bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide Identification and Expression Analysis of RcMYB Genes in Rhodiola crenulata
Authors: Xu Binjie , Chen Bang , Qi Xiaoli , Liu Shunli , Zhao Yibing , Tang Ce , Meng Xianli
Published: March 2022

Modern research has proved that the main medicinal component of Rhodiola crenulata, which has a wide range of medicinal value, is its secondary metabolite salidroside. The MYB transcription factor family is widely involved in biosynthesis of second metabolism and other roles in the stress response in plants, so a genome-wide identification and analysis for this family in R. crenulata is worth conducting. In this research, genome-wide analysis identified 139 MYB genes based on conserved domains in the R. crenulata genome, and 137 genes were used to construct a phylogenetic tree and modified with expression files to reveal evolutionary characteristics. Physical and chemical characteristics, gene structure, and conserved motif analysis were also used to further analyze RcMYBs. Additionally, cis-acting elements related to transcription, hormone, and MYB binding were found in the promoter region of the selected RcMYBs. Four RcMYBs were cloned, sequenced, and their gene expression pattern was analyzed for further analysis of their functions. The research results lay the foundation for further research on the function of RcMYB and R. crenulata.
LDL-C Concentrations and the 12-SNP LDL-C Score for Polygenic Hypercholesterolaemia in Self-Reported South Asian, Black and Caribbean Participants of the UK Biobank
Authors: Gratton Jasmine , Finan Chris , Hingorani Aroon D. , Humphries Steve E. , Futema Marta
Published: March 2022

Background: Monogenic familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) concentrations due to monogenic mutations in LDLR, APOB, PCSK9, and APOE. Some mutation-negative patients have a polygenic cause for elevated LDL-C due to a burden of common LDL-C-raising alleles, as demonstrated in people of White British (WB) ancestry using a 12-single nucleotide polymorphism (SNP) score. This score has yet to be evaluated in people of South Asian (SA), and Black and Caribbean (BC) ethnicities.

Objectives: 1) Compare the LDL-C and 12-SNP score distributions across the three major ethnic groups in the United Kingdom: WB, SA, and BC individuals; 2) compare the association of the 12-SNP score with LDL-C in these groups; 3) evaluate ethnicity-specific and WB 12-SNP score decile cut-off values, applied to SA and BC ethnicities, in predicting LDL-C concentrations and hypercholesterolaemia (LDL-C>4.9 mmol/L).

Methods: The United Kingdom Biobank cohort was used to analyse the LDL-C (adjusted for statin use) and 12-SNP score distributions in self-reported WB (n = 353,166), SA (n = 7,016), and BC (n = 7,082) participants. To evaluate WB and ethnicity-specific 12-SNP score deciles, the total dataset was split 50:50 into a training and testing dataset. Regression analyses (logistic and linear) were used to analyse hypercholesterolaemia (LDL-C>4.9 mmol/L) and LDL-C.

Findings: The mean (±SD) measured LDL-C differed significantly between the ethnic groups and was highest in WB [3.73 (±0.85) mmol/L], followed by SA [3.57 (±0.86) mmol/L, p < 2.2 × 10−16], and BC [3.42 (±0.90) mmol/L] participants (p < 2.2 × 10−16). There were significant differences in the mean (±SD) 12-SNP score between WB [0.90 (±0.23)] and BC [0.72 (±0.25), p < 2.2 × 10−16], and WB and SA participants [0.86 (±0.19), p < 2.2 × 10−16]. In all three ethnic groups the 12-SNP score was associated with measured LDL-C [R2 (95% CI): WB = 0.067 (0.065–0.069), BC = 0.080 (0.063–0.097), SA = 0.027 (0.016–0.038)]. The odds ratio and the area under the curve for hypercholesterolaemia were not statistically different when applying ethnicity-specific or WB deciles in all ethnic groups.

Interpretation: We provide information on the differences in LDL-C and the 12-SNP score distributions in self-reported WB, SA, and BC individuals of the United Kingdom Biobank. We report the association between the 12-SNP score and LDL-C in these ethnic groups. We evaluate the performance of ethnicity-specific and WB 12-SNP score deciles in predicting LDL-C and hypercholesterolaemia.
Therapeutic Targeting Hypoxia-Inducible Factor (HIF-1) in Cancer: Cutting Gordian Knot of Cancer Cell Metabolism
Authors: Sharma Abhilasha , Sinha Sonam , Shrivastava Neeta
Published: March 2022

Metabolic alterations are one of the hallmarks of cancer, which has recently gained great attention. Increased glucose absorption and lactate secretion in cancer cells are characterized by the Warburg effect, which is caused by the metabolic changes in the tumor tissue. Cancer cells switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis due to changes in glucose degradation mechanisms, a process known as “metabolic reprogramming”. As a result, proteins involved in mediating the altered metabolic pathways identified in cancer cells pose novel therapeutic targets. Hypoxic tumor microenvironment (HTM) is anticipated to trigger and promote metabolic alterations, oncogene activation, epithelial-mesenchymal transition, and drug resistance, all of which are hallmarks of aggressive cancer behaviour. Angiogenesis, erythropoiesis, glycolysis regulation, glucose transport, acidosis regulators have all been orchestrated through the activation and stability of a transcription factor termed hypoxia-inducible factor-1 (HIF-1), hence altering crucial Warburg effect activities. Therefore, targeting HIF-1 as a cancer therapy seems like an extremely rational approach as it is directly involved in the shift of cancer tissue. In this mini-review, we present a brief overview of the function of HIF-1 in hypoxic glycolysis with a particular focus on novel therapeutic strategies currently available.
Eosinophil Progenitors in Patients With Non-Asthmatic Eosinophilic Bronchitis, Eosinophilic Asthma, and Normal Controls
Authors: Zhan Chen , Xu Rong , Li Bizhou , Liu Jiaxing , Liang Wanqin , Zhang Shengfang , Fang Liman , Zhong Shuxin , de Silva S. Dushinka Shaniya Helen , Sivapalan Dhinesan , Luo Wei , Li Jing , Lai Kefang , Zhong Nanshan , Sehmi Roma , O’Byrne Paul M. , Chen Ruchong
Published: March 2022

