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1.
Neuroimage ; 290: 120580, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38508294

ABSTRACT

Diagnosis of disorders of consciousness (DOC) remains a formidable challenge. Deep learning methods have been widely applied in general neurological and psychiatry disorders, while limited in DOC domain. Considering the successful use of resting-state functional MRI (rs-fMRI) for evaluating patients with DOC, this study seeks to explore the conjunction of deep learning techniques and rs-fMRI in precisely detecting awareness in DOC. We initiated our research with a benchmark dataset comprising 140 participants, including 76 unresponsive wakefulness syndrome (UWS), 25 minimally conscious state (MCS), and 39 Controls, from three independent sites. We developed a cascade 3D EfficientNet-B3-based deep learning framework tailored for discriminating MCS from UWS patients, referred to as "DeepDOC", and compared its performance against five state-of-the-art machine learning models. We also included an independent dataset consists of 11 DOC patients to test whether our model could identify patients with cognitive motor dissociation (CMD), in which DOC patients were behaviorally diagnosed unconscious but could be detected conscious by brain computer interface (BCI) method. Our results demonstrate that DeepDOC outperforms the five machine learning models, achieving an area under curve (AUC) value of 0.927 and accuracy of 0.861 for distinguishing MCS from UWS patients. More importantly, DeepDOC excels in CMD identification, achieving an AUC of 1 and accuracy of 0.909. Using gradient-weighted class activation mapping algorithm, we found that the posterior cortex, encompassing the visual cortex, posterior middle temporal gyrus, posterior cingulate cortex, precuneus, and cerebellum, as making a more substantial contribution to classification compared to other brain regions. This research offers a convenient and accurate method for detecting covert awareness in patients with MCS and CMD using rs-fMRI data.


Subject(s)
Consciousness Disorders , Deep Learning , Humans , Brain/diagnostic imaging , Persistent Vegetative State , Unconsciousness , Consciousness
2.
Eur Radiol ; 34(3): 2048-2061, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37658883

ABSTRACT

OBJECTIVES: With the popularization of chest computed tomography (CT) screening, there are more sub-centimeter (≤ 1 cm) pulmonary nodules (SCPNs) requiring further diagnostic workup. This area represents an important opportunity to optimize the SCPN management algorithm avoiding "one-size fits all" approach. One critical problem is how to learn the discriminative multi-view characteristics and the unique context of each SCPN. METHODS: Here, we propose a multi-view coupled self-attention module (MVCS) to capture the global spatial context of the CT image through modeling the association order of space and dimension. Compared with existing self-attention methods, MVCS uses less memory consumption and computational complexity, unearths dimension correlations that previous methods have not found, and is easy to integrate with other frameworks. RESULTS: In total, a public dataset LUNA16 from LIDC-IDRI, 1319 SCPNs from 1069 patients presenting to a major referral center, and 160 SCPNs from 137 patients from three other major centers were analyzed to pre-train, train, and validate the model. Experimental results showed that performance outperforms the state-of-the-art models in terms of accuracy and stability and is comparable to that of human experts in classifying precancerous lesions and invasive adenocarcinoma. We also provide a fusion MVCS network (MVCSN) by combining the CT image with the clinical characteristics and radiographic features of patients. CONCLUSION: This tool may ultimately aid in expediting resection of the malignant SCPNs and avoid over-diagnosis of the benign ones, resulting in improved management outcomes. CLINICAL RELEVANCE STATEMENT: In the diagnosis of sub-centimeter lung adenocarcinoma, fusion MVCSN can help doctors improve work efficiency and guide their treatment decisions to a certain extent. KEY POINTS: • Advances in computed tomography (CT) not only increase the number of nodules detected, but also the nodules that are identified are smaller, such as sub-centimeter pulmonary nodules (SCPNs). • We propose a multi-view coupled self-attention module (MVCS), which could model spatial and dimensional correlations sequentially for learning global spatial contexts, which is better than other attention mechanisms. • MVCS uses fewer huge memory consumption and computational complexity than the existing self-attention methods when dealing with 3D medical image data. Additionally, it reaches promising accuracy for SCPNs' malignancy evaluation and has lower training cost than other models.


