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1.
Omega (Westport) ; : 302228241254001, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744535

RESUMO

The number of parents in China who have lost their only child, referred to as shidu parents, currently exceeds one million and is increasing by approximately 76,000 annually. Shidu parents face a unique challenge in long-term care, primarily stemming from the sudden and tragic loss of their only child, which leads to a substantial decrease in their social support network. A multi-stage, stratified, and cluster sampling method was employed across various economic belts. Linear regression analysis was utilized to examine factors associated with the social support status of shidu and non-shidu parents. The level of social support decreases as the severity of depression increases. Shidu parents with grandchildren tend to have good social support. The city of Hangzhou exhibits relatively high levels of social support. Married individuals typically report higher levels of social support. It is recommended to prioritize shidu parents without grandchildren as a primary focus for government and societal support. Key recommendations include strengthening social skills training and developing social support networks. Drive economic development, particularly in relatively underdeveloped regions. Strengthen social organizations and community development. Enhancing access to support services, leveraging technology, and encouraging volunteerism for non-married parents.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38730034

RESUMO

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

3.
Environ Sci Technol ; 58(15): 6552-6563, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38571383

RESUMO

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.


Assuntos
Desinfetantes , Desinfecção , Desinfecção/métodos , Matriz Extracelular de Substâncias Poliméricas , Desinfetantes/farmacologia , Cloro/farmacologia , Cinética
4.
Opt Express ; 32(7): 12645-12655, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571082

RESUMO

The space time frequency transfer plays a crucial role in applications such as space optical clock networks, navigation, satellite ranging, and space quantum communication. Here, we propose a high-precision space time frequency transfer and time synchronization scheme based on a simple intensity modulation/direct detection (IM/DD) laser communication system, which occupies a communication bandwidth of approximately 0.2%. Furthermore, utilizing an optical-frequency comb time frequency transfer system as an out-of-loop reference, experimental verification was conducted on a 113 km horizontal atmospheric link, with a long-term stability approximately 8.3 × 10-16 over a duration of 7800 seconds. Over an 11-hour period, the peak-to-peak wander is approximately 100 ps. Our work establishes the foundation of the time frequency transfer, based on the space laser communication channel, for future ground-to-space and inter-satellite links.

5.
Angew Chem Int Ed Engl ; : e202401635, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597773

RESUMO

The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,ß-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction at high conversions with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.

6.
ACS Synth Biol ; 13(4): 1259-1272, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38513222

RESUMO

We present the newly isolated Streptomyces sungeiensis SD3 strain as a promising microbial chassis for heterologous production of secondary metabolites. S. sungeiensis SD3 exhibits several advantageous traits as a microbial chassis, including genetic tractability, rapid growth, susceptibility to antibiotics, and metabolic capability supporting secondary metabolism. Genomic and transcriptomic sequencing unveiled the primary metabolic capabilities and secondary biosynthetic pathways of S. sungeiensis SD3, including a previously unknown pathway responsible for the biosynthesis of streptazone B1. The unique placement of S. sungeiensis SD3 in the phylogenetic tree designates it as a type strain, setting it apart from other frequently employed Streptomyces chassis. This distinction makes it the preferred chassis for expressing biosynthetic gene clusters (BGCs) derived from strains within the same phylogenetic or neighboring phylogenetic clade. The successful expression of secondary biosynthetic pathways from a closely related yet slow-growing strain underscores the utility of S. sungeiensis SD3 as a heterologous expression chassis. Validation of CRISPR/Cas9-assisted genetic tools for chromosomal deletion and insertion paved the way for further strain improvement and BGC refactoring through rational genome editing. The addition of S. sungeiensis SD3 to the heterologous chassis toolkit will facilitate the discovery and production of secondary metabolites.


