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BACKGROUND: Promoting patient participation stands as a global priority in nursing care. Currently, there is a lack of a standardized tool to assess the culture of patient participation from the perspective of nurses in China. AIMS: To translate and examine the validity and reliability of the Patient Participation Culture Tool for healthcare workers (PaCT-HCW) on general hospital wards in Chinese nursing context. METHODS: A cross-sectional research study was conducted among 812 nurses. Brislin's recommendations were adhered to during the translation of the scale. Validity was assessed using construct validity, content validity, and face validity. Split-half reliability, test-retest reliability, and internal consistency reliability were used to evaluate dependability. The study was guided and reported following the STROBE checklist and recommendations for reporting the results of studies of instrument and scale development and testing. RESULTS: The Chinese version of PaCT-HCW (the PaCT-HCW-C) exhibits good face validity and content validity. A rigorous exploratory factor analyse verified a six-factor (competence, support, perceived lack of time, information sharing and dialogue, response to questions and acceptance of a new role) scale structure with a cumulative variance contribution of the factors with 44 items of 68.840%. With a Cronbach's α coefficient of 0.962, split-half reliability of 0.866, and intraclass correlation coefficients of 0.989, the instrument demonstrates great reliability. Confirmatory factor analysis results validated the consistency of the six factors with the structure of the PaCT-HCW-C scale. CONCLUSIONS: The 44-item PaCT-HCW-C is a valid and reliable instrument with satisfactory psychometric properties. It could serve as a tool for assessing the effectiveness of international programs aimed at fostering patient participation from the perspective of nurses, while also providing insights from China's practical experiences.
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Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.
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Anticorpos Monoclonais Humanizados , Antígeno B7-H1 , Bevacizumab , Microbioma Gastrointestinal , Inibidores de Checkpoint Imunológico , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Bevacizumab/uso terapêutico , Bevacizumab/farmacologia , Masculino , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Pessoa de Meia-Idade , Idoso , Mesotelioma Maligno/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Mesotelioma/imunologia , Mesotelioma/tratamento farmacológico , Mesotelioma/microbiologia , Mesotelioma/patologia , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiologia , Resultado do TratamentoRESUMO
Abnormal immune and inflammatory responses are considered to contribute to schizophrenia (SZ). The neutrophil/lymphocyte ratio (NLR) is an inexpensive and reproducible marker of systemic inflammatory responses. Accumulating studies have demonstrated that NLR values are increased in SZ compared to healthy controls and closely related to clinical symptoms in antipsychotic-naïve first-episode SZ (ANFES) patients. However, to our knowledge, only one study has examined NLR in relation to neurocognition in 27 first-episode psychosis patients and 27 controls. This study aimed to examine the relationship of NLR values with cognitive performances in ANFES patients with a larger sample size. Whole blood cell counts were measured in ninety-seven ANFES patients and fifty-six control subjects. The neurocognitive functions of all subjects were measured by the repeatable battery for the assessment of neuropsychological status (RBANS). ANFES patients performed worse on cognition and had increased NLR values relative to healthy controls. In addition, increased NLR was negatively associated with cognitive functions in ANFES patients. Lymphocyte count was positively correlated with cognitive functions in patients. These findings suggest that the abnormal immune and inflammation system indicated by NLR may be involved in the cognitive functions in ANFES patients.
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The morphology of the active layer is crucial for highly efficient organic solar cells (OSCs), which can be regulated by selecting a rational third component. In this work, the highly crystalline nonfullerene acceptor BTP-eC9 is selected as the morphology regulator in OSCs with PM6:BTP-BO-4Cl as the main system. The addition of BTP-eC9 can prolong the nucleation and crystallization progress of acceptor and donor molecules, thereby enhancing the order of molecular arrangement. Meanwhile, the nucleation and crystallization time of the donor is earlier than that of the acceptors after introducing BTP-eC9, which is beneficial for obtaining a better vertical structural phase separation. The exciton dissociation, charge transport, and charge collection are promoted effectively by the optimized morphology of the active layer, which improves the short-circuit current density and filling factor. After introducing BTP-eC9, the power conversion efficiencies (PCEs) of the ternary OSCs are improved from 17.31% to 18.15%. The PCE is further improved to 18.39% by introducing gold nanopyramid (Au NBPs) into the hole transport layer to improve photon utilization efficiency. This work indicates that the morphology can be optimized by selecting a highly crystalline third component to regulate the nucleation and crystallization progress of the acceptor and donor molecules.
