bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal flora plays a role in the progression of hepatitis-cirrhosis-liver cancer
Authors: Liu Shuyu , Yang Xilan
Published: March 2023

The liver is a vital metabolism and detoxification organ of human body, which is involved in the biotransformation and metabolism of the organism. Hepatitis - cirrhosis - liver cancer are significant and common part of liver diseases. The pathogenesis of liver diseases is generally as followed: inflammation and other pathogenic factors cause persistent damage to the liver, leading to the activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix. Patients with chronic hepatitis have a high risk of developing into liver fibrosis, cirrhosis, and even life-threatening liver cancer, which poses a great threat to public health.As the first organ to come into contact with blood from the gut, the liver is profoundly affected by the intestinal flora and its metabolites, with leaky gut and flora imbalance being the triggers of the liver’s pathological response. So far, no one has reviewed the role of intestinal flora in this process from the perspective of the progression of hepatitis-cirrhosis-liver cancer and this article reviews the evidence supporting the effect of intestinal flora in the progression of liver disease.
Daily meals in context: A quantitative analysis of elementary school students' drawings
Authors: Kinoshita Luna , Goto Aya , Okabe Satoko , Satoh Kenichi , Honda Kaori , Ueda Kimiko , Murakami Michio , Nollet Kenneth E.
Published: March 2023

To investigate school-age children's perspectives on food and nutrition, we pilot tested a method to quantify and analyze crayon drawings collected from students in health education classes at two elementary schools in Fukushima, Japan. Included were 28 students in a mixed class of first and second graders and 26 students in a fourth-grade class. Specific foods, general shapes, and color choices in children's drawings were entered into a spreadsheet and analyzed quantitatively. From first- and second-graders' data, co-occurrence network analysis put meals into three groups: at home, eating out, and lunch boxes. Among fourth graders, co-occurrence network analysis called attention to the cucumber, noteworthy for being a local agricultural product. In addition, students who drew more side dishes also drew more staple foods and main dishes (p = 0.04), used more colors (p = 0.006), and showed satisfaction with their community (p = 0.04). These results suggest that students' understanding of eating was centered on the places where they eat and that they valued regional specialty products. Furthermore, the drawing of side dishes was indicative of a balanced diet, which in turn was associated with higher satisfaction with their community. Our trial indicates that children's drawings can be a useful tool for adults to grasp children's understanding of health-related information in daily living.
Applying a gender lens to biodiversity conservation in High Asia
Authors: Alexander Justine Shanti , Murali Ranjini , Mijiddorj Tserennadmid Nadia , Agvaantseren Bayarjargal , Lhamo Chemi , Sharma Deepshikha , Suryawanshi Kulbhushansingh Ramesh , Zhi Lu , Sharma Koustubh , Young Juliette Claire
Published: March 2023

Community-based conservation efforts represent an important approach to facilitate the coexistence of people and wildlife. A concern, however, is that these efforts build on existing community structures and social norms, which are commonly dominated by men. Some biodiversity conservation approaches may consequently neglect women’s voices and deepen existing inequalities and inequities. This paper presents two community case studies that draw upon the knowledge and experience gained in our snow leopard conservation practice in pastoral and agro-pastoral settings in Mongolia and India to better understand women’s roles and responsibilities. In these settings, roles and responsibilities in livestock management and agriculture are strongly differentiated along gender lines, and significant gaps remain in women’s decision-making power about natural resources at the community level. We argue that context-specific and gender-responsive approaches are needed to build community support for conservation actions and leverage women’s potential contributions to conservation outcomes.
Gender differences in wildlife-dependent recreation on public lands
Authors: Rizzolo Jessica Bell , Delie Jackie , Carlson Shelby C. , Dietsch Alia M.
Published: March 2023

Different groups of people may desire and respond to social and ecological conditions in myriad ways (e.g., increased engagement, avoidance). Thus, managers of nature-based recreation sites open for public use (i.e., “public lands”) would benefit from understanding how people with different lived experiences respond under new conditions brought about by regulatory changes (e.g., infrastructural improvements, reduction of access) or environmental changes (e.g., drought, population declines). From a survey of visitors to public lands, specifically National Wildlife Refuges (i.e., refuges) in the United States, we examine gender differences in (a) participation in wildlife-dependent recreation, (b) visitor experiences, and (c) the effect of regulatory and environmental changes on future participation in preferred activities. Our sample (n= 9,918; 40% who self-selected female) included visitors to 69 refuges during 2018 and 2019. Results indicated that people who self-selected female were more likely to indicate that they don’t like being in nature by themselves, and that people close to them enjoy nature-based recreation. People who self-selected female were less likely to engage in hunting or fishing as their primary activity and noted that regulatory changes supporting these activities (specifically, fewer regulations on fishing, fewer regulations on hunting, and more acreage open to fishing/hunting) could decrease their future participation in their primary activity. Thus, respondents who self-selected female may be displaced or alienated from visiting a site if consumptive activities (e.g., hunting) are prioritized as regulatory mechanisms (e.g., for controlling abundant wildlife populations). Adaptive processes that anticipate - in advance of decisions being made - the potential ramifications of regulations on different subgroups of visitors to public lands can identify differential and inequitable impacts, and thus lead to inclusive management decisions when those impacts are preemptively addressed.
3D-electroanatomical mapping of the left atrium and catheter-based pulmonary vein isolation in pigs: A practical guide
Authors: Hertel Julie Norup , Jerltorp Kezia , Hansen Malthe Emil Høtbjerg , Isaksen Jonas L. , Sattler Stefan Michael , Linz Benedikt , Chaldoupi Sevasti-Maria , Jespersen Thomas , Saljic Arnela , Gang Uffe , Manninger Martin , Linz Dominik
Published: March 2023

Aim

To propose a standardized workflow for 3D-electroanatomical mapping guided pulmonary vein isolation in pigs.

