Role of nutritional support in nursing practice for improving surgical site wound healing in patients post-surgery with risk of pressure ulcers.

To explore the role of nutritional support in nursing practice on postoperative surgical site wound healing in patients undergoing surgery at risk for pressure ulcers. This study adopted a retrospective experimental design and included a total of 60 patients at risk of pressure ulcers, divided into a nutritional support group and a control group, with 30 people in each group. The nutritional support group implemented specific nutritional support measures after surgery, while the control group received standard postoperative care. Outcome measures included redness and swelling scores, edema scores, anxiety assessments, pain scores, bleeding volume, recovery time and incidence of pressure ulcers. The result indicates that patients who received nutritional support exhibited lower postoperative wound redness and swelling scores compared to the control group (3.11 ± 0.45 vs. 4.85 ± 0.74, p < 0.05). Additionally, the nutritional support group showed significantly lower edema scores (2.75 ± 0.37 vs. 3.53 ± 0.62, p < 0.05). Anxiety levels, as measured by the anxiety assessment scale (SAS), were also lower in the nutritional support group (6.52 ± 1.19 vs. 7.60 ± 1.62, p < 0.05). Moreover, the average healing time was shorter for the nutritional support group (7.27 ± 1.36 days) compared to the control group (9.71 ± 1.84 days, p < 0.05). Postoperative pain scores were lower in the nutritional support group (4.13 ± 0.72 vs. 5.43 ± 0.62, p < 0.05), and patient satisfaction scores were higher (9.42 ± 0.76 vs. 7.25 ± 0.81, p < 0.05). Nutritional support has a positive effect on postoperative wound healing at surgical sites in patients at risk of pressure ulcers in nursing practice. It can significantly reduce redness, swelling, edema, anxiety, and pain scores, reduce bleeding, shorten recovery time, and reduce pressure ulcers. incidence rate.

Colonoscopic titanium clipping to Maddress appendiceal stump leakage: a case report.

The incidence of appendiceal stump leakage (ASL) is extremely low and heterogeneous, which has been reported to be approximately 0.5%-1.0%. It is a catastrophic complication with high mortality rate despite its low morbidity. Once it occurs, it will put the doctor in a passive position because dealing with the leakage is much more cumbersome than appendectomy. We extensively reviewed the literature on ASL, focusing on the management and prognosis. Unsurprisingly, all of the physicians advocated extended resection, which apparently gave them sufficient confidence. However, partial cecum resection, cecostomy, or terminal ileectomy is extremely invasive and destructive. So, the patients had to experience great mental and physical trauma, longer hospital stays, higher rates of wound infection, more costs, and even a third surgery. Therefore, are there any better approaches for ASL? In this article, we report a case of ASL who successfully underwent endoscopic treatment. A 70-year-old male was admitted with gangrenous perforated appendicitis with a large iliopsoas abscess. Appendectomy, iliopsoas abscess debridement and sufficient drainage, appendicular stump repair and closure, and terminal ileostomy were performed. Three months later, the patient was readmitted and the stoma reversal was performed as scheduled. Seven days later, ASL was found when a liquid diet was applied routinely due to right lower quadrant pain and low fever. Finally, with the periappendiceal abscess completely drained, we clamped the appendiceal orifice with five titanium clips under an electronic colonoscope, which eventually sealed the leakage and avoided extended resection.

