RESUMO

The major female ovarian hormone, 17ß-estradiol (E2), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2-induced rapid excitations in multiple brain ERα populations. Further, genetic disruption of Clic1 in hypothalamic ERα neurons blunts the regulations of E2 on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E2-induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E2.

Assuntos

Canais de Cloreto , Receptor alfa de Estrogênio , Neurônios , Neurônios/metabolismo , Canais de Cloreto/metabolismo , Canais de Cloreto/genética , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Animais , Feminino , Humanos , Estradiol/metabolismo , Estradiol/farmacologia , Camundongos , Hipotálamo/metabolismo , Hipotálamo/citologia , Ligação Proteica

RESUMO

BACKGROUND: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. MATERIALS AND METHODS: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 µM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. RESULTS: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. CONCLUSION: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.

RESUMO

Alzheimer's Disease and Alzheimer's Disease-related dementias (AD/ADRD) pose major global healthcare challenges, with diabetes mellitus (DM) being a key risk factor. Both AD and DM-related ADRD are characterized by reduced cerebral blood flow, although the exact mechanisms remain unclear. We previously identified compromised cerebral hemodynamics as early signs in TgF344-AD and type 2 DM-ADRD (T2DN) rat models. Genome-wide studies have linked AD/ADRD to SNPs in soluble epoxide hydrolase (sEH). This study explored the effects of sEH inhibition with TPPU on cerebral vascular function and cognition in AD and DM-ADRD models. Chronic TPPU treatment improved cognition in both AD and DM-ADRD rats without affecting body weight. In DM-ADRD rats, TPPU reduced plasma glucose and HbA1C levels. Transcriptomic analysis of primary cerebral vascular smooth muscle cells from AD rats treated with TPPU revealed enhanced pathways related to cell contraction, alongside decreased oxidative stress and inflammation. Both AD and DM-ADRD rats exhibited impaired myogenic responses and autoregulation in the cerebral circulation, which were normalized with chronic sEH inhibition. Additionally, TPPU improved acetylcholine-induced vasodilation in the middle cerebral arteries (MCA) of DM-ADRD rats. Acute TPPU administration unexpectedly caused vasoconstriction in the MCA of DM-ADRD rats at lower doses. In contrast, higher doses or longer durations were required to induce effective vasodilation at physiological perfusion pressure in both control and ADRD rats. Additionally, TPPU decreased reactive oxygen species production in cerebral vessels of AD and DM-ADRD rats. These findings provide novel evidence that chronic sEH inhibition can reverse cerebrovascular dysfunction and cognitive impairments in AD/ADRD, offering a promising avenue for therapeutic development.

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Rational construction of high-efficiency photoelectrodes with optimized carrier migration to the ideal active sites, is crucial for enhancing solar water oxidation. However, complexity in precisely modulating interface configuration and directional charge transfer pathways retards the design of robust and stable artificial photosystems. Herein, a straightforward yet effective strategy is developed for compact encapsulation of metal oxides (MOs) with an ultrathin non-conjugated polymer layer to modulate interfacial charge migration and separation. By periodically coating highly ordered TiO2 nanoarrays with oppositely charged polyelectrolyte of poly(dimethyl diallyl ammonium chloride) (PDDA), MOs/polymer composite photoanodes are readily fabricated under ambient conditions. It is verified that electrons photogenerated from the MOs substrate can be efficiently extracted by the ultrathin solid insulating PDDA layer, significantly boosting the carrier transport kinetics and enhancing charge separation of MOs, and thus triggering a remarkable enhancement in the solar water oxidation performance. The origins of the unexpected electron-withdrawing capability of such non-conjugated insulating polymer are unambiguously uncovered, and the scenario occurring at the interface of hybrid photoelectrodes is elucidated. The work would reinforce the fundamental understanding on the origins of generic charge transport capability of insulating polymer and benefit potential wide-spread utilization of insulating polymers as co-catalysts for solar energy conversion.

