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1.
J Orthop ; 60: 83-88, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39355805

RESUMO

Background: Primary malignant bone tumor is a disease that can lead to death. The usually applied clinical treatment strategy is surgical resection of the primary tumor. However, tumor cells are difficult to clean up, easy to make the tumor recurrence, and the bone defect caused by surgical resection also hindered the postoperative recovery. Materials and methods: Herein, in this work, mesoporous hydroxyapatite (HA) coating with petal-structure was prepared on titanium (Ti) implant surfaces by micro-arc oxidation (MAO) to accelerate the bone growth, and then paclitaxel (PTX) loaded lignin nanospheres were deposited into the HA coatings to get a sustained release for killing residual tumor cells. Results: The results showed that many gaps and holes of micro-scale were formed in the petal-structured HA coatings, they worked as traps for the PTX loaded nanospheres to enhance the deposited amount and immobilization stability, playing good role of drug loading platform. The encapsulation of PTX by lignin ensured a lower release rate and a higher sustaining release time when compared with the PTX without encapsulation. In addition, the HA coating with PTX loaded lignin nanospheres showed higher killing effect to tumor cells than to osteoblast. Conclusion: The mesoporous HA coating with paclitaxel loaded lignin nanospheres endowed the titanium surface with good biological property and tumor cell-killing effect, so the obtained Ti-based material had a highly hopeful application as the localized implant for therapy of primary malignant bone tumor.

2.
Chem Biodivers ; : e202402016, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392379

RESUMO

To remove the toxicity of 10-Pterostilbene methylamine hydrochloride derivatives (PMDS . HCl) and develop novel anti-inflammatory agents, twenty-five Pterostilbene-urea derivatives (PUDs, Q1-Q25) derived from PMDs were designed, synthesized, characterized by spectroscopic techniques and their anti-inflammatory activity in vitro were evaluated. Results exhibited that compounds (Q1-Q25) were low toxic or non-toxic toward RAW264.7 and L02 cell lines at 20 µM/L. Eight bioactive agents (Q4-Q10, Q20) displayed obvious inhibition ability against LPS-induced NO release, with IC50(NO) values ranged from 9.96 to 33.89 µM/L. Meanwhile, they were potential COX-2 inhibitors with IC50(COX-2) values ranging from 39.42 to 179.84 nM/L. A roughly positive correlation were observed between the inhibitory abilities on LPS-induced NO release and those on COX-2. Q7 , Q10and Q20 manifested stronger COX-2 inhibitory abilities than Celecoxib . The strongest anti-inflammatory agent, Q20 (IC50 (NO) = 9.96 µM/L, IC50(COX-2) = 39.42 nM/L) effectively inhibited the secretion of pro-inflammatory factors such as IL-1ß (IC50 = 12.30 µM/L) and TNF-α (IC50 = 9.07 µM/L) in a dose-dependent manner. Western Blot analysis indicated that at low micromolar concentrations, Q20 obviously down-regulated the expression of COX-2, iNOS as well as TLR4 protein, and suppressed the activation of NLRP3 inflammasome and NF-κB signal pathway.

