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1.
Cell ; 186(17): 3593-3605.e12, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37516107

RESUMO

Animal fertilization relies on hundreds of sperm racing toward the egg, whereas, in angiosperms, only two sperm cells are delivered by a pollen tube to the female gametes (egg cell and central cell) for double fertilization. However, unsuccessful fertilization under this one-pollen-tube design can be detrimental to seed production and plant survival. To mitigate this risk, unfertilized-gamete-controlled extra pollen tube entry has been evolved to bring more sperm cells and salvage fertilization. Despite its importance, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we report that, in Arabidopsis, the central cell secretes peptides SALVAGER1 and SALVAGER2 in a directional manner to attract pollen tubes when the synergid-dependent attraction fails or is terminated by pollen tubes carrying infertile sperm cells. Moreover, loss of SALs impairs the fertilization recovery capacity of the ovules. Therefore, this research uncovers a female gamete-attraction system that salvages seed production for reproductive assurance.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Animais , Arabidopsis/fisiologia , Fertilização , Tubo Polínico , Sementes , Células Germinativas Vegetais
2.
Proc Natl Acad Sci U S A ; 120(52): e2314193120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38109549

RESUMO

Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their binding epitopes. However, most of these antibodies are seriously impaired by SARS-CoV-2 Omicron and its subvariants, especially the recent BQ.1.1, XBB and its derivatives. Identification of broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a "breathing" cryptic epitope in the S protein, named as RBD-8. Two human MAbs, BIOLS56 and IMCAS74, were isolated recognizing this epitope with broad neutralization abilities against tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, and all the SARS-CoV-2 variants tested (Omicron BA.4/BA.5, BQ.1.1, and XBB subvariants). Searching through the literature, some more RBD-8 MAbs were defined. More importantly, BIOLS56 rescues the immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, by making a bispecific MAb, to neutralize BQ.1 and BQ.1.1, thereby producing an MAb to cover all the currently circulating Omicron subvariants. Structural analysis reveals that the neutralization effect of RBD-8 antibodies depends on the extent of epitope exposure, which is affected by the angle of antibody binding and the number of up-RBDs induced by angiotensin-converting enzyme 2 binding. This cryptic epitope which recognizes non- receptor binding motif (non-RBM) provides guidance for the development of universal therapeutic antibodies and vaccines against COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Vacinas contra COVID-19 , Anticorpos Monoclonais , Epitopos , Anticorpos Neutralizantes , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus
3.
Proc Natl Acad Sci U S A ; 120(5): e2214684120, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36693099

RESUMO

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.


Assuntos
Progesterona , Receptores de Progesterona , Feminino , Camundongos , Humanos , Animais , Progesterona/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Implantação do Embrião/genética , Útero/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos Knockout , RNA Mensageiro/metabolismo
4.
Nat Methods ; 19(10): 1230-1233, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36109679

RESUMO

Complex structural variants (CSVs) encompass multiple breakpoints and are often missed or misinterpreted. We developed SVision, a deep-learning-based multi-object-recognition framework, to automatically detect and haracterize CSVs from long-read sequencing data. SVision outperforms current callers at identifying the internal structure of complex events and has revealed 80 high-quality CSVs with 25 distinct structures from an individual genome. SVision directly detects CSVs without matching known structures, allowing sensitive detection of both common and previously uncharacterized complex rearrangements.


Assuntos
Aprendizado Profundo , Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA
5.
Brief Bioinform ; 24(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37200087

