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1.
Development ; 149(12)2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35616329

RESUMO

The perinuclear theca (PT) is a cytoskeletal element encapsulating the sperm nucleus; however, the physiological roles of the PT in sperm are largely uncertain. Here, we reveal that ACTRT1, ACTRT2, ACTL7A and ACTL9 proteins interact to form a multimeric complex and localize to the subacrosomal region of spermatids. Furthermore, we engineered Actrt1-knockout (KO) mice to define the functions of ACTRT1. Despite normal sperm count and motility, Actrt1-KO males were severely subfertile owing to a deficiency in fertilization. Loss of ACTRT1 caused a high incidence of malformed heads and detachment of acrosomes from sperm nuclei, caused by loosened acroplaxome structure during spermiogenesis. Furthermore, Actrt1-KO sperm showed reduced ACTL7A and PLCζ protein content as a potential cause of fertilization defects. Moreover, we reveal that ACTRT1 anchors developing acrosomes to the nucleus, likely by interacting with the inner acrosomal membrane protein SPACA1 and the nuclear envelope proteins PARP11 and SPATA46. Loss of ACTRT1 weakened the interaction between ACTL7A and SPACA1. Our study and recent findings of ACTL7A/ACTL9-deficient sperm together reveal that the sperm PT-specific ARP complex mediates the acrosome-nucleus connection.


Assuntos
Acrossomo , Infertilidade Masculina , Acrossomo/metabolismo , Animais , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Espermátides/metabolismo , Espermatogênese/genética , Espermatozoides/metabolismo
2.
Cell Mol Life Sci ; 81(1): 118, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38448737

RESUMO

Tektins are microtubule inner proteins (MIPs) and localize at the inside lumen of doublet microtubules (DMTs) of cilia/flagella. TEKTIP1, a newly identified protein by cryo-electron microscopy (cryo-EM), is proposed to be localized at the center of the tektin bundle and hypothesized to recruit tektins or stabilize the bundle. However, the physiological role of TEKTIP1 is unknown. In this study, we generated Tektip1-knockout (Tektip1-/-) mice and showed that they were male subfertile primarily due to reduced sperm motility. A high percentage of sperm from Tektip1-/- mice showed moderately disorganized axoneme structures and abnormal flagellar waveforms. TEKTIP1 predominately interacted with TEKT3 among tektins. Loss of TEKTIP1 partially disturbed the organization of tektin bundle by mainly affecting the native status of TEKT3 and its interaction with other tektins. Collectively, our study reveals the physiological role and potential molecular mechanism of TEKTIP1 in axonemal structure and sperm motility, highlights the importance of MIPs in stabilizing DMTs, and suggests a potential relevance of TEKTIP1 deficiency to human asthenospermia. Tektip1-/- mice will be an excellent animal model to study the DMT organization of sperm flagella using cryo-EM in future.


Assuntos
Axonema , Proteínas dos Microtúbulos , Sêmen , Humanos , Masculino , Animais , Camundongos , Feminino , Microscopia Crioeletrônica , Motilidade dos Espermatozoides , Espermatozoides , Flagelos
3.
Cell Mol Life Sci ; 81(1): 155, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38538986

RESUMO

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


Assuntos
Hiperplasia Prostática , Animais , Humanos , Masculino , Camundongos , Androgênios/metabolismo , Mamíferos/metabolismo , Mitocôndrias/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais
4.
Microb Pathog ; 191: 106660, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657710