3.
Environ Health Perspect ; 132(10): 107005, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39422607

RESUMO

BACKGROUND: Some pesticides have been shown to interfere with thyroid functions through changes in thyroid hormone (TH) levels. However, few human studies have explored associations between TH levels and environmental exposure to currently used pesticides, including neonicotinoids, phenylpyrazoles, phenoxy acids, and azoles. Moreover, such studies often measure biomarkers of exposure in urine or blood, and thus reveal only recent exposure. In contrast, hair has been demonstrated to be a suitable matrix for assessing chronic exposure to both persistent and nonpersistent organic pollutants. OBJECTIVES: We investigated 54 biomarkers of pollutant exposure in relation to tetraiodothyronine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), and 3,3'-diiodothyronine (T2). METHODS: In a cross-sectional study of 196 healthy Chinese women of reproductive age (25-45 years of age), concentrations of both pollutants and THs were analyzed in the first 12cm (starting from the scalp) of the hair matrix, collected in 2016. Associations between pollutants and TH levels were explored using stability-enhanced least absolute shrinkage and selection operator (lasso) by regressing all exposures against each outcome of interest, adjusted for age, body mass index, and city. RESULTS: Each TH was associated with the mixture of at least eight of the examined pesticides. We found associations of ß-HCH, PCP, DMP, DETP, 3Me4NP, carbofuran, ClCF3CA, imidacloprid, 2,4-D, metolachlor, difenoconazole, and tebuconazole with THs. For example, a 2-standard deviation (SD) increase in log10-transformed hair DMP concentration was associated with lower hair T4 concentration [-15.0% (95% CI: -26.1, -2.21%)] and higher hair T3 concentration [8.16% (95% CI: 1.73, 15.0%)] in the adjusted unpenalized regression models. We also found associations of some pesticides with T3/T4, rT3/T4, and rT3/T3 molar ratios, including PCP, DMP, 2,4-D, metolachlor, difenoconazole, and tebuconazole. DISCUSSION: Our results suggest that exposure to the low levels of pesticides examined here may disrupt thyroid homeostasis in humans. Further studies are needed to confirm our results and to evaluate the long-term consequences of these subtle interferences. https://doi.org/10.1289/EHP14378.


Assuntos
Exposição Ambiental , Praguicidas , Hormônios Tireóideos , Humanos , Feminino , Exposição Ambiental/estatística & dados numéricos , Estudos Transversais , Adulto , China , Praguicidas/análise , Hormônios Tireóideos/sangue , Pessoa de Meia-Idade , Cabelo/química , Poluentes Ambientais/análise , Biomarcadores/urina
4.
J Hazard Mater ; 480: 136033, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39368358

RESUMO

Triclosan (TCS) is an antimicrobial agent commonly used in personal care products. However, little is known about its toxicity to corals. Here, we examined the acute toxic effects (96 h) of TCS at different levels to the coral Porites lutea. Results showed that the bioaccumulation factors (BAFs) of TCS in Porites lutea decreased with increasing TCS exposure levels. Exposure to TCS at the level up to 100 µg/L did not induce bleaching of Porites lutea. However, by the end of the experiment, both the density and chlorophyll a content of the symbiotic zooxanthellae were 19-52 % and 19.9-45.6 % lower in the TCS treatment groups than in the control, respectively. For the coral host, its total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT) activities were all significantly lower in the TCS treatment groups than the control. Transcriptome analysis showed that 942 and 1077 differentially expressed genes (DEGs) were identified in the coral host in the 0.5 and 100 µg/L TCS treatment groups, respectively. Meanwhile, TCS can interfere with pathways related to immune system and reproductive system in coral host. Overall, our results suggest that environmentally relevant concentrations of TCS can impact both the coral host and the symbiotic zooxanthellae.

5.
Int J Biol Macromol ; : 135930, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39443170

RESUMO

Developing sustainable matrix and efficient bonding mode for preparing room temperature phosphorescence (RTP) materials with full-color afterglows is attractive but still challenging. Here, xylan, a hemicellulose by-product from the paper mill, is used to construct full-color RTP materials based on imine bonds. Xylan is oxidation by periodate to introduce aldehyde groups to increase reaction sites; aromatic amines with different π conjugations can be readily anchored to dialdehyde xylan (DAX) by imine chemistry. The dual rigid environments were constructed by hydrogen bonding and imine covalent bonding, which can facilitate the triplet population and suppress non-radiative transitions, thus the xylan derivatives display satisfactory RTP performances. As the degree of conjugation of the chromophore increases, the afterglow colors can be changed from blue to green, yellow, and then to red. Thus, such a universal, facile, and eco-friendly strategy can be used to fabricate full-color RTP materials, which show a bright future in information encryption and advanced anti-counterfeiting. These results unambiguously state that the biodegradable paper mill waste-based RTP materials are convincingly expected to replace and surpass petroleum polymer-based counterparts.

