bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Overnutrition During Gestation in Sheep Alters Autophagy Associated Pathways in Offspring Heart
Authors: Liu Yang , Ding Qiyue , Halderson Steven J. , Arriola Apelo Sebastian I. , Jones Amanda K. , Pillai Sambhu M. , Hoffman Maria L. , Reed Sarah , Govoni Kristen E. , Zinn Steven A. , Guo Wei
Published: January 2022

Poor maternal nutrition during gestation can negatively affect offspring growth, development, and health pre- and post-natally. Overfeeding during gestation or maternal obesity (MO) results in altered metabolism and imbalanced endocrine hormones in animals and humans which will have long-lasting and detrimental effects on offspring growth and health. In this study, we examined the effects of overnutrition during gestation on autophagy associated pathways in offspring heart muscles at two gestational and one early postnatal time point (n = 5 for treated and untreated male and female heart respectively at each time point). Two-way ANOVA was used to analyze the interaction between treatment and sex at each time point. Our results revealed significant interactions of maternal diet by developmental stages for offspring autophagy signaling. Overfeeding did not affect the autophagy signaling at mid-gestation day 90 (GD90) in both male and female offspring while the inflammatory cytokines were increased in GD90 MO male offsrping; however, overfeeding during gestation significantly increased autophagy signaling, but not inflammation level at a later developmental stage (GD135 and day 1 after birth) in both males and females. We also identified a sexual dimorphic response in which female progeny were more profoundly influenced by maternal diet than male progeny regardless of developmental stages. We also determined the cortisol concentrations in male and female hearts at three developmental stages. We did not observe cortisol changes between males and females or between overfeeding and control groups. Our exploratory studies imply that MO alters autophagy associated pathways in both male and female at later developmental stages with more profound effects in female. This finding need be confirmed with larger sample numbers in the future. Our results suggest that targeting on autophagy pathway could be a strategy for correction of adverse effects in offspring of over-fed ewes.
Clinical Selection of Prenatal Diagnostic Techniques Following Positive Noninvasive Prenatal Screening Results in Southwest China
Authors: Jing Xiaosha , Liu Hongqian , Zhu Qian , Liu Sha , Liu Jianlong , Bai Ting , Deng Cechuan , Xia Tianyu , Liu Yunyun , Cheng Jing , Wei Xiang , Xing Lingling , Luo Yuan , Zhou Quanfang , Chen Lin , Li Lingping , Wang Jiamin
Published: January 2022

Background: This study aims to evaluate prenatal diagnosis methods following positive noninvasive prenatal screening (NIPS) results.

Methods: According to the positive noninvasive prenatal screening results, 926 pregnant women were divided into three groups: main target disease group (high risk for trisomy 21, trisomy 18, or trisomy 13), sex chromosome aneuploidy (SCA) group, and other chromosomal abnormalities group [abnormal Z-scores for chromosomes other than trisomy (T)21/T18/T13 or SCAs]. The verification methods and results were then retrospectively analysed.

Results: In the main target disease group, the positive rate of chromosomal abnormalities confirmed by quantitative fluorescence polymerase chain reaction (QF-PCR) was 75.18% (212/282), which was not significantly different from that by karyotyping (79.36%, 173/218) and copy number variation (CNV) detection methods (71.43%, 65/91). The positive rate of additional findings confirmed by karyotyping and copy number variation detection methods in main target disease group was 0.46% (1/218) and 8.79% (8/91), respectively. The positive rate of chromosomal abnormalities confirmed by karyotyping and CNV detection methods were 27.11% (45/166) and 38.46% (95/247) in the SCA group and 4.17% (1/24) and 20% (36/180) in the other chromosomal abnormalities group, respectively. Fetal sex chromosome mosaicism was detected in 16.13% (20/124) of the confirmed SCA cases. There were no significant differences in the detection rates of chromosomal microarray analysis (CMA) and CNV sequencing (CNVseq) among the three groups (p > 0.05).

Conclusion: QF-PCR can quickly and accurately identify aneuploidies following NIPS-positive results for common aneuploidy, and in combination with karyotyping and CNV detection techniques can provide more comprehensive results. With the NIPS-positive results for SCA or other abnormalities, CMA and CNVseq may have the same effect on increasing the detection rate. The addition of fluorescence in situ hybridization assay may help to identify true fetal mosaicism.
Activation of DNA Transposons and Evolution of piRNA Genes Through Interspecific Hybridization in Xenopus Frogs
Authors: Suda Kosuke , Hayashi Shun R. , Tamura Kei , Takamatsu Nobuhiko , Ito Michihiko
Published: January 2022

