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1.
J Thorac Dis ; 16(6): 3740-3752, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38983149

RESUMO

Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.

2.
Research (Wash D C) ; 7: 0410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966747

RESUMO

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

3.
Neurospine ; 21(2): 606-619, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38955532

RESUMO

OBJECTIVE: Cervical hybrid surgery optimizes the use of cervical disc arthroplasty (CDA) and zero-profile (ZOP) devices in anterior cervical discectomy and fusion (ACDF) but lacks uniform combination and biomechanical standards, especially in revision surgery (RS). This study aimed to investigate the biomechanical characteristics of adjacent segments of the different hybrid RS constructs in ACDF RS. METHODS: An intact 3-dimensional finite element model generated a normal cervical spine (C2-T1). This model was modified to the primary C5-6 ACDF model. Three RS models were created to treat C4-5 adjacent segment degeneration through implanting cages plus plates (Cage-Cage), ZOP devices (ZOP-Cage), or Bryan discs (CDA-Cage). A 1.0-Nm moment was applied to the primary C5-6 ACDF model to generate total C2-T1 range of motions (ROMs). Subsequently, a displacement load was applied to all RS models to match the total C2-T1 ROMs of the primary ACDF model. RESULTS: The ZOP-Cage model showed lower biomechanical responses including ROM, intradiscal pressure, maximum von Mises stress in discs, and facet joint force in adjacent segments compared to the Cage-Cage model. The CDA-Cage model exhibited the lowest biomechanical responses and ROM ratio at adjacent segments among all RS models, closely approached or lower than those in the primary ACDF model in most motion directions. Additionally, the maximum von Mises stress on the C3-4 and C6-7 discs increased in the Cage-Cage and ZOP-Cage models but decreased in the CDA-Cage model when compared to the primary ACDF model. CONCLUSION: The CDA-Cage construct had the lowest biomechanical responses with minimal kinematic change of adjacent segments. ZOP-Cage is the next best choice, especially if CDA is not suitable. This study provides a biomechanical reference for clinical hybrid RS decision-making to reduce the risk of ASD recurrence.

4.
Angew Chem Int Ed Engl ; : e202409931, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38957113

RESUMO

The alkylation of nucleophiles is among the most fundamental and well-developed transformations in chemistry. However, to achieve selective alkylation of complex substrates remains a nontrivial task. We report herein a general and selective alkylation method without using strong acids, bases, or metals. In this method, the readily available phosphinites/phosphites, in combination with ethyl acrylate, function as effective alkylating agents. Various nucleophilic groups, including alcohols, phenols, carboxylic acids, imides, and thiols can be alkylated. This method can be applied in the late-stage alkylation of natural products and pharmaceutical agents, achieving chemo- and site-selective modification of complex substrates. Experimental studies indicate the relative reactivity of a nucleophile depends on its acidity and its steric environment. Mechanistic studies suggest the reaction pathway resembles that of the Arbuzov-Michalis reaction.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38973165

RESUMO

Two-dimensional (2D) transition-metal dichalcogenides (TMDCs) are regarded as promising materials for next-generation logic circuits. Top gate field-effect transistors (FETs) have independent gate control ability and can be fabricated directly on TMDC materials without a transfer process. Therefore, it has the merits of device reliability and complementary metal-oxide semiconductor (CMOS) process compatibility, which are demanded in practical circuit-level integration. However, the fabrication of the top gate FET involves depositing an insulating dielectric layer and a gate electrode in sequence on the TMDC channel material, which may affect the device performance. Insightfully investigating the influences of different top-gate-deposition methods on the electrical properties of the TMDC channel and further harnessing these influences to realize a homogeneous CMOS device on an identical 2D TMDC platform are with practice significance. In this work, p/n-type controllable top gate FET arrays based on 2H-MoTe2 are fabricated by using different top-gate-deposition methods. The electron-beam evaporation (EBE) of top metal gate exhibits an obvious n-doping effect on the 2H-MoTe2 channel and converts it from p-type to n-type, whereas the thermal evaporation of top gate affects little to the channel. High-resolution transmission electron microscopy (HR-TEM) analysis reveals that the high-energy metal atoms from the EBE process can penetrate through the 30 nm gate dielectric layers (including 10 nm Al2O3 seeding layer), leading to multiple atomic defects in both MoTe2 and the interface between MoTe2 and Al2O3. Furthermore, by utilizing the top gate engineering, a large-scale double-top-gate MoTe2 homogeneous CMOS inverter array is fabricated. The CMOS inverters exhibit clear logic swing, negligible hysteresis, and high device yield (∼93%), indicating high device reliability and stability. Notably, the fabrication process is facile, free from transfer procedure, and compatible with traditional silicon technology. This work promotes the application of 2D TMDCs in nanoelectronics integration.

