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1.
Proc Natl Acad Sci U S A ; 121(15): e2321502121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38564636

RESUMO

The release of paused RNA polymerase II (RNAPII) from promoter-proximal regions is tightly controlled to ensure proper regulation of gene expression. The elongation factor PTEF-b is known to release paused RNAPII via phosphorylation of the RNAPII C-terminal domain by its cyclin-dependent kinase component, CDK9. However, the signal and stress-specific roles of the various RNAPII-associated macromolecular complexes containing PTEF-b/CDK9 are not yet clear. Here, we identify and characterize the CDK9 complex required for transcriptional response to hypoxia. Contrary to previous reports, our data indicate that a CDK9 complex containing BRD4 but not AFF1/4 is essential for this hypoxic stress response. We demonstrate that BRD4 bromodomains (BET) are dispensable for the release of paused RNAPII at hypoxia-activated genes and that BET inhibition by JQ1 is insufficient to impair hypoxic gene response. Mechanistically, we demonstrate that the C-terminal region of BRD4 is required for Polymerase-Associated Factor-1 Complex (PAF1C) recruitment to establish an elongation-competent RNAPII complex at hypoxia-responsive genes. PAF1C disruption using a small-molecule inhibitor (iPAF1C) impairs hypoxia-induced, BRD4-mediated RNAPII release. Together, our results provide insight into potentially targetable mechanisms that control the hypoxia-responsive transcriptional elongation.


Assuntos
Proteínas Nucleares , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regulação da Expressão Gênica , Quinases Ciclina-Dependentes/metabolismo , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Fosforilação , Hipóxia , Transcrição Gênica , Fator B de Elongação Transcricional Positiva/genética , Fator B de Elongação Transcricional Positiva/metabolismo , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
2.
RSC Adv ; 14(16): 11112-11120, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38590358

RESUMO

In recent years, finding high-performance energy storage materials has become a major challenge for Li-ion batteries. B-based two-dimensional materials have become the focus of attention because of their abundant reserves and non-toxic characteristics. A series of two-dimensional transition metal borides (MBenes) are reported and their electrochemical properties as anode materials for Li-ion batteries are investigated by density functional theory (DFT) calculations. The surface of MB2 possesses medium adsorption strength and diffusion energy barrier for Li atoms, which are conducive to the insertion and extraction of Li-ions during the charge/discharge process of Li-ion batteries. Herein, we explore the potential of MB2 (M = Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Fe, Co, Ni, Cu and Zn) as the anode material for LIBs. Excitingly, the Li atom can be stably adsorbed on the surface of MB2 (M = Sc, Ti, V, Nb, Mo, W) monolayers, and the theoretical capacity of the MB2 monolayer is high (521.77-1610.20 mA h g-1). The average open circuit voltage range is within 0.10-1.00 V (vs. Li/Li+). The relationship between the p-band center of the B atom and the adsorption energy of Li on the surface of MB2 is also investigated. Furthermore, it is found that the charge transfer of Li atom and metallic center in the most stable position is strongly related to the corresponding value of diffusion energy barrier. These results confirm that MB2 monolayers are promising 2D anode materials for Li-ion batteries, demonstrating the application prospects of B-based 2D materials.

3.
World J Gastroenterol ; 30(6): 542-555, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38463023

RESUMO

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.


Assuntos
Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Prognóstico , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X/métodos , Aprendizado de Máquina
4.
Adv Sci (Weinh) ; : e2307409, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477567

RESUMO

Uncontrollable massive bleeding caused by trauma will cause the patient to lose a large amount of blood and drop body temperature quickly, resulting in hemorrhagic shock. This study aims to develop a hemostatic product for hemorrhage management. In this study, waste pomelo peel as raw material is chosen. It underwent processes of carbonization, purification, and freeze-drying. The obtained carbonized pomelo peel (CPP) is hydrophilic and exhibits a porous structure (nearly 80% porosity). The water/blood absorption ratio is significantly faster than the commercial Gelfoam and has a similar water/blood absorption capacity. In addition, the CPP showed a water-triggered shape-recoverable ability. Moreover, the CPP shows ideal cytocompatibility and blood compatibility in vitro and favorable tissue compatibility after long terms of subcutaneous implantation. Furthermore, CPP can absorb red blood cells and fibrin. It also can absorb platelets and activate platelets, and it is capable of achieving rapid hemostasis on the rat tail amputation and hepatectomized hemorrhage model. In addition, the CPP not only can quickly stop bleeding in the rat liver-perforation and rabbit heart uncontrolled hemorrhage models, but also promotes rat liver and rabbit heart tissue regeneration in situ. These results suggest the CPP has shown great potential for managing uncontrolled hemorrhage.