Interspecific hybridization between two closely related species sometimes resulted in a new species with allotetraploid genomes. Many clawed frog species belonging to the Xenopus genus have diverged from the allotetraploid ancestor created by the hybridization of two closely related species with the predicted L and S genomes. There are species-specific repeated sequences including transposable elements in each genome of organisms that reproduce sexually. To understand what happened on and after the hybridization of the two distinct systems consisting of repeated sequences and their corresponding piRNAs, we isolated small RNAs from ovaries and testes of three Xenopus species consisting of allotetraploid X. laevis and X. borealis and diploid X. tropicalis as controls. After a comprehensive sequencing and selection of piRNAs, comparison of their sequences showed that most piRNA sequences were different between the ovaries and testes in all three species. We compared piRNA and genome sequences and specified gene clusters for piRNA expression in each genome. The synteny and homology analyses showed many distinct piRNA clusters among the three species and even between the two L and/or S subgenomes, indicating that most clusters of the two allotetraploid species changed after hybridization. Moreover, evolutionary analysis showed that DNA transposons including Kolobok superfamily might get activated just after hybridization and then gradually inactivated. These findings suggest that some DNA transposons and their piRNAs might greatly influence allotetraploid genome evolution after hybridization.
Comparative Transcriptomics Uncover the Uniqueness of Oocyte Development in the Donkey
Authors: Zhang Fa-Li , Zhang Shu-Er , Sun Yu-Jiang , Wang Jun-Jie , Shen Wei
Published: January 2022

The donkey is an important domestic animal, however the number of donkeys world-wide is currently declining. It is therefore important to protect their genetic resources and to elaborate the regulatory mechanisms of donkey reproduction, particularly, oocyte development. Here, we adopted comparative transcriptomic analysis and weighted gene co-expression network analysis (WGCNA) to uncover the uniqueness of donkey oocyte development compared to cattle, sheep, pigs, and mice, during the period from germinal vesicle (GV) to metaphase II (MII). Significantly, we selected 36 hub genes related to donkey oocyte development, including wee1-like protein kinase 2 (WEE2). Gene Ontology (GO) analysis suggested that these genes are involved in the negative regulation of cell development. Interestingly, we found that donkey specific differentially expressed genes (DEGs) were involved in RNA metabolism and apoptosis. Moreover, the results of WGCNA showed species-specific gene expression patterns. We conclude that, compared to other species, donkey oocytes express a large number of genes related to RNA metabolism to maintain normal oocyte development during the period from GV to MII.
Association Between Objectively Assessed Sleep and Depressive Symptoms During Pregnancy and Post-partum
Authors: Pitsillos Tryfonas , Wikström Anna-Karin , Skalkidou Alkistis , Derntl Birgit , Hallschmid Manfred , Lutz Nicolas D. , Ngai Edith , Sundström Poromaa Inger , Wikman Anna
Published: January 2022

Introduction

Sleep problems are common in pregnancy but many studies have relied only on self-reported sleep measures. We studied the association between objectively measured sleep and peripartum depressive symptoms in pregnant women.

Material and Methods

Sleep was assessed using Actiwatch accelerometers in a sample of 163 pregnant women in the late first (weeks 11–15) or early second trimester (weeks 16–19). Depressive symptoms were assessed in gestational weeks 17, 32 and at 6 weeks post-partum using the Edinburgh Postnatal Depression Scale (EPDS). Multiple linear regression and logistic regression analyses, adjusting for age, BMI, pre-pregnancy smoking, ongoing mental health problems, trimester and season of sleep assessment were carried out to test the association between sleep and depression. Sleep was measured by total sleep time and sleep efficiency, whereas depression was indicated by depressive symptoms and depression caseness. Results are presented as unstandardized beta (B) coefficients or adjusted odds ratios (AOR) and 95% confidence intervals (CI).

Results

Total sleep time ranged from 3 to 9 h (mean 7.1, SD 0.9) and average sleep efficiency was 83% (SD 6.0). Women with the shortest total sleep time, i.e., in the lowest quartile (<6.66 h), reported higher depressive symptoms during pregnancy (week 17, B = 2.13, 95% CI 0.30–3.96; week 32, B = 1.70, 95% CI 0.03–3.37) but not post-partum. Their probability to screen positive for depression in gestational week 17 was increased more than 3-fold (AOR = 3.46, 95% CI 1.07–11.51) but unchanged with regards to gestational week 32 or 6 weeks post-partum. Sleep efficiency was not associated with depressive symptoms at any stage of pregnancy or post-partum.

Discussion

In one of the few studies to use objective sleep measures to date, mental health of pregnant women appeared to be affected by shortened sleep, with total sleep time being negatively associated with depressive symptoms in the early second and third trimester. This finding highlights the relevance of identifying and treating sleep impairments in pregnant women early during antenatal care to reduce the risk of concomitant depression.
Evaluation of the Immune Response Induced by CoronaVac 28-Day Schedule Vaccination in a Healthy Population Group
Authors: Escobar Alejandro , Reyes-López Felipe E. , Acevedo Mónica L. , Alonso-Palomares Luis , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Portillo Hugo , Gatica Jimena , Flores Ivan , Nova-Lamperti Estefanía , Barrera-Avalos Carlos , Bono María Rosa , Vargas Leonardo , Simon Valeska , Leiva-Salcedo Elias , Vial Cecilia , Hormazabal Juan , Cortes Lina Jimena , Valdés Daniel , Sandino Ana M. , Imarai Mónica , Acuña-Castillo Claudio
Published: January 2022

