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1.
Cell Discov ; 9(1): 11, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693846

RESUMO

Chromosomes occupy discrete spaces in the interphase cell nucleus, called chromosome territory. The structural and functional relevance of chromosome territory remains elusive. We fused chromosome 15 and 17 in mouse haploid embryonic stem cells (haESCs), resulting in distinct changes of territories in the cognate chromosomes, but with little effect on gene expression, pluripotency and gamete functions of haESCs. The karyotype-engineered haESCs were successfully implemented in generating heterozygous (2n = 39) and homozygous (2n = 38) mouse models. Mice containing the fusion chromosome are fertile, and their representative tissues and organs display no phenotypic abnormalities, suggesting unscathed development. These results indicate that the mammalian chromosome architectures are highly resilient, and reorganization of chromosome territories can be readily tolerated during cell differentiation and mouse development.

2.
BMC Anesthesiol ; 23(1): 28, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650434

RESUMO

BACKGROUND: The present study aimed to evaluate whether the operating table height affected the success rate and incidences of complications of combined spinal-epidural anesthesia administered by residents during training. METHODS: One-hundred-and-eighty patients were randomly allocated according to landmarks on the resident's body: umbilicus (group U), lowest rib margin (R), and xiphoid process (X). The success rates of combined spinal-epidural anesthesia, and the incidences of paresthesia and vessel trauma were recorded. RESULTS: There were no differences between the three groups in the success rates of combined spinal-epidural anesthesia, and the incidences of paresthesia and vessel trauma. However, paresthesia during epidural catheter advancement was more common on the left side (66.7%) than the right side (33.3%) (P = 0.03). In group R, the success rate of epidural anesthesia was higher during the residents' third time (100%) than their first time (50%; P = 0.01). Most residents (83%) preferred the table height at which the needle insertion point was at the level of their lowest rib margin. CONCLUSIONS: Neither the success nor the complication of combined spinal-epidural anesthesia in lateral decubitus position during residents' training affected by the operating table height. However, paresthesia was more likely to occur on the left side when a stiff catheter was inserted into the epidural space. It may be better to keep the table height at residents' lowest rib margin. It was not just preferred by most of residents but also better for their training of performing epidural anesthesia. TRIAL REGISTRATION: The trial was registered prior to patient enrollment at Chinese Clinical Trial Registry (NCT: ChiCTR1800016078, Principal investigator: Juan Gu, Date of registration: 9 May 2018). Registry URL http://www.chictr.org.cn.


Assuntos
Anestesia Epidural , Raquianestesia , Mesas Cirúrgicas , Humanos , Parestesia/etiologia , Mesas Cirúrgicas/efeitos adversos , Punção Espinal , Anestesia Epidural/efeitos adversos , Raquianestesia/efeitos adversos , Espaço Epidural
3.
BMC Surg ; 23(1): 13, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650515

RESUMO

BACKGROUND: Controversies regarding the anatomical structure of Denonvilliers' fascia and its relationship with surrounding fasciae have sparked a heated discussion, especially concerning whether Denonvilliers' fascia is multilayered. This study aimed to expound on the anatomical structure of Denonvilliers' fascia and its correlation with the peritoneum from the sagittal view and clarify the complex fascial relationship. METHODS: Our study was performed on 20 adult male pelvic specimens fixed in formalin, including 2 entire pelvic specimens and 18 semipelvic specimens. The local adjacent organs and fasciae were dissected, and Denonvilliers' fascia was observed and removed for histological examination. RESULTS: Denonvilliers' fascia was typically single-layered and tough. On the sagittal plane, the peritoneum constituting the peritoneal reflection and Denonvilliers' fascia formed a "Y" shape. Denonvilliers' fascia originated from the peritoneal reflection, extended along the ventral side of the seminal vesicles and prostate, continuing caudally; its bilateral sides closely connected to the urogenital fascia (UGF) of the pelvic wall. In addition, histology preliminarily indicated that the basal cell layers of the peritoneum and Denonvilliers' fascia were continuous and formed a "Y" shape. Furthermore, the basal cells of the two peritonea extended to Denonvilliers' fascia, creating a fused double-layered structure. Some tiny blood vessels or a network of such vessels extended from the peritoneum to Denonvilliers' fascia. CONCLUSION: Denonvilliers' fascia, the extension of the peritoneum in the pelvic floor, appears as a single-layered "Y"-shape on the sagittal plane. Our study provides new support for the peritoneal fusion theory. Understanding the anatomical characteristics of Denonvilliers' fascia and its relationship with the UGF is of guiding significance for inexperienced colorectal surgeons to conduct rectal cancer surgery.