Assuntos
Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Filogenia , Antibacterianos/metabolismo , Genômica , Metabolismo Secundário/genética , Família Multigênica
7.
Sheng Li Xue Bao ; 76(1): 45-51, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38444130

RESUMO

The present study aims to investigate the effect of cathepsin K (CatK) on ischemic angiogenesis in high-fat diet fed mice. The mice were subjected to unilateral hindlimb ischemic surgery, and the ischemic blood flow was measured with a laser Doppler blood flow imager. Immunohistochemical staining was used to observe the quantity of new capillaries in the ischemic lower extremity, and Western blot was used to detect the expression of insulin receptor substrate-1 (IRS-1), p-Akt, Akt and vascular endothelial growth factor (VEGF). Firstly, the effect of high-fat diet on ischemic angiogenesis was observed in wild-type mice, which were randomly divided into control group and high-fat diet group and were fed with normal diet or 60% high-fat diet respectively for 16 weeks. The results showed the body weight and the plasma CatK concentration of the high-fat diet group was significantly increased compared with the control group (P < 0.05), and the blood flow recovery of the high-fat diet group was significantly lower than control group (P < 0.05). Then, wild-type and CatK knock out (CatK-/-) mice were both fed with high-fat diet to further observe the effect and mechanism of CatK on ischemic angiogenesis under high-fat diet. The results showed that the blood flow recovery in the CatK-/- group was significantly greater than the wild-type group, and the number of CD31 positive cells was significantly increased (P < 0.05). At the same time, the protein expression levels of IRS-1, p-Akt and VEGF in the ischemic skeletal muscle were significantly increased in the CatK-/- group compared with the wild-type group (P < 0.05). These results suggest that the deficiency of CatK improves ischemic angiogenesis in high-fat diet fed mice through IRS-1-Akt-VEGF signaling pathway.


Assuntos
Dieta Hiperlipídica , Fator A de Crescimento do Endotélio Vascular , Animais , Camundongos , Angiogênese , Catepsina K , Dieta Hiperlipídica/efeitos adversos , Proteínas Proto-Oncogênicas c-akt/genética , Fator A de Crescimento do Endotélio Vascular/genética
8.
Anal Chem ; 96(13): 5106-5114, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38490960

RESUMO

In this work, a novel MXene-Au nanoparticle (Ti3C2@Au) was synthesized with a high molar extinction coefficient, strong fluorescence quenching ability, ultrahigh antibody affinity, high stability, and good dispersibility, and it was used to develop a colorimetric-fluorescence dual-mode lateral flow immunoassay (LFIA). The detection limits of this method for the detection of dexamethasone in milk, beef, and pork were 0.0018, 0.12, and 0.084 µg/kg in the "turn-off" mode (colorimetric signal), and 0.0013, 0.080, and 0.070 µg/kg in the "turn-on" mode (fluorescent signal), respectively, which was up to 231-fold more sensitive compared with that of the reported LFIAs. The recovery rates ranged from 81.1-113.7%, and 89.2-115.4%, with the coefficients of variation ranging from 1.4-15.0%, and 1.9-14.8%, respectively. The results of the LC-MS/MS confirmation test on 30 real samples had a good correlation with that of our established method (R2 > 0.97). This work not only developed novel nanocarriers for antibody-based LFIA but also ensured high-performance detection.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Bovinos , Colorimetria , Cromatografia Líquida , Espectrometria de Massas em Tandem , Titânio , Imunoensaio/métodos , Limite de Detecção
9.
Adv Sci (Weinh) ; 11(19): e2306850, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38477543

RESUMO

Micro-Doppler effect is a vital feature of a target that reflects its oscillatory motions apart from bulk motion and provides an important evidence for target recognition with radars. However, establishing the micro-Doppler database poses a great challenge, since plenty of experiments are required to get the micro-Doppler signatures of different targets for the purpose of analyses and interpretations with radars, which are dramatically limited by high cost and time-consuming. Aiming to overcome these limits, a low-cost and powerful simulation platform of the micro-Doppler effects is proposed based on time-domain digital coding metasurface (TDCM). Owing to the outstanding capabilities of TDCM in generating and manipulating nonlinear harmonics during wave-matter interactions, it enables to supply rich and high-precision electromagnetic signals with multiple micro-Doppler frequencies to describe the micro-motions of different objects, which are especially favored for the training of artificial intelligence algorithms in automatic target recognition and benefit a host of applications like imaging and biosensing.

