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1.
Mol Neurobiol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865078

RESUMO

Chronic inflammatory pain caused by neuronal hyperactivity is a common and refractory disease. Kv3.1, a member of the Kv3 family of voltage-dependent K+ channels, is a major determinant of the ability of neurons to generate high-frequency action potentials. However, little is known about its role in chronic inflammatory pain. Here, we show that although Kv3.1 mRNA expression was unchanged, Kv3.1 protein expression was decreased in the dorsal spinal horn of mice after plantar injection of complete Freund's adjuvant (CFA), a mouse model of inflammatory pain. Upregulating Kv3.1 expression alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas downregulating Kv3.1 induced nociception-like behaviors. Additionally, we found that ubiquitin protein ligase E3 component n-recognin 5 (UBR5), a key factor in the initiation of chronic pain, binds directly to Kv3.1 to drive its ubiquitin degradation. Intrathecal injection of the peptide TP-CH-401, a Kv3.1 ubiquitination motif sequence, rescued the decrease in Kv3.1 expression and Kv currents through competitive binding to UBR5, and consequently attenuated mechanical and thermal hypersensitivity. These findings demonstrate a previously unrecognized pathway of Kv3.1 abrogation by UBR5 and indicate that Kv3.1 is critically involved in the regulation of nociceptive behavior. Kv3.1 is thus a promising new target for treating inflammatory pain.

2.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1310-1317, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621978

RESUMO

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD_L, 6 g·kg~(-1)), medium-dose ECD group(ECD_M, 12 g·kg~(-1)), and high-dose ECD group(ECD_H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD_M and ECD_H groups were significantly decreased, and the AST level in the ECD_L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD_H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD_M and ECD_H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD_M and ECD_H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Metionina/metabolismo , Metionina/farmacologia , Interleucina-10/genética , Colina/metabolismo , Colina/farmacologia , Colina/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos Endogâmicos C57BL , Fígado , Racemetionina/metabolismo , Racemetionina/farmacologia , Dieta , RNA Mensageiro/metabolismo
3.
Molecules ; 29(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338343

RESUMO

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Lactente , Idoso , Antivirais/farmacologia , Antivirais/uso terapêutico , Palivizumab/farmacologia , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Antirretrovirais/uso terapêutico
4.
Hum Reprod Open ; 2024(1): hoae003, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312775

RESUMO

STUDY QUESTION: Are there other pathogenic genes for asthenoteratozoospermia (AT)? SUMMARY ANSWER: DNAH3 is a novel candidate gene for AT in humans and mice. WHAT IS KNOWN ALREADY: AT is a major cause of male infertility. Several genes underlying AT have been reported; however, the genetic aetiology remains unknown in a majority of affected men. STUDY DESIGN SIZE DURATION: A total of 432 patients with AT were recruited in this study. DNAH3 mutations were identified by whole-exome sequencing (WES). Dnah3 knockout mice were generated using the genome editing tool. The morphology and motility of sperm from Dnah3 knockout mice were investigated. The entire study was conducted over 3 years. PARTICIPANTS/MATERIALS SETTING METHODS: WES was performed on 432 infertile patients with AT. In addition, two lines of Dnah3 knockout mice were generated. Haematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunostaining, and computer-aided sperm analysis (CASA) were performed to investigate the morphology and motility of the spermatozoa. ICSI was used to overcome the infertility of one patient and of the Dnah3 knockout mice. MAIN RESULTS AND THE ROLE OF CHANCE: DNAH3 biallelic variants were identified in three patients from three unrelated families. H&E staining revealed various morphological abnormalities in the flagella of sperm from the patients, and TEM and immunostaining further showed the loss of the central pair of microtubules, a dislocated mitochondrial sheath and fibrous sheath, as well as a partial absence of the inner dynein arms. In addition, the two Dnah3 knockout mouse lines demonstrated AT. One patient and the Dnah3 knockout mice showed good treatment outcomes after ICSI. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This is a preliminary report suggesting that defects in DNAH3 can lead to asthenoteratozoospermia in humans and mice. The pathogenic mechanism needs to be further examined in a future study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings show that DNAH3 is a novel candidate gene for AT in humans and mice and provide crucial insights into the biological underpinnings of this disorder. The findings may also be beneficial for counselling affected individuals. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from National Natural Science Foundation of China (82201773, 82101961, 82171608, 32322017, 82071697, and 81971447), National Key Research and Development Program of China (2022YFC2702604), Scientific Research Foundation of the Health Committee of Hunan Province (B202301039323, B202301039518), Hunan Provincial Natural Science Foundation (2023JJ30716), the Medical Innovation Project of Fujian Province (2020-CXB-051), the Science and Technology Project of Fujian Province (2023D017), China Postdoctoral Science Foundation (2022M711119), and Guilin technology project for people's benefit (20180106-4-7). The authors declare no competing interests.

