bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitosan nanoparticles for sustained release of metformin and its derived synthetic biopolymer for bone regeneration
Authors: Chen Ning-Xin , Su Xiao-Lin , Feng Yao , Liu Qiong , Tan Li , Yuan Hui , Chen Yun , Zhao Jie , Zhao Ya-Qiong , Dusenge Marie Aimee , Hu Jing , Ye Qin , Ou-Yang Ze-Yue , Zhong Meng-Mei , Zhang Qian , Guo Yue , Feng Yun-Zhi , Peng Yong-Bo
Published: July 2023

Background: There are considerable socioeconomic costs associated with bone defects, making regenerative medicine an increasingly attractive option for treating them. Chitosan is a natural biopolymer; it is used in approaches for sustained slow release and osteogenesis, and metformin has osteoinductivity. Our study aimed to synthesize chitosan and human serum albumin (HSA) with a metformin nanoformulation to evaluate the therapeutic effects of this nanoformulation on bone defects in vitro.

Methods: A pluripotent differentiation assay was performed in vitro on mouse bone marrow mesenchymal stem cells (BMSCs). Cell Counting Kit-8 was used to detect whether metformin was toxic to BMSCs. The osteogenesis-related gene expression of osteocalcin (OCN) and osteoprotegerin (OPG) from BMSCs was tested by real-time polymerase chain reaction (PCR). HSA, metformin hydrochloride, and chitosan mixtures were magnetically stirred to finish the assembly of metformin/HSA/chitosan nanoparticles (MHC NPs). The MHC NPs were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR). To test the expression of OCN and OPG, western blot were used. MHC NPs were evaluated in vitro for their osteoinductivity using alkaline phosphatase (ALP).

Results: BMSCs successfully differentiated into osteogenic and adipogenic lineages in vitro. According to real-time PCR, a 50 µM concentration of metformin promoted osteogenesis in BMSCs most effectively by upregulating the osteogenic markers OCN and OPG. The microstructure of MHC NPs was spherical with an average nanosize of 20 ± 4.7 nm and zeta potential of −8.3 mV. A blueshift and redshift were observed in MHC NPs following exposure to wavelengths of 1,600–1,900 and 2,000–3,700 nm, respectively. The encapsulation (%) of metformin was more than 90%. The simulation study showed that MHC NPs have good stability and it could release metformin slowly in vitro at room temperature. Upon treatment with the studied MHC NPs for 3 days, ALP was significantly elevated in BMSCs. In addition, the MHC NPs-treated BMSCs upregulated the expression of OPG and OCN, as shown by real-time PCR and western blot.

Conclusion: MHC NPs have a stable metformin release effect and osteogenic ability. Therefore, as a derived synthetic biopolymer, it is expected to play a role in bone tissue regeneration.
A multi-mineral intervention to counter pro-inflammatory activity and to improve the barrier in human colon organoids
Authors: Varani James , McClintock Shannon D. , Nadeem Daniyal M. , Harber Isabelle , Zeidan Dania , Aslam Muhammad N.
Published: July 2023

Introduction: Ulcerative colitis is a chronic inflammatory condition, and continuous inflammatory stimulus may lead to barrier dysfunction. The goal of this study was to assess barrier proteomic expression by a red algae-derived multi-mineral intervention in the absence or presence of pro-inflammatory insult.

Methods: Human colon organoids were maintained in a control culture medium alone or exposed to lipopolysaccharide with a combination of three pro-inflammatory cytokines [tumor necrosis factor-α, interleukin-1β and interferon-γ (LPS-cytokines)] to mimic the environment in the inflamed colon. Untreated organoids and those exposed to LPS-cytokines were concomitantly treated for 14 days with a multi-mineral product (Aquamin®) that has previously been shown to improve barrier structure/function. The colon organoids were subjected to proteomic analysis to obtain a broad view of the protein changes induced by the two interventions alone and in combination. In parallel, confocal fluorescence microscopy, tissue cohesion and transepithelial electrical resistance (TEER) measurements were used to assess barrier structure/function.

Results: The LPS-cytokine mix altered the expression of multiple proteins that influence innate immunity and promote inflammation. Several of these were significantly decreased with Aquamin® alone but only a modest decrease in a subset of these proteins was detected by Aquamin® in the presence of LPS-cytokines. Among these, a subset of inflammation-related proteins including fibrinogen-β and -γ chains (FGB and FGG), phospholipase A2 (PLA2G2A) and SPARC was significantly downregulated in the presence of Aquamin® (alone and in combination with LPS-cytokines); another subset of proteins with anti-inflammatory, antioxidant or anti-microbial activity was upregulated by Aquamin® treatment. When provided alone, Aquamin® strongly upregulated proteins that contribute to barrier formation and tissue strength. Concomitant treatment with LPS-cytokines did not inhibit barrier formation in response to Aquamin®. Confocal microscopy also displayed increased expression of desmoglein-2 (DSG2) and cadherin-17 (CDH17) with Aquamin®, either alone or in the presence of the pro-inflammatory stimulus. Increased cohesion and TEER with Aquamin® (alone or in the presence of LPS-cytokines) indicates improved barrier function.