10.
J Comput Biol ; 31(3): 241-256, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38377572

RESUMO

More and more studies have shown that microRNAs (miRNAs) play an indispensable role in the study of complex diseases in humans. Traditional biological experiments to detect miRNA-disease associations are expensive and time-consuming. Therefore, it is necessary to propose efficient and meaningful computational models to predict miRNA-disease associations. In this study, we aim to propose a miRNA-disease association prediction model based on sparse learning and multilayer random walks (SLMRWMDA). The miRNA-disease association matrix is decomposed and reconstructed by the sparse learning method to obtain richer association information, and at the same time, the initial probability matrix for the random walk with restart algorithm is obtained. The disease similarity network, miRNA similarity network, and miRNA-disease association network are used to construct heterogeneous networks, and the stable probability is obtained based on the topological structure features of diseases and miRNAs through a multilayer random walk algorithm to predict miRNA-disease potential association. The experimental results show that the prediction accuracy of this model is significantly improved compared with the previous related models. We evaluated the model using global leave-one-out cross-validation (global LOOCV) and fivefold cross-validation (5-fold CV). The area under the curve (AUC) value for the LOOCV is 0.9368. The mean AUC value for 5-fold CV is 0.9335 and the variance is 0.0004. In the case study, the results show that SLMRWMDA is effective in inferring the potential association of miRNA-disease.


Assuntos
MicroRNAs , Humanos , MicroRNAs/genética , Algoritmos , Área Sob a Curva , Biologia Computacional/métodos , Predisposição Genética para Doença
11.
J Agric Food Chem ; 72(7): 3247-3258, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38320115

RESUMO

Gizzerosine is responsible for gizzard erosion and black vomit, owing to excessive gastric acid secretion in poultry. It is a biogenic amine that forms during feed processing. Gizzerosine, a derivative of histamine, is a serious threat to animal feed safety and poultry production because it is more potent after ingestion and more harmful to poultry than histamine. The difficulty of obtaining gizzerosine and the lack of simple, rapid, and sensitive in vitro detection techniques have hindered studies on the effects of gizzerosine on gizzard health and poultry production. In this review, we evaluated the natural formation and the chemical synthesis methods of gizzerosine and introduced seven detection methods and their principles for analyzing gizzerosine. This review summarizes the issues of gizzerosine research and suggests methods for the future development of gizzerosine detection methods.


Assuntos
Galinhas , Histamina , Animais , Imidazóis/farmacologia , Ração Animal/análise
12.
Front Neurol ; 15: 1255621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361636

RESUMO

Objective: The aim of this study is to investigate the clinical value of radiomics based on non-enhanced head CT in the prediction of hemorrhage transformation in acute ischemic stroke (AIS). Materials and methods: A total of 140 patients diagnosed with AIS from January 2015 to August 2022 were enrolled. Radiomic features from infarcted areas on non-enhanced CT images were extracted using ITK-SNAP. The max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select features. The radiomics signature was then constructed by multiple logistic regressions. The clinicoradiomics nomogram was constructed by combining radiomics signature and clinical characteristics. All predictive models were constructed in the training group, and these were verified in the validation group. All models were evaluated with the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Of the 140 patients, 59 experienced hemorrhagic transformation, while 81 remained stable. The radiomics signature was constructed by 10 radiomics features. The clinicoradiomics nomogram was constructed by combining radiomics signature and atrial fibrillation. The area under the ROC curve (AUCs) of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the training group were 0.64, 0.86, and 0.86, respectively. The AUCs of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the validation group were 0.63, 0.90, and 0.90, respectively. The DCA curves showed that the radiomics signature performed well as well as the clinicoradiomics nomogram. The DCA curve showed that the clinical application value of the radiomics signature is similar to that of the clinicoradiomics nomogram. Conclusion: The radiomics signature, constructed without incorporating clinical characteristics, can independently and effectively predict hemorrhagic transformation in AIS patients.