CoronaVac vaccine from Sinovac Life Science is currently being used in several countries. In Chile, the effectiveness of preventing hospitalization is higher than 80% with a vaccination schedule. However, to date, there are no data about immune response induction or specific memory. For this reason, we recruited 15 volunteers without previous suspected/diagnosed COVID-19 and with negative PCR over time to evaluate the immune response to CoronaVac 28 and 90 days after the second immunization (dpi). The CoronaVac administration induces total and neutralizing anti-spike antibodies in all vaccinated volunteers at 28 and 90 dpi. Furthermore, using ELISpot analysis to assay cellular immune responses against SARS-CoV-2 spike protein, we found an increase in IFN-gamma- and Granzyme B-producing cells in vaccinated volunteers at 28 and 90 dpi. Together, our results indicate that CoronaVac induces a robust humoral immune response and cellular immune memory of at least 90 dpi.
Phenotypic and Functional Plasticity of CXCR6+ Peripheral Blood NK Cells
Authors: Angelo Laura S. , Hogg Graham D. , Abeynaike Shawn , Bimler Lynn , Vargas-Hernandez Alexander , Paust Silke
Published: January 2022

Human NK cells are comprised of phenotypic subsets, whose potentially unique functions remain largely unexplored. C-X-C-motif-chemokine-receptor-6 (CXCR6)+NK cells have been identified as phenotypically immature tissue-resident NK cells in mice and humans. A small fraction of peripheral blood (PB)-NK cells also expresses CXCR6. However, prior reports about their phenotypic and functional plasticity are conflicting. In this study, we isolated, expanded, and phenotypically and functionally evaluated CXCR6+and CXCR6–PB-NK cells, and contrasted results to bulk liver and spleen NK cells. We found that CXCR6+and CXCR6–PB-NK cells preserved their distinct phenotypic profiles throughout 14 days ofin vitroexpansion (“day 14”), after which phenotypically immature CXCR6+PB-NK cells became functionally equivalent to CXCR6–PB-NK cells. Despite a consistent reduction in CD16 expression and enhanced expression of the transcription factor Eomesodermin (Eomes), day 14 CXCR6+PB-NK cells had superior antibody-dependent cellular cytotoxicity (ADCC) compared to CXCR6–PB-NK cells. Further, bulk liver NK cells responded to IL-15, but not IL-2 stimulation, with STAT-5 phosphorylation. In contrast, bulk splenic and PB-NK cells robustly responded to both cytokines. Our findings may allow for the selection of superior NK cell subsets for infusion products increasingly used to treat human diseases.
Complement System: An Immunotherapy Target in Colorectal Cancer
Authors: Talaat Iman M. , Elemam Noha Mousaad , Saber-Ayad Maha
Published: January 2022

Colorectal cancer (CRC) is the third most common malignant tumor and the second most fatal cancer worldwide. Several parts of the immune system contribute to fighting cancer including the innate complement system. The complement system is composed of several players, namely component molecules, regulators and receptors. In this review, we discuss the complement system activation in cancer specifically CRC and highlight the possible interactions between the complement system and the various TME components. Additionally, the role of the complement system in tumor immunity of CRC is reviewed. Hence, such work could provide a framework for researchers to further understand the role of the complement system in CRC and explore the potential therapies targeting complement activation in solid tumors such as CRC.
Clinical Isolates of Acinetobacter spp. Are Highly Serum Resistant Despite Efficient Recognition by the Complement System
Authors: Magda Michal , Bettoni Serena , Laabei Maisem , Fairley Derek , Russo Thomas A. , Riesbeck Kristian , Blom Anna M.
Published: January 2022

Gram-negative bacteria from the genusAcinetobacterare responsible for life-threating hospital-related infections such as pneumonia, septicemia, and meningitis, especially in immunocompromised patients. Worryingly,Acinetobacterhave become multi- and extensively drug resistant (MDR/XDR) over the last few decades. The complement system is the first line of defense against microbes, thus it is highly important to increase our understanding of evasion mechanisms used byAcinetobacterspp. Here, we studied clinical isolates ofAcinetobacterspp. (n=50), aiming to characterize their recognition by the complement system. Most isolates tested survived 1 h incubation in 30% serum, and only 8 isolates had a lower survival rate, yet none of those isolates were fully killed. Intriguingly, four isolates survived in human whole blood containing all cell component. Their survival was, however, significantly reduced. Flow cytometry analyses revealed that most of the isolates were detected by human IgG and IgM. Interestingly, we could not detect any significant concentration of deposited C1q, despite observing C4b deposition that was abolished in C1q-deficient serum, indicating transient binding of C1q to bacteria. Moreover, several isolates were recognized by MBL, with C4b deposition abolished in MBL-deficient serum. C3b was deposited on most isolates, but this was not, however, seen with respect to C5b and formation of the membrane attack complex (MAC), indicating that many isolates could avoid complement-mediated lysis. India ink staining showed that isolates were capsulated, and capsule thickness varied significantly between isolates. Studies performed on a wild-type strain and capsule mutant strains, demonstrated that the production of a capsular polysaccharide is one mechanism that mediates resistance to complement-mediated bactericidal activity by preventing MAC deposition and lysis. Our data showed that most clinicalAcinetobacterspp. isolates are highly serum resistant despite being efficiently recognized by the complement system.
Direct Inhibition of GSDMD by PEITC Reduces Hepatocyte Pyroptosis and Alleviates Acute Liver Injury in Mice
Authors: Wang Jie , Shi Ke , An Ning , Li Shuaifei , Bai Mei , Wu Xudong , Shen Yan , Du Ronghui , Cheng Jingcai , Wu Xuefeng , Xu Qiang
Published: January 2022

