bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-tiered mentoring community approach to research experiences for local students from disadvantaged and underrepresented minority backgrounds
Authors: McKean Thomas , Bates LaShall , Bates Gary , Wiersma-Mosley Jacquelyn D. , Wickramasinghe S. Ranil
Published: June 2024

Introduction

A research and mentoring program was developed to provide local first-generation students, students returning to school after a professional experience, and underrepresented minority students resources and relationships to guide them toward a STEM degree from a four-year university.

Methods

A multi-tiered mentoring community was formed including direct mentoring from graduate students and faculty advisors, peer mentoring among undergraduate students from different colleges and universities, and high school students to increase the accessibility of research opportunities for this demographic. Local students were recruited from Northwest Arkansas Community College and Upward Bound to combine community college and high school students in a novel manner. The programs were integrated whenever possible to emphasize peer mentoring, including mentoring lunches, research meetings, presentation sessions, conference presentations, and professional development mentoring sessions.

Results

On the post-program survey, students indicated the community formed in the program supported their STEM identity development, provided them with quality relationships, and developed skills valuable to completion of a STEM degree. This identity development was further evidenced by the students presenting their work at a conference and obtaining additional research positions after the summer program ended.

Conclusion

The post-program scores and continued efforts of different demographics of students to pursue STEM highlight the versatility of the multi-tiered mentoring community model to serve students from different ages, backgrounds, and demographics.
Differential involvement of cAMP/PKA-, PLC/PKC- and Ca2+/calmodulin-dependent pathways in GnRH-induced prolactin secretion and gene expression in grass carp pituitary cells
Authors: Li Wensheng , Ye Cheng , He Mulan , Ko Wendy K. W. , Cheng Christopher H. K. , Chan Ying Wai , Wong Anderson O. L.
Published: June 2024

Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in vertebrates. In fish models, GnRH can also induce prolactin (PRL) release, but little is known for the corresponding effect on PRL gene expression as well as the post-receptor signalling involved. Using grass carp as a model, the functional role of GnRH and its underlying signal transduction for PRL regulation were examined at the pituitary level. Using laser capture microdissection coupled with RT-PCR, GnRH receptor expression could be located in carp lactotrophs. In primary cell culture prepared from grass carp pituitaries, the native forms of GnRH, GnRH2 and GnRH3, as well as the GnRH agonist [D-Arg6, Pro9, NEt]-sGnRH were all effective in elevating PRL secretion, PRL mRNA level, PRL cell content and total production. In pituitary cells prepared from the rostral pars distalis, the region in the carp pituitary enriched with lactotrophs, GnRH not only increased cAMP synthesis with parallel CREB phosphorylation and nuclear translocation but also induced a rapid rise in cytosolic Ca2+ by Ca2+ influx via L-type voltage-sensitive Ca2+ channel (VSCC) with subsequent CaM expression and NFAT2 dephosphorylation. In carp pituitary cells prepared from whole pituitaries, GnRH-induced PRL secretion was reduced/negated by inhibiting cAMP/PKA, PLC/PKC and Ca2+/CaM/CaMK-II pathways but not the signalling events via IP3 and CaN/NFAT. The corresponding effect on PRL mRNA expression, however, was blocked by inhibiting cAMP/PKA/CREB/CBP and Ca2+/CaM/CaN/NFAT2 signalling but not PLC/IP3/PKC pathway. At the pituitary cell level, activation of cAMP/PKA pathway could also induce CaM expression and Ca2+ influx via VSCC with parallel rises in PRL release and gene expression in a Ca2+/CaM-dependent manner. These findings, as a whole, suggest that the cAMP/PKA-, PLC/PKC- and Ca2+/CaM-dependent cascades are differentially involved in GnRH-induced PRL secretion and PRL transcript expression in carp lactotrophs. During the process, a functional crosstalk between the cAMP/PKA- and Ca2+/CaM-dependent pathways may occur with PRL release linked with CaMK-II and PKC activation and PRL gene transcription caused by nuclear action of CREB/CBP and CaN/NFAT2 signalling.
Temporal trend of age at menarche in Korean females born between 1927 and 2004: a population-based study
Authors: Lee Da Hye , Kim Jaehyun , Kim Hwa Young
Published: June 2024

Backgrounds

The age at menarche has decreased worldwide. Previous studies on Korean adolescents have reported a downward trend in age at menarche. This study aimed to investigate the current trends in age at menarche among Korean adolescents using nationally representative data.

Materials and methods

The study used data from the Korea National Health and Nutrition Examination Survey 2007–2021. A total of 50,730 females born between 1927 and 2004 with information on age at menarche were included. The trend in age at menarche was analyzed according to 15 birth-year groups (with 5-year intervals) using quantile regression analysis.