Identification of survival-associated biomarkers based on three datasets by bioinformatics analysis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors with poor prognosis in terms of advanced stage. However, the survival-associated biomarkers for GC remains unclear. AIM: To investigate the potential biomarkers of the prognosis of patients with GC, so as to provide new methods and strategies for the treatment of GC. METHODS: RNA sequencing data from The Cancer Genome Atlas (TCGA) database of STAD tumors, and microarray data from Gene Expression Omnibus (GEO) database (GSE19826, GSE79973 and GSE29998) were obtained. The differentially expressed genes (DEGs) between GC patients and health people were picked out using R software (x64 4.1.3). The intersections were underwent between the above obtained co-expression of differential genes (co-DEGs) and the DEGs of GC from Gene Expression Profiling Interactive Analysis database, and Gene Ontology (GO) analysis, Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA), Protein-protein Interaction (PPI) analysis and Kaplan-Meier Plotter survival analysis were performed on these DEGs. Using Immunohistochemistry (IHC) database of Human Protein Atlas (HPA), we verified the candidate Hub genes. RESULTS: With DEGs analysis, there were 334 co-DEGs, including 133 up-regulated genes and 201 down-regulated genes. GO enrichment analysis showed that the co-DEGs were involved in biological process, cell composition and molecular function pathways. KEGG enrichment analysis suggested the co-DEGs pathways were mainly enriched in ECM-receptor interaction, protein digestion and absorption pathways, etc. GSEA pathway analysis showed that co-DEGs mainly concentrated in cell cycle progression, mitotic cell cycle and cell cycle pathways, etc. PPI analysis showed 84 nodes and 654 edges for the co-DEGs. The survival analysis illustrated 11 Hub genes with notable significance for prognosis of patients were screened. Furtherly, using IHC database of HPA, we confirmed the above candidate Hub genes, and 10 Hub genes that associated with prognosis of GC were identified, namely BGN, CEP55, COL1A2, COL4A1, FZD2, MAOA, PDGFRB, SPARC, TIMP1 and VCAN. CONCLUSION: The 10 Hub genes may be the potential biomarkers for predicting the prognosis of GC, which can provide new strategies and methods for the diagnosis and treatment of GC.

Construction and Identification of an NLR-Associated Prognostic Signature Revealing the Heterogeneous Immune Response in Skin Cutaneous Melanoma.

Background: Skin cutaneous melanoma (SKCM) is the deadliest dermatology tumor. Ongoing researches have confirmed that the NOD-like receptors (NLRs) family are crucial in driving carcinogenesis. However, the function of NLRs signaling pathway-related genes in SKCM remains unclear. Objective: To establish and identify an NLRs-related prognostic signature and to explore its predictive power for heterogeneous immune response in SKCM patients. Methods: Establishment of the predictive signature using the NLRs-related genes by least absolute shrinkage and selection operator-Cox regression analysis (LASSO-COX algorithm). Through univariate and multivariate COX analyses, NLRs signature's independent predictive effectiveness was proven. CIBERSORT examined the comparative infiltration ratios of 22 distinct types of immune cells. RT-qPCR and immunohistochemistry implemented expression validation for critical NLRs-related prognostic genes in clinical samples. Results: The prognostic signature, including 7 genes, was obtained by the LASSO-Cox algorithm. In TCGA and validation cohorts, SKCM patients with higher risk scores had remarkably poorer overall survival. The independent predictive role of this signature was confirmed by multivariate Cox analysis. Additionally, a graphic nomogram demonstrated that the risk score of the NLRs signature has high predictive accuracy. SKCM patients in the low-risk group revealed a distinct immune microenvironment characterized by the significantly activated inflammatory response, interferon-α/γ response, and complement pathways. Indeed, several anti-tumor immune cell types were significantly accumulated in the low-risk group, including M1 macrophage, CD8 T cell, and activated NK cell. It is worth noting that our NLRs prognostic signature could serve as one of the promising biomarkers for predicting response rates to immune checkpoint blockade (ICB) therapy. Furthermore, the results of expression validation (RT-qPCR and IHC) were consistent with the previous analysis. Conclusion: A promising NLRs signature with excellent predictive efficacy for SKCM was developed.

Pediatric Primary Cutaneous Lymphoma in China: A Retrospective Study.

BACKGROUND: The incidence and clinical features of primary cutaneous lymphoma (PCL) tend to differ by age, gender, geographical, and racial variation. All-aged and adult groups of PCL in various regions have been well demonstrated and compared, while the research concentrating on pediatric PCL is rare, especially in Asian countries. OBJECTIVE: The aim of this study was to investigate the clinical characteristics of PCL in pediatric population at a single center in China. METHODS: We conducted a retrospective study of 101 pediatric cases with PCL, diagnosed at the Institute of Dermatology, Chinese Academy of Medical Sciences, from January 2010 to December 2021. RESULTS: Mycosis fungoides (MF), accounting for 41.6% of the total cases, was the most common subtype in pediatric PCL, and the hypopigmented MF accounted for 47.6% of all the MF cases. Lymphomatoid papulosis and chronic active Epstein-Barr virus infection tied for second place with a proportion of 22.8%. Primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous peripheral T-cell lymphoma, rare subtypes and primary cutaneous B-cell lymphoma, respectively, accounted for 2.0%, 4.0%, 4.0%, and 3.0%. Most patients had favorable prognosis during the follow-up. CONCLUSION: The study suggested that MF was the most common subtype in pediatric PCL in China, and most types of pediatric PCL had favorable prognosis.