Objective

This study aims to explore the potential of in situ airway differentiation of eosinophil progenitors (EoPs) and hematopoietic progenitor cells (HPCs) in sputum and peripheral blood from patients with non-asthmatic eosinophilic bronchitis (NAEB), eosinophilic asthma (EA), and healthy controls (HC).

Methods

Using flow cytometry, we enumerated sputum and blood HPCs and EoPs in patients with NAEB (n=15), EA (n=15), and HC (n=14) at baseline. Patients with NAEB and EA were then treated for 1 month with budesonide (200 μg, bid) or budesonide and formoterol (200/6 μg, bid), respectively. HPCs and EoPs in both compartments were re-evaluated.

Results

At baseline, NAEB and EA both had significantly greater numbers of sputum but not blood HPCs and EoPs (p<0.05) compared to HC. There were no differences between NAEB and EA. After 1 month of inhaled corticosteroid (ICS) treatment, NAEB patients showed a significant improvement in cough symptoms, but the attenuation of sputum HPC and EoP levels was not significant.

Conclusions

NAEB patients have increased airway levels of HPCs and EoPs. One-month treatment with ICS did not fully suppress the level of EoPs in NAEB. Controlling in situ airway differentiation of EoPs may control airway eosinophilia and provide long-term resolution of symptoms in NAEB.
Pan-Cancer Analysis Reveals a Distinct Neutrophil Extracellular Trap-Associated Regulatory Pattern
Authors: Shen Xiao-Tian , Xie Sun-Zhe , Xu Jing , Yang Lu-Yu , Qin Lun-Xiu
Published: March 2022

Background

Neutrophils form extracellular net-like structures called neutrophil extracellular traps (NETs). Emerging evidence has shown that cancer can induce NET formation; however, it is not fully understood how NETs influence cancer biology, and no consensus has been reached on their pro- or antitumor effects. A comprehensive analysis of the global NET-associated gene regulatory network is currently unavailable and is urgently needed.

Methods

We systematically explored and discussed NET enrichment, NET-associated gene regulatory patterns, and the prognostic implications of NETs in approximately 8,000 patients across 22 major human cancer types. We identified NET-associated regulatory gene sets that we then screened for NET-associated regulatory patterns that might affect patient survival. We functionally annotated the NET-associated regulatory patterns to compare the biological differences between NET-related survival subgroups.

Results

A gene set variation analysis (GSVA) based on 23 major component genes was used to calculate a metric called the NET score. We found that the NET score was closely associated with many important cancer hallmarks, particularly inflammatory responses and epithelial-to-mesenchymal transition (EMT)-induced metastasis. Higher NET scores were related to poor immunotherapy response. Survival analysis revealed that NETs had diverse prognostic impacts among various cancer types. The NET-associated regulatory patterns linked to shorter or longer cancer patient survival were distinct from each other. Functional analysis revealed that more of the NET-associated regulatory genes linked to poor cancer survival were associated with extracellular matrix (ECM) remodeling and pan-cancerous risk factors. SPP1 was found to be highly expressed and correlated with NET formation in cancers with poor survival. We also found that the co-upregulation of NET formation and SPP1 expression was closely linked to increased EMT and poor survival, that SPP1 influenced NET-induced malignant capacity, and that SPP1 overproduction induced a robust formation of metastatic-promoting NETs.

Conclusion

NETs were common across cancers but displayed a diverse regulatory pattern and outcome readouts in different cancer types. SPP1 is potentially the key to NET-related poor outcomes.
Mutation of the Polyproline Sequence in CD3ε Evidences TCR Signaling Requirements for Differentiation and Function of Pro-Inflammatory Tγδ17 Cells
Authors: Borroto Aldo , Alarcón Balbino , Navarro María N.
Published: March 2022

Tγδ17 cells have emerged as a key population in the development of inflammatory and autoimmune conditions such as psoriasis. Thus, the therapeutic intervention of Tγδ17 cells can exert protective effects in this type of pathologies. Tγδ cells commit to IL-17 production during thymus development, and upon immune challenge, additional extrathymic signals induce the differentiation of uncommitted Tγδ cells into Tγδ17 effector cells. Despite the interest in Tγδ17 cells during the past 20 years, the role of TCR signaling in the generation and function of Tγδ17 cells has not been completely elucidated. While some studies point to the notion that Tγδ17 differentiation requires weak or no TCR signaling, other works suggest that Tγδ17 require the participation of specific kinases and adaptor molecules downstream of the TCR. Here we have examined the differentiation and pathogenic function of Tγδ17 cells in “knockin” mice bearing conservative mutations in the CD3ε polyproline rich sequence (KI-PRS) with attenuated TCR signaling due to lack of binding of the essential adaptor Nck. KI-PRS mice presented decreased frequency and numbers of Tγδ17 cells in adult thymus and lymph nodes. In the Imiquimod model of skin inflammation, KI-PRS presented attenuated skin inflammation parameters compared to wild-type littermates. Moreover, the generation, expansion and effector function Tγδ17 cells were impaired in KI-PRS mice upon Imiquimod challenge. Thus, we conclude that an intact CD3ε-PRS sequence is required for optimal differentiation and pathogenic function of Tγδ17 cells. These data open new opportunities for therapeutic targeting of specific TCR downstream effectors for treatment of Tγδ17-mediated diseases.
Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2
Authors: Fragoso-Saavedra Mario , Ramírez-Estudillo Carmen , Peláez-González Diana L. , Ramos-Flores Jorge O. , Torres-Franco Gustavo , Núñez-Muñoz Leandro , Marcelino-Pérez Gabriel , Segura-Covarrubias María G. , González-González Rogelio , Ruiz-Medrano Roberto , Xoconostle-Cázares Beatriz , Gayosso-Vázquez Amanda , Reyes-Maya Silvia , Ramírez-Andoney Vianey , Alonso-Morales Rogelio A. , Vega-López Marco A.
Published: March 2022

