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1.
EMBO J ; 43(21): 5114-5140, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39300210

RESUMO

Astrocytes in the brain exhibit regional heterogeneity contributing to regional circuits involved in higher-order brain functions, yet the mechanisms controlling their distribution remain unclear. Here, we show that the precise allocation of astrocytes to specific brain regions during development is achieved through transcription factor 4 (Tcf4)-mediated fate restriction based on their embryonic origin. Loss of Tcf4 in ventral telencephalic neural progenitor cells alters the fate of oligodendrocyte precursor cells to transient intermediate astrocyte precursor cells, resulting in mislocalized astrocytes in the dorsal neocortex. These ectopic astrocytes engage with neocortical neurons and acquire features reminiscent of dorsal neocortical astrocytes. Furthermore, Tcf4 functions as a suppressor of astrocyte fate during the differentiation of oligodendrocyte precursor cells derived from the ventral telencephalon, thereby restricting the fate to the oligodendrocyte lineage in the dorsal neocortex. Together, our findings highlight a previously unappreciated role for Tcf4 in regulating astrocyte allocation, offering additional insights into the mechanisms underlying neurodevelopmental disorders linked to Tcf4 mutations.


Assuntos
Astrócitos , Diferenciação Celular , Fator de Transcrição 4 , Animais , Astrócitos/metabolismo , Camundongos , Fator de Transcrição 4/metabolismo , Fator de Transcrição 4/genética , Encéfalo/metabolismo , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Neocórtex/metabolismo , Neocórtex/embriologia , Neocórtex/crescimento & desenvolvimento , Neocórtex/citologia , Oligodendroglia/metabolismo , Oligodendroglia/citologia , Regulação da Expressão Gênica no Desenvolvimento
2.
Nano Lett ; 24(21): 6344-6352, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38687224

RESUMO

Anisotropic two-dimensional materials present a diverse range of physical characteristics, making them well-suited for applications in photonics and optoelectronics. While mechanical properties play a crucial role in determining the reliability and efficacy of 2D material-based devices, the fracture behavior of anisotropic 2D crystals remains relatively unexplored. Toward this end, we herein present the first measurement of the anisotropic fracture toughness of 2D Ta2NiSe5 by microelectromechanical system-based tensile tests. Our findings reveal a significant in-plane anisotropic ratio (∼3.0), accounting for crystal orientation-dependent crack paths. As the thickness increases, we observe an intriguing intraplanar-to-interplanar transition of fracture along the a-axis, manifesting as stepwise crack features attributed to interlayer slippage. In contrast, ruptures along the c-axis surprisingly exhibit persistent straightness and smoothness regardless of thickness, owing to the robust interlayer shear resistance. Our work affords a promising avenue for the construction of future electronics based on nanoribbons with atomically sharp edges.

3.
J Am Chem Soc ; 146(13): 9205-9215, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38523309

RESUMO

The nonfused thiophene-benzene-thiophene (TBT) unit offers advantages in obtaining low-cost organic photovoltaic (OPV) materials due to its simple structure. However, OPV cells, including TBT-based acceptors, exhibit significantly lower energy conversion efficiencies. Here, we introduce a novel approach involving the design and synthesis of three TBT-based acceptors by substituting different position-branched side chains on the TBT unit. In comparison to TBT-10 and TBT-11, TBT-13, which exclusively incorporates α-position branched side chains with a large steric hindrance, demonstrates a more planar and stable conformation. When blended with the donor PBQx-TF, TBT-13-based blend film achieves favorable π-π stacking and aggregation characteristics, resulting in excellent charge transfer performance in the corresponding device. Due to the simultaneous enhancements in short-circuit current density and fill factor, the TBT-13-based OPV cell obtains an outstanding efficiency of 16.1%, marking the highest value for the cells based on fully nonfused acceptors. Our work provides a practical molecular design strategy for high-performance and low-cost OPV materials.