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DNA damage causes genomic instability. To maintain genome integrity, cells have evolved DNA damage response, which is involved in replication fork disassembly and DNA replication termination. However, the mechanism underlying the regulation of replication fork disassembly and its connection with DNA damage repair remain elusive. The CMG-MCM7 subunit ubiquitination functions on the eukaryotic replication fork disassembly at replication termination. Until now, only ubiquitin ligases CUL2LRR1 have been reported catalyzing MCM7 ubiquitination in human cells. This study discovered that in human cells, the ubiquitin ligase RNF8 catalyzes K63-linked multi-ubiquitination of MCM7 at K145 both in vivo and in vitro. The multi-ubiquitination of MCM7 is dynamically regulated during the cell cycle, primarily presenting on chromatin during the late S phase. Additionally, MCM7 polyubiquitylation is promoted by RNF168 and BRCA1 during DNA replication termination. Upon DNA damage, the RNF8-mediated polyubiquitination of MCM7 decreased significantly during the late S phase. This study highlights the novel role of RNF8-catalyzed polyubiquitination of MCM7 in the regulation of replication fork disassembly in human cells and linking it to DNA damage response.
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Dano ao DNA , Replicação do DNA , Proteínas de Ligação a DNA , Componente 7 do Complexo de Manutenção de Minicromossomo , Ubiquitina-Proteína Ligases , Ubiquitinação , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Componente 7 do Complexo de Manutenção de Minicromossomo/metabolismo , Componente 7 do Complexo de Manutenção de Minicromossomo/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteína BRCA1/metabolismo , Proteína BRCA1/genética , Células HEK293 , Reparo do DNA , Células HeLaRESUMO
Background: The incidence of cardiac arrest (CA) during percutaneous coronary intervention (PCI) is relatively rare. However, when it does occur, the mortality rate is extremely high. Extracorporeal cardiopulmonary resuscitation (ECPR) has shown promising survival rates for in-hospital cardiac arrests (IHCA), with low-flow time being an independent prognostic factor for CA. However, there is no definitive answer on how to reduce low-flow time. Methods: This retrospective study, conducted at a single center, included 39 patients who underwent ECPR during PCI between January 2016 and December 2022. The patients were divided into two cohorts based on whether standby extracorporeal membrane oxygenation (ECMO) was utilized during PCI: standby ECPR (SBE) (n = 13) and extemporaneous ECPR (EE) (n = 26). We compared the 30-day mortality rates between these two cohorts and investigated factors associated with survival. Results: Compared to the EE cohort, the SBE cohort showed significantly lower low-flow time (P < 0.01), ECMO operation time (P < 0.01), and a lower incidence of acute kidney injury (AKI) (P = 0.017), as well as peak lactate (P < 0.01). Stand-by ECMO was associated with improved 30-day survival (p = 0.036), while prolonged low-flow time (p = 0.004) and a higher SYNTAX II score (p = 0.062) predicted death at 30 days. Conclusions: Standby ECMO can provide significant benefits for patients who undergo ECPR for CA during PCI. It is a viable option for high-risk PCI cases and may enhance the overall prognosis. The low-flow time remains a critical determinant of survival.
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Hebei Province's Huanghua "Mianhua" is a province intangible cultural property made from arid alkaline wheat (AAW). This study aims to assess how different soil conditions affect the volatile organic compounds (VOCs) of "Mianhua" and identify distinct VOCs for land type discrimination. These findings will guide future research on AAW products, enhancing their processing and utilization. 51 VOCs in "Mianhua" from wheat samples grown in arid alkaline land and general land in Huanghua were analyzed by Gas Chromatography-Ion Mobility Spectrometry (GC-IMS). The result of ANOVA, VOC fingerprint, T test, and OPLS-DA revealed VOCs differences based on planting environments. According to multivariate variance contribution rate analysis, most VOCs were more affected by the variety. Land type significantly influenced (E)-2-heptenal (75.3%), Butanol (60.6%), Propyl acetate (60.0%), ethyl pentanoate (45.5%), and ethyl acetate (44.4%). LDA progressively identified Butanol as the characteristic VOC to distinguish "Mianhua" between it made from AAW and general wheat (GW), with a classification accuracy of 75%.
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Cromatografia Gasosa-Espectrometria de Massas , Solo , Triticum , Compostos Orgânicos Voláteis , Triticum/química , Compostos Orgânicos Voláteis/análise , Solo/química , Espectrometria de Mobilidade Iônica/métodos , ChinaRESUMO
Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. STATEMENT OF SIGNIFICANCE: The advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.