6.
JAMA ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949806

RESUMO

A patient had bilateral leg edema, insomnia, myalgias, paresthesias in the fingertips, lighter pigmentation of the facial skin compared with other areas of the body, proteinuria, and an elevated creatinine level. What is the diagnosis and what would you do next?

7.
J Ethnopharmacol ; 333: 118416, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38848975

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia rupestris L. (AR) is a traditional medicinal herb commonly used in the Uyghurs and Kazakhs; it was first documented in the Supplement to Compendium of Materia Medica written by Zhao Xuemin in the Qing Dynasty of China and is used clinically to treat colds, hepatitis, and allergic diseases. AIM OF THE STUDY: The material basis and mechanisms of AR in acute liver injury (ALI) remain unclear. The purpose of this study was to reveal the possible active components involved in liver protection in AR and to preliminarily explore their pharmacological mechanisms. MATERIALS AND METHODS: The chemical composition of the ethanolic extract (ARA) was identified by UPLC-Q-Exactive-MS/MS and confirmed by 32 reference standards. The pharmacodynamic results were utilized to screen the active part within the ARA that contribute to the amelioration of CCl4/ConA-induced ALI. The main active components and core targets were predicted by network pharmacology and verified by molecular docking combined with qPCR and Western blotting. RESULTS: A total of 131 chemical components were identified in the ARA. The extraction parts of ARA had different therapeutic effects on ALI, among which the dichloromethane extract (ARA-D), which might constitute the main effective fraction of ARA, had significant anti-ALI effects. The network pharmacology results showed that targets including PIK3R1, AKT1, and EGFR, as well as 7 compounds, such as artemetin, vitexicarpin and rupestonic acid may play pivotal roles in treating CCl4/ConA-induced ALI. GO and KEGG pathway enrichment analyses revealed that the PI3K-AKT signaling pathway was the main pathway involved. In each model, ARA-D dose-dependently reduced the increase in ALT levels. High-dose ARA-D markedly decreased ALT activity from 196.79 ± 24.82 to 66.37 ± 16.19 U/L in the CCl4 model group and from 178.00 ± 28.39 to 50.67 ± 7.39 U/L in the ConA model group. Further studies revealed that ARA-D significantly inhibited TNF-α, IL-1ß, and IL-6 expression and inhibited the protein expression of PI3K, p-PI3K, and p-AKT in CCl4/ConA-induced ALI. CONCLUSION: ARA-D exhibits protective effects against ALI induced by CCl4/ConA, potentially through inhibition of the PI3K-AKT signaling pathway. These findings may help to determine the material basis and mechanisms of action of ARA-D for liver protection and provide ideas for future comprehensive studies.


Assuntos
Artemisia , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Fosfatidilinositol 3-Quinases , Extratos Vegetais , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Artemisia/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Animais , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Cloreto de Metileno/química , Camundongos , Simulação de Acoplamento Molecular , Fígado/efeitos dos fármacos , Fígado/metabolismo
8.
Neoplasia ; 55: 101012, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38875930

RESUMO

Increased mutational burden and EBV load have been revealed from normal tissues to Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs). BPLF1, encoded by EBV, is a lytic cycle protein with deubiquitinating activity has been found to participate in disrupting repair of DNA damage. We first confirmed that BPLF1 gene in gastric cancer (GC) significantly increased the DNA double strand breaks (DSBs). Ubiquitination mass spectrometry identified histones as BPLF1 interactors and potential substrates, and co-immunoprecipitation and in vitro experiments verified that BPLF1 regulates H2Bub by targeting Rad6. Over-expressing Rad6 restored H2Bub but partially reduced γ-H2AX, suggesting that other downstream DNA repair processes were affected. mRNA expression of BRCA2 were significantly down-regulated by next-generation sequencing after over-expression of BPLF1, and over-expression of p65 facilitated the repair of DSBs. We demonstrated BPLF1 may lead to the accumulation of DSBs by two pathways, reducing H2B ubiquitination (H2Bub) and blocking homologous recombination which may provide new ideas for the treatment of gastric cancer.


