Inhibiting IL11RA to mitigate hepatic metastasis in skin cutaneous melanoma: Comprehensive insights from in vitro and in vivo investigations.

OBJECTIVE: This study aimed to investigate the role of Interleukin-11 receptor alpha (IL11RA) in skin cutaneous melanoma (SKCM) metastasis to the liver. METHODS: Human SKCM cell lines (A375, A375-MA2, SK-MEL-28, RPMI-7951) and primary dermal fibroblasts (HDFa) were utilized to assess IL11RA expression. IL11RA siRNA was transfected into RPMI-7951 and A375-MA2 cells for Wound healing and Transwell invasion assays. Il11ra knockout (KO) mice and wild-type (WT) mice were injected with B16-F10 cells into the spleen to evaluate hepatic melanoma metastasis. Correlation between IL11RA and MMP family genes was explored using online databases, including LinkedOmics, TIMER (Tumor Immune Estimation Resource), and GEPIA (Gene Expression Profiling Interactive Analysis). RT-qPCR and Western blotting were performed for expression analysis of Mmp2 and Mmp9 in liver tissues of mice. The impact of IL11RA on the STAT3 pathway was investigated in vitro and in vivo. RESULTS: Elevated expression of IL11RA was observed in SKCM cell lines compared to normal cells. IL11RA downregulation significantly inhibited migratory and invasive capabilities of A375-MA2 and RPMI-7951 in vitro. Il11ra gene knockout in mice demonstrated a substantial reduction in hepatic melanoma metastasis. Correlation analyses revealed associations between IL11RA and MMP2/MMP8. Il11ra gene knockout significantly decreased Mmp2 expression while increasing Mmp8 in liver tissues. IL11RA correlated positively with STAT3, and its inhibition led to a suppressed STAT3 pathway in SKCM cells and mouse liver tissue. CONCLUSION: IL11RA plays a crucial role in SKCM metastasis, affecting migratory and invasive abilities. Targeting IL11RA may offer a promising avenue for therapeutic interventions in cutaneous melanoma progression.

Citations of microRNA Biomarker Articles That Were Retracted: A Systematic Review.

Importance: Retraction is a tool that journals can use to deter research misconduct and alert their audience to erroneous content published in the journals. However, retracted articles may continue to damage science if they are still cited as legitimate articles. Objective: To characterize patterns of postretraction citations, particularly in microRNA biomarker research, a field with one of the highest rates of retraction. Evidence Review: Retracted scientific articles on microRNAs were retrieved from PubMed, Web of Science, and Retraction Watch between database inception and July 17, 2021, according to preestablished search strategies. Control articles with characteristics in common with retracted articles (ie, published in the same journals in the same years and months and with the same number of authors) were matched and retrieved from PubMed. Citation metrics of retractions and control articles were collected from Web of Science. PubPeer was referenced to examine the public response or comments on included retractions. Data were analyzed from September 2021 through March 2023. Findings: A total of 10 461 articles were analyzed, with 887 retractions and 9574 articles as controls. Among retracted articles, which were published from 1999 to 2021, there were 756 articles (85.23%) written by researchers affiliated with Chinese institutions. Retracted articles were cited 6327 times after retraction. Of 792 retracted articles that were cited, 621 articles (78.41%) were cited at least once after retraction and 238 articles (30.05%) were cited more often after retraction than before retraction. Overall citations (comprising citations before and after retraction) and postretraction citations accumulated over time (eg, the median [IQR] number of postretraction citations was 1 [1-2] and 23 [9-44] citations at the first 6 and 66 months, respectively, between retraction and citation retrieval). A random sample of 87 retracted articles (9.81%) recorded 478 citations after retraction, with 208 citations (43.51%) in articles published 12 months or longer after retraction. Of these citing articles, 19 articles (3.97%) mentioned the retractions. Compared with the control group of 1620 nonretracted articles, no significant differences were found in overall number of citations or citations after retraction. Among 478 articles citing retracted articles, 414 articles were found on PubMed and had matched control articles; these articles had higher odds of being subsequently retracted than 7954 matched control articles (odds ratio, 6.57; 95% CI, 3.39-12.72). Conclusions and Relevance: In this study, retraction was not associated with a reduction in citations of retracted articles, but articles that cited retracted publications had higher odds of later retraction. These findings suggest that journals may need to implement mechanisms for detection of postretraction citations.