Results

The mean age at menarche decreased from 16.92 ± 0.06 years for females born before 1935 to 12.45 ± 0.04 years for females born between 2000 and 2004 (p <.001). According to the percentile group of age at menarche, mean menarche age decreased by –0.071 years per year (95% confidence interval [CI], –0.072 to –0.070) in total, –0.050 years per year (95% CI, –0.052 to –0.048) in the 3rd percentile group, –0.088 years per year (95% CI, –0.091 to –0.085) in the 97th percentile group (p <.001 for all). A decreasing trend of age at menarche was more prominent in the obesity group (–0.080 years per year, 95% CI, –0.082 to –0.078) compared to the non-obesity group (–0.069 years per year, 95% CI, –0.071 to –0.068) (p <.001 for both).

Conclusion

Ongoing downward trend in age at menarche was observed in Korean females born until 2004, decreasing by 0.71 years per decade. The downward trend was faster in individuals with a higher percentile of age at menarche and in those with obesity.
Dependency of mitochondrial quantity on blastocyst timeline obscures its actual effect to pregnancy outcomes
Authors: Chuang Tzu-Hsuan , Chou Hsin-Hua , Kuan Chin-Sheng , Liu Shu-Cheng , Kao Chia-Wei , Wu Yi-Hsin , Lai Hsing-Hua , Hsieh Chia-Lin , Liang Yi-Ting , Chen Chien-Yu , Chen Shee-Uan
Published: June 2024

Objectives

To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy.

Methods

A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints.

Results

Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman’s ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints.

Conclusions

Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.
Loss of carbon stock in the forests of Uttarakhand due to unprecedented seasonal forest fires
Authors: Bargali Himanshu , Pandey Aseesh , Bhatt Dinesh , Sundriyal R. C.
Published: June 2024

Unprecedented seasonal forest fires pose a significant threat to the carbon stocks of diverse ecosystems, particularly in regions like Uttarakhand, west Himalaya. Understanding the impact of varying fire frequencies on different forest types is crucial for effective conservation and management strategies. This study aims to assess the loss of carbon stock in three distinct forest types—Sal, Pine, and Mixed across an elevation gradient in Uttarakhand, facing unprecedented seasonal forest fires. By investigating pre- and post-fire conditions, analyzing biomass dynamics, and mapping fire frequencies, the research aims to provide insights into the complex interplay of fire regimes and forest resilience. The investigation covers vegetation analysis, biomass assessment, and fire frequency mapping. Biomass and carbon stock calculations were carried out using a non-destructive sampling method. Fire frequency maps were generated using Landsat satellite imagery spanning a decade, integrating MODIS hotspot data for classification. The study reveals distinct patterns in biomass changes across Sal, Pine, and Mixed forests in response to varying fire frequencies. Sal forests exhibit resilience to low-intensity fires, while Pine forests show higher sensitivity. Carbon stock contributions of dominant species varied significantly, with Sal and Chir-Pine forests emerging as crucial contributors. High fire frequencies lead to substantial carbon stock reduction in all forest types. The findings emphasize the sensitivity of aboveground biomass to fire frequency, with significant carbon stock loss observed in higher fire frequency classes. The study underscores the importance of nuanced conservation strategies tailored to distinct forest types and species characteristics. This research provides valuable insights for policymakers, forest managers, and conservationists in formulating targeted conservation and management approaches.
Time is of the essence: unveiling the rapid response of Populus to insect feeding
Authors: Pastierovič Filip , Čepl Jaroslav , Kalyniukova Alina , Mogilicherla Kanakachari , Hradecký Jaromír , Bláha Jaromír , Tomášková Ivana
Published: June 2024

Plant metabolism response to insect herbivores is the central theme of this publication. Genetically uniform individuals of European aspen (Populus tremula) were exposed to recurrent feeding by spongy moths (Lepidoptera) at specific time intervals. Changes in physiology, contents of phenolics and saccharides were quantified over the first hour. The unconventional experiment design, integrating analytical methods, and timeline led to the revealing of unexpected dynamics in plant metabolism. The time interval between herbivory initiation and sample collection revealed a pivotal moment, with induced defense activating strongly after 5 min of chewing resulting in an increase in catechin and procyanidin B1. After 10 min, a shift to a tolerant strategy occurs and induced substance concentrations return to control levels. Delayed physiological response was recorded as the first significant difference in transpiration between affected and nonaffected plants and was found after 10 min. A different strategy in exploitation of saccharides after spongy moths infestation was applied because the pool of selected saccharides was rising in the leaves but decreasing in the roots. Placing our results in the context of existing knowledge highlights the uncertain conceptual basis behind the often rigid and definitive classifications in induced plant defense or tolerance strategy.
Advances in next-generation sequencing for relapsed pediatric acute lymphoblastic leukemia: current insights and future directions
Authors: Mohd Nippah Nur Farhana , Abu Nadiah , Ab Mutalib Nurul Syakima , Alias Hamidah
Published: June 2024