Subject(s)
Deep Learning , Lung Neoplasms , Multiple Pulmonary Nodules , Precancerous Conditions , Solitary Pulmonary Nodule , Humans , Overdiagnosis , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/surgery , Multiple Pulmonary Nodules/pathology , Algorithms , Solitary Pulmonary Nodule/diagnostic imaging , Solitary Pulmonary Nodule/surgery , Radiographic Image Interpretation, Computer-Assisted/methods , Lung/pathology
3.
Nature ; 564(7734): 119-124, 2018 12.
Article in English | MEDLINE | ID: mdl-30455424

ABSTRACT

Haematopoietic stem and progenitor cells (HSPCs) give rise to all blood lineages that support the entire lifespan of vertebrates1. After HSPCs emerge from endothelial cells within the developing dorsal aorta, homing allows the nascent cells to anchor in their niches for further expansion and differentiation2-5. Unique niche microenvironments, composed of various blood vessels as units of microcirculation and other niche components such as stromal cells, regulate this process6-9. However, the detailed architecture of the microenvironment and the mechanism for the regulation of HSPC homing remain unclear. Here, using advanced live imaging and a cell-labelling system, we perform high-resolution analyses of the HSPC homing in caudal haematopoietic tissue of zebrafish (equivalent to the fetal liver in mammals), and reveal the role of the vascular architecture in the regulation of HSPC retention. We identify a VCAM-1+ macrophage-like niche cell population that patrols the inner surface of the venous plexus, interacts with HSPCs in an ITGA4-dependent manner, and directs HSPC retention. These cells, named 'usher cells', together with caudal venous capillaries and plexus, define retention hotspots within the homing microenvironment. Thus, the study provides insights into the mechanism of HSPC homing and reveals the essential role of a VCAM-1+ macrophage population with patrolling behaviour in HSPC retention.


Subject(s)
Endothelial Cells/cytology , Hematopoietic Stem Cells/cytology , Macrophages/metabolism , Stem Cell Niche , Vascular Cell Adhesion Molecule-1/metabolism , Animals , Cell Differentiation , Cell Movement , Cellular Microenvironment , Integrins/genetics , Integrins/metabolism , Zebrafish , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
4.
J Youth Adolesc ; 53(6): 1383-1395, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38564098

ABSTRACT

It is estimated that there are about 23% of all children in China experiencing parental migration and being left behind at hometown. Existing research indicated a significant association between parental migration and children development but overlooked the dynamic changes in family structure caused by parental migration. In this study, data was derived from a nationally representative longitudinal survey-the China Family Panel Studies. The main analyses employed four waves of data (2012, 2014, 2016, and 2018) and included 1401 adolescents aged 10-15 years (Mean:12.35, SD:1.67; 54.2% female). Six typical trajectories of parental migration capturing both migration status at each timepoint and changes in the status across six years were created. Children's depression and internalizing problems and externalizing problems were concerned outcomes. The mediating roles of the caregiver-child interaction and caregiver's depression were examined. Adolescents in the trajectory group described as experiencing transitions between being left behind by both parents and non had a higher risk of depression and internalizing and externalizing problems. Caregivers' depression was a significant mediator between parental migration and adolescent depression.


Subject(s)
Depression , Adolescent , Child , Female , Humans , Male , Adolescent Behavior/psychology , Caregivers/psychology , Caregivers/statistics & numerical data , China , Depression/psychology , Depression/epidemiology , East Asian People , Longitudinal Studies , Parent-Child Relations , Parents/psychology , Problem Behavior/psychology , Human Migration
5.
Hum Mol Genet ; 31(2): 232-243, 2021 12 27.
Article in English | MEDLINE | ID: mdl-34415307

