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1.
Angew Chem Int Ed Engl ; : e202410246, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046089

RESUMO

In the field of industrial semi-hydrogenation of trace alkynes amidst alkene feedstocks, the pivotal challenge lies in circumventing the hydrogenation of alkenes. Herein, we present Zr(OH)4 as an innovative catalyst for the semi-hydrogenation of phenylacetylene, demonstrating remarkable selectivity towards styrene (>96%), while exhibiting inactivity towards free styrene. Notably, Zr(OH)4 achieves a 95% conversion of quasi-industry 1 mol% phenylacetylene within styrene, with a mere 0.44% styrene loss. Experimental and theoretical results confirm both terminal Zr-O-H and bridge Zr-O-H can dissociate H2, while the terminal Zr-O-H plays a crucial role on activating phenylacetylene through the sequential hydrogenation process of C6H5C≡CH→C6H5C=CH2→C6H5CH=CH2. The high rate of phenylacetylene removal is attributed to its strong adsorption capacity, while Zr(OH)4 has a significantly weaker adsorption capacity for styrene.

2.
Mol Pharm ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046432

RESUMO

This study aimed to evaluate a novel albumin-binding strategy for addressing the challenge of insufficient tumor retention of fibroblast activation protein inhibitors (FAPIs). Maleimide, a molecule capable of covalent binding to free thiol groups, was modified to conjugate with FAPI-04 in order to enhance its binding to endogenous albumin, resulting in an extended blood circulation half-life and increased tumor uptake. DOTA-FAPI-maleimide was prepared and radiolabeled with Ga-68 and Lu-177, followed by cellular assays, pharmacokinetic analysis, PET/CT, and SPECT/CT imaging to assess the probe distribution in various tumor-bearing models. Radiolabeling of the modified probe was successfully achieved with a radiochemical yield of over 99% and remained stable for 144 h. Cellular assays showed that the ligand concentration required for 50% inhibition of the probe was 1.20 ± 0.31 nM, and the Kd was 0.70 ± 0.07 nM with a Bmax of 7.94 ± 0.16 fmol/cell, indicative of higher specificity and affinity of DOTA-FAPI-maleimide compared to other FAPI-04 variants. In addition, DOTA-FAPI-maleimide exhibited a persistent blood clearance half-life of 7.11 ± 0.34 h. PET/CT images showed a tumor uptake of 2.20 ± 0.44%ID/g at 0.5 h p.i., with a tumor/muscle ratio of 5.64 in HT-1080-FAP tumor-bearing models. SPECT/CT images demonstrated long-lasting tumor retention. At 24 h p.i., the tumor uptake of [177Lu]Lu-DOTA-FAPI-maleimide reached 5.04 ± 1.67%ID/g, with stable tumor retention of 3.40 ± 1.95%ID/g after 4 days p.i. In conclusion, we developed and evaluated the thiol group-attaching strategy, which significantly extended the circulation and tumor retention of the adapted FAPI tracer. We envision its potential application for clinical cancer theranostics.

3.
J Immunother Cancer ; 12(7)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043603

RESUMO

BACKGROUND: Lymphocyte activation gene 3 (LAG-3) is expressed on activated immune cells and has emerged as a promising target for immune checkpoints blockade. However, conflicting findings have been reported regarding the association between LAG-3 expression in tumors and patient prognosis, indicating the need for further investigation into the significance of LAG-3 expression levels in tumor therapies. In this study, 68Ga-NOTA-XH05, a novel peptide-based positron emission tomography (PET) tracer targeting LAG-3, was constructed to non-invasively detect LAG-3 expression in melanoma after CpG oligonucleotide (CpG) treatment and explore the relationship between LAG-3 expression and therapeutic effect. METHODS: The tracer 68Ga-NOTA-XH05 was identified by high-performance liquid chromatography after being prepared and purified. Cell uptake and blocking essays were performed to verify the specificity of the tracer in vitro. The expression of LAG-3 in B16-F10 subcutaneous tumors was monitored by flow cytometry, and its correlation with the tracer uptake was analyzed to evaluate the tracer specificity. PET imaging and biodistribution studies were conducted after CpG treatment of unilateral or bilateral B16-F10 subcutaneous tumor models to assess the ability of 68Ga-NOTA-XH05 in monitoring immunotherapy efficacy and the abscopal effect of CpG. RESULTS: Following purification, 68Ga-NOTA-XH05 exhibited high radiochemical purity and specificity. Flow cytometry analysis revealed a positive correlation between LAG-3 expression in tumors and the uptake of 68Ga-NOTA-XH05. In B16-F10 bearing mice treated with CpG, PET imaging using 68Ga-NOTA-XH05 demonstrated a higher tumor to blood ratio (TBR) compared with the control group. Furthermore, TBR values obtained from CpG-treated mice allowed for differentiation between responders and non-responders. In a bilateral subcutaneous tumor model where only right-sided tumors were treated with intratumoral injection of CpG, TBR values of left-sided tumors were significantly higher than those in the control group, indicating that 68Ga-NOTA-XH05 could effectively monitor the systemic effect of local CpG injection. CONCLUSION: Our findings highlight the detection capability of 68Ga-NOTA-XH05 in assessing LAG-3 expression levels within tumors and evaluating response to immunotherapy, thereby suggesting promising clinical translational prospects.