Acute liver injury (ALI), often caused by viruses, alcohol, drugs, etc., is one of the most common clinical liver diseases. Although pyroptosis plays an important role in ALI, there is still a lack of effective clinical drugs related to this mechanism. Here, we show that phenethyl isothiocyanate (PEITC), a natural compound present in cruciferous vegetables, can significantly alleviate concanavalin A (ConA)-induced inflammatory liver damage and carbon tetrachloride (CCl4)-induced chemical liver damage in a dose-dependent manner. PEITC dose-dependently reversed the ALI-induced increase in plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interferon (IFN)-γ and reduced the protein levels of hepatocyte pyroptosis markers such as Nod-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, and cleaved gasdermin D (GSDMD).In vitroexperiments have also verified the inhibitory effect of PEITC on hepatocyte pyroptosis. Furthermore, PEITC inhibits pyroptosis by interacting with cysteine 191 of GSDMD. In summary, our findings establish a role for PEITC in rescuing hepatocyte pyroptosisviadirect inhibition of GSDMD, which may provide a new potential therapeutic strategy for ALI.
Peptide-Based Vaccines for Tuberculosis
Authors: Gong Wenping , Pan Chao , Cheng Peng , Wang Jie , Zhao Guangyu , Wu Xueqiong
Published: January 2022

Tuberculosis (TB) is an infectious disease caused byMycobacterium tuberculosis. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 is rising, making TB prevention and control more challenging. Vaccination has been considered the best approach to reduce the TB burden. Unfortunately, BCG, the only TB vaccine currently approved for use, offers some protection against childhood TB but is less effective in adults. Therefore, it is urgent to develop new TB vaccines that are more effective than BCG. Accumulating data indicated that peptides or epitopes play essential roles in bridging innate and adaptive immunity and triggering adaptive immunity. Furthermore, innovations in bioinformatics, immunoinformatics, synthetic technologies, new materials, and transgenic animal models have put wings on the research of peptide-based vaccines for TB. Hence, this review seeks to give an overview of current tools that can be used to design a peptide-based vaccine, the research status of peptide-based vaccines for TB, protein-based bacterial vaccine delivery systems, and animal models for the peptide-based vaccines. These explorations will provide approaches and strategies for developing safer and more effective peptide-based vaccines and contribute to achieving the WHO’s End TB Strategy.
Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation
Authors: Díaz-García Elena , García-Tovar Sara , Alfaro Enrique , Zamarrón Ester , Mangas Alberto , Galera Raúl , Ruíz-Hernández José Juan , Solé-Violán Jordi , Rodríguez-Gallego Carlos , Van-Den-Rym Ana , Pérez-de-Diego Rebeca , Nanwani-Nanwani Kapil , López-Collazo Eduardo , García-Rio Francisco , Cubillos-Zapata Carolina
Published: January 2022

CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients’ plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.
Long-Term Ammonia Toxicity in the Hepatopancreas of Swimming Crab Portunus trituberculatus: Cellular Stress Response and Tissue Damage
Authors: Lu Yunliang , Zhang Jingyan , Cao Jianwei , Liu Ping , Li Jian , Meng Xianliang
Published: January 2022

Ammonia is the most common contaminant in aquaculture systems. Due to the unexpected deterioration of natural seawater quality caused by harmful alga blooms in summer, the water exchange cycle for the culture ponds of the swimming crab Portunus trituberculatus, an important aquaculture species in China, is often much longer, and the crabs may be exposed to long-term ammonia stress. However, less information is available regarding the long-term effects of ammonia in marine decapod crustaceans. Therefore, it is of great significance to understand the toxic effects of prolonged ammonia in decapods. In this study, alteration of histology, cellular stress responses (CSRs), and apoptosis in the hepatopancreas of P. trituberculatus, an important aquaculture species, during ammonia stress (5, 15, and 45 mg⋅L–1) for 1, 7, and 15 days and recovery at the normal condition for 7 days, were analyzed. Our results demonstrated a serious impact of long-term (15 days) ammonia stress by depressing crab CSR especially when ammonia concentration exceeds 15 mg⋅L–1. Overall, short- (1 day) and medium-term (7 days) ammonia stress induced CSR, evidenced by upregulated expression of the genes involved in antioxidant defense (SOD, CAT, and GPX), apoptosis (p53, Bax, and Caspase-3), heat shock response (HSR) (Hsp70 and Hsp90), unfolded protein response (UPR) (IRE1, ATF6, and XBP1), and DNA damage response (DDR) (ATR and DNA-PKcs). However, long-term (15 days) ammonia stress, especially when exposed to the ammonia of 15 and 45 mg⋅L–1, resulted in a higher level of apoptosis and severe damage of hepatopancreas, which may be related to the depressed CSR including antioxidant defense, HSR, UPR, and DDR. Notably, after recovery, the expressions of many genes involved in apoptosis, antioxidant response, HSR, UPR, and DDR in the groups exposed to ammonia at 15 and 45 mg⋅L–1 were still significantly different to that of the control group. In summary, care should be taken when P. trituberculatus is exposed to ammonia over 15 mg⋅L–1 especially when exposure duration is longer than 15 days, as the CSR could be compromised. This study provides a reference for a comprehensive understanding of CSR in decapod crustaceans under ammonia stress and will be beneficial for management in the intensive culture of the swimming crab.
Exploring Minimum Secondary Injury for the Treatment of Ocular Trauma With Giant Intraocular Foreign Bodies
Authors: Ma Jing , Zhang Xiaofang , Jin Xuemin , Wang Wenzhan
Published: January 2022

Purpose

To investigate the clinical therapy for giant intraocular foreign bodies (IOFBs) and evaluate the best treatment method with minimum secondary injury.

