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Drug-drug interaction (DDI) identification is essential to clinical medicine and drug discovery. The two categories of drugs (i.e. chemical drugs and biotech drugs) differ remarkably in molecular properties, action mechanisms, etc. Biotech drugs are up-to-comers but highly promising in modern medicine due to higher specificity and fewer side effects. However, existing DDI prediction methods only consider chemical drugs of small molecules, not biotech drugs of large molecules. Here, we build a large-scale dual-modal graph database named CB-DB and customize a graph-based framework named CB-TIP to reason event-aware DDIs for both chemical and biotech drugs. CB-DB comprehensively integrates various interaction events and two heterogeneous kinds of molecular structures. It imports endogenous proteins founded on the fact that most drugs take effects by interacting with endogenous proteins. In the modality of molecular structure, drugs and endogenous proteins are two heterogeneous kinds of graphs, while in the modality of interaction, they are nodes connected by events (i.e. edges of different relationships). CB-TIP employs graph representation learning methods to generate drug representations from either modality and then contrastively mixes them to predict how likely an event occurs when a drug meets another in an end-to-end manner. Experiments demonstrate CB-TIP's great superiority in DDI prediction and the promising potential of uncovering novel DDIs.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Interações Medicamentosas , Descoberta de Drogas , Estrutura Molecular , ProteínasRESUMO
BACKGROUND: Flowering time has an important effect on regional adaptation and yields for crops. The tyrosine kinase-like (TKL) gene family is widely existed and participates in many biological processes in plants. Furthermore, only few TKLs have been characterized functions in controlling flowering time in wheat. RESULTS: Here, we report that TaCTR1, a tyrosine kinase-like (TKL) gene, regulates flowering time in wheat. Based on identification and evolutionary analysis of TKL_CTR1-DRK-2 subfamily in 15 plants, we proposed an evolutionary model for TaCTR1, suggesting that occurrence of some exon fusion events during evolution. The overexpression of TaCTR1 caused early flowering time in transgenic lines. Transcriptomics analysis enabled identification of mass differential expression genes including plant hormone (ET, ABA, IAA, BR) signaling, flavonoid biosynthesis, phenolamides and antioxidant, and flowering-related genes in TaCTR1 overexpression transgenic lines compared with WT plants. qRT-PCR results showed that the expression levels of ethylene (ET) signal-related genes (ETR, EIN, ERF) and flowering-related genes (FT, PPD1, CO, PRR, PHY) were altered in TaCTR1-overexpressing wheat compared with WT plants. Metabonomics analysis showed that flavonoid contents were altered. CONCLUSIONS: Thus, the results show that TaCTR1 plays a positive role in controlling flowering time by activating various signaling pathways and regulating flowering-related genes, and will provide new insights on the mechanisms of wheat flowering regulation.
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Evolução Molecular , Flores , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Plantas Geneticamente Modificadas/genética , Reguladores de Crescimento de Plantas/metabolismo , Perfilação da Expressão Gênica , Genoma de PlantaRESUMO
Perioperative sleep disturbance may increase delirium risk. However, the role of perioperative sleep disturbance in delirium following total joint arthroplasty remains unclear. This prospective cohort study aimed to observe the delirium risk in patients with sleep disturbances. After excluding pre-existing sleep disturbances, older patients scheduled for total joint arthroplasty from July 17, 2022, to January 12, 2023, were recruited. Preoperative sleep disturbance or postoperative sleep disturbance was defined as a Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ) score of <50 during hospitalisation. A cut-off score of 25 was used to classify the severity of sleep disturbance. The primary outcome was the incidence of postoperative delirium. In all, 11.6% of cohort patients (34/294) developed delirium. After multivariate analysis, a preoperative Day 1 RCSQ score of ≤25 (odds ratio [OR] 3.62, 95% confidence interval [CI] 1.19-10.92; p = 0.02), occurrence of sleep disturbances (OR 2.76, 95% CI 1.19-6.38; p = 0.02) and RCSQ score of ≤25(OR 2.91, 95% CI 1.33-6.37; p = 0.007) postoperatively were strong independent predictors of delirium. After sensitivity analysis for daily delirium, a postoperative Day 1 RCSQ score of ≤25 (OR 9.27, 95% CI 2.72-36.15; p < 0.001) was associated with a greater risk of delirium on postoperative Day 1, with a reasonable discriminative area under the curve of 0.730. We concluded that postoperative but not preoperative sleep disturbances may be an independent factor for delirium risk. Sleep disturbance on the first night after surgery was a good predictor of subsequent delirium, no matter the nature of self-reported sleep disturbance.
