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1.
Nature ; 605(7909): 262-267, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35546188

RESUMO

The scaling of silicon metal-oxide-semiconductor field-effect transistors has followed Moore's law for decades, but the physical thinning of silicon at sub-ten-nanometre technology nodes introduces issues such as leakage currents1. Two-dimensional (2D) layered semiconductors, with an atomic thickness that allows superior gate-field penetration, are of interest as channel materials for future transistors2,3. However, the integration of high-dielectric-constant (κ) materials with 2D materials, while scaling their capacitance equivalent thickness (CET), has proved challenging. Here we explore transferrable ultrahigh-κ single-crystalline perovskite strontium-titanium-oxide membranes as a gate dielectric for 2D field-effect transistors. Our perovskite membranes exhibit a desirable sub-one-nanometre CET with a low leakage current (less than 10-2 amperes per square centimetre at 2.5 megavolts per centimetre). We find that the van der Waals gap between strontium-titanium-oxide dielectrics and 2D semiconductors mitigates the unfavourable fringing-induced barrier-lowering effect resulting from the use of ultrahigh-κ dielectrics4. Typical short-channel transistors made of scalable molybdenum-disulfide films by chemical vapour deposition and strontium-titanium-oxide dielectrics exhibit steep subthreshold swings down to about 70 millivolts per decade and on/off current ratios up to 107, which matches the low-power specifications suggested by the latest International Roadmap for Devices and Systems5.

2.
Brief Bioinform ; 24(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37232385

RESUMO

The volume of ribonucleic acid (RNA)-seq data has increased exponentially, providing numerous new insights into various biological processes. However, due to significant practical challenges, such as data heterogeneity, it is still difficult to ensure the quality of these data when integrated. Although some quality control methods have been developed, sample consistency is rarely considered and these methods are susceptible to artificial factors. Here, we developed MassiveQC, an unsupervised machine learning-based approach, to automatically download and filter large-scale high-throughput data. In addition to the read quality used in other tools, MassiveQC also uses the alignment and expression quality as model features. Meanwhile, it is user-friendly since the cutoff is generated from self-reporting and is applicable to multimodal data. To explore its value, we applied MassiveQC to Drosophila RNA-seq data and generated a comprehensive transcriptome atlas across 28 tissues from embryogenesis to adulthood. We systematically characterized fly gene expression dynamics and found that genes with high expression dynamics were likely to be evolutionarily young and expressed at late developmental stages, exhibiting high nonsynonymous substitution rates and low phenotypic severity, and they were involved in simple regulatory programs. We also discovered that human and Drosophila had strong positive correlations in gene expression in orthologous organs, revealing the great potential of the Drosophila system for studying human development and disease.


Assuntos
Drosophila melanogaster , Transcriptoma , Humanos , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Perfilação da Expressão Gênica/métodos , RNA/genética , RNA-Seq , Análise de Sequência de RNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Drosophila
3.
Chem Rev ; 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36757873

RESUMO

Lithium-ion batteries have received significant attention over the last decades due to the wide application of portable electronics and increasing deployment of electric vehicles. In order to further enhance the performance of the batteries and overcome the capacity limitations of inorganic electrode materials, it is imperative to explore new cathode and functional materials for rechargeable lithium batteries. Organosulfur materials containing sulfur-sulfur bonds as a kind of promising organic electrode materials have the advantages of high capacities, abundant resources, tunable structures, and environmental benignity. In addition, organosulfur materials have been widely used in almost every aspect of rechargeable batteries because of their multiple functionalities. This review aims to provide a comprehensive overview on the development of organosulfur materials including the synthesis and application as cathode materials, electrolyte additives, electrolytes, binders, active materials in lithium redox flow batteries, and other metal battery systems. We also give an in-depth analysis of structure-property-performance relationship of organosulfur materials, and guidance for the future development of organosulfur materials for next generation rechargeable lithium batteries and beyond.