Methods

We retrospectively analyzed the data of 73 eyes of 73 patients with ocular trauma caused by giant IOFBs between January 2016 and December 2018. The IOFB size, localization, shape, and magnetic properties were recorded. The best corrected visual acuity (BCVA), ocular tissue injuries, entrance wound, interval time from injury to second phase surgery, silicone oil removal, and globe recovery were also observed. The cases were divided into three groups based on the following IOFB extraction paths: limbus path, the pars plana path, and the entrance wound path. The BCVA, IOFB size and shape, the wound, endophthalmitis, and silicone oil removal were compared among the three groups.

Results

The IOFBs were 46 cases of magnetic and 27 cases of nonmagnetic, with a shape of thin flat in 19 cases, thick flat in 12 cases, long in seven cases, and irregular in 35 cases. Multiple damages were caused by the giant IOFBs, mainly involving the severe cornea, lens, and retina injuries. The postoperative BCVA increased compared with the preoperative BCVA (z = −6.06, P < 0.01). The rate of recovery from blindness was 40.85% (29/71). The thin flat IOFB and long IOFB resulted in a better postoperative BCVA than the other two IOFB shapes (all P < 0.05). The irregular IOFB had a poorer silicone oil removal rate than the other three IOFB shapes (all P < 0.05). The IOFB extraction followed the limbus path in 18 cases, pars plana path in 27 cases, and entrance wound path in 28 cases. The IOFB length and width in the pars plana path group were significantly lower than that in the limbus path group (all P < 0.05), the preoperative BCVA of the pars plana path group was superior to that of the limbus path group (P < 0.05), and the IOFB length, width, and entrance wound length in the pars plana path group were significantly lower than in the entrance wound path group (all P < 0.05). But the postoperative BCVA in the pars plana path group was not better than that in the other two groups (all P > 0.05). The postoperative BCVA of the entrance wound path group was significantly superior to that of the limbus path group (z = −2.01, P = 0.04), while there was no difference between the two groups in IOFB length, width, entrance wound length, or preoperative BCVA (all P > 0.05).

Conclusion

The entrance wound path would benefit to minimize secondary injury in giant IOFB extraction procedure, compared with the limbus and pars plana path.
Case Report: A New Subtype of Lynch Syndrome Associated With MSH2 c.1024_1026 Identified in a Chinese Family
Authors: Li Lu , Zhao Zhe , Dong Lin , Jia Jia , Su Ke , Bai Hua , Wang Jie
Published: January 2022

Background

Lynch syndrome is an autosomal dominant disorder associated with a high incidence of various cancer types. Multiple variants of mismatch repair genes have been reported for Lynch syndrome. However, the diagnosis in patients with atypical cancer types remains challenging. Specifically, little is known about the genetic background of Lynch syndrome-related renal carcinoma. We present a case wherein a renal carcinoma patient with multiple primary skin tumors harbored a variant that has not been previously shown to be associated with Lynch syndrome.

Case Presentation

The proband was a 60-year-old Chinese man with a history of Lynch syndrome-related renal carcinoma and recurrent primary skin tumors. Immunohistochemistry revealed loss of MSH2 and MSH6. Sequencing of mismatch repair genes revealed a previously unknown germline MSH2 mutation (c.1024_1026), which results in an amino acid deletion (p.V342). This variant was co-segregated among the carcinoma-affected family members. After six cycles of immunotherapy, a marked regression of the skin tumors was observed.

Conclusions

We clarify the pathogenic significance of this newly described mutation and suggest immunotherapy for patients with this subtype of Lynch syndrome.
The Bacterial and Fungal Microbiota of “Robiola di Roccaverano” Protected Designation of Origin Raw Milk Cheese
Authors: Biolcati Federica , Ferrocino Ilario , Bottero Maria Teresa , Dalmasso Alessandra
Published: January 2022

Robiola di Roccaverano is an artisanal Protected Designation of Origin (PDO) soft cheese made with raw goat’s milk and by the addition of Natural Milk Culture (NMC) to drive the fermentation process. Cheeses collected from five different dairy plants were analyzed for their bacterial and fungal microbiota diversity. Lactococcus lactis and Leuconostoc mesenteroides were the main bacterial population, while Galactomyces candidum and Kluyveromyces marxianus constituted the core mycobiota but many other minor taxa were observed, suggesting a high level of complexity in fungal composition by these cheeses compared to bacteria population.
Geochemically Defined Space-for-Time Transects Successfully Capture Microbial Dynamics Along Lacustrine Chronosequences in a Polar Desert
Authors: Monteiro Maria R. , Marshall Alexis J. , Hawes Ian , Lee Charles K. , McDonald Ian R. , Cary Stephen Craig
Published: January 2022