RESUMO

BACKGROUND: The nomenclature, classification, and surgical approaches for spinal dural cysts (SDCs) remain a subject of controversy. PURPOSE: The present study proposes a novel subtype classification system and corresponding surgical strategies, with the aim of enhancing comprehension of this entity and standardizing surgical treatment. STUDY DESIGN: A retrospective review. PATIENT SAMPLE: A total of 104 patients with SDCs underwent novel subtype classification and corresponding surgical strategies from January 2015 to December 2021. Fifty-four patients who underwent conventional surgery from January 2012 to December 2014 as the control group for preliminary validation. OUTCOME MEASURES: The outcomes are categorized into 4 levels: excellent, good, unchanged, and deteriorated, based on neurological improvement and pain relief. Grades of excellent and good were identified as improvements. Follow-up magnetic resonance imaging and complications were also evaluated. METHODS: Based on the shared pathogenic factor of dural defects, the dural-associated cysts in the spinal canal are uniformly referred to as SDCs. They are further classified into Type 1 (no nerve roots) and Type 2 (containing nerve roots), with 4 additional subtypes based on the shape of the leak and the flow of leakage. The fissure-shaped leak of Type 1a SDCs is directly sutured, whereas the aperture-shaped leak of Type 1b is repaired using a patch. Low-flow leakage of Type 2a is directly sealed using a combination of adipose tissue and fibrin glue, whereas high-flow Type 2b necessitates suturing at the end of the leak to attenuate cerebrospinal fluid flow prior to sealing. RESULTS: The follow-up period averaged 23.8 months. Excellent or good outcomes were achieved in 100%, 88.9%, 100%, and 97.3% for the 4 subtypes respectively. The overall improvement rate of SDCs was 97.1%, which was significantly higher than that of the conventional surgery group (85.2%, p=.008). MRI follow-up showed a significant reduction in cyst size of 100%, 100%, 97.8%, and 97.3% for the 4 subtypes, respectively. The primary complications included pseudomeningocele in 4 cases (3.8%) and delayed wound healing in 5 cases (4.8%). The complication rate was also significantly lower than that of the control group (8.7% vs 24.1%, p=.008). CONCLUSIONS: Subtyping SDCs based on the variation of leaks and leakage can enable more targeted surgical strategies, which are helpful for improving treatment effectiveness and reducing complications.

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Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBBPenk neurons that project to the paraventricular nucleus of the hypothalamus are preferentially activated upon food presentation during fasting periods and transmit a positive valence to facilitate feeding. On the other hand, a separate subset of DBBPenk neurons that project to the lateral hypothalamus are preferentially activated when detecting a high-fat high-sugar (HFHS) diet and transmit a negative valence to inhibit food consumption. Notably, when given free choice of chow and HFHS diets, mice with the whole DBBPenk population ablated exhibit reduced consumption of chow but increased intake of the HFHS diet, resulting in accelerated development of obesity and metabolic disturbances. Together, we identify a molecularly defined neural population in male mice that is crucial for the maintenance of energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.

Assuntos

Prosencéfalo Basal , Comportamento Alimentar , Animais , Masculino , Camundongos , Comportamento Alimentar/fisiologia , Prosencéfalo Basal/fisiologia , Prosencéfalo Basal/metabolismo , Encefalinas/metabolismo , Ingestão de Alimentos/fisiologia , Precursores de Proteínas/metabolismo , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Vias Neurais/fisiologia , Obesidade/etiologia , Neurônios/fisiologia , Neurônios/metabolismo

RESUMO

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.

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Atomically precise metal nanoclusters (NCs) have been deemed a new generation of photosensitizers for light harvesting on account of their quantum confinement effect, peculiar atom-stacking mode, and enriched catalytic active sites. Nonetheless, to date, precise charge modulation over metal NCs has still been challenging considering their ultra-short carrier lifetime and poor stability. In this work, we conceptually demonstrate the integration of metal NCs with MXene in transition metal chalcogenide (TMC) photosystems via a progressive, exquisite, and elegant interface design to trigger tunable, precise and high-efficiency charge motion over metal NCs, stimulating a directional carrier transport pathway. In this customized ternary heterostructured photosystem, metal NCs function as light-harvesting antennas, MXene serves as a terminal electron reservoir, and the TMC substrate provides suitable energy level alignment for retracting photocarriers of metal NCs, giving rise to a spatial cascade charge transport route and markedly boosting charge separation efficiency. The interface configuration and energy level alignment engineering synergistically contribute to the considerably enhanced visible-light-driven photocatalytic CO2-to-CO reduction performance of the metal NCs/TMCs/MXene heterostructure. The intermediate active species during the photocatalytic CO2 reduction are unambiguously determined, based on which the photocatalytic mechanism is elucidated. Our work will provide an inspiring idea to bridge the gap between atomically precise metal NCs and MXene in terms of controllable charge migration for solar-to-fuel conversion.