Materials and methods

Danish female landrace pigs were anaesthetized. Ultrasound-guided puncture of both femoral veins was performed and arterial access for blood pressure measurement established. Fluoroscopy- and intracardiac ultrasound-guided passage of the patent foramen ovale or transseptal puncture was performed. Then, 3D-electroanatomical mapping of the left atrium was conducted using a high-density mapping catheter. After mapping all pulmonary veins, an irrigated radiofrequency ablation catheter was used to perform ostial ablation to achieve electrical pulmonary vein isolation. Entrance- and exit-block were confirmed and re-assessed after a 20-min waiting period. Lastly, animals were sacrificed to perform left atrial anatomical gross examination.

Results

We present data from 11 consecutive pigs undergoing pulmonary vein isolation. Passage of the fossa ovalis or transseptal puncture was uneventful and successful in all animals. Within the inferior pulmonary trunk 2–4 individual veins as well as 1–2 additional left and right pulmonary veins could be cannulated. Electrical isolation by point-by-point ablation of all targeted veins was successful. However, pitfalls including phrenic nerve capture during ablation, ventricular arrhythmias during antral isolation close to the mitral valve annulus and difficulties in accessing right pulmonary veins were encountered.

Conclusion

Fluoroscopy- and intracardiac ultrasound-guided transseptal puncture, high-density electroanatomical mapping of all pulmonary veins and complete electrical pulmonary vein isolation can be achieved reproducibly and safely in pigs when using current technologies and a step-by-step approach.
Differential expression of epigenetic modifiers in early and late cardiotoxic heart failure reveals DNA methylation as a key regulator of cardiotoxicity
Authors: Robinson Emma L. , Ameri Pietro , Delrue Leen , Vanderheyden Marc , Bartunek Jozef , Altieri Paola , Heymans Stephane , Heggermont Ward A.
Published: March 2023

Background

Anthracycline-induced cardiotoxicity is a well-known serious clinical entity. However, detailed mechanistic insights on how short-term administration leads to late and long-lasting cardiotoxicity, are still largely undiscovered. We hypothesize that chemotherapy provokes a memory effect at the level of epigenomic DNA modifications which subsequently lead to cardiotoxicity even years after cessation of chemotherapy.

Methods

We explored the temporal evolution of epigenetic modifiers in early and late cardiotoxicity due to anthracyclines by means of RNA-sequencing of human endomyocardial left ventricular biopsies and mass spectrometry of genomic DNA. Based on these findings, validation of differentially regulated genes was obtained by performing RT-qPCR. Finally, a proof-of-concept in vitro mechanistic study was performed to dissect some of the mechanistic aspects of epigenetic memory in anthracycline-induced cardiotoxicity.

Results

Correlation of gene expression between late and early onset cardiotoxicity revealed an R2 value of 0.98, demonstrating a total of 369 differentially expressed genes (DEGs, FDR < 0.05). of which 72% (n = 266) were upregulated, and 28% of genes, (n = 103) downregulated in later as compared to earlier onset cardiotoxicity. Gene ontology analysis showed significant enrichment of genes involved in methyl-CpG DNA binding, chromatin remodeling and regulation of transcription and positive regulation of apoptosis. Differential mRNA expression of genes involved in DNA methylation metabolism were confirmed by RT-qPCR in endomyocardial biopsies. In a larger biopsy cohort, it was shown that Tet2 was more abundantly expressed in cardiotoxicity biopsies vs. control biopsies and vs. non-ischemic cardiomyopathy patients. Moreover, an in vitro study was performed: following short-term doxorubicin treatment, H9c2 cells were cultured and passaged once they reached a confluency of 70%–80%. When compared to vehicle-only treated cells, in doxorubicin-treated cells, three weeks after short term treatment, Nppa, Nppb, Tet1/2 and other genes involved in active DNA demethylation were markedly upregulated. These alterations coincided with a loss of DNA methylation and a gain in hydroxymethylation, reflecting the epigenetic changes seen in the endomyocardial biopsies.

