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1.
Nano Lett ; 24(19): 5754-5760, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38708987

RESUMO

Two-dimensional (2D) FenGeTe2, with n = 3, 4, and 5, has been realized in experiments, showing strong magnetic anisotropy with enhanced critical temperature (Tc). The understanding of its magnetic anisotropy is crucial for the exploration of more stable 2D magnets and its spintronic applications. Here, we report a quantitative reconstruction of the magnetization magnitude and its direction in ultrathin Fe4GeTe2 using nitrogen vacancy centers. Through imaging stray magnetic fields, we identified the spin-flop transition at approximately 80 K, resulting in a change of the easy axis from the out-of-plane direction to the in-plane direction. Moreover, by analyzing the thermally activated escape behavior of the magnetization near Tc in terms of the Ginzburg-Landau model, we observed the in-plane magnetic anisotropy effect and the formation capability of magnetic domains at ∼0.4 µm2 µT-1. Our findings contribute to the quantitative understanding of the magnetic anisotropy effect in a vast range of 2D van der Waals magnets.

2.
Natl Sci Rev ; 11(6): nwad262, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38715704

RESUMO

Surface electrons in axion insulators are endowed with a topological layer degree of freedom followed by exotic transport phenomena, e.g., the layer Hall effect. Here, we propose that such a layer degree of freedom can be manipulated in a dissipationless way based on the antiferromagnetic [Formula: see text] with tailored domain structure. This makes [Formula: see text] a versatile platform to exploit the 'layertronics' to encode, process and store information. Importantly, the layer filter, layer valve and layer reverser devices can be achieved using the layer-locked chiral domain wall modes. The dissipationless nature of the domain wall modes makes the performance of the layertronic devices superior to those in spintronics and valleytronics. Specifically, the layer reverser, a layer version of the Datta-Das transistor, also fills up the blank in designing the valley reverser in valleytronics. Our work sheds light on constructing new generation electronic devices with high performance and low-energy consumption in the framework of layertronics.

3.
Front Surg ; 11: 1329771, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655210

RESUMO

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38580777

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers rapid hematopoietic and immune reconstitution for aplastic anemia (AA). As a non-malignant disorder, attenuation of GVHD remains a clinical priority in AA patients. Our study sought to investigate the safety and efficacy of the prophylactic use of ruxolitinib in allogeneic HSCT. A total of 35 AA patients were retrospectively consecutively treated with allo-HSCT whereby ruxolitinib was added to the standard GVHD prophylaxis regimen (rux group). The addition of peri-transplant ruxolitinib did not impact the engraftment and graft function, while better recovery of CD4+ Tregs in the rux group was observed. Interestingly, the rux group demonstrated significantly lower incidence of bacterial/fungal infections (17.14% vs 45.71%). Compared to the control group, the rux group exhibited significantly lower incidence of moderate to severe aGVHD (17.1% vs 48.6%) with a trend toward lower severe aGVHD (8.6% vs 20%) and cGVHD (26.2 vs 38.3). The rux group also demonstrated a trend toward higher GVHD and failure-free survival (GFFS: 85.7% vs 68.6%) and lower TRM (2.9% vs 14.3%). Addition of ruxolitinib to standard GVHD prophylaxis regimen, thus, represents a safe and highly efficient method for the attenuation of GVHD with better outcome of allo-HSCT.

5.
Front Immunol ; 15: 1327779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596674

RESUMO

Neoadjuvant chemoimmunotherapy has revolutionized the therapeutic strategy for non-small cell lung cancer (NSCLC), and identifying candidates likely responding to this advanced treatment is of important clinical significance. The current multi-institutional study aims to develop a deep learning model to predict pathologic complete response (pCR) to neoadjuvant immunotherapy in NSCLC based on computed tomography (CT) imaging and further prob the biologic foundation of the proposed deep learning signature. A total of 248 participants administrated with neoadjuvant immunotherapy followed by surgery for NSCLC at Ruijin Hospital, Ningbo Hwamei Hospital, and Affiliated Hospital of Zunyi Medical University from January 2019 to September 2023 were enrolled. The imaging data within 2 weeks prior to neoadjuvant chemoimmunotherapy were retrospectively extracted. Patients from Ruijin Hospital were grouped as the training set (n = 104) and the validation set (n = 69) at the 6:4 ratio, and other participants from Ningbo Hwamei Hospital and Affiliated Hospital of Zunyi Medical University served as an external cohort (n = 75). For the entire population, pCR was obtained in 29.4% (n = 73) of cases. The areas under the curve (AUCs) of our deep learning signature for pCR prediction were 0.775 (95% confidence interval [CI]: 0.649 - 0.901) and 0.743 (95% CI: 0.618 - 0.869) in the validation set and the external cohort, significantly superior than 0.579 (95% CI: 0.468 - 0.689) and 0.569 (95% CI: 0.454 - 0.683) of the clinical model. Furthermore, higher deep learning scores correlated to the upregulation for pathways of cell metabolism and more antitumor immune infiltration in microenvironment. Our developed deep learning model is capable of predicting pCR to neoadjuvant chemoimmunotherapy in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Neoadjuvante , Resposta Patológica Completa , Estudos Retrospectivos , Imunoterapia , Tomografia Computadorizada por Raios X , Microambiente Tumoral
6.
Sci Rep ; 14(1): 8088, 2024 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582794