5.
J Chem Phys ; 160(5)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38341707

RESUMO

To control the growth of layered two-dimensional structures, such as transition metal dichalcogenide materials or heterostructures, understanding the growth mechanism is crucial. Here, we report the synthesis of ultra-thin MoO2 nanoplatelets through the sublimation of MoO3. Rhombus MoO2 nanoplatelets with the P21/c space group were characterized using various microscopic and spectroscopic techniques. Introducing sulfur sources into the chemical vapor deposition system also leads to the formation of monoclinic MoO2 nanoflakes due to the incomplete sulfurization of MoO3. With a gradual increase in the vapor concentration of sulfur, MoO3 undergoes stepwise reduction into MoS2/MoO2 and eventually into MoS2. Additionally, utilizing MoO2 as a precursor for Mo sources enables the formation of monolayer MoS2 single crystals. This work provides an effective approach for growing MoO2 nanoplatelets and elucidates the mechanism behind the stepwise sulfurization of MoO3.

6.
Mol Divers ; 28(1): 125-131, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36881209

RESUMO

Copper-catalyzed selective alkynylation with N-propargyl carboxamides as nucleophiles has been successfully developed for the synthesis of C2-functionalized chromanones. Under optimized reaction conditions, 21 examples were obtained in one-pot procedure through 1,4-conjugate addition. This protocol features readily available feedstocks, easy operations, and moderate to good yields, which provides viable access to pharmacologically active C2-functionalized chromanones.


Assuntos
Cromonas , Cobre , Estrutura Molecular , Catálise
7.
Clin Infect Dis ; 78(4): 880-888, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38015658

RESUMO

BACKGROUND: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at evaluating the efficacy of premedication with duloxetine in the prevention of PHN. METHODS: The PROCESS trial is a multicenter, randomized, open-label, blinded-endpoint trial used a 1:1 duloxetine:control ratio. Adults 50 years or older with HZ who presented with vesicles within 72 hours were recruited. The primary outcome was the incidence of PHN at 12 weeks. PHN was defined as any pain intensity score other than 0 mm on the visual analog scale (VAS) at week 12 after the onset of the rash. The secondary outcomes were the number of participants with VAS >0 and VAS ≥3. The modified intention-to-treat (mITT) principle and per-protocol (PP) principle were used for the primary outcome analysis. RESULTS: A total of 375 participants were randomly assigned to the duloxetine group and 375 were assigned to the control group. There was no significant difference in the incidence of PHN in the duloxetine group compared with the control group in the mITT analysis (86 [22.9%] of 375 vs 108 [28.8%] of 375; P = .067). PP analysis produced similar results. However, there were significant differences between the 2 groups in the number of participants with VAS >0 and VAS ≥3 (P < .05 for all comparisons). CONCLUSIONS: Although absolute prevention of PHN does not occur, this trial found that premedication with duloxetine can reduce pain associated with HZ, and therefore can have clinically relevant benefits. Clinical Trials Registration. Clinicaltrials.gov, NCT04313335. Registered on 18 March 2020.


Assuntos
Herpes Zoster , Neuralgia Pós-Herpética , Adulto , Humanos , Neuralgia Pós-Herpética/tratamento farmacológico , Neuralgia Pós-Herpética/prevenção & controle , Neuralgia Pós-Herpética/epidemiologia , Cloridrato de Duloxetina/uso terapêutico , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Medição da Dor/efeitos adversos , Medição da Dor/métodos
8.
HGG Adv ; 5(1): 100256, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37981762

RESUMO

In this study, we report on mosaic variegated aneuploidy (MVA) syndrome with tetraploidy and predisposition to infertility in a family. Sequencing analysis identified that the CEP192 biallelic variants (c.1912C>T, p.His638Tyr and c.5750A>G, p.Asn1917Ser) segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size, while CEP192 monoallelic variants segregated with infertility and/or reduced testicular size in the family. In 1,264 unrelated patients, variant screening for CEP192 identified a same variant (c.5750A>G, p.Asn1917Ser) and other variants significantly associated with infertility. Two lines of Cep192 mice model that are equivalent to human variants were generated. Embryos with Cep192 biallelic variants arrested at E7 because of cell apoptosis mediated by MVA/tetraploidy cell acumination. Mice with heterozygous variants replicated the predisposition to male infertility. Mouse primary embryonic fibroblasts with Cep192 biallelic variants cultured in vitro showed abnormal morphology, mitotic arresting, and disruption of spindle formation. In patient epithelial cells with biallelic variants cultured in vitro, the number of cells arrested during the prophase increased because of the failure of spindle formation. Accordingly, we present mutant CEP192, which is a link for the MVA syndrome with tetraploidy and the predisposition to male infertility.


