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1.
Immunity ; 56(6): 1410-1428.e8, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37257450

RESUMO

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.


Assuntos
Plaquetas , COVID-19 , Humanos , SARS-CoV-2 , Infecções Irruptivas , Multiômica , Anticorpos Neutralizantes , Anticorpos Antivirais
2.
Nat Immunol ; 17(5): 495-504, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27019227

RESUMO

Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA:DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response.


Assuntos
DNA Polimerase I/metabolismo , DNA/biossíntese , Interferon Tipo I/metabolismo , RNA/biossíntese , Sequência de Bases , Células Cultivadas , Citosol/metabolismo , DNA/genética , DNA Polimerase I/genética , Saúde da Família , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Células HEK293 , Células HeLa , Humanos , Immunoblotting , Masculino , Microscopia Confocal , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Transtornos da Pigmentação/genética , Transtornos da Pigmentação/metabolismo , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Nature ; 609(7927): 496-501, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36104554

RESUMO

Lithium niobate (LiNbO3) is viewed as a promising material for optical communications and quantum photonic chips1,2. Recent breakthroughs in LiNbO3 nanophotonics have considerably boosted the development of high-speed electro-optic modulators3-5, frequency combs6,7 and broadband spectrometers8. However, the traditional method of electrical poling for ferroelectric domain engineering in optic9-13, acoustic14-17 and electronic applications18,19 is limited to two-dimensional space and micrometre-scale resolution. Here we demonstrate a non-reciprocal near-infrared laser-writing technique for reconfigurable three-dimensional ferroelectric domain engineering in LiNbO3 with nanoscale resolution. The proposed method is based on a laser-induced electric field that can either write or erase domain structures in the crystal, depending on the laser-writing direction. This approach offers a pathway for controllable nanoscale domain engineering in LiNbO3 and other transparent ferroelectric crystals, which has potential applications in high-efficiency frequency mixing20,21, high-frequency acoustic resonators14-17 and high-capacity non-volatile ferroelectric memory19,22.

4.
Nat Methods ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890427

RESUMO

The dry mass and the orientation of biomolecules can be imaged without a label by measuring their permittivity tensor (PT), which describes how biomolecules affect the phase and polarization of light. Three-dimensional (3D) imaging of PT has been challenging. We present a label-free computational microscopy technique, PT imaging (PTI), for the 3D measurement of PT. PTI encodes the invisible PT into images using oblique illumination, polarization-sensitive detection and volumetric sampling. PT is decoded from the data with a vectorial imaging model and a multi-channel inverse algorithm, assuming uniaxial symmetry in each voxel. We demonstrate high-resolution imaging of PT of isotropic beads, anisotropic glass targets, mouse brain tissue, infected cells and histology slides. PTI outperforms previous label-free imaging techniques such as vector tomography, ptychography and light-field imaging in resolving the 3D orientation and symmetry of organelles, cells and tissue. We provide open-source software and modular hardware to enable the adoption of the method.

5.
Proc Natl Acad Sci U S A ; 120(36): e2301954120, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37639595

RESUMO

Accurate understanding of permafrost dynamics is critical for evaluating and mitigating impacts that may arise as permafrost degrades in the future; however, existing projections have large uncertainties. Studies of how permafrost responded historically during Earth's past warm periods are helpful in exploring potential future permafrost behavior and to evaluate the uncertainty of future permafrost change projections. Here, we combine a surface frost index model with outputs from the second phase of the Pliocene Model Intercomparison Project to simulate the near-surface (~3 to 4 m depth) permafrost state in the Northern Hemisphere during the mid-Pliocene warm period (mPWP, ~3.264 to 3.025 Ma). This period shares similarities with the projected future climate. Constrained by proxy-based surface air temperature records, our simulations demonstrate that near-surface permafrost was highly spatially restricted during the mPWP and was 93 ± 3% smaller than the preindustrial extent. Near-surface permafrost was present only in the eastern Siberian uplands, Canadian high Arctic Archipelago, and northernmost Greenland. The simulations are similar to near-surface permafrost changes projected for the end of this century under the SSP5-8.5 scenario and provide a perspective on the potential permafrost behavior that may be expected in a warmer world.