ABSTRACT

Nephronophthisis (NPH) is the most prevalent monogenetic disorder leading to end-stage renal failure (ESRD) in childhood. Mutations in Nphp1, encoding a cilia-localized protein, account for the majority of NPH cases. Despite its identification many years ago, Nphp1 deletions targeting exon 4 or exon 20 have not reproduced the histological features of human NPH in murine models. In this study, we deleted exon 2-20 of Nphp1 by CRISPR/Cas9 gene editing to create a near-total knockout (KO) mouse model (Nphp1del2-20/del2-20). Nphp1del2-20/del2-20 mice faithfully reproduced the renal and extrarenal phenotypes associated with human NPH, including renal cyst development, tubular basement membrane thickening, retinal degeneration and abnormal spermatogenesis. Importantly, Nphp1 re-expression using an adenoviral-associated-virus-9 vector could partially rescue both renal and retinal phenotypes in Nphp1del2-20/del2-20 mice. Our results reported the first relevant Nphp1 mouse model with renal phenotypes for human disease. It will be a valuable model for future studies of Nphp1 function and to develop novel treatments for this common childhood disease.


Subject(s)
Kidney Diseases, Cystic , Polycystic Kidney Diseases , Adaptor Proteins, Signal Transducing/genetics , Animals , Cytoskeletal Proteins/genetics , Exons/genetics , Humans , Kidney Diseases, Cystic/genetics , Kidney Diseases, Cystic/pathology , Male , Membrane Proteins/genetics , Mice , Mice, Knockout , Phenotype , Polycystic Kidney Diseases/genetics
6.
Phys Rev Lett ; 130(17): 170201, 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37172250

ABSTRACT

The existence of incompatible observables is a cornerstone of quantum mechanics and a valuable resource in quantum technologies. Here we introduce a measure of incompatibility, called the mutual eigenspace disturbance (MED), which quantifies the amount of disturbance induced by the measurement of a sharp observable on the eigenspaces of another. The MED provides a metric on the space of von Neumann measurements, and can be efficiently estimated by letting the measurement processes act in an indefinite order, using a setup known as the quantum switch, which also allows one to quantify the noncommutativity of arbitrary quantum processes. Thanks to these features, the MED can be used in quantum machine learning tasks. We demonstrate this application by providing an unsupervised algorithm that clusters unknown von Neumann measurements. Our algorithm is robust to noise and can be used to identify groups of observers that share approximately the same measurement context.

7.
Reprod Domest Anim ; 58(2): 298-306, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36269155

ABSTRACT

Although Silymarin (SMN) has powerful antioxidant properties, little is known about its effects on the quality of frozen-thawed boar sperm. The present study aimed to evaluate the influences of SMN added to the thawing extender on boar sperm parameters essential for fertilization. The frozen-thawed semen was diluted in a Modena thawing extender supplemented with different concentrations of SMN (0, 5, 10, 20 and 50 µM respectively), and then the changes in quality parameters, antioxidant capacity, mitochondrial function and in vitro fertilization (IVF) capability of frozen-thawed sperm were assessed. Here we demonstrated that the motility, plasma membrane integrity and acrosomal integrity of frozen-thawed sperm improved efficiently by SMN (p < .05). In antioxidant parameters evaluation, the tROS level and MDA content of frozen-thawed spermatozoa were reduced in the 20 µM SMN group, while the T-AOC activity significantly increased (p < .05), indicating that the supplementation with SMN can promote the antioxidant capacity of frozen-thawed boar sperm. Besides, we also discovered that the addition of SMN significantly upregulated ATP content and enhanced the mitochondrial activity of sperm. More interestingly, SMN promoted the activities of mitochondrial respiratory chain complexes (MRCC) I, II, III and IV in frozen-thawed sperm significantly. Functionally, the higher penetration rate and increased total efficiency of fertilization were observed in the 20 µM SMN group. In summary, supplementation with SMN in the thawing medium ameliorates the quality of frozen-thawed boar sperm by enhancing mitochondrial respiratory capacity, producing large amounts of ATP and regulating ROS formation.