New vaccine design approaches, platforms, and immunization strategies might foster antiviral mucosal effector and memory responses to reduce asymptomatic infection and transmission in vaccinated individuals. Here, we investigated a combined parenteral and mucosal immunization scheme to induce local and serum antibody responses, employing the epitope-based antigens 3BT and NG19m. These antigens target the important emerging and re-emerging viruses PRRSV-2 and SARS-CoV-2, respectively. We assessed two versions of the 3BT protein, which contains conserved epitopes from the GP5 envelope protein of PRRSV-2: soluble and expressed by the recombinant baculovirus BacDual-3BT. On the other hand, NG19m, comprising the receptor-binding motif of the S protein of SARS-CoV-2, was evaluated as a soluble recombinant protein only. Vietnamese mini-pigs were immunized employing different inoculation routes: subcutaneous, intranasal, or a combination of both (s.c.-i.n.). Animals produced antigen-binding and neut1ralizing antibodies in serum and mucosal fluids, with varying patterns of concentration and activity, depending on the antigen and the immunization schedule. Soluble 3BT was a potent immunogen to elicit binding and neutralizing antibodies in serum, nasal mucus, and vaginal swabs. The vectored immunogen BacDual-3BT induced binding antibodies in serum and mucosae, but PRRSV-2 neutralizing activity was found in nasal mucus exclusively when administered intranasally. NG19m promoted serum and mucosal binding antibodies, which showed differing neutralizing activity. Only serum samples from subcutaneously immunized animals inhibited RBD-ACE2 interaction, while mini-pigs inoculated intranasally or via the combined s.c.-i.n. scheme produced subtle neutralizing humoral responses in the upper and lower respiratory mucosae. Our results show that intranasal immunization, alone or combined with subcutaneous delivery of epitope-based antigens, generates local and systemic binding and neutralizing antibodies. Further investigation is needed to evaluate the capability of the induced responses to prevent infection and reduce transmission.
Application of High-Throughput Imaging Mass Cytometry Hyperion in Cancer Research
Authors: Le Rochais Marion , Hemon Patrice , Pers Jacques-Olivier , Uguen Arnaud
Published: March 2022

Imaging mass cytometry (IMC) enables the in situ analysis of in-depth-phenotyped cells in their native microenvironment within the preserved architecture of a single tissue section. To date, it permits the simultaneous analysis of up to 50 different protein- markers targeted by metal-conjugated antibodies. The application of IMC in the field of cancer research may notably help 1) to define biomarkers of prognostic and theragnostic significance for current and future treatments against well-established and novel therapeutic targets and 2) to improve our understanding of cancer progression and its resistance mechanisms to immune system and how to overcome them. In the present article, we not only provide a literature review on the use of the IMC in cancer-dedicated studies but we also present the IMC method and discuss its advantages and limitations among methods dedicated to deciphering the complexity of cancer tissue.
The Impact of Alcohol Use Disorder on Tuberculosis: A Review of the Epidemiology and Potential Immunologic Mechanisms
Authors: Wigger Gregory W. , Bouton Tara C. , Jacobson Karen R. , Auld Sara C. , Yeligar Samantha M. , Staitieh Bashar S.
Published: March 2022

Globally, an estimated 107 million people have an alcohol use disorder (AUD) leading to 2.8 million premature deaths each year. Tuberculosis (TB) is one of the leading causes of death globally and over 8% of global TB cases are estimated to be attributable to AUD. Social determinants of health such as poverty and undernutrition are often shared among those with AUD and TB and could explain the epidemiologic association between them. However, recent studies suggest that these shared risk factors do not fully account for the increased risk of TB in people with AUD. In fact, AUD has been shown to be an independent risk factor for TB, with a linear increase in the risk for TB with increasing alcohol consumption. While few studies have focused on potential biological mechanisms underlying the link between AUD and TB, substantial overlap exists between the effects of alcohol on lung immunity and the mechanisms exploited by Mycobacterium tuberculosis (Mtb) to establish infection. Alcohol misuse impairs the immune functions of the alveolar macrophage, the resident innate immune effector in the lung and the first line of defense against Mtb in the lower respiratory tract. Chronic alcohol ingestion also increases oxidative stress in the alveolar space, which could in turn facilitate Mtb growth. In this manuscript, we review the epidemiologic data that links AUD to TB. We discuss the existing literature on the potential mechanisms by which alcohol increases the risk of TB and review the known effects of alcohol ingestion on lung immunity to elucidate other mechanisms that Mtb may exploit. A more in-depth understanding of the link between AUD and TB will facilitate the development of dual-disease interventions and host-directed therapies to improve lung health and long-term outcomes of TB.
Impact of Drp1-Mediated Mitochondrial Dynamics on T Cell Immune Modulation
Authors: Song Jun , Yi Xiaofang , Gao Ruolin , Sun Li , Wu Zhixuan , Zhang Shuling , Huang Letian , Han Chengbo , Ma Jietao
Published: March 2022