Assuntos
Neoplasias Retais , Reto , Adulto , Humanos , Masculino , Reto/cirurgia , Fáscia , Pelve , Neoplasias Retais/cirurgia , Peritônio , Diafragma da Pelve , Cadáver
4.
Arch Physiol Biochem ; : 1-11, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594510

RESUMO

BACKGROUND: One of the pathological characteristics of obesity is fat accumulation of skeletal muscles (SKM) and the myocardium, involving mechanisms of insulin resistance and abnormal lipid metabolism. Apolipoprotein A-IV (ApoA-IV) is an essential gene in both glucose and lipid metabolisms. MATERIALS AND METHODS: Using high-fat diet (HFD) induced obese apoA-IV-knockout mice and subsequent introduction of exogenous recombinant-ApoA-IV protein and adeno-associated virus (AAV)-transformed apoA-IV, we examined lipid metabolism indicators of SKM and the myocardium, which include triglyceride (TG) content, RT-PCR for lipogenic indicators and western blotting for AKT phosphorylation. Similarly, we used high-glucose-fed or palmitate (Pal)-induced C2C12 cells co-cultured with ApoA-IV protein to evaluate glucose uptake, the phosphoinositide 3-kinase (PI3K)-AKT pathway, and lipid metabolisms. RESULTS: In stable obese animal models, we find ApoA-IV-knockout mice show elevated TG content, enhanced expression of lipogenic enzymes and diminished phosphorylated AKT in SKM and the myocardium, but both stable hepatic expression of AAV-apoA-IV and brief ApoA-IV protein administration suppress lipogenesis and promote AKT phosphorylation. In a myoblast cell line C2C12, ApoA-IV protein suppresses Pal-induced lipid accumulation and lipogenesis but enhances AKT activation and glucose uptake, and the effect is abolished by a PI3K inhibitor. CONCLUSION: We find that ApoA-IV reduces fat accumulation by suppressing lipogenesis and improves glucose uptake in SKM and the myocardium by regulating the PI3K-AKT pathway.

5.
Radiol Med ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627501

RESUMO

PURPOSE: To explore the characteristics of the hepatic fat content in athletes, and predict late gadolinium enhancement (LGE) based on magnetic resonance imaging-proton density fat fraction (MRI-PDFF). MATERIAL AND METHODS: From March 2020 to March 2021, 233 amateur athletes and 42 healthy sedentary controls were prospectively recruited. The liver fat content of four regions of interest (ROIs 1-4), the mean liver fat fraction (FF), cardiac function, and myocardium LGE were recorded, respectively. The values of ROIs 1-4 and FF were compared between athletes and controls. According to the liver fat content threshold for distinguishing athletes and controls, the cutoff total exercise time that induced a change in liver fat was obtained. The correlations among the liver fat content, cardiac function, and other parameters were analyzed. Moreover, the liver fat content was used to predict myocardium LGE by logistic regression. RESULTS: There were significant differences for the values of ROI 1, ROI 3, ROI 4, and FF between athletes and controls (allp< 0.05). The cutoff total exercise time for inducing a change in the liver fat content was 1680 h (area under the curve [AUC] = 0.593, specificity = 83.3,p< 0.05). Blood indexes, cardiac function, and basic clinical parameters were related to liver fat content (allp< 0.05). The prediction model for LGE had an AUC value of 0.829 for the receiver operator characteristic curve. CONCLUSION: MRI-PDFF could assess liver fat content and predict cardiac fibrosis in athletes for risk stratification and follow-up.

