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Objective: To study the clinical effects of anlotinib combined with second-line chemotherapy (SLC) on immunosuppression in patients with advanced non-small cell lung cancer (NSCLC). Methods: In this retrospective study, the medical records of 106 patients with advanced NSCLC admitted to the Lianyungang First People's Hospital from November 2020 to March 2022 were retrospectively analyzed. Amongst 106 patients, 53 patients received second-line single-agent chemotherapy regimens (SLC group), and 53 patients received anlotinib combined with SLC (ASLC group). Prognosis, levels of immune cells and inflammatory cytokine, and adverse reactions were analyzed. Results: Clinical efficacy of the ASLC group was significantly higher than the SLC group (p<0.05). After treatment, patients in the ASLC group exhibited significantly higher levels of CD4+/CD8+ and CD4+ compared to those in the SLC group (p<0.05), while the difference in CD8+ level between the two groups was not statistically significant (p>0.05). After treatment, levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6) in the ASLC group were lower compared to the SLC group (p<0.05). Conclusion: In patients with advanced NSCLC, anlotinib combined with SLC is associated with higher levels of immune cells and reduced inflammatory factors. This treatment regimen, thus, can reduce immunosuppression and improve the prognosis of NSCLC patients.
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PURPOSE: To evaluate the effectiveness of trigger point manual therapy (TPMT) in treating rotator cuff related shoulder pain (RCRSP). METHODS: Randomized controlled trials that compared the effects of TPMT with no or other conservative treatments in patients with RCRSP were included. Primary outcomes were shoulder pain intensity and function. Secondary outcomes were pressure pain threshold (PPT) and number of myofascial trigger points (MTrPs). The Cochrane Risk of Bias 2.0 tool, PEDro scale and GRADE approach were employed. RESULTS: Ten studies were included in this systematic review and seven in the meta-analysis. Very low to low quality of evidence showed no statistically significant difference between TPMT and other conservative treatments in rest and activity pain reduction in the short term (3 days to 12 weeks), and the difference in shoulder function was statistically significant in favor of TPMT. Furthermore, TPMT was found to be effective in the improvement of PPT and the inactivation of active MTrPs in the short term. CONCLUSION: TPMT may be equally effective as other passive treatments for the pain reduction in patients with RCRSP in the short term, and slightly more effective for functional improvement. TPMT seems to be effective to treat the active MTrPs in RCRSP. REGISTRATION NUMBER: CRD42023409101.
Trigger point manual therapy (TPMT) seems to be effective to treat the active trigger points of rotator cuff related shoulder pain (RCRSP) in the short term (3 days to 12 weeks).TPMT may be equally effective as other passive treatments for the pain reduction in patients with RCRSP in the short term (3 days to 12 weeks), and slightly more effective for functional improvement.TPMT may be recommended for use in comprehensive treatment programs which may include active components such as exercise therapy and education for the rehabilitation of RCRSP.