In recent years, various breakthroughs have been made in tumor immunotherapy that have contributed to prolonging the survival of tumor patients. However, only a subset of patients respond to immunotherapy, which limits its use. One reason for this is that the tumor microenvironment (TME) hinders the migration and infiltration of T cells and affects their continuous functioning, resulting in an exhausted phenotype. Therefore, clarifying the mechanism by which T cells become exhausted is of significance for improving the efficacy of immunotherapy. Several recent studies have shown that mitochondrial dynamics play an important role in the immune surveillance function of T cells. Dynamin-related protein 1 (Drp1) is a key protein that mediates mitochondrial fission and maintains the mitochondrial dynamic network. Drp1 regulates various activities of T cells in vivo by mediating the activation of a series of pathways. In addition, abnormal mitochondrial dynamics were observed in exhausted T cells in the TME. As a potential target for immunotherapy, in this review, we describe in detail how Drp1 regulates various physiological functions of T cells and induces changes in mitochondrial dynamics in the TME, providing a theoretical basis for further research.
Role of Cytokines in Thymic Regulatory T Cell Generation: Overview and Updates
Authors: Tang Mei , Jia Fuya , Nan Fang , Zuo Fengqiong , Yuan Zhu , Zhang Dunfang
Published: March 2022

CD4+CD25+Foxp3+Regulatory (Treg) T cells are mainly generated within the thymus. However, the mechanism of thymic Treg cell (tTreg cell) generation remains to be fully revealed. Although the functions of TCR/CD28 co-stimulation have been widely accepted, the functions of cytokines in the generation of tTreg cells remain highly controversial. In this review, we summarize the existing studies on cytokine regulation of tTreg cell generation. By integrating the key findings of cytokines in tTreg cell generation, we have concluded that four members of γc family cytokines (IL-2, IL-4, IL-7 and IL-15), transforming growth factor β (TGF-β), and three members of TNF superfamily cytokines (GITRL, OX40L and TNF-α) play vitally important roles in regulating tTreg cell generation. We also point out all disputed points and highlight critical scientific questions that need to be addressed in the future.
Identifying Central Carriers and Detecting Key Communities Within the Global Fish Transshipment Networks
Authors: Petrossian Gohar A. , Barthuly Bryce , Sosnowski Monique C.
Published: March 2022

To effectively monitor fisheries resources and combat illegal, unreported, and unregulated fishing, human labor exploitation onboard fishing vessels amongst other crimes, such as the trafficking of weapons, humans, and narcotics, it is important that more attention is paid to the likely facilitators of these activities, one of these being at-sea transshipment of fish. Even though transshipment is a common practice that has taken place for decades, little is known about the overall networks, operational practices, and global spatial patterns of thecentral actorsinvolved in such activities. This research aims to fill that knowledge gap by understanding the networks of activities of the actors who play a central role in these global transshipment activities. Using data from Global Fishing Watch on global transshipment events that took place between 2015 and 2020, this research (a) identifies thecentral carriersinvolved in transshipment events, (b) visualizes their networks of activities and interactions with fishing vessels, (c) examines the spatial distribution of their activities; and (d) determines whether these vessels use open-registry flags when engaging in transshipments, and if so, which. In exploring the role that central actors play within networks of transshipments, targeted mechanisms can be designed to better monitor such activities.
Effects of Dietary Lipid Sources on Alleviating the Negative Impacts Induced by the Fishmeal Replacement With Clostridium autoethanogenum Protein in the Diet of Pacific White Shrimp (Litopenaeus vannamei)
Authors: Zheng Chaozhong , Gong Shunlian , Cao Junming , Dong Xiaohui , Chi Shuyan , Yang Qihui , Liu Hongyu , Zhang Shuang , Xie Shiwei , Tan Beiping
Published: March 2022

This study evaluated the effects of lipid sources on the replacement of fishmeal with Clostridium autoethanogenum protein (CAP) in the diet of Pacific white shrimp (Litopenaeus vannamei). By using CAP to replace 40% fishmeal in the basal diet (contains 25% fishmeal), four diets (PC as the control diet, LSO as the low soybean oil level, MSO as the middle soybean oil level, and HSO as the high soybean oil level) were formulated by adding different proportions of fish oil and soybean oil. Each diet was assigned to four replicates (40 shrimps per replicate, initial weight = 1.79 ± 0.02 g). A 7-day Vibrio parahaemolyticus challenge test was conducted at the end of the 50-day feeding experiment. Weight gain was significantly higher and the cumulative mortality after challenge was lower in HSO treatment. The total antioxidant capacity (T-AOC) in hepatopancreas was significantly raised with increasing dietary soybean oil based on CAP substitution. After challenge, Pen3 mRNA expression was significantly higher in hepatopancreas and NF-κB pathway-related mRNA (dorsal, relish, and IKKβ) expression was higher in the intestine in HSO treatment. The height of mucosal folds and the thickness of the muscle layer were positively correlated with the level of dietary soybean oil. Transmission electron microscopy (TEM) analysis showed that the microvilli were damaged and the endoplasmic reticulum was swollen in shrimp fed the LSO diet. Diversity of intestinal microbiota was increased in shrimp fed the LSO diet, with a significant increase in beneficial bacteria such as Halocynthiibacter and Ruegeria as well as less harmful bacteria such as Vibrio. These results suggested that the replacement of fishmeal with CAP and the high proportion of soybean oil in the diet could improve the growth performance, disease resistance, and intestinal structure of Pacific white shrimp, and high fish oil in a low-FM diet raised the percentage of beneficial bacteria in the intestine of shrimp.
Identification of Melanin in the Mantle of the Pacific Oyster Crassostrea gigas
Authors: Han Yijing , Xie Chaoyi , Fan Nini , Song Hongce , Wang Xiaomei , Zheng Yanxin , Zhang Meiwei , Liu Yaqiong , Huang Baoyu , Wei Lei , Wang Xiaotong
Published: March 2022