Assuntos
Imunoterapia , Proteína do Gene 3 de Ativação de Linfócitos , Tomografia por Emissão de Pósitrons , Animais , Camundongos , Tomografia por Emissão de Pósitrons/métodos , Imunoterapia/métodos , Humanos , Antígenos CD/metabolismo , Linhagem Celular Tumoral , Melanoma Experimental/diagnóstico por imagem , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Melanoma Experimental/metabolismo , Peptídeos , Radioisótopos de Gálio , Melanoma/diagnóstico por imagem , Melanoma/imunologia , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Feminino , Compostos Radiofarmacêuticos
4.
J Mech Behav Biomed Mater ; 157: 106646, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38981181

RESUMO

Graphene oxide (GO) exhibits excellent mechanical strength and modulus. However, its effectiveness in mechanically reinforcing polymer materials is limited due to issues with interfacial bonding and dispersion arising from differences in the physicochemical properties between GO and polymers. Surface modification using coupling agents is an effective method to improve the bonding problem between polymer and GO, but there may be biocompatibility issues when used in the biomedical field. In this study, the biomolecule L-lysine, was applied to improve the interfacial bonding and dispersion of GO in polylactic acid (PLA) without compromising biocompatibility. The PLA/L-lysine-modified GO (PLA/L-GO) bone scaffold with triply periodic minimal surface (TPMS) structure was prepared using fused deposition modeling (FDM). The FTIR results revealed successful grafting of L-lysine onto GO through the reaction between their -COOH and -NH2 groups. The macroscopic and microscopic morphology characterization indicated that the PLA/L-GO scaffolds exhibited an characteristics of dynamic diameter changes, with good interlayer bonding. It was noteworthy that the L-lysine modification promoted the dispersion of GO and the interfacial bonding with the PLA matrix, as characterized by SEM. As a result, the PLA/0.1L-GO scaffold exhibited higher compressive strength (13.2 MPa) and elastic modulus (226.8 MPa) than PLA/0.1GO. Moreover, PLA/L-GO composite scaffold exhibited superior biomineralization capacity and cell response compared to PLA/GO. In summary, L-lysine not only improved the dispersion and interfacial bonding of GO with PLA, enhancing the mechanical properties, but also improved the biological properties. This study suggests that biomolecules like L-lysine may replace traditional modifiers as an innovative bio-modifier to improve the performance of polymer/inorganic composite biomaterials.

5.
Wideochir Inne Tech Maloinwazyjne ; 19(2): 223-232, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38973788

RESUMO

Introduction: Lateral lymph node dissection (LLND) has now been widely accepted as the optimal procedure to minimize lateral local recurrence (LLR) for selected cases with advanced lower rectal cancer in Asian countries. However, there is still controversy over the preservation or resection of the inferior vesical vessels (IVVs) during LLND due to concerns of impaired post-operative urinary function. Moreover, the standardized procedure for autonomic nerve preservation has not yet been established. Aim: To evaluate the early-stage postoperative voiding function in patients who underwent LLND with uni- versus bilateral resection of the IVVs and to introduce an autonomic nerve sparing technique with a fascial space priority approach (FSPA). Material and methods: LLND was performed in 106 consecutive patients with advanced low rectal cancer at Tianjin Union Medical Center from May 2017 to October 2022. Prospectively collected clinical data were retrospectively compared between patients who received uni-lateral and bilateral LLND. A video with narration was provided to introduce the stepwise procedure of autonomic nerve preservation during IVV resection. Results: The unilateral lymph node dissection (LND) group and the bilateral LND group included 75 and 31 cases, respectively. All LLNDs were performed with FSPA with IVV resection as a standard procedure. No significant differences were observed in overall catheterization days (p = 0.336) and re-catheterization rate (p = 0.575) between groups. No patients in either group suffered from long-term (≥ 30 days) voiding dysfunction. Conclusions: Autonomic nerve sparing is achievable with resection of IVVs during LLND. Satisfactory early-stage voiding function could be obtained with IVV resection on both sides.

