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Background and purpose: The response of human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer to HER2 targeted neoadjuvant therapy is significant. However, the response is not uniform, and a proportion of patients respond poorly. This study aimed to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive breast cancer. Methods: The study group included 110 HER2-positive breast cancer patients treated with neoadjuvant therapy and surgery who were diagnosed from 2019 to 2021 in Shenzhen People’s Hospital. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to detect the expression of HER2 in core needle biopsy specimens. Pathological complete response (pCR) and residual cancer burden (RCB) of surgically resected specimens after neoadjuvant therapy were used to assess the therapy response of patients. HER2, estrogen receptor (ER) and progesterone receptor (PR) status were further assessed in the residual invasive carcinoma present after neoadjuvant therapy. Results: One hundred and ten breast cancer patients were divided into IHC diffuse 3+ group (n=81), heterogeneous 3+ group (n=20), IHC 2+ and FISH amplified (2+FISH+) group (n=9). The pCR rate of HER2 diffuse 3+ group was 54.3%, which was significantly higher compared with heterogeneous 3+ group (5.0%) and 2+FISH+ group (11.1%), and the difference was statistically significant (P

Dear Editor, Fibrosis is characterized by fibroblast dysfunction and excessive deposition of cell-matrix that affect the normal functioning of the original tissue or organ.[1] The pathogenesis of keloids is complex and remains elusive. Fibroblasts interacted with endothelial cells via I ACKR1 i , while multiple chemokines ( I CXCL2 i , I CCL3L3 i ) secreted by myeloid cells interacted with I DPP4 i in fibroblasts (Figure 4D). (F) Interaction of macrophages and fibroblasts based on molecular patterns indicated that macrophages interact with fibroblasts via SPP1. CTHRC1+ fibroblasts are stimulated by macrophage-secreted SPP1 to induce excessive collagen deposition in keloids. [Extracted from the article]

Anthracycline is a mainstay of treatment for breast cancer patients because of its antitumor activity. However, anthracycline resistance is a critical barrier in treating breast cancer. Thus, it is of great importance to uncover the molecular mechanisms underlying anthracycline resistance in breast cancer. Herein, we integrated transcriptome data, genetic alterations data, and clinical data of The Cancer Genome Atlas (TCGA) to identify the molecular mechanisms involved in anthracycline resistance in breast cancer. Two hundred and four upregulated genes and 1376 downregulated genes were characterized between the anthracycline-sensitive and anthracycline-resistant groups. It was found that drug resistance-associated genes such as ABCB5, CYP1A1, and CYP4Z1 were significantly upregulated in the anthracycline-resistant group. The gene set enrichment analysis (GSEA) suggested that the P53 signaling pathway, DNA replication, cysteine, and methionine metabolism pathways were associated with anthracycline sensitivity. Somatic TP53 mutation was a common genetic abnormality observed in the anthracycline-sensitive group, while CDH1 mutation was presented in the anthracycline-resistant group. Immune infiltration patterns were extremely different between the anthracycline-sensitive and anthracycline-resistant groups. Immune-associated chemokines and cytokines, immune regulators, and human leukocyte antigen genes were significantly upregulated in the anthracycline-sensitive group. These results reveal potential molecular mechanisms associated with anthracycline resistance. [ABSTRACT FROM AUTHOR]

In this paper, a better particle filter algorithm is put forth to address the issues of particle filter sample exhaustion and weight degradation. The algorithm frames the received signal and separates the signals in two steps based on the slow-varying properties of system parameters in practical applications, such as phase shift and transmission delay. In addition, the network model and energy consumption model are built while the sensor data is being collected and processed using the industrial IoT's communication mechanism and algorithm. The repeater is chosen as the node with the lowest transmission energy consumption, and the industrial field's sensor data is gathered via the fog server node. The simulation results demonstrate that the proposed algorithm's accuracy rate is 95.54 percent, higher than that of the comparison algorithm. The enhanced algorithm suggested in this paper can simultaneously achieve improved parameter estimation performance and achieve signal separation with low bit error rates. Additionally, the communication system and algorithm can efficiently gather the sensing information from the industrial field, and the indicators like energy consumption and the first dead node are better than other algorithms. It offers an innovative method for enhancing industrial field application. [ABSTRACT FROM AUTHOR]