6.
Hum Mol Genet ; 31(15): 2508-2520, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35220433

RESUMO

Neonatal white matter dysplasia (NWMD) is characterized by developmental abnormity of CNS white matter, including abnormal myelination. Besides environmental factors such as suffocation at birth, genetic factors are also main causes. Signaling pathway is an important part of gene function and several signaling pathways play important roles in myelination. Here, we performed genetic analysis on a cohort of 138 patients with NWMD and found that 20% (5/25) cause genes which referred to 28.57% (8/28) patients enriched in mammalian target of rapamycin (mTOR) signaling pathway. Depletion of mTOR reduced genesis and proliferation of oligodendrocyte progenitor cells (OPC) during embryonic stage and reduced myelination in corpus callosum besides cerebellum and spinal cord during early postnatal stages which is related to not only differentiation but also proliferation of oligodendrocyte (OL). Transcriptomic analyses indicated that depletion of mTOR in OLs upregulated expression of forkhead box O3 (FoxO3), which is a repressor of expression of myelin basic protein, and downregulating expression of FoxO3 by short interfering RNA promoted OPCs develop into MBP+ OLs. Thus, our findings suggested that mTOR signaling pathway is NWMD-related pathway and mTOR is important for myelination of the entire CNS during early developmental stages through regulating expression of FoxO3 at least partially.


Assuntos
Substância Branca , Diferenciação Celular/genética , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Humanos , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Transdução de Sinais , Sirolimo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Substância Branca/metabolismo
7.
Opt Lett ; 49(9): 2385-2388, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691725

RESUMO

We demonstrate that the temporal contrast of femtosecond light pulses is a critical parameter in laser writing inside transparent dielectrics, allowing different material modifications. In particular, anisotropic nanopores in silica glass are produced by high-contrast of 107 femtosecond Yb:KGW laser pulses rather than low-contrast of 103 Yb fiber laser pulses. The difference originates in the fiber laser storing a third of its energy in a post-pulse of up to 200 ps duration. The absorption of this low-intensity fraction of the pulse by laser-induced transient defects with relatively long lifetime and low excitation energy, such as self-trapped holes, drastically changes the kinetics of energy deposition and the type of material modification. We also demonstrate that low-contrast pulses are effective in creating lamellar birefringent structures, possibly driven by a quadrupole nonlinear current.

8.
Br J Dermatol ; 191(1): 107-116, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38489583

RESUMO

BACKGROUND: Inherited hyperpigmented skin disorders comprise a group of entities with considerable clinical and genetic heterogenicity. The genetic basis of a majority of these disorders remains to be elucidated. OBJECTIVES: This study aimed to identify the underlying gene for an unclarified disorder of autosomal-dominant generalized skin hyperpigmentation with or without glomuvenous malformation. METHODS: Whole-exome sequencing was performed in five unrelated families with autosomal-dominant generalized skin hyperpigmentation. Variants were confirmed using Sanger sequencing and a minigene assay was employed to evaluate the splicing alteration. Immunofluorescence and transmission electron microscopy (TEM) were used to determine the quantity of melanocytes and melanosomes in hyperpigmented skin lesions. GLMN knockdown by small interfering RNA assays was performed in human MNT-1 cells to examine melanin concentration and the underlying molecular mechanism. RESULTS: We identified five variants in GLMN in five unrelated families, including c.995_996insAACA(p.Ser333Thrfs*11), c.632 + 4delA, c.1470_1473dup(p.Thr492fs*12), c.1319G > A(p.Trp440*) and c.1613_1614insTA(Thr540*). The minigene assay confirmed that the c.632 + 4delA mutant resulted in abolishment of the canonical donor splice site. Although the number of melanocytes remained unchanged in skin lesions, as demonstrated by immunofluorescent staining of tyrosinase and premelanosome protein, TEM revealed an increased number of melanosomes in the skin lesion of a patient. The GLMN knockdown MNT-1 cells demonstrated a higher melanin concentration, a higher proportion of stage III and IV melanosomes, upregulation of microphthalmia-associated transcription factor and tyrosinase, and downregulation of phosphorylated p70S6 K vs. mock-transfected cells. CONCLUSIONS: We found that loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation. Our study implicates a potential role of glomulin in human skin melanogenesis, in addition to vascular morphogenesis.