Endothelial LAT1 (SLC7A5) Mediates S-Nitrosothiol Import and Modulates Respiratory Sequelae of Red Blood Cell Transfusion In Vivo.

BACKGROUND: Increased adhesivity of red blood cells (RBCs) to endothelial cells (ECs) may contribute to organ dysfunction in malaria, sickle cell disease, and diabetes. RBCs normally export nitric oxide (NO)-derived vascular signals, facilitating blood flow. S-nitrosothiols (SNOs) are thiol adducts formed in RBCs from precursor NO upon the oxygenation-linked allosteric transition in hemoglobin. RBCs export these vasoregulatory SNOs on demand, thereby regulating regional blood flow and preventing RBC-EC adhesion, and the large (system L) neutral amino acid transporter 1 (LAT1; SLC7A5) appears to mediate SNO export by RBCs. METHODS: To determine the role of LAT1-mediated SNO import by ECs generally and of LAT1-mediated SNO import by ECs in RBC SNO-dependent modulation of RBC sequestration and blood oxygenation in vivo, we engineered LAT1fl/fl; Cdh5-Cre+ mice, in which the putative SNO transporter LAT1 can be inducibly depleted (knocked down, KD) specifically in ECs ("LAT1ECKD"). RESULTS: We show that LAT1 in mouse lung ECs mediates cellular SNO uptake. ECs from LAT1ECKD mice (tamoxifen-induced LAT1fl/fl; Cdh5-Cre+) import SNOs poorly ex vivo compared with ECs from wild-type (tamoxifen-treated LAT1fl/fl; Cdh5-Cre-) mice. In vivo, endothelial depletion of LAT1 increased RBC sequestration in the lung and decreased blood oxygenation after RBC transfusion. CONCLUSION: This is the first study showing a role for SNO transport by LAT1 in ECs in a genetic mouse model. We provide the first direct evidence for the coordination of RBC SNO export with EC SNO import via LAT1. SNO flux via LAT1 modulates RBC-EC sequestration in lungs after transfusion, and its disruption impairs blood oxygenation by the lung.

Excitatory action of low frequency depolarizing GABA/glycine synaptic inputs is prevalent in prenatal spinal SOD1G93A motoneurons.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1G93A mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an ex vivo preparation and patch clamp recording from MNs with a chloride equilibrium set below spike threshold, we report that low input resistance (Rin ) E17.5 MNs from the SOD1G93A ALS mouse model do not correctly integrate dGPSPs evoked by electrical stimulations of GABA/glycine inputs at different frequencies. Indeed, firing activity of most wild-type (WT) MNs with low Rin was inhibited by incoming dGPSPs, whereas low Rin SOD1G93A MNs were excited or exhibited a dual response (excited by low frequency dGPSPs and inhibited by high frequency dGPSPs). Simulation highlighted the importance of the GABA/glycine input density and showed that pure excitation could be obtained in SOD-like MNs by moving GABA/glycine input away from the cell body to dendrites. This was in agreement with confocal imaging showing a lack of peri-somatic inhibitory terminals in SOD1G93A MNs compared to WT littermates. Putative fast ALS-vulnerable MNs with low Rin are therefore lacking functional inhibition at the near-term prenatal stage. KEY POINTS: We analysed the integration of GABAergic/glycinergic synaptic events by embryonic spinal motoneurons (MNs) in a mouse model of the amyotrophic lateral sclerosis (ALS) neurodegenerative disease. We found that GABAergic/glycinergic synaptic events do not properly inhibit ALS MNs with low input resistance, most probably corresponding to future vulnerable MNs. We used a neuron model to highlight the importance of the GABA/glycine terminal location and density in the integration of the GABAergic/glycinergic synaptic events. Confocal imaging showed a lack of GABA/glycine terminals on the cell body of ALS MNs. The present study suggests that putative ALS vulnerable MNs with low Rin lack functional inhibition at the near-term stage.

Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum-Mitochondria Interaction.

Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER-mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood-brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER-mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.

A prenatal case misunderstood as specimen confusion: 46,XY/46,XY chimerism.

Chimerism results from the fusion of two zygotes in a single embryo, whereas mosaicism results from mitotic errors in a single zygote. True human chimerism is rare, with fewer than 100 cases reported in the literature. Here, we report a case in which the fetus was identified as having tetragametic chimerism based on short tandem repeat - polymerase chain reaction analysis of the family observed during amniocentesis for advanced maternal age. The chimerism occurred via the fertilization of two ova by two spermatozoa, followed by the fusion of early embryos. The genotypes of the two amniotic fluid samples obtained successively by one puncture were completely different, and the sex chromosomes were XY. Karyotyping and copy number variation sequencing showed no abnormalities. The fetus was delivered at term and the phenotype of the newborn was normal.

SNAT2-mediated regulation of estrogen and progesterone in the proliferation of goat mammary epithelial cells.

The development of the goat mammary gland is mainly under the control of ovarian hormones particularly estrogen and progesterone (P4). Amino acids play an essential role in mammary gland development and milk production, and sodium-coupled neutral amino acid transporter 2 (SNAT2) was reported to be expressed in the mammary gland of rats and bovine mammary epithelial cells, which may affect the synthesis of milk proteins or mammary cell proliferation by mediating prolactin, 17ß-estradiol (E2) or methionine function. However, whether SNAT2 mediates the regulatory effects of E2 and P4 on the development of the ruminant mammary gland is still unclear. In this study, we show that E2 and P4 could increase the proliferation of goat mammary epithelial cells (GMECs) and regulate SNAT2 mRNA and protein expression in a dose-dependent manner. Further investigation revealed that SNAT2 is abundantly expressed in the mammary gland during late pregnancy and early lactation, while knockdown and overexpression of SNAT2 in GMECs could inhibit or enhance E2- and P4-induced cell proliferation as well as mammalian target of rapamycin (mTOR) signaling. We also found that the accelerated proliferation induced by SNAT2 overexpression in GMECs was suppressed by the mTOR signaling pathway inhibitor rapamycin. This indicates that the regulation of GMECs proliferation mediated by SNAT2 in response to E2 and P4 is dependent on the mTOR signaling pathway. Finally, we found that the total content of the amino acids in GMECs changed after knocking-down and overexpressing SNAT2. In summary, the results demonstrate that the regulatory effects of E2 and P4 on GMECs proliferation may be mediated by the SNAT2-transported amino acid pathway. These results may offer a novel nutritional target for improving the development of the ruminant mammary gland and milk production.

Prenatal prevalence and postnatal manifestations of 16p11.2 deletions: A new insights into neurodevelopmental disorders based on clinical investigations combined with multi-omics analysis.