4.
Cancer Sci ; 115(11): 3552-3569, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39183447

RESUMO

Combination therapy of anti-programmed cell death protein-1 (PD-1) antibodies and tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis for hepatocellular carcinoma (HCC), but many patients still have unsatisfactory outcomes. CD8 T cells are known to exert a pivotal function in the immune response against tumors. Nevertheless, most CD8 T cells in HCC tissues are in a state of exhaustion, losing the cytotoxic activity against malignant cells. Cytokines, mainly secreted by immune cells, play an important role in the occurrence and development of tumors. Here, we demonstrated the changes in exhausted CD8T cells during combination therapy by single-cell RNA sequencing (scRNA-seq) analysis on tumor samples before and after treatment. Combination therapy exerted a substantial impact on the exhausted CD8T cells, particularly in terms of cytokine expression. CCL5 was the most abundantly expressed cytokine in CD8T cells and exhausted CD8T cells, and its expression increased further after treatment. Subsequently, we discovered the CCL5/CCR5/CYP1A1 pathway through RNA sequencing (RNA-seq) on CCL5-stimulated Huh7 cells and verified through a series of experiments that this pathway can mediate the resistance of liver cancer cells to lenvatinib. Tissue experiments showed that after combination therapy, the CCL5/CCR5/CYP1A1 pathway was activated, which can benefit the residual tumor cells to survive treatment. Tumor-bearing mouse experiments demonstrated that bergamottin (BGM), a competitive inhibitor of CYP1A1, can enhance the efficacy of both lenvatinib and combination therapy. Our research revealed one mechanism by which hepatoma cells can survive the combination therapy, providing a theoretical basis for the refined treatment of HCC.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma Hepatocelular , Quimiocina CCL5 , Citocromo P-450 CYP1A1 , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Receptores CCR5 , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Humanos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Camundongos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Quimiocina CCL5/metabolismo , Compostos de Fenilureia/farmacologia , Quinolinas/farmacologia , Receptores CCR5/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Imunoterapia/métodos , Resistencia a Medicamentos Antineoplásicos , Masculino
5.
BMC Plant Biol ; 24(1): 26, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172661

RESUMO

To investigate the relationship between stem puncture mechanical characteristics and NK stress diagnosis, the microstructure, surface morphology, cellulose and lignin content, puncture mechanical characteristics, and epidermal cell morphology of cucumber stems were measured herein. The results indicated that the middle stem, which had a diameter of approximately 7000 µm, was more suitable for puncturing due to its lower amount of epidermal hair, and its gradual regularity in shape. Further, the cucumber stems were protected from puncture damage due to their ability to rapidly heal within 25 h.. The epidermal penetration of the cucumber stems increased with the increase in cellulose and lignin, though cellulose played a more decisive role. The epidermal break distance increased with an increase in N application and decreased with an increase in K+ application, but the change in intercellular space caused by K+ supply was the most critical factor affecting the epidermal break distance. In addition, a decrease in K+ concentration led to a decrease in epidermal brittleness, whereas the factors affecting epidermal toughness were more complex. Finally, we found that although the detection of epidermal brittleness and toughness on nutrient stress was poor under certain treatment, the puncture mechanical characteristics of the stem still had a significant indicative effect on N application rate. Therefore, elucidating of the relationship between the puncture mechanical characteristics of the stems and crop nutritional stress is not only beneficial for promoting stem stress physiology research but also for designing on-site nutritional testing equipment in the future.


Assuntos
Cucumis sativus , Cucumis sativus/fisiologia , Lignina , Celulose , Punções
6.
Small ; : e2408557, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420697

RESUMO

Flexible bioelectronic devices seamlessly interface with organs and tissues, offering unprecedented opportunity for timely prevention, early diagnosis, and medical therapies. However, the majority of flexible substrates utilized in bioelectronics still encounter significant challenges in terms of recyclability and reprocessing, leading to the accumulation of environmentally and biologically hazardous toxic waste. Here, the study reports the design of recyclable polyurethane (PU) vitrimers engineered with internal boron-nitrogen coordination bonds that can reversibly dissociate to boronic acids and hydroxyl, or undergo metathesis reaction following an associative pathway. The study demonstrates the capacity of these recyclable PU vitrimers as flexible substrates in various wearable and implantable bioelectronic applications, achieving high-quality electrophysiological recordings and stimulation. Furthermore, the study establishes a sustainable recycling process by reconstructing a range of bioelectronic devices from the recycled PU vitrimers without compromising the mechanical performance. This closed-loop approach not only addresses the critical challenge of the reclaiming medical electronic waste but also paves the way for the development of sustainable flexible bioelectronics for healthcare applications.