RESUMO

Endometritis is the inflammation of the endothelial lining of the uterine lumen and is multifactorial in etiology. Escherichia (E.) coli is a Gram-negative bacteria, generally considered as a primary causative agent for bovine endometritis. Bovine endometritis is characterized by the activation of Toll-like receptors (TLRs) by E. coli, which in turn triggers inflammation, oxidative stress, and apoptosis. The objective of this study was to investigate the gene expression of inflammatory, oxidative stress, and apoptotic markers related to endometritis in the uteri of cows. Twenty uterine tissues were collected from the abattoir. Histologically, congestion, edema, hyperemia, and hemorrhagic lesions with massive infiltration of neutrophil and cell necrosis were detected markedly (P < 0.05) in infected uterine samples. Additionally, we identify E. coli using the ybbW gene (177 base pairs; E. coli-specific gene) from infected uterine samples. Moreover, qPCR and western blot results indicated that TLR2, TLR4, proinflammatory mediators, and apoptosis-mediated genes upregulated except Bcl-2, which is antiapoptotic, and there were downregulations of oxidative stress-related genes in the infected uterine tissue. The results of our study suggested that different gene expression regimes related to the immune system reflex were activated in infected uteri. This research gives a novel understanding of active immunological response in bovine endometritis.


Assuntos
Apoptose , Doenças dos Bovinos , Endometrite , Infecções por Escherichia coli , Escherichia coli , Estresse Oxidativo , Regulação para Cima , Útero , Bovinos , Animais , Feminino , Endometrite/veterinária , Endometrite/microbiologia , Endometrite/patologia , Endometrite/metabolismo , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/metabolismo , Doenças dos Bovinos/imunologia , Escherichia coli/genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/patologia , Útero/patologia , Útero/microbiologia , Útero/metabolismo , Inflamação , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Mediadores da Inflamação/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
5.
Phys Rev Lett ; 132(18): 180803, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38759186

RESUMO

Solid-state qubits with a photonic interface is very promising for quantum networks. Color centers in silicon carbide have shown excellent optical and spin coherence, even when integrated with membranes and nanostructures. Additionally, nuclear spins coupled with electron spins can serve as long-lived quantum memories. Pioneering work previously has realized the initialization of a single nuclear spin and demonstrated its entanglement with an electron spin. In this Letter, we report the first realization of single-shot readout for a nuclear spin in SiC. We obtain a deterministic nuclear spin initialization and readout fidelity of 94.95% with a measurement duration of 1 ms. With a dual-step readout scheme, we obtain a readout fidelity as high as 99.03% within 0.28 ms by sacrificing the success efficiency. Our Letter complements the experimental toolbox of harnessing both electron and nuclear spins in SiC for future quantum networks.

6.
Phys Rev Lett ; 132(16): 160801, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38701444

RESUMO

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

7.
Chemistry ; : e202401540, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805347

RESUMO

Imines are essential intermediates in organic transformations, and is generally produced by dehydrogenative condensation of alcohols and amines with the assist of specialized catalysts and additives. Heterogeneous photocatalysis provides a sustainable platform for such process without the using of toxic oxidants, yet a functionalized photocatalyst with optimized co-adsorption of reactants needs to be developed to promote the stoichiometric oxidative condensation under ambient conditions. Here, we show that benzyl alcohol and aniline adsorb non-interferingly on the Fe node and the linker sites of the MIL-53(Fe) metal organic frameworks (MOFs), respectively. The co-adsorption of both reactants barely influences the reduction of molecular oxygen to generate oxygen radicals, resulting in efficient formation of benzaldehyde under visible light. Additionally, the weak adsorption of water together with surface acidity of the MIL-53(Fe) promote a rapid condensation of benzaldehyde with aniline and the depletion of generated water, achieving an efficient C-N bond creation for a wide range of substrates.

8.
FASEB J ; 37(7): e22983, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37249327

RESUMO

In mammals, the endometrium undergoes dynamic changes in response to estrogen and progesterone to prepare for blastocyst implantation. Two distinct types of endometrial epithelial cells, the luminal (LE) and glandular (GE) epithelial cells play different functional roles during this physiological process. Previously, we have reported that Notch signaling plays multiple roles in embryo implantation, decidualization, and postpartum repair. Here, using the uterine epithelial-specific Ltf-iCre, we showed that Notch1 signaling over-activation in the endometrial epithelium caused dysfunction of the epithelium during the estrous cycle, resulting in hyper-proliferation. During pregnancy, it further led to dysregulation of estrogen and progesterone signaling, resulting in infertility in these animals. Using 3D organoids, we showed that over-activation of Notch1 signaling increased the proliferative potential of both LE and GE cells and reduced the difference in transcription profiles between them, suggesting disrupted differentiation of the uterine epithelium. In addition, we demonstrated that both canonical and non-canonical Notch signaling contributed to the hyper-proliferation of GE cells, but only the non-canonical pathway was involved with estrogen sensitivity in the GE cells. These findings provided insights into the effects of Notch1 signaling on the proliferation, differentiation, and function of the uterine epithelium. This study demonstrated the important roles of Notch1 signaling in regulating hormone response and differentiation of endometrial epithelial cells and provides an opportunity for future studies in estrogen-dependent diseases, such as endometriosis.