BACKGROUND: The 16p11.2 deletion is one of the most common genetic aetiologies of neurodevelopmental disorders (NDDs). The prenatal phenotype of 16p11.2 deletion and the potential mechanism associated with postnatal clinical manifestations were largely unknow. We revealed the developmental trajectories of 16p11.2 deletion from the prenatal to postnatal periods and to identify key signaling pathways and candidate genes contributing to neurodevelopmental abnormalities. METHODS: In this 5-y retrospective cohort study, women with singleton pregnancies who underwent amniocentesis for chromosomal abnormalities were included. Test of copy-number variations (CNVs) involved single nucleotide polymorphism-array and CNV-seq was performed to detected 16p11.2 deletion. For infants born carrying the 16p11.2 deletion, neurological and intellectual evaluations using the Chinese version of the Gesell Development Scale. For patients observed to have vertebral malformations, Sanger sequencing for T-C-A haplotype of TBX6 was performed. For those infants with clinical manifestations, whole-exome sequencing was consecutively performed in trios to rule out single-gene diseases, and transcriptomics combined with untargeted metabolomics were performed. RESULTS: The prevalence of 16p11.2 deletion was 0.063% (55/86,035) in the prenatal period. Up to 80% (20/25) of the 16p11.2 deletions were proven de novo by parental confirmation. Approximately half of 16p11.2 deletions (28/55) were detected with prenatal abnormal ultrasound findings. Vertebral malformations were identified as the most distinctive structural malformations and were enriched in fetuses with 16p11.2 deletions compared with controls (90.9‰ [5/55] vs. 8.4‰ [72/85,980]; P < 0.001). All 5 fetuses with vertebral malformations were confirmed to have the TBX6 haplotype of T-C-A. Overall, 47.6% (10/21) infants birthed were diagnosed with NDDs of different degrees. Language impairment was the predominant manifestation (7/10; 70.0%), followed by motor delay (5/10; 50%). Multi-omics analysis indicated that MAPK3 was the central hub of the differentially expressed gene (DEG) network. We firstly reported that histidine-associated metabolism may be the core metabolic pathway related to the 16p11.2 deletion. CONCLUSION: We demonstrated the prenatal presentation, incomplete penetrance and variable expressivity of the 16p11.2 deletion. We identified vertebral malformations were the most distinctive prenatal phenotypes, and language impairment was the predominant postnatal manifestation. Most of the 16p11.2 deletion was de novo. Meanwhile, we suggested that MAPK3 and histidine-associated metabolism may contribute to neurodevelopmental abnormalities of 16p11.2 deletion.

Spin Quantum Dot Light-Emitting Diodes Enabled by 2D Chiral Perovskite with Spin-Dependent Carrier Transport.

Chiral-induced spin selectivity (CISS) effect provides innovative approach to spintronics and quantum-based devices for chiral materials. Different from the conventional ferromagnetic devices, the application of CISS effect is potential to operate under room temperature and zero applied magnetic field. Low dimensional chiral perovskites by introducing chiral amines are beginning to show significant CISS effect for spin injection, but research on chiral perovskites is still in its infancy, especially on spin-light emitting diode (spin-LED) construction. Here, the spin-QLEDs enabled by 2D chiral perovskites as CISS layer for spin-dependent carrier injection and CdSe/ZnS quantum dots (QDs) as light emitting layer are reported. The regulation pattern of the chirality and thickness of chiral perovskites, which affects the circularly polarized electroluminescence (CP-EL) emission of spin-QLED, is discovered. Notably, the spin injection polarization of 2D chiral perovskites is higher than 80% and the CP-EL asymmetric factor (gCP-EL ) achieves up to 1.6 × 10-2 . Consequently, this work opens up a new and effective approach for high-performance spin-LEDs.

The Effects of Reinforcement Techniques in Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: Protocol for a Web-Based Survey, Systematic Review, and Meta-Analysis.

