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Pleosmaranes A-R (1-18), 18 new isopimarane-type diterpenoids, together with four known analogs (19-22), were isolated from the mangrove endophytic fungus Pleosporales sp. HNQQJ-1. Their structures and absolute configurations were established by analysis of their spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-9 possess an unusual aromatic B ring and a 20-nor-isopimarane skeleton. Compounds 15-17 contain a unique 2-oxabicyclo[2.2.2]octane moiety. Compound 18 features an unexpected 2-oxabicyclo[3.2.1]octane moiety. Compounds 8 and 12 exhibited a moderate inhibitory effect against LPS-induced NO production, with IC50 values of 19 and 25 µM, respectively.
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Ascomicetos , Diterpenos , Abietanos/farmacologia , Octanos , Ascomicetos/química , Diterpenos/farmacologia , Estrutura MolecularRESUMO
The impact of NaOH-modified biochar on the release of NH3 and H2S from laying hens' manure was examined for 44 days, using a small-scale simulated aerobic composting system. The findings revealed that the NaOH-modified biochar reduced NH3 and H2S emissions by 40.63% and 77.78%, respectively, compared to the control group. Moreover, the emissions of H2S were significantly lower than those of the unmodified biochar group (p < 0.05). The increased specific surface area and microporous structure of the biochar, as well as the higher content of alkaline and oxygenated functional groups, were found to facilitate the adsorption of NH3 and H2S. This enhanced adsorption capability was the primary reason for the significant reduction in NH3 emissions. Furthermore, during the high-temperature phase of composting, there was a notable alteration in the microbial community. The abundance of Limnochordaceae, Savagea, and IMCC26207 increased significantly which aided in the conversion of H2S to stable sulfate. These microorganisms also influenced the abundance of functional genes involved in sulfur metabolism, thereby inhibiting cysteine synthesis, along with the decomposition and conversion of sulfate to sulfite. This led to a significant decrease in H2S emissions. This study provides valuable data for the selection of deodorizers in the composting process of egg-laying hens. The results have significant implications for the application of NaOH-modified biochar for odor reduction in aerobic composting processes.
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Amônia , Carvão Vegetal , Galinhas , Compostagem , Sulfeto de Hidrogênio , Esterco , Sulfeto de Hidrogênio/química , Animais , Carvão Vegetal/química , Amônia/química , Hidróxido de Sódio/química , FemininoRESUMO
Six previously undescribed cytosporone derivatives (phomotones A-E (1-5) and phomotone F (13)), two new spiro-alkanol phombistenes A-B (14-15), and seven known analogs (6-12) were isolated from the mangrove endophytic fungus Phomopsis sp. QYM-13. The structures of these compounds were elucidated using spectroscopic data analysis, electronic circular dichroism (ECD), and 13C NMR calculations. Compound 14 features an unprecedented 1,6-dioxaspiro[4.5]decane ring system. All isolates were evaluated for their inhibitory effect on nitric oxide (NO) in LPS-induced RAW264.7 cells. The results showed that compounds 1, 6, 8, and 11 exhibited potent bioactivities by comparing with positive control. Then, compound 1 displayed the anti-inflammatory effect by inhibiting the MAPK/NF-κB signaling pathways. Molecular docking further revealed the possible mechanism of compound 1 interaction with ERK protein.
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Fungos , Phomopsis , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Transdução de Sinais , Estrutura MolecularRESUMO
Object detection based on wood defects involves using bounding boxes to label defects in the surface image of the wood. This step is crucial before the transformation of wood products. Due to the small size and diverse shape of wood defects, most previous object detection models are unable to filter out critical features effectively. Consequently, they have faced challenges in generating adequate contextual information to detect defects accurately. In this paper, we proposed a YOLOv5 model based on a Semi-Global Network (SGN) to detect wood defects. Unlike previous models, firstly, a lightweight SGN is introduced in the backbone to model the global context, which can improve the accuracy and reduce the complexity of the network at the same time; the backbone is embedded with the Extended Efficient Layer Aggregation Network (E-ELAN), which continuously enhances the learning ability of the network; and finally, the Efficient Intersection and Merger (EIOU) loss is used to solve the problems of slow convergence speed and inaccurate regression results. Experimental results on public wood defect datasets demonstrated that our approach outperformed existing target detection models. The mAP value was 86.4%, a 3.1% improvement over the baseline network model, a 7.1% improvement over SSD, and a 13.6% improvement over Faster R-CNN. These results show the effectiveness of our proposed methodology.