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Forecasting alterations in ambient air pollution and the consequent health implications is crucial for safeguarding public health, advancing environmental sustainability, informing economic decision making, and promoting appropriate policy and regulatory action. However, predicting such changes poses a substantial challenge, requiring accurate data, sophisticated modeling methodologies, and a meticulous evaluation of multiple drivers. In this study, we calculate premature deaths due to ambient fine particulate matter (PM2.5) exposure in India from the 2020s (2016-2020) to the 2100s (2095-2100) under four different socioeconomic and climate scenarios (SSPs) based on four CMIP6 models. PM2.5 concentrations decreased in all SSP scenarios except for SSP3-7.0, with the lowest concentration observed in SSP1-2.6. The results indicate an upward trend in the five-year average number of deaths across all scenarios, ranging from 1.01 million in the 2020s to 4.12-5.44 million in the 2100s. Further analysis revealed that the benefits of reducing PM2.5 concentrations under all scenarios are largely mitigated by population aging and growth. These findings underscore the importance of proactive measures and an integrated approach in India to improve atmospheric quality and reduce vulnerability to aging under changing climate conditions.
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Poluentes Atmosféricos , Poluição do Ar , Material Particulado , Índia , Humanos , Poluentes Atmosféricos/análise , Exposição Ambiental , ClimaRESUMO
Air pollution exposure has been linked to a variety of adverse health outcomes among minors; yet little is known about the associated health inequity across regions and schools. Here, we assessed the unequal health burden linked to particulate matter exposure among minors of 10,358 schools in China through 12,439,232 individual health records. Our findings highlight the persistent health risks with superlinear concentration-response patterns and following inverted U-shaped risk trends, that each 10 µg/m3 increase in PM2.5 exposure resulted in 4.1% (3.9-4.2%) additional school absenteeism risk. Compared to urban well-built schools, minors in rural poor-built schools experienced significantly higher exposure and slower rate of risk reduction and had over 80.0% less medical resources while bearing 145.2% of the health burden. Disparities in pollution exposure, built environment, and resource allocation are intertwined to shape the health inequity pattern, especially between rural and urban schools. These findings underscore the urgency for persistent efforts aimed at disadvantaged schools to reduce pollution exposure and equitably distribute social resources, ultimately securing an impartial health-centered education for minors.
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Poluição do Ar , Humanos , China , Material Particulado , Instituições Acadêmicas , Adolescente , Exposição Ambiental , Criança , Poluentes Atmosféricos , Feminino , Masculino , População RuralRESUMO
Although brown adipose tissue (BAT) has historically been viewed as a major site for energy dissipation through thermogenesis, its endocrine function has been increasingly recognized. However, the circulating factors in BAT that play a key role in controlling systemic energy homeostasis remain largely unexplored. Here, we performed a peptidomic analysis to profile the extracellular peptides released from human brown adipocytes upon exposure to thermogenic stimuli. Specifically, we identified a secreted peptide that modulates adipocyte thermogenesis in a cell-autonomous manner, and we named it BATSP1. BATSP1 promoted BAT thermogenesis and induced browning of white adipose tissue in vivo, leading to increased energy expenditure under cold stress. BATSP1 treatment in mice prevented high-fat diet-induced obesity and improved glucose tolerance and insulin resistance. Mechanistically, BATSP1 facilitated the nucleocytoplasmic shuttling of forkhead transcription factor 1 (FOXO1) and released its transcriptional inhibition of uncoupling protein 1 (UCP1). Overall, we provide a comprehensive analysis of the human brown adipocyte extracellular peptidome following acute forskolin (FSK) stimulation and identify BATSP1 as a novel regulator of thermogenesis that may offer a potential approach for obesity treatment.