13.
Chin J Integr Med ; 30(3): 195-202, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374490

RESUMO

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Plantas Medicinais , Humanos , Neuropatias Diabéticas/tratamento farmacológico , Banhos , Método Duplo-Cego , Extratos Vegetais/uso terapêutico
14.
Mol Cancer Ther ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38346939

RESUMO

Many colorectal cancer (CRC) patients do not respond to immune checkpoint blockade (ICB) therapy, highlighting the urgent need to understand tumor resistance mechanisms. Recently, the link between the IFNγ signaling pathway integrity and ICB resistance in the CRC tumor microenvironment has been revealed. The immunosuppressive microenvironment poses a significant challenge to antitumor immunity in CRC development. Tumor-associated neutrophils (TANs) found in tumor tissues exhibit an immunosuppressive phenotype and are associated with CRC patient prognosis. Neutrophil extracellular traps (NETs), DNA meshes containing cytotoxic enzymes released into the extracellular space, may be promising therapeutic targets in cancer. This study showed increased NETs in tumor tissues and peripheral neutrophils of high levels of microsatellite instability (MSI-H) CRC patients compared to microsatellite stable (MSS) CRC patients. IFNγ response genes were enriched in MSI-H CRC patients compared to MSS CRC patients. Co-culturing neutrophils with MSI-H CRC cell lines induced more NET formation and higher cellular apoptosis than MSS CRC cell lines. IFNγ treatment induced more NET formation and apoptosis in MSS CRC cell lines. Using subcutaneous or orthotopic CT-26 (MSS)-tumor-bearing mice models, IFNγ reduced tumor size and enhanced PD-1 antibody-induced tumor-killing activity, accompanied by upregulated NETs and cellular apoptosis. These findings suggest IFNγ could be a therapeutic strategy for MSS CRC.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 45-51, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387898

RESUMO

OBJECTIVE: To investigate the effect of tripipartite motif 59 (TRIM59) expression interference on the chemosensitivity of daunorubicin (DNR) in chronic myeloid leukemia (CML) K562 cells and the related molecular mechanism. METHODS: The expressions of TRIM59 mRNA in bone marrow tissues of patients with CML and K562 cells were detected by RT-qPCR. Liposome-based transfection technology was used to transfect TRIM59-specific siRNA (si-TRIM59) into K562 cells which then were treated with DNR. The proliferation and apoptosis of cells were detected by CCK-8 assay and flow cytometry, respectively, and the expressions of apoptosis-related protein and Wnt/ß-catenin signaling pathway-related protein were detected by Western blot. RESULTS: Compared with the bone marrow tissue of CML patients at the time of initial treatment, the expression of TRIM59 mRNA in bone marrow tissue of CML patients at the time of chemotherapy resistance was significantly increased (P <0.05). Compared with control group, the cell proliferation inhibition rate and apoptosis rate in si-TRIM59 group and DNR group were significantly increased (P <0.05), the expression of Bax, Caspase3 and Cleaved-Caspase3 protein were significantly increased (P <0.05), while the expressions of Bcl-2, Wnt3α, GSK-3ß protein and the ratio of p-ß-catenin/ß-catenin were significantly decreased (P <0.05). Compared with si-TRIM59 group and DNR group, the proliferation inhibition rate and apoptosis rate of si-TRIM59+DNR group were significantly increased (P <0.05), the expression of Bax, Caspase3 and Cleaved-Caspase3 protein were significantly increased, while the expression of Bcl-2, Wnt3α, GSK-3ß protein and the ratio of p-ß-catenin/ß-catenin were significantly decreased (P <0.05). CONCLUSION: TRIM59 expression interference may enhance the chemosensitivity of K562 cells to DNR, and its mechanism may be related to the regulation of Wnt/ß-catenin signaling pathway.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide , Humanos , Glicogênio Sintase Quinase 3 beta , beta Catenina , Células K562 , Proteína X Associada a bcl-2 , Daunorrubicina/farmacologia , RNA Mensageiro , Proteínas com Motivo Tripartido , Peptídeos e Proteínas de Sinalização Intracelular
16.
Sci Rep ; 13(1): 21355, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049518