4.
Opt Express ; 32(2): 1391-1405, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297692

RESUMO

In this paper, a scheme to realize unclonable physical-layer security key generation and distribution (PL-SKGD) based on historical fiber channel state information (HFCSI) is proposed. PL-SKGD schemes based on channel characteristics for enhancing the physical-layer security of optical networks have been proposed in recent years. However, there are potential disadvantages in these schemes, such as 1) low key generation rate (KGR): the slow frequency of the analog waveform change of the channel characteristic leading to low KGR; 2) incompatibility with existing infrastructure: active scrambling to increase the frequency of channel characteristic changes, or tracking changes of channel characteristics requires additional devices; 3) easy to be cloned: all of the optical channel state information is reflected in the signal transmitted inside the fiber, which makes it easy to reproduce by illegal eavesdropper through features analysis and other methods. In order to solve the above problems, a PL-SKGD scheme is designed which uses the chain structure composed of long short-term memory neural network (LSTM-NN) units to learn and store the unique mapping relationship between historical channel time series and provides unclonability based on the fundamental fact that the eavesdropper Eve can never obtain the full HFCSI. The simulation conducted in a quadrature phase shift keying point-to-point optical link system verified successfully that KGR = 0.82 Gbit/s error-free SKGD. The loss function of LSTM-NN drops sharply in the early stages of training and remains a small value. The security of the SKGD system is analyzed, which effectively improves the unclonability of the system. Finally, it is verified that the optimal fiber channel length for error-free SKGD of the proposed scheme is 150 km considering the error correction capability of information reconciliation and weighing key sequence error rate and valid bit generation rate.

5.
Hum Reprod ; 39(2): 303-309, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38140699

RESUMO

Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.


Assuntos
Azoospermia , Testículo , Adulto , Humanos , Masculino , Criança , Testículo/patologia , Sêmen , Espermatozoides/patologia , Espermatogônias , Células de Sertoli , Azoospermia/cirurgia , Azoospermia/patologia , Recuperação Espermática
6.
Int J Legal Med ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38858273

RESUMO

Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites-methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid-were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine.

7.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38396684

RESUMO

Polysaccharides are one of the main active ingredients of Polygonum sibiricum (PS), which is a food and medicine homolog used throughout Chinese history. The antidepressant-like effects of PSP and its underlying mechanisms remain elusive, especially the regulation of microglial polarization. The current study determined the chemical composition and structural characteristics of PSP. Then, the chronic unpredictable mild stress (CUMS) procedure was carried out on the zebrafish for 5 weeks, and PSP was immersed for 9 days (1 h/d). The body weight of zebrafish was monitored, and behavioral tests, including the novel tank test and light and dark tank test, were performed to evaluate the antidepressant-like effects of PSP. Then, the function of the hypothalamic-pituitary-interrenal (HPI) axis, the levels of peripheral inflammation, neuronal and blood-brain barrier damage in the mesencephalon and telencephalon, and the mRNA expression of M1/M2 phenotype genes in the brain were examined. PSP samples had the typical structural characteristics of polysaccharides, consisting of glucose, mannose, and galactose, with an average Mw of 20.48 kDa, which presented porous and agglomerated morphologies. Compared with untreated zebrafish, the depression-like behaviors of CUMS-induced zebrafish were significantly attenuated. PSP significantly decreased the levels of cortisol and pro-inflammatory cytokines and increased the levels of the anti-inflammatory cytokines in the body of CUMS-induced depressive zebrafish. Furthermore, PSP remarkably reversed the neuronal and blood-brain barrier damage in the mesencephalon and telencephalon and the mRNA expression of M1/M2 phenotype genes in the brain. These findings indicated that the antidepressant-like effects of PSP were related to altering the HPI axis hyperactivation, suppressing peripheral inflammation, inhibiting neuroinflammation induced by microglia hyperactivation, and modulating microglial M1/M2 polarization. The current study provides the foundations for future examinations of PSP in the functional foods of emotional regulation.