Conclusions

Short-term administration of anthracyclines provokes long-lasting epigenetic modifications in cardiomyocytes both in vivo and in vitro, which explain in part the time lapse between the use of chemotherapy and the development of cardiotoxicity and, eventually, heart failure.
A qualitative study to explore strategies to improve the Road to Health Application for maternal and child health outcomes in South Africa
Authors: Dietrich Janan Janine , Tsotetsi Lerato , Dubazane Thenjiwe , Tshabalala Gugulethu , Maimela Boitumelo , Weiss Martin , Mulaudzi Mamakiri
Published: March 2023

Background

The Road to Health Application (RTHA) is essentially a digitalized version of the National Department of Health’s Road to Health book, and a hand-printed booklet given to mothers at the birth of each baby. The RTHA, like the booklet, provides guidelines for maternal and child health outcomes, with the goal of creating a database of children and caregivers in South Africa and teaching them how to raise a healthy child. This paper explored potential barriers and enablers to using the RTHA in the South African context based on user experiences.

Methods

Using a qualitative design, we conducted 50 serial interviews (two separate interviews, 1 month apart). Through convenience, sampling eligible participants were 18 years  or older women who were pregnant and/or had a child under the age of 5 years. Participants included 25 existing users and 25 new users of the RTHA, who owned android smart phones at enrollment. Existing users were recruited telephonically through the National Department of Health database, and new users were approached at the antenatal care unit and wellness baby clinic (women with children under 5 years) at the Chris Hani Baragwaneth Academic Hospital. Upon enrollment, participants completed a brief survey on sociodemographics and mobile phone use, and thereafter, they had a baseline interview followed by a telephonic interview 1 month later. A semistructured interview guide was used to explore barriers, enablers, and the usability of the RTHA. Using thematic data analysis, we identified enablers and barriers to the use of the RTHA.

Results

A third (33%) of all participants reported IsiZulu as their main language of communication, and 6% of the participants reported English as their main language of communication. The RTHA was an important addition to the booklet that helped keep new mothers informed about child immunization and provided important information about healthy child rearing practices. However, multiple barriers were cited to using the RTHA; these included the fact that the app was only available in two languages, high data costs, lack of access to smart phones, and app functionalities. The enablers to using the RTHA included the accessibility of important information regarding prenatal and postnatal childcare.

Conclusion

This study gives insight into the barriers and enablers from the end-user perspective to improve the RTHA for future use in South Africa and offers guidance on how to improve the RTHA to be more user-friendly, which could increase its usability among mothers. It further emphasizes the need to consider the challenges experienced by users in South Africa when developing future mobile health interventions to increase uptake.
Pharmacological approaches to the prevention of type 2 diabetes mellitus
Authors: Majety Priyanka , Lozada Orquera Faustina Alejandra , Edem Dinesh , Hamdy Osama
Published: March 2023

About 1 in 10 adults worldwide are estimated to have diabetes mellitus. They are at risk of developing life-threatening complications resulting in reduced quality of life, increased mortality and higher healthcare costs. The ability to prevent or delay type 2 diabetes mellitus (T2DM) by modifying some of its risk factors has been hypothesized for decades. The long and often gradual time-course of increasing dysglycemia prior to diabetes diagnosis suggests that interventions during that period could be effective in preventing T2DM. In addition to lifestyle modifications, certain drugs prevent or slow development of hyperglycemia. Recently, drugs used for obesity management were shown to prevent T2DM. In this review, we discuss various pharmacotherapeutic options for preventing T2DM.
Global publication trends and research hotspots of the gut-liver axis in NAFLD: A bibliometric analysis
Authors: Yang Shuangjie , Yu Deshuai , Liu Junjie , Qiao Yanfang , Gu Shuxiao , Yang Ran , Chai Xinlou , Wang Wei
Published: March 2023

Background

Nonalcoholic Fatty Liver Disease(NAFLD)refers to a spectrum of diseases ranging from simple liver steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Bidirectional cross-talk between the gut-liver axis plays an important role in the pathogenesis of NAFLD. To learn more about the gut-liver axis in NAFLD, this study aims to provide a comprehensive analysis from a bibliometric perspective.

Method

Literature related to the gut-liver axis in NAFLD from 1989 to 2022 was extracted from the Web of Science Core Collection. Based on Microsoft Excel, CiteSpace and Vosviewer, we conducted to analyze the number of publications, countries/regions, institutions, authors, journals, references, and keywords.

Results

A total of 1,891 literature since 2004 was included, with the rapid growth of the number of papers on the gut-liver axis in NAFLD annually. These publications were mainly from 66 countries and 442 institutions. Of the 638 authors analyzed, Bernd Schnabl was the one with the most publications, and Patrice D. Cani was the one with the most co-citations. International Journal of Molecular Sciences is the journal with the most articles published, and Hepatology is the journal with the most citations. The most common keywords are gut microbiota, inflammation, and insulin instance, which are current research hotspots. Short-chain fatty acid, in vitro, randomized controlled trial in clinical, and diabetes mellitus represent the research frontiers in this field and are in a stage of rapid development.