Subject(s)
Semen Preservation , Silymarin , Swine , Male , Animals , Antioxidants/pharmacology , Antioxidants/metabolism , Silymarin/pharmacology , Silymarin/metabolism , Cryopreservation/veterinary , Semen/metabolism , Spermatozoa/physiology , Semen Preservation/veterinary , Adenosine Triphosphate/metabolism , Sperm Motility
8.
Eur Respir J ; 59(2)2022 02.
Article in English | MEDLINE | ID: mdl-34289974

ABSTRACT

The current pandemic of coronavirus disease 2019 (COVID-19) has affected >160 million individuals to date, and has caused millions of deaths worldwide, at least in part due to the unclarified pathophysiology of this disease. Identifying the underlying molecular mechanisms of COVID-19 is critical to overcome this pandemic. Metabolites mirror the disease progression of an individual and can provide extensive insights into their pathophysiological significance at each stage of disease. We provide a comprehensive view of metabolic characterisation of sera from COVID-19 patients at all stages using untargeted and targeted metabolomic analysis. As compared with the healthy controls, we observed different alteration patterns of circulating metabolites from the mild, severe and recovery stages, in both the discovery cohort and the validation cohort, which suggests that metabolic reprogramming of glucose metabolism and the urea cycle are potential pathological mechanisms for COVID-19 progression. Our findings suggest that targeting glucose metabolism and the urea cycle may be a viable approach to fight COVID-19 at various stages along the disease course.


Subject(s)
COVID-19 , Cohort Studies , Humans , Metabolomics , Pandemics , SARS-CoV-2
9.
FASEB J ; 35(8): e21822, 2021 08.
Article in English | MEDLINE | ID: mdl-34314061

ABSTRACT

Pulmonary hypertension (PH), a rare but deadly cardiopulmonary disorder, is characterized by extensive remodeling of pulmonary arteries resulting from enhancement of pulmonary artery smooth muscle cell proliferation and suppressed apoptosis; however, the underlying pathophysiological mechanisms remain largely unknown. Recently, epigenetics has gained increasing prominence in the development of PH. We aimed to investigate the role of vestigial-like family member 4 (VGLL4) in chronic normobaric hypoxia (CNH)-induced PH and to address whether it is associated with epigenetic regulation. The rodent model of PH was established by CNH treatment (10% O2 , 23 hours/day). Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, immunoprecipitation, and adeno-associated virus tests were performed to explore the potential mechanisms involved in CNH-induced PH in mice. VGLL4 expression was upregulated and correlated with CNH in PH mouse lung tissues in a time-dependent manner. VGLL4 colocalized with α-smooth muscle actin in cultured pulmonary arterial smooth muscle cells (PASMCs), and VGLL4 immunoactivity was increased in PASMCs following hypoxia exposure in vitro. VGLL4 knockdown attenuated CNH-induced PH and pulmonary artery remodeling by blunting signal transducer and activator of transcription 3 (STAT3) signaling; conversely, VGLL4 overexpression exacerbated the development of PH. CNH enhanced the acetylation of VGLL4 and increased the interaction of ac-H3K9/VGLL4 and ac-H3K9/STAT3 in the lung tissues, and levels of ac-H3K9, p-STAT3/STAT3, and proliferation-associated protein levels were markedly up-regulated, whereas apoptosis-related protein levels were significantly downregulated, in the lung tissues of mice with CNH-induced PH. Notably, abrogation of VGLL4 acetylation reversed CNH-induced PH and pulmonary artery remodeling and suppressed STAT3 signaling. Finally, STAT3 knockdown alleviated CNH-induced PH. In conclusion, VGLL4 acetylation upregulation could contribute to CNH-induced PH and pulmonary artery remodeling via STAT3 signaling, and abrogation of VGLL4 acetylation reversed CNH-induced PH. Pharmacological or genetic deletion of VGLL4 might be a potential target for therapeutic interventions in CNH-induced PH.


Subject(s)
Hypertension, Pulmonary/metabolism , Lung , Muscle, Smooth, Vascular , Pulmonary Artery , Transcription Factors/physiology , Vascular Remodeling , Animals , Cell Proliferation , Cells, Cultured , Chronic Disease , Lung/metabolism , Lung/pathology , Male , Mice , Mice, Inbred C57BL , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , STAT3 Transcription Factor/metabolism
10.
Appl Opt ; 61(22): G9-G14, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-36255858

ABSTRACT

A novel, to the best of our knowledge, bionic coaxial micro-displacement sensor based on the shadow method is developed and experimentally demonstrated inspired by the water strider walking on the water. The water is used as the sensitive element to measure the micro- displacement. A meniscus is formed by the superhydrophobic circular plate subjected to a coaxial displacement excitation. Then a shadow is formed because of the refraction when the parallel light illuminates the meniscus. A maximum coaxial displacement sensitivity of 62 nm/pixel over the displacement range of 50 µm is achieved experimentally. The linearity error in the measurement range was 1.58%. Therefore, it is expected that this displacement sensor can be used in many important ultraprecision measurement fields because of the advantages of the easy structure and high resolution.