6.
Neurospine ; 21(2): 656-664, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38955535

RESUMO

OBJECTIVE: To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors. METHODS: A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs. RESULTS: The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively. CONCLUSION: Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.

7.
World J Oncol ; 15(4): 662-674, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38993257

RESUMO

Background: The clinical role of claudin 8 (CLDN8) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of CLDN8 underlying KIRC were determined. Methods: High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the CLDN8. In-house tissue microarrays and immunochemistry were performed to examine CLDN8 protein expression. A summary receiver operating characteristic curve (SROC) and standardized mean difference (SMD) forest plot were generated using Stata v16.0. Single-cell analysis was conducted to further prove the expression level of CLDN8. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of CLDN8. Functional enrichment analysis was conducted using the Metascape database. Additionally, single-sample gene set enrichment analysis was implied to explore immune cell infiltration in KIRC. Results: A total of 17 mRNA datasets comprising 1,060 KIRC samples and 452 non-cancerous control samples were included in this study. Additionally, 105 KIRC and 16 non-KIRC tissues were analyzed using in-house immunohistochemistry. The combined SMD was -5.25 (95% confidence interval (CI): -6.13 to -4.37), and CLDN8 downregulation yielded an SROC area under the curve (AUC) close to 1.00 (95% CI: 0.99 - 1.00). CLDN8 downregulation was also confirmed at the single-cell level. Knocking out CLDN8 stimulated KIRC cell proliferation. Lower CLDN8 expression was correlated with worse overall survival of KIRC patients (hazard ratio of CLDN8 downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with CLDN8 co-expressed genes were centered on carbon metabolism obstruction, with key hub genes ACADM, ACO2, NDUFS1, PDHB, SDHD, SUCLA2, SUCLG1, and SUCLG2. Conclusions: CLDN8 is downregulated in KIRC and is considered a potential tumor suppressor. CLDN8 deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.

8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 680-686, 2024 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-38948264

RESUMO

Objective: To investigate the effect of empathy on depressive symptoms in adolescents and to explore the potential mediating role of family functioning in the effect of empathy on depressive symptoms. Methods: The 2022 cross-sectional data from the Chengdu Positive Child Development (CPCD) cohort were analyzed in the study. A survey was conducted in Chengdu in June 2022, involving 3020 students in grades 5-8 from three randomly selected stratified schools. The Interpersonal Reactivity Index (IRI-C), the Chinese Family Assessment Instrument (C-FAI), and the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) were used in the survey. Chi-square test or one-way analysis of variance was performed to examine the differences in various demographic characteristics (sex, grade, region, and total monthly household income) between groups of respondents, as well as the differences in family functioning, empathy, and depression. Pearson correlation coefficient was used to examine the correlation between family functioning, empathy, and depressive symptoms. Structural equation modeling and SPSS PROCESS component Model 4 were used to analyze whether family functioning played a mediating role in the effect of empathy on depressive symptoms in adolescents. Results: The detection rate of depressive symptoms among survey respondents was 25.40%. The results of the difference analysis revealed significant differences in the detection rates of depressive symptoms among respondents of different grades, regions, and monthly household incomes (P<0.05). There was no significant difference in the detection rates of depressive symptoms between male and female students. There was a significant difference in the detection rate of depressive symptoms between respondents with different scores for family dysfunction and empathy ability (P<0.001). Correlation analysis results showed that empathy scores were negatively correlated with depression (r=-0.11, P<0.001), that family dysfunction was positively correlated with depression (r=0.29, P<0.001), and that empathy scores were negatively correlated with family functioning (r=-0.37, P<0.001). The mediating role of family dysfunction in the relationship between empathy and depressive symptoms was established, with the direct effect being 0.039 (95% confidence interval [CI]: 0.010-0.069, P<0.001) and the indirect effect value being -0.096 (95% CI: -0.115--0.079, P<0.001). The direct effect value accounted for 28.89% of the total effect value, while the mediation effect value accounted for 71.11% of the total effect value. Conclusion: The empathy ability of adolescents is correlated to depressive symptoms, and family functioning plays a mediating role between empathy and depressive symptoms in adolescents. It is suggested that adolescents' empathy ability and family functioning should be enhanced through multiple channels to reduce the occurrence of depressive symptoms.