Conclusion

This is the first study to conduct a comprehensive bibliometric analysis of publications related to the gut-liver axis in NAFLD. This study reveals that gut microbiota, inflammation, insulin resistance, short-chain fatty acids, and randomized controlled trial will be the hotspots and new trends in the gut-liver axis in NAFLD research, which could provide researchers with key research information in this field and is helpful for further exploration of new research directions.
Artificial oocyte activation using Ca2+ ionophores following intracytoplasmic sperm injection for low fertilization rate
Authors: Akashi Kazuhiro , Yamada Mitsutoshi , Jwa Seung Chik , Utsuno Hiroki , Kamijo Shintaro , Hirota Yasushi , Tanaka Mamoru , Osuga Yutaka , Kuji Naoaki
Published: March 2023

This large multi-center retrospective study examined whether artificial oocyte activation (AOA) using Ca2+ ionophore following ICSI improves the live birth rate for couples with previous ICSI cycles of unexplained low fertilization rate. In this large-scale multi-center retrospective study conducted in Japan, data were collected from Keio University and 17 collaborating institutions of the Japanese Institution for Standardizing Assisted Reproductive Technology. Between January 2015 and December 2019, 198 couples were included in this study. Oocytes for both the intervention and control groups were procured from the same pool of couples. Oocytes obtained from ICSI cycles with no or low fertilization rate (<50%) with unknown causes were included in the control (conventional ICSI) group while oocytes procured from ICSI cycles followed by performing AOA were assigned to the intervention (ICSI-AOA) group. Those fertilized with surgically retrieved sperm were excluded. ICSI-AOA efficacy and safety were evaluated by comparing these two groups. Live birth rate was the primary outcome. The ICSI-AOA group (2,920 oocytes) showed a significantly higher live birth per embryo transfer rate (18.0% [57/316]) compared to that of the conventional ICSI group with no or low fertilization rate (1,973 oocytes; 4.7% [4/85]) (odds ratio 4.5, 95% confidence interval 1.6–12.6; P<0.05). A higher live birth rate was observed in younger patients without a history of oocyte retrieval. Miscarriage, preterm delivery, and fetal congenital malformation rates were similar between the two groups. ICSI-AOA may reduce fertilization failure without increasing risks during the perinatal period. AOA may be offered to couples with an ICSI fertilization rate < 50%.
A novel mechanism for high-altitude adaptation in hemoglobin of black-spotted frog (Pelophylax nigromaculatus)
Authors: Ma Ming , Pu Peng , Niu Zhiyi , Zhang Tao , Wu Juan , Tang Xiaolong , Chen Qiang
Published: March 2023

Understanding how animals living in highland adapt to extreme conditions is critical to evolutionary biology. In contrast to birds and mammals, little information was available on the adaptation mechanisms for O2 transport in high-altitude ectothermic vertebrates. Here we report for the first time on hematological parameters, amino acid sequences of α and β chains of hemoglobin (Hb), O2 affinity of purified hemoglobins (Hbs) and their sensitivities to anion allosteric effector (H+, Cl−, ATP) and temperature in the high-altitude (2,292 m) black-spotted frogs (Pelophylax nigromaculatus) from the Qinghai-Tibet plateau (QTP) compared with the low-altitude (135 m) population. Our results showed that high-altitude black-spotted frogs exhibit significantly increased relative lung mass, hematocrit, and hemoglobin concentration, but significantly decreased body mass and erythrocyte volume, which could improve the blood O2 carrying capability. Compared with the low-altitude population, the purified Hbs of high-altitude black-spotted frogs possessed significantly higher intrinsic Hb-O2 affinity, similar low anion allosteric effector sensitivities, Bohr effects and temperature sensitivities. The elevated Hb-O2 affinity of highland frogs could maximize the O2 extraction from the lungs. Molecular dynamics simulations showed that the Gln123Glu substitution on α2 chain in highland frogs could form a hydrogen bond with 127Lys on α2 chain, resulting in the elimination of a hydrogen bond between 127Lys on α2 chain and 141Arg on α1 chain. This could weaken the interaction between two semirigid dimers (α1β1 and α2β2) and then lead to the high intrinsic Hb-O2 affinity in high-altitude black-spotted frogs.
Integrating traditional ecological knowledge into US public land management: Knowledge gaps and research priorities
Authors: Souther Sara , Colombo Sarah , Lyndon Nanebah N.
Published: March 2023

Traditional Ecological Knowledge (TEK) is an understanding of natural systems acquired through long-term human interactions with particular landscapes. Traditional knowledge systems complement western scientific disciplines by providing a holistic assessment of ecosystem dynamics and extending the time horizon of ecological observations. Integration of TEK into land management is a key priority of numerous groups, including the United Nations and US public land management agencies; however, TEK principles have rarely been enshrined in national-level US policy or planning. We review over 20 years of TEK literature to describe key applications of TEK to ecological understanding, conservation, restoration and land management generally. By identifying knowledge gaps, we highlight research avenues to support the integration of TEK into US public land management, in order to enhance conservation approaches and participation of historically underrepresented groups, particularly American Indian Tribes, in the stewardship of ancestral lands critical to the practice of living cultural traditions.
Mixed planting improves soil aggregate stability and aggregate-associated C-N-P accumulation in subtropical China
Authors: He Yaqin , Zhang Qianchun , Jiang Chenyang , Lan Yahui , Zhang Han , Ye Shaoming
Published: March 2023