Conclusion: Taken together, these findings suggest that multi-mineral intervention (Aquamin®) may provide a novel approach to combating inflammation in the colon by improving barrier structure/function as well as by directly altering the expression of certain pro-inflammatory proteins.
Fibrosis—the tale of H3K27 histone methyltransferases and demethylases
Authors: Basta Morgan D. , Petruk Svetlana , Mazo Alexander , Walker Janice L.
Published: July 2023

Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 (EZH1, EZH2), which are the alternative subunits of the Polycomb Repressive Complex 2 (PRC2) and demethylase (KDM) enzymes, Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and Lysine demethylase 6B (KDM6B), are responsible for regulating methylation status of H3K27me3. In this review, we explore how these key enzymes regulate chromatin structure to alter gene expression in fibrosis, highlighting them as attractive targets for the treatment of fibrosis.
Infiltrated IL-17A-producing gamma delta T cells play a protective role in sepsis-induced liver injury and are regulated by CCR6 and gut commensal microbes
Authors: Wan Jian , Zhang Qian , Hao Yilong , Tao Zhang , Song Wei , Chen Song , Qin Long , Song Weidong , Shan Yi
Published: July 2023

Introduction

Sepsis is a common but serious disease in intensive care units, which may induce multiple organ dysfunctions such as liver injury. Previous studies have demonstrated that gamma delta (γδ) T cells play a protective role in sepsis. However, the function and mechanism of γδ T cells in sepsis-induced liver injury have not been fully elucidated. IL-17A-producing γδ T cells are a newly identified cell subtype.

Methods

We utilized IL-17A-deficient mice to investigate the role of IL-17A-producing γδ T cells in sepsis using the cecum ligation and puncture (CLP) model.

Results

Our findings suggested that these cells were the major source of IL-17A and protected against sepsis-induced liver injury. Flow cytometry analysis revealed that these γδ T cells expressed Vγ4 TCR and migrated into liver from peripheral post CLP, in a CCR6-dependent manner. When CLP mice were treated with anti-CCR6 antibody to block CCR6-CCL20 axis, the recruitment of Vγ4+ γδ T cells was abolished, indicating a CCR6-dependent manner of migration. Interestingly, pseudo germ-free CLP mice treated with antibiotics showed that hepatic IL-17A+ γδ T cells were regulated by gut commensal microbes. E. coli alone were able to restore the protective effect in pseudo germ-free mice by rescuing hepatic IL-17A+ γδ T cell population.

Conclusion

Our research has shown that Vγ4+ IL-17A+ γδ T cells infiltrating into the liver play a crucial role in protecting against sepsis-induced liver injury. This protection was contingent upon the recruitment of CCR6 and regulated by gut commensal microbes.
Identification of 5 hub genes for diagnosis of coronary artery disease
Authors: Zhu Pengyuan , Huang Haitao , Xie Tian , Liang Huoqi , Li Xing , Li Xingyi , Dong Hao , Yu Xiaoqiang , Xia Chunqiu , Zhong Chongjun , Ming Zhibing
Published: July 2023

Background

Coronary artery disease (CAD) is a main cause leading to increasing mortality of cardiovascular disease (CVD) worldwide. We aimed to discover marker genes and develop a diagnostic model for CAD.

Methods

CAD-related target genes were searched from DisGeNET. Count expression data and clinical information were screened from the GSE202626 dataset. edgeR package identified differentially expressed genes (DEGs). Using online STRING tool and Cytoscape, protein-protein reactions (PPI) were predicted. WebGestaltR package was employed to functional enrichment analysis. We used Metascape to conduct module-based network analysis. VarElect algorithm provided genes-phenotype correlation analysis. Immune infiltration was assessed by ESTIMATE package and ssGSEA analysis. mRNAsi was determined by one class logistic regression (OCLR). A diagnostic model was constructed by SVM algorithm.

Results

162 target genes were screened by intersection 1,714 DEGs and 1,708 CAD related target genes. 137 target genes of the 162 target genes were obtained using PPI analysis, in which those targets were enriched in inflammatory cytokine pathways, such as chemokine signaling pathway, and IL-17 signaling pathway. From the above 137 target genes, four functional modules (MCODE1-4) were extracted. From the 162 potential targets, CAD phenotype were directly and indirectly associated with 161 genes and 22 genes, respectively. Finally, 5 hub genes (CCL2, PTGS2, NLRP3, VEGFA, LTA) were screened by intersections with the top 20, directly and indirectly, and genes in MCODE1. PTGS2, NLRP3 and VEGFA were positively, while LTA was negatively correlated with immune cells scores. PTGS2, NLRP3 and VEGFA were negatively, while LTA was positively correlated with mRNAsi. A diagnostic model was successfully established, evidenced by 92.59% sensitivity and AUC was 0.9230 in the GSE202625 dataset and 94.11% sensitivity and AUC was 0.9706 in GSE120774 dataset.