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BACKGROUND: Cardiac T1 mapping is valuable for evaluating myocardial fibrosis, yet its resolution and acquisition efficiency are limited, potentially obscuring visualization of small pathologies. PURPOSE: To develop a technique for high-resolution cardiac T1 mapping with a less-than-100-millisecond acquisition window based on radial MOdified Look-Locker Inversion recovery (MOLLI) and a calibrationless space-contrast-coil locally low-rank tensor (SCC-LLRT) constrained reconstruction. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Sixteen healthy subjects (age 25 ± 3 years, 44% females) and 12 patients with suspected cardiomyopathy (age 57 ± 15 years, 42% females), NiCl2-agar phantom. FIELD STRENGTH/SEQUENCE: 3-T, standard MOLLI, radial MOLLI, inversion-recovery spin-echo, late gadolinium enhancement. ASSESSMENT: SCC-LLRT was compared to a conventional locally low-rank (LLR) method through simulations using Normalized Root-Mean-Square Error (NRMSE) and Structural Similarity Index Measure (SSIM). Radial MOLLI was compared to standard MOLLI across phantom, healthy subjects, and patients. Three independent readers subjectively evaluated the quality of T1 maps using a 5-point scale (5 = best). STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient analysis, linear regression, Bland-Altman analysis. P < 0.05 was considered statistically significant. RESULTS: In simulations, SCC-LLRT demonstrated a significant improvement in NRMSE and SSIM compared to LLR. In phantom, both radial MOLLI and standard MOLLI provided consistent T1 estimates across different heart rates. In healthy subjects, radial MOLLI exhibited a significantly lower mean T1 (1115 ± 39 msec vs. 1155 ± 36 msec), similar T1 SD (74 ± 14 msec vs. 67 ± 23 msec, P = 0.20), and similar T1 reproducibility (28 ± 18 msec vs. 22 ± 15 msec, P = 0.34) compared to standard MOLLI. In patients, the proposed method significantly improved the sharpness of myocardial boundaries (4.50 ± 0.65 vs. 3.25 ± 0.43), the conspicuity of papillary muscles and fine structures (4.33 ± 0.74 vs. 3.33 ± 0.47), and artifacts (4.75 ± 0.43 vs. 3.83 ± 0.55). The reconstruction time for a single slice was 5.2 hours. DATA CONCLUSION: The proposed method enables high-resolution cardiac T1 mapping with a short acquisition window and improved image quality. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
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Elastic aerogels have become a research hot spot in both academia and industry recently. The reported elastic aerogels are all made of hard materials by controlling their shapes. Herein we report an elastic aerogel made of a polymer elastomer with entropy elasticity. In the aerogel, cross-linked carboxyl nitrile rubber nanoparticles with hydrophilicity are dispersed in hydrophobic derivative of styrene-maleic anhydride alternating copolymer, forming a very special micro-nano surface structure with hydrophilic protrusions and hydrophobic depressions on the aerogel wall; therefore, the aerogel is not only superelastic but also superamphiphilic. A leak-free phase-change composite was prepared using the aerogel and paraffin, which can maintain at phase change temperature of paraffin for a longer time than the traditional one. The aerogel is also extremely suitable for desalination evaporators in solar-driven interfacial evaporation technology due to its superamphiphilicity, superelasticity, and ability to absorb sunlight. Exceptional evaporation rate of 2.78 kg·m-2·h-1 and evaporation efficiency of 170% could be reached even without using expensive light-absorbing materials. The evaporation rate exceeds that of most evaporators with expensive light-absorbing materials, and the evaporation efficiency exceeds the theoretical limit of conventional 2D solar evaporators. Both the phase-change composite and the evaporator can be easily recovered because the novel superelastic aerogel reported in this work is also recyclable.
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B7-H3 (CD276), an immune checkpoint molecule, is overexpressed in various types of cancer and their tumor vasculature, demonstrating significant associations with adverse clinical outcomes. In addition to its well-known immune functions, B7-H3 exhibits dual co-stimulatory/co-inhibitory roles in normal physiology and the tumor microenvironment. The non-immune functions of B7-H3 in tumor cells and the tumor vasculature, including promoting tumor cell anti-apoptosis, proliferation, invasion, migration, drug resistance, radioresistance, as well as affecting cellular metabolism and angiogenesis, have increasingly gained attention from researchers. Particularly, the co-expression of B7-H3 in both tumor cells and tumor endothelial cells highlights the higher potential and clinical utility of therapeutic strategies targeting B7-H3. This review aims to summarize the recent advances in understanding the non-immune functions of B7-H3 in tumors and provide insights into therapeutic approaches targeting B7-H3, focusing on its co-expression in tumor cells and endothelial cells. The aim is to establish a theoretical foundation and practical reference for the development and optimization of B7-H3-targeted therapies.
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BACKGROUND: Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further. CASE PRESENTATION: In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR. CONCLUSIONS: The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and the related mechanisms need to be further studied.