Assuntos
Quebras de DNA de Cadeia Dupla , Infecções por Vírus Epstein-Barr , Instabilidade Genômica , Herpesvirus Humano 4 , Histonas , Neoplasias Gástricas , Ubiquitinação , Humanos , Herpesvirus Humano 4/genética , Neoplasias Gástricas/virologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/etiologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Histonas/metabolismo , Linhagem Celular Tumoral , Reparo do DNA , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/genética , Regulação Neoplásica da Expressão Gênica , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Carcinogênese/genética , Proteínas Virais Reguladoras e Acessórias
9.
Phys Rev Lett ; 132(20): 206903, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829069

RESUMO

Emitter dephasing is one of the key issues in the performance of solid-state single-photon sources. Among the various sources of dephasing, acoustic phonons play a central role in adding decoherence to the single-photon emission. Here, we demonstrate that it is possible to tune and engineer the coherence of photons emitted from a single WSe_{2} monolayer quantum dot via selectively coupling it to a spectral cavity resonance. We utilize an open cavity to demonstrate spectral enhancement, leveling, and suppression of the highly asymmetric phonon sideband, finding excellent agreement with a microscopic description of the exciton-phonon dephasing in a truly two-dimensional system. Moreover, the impact of cavity tuning on the dephasing is directly assessed via optical interferometry, which points out the capability to utilize light-matter coupling to steer and design dephasing and coherence of quantum emitters in atomically thin crystals.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38924338

RESUMO

OBJECTIVE: The molecular era of glioma diagnosis and treatment has arrived, and a single rapid histopathology is no longer sufficient for surgery. This study sought to present an automatic integrated gene detection system (AIGS), which enables rapid intraoperative detection of IDH/TERTp mutations. METHODS: A total of 78 patients with gliomas were included in this study. IDH/TERTp mutations were detected intraoperatively using AIGS in 41 of these patients, and they were guided to surgical resection (AIGS detection group). The remaining 37 underwent histopathology-guided conventional surgical resection (non-AIGS detection group). The clinical utility of this technique was evaluated by comparing the accuracy of glioma subtype diagnosis before and after TERTp mutation results were obtained by pathologists and the extent of resection (EOR) and patient prognosis for molecular pathology-guided glioma surgery. RESULTS: With NGS/Sanger sequencing and chromosome detection as the gold standard, the accuracy of AIGS results was 100%. And the timing was well matched to the intraoperative rapid pathology report. After obtaining the TERTp mutation detection results, the accuracy of the glioma subtype diagnosis made by the pathologists increased by 19.51%. Molecular pathology-guided surgical resection of gliomas significantly increased EOR (99.06% vs. 93.73%, p < 0.0001) and also improved median OS (26.77 vs. 13.47 months, p = 0.0289) and median PFS (15.90 vs. 10.57 months, p = 0.0181) in patients with glioblastoma. INTERPRETATION: Using AIGS intraoperatively to detect IDH/TERTp mutations to accurately diagnose glioma subtypes can help achieve maximum safe resection of gliomas, which in turn improves the survival prognosis of patients.

11.
J Microbiol Biotechnol ; 34(6): 1249-1259, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38938004

RESUMO

It remains to be determined whether there is a geographical distribution pattern and phylogenetic signals for the Mycena strains with seed germination of the orchid plant Gastrodia elata. This study analyzed the community composition and phylogenetics of 72 Mycena strains associated with G. elata varieties (G. elata. f. glauca and G. elata. f. viridis) using multiple gene fragments (ITS+nLSU+SSU). We found that (1) these diverse Mycena phylogenetically belong to the Basidiospore amyloid group. (2) There is a phylogenetic signal of Mycena for germination of G. elata. Those strains phylogenetically close to M. abramsii, M. polygramma, and an unclassified Mycena had significantly higher germination rates than those to M. citrinomarginata. (3) The Mycena distribution depends on geographic site and G. elata variety. Both unclassified Mycena group 1 and the M. abramsii group were dominant for the two varieties of G. elata; in contrast, the M. citrinomarginata group was dominant in G. elata f. glauca but absent in G. elata f. viridis. Our results indicate that the community composition of numerous Mycena resources in the Zhaotong area varies by geographical location and G. elata variety. Importantly, our results also indicate that Mycena's phylogenetic status is correlated with its germination rate.


Assuntos
Gastrodia , Germinação , Filogenia , Gastrodia/microbiologia , Gastrodia/genética , DNA Fúngico/genética , Sementes/microbiologia , Sementes/crescimento & desenvolvimento , Basidiomycota/genética , Basidiomycota/classificação , Basidiomycota/fisiologia
12.
Biomedicines ; 12(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38927463

RESUMO

Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor ß1 (TGF-ß1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-ß1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-ß1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI.