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In this study, the effects of manure on the availability of sulfonamide antibiotics (SAs) in soils were explored in situ by the Diffusive gradients in thin films (DGT) technique. Five antibiotics, including sulfadiazine (SDZ), sulfamethoxazole (SMX), sulfamethazine (SMZ), sulfachloropyridazine (SCP), and sulfadimethoxine (SDM), were selected as target compounds. Results showed that the manure application to soil could reduce the antibiotic availability indicated by DGT. DGT measurement (CDGT) showed good correlations with the soil solution concentrations (Cd). Manure application can suppress the fluxes of SAs from the soil to the soil solution. Using the DGT-induced soil/sediment flux model (DIFS), the labile pool size (Kdl), the rate constants (k1, k-1) of adsorption and desorption and response time (Tc) of SAs in soils were obtained. The addition of manure increased extractable fraction, labile pool size (Kdl) and k1 but decreased k-1. Together with the nonlinear relationship between DGT fluxes and the reciprocal of diffusive layer thickness (Δg), these findings suggested that the release of SAs from soil particles into the soil solution is thermodynamically and kinetically limited, and the manure application could enhance this limitation. This study offers insight into antibiotic availability in soils caused by manure application.
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Antibacterianos , Poluentes do Solo , Solo , Esterco , Sulfanilamida , Sulfonamidas , Poluentes do Solo/análiseRESUMO
BACKGROUND: Mental disorders impose heavy burdens on patients' families and children. It is imperative to provide family-focused services to avoid adverse effects from mental disorders on patients' families and children. However, implementing such services requires a great deal of involvement of mental health workers. This study investigated the attitudes, knowledge, skills, and practices in respect to family-focused practices (FFP) in a sample of Chinese mental health workers. METHODS: A cross-sectional study design was employed to examine the attitudes, knowledge, skills, and practices of a convenience sample of Chinese mental health workers in respect to FFP, using the Chinese version of the Family-Focused Mental Health Practice Questionnaire (FFMHPQ). RESULTS: In total, 515 mental health workers participated in our study, including 213 psychiatrists, 269 psychiatric nurses, and 34 allied mental health professionals (20 clinical psychologists, 9 mental health social workers, and 4 occupational therapists). Compared with psychiatric nurses, psychiatrists and allied mental health professionals provided more support for families and children of patients with mental illness and were more willing to receive further training in FFP. However, there were no significant differences on knowledge, skills, and confidence across different profession types. After adjusting for demographic and occupational variables, previous training in FFP was positively associated with mental health workers' knowledge, skills, and confidence about FFP, but not actual support to families and children. CONCLUSIONS: Professional differences on FFP exist in Chinese mental health workers. Training is needed to engage psychiatrists and other allied workforce in dissemination and implementation of FFP in China.
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Transtornos Mentais , Enfermagem Psiquiátrica , Criança , China , Estudos Transversais , Pessoal de Saúde , Humanos , Transtornos Mentais/terapia , Saúde MentalRESUMO
Auxin is one of the most critical hormones in plants. YUCCA (Tryptophan aminotransferase of Arabidopsis (TAA)/YUCCA) enzymes catalyze the key rate-limiting step of the tryptophan-dependent auxin biosynthesis pathway, from IPA (Indole-3-pyruvateacid) to IAA (Indole-3-acetic acid). Here, 13 YUCCA family genes were identified from Isatis indigotica, which were divided into four categories, distributing randomly on chromosomes (2n = 14). The typical and conservative motifs, including the flavin adenine dinucleotide (FAD)-binding motif and flavin-containing monooxygenases (FMO)-identifying sequence, existed in the gene structures. IiYUCCA genes were expressed differently in different organs (roots, stems, leaves, buds, flowers, and siliques) and developmental periods (7, 21, 60, and 150 days after germination). Taking IiYUCCA6-1 as an example, the YUCCA genes functions were discussed. The results showed that IiYUCCA6-1 was sensitive to PEG (polyethylene glycol), cold, wounding, and NaCl treatments. The over-expressed tobacco plants exhibited high auxin performances, and some early auxin response genes (NbIAA8, NbIAA16, NbGH3.1, and NbGH3.6) were upregulated with increased IAA content. In the dark, the contents of total chlorophyll and hydrogen peroxide in the transgenic lines were significantly lower than in the control group, with NbSAG12 downregulated and some delayed leaf senescence characteristics, which delayed the senescence process to a certain extent. The findings provide comprehensive insight into the phylogenetic relationships, chromosomal distributions, and expression patterns and functions of the YUCCA gene family in I. indigotica.