RESUMO

Structural variant (SV) detection is essential for genomic studies, and long-read sequencing technologies have advanced our capacity to detect SVs directly from read or de novo assembly, also known as read-based and assembly-based strategy. However, to date, no independent studies have compared and benchmarked the two strategies. Here, on the basis of SVs detected by 20 read-based and eight assembly-based detection pipelines from six datasets of HG002 genome, we investigated the factors that influence the two strategies and assessed their performance with well-curated SVs. We found that up to 80% of the SVs could be detected by both strategies among different long-read datasets, whereas variant type, size, and breakpoint detected by read-based strategy were greatly affected by aligners. For the high-confident insertions and deletions at non-tandem repeat regions, a remarkable subset of them (82% in assembly-based calls and 93% in read-based calls), accounting for around 4000 SVs, could be captured by both reads and assemblies. However, discordance between two strategies was largely caused by complex SVs and inversions, which resulted from inconsistent alignment of reads and assemblies at these loci. Finally, benchmarking with SVs at medically relevant genes, the recall of read-based strategy reached 77% on 5X coverage data, whereas assembly-based strategy required 20X coverage data to achieve similar performance. Therefore, integrating SVs from read and assembly is suggested for general-purpose detection because of inconsistently detected complex SVs and inversions, whereas assembly-based strategy is optional for applications with limited resources.


Assuntos
Benchmarking , Genoma Humano , Humanos , Análise de Sequência , Genômica/métodos , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
6.
Cell Mol Life Sci ; 81(1): 155, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38538986

RESUMO

The prostate is a vital accessory gonad in the mammalian male reproductive system. With the ever-increasing proportion of the population over 60 years of age worldwide, the incidence of prostate diseases, such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), is on the rise and is gradually becoming a significant medical problem globally. The notch signaling pathway is essential in regulating prostate early development. However, the potential regulatory mechanism of Notch signaling in prostatic enlargement and hyperplasia remains unclear. In this study, we proved that overactivation of Notch1 signaling in mouse prostatic epithelial cells (OEx) led to prostatic enlargement via enhancing proliferation and inhibiting apoptosis of prostatic epithelial cells. Further study showed that N1ICD/RBPJ directly up-regulated the androgen receptor (AR) and enhanced prostatic sensitivity to androgens. Hyper-proliferation was not found in orchidectomized OEx mice without androgen supply but was observed after Dihydrotestosterone (DHT) supplementation. Our data showed that the number of mitochondrion in prostatic epithelial cells of OEx mice was increased, but the mitochondrial function was impaired, and the essential activity of the mitochondrial respiratory electron transport chain was significantly weakened. Disordered mitochondrial number and metabolic function further resulted in excessive accumulation of reactive oxygen species (ROS). Importantly, anti-oxidant N-Acetyl-L-Cysteine (NAC) therapy could alleviate prostatic hyperplasia caused by the over-activation of Notch1 signaling. Furthermore, we observed the incremental Notch signaling activity in progenitor-like club cells in the scRNA-seq data set of human BPH patients. Moreover, the increased number of TROP2+ progenitors and Club cells was also confirmed in our OEx mice. In conclusion, our study revealed that over-activated Notch1 signaling induces prostatic enlargement by increasing androgen receptor sensitivity, disrupting cellular mitochondrial metabolism, increasing ROS, and a higher number of progenitor cells, all of which can be effectively rescued by NAC treatment.


Assuntos
Hiperplasia Prostática , Animais , Humanos , Masculino , Camundongos , Androgênios/metabolismo , Mamíferos/metabolismo , Mitocôndrias/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais
7.
Plant Biotechnol J ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683692