Background: Regenerative Epithelial Suspension can lead to the restoration of wound and repigmentation, which can be gained by ReCell medical device to treat scar and depigmentation diseases. Objectives: To report the effectivity of ReCell combined with microdermabrasion in scar and depigmentation diseases and review the literature of this new technology. Methods: We gave a differential donor⁄recipient ratio of about 1:20‐30 with vitiligo, 1:40 with postburn construction, 1:80 with acne scar, and 1:120 with adult congenital melanocytic nevus, 1:80 with pediatrics, respectively. Photographs of patients before treatment and 3 months following the last treatment session were used to evaluate the effectivity. Results: A total of 8 patients including vitiligo vulgaris, postburn reconstruction, acne scars, and congenital melanocytic nevi treated by ReCell technology combined with microdermabrasion showed significant improvement in skin texture and color. And 17 studies of the research on ReCell technology were totally included in the systematic review. Conclusion: Our investigation showed that Regenerative Epithelial Suspension gained by ReCell technology combined with microdermabrasion may improve scar and depigmentation diseases. [ABSTRACT FROM AUTHOR]

GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer. [ABSTRACT FROM AUTHOR]

Highlights • It's the first time to evidence that Exendin-4 is effective in promoting ADSCs proliferation via PI3K-Akt-Wnt pathway. • Exendin-4 activates the PI3K-Akt-GSK3β signaling pathway. • Exendin-4 activates the Wnt signaling pathway. Abstract Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease and skin wounds. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of Exendin-4, a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and Wnt signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD44, CD90 and CD29 but negative for CD31, CD34, and CD45. Exendin-4 (0–200 nM) treatment increased ADSC proliferation. In order to examine specific signaling pathways, a western blotting assay was performed. Our results demonstrate that after treated with 50 nM Exendin-4 for 48 h, the phosphorylation of PI3K, Akt, and GSK3β were increased and phosphorylation of β-catenin was decreased. From these results, we concluded that PI3K-Akt and Wnt-β-catenin signaling pathways mediate Exendin-4 induced ADSC proliferation, the function of which might contribute to the regulation of ADSC proliferation. Our findings provided new insights into the function of the mechanisms underlying Exendin-4 of ADSCs. [ABSTRACT FROM AUTHOR]

GNB2L1 is an intercellular scaffold protein of the Trp-Asp (WD) repeat protein family, and has been reported to play suppressive roles in the progression of gastric cancer. However, the regulatory mechanisms of GNB2L1 in gastric cancer still remain largely elusive. In the present study, we found that OGT was capable to interact with GNB2L1 directly and modify GNB2L1 with O-GlcNAcylation in gastric cancer, and this O-GlcNAcylation hindered the inhibition of GNB2L1 on migration of gastric cancer cells. Moreover, O-GlcNAcylation regulated the degradation instead of the synthesis of GNB2L1 in gastric cancer, and our data suggested the O-GlcNAcylation on GNB2L1 influenced its stability directly. In addition, the clinical data revealed the negative correlation of the protein level instead of the mRNA level of GNB2L1 with OGT expression, and showed that OGT reversed the inhibition of GNB2L1 on metastasis, and worsened the prognosis of GNB2L1 High patients. In summary, this study indicated the O-GlcNAcylation on GNB2L1 reversed its inhibition on gastric tumour metastasis via promoting its degradation. [ABSTRACT FROM AUTHOR]