Subject(s)
Transducers , Water
11.
Microcirculation ; 28(4): e12680, 2021 05.
Article in English | MEDLINE | ID: mdl-33486837

ABSTRACT

OBJECTIVE: To investigate the effect of Yiqifumai injection (YQFM), a compound Chinese medicine, and its main active ingredients on lipopolysaccharide (LPS)-induced microvascular disturbance in mesentery and ileum. METHODS: Rats were infused with LPS (5 mg/kg/h) for 90 min. Thirty minutes after initiation of LPS administration, YQFM (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), or Rb1+Sch (5 mg/kg/h + 2.5 mg/kg/h) was infused until 90 min. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (100 ng/ml) for 90 min. YQFM (1 mg/ml), Rb1 (100 µM), Sch (100 µM), or Rb1+Sch (200 µM) was added 30 min after initiation of LPS stimulation. RESULTS: Yiqifumai injection and Rb1+Sch inhibited mesenteric venule hyperpermeability, suppressed microvillar erosion and submucosal edema, and protected claudin-5 from downregulation and interleukin-1ß from upregulation in ileal tissues after LPS. Study in HUVECs confirmed the effect of YQFM and Rb1+Sch on JAM-1 after LPS and revealed a similar effect on other junction proteins. Moreover, YQFM and Rb1+Sch attenuated the dysfunctional energy metabolism and the activation of TLR-4/Src/NF-κB signaling with Rb1 and Sch being partially effective. CONCLUSION: These results demonstrated the beneficial effect of post-treatment with YQFM, which is attributable to its main ingredient Rb1 and Sch, and likely mediated by targeting TLR-4/Src/NF-κB signaling pathway.


Subject(s)
Cardiovascular Agents , Drugs, Chinese Herbal , Ileum/blood supply , Mesentery/blood supply , Microvessels/drug effects , Vascular Diseases/drug therapy , Animals , Cardiovascular Agents/administration & dosage , Drugs, Chinese Herbal/administration & dosage , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Lipopolysaccharides/toxicity , NF-kappa B , Rats , Toll-Like Receptor 4 , Vascular Diseases/etiology
12.
Toxicol Appl Pharmacol ; 408: 115261, 2020 12 01.
Article in English | MEDLINE | ID: mdl-33010263