Leukemia is one of the most common cancers in children; and its genetic diversity in the landscape of acute lymphoblastic leukemia (ALL) is important for diagnosis, risk assessment, and therapeutic approaches. Relapsed ALL remains the leading cause of cancer deaths among children. Almost 20% of children who are treated for ALL and achieve complete remission experience disease recurrence. Relapsed ALL has a poor prognosis, and relapses are more likely to have mutations that affect signaling pathways, chromatin patterning, tumor suppression, and nucleoside metabolism. The identification of ALL subtypes has been based on genomic alterations for several decades, using the molecular landscape at relapse and its clinical significance. Next-generation sequencing (NGS), also known as massive parallel sequencing, is a high-throughput, quick, accurate, and sensitive method to examine the molecular landscape of cancer. This has undoubtedly transformed the study of relapsed ALL. The implementation of NGS has improved ALL genomic analysis, resulting in the recent identification of various novel molecular entities and a deeper understanding of existing ones. Thus, this review aimed to consolidate and critically evaluate the most current information on relapsed pediatric ALL provided by NGS technology. In this phase of targeted therapy and personalized medicine, identifying the capabilities, benefits, and drawbacks of NGS will be essential for healthcare professionals and researchers offering genome-driven care. This would contribute to precision medicine to treat these patients and help improve their overall survival and quality of life.
Mitochondrial genome complexity in Stemona sessilifolia: nanopore sequencing reveals chloroplast gene transfer and DNA rearrangements
Authors: Xie Yuning , Liu Wenqiong , Guo Liwen , Zhang Xuemei
Published: June 2024

Mitochondria are semi-autonomous organelles in eukaryotic cells with their own genome. Plant mitogenomes differ from animal mitogenomes in size, structure, and repetitive DNA sequences. Despite larger sizes, plant mitogenomes do not have significantly more genes. They exhibit diverse structures due to variations in size, repetitive DNA, recombination frequencies, low gene densities, and reduced nucleotide substitution rates. In this study, we analyzed the mitochondrial genome of Stemona sessilifolia using Nanopore and Illumina sequencing. De-novo assembly and annotation were conducted using Unicycler, Geseq, tRNAscan-SE and BLASTN, followed by codon usage, repeat sequence, RNA-editing, synteny, and phylogenetic analyses. S. sessilifolia’s mitogenome consisted of one linear contig and six circular contigs totaling 724,751 bp. It had 39 protein-coding genes, 27 tRNA genes, and 3 rRNA genes. Transfer of chloroplast sequences accounted for 13.14% of the mitogenome. Various analyses provided insights into genetic characteristics, evolutionary dynamics, and phylogenetic placement. Further investigations can explore transferred genes’ functions and RNA-editing’s role in mitochondrial gene expression in S. sessilifolia.
Health care and contraceptive decision-making autonomy and use of female sterilisation among married women in Malawi
Authors: Alhassan Nurudeen
Published: June 2024

Introduction

Female sterilisation is the most common contraceptive method used globally. The use of female sterilisation is disproportionately low in sub-Sahara Africa (SSA) at just 1%. Nonetheless, the prevalence of sterilisation among married women in Malawi is quite high at about 11%. While a few recent studies in SSA have examined the relationship between women's decision-making autonomy and use of long-acting contraceptives, very few have investigated whether different dimensions of decision-making autonomy predict the use of female sterilisation differently. The objective of this study was therefore to examine the relationship between health care and contraceptive decision-making autonomy and the use of female sterilisation in Malawi.

Data and methods

The study relied on secondary data from the 2015–16 Malawi Demographic and Health Survey. The sample comprised 9,164 married women in Malawi that were using a modern contraceptive. Multinomial logistic regression analysis was used to examine the association between health care and contraceptive decision-making autonomy and the use of female sterilisation, controlling for key socio-demographic characteristics.

Results

The study revealed that the percentage of married women that made health care and contraceptive decisions independently was quite low. The main finding of this study was that contraceptive decision-making autonomy increased the relative likelihood of using female sterilisation while health care autonomy was associated with a lower likelihood of being sterilized. The socio- demographic characteristics that significantly predicted the use of female sterilisation included age, place of residence, household wealth and the number of children a woman had.