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Isatis/genética , Oxigenases de Função Mista/genética , Família Multigênica , Proteínas de Plantas/genética , Triptofano Transaminase/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Ácidos Indolacéticos/metabolismo , Isatis/metabolismo , Oxigenases de Função Mista/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Triptofano Transaminase/metabolismoRESUMO
Intestinal microbial metabolism has an important impact on the health of laying hens, and microbes are also important hosts for ARGs. However, the relationship between intestinal microbes and antibiotic resistance in laying hens is unclear. In this study, a slaughtering experiment, an in vitro fermentation experiment and a single-bacteria culture experiment were carried out, and metagenomic and metabolomic analyses were used to investigate the relationships between microbial metabolism and the antibiotic resistome in the cecum of laying hens. The results showed that there were different types of ARGs in the intestines of laying hens, and the risk scores of the ARGs tended to decrease with growth stage. A total of 1142 metagenome-assembled genomes (MAGs) were obtained, and Escherichia coli was found to be the dominant ARG host, carrying 62 ARGs. Metabolomics revealed that indole and its derivatives, such as indole-3-lactic acid, were negatively correlated with a variety of ARGs. Moreover, in vitro fermentation experiment and single-bacteria culture experiment demonstrated that indole-3-lactic acid reduced the abundance and risk of multiple ARGs in the intestine and inhibited the growth of the ARG host Escherichia coli. In the context of high concern about intestinal microbial metabolism and antibiotic resistance, this is the first study to focus on the relationship between intestinal microbial metabolism and antibiotic resistance in laying hens. These findings have important implications for healthy farming and antibiotic resistance control.
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The gut microbiome plays a crucial role in maintaining animal health and is influenced by various factors, including light exposure; however, the response in laying hens of the gut microbiome to intermittent light regimes and the related impact on antibiotic resistance genes (ARGs) remain poorly understood. In this study, we divided 20-week-old laying hens into two groups. These groups were exposed to either continuous normal light or intermittent light for 8 weeks. The feces and cecal contents of laying hens were collected for analysis. Metagenomic analysis of both feces and cecal content samples revealed significant shifts in the microbial composition and abundance of ARGs under intermittent light exposure compared to normal light exposure (P < 0.05). Furthermore, metabolomic analysis of the cecal contents revealed substantial alterations in the abundance and composition of ARGs and mobile genetic elements (MGEs) in response to intermittent light exposure (P < 0.05). Network analysis revealed intricate co-occurrence patterns among bacterial communities, metabolites, and ARGs, highlighting correlations between Bacteroidetes species, ARGs, and metabolites. Although certain bacterial species showed differential associations, the dominant bacteria carrying ARGs or MGEs had relatively low numbers, suggesting that other bacterial communities may have had a greater influence on ARG dissemination. Moreover, our observations highlight the crucial role of metabolites as mediators between bacterial communities and ARGs, providing novel insights into the dynamics of antibiotic resistance development. Our findings underscore the impact of intermittent light exposure on ARG proliferation in poultry farming and emphasize interconnections among ARGs, bacterial communities, and metabolic pathways. The results underscore the importance of considering both microbial communities and metabolic processes to understand antibiotic resistance in agricultural settings.