5.
Sensors (Basel) ; 24(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38475054

RESUMO

Working on a moving platform can significantly impede human performance. Previous studies on moving vehicles have often focused on the overall impact on general task performance, whereas our study's emphasis is on precise hand movements, exploring the interaction between body motion and the escalation of task difficulty. We recruited 28 participants to engage in reciprocal aiming tasks, following Paul Fitts's setting, under both in-motion and stationary conditions. The task index of difficulty (ID) was manipulated by varying the width of the targets and the distance between the targets. We measured participants' movement time (MT), performance errors, and monitored their eye movements using an eye-tracking device, heart rate (HR), and respiration rate (RR) during the tasks. The measured parameters were compared across two experimental conditions and three ID levels. Compared to the stationary conditions, the in-motion conditions degraded human aiming performance, resulting in significantly prolonged MT, increased errors, and longer durations of eye fixations and saccades. Furthermore, HR and RR increased under the in-motion conditions. Linear relationships between MT and ID exhibited steeper slopes under the in-motion conditions compared to the stationary conditions. This study builds a foundation for us to explore the control mechanisms of individuals working in dynamic and demanding environments, such as pilots in airplanes and paramedics in ambulances.


Assuntos
Tecnologia de Rastreamento Ocular , Movimento , Humanos , Movimento (Física) , Movimento/fisiologia , Movimentos Oculares , Extremidade Superior
6.
Int J Surg ; 110(4): 2134-2140, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466083

RESUMO

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups ( P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups ( P =0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups ( P =0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.


Assuntos
Anastomose Cirúrgica , Competência Clínica , Laparoscopia , Impressão Tridimensional , Treinamento por Simulação , Anastomose Cirúrgica/educação , Anastomose Cirúrgica/métodos , Laparoscopia/educação , Treinamento por Simulação/métodos , Animais , Suínos , Humanos , Modelos Anatômicos , Procedimentos Cirúrgicos do Sistema Biliar/educação , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Masculino
7.
Materials (Basel) ; 17(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38541548

RESUMO

Brazing a SiO2f/SiO2 composite with metals is often faced with two problems: poor wettability with the brazing alloy and high residual stress in the joint. To overcome these problems, we report a combined method of selective etching and depositing reduced graphene oxide (rGO) on the surface of a SiO2f/SiO2 composite (3D-rGO-SiO2f/SiO2) to assist brazing with TC4. After the combined treatment, a "3D-rGO" buffer layer formed on the surface layer of the SiO2f/SiO2, and the contact angle was reduced from 130° to 38°, which meant the wettability of active brazing alloy on the surface of SiO2f/SiO2 was obviously improved. In addition, the "3D-rGO" buffer layer contributed to fully integrating the brazing alloy and SiO2f/SiO2; then, the infiltration of the brazing alloy into the surface layer of the SiO2f/SiO2 was enhanced and formed the reduced graphene oxide with a pinning structure in the three dimensional ("3D-pinning-rGO") structure. Moreover, the joining area of the brazing alloy and SiO2f/SiO2 was expanded and the mismatch degree between the SiO2f/SiO2 and TC4 was reduced, which was achieved by the "3D-pinning-rGO" structure. Furthermore, the concentration of the residual stress in the SiO2f/SiO2-TC4 joints transferred from the SiO2f/SiO2 to the braided quartz fibers, and the residual stress reduced from 142 MPa to 85 MPa. Furthermore, the 3D-pinning-rGO layer facilitated the transfer of heat between the substrates during the brazing process. Finally, the shear strength of the SiO2f/SiO2-TC4 joints increased from 12.5 MPa to 43.7 MPa by the selective etching and depositing rGO method.

8.
J Med Chem ; 67(6): 4904-4915, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38499004

RESUMO

A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.


Assuntos
Neoplasias da Bexiga Urinária , Camundongos , Animais , Administração Intravesical , Neoplasias da Bexiga Urinária/patologia
10.
Chempluschem ; : e202400080, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514396

RESUMO

Gaseous signaling molecules (GSMs) including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have presented excellent therapeutic efficacy such as anti-inflammatory, anti-microbial and anti-cancer effects and multiple biomedical applications in recent years. As the three most vital signaling molecules in human physiology, these three GSMs show so intertwined and orchestrated interactions that the synergy of multiple gases may demonstrate a more complex therapeutic potential than single gas delivery. Consequently, researchers have been devoted to developing codelivery systems of GSMs by synthesizing a single molecule as a dual donor to maximize the gaseous therapeutic efficacy. In this minireview, we summarize the recent developments of molecules or materials enabling codelivery of GSMs for biomedical applications. It appears that compared with the abundant cases of codelivery of NO and H2S, research on codelivery of CO and the other two GSMs separately remains to be explored.