The space-for-time substitution approach provides a valuable empirical assessment to infer temporal effects of disturbance from spatial gradients. Applied to predict the response of different ecosystems under current climate change scenarios, it remains poorly tested in microbial ecology studies, partly due to the trophic complexity of the ecosystems typically studied. The McMurdo Dry Valleys (MDV) of Antarctica represent a trophically simple polar desert projected to experience drastic changes in water availability under current climate change scenarios. We used this ideal model system to develop and validate a microbial space-for-time sampling approach, using the variation of geochemical profiles that follow alterations in water availability and reflect past changes in the system. Our framework measured soil electrical conductivity, pH, and water activity in situ to geochemically define 17 space-for-time transects from the shores of four dynamic and two static Dry Valley lakes. We identified microbial taxa that are consistently responsive to changes in wetness in the soils and reliably associated with long-term dry or wet edaphic conditions. Comparisons between transects defined at static (open-basin) and dynamic (closed-basin) lakes highlighted the capacity for geochemically defined space-for-time gradients to identify lasting deterministic impacts of historical changes in water presence on the structure and diversity of extant microbial communities. We highlight the potential for geochemically defined space-for-time transects to resolve legacy impacts of environmental change when used in conjunction with static and dynamic scenarios, and to inform future environmental scenarios through changes in the microbial community structure, composition, and diversity.
Evasion of Host Antiviral Innate Immunity by Paramyxovirus Accessory Proteins
Authors: Wang Chongyang , Wang Ting , Duan Liuyuan , Chen Hui , Hu Ruochen , Wang Xiangwei , Jia Yanqing , Chu Zhili , Liu Haijin , Wang Xinglong , Zhang Shuxia , Xiao Sa , Wang Juan , Dang Ruyi , Yang Zengqi
Published: January 2022

For efficient replication, viruses have developed multiple strategies to evade host antiviral innate immunity. Paramyxoviruses are a large family of enveloped RNA viruses that comprises diverse human and animal pathogens which jeopardize global public health and the economy. The accessory proteins expressed from the P gene by RNA editing or overlapping open reading frames (ORFs) are major viral immune evasion factors antagonizing type I interferon (IFN-I) production and other antiviral innate immune responses. However, the antagonistic mechanisms against antiviral innate immunity by accessory proteins differ among viruses. Here, we summarize the current understandings of immune evasion mechanisms by paramyxovirus accessory proteins, specifically how accessory proteins directly or indirectly target the adaptors in the antiviral innate immune signaling pathway to facilitate virus replication. Additionally, some cellular responses, which are also involved in viral replication, will be briefly summarized.
Investigation of the Importance of Protein 3D Structure for Assessing Conservation of Lysine Acetylation Sites in Protein Homologs
Authors: Jew Kristen M. , Le Van Thi Bich , Amaral Kiana , Ta Allysa , Nguyen May Nina M. , Law Melissa , Adelstein Nicole , Kuhn Misty L.
Published: January 2022

Acetylation is a protein post-translational modification (PTM) that can affect a variety of cellular processes. In bacteria, two PTM Nε-acetylation mechanisms have been identified: non-enzymatic/chemical acetylation via acetyl phosphate or acetyl coenzyme A and enzymatic acetylation via protein acetyltransferases. Prior studies have shown that extensive acetylation of Nε-lysine residues of numerous proteins from a variety of bacteria occurs via non-enzymatic acetylation. In Escherichia coli, new Nε-lysine acetyltransferases (KATs) that enzymatically acetylate other proteins have been identified, thus expanding the repertoire of protein substrates that are potentially regulated by acetylation. Therefore, we designed a study to leverage the wealth of structural data in the Protein Data Bank (PDB) to determine: (1) the 3D location of lysine residues on substrate proteins that are acetylated by E. coli KATs, and (2) investigate whether these residues are conserved on 3D structures of their homologs. Five E. coli KAT substrate proteins that were previously identified as being acetylated by YiaC and had 3D structures in the PDB were selected for further analysis: adenylate kinase (Adk), isocitrate dehydrogenase (Icd), catalase HPII (KatE), methionyl-tRNA formyltransferase (Fmt), and a peroxide stress resistance protein (YaaA). We methodically compared over 350 protein structures of these E. coli enzymes and their homologs; to accurately determine lysine residue conservation requires a strategy that incorporates both flexible structural alignments and visual inspection. Moreover, our results revealed discrepancies in conclusions about lysine residue conservation in homologs when examining linear amino acid sequences compared to 3D structures.
ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets
Authors: Duwaerts Caroline C. , Maiers Jessica L.
Published: January 2022