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Ceco , Galinhas , Resistência Microbiana a Medicamentos , Fezes , Microbioma Gastrointestinal , Animais , Galinhas/microbiologia , Ceco/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Resistência Microbiana a Medicamentos/genética , Luz , Feminino , Bactérias/genética , Genes Bacterianos , Antibacterianos/farmacologiaRESUMO
Nowadays, more people are choosing to use cloud storage services to save space and reduce costs. To enhance the durability and persistence, users opt to store important data in the form of multiple copies on cloud servers. However, outsourcing data in the cloud means that it is not directly under the control of users, raising concerns about security and integrity. Recent research has found that most existing multicopy integrity verification schemes can correctly perform integrity verification even when multiple copies are stored on the same Cloud Service Provider (CSP), which clearly deviates from the initial intention of users wanting to store files on multiple CSPs. With these considerations in mind, this paper proposes a scheme for synchronizing the integrity verification of copies, specifically focusing on strongly privacy Internet of Things (IoT) electronic health record (EHR) data. First, the paper addresses the issues present in existing multicopy integrity verification schemes. The scheme incorporates the entity Cloud Service Manager (CSM) to assist in the model construction, and each replica file is accompanied with its corresponding homomorphic verification tag. To handle scenarios where replica files stored on multiple CSPs cannot provide audit proof on time due to objective reasons, the paper introduces a novel approach called probability audit. By incorporating a probability audit, the scheme ensures that replica files are indeed stored on different CSPs and guarantees the normal execution of the public auditing phase. The scheme utilizes identity-based encryption (IBE) for the detailed design, avoiding the additional overhead caused by dealing with complex certificate issues. The proposed scheme can withstand forgery attack, replace attack, and replay attack, demonstrating strong security. The performance analysis demonstrates the feasibility and effectiveness of the scheme.
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The rate of soybean canopy establishment largely determines photoperiodic sensitivity, subsequently influencing yield potential. However, assessing the rate of soybean canopy development in large-scale field breeding trials is both laborious and time-consuming. High-throughput phenotyping methods based on unmanned aerial vehicle (UAV) systems can be used to monitor and quantitatively describe the development of soybean canopies for different genotypes. In this study, high-resolution and time-series raw data from field soybean populations were collected using UAVs. The RGB (red, green, and blue) and infrared images are used as inputs to construct the multimodal image segmentation model-the RGB & Infrared Feature Fusion Segmentation Network (RIFSeg-Net). Subsequently, the segment anything model was employed to extract complete individual leaves from the segmentation results obtained from RIFSeg-Net. These leaf aspect ratios facilitated the accurate categorization of soybean populations into 2 distinct varieties: oval leaf type variety and lanceolate leaf type variety. Finally, dynamic modeling was conducted to identify 5 phenotypic traits associated with the canopy development rate that differed substantially among the classified soybean varieties. The results showed that the developed multimodal image segmentation model RIFSeg-Net for extracting soybean canopy cover from UAV images outperformed traditional deep learning image segmentation networks (precision = 0.94, recall = 0.93, F1-score = 0.93). The proposed method has high practical value in the field of germplasm resource identification. This approach could lead to the use of a practical tool for further genotypic differentiation analysis and the selection of target genes.
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Phages are among the most widely spread viruses, but their profiles and the antibiotic resistance genes (ARGs) they carry in swine wastewater remain underexplored. The present study investigated the distribution characteristics of phages and their ARG risk in anoxic/oxic (A/O) wastewater treatment processes of swine farms using short- and long-read metagenome and virome. The results demonstrated that the virome could extract more phage sequences than the total metagenome; thus, it was more suited for studying phages in wastewater settings. Intriguingly, phages had significantly lower abundance of ARG than ARGs harbored by total microorganisms (P < 0.01). Eleven ARGs co-occurred with phages and bacteria (R > 0.6 and P < 0.05), with Siphoviridae being the phage co-occurring with the most ARGs (5). Horizontal gene transfer (HGT) events were observed between Proteobacteria and the major phyla except for Bacteroidota. Furthermore, there were prophage sequences and ARGs on the same contig in bacterial MAGs. These data strongly demonstrate that phages promote horizontal transfer of ARG between bacterial hosts in A/O processes for swine wastewater treatment. Therefore, the risk of phage-mediated horizontal transfer of ARGs cannot be overlooked despite the low abundance of phage ARGs (pARG).
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Antibacterianos , Bacteriófagos , Animais , Suínos , Antibacterianos/farmacologia , Metagenoma , Águas Residuárias , Bacteriófagos/genética , Viroma , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Genes BacterianosRESUMO
Metal peroxide nanomaterials as efficient hydrogen peroxide (H2O2) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide H2O2 is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO2/Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO2) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO2/Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of H2O2 was released. Simultaneously, Pd NPs catalyze self-supplied H2O2 to generate abundant hydroxyl radicals (â¢OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant â¢OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO2/Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.