Conclusion

In this work, we identified 5 hub genes, which may be associated with CAD development.
Prevalence, awareness, treatment, and control of dyslipidemia in Chinese adults: a systematic review and meta-analysis
Authors: Xia Qianhang , Chen Yuquan , Yu Zijing , Huang Zhongyue , Yang Yujie , Mao Ayan , Qiu Wuqi
Published: July 2023

Background

Researchers have conducted a considerable number of epidemiological studies on dyslipidemia in China over recent years. Nevertheless, a representative study to comprehensively appraise for the epidemiological status of dyslipidemia is still lacked. This meta-analysis is intended to explore the pooled prevalence, rates of awareness, treatment, and control of dyslipidemia among adults in Chinese Mainland.

Materials and methods

A systematic review was performed on relevant cross-sectional studies published since January 2012 by searching six authoritative literature databases. Meta-analyses were conducted in included studies based on a random-effect model to summarize the epidemiological status of dyslipidemia in China. A potential source of heterogeneity was detected by subgroup analysis and meta-regression. Publication bias was assessed by Egger's test and funnel plots. A sensitivity analysis was conducted to examine the study quality's influence on the pooled estimate of prevalence and rates of awareness, treatment, and control.

Results

Forty-one original researches with a total of 1,310,402 Chinese participants were finally included in the meta-analysis. The prevalence, rates of awareness, treatment, and control of dyslipidemia were 42.1%, 18.2%, 11.6%, and 5.4%, respectively. With a pooled prevalence estimate at 24.5%, low HDL-C was the most prevalent among various dyslipidemia types, followed by hypertriglyceridemia (TG) (15.4%), hypercholesterolemia (TC) (8.3%), and high LDL-C (7.1%). The pooled prevalence of elevated serum lipoprotein(a) [Lp(a)] was 19.4%. By gender, the prevalence of dyslipidemia was 47.3% in males and 38.8% in females. Subgroup analyses revealed that the prevalence in southern and urban areas were higher than their counterparts. Females and population in urban areas tended to possess higher rates of awareness, treatment, and control. Meta-regression analyses suggested that the year of screening influenced prevalence estimates for dyslipidemia. The impact of the study's quality on the pooled estimates is insignificant.

Conclusion

Our study suggested a severe epidemic situation of dyslipidemia among adults in Chinese Mainland. More importantly, the awareness, treatment, and control rates were extremely low, revealing that dyslipidemia is a grave health issue. Consequently, we should attach more importance to the management of dyslipidemia, especially in economically underdeveloped areas.

Systematic review registration

PROSPERO [CRD42022366456].
Carbon flux in supraglacial debris over two ablation seasons at Miage Glacier, Mont Blanc massif, European Alps
Authors: Brown Grace L. , Brock Ben W.
Published: July 2023

The cryosphere plays an important role in the global carbon cycle, but few studies have examined carbon fluxes specifically on debris-covered glaciers. To improve understanding of the magnitude and variability of the atmospheric carbon flux in supraglacial debris, and its environmental controls, near-surface CO2 fluxes and meteorological variables were monitored over thick (0.23 m) and thin (0.04 m) debris at Miage Glacier, European Alps, over two ablation seasons, using an eddy covariance system. The CO2 flux alternates between downward and upward orientation in the day and night, respectively, and is dominated by uptake of CO2 in thick debris (mean flux = 1.58 g CO2 m−2 d−1), whereas flux magnitude is smaller and near net zero on thin debris (mean flux = −0.06 g CO2 m−2 d−1). These values infer a potential drawdown of >150 t CO2 km−2 over an ablation season, and >500 t CO2 (0.5 Gg CO2) for the whole debris-covered zone. The strong correlation of daytime CO2 flux magnitude with debris surface temperature suggests that atmospheric CO2 is consumed in hydrolysis and carbonation reactions at sediment-water interfaces in debris. Incoming shortwave radiation is key in heating debris, generating dilute meltwater, and providing energy for chemical reactions. CO2 drawdown on thin debris increases by an order of magnitude on days following frost events, implying that frost shattering generates fresh reactive sediment, which is rapidly chemically weathered with the onset of ice melting. Net CO2 release in the night, and in the daytime when debris surface temperature is below 7°C, is likely due to respiration by debris microorganisms. The combination of dilute meltwater, high temperature, and reactive mineral surfaces open to the atmosphere, makes supraglacial debris an ideal environment for rock chemical weathering. Debris-covered glaciers could be important to local and regional carbon cycling, and measurement of CO2 fluxes and controlling processes at other sites is warranted.
Non-linear dose-response relationship between body mass index and stroke risk in middle-aged and elderly Chinese men: a nationwide Longitudinal Cohort Study from CHARLS
Authors: Wei Gang , Lin Feng , Cao Changchun , Hu Haofei , Han Yong
Published: July 2023

Objective

Body mass index (BMI) and stroke risk have been linked, but these findings are still debated. This study investigated the relationship between BMI and stroke risk in a middle-aged and elderly Chinese population.

Methods

This study used four waves of CHARLS data (2011, 2013, 2015, and 2018), including 12,161 participants. The CHARLS sample was obtained by multi-stage probability sampling and all participants were assessed by one-to-one interviews using a standardized questionnaire. We used a Cox proportional-hazards regression model to examine the relationship between BMI and stroke risk. We used Cox proportional hazards regression with cubic spline functions and smooth curve fitting to identify the non-linear relationship between them. A series of sensitivity analyses were also conducted.