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Tecido Adiposo Marrom , Obesidade , Camundongos , Humanos , Animais , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Adipócitos Marrons/metabolismo , Tecido Adiposo Branco/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , Termogênese/fisiologia , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Previous observational studies have indicated that metabolic abnormalities are associated with benign prostatic hyperplasia (BPH). The limitations of the research methodology of observational studies do not allow causal inference to be drawn; however, Mendelian randomization (MR) can clarify this. METHODS: Using summary-level data from genome-wide association studies, we conducted a two-sample MR study to examine the causality of the metabolic syndrome (MetS) and its components on BPH (26,358 BPH cases and 110,070 controls). The random-effects inverse-variance weighted was employed as the primary method for MR analyses. RESULTS: We observed that genetically predicted waist circumference (WC) (odds ratio [OR] = 1.236, 95% confidence interval [CI]: 1.034-1.478, p = 0.020) and diastolic blood pressure (DBP) (OR = 1.011, 95% CI: 1.002-1.020, p = 0.020) were significantly positively associated with BPH risk. We did not identify a causal effect of MetS (OR = 0.975, 95% CI: 0.922-1.031, p = 0.375), systolic blood pressure (OR = 1.004, 95% CI: 0.999-1.008, p = 0.115), triglycerides (OR = 1.016, 95% CI: 0.932-1.109, p = 0.712), high-density lipoprotein (OR = 1.005, 95% CI: 0.930-1.086, p = 0.907), and fasting blood glucose (OR = 1.037, 95% CI: 0.874-1.322, p = 0.678) on BPH. In the multivariable MR analysis, we observed that the risk effect of DBP (OR = 1.013, 95% CI: 1.000-1.026, p = 0.047) on BPH persisted after conditioning with WC (OR = 1.132, 95% CI: 0.946-1.356, p = 0.177). CONCLUSIONS: Our study provides genetic evidence supporting the causal effect of DBP on BPH, although the effect of WC needs to be further validated.
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Síndrome Metabólica , Hiperplasia Prostática , Masculino , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/genética , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Bladder cancer (BC) invasion is a critical factor that impacts the prognosis and quality of life of patients. However, the underlying mechanisms of BC invasion is far from clear. Fibroblast growth factor 13 (FGF13), a non-secretory FGF, has been found to be ectopically expressed in various tumors and implicated in tumor development, but its potential association to BC has not been investigated. Here, we reported that the expression of FGF13A, one nucleolar isoform of FGF13, was downregulated in BC patients and negatively associated with tumor invasion. Additionally, we demonstrated that overexpression of FGF13A could inhibit the migration and invasion of BC 5637 and T24 cells. We also confirmed the localization of FGF13A in the nucleolus and its interaction with nucleoproteins NPM1 and UBP. Subsequently, we identified that the N-terminal region of FGF13A was essential for its nucleolus location and interaction with NPM1. Furthermore, we found that FGF13A inhibited the generation of nascent ribosomal RNA and suppressed the migration and invasion of BC cells through its N-terminal region. Our research establishes, for the first time, a correlation between the expression of FGF13A and the onset and progression of BC. This provides novel insights into the role of FGF13A in the development of BC.