RESUMO

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population's genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.


Assuntos
Leões , Tigres , Animais , Feminino , Tigres/genética , Espécies em Perigo de Extinção , Heterozigoto , Densidade Demográfica , Repetições de Microssatélites/genética , Leões/genética , Conservação dos Recursos Naturais , Variação Genética
7.
ESC Heart Fail ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38520316

RESUMO

Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end-stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62-year-old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH-VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision-making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post-operative care, and rehabilitation.

8.
Integr Zool ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509845

RESUMO

We found that the area of black round or irregular-shaped spots on the tiger's nose increased with age, indicating a positive relationship between age and nose features. We used the deep learning model to train the facial and nose image features to identify the age of Amur tigers, using a combination of classification and prediction methods to achieve age determination with an accuracy of 87.81%.

9.
Angew Chem Int Ed Engl ; : e202403466, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451163

RESUMO

Tailoring the selectivity at the electrode-electrolyte interface is one of the greatest challenges for heterogeneous electrocatalysis, and complementary strategies to catalyst structural designs need to be developed. Herein, we proposed a new strategy of controlling the electrocatalytic pathways by lateral adsorbate interaction for the bio-polyol oxidation. Redox-innocent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) anion possesses the alcoholic property that facilely adsorbs on the nickel oxyhydroxide catalyst, but is resistant to oxidation due to the electron-withdrawing trifluoromethyl groups. The alien HFIP adsorbents can compete with bio-polyols and form a mixed adsorbate layer that creates lateral adsorbate interaction via hydrogen bonding, which achieved a >2-fold enhancement of the oxalate selectivity to 55 % for the representative glycerol oxidation and can be extended to various bio-polyol substrates. Through in situ spectroscopic analysis and DFT calculation on the glycerol oxidation, we reveal that the hydrogen-bonded adsorbate interaction can effectively tune the adsorption energies and tailor the oxidation capabilities toward the targeted products. This work offers an additional perspective of tuning electrocatalytic reactions via introducing redox-innocent adsorbates to create lateral adsorbate interactions.

10.
Angew Chem Int Ed Engl ; 63(21): e202319642, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38554014

RESUMO

Maximizing the loadings of active centers without aggregation for a supported catalyst is a grand challenge but essential for achieving high gravimetric catalytic activity, especially toward multi-step reactions. The oxidation of 5-hydroxymethylfurfural (HMF), a key biomass-derived platform molecule, into 2,5-furandicarboxylic acid (FDCA), a promising alternative to polyester monomer, is such a multi-step reaction that involves 6 proton and electron transfers. This process often demands strong alkaline environment but also suffers from the alkali-driven polymerization side-reaction. Meanwhile, neutral media ameliorates the polymerization, but lacks efficient catalyst toward deep oxidation. Herein, we devised a strategy of creating ultra-dense supported Ru oxide clusters via directed ion exchange in a Co hydroxyanion (CoHA) support material. Pyrimidine ligands were first incorporated into the CoHA interlayers, and the subsequent evacuation of pyrimidines created porous channels for the directed ion exchange with the built-in anions in CoHA, which allowed the dense and mono-disperse functionalization of RuCl6 2- anions and their resulting Ru oxide clusters. These ultra-dense Ru oxide clusters not only enable high HMF electrooxidation currents under neutral conditions but also create microscopic channels in-between the clusters for the expedited re-adsorption and oxidation of intermediates toward highly oxidized product, such as 5-formyl-2-furoic acid (FFCA) and FDCA. A two-stage HMF oxidation process, consisting of ambient conversion of HMF into FFCA and FFCA oxidation into FDCA under 60 °C, was eventually developed to first achieve a high FDCA yield of 92.1 % under neutral media with significantly reduced polymerization.