6.
Phytomedicine ; 109: 154588, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610131

RESUMO

BACKGROUND: Ebracteolatain A (EA) is an acetyl-phloroglucinol compound extracted from Euphorbiae Ebracteolatae Radix, which has been shown to have antitumor activity. PURPOSE: Current research addressed the antitumor activity of EA in breast cancer and further clarified its mechanism. STUDY DESIGN: Based on the pharmacodynamic evaluation in breast cancer cells and animal models, the antitumor effects of EA will be validated in vitro and in vivo. METHODS: Breast cancer cells were processed with increasing concentrations of EA. CCK-8 and colony formation assays were employed to examine the effects of EA on proliferation and survival. Flow cytometry detected the blocking function of EA on the cell cycle. The specific mechanism of EA in breast cancer was studied by transfection experiments and Western Blot analysis. Finally, a nude mice xenograft tumor model was constructed to assess the therapeutic and potential mechanism of EA. RESULTS: We proved that EA caused a dose-dependent inhibition on MCF-7 and MDA-MB-415 cells with IC50 of 6.164 and 6.623 µmol/l, respectively. While EA reduced cell proliferation and clone formation, and markedly arrested cells in the G0/G1 phase. In vivo, EA remarkably suppressed the tumor weight and volume in xenograft nude mice. Besides, PKD1 reversed the inhibition of EA on breast cancer cell proliferation, clone formation, and cycle arrest, and restored tumor growth in xenograft nude mice. Western Blot confirmed that EA regulates breast cancer by suppressing PKD1 in MEK/ERK and PI3K/AKT signaling pathways. CONCLUSION: Herein, we first confirmed EA exerts anti-proliferation by inhibiting PKD1 in MEK/ERK and PI3K/AKT signaling pathways, indicating that EA is a prodigious breast cancer drug candidate.


Assuntos
Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Humanos , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Transdução de Sinais , Neoplasias da Mama/patologia , Proliferação de Células , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose
7.
Small ; : e2207048, 2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36709483

RESUMO

Hydrogels have extremely high moisture content, which makes it very soft and excellently biocompatible. They have become an important soft material and have a wide range of applications in various fields such as biomedicine, bionic smart material, and electrochemistry. Carbon dot (CD)-based hydrogels are based on carbon dots (CDs) and auxiliary substances, forming a gel material with comprehensive properties of individual components. CDs embedding in hydrogels could not only solve their aggregation-caused quenching (ACQ) effect, but also manipulate the properties of hydrogels and even bring some novel properties, achieving a win-win situation. In this review, the preparation methods, formation mechanism, and properties of CD-based hydrogels, and their applications in biomedicine, sensing, adsorption, energy storage, and catalysis -are summarized. Finally, a brief discussion on future research directions of CD-based hydrogels will be given.

8.
Pharmacol Res ; 188: 106644, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603607

RESUMO

poorly cohesive (PC) gastric cancer (GC) (PC-GC) is a distinct histological subtype of GC and is defined as a tumor consisting of isolated or small clusters of tumor cells with poorly differentiated and metastatic characteristics. According to multiple studies, PC-GC is intrinsically heterogeneous, with mesenchymal variants being the most aggressive. However, to date, the molecular mechanisms associated with PC-GC are still not fully understood. This study investigated the role of the USP51/ZEB1/ACTA2 axis in promoting GC metastasis. Single-cell sequencing revealed that E-box binding homeobox 1 (ZEB1) expression was significantly increased in a subpopulation of low-adherent cells and was an independent prognostic factor in GC patients. Furthermore, the bulk transcriptome analysis revealed a significant positive correlation between Ubiquitin Specific Peptidase 51 (USP51), ZEB1, and Actin Alpha 2 (ACTA2), and our data further confirmed that all three were highly co-localized in PC-GC tissues. According to the findings of in vitro and in vivo experiments, USP51 was able to maintain ZEB1 expression to promote ACTA2 transcription, thereby activating the mesenchymal phenotype of GC cells and promoting tumor metastasis. Moreover, USP51 could recruit and activate stromal cells, including M2-like macrophages and fibroblasts, through cancer cells. Clinical data suggested that overexpression of USP51 predicts that patients have difficulty benefiting from immunotherapy and is associated with immune-exclusion tumor characteristics. Collectively, the findings of this study shed light on a key mechanism by which elevated USP51 expression induces Epithelial-mesenchymal transition (EMT) in GC cells, hence facilitating GC cell proliferation, survival, and dissemination. In this view, USP51/ZEB1/ACTA2 may serve as a candidate therapeutic target against GC metastasis.