RESUMO

Glomerella leaf spot (GLS), caused by the fungus Colletotrichum fructicola, is considered one of the most destructive diseases affecting apples. The VQ-WRKY complex plays a crucial role in the response of plants to biotic stresses. However, our understanding of the defensive role of the VQ-WRKY complex on woody plants, particularly apples, under biotic stress, remains limited. In this study, we elucidated the molecular mechanisms underlying the defensive role of the apple MdVQ37-MdWRKY100 module in response to GLS infection. The overexpression of MdWRKY100 enhanced resistance to C. fructicola, whereas MdWRKY100 RNA interference in apple plants reduced resistance to C. fructicola by affecting salicylic acid (SA) content and the expression level of the CC-NBS-LRR resistance gene MdRPM1. DAP-seq, Y1H, EMSA, and RT-qPCR assays indicated that MdWRKY100 inhibited the expression of MdWRKY17, a positive regulatory factor gene of SA degradation, upregulated the expression of MdPAL1, a key enzyme gene of SA biosynthesis, and promoted MdRPM1 expression by directly binding to their promotors. Transient overexpression and silencing experiments showed that MdPAL1 and MdRPM1 positively regulated GLS resistance in apples. Furthermore, the overexpression of MdVQ37 increased the susceptibility to C. fructicola by reducing the SA content and expression level of MdRPM1. Additionally, MdVQ37 interacted with MdWRKY100, which repressed the transcriptional activity of MdWRKY100. In summary, these results revealed the molecular mechanism through which the apple MdVQ37-MdWRKY100 module responds to GLS infection by regulating SA content and MdRPM1 expression, providing novel insights into the involvement of the VQ-WRKY complex in plant pathogen defence responses.

8.
J Virol ; 97(6): e0053323, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37255438

RESUMO

Ubiquitination, as one of the most prevalent posttranslational modifications of proteins, enables a tight control of host immune responses. Many viruses hijack the host ubiquitin system to regulate host antiviral responses for their survival. Here, we found that the fish pathogen nervous necrosis virus (NNV) recruited Lateolabrax japonicus E3 ubiquitin ligase ring finger protein 34 (LjRNF34) to inhibit the RIG-I-like receptor (RLR)-mediated interferon (IFN) response via ubiquitinating Lateolabrax japonicus TANK-binding kinase 1 (LjTBK1) and interferon regulatory factor 3 (LjIRF3). Ectopic expression of LjRNF34 greatly enhanced NNV replication and prevented IFN production, while deficiency of LjRNF34 led to the opposite effect. Furthermore, LjRNF34 targeted LjTBK1 and LjIRF3 via its RING domain. Of note, the interactions between LjRNF34 and LjTBK1 or LjIRF3 were conserved in different cellular models derived from fish. Mechanically, LjRNF34 promoted K27- and K48-linked ubiquitination and degradation of LjTBK1 and LjIRF3, which in turn diminished LjTBK1-induced translocation of LjIRF3 from the cytoplasm to the nucleus. Ultimately, NNV capsid protein (CP) was found to bind with LjRNF34, CP induced LjTBK1 and LjIRF3 degradation, and IFN suppression depended on LjRNF34. Our finding demonstrates a novel mechanism by which NNV CP evaded host innate immunity via LjRNF34 and provides a potential drug target for the control of NNV infection. IMPORTANCE Ubiquitination plays an essential role in the regulation of innate immune responses to pathogens. NNV, a type of RNA virus, is the causal agent of a highly destructive disease in a variety of marine and freshwater fish. A previous study reported NNV could hijack the ubiquitin system to manipulate the host's immune responses; however, how NNV utilizes ubiquitination to facilitate its own replication is not well understood. Here, we identified a novel distinct role of E3 ubiquitin ligase LjRNF34 as an IFN antagonist to promote NNV infection. NNV capsid protein utilized LjRNF34 to target LjTBK1 and LjIRF3 for K27- and K48-linked ubiquitination and degradation. Importantly, the interactions between LjRNF34 and CP, LjTBK1, or LjIRF3 are conserved in different cellular models derived from fish, suggesting it is a general immune evasion strategy exploited by NNV to target the IFN response via RNF34.


Assuntos
Proteínas do Capsídeo , Proteínas de Peixes , Imunidade Inata , Infecções por Vírus de RNA , Animais , Proteínas do Capsídeo/genética , Fator Regulador 3 de Interferon/metabolismo , Necrose , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Peixes , Proteínas de Peixes/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Nodaviridae , Infecções por Vírus de RNA/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia
9.
Dement Geriatr Cogn Disord ; 53(1): 19-28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38232713