11.
BMC Public Health ; 24(1): 865, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509529

RESUMO

BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.


Assuntos
Malária , Humanos , Reprodutibilidade dos Testes , Malária/epidemiologia , Medição de Risco , China/epidemiologia , Aprendizado de Máquina
12.
Transl Lung Cancer Res ; 13(2): 423-433, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38496704

RESUMO

Background: The morbidity and mortality of lung cancer have always ranked first among malignant tumors (MTs). Previous studies have shown that neoadjuvant chemotherapy can improve the 5-year survival rate of patients with non-small cell lung cancer (NSCLC), but the benefit is limited. Studies have proven that neoadjuvant immunotherapy combined with chemotherapy has unique advantages in prolonging patient survival, reducing distant recurrence, and inducing antitumor immunity. However, its impact remains to be more comprehensively investigated. Case Description: A 59-year-old male who was admitted to the hospital with a primary complaint of repeated cough and expectoration for 6 months. Preoperative assessment showed right upper lung squamous cell carcinoma with multiple hilar and mediastinal lymph node metastasis, and the clinical stage was cT2aN2M0 stage (IIIA). After three cycles of pembrolizumab + carboplatin + paclitaxel therapy were administered, the reexamination of the tumor was evaluated as partial response (PR), and a sleeve lobectomy of the right upper lung was performed under single-port thoracoscopic surgery. The operation proceeded smoothly without conversion to thoracotomy, and R0 resection was successfully achieved. Postoperative pathological stage was ypT1bN0M0 stage IA, and postoperative pathological remission was evaluated as major pathological response (MPR). After the operation, three cycles of immunotherapy combined with chemotherapy were completed, which was followed by maintenance therapy with pembrolizumab monotherapy for 1 year, and no signs of tumor recurrence and metastasis have been found in follow-up thus far. Conclusions: Through this case, we believe that for locally advanced NSCLC sleeve lobectomy after neoadjuvant therapy may be a safe and feasible treatment option, can avoid pneumonectomy, protect the lung function of patients, and still ensure the R0 resection rate. Moreover, it may does not significantly increase the difficulty of surgical operation or reduce safety. However, further research is needed to confirm our conclusion. And then, neoadjuvant therapy in the perioperative period may induce a series of side effects or adverse reactions, and thus greater attention should be paid to its timely management.

13.
Drug Des Devel Ther ; 18: 639-650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476203

RESUMO

Background: Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section. Methods: A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness. Results: No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups. Conclusion: A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.


Assuntos
Raquianestesia , Cesárea , Hipotensão , Pré-Eclâmpsia , Feminino , Humanos , Recém-Nascido , Gravidez , Raquianestesia/efeitos adversos , Bradicardia/induzido quimicamente , Método Duplo-Cego , Hipotensão/tratamento farmacológico , Norepinefrina , Fenilefrina , Pré-Eclâmpsia/tratamento farmacológico , Vasoconstritores
14.
Angew Chem Int Ed Engl ; : e202403492, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482742

RESUMO

The development of self-replicating systems is of great importance in research on the origin of life. As the most iconic molecules, nucleic acids have provided prominent examples of the fabrication of self-replicating artificial nanostructures. However, it is still challenging to construct sophisticated synthetic systems that can create large-scale or three-dimensionally ordered nanomaterials using self-replicating nanostructures. By integrating a template system containing DNA-functionalized colloidal seeds with a simplified DNA strand-displacement circuit programmed subsystem to produce DNA-functionalized colloidal copies, we developed a facile enthalpy-mediated strategy to control the replication and catalytic assembly of DNA-functionalized colloids in a time-dependent manner. The replication efficiency and crystal quality of the resulting superlattice structures can be effectively increased by regulating the molar ratio of the template to the copy colloids. By constructing binary systems from two types of gold nanoparticles (or proteins), superlattice structures with different crystal symmetries can be obtained through the replication and catalytic assembly processes. This programmable enthalpy-mediated approach was easily leveraged to achieve the phase transformation and catalytic amplification of colloidal crystals starting from different initial template crystals. This work offers a potential way to construct self-replicating artificial systems that exhibit complicated phase behaviors and can produce large-scale superlattice nanomaterials.