RESUMO

Benefiting from their excellent light-capturing ability, suitable energy band structure and abundant active sites, transition metal chalcogenides (TMCs) have been attracting widespread attention in heterogeneous photocatalysis. Nonetheless, TMCs still suffer from sluggish charge transfer kinetics, a rapid charge recombination rate and poor stability, rendering the construction of high-performance artificial photosystems challenging. Here, a ternary dumbbell-shaped CdS/MoS2/CuS heterostructure with spatially separated catalytically active sites has been elaborately designed. In such a heterostructured nanoarchitecture, MoS2 clusters, selectively grown on both ends of the CdS nanowires (NWs), act as terminal electron collectors, while CuS nanolayers, coated on the sidewalls of CdS NWs through ion exchange, form a P-N heterojunction with the CdS NW framework, which accelerates the migration of holes from CdS to CuS, effectively suppressing the oxidation of sulfide ions and improving the stability of CdS NWs. The well-defined dumbbell-shaped CdS/MoS2/CuS ternary heterostructure provides a structural basis for spatially precise regulation of the charge migration pathway, where photogenerated electrons and holes directionally migrate to the MoS2 and CuS catalytic sites, respectively, ultimately achieving efficient carrier separation and significantly enhancing photoactivity for both photocatalytic hydrogen generation and selective organic transformation under visible light. Moreover, we have also ascertained that such ion exchange and interface configuration engineering strategies are universal. Our work features a simple yet efficient strategy for smartly designing multi-component heterostructures to precisely modulate spatially vectorial charge separation at the nanoscale for solar-to-hydrogen conversion.

RESUMO

Recent advancements have brought significant attention to photonic terahertz (THz)-integrated sensing and communication (ISAC) systems. In this work, we present an adaptive frequency offset (FO) compensation method for dual-chirp-based ISAC waveforms, using the fractional Fourier transform (FrFT) method. The proposed scheme can enable frequency synchronization without a need for training preambles and exhibit robustness against system noise. We validate this approach through an experimental demonstration in a 300 GHz photonic THz-ISAC system with 20 Gbps quadrature-phase shift keying (QPSK) data transmission and 1.5 cm range resolution. The experiment successfully compensates for frequency offsets ranging from -5 to 5 GHz, achieving an estimation error of less than 0.08% and a chirp-pilot power overhead of 0.5%.

RESUMO

A visible-light-initiated energy-transfer enabled radical cyclization for the divergent synthesis of polycyclic γ-sultine derivatives has been developed. The reaction provides an alternative and expeditious access to benzofused γ-sultine frameworks, the analogues of γ-lactones and γ-sultones, and features good functional group compatibility, mild reaction conditions and excellent diastereoselectivity. The robustness and application potential of this method have also been successfully displayed by two gram-scale reactions and the synthesis of polycyclic sultones. Mechanistic studies indicated the transformations through a possible energy-transfer enabled intramolecular radical homolytic substitution or hydrogen atom transfer process mainly.