Results

The multivariate Cox proportional hazards regression model identified a positive association between BMI and stroke risk (HR=1.025, 95% CI: 1.010-1.040). We also found a non-linear relationship between BMI and stroke incidence, with an inflection point at 26.63 kg/m2 for BMI. Each 1 kg/m2 increase in BMI to the left of the inflection point was related to a 4.4% increase in stroke risk (HR=1.044, 95% CI: 1.019-1.069). We stratified individuals by gender to further investigate their association and found a particular non-linear relationship and saturation effect between BMI and stroke risk in men, with the inflection point at 25.94 kg/m2. Each 1 kg/m2 increase in BMI to the left of the inflection point was related to a 7.6% increase in stroke risk (HR=1.076, 95% CI 1.034-1.119). The association was linear in women, with each 1 kg/m2 increase in BMI associated with a 2.1% increase in stroke risk (HR=1.021, 95% CI 1.002, 1.040).

Conclusion

In men, there was a specific non-linear association and saturation effect of BMI with stroke (inflection point of 25.94 kg/m2), while in women, there was none. When males had a BMI below 25.94 kg/m2, the risk of stroke was significantly and positively associated with BMI. By controlling BMI below 25.94 kg/m2 in men, a further decrease in BMI may promote a significant reduction in stroke risk.
Natal environmental conditions modulate senescence of antler length in roe deer
Authors: Cambreling Solène , Gaillard Jean-Michel , Pellerin Maryline , Vanpé Cécile , Débias François , Delorme Daniel , Garcia Rébecca , Hewison A. J. Mark , Lemaître Jean-François
Published: July 2023

It is now broadly admitted that female reproductive senescence – a decline in reproductive performance with increasing age – occurs in most species, at least among birds and mammals. Although information is more limited, male reproductive senescence has been regularly inferred from the decline in the size or performance of phenotypic traits that underly male reproductive success, particularly secondary sexual traits. However, the degree to which environmental conditions influence the pattern of senescence in sexual traits remains largely unknown. From the analysis of two long-term studies of populations of European roe deer (Capreolus capreolus) subjected to markedly different environmental contexts in the wild, we tested the hypothesis that harsh natal and/or current conditions should lead to earlier and/or stronger rates of senescence in the length of fully-grown antlers than good natal and/or current conditions. We found evidence of similar patterns of antler length senescence in both populations, with an onset of senescence around 7 years of age and a decrease of length by about 1–1.5 cm per additional year of life from 7 years of age onwards. We found that good early-life conditions delay senescence in antler length in roe deer. Our results also revealed that senescent males seem to be unable to allocate substantially to antler growth, confirming that antler size is, therefore, an honest signal of male individual quality. By modulating age-specific allocation to secondary sexual traits, natal and current conditions could influence female mate choice and male–male competition over mates, and as a result age-specific reproductive success, and should be accounted for when studying the dynamics of sexual selection.
T cell receptor β repertoires in patients with COVID-19 reveal disease severity signatures
Authors: Xu Jing , Li Xiao-xiao , Yuan Na , Li Chao , Yang Jin-gang , Cheng Li-ming , Lu Zhong-xin , Hou Hong-yan , Zhang Bo , Hu Hui , Qian Yu , Liu Xin-xuan , Li Guo-chao , Wang Yue-dan , Chu Ming , Dong Chao-ran , Liu Fan , Ge Qing-gang , Yang Yue-jin
Published: July 2023

Background

The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity.

Methods

In this study, we employed high-throughput T cell receptor (TCR) β repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes.

Results

We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression.

Conclusions

Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR β repertoires in monitoring disease development and indicating disease severity.
Potential value of neuroimmunotherapy for COVID-19: efficacies and mechanisms of vagus nerve stimulation, electroacupuncture, and cholinergic drugs
Authors: Yu Xianqiang , Kong Qingming
Published: July 2023

COVID-19 is an inflammatory disease with multiple organs involved, mainly respiratory symptoms. Although the majority of patients with COVID-19 present with a mild to moderate self-limited course of illness, about 5-10% of patients with inflammatory disorders in severe COVID-19 have life-threatening progression. With the exception of a few drugs that have shown outstanding anti-COVID-19 effects, the efficacy of most drugs remains controversial. An increasing number of animal and clinical studies have shown that neuromodulation has a significant effect on reducing inflammatory markers of COVID-19, thus exerting an effective neuroimmunotherapeutic value. Currently, the main neuroimmunomodulatory measures effective against COVID-19 include vagus nerve stimulation, electroacupuncture, and cholinergic drugs. In this review, we will summarize the research progress of potential value of this neuroimmunotherapy measures for COVID-19 and elaborate its efficacies and mechanisms, in order to provide reliable evidence for clinical intervention.
The role of neutrophils in chorioamnionitis
Authors: Zhang Cunling , Cao Jiasong , Xu Meiyi , Wu Dan , Li Wen , Chang Ying
Published: July 2023