The Pacific oyster, Crassostrea gigas, is widely distributed and is substantially important to shellfish cultivation. Oysters with melanin-colored shells and soft parts are increasingly popular and are of high economic value. However, the distribution and synthesis of melanin in C. gigas remains unclear and there have been only few relevant studies on it. In this study, transmission electron microscopy (TEM) was used to observe melanin in the epidermis of dark mantle tissue. Melanocytes containing melanosomes were observed below the epidermis, suggesting the possibility of a gradual transfer of melanin from the mantle tissue to the epithelium. The frozen section technique and three melanin staining methods were used to confirm the presence of melanin. The results suggest that enzyme identification (DOPA) is a suitable method of melanin staining in the mantle tissues of C. gigas. This study preliminarily identified the existence of melanin in the mantle tissues of C. gigas and is a foundation for the study of melanin synthesis. Furthermore, it provides new insights into the mechanism of shell color formation.
Analysis of Aneuploidy Rate and Pregnancy Outcomes in Unexplained Recurrent Pregnancy Loss Couples With Chromosome Polymorphism After PGT-A
Authors: Cao Mingzhu , Zhang Qian , Zhou Wei , Zhu Yueting , Li Hongchang , Yan Junhao
Published: March 2022

Purpose

The study aims to investigate whether chromosomal polymorphism affects embryo development and pregnancy outcomes of unexplained recurrent pregnancy loss (uRPL) couples undergoing PGT-A.

Methods

A total of 585 couples with uRPL history who performed PGT-A were included in the retrospective study from January 2016 to December 2020. We included 415 couples with normal karyotype and 170 couples with chromosomal polymorphism. Furthermore, the polymorphism group was divided into two subgroups: 113 couples in the male group and 57 couples in the female group. The embryo development and pregnancy outcomes were analyzed in different groups.

Results

The blastocyst rate and aneuploidy rate are statistically different in the normal group, male polymorphism group, and female polymorphism group. Compared with normal and female groups, the male group has a lower blastocyst rate, which is statistically different (48.3 vs. 53.9%, p = 0.003; 48.3 vs. 54.1%, p = 0.043). Moreover, the aneuploidy rate of the male polymorphism group is significantly higher than female carriers (29.5 vs. 18.6%, p = 0.003). However, there were no statistically significant differences in clinical pregnancy rate, early miscarriage rate, and live birth rate after PGT-A (p > 0.05).

Conclusion

Male with chromosome polymorphism (CPM) have a lower blastocyst rate and a higher aneuploidy rate than female carriers in uRPL couples undergoing PGT-A. However, when a euploid blastocyst was first transferred, no difference in pregnancy outcomes was found between the male and female polymorphism carriers. It indicated that CPM may have an adverse effect on the embryos of male carriers with uRPL history, and the occurrence of uRPL may be decreased in male polymorphism carriers after PGT-A.
Experience of Dry Eye Patients With Anxiety and Depression: A Qualitative Study
Authors: Yu Haozhe , Zeng Weizhen , Xu Minhui , Wu Wenyu , Feng Yun
Published: March 2022

Purpose

Anxiety and depression are important risk factors for dry eye disease (DED). The aims of this research are to identify the cause of anxiety and depression in DED patients and explore their strategies in coping with DED.

Methods

This is a qualitative study based on semi-structured interviews, and the interviews records were analyzed through inductive thematic analysis. Participants were recruited from a large university affiliated hospital in the north of China, including 47 participants affected by depression and anxiety.

Results

Analysis revealed the causes of anxiety and depression in DED patients could be divided into three major themes and nine subthemes: (1) From hospital: including difficulties in diagnosing and seeking medical advice, neglect or lack of attention from clinicians, low treatment satisfaction and complex comorbidities; (2) From daily life: including life satisfaction and well-being, changes in lifestyle pattern and changes in workstyle pattern; (3) From society: including burden of disease and reduction of social interaction. Most DED Patients with anxiety and depression were more likely to face the condition as well as receive treatments negatively, while the others tended to seek treatments unduly and blindly.