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Ferroptose , Ácido Hialurônico , Óxido de Magnésio , Nanocompostos , Paládio , Terapia Fototérmica , Microambiente Tumoral , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Ferroptose/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Óxido de Magnésio/química , Óxido de Magnésio/farmacologia , Nanocompostos/química , Nanocompostos/uso terapêutico , Terapia Fototérmica/métodos , Animais , Humanos , Paládio/química , Paládio/farmacologia , Paládio/uso terapêutico , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Peróxido de HidrogênioRESUMO
Under the shared big data environment, the existing shared data auditing schemes rarely consider the authorization management of group users. Thus, in this paper, we propose a novel remote shared data checking possession scheme that support group authority management. To implement group user rights management, we firstly introduce a trusted entity group manager. To assist the group manager in authorization management, we formalize a new algebraic structure operator named authorization invisible authenticator (AIA). Meanwhile, we provide a basic AIA scheme for general security scenarios and a standard AIA scheme suitable for high-level security scenarios respectively. The standard AIA scheme can fully meet the needs of the group manager to safely perform rights management work. It is composed of the User Information Table (UIT) and the basic AIA scheme, which has higher security and is applicable to a wider range of scenarios. By distributing AIA through the standard AIA scheme, the group manager can easily carry out authority management, including enrolling, revoking, updating. After solving the problem of authorization management, the detailed design of the scheme based on identity-based encryption (IBE) is given. Furthermore, the security analysis and performance evaluation demonstrate that the scheme is safe and feasible.
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Two new 12- or 13- membered-ring macrocyclic alkaloids ascomylactam D and E (1 & 2), and a pair of new enantiomer (+)- and (-)- didymetone (3) were purified from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures and absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction, ECD and 13C NMR calculations. Compound 2 exhibited significant cytotoxicity against human A549 and KYSE 150 cancer cell lines with IC50 values of 2.8 µM and 5.9 µM, respectively.
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Antineoplásicos , Ascomicetos , Humanos , Estrutura Molecular , Ascomicetos/química , Cristalografia por Raios X , Espectroscopia de Ressonância MagnéticaRESUMO
Light mainly synergistically regulates the central biological clock system. In farming, long-term light exposure may induce metabolic disorders and increase the load on the liver in laying hens. In contrast, intermittent photoperiods can reduce light exposure and increase rest time to improve the health of laying hens. The circadian rhythms of gut microbes are essential for the health of the host. However, the circadian rhythms of gut microbes and how those microbes interact with the host under intermittent photoperiods are not clear. We used laying hens as a model to evaluate the circadian rhythms of gut microbes and biological clock genes under different intermittent photoperiods. Intermittent photoperiod 1 (IP1, 16 [3 h -L/1 h -D]: 8 D) enhanced the circadian rhythms of cBmal1, cBmal2, cCry1, and cCry2 in the hypothalamus and increased the expression of cClock, cBmal1, and cCry2 in the liver and seven clock genes in the cecal wall. The intermittent photoperiod also significantly altered the composition and metabolic function of the cecal microbiota via the melatonin pathway. The concentrations of short-chain fatty acids (SCFAs) and the abundance of SCFA-producing genera such as Odoribacter significantly increased under the IP1 treatment and might have further fed back into and strengthened the peripheral and central rhythms by activating the SCFA receptor gene pathway in cecal wall. These findings clarify the mediation mechanisms for the circadian rhythms of the central circadian clock and highlight the role of intermittent photoperiod-induced regulation of the interaction between the host clock and the cecal microbial community.
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Galinhas , Proteínas Repressoras , Animais , Feminino , Relógios BiológicosRESUMO
BACKGROUND: Companion animals can contribute to the physical and mental health of people and often live in very close association with their owners. However, the antibiotic resistome carried by companion animals and the impact they have on their owners and living environment remain unclear. In this study, we compared the ARG profiles of cats, humans, and their living environments using metagenomic analysis to identify the core ARGs in the cat and human gut and explore the potential impact of cats on ARGs in the human gut through the environment. RESULTS: Results showed that the abundance of ARGs in the cat gut was significantly higher than that in the human gut (P < 0.0001), with aminoglycoside and tetracycline resistance genes being the dominant ARGs in the cat gut. There was no significant difference in the abundance of total ARGs in the guts of cat owners and non-owners (P > 0.05). However, the abundance of aminoglycoside resistance genes including APH(2'')-IIa and AAC(6')-Im was significantly higher in cat owners than that in non-cat owners (P < 0.001). Also, ARG abundance was positively correlated with the frequency of cat activity in the living environment. Enterobacteriaceae was the dominant ARG host co-occurring in the cat gut, human gut, and living environment. CONCLUSIONS: Our results show that cats may shape the living environment resistome and thus the composition of some ARGs in the human gut, highlighting the importance of companion animal environment health. Video Abstract.