13.
Genes (Basel) ; 15(6)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38927644

RESUMO

In previous work, we found that PC was differentially expressed in cows at different lactation stages. Thus, we deemed that PC may be a candidate gene affecting milk production traits in dairy cattle. In this study, we found the polymorphisms of PC by resequencing and verified their genetic associations with milk production traits by using an animal model in a cattle population. In total, we detected six single-nucleotide polymorphisms (SNPs) in PC. The single marker association analysis showed that all SNPs were significantly associated with the five milk production traits (p < 0.05). Additionally, we predicted that allele G of 29:g.44965658 in the 5' regulatory region created binding sites for TF GATA1 and verified that this allele inhibited the transcriptional activity of PC by the dual-luciferase reporter assay. In conclusion, we proved that PC had a prominent genetic effect on milk production traits, and six SNPs with prominent genetic effects could be used as markers for genomic selection (GS) in dairy cattle, which is beneficial for accelerating the improvement in milk yield and quality in Chinese Holstein cows.


Assuntos
Lactação , Leite , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Feminino , Leite/metabolismo , Lactação/genética , Fator de Transcrição GATA1/genética , Alelos
14.
Cell Commun Signal ; 22(1): 339, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898473

RESUMO

BACKGROUND: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. METHODS: Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. RESULTS: RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. CONCLUSION: In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Proteínas Ativadoras de GTPase , Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Linhagem Celular Tumoral , Animais , Proto-Oncogene Mas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Feniltioidantoína/farmacologia , Camundongos Nus , Nitrilas/farmacologia , Camundongos , Benzamidas/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
15.
Cancer Lett ; 598: 217079, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936505

RESUMO

Immunogenic cell death (ICD) is a stress-driven form of regulated cell death (RCD) in which dying tumor cells' specific signaling pathways are activated to release damage-associated molecular patterns (DAMPs), leading to the robust anti-tumor immune response as well as a reversal of the tumor immune microenvironment from "cold" to "hot". Chimeric antigen receptor (CAR)-T cell therapy, as a landmark in anti-tumor immunotherapy, plays a formidable role in hematologic malignancies but falls short in solid tumors. The Gordian knot of CAR-T cells for solid tumors includes but is not limited to, tumor antigen heterogeneity or absence, physical and immune barriers of tumors. The combination of ICD induction therapy and CAR-T cell immunotherapy is expected to promote the intensive use of CAR-T cell in solid tumors. In this review, we summarize the characteristics of ICD, stress-responsive mechanism, and the synergistic effect of various ICD-based therapies with CAR-T cells to effectively improve anti-tumor capacity.

16.
Int J Surg ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913429

RESUMO

BACKGROUND: To evaluate the safety and efficacy of intra-wound vancomycin powder in reducing surgical site infections (SSIs) after spine surgery. DESIGN: A prospective, double-blind, randomized controlled study. PARTICIPANTS: Patients who underwent posterior lumbar interbody fusion (PLIF) surgery from May 2021 to September 2022. METHODS: Patients who underwent posterior lumbar interbody fusion (PLIF) surgery between May 2021 and September 2022 were included. Participants were randomized to the vancomycin treatment or control groups using block randomization (block size 4). Except for baseline and surgical data, the plasma levels of white blood cells, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), aspartate aminotransferase, alanine aminotransferase, and serum vancomycin concentration in the groups were analyzed on postoperative days (PODs) 1, 3, and 5. Vancomycin concentration was measured daily until the drainage tubes were removed. The primary outcomes were the 90-day vancomycin-related adverse reactions and SSI rates. Secondary outcomes were perioperative hematological parameters and vancomycin serum (drain) concentrations. RESULTS: A total of 156 participants (78 each in each group) were analyzed by an independent researcher. The follow-up rate was 91%. All participants were followed up for at least 90 days. The 90-day SSI rate in the vancomycin group was 1.3% (1/78), comprising one case of superficial infection. The SSI rate in the control group was 10.3% (8/78), comprising seven cases of superficial infection and one case of deep infection. Compared with that in the control group, the SSI rate in the vancomycin group was decreased by 87.5%, with a statistically significant difference (RR=0.125, 95% CI=0.016-0.976). Additionally, the vancomycin group demonstrated a statistically significant decrease in serum ESR on POD 3 (P=0.039) and CRP on POD 5 (P=0.024) compared to the control group. The local plasma concentration of vancomycin remained elevated for at least 4 days postoperatively, while the serum concentration of vancomycin remined low. Vancomycin-associated adverse reactions were not observed. CONCLUSION: Intra-wound application of vancomycin powder is a safe and effective procedure for reducing the risk of SSI during PLIF surgery.