Assuntos
Depressão , Empatia , Humanos , Adolescente , Depressão/psicologia , Masculino , Feminino , Estudos Transversais , Inquéritos e Questionários , Relações Familiares/psicologia , Estudantes/psicologia , China , Família/psicologia
9.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1426-1434, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38886442

RESUMO

Biofilm has been used in environmental pollution control in recent years due to its characteristics of adsorption and biodegradation. Beyond the success of its utilization in wastewater treatment, biofilm technique has high application value in the remediation of heavy metals and organic pollutants in soils. With the extensive attention and research of emerging pollutants such as microplastics and antibiotic resistance genes (ARGs), the pivotal role of biofilm can not be overlooked. Here, we presented a comprehensive review of the structure, formation mecha-nism, population, and functional aspects of biofilm, as well as its applications and mechanisms in environmental pollution control in recent years. We emphatically discussed the removal mechanism and application progress of biofilm on heavy metals and organic pollutants. We further expounded some novel environmental challenges posed by biofilm under new circumstances, including the coexistence of various pollutants in plastisphere, the spread of ARGs, and the accumulation of pathogens. Finally, we put forward the gaps of current research and prospects for future research, especially the importance of exploring the interaction relationship and mechanism between biofilm and various pollutants. It is expected to provide theoretical basis for the development of new technology of biofilm remediation.


Assuntos
Biodegradação Ambiental , Biofilmes , Poluição Ambiental , Metais Pesados , Biofilmes/crescimento & desenvolvimento , Poluição Ambiental/prevenção & controle , Poluentes Ambientais , Compostos Orgânicos
10.
Opt Express ; 32(11): 19210-19220, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859060

RESUMO

Optical-fiber-based polarization scramblers can reduce the impact of polarization sensitive performance of various optical fiber systems. Here, we propose a simple and efficient polarization scrambler based on an all-optical Mach-Zehnder structure by combining a polarization beam splitter and an amplified fiber ring. To totally decoherence one polarization split beam, a fiber ring together with an amplifier is incorporated. The ratio of two orthogonal beams can be controlled by varying the amplification factor, and we observe different evolution trajectories of the output state of polarizations on the Poincaré sphere. When the amplification factor exceeds a certain threshold, the scrambler system exhibits nearly ideal polarization scrambling behavior. A commercial single wavelength laser with a linewidth of 3 MHz is utilized to characterize the scrambling performance. We found that when the sampling rate is 1.6 MSa/s, a scrambling speed up to 2000krad/s can be obtained for the average degree of polarization being less than 0.1. We also exploit these random polarization fluctuations to generate random binary numbers, indicating that the proposed technique is a good candidate for a random bit generator.

11.
Neurosci Lett ; 836: 137869, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-38852766

RESUMO

Dietary administration of a copper chelator, cuprizone (CPZ), has long been reported to induce intense and reproducible demyelination of several brain structures such as the corpus callosum. Despite the widespread use of CPZ as an animal model for demyelinating diseases such as multiple sclerosis (MS), the mechanism by which it induces demyelination and then allows robust remyelination is still unclear. An intensive mapping of the cell dynamics of oligodendrocyte (OL) lineage during the de- and remyelination course would be particularly important for a deeper understanding of this model. Here, using a panel of OL lineage cell markers as in situ hybridization (ISH) probes, including Pdgfra, Plp, Mbp, Mog, Enpp6, combined with immunofluorescence staining of CC1, SOX10, we provide a detailed dynamic profile of OL lineage cells during the entire course of the model from 1, 2, 3.5 days, 1, 2, 3, 4,5 weeks of CPZ treatment, as well as after 1, 2, 3, 4 weeks of recovery from CPZ treatment. The result showed an unexpected early death of mature OLs and response of OL progenitor cells (OPCs) in vivo upon CPZ challenge, and a prolonged upregulation of myelin-forming OLs compared to the intact control even 4 weeks after CPZ withdrawal. These data may serve as a basic reference system for future studies of the effects of any intervention on de- and remyelination using the CPZ model, and imply the need to optimize the timing windows for the introduction of pro-remyelination therapies in demyelinating diseases such as MS.