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To overcome the two main obstacles of large-scale application of superspreading material, self assembly is used to prepare superspreading polymer membrane (SPPM) in this work. An amphiphilic SPPM is prepared by capillary force-driven self assembly using PP melt-blown nonwovens and polyvinyl alcohol (PVA). The prepared SPPM has low preparation cost and stable performance since self assembly needs low energy consumption, and the production is thermodynamically stable. By using cryo-electron microscopy, transmission electron microscopy, X-ray photoelectron spectrum and scanning electron microscope with energy dispersive X-ray spectroscopy. It is proved that PVA is successfully assembled on the fiber surface of PP melt-blown nonwovens. The prepared SPPM has excellent spreading performance, the "spreading times" of both water and oil are less than 0.5 s. They showed much superior performance compared to traditional materials when applied in oil-water separation, seawater desalination, and ion separation. This work will definitely promote the development of self assembly, superspreading materials, and related sciences.
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BACKGROUND: Flies are acknowledged as vectors of diseases transmitted through mechanical means and represent a significant risk to human health. The study aimed to determine the prevalence of enteropathogens carried by flies in Pudong New Area to inform strategies for preventing and controlling flies. METHODS: Samples were collected from various locations in the area using cage trapping techniques between April and November 2021, encompassing various habitats such as parks, residential areas, restaurants, and farmers' markets. The main fly species were identified using cryomicrography and taxonomic enumeration, with 20 samples per tube collected from different habitats. Twenty-five enteropathogens were screened using GI_Trial v3 TaqManTM microbial arrays. RESULTS: A total of 3,875 flies were collected from 6,400 placements, resulting in an average fly density of 0.61 flies per cage. M. domestica were the most common species at 39.85%, followed by L. sericata at 16.57% and B. peregrina at 13.14%. Out of 189 samples, 93 tested positive for enteropathogens, with nine different pathogens being found. 12.70% of samples exclusively had parasites, a higher percentage than those with only bacteria or viruses. The study found that M. domestica had fewer enteropathogens than L. sericata and B. peregrina, which primarily harbored B. hominis instead of bacteria and viruses such as E. coli, Astrovirus, and Sapovirus. During spring testing, all three fly species exhibited low rates of detecting enteropathogens. M. domestica were found in residential areas with the highest number of pathogen species, totaling six. In contrast, L. sericata and B. peregrina were identified in farmers' markets with the highest number of pathogen species, totaling six and seven, respectively. CONCLUSIONS: Flies have the potential to serve as vectors for the transmission of enteropathogens, thereby posing a substantial risk to public health.
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Insectos Vectores , Animales , Humanos , Insectos Vectores/microbiología , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/genética , China/epidemiología , Dípteros/microbiología , Virus/aislamiento & purificación , Virus/clasificación , Virus/genética , Muscidae/microbiologíaRESUMEN
OBJECTIVE: To improve image quality in highly accelerated parameter mapping by incorporating a linear constraint that relates consecutive images. APPROACH: In multi-echo T1 or T2 mapping, scan time is often shortened by acquiring undersampled but complementary measures of k-space at each TE or TI. However, residual undersampling artifacts from the individual images can then degrade the quality of the final parameter maps. In this work, a new reconstruction method, dubbed Constrained Alternating Minimization for Parameter mapping (CAMP), is introduced. This method simultaneously extracts T2 or T1* maps in addition to an image for each TE or TI from accelerated datasets, leveraging the constraints of the decay to improve the reconstructed image quality. The model enforces exponential decay through a linear constraint, resulting in a biconvex objective function that lends itself to alternating minimization. The method was tested in four in vivo volunteer experiments and validated in phantom studies and healthy subjects, using T2 and T1 mapping, with accelerations of up to 12. MAIN RESULTS: CAMP is demonstrated for accelerated radial and Cartesian acquisitions in T2 and T1 mapping. The method is even applied to generate an entire T2 weighted image series from a single TSE dataset, despite the blockwise k-space sampling at each echo time. Experimental undersampled phantom and in vivo results processed with CAMP exhibit reduced artifacts without introducing bias. SIGNIFICANCE: For a wide array of applications, CAMP linearizes the model cost function without sacrificing model accuracy so that the well-conditioned and highly efficient reconstruction algorithm improves the image quality of accelerated parameter maps.