7.
J Transl Med ; 22(1): 730, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103879

RESUMO

BACKGROUND: Inflammation plays a critical role in tumor development. Inflammatory cell infiltration and inflammatory mediator synthesis cause changes in the tumor microenvironment (TME) in several cancers, especially in intrahepatic cholangiocellular carcinoma (ICC). However, methods to ascertain the inflammatory state of patients using reliable biomarkers are still being explored. METHOD: We retrieved the RNA sequencing and somatic mutation analyses results and the clinical characteristics of 244 patients with ICC from published studies. We performed consensus clustering to identify the molecular subtypes associated with inflammation. We compared the prognostic patterns, clinical characteristics, somatic mutation profiles, and immune cell infiltration patterns across inflammatory subtypes. We performed quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to confirm gene expression. We performed logistic regression analyses to construct a nomogram predicting the inflammatory status of patients with ICC. RESULTS: Our results confirmed that ICC can be categorized into an inflammation-high subtype (IHS) and an inflammation-low subtype (ILS). Patients from each group had distinct prognosis, clinical characteristics, and TME composition. Patients with ICC in the IHS group showed poorer prognosis owing to the immunosuppressive microenvironment and high frequency of KRAS and TP53 mutations. Cancer-associated fibroblast (CAF)-derived COLEC11 reduced myeloid inflammatory cell infiltration and attenuated inflammatory responses. The results of qRT-PCR and IHC experiments confirmed that COLEC11 expression levels were significantly reduced in tumor tissues compared to those in paracancerous tissues. Patients with ICC in the IHS group were more likely to respond to treatment with immune checkpoint inhibitors (ICIs) owing to their higher tumor mutational burden (TMB) scores, tumor neoantigen burden (TNB) scores, neoantigen counts, and immune checkpoint expression levels. Finally, we developed a nomogram to effectively predict the inflammatory status of patients with ICC based on their clinical characteristics and inflammatory gene expression levels. We evaluated the calibration, discrimination potential, and clinical utility of the nomogram. CONCLUSION: The inflammatory response in IHS is primarily induced by myeloid cells. COLEC11 can reduce the infiltration level of this group of cells, and myeloid inflammatory cells may be a novel target for ICC treatment. We developed a novel nomogram that could effectively predict the inflammatory state of patients with ICC, which will be useful for guiding individualized treatment plans.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Inflamação , Microambiente Tumoral , Humanos , Colangiocarcinoma/patologia , Colangiocarcinoma/genética , Inflamação/patologia , Inflamação/genética , Microambiente Tumoral/imunologia , Masculino , Feminino , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/genética , Pessoa de Meia-Idade , Prognóstico , Mutação/genética , Idoso , Regulação Neoplásica da Expressão Gênica , Nomogramas , Reprodutibilidade dos Testes
8.
J Transl Med ; 22(1): 948, 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39427165