Chorioamnionitis, commonly referred to as intrauterine infection or inflammation, is pathologically defined by neutrophil infiltration and inflammation at the maternal-fetal interface. Chorioamnionitis is the common complication during late pregnancy, which lead to a series of serious consequences, such as preterm labor, preterm premature rupture of the fetal membranes, and fetal inflammatory response syndrome. During infection, a large number of neutrophils migrate to the chorio-decidua in response to chemokines. Although neutrophils, a crucial part of innate immune cells, have strong anti-inflammatory properties, over-activating them can harm the body while also eliminating pathogens. This review concentrated on the latest studies on chorioamnionitis-related consequences as well as the function and malfunction of neutrophils. The release of neutrophil extracellular traps, production of reactive oxygen species, and degranulation from neutrophils during intrauterine infection, as well as their pathological roles in complications related to chorioamnionitis, were discussed in detail, offering fresh perspectives on the treatment of chorioamnionitis.
Architecture of the motor and premotor cortex of the capuchin monkey
Authors: Magalhães-Junior Erli G. , Mayer Andrei , Nascimento-Silva Márcio L. , Bonfim Vânio , Lima Bruss , Gattass Ricardo , Soares Juliana G. M.
Published: July 2023

Introduction

Over the last 65 million years, primates have evolved hind- and forelimbs capable of skilled grasping (e.g., tree branches) and manipulation of tools and other objects. The New World capuchin monkey and the Old World macaque monkey stand out among other primates for their manual dexterity. The capuchin monkey is distributed throughout the Amazon and the Atlantic Forests and is the only New World monkey to have evolved an opposable thumb and to have developed the capability of using tools in the wild.

Methods

The present work analyzes the cyto-, myelo- and immunoarchitecture of the motor and premotor areas of the capuchin monkey using Nissl, Gallyas and SMI-32 immunolabeling techniques.

Results

These different staining techniques allowed for the parcellation of Brodmann area 4 into the ventral (F1v), medial (F1m) and dorsal (F1d) areas. Additionally, lateral area 6 was subdivided into the dorsal (F2 and F7) and ventral (F4 and F5) areas. Area F5 was subsequently subdivided into the convexity (F5c), anterior (F5a) and posterior (F5p) areas. Medial area 6 was subdivided into F3 and F6 areas.

Discussion

These motor and premotor areas of the capuchin monkey are similar to those of macaque and humans, and different from those of other New World monkeys. We argue that this is due to differences in manual dexterity across New World monkeys: capuchin monkeys have evolved different types of precision grips, while most of the other New World monkeys exclusively perform whole-hand grips during object manipulation.
Drivers of diatom production and the legacy of eutrophication in two river plume regions of the northern Gulf of Mexico
Authors: Krause Jeffrey W. , Boyette Adam D. , Marquez Israel A. , Pickering Rebecca A. , Maiti Kanchan
Published: July 2023

In the northern Gulf of Mexico (nGoM), the Louisiana Shelf (LS) and Mississippi Bight (MB) subregions are influenced by eutrophication to varying degrees. Despite recognition that dissolved silicon may regulate diatom productivity in the nGoM, there is only one published data set reporting biogenic silica (bSiO2) production rates for each subregion. We report that bSiO2 production rates on the LS and MB are high and appear to be controlled by different nutrients among seasons. Despite exceptional upper trophic level biomass regionally, which suggests significant primary production by diatoms (as in other systems), gross euphotic-zone integrated bSiO2 production rates are lower than major bSiO2 producing regions (e.g. upwelling systems). However, when normalizing to the depth of the euphotic zone, the bSiO2 production rates on the LS are like normalized rates in upwelling systems. We suggest local river-plume influenced hydrography concentrates diatom productivity within shallow euphotic zones, making production more accessible to higher trophic organisms. Comparison of rates between the LS and MB suggest that the fluvial nitrate within the LS stimulates bSiO2 production above that in the MB, which has a smaller watershed and is less eutrophic (relatively). Beyond understanding the factors controlling regional bSiO2 production, these data offer the most comprehensive Si-cycle baseline to date as the LS and MB will likely exchange freely in the mid to late century due to land subsidence of the Mississippi River delta and/or sea-level rise.
Influence of lactic-acid bacteria feed supplementation on free amino acid levels in serum and feces of rainbow trout (Oncorhynchus mykiss, Walbaum 1792)
Authors: Carneiro Gabriel R. A. , Opazo Constanza , Do Santos Gustavo Ramalho Cardoso , Pereira Henrique Marcelo Gualberto , Monnerat Gustavo , Opazo Rafael
Published: July 2023

Introduction

The influence of intestinal microbiota, particularly lactic-acid bacteria, on digestion and nutrient metabolic activities has been extensively studied. In this research, we investigated the effects of supplementing the feed of rainbow trout (O. mykiss) with P. acidilactici or L. lactis probiotics. A Control group without probiotic supplementation was also included. The study aimed to evaluate growth, feed conversion indices, free amino acid levels in serum and feces, and the relative gene expression of amino acid solute carrier transporters (SLC).

Methods

Rainbow trout weighing 73.9±10 g were fed with a basal commercial diet supplemented with mono-strains of P. acidilactici or L. lactis at a dosage of 5 x 108 CFU per gram of feed for 60 days. The trout were reared in 100-liter tanks with independent closed recirculation systems, with a water replacement rate of 80% of the total volume daily and a controlled temperature of 15 ± 0.3 °C. The proximate composition of the basal diet consisted of crude protein (49.8%), fat (32.1%), fiber (1.31%), ash (13%), and moisture (8.3%) on a dry matter basis. The diet was provided at a rate of 2% of bodyweight per day.