17.
Int J Biol Macromol ; 275(Pt 1): 133303, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38917923

RESUMO

The use of facile methods to synthesize environmentally friendly and multifunctional hydrogel dressings is still a major challenge in development. Herein, Turkish gall extract (TGE) and carboxymethyl chitosan (CMCS) were combined and sprayed using a dual syringe to form a multifunctional TGE-CMCS hydrogel (TC gel) in one step through abundant hydrogen bonding between functional groups as a green approach. TC gel showed rapid gelation at 19.0 ± 2.9 s. Apart from the advantage of being able to adapt to different wound shapes, TC gel retained the antioxidant, antibacterial, hemostatic and anti-inflammatory properties of TGE. In vitro antibacterial experiments showed that TC-gel eliminated 98.27 ± 0.79 % of Staphylococcus aureus and 98.87 ± 1.08 % of Escherichia coli. Compared with TGE or CMCS alone, TC gel accelerates skin wound healing due to its three-dimensional network structure and continuous release of active components at the wound site, enhancing re-epithelialization, improving collagen deposition, and increasing angiogenesis. The wound healing rate of full-thickness skin defect rats treated with TC gel was 93.98 ± 0.63 % on the 10th day. These results suggest that TC gel combined with a facile and scalable manufacturing method is a promising multifunctional wound dressing for clinical wound management.

18.
Phys Chem Chem Phys ; 26(27): 18776-18787, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38935024

RESUMO

Non-transition metal doping, especially for Mg, has been gradually employed to optimize the electrochemical performance of Li-rich cathode material Li2MnO3. However, the effects of Mg doping on the electrochemical behavior of Li2MnO3 have not been studied extensively. In this work, we investigate the effect of Mg doping at both the 2b (in the Li/Mn mixed layer) and 4h (in the Li layer) Li sites on the electrochemical properties of Li2MnO3 through first-principles calculations and ab initio molecular dynamics simulations. The local lattice structure, electronic density of states, Bader charge, delithiation voltage, lattice oxygen stability and Li diffusion kinetics are examined. Electronic structure analysis shows that Mg can activate the electrochemical activity of surrounding Mn by charge transfer, making Mn participate in charge compensation at the initial delithiation stage. Mg doping can also cause an increase in the average oxygen vacancy formation energy and hence depress the oxygen release during the delithiation process. Molecular dynamics simulations show that the diffusion kinetics of Li ions in Mg2b-Li2MnO3 is enhanced with respect to the undoped one, whereas Mg doped at the 4h site cannot improve the diffusion kinetics of Li ions. Further studies found that Mg doped at the 2b site results in a decrease in the energy barrier for the intra-layer diffusion and an increase in the energy barrier for the inter-layer diffusion of the nearby Li vacancies.

19.
Elife ; 132024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896455

RESUMO

Microbes strongly affect invasive plant growth. However, how phyllosphere and rhizosphere soil microbes distinctively affect seedling mortality and growth of invaders across ontogeny under varying soil nutrient levels remains unclear. In this study, we used the invader Ageratina adenophora to evaluate these effects. We found that higher proportions of potential pathogens were detected in core microbial taxa in leaf litter than rhizosphere soil and thus leaf inoculation had more adverse effects on seed germination and seedling survival than soil inoculation. Microbial inoculation at different growth stages altered the microbial community and functions of seedlings, and earlier inoculation had a more adverse effect on seedling survival and growth. The soil nutrient level did not affect microbe-mediated seedling growth and the relative abundance of the microbial community and functions involved in seedling growth. The effects of some microbial genera on seedling survival are distinct from those on growth. Moreover, the A. adenophora seedling-killing effects of fungal strains isolated from dead seedlings by non-sterile leaf inoculation exhibited significant phylogenetic signals, by which strains of Allophoma and Alternaria generally caused high seedling mortality. Our study stresses the essential role of A. adenophora litter microbes in population establishment by regulating seedling density and growth.


Assuntos
Ageratina , Folhas de Planta , Rizosfera , Plântula , Microbiologia do Solo , Ageratina/microbiologia , Plântula/microbiologia , Plântula/crescimento & desenvolvimento , Folhas de Planta/microbiologia , Folhas de Planta/crescimento & desenvolvimento , Microbiota , Espécies Introduzidas , Germinação
20.
Int J Oncol ; 65(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38873997

RESUMO

Non­small cell lung cancer (NSCLC) is one of the major causes of cancer­related death worldwide. Cisplatin is a front­line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin­mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription­quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS­mediated endoplasmic reticulum stress, and the C­Jun­amino­terminal kinase and p38 mitogen­activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS­mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Sinergismo Farmacológico , Glucosídeos , Neoplasias Pulmonares , NADPH Oxidase 5 , Estresse Oxidativo , Espécies Reativas de Oxigênio , Estilbenos , Ensaios Antitumorais Modelo de Xenoenxerto , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Animais , Humanos , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Células A549 , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino
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