RESUMO

This study aims to investigate the interplay between tumor-associated endothelial cells (TECs) and immune cells within the tumor microenvironment (TME) and its impact on tumor prognosis. We conducted single-cell RNA sequencing (scRNA-seq) of tumor, normal, and lymph node tissues obtained from intrahepatic cholangiocarcinoma (ICC) patients to reveal the role of TECs in tumor angiogenesis and their significant heterogeneity. Meanwhile, we identified genes highly expressed in TECs and constructed TEC signatures (TEC.Sig). Next, we calculated TEC scores of samples based on TEC.Sig. Patients with higher TEC scores exhibited a higher frequency of KRAS mutations, which was associated with increased infiltration of neutrophils and immature dendritic cells (iDCs), and decreased numbers of natural killer (NK), CD4 + T, and CD8 + T effector memory (Tem) cells, indicating an inflammation-dominated immunosuppressive phenotype. In contrast, BAP1 mutations and CXCL12 overexpression showed a contrasting trend. Spatial transcriptomics analysis and histological experiments further confirmed that TECs interacted with various tumor-killing immune cells through the CXCL12/CXCR4 axis. Multiple tumor immunotherapy datasets confirmed that the TEC.Sig could predict patient responses to immunotherapy. The TEC score is a promising and reliable biomarker for predicting genetic mutations and prognosis in ICC patients. Enhancing the regulation of the CXCL12/CXCR4 signaling pathway may represent a potential novel therapeutic target for ICC treatment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Células Endoteliais , Microambiente Tumoral , Humanos , Colangiocarcinoma/patologia , Colangiocarcinoma/genética , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/genética , Células Endoteliais/patologia , Células Endoteliais/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Mutação/genética , Imunoterapia , Perfilação da Expressão Gênica , Análise de Célula Única , Transcriptoma/genética , Multiômica
9.
Opt Express ; 32(7): 11271-11280, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570978

RESUMO

The advent of optical metrology applications has necessitated the development of compact, reliable, and cost-effective picosecond lasers operating around 900 nm, specifically catering to the requirements of precise ranging. In response to this demand, our work introduces an innovative solution-an all-fiber, all-polarization-maintaining (PM) figure-9 mode-locked laser operating at 915 nm. The proposed figure-9 Nd-doped fiber laser has a 69.2 m long cavity length, strategically designed and optimized to yield pulses with a combination of high pulse energy and low repetition rate. The laser can generate 915 nm laser pulses with a pulse energy of 4.65 nJ, a pulse duration of 15.2 ps under the repetition rate of 3.05 MHz. The 1064 nm amplified spontaneous emission (ASE) is deliberately filtered out, in order to prevent parasitic lasing and increase the spectral proportion of the 915 nm laser. The all-PM fiber configuration of this laser imparts exceptional mode-locking performance and environmental robustness, which is confirmed by long-term output power and spectral stability test. This compact and long-term reliable fiber laser could be a promising light source for applications like inter-satellite ranging.

10.
Opt Express ; 32(10): 17571-17580, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858938

RESUMO

Monolithic distributed Bragg reflector (DBR) cavity which directly integrates fiber Bragg gratings (FBGs) into the photosensitive RE-doped fibers is a promising configuration in constructing compact and efficient single frequency fiber lasers (SFFLs). Yet, the doping level of rare-earth (RE) ions has generally to be sacrificed in the classical Ge-photosensitized RE-doped silica fibers because of the dramatic refractive index increase caused by the introduction of Ge. Here, we demonstrate an approach to realize the trade-off between photosensitivity and RE doping concentration. We validate that the addition of a small amount of cerium (0.37wt.%) instead of Ge could photosensitize Yb3+-doped silica fiber (YDF), while maintaining fiber numerical aperture (NA) at 0.12 under a high 2.5-wt.% Yb doping level. Based on the short monolithic DBR cavity constructed by this germanium-free photosensitive highly YDF, a 1064 nm fiber laser with a 48.6% slope efficiency and an over 200 mW power on two orthogonally polarized modes could be realized. Further stable and linear-polarized 1064 nm SFFL is also demonstrated in a designed monolithic polarization maintaining cavity with an output power of 119 mW and an efficiency of 26.4%. Our results provide an alternative way to develop photosensitive highly RE-doped fibers towards monolithic laser cavity application.

11.
Cytokine ; 179: 156618, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38663252

RESUMO

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.