ABSTRACT

Resveratrol, a type of natural polyphenol mainly extracted from the skin of grapes, has been reported to protect against inflammatory responses and exert anxiolytic effect. Yes-associated protein (YAP), a major downstream effector of the Hippo signaling pathway, plays a critical role in inflammation. The present study aimed to explore whether YAP pathway was involved in the anxiolytic effect of resveratrol in lipopolysaccharide (LPS)-treated C57BL/6J male mice. LPS treatment induced anxiety-like behavior and decreased sirtuin 1 while increased YAP expression in the hippocampus. Resveratrol attenuated LPS-induced anxiety-like behavior, which was blocked by EX-527 (a sirtuin 1 inhibitor). Mechanistically, the anxiolytic effects of resveratrol were accompanied by a marked decrease in YAP, interleukin-1ß and ionized calcium binding adaptor molecule 1 (Iba-1) while a significant increase in autophagic protein expression in the hippocampus. Pharmacological study using XMU-MP-1, a YAP activator, showed that activating YAP could induce anxiety-like behavior and neuro-inflammation as well as decrease hippocampal autophagy. Moreover, activation of YAP by XMU-MP-1 treatment attenuated the ameliorative effects of resveratrol on LPS-induced anxiety-like behavior, while blockade of YAP activation with verteporfin, a YAP inhibitor, attenuated LPS-induced anxiety-like behavior and neuro-inflammation as well as hippocampal autophagy. Finally, rapamycin-mediated promotion of autophagy attenuated LPS-induced anxiety-like behavior and decreased interleukin-1ß and Iba-1 expression in the hippocampus. Collectively, these results indicate that amelioration by resveratrol in LPS-induced anxiety-like behavior is through attenuating YAP-mediated neuro-inflammation and promoting hippocampal autophagy, and suggest that inhibition of YAP pathway could be a potential therapeutic target for anxiety-like behavior induced by neuro-inflammation.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , Cell Cycle Proteins/metabolism , Encephalitis/drug therapy , Resveratrol/therapeutic use , Adaptor Proteins, Signal Transducing/genetics , Animals , Anti-Anxiety Agents/pharmacology , Anxiety/chemically induced , Anxiety/genetics , Anxiety/metabolism , Autophagy/drug effects , Behavior, Animal/drug effects , Cell Cycle Proteins/genetics , Encephalitis/chemically induced , Encephalitis/genetics , Encephalitis/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Lipopolysaccharides , Male , Mice, Inbred C57BL , Resveratrol/pharmacology , YAP-Signaling Proteins
13.
Microcirculation ; 26(7): e12553, 2019 10.
Article in English | MEDLINE | ID: mdl-31059171

ABSTRACT

OBJECTIVE: Yiqifumai injection is a compound Chinese medicine used to treat microcirculatory disturbance-related diseases clinically. Our previous study proved that Yiqifumai injection pretreatment inhibited lipopolysaccharide-induced venular albumin leakage in rat mesentery. This study aimed to investigate whether Yiqifumai injection attenuated cerebral microvascular hyperpermeability and corresponding contribution of its main ingredients. METHODS: Rats were challenged by lipopolysaccharide infusion (5 mg/kg/h) for 90 minutes. Yiqifumai injection (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), and Rb1 (5 mg/kg/h) + Sch (2.5 mg/kg/h) were infused 30 minutes before (pretreatment) or after (post-treatment) lipopolysaccharide administration. RESULTS: Both pretreatment and post-treatment with Yiqifumai injection attenuated cerebral venular albumin leakage during lipopolysaccharide infusion and cerebrovascular hyperpermeability at 72 hours after lipopolysaccharide infusion. Yiqifumai injection restrained the decreased junction protein expression, adenosine triphosphate content, and mitochondria complex I, II, IV, and V activities. Moreover, Yiqifumai injection inhibited toll-like receptor-4 expression, Src phosphorylation, and caveolin-1 expression. Its main ingredients Rb1 and Sch alone worked differently, with Rb1 being more effective for enhancing energy metabolism, while Sch attenuating toll-like receptor-4 expression and Src activation. CONCLUSION: Yiqifumai injection exerts a protective and ameliorated effect on cerebral microvascular hyperpermeability, which is more effective than any of its ingredients, possibly due to the interaction of its main ingredients through a multi-pathway mode.


Subject(s)
Capillary Permeability/drug effects , Cerebrovascular Circulation/drug effects , Drugs, Chinese Herbal/pharmacology , Lipopolysaccharides/toxicity , Microcirculation/drug effects , Animals , Male , Rats , Rats, Wistar
14.
PLoS Genet ; 11(7): e1005346, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26131719

ABSTRACT

In vertebrate definitive hematopoiesis, nascent hematopoietic stem/progenitor cells (HSPCs) migrate to and reside in proliferative hematopoietic microenvironment for transitory expansion. In this process, well-established DNA damage response pathways are vital to resolve the replication stress, which is deleterious for genome stability and cell survival. However, the detailed mechanism on the response and repair of the replication stress-induced DNA damage during hematopoietic progenitor expansion remains elusive. Here we report that a novel zebrafish mutantcas003 with nonsense mutation in topbp1 gene encoding topoisomerase II ß binding protein 1 (TopBP1) exhibits severe definitive hematopoiesis failure. Homozygous topbp1cas003 mutants manifest reduced number of HSPCs during definitive hematopoietic cell expansion, without affecting the formation and migration of HSPCs. Moreover, HSPCs in the caudal hematopoietic tissue (an equivalent of the fetal liver in mammals) in topbp1cas003 mutant embryos are more sensitive to hydroxyurea (HU) treatment. Mechanistically, subcellular mislocalization of TopBP1cas003 protein results in ATR/Chk1 activation failure and DNA damage accumulation in HSPCs, and eventually induces the p53-dependent apoptosis of HSPCs. Collectively, this study demonstrates a novel and vital role of TopBP1 in the maintenance of HSPCs genome integrity and survival during hematopoietic progenitor expansion.