6.
Front Pharmacol ; 15: 1439232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39318775

RESUMO

Objectives: Significant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens. Methods: We conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis. Results: Nineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39 h-1, 2690 L, and 42.87 L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F. Conclusion: Our findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.

7.
Pest Manag Sci ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39344702

RESUMO

BACKGROUND: The development of fungicides with low cross resistance, high efficacy and low resistance plays a central role in protecting crops, reducing yield losses, improving quality and maintaining global food security. Based on this important role, after a systematic optimization strategy, novel heterocyclic amide derivatives bearing diphenylmethyl fragment were screened, synthesized and verified with the spectrographic and x-ray diffraction analysis. RESULTS: In this study, the aforementioned optimization obtained compound B19 that was measured for antifungal activity against Rhizoctonia solani (median effective concentration, EC50 = 1.11 µg mL-1). Meanwhile, the anti-R. solani protective effect (79.34%) of compound B19 was evaluated in vivo at 100 µg mL-1, which is comparable to that of the control agent fluxapyroxad (80.67%). Thence, morphological observations revealed that compound B19 induced mycelium disruption and shrinking, mitochondrial number reduction and apoptosis acceleration, consistent with the results of the mitochondrial membrane potential and cell membrane permeability. Further investigations found that the potential target enzyme of compound B19 was SDH, which exerted fluorescence quenching dynamic curves similar to that of the commercialized SDHI fluxapyroxad. Additionally, research by molecular docking and MD simulations demonstrated that compound B19 had a similar binding mode acting on the surrounding residues in the SDH active pocket to that offluxapyroxad. CONCLUSION: The above results demonstrated that heterocyclic amide derivatives containing a diphenylmethyl moiety are promising scaffolds for targeting SDH of fungi and provide valuable antifungal leads with the potential to develop new SDH inhibitors. © 2024 Society of Chemical Industry.

8.
Environ Pollut ; 361: 124885, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233271

RESUMO

Polybrominated diphenyl ethers (PBDEs) and their alternatives (e.g., dechlorane plus (DPs) and decabromodiphenyl ethane (DBDPE)) are ubiquitous in various environmental media. However, limited data is available on these chemicals in edible fish species from the wide-open South China Sea (SCS). In the present study, ten legacy PBDEs and three substitutions (DBDPE and two DPs) were analyzed in 16 wild fish species sampled from the open SCS to investigate their spatial and species-specific variations. The results showed that the total concentrations of PBDEs, DBDPE, and DPs in fish samples were in the range of 1.69-47.6, not detected (nd) to 21.0, and nd to 3.80 ng/g lipid weight (lw), respectively. BDEs 47, 209 and 100 were the dominant target PBDE congeners, representing 49.2%, 17.2% and 9.93% of the total PBDE concentrations, respectively. Higher concentrations of PBDEs, DBDPE, and DPs were found in fish species from the Wanshan Archipelago compared to those from the Mischief Reef and the Yongxing Island, suggesting the significant influence of anthropogenic activities. Species-specific differences in levels of PBDEs were observed, with the order of bathydemersal > demersal > pelagic ≈ reef-associated > benthopelagic species. The average fanti value of all fish samples was 0.68, suggesting commercial DP products as a contamination source. The levels of PBDEs, DPs, and DBDPE in fish samples were relatively low compared with those from other locations around the globe. Finally, the health risks concerning the ingestion of BDEs 47, 99, 153 and 209 via fish consumption collected from the SCS are negligible.