15.
Cell Mol Life Sci ; 81(1): 121, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457049

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality worldwide. Emerging evidence indicates that long noncoding RNAs (lncRNAs) are involved in human cancers, including ESCC. However, the detailed mechanisms of lncRNAs in the regulation of ESCC progression remain incompletely understood. LUESCC was upregulated in ESCC tissues compared with adjacent normal tissues, which was associated with gender, deep invasion, lymph node metastasis, and poor prognosis of ESCC patients. LUESCC was mainly localized in the cytoplasm of ESCC cells. Knockdown of LUESCC inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in vivo. Mechanistic investigation indicated that LUESCC functions as a ceRNA by sponging miR-6785-5p to enhance NRSN2 expression, which is critical for the malignant behaviors of ESCC. Furthermore, ASO targeting LUESCC substantially suppressed ESCC both in vitro and in vivo. Collectively, these data demonstrate that LUESCC may exerts its oncogenic role by sponging miR-6785-5p to promote NRSN2 expression in ESCC, providing a potential diagnostic marker and therapeutic target for ESCC patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Progressão da Doença , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
16.
Cell Death Discov ; 10(1): 110, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431720

RESUMO

The oncogenic role of circRNA in cancers including esophageal cancer (EC) has been well studied. However, whether and how circRNAs are involved in cancer cell metabolic processes remains largely unknown. Here, we reported that circRNA, circHIPK3, is highly expressed in ESCC cell lines and tissues. Knockdown of circHIPK3 significantly restrained cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, circHIPK3 was found to act as a ceRNA by sponging miR-637 to regulate FASN expression and fatty acid metabolism in ESCC cells. Anti-sense oligonucleotide (ASO) targeting circHIPK3 substantially inhibited ESCC both in vitro and in vivo. Therefore, these results uncover a modulatory axis constituting of circHIPK3/miR-637/FASN may be a potential biomarker and therapeutic target for ESCC in the clinic.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38342430

RESUMO

BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

19.
Natl Sci Rev ; 11(3): nwad171, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38312374

RESUMO

Transformation optics (TO) provides an unprecedented technique to control electromagnetic (EM) waves by engineering the constitutive parameters of the surrounding medium through a proper spatial transformation. In general, ideal transformation optical devices require simultaneous electric and magnetic responses along all three dimensions. To ease the practical implementation, previous studies usually made use of reduced parameters or other simplified approaches, which inevitably introduce extra reflection or unwanted phase shift. Up to today, experimental realizations of full-parameter transformation optical devices in free space are still quite limited. Here, a general design strategy is proposed to solve this problem. As a specific example, a full-parameter spatial-compression TO medium with constitutive parameters taking the diagonal form diag(a, a, 1/a) for the TM wave incidence was designed and realized experimentally. Such spatial-compression TO media were then applied to the implementation of an ideal omnidirectional invisibility cloak capable of concealing a large-scale object over a wide range of illumination angles. Both the simulation and experiment confirm that the cloak allows for nearly unity transmission of EM waves in the forward direction without introducing extra scattering or phase shift. This work constitutes an important stepping stone for future practical implementation of arbitrary full-parameter omnidirectional transformation optical devices.

20.
Health Sci Rep ; 7(2): e1870, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38357492

RESUMO

Background and Aims: The National Standardized Training for Resident Doctors (STRD) in mainland China encounters many challenges in its implementation. To investigate whether outpatients are willing to undergo indirect ophthalmoscopy examination conducted by ophthalmology residents in the ophthalmology STRD program in China. Methods: This study conducted a cross-sectional survey at the Eye Hospital of Wenzhou Medical University between September 2021 and September 2023. A cohort of 300 initial outpatients requiring indirect ophthalmoscopy examinations were enlisted from the outpatient department. Based on whether the patients are willing to undergo an indirect ophthalmoscopy examination by resident doctors, patients were divided into two groups: Group 1 (willing) and Group 2 (unwilling), and their questionnaire responses were comparatively analyzed. Results: A total of 261/300 (87%) valid questionnaires were returned in the survey, which included 149 males and 112 females. No notable gender difference (p = 0.400) or disparity in medical expense categories (p = 0.786) was observed between the two groups. However, variables such as outpatient marital status (p = 0.002), the presence of training faculty during fundus examinations with residents and outpatients (p < 0.001), the demeanor of training residents toward patients (p < 0.001), and the quality of doctor-patient communication (p < 0.001) significantly varied between the groups. Conclusion: The level of outpatients' cooperation with ophthalmology residents during fundus examinations in the Chinese ophthalmology STRD program was observed to be low. Enhancing the presence of training faculty during examinations and enhancing the communication skills of training residents could significantly improve this situation.

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