Conclusion

This investigation offers new insights into the understanding difficulties in DED patients with anxiety and depression, and provides valuable guidance for supporting them to reduce depression and anxiety as well as improve prognosis.
SUMO1 Promotes Mesangial Cell Proliferation Through Inhibiting Autophagy in a Cell Model of IgA Nephropathy
Authors: Tan Xia , Liu Yexin , Liu Di , Tang Xiaofang , Xia Ming , Chen Guochun , He Liyu , Zhu Xuejing , Liu Hong
Published: March 2022

IgA nephropathy (IgAN) is a common form of primary glomerulonephritis and its main pathological changes are mesangial cell proliferation and matrix expansion. Autophagy inhibition may result in its mesangial cell proliferation and renal lesions. SUMOylation is a eukaryotic-reversible post-translational modification where SUMO is covalently attached to target proteins to regulate their properties. It is largely unclear whether SUMOylation contributes to the pathogenesis of IgAN. This study was designed to investigate the change of protein SUMO1 in mesangial cells of IgAN and its association with autophagy. We found the expression of SUMO1 was upregulated in IgAN, IgA mouse model, and aIgA1-stimulated mesangial cells. In aIgA1-stimulated mesangial cell model, we tested LC3II/I and p62, the autophagy-related proteins suggested the inhibition of autophagy. Inhibited SUMOylation with ginkgolic acid (GA) or silencing SUMO1 could downregulate SUMO1 and SUMO1-p53, promote autophagy, and lessen cell proliferation. In summary, in the mesangial cells stimulated with aIgA1, SUMO1 may contribute to its cell proliferation through inhibited autophagy, and SUMO1-p53 may play a role in this process.
Air Pollution Effects to the Subtype and Severity of Lung Cancers
Authors: Lee Hung-Chi , Lu Yueh-Hsun , Huang Yen-Lin , Huang Shih Li , Chuang Hsiao-Chi
Published: March 2022

The correlation between lung cancer incidence and air pollution has been established in previous research, but the other detail impact of air pollution to lung cancer is still under investigation. This study aimed to explore if air pollution affected the subtype and staging of lung cancer. At the same time, we investigated the effect of individual pollutant to subtypes and staging. Single center data were extracted from January 1, 2020 to June 30, 2020 using the search engine in the radiology reporting system of Shuang-Ho Hospital, New Taipei City, Taiwan. There were 169 patients finally included for analysis. The nationwide statistics data of lung cancer were extracted from the Taiwan Cancer Registry. The air quality data were extracted from the Taiwan air quality monitoring network. Comparison of the single center lung cancer characteristics with nationwide data was made using the chi-square test. Comparison of the air quality of the living space of the included cases with the average quality in Taiwan in 2020 was made using the Z-test. The result shows there was significant difference of cancer subtype and staging between the regional data and the nationwide data. The regional data demonstrated a tendency of higher incidence of adenocarcinoma and advanced stage disease. As for air quality, there was no significant difference. The regional PM10 level presented generally lower levels in regional data as compared to Taiwan in 2020 with near statistically significant P-value (0.052); the regional NO2 level presented generally higher levels in regional data as compared to Taiwan in 2020 with near statistically significant P-value (0.060). The results indicate that air pollution might be related to increase in adenocarcinoma ratio and advanced stage of lung cancer at initial presentation. The NO2 was probably the leading pollutant causing this trend.
Risk Factors for Pulmonary Air Leak and Clinical Prognosis in Patients With COVID-19 Related Acute Respiratory Failure: A Retrospective Matched Control Study
Authors: Tonelli Roberto , Bruzzi Giulia , Manicardi Linda , Tabbì Luca , Fantini Riccardo , Castaniere Ivana , Andrisani Dario , Gozzi Filippo , Pellegrino Maria Rosaria , Trentacosti Fabiana , Dall’Ara Lorenzo , Busani Stefano , Franceschini Erica , Baroncini Serena , Manco Gianrocco , Meschiari Marianna , Mussini Cristina , Girardis Massimo , Beghè Bianca , Marchioni Alessandro , Clini Enrico
Published: March 2022

Background

The role of excessive inspiratory effort in promoting alveolar and pleural rupture resulting in air leak (AL) in patients with SARS-CoV-2 induced acute respiratory failure (ARF) while on spontaneous breathing is undetermined.

Methods

Among all patients with COVID-19 related ARF admitted to a respiratory intensive care unit (RICU) and receiving non-invasive respiratory support, those developing an AL were and matched 1:1 [by means of PaO2/FiO2 ratio, age, body mass index-BMI and subsequent organ failure assessment (SOFA)] with a comparable population who did not (NAL group). Esophageal pressure (ΔPes) and dynamic transpulmonary pressure (ΔPL) swings were compared between groups. Risk factors affecting AL onset were evaluated. The composite outcome of ventilator-free-days (VFD) at day 28 (including ETI, mortality, tracheostomy) was compared between groups.

Results

Air leak and NAL groups (n = 28) showed similar ΔPes, whereas AL had higher ΔPL (20 [16–21] and 17 [11–20], p = 0.01, respectively). Higher ΔPL (OR = 1.5 95%CI[1–1.8], p = 0.01), positive end-expiratory pressure (OR = 2.4 95%CI[1.2–5.9], p = 0.04) and pressure support (OR = 1.8 95%CI[1.1–3.5], p = 0.03), D-dimer on admission (OR = 2.1 95%CI[1.3–9.8], p = 0.03), and features suggestive of consolidation on computed tomography scan (OR = 3.8 95%CI[1.1–15], p = 0.04) were all significantly associated with AL. A lower VFD score resulted in a higher risk (HR = 3.7 95%CI [1.2–11.3], p = 0.01) in the AL group compared with NAL. RICU stay and 90-day mortality were also higher in the AL group compared with NAL.