Research on the variations in soil aggregate stability and ecological stoichiometry at aggregate scales by stand type is of great significance in investigating the distribution, limitation, balance, and cycling of organic carbon, nitrogen, and phosphorus (C-N-P). However, the effect of pure and mixed Chinese fir plantations on soil aggregate stability, organic carbon (OC), total nitrogen (TN), and total phosphorus (TP) stoichiometry characteristics at aggregate scales is still unclear. In this research, we explored the variations in soil aggregate mean weight diameter (MWD) and geometric mean diameter (GMD); soil OC, TN, and TP contents and stocks and the C:N:P ratios as affected by different stand types (mixed stands of Chinese fir and Mytilaria laosensis, mixed stands of Chinese fir and Michelia macclurei, and pure stand of Chinese fir); and aggregate size (<0.25, 0.25–1, 1–2, and >2 mm) at 0–20 and 20–40 cm depths in subtropical China. The soil OC and TN contents, as well as C:N:P ratios declined as aggregate size increased, whereas the C-N-P stocks showed the opposite tendencies, which were more distributed in >2 mm aggregates. Mixed stands of Chinese fir and M. laosensis with Chinese fir and M. macclurei displayed significantly higher soil aggregate stability, aggregate-associated TP content, OC and TN contents and stocks, and C:N and C:P ratios than did pure stands of Chinese fir. Soil aggregate stability was significantly positively correlated with the C-N-P contents and stocks as well as the C:N and C:P ratios, especially the C:N ratio and TN content. Overall, this work offers further information for scientific management and sustainable development of Chinese fir plantations, soil OC and nutrient cycling with ecological stoichiometry in the global terrestrial ecosystem.
Logging has legacy effects on the structure of soil fungal communities several decades after cessation in Western Cascade forest stands
Authors: Spencer Max W. , Roy Bitty A. , Thornton Tiffany E. , Silva Lucas C. R. , McGuire Krista L.
Published: March 2023

Introduction

Logging impacts millions of hectares of forests globally every year, and not only affects tree cover, but also disrupts below-ground soil communities that are essential for forest ecosystems. Soil fungi are particularly vulnerable to such disturbances due to their reliance upon plant hosts as their source of carbon. Fluctuations within the major guilds of fungi important for forest function can have ramifications for plant communities and biogeochemical processes. We addressed questions about soil fungal communities in temperate forest stands with varying logging histories: (1) Do assembly patterns of soil fungal communities and functional guilds reflect historical differences in logging legacies? (2) Does sequencing of below-ground communities of fungi resemble the composition of surveys of fungal fruiting bodies? (3) How do fungal communities in the litter layer differ from those in the soil and do these assembly patterns change with logging history?

Methods

Our study took place in the H. J. Andrews Experimental Forest in western Oregon, USA. We sampled soil and litter (Oi—Oe) in three sites with different logging histories: one clear cut in 1974, one selectively logged and thinned three times between 1974 and 2001, and one unlogged. We sequenced soil fungi separately for mineral soil samples and litter samples. Additionally, we compiled fruiting-body studies from 1972 through the present to compare with our eDNA samples.

Results

We found that four decades after logging had ceased there were detectable signatures within the soil fungal communities that distinguished logged from unlogged sites, indicating a legacy that affects many generations of fungi (PERMANOVA; p < 0.001 for both soil and litter fungi). There were also significant differences between litter and mineral soil communities (PERMANOVA; p < 0.001) with higher relative abundances of pathogens within the litter layer and a greater proportion of mycorrhizal fungi in the soil.

Discussion

These results highlight the importance of including forest litter in studies, as entire guilds of fungi can be underestimated when considering a single fraction. Together, these results have repercussions for the regeneration of forests following logging, as the composition of fungal guilds important to plant functions do not fully recover even after decades of cessation.
Analysis of common genetic variation across targets of microRNAs dysregulated both in ASD and epilepsy reveals negative correlation
Authors: Stella Carol , Díaz-Caneja Covadonga M. , Penzol Maria Jose , García-Alcón Alicia , Solís Andrea , Andreu-Bernabeu Álvaro , Gurriarán Xaquín , Arango Celso , Parellada Mara , González-Peñas Javier
Published: March 2023

Genetic overlap involving rare disrupting mutations may contribute to high comorbidity rates between autism spectrum disorders and epilepsy. Despite their polygenic nature, genome-wide association studies have not reported a significant contribution of common genetic variation to comorbidity between both conditions. Analysis of common genetic variation affecting specific shared pathways such as miRNA dysregulation could help to elucidate the polygenic mechanisms underlying comorbidity between autism spectrum disorders and epilepsy. We evaluated here the role of common predisposing variation to autism spectrum disorders and epilepsy across target genes of 14 miRNAs selected through bibliographic research as being dysregulated in both disorders. We considered 4,581 target genes from various in silico sources. We described negative genetic correlation between autism spectrum disorders and epilepsy across variants located within target genes of the 14 miRNAs selected (p = 0.0228). Moreover, polygenic transmission disequilibrium test on an independent cohort of autism spectrum disorders trios (N = 233) revealed an under-transmission of autism spectrum disorders predisposing alleles within miRNAs’ target genes across autism spectrum disorders trios without comorbid epilepsy, thus reinforcing the negative relationship at the common genetic variation between both traits. Our study provides evidence of a negative relationship between autism spectrum disorders and epilepsy at the common genetic variation level that becomes more evident when focusing on the miRNA regulatory networks, which contrasts with observed clinical comorbidity and results from rare variation studies. Our findings may help to conceptualize the genetic heterogeneity and the comorbidity with epilepsy in autism spectrum disorders.
The construction and analysis of tricarboxylic acid cycle related prognostic model for cervical cancer
Authors: Chen Guanqiao , Hong Xiaoshan , He Wanshan , Ou Lingling , Chen Bin , Zhong Weitao , Lin Yu , Luo Xiping
Published: March 2023