Assuntos
Linhagem da Célula , Cuprizona , Doenças Desmielinizantes , Oligodendroglia , Cuprizona/toxicidade , Animais , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/patologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Oligodendroglia/metabolismo , Modelos Animais de Doenças , Hibridização In Situ/métodos , Camundongos Endogâmicos C57BL , Camundongos , Remielinização/efeitos dos fármacos , Remielinização/fisiologia , Masculino , Quelantes/toxicidade , Quelantes/farmacologia , Bainha de Mielina/patologia , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo
12.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38931393

RESUMO

PURPOSE: This study aimed to evaluate the feasibility of using [68Ga]-fibroblast-activating protein inhibitor (FAPI) positron emission tomography (PET) imaging for diagnosing pulmonary fibrosis in a mouse model. We also examined its value in monitoring treatment response and compared it with traditional [18F]-fluorodeoxyglucose (FDG) PET and computed tomography (CT) imaging. METHODS: A model of idiopathic pulmonary fibrosis was established using intratracheal injection of bleomycin (BLM, 2 mg/kg) into C57BL/6 male mice. For the treatment of IPF, a daily oral dose of 400 mg/kg/day of pirfenidone was administered from 9 to 28 days after the establishment of the model. Disease progression and treatment efficacy were assessed at different stages of the disease every week for four weeks using CT, [18F]FDG PET, and [68Ga]FAPI PET (baseline imaging performed at week 0). Mice were sacrificed and lung tissues were harvested for hematoxylin-eosin staining, picrosirius red staining, and immunohistochemical staining for glucose transporter 1 (GLUT1) and FAP. Expression levels of GLUT1 and FAP in pathological sections were quantified. Correlations between imaging parameters and pathological quantitative values were analyzed. RESULTS: CT, [18F]FDG PET and [68Ga]FAPI PET revealed anatomical and functional changes in the lung that reflected progression of pulmonary fibrosis. In untreated mice with pulmonary fibrosis, lung uptake of [18F]FDG peaked on day 14, while [68Ga]FAPI uptake and mean lung density peaked on day 21. In mice treated with pirfenidone, mean lung density and lung uptake of both PET tracers decreased. Mean lung density, [18F]FDG uptake, and [68Ga]FAPI uptake correlated well with quantitative values of picrosirius red staining, GLUT1 expression, and FAP expression, respectively. Conclusions: Although traditional CT and [18F]FDG PET reflect anatomical and metabolic status in fibrotic lung, [68Ga]FAPI PET provides a means of evaluating fibrosis progression and monitoring treatment response.

13.
Nanotechnology ; 35(38)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38906124

RESUMO

A variety of strategies have been developed to enhance the cycling stability of Si-based anodes in lithium-ion batteries. Although significant progress has been made in enhancing the cycling stability of Si-based anodes, the low initial Coulombic efficiency (ICE) remains a significant challenge to their commercial application. Herein, pitch-based carbon (C) coated Si nanoparticles (NPs) were wrapped by graphene (G) to obtain Si@C/G composite with a small specific surface area of 11.3 m2g-1, resulting in a high ICE of 91.2% at 500 mA g-1. Moreover, the integrated utilization of graphene and soft carbon derived from the low-cost petroleum pitch strongly promotes the electrical conductivity, structure stability, and reaction kinetics of Si NPs. Consequently, the synthesized Si@C/G with a Si loading of 54.7% delivers large reversible capacity (1191 mAh g-1at 500 mA g-1), long cycle life over 200 cycles (a capacity retention of 87.1%), and superior rate capability (952 mAh g-1at 1500 mA g-1). When coupled with a homemade LiNi0.8Co0.1Mn0.1O2(NCM811) cathode in a full cell, it exhibits a promising cycling stability for 200 cycles. This work presents an innovative approach for the manufacture of Si-based anode materials with commercial application.