Results

No significant differences (p > 0.05) were observed in growth and feed conversion indices between the experimental groups. However, significant differences in free amino acid levels in feces and serum samples (p ≤ 0.05) were observed. The P. acidilactici group exhibited significantly higher levels of glutamate, lysine, proline, and tyrosine in feces samples, and higher levels of arginine, iso/leucine, phenylalanine, proline, serine, threonine, and valine in serum samples compared to the Control group. Additionally, the supplemented probiotic groups showed significant downregulation (p ≤ 0.05) of theslc6a19 and slc7a9 genes, which encode transporters for neutral and cationic amino acids.

Discussion

The autochthonous rainbow trout strain, P. acidilactici, demonstrated more pronounced effects on amino acid levels in feces and serum compared to the non-autochthonous L. lactis strain. However, the increased amino acid levels, particularly in the serum, resulting from P. acidilactici supplementation, did not lead to improved trout growth or feed conversion. Nonetheless, lactic-acid bacteria supplementation induced measurable metabolic effects, as evidenced by elevated levels of specific amino acids in the serum and feces.

Future research should focus on evaluating these probiotic effects using specialized diets and considering the observed metabolic effects in this study.
The prevalence of pelvic organ prolapse and associated factors in Ethiopia: a systematic review and meta-analysis
Authors: Addisu Dagne , Mekie Maru , Belachew Yismaw Yimam , Degu Alemu , Gebeyehu Natnael Atnafu
Published: July 2023

Background

Pelvic organ prolapse (POP) affects millions of women globally, with resource-limited countries, such as Ethiopia, carrying the highest burden. Previously, the prevalence of POP was estimated using seven studies. However, this study lacks generalization because of the limited number of studies and low geographical representation. In total, 12 additional primary studies were conducted after this review, and their reported prevalence was significantly variable across the studies. In addition, different new factors were reported in the primary studies. Therefore, this study aimed to update the pooled prevalence of POP and its associated factors in Ethiopia.

Methods

This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Articles that were published between 2000 and 2023 were searched using the African Journal of Online, ScienceDirect, DOAJ, PubMed, and Google Scholar. The quality of the studies was evaluated using the modified Newcastle-Ottawa quality assessment tool. The data were extracted using Microsoft Excel and analyzed by Stata version 11. A random effect model was used to investigate the pooled prevalence of POP and its associated factors. The I2test and Egger's regression test were used to detect the presence of heterogeneity and publication bias across studies, respectively.

Result

A total of 21 studies met the inclusion criteria and represented the data of 14,575 women. The pooled prevalence of POP was found to be 22.70%. History of home delivery (pooled odds ratio (OR) =2.93, 95% CI =1.46, 5.91), prolonged labor (OR = 4.63, 95% CI = 2.56, 8.38), history of perineal tear (OR = 4.83, 95% CI = 2.31, 10.11), instrumental delivery (OR =3.70, 95% CI =2.01, 6.81), grand multipara (OR = 5.42, 95% CI = 4.06, 7.23), family history of POP (OR = 3.30, 95% CI = 2.07, 5.25), and carrying heavy objects (OR = 3.23, 95% CI = 2.22, 4.70) were significantly associated with POP.

Conclusion

The pooled prevalence of POP was high in Ethiopia. The Ministry of Health and clinicians should emphasize counseling on modifiable risk factors and develop further prevention strategies.
The human gut phageome: composition, development, and alterations in disease
Authors: Zhang Yingying , Wang Ran
Published: July 2023

The human gastrointestinal tract is colonized by a large number of microorganisms, including bacteria, archaea, viruses, and eukaryotes. The bacterial community has been widely confirmed to have a significant impact on human health, while viruses, particularly phages, have received less attention. Phages are viruses that specifically infect bacteria. They are abundant in the biosphere and exist in a symbiotic relationship with their host bacteria. Although the application of high-throughput sequencing and bioinformatics technology has greatly improved our understanding of the genomic diversity, taxonomic composition, and spatio-temporal dynamics of the human gut phageome, there is still a large portion of sequencing data that is uncharacterized. Preliminary studies have predicted that the phages play a crucial role in driving microbial ecology and evolution. Prior to exploring the function of phages, it is necessary to address the obstacles that hinder establishing a comprehensive sequencing database with sufficient biological properties and understanding the impact of phage–bacteria interactions on human health. In this study, we provide an overview of the human gut phageome, including its composition, structure, and development. We also explore the various factors that may influence the phageome based on current research, including age, diet, ethnicity, and geographical location. Additionally, we summarize the relationship between the phageome and human diseases, such as IBD, IBS, obesity, diabetes, and metabolic syndrome.
Role of gender and age in features of Wilson’s disease
Authors: Cai Lin , Huang Xiaotao , Ye Yan , Yang Dailan , Xie Linshen , Fu Daigang , Peng Lijun , Zhou Dingzi , Liao Juan
Published: July 2023

Background

Wilson’s disease (WD) is a recessive genetic disorder characterized by copper metabolism dysfunction. It is difficult to obtain an accurate diagnosis due to its variable clinical presentation. This study aimed to describe the clinical characteristics and diagnostic particularities in a series of Chinese WD patients.