The endoplasmic reticulum is a central player in liver pathophysiology. Chronic injury to the ER through increased lipid content, alcohol metabolism, or accumulation of misfolded proteins causes ER stress, dysregulated hepatocyte function, inflammation, and worsened disease pathogenesis. A key adaptation of the ER to resolve stress is the removal of excess or misfolded proteins. Degradation of intra-luminal or ER membrane proteins occurs through distinct mechanisms that include ER-associated Degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD), which includes macro-ER-phagy, micro-ER-phagy, and Atg8/LC-3-dependent vesicular delivery. All three of these processes are critical for removing misfolded or unfolded protein aggregates, and re-establishing ER homeostasis following expansion/stress, which is critical for liver function and adaptation to injury. Despite playing a key role in resolving ER stress, the contribution of these degradative processes to liver physiology and pathophysiology is understudied. Analysis of publicly available datasets from diseased livers revealed that numerous genes involved in ER-related degradative pathways are dysregulated; however, their roles and regulation in disease progression are not well defined. Here we discuss the dynamic regulation of ER-related protein disposal pathways in chronic liver disease and cell-type specific roles, as well as potentially targetable mechanisms for treatment of chronic liver disease.
Overexpressed CMTM6 Improves Prognosis and Associated With Immune Infiltrates of Ovarian Cancer
Authors: Yin Bo , Ding Jianyi , Hu Haoran , Yang Meiqin , Huang Baoyou , Dong Wei , Li Fang , Han Lingfei
Published: January 2022

Ovarian cancer (OV) is an epithelial malignancy that intrigues people for its high mortality and lack of efficient treatment. Chemokine-like factor (CKLF)–like MARVEL transmembrane domain containing 6 (CMTM6) can be observed in various cancers, but its part in OV remains little known. Hence, the prognostic value and underlying mechanism of CMTM6 in OV were preliminarily evaluated. Here, we determined that CMTM6 expression was higher than that in normal controls. However, the upregulation of CMTM6 was associated with better prognosis. GSEA results suggested that CMTM6 is involved in the immune-related and metabolism-related pathways. GO/KEGG analysis of CMTM6 coexpressed genes was performed to survey the possible regulatory roles of CMTM6 in OV. Subsequently, CMTM6 expression was positively correlated with the infiltration levels of immune cells and the expression of diverse immune cell marker sets. Importantly, CMTM6 may influence prognosis partially by regulating immune infiltration in OV. Last, copy number variations (CNVs) and DNA methylation might prompt the abnormal CMTM6 expression in OV. In conclusion, CMTM6 can serve as a novel prognostic biomarker in patients with OV.
Prefrontal-Hippocampal Pathways Through the Nucleus Reuniens Are Functionally Biased by Brain State
Authors: Hauer Brandon E. , Pagliardini Silvia , Dickson Clayton T.
Published: January 2022

Circuit-level communication between disparate brain regions is fundamental for the complexities of the central nervous system operation. Co-ordinated bouts of rhythmic activity between the prefrontal cortex (PFC) and hippocampus (HPC), in particular, are important for mnemonic processes. This is true during awake behavior, as well as during offline states like sleep. We have recently shown that the anatomically interposed thalamic nucleus reuniens (RE) has a role in coordinating slow-wave activity between the PFC and HPC. Here, we took advantage of spontaneous brain state changes occurring during urethane anesthesia in order to assess if PFC-HPC communication was modified during activated (theta) vs. deactivated (slow oscillation: SO) states. These forebrain states are highly similar to those expressed during rapid eye movement (REM) and non-REM stages of natural sleep, respectively. Evoked potentials and excitatory current sinks in the HPC were consistently larger during SO states, regardless of whether PFC or RE afferents were stimulated. Interestingly, PFC stimulation during theta appeared to preferentially use a cortico-cortical pathway, presumably involving the entorhinal cortex as opposed to the more direct RE to HPC conduit. Optogenetic and chemogenetic manipulations of the RE suggested that this state-dependent biasing was mediated by responding in the RE itself. Finally, the phase of both ongoing rhythms also appeared to be an important factor in modulating HPC responses, with maximal field excitatory postsynaptic potentials (EPSPs) occurring during the negative-going phase of both rhythms. Thus, forebrain state plays an important role in how communication takes place across the PFC and HPC, with the RE as a determining factor in how this is shaped. Furthermore, ongoing sleep-like rhythms influence the coordination and perhaps potentiate excitatory processing in this extended episodic memory circuit. Our results have direct implications for activity-dependent processes relevant to sleep-dependent memory consolidation.
Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice
Authors: Tao Enfu , Long Gao , Yang Ting , Chen Bo , Guo Rui , Ye Diya , Fang Marong , Jiang Mizu
Published: January 2022