RESUMO

Osteoarthritis (OA) is the most common degenerative joint disease. Currently, no satisfactory pharmacological treatment exists for OA. The potential anti-inflammatory properties of Dihydrotanshinone I (DHT) have been reported, but its effects on OA are unclear. In this study, we assess the impact of DHT on the viability of human chondrocytes in vitro. We then use a guinea pig model to investigate the effects of DHT on knee osteoarthritis progression. Twelve-week-old Dunkin Hartley guinea pigs spontaneously developing OA were intraperitoneally injected with different doses of DHT for eight weeks. Micro-CT analysis was performed on the subchondral bone in the knee, and histological assessment of the knee joint was done using stained sections, the ratio of hyaline to calcified cartilage, and Mankin scores. DHT successfully restored IL-1ß-induced decreases in cell viability in human primary chondrocytes. In the guinea pig model, intraperitoneal injections of DHT ameliorated age-induced OA, effectively reduced the expression level of two cartilage metabolism-related genes (ADAMTS4 and MMP13) and decreased the inflammatory biomarker IL-6 in the serum of guinea pigs developing spontaneous osteoarthritis. These findings demonstrate DHT's protective effects on chondrocytes and suggest that it alleviates cartilage degradation and proteoglycan loss in OA.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Humanos , Cobaias , Animais , Cartilagem Articular/patologia , Condrócitos , Osteoartrite do Joelho/patologia , Osso e Ossos
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(12): 1276-1281, 2023 Dec 15.
Artigo em Chinês | MEDLINE | ID: mdl-38112147

RESUMO

A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.


Assuntos
Glicosilfosfatidilinositóis , Doenças Raras , Humanos , Masculino , Febre , Glicosilfosfatidilinositóis/genética , Glicoproteínas de Membrana/genética , Mutação , Convulsões , Criança
18.
Sci Adv ; 9(50): eadi2134, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100583

RESUMO

The lithosphere, as the outermost solid layer of our planet, preserves a progressively more fragmentary record of geological events and processes from Earth's history the further back in time one looks. Thus, the evolution of lithospheric thickness and its cascading impacts in Earth's tectonic system are presently unknown. Here, we track the lithospheric thickness history using machine learning based on global lithogeochemical data of basalt. Our results demonstrate that four marked lithospheric thinning events occurred during the Paleoarchean, early Paleoproterozoic, Neoproterozoic, and Phanerozoic with intermediate thickening scenarios. These events respectively correspond to supercontinent/supercraton breakup and assembly periods. Causality investigation further indicates that crustal metamorphic and deformation styles are the feedback of lithospheric thickness. Cross-correlation between lithospheric thickness and metamorphic thermal gradients records the transition from intraoceanic subduction systems to continental margin and intraoceanic in the Paleoarchean and Mesoarchean and a progressive emergence of large thick continents that allow supercontinent growth, which promoted assembly of the first supercontinent during the Neoarchean.

19.
Neuropsychiatr Dis Treat ; 19: 2469-2483, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029049

RESUMO

Depression, as a common mental illness that is often accompanied by suicidal and homicidal behaviors, is one of the most important diseases in the medical field that requires urgent attention. The pathogenesis of depression is complex, and the current therapeutic drugs such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, and secondary serotonin reuptake inhibitors have certain shortcomings. The inflammatory factor hypothesis, one of the pathogenesis of depression, suggests that inflammatory response is a key factor leading to the occurrence and development of depression, and that overactivation of inflammatory factors such as NLRP3, Toll-like receptor 4, and IDO leads to immune-system dysfunction and depression. The other pathogenic hypothesis, the gut flora hypothesis, has also been the focus of recent research. The gut flora may work together with inflammatory factors to cause depression. The approach to treating depression has been by altering the gut flora through drugs or probiotics. However, effective and clear treatment methods are lacking. In this study, by exploring the involvement of intestinal flora and inflammatory factors in the pathogenesis of depression, we found that improving the intestinal flora can affect inflammatory factors and, therefore, provide research ideas for the development of novel drugs to treat depression.

20.
Pestic Biochem Physiol ; 196: 105613, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945230

RESUMO

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.


Assuntos
Aspergillus oryzae , Vírus do Mosaico do Tabaco , Nicotiana , Antraquinonas/farmacologia , Bioensaio , Antivirais/farmacologia
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