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Algoritmos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Fantasmas de Imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Artefactos , Encéfalo/diagnóstico por imagen , Reproducibilidad de los Resultados , Aumento de la Imagen/métodosRESUMEN
Malignant pleural effusion (MPE) is one of the common complications of lung cancer. The quality of life and prognoses for MPE patients are significantly compromised. Controlling the production of MPE can relieve patients' symptoms, improve their quality of life, and prolong their survival. This article presents a case of advanced non-small cell lung cancer (NSCLC) with MPE and negative driver genes. The patient received envafolimab and Endostar in combination, resulting in a complete reduction of MPE and durable clinical benefits. The exploratory use of this treatment method improved the quality of life of this patient and has the potential to prolong the survival of this patient.
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Mucopolysaccharidoses (MPSs) are caused by a deficiency in the enzymes needed to degrade glycosaminoglycans (GAGs) in the lysosome. The storage of GAGs leads to the involvement of several systems and even to the death of the patient. In recent years, an increasing number of therapies have increased the treatment options available to patients. Early treatment is beneficial in improving the prognosis, but children with MPSs are often delayed in their diagnosis. Therefore, there is an urgent need to develop a method for early screening and diagnosis of the disease. Tandem mass spectrometry (MS/MS) is an analytical method that can detect multiple substrates or enzymes simultaneously. GAGs are reliable markers of MPSs. MS/MS can be used to screen children at an early stage of the disease, to improve prognosis by treating them before symptoms appear, to evaluate the effectiveness of treatment, and for metabolomic analysis or to find suitable biomarkers. In the future, MS/MS could be used to further identify suitable biomarkers for MPSs for early diagnosis and to detect efficacy.
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Mucopolisacaridosis , Espectrometría de Masas en Tándem , Humanos , Mucopolisacaridosis/diagnóstico , Mucopolisacaridosis/metabolismo , Espectrometría de Masas en Tándem/métodos , Biomarcadores/metabolismo , Glicosaminoglicanos/metabolismoRESUMEN
PURPOSE: Multi-Shot (MS) Echo-Planar Imaging (EPI) may improve the in-plane resolution of multi-b-value DWI, yet it also considerably increases the scan time. Here we explored the combination of EPI with Keyhole (EPIK) and a calibrationless reconstruction algorithm for acceleration of multi-b-value MS-DWI. METHODS: We firstly analyzed the impact of nonuniform phase accrual in EPIK on the reconstructed image. Based on insights gained from the analysis, we developed a calibrationless reconstruction algorithm based on a Space-Contrast-Coil Locally Low-Rank Tensor (SCC-LLRT) constraint for reconstruction of EPIK-acquired data. We compared the algorithm with a modified SPatial-Angular Locally Low-Rank (SPA-LLR) algorithm through simulations, phantoms, and in vivo study. We then compared EPIK with uniformly undersampled EPI for accelerating multi-b-value DWI in 6 healthy subjects. RESULTS: Through theoretical derivations, we found that the reconstruction of EPIK with a SENSE-encoding-based algorithm, such as SPA-LLR, may cause additional aliasing artifacts due to the frequency-dependent distortion of the coil sensitivity. Results from simulations, phantoms, and in vivo study verified the theoretical finding by showing that the calibrationless SCC-LLRT algorithm reduced aliasing artifacts compared with SPA-LLR. Finally, EPIK with SCC-LLRT substantially reduced the ghosting artifacts compared with uniform undersampled multi-b-value DWI, decreasing the fitting errors in ADC (0.05 ± 0.01 vs 0.10 ± 0.01, P < 0.001) and IVIM mapping (0.026 ± 0.004 vs 0.06 ± 0.006, P < 0.001). CONCLUSION: The SCC-LLRT algorithm reduced the aliasing artifacts of EPIK by using a calibrationless modeling of the multi-coil data. The dense sampling of k-space center offers EPIK a potential to improve image quality for acceleration of multi-b-value MS-DWI.