Subject(s)
Carrier Proteins/genetics , Cell Survival/genetics , DNA Repair/genetics , Hematopoiesis/genetics , Hematopoietic Stem Cells/cytology , Zebrafish Proteins/genetics , Animals , Apoptosis/physiology , Ataxia Telangiectasia Mutated Proteins , Carrier Proteins/metabolism , Cell Movement/genetics , Cell Proliferation , Checkpoint Kinase 1 , Codon, Nonsense/genetics , DNA Damage/genetics , DNA Replication/genetics , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/metabolism , Embryo, Nonmammalian/metabolism , Enzyme Activation/genetics , Hematopoietic Stem Cells/metabolism , Hydroxyurea/pharmacology , Protein Kinases/metabolism , Tumor Suppressor Protein p53/metabolism , Zebrafish , Zebrafish Proteins/metabolism
15.
Int J Infect Dis ; 143: 106981, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38458425

ABSTRACT

OBJECTIVES: We aimed to estimate the effectiveness of telemedicine for the prevention of mother-to-child transmission (PMTCT) program of HIV in low- and middle-income countries (LMICs). METHODS: We did a systematic literature search of 15 databases for articles published from database inception to October 26, 2022, and performed meta-analyses to estimate the pooled risk ratio of intervention effect (RR) and its 95% confidence interval (CI). We used subgroup analyses and meta-regressions to explore variation in the RRs. Funnel plots and Egger regression tests were also performed to assess publication bias. RESULTS: Seventeen studies were included in the systematic review, with a total sample size of 9118 participants. We found that telemedicine was beneficial for early infant diagnosis (EID) in the sixth week (RR 1.04 [95% CI 1.00-1.09]), exclusive breastfeeding (RR 1.12 [95% CI 1.01-1.24]) and PMTCT retention (RR 1.34 [95% CI 1.16-1.55]). However, we did not find a significant effect of telemedicine on infant prophylaxis, HIV transmission, and ART adherence. Besides, the heterogeneity of ART adherence was associated with enrollment time, while retention was related to ART initiation. CONCLUSIONS: Our meta-analysis demonstrated the benefits of telemedicine in improving PMTCT, especially for EID, exclusive breastfeeding, and PMTCT retention.


Subject(s)
Breast Feeding , Developing Countries , HIV Infections , Infectious Disease Transmission, Vertical , Telemedicine , Humans , Infectious Disease Transmission, Vertical/prevention & control , HIV Infections/transmission , HIV Infections/prevention & control , Telemedicine/methods , Female , Pregnancy , Infant , Infant, Newborn , Pregnancy Complications, Infectious/prevention & control
17.
Nat Commun ; 15(1): 976, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38302502

ABSTRACT

Early detection is critical to achieving improved treatment outcomes for child patients with congenital heart diseases (CHDs). Therefore, developing effective CHD detection techniques using low-cost and non-invasive pediatric electrocardiogram are highly desirable. We propose a deep learning approach for CHD detection, CHDdECG, which automatically extracts features from pediatric electrocardiogram and wavelet transformation characteristics, and integrates them with key human-concept features. Developed on 65,869 cases, CHDdECG achieved ROC-AUC of 0.915 and specificity of 0.881 on a real-world test set covering 12,000 cases. Additionally, on two external test sets with 7137 and 8121 cases, the overall ROC-AUC were 0.917 and 0.907 while specificities were 0.937 and 0.907. Notably, CHDdECG surpassed cardiologists in CHD detection performance comparison, and feature importance scores suggested greater influence of automatically extracted electrocardiogram features on CHD detection compared with human-concept features, implying that CHDdECG may grasp some knowledge beyond human cognition. Our study directly impacts CHD detection with pediatric electrocardiogram and demonstrates the potential of pediatric electrocardiogram for broader benefits.