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Antibacterianos , Biofilmes , Cobre , Staphylococcus aureus , Cicatrização , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Cicatrização/efeitos dos fármacos , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Nanopartículas/química , Escherichia coli/efeitos dos fármacos , Terapia Fototérmica , Humanos , Terapia Combinada , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Microambiente Celular/efeitos dos fármacos , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismoRESUMO
Green innovation is essential for environmentally sustainable development. The construction of smart cities offers significant potential for developing green innovation through optimizing urban administration and improving the allocation of critical resources. Using Chinese city data from 2005 to 2019, this study adopts a causal identification framework based on the multi-temporal difference-in-difference method to explore the impact of smart city construction on green innovation and the mechanism and joint industrial emission reduction effect between them. A positive and significant relationship with a weak inverted U-shaped trend was found between smart city construction and green innovation. Besides the direct channel, labor factor allocation, venture capital attractiveness, and market accessibility are essential indirect channels between the two concepts. Furthermore, the effects of smart city construction on green innovation varied depending on the marketization level, administrative rank, population size, and geographic location of the city. In addition, the interaction of the two constructs negatively affected industrial emissions, which helped optimize the environment. These findings suggest that smart city construction offers a digital dividend for developing green innovation and creating an efficient, sustainable environment.
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Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) has been widely used in the treatment of a variety of tumors. Compared with other therapeutic methods, this treatment has the advantages of high efficiency, strong penetration, and controllable treatment range. PDT kills tumors by generating a large amount of reactive oxygen species (ROS), which causes oxidative stress in the tumor. However, this killing effect is significantly inhibited by the tumor's own resistance to ROS. This is because tumors can either deplete ROS by high concentration of glutathione (GSH) or stimulate autophagy to eliminate ROS-generated damage. Furthermore, the tumor can also consume ROS through the lactic acid metabolic pathway, ultimately hindering therapeutic progress. To address this conundrum, we developed a UCNP-based nanocomposite for enhanced PDT by reducing tumor ROS resistance. First, Ce6-doped SiO2 encapsulated UCNPs to ensure the efficient energy transfer between UCNPs and Ce6. Then, the biodegradable tetrasulfide bond-bridged mesoporous organosilicon (MON) was coated on the outer layer to load chloroquine (CQ) and α-cyano4-hydroxycinnamic acid (CHCA). Finally, hyaluronic acid was utilized to modify the nanomaterials to realize an active-targeting ability. The obtained final product was abbreviated as UCNPs@MON@CQ/CHCA@HA. Under 980 nm laser irradiation, upconverted red light from UCNPs excited Ce6 to produce a large amount of singlet oxygen (1O2), thus achieving efficient PDT. The loaded CQ and CHCA in MON achieved multichannel enhancement of PDT. Specifically, CQ blocked the autophagy process of tumor cells, and CHCA inhibited the uptake of lactic acid by tumor cells. In addition, the coated MON consumed a high level of intracellular GSH. In this way, these three functions complemented each other, just as the "three musketeers" punctured ROS resistance in tumors from multiple angles, and both in vitro and in vivo experiments had demonstrated the elevated PDT efficacy of nanomaterials.
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Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Dióxido de Silício/química , Cloroquina/farmacologia , Cloroquina/química , Camundongos Endogâmicos BALB CRESUMO
OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.
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Braquiterapia , Craniofaringioma , Neoplasias Hipofisárias , Humanos , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Craniofaringioma/radioterapia , Seguimentos , Neoplasias Hipofisárias/radioterapia , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
OBJECTIVE: We aimed to determine whether BMI categories and BMI trajectories were longitudinally associated with frailty in older adults via systematic review and meta-analysis of prospective cohort studies. METHOD: 3 databases (PubMed/MEDLINE, EMBASE and Web of Science) were systematically searched from inception to 8 September 2023. Two independent reviewers extracted data and appraised study quality. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data were pooled using random-effects models. RESULTS: 7 prospective cohort studies with 23043 participants were included in final BMI categories analyses, and 3 studies included BMI trajectory(23725 individuals). Compared with normal weight, we found a positive association between obesity (odds ratios(OR) = 1.74, 95 % confidence interval (CI): 1.21-2.51, P = 0.003), underweight (OR = 1.70, 95 % CI: 1.13-2.57, P = 0.011) and frailty in older adults. In middle age subgroup, compared with normal weight, OR of 2.21 (95 % CI: 1.44-3.38;I2 = 0 %) for overweight and OR of 5.20 (95 % CI: 2.56-10.55; I2 = 0 %) for obesity were significantly associated with frailty. In old age subgroup, compared with normal weight, only OR of 1.41 (95 % CI: 1.13-1.77; I2 = 65 %) for obesity was significantly associated with frailty. The results of BMI trajectories found that decreasing BMI (OR = 3.25, 95 % CI: 2.20-4.79, P < 0.0001) and consistently high BMI (OR = 3.66, 95 % CI: 2.03-6.61, P < 0.0001) increase the risk of frailty compared to consistently normal or overweight. CONCLUSION: Overweight and obesity in middle age were associated with significantly higher frailty in older adults, while obesity and underweight in old age were associated with relatively higher frailty in older adults. Early weight control may be beneficial for old age.