Introduction: Cervical cancer (CC) is the fourth most common malignant tumor in term of in incidence and mortality among women worldwide. The tricarboxylic acid (TCA) cycle is an important hub of energy metabolism, networking one-carbon metabolism, fatty acyl metabolism and glycolysis. It can be seen that the reprogramming of cell metabolism including TCA cycle plays an indispensable role in tumorigenesis and development. We aimed to identify genes related to the TCA cycle as prognostic markers in CC.

Methods: Firstly, we performed the differential expressed analysis the gene expression profiles associated with TCA cycle obtained from The Cancer Genome Atlas (TCGA) database. Differential gene list was generated and cluster analysis was performed using genes with detected fold changes >1.5. Based on the subclusters of CC, we analysed the relationship between different clusters and clinical information. Next, Cox univariate and multivariate regression analysis were used to screen genes with prognostic characteristics, and risk scores were calculated according to the genes with prognostic characteristics. Additionally, we analyzed the correlation between the predictive signature and the treatment response of CC patients. Finally, we detected the expression of ench prognostic gene in clinical CC samples by quantitative polymerase chain reaction (RT-qPCR).

Results: We constructed a prognostic model consist of seven TCA cycle associated gene (ACSL1, ALDOA, FOXK2, GPI, MDH1B, MDH2, and MTHFD1). Patients with CC were separated into two groups according to median risk score, and high-risk group had a worse prognosis compared to the low-risk group. High risk group had lower level of sensitivity to the conventional chemotherapy drugs including cisplatin, paclitaxel, sunitinib and docetaxel. The expression of ench prognostic signature in clinical CC samples was verified by qRT-PCR.

Conclusion: There are several differentially expressed genes (DEGs) related to TCA cycle in CC. The risk score model based on these genes can effectively predict the prognosis of patients and provide tumor markers for predicting the prognosis of CC.
Tissue-resident memory T cells in gastrointestinal tumors: turning immune desert into immune oasis
Authors: Liang Mengjie , Wang Xingzhou , Cai Daming , Guan Wenxian , Shen Xiaofei
Published: March 2023

Tissue-resident memory T cells (Trm) are a particular type of T cell subgroup, which stably reside in tissues and have been revealed to be the most abundant memory T cell population in various tissues. They can be activated in the local microenvironment by infection or tumor cells and rapidly clean them up to restore homeostasis of local immunity in gastrointestinal tissues. Emerging evidence has shown that tissue-resident memory T cells have great potential to be mucosal guardians against gastrointestinal tumors. Therefore, they are considered potential immune markers for immunotherapy of gastrointestinal tumors and potential extraction objects for cell therapy with essential prospects in clinical translational therapy. This paper systematically reviews the role of tissue-resident memory T cells in gastrointestinal tumors and looks to the future of their prospect in immunotherapy to provide a reference for clinical application.
The causality between intestinal flora and allergic diseases: Insights from a bi-directional two-sample Mendelian randomization analysis
Authors: Jin Qiubai , Ren Feihong , Dai Dan , Sun Nan , Qian Yiyun , Song Ping
Published: March 2023

Background

Growing evidence shows a significant association between intestinal flora and allergic diseases, specifically atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). However, the causality has not yet been clarified.

Objective

We conducted a bidirectional two-sample Mendelian randomization (TSMR) analysis to study the causal relationships between intestinal flora classification and AD, AR, or AA.

Materials and methods

We obtained summary data of intestinal flora, AD, AR, and AA from a genome-wide association research. The inverse-variance weighted method is the primary method for analyzing causality in the TSMR analysis. Several sensitivity analyses were conducted to examine the stability of TSMR results. Reverse TSMR analysis was also performed to assess whether there was a reverse causality.

Results

A total of 7 bacterial taxa associated with AD, AR, and AA were identified by the current TSMR analysis. Specifically, the genus Dialister(P=0.034)and genus Prevotella(P=0.047)were associated with a higher risk of AD, whereas class Coriobacteriia (P=0.034) and its child taxon, order Coriobacteriales (P=0.034) and family Coriobacteriaceae (P=0.034), all had a protective effect on AR. In addition, the family Victivallaceae (P=0.019) was identified as a risk factor for AR. We also noticed a positive association between the genus Holdemanella (P=0.046) and AA. The reverse TSMR analysis didn’t suggest any evidence of reverse causality from allergic diseases to the intestinal flora.

