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Uncontrollable dendrite growth and corrosion induced by reactive water molecules and sulfate ions (SO42-) seriously hindered the practical application of aqueous zinc ion batteries (AZIBs). Here we construct artificial solid electrolyte interfaces (SEIs) realized by sodium and calcium bentonite with a layered structure anchored to anodes (NB@Zn and CB@Zn). This artificial SEI layer functioning as a protective coating to isolate activated water molecules, provides high-speed transport channels for Zn2+, and serves as an ionic sieve to repel negatively charged anions while attracting positively charged cations. The theoretical results show that the bentonite electrodes exhibit a higher binding energy for Zn2+. This demonstrates that the bentonite protective layer enhances the Zn-ion deposition kinetics. Consequently, the NB@Zn//MnO2 and CB@Zn//MnO2 full-battery capacities are 96.7 and 70.4 mAh g-1 at 2.0 A g-1 after 1000 cycles, respectively. This study aims to stabilize Zn anodes and improve the electrochemical performance of AZIBs by ion-selection sieving.
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Actinobacteria have a complex life cycle, including morphological and physiological differentiation which are often associated with the biosynthesis of secondary metabolites. Recently, increased interest in post-translational modifications (PTMs) in these Gram-positive bacteria has highlighted the importance of PTMs as signals that provide functional diversity and regulation by modifying proteins to respond to diverse stimuli. Here, we review the developments in research on acylation, a typical PTM that uses acyl-CoA or related metabolites as donors, as well as the understanding of the direct link provided by acylation between cell metabolism and signal transduction, transcriptional regulation, cell growth, and pathogenicity in Actinobacteria.
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Actinobacteria , Virulência , Transdução de Sinais , Acilação , Proteínas , Processamento de Proteína Pós-TraducionalRESUMO
BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.
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Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Instabilidade de Microssatélites , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Idoso , Adulto , Reparo de Erro de Pareamento de DNA , Quimioterapia Adjuvante/métodos , SeguimentosRESUMO
BACKGROUND AND AIMS: We evaluated the efficacy and safety of the antiangiogenic tyrosine kinase inhibitor anlotinib plus TQB2450, a programmed death-ligand 1 inhibitor in pretreated advanced biliary tract cancers (BTCs). APPROACH AND RESULTS: In this pooled analysis of two single-center, phase Ib clinical trials (TQB2450-Ib-05 and TQB2450-Ib-08 trials), 66 patients with advanced BTCs who had progressed or declined or were ineligible for first-line chemotherapy were included. With the treatment of anlotinib plus TQB2450, two patients achieved complete response, and 12 had a partial response assessed by Response Evaluation Criteria in Solid Tumors 1.1, yielding an objective response rate of 21.21%, a disease control rate (DCR) of 72.73%, and a clinical benefit rate (CBR) of 42.42%. With a median follow-up of 19.68 months, median progression-free survival (PFS) and overall survival (OS) were 6.24 (95% confidence interval [CI], 4.11-8.25) and 15.77 (95% CI, 10.74-19.71) months, respectively. Adverse events (AEs) were reported in 64 (96.97%) patients, and the most common grade 3 or worse treatment-related AEs included elevated levels of aspartate aminotransferase (7.58%), alanine aminotransferase (6.06%), and hypertension (6.06%). Patients with high tumor mutational burden (TMB; ≥5 mutations/Mbp) had a better CBR (70.8% vs. 22.2%), longer OS (14.32 vs. 9.64 months), and a trend toward longer PFS (7.03 vs. 4.06 months). Patients with kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations showed a lower CBR (12.5% vs. 58.8%) and shorter PFS (2.02 vs. 6.80 months) and OS (10.53 vs. 13.13 months). CONCLUSIONS: Anlotinib combined with TQB2450 showed promising efficacy and was well tolerated in advanced BTCs. KRAS mutation and high TMB might serve as predictors of treatment efficacy.