Assuntos
Progesterona , Útero , Animais , Feminino , Camundongos , Gravidez , Proliferação de Células , Implantação do Embrião/fisiologia , Endométrio/metabolismo , Epitélio/metabolismo , Estrogênios/farmacologia , Estrogênios/metabolismo , Progesterona/farmacologia , Progesterona/metabolismo , Útero/metabolismo
9.
BMC Geriatr ; 24(1): 374, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664613

RESUMO

BACKGROUND: The Square Stepping Exercise (SSE) is an exercise training program that integrates physical exercise and cognitive elements and can be conducted in a group setting. The potential of SSE in delaying cognitive decline in older adults is promising. However, the coronavirus pandemic has made it more difficult for older adults worldwide to exercise together in person. To address this issue, this study conducted a wholistic evaluation of the effects of a center-based hybrid SSE trial on cognitive, physical, psychological, and group functioning in sedentary older adults. METHODS: A total of 93 older adults (19 men, 74 women) participated in the study. Fifty-eight participants (9 men, 49 women) completed center-based hybrid SSE sessions over 12 weeks under coronavirus pandemic circumstances, whereas other 35 participants in the control group maintained their current level of daily activities. Cognitive functions focused on executive functions assessed by the Stroop Color-Word Test (inhibition) and the Trail Marking Test (TMT) (set-shifting). Psychological and group functioning were assessed by the Subjective Vitality Scale and the Physical Activity Group Environment Questionnaire. Physical function was evaluated by measuring gait speeds. A repeated ANOVA was conducted on the measured variables separately for the intervention and control groups to focus on the change of participant's performance over data collection points. RESULTS: Outcomes of the Stroop Color-Word Test and the TMT revealed that the hybrid SSE was highly effective in improving executive function. Stroop performance (correct trials) was significantly improved in the incongruent condition, as well as both TMT-A and -B over the intervention period in the intervention group. The hybrid SSE was also beneficial to improve physical (gait speed at usual pace and at the maximum pace) as well as psychological functioning (subjective vitality). Furthermore, SSE participants reported increased engagement with the SSE task, social communication, and increased bonding and closeness with their group members through the hybrid SSE. CONCLUSIONS: In this study, hybrid SSE was found to be effective in enhancing cognitive, physical, psychological, and group functioning in sedentary older adults. The findings of this study are crucial to provide older adults with a safer and efficient option to exercise.


Assuntos
COVID-19 , Cognição , Comportamento Sedentário , Humanos , Masculino , Feminino , Idoso , Cognição/fisiologia , COVID-19/psicologia , COVID-19/epidemiologia , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Exercício Físico/psicologia , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/terapia , Idoso de 80 Anos ou mais , Função Executiva/fisiologia , Pessoa de Meia-Idade
10.
J Am Chem Soc ; 145(9): 5353-5362, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36853085