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Índice de Massa Corporal , Fragilidade , Idoso , Feminino , Humanos , Masculino , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , Estudos Longitudinais , Obesidade/epidemiologia , Obesidade/complicações , Sobrepeso/epidemiologia , Sobrepeso/complicações , Estudos Prospectivos , Fatores de Risco , Magreza/epidemiologia , Magreza/complicaçõesRESUMO
Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an "active" state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the "immunosilent" TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a "reactive oxygen species (ROS) storm". Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.
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Clorofilídeos , Cobre , Imunoterapia , Camundongos Endogâmicos BALB C , Porfirinas , Piroptose , Espécies Reativas de Oxigênio , Microambiente Tumoral , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Porfirinas/administração & dosagem , Imunoterapia/métodos , Animais , Cobre/administração & dosagem , Linhagem Celular Tumoral , Humanos , Feminino , Terapia por Ultrassom/métodos , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , CamundongosRESUMO
The wheat grains that are cultivated in saline-alkali soil exhibit a richer "wheat aroma" compared to their counterparts. This study characterized the composition and content of volatiles in five wheat kernel varieties, harvested from two fields with varying pH levels and total salt content in the soil. The wheat grown in soil with high pH and total salt content had significantly lower levels (p < 0.05) of ethyl 3-methylbutanoate and 1-octen-3-one and significantly higher levels (p < 0.05) of 1-butanol and 1-octen-3-ol. Among all factors, plant site contributed the highest F-value contribution rate (more than 77 %) for these four volatile compounds. Six e-nose sensors responsive to these four compounds exhibited consistent trends. Therefore, the lower of ethyl 3-methylbutanoate and 1-octen-3-one, the higher of 1-butanol and 1-octen-3-ol in wheat, grown on saline-alkali soil, served as characteristic markers for "wheat aroma".
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Odorantes , Solo , Triticum , Compostos Orgânicos Voláteis , Triticum/química , Compostos Orgânicos Voláteis/análise , Solo/química , Odorantes/análise , Concentração de Íons de Hidrogênio , Álcalis/química , Cromatografia Gasosa-Espectrometria de Massas , Nariz EletrônicoRESUMO
PURPOSE: This study aims to investigate the functions of exocrine islet cell subtypes in the early stage of obesity induced by high-fat diet (HFD), which is accompanied with deterioration of the systemic insulin response and islet subpopulation abnormalities. METHODS: In this study, we analyzed published islet single-cell RNA sequencing (scRNA-seq) datasets from the early stage induced by HFD feeding. Bioinformatics tools such as findMarkers, Cellchat, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology (GO) terms were applied to identify the different functions of exocrine cell clusters. RESULTS: A total of 26 cell clusters were obtained were identified from this dietary intervention model. Most proportions of cell subtypes were consistent between high-fat diet (HFD) and low-fat diet (LFD) groups, except for partial endocrine islet clusters and exocrine clusters. Most differentiated expression of genes in the HFD group was found in exocrine cluster. And we also found that the cell-cell interactions between ductal and endothelial cells were reduced in the HFD group, with the significant alteration in C17 (ductal) cluster. By further analyzing the co-expression regulatory network of transcription in the C17 cluster, we speculate that differentially expressed transcription factors affected the function of duct cells by affecting the expression of related genes in intercellular interaction networks, thereby promoting insulin resistance (IR) development. CONCLUSION: Our results provide a reference for the function and regulatory mechanisms of exocrine cells in the obesity induced by HFD and probably influence the process of following insulin resistance.
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Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1,2. TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications3. Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and Gi1 proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery.
