DNA topoisomerases are essential to modulate DNA topology during various cellular genetic processes. The expression and distinct prognostic value of topoisomerase isoforms in non-small-cell lung ...cancer (NSCLC) is not well established. In the current study, we have examined the mRNA expression of topoisomerase isoforms by using Oncomine analysis and investigated their prognostic value via the Kaplan-Meier plotter database in NSCLC patients. Our analysis indicated that the expression level of topoisomerases in lung cancer was higher compared with normal tissues. Especially, high expression of two topoisomerase isoforms, TOP2A and TOP3A, was found to be correlated to worse overall survival (OS) in all NSCLC and lung adenocarcinoma (Ade) patients, but not in lung squamous cell carcinoma (SCC) patients. In a contrast, high expression of isoforms TOP1 and TOP2B indicated better OS in all NSCLC and Ade, but not in SCC patients. Meanwhile, high expression of TOP1MT and TOP3B was not correlated with OS in NSCLC patients. Furthermore, we also demonstrated a relationship between topoisomerase isoforms and the clinicopathological features for the NSCLC patients, such as grades, clinical stages, lymph node status, smoking status, gender, chemotherapy and radiotherapy. These results support that TOP2A and TOP3A are associated with worse prognosis in NSCLC patients. In addition, our study also shows that TOP1 and TOP2B contribute to favorable prognosis in NSCLC patients. The exact prognostic significance of TOP1MT and TOP3B need to be further elucidated. Comprehensive evaluation of expression and prognosis of topoisomerase isoforms will be a benefit for the better understanding of heterogeneity and complexity in the molecular biology of NSCLC, paving a way for more accurate prediction of prognosis and discovery of potential drug targets for NSCLC patients.
Combining immune checkpoint inhibitors with vascular endothelial growth factor/vascular endothelial growth factor receptor inhibitors is effective in treating a number of solid tumors; however, ...evidence in advanced gastric/gastroesophageal junction (G/GEJ) cancer is limited. This retrospective study included consecutive patients who received a programmed cell death protein 1 (PD‐1) inhibitor plus the vascular endothelial growth factor receptor 2 inhibitor apatinib, second‐line or later to treat unresectable advanced or metastatic, histologically proven, human epidermal growth factor receptor 2–negative G/GEJ cancer in a single center between November 1, 2018, and March 31, 2021. Treatment was continued until the disease progressed or the toxicity became intolerable. We examined data from 52 patients. The primary tumor site was the stomach in 29 patients and the GEJ in 23 patients. PD‐1 inhibitors administered included camrelizumab (n = 28), sintilimab (n = 18), pembrolizumab (n = 3), and tislelizumab (n = 1), and all patients were given 200 mg every 3 weeks, and toripalimab (240 mg every 3 weeks) and nivolumab (200 mg every 2 weeks) were given to 1 patient each. For 28 days, apatinib 250 mg was administered orally once a day. The objective response rate was 15.4% (95% confidence interval CI, 6.9‐28.1), and the disease control rate was 61.5% (95%CI, 47.0‐74.7). After 14.8 months of median follow‐up, the median progression‐free survival was 4.2 months (95%CI, 2.6‐4.8), and the overall survival was 9.3 months (95%CI, 7.9‐12.9). Twelve patients underwent grade 3‐4 treatment‐related adverse events (23.1%). There was no unexpected toxicity or death. This trial demonstrated combination therapy with an anti–PD‐1 antibody and apatinib was effective and safe in patients with previously treated unresectable advanced or metastatic G/GEJ cancer.
Flexible electronic skins (e‐skins) play a very important role in the development of human–machine interaction and wearable devices. To fully mimic the functions of human skin, e‐skins should be able ...to perceive multiple external stimuli (such as temperature, touch, and friction) and be resistant to injury. However, both objectives are highly challenging. The fabrication of multifunctional e‐skins is difficult because of the complex lamination scheme and the integration of different sensors. The design of skin‐like materials is hindered by the trade‐off problem between flexibility, toughness, and self‐healing ability. Herein, flexible sodium methallyl sulfonate functionalized poly(thioctic acid) polymer chains are combined with rigid conductive polyaniline rods through ionic bonds to obtain a solvent‐free polymer conductive gel. The conductive gel has a modulus similar to that of skin, and shows good flexibility, puncture‐resistance, notch‐insensitivity, and fast self‐healing ability. Moreover, this conductive gel can convert changes in temperature and strain into electrical signal changes, thus leading to multifunctional sensing performance. Based on these superior properties, a flexible e‐skin sensor is prepared, demonstrating its great potential in the wearable field and physiological signal detection.