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Neoplasias do Sistema Biliar , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Indóis/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia , BiomarcadoresRESUMO
BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Invasividade Neoplásica , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Microvasos/diagnóstico por imagem , Microvasos/patologia , Intervalo Livre de Doença , Recidiva Local de NeoplasiaRESUMO
This study investigated the potential role of the mouse homolog of bombesin receptor-activated protein (BRAP) in imiquimod (IMQ) induced psoriasis - like skin inflammation. The expression of both human BRAP, encoded by C6orf89, and its mouse homolog, encoded by BC004004, has been found to be expressed abundantly in the keratinocytes. BC004004 knockout mice (BC004004-/-) were topically treated with IMQ daily for 7 days to test whether they were more vulnerable to psoriasis - like inflammation. We found that those mice exhibited an altered pattern of inflammation process compared to isogenic wild type control mice (BC004004+/+). BC004004-/- mice developed skin lesions with earlier and more acute onset, as well as a quicker remission. The cytokines related to pathogenesis of psoriasis also exhibited different expression patterns in IMQ treated BC004004-/- mice. On day 4 of IMQ treatment, BC004004-/- mice exhibited a higher expression level of IL-17A compared to BC004004+/+ mice, suggesting a more robust activation of Th17 cells in the knockout mice. The serum level of thymic stromal lymphopoietin (TSLP), one of the keratinocyte derived cytokines, was also increased in BC004004-/- mice and reached its peak on day 4. Knockdown of BRAP in cultured human keratinocyte-derived HaCaT cells by siRNA silencing led to increased release of TSLP. Our data suggest that the elevated of level of TSLP released from keratinocytes due to BRAP deficiency might mediate the crosstalk between the epidermal cells and immune cells and thereby contributing to the altered pathological changes observed in psoriasis - like skin lesion in knockout mice.
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Psoríase , Receptores da Bombesina , Camundongos , Humanos , Animais , Receptores da Bombesina/genética , Receptores da Bombesina/metabolismo , Queratinócitos/metabolismo , Imiquimode/metabolismo , Inflamação/patologia , Citocinas/metabolismo , Camundongos Knockout , Modelos Animais de Doenças , Pele/patologia , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common consequence of osteoporosis and can significantly impact the quality of life for affected individuals. Despite treatment options such as vertebroplasty and kyphoplasty, many patients continue to experience residual back pain (RBP) even after the fracture has healed. The incidence of RBP after OVCF treatment varies among studies, and there is a need for further research to understand the risk factors associated with RBP. METHODS: A systematic review and meta-analysis were conducted following the PRISMA guidelines. Electronic databases were searched, and relevant studies were selected based on inclusion and exclusion criteria. Data extraction and quality assessment were performed independently by two authors. Statistical analysis included single-proportion meta-analyses and pooling of odds ratios (OR) using the inverse-variance method, to calculate the overall incidences of RBP and cement leakage and identify risk factors associated with RBP. RESULTS: A total of 19 studies were included in the analysis. The overall incidences of RBP and cement leakage were found to be 16% and 18%, respectively. Several risk factors were identified, including gender, bone mineral density, depression, baseline visual analog scale (VAS) score, intravertebral vacuum cleft, number of fractured segments, cement distribution, history of vertebral fracture, thoracolumbar fascial injury, and fracture non-union. CONCLUSIONS: This study provides potential value within the scope of the incidence and risk factors of RBP following treatment of OVCFs. The identified risk factors can help clinicians identify high-risk patients and tailor appropriate interventions. Future research should focus on standardizing the definition of RBP and patient selection criteria to improve the accuracy of estimates and facilitate better management strategies for OVCF patients.