Subject(s)
Deep Learning , Heart Defects, Congenital , Humans , Child , Heart Defects, Congenital/diagnosis , Electrocardiography , Cognition
18.
Sci Data ; 11(1): 704, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937514

ABSTRACT

Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored treatment strategies, yet public data scarcity hampers understanding. Given the higher incidence of both conditions in women, this study prospectively enrolled 80 female ANOCA and 39 age-matched female controls, subjecting them to three types of mental stress tasks. ECGs were continuously monitored across Rest, Stress, and Recover stages of the mental stress tasks, with PET/CT imaging during the Stress stage to evaluate myocardial perfusion. With PET/CT serving as the gold standard for MSIMI diagnosis, 35 of the 80 ANOCA patients were diagnosed as MSIMI. Using ECG variables from different stages of mental stress tasks, we developed five machine learning models to diagnose MSIMI. The results showed that ECG data from different stages provide valuable information for MSIMI classification. Additionally, the dataset encompassed demographic details, physiological, and blood sample test results of the patients. We anticipate this new dataset will significantly push further progress in ANOCA and MSIMI research.


Subject(s)
Electrocardiography , Myocardial Ischemia , Stress, Psychological , Humans , Female , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/physiopathology , Myocardial Ischemia/psychology , Stress, Psychological/complications , Machine Learning , Positron Emission Tomography Computed Tomography , Middle Aged , Angina Pectoris/physiopathology , Prospective Studies
19.
Water Res ; 253: 121287, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38387264

ABSTRACT

Biological aqua crust (biogenic aqua crust-BAC) is a potentially sustainable solution for metal(loid) bioremediation in global water using solar energy. However, the key geochemical factors and underlying mechanisms shaping microbial communities in BAC remain poorly understood. The current study aimed at determining the in situ metal(loid) distribution and the key geochemical factors related to microbial community structure and metal(loid)-related genes in BAC of a representative Pb/Zn tailing pond. Here we showed that abundant metal(loid)s (e.g. Pb, As) were co-distributed with Mn/Fe-rich minerals (e.g. biogenic Mn oxide, FeOOH) in BAC. Biogenic Mn oxide (i.e. Mn) was the most dominant factor in shaping microbial community structure in BAC and source tailings. Along with the fact that keystone species (e.g. Burkholderiales, Haliscomenobacter) have the potential to promote Mn ion oxidization and particle agglomeration, as well as Mn is highly associated with metal(loid)-related genes, especially genes related to As redox (e.g. arsC, aoxA), and Cd transport (e.g. zipB), biogenic Mn oxides thus effectively enhance metal(loid) remediation by accelerating the formation of organo-mineral aggregates in biofilm-rich BAC system. Our study indicated that biogenic Mn oxides may play essential roles in facilitating in situ metal(loid) bioremediation in BAC of mine drainage.


Subject(s)
Manganese Compounds , Metals, Heavy , Microbiota , Manganese , Lead , Bacteria/genetics , Oxides , Minerals
20.
ISA Trans ; 134: 442-450, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36123190

ABSTRACT

The precision of micro-force measurement depends on the force sensor sensitivity and the environmental disturbance magnitude. However, micro-force sensors generally have the poor anti-disturbance ability. Inspired by the shadow formed by water striders walking on water surface under sunlight, a viscoelastic-polymer micro-force (VPMF) sensor based on the shadow method was proposed, which could suppress disturbances effectively due to the high damping ratio of 0.22. The shadow diameter change and the applied force were proportional. The experimental results indicated that the sensitivity could reach 2.15 µN/pixel with a good linear performance. Furthermore, compared with the cantilever, it was capable of the reduction of the disturbance influence by approximately 96.35%. Therefore, the VPMF sensor can be applied to reliable micro-force measurement in complex environments such as industrial sites.

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