11.
J Hazard Mater ; 468: 133850, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38401219

RESUMO

The reduction of selenite [Se(Ⅳ)] by microorganisms is a green and efficient detoxification strategy. We found that Se(Ⅳ) inhibited exopolysaccharide and protein secretion by Lactiplantibacillus plantarum BSe and compromised cell integrity. In this study, L. plantarum BSe reduced Se(Ⅳ) by increasing related enzyme activity and electron transfer. Genomic analysis demonstrated that L. plantarum BSe should be able to reduce Se(Ⅳ). Further transcriptome analysis showed that L. plantarum BSe enhanced its tolerance to Se(Ⅳ) by upregulating the expression of surface proteins and transporters, thus reducing the extracellular Se(Ⅳ) concentration through related enzymatic reactions and siderophore-mediated pathways. Lactiplantibacillus plantarum BSe was able to regulate the expression of related genes involved in quorum sensing and a two-component system and then select appropriate strategies for Se(Ⅳ) transformation in response to varying environmental Se(Ⅳ) concentrations. In addition, azo reductase was linked to the reduction of Se(Ⅳ) for the first time. The present study established a multipath model for the reduction of Se(Ⅳ) by L. plantarum, providing new insights into the biological reduction of Se(Ⅳ) and the biogeochemical cycle of selenium.


Assuntos
Ácido Selenioso , Selênio , Ácido Selenioso/metabolismo , Oxirredução , Genômica , Selênio/metabolismo , Transporte de Elétrons
12.
Metabolites ; 14(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38392986

RESUMO

γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous GABA on mycelial growth and the response to stress. Mycelial growth, microscopic morphology, antioxidant profile, and gad2 expression in H. marmoreu were investigated under salt, dehydration, or cold stress. The results indicated that 5 mM GABA stimulated mycelial growth under standard cultivation conditions, whereas GABA addition over 10 mM hindered the growth. Under salt, dehydration, or cold stress, treatment with 5 mM GABA significantly enhanced the mycelial growth rate and density of both H. marmoreus strains by promoting front hyphae branching. Meanwhile, the activities of key antioxidant enzymes such as peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were enhanced by GABA, thereby augmenting the defensive network against abiotic stress. Additionally, gad2 expression and GABA concentration were increased under abiotic stresses as a resistance regulation response. The exogenous addition of GABA strengthened the upregulation of gad2 expression and GABA production. These findings indicated that exogenously adding low concentrations of GABA effectively enhanced the mycelial growth and antioxidant profile of H. marmoreus, thereby improving its resistance against stresses.

13.
Front Neurosci ; 18: 1293962, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419660

RESUMO

Introduction: When constructing machine learning and deep neural networks, the domain shift problem on different subjects complicates the subject independent electroencephalography (EEG) emotion recognition. Most of the existing domain adaptation methods either treat all source domains as equivalent or train source-specific learners directly, misleading the network to acquire unreasonable transfer knowledge and thus resulting in negative transfer. Methods: This paper incorporates the individual difference and group commonality of distinct domains and proposes a multi-source information-shared network (MISNet) to enhance the performance of subject independent EEG emotion recognition models. The network stability is enhanced by employing a two-stream training structure with loop iteration strategy to alleviate outlier sources confusing the model. Additionally, we design two auxiliary loss functions for aligning the marginal distributions of domain-specific and domain shared features, and then optimize the convergence process by constraining gradient penalty on these auxiliary loss functions. Furthermore, the pre-training strategy is also proposed to ensure that the initial mapping of shared encoder contains sufficient emotional information. Results: We evaluate the proposed MISNet to ascertain the impact of several hyper-parameters on the domain adaptation capability of network. The ablation experiments are conducted on two publically accessible datasets SEED and SEED-IV to assess the effectiveness of each loss function. Discussion: The experimental results demonstrate that by disentangling private and shared emotional characteristics from differential entropy features of EEG signals, the proposed MISNet can gain robust subject independent performance and strong domain adaptability.