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Algoritmos , Imagen de Difusión por Resonancia Magnética , Imagen Eco-Planar , Procesamiento de Imagen Asistido por Computador , Fantasmas de Imagen , Humanos , Imagen Eco-Planar/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Adulto , Masculino , Artefactos , Simulación por Computador , Femenino , Reproducibilidad de los Resultados , Aumento de la Imagen/métodosRESUMEN
The aging process leads to the degeneration of body structure and function. The objective of this study is to conduct a systematic review and meta-analysis of the effects of resistance circuit training (RCT) on comprehensive health indicators of older adults. PubMed, Embase, and Web of Science were searched until August 2023. Primary outcomes were body composition, muscle strength, cardiorespiratory endurance, blood pressure, and functional autonomy. Muscle function and exercise intensity subgroups were analyzed. RCT reduces body fat (MD = - 5.39 kg, 95% CI - 10.48 to - 0.29), BMI (MD = - 1.22, 95% CI - 2.17 to - 0.26), and body weight (MD = - 1.28 kg, 95% CI - 1.78 to - 0.78), and increases lean body mass (MD = 1.42 kg, 95% CI 0.83-2.01) in older adults. It improves upper limb strength (SMD = 2.09, 95% CI 1.7-2.48), lower limb strength (SMD = 2.03, 95% CI 1.56-2.51), cardiorespiratory endurance (MD = 94 m, 95% CI 25.69-162.67), and functional autonomy (MD = - 1.35, 95% CI - 1.73 to - 0.96). High-intensity RCT benefits BMI and body weight, while low-intensity exercise reduces blood pressure. RCT improves muscle function in push, pull, hip, and knee movements in older adults. RCT improves body composition, muscle strength, cardiorespiratory endurance, blood pressure, and functional autonomy in older adults. High-intensity training is superior for body composition, while moderate to low intensity training is more effective for lowering blood pressure.
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Composición Corporal , Fuerza Muscular , Entrenamiento de Fuerza , Humanos , Entrenamiento de Fuerza/métodos , Fuerza Muscular/fisiología , Anciano , Ejercicio en Circuitos/métodos , Presión Sanguínea/fisiología , Masculino , FemeninoRESUMEN
Aerogels prepared using freeze-drying methods have the potential to be insulation materials or absorbents in the fields of industry, architecture, agriculture, etc., for their low heat conductivity, high specific area, low density, degradability, and low cost. However, their native, poor water resistance caused by the hydrophilicity of their polymer matrix limits their practical application. In this work, a novel, controllable, and efficient templating method was utilized to construct a highly hydrophobic surface for freeze-drying aerogels. The influence of templates on the macroscopic morphology and hydrophobic properties of materials was investigated in detail. This method provided the economical and rapid preparation of a water-resistant aerogel made from polyvinyl alcohol (PVA) and montmorillonite (MMT), putting forward a new direction for the research and development of new, environmentally friendly materials.
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The mounting body of evidence demonstrates the growing importance of long noncoding RNAs in the advancement of tumors. This study aimed to investigate the molecular mechanism of lnc-SNAPC5-3:4 in non-small cell lung cancer (NSCLC). We investigated the expression of miR-224-3p and lnc-SNAPC5-3:4 in clinical NSCLC samples and NSCLC cell lines using reverse transcription polymerase chain reaction (RT-PCR). In vitro studies, A549 cell growth was estimated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EDU), and flow cytometry assays. In vivo studies, NSCLC tumorigenesis was determined using xenograft tumor mouse models, tumor growth was evaluated using antigen Kiel 67 (Ki67) staining, and tumor apoptosis was detected through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The relationship between lnc-SNAPC5-3:4 and miR-224-3p was determined by luciferase reporter gene assay. Results indicated that the expression of lnc-SNAPC5-3:4 was observed to be downregulated in NSCLC tissues and cell lines. After overexpression of lnc-SNAPC5-3:4 in cultured A549 cells, proliferation decreased and apoptosis increased. Furthermore, the expression of miR-224-3p was targeted and negatively regulated by lnc-SNAPC5-3:4. The lnc-SNAPC5-3:4 upregulation inhibited cell proliferation and promoted apoptosis, which was partially blocked by miR-224-3p overexpression in A549 cells. In addition, we constructed a subcutaneous inoculation model using BALB/c nude mice, and the results indicated that lnc-SNAPC5-3:4 overexpression restrained the growth of subcutaneous tumors, decreased Ki67 expression levels, and increased apoptosis, as indicated by TUNEL staining in nude mice. However, miR-224-3p transfection resulted in the reversal of the inhibitory effect of lnc-SNAPC5-3:4 on tumor growth. In conclusion, our study revealed that lnc-SNAPC5-3:4 inhibits tumor progression in NSCLC by targeting miR-224-3p. This study provides a potential therapeutic target for inhibiting NSCLC progression.