Conclusion

This study demonstrates that health care and contraceptive decision making have different effects on the use of female sterilisation among married women in Malawi. Specifically, women with autonomy in health care decision making had a relatively lower likelihood of using female sterilisation while those with contraceptive decision-making autonomy had a higher likelihood of using female sterilisation. This suggests that intervention aimed at increasing the uptake of female sterilisation in Malawi need to focus on empowering women in the contraceptive decision-making domain.
The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients
Authors: Abdurrahman Goran , Pospich Rebecca , Steil Leif , Gesell Salazar Manuela , Izquierdo González Juan José , Normann Nicole , Mrochen Daniel , Scharf Christian , Völker Uwe , Werfel Thomas , Bröker Barbara M. , Roesner Lennart M. , Gómez-Gascón Lidia
Published: June 2024

Background

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis).

Objective

To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp).

Methods

To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry.

Results

We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients’ T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33.

Conclusion

The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.
Exploring gut microbiota’s role in rheumatic valve disease: insights from a Mendelian randomization study and mediation analysis
Authors: Chen Xiwei , Hu Guangwen , Ning Dong , Wang Daxin
Published: June 2024

Background

Investigating the relationship between gut microbiota and Rheumatic Valve Disease (RVD) is crucial for understanding the disease’s etiology and developing effective interventions. Our study adopts a novel approach to examine the potential causal connections between these factors.

Methods

Utilizing a two-sample Mendelian Randomization (MR) framework, we incorporated a multi-variable MR (MVMR) strategy to assess the mediatory mechanisms involved. This approach involved analyzing data from the MiBioGen consortium for gut microbiota and the FinnGen for RVD, among other sources. Instrumental variables (IVs) were carefully selected based on rigorous MR principles, and statistical analysis was conducted using bidirectional two-sample MR, such as inverse variance-weighted (IVW), weighted median, MR-Egger regression and MR Steiger Test methods. The MR-PRESSO strategy was employed for outlier detection, and MVMR was used to untangle the complex relationships between multiple microbiota and RVD.

Results

Our analysis highlighted several gut microbiota classes and families with potential protective effects against RVD, including Lentisphaerae, Alphaproteobacteria, and Streptococcaceae. In contrast, certain genera, such as Eubacterium eligens and Odoribacter, were identified as potential risk factors. The MVMR analysis revealed significant mediation effects of various immune cell traits and biomarkers, such as CD4-CD8- T cells, CD3 on Terminally Differentiated CD8+ T cell and Pentraxin-related protein PTX, elucidating the complex pathways linking gut microbiota to RVD.

Conclusion

This study underscores the intricate and potentially causal relationship between gut microbiota and RVD, mediated through a range of immune and hormonal factors. The use of MVMR in our methodological approach provides a more comprehensive understanding of these interactions, highlighting the gut microbiota’s potential as therapeutic targets in RVD management. Our findings pave the way for further research to explore these complex relationships and develop targeted interventions for RVD.
Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection
Authors: Belean Andrei , Xue Eden , Cisneros Benjamin , Roberson Elisha D. O. , Paley Michael A. , Bigley Tarin M.
Published: June 2024

Introduction

Herpesviruses, including the roseoloviruses, have been linked to autoimmune disease. The ubiquitous and chronic nature of these infections have made it difficult to establish a causal relationship between acute infection and subsequent development of autoimmunity. We have shown that murine roseolovirus (MRV), which is highly related to human roseoloviruses, induces thymic atrophy and disruption of central tolerance after neonatal infection. Moreover, neonatal MRV infection results in development of autoimmunity in adult mice, long after resolution of acute infection. This suggests that MRV induces durable immune dysregulation.

Methods

In the current studies, we utilized single-cell RNA sequencing (scRNAseq) to study the tropism of MRV in the thymus and determine cellular processes in the thymus that were disrupted by neonatal MRV infection. We then utilized tropism data to establish a cell culture system.

Results

Herein, we describe how MRV alters the thymic transcriptome during acute neonatal infection. We found that MRV infection resulted in major shifts in inflammatory, differentiation and cell cycle pathways in the infected thymus. We also observed shifts in the relative number of specific cell populations. Moreover, utilizing expression of late viral transcripts as a proxy of viral replication, we identified the cellular tropism of MRV in the thymus. This approach demonstrated that double negative, double positive, and CD4 single positive thymocytes, as well as medullary thymic epithelial cells were infected by MRV in vivo. Finally, by applying pseudotime analysis to viral transcripts, which we refer to as “pseudokinetics,” we identified viral gene transcription patterns associated with specific cell types and infection status. We utilized this information to establish the first cell culture systems susceptible to MRV infection in vitro.