BACKGROUND: The effects of reinforcement are still controversial in bariatric surgery, and variations may exist in using this technique. OBJECTIVE: This protocol describes a study that aims to survey the views of bariatric surgeons on reinforcement techniques and evaluate the effects of applying reinforcement techniques in sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). METHODS: This study is composed of 2 parts. Part 1 will investigate the differences of using reinforcement techniques among surgeons worldwide who perform SG or RYGB through a survey. The survey will be conducted by email and social media. Part 2 will evaluate the safety and effectiveness of using omentopexy or staple line reinforcement in SG and RYGB by systematic review and meta-analysis. In this part, literature searches will be performed in English databases, including CENTRAL, EMBASE CINAHL, Web of Science, and PubMed, and Chinese databases, including Wanfang, China National Knowledge Infrastructure, Database of Chinese Technical Periodicals, and Chinese Biological Medicine, from their establishment to November 2023. Randomized controlled trials and case-control studies will be included. The primary outcomes are rates of postoperative bleeding and gastric leakage. The secondary outcomes include anastomotic stenosis, surgical site infection, reoperation, estimated intraoperative blood loss, operative time (minutes), length of hospital stay (days), overall complications, and 30-day mortality. The meta-analysis will be conducted using RevMan 5.4 under the random-effects model, as well as through extensive subgroup and sensitivity analyses. P values <0.05 will be considered statistically significant. This study was registered with PROSPERO (Prospective Register of Systematic Reviews) in accordance with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols). RESULTS: The results of this study will be published in a peer-reviewed journal. The web-based survey and initial title or abstract review of papers identified by the search strategy will be completed in November 2023. The second round of title or abstract review and downloading of the papers for full-text inclusion will be completed in January 2024. We aim to complete data extraction and meta-analysis by February 2024 and expect to publish the findings by the end of March 2024. CONCLUSIONS: This study aims to investigate the impact of reinforcement techniques on reducing the incidence of postoperative complications in SG and RYGB procedures and provide assistance for standardizing the procedures of SG and RYGB operations for bariatric surgeons. TRIAL REGISTRATION: PROSPERO CRD42022376438; https://tinyurl.com/2d53uf8n. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50677.

Use of different food additives to control browning in fresh-cut potatoes.

Fresh-cut potato browning is a severe problem in the potato processing industry. Ascorbic acid, L-cysteine, hydrogen sulfide (H2S), and nitric oxide (NO) have been reported to reduce the browning in fresh-cut vegetables and fruits. We compared the effect of each food additive at its commonly used concentration on fresh-cut potato browning in order to choose a highly efficient treatment and explore its mechanism. Fresh-cut potato slices were immersed in 0.3 mmol L-1 ascorbic acid, 0.7 mmol L-1 L-cysteine, 0.7 mmol L-1 H2S, or 2.0 mmol L-1 NO for 10 min and stored at 4°C until the measurements finished. Results showed that the ascorbic acid and L-cysteine treatments showed less browning than the control treatment, while the H2S and NO treatments did not. Ascorbic acid increased total phenolic content, polyphenol oxidase (PPO) and peroxidase (POD) activities, while L-cysteine decreased PPO and POD activities with no change in total phenolic content. In addition, these two treatments did not influence respiration rate, weight loss, or rot index. In conclusion, ascorbic acid (0.3 mmol L-1) and L-cysteine (0.7 mmol L-1) can be valuable means to control fresh-cut potato browning. Ascorbic acid inhibits the browning mainly by reducing quinones back to phenolic compounds, but L-cysteine inhibits the browning mainly by decreasing PPO and POD activities.

Biological Evaluation of 8-Methoxy-2,5-dimethyl-5H-indolo[2,3-b] Quinoline as a Potential Antitumor Agent via PI3K/AKT/mTOR Signaling.

Chemotherapy is commonly used clinically to treat colorectal cancer, but it is usually prone to drug resistance, so novel drugs need to be developed continuously to treat colorectal cancer. Neocryptolepine derivatives have attracted a lot of attention because of their good cytotoxic activity; however, cytotoxicity studies on colorectal cancer cells are scarce. In this study, the cytotoxicity of 8-methoxy-2,5-dimethyl-5H-indolo[2,3-b] quinoline (MMNC) in colorectal cells was evaluated. The results showed that MMNC inhibits the proliferation of HCT116 and Caco-2 cells, blocks the cell cycle in the G2/M phase, decreases the cell mitochondrial membrane potential and induces apoptosis. In addition, the results of western blot experiments suggest that MMNC exerts cytotoxicity by inhibiting the expression of PI3K/AKT/mTOR signaling pathway-related proteins. Based on these results, MMNC is a promising lead compound for anticancer activity in the treatment of human colorectal cancer.

Performance of iCare quantitative computed tomography in bone mineral density assessment of the hip and vertebral bodies in European spine phantom.