Assuntos
Polygonum , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Microglia/metabolismo , Polygonum/metabolismo , Antidepressivos/farmacologia , Inflamação/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Citocinas/metabolismo , RNA Mensageiro/metabolismo , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Estresse Psicológico/metabolismo , Modelos Animais de Doenças
8.
J Neurosci ; 42(30): 5930-5943, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35760532

RESUMO

Human society operates on large-scale cooperation. However, individual differences in cooperativeness and incentives to free ride on others' cooperation make large-scale cooperation fragile and can lead to reduced social welfare. Thus, how individual cooperation spreads through human social networks remains puzzling from ecological, evolutionary, and societal perspectives. Here, we identify oxytocin and costly punishment as biobehavioral mechanisms that facilitate the propagation of cooperation in social networks. In three laboratory experiments (n = 870 human participants: 373 males, 497 females), individuals were embedded in heterogeneous networks and made repeated decisions with feedback in games of trust (n = 342), ultimatum bargaining (n = 324), and prisoner's dilemma with punishment (n = 204). In each heterogeneous network, individuals at central positions (hub nodes) were given intranasal oxytocin (or placebo). Giving oxytocin (vs matching placebo) to central individuals increased their trust and enforcement of cooperation norms. Oxytocin-enhanced norm enforcement, but not elevated trust, explained the spreading of cooperation throughout the social network. Moreover, grounded in evolutionary game theory, we simulated computer agents that interacted in heterogeneous networks with central nodes varying in terms of cooperation and punishment levels. Simulation results confirmed that central cooperators' willingness to punish noncooperation allowed the permeation of the network and enabled the evolution of network cooperation. These results identify an oxytocin-initiated proximate mechanism explaining how individual cooperation facilitates network-wide cooperation in human society and shed light on the widespread phenomenon of heterogeneous composition and enforcement systems at all levels of life.SIGNIFICANCE STATEMENT Human society operates on large-scale cooperation. Yet because cooperation is exploitable by free riding, how cooperation in social networks emerges remains puzzling from evolutionary and societal perspectives. Here we identify oxytocin and altruistic punishment as key factors facilitating the propagation of cooperation in human social networks. Individuals played repeated economic games in heterogeneous networks where individuals at central positions were given oxytocin or placebo. Oxytocin-enhanced cooperative norm enforcement, but not elevated trust, explained cooperation spreading throughout the social network. Evolutionary simulations confirmed that central cooperators' willingness to punish noncooperation allowed the permeation of the network and enabled the evolution of cooperation. These results identify an oxytocin-initiated proximate mechanism explaining how individual cooperation facilitates network-wide cooperation in human social networks.


Assuntos
Teoria dos Jogos , Ocitocina , Comportamento Cooperativo , Feminino , Humanos , Masculino , Dilema do Prisioneiro , Punição , Rede Social
9.
Curr Issues Mol Biol ; 45(4): 2895-2907, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37185713

RESUMO

Inflammatory bowel diseases (IBDs), such as Crohn's disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice.

10.
Opt Express ; 31(7): 11829-11845, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37155810

RESUMO

In this paper, a scheme to realize encryption and digital identity authentication at the same time is proposed for enhancing the physical-layer security of point-to-point optical links (PPOL). Exploiting identity code encrypted by the key as authentication information effectively resists passive eavesdropping attacks in fingerprint authentication. The proposed scheme theoretically realizes secure key generation and distribution (SKGD) by phase noise estimation of the optical channel and the generation of identity codes with good randomness and unpredictability by the four-dimensional (4D) hyper-chaotic system. The local laser, erbium doped fiber amplifier (EDFA), and public channel provide the entropy source of uniqueness and randomness to extract symmetric key sequences for legitimate partners. The simulation conducted in a quadrature phase shift keying (QPSK) PPOL system over 100km standard single mode fiber verify successfully that 0.95Gbit/s error-free SKGD. The unpredictability and high sensitivity to the initial value and control parameters of the 4D hyper-chaotic system provide a huge space of ~10125 for identity codes, which is sufficient to resist exhaustive attack. With the proposed scheme, the security level of key and identity can be increased markedly.