Conclusion

In spontaneously breathing patients with COVID-19 related ARF, higher levels of ΔPL, blood D-dimer, NIV delivery pressures and a consolidative lung pattern were associated with AL onset.
Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma
Authors: Chung Taek , Park Young Nyun
Published: March 2022

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver malignancy with an increasing incidence worldwide. Recently, histopathologic classification of small duct type and large duct type iCCA has been introduced. Both these types of tumors exhibit differences in clinicopathological features, mutational profiles, and prognosis. Small duct type iCCA is composed of non-mucin-producing cuboidal cells, whereas large duct type iCCA is composed of mucin-producing columnar cells, reflecting different cells of origin. Large duct type iCCA shows more invasive growth and poorer prognosis than small duct type iCCA. The background liver of small duct type iCCA often shows chronic liver disease related to hepatitis B or C viral infection, or alcoholic or non-alcoholic fatty liver disease/steatohepatitis, in contrast to large duct type iCCA that is often related to hepatolithiasis and liver fluke infection. Cholangiolocarcinoma is a variant of small duct type iCCA composed of naïve-looking cuboidal cells forming cords or ductule-like structures, and shows better prognosis than the conventional small duct type. Fibrous tumor stroma, one of the characteristic features of iCCA, contains activated fibroblasts intermixed with innate and adaptive immune cells. The types of stroma (mature versus immature) are related to tumor behavior and prognosis. Low tumor-infiltrating lymphocyte density, KRAS alteration, and chromosomal instability are related to immune-suppressive tumor microenvironments with resistance to programmed death 1/ programmed death ligand 1 blockade. Data from recent large-scale exome analyses have revealed the heterogeneity in the molecular profiles of iCCA, showing that small duct type iCCA exhibit frequent BAP1, IDH1/2 hotspot mutations and FGFR2 fusion, in contrast to frequent mutations in KRAS, TP53, and SMAD4 observed in large duct type iCCA. Multi-omics analyses have proposed several molecular classifications of iCCA, including inflammation class and proliferation class. The inflammation class is enriched in inflammatory signaling pathways and expression of cytokines, while the proliferation class has activated oncogenic growth signaling pathways. Diverse pathologic features of iCCA and its associated multi-omics characteristics are currently under active investigation, thereby providing insights into precision therapeutics for patients with iCCA. This review provides the latest knowledge on the histopathologic classification of iCCA and its associated molecular features, ranging from tumor microenvironment to genomic and transcriptomic research.
Tenecteplase in Pulmonary Embolism Patients: A Meta-Analysis and Systematic Review
Authors: Zhang Zhu , Xi Linfeng , Zhang Shuai , Zhang Yunxia , Fan Guohui , Tao Xincao , Gao Qian , Xie Wanmu , Yang Peiran , Zhai Zhenguo , Wang Chen
Published: March 2022

Objective

To assess the efficacy and safety of tenecteplase in patients with pulmonary embolism (PE).

Methods

We completed the literature search on May 31, 2021 using PubMed, EMBASE and the Web of Science. Analyses were conducted according to PE risk stratification, study design and duration of follow-up. The pooled risk ratios (RRs) and its 95% confident intervals (CIs) for death and major bleeding were calculated using a random-effect model.

Results

A total of six studies, with four randomized controlled trials (RCTs) and two cohort studies, were included in this study out of the 160 studies retrieved. For patients with high-risk PE, tenecteplase increased 30-day survival rate (16% vs 6%; P = 0.005) and did not increase the incidence of bleeding (6% vs 5%; P = 0.73). For patients with intermediate-risk PE, four RCTs suggested that tenecteplase reduced right ventricular insufficiency at 24h early in the onset and the incidence of hemodynamic failure without affecting mortality in a short/long-term [<30 days RR = 0.83, 95% CI (0.47, 1.46);≥30 days RR = 1.04, 95% CI (0.88, 1.22)]. However, tenecteplase was associated with high bleeding risk [<30 days RR = 1.79, 95% CI (1.61, 2.00); ≥30 days RR = 1.28, 95% CI (0.62, 2.64)].

Conclusions

Tenecteplase may represent a promising candidate for patients with high risk PE. However, tenecteplase is not recommended for patients with intermediate-risk PE because of high bleeding risk. More large-scale studies focused on tenecteplase are still needed for PE patients.
Sputum Bacterial Metacommunities in Distinguishing Heterogeneity in Respiratory Health and Disease
Authors: Si Jiyeon , Choi Yongbin , Raes Jeroen , Ko Gwangpyo , You Hyun Ju
Published: March 2022

Background and Objective

Cluster-based analysis, or community typing, has been attempted as a method for studying the human microbiome in various body niches with the aim of reducing variations in the bacterial composition and linking the defined communities to host health and disease. In this study, we have presented the bacterial subcommunities in the healthy and the diseased population cohorts and have assessed whether these subcommunities can distinguish different host health conditions.

Methods

We performed community typing analysis on the sputum microbiome dataset obtained from a healthy Korean twin-family cohort (n = 202) and an external chronic obstructive pulmonary disease (COPD) cohort (n = 324) and implemented a networks analysis to investigate the associations of bacterial metacommunities with host health parameters and microbial interactions in disease.