BACKGROUND: Osteoporosis is a systemic bone disease which can increase the risk of osteoporotic fractures. Dual-energy X-ray absorptiometry (DXA) is considered as the clinical standard for diagnosing osteoporosis by detecting the bone mineral density (BMD) in patients, but it has flaws in distinguishing between calcification and other degenerative diseases, thus leading to inaccurate BMD levels in subjects. Mindways quantitative computed tomography (Mindways QCT) is a classical QCT system. Similar to DXA, Mindways QCT can directly present the density of trabecular bone, vascular or tissue calcification; therefore, it is more accurate and sensitive than DXA and has been widely applied in clinic to evaluate osteoporosis. iCare QCT osteodensitometry was a new phantom-based QCT system, recently developed by iCare Inc. (China). It has been gradually applied in clinic by its superiority of taking 3-dimensional BMD of bone and converting BMD values to T value automatically. This study aimed at evaluating the osteoporosis detection rate of iCare QCT, compared with synchronous Mindways QCT (USA). METHODS: In this study, 131 patients who underwent hip phantom-based CT scan were included. Bone mineral density (BMD) of the unified region of interests (ROI) defined at the European spine phantom (ESP, German QRM) including L1 (low), L2 (medium), and L3 (high) vertebral bodies was detected for QCT quality control and horizontal calibration. Every ESP scan were taken for 10 times, and the mean BMD values measured by iCare QCT and Mindways QCT were compared. Hip CT scan was conducted with ESP as calibration individually. T-scores gained from iCare QCT and Mindways QCT were analyzed with Pearson correlation test. The detection rates of osteoporosis were compared between iCare QCT and Mindways QCT. The unified region of interests (ROI) was delineated in the QCT software. RESULTS: The results showed that there was no significant difference between iCare QCT and Mindways QCT in the evaluation of L1, L2, and L3 vertebrae bodies in ESP. A strong correlation between iCare QCT and Mindways QCT in the assessment of hip T-score was found. It was illustrated that iCare QCT had a higher detection rate of osteoporosis with the assessment of hip T-score than Mindways QCT did. In patients < 50 years subgroup, the detection rate of osteoporosis with iCare QCT and Mindways QCT was equal. In patients ≥ 50 years subgroup, the detection rate of osteoporosis with iCare QCT (35/92, 38.0%) was higher than that with Mindways QCT. In female subgroup, the detection rate of osteoporosis with iCare QCT was significantly higher than Mindways QCT. In male subgroup, the detection rate of osteoporosis with iCare QCT was also markedly higher than Mindways QCT. The detection rate of osteoporosis by iCare QCT was higher than Mindways QCT with hip bone assessment. Of course, the results of the present study remain to be further verified by multicenter studies in the future.

Developing a prediction model of career plateau for nurses: A cross-sectional study.

AIM: The study aimed to understand the current situation regarding career plateaus experienced by nurses. The objectives were to analyze factors influencing career plateau, and develop a prediction model for career plateau for nurses. DESIGN: A cross-sectional survey was conducted using convenience sampling. METHODS: Participants were 2680 nurses from six tertiary hospitals. Univariable and multivariable logistic regression analyses were carried out to investigate the influencing factors and develop a prediction model of career plateau. RESULTS: The overall incidence rate of nurses reaching a career plateau was 34%. Logistic regression analysis showed that age, position, whether specialized nurses, life satisfaction, organizational support, personal ability and selection tendency were the factors influencing career plateau. The prediction model indicates that older nurses are more likely to reach a career plateau than their younger counterparts, and those who think they have strong personal ability and do not value their work very much are more likely to have a career plateau. Giving nurses more promotion space and learning opportunities, improving life satisfaction, and organizational support are conducive to reducing the occurrence of career plateau.

Phenotypic Analysis and Molecular Characterization of Enlarged Cell Size Mutant in Nannochloropsis oceanica.