15.
Am J Physiol Renal Physiol ; 326(4): F611-F621, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38385173

RESUMO

Soluble prorenin receptor (sPRR), a component of the renin-angiotensin system (RAS), has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. Despite studies showing that sPRR in the kidney is produced by tubular cells in the renal collecting duct (CD), its biological actions modulating cardiorenal function in physiological conditions remain unknown. Therefore, the objective of our study was to investigate whether CD-derived human sPRR (HsPRR) expression influences cardiorenal function and examine sex and circadian differences. Thus, we investigated the status of the intrarenal RAS, water and electrolyte balance, renal filtration capacity, and blood pressure (BP) regulation in CD-HsPRR and control (CTL) mice. CD-HsPRR mice were generated by breeding human sPRR-Myc-tag mice with Hoxb7/Cre mice. Renal sPRR expression increased in CD-HsPRR mice, but circulating sPRR and RAS levels were unchanged compared with CTL mice. Only female littermates expressing CD-HsPRR showed 1) increased 24-h BP, 2) an impaired BP response to an acute dose of losartan and attenuated angiotensin II (ANG II)-induced hypertension, 3) reduced angiotensin-converting enzyme activity and ANG II content in the renal cortex, and 4) decreased glomerular filtration rate, with no changes in natriuresis and kaliuresis despite upregulation of the ß-subunit of the epithelial Na+ channel in the renal cortex. These cardiorenal alterations were displayed only during the active phase of the day. Taken together, these data suggest that HsPRR could interact with ANG II type 1 receptors mediating sex-specific, ANG II-independent renal dysfunction and a prohypertensive phenotype in a sex-specific manner.NEW & NOTEWORTHY We successfully generated a humanized mouse model that expresses human sPRR in the collecting duct. Collecting duct-derived human sPRR did not change circulating sPRR and RAS levels but increased daytime BP in female mice while showing an attenuated angiotensin II-dependent pressor response. These findings may aid in elucidating the mechanisms by which women show uncontrolled BP in response to antihypertensive treatments targeting the RAS, improving approaches to reduce uncontrolled BP and chronic kidney disease incidences in women.


Assuntos
Hipertensão , ATPases Vacuolares Próton-Translocadoras , Masculino , Humanos , Feminino , Camundongos , Animais , Angiotensina II/farmacologia , Receptor de Pró-Renina , Rim/metabolismo , Sistema Renina-Angiotensina , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Renina/metabolismo , ATPases Vacuolares Próton-Translocadoras/genética , ATPases Vacuolares Próton-Translocadoras/metabolismo
16.
Opt Express ; 32(3): 3989-3996, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297608

RESUMO

With the rapid development of superconducting quantum computing and the implementation of surface code, large-scale quantum computing is emerging as an urgent demand. In a superconducting computing system, the qubit is maintained in a cryogenic environment to avoid thermal excitation. Thus, the transmission of control signals, which are generated at room temperature, is needed. Typically, the transmission of these signals to the qubit relies on a coaxial cable wiring approach. However, in a large-scale computing system with hundreds or even thousands of qubits, the coaxial cables will pose great space and heat load to the dilution refrigerator. Here, to tackle this problem, we propose and demonstrate a direct-modulation-based optical transmission line. In our experiment, the average single-qubit XEB error and control error are measured as 0.139% and 0.014% separately, demonstrating the feasibility of the optical wiring approach and paving the way for large-scale superconducting quantum computing.

17.
Cancer Res ; 84(7): 994-1012, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295227

RESUMO

Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single-cell RNA sequencing and identified a stem cell-like cluster with tumor cell-initiating properties and prometastatic traits. CXCL14 was specifically enriched in the stem cell-like cluster and was also significantly upregulated in lung metastases compared with primary tumors. CXCL14 induced stromal reprogramming and evoked a malignant phenotype in fibroblasts to form a supportive lung metastatic niche. Binding of CXCL14 to heterodimeric integrin α11ß1 on fibroblasts activated actomyosin contractility and matrix remodeling properties. CXCL14-stimulated fibroblasts produced TGFß and increased osteosarcoma invasion and migration. mAbs targeting the CXCL14-integrin α11ß1 axis inhibited fibroblast TGFß production, enhanced CD8+ T cell-mediated antitumor immunity, and suppressed osteosarcoma lung metastasis. Taken together, these findings identify cross-talk between osteosarcoma cells and fibroblasts that promotes metastasis and demonstrate that targeting the CXCL14-integrin α11ß1 axis is a potential strategy to inhibit osteosarcoma lung metastasis. SIGNIFICANCE: Cooperation between stem-like osteosarcoma cells and fibroblasts mediated by a CXCL14-integrin α11ß1 axis creates a tumor-supportive lung metastatic niche and represents a therapeutic target to suppress osteosarcoma metastasis.