Results

The analysis of the sputum microbiome of a healthy Korean cohort revealed high levels of interindividual variation, which was driven by two dominant bacteria: Neisseria and Prevotella. Community typing of the cohort samples identified three metacommunities, namely, Neisseria 1 (N1), Neisseria 2 (N2), and Prevotella (P), each of which showed different functional potential and links to host traits (e.g., triglyceride levels, waist circumference, and levels of high-sensitivity C-reactive protein). In particular, the Prevotella-dominant metacommunity showed a low-community diversity, which implies an adverse health association. Network analysis of the healthy twin cohort illustrated co-occurrence of Prevotella with pathogenic anaerobic bacteria; this bacterial cluster was negatively associated with high-density lipoproteins but positively correlated with waist circumference, blood pressure, and pack-years. Community typing of the external COPD cohort identified three sub-metacommunities: one exclusively comprising healthy subjects (HSs) and the other two (CS1 and CS2) comprising patients. The two COPD metacommunities, CS1 and CS2, showed different abundances of specific pathogens, such as Serratia and Moraxella, as well as differing functional potential and community diversity. Network analysis of the COPD cohort showed enhanced bacterial coexclusions in the CS metacommunities when compared with HS metacommunity.

Conclusion

Overall, our findings point to a potential association between pulmonary Prevotella and host health and disease, making it possible to implement community typing for the diagnosis of heterogenic respiratory disease.
Effect of Bacterial Resistance of Escherichia coli From Swine in Large-Scale Pig Farms in Beijing
Authors: Liu Xiaoxia , Liu Qian , Cheng Yongyou , Liu Rui , Zhao Ruting , Wang Jishi , Wang Yanyun , Yang Shuming , Chen Ailiang
Published: March 2022

With widespread use of antibiotics in the aquaculture industry, bacterial resistance has recently attracted increasing attention. Continuous emergence of multi-resistant bacteria has greatly threatened human and animal health, as well as the quality and safety of livestock products. To control bacterial resistance, the effect of bacterial resistance needs to be well understood. The purpose of this study was to explore the factors influencing Escherichia coli (E. coli) drug resistance in large-scale pig farms. In this study, 296 strains of E. coli isolated and identified from large-scale pig farms in Beijing were used as the research objects. In vitro drug sensitivity tests were used to determine the sensitivity to 10 antibiotics of pig-derived E. coli. SPSS logistic regression was employed to analyze the effects of the season, pig type, sampling point (medication type) and sampling location on resistance and multi-drug resistance of E. coli from pigs. The degrees of drug resistance to 10 antibiotics of the 296 strains of pig-derived E. coli were varied, their resistance rates were between 4.05 and 97.64%, and their multi-drug resistance was appalling, with the highest resistance to six antibiotics being 26.35%. The isolated strains were proven more resistant to tetracyclines, penicillin and chloramphenicol, which are commonly used for disease prevention in pig farms, and less resistant to quinolones and aminoglycosides, which are not used in pig farms. The resistance of the isolated strains in spring and summer was generally higher than that in winter. E. coli resistance in piglets, fattening pigs and sows was more serious than that in nursery and sick pigs. The results showed that the season, type of medication and type of pig had an influence on the pig-derived E. coli resistance, among which the type of medication was the most influencing factor.
Microbial Dispersal, Including Bison Dung Vectored Dispersal, Increases Soil Microbial Diversity in a Grassland Ecosystem
Authors: Hawkins Jaide H. , Zeglin Lydia H.
Published: March 2022

Microbial communities display biogeographical patterns that are driven by local environmental conditions and dispersal limitation, but the relative importance of underlying dispersal mechanisms and their consequences on community structure are not well described. High dispersal rates can cause soil microbial communities to become more homogenous across space and therefore it is important to identify factors that promote dispersal. This study experimentally manipulated microbial dispersal within different land management treatments at a native tallgrass prairie site, by changing the relative openness of soil to dispersal and by simulating vector dispersalviabison dung addition. We deployed experimental soil bags with mesh open or closed to dispersal, and placed bison dung over a subset of these bags, to areas with three different land managements: active bison grazing and annual fire, annual fire but no bison grazing, and no bison grazing with infrequent fire. We expected microbial dispersal to be highest in grazed and burned environments, and that the addition of dung would consistently increase overall microbial richness and lead to homogenization of communities over time. Results show that dispersal rates, as the accumulation of taxa over the course of the 3-month experiment, increase taxonomic richness similarly in all land management treatments. Additionally, bison dung seems to be serving as a dispersal and homogenization vector, based on the consistently higher taxon richness and increased community similarity across contrasting grazing and fire treatments when dung is added. This finding also points to microbial dispersal as an important function that herbivores perform in grassland ecosystems, and in turn, as a function that was lost at a continental scale following bison extermination across the Great Plains of North America in the nineteenth century. This study is the first to detect that dispersal and vector dispersal by grazing mammals promote grassland soil microbial diversity and affect microbial community composition.
Experimental Adaptation of Murine Norovirus to Calcium Hydroxide
Authors: Oishi Wakana , Sato Mikiko , Kubota Kengo , Ishiyama Ryoka , Takai-Todaka Reiko , Haga Kei , Katayama Kazuhiko , Sano Daisuke
Published: March 2022

Slaked lime (calcium hydroxide) is a commonly used disinfectant for fecal sludge. Although viruses are inactivated by lime treatment, whether RNA viruses adapt to lime treatment has not yet been determined. Here, we show that murine norovirus developed higher tolerance during serial passages with lime treatment. We compared synonymous and non-synonymous nucleotide diversities of the three open reading frames of viral genome and revealed that virus populations were subjected to enhanced purifying selection over the course of serial passages with lime treatment. Virus adaptation to lime treatment was coincident with amino acid substitution of lysine to arginine at position 345 (K345R) on the major capsid protein VP1, which accounted for more than 90% of the population. The infectious clones with the K345R produced using a plasmid-based reverse genetics system exhibited greater tolerance in a lime solution, which indicated that the specific amino acid substitution was solely involved in the viral tolerance in lime treatment.