Assuntos
Transtornos Cromossômicos , Infertilidade Masculina , Humanos , Masculino , Camundongos , Animais , Tetraploidia , Aneuploidia , Suscetibilidade a Doenças , Infertilidade Masculina/genética , Proteínas Cromossômicas não Histona/genética , Mosaicismo
9.
J Fungi (Basel) ; 9(11)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37998901

RESUMO

Endophytic fungi isolated from medicinal ferns serve as significant natural resources for drug precursors or bioactive metabolites. During our survey on the diversity of endophytic fungi from Dicranopteris species (a genus of medicinal ferns) in Guizhou, Apoiospora was observed as a dominant fungal group. In this study, seven Apiospora strains, representing four new species, were obtained from the healthy plant tissues of three Dicranopteris species-D. ampla, D. linearis, and D. pedata. The four new species, namely Apiospora aseptata, A. dematiacea, A. dicranopteridis, and A. globosa, were described in detail with color photographs and subjected to phylogenetic analyses using combined LSU, ITS, TEF1-α, and TUB2 sequence data. This study also documented three new hosts for Apiospora species.

10.
World J Pediatr ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38019382

RESUMO

BACKGROUND: Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to two years and to identify the critical exposure periods. METHODS: A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24 months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. RESULTS: The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). CONCLUSION: Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first two years, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033 kb).

11.
Phys Chem Chem Phys ; 25(40): 27766-27773, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37814790

RESUMO

Type-II van der Waals (vdW) heterostructures are regarded as the optimum candidates for unipolar electronic device applications due to their capacity for spontaneous electron-hole separation. Here, we studied the electronic properties of the AlAs/SiC vdW heterostructure via density functional theory calculations. Results show that the conduction band minimum (CBM) and valence band maximum (VBM) of this heterostructure are mainly contributed by different materials, illustrating that the AlAs/SiC heterostructure has a type-II band alignment. Interestingly, this heterostructure possesses flat valence bands near the Fermi level. In addition, under the modulation of external electric field ranging between -1 V Å-1∼0.8 V Å-1, the band gap of the heterostructure can be tuned continuously, while the band structure maintains a stable type-II band alignment with flat top valence bands. When the electric field exceeds -1 or 0.8 V Å-1, the heterostructure transitions from semiconductor material to metal, indicating the tunability of electronic properties under external fields. These results indicate that the AlAs/SiC heterostructure shows great potential for application in high-performance optoelectronic devices and a strong correlation may exist in this system.

12.
Nucleic Acids Res ; 51(19): 10428-10450, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37739418

RESUMO

Arginine methylation, catalyzed by the protein arginine methyltransferases (PRMTs), is a common post-translational protein modification (PTM) that is engaged in a plethora of biological events. However, little is known about how the methylarginine-directed signaling functions in germline development. In this study, we discover that Prmt1 is predominantly distributed in the nuclei of spermatogonia but weakly in the spermatocytes throughout mouse spermatogenesis. By exploiting a combination of three Cre-mediated Prmt1 knockout mouse lines, we unravel that Prmt1 is essential for spermatogonial establishment and maintenance, and that Prmt1-catalyzed asymmetric methylarginine coordinates inherent transcriptional homeostasis within spermatogonial cells. In conjunction with high-throughput CUT&Tag profiling and modified mini-bulk Smart-seq2 analyses, we unveil that the Prmt1-deposited H4R3me2a mark is permissively enriched at promoter and exon/intron regions, and sculpts a distinctive transcriptomic landscape as well as the alternative splicing pattern, in the mouse spermatogonia. Collectively, our study provides the genetic and mechanistic evidence that connects the Prmt1-deposited methylarginine signaling to the establishment and maintenance of a high-fidelity transcriptomic identity in orchestrating spermatogonial development in the mammalian germline.