Conclusion

Our research provides the first complete picture of roseolovirus tropism in the thymus after neonatal infection. Additionally, we identified major transcriptomic alterations in cell populations in the thymus during acute neonatal MRV infection. These studies offer important insight into the early events that occur after neonatal MRV infection that disrupt central tolerance and promote autoimmune disease.
Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis
Authors: Damerau Alexandra , Rosenow Emely , Alkhoury Dana , Buttgereit Frank , Gaber Timo
Published: June 2024

Osteoarthritis (OA) is the most common form of arthritis, characterized by osteophyte formation, cartilage degradation, and structural and cellular alterations of the synovial membrane. Activated fibroblast-like synoviocytes (FLS) of the synovial membrane have been identified as key drivers, secreting humoral mediators that maintain inflammatory processes, proteases that cause cartilage and bone destruction, and factors that drive fibrotic processes. In normal tissue repair, fibrotic processes are terminated after the damage has been repaired. In fibrosis, tissue remodeling and wound healing are exaggerated and prolonged. Various stressors, including aging, joint instability, and inflammation, lead to structural damage of the joint and micro lesions within the synovial tissue. One result is the reduced production of synovial fluid (lubricants), which reduces the lubricity of the cartilage areas, leading to cartilage damage. In the synovial tissue, a wound-healing cascade is initiated by activating macrophages, Th2 cells, and FLS. The latter can be divided into two major populations. The destructive thymocyte differentiation antigen (THY)1─ phenotype is restricted to the synovial lining layer. In contrast, the THY1+ phenotype of the sublining layer is classified as an invasive one with immune effector function driving synovitis. The exact mechanisms involved in the transition of fibroblasts into a myofibroblast-like phenotype that drives fibrosis remain unclear. The review provides an overview of the phenotypes and spatial distribution of FLS in the synovial membrane of OA, describes the mechanisms of fibroblast into myofibroblast activation, and the metabolic alterations of myofibroblast-like cells.
SLE: a cognitive step forward—a synthesis of rethinking theories, causality, and ignored DNA structures
Authors: Rekvig Ole Petter
Published: June 2024

Systemic lupus erythematosus (SLE) is classified by instinctual classification criteria. A valid proclamation is that these formally accepted SLE classification criteria legitimate the syndrome as being difficult to explain and therefore enigmatic. SLE involves scientific problems linked to etiological factors and criteria. Our insufficient understanding of the clinical condition uniformly denoted SLE depends on the still open question of whether SLE is, according to classification criteria, a well-defined one disease entity or represents a variety of overlapping indistinct syndromes. Without rational hypotheses, these problems harm clear definition(s) of the syndrome. Why SLE is not anchored in logic, consequent, downstream interdependent and interactive inflammatory networks may rely on ignored predictive causality principles. Authoritative classification criteria do not reflect consequent causality criteria and do not unify characterization principles such as diagnostic criteria. We need now to reconcile legendary scientific achievements to concretize the delimitation of what SLE really is. Not all classified SLE syndromes are “genuine SLE”; many are theoretically “SLE-like non-SLE” syndromes. In this study, progressive theories imply imperative challenges to reconsider the fundamental impact of “the causality principle”. This may offer us logic classification and diagnostic criteria aimed at identifying concise SLE syndromes as research objects. Can a systems science approach solve this problem?
Circadian rhythm disruption-mediated downregulation of Bmal1 exacerbates DSS-induced colitis by impairing intestinal barrier
Authors: Zhang Zhongchao , Li Wanneng , Han Xu , Tian Dean , Yan Wei , Liu Mei , Cao Li
Published: June 2024

Background

Circadian rhythm disruption (CRD) is thought to increase the risk of inflammatory bowel disease. The deletion of Bmal1, a core transcription factor, leads to a complete loss of the circadian rhythm and exacerbates the severity of dextran sodium sulfate (DSS)-induced colitis in mice. However, the underlying mechanisms by which CRD and Bmal1 mediate IBD are still unclear.

Methods

We used a CRD mouse model, a mouse colitis model, and an in vitro model of colonic epithelial cell monolayers. We also knocked down and overexpressed Bmal1 in Caco-2 cells by transfecting lentivirus in vitro. The collected colon tissue and treated cells were assessed and analyzed using immunohistochemistry, immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction, western blot, flow cytometry, transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining.

Results

We found that CRD mice with downregulated Bmal1 expression were more sensitive to DSS-induced colitis and had more severely impaired intestinal barrier function than wild-type mice. Bmal1-/- mice exhibited more severe colitis, accompanied by decreased tight junction protein levels and increased apoptosis of intestinal epithelial cells compared with wild-type mice, which were alleviated by using the autophagy agonist rapamycin. Bmal1 overexpression attenuated Lipopolysaccharide-induced apoptosis of intestinal epithelial cells and impaired intestinal epithelial cells barrier function in vitro, while inhibition of autophagy reversed this protective effect.