RESUMO

Solar CO2 reduction to renewable hydrocarbon fuels offers a promising pathway to carbon neutrality, but it is retarded by tough CO2 activation, complicated mechanisms, sluggish charge transport kinetics, and a scarcity of strategies for precise tuning of charge transport pathways. Herein, we first conceptually design a novel insulating polymer-mediated electron-tunneling artificial photosystem via progressive interface configuration regulation, wherein tailor-made Ag@citrate nanocrystals (NCs) are controllably self-assembled on transition metal chalcogenides (TMCs) assisted by an ultrathin insulating polymer interim layer, i.e., poly(allylamine hydrochloride) (PAH). In this multilayered nano-architecture, a solid ultra-thin insulating PAH interim layer serves as an unexpected charge tunneling mediator to stimulate smooth electron transfer from the TMC substrate to the terminal electron reservoirs of Ag@citrate NCs, engendering the tandem charge transfer route and significantly boosting the visible-light-driven photocatalytic CO2-to-syngas conversion performances. Furthermore, we have ascertained that such TMC-insulating polymer-metal NC tunneling photosystems are universal. This study would spark new inspiration for unleashing the long-term neglected charge tunneling capability of insulating polymers and diversifying non-conjugated polymer-based artificial photosystems for solar-to-fuel energy conversion.

RESUMO

Visual object tracking is an important technology in camera-based sensor networks, which has a wide range of practicability in auto-drive systems. A transformer is a deep learning model that adopts the mechanism of self-attention, and it differentially weights the significance of each part of the input data. It has been widely applied in the field of visual tracking. Unfortunately, the security of the transformer model is unclear. It causes such transformer-based applications to be exposed to security threats. In this work, the security of the transformer model was investigated with an important component of autonomous driving, i.e., visual tracking. Such deep-learning-based visual tracking is vulnerable to adversarial attacks, and thus, adversarial attacks were implemented as the security threats to conduct the investigation. First, adversarial examples were generated on top of video sequences to degrade the tracking performance, and the frame-by-frame temporal motion was taken into consideration when generating perturbations over the depicted tracking results. Then, the influence of perturbations on performance was sequentially investigated and analyzed. Finally, numerous experiments on OTB100, VOT2018, and GOT-10k data sets demonstrated that the executed adversarial examples were effective on the performance drops of the transformer-based visual tracking. White-box attacks showed the highest effectiveness, where the attack success rates exceeded 90% against transformer-based trackers.

RESUMO

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of Trpc5 from oxytocin neurons in the hypothalamic paraventricular nucleus caused obesity in both sexes and postpartum depressive behavior in females, while Trpc5 overexpression in oxytocin neurons in knock-in mice reversed these phenotypes. We demonstrate that TRPC5 plays a pivotal role in mediating innate human behaviors fundamental to survival, including food seeking and maternal care.

Assuntos

Depressão Pós-Parto , Neurônios , Obesidade , Canais de Cátion TRPC , Animais , Feminino , Camundongos , Obesidade/metabolismo , Obesidade/genética , Masculino , Humanos , Canais de Cátion TRPC/metabolismo , Canais de Cátion TRPC/genética , Depressão Pós-Parto/metabolismo , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Camundongos Endogâmicos C57BL , Ocitocina/metabolismo , Comportamento Materno

RESUMO

Currently, new clean energy storage technology must be effective, affordable, and ecologically friendly so as to meet the diverse and sustainable needs of the energy supply. In this work, NiCo-LDH containing intercalated EG was successfully prepared within 210 s using an ultrafast microwave radiation technique. Subsequently, a series of characterization and systematic electrochemical tests were conducted to analyze the composition, structure, and energy storage mechanism of the NiCo-LDH material. The Ni:Co ratio of 5:5 results in the highest capacitance value of 2156 F/g at 1 A/g and an outstanding rate performance of 86.8% capacity retention rate at 10 A/g. The results demonstrated that the unique porous structure of NiCo-LDH and large layer spacing were conducive to more electrochemical reactions. Additionally, an electrochemical test was carried out on the NiCo-LDH as a hybrid supercapacitor electrode material, with NiCo-LDH-5:5 serving as the positive electrode and activated carbon as the negative electrode, the asymmetric supercapacitor can achieve a maximum energy density of 82.5 Wh kg-1 and power density of 8000 W kg-1. The NiCo-LDH-5:5//AC hybrid supercapacitors own 81.5% cycle stability and 100% coulombic efficiency after 6000 cycles at 10 A/g.