Assuntos
Epigenoma , Espermatogônias , Animais , Masculino , Camundongos , Arginina/metabolismo , Fertilidade/genética , Mamíferos/genética , Camundongos Knockout , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Espermatogônias/metabolismo
13.
Stem Cell Res Ther ; 14(1): 231, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649110

RESUMO

BACKGROUND: Stem cells play a therapeutic role mainly through immunoregulation. However, the immunomodulatory function of stem cells may be affected by inflammation-related factors in patients' serum. Therefore, this study aims to investigate the possible mechanism by which acute-on-chronic liver failure (ACLF) patient serum influences the efficacy of hUC-MSCs. METHODS: The serum of surviving and dead ACLF patients was collected to culture hUC-MSCs in vitro, and the hUC-MSCs cultured in the serum of ACLF patients were used to treat acute liver failure (ALF) rats. The therapeutic effect on the rats was evaluated by a survival curve, the transaminase level and liver histopathology. The expression of cytokines in hUC-MSCs was detected by Q-PCR and ELISA. RESULTS: Serum pretreatment reduced the therapeutic effect of hUC-MSCs on ALF, especially pretreatment in the serum from dead ACLF patients. After hUC-MSCs were cultured in the serum of surviving or dead ACLF patients, the most differentially expressed factor was IL-8. Interfering with the expression of IL-8 in hUC-MSCs can improve the therapeutic effect of hUC-MSCs on ALF. The high level of IL-1ß in the serum of dead ACLF patients causes the increased expression of IL-8 in hUC-MSCs through the activation of the NF-κB signaling pathway. Meanwhile, we found that the neutralizing IL-1ß in serum from dead ACLF patients can improve the therapeutic effect of hUC-MSCs on ALF. CONCLUSION: The high level of IL-1ß in ACLF serum can promote the expression of IL-8 in hUC-MSCs through the NF-κB signaling pathway, thus reducing the effect of hUC-MSCs on ALF.


Assuntos
Insuficiência Hepática Crônica Agudizada , Interleucina-1beta , Interleucina-8 , Animais , Ratos , Insuficiência Hepática Crônica Agudizada/terapia , Interleucina-8/genética , NF-kappa B , Transdução de Sinais , Humanos , Interleucina-1beta/sangue
14.
Ann Hepatol ; 28(5): 101119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37271480

RESUMO

INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.


Assuntos
Hepatite B Crônica , Humanos , Adulto , Tenofovir/efeitos adversos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Estudos Retrospectivos , Alanina/uso terapêutico , Adenina/uso terapêutico , Rim/fisiologia , Antivirais/efeitos adversos , Resultado do Tratamento
15.
Nat Commun ; 14(1): 3729, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349316

RESUMO

In mammals, the production of mature oocytes necessitates rigorous regulation of the discontinuous meiotic cell-cycle progression at both the transcriptional and post-transcriptional levels. However, the factors underlying this sophisticated but explicit process remain largely unclear. Here we characterize the function of N-acetyltransferase 10 (Nat10), a writer for N4-acetylcytidine (ac4C) on RNA molecules, in mouse oocyte development. We provide genetic evidence that Nat10 is essential for oocyte meiotic prophase I progression, oocyte growth and maturation by sculpting the maternal transcriptome through timely degradation of poly(A) tail mRNAs. This is achieved through the ac4C deposition on the key CCR4-NOT complex transcripts. Importantly, we devise a method for examining the poly(A) tail length (PAT), termed Hairpin Adaptor-poly(A) tail length (HA-PAT), which outperforms conventional methods in terms of cost, sensitivity, and efficiency. In summary, these findings provide genetic evidence that unveils the indispensable role of maternal Nat10 in oocyte development.


Assuntos
Meiose , Oócitos , Animais , Camundongos , Mamíferos/genética , Oócitos/metabolismo , Oogênese/genética , RNA Mensageiro/metabolismo
16.
Curr Med Sci ; 43(3): 572-578, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37142817

RESUMO

OBJECTIVE: This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. METHODS: A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. RESULTS: The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. CONCLUSION: The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Procedimentos Cirúrgicos Robóticos , Marcadores Fiduciais , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/cirurgia , Incerteza , Planejamento da Radioterapia Assistida por Computador
17.
Phys Chem Chem Phys ; 25(22): 15295-15301, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37222137