RESUMO

Photocatalysis provides an eco-friendly route for the hydrogenation of aromatic carbonyls to O-free aromatics, which is an important refining process in the chemical industry that is generally carried out under high pressure of hydrogen at elevated temperatures. However, aromatic carbonyls are often only partially hydrogenated to alcohols, which readily desorbs and are hardly further deoxygenated under ambient conditions. Here, we show that by constructing an oxide surface over the Pd cocatalyst supported on graphitic carbon nitride, an alternative hydrogenation path of aromatic carbonyls becomes available via a step-wise acetalization and hydrogenation, thus allowing efficient and selective production of O-free aromatics. The PdO surface allows for optimum adsorption of reactants and intermediates and rapid abstraction of hydrogen from the alcohol donor, favoring fast acetalization of the carbonyls and their consecutive hydrogenation to O-free hydrocarbons. The photocatalytic hydrogenation of benzaldehyde into toluene shows a high selectivity of >90% and a quantum efficiency of ∼10.2% under 410 nm irradiation. By adding trace amounts of HCl to the reaction solution, the PdO surface remains stable and active for long-term operation at high concentrations, offering perspective for practical applications.

11.
Chemistry ; 29(35): e202300882, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37069325

RESUMO

Heterogeneous photocatalysis is a promising approach for a wide range of hydrogenative reactions owing to the mild reaction conditions and the possibility of employing liquid hydrogen donors. Currently, the major interest is focused on the development of high performance photocatalyst materials and the expansion of reaction scope. An overview from a perspective of hydrogen donor and thus the related mechanistic understanding of the light-induced hydrogenative reactions is rare. Here, we have categorized the photocatalytic hydrogenative reactions by the type of employed liquid hydrogen donors (hydrocarbons and water), discussed the basic criteria of hydrogen abstraction from these donors, and elaborated the design strategy of the photocatalyst materials.


Assuntos
Hidrocarbonetos , Hidrogênio , Catálise , Água
12.
Angew Chem Int Ed Engl ; 62(22): e202302979, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-36988035

RESUMO

Heterogeneous photocatalysis is effective for the selective synthesis of value-added chemicals at lab-scale, yet falls short of requirements for mass production (low cost and user friendliness). Here we report the design and fabrication of a modular tubular flow system embedded with replaceable photocatalyst membranes for scalable photocatalytic C-C, C-N homocoupling and hydrogenation reactions, which can be operated in either circular and continuous flow mode with high performance. The photocatalyst membranes almost fully occupy the volume of the reactor, thus enabling optimal absorption of the incident light. Additionally, the porous structured photocatalyst membranes facilitate the mass transfer of the reactants to efficiently use the active sites, resulting in 0th -order reaction kinetics and a high space-time yield compared to the batch reaction system at practical application levels and prolonged reaction times.

13.
Angew Chem Int Ed Engl ; 62(51): e202313313, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37930876

RESUMO

Heterogeneous catalytic ammoxidation provides an eco-friendly route for the cyanide-free synthesis of nitrile compounds, which are important precursors for synthetic chemistry and pharmaceutical applications. However, in general such a process requires high pressures of molecular oxygen at elevated temperatures to accelerate the oxygen reduction and imine dehydrogenation steps, which is highly risky in practical applications. Here, we report an electric field enhanced ammoxidation system using a supported Fe clusters catalyst (Fe/NC), which enables efficient synthesis of nitriles from the corresponding aldehydes under ambient air pressure at room temperature (RT). A synergistic effect between the external electric field and the Fe/NC catalyst promotes the ammonia activation and the dehydrogenation of the generated imine intermediates and avoids the unwanted backwards reaction to aldehydes. This electric field enhanced ammoxidation system presents high efficiency and selectivity for the conversion of a series of aldehydes under mild conditions with high durability, rendering it an attractive process for the green synthesis of nitriles with fragile functional groups.

14.
Angew Chem Int Ed Engl ; 62(23): e202302994, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37013857

RESUMO

Environmental-friendly halogenation of C-H bonds using abundant, non-toxic halogen salts is in high demand in various chemical industries, yet the efficiency and selectivity of laboratory available protocols are far behind the conventional photolytic halogenation process which uses hazardous halogen sources. Here we report an FeX2 (X=Br, Cl) coupled semiconductor system for efficient, selective, and continuous photocatalytic halogenation using NaX as halogen source under mild conditions. Herein, FeX2 catalyzes the reduction of molecular oxygen and the consumption of generated oxygen radicals, thus boosting the generation of halogen radicals and elemental halogen for direct halogenation and indirect halogenation via the formation of FeX3 . Recycling of FeX2 and FeX3 during the photocatalytic process enables the halogenation of a wide range of hydrocarbons in a continuous flow, rendering it a promising method for applications.