14.
Materials (Basel) ; 17(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38730927

RESUMO

A new approach is proposed that identifies three different zones of the Si-rich network structure (the cellular structure) in laser powder bed fused (LPBF) AlSi10Mg alloy, based on the variation in morphology, grain growth transition, and melt pool solidification conditions. The three identified zones are denoted in the present work as the liquid solidification zone (LSZ), the mushy solidification zone (MSZ), and the heat affected zone (HAZ). The LSZ is the result of liquid-solid transformation, showing small planar growth at the boundary and large cellular growth in the center, while the MSZ is related to a semisolid reaction, and the HAZ arises from a short-time aging process. The boundary between the LSZ and MSZ is identified by the change of grain growth direction and the Si-rich network advancing direction. The boundary between MSZ and HAZ is identified by the start of the breakdown of the Si-rich network. In addition, it is found that the fracture is generated in and propagates along the HAZ during tensile tests.

15.
Transl Pediatr ; 13(4): 542-554, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38715667

RESUMO

Background: Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. Methods: This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Results: Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Conclusions: Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

16.
J Plant Physiol ; 299: 154258, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38761672

RESUMO

Vacuoles account for 90% of plant cell volume and play important roles in maintaining osmotic pressure, storing metabolites and lysosomes, compartmentalizing harmful ions, and storing and reusing minerals. These functions closely relay on the ion channels and transporters located on the tonoplast. The separation of intact vacuoles from plant cells is the key technology utilized in the study of tonoplast-located ion channels and transporters. However, the current vacuole separation methods are available for Arabidopsis and some other dicotyledons but are lacking for monocot crops. In this study, we established a new method for the vacuole separation from wheat mesophyll cells and investigated the transmembrane proton flux of tonoplasts with non-invasive micro-test technology (NMT). Moreover, our study provides a technology for the study of vacuole functions in monocot crops.


Assuntos
Células do Mesofilo , Triticum , Vacúolos , Triticum/metabolismo , Vacúolos/metabolismo , Células do Mesofilo/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2666-2679, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812167

RESUMO

This study aims to explore the molecular regulatory mechanism of the differential accumulation of flavonoids between 'Xianglei' and the wild type of Lonicera macranthoides. The flowers, stems, and leaves of the two varieties of L. macranthoides were collected. Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS) and high-throughput sequencing(RNA-seq) were employed to screen out the differential flavonoids, key differentially expressed genes(DEGs) and transcription factors(TFs). Fourteen DEGs were randomly selected for verification by qRT-PCR. The results showed that a total of 17 differential flavonoids were obtained, including naringin chalcone, apigenin, and quercetin. The transcriptomic analysis predicted 19 DEGs associated with flavonoids, including 2 genes encoding chitin synthase(CHS) and 3 genes encoding chalcone isomerase(CHI). The regulatory network analysis and weighted gene co-expression network analysis(WGCNA) screen out the key enzyme genes CHS1, FLS1, and HCT regulating the accumulation of flavonoids. MYB12 and LBD4 may be involved in the biosynthesis of flavonoids by regulating the expression of key enzyme genes CHS1, FLS1, and HCT. The qRT-PCR and RNA-seq results were similar regarding the expression patterns of the 14 randomly selected DEGs. This study preliminarily analyzed the transcriptional regulatory mechanism for the differential accumulation of flavonoids in the two varieties of L. macranthoides and laid a foundation for further elucidating the regulatory effects of key enzyme genes and TFs on the accumulation of flavonoids.


Assuntos
Flavonoides , Regulação da Expressão Gênica de Plantas , Lonicera , Metabolômica , Transcriptoma , Lonicera/genética , Lonicera/metabolismo , Lonicera/química , Flavonoides/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-38787395