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Objective To evaluate the effect of surgical treatment on extracranial supra-aortic aneurysms and summarize the experience.Methods The clinical data of 10 patients undergoing surgical treatment of extracranial supra-aortic aneurysms from May 2019 to November 2023 in the Department of Vascular Surgery of Beijing Tiantan Hospital affiliated to Capital Medical University were collected.The 10 patients included 5 patients with internal carotid artery aneurysm,2 patients with subclavian artery aneurysm,2 patients with vertebral artery aneurysm,and 1 patient with internal carotid artery aneurysm combined with ipsilateral subclavian artery aneurysm.The surgical indications,surgical regimens,clinical efficacy,and complications were retrospectively analyzed. Results All the 10 patients underwent surgery successfully,with the surgery duration range of 60-420 min and the median surgery duration of 180.0 (121.5,307.5) min.Intraoperative bleeding volume varied within 30-400 mL,with a median of 90 (50,125) mL.The time of carotid artery blocking and vertebral artery blocking varied within the ranges of 10-20 min and 20-30 min,with the medians of 15.0 (11.5,16.3) min and 25.0 (15.0,22.5) min,respectively.No cardiac accident,cerebral infarction,or cerebral hemorrhage occurred during the perioperative period.The 10 patients were followed up for 3-58 months,with the median follow-up time of 8.5 (5.3,17.0) months.One patient with subclavian artery aneurysm developed artificial vessel occlusion 20 months after surgery.One patient with internal carotid artery aneurysm developed distal carotid artery stenosis 6 months after surgery. Conclusion Surgical treatment should be actively adopted for extracranial supra-aortic aneurysms,and individualized surgical regimens should be designed according to patient conditions.
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Objective: There is an ongoing debate about whether the management of gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) should follow the guidelines of small-cell lung cancer (SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart. Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing (NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC (LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes. Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas. Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC ( TERT amplification), colorectal NEC ( KRAS mutation), and bile tract NEC ( ARID1A mutation). The gene disparities between small-cell NEC (SCNEC) and large-cell NEC (LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/ RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in 22.2% of the patients, and they had longer progression-free survival (PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40 (0.21-0.75), P=0.006]. Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.
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When it comes to mass spectrometry data analysis for identification of peptide pairs linked by N-hydroxysuccinimide (NHS) ester cross-linkers, search engines bifurcate in their setting of cross-linkable sites. Some restrict NHS ester cross-linkable sites to lysine (K) and protein N-terminus, referred to as K only for short, whereas others additionally include serine (S), threonine (T), and tyrosine (Y) by default. Here, by setting amino acids with chemically inert side chains such as glycine (G), valine (V), and leucine (L) as cross-linkable sites, which serves as a negative control, we show that software-identified STY-cross-links are only as reliable as GVL-cross-links. This is true across different NHS ester cross-linkers including DSS, DSSO, and DSBU, and across different search engines including MeroX, xiSearch, and pLink. Using a published data set originated from synthetic peptides, we demonstrate that STY-cross-links indeed have a high false discovery rate. Further analysis revealed that depending on the data and the search engine used to analyze the data, up to 65% of the STY-cross-links identified are actually K-K cross-links of the same peptide pairs, up to 61% are actually K-mono-links, and the rest tend to contain short peptides at high risk of false identification.
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Ésteres , Proteínas , Reagentes de Ligações Cruzadas/química , Espectrometria de Massas/métodos , Peptídeos/química , Proteínas/metabolismoRESUMO
Aqueous Zn-ion batteries (AZIBs) attract intensive attention owing to their environmental friendliness, cost-effectiveness, innate safety, and high specific capacity. However, the practical applications of AZIBs are hindered by several adverse phenomena, including corrosion, Zn dendrites, and hydrogen evolution. Herein, a Zn anode decorated with a 3D porous-structured Na3 V2 (PO4)3 (NVP@Zn) is obtained, where the NVP reconstruct the electrolyte/anode interface. The resulting NVP@Zn anode can provide a large quantity of fast and stable channels, facilitating enhanced Zn ion deposition kinetics and regulating the Zn ions transport process through the ion confinement effect. The NASICON-type NVP protective layer promote the desolvation process due to its nanopore structure, thus effectively avoiding side reactions. Theoretical calculations indicate that the NVP@Zn electrode has a higher Zn ion binding energy and a higher migration barrier, which demonstrates that NVP protective layer can enhance Zn ion deposition kinetics and prevent the unfettered 2D diffusion of Zn ions. Therefore, the results show that NVP@Zn/MnO2 full cell can maintain a high specific discharge capacity of 168 mAh g-1 and a high-capacity retention rate of 74.6% after cycling. The extraordinary results obtained with this strategy have confirmed the promising applications of NVP in high-performance AZIBs.