9.
Chemosphere ; 316: 137880, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36649892

RESUMO

This study explored the feasibility of a coupled system for antibiotic removal and biofuel production through microalgae cultivation. Initial, batch culture experiments demonstrated that sulfadiazine (SDZ) had an inhibitory effect on Chlorella sp. G-9, and 100.0 mg L-1 SDZ completely inhibited its growth. In order to improve SDZ removal efficiency by microalgae, three membrane photobioreactors (MPBRs) with different hydraulic retention times (HRTs) were established for continuous microalgae cultivation. The efficient coupling of SDZ removal and microalgal lipid production was achieved through the gradual increment of influent SDZ concentration from 0 to 100.0 mg L-1. The reduction in SDZ ranged between 57.8 and 89.7%, 54.7-91.7%, and 54.6-93.5% for the MPBRs with HRT of 4 d, 2 d, and 1 d, respectively. Chlorella sp. Was found to tolerate higher concentrations of SDZ in the MPBR system, and the resulting stress from high concentrations of SDZ effectively increased the lipid content of microalgae for potential biodiesel production. With the increase of influent SDZ concentration from 0 to 100.0 mg L-1, the lipid content of microalgae increased by 43.5%. Chlorophyll content, superoxide dismutase activity, and malondialdehyde content of microalgae were also evaluated to explore the mechanism of microalgae tolerance to SDZ stress in MPBR.


Assuntos
Chlorella , Microalgas , Sulfadiazina , Fotobiorreatores , Biomassa , Biocombustíveis , Lipídeos
10.
Phytomedicine ; 111: 154658, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36706698

RESUMO

BACKGROUND: Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism of its action remains to be further clarified. PURPOSE: To investigate the underlying mechanisms of WMW in the treatment of chronic ulcerative colitis (UC) through network pharmacology and experimental validation. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform were used to identify the ingredients and potential targets of WMW. The microarray gene data GSE75214 datasets from GEO database was used to define UC-associated targets. Cytoscape3.7.2 was employed to construct the protein-protein interaction (PPI) network and compounds-disease targets network. GO enrichment analysis and KEGG pathway analysis were performed by R software for functional annotation. UPLC-TOF-MS/MS method was used to quantitatively analyze the active ingredients of WMW. For experimental validation, three cycles of 2% dextran sulfate sodium salt (DSS) were used to construct chronic colitis model. The hub targets and signal pathway were detected by qPCR, ELISA, western blotting , immunohistochemical and immunofluorescence. RESULTS: Through network analysis, 104 active ingredients were obtained from WMW, and 47 of these ingredients had potential targets for UC. A total of 41 potential targets of WMW and 13 hub targets were identified. KEGG analysis showed that WMW involved in advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, and luteolin of WMW were the more highly predictive components related to the AGE-RAGE signaling pathway. In vivo validation, WMW improved DSS-induced colitis, reduced the expression of inflammatory cytokines and chemokines. Notably, it significantly decreased the mRNA expression of Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr and Icam1, which were associated with angiogenesis. In addition, we confirmed WMW inhibited RAGE expression and diminished DSS-induced epithelial barrier alterations CONCLUSION: Our results initially demonstrated the effective components and the strong anti-angiogenic activity of WMW in experimental chronic colitis. Sufficient evidence of the satisfactory anti-colitis action of WMW was verified in this study, suggesting its potential as a quite prospective agent for the therapy of UC.

11.
BMC Cancer ; 23(1): 76, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690975

RESUMO

BACKGROUND: Gastric cancer peritoneal metastasis (GCPM) is an important cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) play a key role in the regulation of GCPM, but the underlying mechanisms have not been elucidated. METHODS: High-throughput RNA sequencing (RNA-seq) was performed on four groups of clinical specimens (non-metastatic gastric cancer primary tumor, adjacent normal gastric mucosal tissue, gastric cancer primary tumor with peritoneal metastasis and adjacent normal gastric mucosal tissue). After sequencing, many lncRNAs and mRNAs were screened for further Weighted Gene Co-expression Network Analysis (WGCNA). GCPM-related hub lncRNAs and genes were identified by cytoHubba and validated by Quantitative real-time PCR (qRT-PCR), Receiver operating characteristic curve (ROC) analysis and Kaplan-Meier survival analysis. GO, KEGG and GSEA showed GCPM-related pathways. Correlation analysis revealed the potential relationship between hub lncRNAs and genes. RESULTS: By analyzing lncRNA expression data by WGCNA, we found that blue module was highly correlated with GCPM (r = 0.44, p = 0.04) and six lncRNAs involved in this module (DNM3OS, lnc-MFAP2-53, lnc-PPIAL4C-4, lnc-RFNG-1, lnc-TRIM28-14 and lnc-YARS2-4) were identified. We then performed qRT-PCR validation of gastric cancer specimens and found that the expression of lnc-RFNG-1 and lnc-TRIM28-14 was significantly increased in gastric cancer tissues with peritoneal metastasis. Kaplan-Meier survival analysis showed shorter overall survival time (OS) for gastric cancer patients with high expression of lnc-TRIM28-14. Receiver operating characteristic curve (ROC) analysis showed that lnc-TRIM28-14 could improve the sensitivity and specificity of GCPM diagnosis. In addition, we identified three key mRNAs (CD93, COL3A1 and COL4A1) associated with gastric cancer peritoneal metastasis through WGCNA analysis and clinical specimen validation. Moreover, there was a positive correlation between lnc-TRIM28-14 and the expression of CD93 and COL4A1 in gastric cancer peritoneal metastasis, suggesting a regulatory relationship between them. Subsequent GO, KEGG and GSEA analysis suggested that ECM-receptor interaction and focal adhesion were the hub pathways of GCPM. CONCLUSION: In summary, lnc-RFNG-1, lnc-TRIM28-14, CD93, COL3A1 and COL4A1 could be novel tumor biomarkers and potential therapeutic targets for GCPM.