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Recent advances in laser technology have enabled tremendous progress in light-induced molecular reactions, at the heart of which the breaking and formation of chemical bonds are located. Such progress has been greatly facilitated by the development of an accurate quantum-mechanical simulation method, which, however, does not necessarily accompany clear dynamical scenarios and is rather computationally heavy. Here, we develop a wave-packet surface propagation (WASP) approach to describe the molecular bond-breaking dynamics from a hybrid quantum-classical perspective. Via the introduction of quantum elements including state transitions and phase accumulations to the Newtonian propagation of the nuclear wave packet, the WASP approach naturally comes with intuitive physical scenarios and accuracies. It is carefully benchmarked with the H_{2}^{+} molecule and is shown to be capable of precisely reproducing experimental observations. The WASP method is promising for the intuitive visualization of light-induced molecular dynamics and is straightforward extensible towards complex molecules.
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Numerous studies have demonstrated that regulatory T (Treg) cells play an important role in the tumour microenvironment (TME). The aim of this study was to investigate whether VEGFR2 affects the expression of miR-3200-3p in exosomes secreted by tumour cells, thereby influencing Treg senescence in the TME. The results showed that VEGFR2 expression level was the highest in Calu-1 cells, and after transfection with si-VEGFR2, the exosomes secreted from Calu-1 cells were extracted and characterised with no significant difference from the exosomes of the untransfected group, but the expression of miR-3200-3p in the exosomes of the transfected si-VEGFR2 group was elevated. The Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) results suggested that exosomes highly expressing miR-3200-3p could inhibit Treg cell viability and promote apoptosis levels when treated with Treg cells. Detection of the senescence-associated proteins p16 INK4A and MMP3 by western blot (WB) revealed that exosomes highly expressing miR-3200-3p were able to elevate their protein expression levels. Tumour xenograft experiments demonstrated that exosomes with high miR-3200-3p expression promoted Treg cell senescence and inhibited subcutaneous tumour growth in nude mice. Dual-luciferase reporter assays and RNA pull-down assays showed that miR-3200-3p could be linked with DDB1. Overexpression of DDB1 reverses changes in DCAF1/GSTP1/ROS protein expression caused by exosomes with high miR-3200-3p expression. In conclusion, inhibition of VEGFR2 expression in tumour cells promotes the expression of miR-3200-3p in exosomes secreted by tumour cells. miR-3200-3p enters the TME through exosomes and acts on DDB1 in Treg cells to promote senescence of Treg cells to inhibit tumour progression.
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Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , MicroARNs , Animales , Ratones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Neoplasias Pulmonares/patología , Exosomas/genética , Exosomas/metabolismo , Ratones Desnudos , Senescencia de Células T , Proliferación Celular/genética , Microambiente TumoralRESUMEN
The clinical significance of plasma soluble programmed cell death ligand 1 (sPD-L1) and vascular endothelial growth factor (VEGF) for non-small cell lung cancer (NSCLC) treated with the combination of anti-angiogenic therapy and anti-PD-L1 antibody (Ab) remain unknown. This study aimed to explore the association between plasma sPD-L1 and VEGF levels and the prognosis of NSCLC patients treated with the combination of Envafolimab and Endostar. Peripheral blood samples were collected from 24 NSCLC patients at baseline and after 6 weeks of treatment and were detected for sPD-L1 and VEGF levels. Both baseline and posttreatment sPD-L1 were significantly higher in progressive disease (PD) group than in controlled disease (CD) group (median: 77.5 pg/ml vs. 64.6 pg/ml, P â =â 0.036, median: 8451 pg/ml vs. 5563 pg/ml, P â =â 0.012). In multivariate analysis, lower baseline sPD-L1 levels were significantly associated with longer progression-free survival (PFS) (HRâ =â 6.834, 95% CI: 1.350-34.592, P â =â 0.020). There were significantly higher posttreatment VEGF levels in PD group compared with CD group (median: 323.7 pg/ml vs. 178.5 pg/ml, P â =â 0.009). Higher posttreatment VEGF levels were significantly associated with shorter PFS in multivariate analysis (HRâ =â 5.911, 95% CI: 1.391-25.122, P â =â 0.016). Plasma sPD-L1 and VEGF levels are associated with the clinical response and prognosis of NSCLC patients treated with the combination of PD-L1 inhibitors and anti-angiogenetic therapy.