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Reconfiguration of zinc anodes efficiently mitigates dendrite formation and undesirable side reactions, thus favoring the long-term cycling performance of aqueous zinc ion batteries (AZIBs). This study synthesizes a Zn@Bi alloy anode (Zn@Bi) using the fusion method, and find that the anode surfaces synthesized using this method have an extremely high percentage of Zn(002) crystalline surfaces. Experimental results indicate that the addition of bismuth inhibits the hydrogen evolution reaction and corrosion of zinc anodes. The finite-element simulation results indicate that Zn@Bi can effectively achieve a uniform anodic electric field, thereby regulating the homogeneous depositions of zinc ions and reducing the production of Zn dendrite. Theoretical calculations reveal that the incorporation of Bi favors the anode structure stabilization and higher adsorption energy of Zn@Bi corresponds to better Zn deposition kinetics. The Zn@Bi//Zn@Bi symmetric cell demonstrates an extended cycle life of 1000 h. Furthermore, when pairing Zn@Bi with an α-MnO2 cathode to construct a Zn@Bi//MnO2 cell, a specific capacity of 119.3 mAh g-1 is maintained even after 1700 cycles at 1.2 A g-1 . This study sheds light on the development of dendrite-free anodes for advanced AZIBs.
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Renal fibrosis is a progressive, fatal renal disease characterized by the aberrant accumulation of myofibroblasts that produce excess extracellular matrix (ECM) in the renal interstitium and glomeruli. Yes-associated protein (YAP) has been regarded as a crucial modulator in myofibroblast transformation, but its upstream regulator remains a mystery. In the present study investigating the participation of m6A methylation during renal fibrosis through bioinformatics analysis, we identified YTHDF1, a modulator of m6A methylation, as a key contributor for renal fibrosis because it was highly expressed in human fibrotic kidneys and had a significant correction with YAP. Their co-localization in human fibrotic kidneys was additionally shown by immunofluorescence. We then found that YTHDF1 was also up-regulated in fibrotic mouse kidneys induced by unilateral ureteral obstruction (UUO), high-dose folic acid administration, or the unilateral ischemia-reperfusion injury, further supporting a causal role of YTHDF1 during renal fibrosis. Consistent with this notion, YTHDF1 knockdown alleviated the progression of renal fibrosis both in cultured cells induced by transforming growth factor-beta administration and in the UUO mouse model. Meanwhile, YAP was accordingly down-regulated when YTHDF1 was inhibited. Furthermore, the specific binding of YTHDF1 to YAP mRNA was detected using RNA Binding Protein Immunoprecipitation, and the up-regulation of fibrotic related molecules in cultured cells induced by YTHDF1 over-expression plasmid was attenuated by YAP siRNA. Taken together, our data highlight the potential utility of YTHDF1 as an indicator for renal fibrosis and suggest that YTHDF1 inhibition might be a promising therapeutic strategy to alleviate renal fibrosis via downregulating YAP.