Conclusion

This study suggests that CRD leads to the downregulation of Bmal1 expression in the colon, which may exacerbate DSS-induced colitis in mice, and that Bmal1 may serve as a novel target for treating inflammatory bowel disease.
Beta cells deficient for Renalase counteract autoimmunity by shaping natural killer cell activity
Authors: Bode Kevin , Wei Siying , Gruber Isabella , Li Jian , Kissler Stephan , Yi Peng
Published: June 2024

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing pancreatic beta cells. Recent advancements in the technology of generating pancreatic beta cells from human pluripotent stem cells (SC-beta cells) have facilitated the exploration of cell replacement therapies for treating T1D. However, the persistent threat of autoimmunity poses a significant challenge to the survival of transplanted SC-beta cells. Genetic engineering is a promising approach to enhance immune resistance of beta cells as we previously showed by inactivating the Renalase (Rnls) gene. Here, we demonstrate that Rnls loss of function in beta cells shapes autoimmunity by mediating a regulatory natural killer (NK) cell phenotype important for the induction of tolerogenic antigen-presenting cells. Rnls-deficient beta cells mediate cell–cell contact-independent induction of hallmark anti-inflammatory cytokine Tgfβ1 in NK cells. In addition, surface expression of regulatory NK immune checkpoints CD47 and Ceacam1 is markedly elevated on beta cells deficient for Rnls. Altered glucose metabolism in Rnls mutant beta cells is involved in the upregulation of CD47 surface expression. These findings are crucial to better understand how genetically engineered beta cells shape autoimmunity, giving valuable insights for future therapeutic advancements to treat and cure T1D.
Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis
Authors: Fererberger Tanja , Buechler Christa , Kandulski Arne , Elger Tanja , Loibl Johanna , Schmid Stephan , Sommersberger Stefanie , Gunawan Stefan , Zundler Sebastian , Huss Muriel , Bettenworth Dominik , Kempa Sally , Weidlich Simon , Föh Bandik , Huang Xinyu , Grzegorzek Marcin , Derer-Petersen Stefanie , Günther Ulrich L. , Marquardt Jens U. , Kunst Claudia , Gülow Karsten , Müller Martina , Sina Christian , Schmelter Franziska , Tews Hauke C.
Published: June 2024

Intoduction

Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification.

Methods

Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC.

Results

In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM.

Discussion

These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.
Lipid safety of tenofovir alafenamide during 96-week treatment in treatment-naive chronic hepatitis B patients
Authors: Zhao Wenjuan , Liu Yi , Zhang Mengdi , Cui Zixin , Qu Zhan , Li Yiyang , Wan Meijuan , Wang Wen , Chen Yunru , Shi Lei , Li Jianzhou , Ye Feng
Published: June 2024

Background

This study was aimed at investigating the dynamics of lipids and the effect of TAF on the lipid profile of patients including fatty liver disease in CHB patients.

Methods

The data of TC, LDL-c, HDL-c, TG, and TC/HDL ratio were collected at baseline, 24 weeks, 48 weeks, 72 weeks, and 96 weeks. CHB patients with fatty liver at baseline were further analyzed in a subgroup.

Results

A total of 137 CHB patients treated with TAF were enrolled in this study. During 96 weeks of TAF treatment, there was no significant change in TC, LDL-c, HDL-c, and TG level (P > 0.05). The TC/HDL-c ratio was increased with no significant change (+0.24, P > 0.05). In CHB patients with fatty liver (n = 48), TC, LDL-c, and TC/HDL-c ratio increased gradually during TAF treatment, TG levels increased to 146.63 mg/dL at 48 weeks (P = 0.057) and then decreased, but there was still no significant change compared with the baseline level by 96 weeks (P > 0.05).

Conclusion

TAF treatment had a low effect on the lipid profile of CHB patients over the course of 96 weeks, and it was safe even in patients with fatty liver.

Clinical trial registration

[https://www.chictr.org.cn/showproj.html?proj=65123], identifier [ChiCTR2000041005].
Same duodenal neuroendocrine tumors, different endoscopic resection methods: a case report and literature review
Authors: Liu Jinguo , Yu Liangliang
Published: June 2024

Duodenal neuroendocrine tumors (NETs), comprising 2–3% of all gastrointestinal NETs and 1–3% of all duodenal tumors, are remarkably uncommon. In this report, we described a patient diagnosed with two submucosal tumors in the duodenal bulb. We used two distinct endoscopic resection methods, including endoscopic submucosal dissection (ESD) and submucosal tunneling endoscopic resection (STER), to achieve en bloc resection of the lesions without complications. Pathological evaluation, involving hematoxylin–eosin staining and immunohistochemistry, confirmed the diagnosis of NET. Given the limited operative field and space in the duodenal bulb, STER proved to be a viable endoscopic resection technique.
Case report: A rare case of malacoplakia resembling a malignant tumor of the cervix: a case report and review of the literature
Authors: Li Jiaorong , Mi Jiaying , Wang Juanjuan , Zhuo Zhihong
Published: June 2024