15.
Biol Reprod ; 107(4): 977-983, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-35835555

RESUMO

The Notch signaling pathway is required for reproductive success. This pathway activates its transcriptional effector, recombination signal binding protein for immunoglobulin kappa J (Rbpj), to induce transcription of its target genes. This signaling pathway is required for successful decidualization, implantation, and uterine repair following parturition. To identify the compartmental specific roles of the Notch signaling pathway in the establishment of pregnancy, we generated epithelial and decidual stromal cell specific knockouts of Rbpj utilizing lactoferrin iCre and Prl8A2 iCre, respectively. Both conditional knockout mouse models were fertile. The Rbpj epithelial knockout mice displayed 27% resorption sites at E15.5, but this did not significantly impact the number of live born pups compared with controls. In addition, the Rbpj epithelial knockout mice displayed increased estrogen signaling in their stromal compartment. Given that both mouse models exhibited fertility comparable to control animals, the epithelial and stromal specific nature of the iCre recombinases utilized, and previously published Rbpj total uterine knockout mouse models, we conclude that Notch effector Rbpj signaling is required at the initiation of pregnancy to support decidualization in stromal cells, but that Rbpj is not required in the epithelial compartment nor is it required for post-implantation pregnancy success.


Assuntos
Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina , Receptores Notch , Animais , Proteínas de Transporte/metabolismo , Estrogênios , Feminino , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Lactoferrina/metabolismo , Camundongos , Camundongos Knockout , Gravidez , Receptores Notch/genética , Receptores Notch/metabolismo , Recombinases/genética , Recombinases/metabolismo , Recombinação Genética , Transdução de Sinais/fisiologia , Células Estromais/metabolismo
16.
Qual Life Res ; 31(6): 1749-1759, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34741249

RESUMO

BACKGROUND AND PURPOSE: Health-Related Quality of Life (HR-QOL) is an important patient-reported domain in patients with rheumatoid arthritis (RA). The uptake of multidisciplinary team (MDT) care in RA is generally low, due to initial high demand for resources. We hypothesised that whilst pharmacological treatments are effective in controlling disease activity, a multipronged intervention in an MDT may have a positive impact on HR-QOL. METHODS: This was a single-centre randomized parallel group, single-blind controlled trial of MDT vs. usual care in an established RA clinic. Data were collected through face-to-face questionnaires, medical records review, and joint counts by a blinded assessor at 0, 3 and 6 months. Adult RA patients were randomly assigned in a single visit to a 6-member MDT (rheumatologist, nurse, social worker, physiotherapist, occupational therapist, and podiatrist) or usual care. MDT providers prescribed medications and counselled patients on managing flares, medication adherence, coping, joint protection, exercise, footwear. The primary outcome was minimal clinically important difference (MCID) in HR-QOL (increase in European QOL-5-Dimension-3-Level, EQ-5D-3L by 0.1) at six months. RESULTS: 140 patients (86.3% female, 53.4% Chinese, median (IQR) age 56.6 (46.7, 62.4) years); 70 were randomized to each arm. Median (IQR) disease duration was 5.5 (2.4, 11.0) years and disease activity in 28 joints (DAS28) was 2.87 (2.08, 3.66). 123 patients completed the study. Twenty-six (40.6%) MDT vs. 23 (34.3%) usual care patients achieved an MCID in EQ-5D-3L, OR 1.3 (0.6, 2.7). In multivariable logistic regression, baseline EQ-5D-3L was the only predictor of achieving MCID. There was more disease modifying anti-rheumatic drug escalation in MDT (34.4% vs. 19.4%). Patients with high disease activity were more likely to achieve MCID in the MDT arm. CONCLUSIONS: A single visit by stable patients with low disease activity to an MDT failed to achieve MCID in the EQ-5D-3L; however, did achieve small but significant improvements in the EQ-5D-3L, DAS28, pain, coping and self-efficacy. To be sustainable, MDT care should be targeted at patients with high disease activity or those with a new diagnosis of RA. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov, identifier: NCT03099668.