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Proteínas de Ciclo Celular/genética , Fibrose/genética , Nefropatias/genética , Rim/patologia , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética , Regulação para Cima/genética , Animais , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo/genética , Matriz Extracelular/genética , Fibroblastos/patologia , Fibrose/patologia , Humanos , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/patologia , RNA Mensageiro/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Obstrução Ureteral/genética , Obstrução Ureteral/patologiaRESUMO
Bombesin receptor-activated protein (BRAP) and its homologous protein in mice, which is encoded by bc004004 gene, were expressed abundantly in brain tissues with unknown functions. We treated bc004004-/- mice with chronic unpredictable mild stress (CUMS) to test whether those mice were more vulnerable to stress-related disorders. The results of forced swimming test, sucrose preference test, and open field test showed that after being treated with CUMS for 28 days or 35 days both bc004004-/- and bc004004+/+ mice exhibited behavioural changes and there was no significant difference between bc004004+/+ and bc004004-/-. However, behavioural changes were observed only in bc004004-/- mice after being exposed to CUMS for 21 days, but not in bc004004+/+ after 21-day CUMS exposure, indicating that lack of BRAP homologous protein may cause vulnerability to stress-related disorders in mice. In addition, bc004004-/- mice showed a reduction in recognition memory as revealed by novel object recognition test. Since memory changes and stress related behavioural changes are all closely related to the hippocampus function we further analyzed the changes of dendrites and synapses of hippocampal neurons as well as expression levels of some proteins closely related to synaptic function. bc004004-/- mice exhibited decreased dendritic lengths and increased amount of immature spines, as well as altered expression pattern of synaptic related proteins including GluN2A, synaptophysin and BDNF in the hippocampus. Those findings suggest that BRAP homologous protein may have a protective effect on the behavioural response to stress via regulating dendritic spine formation and synaptic plasticity in the hippocampus.
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Bombesina , Espinhas Dendríticas , Hipocampo , Plasticidade Neuronal , Receptores da Bombesina , Estresse Psicológico , Animais , Camundongos , Bombesina/genética , Bombesina/metabolismo , Doença Crônica , Espinhas Dendríticas/genética , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/patologia , Depressão/genética , Depressão/metabolismo , Depressão/patologia , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/patologia , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Receptores da Bombesina/genética , Receptores da Bombesina/metabolismo , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Estresse Psicológico/patologiaRESUMO
Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKCγ-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKCγ knockdown remarkably increased neuronal death after OGD. We also found that cPKCγ knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKCγ could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKCγ knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKCγ knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKCγ partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.
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Traumatismo por Reperfusão , Transdução de Sinais , Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Glucose/metabolismo , Isquemia/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/uso terapêutico , Animais , CamundongosRESUMO
Over the past few decades, the design and construction of high-efficiency artificial light-harvesting systems (LHSs) involving multistep fluorescence-resonance energy transfer (FRET) processes have gradually received considerable attention within wide fields ranging from supramolecular chemistry to chemical biology and even materials science. Herein, through coordination-driven self-assembly, a novel tetragonal prismatic metallacage featuring a FRET process using tetraphenylethene (TPE) units as donors and BODIPY units as acceptors has been conveniently synthesized. Subsequently, taking advantage of supramolecular hydrophobic interactions, a promising artificial LHS involving two-step FRET processes from TPE to BODIPY and then to Nile Red (NiR) has been successfully fabricated in an aqueous solution using the FRET-featuring metallacage, NiR, and an amphiphilic polymer (mPEG-DSPE). Notably, this obtained aqueous LHS exhibits highly efficient photocatalytic activity in the dehalogenation of a bromoacetophenone derivate. This study provides a unique strategy for fabricating artificial LHSs in aqueous solutions with multistep FRET processes and further promotes the future development of mimicking the photosynthesis process.
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The inherent cross-sensitivity of semiconductor gas sensors makes them extremely challenging to accurately detect mixed gases. In order to solve this problem, this paper designed an electronic nose (E-nose) with seven gas sensors and proposed a rapid method for identifying CH4, CO, and their mixtures. Most reported methods for E-nose were based on analyzing the entire response process and employing complex algorithms, such as neural network, which result in long time-consuming processes for gas detection and identification. To overcome these shortcomings, this paper firstly proposes a way to shorten the gas detection time by analyzing only the start stage of the E-nose response instead of the entire response process. Subsequently, two polynomial fitting methods for extracting gas features are designed according to the characteristics of the E-nose response curves. Finally, in order to shorten the time consumption of calculation and reduce the complexity of the identification model, linear discriminant analysis (LDA) is introduced to reduce the dimensionality of the extracted feature datasets, and an XGBoost-based gas identification model is trained using the LDA optimized feature datasets. The experimental results show that the proposed method can shorten the gas detection time, obtain sufficient gas features, and achieve nearly 100% identification accuracy for CH4, CO, and their mixed gases.