RESUMO

INTRODUCTION: Mental health symptoms and cognitive impairment are highly prevalent and intertwined among aging people living with HIV (PLWH). This study aimed to assess the interrelationships and strength of connections between individual mental health symptoms and cognitive impairment. We sought to identify specific symptoms linking mental health and cognitive impairment in aging PLWH. METHODS: Participants in the Sichuan Older People with HIV Infections Cohort Study (SOHICS) were recruited between November 2018 and April 2021 in China. Mental health symptoms, including depression and anxiety, were assessed by the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder-7 (GAD-7), respectively. Cognitive impairment was assessed by the Montreal Cognitive Assessment-Basic (MoCA-B). Partial correlation networks were used to depict the interrelationships between mental health symptoms and cognitive impairment, and bridge strength was used to identify specific symptoms linking mental health and cognitive impairment. RESULTS: Of the 1,587 recruited participants with a mean age of 63.0 years old, 47.0% had mild or severe cognitive impairment. Network analysis revealed that cognitive function, visual perception, and problem-solving task of the MoCA-B were negatively correlated with appetite, energy, and motor of the PHQ-9, respectively. Based on their interrelationships, problem-solving task and motor acted as bridge symptoms. CONCLUSION: Problem-solving task and motor may be potential intervention targets to reduce the overall risk of mental health symptoms and cognitive impairment. Future research could assess the feasibility and effectiveness of specific interventions designed for the two symptoms of aging PLWH.


Assuntos
Transtornos de Ansiedade , Disfunção Cognitiva , Infecções por HIV , Humanos , Idoso , Infecções por HIV/complicações , Infecções por HIV/psicologia , Saúde Mental , Estudos de Coortes , Envelhecimento , China/epidemiologia
10.
J Immunol ; 208(5): 1076-1084, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35181639

RESUMO

Upon virus invasion of the host, APCs process Ags to short peptides for presentation by MHC class II (MHC-II). The recognition of virus-derived peptides in the context of MHC-II by CD4+ T cells initiates the adaptive immune response for virus clearance. As a survival instinct, viruses have evolved mechanisms to evade Ag processing and presentation. In this study, we discovered that IFN-γ induced endogenous MHC-II expression by a sea perch brain cell line through the STAT1/IFN regulatory factor 1 (IRF1)/CIITA signaling pathway. Furthermore, viral hemorrhagic septicemia virus infection significantly inhibited the IFN-γ-induced expression of IRF1, CIITA, MHC-II-α, and MHC-II-ß genes. By contrast, although STAT1 transcript was upregulated, paradoxically, the STAT1 protein level was attenuated. Moreover, overexpression analysis revealed that viral hemorrhagic septicemia virus N protein blocked the IFN-γ-induced expression of IRF1, CIITA, MHC-II-α, and MHC-II-ß genes, but not the STAT1 gene. We also found out that N protein interacted with STAT1 and enhanced the overall ubiquitination level of proteins, including STAT1 in Lateolabrax japonicus brain cells. Enhanced ubiquitination of STAT1 through K48-linked ubiquitination led to its degradation through the ubiquitin-proteasome pathway, thereby inhibiting the biological function of STAT1. Our study suggests that aquatic viruses target Ag presentation in lower vertebrates for immune evasion as do mammalian viruses.


Assuntos
Antígenos de Histocompatibilidade Classe II/imunologia , Evasão da Resposta Imune/imunologia , Novirhabdovirus/imunologia , Nucleoproteínas/metabolismo , Percas/imunologia , Fator de Transcrição STAT1/metabolismo , Imunidade Adaptativa/imunologia , Animais , Apresentação de Antígeno/imunologia , Encéfalo/citologia , Encéfalo/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Doenças dos Peixes/patologia , Doenças dos Peixes/virologia , Genes MHC da Classe II/genética , Antígenos de Histocompatibilidade Classe II/biossíntese , Fator Regulador 1 de Interferon/metabolismo , Interferon gama/imunologia , Novirhabdovirus/metabolismo , Proteínas Nucleares/metabolismo , Percas/virologia , Transdução de Sinais/imunologia , Transativadores/metabolismo , Transcrição Gênica/genética , Ubiquitinação/fisiologia
11.
J Immunol ; 209(2): 326-336, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35777851