Assuntos
Quimiocina CXCL11 , Quimiocina CXCL9 , Derrame Pleural , Receptores CXCR3 , Tuberculose Pleural , Humanos , Quimiocina CXCL9/metabolismo , Quimiocina CXCL11/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Derrame Pleural/metabolismo , Derrame Pleural/diagnóstico , Receptores CXCR3/metabolismo , Tuberculose Pleural/diagnóstico , Tuberculose Pleural/metabolismo , Adulto , Ligantes , Método Duplo-Cego , Células THP-1 , Biomarcadores/metabolismo , Macrófagos/metabolismo , Estudos Prospectivos , Idoso , Curva ROC
12.
Opt Lett ; 49(4): 989-992, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359243

RESUMO

We demonstrated an efficient way to enhance and flatten the emission cross sections of Er3+ ions at the L-band in the silicate fiber amplifier by increasing Mg2+ (up to 22.5 mol%) with high field strength. High values of Er3+ concentration, lifetime, and L-band emission cross section were achieved in our silicate fibers. Particularly, the flatness at the L-band was achieved to be 0.8 dB, and a high gain coefficient at 1625 nm (4.7 dB/m) was demonstrated by pumping meter-scale Er-silicate fibers. The as-prepared Er-silicate fibers are attractive for the L-band fiber amplifier.

13.
Ann Hematol ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39227450

RESUMO

The superiority and tolerability of daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) was previously described in the global phase 3 ALCYONE study. The primary analysis of the phase 3 OCTANS study further demonstrated the superiority and tolerability of D-VMP (n = 144) versus VMP (n = 71) in transplant-ineligible Asian patients with NDMM. The current analysis describes the final efficacy and safety outcomes for D-VMP versus VMP in OCTANS, with a follow-up of > 3 years. D-VMP demonstrated a benefit versus VMP with regard to the rate of very good partial response or better (80.1% vs. 47.3%), median progression-free survival (38.7 vs. 19.2 months), median time to next treatment (46.8 vs. 20.6 months), rate of complete response or better (46.6% vs. 18.9%), median duration of response (41.3 vs. 18.5 months), achievement of minimal residual disease (MRD) negativity (40.4% vs. 10.8%), and sustained MRD negativity for ≥ 12 months (24.7% vs. 1.4%) and ≥ 18 months (15.1% vs. 1.4%). Median progression-free survival was longer among patients who achieved MRD negativity and sustained MRD negativity. The progression-free survival benefit observed with D-VMP was preserved across most clinically relevant subgroups, including patients with high-risk cytogenetics. No new safety concerns were identified with extended follow-up. This final analysis of OCTANS continues to demonstrate a clinical benefit for D-VMP versus VMP in transplant-ineligible Asian patients with NDMM, consistent with the global ALCYONE study, and supports the use of daratumumab combinations in this population. Trial registration: ClinicalTrials.gov Identifier NCT03217812 submitted July 13, 2017.

14.
Ann Hematol ; 103(3): 855-868, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38112795

RESUMO

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.


Assuntos
Mieloma Múltiplo , Talidomida/análogos & derivados , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Mieloma Múltiplo/tratamento farmacológico , Dexametasona , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
15.
Cell Commun Signal ; 22(1): 448, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327550

RESUMO

Immunotherapy has emerged as a highly effective treatment for various tumors. However, the variable response rates associated with current immunotherapies often restrict their beneficial impact on a subset of patients. Therefore, more effective treatment approaches that can broaden the scope of therapeutic benefits to a larger patient population are urgently needed. Studies have shown that some parasites and their products, for example, Plasmodium, Toxoplasma, Trypanosoma, and Echinococcus, can effectively transform "cold" tumors into "hot" battlefields and reshape the tumor microenvironment, thereby stimulating innate and adaptive antitumor immune responses. These parasitic infections not only achieve the functional reversal of innate immune cells, such as neutrophils, macrophages, myeloid-derived suppressor cells, regulatory T cells, and dendritic cells, in tumors but also successfully activate CD4+/CD8+ T cells and even B cells to produce antibodies, ultimately resulting in an antitumor-specific immune response and antibody-dependent cellular cytotoxicity. Animal studies have confirmed these findings. This review discusses the abovementioned content and the challenges faced in the future clinical application of antitumor treatment strategies based on parasitic infections. With the potential of these parasites and their byproducts to function as anticancer agents, we anticipate that further investigations in this field could yield significant advancements in cancer treatment.