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Objective To evaluate the effect of surgical reconstruction of extracranial vertebral artery and to summarize the experience. Methods The clinical data of 15 patients undergoing surgical reconstruction of extracranial vertebral artery from September 2018 to June 2022 were collected.The operation methods,operation duration,intraoperative blood loss,operation complications,and relief of symptoms were retrospectively analyzed. Results Eleven patients underwent vertebral artery (V1 segment) to common carotid artery transposition,two patients underwent endarterectomy of V1 segment,two patients underwent V3 segment to external carotid artery bypass or transposition.The operation duration,intraoperative blood loss,and blocking time of common carotid artery varied within 120-340 min,50-300 ml,and 12-25 min,with the medians of 240 min,100 ml,and 16 min,respectively.There was no cardiac accident,cerebral hyperperfusion syndrome,cerebral hemorrhage or lymphatic leakage during the perioperative period.One patient suffered from cerebral infarction and three patients suffered from incomplete Horner's syndrome after the operation.During the follow-up (4-45 months,median of 26 months),there was no anastomotic stenosis,new cerebral infarction or cerebral ischemia. Conclusion Surgical reconstruction of extracranial vertebral artery is safe and effective,and individualized reconstruction strategy should be adopted according to different conditions.
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Isquemia Encefálica , Artéria Vertebral , Humanos , Artéria Vertebral/cirurgia , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Infarto CerebralRESUMO
OBJECTIVES: To investigate changes in complement component 3 (C3) levels in children with sepsis and its correlation with the severity of sepsis and to explore the significance of C3 in predicting mortality in children with sepsis. METHODS: A retrospective analysis was conducted on 529 children with sepsis who were admitted to the Pediatric Intensive Care Unit in Hunan Children's Hospital between November 2019 and September 2021. The children were categorized into two groups based on their prognosis at day 28 after sepsis diagnosis: the survival group (n=471) and the death group (n=58). Additionally, the children were divided into normal C3 group (n=273) and reduced C3 group (n=256) based on the median C3 level (0.77 g/L) within 24 hours of admission. Clinical data and laboratory markers were compared between the groups, and assess the predictive value of C3 levels in relation to sepsis-related mortality. RESULTS: The death group exhibited significantly lower C3 levels compared to the survival group (P<0.05). Multivariate logistic regression analysis revealed that higher pediatric Sequential Organ Failure Assessment (p-SOFA) scores and lower C3 levels were closely associated with sepsis-related mortality (P<0.05). The receiver operating characteristic curve (ROC) analysis demonstrated that combination of p-SOFA scores and C3 levels yielded an area under the ROC curve of 0.852, which was higher than that of each indicator alone (P<0.05). CONCLUSIONS: C3 can serve as an indicator to assess the severity and prognosis of sepsis in children. The combination of p-SOFA scores and C3 levels holds good predictive value for mortality in children with sepsis.
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The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol is realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) with organophotoredox catalysis under blue light irradiation. A broad scope of readily accessible alkenes featuring a variety of functional groups and drug and natural product moieties could be selectively difluoromethylated with good efficiency in a metal-free manner. Combined experimental and computational studies suggest that the key XAT process of ClCF2H is both thermodynamically and kinetically favored over the hydrogen atom transfer pathway owing to the formation of a strong boron-chlorine (B-Cl) bond and the low-lying antibonding orbital of the carbon-chlorine (C-Cl) bond.