RESUMO

Nervous necrosis virus (NNV), a highly pathogenic RNA virus, is a major pathogen in the global aquaculture industry. To efficiently infect fish, NNV must evade or subvert the host IFN for their replication; however, the precise mechanisms remain to be elucidated. In this study, we reported that capsid protein (CP) of red-spotted grouper NNV (RGNNV) suppressed the IFN antiviral response to promote RGNNV replication in Lateolabrax japonicus brain cells, which depended on the ARM, S, and P domains of CP. CP showed an indirect or direct association with the key components of retinoic acid-inducible gene-I-like receptors signaling, L. japonicus TNFR-associated factor 3 (LjTRAF3) and IFN regulatory factor (LjIRF3), respectively, and degraded LjTRAF3 and LjIRF3 through the ubiquitin-proteasome pathway in HEK293T cells. Furthermore, we found that CP potentiated LjTRAF3 K48 ubiquitination degradation in a L. japonicus ring finger protein 114-dependent manner. LjIRF3 interacted with CP through the S domain of CP and the transcriptional activation domain or regulatory domain of LjIRF3. CP promoted LjIRF3 K48 ubiquitination degradation, leading to the reduced phosphorylation level and nuclear translocation of LjIRF3. Taken together, we demonstrated that CP inhibited type I IFN response by a dual strategy to potentiate the ubiquitination degradation of LjTRAF3 and LjIRF3. This study reveals a novel mechanism of RGNNV evading host immune response via its CP protein that will provide insights into the complex pathogenesis of NNV.


Assuntos
Doenças dos Peixes , Nodaviridae , Infecções por Vírus de RNA , Animais , Proteínas do Capsídeo , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Células HEK293 , Humanos , Fatores Reguladores de Interferon/metabolismo , Interferons/biossíntese , Necrose , Nodaviridae/fisiologia , Tretinoína
12.
BMC Geriatr ; 24(1): 478, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822230

RESUMO

BACKGROUND: Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability. METHODS: This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. RESULTS: The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index < 40). In mild-moderate disability group, SBP < 135 mmHg was associated with elevated all-cause mortality risks (HR 1.21, 95% CI, 1.10-1.33), compared to SBP between 135 and 150 mmHg. In severe disability group, SBP < 150 mmHg increased all-cause mortality risks (HR 1.21, 95% CI, 1.16-1.27), compared to SBP between 150 and 170 mmHg. The associations were robust in subgroup analyses in terms of age, gender, cardiovascular comorbidity and antihypertensive treatment. Diastolic blood pressure (DBP) < 67 mmHg (HR 1.29, 95% CI, 1.18-1.42) in mild-moderate disability group and < 79 mmHg (HR 1.15, 95% CI, 1.11-1.20) in severe disability group both demonstrated an increased all-cause mortality risk. CONCLUSION: The optimal SBP range was found to be higher in older individuals in long-term care with severe disability (150-170mmHg) compared to those with mild to moderate disability (135-150mmHg). This study provides new evidence that antihypertensive treatment should be administered cautiously in severe disability group in long-term care setting. Additionally, assessment of disability using the Barthel index can serve as a valuable tool in customizing the optimal BP management strategy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2100049973).


Assuntos
Pressão Sanguínea , Pessoas com Deficiência , Assistência de Longa Duração , Humanos , Masculino , Feminino , Idoso , China/epidemiologia , Estudos Prospectivos , Assistência de Longa Duração/métodos , Assistência de Longa Duração/tendências , Pressão Sanguínea/fisiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos de Coortes , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Hipertensão/epidemiologia , Mortalidade/tendências , População do Leste Asiático
13.
BMC Public Health ; 24(1): 32, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166669