Assuntos
Neoplasias Peritoneais , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , RNA Longo não Codificante/genética , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Proteína 28 com Motivo Tripartido/genética
12.
PeerJ ; 11: e14591, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36691477

RESUMO

Emerging articles have reported that N6-methyladenosine (m6A) modification is mainly involved in clear-cell renal cell carcinoma (ccRCC) tumorigenesis. However, the regulatory mechanisms of m6A reader IGF2BP1 involved in ccRCC tumor energy metabolism are currently unknown. Results showed that the m6A reader IGF2BP1 exhibited significantly higher expression in ccRCC cells. Functionally, results by gain/loss functional assays indicated that IGF2BP1 promoted the glycolytic characteristics, including glucose uptake, lactate production and extracellular acidification rate (ECAR). Mechanistically, IGF2BP1 recognized the m6A modified sites on LDHA mRNA and enhanced its mRNA stability, thereby accelerating tumor energy metabolism. Thus, our work reveals a novel facet of the m6A that promoted mRNA stability and highlighted the functional importance of IGF2BP1 as m6A readers in post-transcriptional gene regulation.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Ácido Láctico/metabolismo , Neoplasias Renais/genética , Glicólise/genética
13.
Artigo em Inglês | MEDLINE | ID: mdl-36694305

RESUMO

Cost-effective and high-performance H2S sensors are required for human health and environmental monitoring. 2D transition-metal carbides and nitrides (MXenes) are appealing candidates for gas sensing due to good conductivity and abundant surface functional groups but have been studied primarily for detecting NH3 and VOCs, with generally positive responses that are not highly selective to the target gases. Here, we report on a negative response of pristine Ti3C2Tx thin films for H2S gas sensing (in contrast to the other tested gases) and further optimization of the sensor performance using a composite of Ti3C2Tx flakes and conjugated polymers (poly[3,6-diamino-10-methylacridinium chloride-co-3,6-diaminoacridine-squaraine], PDS-Cl) with polar charged nitrogen. The composite, preserving the high selectivity of pristine Ti3C2Tx, exhibits an H2S sensing response of 2% at 5 ppm (a thirtyfold sensing enhancement) and a low limit of detection of 500 ppb. In addition, our density functional theory calculations indicate that the mixture of MXene surface functional groups needs to be taken into account to describe the sensing mechanism and the selectivity of the sensor in agreement with the experimental results. Thus, this report extends the application range of MXene-based composites to H2S sensors and deepens the understanding of their gas sensing mechanisms.

14.
ACS Nano ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695873

RESUMO

Injectable functional biomaterials have made significant progress in cardiac regenerative. In addition, how to adjust the abominable infarction microenvironment and introduce therapeutic stem cells to improve the healing effect has become a hotspot. Herein, injectable stem cell vector is prepared by combining natural alginate hydrogel and Au@Pt nanoparticles (Au@Pt/Alg hydrogel) to encapsulate brown adipose stem cells (BASCs). Au@Pt nanoparticles with both antioxidative and conductive properties could effectively eliminate reactive oxygen species, enhance the frequency of action potential release of cardiomyocytes, and further reduce the inflammatory factors of macrophage in vitro. The Au@Pt/Alg hydrogel enhances the antioxidant, differentiation, and paracrine capability of BASCs. The effect of BASCs loaded Au@Pt/Alg hydrogel is evaluated in a rat myocardial infarction (MI) model. The antioxidant, anti-inflammatory, and heart electrical integration are showed in the MI model. More interestingly, Au@Pt/Alg hydrogel can effectively maintain the paracrine efficiency and pro-angiogenesis effects of BASCs in the infarcted area. This study led us to recognize the great value of Au@Pt/Alg hydrogels for their ability to actively regulate the microenvironment and carry stem cells for MI treatment.