9.
Small ; : e2404929, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180452

RESUMO

The rational design and synthesis of novel semiconductor nano-/quantum materials have been ambitiously pursued in the field of photocatalysis as the technology is promising and critical for attaining future energy and environmental sustainability. Herein, the integrity of aromatic carbon into graphitic carbon nitride (CN) at the same molecular plane with a few 2D layers is achieved by using modulated precursors of CN, forming carbon regulated ultrathin CN (CUCN) with improved charge transfer kinetics and photocatalytic hydrogen production. The grafted graphite rings adjacent to carbon nitride frameworks induce a significant rearrangement and relocalization of the overall framework, and form conjugated sp2 hybridized interfaces and internal electric fields that drive the separation and directional transfer of photogenerated electrons from CN sheets towards intralayer graphite regions, where the photocatalytic hydrogen evolution reaction occurs extensively, yielding largely increased HER rate of 2231.8 µmol g-1 h-1 by 8.2 times relative to CN, as well as a remarkable apparent quantum yield of 2.93% under monochromatic light at 420 nm. The high physicochemical stability and low synthesis cost of CUCN make it a potential benchmark photocatalyst that can be readily modified via element doping, heterojunction introduction, defect engineering, and so on, to further enhance its HER performance.

10.
Nano Lett ; 24(35): 10827-10833, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39167695

RESUMO

Herein, Cu-foam-supported CuO nanowire arrays covered with Cu2S nanosheet substrates (Cu/CuO/Cu2S) are adopted as efficient photoelectrodes for photorechargeable lithium-ion batteries (PR-LIBs). The assembled PR-LIB exhibits remarkable solar energy conversion efficiency alongside superior lithium storage capabilities. Without an electrical power supply, the photocharged PR-LIB sustained a discharge process for 63.0 h under a constant current density of 0.05 mA cm-2. The corresponding solar-to-electrical energy conversion efficiency is 4.50%, which is an impressive achievement among recently reported contemporary technologies. Mechanism investigation shows that the Cu/CuO/Cu2S photogenerated carriers augment the extraction and insertion of Li+ according to different oxidation and reduction reactions in the charging and discharging reactions. This research delineates a refined model system and proposes innovative directions for developing efficient heterojunction photoelectrodes, significantly propelling the development of PR-LIB technology.

11.
Mol Divers ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150608

RESUMO

To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.

12.
J Gene Med ; 26(8): e3722, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39117601

RESUMO

BACKGROUND: Lovastatin, a type of statin usually considered as a lipid-lowering drug that lowers blood cholesterol and low-density lipoprotein cholesterol levels, has been rediscovered to have anticancer activity. Fewer studies exist regarding the effect of lovastatin on esophageal squamous cell carcinoma (ESCC). METHODS: Here, we report that lovastatin shows anticancer effect on ESCC By affecting the mitochondrial autophagy pathway. Moreover, based on proteomics and computer molecular simulations found that RAB38 and RAB27A may be a target of lovastatin. RESULTS: We observed that autophagy of mitochondria is inhibited by lovastatin, affecting esophageal squamous cell proliferation. There is a possible link between the expression of RAB38, RAB27A and immune cell invasion in esophageal cancer. CONCLUSIONS: These results demonstrate the huge potential of lovastatin as an RAB38, RAB27A inhibitor in esophageal cancer chemotherapy and chemoprevention.


Assuntos
Autofagia , Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lovastatina , Proteômica , Lovastatina/farmacologia , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Proliferação de Células/efeitos dos fármacos , Proteômica/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Linhagem Celular Tumoral , Autofagia/efeitos dos fármacos , Proteínas rab de Ligação ao GTP/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Simulação de Acoplamento Molecular
13.
J Gene Med ; 26(8): e3725, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39134478

RESUMO

INTRODUCTION: Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer. METHODS: In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail. RESULTS: When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth. CONCLUSION: The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.


Assuntos
Diterpenos do Tipo Caurano , Docetaxel , Neoplasias Esofágicas , Lipossomos , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Docetaxel/farmacologia , Docetaxel/administração & dosagem , Docetaxel/química , Lipossomos/química , Animais , Humanos , Linhagem Celular Tumoral , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Nanopartículas/química , Tamanho da Partícula , Ensaios Antitumorais Modelo de Xenoenxerto , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Camundongos Nus , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Fármacos por Nanopartículas/química
14.
Commun Biol ; 7(1): 960, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39117859

RESUMO

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.