Methods

The medical records of 371 patients with WD retrieved from January 2005 to December 2020 were retrospectively reviewed.

Results

The incidence of WD has a male predominance in the adult population. However, the difference in sex distribution is not significant in the pediatric population. Females have an earlier symptom onset than males. The most common initial symptoms were neuropsychiatric manifestations both in the pediatric population (49.7%) and adult population (69.8%), and there was a male predominance (61.8%). Eighty-two percent of patients presented with more than two neurologic symptoms. Fifty-two (14%) patients presented with psychiatric symptoms. The most common WD phenotype was the neuropsychiatric form (48%). The age of onset occurred earlier in patients with the hepatic phenotype than in those with the neuropsychiatric phenotype. Moreover, there was a significant difference in sex distribution regarding phenotype. Females presented with a hepatic phenotype more often than males, and the neuropsychiatric phenotype occurred more frequently in males with an older onset age. Further study showed that the age at onset was a deciding factor for predicting the neuropsychiatric phenotype among the hepatic phenotype. However, sex did not correlate with the phenotype.

Conclusion

Males seem to have a higher disease susceptibility, with symptom onset later than females. Males frequently present with a neuropsychiatric phenotype, while females present with a hepatic phenotype. Age at onset was a deciding factor for predicting the WD phenotype. Further studies focusing on the effect of estrogens on the pathology of WD are suggested.
Involvement of brain cell phenotypes in stress-vulnerability and resilience
Authors: Favoretto Cristiane Aparecida , Pagliusi Marco , Morais-Silva Gessynger
Published: July 2023

Stress-related disorders’ prevalence is epidemically increasing in modern society, leading to a severe impact on individuals’ well-being and a great economic burden on public resources. Based on this, it is critical to understand the mechanisms by which stress induces these disorders. The study of stress made great progress in the past decades, from deeper into the hypothalamic–pituitary–adrenal axis to the understanding of the involvement of a single cell subtype on stress outcomes. In fact, many studies have used state-of-the-art tools such as chemogenetic, optogenetic, genetic manipulation, electrophysiology, pharmacology, and immunohistochemistry to investigate the role of specific cell subtypes in the stress response. In this review, we aim to gather studies addressing the involvement of specific brain cell subtypes in stress-related responses, exploring possible mechanisms associated with stress vulnerability versus resilience in preclinical models. We particularly focus on the involvement of the astrocytes, microglia, medium spiny neurons, parvalbumin neurons, pyramidal neurons, serotonergic neurons, and interneurons of different brain areas in stress-induced outcomes, resilience, and vulnerability to stress. We believe that this review can shed light on how diverse molecular mechanisms, involving specific receptors, neurotrophic factors, epigenetic enzymes, and miRNAs, among others, within these brain cell subtypes, are associated with the expression of a stress-susceptible or resilient phenotype, advancing the understanding/knowledge on the specific machinery implicate in those events.
Knowledge domain and research trends for Gestational Diabetes Mellitus and nutrition from 2011 to 2021: a bibliometric analysis
Authors: Hu Zhefang , Chen Qianyi , Luo Man , Ren Yanwei , Xu Jianyun , Feng Lijun
Published: July 2023

Objective

Nutrient management and lifestyle changes are the frontlines of treatment for all pregnant women diagnosed with Gestational Diabetes Mellitus (GDM). This study aimed to identify the global research architecture, trends, and hotpots of GDM and nutrition.

Methods

We obtained publications from the sub-databases of Science Citation Index Expanded and Social Science Citation Index sourced from the Web of Science Core Collection database on January 4, 2022, using publication years between 2011 and 2021. CiteSpace software, VOSviewer, and Microsoft Excel 2019 were used to conduct the bibliometric analyses.

Results

A growing publication trend was observed for GDM and nutrition, and this field has great potential. More GDM and nutrition research has been conducted in developed countries than developing countries. The top three authors with a high publication frequency, co-citations, and a good h-index were from the United States. There were the four studies of randomized controlled trials (RCTs) or meta-analyses of RCTs, as well as one review in the top five items of cited literature. Keywords were categorized into four clusters based on the keywords visualization.

Conclusion

It is important to strengthen the collaboration between nations of different economies to produce more high-quality research on GDM and nutrition. It may be beneficial to further study the etiology, diagnosis, and treatment of GDM based on current results to provide a new perspective on GDM and nutrition.
The association between dietary intake of flavonoids and its subclasses and the risk of metabolic syndrome
Authors: Zhao Zhenlei , Gao Wenyan , Ding Xiaoli , Xu Xiaogang , Xiao Changqian , Mao Genxiang , Xing Wenmin
Published: July 2023

Background

The healthiest way to prevent metabolic syndrome (MetS) is through behavioral and nutritional adjustments. We examined the relationship between total flavonoids intake, flavonoid subclasses, and clinically manifest MetS.