Malacoplakia is a rare chronic granulomatous disease that mostly affects the gastrointestinal tract and urinary tract of immunocompromised patients; malacoplakia rarely effects the female reproductive tract. Here, we report a 56-year-old patient who underwent thymectomy for thymoma and myasthenia gravis prior to developing cervical and vaginal malacoplakia. The patient presented with recurrent vaginal bleeding. We discovered that there were alterations in the cervical cauliflower pattern during colposcopy, which is suggestive of cervical cancer. Pathological examination of the lesion tissue showed that a large number of macrophages aggregated, and M-G bodies with concentric circles and refractive properties were observed between cells. Immunostaining for CD68 and CD163 was positive, and special staining for D-PAS and PAS was positive. The discovery of Escherichia coli in bacterial culture can aid in the diagnosis of malacoplakia. Following surgery, we performed vaginal lavage with antibiotics in addition to resection of local cervical and vaginal lesions. This study provides a fresh perspective on the management of genital malacoplakia.
The impact of pre-rehydration guided by carotid corrected flow time on hypotension prevention following general anesthesia induction in patients undergoing gastrointestinal surgery: a prospective randomized controlled trial
Authors: Li Min , Li Feng , Yu Jiali , Tang Xixi , Zhou Chengfu , Chen Qi , Liu Hongliang
Published: June 2024

Background

Patients undergoing gastrointestinal surgery often experience hypotension following general anesthesia induction due to insufficient volume. This study aimed to assess whether pre-rehydration guided by carotid corrected flow time (FTc) could mitigate post-induction hypotension induced by general anesthesia.

Methods

Patients undergoing resection of gastrointestinal tumors were assigned to either the conventional treatment group (Group C) or the fluid treatment group based on FTc (Group F). Within Group F, patients were further divided into Group A (carotid FTc <340.7 ms) and Group B (carotid FTc ≥340.7 ms) based on pre-rehydration carotid FTc values. Group A patients received pre-rehydration with 250 mL of colloids (hydroxyethyl starch—HES) administered within 15 min until carotid FTc reached ≥340.7 ms to counteract hypovolemia prior to induction. Patients in Group B and Group C received a continuous HES infusion at a rate of 6 mL/kg/h 30 min before induction to compensate for physiological fluid loss. All patients received a perioperative background infusion of 3 mL/kg/h compound sodium chloride, with infusion rates optimized based on mean arterial pressure (MAP) and heart rate (HR). The incidence of post-induction hypotension was compared between Group C and Group F, as well as between Group A and Group B.

Results

The incidence of hypotension after induction was significantly lower in Group F compared to Group C (26.4% vs. 46.7%, respectively; p < 0.001). Patients in Group A received significantly more pre-rehydration, leading to a greater increase in carotid FTc values compared to Group B (336.5 ± 64.5 vs. 174.3 ± 34.1 ms, p = 0.002). However, no significant difference in carotid FTc values after pre-rehydration was observed between the groups. There was no significant difference in the incidence of hypotension after general anesthesia induction between Group A and Group B (22.9% vs. 28.8%, p = 0.535).

Conclusion

Pre-rehydration based on FTc can effectively reduce the occurrence of post-induction hypotension in patients undergoing gastrointestinal surgery who present with insufficient volume.

Clinical trial registration

https://www.chictr.org.cn/showprojEN.html?proj=201481.
Radiation-resistant bacteria in desiccated soil and their potentiality in applied sciences
Authors: Khan Asaf , Liu Guangxiu , Zhang Gaosen , Li Xiangkai
Published: June 2024

A rich diversity of radiation-resistant (Rr) and desiccation-resistant (Dr) bacteria has been found in arid habitats of the world. Evidence from scientific research has linked their origin to reactive oxygen species (ROS) intermediates. Rr and Dr. bacteria of arid regions have the potential to regulate imbalance radicals and evade a higher dose of radiation and oxidation than bacterial species of non-arid regions. Photochemical-activated ROS in Rr bacteria is run through photo-induction of electron transfer. A hypothetical model of the biogeochemical cycle based on solar radiation and desiccation. These selective stresses generate oxidative radicals for a short span with strong reactivity and toxic effects. Desert-inhibiting Rr bacteria efficiently evade ROS toxicity with an evolved antioxidant system and other defensive pathways. The imbalanced radicals in physiological disorders, cancer, and lung diseases could be neutralized by a self-sustaining evolved Rr bacteria antioxidant system. The direct link of evolved antioxidant system with intermediate ROS and indirect influence of radiation and desiccation provide useful insight into richness, ecological diversity, and origin of Rr bacteria capabilities. The distinguishing features of Rr bacteria in deserts present a fertile research area with promising applications in the pharmaceutical industry, genetic engineering, biological therapy, biological transformation, bioremediation, industrial biotechnology, and astrobiology.
Correlation of methane production with physiological traits in Trichodesmium IMS 101 grown with methylphosphonate at different temperatures
Authors: Zou Chuze , Yi Xiangqi , Li He , Bizic Mina , Berman-Frank Ilana , Gao Kunshan
Published: June 2024