Assuntos
Transtorno Depressivo Maior , Transcriptoma , Humanos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/fisiopatologia , Feminino , Masculino , Adulto , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Perfilação da Expressão Gênica
15.
Med ; 5(10): 1237-1254.e9, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-38964333

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).


Assuntos
Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Animais , Humanos , Camundongos , Feminino , Masculino , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Idoso , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Estudos Prospectivos , Terapia Combinada , Dosagem Radioterapêutica , Intervalo Livre de Progressão
16.
J Colloid Interface Sci ; 675: 857-869, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39002236

RESUMO

Portal vein tumor thrombus (PVTT) formed by cancer cell invasion is a major cause of high mortality in hepatocellular carcinoma (HCC), and the formation of thrombus will be accelerated by bacterial colonization on the surface of the implant after surgery. In this work, Polypyrrole-coated arsenic-loaded layered double hydroxide films were in situ constructed on the nickel-titanium alloy for the efficient killing of tumour cells by thermo-therapeutic synergistic chemotherapy. The good near-infrared photothermal conversion ability of polypyrrole enables the sample surface temperature to be raised to about 51 °C at a low photothermal power (0.5 w/cm2), while the elevated temperature could further accelerate the release of drug arsenic. In addition, when NIR light is not applied, the polypyrrole coating also cleverly acts as a "barrier layer" to reduce the natural release of arsenic in normal tissues to avoid toxicity issues. In vivo and in vitro experiments have demonstrated that the platform exhibits excellent antitumor and antibacterial abilities. In contrast to the systemic toxicity issues associated with systemic circulation of nanotherapeutic drugs, this in situ functional film is expected to be used in localised interventions for precise drug delivery, and is also more suitable for surgical treatment scenarios in PVTT surgeries.


Assuntos
Antineoplásicos , Arsênio , Hidróxidos , Raios Infravermelhos , Hidróxidos/química , Hidróxidos/farmacologia , Humanos , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Arsênio/química , Arsênio/farmacologia , Animais , Polímeros/química , Polímeros/farmacologia , Pirróis/química , Pirróis/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Antibacterianos/farmacologia , Antibacterianos/química , Liberação Controlada de Fármacos , Propriedades de Superfície , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade Microbiana
17.
Adv Sci (Weinh) ; 11(36): e2403724, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39054638

RESUMO

Natural polymer-derived nanofibrils have gained significant interest in diverse fields. However, production of bio-nanofibrils with the hierarchical structures such as fibrillar structures and crystalline features remains a great challenge. Herein, an all-natural strategy for simple, green, and scalable top-down exfoliation silk nanofibrils (SNFs) in novel renewable deep eutectic solvent (DES) composed by amino acids and D-sorbitol is innovatively developed. The DES-exfoliated SNFs with a controllable fibrillar structures and intact crystalline features, novelty preserving the hierarchical structure of natural silk fibers. Owing to the amphiphilic nature, the DES-exfoliated SNFs show excellent capacity of assisting the exfoliation of several 2D-layered materials, i.e., h-BN, MoS2, and WS2. More importantly, the SNFs-assisted dispersion of BNNSs with a concentration of 59.3% can be employed to construct SNFs/BNNSs nanocomposite membranes with excellent mechanical properties (tensile strength of 416.7 MPa, tensile modulus of 3.86 GPa and toughness of 1295.4 KJ·m-3) and thermal conductivity (in-plane thermal conductivity coefficient of 3.84 W·m-1·K-1), enabling it to possess superior cooling efficiency compared with the commercial silicone pad.