Methods

A cross-sectional analysis was conducted among 28,719 individuals from the National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2007–2011 and 2017–2018. Two 24-h reviews were conducted to determine flavonoids intake and subclasses. The link between flavonoids intake and MetS was investigated using a multivariate logistic regression model.

Results

Q2 and Q3 of total flavonoids intake were associated with 20 and 19% lower risk of incident MetS after adjusting age and sex. Anthocyanidins and flavanones intake in Q2 and Q3 substantially reduced the MetS risk compared to Q1. MetS risk decreased steadily as the total intake of flavonoids increased to 237.67 mg/d. Flavanones and anthocyanidins also displayed V-shaped relationship curves (34.37 and 23.13 mg/d).

Conclusion

MetS was adversely linked with total flavonoids intake, flavanones, and anthocyanidins. Moreover, the most effective doses of total flavonoids, flavanones, and anthocyanidins were 237.67, 34.37, and 23.13 mg/d, respectively, potentially preventing MetS.
Lung adenocarcinoma with bladder metastasis: A case report and literature review
Authors: Liu Yuying , Dong Xinyue , Li Tao , Xing Yanke , Liu Na
Published: July 2023

Background

Lung cancer is the most common cause of cancer-related mortality in the world. Unfortunately, more than 50% of patients have already metastasized at the time of diagnosis, contributing to morbidity and mortality. Common sites of metastasis are adrenal glands, liver, bone, and brain. Bladder metastasis is rare and should prompt a careful differential consideration of primary bladder cancer.

Case description

Here, we report a 72-year-old female who went to the hospital for “gross hematuria for one day”. Cystoscopy showed space-occupying lesions in the bladder. During the general CT examination, space-occupying lesions in the lower lobe of the lung were found. Peripheral lung cancer with multiple lymph node metastases, pulmonary metastasis, and left pleural effusion were considered. Transurethral cystoscopic resection of the bladder tumor and pleural effusion cell block examination were performed to clarify the diagnosis. Combined with morphological and immunohistochemical results, both pathological results supported a diagnosis of lung adenocarcinoma metastasis, and gene detection was carried out. EGFR, ALK, and ROS-1 were negative. According to the genetic testing results, there was no corresponding targeted drug, so we administered chemotherapy, and one-year survival was achieved, which was better than expected based on other studies.

Conclusion

This paper describes a case of lung adenocarcinoma metastatic to the bladder and includes a review of the literature to provide clinicians with diagnostic and treatment experience and help avoid misdiagnosis and mistreatment.
Hypermethylated GRIA4, a potential biomarker for an early non-invasive detection of metastasis of clinically known colorectal cancer
Authors: Lukacova Eva , Burjanivova Tatiana , Podlesniy Petar , Grendar Marian , Turyova Eva , Kasubova Ivana , Laca Ludovit , Mikolajcik Peter , Kudelova Eva , Vanochova Andrea , Miklusica Juraj , Mersakova Sandra , Lasabova Zora
Published: July 2023

Introduction

Colorectal cancer (CRC) can develop through several dysregulated molecular pathways, including the serrated pathway, characterized by CpG island methylator (CIMP) phenotype. Although the tumor tissue is a commonly tested material, sample types such as stool or plasma, bring a new, non-invasive approach. Several cancer-related methylated genes have been identified in CRC patients, including geneGRIA4, showing promising diagnostic potential. The aim of our study was to develop a sensitive droplet digital PCR (ddPCR) assay to examineGRIA4hypermethylation status in CRC patients and evaluate its diagnostic potential in tissue and liquid biopsy samples.

Methods

In total, 23 patients participated in this study, 7 patients with primary CRC and 16 patients with liver metastasis of clinically known CRC. We obtained tumor and non-tumor tissues (N=17), blood samples pre- and post-surgery (N=22), and blood of five volunteers without a personal cancer history. We have developed and optimized a ddPCR assay forGRIA4hypermethylation detection, from tissue and plasma samples.

Results

We detected significantly increasedGRIA4methylation in tumor tissues compared to their adjacent non-tumor tissue, p<0.0001. Receiver operating characteristic (ROC) analysis defined cutoff values to separate primary tumors and metastases from non-tumor colon/rectum, specifically 36.85% for primary tumors and 34.81% for metastases. All primary tumors were above this threshold. When comparing the methylation levels of metastatic vs. non-tumor tissue, a smaller increase was observed in liver metastasis versus colon tissue (3.6× gain; p=0.001), then in liver metastasis versus adjacent liver tissue (17.4× gain; p<0.0001). On average,GRIA4hypermethylation in primary tumor plasma was 2.8-fold higher (p=0.39), and in metastatic plasma, 16.4-fold higher (p=0.0011) compared to healthy individuals. Hypermethylation in metastatic plasma was on average 5.9 times higher (p=0.051) than in primary tumor plasma. After tumor removal surgery, average hypermethylation decrease in plasma was 1.6× for primary (p=0.037) and 4.5× for metastatic patients (p=0.023).

Discussion

Based on our data, it can be inferred thatGRIA4serves as a tissue specific biomarker for the colon/rectum tissue, thus is suitable for cancer classification. This biomarker showed the potential to be an attractive target for early non-invasive detection of metastases of clinically known CRC, although additional analysis has to be performed.