Conclusion

We confirmed the causal relationship between intestinal flora and allergic diseases and provided an innovative perspective for research on allergic diseases: targeted regulation of dysregulation of specific bacterial taxa to prevent and treat AD, AR, and AA.
Immunization with Tp0954, an adhesin of Treponema pallidum, provides protective efficacy in the rabbit model of experimental syphilis
Authors: He Yuxing , Chen Dejun , Fu Yue , Huo Xinzhuo , Zhao Feijun , Yao Ling , Zhou Xiuping , Qi Pengfei , Yin Haoquan , Cao Longgu , Ling Hui , Zeng Tiebing
Published: March 2023

Syphilis, a chronic multisystemic disease caused by spirochete Treponema pallidum subspecies pallidum infection, continues to be a serious global health problem and congenital syphilis remains a major cause of adverse outcomes in pregnancy in developing countries. The development of an effective vaccine is the most cost-effective way to eliminate syphilis, but so far has been elusive. Here, we evaluated the immunogenicity and protective efficacy of Tp0954, a T. pallidum placental adhesin, as a potential vaccine candidate in a New Zealand White rabbit model of experimental syphilis. Animals immunized with recombinant Tp0954 (rTp0954) produced high titers of Tp0954-specific serum IgG, high levels of IFN-γ from splenocytes and specific splenocyte proliferation response when compared to control animals immunized with PBS and Freund’s adjuvant (FA). Furthermore, rTp0954 immunization significantly delayed the development of cutaneous lesions, promoted inflammatory cellular infiltration at the primary lesion sites, as well as inhibited T. pallidum dissemination to distal tissues or organs when compared with that of the control animals. In addition, the naïve rabbits receiving popliteal lymph nodes from Tp0954-immunized, T. pallidum-challenged animals were not infected by T. pallidum, confirming sterile immunity. These findings suggest that Tp0954 is a potential vaccine candidate against syphilis.
Transcription factors in megakaryocytes and platelets
Authors: Yuan Hengjie , Liu Yafan , Zhang Jianning , Dong Jing-fei , Zhao Zilong
Published: March 2023

Transcription factors bind promoter or regulatory sequences of a gene to regulate its rate of transcription. However, they are also detected in anucleated platelets. The transcription factors RUNX1, GATA1, STAT3, NFκB, and PPAR have been widely reported to play key roles in the pathophysiology of platelet hyper-reactivity, thrombosis, and atherosclerosis. These non-transcriptional activities are independent of gene transcription or protein synthesis but their underlying mechanisms of action remain poorly defined. Genetic and acquired defects in these transcription factors are associated with the production of platelet microvesicles that are known to initiate and propagate coagulation and to promote thrombosis. In this review, we summarize recent developments in the study of transcription factors in platelet generation, reactivity, and production of microvesicles, with a focus on non-transcriptional activities of selected transcription factors.
Case report: Mucous membrane pemphigoid with complicated autoantibody profile indicating the necessity of comprehensive diagnostic methods and the contribution of IgA autoantibodies
Authors: Liu Weijun , Li Huicheng , Jin Yun , Cheng Lifang , Shi Luhuai , Gao Yangmin , Zhou Zhijun , Feng Suying , Qian Hua , Hashimoto Takashi , Li Xiaoguang
Published: March 2023

Mucous membrane pemphigoid (MMP) is a type of subepithelial autoimmune bullous disease, affecting various mucosae, occasionally with skin lesions. Both diagnosis and treatment of MMP are difficult. Although multiple autoantigens have been identified for MMP, the pathogenesis of MMP is still unclear. In this study, we presented a female MMP case with extensive oral mucosal lesions and skin lesions, particularly on the extremities. IgG and IgA autoantibodies against multiple autoantigens including BP180, laminin 332, integrinα6β4 and desmoglein 3, and IgM autoantibodies against BP180 were identified during the disease course. Compared with IgG autoantibodies, the levels of IgA autoantibodies against various autoantigens decreased more significantly with improvement of clinical features after the initiation of treatments. Our findings indicated the importance of comprehensive autoantibody screening for different immunoglobulin types and autoantigens at multiple time points for the precise diagnosis of various autoimmune bullous diseases, and the significant involvement of IgA autoantibodies into the pathogenesis of MMP.
TOX regulates T lymphocytes differentiation and its function in tumor
Authors: Niu Haiyue , Wang Huaquan
Published: March 2023

Thymocyte selection-associated high mobility group box protein (TOX) is expressed differently at all T lymphocytes development stages. Owing to more advanced scientific and technological means, including single-cell sequencing technology, heterogeneity of T lymphocytes and TOX has gradually been revealed. Further exploration of such heterogeneity will help us comprehend the developmental stage and functional characteristics of T lymphocytes in greater detail. Emerging evidence supports its regulation not only in exhausting, but also in activating T lymphocytes, thereby verifying TOX heterogeneity. TOX can be used not only as a latent intervention target for tumor diseases and chronic infections, and a therapeutic strategy for autoimmune diseases, but also as a critical factor predicting the drug response and overall survival of patients with malignant tumors.
Assessment of marine ecosystem health and its key influencing factors in Laizhou Bay, China
Authors: Wu Wen , Hu Jinming , Song Dehai
Published: March 2023

Introduction

Major bays worldwide have been disturbed by human pressures to varying degrees in recent years, resulting in many ecological and environmental issues. Maintaining the health of the bay ecosystem has national and international significances, as it enhances the environmental regulation function and resource development value of the region. This study aims to examine the evolution trend and regulatory mechanism of ecosystem health in Laizhou Bay (LZB), China.