A group of skin conditions known as 'inherited hyperpigmented skin disorders' includes some diseases with different clinical and genetic traits. The genetic basis of the majority of these diseases is not understood. To identify the gene responsible for a disease that causes darker patches of skin (hyperpigmentation) with or without the abnormal growth of blood vessels and the presence of cells named glomus cells (a glomuvenous malformation), we used genetic techniques called whole-exome sequencing and Sanger sequencing in five unrelated families with this disease. We also used a technique called a 'minigene assay' to evaluate genetic alterations in a gene called GLMN, which encodes a protein called glomulin. Immunofluorescence and transmission electron microscopy (TEM) were used to determine the number of pigment-producing cells (called melanocytes) and melanosomes (where the pigment melanin is synthesized, stored and transported) in hyperpigmented skin lesions. We identified five different variants of the GLMN gene in five unrelated families. Although the number of melanocytes remained unchanged in skin lesions, TEM revealed an increased number of melanosomes. By 'switching off' the GLMN gene, we found that skin cells produced more pigment, as well as the proteins MITF and tyrosinase; they also showed a decrease in the phosphorylated protein p-p70S6 K. Overall, we found that loss-of-function mutations in GLMN caused skin hyperpigmentation with or without abnormal blood vessels. The results suggest there could be a potential role of the protein glomulin in human skin colour and blood vessel changes.


Assuntos
Sequenciamento do Exoma , Hiperpigmentação , Melanócitos , Linhagem , Humanos , Hiperpigmentação/genética , Hiperpigmentação/patologia , Feminino , Masculino , Melanócitos/metabolismo , Adulto , Mutação com Perda de Função , Tumor Glômico/genética , Tumor Glômico/patologia , Melanossomas/genética , Criança , Melaninas/metabolismo , Adolescente , Pele/patologia , Pele/irrigação sanguínea , Pessoa de Meia-Idade , Paraganglioma Extrassuprarrenal , Proteínas Adaptadoras de Transdução de Sinal
9.
Ann Hematol ; 103(4): 1305-1315, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38049586

RESUMO

Prognostic significance of multiple immune antigens in multiple myeloma has been well established. However, a level of uncertainty remains regarding the intrinsic relationship between immunophenotypes and cytogenetic stability and precise risk stratification. To address these unresolved issues, we conducted a study involving 1389 patients enrolled in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Our results revealed that the correlation between antigen expression and cytogenetics is more prominent than cytopenia or organ dysfunction. Most immune antigens, apart from CD38, CD138, and CD81, exhibit significant associations with the incidence of at least one cytogenetic abnormality. In turn, we identified CD138-low/CD27-neg as specific adverse immunophenotypic profile, which remaining independent impact on progression-free survival (HR, 1.49; P = 0.007) and overall survival (HR, 1.77; P < 0.001) even in the context of cytogenetics. Importantly, CD138-low/CD27-neg profile was also associated with inferior survival after first relapse (P < 0.001). Moreover, the antigen expression profiles were not strictly similar when comparing diagnosis and relapse; in particular, the CD138-low/CD27-neg pattern was notably increased after disease progression (19.1 to 29.1%; P = 0.005). Overall, our study demonstrates that diverse immune profiles are strongly associated with cytogenetic stability, and a specific immunophenotype (CD138-low/CD27-neg) could effectively predict prognoses across different disease stages.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Prognóstico , Aberrações Cromossômicas , Análise Citogenética , Recidiva
10.
Eur J Nutr ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563983

RESUMO

AIMS: Evidence regarding impact of protein intake distribution on skeletal muscle mass in older adults is limited and inconsistent. This study aims to investigate the relationship of evenness of dietary protein distribution and number of meals exceeding a threshold with appendicular skeletal muscle mass (ASM) in healthy and free-living Chinese older adults. METHODS: Repeated measured data of 5689 adult participants aged ≥ 60 years from the China Health and Nutrition Survey (CHNS) 2015 and 2018 waves were analyzed. Mixed-effects linear regression model was performed to examine the relationship between coefficient of variance (CV) of protein intake across meals, number of meals ≥ 0.4 g protein/kg BW and ASM, respectively. Analyses were conducted separately for male and female. RESULTS: The average CV of protein intake in each wave was in the range of 0.34-0.35. More than 40% male and female participants in each wave had no meal reaching 0.4 g protein/kg BW. Female participants in the highest quartile of protein intake CV had significantly lower ASM (ß = -0.18, 95%CI = -0.32, -0.04) compared with those in the lowest quartile, after adjustment for multiple confounders. Significant negative trends were observed across dietary protein CV quartiles with ASM both in male (P trend = 0.043) and female (P trend = 0.007). Significant positive association between number of meals exceeding 0.4 g protein /kg BW and relative ASM were observed in females (2 meals vs. 0 meal: ß = 0.003, 95%CI = 0.0007,0.006;≥3 meals vs. 0 meal: ß = 0.008, 95%CI = 0.003,0.013), after adjusting for multiple covariates. CONCLUSIONS: A more even-distributed protein intake pattern and more meals reaching protein intake threshold were respectively associated with higher appendicular skeletal muscle mass in healthy and free-living older Chinese adults. Prospective studies and intervention trials are needed to confirm these cross-sectional findings.