11.
Opt Express ; 31(2): 1014-1024, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785137

RESUMO

We demonstrate an X-band distributed receiving system with 4 remote ends for signal-to-noise ratio (SNR) enhancement. The X-band analog signal received by 4 remote ends is first transmitted to the local end through optical fiber links and is then down-converted with a photonic method for digitization and further coherent combination. Finally, a combined signal with a higher SNR can be obtained. In the proposed system, a frequency-tunable single-tone signal is stably transmitted to the remote end for both down-converting the received signal and for generating a dithered sample clock to eliminate the transmission delay jitter with an unlimited compensation range. Experimentally, X-band binary phase shift keying signals are used for system performance evaluation. After 20 to 25 km transmission, the relative timing drifts between different links are at the order of picoseconds, and a near-theoretical SNR enhancement is achieved. The proposed scheme has a simple remote structure with no need for time synchronization, increasing its signal combining precision, flexibility, and scalability, making it an ideal candidate for long-distance weak signal detection.

12.
Ann Fam Med ; 21(Suppl 1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38226951

RESUMO

Context: Teaching kitchens are emerging innovative and engaging models for creating lifestyle behavior change. They are increasingly being utilized in workplace settings. Objective: The Emory Healthy Kitchen Collaborative (EHKC) year-long worksite wellness teaching kitchen program sought to improve self-reported health behaviors, including food choices, cooking skills, and mindful eating habits. Study Design and Analysis: This 12-month program included a 10-week didactic and experiential curriculum followed by continued support and access to health coaching. Participant t-tests were used to compare results at different time points. Setting: Emory worksite wellness program Population Studied: Forty benefits-eligible Emory employees aged 18-65, were recruited to participate in the EHKC. Preference was given to employees with elevated body mass index, co-morbid conditions, and high lifestyle change motivation levels. Intervention/Instrument and Outcome Measures: Self-assessment instruments were obtained at baseline, 3-months, 6-months and 12-months. This included the 8-item Starting the Conversation (STC) food frequency instrument, eight questions from a 17-item cooking frequency and confidence questionnaire, and a 28-item mindful eating questionnaire. Results: Between May 30 - June 30, 2019, 40 benefits-eligible Emory employees were enrolled in the EHKC. Dietary eating patterns improved significantly throughout the duration of the program year, as measured by the STC. The largest improvement in STC occurred from baseline to three months (mean: - 2.18, standard deviation: 2.35, p-value: p=0.002). Although cooking frequency and confidence trended towards improvement, there were no significant changes. The mindfulness eating questionnaire improved significantly at 3-months (0.27, 0.32, p<0.001), 6-months (0.23, 0.33, p<0.001), and 12 months (0.33, 0.28, p<0.001), as compared to baseline. Conclusion: The EHKC worksite wellness program provided valuable knowledge and insight into the use of a teaching kitchen as a unique health care delivery model. The program significantly improved participant dietary patterns and mindful eating habits; though did not significantly improve cooking confidence or frequency. Further research is needed to understand long term health consequences and disease risk reduction of the EHKC program.


Assuntos
Culinária , Comportamento Alimentar , Humanos , Padrões Dietéticos , Comportamentos Relacionados com a Saúde , Promoção da Saúde
13.
Exp Brain Res ; 241(10): 2561-2574, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37716929