The cell cycle is the fundamental cellular process of eukaryotes. Although cell-cycle-related genes have been identified in microalgae, their cell cycle progression differs from species to species. Cell enlargement in microalgae is an essential biological trait. At the same time, there are various causes of cell enlargement, such as environmental factors, especially gene mutations. In this study, we first determined the phenotypic and biochemical characteristics of a previously obtained enlarged-cell-size mutant of Nannochloropsis oceanica, which was designated ECS. Whole-genome sequencing analysis of the insertion sites of ECS indicated that the insertion fragment is integrated inside the 5'-UTR of U/P-type cyclin CYCU;1 and significantly decreases the gene expression of this cyclin. In addition, the transcriptome showed that CYCU;1 is a highly expressed cyclin. Furthermore, cell cycle analysis and RT-qPCR of cell-cycle-related genes showed that ECS maintains a high proportion of 4C cells and a low proportion of 1C cells, and the expression level of CYCU;1 in wild-type (WT) cells is significantly increased at the end of the light phase and the beginning of the dark phase. This means that CYCU;1 is involved in cell division in the dark phase. Our results explain the reason for the larger ECS size. Mutation of CYCU;1 leads to the failure of ECS to fully complete cell division in the dark phase, resulting in an enlargement of the cell size and a decrease in cell density, which is helpful to understand the function of CYCU;1 in the Nannochloropsis cell cycle.

Defining the scope of extended NIPS in Western China: evidence from a large cohort of fetuses with normal ultrasound scans.

BACKGROUND: Standard noninvasive prenatal screening(NIPS) is an accurate and reliable method to screen for common chromosome aneuploidies, such as trisomy 21, 18 and 13. Extended NIPS has been used in clinic for not only aneuploidies but also copy number variants(CNVs). Here we aim to define the range of chromosomal abnormalities that should be able to identify by NIPS in order to be an efficient extended screening test for chromosomal abnormalities. METHODS: A prospective study was conducted, involving pregnant women without fetal sonographic structural abnormalities who underwent amniocentesis. Prenatal samples were analyzed using copy number variation sequencing(CNV-seq) to identify fetal chromosomal abnormalities. RESULTS: Of 28,469 pregnancies included 1,022 (3.59%) were identified with clinically significant fetal chromosome abnormalities, including 587 aneuploidies (2.06%) and 435 (1.53%) pathogenic (P) / likely pathogenic (LP) CNVs. P/LP CNVs were found in all chromosomes, but the distribution was not uniform. Among them, P/LP CNVs in chromosomes 16, 22, and X exhibited the highest frequencies. In addition, P/LP CNVs were most common on distal ends of the chromosomes and in low copy repeat regions. Recurrent microdeletion/microduplication syndromes (MMS) accounted for 40.69% of total P/LP CNVs. The size of most P/LP CNVs (77.47%) was < 3 Mb. CONCLUSIONS: In addition to aneuploidies, the scope of extended NIPS should include the currently known P/LP CNVs, especially the regions with recurrent MMS loci, distal ends of the chromosomes, and low copy repeat regions. To be effective detection should include CNVs of < 3 Mb. Meanwhile, sufficient preclinical validation is still needed to ensure the clinical effect of extended NIPS.

Diverse roles of glucocorticoids in the ruminant mammary gland: modulation of mammary growth, milk production, and mastitis.

As endocrine hormones, glucocorticoids (GCs) play a pivotal role in numerous physiological processes, including mammary growth and lactation, circulatory metabolism, and responses to external stimuli. In the dairy industry, milk production from cows or goats is important for newborns and economic benefits. However, the milk yields from ruminant animals are always affected by the extent of mammary development, mammary disease, stress, or changes in metabolism. Thus, it is necessary to clarify how GCs changes in ruminants affect ruminant mammary gland function and mammary disease. This review summarizes the findings identifying that GCs modulate mammary gland development before lactation, but the stress-induced excessive release of GCs leads to milk production loss. In addition, the manner of GCs release may change under different concentrations of metabolites or during mastitis or inflammatory challenge. Nevertheless, exogenous GCs administration to animals may alleviate the clinical symptoms of mastitis. This review demonstrates that GCs offer a fascinating contribution to both physiologic and pathogenic conditions of the mammary gland in ruminant animals. Characterizing and understanding these changes or functions of endogenous and exogenous GCs in animals will be crucial for developing more endocrine regulators and therapies for improving milk production in ruminants.