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Antibacterianos , Genes Bacterianos , Animais , Humanos , Gatos , Antibacterianos/farmacologia , Genes Bacterianos/genética , Aminoglicosídeos , Tetraciclina , EnterobacteriaceaeRESUMO
INTRODUCTION: Family-focused practice has become an emerging paradigm in mental health services. However, little is known about family-focused practice and associated factors in Chinese mental health workers. AIM: To examine family-focused practice and associated factors in Chinese mental health workers. METHOD: A cross-sectional survey was conducted in a convenience sample of mental health workers (n = 515) in Beijing, China. The Family-Focused Mental Health Practice Questionnaire was used to measure family-focused practice, as well as worker, workplace and client factors that might influence family-focused practice. Multiple linear regression analysis was performed to investigate the factors associated with family-focused practice. RESULTS: On average, the participants exhibited a moderate level of engagement in family-focused practice. The factors that most significantly influenced family-focused practice in Chinese mental health workers were skill and knowledge, worker confidence and time and workload. Moreover, psychiatrists were found to engage more in family-focused practice than psychiatric nurses, and community mental health workers were more active in family-focused practice than hospital-based ones. DISCUSSION: This study provided important data concerning family-focused practice and associated factors in Chinese mental health workers. IMPLICATIONS FOR PRACTICE: The varying level of Chinese mental health workers to engage in family-focused practice has advocacy, training, research and organizational implications for mental health services in China and elsewhere.
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Transtornos Mentais , Serviços de Saúde Mental , Humanos , Saúde Mental , Estudos Transversais , Transtornos Mentais/psicologia , População do Leste AsiáticoRESUMO
Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.6% of preexisting heterozygous loci in control single blastomere samples appear as homozygous after whole genome amplification indicative of allelic dropouts. To overcome these limitations, we validate on-target modifications seen in gene edited human embryos in embryonic stem cells. We show that, in addition to frequent indel mutations, biallelic double-strand breaks can also produce large deletions at the target site. Moreover, some embryonic stem cells show copy-neutral loss of heterozygosity at the cleavage site which is likely caused by interallelic gene conversion. However, the frequency of loss of heterozygosity in embryonic stem cells is lower than in blastomeres, suggesting that allelic dropouts is a common whole genome amplification outcome limiting genotyping accuracy in human preimplantation embryos.
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Blastocisto , Edição de Genes , Humanos , Blastômeros , Embrião de Mamíferos , AlelosRESUMO
The effect of glucocorticoid therapy on women with unexplained positive autoantibodies is under debate. This systemic review and meta-analysis were performed to evaluate whether glucocorticoid administration can improve the pregnancy outcome of this population. Relevant publications were searched from databases, and a total of seven prospective and retrospective cohort studies that investigated the effects of glucocorticoid administration on women with unexplained positive autoantibodies, were included. The outcomes of our systematic review and meta-analysis were measured in terms of risk ratios (RR) with 95% confidence intervals (CI) using fixed or random effect models. We found that glucocorticoid treatment improved the clinical pregnancy rate (RR 2.19, 95% CI 1.64-2.92) and live birth rate (RR 1.92, 95% CI 1.17-3.16), especially when glucocorticoid administration was started before pregnancy (clinical pregnancy rate: RR 2.30, 95% CI 1.58-3.34; live birth rate: RR 2.30, 95% CI 1.58-3.34). However, no effect of glucocorticoids on the miscarriage rate was found (RR 0.75, 95% CI 0.55-1.02) regardless of the time of drug administration. Our systematic review and meta-analysis support the rational use of glucocorticoids in women with unexplained positive autoantibodies. Systematic Review Registration: [www.ClinicalTrials.gov], identifier [CRD42019124442].