A new solvent‐free polymer conductive gel is obtained by combining flexible sulfonate‐containing poly(thioctic acid) polymer chains and rigid conductive polyaniline rods. The conductive gel shows good flexibility, puncture‐resistance, notch‐insensitivity, and fast self‐healing ability. Moreover, this conductive gel can convert changes in temperature and strain into electrical signal changes, and thus can be used for multifunctional electronic skin.
To investigate the clinical significance of the CHA
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-VASc-60 score, lipoprotein (a) Lp(a), red blood cell distribution width (RDW), and their combined effect in patients with non-valvular atrial ...fibrillation (NVAF) who experience acute ischemic stroke (AIS). This retrospective analysis was conducted on the clinical data of hospitalized patients with NVAF at the Third Affiliated Hospital of Anhui Medical University between April 1, 2020, and April 1, 2023. Based on the diagnosis of acute ischemic stroke (AIS), the patients were divided into two groups: the AIS group (150 cases of NVAF patients with comorbid AIS) and the non-AIS group (163 cases of NVAF patients without AIS). We performed CHA
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-VASc-60 scoring for all patients and collected their laboratory indicators and echocardiographic indicators during hospitalization. The study comprised 313 individuals with NVAF in total. There is a statistically significant difference (P < 0.05) in the comparison of CHA
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-VASc-60 score (5.68 ± 1.12 vs. 3.67 ± 1.47), Lp(a) 23.98 (13.28, 42.22) vs. 14.32 (7.96, 21.91) and RDW (13.67 ± 1.25 vs. 12.94 ± 0.76) between NVAF patients with and without concomitant AIS. The results of the Spearman correlation analysis demonstrate a positive association between Lp(a) and RDW levels and both the CHA
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-VASc score and the CHA
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-VASc-60 score in patients with NVAF. Multivariate logistic regression analysis revealed that CHA
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-VASc-60 score OR = 6.549, 95% CI: 4.110-10.433, P < 0.05, Lp(a) OR = 1.023, 95% CI: 1.005-1.041, P < 0.05, and RDW OR = 1.644, 95% CI: 1.071-2.525, P < 0.05 were independent risk factors for AIS in patients with non-valvular atrial fibrillation (NVAF). The receiver operator characteristic (ROC) curves showed that the area under the curve of CHA
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-VASc-60 score, Lp(a), RDW, and CHA
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-VASc-60 score combined with Lp(a) and RDW predicted that NVAF patients with AIS were 0.881 95% CI: 0.804-0.906, 0.685 95% CI: 0.626-0.744, 0.695 95% CI: 0.637-0.754, and 0.906 95% CI: 0.845-0.921, respectively. The CHA
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-VASc-60 score, Lp(a), and RDW were significantly increased in NVAF patients with AIS, which were independent risk factors for NVAF patients with AIS. The combination of the three has a high predictive capacity for NVAF patients with AIS.
Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2 macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ ...during pregnancy have not been completely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in the maintenance of maternal-fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces the polarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, which facilitates the inactivation of NK cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2 MΦ. The data shown in the present study provide evidence to support the hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involved in decidual M2 MΦ polarization, which in turn regulates the killing ability of NK cells, thereby contributing to the homeostatic and immune-tolerant milieu required for successful fetal development.
The relationship between biodiversity and litter decomposition has received considerable attention, but the complex biodiversity effects on decomposition and the underlying mechanisms are still ...unclear, especially in boreal riparian forest ponds. Here, we collected leaf litter from an N₂⁻fixing species (Alnus sibirica) and two non-N₂⁻fixing species (Betula platyphylla and Betula fruticosa) in a boreal riparian forest, northeast China. Then, we mixed leaf litter with varying composition and evenness to create a large gradient of litter functional identity and functional diversity, and used the litterbag method to examine the effect of altering plant composition on litter mass loss and nitrogen (N) release during 2 years of decomposition in forest ponds. Over 2 years of decomposition, the presence of A. sibirica in litter assemblages accelerated mass loss and N release by improving functional identity and increasing functional diversity of litter mixtures. Irrespective of the dominant species, litter mass loss generally increased with rising evenness, whereas the effect of species evenness on N release was dependent on the dominant species. When all litter mixtures were pooled, litter mixing effects on mass loss and N release correlated positively with litter functional diversity. Moreover, the decomposition dynamics of litter mixtures were regulated by litter functional diversity and the resulting mixing effects, as well as the community-weighted mean traits such as N and lignin concentrations. These findings confirm the importance of litter functional identity and functional diversity in driving decomposition processes of litter mixtures, and also indicate that increased abundance of N₂⁻fixing species will accelerate litter decomposition and enhance N release in boreal riparian forest ponds.