11.
Environ Res ; 247: 118255, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266890

RESUMO

Lewis acids of solid catalysts have been featured for a pivotal role in promoting various reactions. Regarding the oxidation protocol to remove formaldehyde, the inherent drawback of the best-studied MnO2 materials in acidic sites has eventually caused deficiency of active hydroxyls to sustain low-temperature activity. Herein, the cryptomelane-type MnO2 was targeted and it was tuned via incorporation of Zr metal, exhibiting great advances in not only the complete HCHO-to-CO2 degradation but also cycling performance. Zr species were existent in doping state in the MnO2 lattice, rendering lower crystallinity and breaking the regular growth of MnO2 crystallites, which thereby tripled surface area and created larger volume of smaller mesopores. Meantime, the local electronic properties of Mn atoms were also changed by Zr doping, i.e., more low-valence Mn species were formed due to the electron transfer from Zr to Mn. The results of infrared studies demonstrate the higher possession of Lewis acid sites on ZrMn, and this high degree of electrophilic agents favored the production of hydroxyl species. Furthermore, the reactivity of surface hydroxyls, as investigated by CO temperature programmed reduction and temperature programmed desorption of adsorbed O2, was obviously improved as well after Zr modification. It is speculated jointly with the characterizations of the post-reaction catalysts that the accelerated production of active hydroxyls helped rapidly convert formaldehyde into key intermediate-formate, which was then degraded into CO2, avoiding the side reaction path with undesired intermediate-hydrocarbonate-over the pristine MnO2, where active sites were blocked and formaldehyde oxidation was inhibited. Additionally, Zr decoration could stabilize Lewis acidity to be more resistant to heat degeneration, and this merit brought about advantageous thermal recyclability for cycled application.


Assuntos
Ácidos de Lewis , Óxidos , Óxidos/química , Compostos de Manganês/química , Dióxido de Carbono , Formaldeído/química , Catálise
12.
J Med Genet ; 60(3): 247-253, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35595280

RESUMO

BACKGROUND: Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied. METHODS: CHD cases were extracted from the China Neonatal Genomes Project (2016-2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes. RESULTS: In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05). CONCLUSION: This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.


Assuntos
Cardiopatias Congênitas , Unidades de Terapia Intensiva Neonatal , Recém-Nascido , Humanos , Estudos Retrospectivos , Estudos de Coortes , Variações do Número de Cópias de DNA , Cardiopatias Congênitas/genética , China
13.
Inj Prev ; 30(3): 224-232, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123988

RESUMO

INTRODUCTION: There are many migrant workers in China's first-tier cities, but little is known about road safety. This paper systematically analysed road traffic injuries and risk factors among migrant workers in Guangzhou, China. METHODS: Road traffic crash data from 2017 to 2021 were obtained from the Guangzhou Public Security Traffic Management Integrated System. We plotted the crash network of road users in road traffic crashes and used logistic regression to analyse the risk factors for migrant workers of motorcycle and four-wheeled vehicle crashes. Moreover, the roles of migrant workers and control individuals as perpetrators in road traffic crashes were also analysed. RESULTS: Between 2017 and 2021, 76% of road traffic injuries were migrant workers in Guangzhou. Migrant workers who were motorcyclist drivers most commonly experienced road traffic injuries. Crashes between motorcyclists and car occupants were the most common. The illegal behaviours of migrant worker motorcyclists were closely related to casualties, with driving without a licence only and driving without a licence and drunk driving accounting for the greatest number. Migrant workers were responsible for many injuries of other road users. Motorcycle drivers have a higher proportion of drunk driving. DISCUSSION: Migrant workers play an important role in road traffic safety. They were both the leading source of road traffic injuries and the main perpetrators of road traffic crashes. Measures such as strict requirements for migrant workers to drive motorcycles with licences, prohibit drunk driving, greater publicity of road safety regulations, and combining compulsory education with punishment for illegal behaviours.