18.
J Phys Condens Matter ; 36(42)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38955332

RESUMO

Stabilized and metallic light elements hydrides have provided a potential route to achieve the goal of room-temperature superconductors at moderate or ambient pressures. Here, we have performed systematic DFT theoretical calculations to examine the effects of different light elements C and N atoms doped in cubic K4B8H32hydrides on the superconductivity at low pressures. As a result of various atoms substituting, we have found that metallic K4B_{8-x}MxH32(M = C, N) hydrides are dynamically stable at 50 GPa, band structures and density of states (DOS) indicate that sizeableTccorrelates with a high B-H DOS at the Fermi level. With the increasing of B atoms in K4B_{8-x}MxH32hydrides, the DOS values at Fermi level have been improved due to the delocalized electrons in B-H bonds, which result in strong electron-phonon coupling (EPC) interaction and increase theTcfrom 19.04 to 77.07 K for KC2H8and KB2H8at 50 GPa. The NH4unit in stable K4B7NH32hydrides has weakened the EPC and led to lowTcvalue of 21.47 K. Our results suggest the light elements hydrides KB2H8and K4B7CH32could estimate highTcvalues at 50 GPa, and the boron hydrides would be potential candidates to design or modulate hydrides superconductors with highTcat moderate or ambient pressures.

19.
Int J Ophthalmol ; 17(7): 1337-1343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026904

RESUMO

AIM: To investigate Omicron's impact on clinical presentation of acute primary angle closure (APAC) in China. METHODS: A consecutive case series with historical controls was conducted at Shenzhen Eye Hospital, the largest specialized hospital in Shenzhen, China. Medical records from a two-month period during the Omicron pandemic (December 1, 2022, to January 31, 2023) were compared with records from two control groups (12/2018-1/2019 and 12/2021-1/2022) before pandemic. Patients with APAC were included, and the prevalence of APAC and demographic characteristics in Omicron-infected and non-infected patients were compared. RESULTS: Seventy-one (23.43%) out of 303 patients were diagnosed with APAC in the pandemic cohort, which was 2.98 and 2.61 times higher than that in control cohorts (7.87% in 2019, 8.96% in 2022, P<0.001). The pandemic cohort has significantly higher Omicron-infected rate (78.87% vs 0 vs 0; P<0.001), lower proportion of glaucoma history (16.90% vs 42.86% vs 41.67%, P=0.005), higher surgical rate (95.77% vs 83.33% vs 78.57%, P=0.024), higher total medical costs and larger pupil diameter (5.63±0.15 vs 4.68±0.15 vs 4.69±0.22 mm, P<0.01). In 83% Omicron-infected patients, ocular symptoms appeared within 3d after systemic symptoms onset. In multivariate analysis, Omicron infection (P<0.001) was the only independent predictor of pupil diameter. CONCLUSION: In the Omicron epidemic in China, there is an increase of prevalence and severity of APAC, particularly focusing on the first 3d following infection.

20.
Bioresour Technol ; 408: 131157, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39059588

RESUMO

The present study successfully synthesized a novel biochar adsorbent (M-L-BC) using litchi seed modified with zinc chloride for PFASs removal in water. M-L-BC greatly enhanced removal of all examined PFASs (>95 %) as compared to the pristine biochar (<40 %). The maximum adsorption capacity was observed for PFOS, reaching 29.6 mg/g. Adsorption kinetics of PFASs followed the pseudo-second-order model (PSO), suggesting the predominance of chemical adsorption. Moreover, characterization and density functional theory (DFT) calculations jointly revealed involvement of surface complexation, electrostatic interactions, hydrogen bonding, and hydrophobic interactions in PFAS adsorption. Robust PFAS removal was demonstrated for M-L-BC across a wide range of pH (3-9), and coexisting ions had limited impact on adsorption of PFASs except PFBA. Furthermore, M-L-BC showed excellent performance in real water samples and retained reusability after five cycles of regeneration. Overall, M-L-BC represents a promising and high-quality adsorbent for efficient and sustainable removal of PFASs from water.


Assuntos
Carvão Vegetal , Cloretos , Litchi , Sementes , Poluentes Químicos da Água , Purificação da Água , Compostos de Zinco , Carvão Vegetal/química , Adsorção , Poluentes Químicos da Água/isolamento & purificação , Sementes/química , Purificação da Água/métodos , Cloretos/química , Compostos de Zinco/química , Litchi/química , Cinética , Concentração de Íons de Hidrogênio , Fluorocarbonos/química , Água/química
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