Abstract: Hyperhomocysteinemia (HHcy), as an independent risk factor of atherosclerosis, facilitates endothelial dysfunction and activation of vascular smooth muscle cells (VSMCs). However, little is known about the crosstalk between endothelial cells (ECs) and VSMCs under HHcy. We investigated whether homocysteine (Hcy) activates VSMCs by aberrant secretion of mitogen platelet-derived growth factors (PDGFs) from ECs in human and in mice. In this study, we found that increased Hcy level did not affect VSMC activity in 24hrs until the concentration reached 500μM. In contrast, Hcy at 100μM significantly promoted proliferation and migration of VSMCs co-cultured with human ECs. This effect was partially reversed by pretreatment with a PDGF receptor inhibitor. Hcy concentration-dependently upregulated the mRNA level of PDGF-A, -C and -D but not PDGF-B in ECs. Hcy reduced the expression and activity of DNA methyltransferase 1, demethylation of PDGF-A, -C and -D promoters and enhanced the binding activity of transcriptional factor SP-1 to the promoter. Hcy upregulation of PDGF was confirmed in the aortic intima of mice with HHcy. Multivariate regression analysis revealed HHcy was a predictor of increased serum PDGF level in patients. Thus, Hcy upregulates PDGF level via DNA demethylation in ECs, affects cross-talk between ECs and VSMCs and leads to VSMC activation. [Copyright &y& Elsevier]

The hospital is a workplace full of stressful events for healthcare workers (HCWs) due to unpredictable changes in their daily routines. Perceptions of stressful events (stress mindset) have a significant impact on an individual's health and well-being. However, few studies have reported the factors and potential counter mechanisms influencing these perceptions. This study aimed to evaluate the relationship between empathy, self-disclosure, social support, and stress mindset of HCWs, and to explore the mechanism of empathy on stress mindset. Five hundred and eight HCWs (35.2% men and 64.8% women) completed the Interpersonal Reactivity Index (IRI), the Distress Disclosure Index (DDI), the Social Support Rating Scale (SSRS), the Stress Mindset Measure (SMM), and demographic questionnaires online in China. The results showed that empathy was positively linked with stress mindset and positively correlated with self-disclosure and social support. In the multiple mediating model, self-disclosure and social support mediated the association between empathy and stress mindset sequentially. The results imply that empathy, self-disclosure, and social support play a significant role in the formation of HCWs' stress mindset. These findings have substantial ramifications for reducing stress and creating successful government interventions to fortify stress mindset in healthcare., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Dou, Wang, Wang, Chen, Lu, Sun and Liu.)

Background/aims: Previous studies have shown that diet and physical activity can influence constipation. However, the combined effect of diet and physical activity on constipation remains unclear., Methods: Constipation was defined based on stool consistency and frequency, while overall diet quality was assessed using Healthy Eating Index (HEI)-2015 scores. Participants were categorized into low (metabolic equivalent [MET]-min/wk < 500) and high physical activity groups (MET-min/wk ≥ 500). The association between diet and constipation across physical activity groups was analyzed using survey logistic regression and restricted cubic splines., Results: Higher HEI-2015 scores were associated with reduced constipation risk in the high physical activity group when constipation was defined by stool consistency (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97-0.99). However, in the low physical activity group, increased HEI-2015 scores did not significantly affect constipation risk (OR, 1.01; 95% CI, 0.97-1.05). Similar results were found when constipation was defined based on stool frequency. In the high physical activity group, increased HEI-2015 scores were significantly associated with a reduced constipation risk (OR, 0.96; 95% CI, 0.94-0.98). Conversely, in the low physical activity group, increased HEI-2015 scores did not affect the risk of constipation (OR, 0.96; 95% CI, 0.90-1.03)., Conclusions: Our findings suggest that a higher HEI-2015 score is negatively associated with constipation among individuals with high physical activity levels but not among those with low physical activity levels. This association was consistent when different definitions of constipation were used. These results highlight the importance of combining healthy diet with regular physical activity to alleviate constipation.