Assuntos
Imunoterapia , Neoplasias , Humanos , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Animais , Parasitos/imunologia , Microambiente Tumoral/imunologia
16.
Eur Radiol ; 34(4): 2576-2589, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37782338

RESUMO

OBJECTIVES: To develop a radiomics model in contrast-enhanced cone-beam breast CT (CE-CBBCT) for preoperative prediction of axillary lymph node (ALN) status and metastatic burden of breast cancer. METHODS: Two hundred and seventy-four patients who underwent CE-CBBCT examination with two scanners between 2012 and 2021 from two institutions were enrolled. The primary tumor was annotated in each patient image, from which 1781 radiomics features were extracted with PyRadiomics. After feature selection, support vector machine models were developed to predict ALN status and metastatic burden. To avoid overfitting on a specific patient subset, 100 randomly stratified splits were made to assign the patients to either training/fine-tuning or test set. Area under the receiver operating characteristic curve (AUC) of these radiomics models was compared to those obtained when training the models only with clinical features and combined clinical-radiomics descriptors. Ground truth was established by histopathology. RESULTS: One hundred and eighteen patients had ALN metastasis (N + (≥ 1)). Of these, 74 had low burden (N + (1~2)) and 44 high burden (N + (≥ 3)). The remaining 156 patients had none (N0). AUC values across the 100 test repeats in predicting ALN status (N0/N + (≥ 1)) were 0.75 ± 0.05 (0.67~0.93, radiomics model), 0.68 ± 0.07 (0.53~0.85, clinical model), and 0.74 ± 0.05 (0.67~0.88, combined model). For metastatic burden prediction (N + (1~2)/N + (≥ 3)), AUC values were 0.65 ± 0.10 (0.50~0.88, radiomics model), 0.55 ± 0.10 (0.40~0.80, clinical model), and 0.64 ± 0.09 (0.50~0.90, combined model), with all the ranges spanning 0.5. In both cases, the radiomics model was significantly better than the clinical model (both p < 0.01) and comparable with the combined model (p = 0.56 and 0.64). CONCLUSIONS: Radiomics features of primary tumors could have potential in predicting ALN metastasis in CE-CBBCT imaging. CLINICAL RELEVANCE STATEMENT: The findings support potential clinical use of radiomics for predicting axillary lymph node metastasis in breast cancer patients and addressing the limited axilla coverage of cone-beam breast CT. KEY POINTS: • Contrast-enhanced cone-beam breast CT-based radiomics could have potential to predict N0 vs. N + (≥ 1) and, to a limited extent, N + (1~2) vs. N + (≥ 3) from primary tumor, and this could help address the limited axilla coverage, pending future verifications on larger cohorts. • The average AUC of radiomics and combined models was significantly higher than that of clinical models but showed no significant difference between themselves. • Radiomics features descriptive of tumor texture were found informative on axillary lymph node status, highlighting a higher heterogeneity for tumor with positive axillary lymph node.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Metástase Linfática/patologia , Axila/patologia , Radiômica , Estudos Retrospectivos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Tomografia Computadorizada de Feixe Cônico
17.
J Org Chem ; 89(13): 9462-9472, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38869450

RESUMO

A BF3·OEt2-catalyzed cascade cyclization reaction of vinyloxirane with coumarin is described, affording the benzocoumarin derivatives with moderate to excellent yields (72-92%). The reaction demonstrates exceptional substrate tolerance and has been extensively explored for its potential in drug development, including scale-up experiments, functional group transformations, and screening of the products for anticancer activity. Moreover, the reaction mechanism has been rigorously validated through intermediate trapping and control experiments. Additionally, this reaction represents the uncommon nonmetal catalyzed intermolecular cyclization of vinyloxiranes.