The diazotrophic cyanobacterium Trichodesmium has been recognized as a potentially significant contributor to aerobic methane generation via several mechanisms including the utilization of methylphophonate (MPn) as a source of phosphorus. Currently, there is no information about how environmental factors regulate methane production by Trichodesmium. Here, we grew Trichodesmium IMS101 at five temperatures ranging from 16 to 31°C, and found that its methane production rates increased with rising temperatures to peak (1.028 ± 0.040 nmol CH4 μmol POC−1 day−1) at 27°C, and then declined. Its specific growth rate changed from 0.03 ± 0.01 d−1 to 0.34 ± 0.02 d−1, with the optimal growth temperature identified between 27 and 31°C. Within the tested temperature range the Q10 for the methane production rate was 4.6 ± 0.7, indicating a high sensitivity to thermal changes. In parallel, the methane production rates showed robust positive correlations with the assimilation rates of carbon, nitrogen, and phosphorus, resulting in the methane production quotients (molar ratio of carbon, nitrogen, or phosphorus assimilated to methane produced) of 227–494 for carbon, 40–128 for nitrogen, and 1.8–3.4 for phosphorus within the tested temperature range. Based on the experimental data, we estimated that the methane released from Trichodesmium can offset about 1% of its CO2 mitigation effects.
Biofilms, mobile genetic elements and the persistence of pathogens on environmental surfaces in healthcare and food processing environments
Authors: Nkemngong Carine , Teska Peter
Published: June 2024

Biofilms are the natural state for bacterial and fungal species. To achieve surface hygiene in commercial facilities, the presence of biofilms must be adequately considered. However, standard disinfectant and sanitizer efficacy tests required by the US-EPA and the European Committee for Standardization (CEN) do not currently consider the role of environmental biofilms. This selective review will discuss what biofilms are and why they are important. We will also cover where they are commonly found in healthcare and food processing facilities and explore how current antimicrobial test methods required for product registration do not test for the presence of biofilms. Additionally, we will explore how a lack of efficacy against biofilms may play a role in the development of antimicrobial resistance in healthcare facilities due to the exchange of mobile genetic elements that occur readily in a biofilm matrix.
Bioinformatics analysis of the potential receptor and therapeutic drugs for Alzheimer’s disease with comorbid Parkinson’s disease
Authors: Zhou Xuerong , Liu Zhifan , Bai Guiqin , Dazhang Bai , Zhao Peilin , Wang Xiaoming , Jiang Guohui
Published: June 2024

Background

Now, there are no sensitive biomarkers for improving Alzheimer’s disease (AD) and comorbid Parkinson’s disease (PD). The aim of the present study was to analyze differentially expressed genes (DEGs) in brain tissue from AD and PD patients via bioinformatics analysis, as well as to explore precise diagnostic and therapeutic targets for AD and comorbid PD.

Methods

GFE122063 and GSE7621 data sets from GEO in NCBI, were used to screen differentially expressed genes (DEGs) for AD and PD, and identify the intersected genes, respectively. Intersected genes were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, STRING site and Cytoscape were used to construct a protein–protein interaction (PPI) network, CytoNCA algorithm to analyze and evaluate centrality, Mcode plug-in to analyze module, and Cytohubba to screen key genes. Combined GO-KEGG enrichment analysis with Cytoscape algorithm to screen the key gene in AD complicated with PD. Then, the DEGs for AD and PD were imported into the Association Map (CMap) online platform to screen out the top 10 small molecule drugs, and using molecular docking techniques to evaluate the interactions between small molecule drugs and key genes receptors.

Results

In total, 231 upregulated genes and 300 downregulated genes were identified. GO analysis revealed that the DEGs were highly enriched in signal transduction, and KEGG analysis revealed that the DEGs were associated with the MAPK and PI3K-Akt signaling pathways. Epidermal growth factor receptor (EGFR) was identified as a potential receptor gene in AD and comorbid PD. EGFR was upregulated in both AD and PD, and the proteins that interact with EGFR were enriched in the Ras/Raf/MAPK and PI3K/Akt signaling pathways. Semagacestat was identified as a drug with therapeutic potential for treating AD complicated with PD. There was a high binding affinity between semagacestat and EGFRNTD, with seven hydrogen bonds and one hydrophobic bond.

Discussion

Semagacestat may improve the health of patients with AD complicated with PD through the regulation of the Ras/Raf/MAPK and PI3K/Akt signaling pathways by EGFR, providing evidence supporting the structural modification of semagacestat to develop a more effective drug for treating AD complicated with PD.