Assuntos
Artrite Reumatoide , Qualidade de Vida , Adulto , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor , Qualidade de Vida/psicologia , Método Simples-Cego , Inquéritos e Questionários
17.
Ecotoxicol Environ Saf ; 241: 113826, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36068753

RESUMO

Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1ß, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model.


Assuntos
Endometriose , Zearalenona , Animais , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Endométrio/metabolismo , Estrogênios/metabolismo , Estrogênios/toxicidade , Feminino , Humanos , Camundongos , Transdução de Sinais , Zearalenona/toxicidade
18.
Hepatobiliary Pancreat Dis Int ; 21(2): 106-112, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34583911

RESUMO

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Humanos , Imunossupressores/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Sirolimo/efeitos adversos , Resultado do Tratamento
19.
Zhongguo Zhong Yao Za Zhi ; 47(24): 6633-6640, 2022 Dec.
Artigo em Zh | MEDLINE | ID: mdl-36604912

RESUMO

Heracles Ⅱ rapid electronic odor analyzer has been gradually applied in the study on the "odor" of Chinese medicine because of its ability to associate volatile substances in the sample with "odor", but its applicability is not clear. In this article, processed ginger products--dried ginger, roasted ginger, and carbonized ginger were chosen as examples to study the volatile chemical components, and the applied scope and accuracy of Heracles Ⅱ rapid electronic odor analyzer were verified by gas chromatography-mass spectrometry(GC-MS). Components in ten batches of ginger from different producing places were detected by GC-MS and Heracles Ⅱ rapid electronic odor analyzer. Principal component analysis(PCA) and discriminant factor analysis(DFA) were performed to investigate the effects of producing place and processing degree on dried ginger, roasted ginger, and carbonized ginger. The results showed that the processing degree had significant impact on the processed ginger products, while producing place was not significant to the processed ginger products. At the same time, 42 and 45 compounds were detected by Heracles Ⅱ rapid electronic odor analyzer and GC-MS, respectively, of which 29 compounds were common detected, with a coincidence rate of 64.4%. This result indicated that compared with GC-MS, Heracles Ⅱ rapid electronic odor analyzer had certain referential value in the qualitative analysis. Heracles Ⅱ rapid electronic odor analyzer, with the characteristics of convenience, high efficiency, and accuracy in processing data, has certain advantages in the "odor" research aiming to comprehensively evaluate volatile substances, and has a good application prospect in the quality control of Chinese medicine and its processed products.


Assuntos
Medicina Tradicional do Leste Asiático , Compostos Orgânicos Voláteis , Zingiber officinale , Cromatografia Gasosa-Espectrometria de Massas/métodos , Zingiber officinale/química , Odorantes/análise , Controle de Qualidade , Compostos Orgânicos Voláteis/análise
20.
Angew Chem Int Ed Engl ; 61(24): e202204256, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35334135

RESUMO

Employing pure water, the ultimate green source of hydrogen donor to initiate chemical reactions that involve a hydrogen atom transfer (HAT) step is fascinating but challenging due to its large H-O bond dissociation energy (BDEH-O =5.1 eV). Many approaches have been explored to stimulate water for hydrogenative reactions, but the efficiency and productivity still require significant enhancement. Here, we show that the surface hydroxylated graphitic carbon nitride (gCN-OH) only requires 2.25 eV to activate H-O bonds in water, enabling abstraction of hydrogen atoms via dehydrogenation of pure water into hydrogen peroxide under visible light irradiation. The gCN-OH presents a stable catalytic performance for hydrogenative N-N coupling, pinacol-type coupling and dehalogenative C-C coupling, all with high yield and efficiency, even under solar radiation, featuring extensive impacts in using renewable energy for a cleaner process in dye, electronic, and pharmaceutical industries.

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