Assuntos
Acidentes de Trânsito , Motocicletas , Migrantes , Humanos , Acidentes de Trânsito/estatística & dados numéricos , China/epidemiologia , Migrantes/estatística & dados numéricos , Masculino , Feminino , Adulto , Fatores de Risco , Motocicletas/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/prevenção & controle , Condução de Veículo/estatística & dados numéricos , Condução de Veículo/legislação & jurisprudência , Dirigir sob a Influência/estatística & dados numéricos , Dirigir sob a Influência/legislação & jurisprudência , Pessoa de Meia-Idade
14.
BMC Anesthesiol ; 24(1): 107, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504220

RESUMO

OBJECTIVES: Ultrasound-guided superior laryngeal nerve (SLN) block is a practical and painless approach to avoid the hemodynamic stress response during endotracheal intubation and relieve sore throat after laryngeal surgery. The main purpose of this study was to establish an optimal dosage of local anesthetic when performing SLN block to help anesthetists balance analgesia and side effects. METHODS: Twenty fresh larynx specimens were obtained immediately after resection and then injected with 2-, 3-, 4-, or 5- mL of a lidocaine-blue dye mixture at bilateral SLN puncture sites. Superficial areas of deposited blue dye were measured. Dye leakage and surrounding dyed tissue were recorded. Another 40 patients were included in the ultrasound investigation. Distances between the internal branch of the SLN (iSLN) and adjacent structures were calculated. RESULTS: The dye spread area was greater with the administration of larger doses, especially to the visceral space. A 2- or 3-mL injection of local anesthetic was sufficient to infiltrate the SLN gap. A higher incidence of dye leaking out of the thyrohyoid membrane and anterior epiglottis space was observed; furthermore, there was substantially more dyed hyoid/thyroid cartilage with 4 and 5 mL of injected dye mixture than 2 mL. There was no significant difference between the specimen and ultrasound measurements of for length of iSLN-adjacent structures. CONCLUSIONS: In the Chinese population, 2- or 3- mL of local anesthetic is a safe dose during SLN block. A larger volume could overflow from the cavity to cause complications. The thyrohyoid membrane combined with the superior laryngeal artery is a reliable target for positioning the iSLN during ultrasound-guided regional anesthesia.


Assuntos
Anestesia por Condução , Bloqueio Nervoso , Humanos , Anestésicos Locais , Nervos Laríngeos , Cartilagem Tireóidea
15.
Ecotoxicol Environ Saf ; 272: 116091, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38340600

RESUMO

BACKGROUND: Whether and to what extent the impact of exposure to various polychlorinated biphenyls (PCBs) congeners on diabetes, as well as the important contributors, have remained unclear. OBJECTIVE: We aimed to investigate the association patterns between PCBs mixture and diabetes, identify the critical congeners, and explore the potential modifiers. METHODS: The present study included 5900 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. Weighted logistic regression, restricted cubic spline regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were applied to estimate the linear and non-linear associations of single and mixed PCB exposure with diabetes. Subgroup analyses were also conducted to explore potential sex differences. RESULTS: In the weighted logistic regression model, total PCBs were positively associated with diabetes (OR = 1.33, P < 0.025), and significant non-linear associations were observed using RCS analyses. The non-linear positive association between PCBs mixed exposure and diabetes was likewise found in the WQS and BKMR results. PCB180, PCB194, PCB196, and PCB167 were with the highest weights in the WQS, and PCB209 and PCB66 were with the highest posterior inclusion probabilities in the BKMR. Additionally, exposure to total PCBs and most of individual PCB congeners were significantly associated with elevated risk of in females (OR = 1.74; P for trend < 0.001), while fewer significant associations were observed in males. CONCLUSION: The present study highlighted the importance of the long-term surveillance of PCBs and the need to enhance protective measures against them. Notably, these associations were non-linear, congener-specific, and significantly stronger in females than males, especially at relatively high levels of PCBs exposure. Further prospective and mechanistic studies were warranted to ascertain the causal effects between PCBs mixture and diabetes.