RESUMO

Circular RNAs (circRNAs) have been revealed to be involved in the pathology of acute ischemic stroke (AIS). Herein, we aimed to study the role and mechanism of circNCOA4 in ischemic stroke. The neuron-like cell line SK-N-SH of the experiment group was cultured in oxygen-glucose deprivation (OGD) condition. Cell viability and apoptosis were evaluated by cell counting kit-8 and flow cytometry. The oxidative damage and endoplasmic reticulum stress (ERS) were analyzed by measuring the production of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and ERS-related markers. The binding between miR-338-5p and circNCOA4 or PDE4B (Phosphodiesterase 4B) was confirmed using dual-luciferase reporter and RIP assays. The commercial kit was used for exosome separation. The levels of circNCOA4 and PDE4B were increased, while miR-338-5p expression was decreased by OGD stimulation. OGD stimulation resulted in the apoptosis of neurons and induced oxidative damage and ERS, these effects were attenuated by circNCOA4 knockdown, while reinforced by circNCOA4 overexpression. Mechanistically, circNCOA4 acted as a sponge for miR-338-5p, and PDE4B was a target of miR-338-5p. MiR-338-5p inhibition reversed the neuroprotective effects of circNCOA4 silencing on neurons. Besides, miR-338-5p overexpression could abolish OGD-induced neuron injury, which was reversed by PDE4B upregulation. In addition, circNCOA4 was packaged into exosomes and showed potential diagnostic value for acute ischemic stroke (AIS) patients. CircNCOA4 has potential diagnostic value for AIS patients and promoted OGD-induced neuron injury via the miR-338-5p/PDE4B axis, providing a new insight into the pathology of AIS.


Assuntos
AVC Isquêmico , MicroRNAs , Humanos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Apoptose , Glucose , MicroRNAs/genética
14.
BMC Public Health ; 23(1): 356, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36800949

RESUMO

BACKGROUND: China has one of the fastest paces of the growing aging population, High-level policymakers have recently recognized the aging population presents significant challenges to the Chinese healthcare system. In this context, the healthcare-seeking behaviors of the elderly population have become an essential field of study. It is necessary to understand their access to health services and to improve their quality of life, as well as to help policymakers to formulate healthcare policy. The study empirically investigates the factors influencing the elderly population's healthcare-seeking behaviors in Shanghai, China, especially in choosing the quality of healthcare facilities to visit. METHODS: We designed a cross-sectional study. The data of this study were derived from the "Shanghai elderly medical demand characteristics questionnaire" in the middle of November to early December 2017. A total of 625 individuals were included in the final sample. Logistic regression was adopted to investigate the differences in healthcare-seeking behaviors between elderly people when suffer from mild illness, severe illness and follow-up treatment. Next, the differences in gender were also discussed. RESULTS: Factors affecting the healthcare-seeking behaviors of the elderly differ in mild illness and severe illness situations. For mild illness, demographic factors (gender and age) and socioeconomic factors (income and employment) play an important role in elderly healthcare choices. Female and older elderlies are more likely to choose local, lower-quality facilities, whereas those with high income and private employment are more likely to choose higher-quality facilities. For severe illness, socioeconomic factors (income and employment) are important. Furthermore, individuals with basic medical insurance are more likely to choose lower-quality facilities. CONCLUSION: This study has shown that the affordability of public health services should be addressed. Medical policy support may be an important way to reduce the gap in access to medical services. We should pay attention to the gender differences in the elderly's choice of medical treatment behavior, consider the differences in the needs of male and female elderly. our findings are only for elderly Chinese participants in the greater Shanghai area.


Assuntos
Instalações de Saúde , Qualidade de Vida , Humanos , Masculino , Feminino , Idoso , Estudos Transversais , China , Atenção à Saúde
15.
Phytother Res ; 37(12): 5991-6005, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37752617