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Neoplasias da Bexiga Urinária , Humanos , Células Epiteliais , Proteínas Nucleares/genética , Isoformas de Proteínas/metabolismo , Qualidade de Vida , Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismoRESUMO
Traditional current-driven spintronics is limited by localized heating issues and large energy consumption, restricting their data storage density and operation speed. Meanwhile, voltage-driven spintronics with much lower energy dissipation also suffers from charge-induced interfacial corrosion. Thereby finding a novel way of tuning ferromagnetism is crucial for spintronics with energy-saving and good reliability. Here, a visible light tuning of interfacial exchange interaction via photoelectron doping into synthetic antiferromagnetic heterostructure of CoFeB/Cu/CoFeB/PN Si substrate is demonstrated. Then, a complete, reversible magnetism switching between antiferromagnetic (AFM) and ferromagnetic (FM) states with visible light on and off is realized. Moreover, a visible light control of 180° deterministic magnetization switching with a tiny magnetic bias field is achieved. The magnetic optical Kerr effect results further reveal the magnetic domain switching pathway between AFM and FM domains. The first-principle calculations conclude that the photoelectrons fill in the unoccupied band and raise the Fermi energy, which increases the exchange interaction. Lastly, a prototype device with visible light control of two states switching with a 0.35% giant magnetoresistance ratio change (maximal 0.4%), paving the way toward fast, compact, and energy-efficient solar-driven memories is fabricated.
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Developing functional nitroxyl (HNO) donors play a significant role in the further exploration of endogenous HNO in biochemistry and pharmacology. In this work, two novel Piloty's acids (SBD-D1 and SBD-D2) were proposed by incorporating benzoxadiazole-based fluorophores, in order to achieve the dual-function of releasing both HNO and a fluorophore in situ. Under physiological conditions, both SBD-D1 and SBD-D2 efficiently donated HNO (t1/2 = 10.96 and 8.18 min, respectively). The stoichiometric generation of HNO was determined by both Vitamin B12 and phosphine compound trap. Interestingly, due to the different substitution groups on the aromatic ring, SBD-D1 with the chlorine showed no fluorescence emission, but SBD-D2 was strongly fluorescent due to the presence of the dimethylamine group. Specifically, the fluorescent signal would decrease during the release process of HNO. Moreover, theoretical calculations were performed to understand the emission difference. A strong radiation derived from benzoxadiazole with dimethylamine group due to the large transition dipole moment (â¼4.3 Debye), while the presence of intramolecular charge transfer process in the donor with chlorine group caused a small transition dipole moment (<0.1 Debye). Finally, these studies would contribute to the future design and application of novel functional HNO donors for the exploration of HNO biochemistry and pharmacology.
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Cloro , Óxidos de Nitrogênio , Óxidos de Nitrogênio/química , Ácidos Hidroxâmicos/química , Corantes FluorescentesRESUMO
Oxidative stress is a major cause of ovarian aging and follicular atresia. There is growing evidence that showed potential roles of rutin in antidiabetic, anti-inflammatory, antitumor, antibacterial and antioxidant, although it is yet unclear what the underlying mechanism is. Here, we looked into the potential effects of rutin on oxidative stress in the prehierarchical small white follicles (SWFs) from 580-day-old (D580) laying chickens. According to the findings, aging D580 layer ferroptosis was much higher than it was for laying hens during the peak period (280-day-old, D280). In both naturally aged and d-gal-induced chicken SWFs, rutin treatment concurrently boosted cell proliferation and prevented apoptosis. In addition, rutin inhibited the increased ferroptosis in aging hens. Meanwhile, rutin markedly suppressed the elevated ferroptosis and descending antioxidant capacity of D280-culture-SWFs from chicken elicited by d-gal. Rutin's activation of the Nrf2/HO-1 pathway hastened the SWFs' verbal battle with oxidative damage and reduced ferroptosis. Furthermore, activation of the ferroptosis signal increased the oxidative damage in SWFs. In conclusion, rutin alleviated oxidative stress that was induced by ferroptosis in aging chicken SWFs through Nrf2/HO-1 pathway. These findings point to a novel mechanism by which rutin protects SWFs from oxidative stress by suppressing ferroptosis, which is presumably a fresh approach to slowing ovarian aging in laying hens.