RESUMO

BACKGROUND: Healthy lifestyles are crucial for preventing chronic diseases. Nonetheless, approximately 90% of Chinese community residents regularly engage in at least one unhealthy lifestyle. Mobile smart devices-based health interventions (mHealth) that incorporate theoretical frameworks regarding behavioral change in interaction with the environment may provide an appealing and cost-effective approach for promoting sustainable adaptations of healthier lifestyles. We designed a randomized controlled trial (RCT) to evaluate the effectiveness of a socioecological model-guided, smart device-based, and self-management-oriented lifestyles (3SLIFE) intervention, to promote healthy lifestyles among Chinese community residents. METHODS: This two-arm, parallel, cluster-RCT with a 6-month intervention and 6-month follow-up period foresees to randomize a total of 20 communities/villages from 4 townships in a 1:1 ratio to either intervention or control. Within these communities, a total of at least 256 community residents will be enrolled. The experimental group will receive a multi-level intervention based on the socioecological model supplemented with a multi-dimensional empowerment approach. The control group will receive information only. The primary outcome is the reduction of modifiable unhealthy lifestyles at six months, including smoking, excess alcohol consumption, physical inactivity, unbalanced diet, and overweight/obesity. A reduction by one unhealthy behavior measured with the Healthy Lifestyle Index Score (HLIS) will be considered favorable. Secondary outcomes include reduction of specific unhealthy lifestyles at 3 months, 9 months, and 12 months, and mental health outcomes such as depression measured with PHQ-9, social outcomes such as social support measured with the modified Multidimensional Scale of Perceived Social Support, clinical outcomes such as obesity, and biomedical outcomes such as the development of gut microbiota. Data will be analyzed with mixed effects generalized linear models with family and link function determined by outcome distribution and accounting for clustering of participants in communities. DISCUSSION: This study will provide evidence concerning the effect of a mHealth intervention that incorporates a behavioral change theoretical framework on cultivating and maintaining healthy lifestyles in community residents. The study will provide insights into research on and application of similar mHealth intervention strategies to promote healthy lifestyles in community populations and settings. TRIAL REGISTRATION NUMBER: ChiCTR2300070575. Date of registration: April 17, 2023. https://www.chictr.org.cn/index.aspx .


Assuntos
Autogestão , Humanos , Exercício Físico , Estilo de Vida , Obesidade , Estilo de Vida Saudável , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
BMC Surg ; 24(1): 44, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302963

RESUMO

BACKGROUND: It's difficult to treat segmental tibial fractures (STFs), which are intricate injuries associated with significant soft tissue damage. The aim of this study was to compare the clinical effect of hexaxial external fixator (HEF) and intramedullary nail (IMN) in treatment of STFs. METHODS: A total of 42 patients with STFs were finally recruited between January 2018 and June 2022. There were 25 males and 17 females with age range of 20 to 60 years. All fractures were classified as type 42C2 using the Arbeitsgemeinschaftfür Osteosythese/Orthopaedic Trauma Association (AO/OTA) classification. 22 patients were treated with HEF and 20 patients were treated with IMN. The condition of vascular and neural injuries, time of full weight bearing, bone union time and infection rate were documented and analyzed between the two groups. The mechanical medial proximal tibial angle (mMPTA), mechanical posterior proximal tibial angle (mPPTA), mechanical lateral distal tibial angle (mLDTA), mechanical anterior distal tibial angle (mADTA), hospital for special surgery (HSS) knee joint score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle joint score, range of motion (ROM) of flexion of keen joint and ROM of plantar flexion and dorsal flexion of ankle joint were compared between the two groups at the last clinical visit. RESULTS: There were no vascular and neural injuries or other severe complications in both groups. All 22 patients in HEF group underwent closed reduction but 3 patients in IMN group were treated by open reduction. The time of full weight bearing was (11.3 ± 3.2) days in HEF group and (67.8 ± 5.8) days in IMN group(P < 0.05), with bone union time for (6.9 ± 0.8) months and (7.7 ± 1.4) months, respectively(P < 0.05). There was no deep infection in both groups. In the HEF group and IMN group, mMPTA was (86.9 ± 1.5)° and (89.7 ± 1.8)°(P < 0.05), mPPTA was (80.8 ± 1.9)° and (78.6 ± 2.0)°(P < 0.05), mLDTA was (88.5 ± 1.7)° and (90.3 ± 1.7)°(P < 0.05), while mADTA was (80.8 ± 1.5)° and (78.4 ± 1.3)°(P < 0.05). No significant differences were found between the two groups at the last clinical visit concerning HSS knee joint score and AOFAS ankle joint score, ROM of flexion of keen joint and ROM of plantar flexion of ankle joint (P > 0.05). The ROM of dorsal flexion of ankle joint in IMN group was (30.4 ± 3.5)°, better than (21.6 ± 2.8)° in HEF group (P < 0.05). CONCLUSION: In terms of final clinical outcomes, the use of either HEF or IMN for STFs can achieve good therapeutic effects. While HEF is superior to IMN in terms of completely closed reduction, early full weight bearing, early bone union and alignment. Nevertheless, HEF has a greater impact on the ROM of dorsal flexion of the ankle joint, and much more care and adjustment are needed for the patients than IMN.