Background: Mast cells, comprising a crucial component of the tumor immune milieu, modulate neoplastic progression by secreting an array of pro- and antitumorigenic factors. Numerous extant studies have produced conflicting conclusions regarding the impact of mast cells on the prognosis of patients afflicted with lung adenocarcinoma (LUAD)., Methods: Employing single-cell RNA sequencing (scRNA-seq) analysis, mast cell-specific marker genes in LUAD were ascertained. Subsequently, a mast cell-related genes (MRGs) signature was devised to stratify LUAD patients into high- and low-risk cohorts based on the median risk value. Further investigations were conducted to assess the influence of distinct risk categories on the tumor microenvironment. The prognostic import and capacity to prognosticate immunotherapy benefits of the MRGs signature were corroborated using four external cohorts. Ultimately, the functional roles of SYAP1 were validated through in vitro experimentation., Results: After scRNA-seq and bulk RNA-seq data analysis, we established a prognostic signature consisting of nine MRGs. This profile effectively distinguished favorable survival outcomes in both the training and validation cohorts. In addition, we identified the low-risk group as a population more effective for immunotherapy. In cellular experiments, we found that silencing SYAP1 significantly reduced the proliferation, invasion and migratory capacity of LUAD cells while increasing apoptosis., Conclusion: Our MRGs signature offers valuable insights into the involvement of mast cells in determining the prognosis of LUAD and may prove instrumental as a navigational aid for immunotherapy selection, as well as a predictor of immunotherapy response in LUAD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Liu, Pei, Wu, Xie, Liu and Li.)

Background: Increasing evidence suggests a correlation between glycosylation and the onset of cancer. However, the clinical relevance of glycosylation-related genes (GRGs) in uveal melanoma (UM) is yet to be fully understood. This study aimed to shed light on the impact of GRGs on UM prognosis., Methods: To identify the most influential genes in UM, we employed the AUCell and WGCNA algorithms. The GRGs signature was established by integrating bulk RNA-seq and scRNA-seq data. UM patients were separated into two groups based on their risk scores, the GCNS&#95;low and GCNS&#95;high groups, and the differences in clinicopathological correlation, functional enrichment, immune response, mutational burden, and immunotherapy between the two groups were examined. The role of the critical gene AUP1 in UM was validated through in vitro and in vivo experiments., Results: The GRGs signature was comprised of AUP1, HNMT, PARP8, ARC, ALG5, AKAP13, and ISG20. The GCNS was a significant prognostic factor for UM, and high GCNS correlated with poorer outcomes. Patients with high GCNS displayed heightened immune-related characteristics, such as immune cell infiltration and immune scores. In vitro experiments showed that the knockdown of AUP1 led to a drastic reduction in the viability, proliferation, and invasion capability of UM cells., Conclusion: Our gene signature provides an independent predictor of UM patient survival and represents a starting point for further investigation of GRGs in UM. It offers a novel perspective on the clinical diagnosis and treatment of UM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhang, Yang, Jiang, Sun, Xia, Yao and Tang.)

Background: Cuproptosis, a unique kind of cell death, has implications for cancer therapy, particularly lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) have been demonstrated to influence cancer cell activity by binding to a wide variety of targets, including DNA, RNA, and proteins., Methods: Cuproptosis-related lncRNAs (CRlncRNAs) were utilized to build a risk model that classified patients into high-and low-risk groups. Based on the CRlncRNAs in the model, Consensus clustering analysis was used to classify LUAD patients into different subtypes. Next, we explored the differences in overall survival (OS), the tumor immune microenvironment (TIME), and the mutation landscape between different risk groups and molecular subtypes. Finally, the functions of LINC00592 were verified through in vitro experiments., Results: Patients in various risk categories and molecular subtypes showed statistically significant variations in terms of OS, immune cell infiltration, pathway activity, and mutation patterns. Cell experiments revealed that LINC00592 knockdown significantly reduced LUAD cell proliferation, invasion, and migration ability., Conclusion: The development of a trustworthy prediction model based on CRlncRNAs may significantly aid in the assessment of patient prognosis, molecular features, and therapeutic modalities and may eventually be used in clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Pei, Liu, Zhang, Feng, Gong, Zeng, Li and Wang.)

