymphocyte ratio, pure CC infarction, and number of angiostenosis were the top-nine significant predictors in the order of importance for the output of LR-model. Meanwhile, we identified that infarction subregion of CC, female, 3-month mRS score and pure CC infarction were the factors which independently associated with the cognitive outcome.

Conclusion

Our study firstly demonstrated that the LR-model with 9 common variables has the best-performance to predict the risk of post-stroke SCD due to CC infarcton. Particularly, the combination of LR-model and SHAP-explainer could aid in achieving personalized risk prediction and be served as a decision-making tool for early intervention since its poor long-term outcome.