Methods

A comprehensive DPSIR-based indicator framework is established, comprising 40 representative indicators of the natural environment status, ecological service function, and social values of the LZB ecosystem. The subjective and objective integrated weighting method is applied to determine the indicator weight. The Ecosystem Health Index is then calculated to assess the LZB ecosystem health from 1980 to 2019 and key influencing factors are identified through the scenario analysis.

Results

The results show that the health status of the LZB ecosystem has fluctuated and then increased overall over the past 40 years, with a fairly healthy state in the 1980s, an unhealthy state in 2005, and then a rebound to a subhealthy state. The key factors affecting the LZB ecosystem health are mostly pressure items, with land-based pollution, particularly agricultural non-point source pollution, having a more significant impact than reclamations.

Discussion

Reasonable recommendations are finally put forward on improving the ecosystem health in the study area, including refining the legislation and integrated mechanism related to regional management, building a coordinated land-sea governance system and exploring new technologies for integrated marine management. This study fills the knowledge gap of ecosystem health assessment for the entire LZB in such a long-time scale, and the research outcomes are expected to provide scientific references and guidance for decision-making and social-economic sustainable development in LZB and other bays.
Geographic information system-based comprehensive oil spill risk assessment in China’s Bohai Sea
Authors: Wang Yebao , Du Peipei , Liu Baijing , Wu Xiaoqing
Published: March 2023

The Chinese Bohai Sea is a semi-enclosed, highly vulnerable continental sea that is exposed to the risk of oil spills due to offshore oil and gas activities. In this study, a geographic information system (GIS)-based “tanks–pipelines–platforms–ships–channels” (TPPSC) comprehensive framework, including a storage tank indicator, a pipeline indicator, a platform indicator, a ship indicator, and a channel indicator, was built to analyze the comprehensive marine oil spill risk in the Bohai Sea and to show the spatial differentiation of risk using GIS and the entropy weight method (EWM). The proposed method will overcome the shortcomings of the traditional statistical and scenario analysis theories. The results show that extremely high-risk areas are mostly located in Liaodong Bay and Bohai Bay; high-risk areas are located in the Bohai Strait and on the north side of the Shandong Peninsula; moderate-risk areas are mainly located on both sides of the Bohai Strait; low-risk areas are located on the south side of Liaodong Bay, in the middle of the Bohai Strait, and in Laizhou Bay; and extremely low-risk areas are located on the west side of Bohai Bay, the south side of Laizhou Bay, and the middle of the Bohai Sea. This framework demonstrated the applicability of the new risk assessment model, and the evaluation tests provided useful information for future research on marine oil spill risk management.
Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis
Authors: Margaroli Camilla , Benson Paul , Gastanadui Maria G. , Song Chunyan , Viera Liliana , Xing Dongqi , Wells J. Michael , Patel Rakesh , Gaggar Amit , Payne Gregory A.
Published: March 2023

Objectives

Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics.

Background

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear.

Methods

Autopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue.

Results

We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels.

Conclusion

Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis, and endothelial activation as key drivers of cardiovascular events during COVID-19.
Molecular insight in intrarenal inflammation affecting four main types of cells in nephrons in IgA nephropathy
Authors: Zhang Haidong , Deng Zhenling , Wang Yue
Published: March 2023

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and the leading cause of kidney failure in the world. The current widely accepted framework for its pathogenesis is the “multi-hit hypothesis.” In this review, we mainly discussed the intrarenal inflammation in IgAN, which is initiated by immune complex deposition with complement molecule activation, by focusing on four main types of cells in nephrons including mesangial cells, endothelial cells, podocytes, and tubular epithelial cells (TECs). Galactose-deficient IgA1 (Gd-IgA1)-containing immune complexes deposit in the mesangium and activate complement molecules and mesangial cells. Activation of mesangial cells by Gd-IgA1 deposition with enhanced cellular proliferation, extracellular matrix (ECM) expansion, and inflammatory response plays a central role in the pathogenesis of IgAN. Regional immune complex deposition and mesangial–endothelial crosstalk result in hyperpermeability of endothelium with loss of endothelial cells and infiltration barrier proteins, and recruitment of inflammatory cells. Podocyte damage is mainly derived from mesangial–podocyte crosstalk, in which tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), renin-angiotensin-aldosterone system (RAAS), and micro-RNAs are the major players in podocyte apoptosis and disorganization of slit diaphragm (SD) related to proteinuria in patients with IgAN. In addition to filtrated proteins into tubulointerstitium and mesangial–tubular crosstalk involved in the injury of TECs, retinoic acid has been discovered innovatively participating in TEC injury.