16.
Kaohsiung J Med Sci ; 39(1): 61-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36519412

RESUMO

Disruption of gamma-amino butyric acid type A receptors (GABAA Rs) synaptic clustering and a decrease in the number of GABAA Rs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction and propagation. The multipass transmembrane protein cleft lip and palate transmembrane protein 1 (Clptm1) controls the forward trafficking of GABAA R, thus decaying miniature inhibitory postsynaptic current (mIPSC) of inhibitory synapses. In this study, using a pentylenetetrazol (PTZ)-induced epilepsy rat model, we found that Clptm1 regulates epileptic seizures by modulating GABAA R-mediated inhibitory synaptic transmission. First, we showed that Clptm1 expression was elevated in the PTZ-induced epileptic rats. Subsequently, we found that downregulation of Clptm1 expression protected against PTZ-induced seizures, which was attributed to an increase in the number of GABAA Rγ2s in the plasma membrane and the amplitude of mIPSC. Taken together, our findings identify a new anti-seizure target that provides a theoretical basis for the development of novel strategies for the prevention and treatment of epilepsy.


Assuntos
Fenda Labial , Fissura Palatina , Epilepsia , Animais , Ratos , Epilepsia/induzido quimicamente , Epilepsia/genética , Ácido gama-Aminobutírico , Pentilenotetrazol/toxicidade , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Convulsões/genética , Transmissão Sináptica/genética , Proteínas de Membrana/metabolismo
17.
Sci Total Environ ; 857(Pt 1): 159178, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36202366

RESUMO

Urine diversion in a No-Mix Toilet is a promising approach for sustainable fertilizers and reduction of the nutrient load for wastewater treatment; however, user adoption remains a challenge. This study evaluates the Urine Trap, a passive No-Mix toilet design based on the teapot effect, wherein the urine stream inlet is invisible to the user and therefore it does not impact the user experience for increased adoption. This study evaluated the nutrient separation performance of a Urine Trap flush toilet in a bathroom shared by women in two sites in India. Over three different testing periods, 841 uses of this squat plate were recorded in 50 days. Analytical measurements found 36 % separation efficiency for total nitrogen (TN). While effective, the Urine Trap under test by users did not yield a 70-80 % TN separation efficiency observed under engineering characterization. High temporal resolution data from sensors on waste collection tanks, the opening of the bathroom door, and cleansing water flow were used to gain insights into hygiene practices. The data showed a frequent habit of wetting the squat plate during physiological excretion, a hygienic practice that eases cleaning but degrades the teapot separation effect of the Urine Trap design. By using sensors, we demonstrate a method to non-invasively gain quantitative insights into hygiene practices to inform sanitation technologies deployment strategies for improved outcomes.


Assuntos
Aparelho Sanitário , Purificação da Água , Feminino , Humanos , Toaletes , Saneamento , Purificação da Água/métodos , Fertilizantes , Nitrogênio , Urina
18.
Mar Pollut Bull ; 186: 114453, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36495614

RESUMO

Some algae possess a multi-morphic life cycle, either in the form of free-living solitary cells or colonies which constantly occur in algal blooms. Though colony formation seems to consume extra energy and materials, many algae tend to outbreak in form of colonies. Here, we hypothesized that colony formation is a selected evolutionary strategy to improve population competitiveness and environmental adaptation. To test the hypothesis, different sizes of colonies and solitary cells in a natural bloom of Phaeocystis globosa were investigated. The large colony showed a relatively low oxidant stress level, a nutrient trap effect, and high nutrient use efficiency. The colonial nitrogen and phosphorus concentrations were about 5-10 times higher than solitary cell phycosphere and cellular nutrient allocation decreased with the enlargement of the colonial diameter following the economies of scale law. These features provide the colony with monopolistic competence and could function as an evolutionary strategy for competitive adaptation.