18.
Environ Sci Technol ; 58(29): 12966-12975, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38990074

RESUMO

Urban blue-green infrastructure (BGI) offers a multitude of ecological advantages to residents, thereby playing a pivotal role in fortifying urban resilience and fostering the development of climate-resilient cities. Nonetheless, current research falls short of a comprehensive analysis of BGI's overall potential for carbon reduction and its indirect carbon reduction impact. To fill this research gap, we utilized the integrated valuation of ecosystem services and trade-offs model and remote sensing estimation algorithm to quantify the direct carbon sequestration and resultant indirect carbon reduction facilitated by the BGI within the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) (China). To identify the regions that made noteworthy contributions to carbon offsets and outliers, spatial autocorrelation analysis was also employed. The findings of this study reveal that in 2019, the BGI within the study area contributed an overall carbon offset of 1.5 × 108 t·C/yr, of which 3.5 × 107 and 11.0 × 107 t·C/yr were the result of direct carbon sequestration and indirect carbon reduction, respectively. The GBA's total CO2 emissions were 1.1 × 108 t in 2019. While the direct carbon sequestration offset 32.0% of carbon emissions, the indirect carbon reduction mitigated 49.9% of potential carbon emissions. These results highlight the critical importance of evaluating BGI's indirect contribution to carbon reduction. The findings of this study provide a valuable reference for shaping management policies that prioritize the protection and restoration of specific areas, thereby facilitating the harmonized development of carbon offset capabilities within urban agglomerations.


Assuntos
Sequestro de Carbono , Carbono , Ecossistema , Cidades , China
19.
Phys Chem Chem Phys ; 26(38): 24931-24940, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39295514

RESUMO

The structure and dynamic properties of Cs in the mixed system of LiCl-KCl molten salt and a liquid metal (Bi and Pb) electrode are investigated through first-principles molecular dynamics simulation. It is found that the dynamic properties of different ions in molten salt could be significantly affected when the liquid metal electrode is coupled and this influence varies with the type of liquid metal applied. The microstructures of the mixed systems of molten salt and liquid metal electrode: MS-Cs-Bi, MS-CsCl-Bi, MS-Cs-Pb, and MS-CsCl-Pb, are also investigated by the bond angle distribution function, Voronoi tessellation analysis, five-fold symmetry parameter, and bond-orientational order parameter. The comparison study of the microstructures of the mixed systems when different liquid metal electrodes are applied provides information on the liquid metal electrode selection when conducting electrolysis. The present study represents the first demonstration of the study of a mixed system of salt and liquid electrode for practical applications and would be greatly beneficial to the development of pyroprocessing of spent nuclear fuel.

20.
BMC Musculoskelet Disord ; 25(1): 174, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409002

RESUMO

PURPOSE: To compare the clinical efficacy of arthroscopic TightRope loop titanium button and clavicular hook plate in the treatment of acromioclavicular joint (ACJ) dislocation of Rockwood III/IV. METHODS: A retrospective analysis of patients with ACJ dislocation in our hospital from January 2018 to December 2020 was conducted. The patients were assigned to be treated with arthroscopic TightRope loop titanium button (TR group) or clavicular hook plate (HP group). The preoperative, intraoperative and postoperative data and imaging findings of the two groups were compared. RESULTS: A total of 58 eligible patients were enrolled in this study. Compared with HP group, TR group had shorter incision length and less blood loss during operation. Postoperative follow-up ranged from 12 to 24 months (mean 15.4 months). At 6 months and 12months postoperatively, compared with HP group, TR group had lower VAS and higher CMS, and the difference was statistically significant. At 12 months postoperatively, compared with HP group, TR group had lower ACJ gap and coracoclavicular joint(CCJ) distance, and the difference was statistically significant.In HP group, there were 3 cases of subacromial impact, 1 case of redislocation, 2 cases of traumatic arthritis and 2 cases of wound infection. There was 1 case of redislocation in TR group. CONCLUSIONS: Compared with clavicular hook plate, arthroscopic TightRope loop titanium button is minimally invasive, safe and effective in the treatment of ACJ dislocation, and has a good trend in clinical application.


Assuntos
Articulação Acromioclavicular , Luxações Articulares , Luxação do Ombro , Humanos , Estudos Retrospectivos , Luxações Articulares/cirurgia , Titânio , Articulação Acromioclavicular/diagnóstico por imagem , Articulação Acromioclavicular/cirurgia , Luxação do Ombro/cirurgia , Placas Ósseas , Resultado do Tratamento
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