Critical quality appraisal of randomized controlled trials with traditional Chinese medicines for the coronavirus disease 2019.

OBJECTIVE: Traditional Chinese medicines (TCM) play an indispensable role during the pandemic of coronavirus disease 2019 (COVID-19), with an increasing number of randomized controlled trials (RCTs) designed and performed to evaluate the efficacy and safety of TCM for COVID-19. This study aimed to critically appraise the quality of currently available RCTs of TCM for COVID-19. METHODS: RCTs of TCM for COVID-19 were searched from three databases by two investigators and selected according to pre-established inclusion and exclusion criteria. General information of included studies was presented by applying descriptive statistics. The methodological and reporting quality of eligible RCTs was critically evaluated based on the risk of bias assessment tool 2 (RoB2) and CONSORT Extension for TCM (CONSORT-CHM Formulas 2017), respectively. The differences of risks and main general information were compared between RCTs published in English and Chinese journals. Microsoft Excel 2019 and SPSS were used for the statistical analysis. A result with p < 0.05 was considered statistically significant. RESULTS: This study finally included 64 RCTs with a total of 10858 participants investigating TCM for COVID-19. All 64 RCTs were evaluated as moderate-to-low RoB including 27 RCTs with high bias, 26 RCTs with some concerns, and 11 with low bias. Results of reporting quality appraisal by CONSORT-CHM Formulas 2017 showed that 61 (95%) RCTs reported more than 18 (50%) items, and 14 (22%) RCTs reported more than 26 (70%) items among all 38 items. Forty-two RCTs were approved by ethics committees and 47 RCTs reported the informed consent information. Twenty-five RCTs and 39 RCTs provided information on trial registration and funding resources, respectively. The quality of 44 RCTs published in Chinese was significantly worse than that of 20 RCTs published in English, especially in the following considerations including the overall RoB, ethics approved, informed consent, trial register, and reporting quality with CONSORT-CHM Formulas 2017. CONCLUSION: The overall quality of RCTs investigating TCM for COVID-19 was appraised as moderate-to-high that was substandard and needs to be continuously improved, especially for RCTs published in Chinese, in the future.

A chromosomal microarray analysis-based laboratory algorithm for the detection of genetic etiology of early pregnancy loss.

Background: Chromosomal abnormalities are a major cause of early pregnancy loss. However, models synthesizing existing genetic technologies to improve pregnancy outcomes are lacking. We aim to provide an integrated laboratory algorithm for the genetic etiology of couples who experienced pregnancy loss. Methods: Over a 6-year period, 3,634 products of conception (POCs) following early pregnancy loss were collected. The clinical outcomes from a laboratory algorithm based on single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and parental chromosomal karyotyping assays were comprehensively evaluated. Results: In total, 3,445 of 3,634 (94.8%) POCs had no maternal-cell contamination. Of those POCs, the detection rate of abnormal results was 65.2% (2,247/3,445), of which 91.2% (2,050/2,247) had numerical chromosomal abnormalities, 2.7% (60/2,247) had copy-number variations (CNVs) ≥10 Mb, 2.7% (61/2,247) had CNVs of terminal deletion and duplication, 2.8% (62/2,247) had CNVs <10 Mb, and 0.6% (14/2,247) had uniparental disomy. Furthermore, FISH confirmed 7 of the 60 POCs with mosaic aneuploids below 30% based on the SNP array results as tetraploid. Of the 52 POCs with CNVs of terminal deletion and duplication, 29 couples had balanced rearrangements based on chromosomal karyotyping. Conclusion: The integrated SNP array-based algorithm combined with optional FISH and parental chromosomal karyotyping is an effective laboratory testing strategy, providing a comprehensive and reliable genetic investigation for the etiology of miscarriage, regardless of the number of miscarriages and the method of conception.