Assuntos
Haptófitas , Eutrofização , Aclimatação
19.
Front Immunol ; 13: 1041126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451825

RESUMO

Purpose: Neoadjuvant chemoradiotherapy (nCRT) is a standard treatment option for patients with stage III oesophageal cancer. Approximately 30% of oesophageal cancer patients will have a pathological complete response (pCR) after nCRT. However, available clinical methods cannot accurately predict pCR for patients. We aimed to find more indicators that could be used to predict the pathological response to nCRT. Method: A total of 84 patients with stage III oesophageal squamous cell cancer were enrolled in this study. Ten patients failed to have surgery as a result of progressive disease (PD). Among the patients who underwent surgery, 32 patients had a pathologic complete response (pCR), whereas 42 patients showed no or partial response (npCR) after nCRT. Routine blood test results and lymphocyte subset assessments before and after nCRT were retrospectively analysed. Univariate and multivariate analyses were used to identify independent predictors of the clinical curative effect of nCRT. Eventually, nomograms were established for predicting the PD and pCR rates. Results: The numbers of lymphocytes, B lymphocytes, T lymphocytes, Th lymphocytes, Ts lymphocytes, and NK cells and the percentages of B lymphocytes and NK cells were decreased significantly after nCRT (P < 0.0001), whereas the percentages of T lymphocytes and Ts lymphocytes increased (P < 0.0001). Univariate analysis showed that age, the length of the lesion, the level of haemoglobin before nCRT, and the amount of change in haemoglobin were related to PD, and the percentage of NK cells after nCRT was related to pCR. Multivariate logistic analysis demonstrated that the length of the lesion, the neutrophil-to-lymphocyte ratio (NLR) before nCRT, and the amount of change in haemoglobin were independent predictors of PD, whereas the percentage of NK cells after nCRT was an independent predictor of pCR. Conclusion: Lymphocyte subsets changed dramatically during nCRT, and these changes together with baseline and posttreatment lymphocyte subsets have predictive value in determining the response to nCRT for oesophageal cancer.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Terapia Neoadjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas do Esôfago/terapia , Subpopulações de Linfócitos , Neoplasias Esofágicas/terapia , Células Matadoras Naturais , Células Epiteliais
20.
Artigo em Inglês | MEDLINE | ID: mdl-36455146

RESUMO

Context: Cardiovascular diseases (CVDs caused by atherosclerosis, such as coronary heart disease and stroke, have become major causes of death and disability worldwide. Atherosclerosis is the primary pathological factor causing CVDs. Managing weight, blood pressure, and lipids is one of the tenets of chronic-disease management, including atherosclerosis. Objective: The study intended to investigate the effects of managing weight, blood pressure, and lipids on disease severity in patients with carotid atherosclerosis. Design: The research team designed a randomized, controlled trial. Setting: The study took place in the pediatric department at the First Hospital of Hebei Medical University in Shijiazhuang, Hebei Province, China. Participants: Participants were 380 patients with carotid atherosclerosis who entered the hospital between March 2018 and June 2020. Intervention: Participants were randomly assigned, using the random-number-table method, to an intervention or a control group, with 190 participants in each group. Both groups received anti-atherosclerotic treatments, and the intervention group also took part in a program for combined management of weight, blood pressure, and blood lipids. Outcome Measures: All measurements occurred at baseline and postintervention. Using a questionnaire, the study measured the changes in the two groups related to alcohol consumption, smoking, high-fat diet, high-salt diet, and lack of exercise. A physical examination provided participants' weights, blood pressures, and lipid levels, and the Self-Care Ability Assessment Scale (ESCA) provided the changes in their self-management ability. A carotid-artery examination measured parameters related to carotid atherosclerosis, including intima-media thickness (IMT), Crouse scores, plaque-class scores, and plaque-grade scores. Results: At baseline, no statistically significant differences existed between the groups. Postintervention, the intervention group had significantly greater decreases than the control group for alcohol consumption, smoking, high-fat diet, high-salt diet, lack of exercise, weight, blood pressure, lipid levels, intima-media thickness (IMT) scores, Crouse scores, and plaque-grade scores. Postintervention, the intervention group had significantly greater increases than the control group for self-responsibility, health knowledge, self-concept, and self-care-skills scores. Conclusions: A program for management of body weight, blood pressure, and blood lipids can effectively control the severity of carotid atherosclerosis, can prevent the disease's progression, and can be promoted as a clinical application.

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