RESUMO

PURPOSE: The advancement of heterodimeric tracers, renowned for their high sensitivity, marks a significant trend in the development of radiotracers for cancer diagnosis. Our prior work on [68Ga]Ga-HX01, a heterodimeric tracer targeting CD13 and integrin αvß3, led to its approval for phase I clinical trials by the China National Medical Production Administration (NMPA). However, its fast clearance and limited tumor retention pose challenges for broader clinical application in cancer treatment. This study aims to develop a new radiopharmaceutical with increased tumor uptake and prolonged retention, rendering it a potential therapeutic candidate. METHODS: New albumin binder-conjugated compounds were synthesized based on the structure of HX01. In vitro and in vivo evaluation of these new compounds were performed after labelling with 68Ga. Small-animal PET/CT imaging were conducted at different time points at 0.5-6 h post injection (p.i.) using BxPC-3 xenograft mice models. The one with the best imaging performance was further radiolabeled with 177Lu for small-animal SPECT/CT and ex vivo biodistribution investigation. RESULTS: We have synthesized novel albumin binder-conjugated compounds, building upon the structure of HX01. When radiolabeled with 68Ga, all compounds demonstrated improved pharmacokinetics (PK). Small-animal PET/CT studies revealed that these new albumin binder-conjugated compounds, particularly [68Ga]Ga-L6, exhibited significantly enhanced tumor accumulation and retention compared with [68Ga]Ga-L0 without an albumin binder. [68Ga]Ga-L6 outperformed [68Ga]Ga-L7, a compound developed using a previously reported albumin binder. Furthermore, [177Lu]Lu-L6 demonstrated rapid clearance from normal tissues, high tumor uptake, and prolonged retention in small-animal SPECT/CT and biodistribution studies, positioning it as an ideal candidate for radiotherapeutic applications. CONCLUSION: A new integrin αvß3 and CD13 targeting compound was screened out. This compound bears a novel albumin binder and exhibits increased tumor uptake and prolonged tumor retention in BxPC-3 tumors and low background in normal organs, making it a perfect candidate for radiotherapy when radiolabeled with 177Lu.

19.
Neurochem Int ; 178: 105768, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38768685

RESUMO

Recently, there has been increasing attention to bidirectional information exchange between the brain and lungs. Typical physiological data is communicated by channels like the circulation and sympathetic nervous system. However, communication between the brain and lungs can also occur in pathological conditions. Studies have shown that severe traumatic brain injury (TBI), cerebral hemorrhage, subarachnoid hemorrhage (SAH), and other brain diseases can lead to lung damage. Conversely, severe lung diseases such as acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure can exacerbate neuroinflammatory responses, aggravate brain damage, deteriorate neurological function, and result in poor prognosis. A brain or lung injury can have adverse effects on another organ through various pathways, including inflammation, immunity, oxidative stress, neurosecretory factors, microbiome and oxygen. Researchers have increasingly concentrated on possible links between the brain and lungs. However, there has been little attention given to how the interaction between the brain and lungs affects the development of brain or lung disorders, which can lead to clinical states that are susceptible to alterations and can directly affect treatment results. This review described the relationships between the brain and lung in both physiological and pathological conditions, detailing the various pathways of communication such as neurological, inflammatory, immunological, endocrine, and microbiological pathways. Meanwhile, this review provides a comprehensive summary of both pharmacological and non-pharmacological interventions for diseases related to the brain and lungs. It aims to support clinical endeavors in preventing and treating such ailments and serve as a reference for the development of relevant medications.

20.
Phytochem Anal ; 35(5): 1221-1248, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38639073

RESUMO

INTRODUCTION: The active constituents in Aurantii Fructus sourced from different regions within Hunan Province exhibit variations, with certain samples demonstrating substandard quality. OBJECTIVES: The aim of this study is to conduct a comparative analysis of the chemical composition and quality of Aurantii Fructus from various sources, establish a robust methodology for quality evaluation, and determine the optimal harvesting period. MATERIALS AND METHODS: The components of Aurantii Fructus were qualitatively analyzed using a non-targeted metabolomics approach. Multivariate statistical analyses were conducted to identify potential markers, enabling qualitative and quantitative evaluation of the quality and optimal harvest period of Aurantii Fructus. RESULTS: Overall, 155 compounds were identified in Aurantii Fructus, with Huangpi exhibiting the highest number of components. Eleven potential markers were selected to assess the quality of Aurantii Fructus. The average content of Huangpi was the highest, indicating a high level of similarity. The samples' overall scores were ordered as follows: Huangpi > Xiangcheng > Choucheng > Daidai. Anren and Changde's Huangpi exhibited high contents, being rich in chemical components, resulting in favorable scores. Similarly, Changde's Xiangcheng displayed significant medicinal value. As the harvest time was delayed, there was an increase in fruit size, accompanied by thinner peels and a continuous decrease in the contents of potential markers. The best harvest period of Aurantii Fructus was within 1 week before and after the Lesser Heat. CONCLUSION: The present study establishes a precise and efficient method for evaluating the quality of Aurantii Fructus, thereby providing more comprehensive insights into its composition. This research lays the foundation for subsequent development and utilization of Aurantii Fructus.


Assuntos
Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Controle de Qualidade , Citrus/química , Frutas/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Metabolômica/métodos
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