Assuntos
Fraturas da Tíbia , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Fraturas da Tíbia/cirurgia , Fixadores Externos , Placas Ósseas
15.
Sensors (Basel) ; 24(2)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38257445

RESUMO

This paper proposed a real-time fault diagnostic method for hydraulic systems using data collected from multiple sensors. The method is based on a proposed multi-sensor convolutional neural network (MS-CNN) that incorporates feature extraction, sensor selection, and fault diagnosis into an end-to-end model. Both the sensor selection process and fault diagnosis process are based on abstract fault-related features learned by a CNN deep learning model. Therefore, compared with the traditional sensor-and-feature selection method, the proposed MS-CNN can find the sensor channels containing higher-level fault-related features, which provides two advantages for diagnosis. First, the sensor selection can reduce the redundant information and improve the diagnostic performance of the model. Secondly, the reduced number of sensors simplifies the model, reducing communication burden and computational complexity. These two advantages make the MS-CNN suitable for real-time hydraulic system fault diagnosis, in which the multi-sensor feature extraction and the computation speed are both significant. The proposed MS-CNN approach is evaluated experimentally on an electric-hydraulic subsea control system test rig and an open-source dataset. The proposed method shows obvious superiority in terms of both diagnosis accuracy and computational speed when compared with traditional CNN models and other state-of-the-art multi-sensor diagnostic methods.

16.
Sensors (Basel) ; 24(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38475153

RESUMO

LiDAR has high accuracy and resolution and is widely used in various fields. In particular, phase-modulated continuous-wave (PhMCW) LiDAR has merits such as low power, high precision, and no need for laser frequency modulation. However, with decreasing signal-to-noise ratio (SNR), the noise on the signal waveform becomes so severe that the current methods to extract the time-of-flight are no longer feasible. In this paper, a novel method that uses deep neural networks to measure the pulse width is proposed. The effects of distance resolution and SNR on the performance are explored. Recognition accuracy reaches 81.4% at a 0.1 m distance resolution and the SNR is as low as 2. We simulate a scene that contains a vehicle, a tree, a house, and a background located up to 6 m away. The reconstructed point cloud has good fidelity, the object contours are clear, and the features are restored. More precisely, the three distances are 4.73 cm, 6.00 cm, and 7.19 cm, respectively, showing that the performance of the proposed method is excellent. To the best of our knowledge, this is the first work that employs a neural network to directly process LiDAR signals and to extract their time-of-flight.