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Antioxidantes , Ferroptose , Feminino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Rutina/farmacologia , Galinhas/metabolismo , Atresia Folicular , Estresse Oxidativo , EnvelhecimentoRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic lipid accumulation, imposes serious challenges on public health worldwide. Breastfeeding has been reported to reduce the risk of NAFLD. Extracellular vesicles (EVs) are bilayer membrane vesicles released from various cells into the extracellular space, participating in multiple life processes. Whether EVs from human milk exert metabolic benefits against NAFLD is worth investigating. METHODS AND RESULTS: In this study, the EVs were isolated from human milk collected from healthy mothers and quantified. Functional analyses were performed using the NAFLD mouse model and free fatty acid (FFA)-stimulated mouse primary hepatocytes. The results showed that human milk-derived EVs could effectively alleviate high fat diet-induced hepatic steatosis and insulin resistance in mice with NAFLD via inhibiting lipogenesis and increasing lipolysis. The FFA-induced lipid accumulation was also inhibited in hepatocytes after treatment with human milk-derived EVs. Mechanistically, the human milk derived-EVs cargo (proteins and miRNAs), which linked to lipid metabolism, may be responsible for these beneficial effects. CONCLUSION: The findings of this study highlighted the therapeutic benefits of human milk-derived EVs and provided a new strategy for NAFLD treatment.
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Vesículas Extracelulares , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Leite Humano/metabolismo , Fígado/metabolismo , Hepatócitos , Metabolismo dos Lipídeos , Vesículas Extracelulares/metabolismo , Lipídeos , Camundongos Endogâmicos C57BLRESUMO
The coupling of topological electronic states and ferroelectricity is highly desired due to their abundant physical phenomenon and potential applications in multifunctional devices. However, it is difficult to achieve such a phenomenon in a single ferroelectric (FE) monolayer because the two polarized states are topologically equivalent. Here, we demonstrate that the symmetry of polarized states can be broken by constructing a Janus structure in a FE monolayer. We illustrate such a general idea by replacing a layer of Te atoms in the In2Te3 monolayer with S atoms. Using first-principles calculations, we show that the In2Te2S monolayer has two asymmetric polarized states, which are characterized by a metal and semiconductor, respectively. Importantly, as the spin-orbit coupling is included, a band gap (50.4 meV) is created in the metallic state, resulting in a non-trivial topological phase. Thus, it proves to be a feasible method to engineer non-volatile FE control of topological order in a single-phase system. We also demonstrate the underlying physical mechanism of topological phase transition, which is unveiled to be related to the weakened intrinsic electric field resulting from charge transfer. These interesting results provide a general way to design asymmetric FE materials and shed light on their potential application in non-volatile multifunctional devices.
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Air pollution is still an important risk factor that endangers the health of Chinese people, leading the government to implement a series of policies to address air pollution. This study takes the Air Pollution Prevention and Control Action Plan (APPCAP) proposed in 2013 as the object and uses the combined data set of China's 2000-2019 economic panel data and PM2.5 remote sensing data to analyse the implementation effect of the policy by the multiperiod difference-in-differences method, considering regional heterogeneity. The results show that the implementation of the APPCAP significantly reduced the PM2.5 concentration in China, and the effect was stronger in the Yangtze River Delta region. Future governance policies should further consider local characteristics and determine pollution control goals and measures according to local conditions.