RESUMO

Black phosphorus (BP), a promising two-dimensional (2D) layered semiconductor material, has gained enormous attention due to its impressive properties over the past several years. Although plenty of methods have been developed to synthesize high-quality BP, most of the currently available BP materials still suffer from unsatisfactory crystallization, purity, and stability in air, hindering their practical application. A facile approach to synthesizing ultrahigh-quality single-crystal BP is of significance to shed light on the nature of 2D semiconductor materials and their massive application. In this work, we present the facile and efficient circulating vapor growth approach to growing bulk single-crystal BP. The as-grown BP material features high crystallinity and ultrahigh purity (higher than 99.999 at %), exceeding those of all the previously reported and some commercially available BP crystals. It also maintains excellent stability in air and water after 15 consecutive days of test. Moreover, the as-synthesized BP material features good thermal stability, oxidation resistance, and excellent electrical properties, as well. This study provides a new approach for the fabrication of ultrahigh-quality BP material and thus promotes its application.

RESUMO

BACKGROUND: Thinning of retinal thickness seen on optical coherence tomography (OCT) is frequent in patients with neuromyelitis optica spectrum disorder (NMOSD). We explored the association between OCT metrics, MRI measurements and clinical outcomes in NMOSD. METHODS: 44 NMOSD and 60 controls underwent OCT and MR imaging. Mean peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thicknesses were measured. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was used to measure the white matter microstructural integrity. In NMOSD patients, Expanded Disability Status Scale (EDSS) was used to quantify disability. Visual acuity (VA) was also performed for all participants. RESULTS: pRNFL thickness was positively associated with mean diffusivity in left posterior thalamic radiation (pp = 0.010) and axial kurtosis in inferior cerebellar peduncle (p = 0.023). Similarly, GCC thickness in NMOSD patients was positively associated with fractional anisotropy in right superior longitudinal fascicules (p = 0. 041) and axial kurtosis of left cerebellar peduncle (p = 0.011). CONCLUSIONS: In NMOSD, pRNFL and GCC reflect integrity of clinically relevant white matter structures underlying the value of OCT metrics as markers of neuronaxonal loss and disability.

Assuntos

Imagem de Tensor de Difusão , Neuromielite Óptica , Retina , Tomografia de Coerência Óptica , Substância Branca , Humanos , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/patologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Retina/diagnóstico por imagem , Retina/patologia , Imageamento por Ressonância Magnética

RESUMO

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.

Assuntos

Células da Granulosa , Mitocôndrias , Síndrome do Ovário Policístico , Proteínas de Ligação a RNA , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Feminino , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Mitocôndrias/metabolismo , Mitocôndrias/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Adulto , Espécies Reativas de Oxigênio/metabolismo , Regulação da Expressão Gênica , Trifosfato de Adenosina/metabolismo , Glicólise/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo

RESUMO

Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRN neurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.

RESUMO

Flexible capacitive sensors are widely deployed in wearable smart electronics. Substantial studies have been devoted to constructing characteristic material architectures to improve their electromechanical sensing performance by facilitating the change of the electrode layer spacing. However, the air gaps introduced by the designed material architectures are easily squeezed when subjected to high-pressure loads, resulting in a limited increase in sensitivity over a wide range. To overcome this limitation, in this work, we embed the liquid metal (LM) in the internally interconnected porous structure of a flexible composite foam to fabricate a flexible and high-performance capacitive sensor. Different from the conventional conductive elements filled composite, the incompressible feature of the embedded fluidic LM leads to significantly improved mechanical stability of the composite foam to withstand high pressure loadings, resulting in a wider pressure sensing range from 10 Pa to 260 kPa for our capacitive composite sensor. Simultaneously, the metal conductivity and liquid ductility of the embedded LM endow the as-fabricated capacitive sensor with outstanding mechanical flexibility and pressure sensitivity (up to 1.91 kPa-1). Meanwhile, the LM-embedded interconnected-porous thermoplastic polyurethane/MXene composite sensor also shows excellent reliability over 4000 long-period load cycles, and the response times are merely 60 ms and 110 ms for the loading and unloading processes, respectively. To highlight their advantages in various applications, the as-proposed capacitive sensors are demonstrated to detect human movements and monitor biophysical heart-rate signals. It is believed that our finding could extend the material framework of flexible capacitive sensors and offer new possibilities and solutions in the development of the next-generation wearable electronics.