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Ácidos Aristolóquicos , Colesterol , Ácido Flufenâmico , Receptores Acoplados a Proteínas G , Paladar , Humanos , Ácidos Aristolóquicos/metabolismo , Ácidos Aristolóquicos/química , Ácidos Aristolóquicos/farmacologia , Sítios de Ligação/efeitos dos fármacos , Colesterol/química , Colesterol/metabolismo , Colesterol/farmacologia , Microscopia Crioeletrônica , Ácido Flufenâmico/química , Ácido Flufenâmico/metabolismo , Ácido Flufenâmico/farmacologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutação , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/ultraestrutura , Paladar/efeitos dos fármacos , Paladar/fisiologia , Transducina/química , Transducina/metabolismoRESUMO
Setting 7 subsection in abstract Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high-glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study was aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE. DESIGN: This is an in vitro experimental study. PARTICIPANTS: A total of 10 pregnant women with severe preeclampsia (PE) and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. METHODS: The expression and localization of necrotic proteins were assayed in human placenta samples and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor). RESULTS: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine-ß-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. LIMITATIONS: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of preeclampsia. CONCLUSIONS: we proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1, and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H2S protected cytotrophoblasts against CER-induced necroptosis via the p38MAPK pathway.
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CONTEXT.: Most patients with non-small cell lung cancers (NSCLC) are diagnosed at advanced stages. The 5-year survival rate of patients with advanced lung cancer is less than 20%, which makes lung cancer the leading cause of cancer-related deaths worldwide. OBJECTIVE.: To identify indicators that can predict the prognosis of lung cancer patients. DESIGN.: To determine the correlation between circulating tumor cells (CTCs), circulating tumor-derived endothelial cells (CTECs), and their subtypes and the prognosis of patients with NSCLC, 80 patients with lung cancer were recruited and 48 patients who met the enrollment criteria were selected in this study. Peripheral blood was collected from the enrolled patients before any treatment and analyzed by the subtraction enrichment and immunostaining-fluorescence in situ hybridization technique to determine the correlation between CTCs and CTECs and lung cancer disease progression and to identify prognostic indicators. RESULTS.: In all patients, the positive rate of CTCs was 100% and the positive rate of CTECs was 81.3%. The CTEC positivity rate was higher in late-stage patients than in early-stage patients (P = .03). Patients with advanced or lymph node metastases had a higher rate of small-size CTC positivity than those with early or no lymph node metastases. Large-size CTEC positivity was higher in patients with advanced NSCLC than in early-stage patients. Patients with ≥1 small-size CTC had shorter progression-free survival, and it was an independent prognostic factor. CONCLUSIONS.: Small-size CTCs are a reliable prognostic indicator and a probable predictor of the severity of disease in NSCLC patients.
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Antimicrobial peptides (AMPs) constitute a group of small molecular peptides that exhibit a wide range of antimicrobial activity. These peptides are abundantly present in the innate immune system of various organisms. Given the rise of multidrug-resistant bacteria, microbiological studies have identified AMPs as potential natural antibiotics. In the context of antimicrobial resistance across various human pathogens, AMPs hold considerable promise for clinical applications. However, numerous challenges exist in the detection of AMPs, particularly by immunological and molecular biological methods, especially when studying of newly discovered AMPs in proteomics. This review outlines the current status of AMPs research and the strategies employed in their development, considering resent discoveries and methodologies. Subsequently, we focus on the advanced techniques of mass spectrometry for the quantification of AMPs in diverse samples, and analyzes their application, advantages, and limitations. Additionally, we propose suggestions for the future development of tandem mass spectrometry for the detection of AMPs.
RESUMO
Bismuth-telluride-based alloy has long been considered as the most promising candidate for low-grade waste heat power generation. However, optimizing the thermoelectric performance of n-type Bi2Te3 is more challenging than that of p-type counterparts due to its greater sensitivity to texture, and thus limits the advancement of thermoelectric modules. Herein, the thermoelectric performance of n-type Bi2Te3 is enhanced by incorporating a small amount of CuGaTe2, resulting in a peak ZT of 1.25 and a distinguished average ZT of 1.02 (300-500 K). The decomposed Cu+ strengthens interlayer interaction, while Ga+ optimizes carrier concentration within an appropriate range. Simultaneously, the emerged numerous defects, such as small-angle grain boundaries, twin boundaries, and dislocations, significantly suppresses the lattice thermal conductivity. Based on the size optimization by finite element modelling, the constructed thermoelectric module yields a high conversion efficiency of 6.9% and output power density of 0.31 W cm-2 under a temperature gradient of 200 K. Even more crucially, the efficiency and output power little loss after subjecting the module to 40 thermal cycles lasting for 6 days. This study demonstrates the efficient and reliable Bi2Te3-based thermoelectric modules for broad applications in low-grade heat harvest.