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Poluição do Ar , Humanos , Poluição Ambiental , China , Fatores de Risco , Material ParticuladoRESUMO
Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly men. It's first-line therapy is drugs. But with the progression of the disease or side effects of drugs, surgical treatment will become a better choice. However, either transurethral resection of the prostate, the standard procedure, or enucleation or resection of the prostate based on various laser platforms or plasma technologies cause a high incidence of retrograde ejaculation in their postoperative follow-up. In the past, retrograde ejaculation was usually regarded as the cost of benign prostatic hyperplasia surgery. In recent years, with the continuous improvement of surgical skills and the emergence of new techniques, retrograde ejaculation has aroused the attention of clinicians. This article mainly introduces the mechanism of retrograde ejaculation after benign prostatic hyperplasia surgery and the methods to reduce the incidence of retrograde ejaculation after surgery. These methods mainly include various modified surgery, as well as novel minimally invasive techniques such as prostate embolization and prostatic urethral lift.
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Hiperplasia Prostática , Ejaculação Retrógrada , Ressecção Transuretral da Próstata , Masculino , Idoso , Pessoa de Meia-Idade , Humanos , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/efeitos adversos , Próstata/cirurgia , Uretra/cirurgia , EjaculaçãoRESUMO
BACKGROUND: Cycas multipinnata and C. panzhihuaensis are two attractive ornamental tree species. With the global climate change, the temperature in the natural habitats of both the species shows a marked rising trend. However, how the two species respond to extreme high temperatures are not clear. Chlorophyll fluorescence parameters, chlorophyll content, chloroplast ultrastructure and lipid metabolism in the two species were determined following plant exposure to heat stress. RESULTS: The results demonstrated that the photosynthetic efficiency decreased significantly in both the species following heat shock and recovery, but to a greater extent in C. panzhihuaensis. Compared to the control, chlorophyll content of C. multipinnata did not change significantly following heat stress and recovery. However, chlorophyll content of C. panzhihuaensis increased significantly after 1 d of recovery in comparison with the control. Chloroplast ultrastructures of C. panzhihuaensis were more severely affected by heat shock than C. multipinnata. C. multipinnata and C. panzhihuaensis followed a similar change trend in the amounts of most of the lipid categories after heat stress. However, only the amounts of lysophospholipids and fatty acyls differed significantly between the two species following heat treatment. Additionally, the unsaturation levels of the major lipid classes in C. multipinnata were significantly lower than or equal to those in C. panzhihuaensis. CONCLUSIONS: C. multipinnata was less affected by extremely high temperatures than C. panzhihuaensis. The differential stability of chlorophyll and chloroplast ultrastructure and the differential adjustment of lipid metabolism might contribute to the different responses to heat shock between the two species.
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Cycas , Clorofila/metabolismo , Cycas/metabolismo , Resposta ao Choque Térmico , Lipídeos , Lisofosfolipídeos , Fotossíntese/fisiologiaRESUMO
Sperm is the ultimate executor of male reproductive function. Normal morphology, quantity, and motility of sperm ensure the normal reproductive process. Palmitoylation is a posttranslational modification mediated by palmitoyltransferases whereby palmitoyl is added to proteins. Seven palmitoyltransferases have been identified in Saccharomyces cerevisiae and 23 in humans (including ZDHHC1-9 and ZDHHC11-24), with corresponding homologs in mice. We identified two testis-specific palmitoyltransferases ZDHHC11 and ZDHHC19 in mice. The Zdhhc11 and Zdhhc19-knockout mouse models were constructed, and it was found that the Zdhhc11 knockout males were fertile, while Zdhhc19 knockout males were sterile. ZDHHC19 is located in the cell membrane of step 4-9 spermatids in the mouse testis, and phenotypic analysis showed that the testicular weight ratio in the Zdhhc19-/- mice decreased along with the number and motility of the sperm decreased, while sperm abnormalities increased, mainly due to the "folded" abnormal sperm caused by sperm membrane fusion, suggesting the involvement of ZDHHC19 in maintaining membrane stability in the male reproductive system. In addition, Zdhhc19-/- mice showed abnormal sperm morphologies and apoptosis during spermatogenesis, suggesting that spermatogenesis in the Zdhhc19-/- mice was abnormal. These results indicate that ZDHHC19 promotes membrane stability in male germ cells.