RESUMO

Hypertension is a progressive metabolic disease characterized by circadian regulation of lipid metabolism disorder. Identifying specific lipid components and maintaining circadian homeostasis of lipid metabolism might be a promising therapeutic strategy for hypertension. Isorhynchophylline (IRP) can regulate lipid metabolism; however, the underlying mechanism of IRP in improving lipid metabolism rhythm disorder is still unclear. The lipid circadian biomarkers and abnormal metabolic pathways intervened by IRP were investigated using diurnal lipidomic research methods. The 24-h circadian changes in mRNA and protein expression levels of circadian genes, including Bmal1, Clock, Cry1, Cry2, Per1, and Per2, and lipid metabolism-related factors (PPARα and LPL) were determined using RT-PCR and western blot analyses, respectively. The underlying mechanisms were intensively investigated by inhibiting Bmal1. Molecular docking and drug affinity responsive target stability analyses were performed to assess the binding affinity of IRP and Bmal1. IRP treatment could effectively improve 24-h blood pressure, ameliorate the lipid metabolic rhythm disorder, reverse the expression levels of circadian rhythm genes, and regulate lipid metabolism-related genes (PPARα and LPL) by mediating Bmal1. This study highlighted the potential effects of IRP in maintaining the circadian homeostasis of lipid metabolism and the treatment of hypertension.


Assuntos
Hipertensão , Transtornos do Metabolismo dos Lipídeos , Ratos , Animais , Ratos Endogâmicos SHR , Metabolismo dos Lipídeos , Simulação de Acoplamento Molecular , PPAR alfa/genética , Ritmo Circadiano/genética , Hipertensão/tratamento farmacológico , Hipertensão/genética , Lipídeos
16.
BMC Biol ; 20(1): 99, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524220

RESUMO

BACKGROUND: The three-dimensional (3D) architecture of the genome has a highly ordered and hierarchical nature, which influences the regulation of essential nuclear processes at the basis of gene expression, such as gene transcription. While the hierarchical organization of heterochromatin and euchromatin can underlie differences in gene expression that determine evolutionary differences among species, the way 3D genome architecture is affected by evolutionary forces within major lineages remains unclear. Here, we report a comprehensive comparison of 3D genomes, using high resolution Hi-C data in fibroblast cells of fish, chickens, and 10 mammalian species. RESULTS: This analysis shows a correlation between genome size and chromosome length that affects chromosome territory (CT) organization in the upper hierarchy of genome architecture, whereas lower hierarchical features, including local transcriptional availability of DNA, are selected through the evolution of vertebrates. Furthermore, conservation of topologically associating domains (TADs) appears strongly associated with the modularity of expression profiles across species. Additionally, LINE and SINE transposable elements likely contribute to heterochromatin and euchromatin organization, respectively, during the evolution of genome architecture. CONCLUSIONS: Our analysis uncovers organizational features that appear to determine the conservation and transcriptional regulation of functional genes across species. These findings can guide ongoing investigations of genome evolution by extending our understanding of the mechanisms shaping genome architecture.


Assuntos
Cromatina , Heterocromatina , Animais , Galinhas/genética , Elementos de DNA Transponíveis , Eucromatina/genética , Heterocromatina/genética , Mamíferos/genética , Vertebrados/genética
17.
Molecules ; 29(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38202722

RESUMO

With the advancement of research on m6A-related mechanisms in recent years, the YTHDF protein family within m6A readers has garnered significant attention. Among them, YTHDF1 serves as a pivotal member, playing a crucial role in protein translation, tumor proliferation, metabolic reprogramming of various tumor cells, and immune evasion. In addition, YTHDF1 also exerts regulatory effects on tumors through multiple signaling pathways, and numerous studies have confirmed its ability to assist in the reprogramming of the tumor cell-related metabolic processes. The focus of research on YTHDF1 has shifted in recent years from its m6A-recognition and -modification function to the molecular mechanisms by which it regulates tumor progression, particularly by exploring the regulatory factors that interact with YTHDF1 upstream and downstream. In this review, we elucidate the latest signaling pathway mechanisms of YTHDF1 in various tumor cells, with a special emphasis on its distinctive characteristics in tumor cell metabolic reprogramming. Furthermore, we summarize the latest pathological and physiological processes involving YTHDF1 in tumor cells, and analyze potential therapeutic approaches that utilize YTHDF1. We believe that YTHDF1 represents a highly promising target for future tumor treatments and a novel tumor biomarker.