Assuntos
Diabetes Mellitus , Poluentes Ambientais , Bifenilos Policlorados , Adulto , Feminino , Humanos , Masculino , Bifenilos Policlorados/toxicidade , Bifenilos Policlorados/análise , Poluentes Ambientais/toxicidade , Poluentes Ambientais/análise , Exposição Ambiental/análise , Inquéritos Nutricionais , Teorema de Bayes , Diabetes Mellitus/epidemiologia
16.
Ecotoxicol Environ Saf ; 279: 116497, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38805827

RESUMO

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.


Assuntos
Ácidos Cafeicos , Metanfetamina , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Álcool Feniletílico , Animais , Ácidos Cafeicos/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Metanfetamina/toxicidade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Camundongos , Masculino , Síndromes Neurotóxicas/prevenção & controle , Síndromes Neurotóxicas/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos
17.
Reprod Domest Anim ; 59(5): e14567, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798178

RESUMO

In this study, Holstein dairy cows raised in Ningxia were selected as the research object. Mammary epithelial cells (BMECs) were extracted from the milk of eight Holstein cows with significantly different milk fat expression rates and transcribed for sequencing. Bioinformatics analysis was used to analyse the correlation of fat milk percentage, and the critical miR-2285f regulating milk fat was screened out. The target gene binding sites were predicted, and 293T cells and mammary epithelial cells were used as miRNA and target gene models for functional verification in vitro. The tissue difference of miR-2285f Holstein cows was quantitatively analysed by transfecting miR-2285f mimic and inhibitor. Assay (dual luciferase reporter gene assay) and quantitative real-time PCR (quantitative real-time PCR, qRT-PCR), triglyceride (TAG) detection, oil red O detection of lipid droplets, Western Blot assay, Edu and Flow cytometry, The molecular regulatory effects of miR-2285f and target gene MAP2K2 on milk fat metabolism of Holstein dairy cows were studied. The wild-type vector and mutant vector of map2k2-3'utr were constructed, and double luciferase reporting experiments were conducted to verify that MAP2K2 was one of the target genes of miR-2285f. According to qRT-PCR and Western Blot analysis, miR-2285f mainly regulates the expression of MAP2K2 protein in BMECs at the translation level. Bta-miR-2285f can promote cell proliferation and slow cell apoptosis by regulating MAP2K2. Bta-miR-2285f can promote triglyceride (TAG) and lipid droplet accumulation in mammary epithelial cells by targeting MAP2K2. Bta-miR-2285f can regulate protein levels of fat milk marker gene PPARG by targeting MAP2K2. In conclusion, miR-2285f can target the expression of the MAP2K2 gene, promote the proliferation of dairy mammary epithelial cells, inhibit cell apoptosis and regulate the milk fat metabolism in dairy mammary epithelial cells. The results of this study revealed the function of miR-2285f in regulating the differential expression of fat milk in Holstein dairy cows at the cellular level. They provided a theoretical and experimental basis for analysing the regulation network of milk fat synthesis of Holstein dairy cows and the molecular breeding of dairy cows.


Assuntos
Células Epiteliais , Glândulas Mamárias Animais , MicroRNAs , Leite , Animais , Bovinos , MicroRNAs/metabolismo , MicroRNAs/genética , Feminino , Leite/química , Glândulas Mamárias Animais/metabolismo , Células Epiteliais/metabolismo , MAP Quinase Quinase Quinase 2/metabolismo , MAP Quinase Quinase Quinase 2/genética , Metabolismo dos Lipídeos , Triglicerídeos/metabolismo , Apoptose , Humanos , Regulação da Expressão Gênica , Proliferação de Células
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(7): 803-806, 2024 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-38946361

RESUMO

OBJECTIVE: To explore the application of an automatic slide-dropping instrument in bone marrow chromosomal karyotyping. METHODS: The effects of manual and automatic dropping methods under different environmental humidity were retrospectively analyzed, and the repeatability of the automatic dropping method was analyzed. RESULTS: No statistical difference was found between the results of automatic and manual dropping methods under the optimum ambient humidity and high humidity (P > 0.05). At low humidity, there was a statistical difference between the two methods (P < 0.05). With regard to the repeatability, the coefficient of variations of the automatic dropping method for the number of split phases, the rate of good dispersion and the rate of overlap were all lower than those of the manual dropping method. A statistical difference was also found in the number of split phases (P < 0.05) but not in the discrete excellent rate and overlapping rate between the two methods (P > 0.05). CONCLUSION: Better effect can be obtained by the automatic dropping instrument. It is suggested to gradually replace manual work with machine.