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Aciltransferases , Infertilidade Masculina , Espermátides , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Membrana Celular/metabolismo , Infertilidade Masculina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Motilidade dos Espermatozoides/genética , Espermátides/metabolismo , Espermatogênese/genética , Espermatozoides/metabolismo , Testículo/metabolismoRESUMO
The most common complication during pregnancy, gestational diabetes mellitus (GDM), can cause adverse pregnancy outcomes and result in the mother and infant having a higher risk of developing type 2 diabetes after pregnancy. However, existing therapies for GDM remain scant, with the most common being lifestyle intervention and appropriate insulin treatment. MOTS-c, a mitochondrial-derived peptide, can target skeletal muscle and enhance glucose metabolism. Here, we demonstrate that MOTS-c can be an effective treatment for GDM. A GDM mouse model was established by short term high-fat diet combined with low-dose streptozotocin (STZ) treatment while MOTS-c was administrated daily during pregnancy. GDM symptoms such as blood glucose and insulin levels, glucose and insulin tolerance, as well as reproductive outcomes were investigated. MOTS-c significantly alleviated hyperglycemia, improved insulin sensitivity and glucose tolerance, and reduced birth weight and the death of offspring induced by GDM. Similar to a previous study, MOTS-c also could activate insulin sensitivity in the skeletal muscle of GDM mice and elevate glucose uptake in vitro. In addition, we found that MOTS-c protects pancreatic ß-cell from STZ-mediated injury. Taken together, our findings demonstrate that MOTS-c could be a promising strategy for the treatment of GDM.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Gestacional/sangue , Diabetes Gestacional/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Proteínas Mitocondriais/uso terapêutico , Adiponectina/sangue , Animais , Peso ao Nascer/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Linhagem Celular , Diabetes Mellitus Experimental/sangue , Feminino , Hiperglicemia/sangue , Insulina/sangue , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , GravidezRESUMO
Fluorescent molecules are important tools in biological detection, and numerous efforts have been made to develop compounds to meet the desired photophysical properties. For example, tuning the wavelength allows an appropriate penetration depth with minimal interference from the autofluorescence/scattering for a better signal-to-noise contrast. However, there are limited guidelines to rationally design or computationally predict the optical properties from first principles, and factors like the solvent effects will make it more complicated. Herein, we established a database (SMFluo1) of 1181 solvated small-molecule fluorophores covering the ultraviolet-visible-near-infrared absorption window and developed new machine learning models based on deep neural networks for accurately predicting photophysical parameters. The optimal system was applied to 120 out-of-sample compounds, and it exhibited remarkable accuracy with a mean relative error of 1.52%. In this new paradigm, a deep learning algorithm is promising to complement conventional theoretical and experimental studies of fluorophores and to greatly accelerate the discovery of new dyes. Due to its simplicity and efficiency, data from newly developed fluorophores can be easily supplemented to this system to further improve the accuracy across various dye families.
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Corantes Fluorescentes , Redes Neurais de Computação , Humanos , Aprendizado de Máquina , SolventesRESUMO
Little is known about the impact of socio-economic and environmental factors on the associations between PM2.5 exposure and health risk for elementary students. We estimated the space variability of effects of PM2.5 on daily illness-related absence rate for 2278 elementary schools from 97 counties across Jiangsu Province with data collected in the 2016-17 academic year. We evaluated the effects at school- and county-scales and examined the role of socio-economic and environmental factors with generalized addictive models (GAM). With an interquartile range (IQR, 32 µg/m3) increase in PM2.5 concentration, the relative risk of absence rate for a given school ranged between 1.00 and 2.81. Factors including high economic development level, low health expenditure, dense road network, dense population and low vegetation coverage drove strong effects for schools/counties. For the implementation of efficient clean air policies and public health interventions, we should concern about not only high-polluted areas but also areas under specific socio-economic and environmental conditions.