Assuntos
Neoplasias , Humanos , Biomarcadores Tumorais , Reprogramação Metabólica , Biossíntese de Proteínas , Reconhecimento Psicológico , Proteínas de Ligação a RNA
18.
J Environ Sci (China) ; 124: 933-951, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182196

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented worldwide health crisis. Many previous research studies have found and investigated its links with one or some natural or human environmental factors. However, a review on the relationship between COVID-19 incidence and both the natural and human environment is still lacking. This review summarizes the inter-correlation between COVID-19 incidence and environmental factors. Based on keyword searching, we reviewed 100 relevant peer-reviewed articles and other research literature published since January 2020. This review is focused on three main findings. One, we found that individual environmental factors have impacts on COVID-19 incidence, but with spatial heterogeneity and uncertainty. Two, environmental factors exert interactive effects on COVID-19 incidence. In particular, the interactions of natural factors can affect COVID-19 transmission in micro- and macro- ways by impacting SARS-CoV-2 survival, as well as human mobility and behaviors. Three, the impact of COVID-19 incidence on the environment lies in the fact that COVID-19-induced lockdowns caused air quality improvement, wildlife shifts and socio-economic depression. The additional value of this review is that we recommend future research perspectives and adaptation strategies regarding the interactions of the environment and COVID-19. Future research should be extended to cover both the effects of the environment on the COVID-19 pandemic and COVID-19-induced impacts on the environment. Future adaptation strategies should focus on sustainable environmental and public policy responses.


Assuntos
Poluição do Ar , COVID-19 , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Pandemias , SARS-CoV-2
19.
J Am Chem Soc ; 144(32): 14647-14656, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35930766

RESUMO

Fluorescence imaging is a powerful method for probing macromolecular dynamics in biological systems; however, approaches for cellular RNA imaging are limited to the investigation of individual RNA constructs or bulk RNA labeling methods compatible primarily with fixed samples. Here, we develop a platform for fluorescence imaging of bulk RNA dynamics in living cells. We show that fluorescent bicyclic and tricyclic cytidine analogues can be metabolically incorporated into cellular RNA by overexpression of uridine-cytidine kinase 2. In particular, metabolic feeding with the tricyclic cytidine-derived nucleoside tC combined with confocal imaging enables the investigation of RNA synthesis, degradation, and trafficking at single-cell resolution. We apply our imaging modality to study RNA metabolism and localization during the oxidative stress response and find that bulk RNA turnover is greatly accelerated upon NaAsO2 treatment. Furthermore, we identify cytoplasmic RNA granules containing RNA transcripts generated during oxidative stress that are distinct from canonical stress granules and P-bodies and co-localize with the RNA helicase DDX6. Taken together, our work provides a powerful approach for live-cell RNA imaging and reveals how cells reshape RNA transcriptome dynamics in response to oxidative stress.


Assuntos
Nucleosídeos , RNA , Citidina/metabolismo
20.
Small ; 18(21): e2200847, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35484474

RESUMO

Hybrid halide perovskites have emerged as highly promising photovoltaic materials because of their exceptional optoelectronic properties, which are often optimized via compositional engineering like mixing halides. It is well established that hybrid perovskites undergo a series of structural phase transitions as temperature varies. In this work, the authors find that phase transitions are substantially suppressed in mixed-halide hybrid perovskite single crystals of MAPbI3-x Brx (MA = CH3 NH3 + and x = 1 or 2) using a complementary suite of diffraction and spectroscopic techniques. Furthermore, as a general behavior, multiple crystallographic phases coexist in mixed-halide perovskites over a wide temperature range, and a slightly distorted monoclinic phase, hitherto unreported for hybrid perovskites, is dominant at temperatures above 100 K. The anomalous structural evolution is correlated with the glassy behavior of organic cations and optical phonons in mixed-halide perovskites. This work demonstrates the complex interplay between composition engineering and lattice dynamics in hybrid perovskites, shedding new light on their unique properties.

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