Assuntos
Cariotipagem , Humanos , Cariotipagem/métodos , Adulto , Feminino , Masculino , Medula Óssea , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , Adolescente , Umidade , Automação , Criança , Idoso , Pré-Escolar
19.
Wei Sheng Yan Jiu ; 53(1): 42-48, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38443171

RESUMO

OBJECTIVE: To analyze the trend of eating out among Chinese male adults and explore the association between eating out and dietary nutrition and health. METHODS: Males aged 18 and above with complete data were selected from China Health and Nutrition Survey 2000, 2004, 2006, 2009, 2011, 2015 and 2018. Eating out behavior was defined as having consumption of food prepared outside the home during the three consecutive 24-h dietary recalls period. Cochran-Armitage trend test was used to analyze the trend of prevalence of eating out and the energy contribution from eating out foods in males from 2000 to 2018. Analysis of covariance was used to compare the differences in several food and dietary nutrient intakes and nutritional indicators by eating out in 2018. RESULTS: The prevalence of eating out among Chinese male adults increased from 48.49% in 2000 to 57.51% in 2018, showing an increased trend followed by a decreased trend. Males in the 18-29 years old group, urban group, high income group, and high education level group had a higher rate of eating out(P<0.05). The energy contribution from eating out foods increased from 21.80% in 2000 to 28.77% in 2018, showing a slow upward trend. In 2018, the intake of rice, tubers and vegetables was lower in the eating out group, while intake of wheat, fruits, livestock and poultry meat, aquatic products, eggs and milk in eating out group was higher than those in the non-eating out group(P<0.05). The eating out group had a higher intake of energy, fat, protein, cholesterol, calcium, zinc, vitamin B_1 and vitamin B_2 than the non-eating out group(P<0.05). The eating out group had lower levels of systolic blood pressure, HDL-C, blood glucose and glycosylated hemoglobin than the counterparts. The levels of BMI, waist, body fat percentage, diastolic blood pressure and TG were higher in the eating out group than in the non-eating out group. CONCLUSION: From 2000 to 2011, the eating out rate of males in China showed an upward trend, and a downward trend after 2011. At the same time, the energy contribution of eating out foods is increasing. Eating out was associated with major food and nutrients intake and indicators of nutritional status in male adults.


Assuntos
Ingestão de Energia , Estado Nutricional , Masculino , Adulto , Humanos , Adolescente , Adulto Jovem , China/epidemiologia , Ovos , Vitaminas
20.
Wei Sheng Yan Jiu ; 53(1): 8-13, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38443183

RESUMO

OBJECTIVE: To investigate the changes in mild cognitive impairment(MCI) and sociodemographic disparity among adults aged 55 years and above in 4 provinces of China. METHODS: A total of 4687 adults aged 55 years and above from Community-based Cohort Study on Nervous System Disease who did not have Alzheimer's disease, participated in both rounds of the survey, and had complete baseline sociodemographic data and two rounds of data on cognitive function were selected. Generalized estimation equations were used to analyse the effect of sociodemographic factors on MCI. RESULTS: The detection rates of MCI in adults aged 55 years and above without Alzheimer's disease in 4 provinces of China in 2018 and 2020 were 48.56% and 42.56% respectively. MCI occurred in 30.11% of those with normal cognition(NC) at baseline, and 44.24% of those with MCI at baseline reverted to NC. The risk of MCI increased and the likelihood of MCI reversion decreased with increasing age and decreasing per capita monthly household income. In the baseline NC population, the risk of MCI in the junior high school and above group was 35% lower than that in the illiterate group(RR=0.65, 95%CI 0.53-0.80), the risk of MCI was lower in those living in rural areas(RR=0.56, 95%CI 0.49-0.65), and the risk of MCI was 1.17 times(95%CI 1.03-1.32) higher in those with a history of chronic diseases than in those without it. In the baseline MCI population, the likelihood of MCI reversion increased with education, the likelihood of MCI reversion was 1.04 times higher for workers than for non-workers(95%CI 1.00-1.08). CONCLUSION: The incidence and reversal rates of MCI were high in adults aged ≥55 years in four provinces of China. Advanced age, low education and low income level are risk factors for cognitive dysfunction.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Adulto , Humanos , Estudos de Coortes , Disfunção Cognitiva/epidemiologia , China/epidemiologia , Fatores de Risco
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