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Factor A de Crecimiento Endotelial Vascular , Humanos , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Pronóstico , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/química , Antígeno B7-H1/sangre , Antígeno B7-H1/químicaRESUMEN
This study investigates the impact of urbanization on extreme winter rainfall in the South China Greater Bay Area (GBA) through the analysis of hourly station observations and simulations using the Weather Research and Forecasting Model with the Single Layer Urban Canopy Model (WRF-SLUCM). Data from 2008 to 2017 reveal that urban areas in the GBA experience lower 99th percentile hourly winter rainfall intensity compared to surrounding rural regions. However, urban locations exhibit higher annual maximum hourly rainfall (Rmax) and very extreme rainfall events (99.99th percentile) in winter, suggesting a positive influence of urbanization on extreme winter precipitation. A case study further underscores the role of the Urban Heat Island (UHI) effect in enhancing extreme rainfall intensity and probability in the GBA urban areas. Additionally, two extreme cases were dynamically downscaled using WRF-SLUCM, involving four parallel experiments: replacing urban land use with cropland (Nourban), using historical urban land use data from 1999 (99LS), projecting near-future urban land use for 2030 (30LS), and considering 2030 urban land use without anthropogenic heat (AH) (30LS-AH0). Synoptic analysis demonstrates that cold air intrusion suppresses the GBA UHI in Case 2013 but not in Case 2015. Reduced evaporation and humidity induced by urban surfaces significantly decrease urban precipitation in Case 2013. In contrast, the persistent UHI in Case 2015 enhances local convection and land-ocean circulation, leading to increased moisture flux convergence and amplified urban precipitation intensity and probability in 30LS compared to Nourban. This amplification is primarily attributed to AH, while the change in 99LS remains insignificant. These findings suggest that urban influences on extreme precipitation in the GBA persist during winter, particularly when the UHI effect is maintained.
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Circular RNAs (circRNAs) are a family of endogenous RNAs that have become a focus of biological research in recent years. Emerging evidence has revealed that circRNAs exert biological functions by acting as transcriptional regulators, microRNA sponges, and binding partners with RNA-binding proteins. However, few studies have identified coding circRNAs, which may lead to a hidden repertoire of proteins. In this study, we unexpectedly discovered a protein-encoding circular RNA circCCDC7(15,16,17,18,19) while we were searching for prostate cancer related chimeric RNAs. circCCDC7(15,16,17,18,19) is derived from exon 19 back spliced to exon 15 of the CCDC7 gene. It is significantly downregulated in patients with high Gleason score. Prostate cancer patients with decreased circCCDC7(15,16,17,18,19) expression have a worse prognosis, while linear CCDC7 had no such association. Overexpressed circCCDC7(15,16,17,18,19) inhibited prostate cancer cell migration, invasion, and viability, supporting classification of circCCDC7(15,16,17,18,19) as a bona fide tumor suppressor gene. We provide evidence that its tumor suppressive activity is driven by the protein it encodes, and that circCCDC7(15,16,17,18,19) encodes a secretory protein. Consistently, conditioned media from circCCDC7(15,16,17,18,19) overexpressing cells has the same tumor suppressive activity. We further demonstrate that the tumor suppressive activity of circCCDC7(15,16,17,18,19) is at least partially mediated by FLRT3, whose expression also negatively correlates with Gleason score and clinical prognosis. In conclusion, circCCDC7(15,16,17,18,19) functions as a tumor suppressor in prostate cancer cells through the circCCDC7-180aa secretory protein it encodes, and is a promising therapeutic peptide for prostate cancer.