17.
Sensors (Basel) ; 24(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38894078

RESUMO

The paper presents a wide-bandwidth, low-polarization semiconductor optical amplifier (SOA) based on strained quantum wells. By enhancing the material gain of quantum wells for TM modes, we have extended the gain bandwidth of the SOA while reducing its polarization sensitivity. Through a combination of tilted waveguide design and cavity surface optical thin film design, we have effectively reduced the cavity surface reflectance of the SOA, thus decreasing device transmission losses and noise figure. At a wavelength of 1550 nm and a drive current of 1.4 A, the output power can reach 188 mW, with a small signal gain of 36.4 dB and a 3 dB gain bandwidth of 128 nm. The linewidth broadening is only 1.032 times. The polarization-dependent gain of the SOA is below 1.4 dB, and the noise figure is below 5.5 dB. The device employs only I-line lithography technology, offering simple fabrication processes and low costs yet delivering outstanding and stable performance. The designed SOA achieves wide gain bandwidth, high gain, low polarization sensitivity, low linewidth broadening, and low noise, promising significant applications in the wide-bandwidth optical communication field across the S + C + L bands.

18.
Water Sci Technol ; 89(9): 2416-2428, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747957

RESUMO

The connectivity of urban river networks plays an important role in cities in many aspects, such as urban water safety, water quality (WQ), and aquatic ecological balance. This study focuses on the river network and the Majiawan Wetland in the Chaoyang District of Beijing by establishing a two-dimensional hydrological WQ model employing various water allocation schemes between the river network and the wetland. Water circulation and WQ are the main indexes, and the effects of different scenarios on improving water circulation and WQ are simulated and compared. This study demonstrates that the addition of water replenishment at the intersection of river network and internal slow-water zones of the wetland (Scheme 2) has greater effectiveness in improving both hydrology and WQ compared to two other schemes. The water area of the Majiawan Wetland has expanded, and water velocity has increased. Using chemical oxygen demand, total nitrogen, and total phosphorus as the index values for determining the water class, the WQ of about 20% of the wetland area was reached Water Class II (domestic drinking water), with Water Class III (general industrial water) accounting for the other 80%. This study provides valuable evaluation and reference for similar areas of urban river network connectivity.


Assuntos
Rios , Qualidade da Água , Áreas Alagadas , Rios/química , Cidades , Modelos Teóricos , China , Simulação por Computador
19.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2128-2137, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812228

RESUMO

The rhizosphere is an important place for material exchange between medicinal plants and soil. Root exudates are the medium of material and signal exchange between plants and soil and are the key factors in the regulation of rhizosphere microecology. Rhizosphere microorganisms are an important part of the rhizosphere microecology of medicinal plants, and the interaction between root exudates and rhizosphere microorganisms has an important influence on the growth and quality formation of medicinal plants. Rational utilization of the interaction between root exudates and rhizosphere microorganisms of medicinal plants is one of the important ways to ensure the healthy growth of medicinal plants and promote the development of ecological planting of Chinese medicinal materials. In the paper, the research status of root exudates and rhizosphere microorganisms of medicinal plants in recent years was summarized. The interaction mechanism between root exudates and rhizosphere microorganisms of medicinal plants, as well as the influence of rhizosphere microorganisms on the growth of medicinal plants, were analyzed. In addition, the advantages and promoting effects of intercropping ecological planting mode on rhizosphere microecology of medicinal plants and quality improvement of Chinese medicinal materials were explained, providing a good basis for the study of the interaction among medicinal plants, microorganisms, and soil. Furthermore, it could produce important theoretical and practical significance for the ecological planting and sustainable utilization of medicinal plants.


Assuntos
Raízes de Plantas , Plantas Medicinais , Rizosfera , Microbiologia do Solo , Plantas Medicinais/metabolismo , Plantas Medicinais/microbiologia , Plantas Medicinais/química , Plantas Medicinais/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Bactérias/metabolismo , Bactérias/classificação , Exsudatos de Plantas/metabolismo , Exsudatos de Plantas/química
20.
BMC Genomics ; 24(1): 57, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721086

RESUMO

OBJECTIVES: To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs.  METHODS: Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. RESULTS: In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. CONCLUSIONS: Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.


Assuntos
Cardiopatias , Humanos , Sequenciamento do Exoma , China , Morte Súbita , Mutação
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