Most existing bioadhesives, even those showing superiority in wound closure effectiveness, do not assist in the post‐wound closure process. A bioinspired, in situ formed, double‐dynamic‐bond ...crosslinked hydrogel bioadhesive that is capable of efficiently closing open wounds and enabling post‐wound closure care is reported. Catechol‐modified ε‐poly‐l‐lysine and oxidized dextran are employed as natural polymer backbones and they are in situ crosslinked using Schiff's base dynamic bond and catecholFe coordinate dynamic bond through a process inspired by that used to cure marine mussel glue, forming a hydrogel bioadhesive. The unique double‐dynamic‐bond crosslinked structure endows the bioadhesive with higher mechanical and adhesive strength while retaining quick dissociation and good self‐healing capacities. Accordingly, the bioadhesive can exhibit multiple desirable functions, such as dissolution on demand, repeatable adhesiveness, adhesive and mechanical strength sufficient for wound closure, injectability, and good biocompatibility (DREAMING). After efficiently closing skin incisions, the bioadhesive can be facilely removed or repeatedly close the reopened wounds, thus enabling post‐wound closure care. On the basis of favorable functions in wound closure and the ability to enable post‐wound closure care, the bioadhesive demonstrates great potential in dealing with skin wounds.
A double‐dynamic‐bond crosslinked bioadhesive with DREAMING functions such as dissolution on demand, repeatable adhesiveness, adhesive and mechanical strength sufficient for wound closure, injectability, and good biocompatibility is presented. The adhesive, synthesized by mimicking the adhesion and curing process of marine mussel glue, is designed for efficient wound closure and post‐wound closure care.
In plants, carotenoids are essential for photosynthesis and photoprotection. However, carotenoids are not the end products of the pathway; apocarotenoids are produced by carotenoid cleavage ...dioxygenases (CCDs) or non-enzymatic processes. Apocarotenoids are more soluble or volatile than carotenoids but they are not simply breakdown products, as there can be modifications post-cleavage and their functions include hormones, volatiles, and signals. Evidence is emerging for a class of apocarotenoids, here referred to as apocarotenoid signals (ACSs), that have regulatory roles throughout plant development beyond those ascribed to abscisic acid (ABA) and strigolactone (SL). In this context we review studies of carotenoid feedback regulation, chloroplast biogenesis, stress signaling, and leaf and root development providing evidence that apocarotenoids may fine-tune plant development and responses to environmental stimuli.
Apocarotenoids regulate plant development and may function as signals in response to stress.
Apocarotenoids are proposed to fine-tune carotenoid biosynthesis flux.
Apocarotenoid formation is largely dependent on the specificities of the CCD family of enzymes.
Apocarotenoid formation is regulated by developmental and environmental stimuli and subcellular compartmentalization.
Studies conducted over several decades have shown that the freeze-thaw cycles are a process of energy input and output in soil, which help drive the formation of soil structure, through water ...expansion by crystallization and the movement of water and salts by thermal gradients. However, most of these studies are published in Russian or Chinese and are less accessible to international researchers. This review brought together a wide range of studies on the effects of freezing and thawing on soil structure. The following findings are summarized： i） soil structure after freeze-thaw cycles changes considerably and the changes are due to the mechanical fragmentation of soil coarse mineral particles and the aggregation of soil fine particles; ii） the particle size of soil becomes homogeneous and the variation in soil structure weakens as the number of freeze-thaw cycles increases; iii） in the freezing process of soil, an important principle in the variation of soil particle bonding is presented as： condensation →aggregation→ crystallization; iv） the freeze-thaw cycling process has a strong effect on soil structure by changing the granulometric composition of mineral particles and structures within the soil. The freeze-thaw cycling process strengthens particle bonding, which causes an overall increase in aggregate stability of soil, showing a process from destruction to reconstruction.
An increased number of highly active regulatory T cells (Tregs) and macrophages has been found in peritoneal fluid from women with endometriosis. Here, we show that the level of Tregs-derived soluble ...fibrinogen-like protein 2 (sFGL2) increases in the peritoneal fluid of women with endometriosis. Higher expression of FGL2 and its receptor CD32B is observed in eutopic endometrium and ectopic tissues. The production of sFGL2 in Tregs may be enhanced by several cytokines. sFGL2 selectively induces pro-repair macrophage polarization mainly through the activation of the SHP2-ERK1/2-STAT3 signaling pathway, and the suppression of the NF-κB signaling pathway. Furthermore, sFGL2 induces a much higher level of metallothionein (MT) expression that in turn facilitates pro-repair macrophages polarization. sFGL2-induced pro-repair macrophages promote Th2 and Tregs differentiation, creating a positive feedback loop. These findings suggest that sFGL2 secreted by Tregs skews macrophages toward a pro-repair phenotype via SHP2-ERK1/2-STAT3 signaling pathway, which is involved in the progression of endometriosis.
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