RESUMO

Two-dimensional (2D) carbon materials integrated with planar tetracoordinate carbon (ptC) and negative Poisson's ratio (NPR) provide a cornerstone for constructing multifunctional energy-storage devices. As a typical 2D carbon material, the pristine graphene is chemically inert, hindering its application in metal-ion batteries. Introducing the ptC in graphene can break the extended conjugation of π-electrons and lead to an enhanced surface reactivity. Inspired by the unique geometry of [4.6.4.6] fenestrane skeleton with ptC, we theoretically design a ptC-containing 2D carbon allotrope, namely THFS-carbon. It is intrinsically metallic with excellent dynamical, thermal, and mechanical stabilities. The Young's modulus along the x direction (311.37 N m-1) is comparable to that of graphene. Intriguingly, THFS-carbon possesses an in-plane half-NPR distinct from most other 2D crystals. As a promising anode for sodium-ion batteries, THFS-carbon delivers an ultra-high theoretical storage capacity (2233 mA h g-1), a low diffusion energy barrier (0.03-0.05 eV), a low open-circuit voltage (0.14-0.40 V), and a good reversibility for Na insertion/extraction.

18.
Phys Chem Chem Phys ; 25(16): 11513-11521, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37039312

RESUMO

Na-ion batteries (NIBs) have attracted a great deal of attention for large-scale electric energy storage due to their inherent safety, natural abundant resources, and low cost. The exploration of suitable anode materials is the major challenge in advancing NIB technology. On the basis of first-principles calculations, we systematically explore the potential performance of two-dimensional (2D) TiCl2 as an electrode material for NIBs. Monolayer TiCl2 can be easily exfoliated from the bulk structure with a small exfoliation energy of 0.64 J m-2. It shows good stability, as demonstrated by its high cohesive energy, positive phonon modes, and high thermal stability. Monolayer TiCl2 has high storage capacity (451.3 mA h g-1), low diffusion energy barrier (0.02-0.14 eV), moderate average open-circuit voltage (0.81 V), and small lattice change (2.37%). Moreover, bilayer TiCl2 can significantly enhance the Na adsorption strength but reduce the Na-ion diffusion ability. These results suggest that TiCl2 is a promising anode candidate for NIBs.

20.
Pain Pract ; 23(6): 609-617, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36929196

RESUMO

BACKGROUND: Whether ultrasound-guided stellate ganglion block (SGB) is a valuable therapeutic option for the treatment of patients with chronic migraine (CM) is worth exploring. If SGB is proven to be effective for CM, the identification of potential predictors for the effectiveness of SGB warrants further investigation. This study aimed to investigate the effectiveness and safety of SGB in patients with CM and to explore the predictive factors for its treatment effectiveness. METHODS: This is a retrospective observational study. We retrospectively analyzed the effects of SGB for the treatment of patients with CM under ultrasound guidance, between January 2018 and June 2022. The follow-up time was approximately 1 month, 2 months, and 3 months after the last SGBs. The response criterion was defined as a reduction in pain intensity of > 50% measured using the most severe numerical rating scale (NRS) score compared to pretreatment baseline, without an increase in the dose or the type of analgesic or anxiolytic/antidepressant medication, otherwise unresponsive to SGB. Univariable and multivariable analyses were performed to identify the predictive factors for SGB response. RESULTS: Ninety-seven patients were included in this study. SGB was effective in most of the CM patients, with an effective rate of 90.7%, 82.5%, and 71.1% after 1, 2, and 3 months of the last SGBs, respectively. At 3-month follow-up, 95.7% responsive patients benefited from repeated SGBs. In patients receiving repeated SGB treatments, the number of SGBs in responsive patients was significantly greater than those in patients with no response at 3-month follow-up (3.41 ± 1.31 vs. 2.68 ± 0.67, p = 0.02). Comorbid anxiety or depression was a negative predictor of SGB effectiveness at 3-month follow-up (B = -0.25, 95% CI -0.45 to -0.05, p = 0.01). The overall adverse events rate associated with ultrasound-guided SGB was 9.3%. There were no serious complications; all adverse events were transient, with hoarseness being the most common adverse event. CONCLUSIONS: Ultrasound-guided SGB was an effective and safe treatment for CM patients. The majority of responsive patients with CM benefited from repeated SGBs. CM patients who needed repeated SGBs may obtain good and sustained analgesic effect after receiving a greater number of SGBs. Patients without comorbidities such as anxiety or depression were more likely to benefit from SGB treatments.


Assuntos
Bloqueio Nervoso Autônomo , Transtornos de Enxaqueca , Humanos , Estudos Retrospectivos , Gânglio Estrelado , Ultrassonografia , Ultrassonografia de Intervenção , Transtornos de Enxaqueca/tratamento farmacológico
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