Assuntos
Quimiocinas CXC , Integrinas , Neoplasias Pulmonares , Osteossarcoma , Microambiente Tumoral , Humanos , Linhagem Celular Tumoral , Quimiocinas CXC/metabolismo , Fibroblastos/metabolismo , Integrinas/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Receptores de Colágeno , Fator de Crescimento Transformador beta/metabolismo
18.
Mol Cancer Res ; 22(4): 402-414, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38226993

RESUMO

Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell-dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM. IMPLICATIONS: SB9 as a therapeutic target for LCBM.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Serpinas , Humanos , Camundongos , Animais , Neoplasias Pulmonares/patologia , Serpinas/genética , Serpinas/metabolismo , Proteômica , Linhagem Celular , Neoplasias Ósseas/genética
19.
Glob Heart ; 19(1): 5, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250704

RESUMO

Introduction: Chronic fluid accumulation or congestion is considered an important pathophysiologic mechanism in heart failure, leading to cardinal symptoms such as dyspnea, pulmonary congestion, and pitting edema. Edema index (EI) recently emerged as a surrogate for extracellular volume status and has been proven to be able to reflect one's congestion status. In this study, we aimed to evaluate the prognostic value of EI in patients with chronic heart failure (CHF). Methods: A total of 401 consecutive patients with CHF between August 2019 and October 2021 were prospectively enrolled. EI was obtained by InBody S10. The primary endpoint was long-term all-cause and cardiovascular mortality. Results: Patients with high EI (>0.397) tended to be older, presented with atrial fibrillation, have higher N-terminal brain natriuretic peptide, and have higher creatinine (all p < 0.05). During a median follow-up of 1200 days, the all-cause and cardiovascular mortality rate was significantly higher in the high EI group compared to the low EI group (all-cause mortality rate 43.8% vs. 30.3%, p < 0.001, and cardiovascular mortality rate 17.5% vs. 13.0%, p < 0.001, respectively). In the multivariate Cox proportional hazard analysis, EI > 0.397 was an independent predictor for both all-cause mortality (HR 1.959; 95% CI 1.304, 2.944; p = 0.001) and cardiovascular mortality (HR 2.051; 95% CI 1.276, 3.296; p = 0.003). Conclusions: Admission EI could be used as a marker for predicting long-term mortality in patients with CHF, and higher EI was associated with an increased risk of all-cause and cardiovascular mortality. Furthermore, EI-guided management could be a promising therapy in patients with CHF.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Estudos Prospectivos , Edema , Doença Crônica
20.
Artigo em Inglês | MEDLINE | ID: mdl-38294749

RESUMO

Objective: Long-term antiviral treatment is necessary for chronic hepatitis B (CHB) patients, and treatment safety is imperative for these patients. Previous studies showed tenofovir alafenamide (TAF) has shown efficacy non-inferior to that of tenofovir disoproxil fumarate (TDF) with improved renal and bone safety. However, there is still a lack of a rapid and convenient method to identify CHB patients at high risk of osteoporosis before initiating antiviral treatment. The International Osteoporosis Foundation (IOF) recommended a one-minute osteoporosis risk test to identify early high-risk patients. Our aim was to evaluate the feasibility of the one-minute osteoporosis risk test, along with evaluating the effectiveness and safety for virologically suppressed CHB patients switching to TAF. Methods: In this multicenter, prospective study, patients with chronic HBV infection who had been receiving TDF or Entecavir (ETV) for 48 weeks or more with HBV DNA less than 20 IU/mL for longer than 6 months were screened by one-minute osteoporosis risk test. Patients with a high risk of osteoporosis and then diagnosed with osteopenia or osteoporosis by dual-energy X-ray absorptiometry (DEXA) were enrolled. Safety in bone and bone turnover markers and antiviral efficacy of TAF were assessed respectively at 24 and 48 weeks. Results: 84.95% (175/206) CHB patients screened by one-minute osteoporosis risk test were at risk of osteoporosis.85.71% (150/175) were diagnosed with osteopenia by DEXA. The analysis included a total of 138 patients, of whom 92(62.3%) were male and 46 (37.7%) were female, with a mean age of 45 years old. HBV DNA was suppressed at 48 weeks at 88% (35/40) in the prior ETV group and 90% (88/98) at 48 weeks group in the prior TDF group. Bone mineral density (BMD) of the lumbar spine (L1-L4) from TDF switching to TAF was improved at 24 weeks (1.03±0.11 vs. 0.97±0.12, P = .001) than baseline. Propeptides of type I procollagen (PINP) and beta-C-terminal telopeptides of type 1 collagen (CTX) in serum at 24 weeks after switching from TDF to TAF declined compared with baseline (50.35±18.90 vs. 63.65±19.17, P = .016 and 0.21±0.13 vs. 0.32±0.10, P = .017). BMD, PINP, and CTX in ETV to TAF group remained stable during treatment. Conclusion: Attention should be paid to osteoporosis risk during lone-term nucleot(s)ide analogue treatment. One minute test of osteoporosis risk could rapidly identify most CHB patients at risk of osteoporosis. Given its convenience, we recommend using this test for early screening in CHB patients prior to initiating antiviral treatment. Our results further demonstrated that an improvement in bone safety after switching to TAF in virologically suppressed CHB patients with osteoporosis.

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