To identify how circular RNA circRNA&#95;0082835 impacts melanoma cells and lymphatic metastasis to observe whether it exerts effects through its action mechanism of sponging microRNA miR-429. Clinical baseline information was collected, and clinical samples were used for detection on circRNA&#95;0082835 and EZH2. The expression of circRNA&#95;0082835, EZH2, and miR-429 was detected by quantitative real-time PCR (RT-qPCR). Cell proliferation was tested with cell counting kit-8 (CCK-8). Flow cytometry was applied to examination of cell cycle levels. Cell invasion and migration were observed by transwell and wound healing. The expression of Wnt/β-catenin pathway, cell cycle and epithelial-mesenchymal transition (EMT) marker proteins was analyzed by western blot. Dual-luciferase determined the binding of miR-429 and circ&#95;0082835. As a result, the expression of circRNA&#95;0082835 was increased and that of miR-429 was decreased with the increase in lymphatic metastasis level. CircRNA&#95;0082835 expression was downregulated by circ&#95;0082835 interference, upregulated by EZH2 interference and also downregulated after transfection of both shRNA-circ&#95;0082835 and shRNA-EZH2. Inhibiting circ&#95;0082835 and EZH2 suppressed the proliferation, invasion and migration, regulated the cell cycle levels, inhibited Wnt/β-catenin and attenuated EMT in melanoma cells. Inhibition of circ&#95;0082835 and/or EZH2 elevated miR-429 expression. The binding among miR-429 and circ&#95;0082835 was verified. MiR-429 inhibitor reversed the effect of circ&#95;0082835 interference while having no significant impact on EZH2. In conclusion, circRNA&#95;0082835 sponges miR-429 to affect the anti-tumor effect of miR-429 in primary melanoma and lymphatic metastasis.

Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression. The orphan nuclear receptor subfamily 4 group A member 1 ( NR4A1 ) acts as an oncogene, and is involved in colorectal cancer (CRC) development. However, the mechanism through which lncRNA regulates NR4A1 expression remains unknown. We aimed to identify lncRNAs that regulate NR4A1 and assess their underlying mechanisms in CRC. We first identified an antisense lncRNA of NR4A1 that was up-regulated in CRC tissues and cells with rapid amplification of cDNA ends (RACE), and designated it as NR4A1AS. Spearman correlation analysis showed that NR4A1AS was positively correlated with NR4A1 mRNA levels in 37 CRC tissues. Mechanistically, NR4A1AS stabilized NR4A1 mRNA by forming RNA-RNA complexes via partial base-pairing and up-regulated NR4A1 expression in CRC cells. RNA immunoprecipitation (RIP) assays revealed that knockdown of NR4A1AS expression by siRNA enhanced up-frameshift 1 (UPF1) recruitment to NR4A1 mRNA, thereby decreasing NR4A1 mRNA stability. Moreover, depletion of NR4A1AS was found to mimic the effect of NR4A1 knockdown, specifically by suppressing cell proliferation, migration and invasion, and inducing apoptosis and cell cycle arrest. Accordingly, restoring NR4A1 expression ameliorated the effects of NR4A1AS knockdown on tumor growth and metastasis of CRC cells in vitro and in vivo Thus, we conclude that NR4A1AS up-regulates NR4A1 expression by forming RNA-RNA complexes and blocking UPF1-mediated mRNA destabilization, and it functions in tumor growth and metastasis of CRC cells at least partly through regulating NR4A1, suggesting that NR4A1AS might be as a potential target for RNA-based anti-CRC drug studies., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Objective: Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity., Approach and Results: When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II-stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation results showed that homocysteine-reduced telomere activity and homocysteine-induced EC senescence might contribute to hTERT promoter demethylation by increasing CCCTC-binding factor repression and interfering in the SP1 binding to the demethylated hTERT promoter, which might relate with reduced of DNA methyltransferase 1. Furthermore, the CCCTC-binding factor-dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels., Conclusions: CCCTC-binding factor and SP1 cross talk may contribute to homocysteine-reduced hTERT DNA methylation and expression in endothelial senescence., (© 2014 American Heart Association, Inc.)

The complete complex anion in the title salt, (C(11)H(19)N(2))(2)[Cu(C(4)N(2)S(2))(2)], has 2/m symmetry while the complete cation is generated by mirror symmetry with the non-H atoms of the alkyl chain lying on the plane. A square-planar geometry based on an S(4) donor set is found in the anion; the Cu-S distance is 2.2663 (5) Å. In the crystal, inter-molecular N-H⋯N hydrogen bonds link the ions into layers in the bc plane comprising alternating rows of cations and anions.