Early life stress (ELS) disposes to functional gastrointestinal diseases in adult, such as irritable bowel syndrome (IBS). Maternal separation (MS) is a well-known animal model of IBS and has been shown to induce visceral hypersensitivity in adult rats and mice. However, to the best of our knowledge, it has not been reported whether MS induces visceral hypersensitivity in young mice, such as the post-weaning mice. Moreover, the method for evaluation of visceral sensitivity also has not been described. Accordingly, the present study aims to evaluate the visceral sensitivity caused by MS in post-weaning mice and develop a novel and small size distention balloon for assessment of visceral sensitivity of such mice. Male pups of C57BL/6 mice were randomly divided into two groups, MS (n = 12) and non-separation (NS) (n = 10). MS pups were separated from the dams through postnatal days (PND) 2 to 14, while NS pups were undisturbed. After, all pups stayed with respective dams and were weaned at PND 22. Visceral sensitivity was evaluated by colorectal distention (CRD) with a novel and small size distention balloon at PND 25. The threshold of abdominal withdrawal reflex (AWR) scores were significantly lower in MS than NS. In addition, AWR scores at different pressures of CRD were significantly higher in MS than NS. The results demonstrate that MS induced visceral hypersensitivity in post-weaning mice. The designed small size distention balloon for evaluation of visceral sensitivity is of significance to further study the pathophysiology of IBS from early life to adulthood.
Exploring the Interobserver Agreement in Computer-Aided Radiologic Tumor Measurement and Evaluation of Tumor Response
Authors: Li Hongsen , Shen Jiaying , Shou Jiawei , Han Weidong , Gong Liu , Xu Yiming , Chen Peng , Wang Kaixin , Zhang Shuangfeng , Sun Chao , Zhang Jie , Niu Zhongfeng , Pan Hongming , Cai Wenli , Fang Yong
Published: January 2022

The accurate, objective, and reproducible evaluation of tumor response to therapy is indispensable in clinical trials. This study aimed at investigating the reliability and reproducibility of a computer-aided contouring (CAC) tool in tumor measurements and its impact on evaluation of tumor response in terms of RECIST 1.1 criteria. A total of 200 cancer patients were retrospectively collected in this study, which were randomly divided into two sets of 100 patients for experiential learning and testing. A total of 744 target lesions were identified by a senior radiologist in distinctive body parts, of which 278 lesions were in data set 1 (learning set) and 466 lesions were in data set 2 (testing set). Five image analysts were respectively instructed to measure lesion diameter using manual and CAC tools in data set 1 and subsequently tested in data set 2. The interobserver variability of tumor measurements was validated by using the coefficient of variance (CV), the Pearson correlation coefficient (PCC), and the interobserver correlation coefficient (ICC). We verified that the mean CV of manual measurement remained constant between the learning and testing data sets (0.33 vs. 0.32, p = 0.490), whereas it decreased for the CAC measurements after learning (0.24 vs. 0.19, p < 0.001). The interobserver measurements with good agreement (CV < 0.20) were 29.9% (manual) vs. 49.0% (CAC) in the learning set (p < 0.001) and 30.9% (manual) vs. 64.4% (CAC) in the testing set (p < 0.001). The mean PCCs were 0.56 ± 0.11 mm (manual) vs. 0.69 ± 0.10 mm (CAC) in the learning set (p = 0.013) and 0.73 ± 0.07 mm (manual) vs. 0.84 ± 0.03 mm (CAC) in the testing set (p < 0.001). ICCs were 0.633 (manual) vs. 0.698 (CAC) in the learning set (p < 0.001) and 0.716 (manual) vs. 0.824 (CAC) in the testing set (p < 0.001). The Fleiss’ kappa analysis revealed that the overall agreement was 58.7% (manual) vs. 58.9% (CAC) in the learning set and 62.9% (manual) vs. 74.5% (CAC) in the testing set. The 80% agreement of tumor response evaluation was 55.0% (manual) vs. 66.0% in the learning set and 60.6% (manual) vs. 79.7% (CAC) in the testing set. In conclusion, CAC can reduce the interobserver variability of radiological tumor measurements and thus improve the agreement of imaging evaluation of tumor response.
Systematic Review With Meta-Analysis: Diagnostic, Prognostic and Clinicopathological Significance of CircRNA Expression in Renal Cancer
Authors: Wang Wujun , Xie Shengfang , Yuan Dongping , He Dandan , Fang Liming , Ge Fengfeng
Published: January 2022

Background

Renal cancer (RC) is one of the most common malignant tumors of the urinary system, and molecular targets for the specific diagnosis and treatment of RC have been widely explored. The purpose of this study was to systematically analyze circular RNAs (circRNAs), which may serve as novel tumor markers in terms of the diagnosis, prognosis and clinicopathological characteristics of RC.

Methods

PubMed and Web of Science were systematically searched for literature as up to July 30, 2021. All included studies were evaluated by the evaluation system, and the results were satisfactory. Hazard ratios (HRs) and odds ratios (ORs) were used to assess the association of circRNAs with diagnostic and clinicopathological indicators. The sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve (AUC) were combined to evaluate the diagnostic performance of circRNAs in RC.

Results

We included 22 studies that met the criteria, including 18 that were prognostic, 4 that were diagnostic, and 12 that were clinicopathologically relevant. In terms of prognosis, we found that upregulated circRNAs were positively associated with poor overall survival in patients with RC (HR=1.63, 95% CI=1.43–1.85). In terms of diagnosis, the combined SEN, SPE and AUC of circRNAs in the diagnosis of RC were 0.82, 0.84 and 0.89 (0.86–0.91), respectively. In terms of clinicopathological features, upregulated circRNAs were associated with the Fuhrman grade (OR=0.641, 95% CI=0.471–0.873), T stage (OR=0.236, 95% CI=0.141–0.396), TNM stage (OR=0.225, 95% CI=0.158–0.321) and lymphatic metastasis (OR=0.329, 95% CI=0.193–0.560).

Conclusion

Our meta-analysis confirms that circRNAs may be candidate biomarkers for the diagnosis, prognosis, and clinicopathological indicators of RC.