Hypopigmented Mycosis Fungoides: A Clinicopathological Review of 32 Patients.

Background: Hypopigmented mycosis fungoides (hMF) is gradually acknowledged by more dermatologists, yet a consensus regarding its characteristics is not reached. The profile of Chinese hMF patients has not been deeply reviewed previously. Our research may contribute to the understanding of hMF, especially the Chinese patients with Fitzpatrick phototypes of III and IV. Aim: To have a better understanding of hMF in terms of clinical, histopathological and immunohistochemical features in the Chinese population and to determine if there are differences between the Chinese population and other ethnic groups. Methods: We made a retrospective analysis of clinical, histopathological and immunohistochemical features of 32 hMF patients in our hospital from 2010 to 2020. These features were then summarized and compared with previous reports. Results: All patients belonged to Fitzpatrick phototypes of III or IV. Twenty-one male (65.63%) patients and 11 female (34.37%) patients were analyzed, and the male to female ratio was 1.9:1. The age at diagnosis of patients ranged from 4 to 39 years, and the average age at diagnosis of these patients was 18 years, the median age was 16.5. Back was the most frequent site (34.37%). The clinical and histological results of lesions had no distinctive points. Immunohistochemically, among these 32 patients, there were 30 patients whose information was complete, there was 19 patients (63.33%) who were CD8 positive lymphocytes predominance, 9 patients (30%) had CD8 and CD4 positive lymphocyte mixed infiltration, and other 2 patients (6.67%) had CD4 positive lymphocytes predominance. Partial loss of CD7 was only observed in 1 patient (3.33%). Nearly all patients adopted topical nitrogen mustard and topical steroid and most of them had an excellent prognosis. Conclusion: The clinical profiles of hMF in Chinese population shared differences with other ethnic groups, but its histopathological, immunohistochemical results and prognosis condition were resembled with other previous reports. Hence, more patients were needed to find the characteristics of hMF.

Effect of Ca2+ binding states of calmodulin on the conformational dynamics and force responses of myosin lever arm.

The mechanochemical coupling and biological function of myosin motors are regulated by Ca2+ concentrations. As one of the regulation pathways, Ca2+ binding induces a conformational change of the light chain calmodulin and its binding modes with a myosin lever arm, which can affect the stiffness of the lever arm and force transmission. However, the underlying molecular mechanism of the Ca2+ regulated stiffness change is not fully understood. Here, we study the effect of Ca2+ binding on the conformational dynamics and stiffness of the myosin VIIa lever arm bound with a calmodulin by performing molecular dynamics simulations and dynamic correlation network analysis. The results showed that the calmodulin bound lever arm at an apo state can sample three different conformations. In addition to the conformation observed in a crystal structure, a calmodulin bound lever arm at the apo condition can also adopt other two conformations featured by different extents of small-angle bending of the lever arm. However, large-angle bending is strongly prohibited. Such results suggest that the calmodulin bound lever arm without Ca2+ binding is plastic for small-angle deformation but shows high stiffness for large-angle deformation. In comparison, after the binding of Ca2+, although the calmodulin bound lever arm is locally more rigid, it can adopt largely deformed or even unfolded conformations, which may render the lever arm incompetent for force transmission. The conformational plasticity of the lever arm for small-angle deformation at the apo condition may be used as a force buffer to prevent the lever arm from unfolding during the power stroke action of the motor domain.

PLA2G6 Silencing Suppresses Melanoma Progression and Affects Ferroptosis Revealed by Quantitative Proteomics.

Although phospholipase A2 group VI (PLA2G6) is involved in oncogenesis in several human tumors, its expression and role in cutaneous malignant melanoma (CMM) pathogenesis remains unclear. Here, by using the Oncomine and CCLE online database, immunohistochemistry, RT-qPCR, and western blotting analysis, we revealed that PLA2G6 was markedly up-regulated in CMM tissues compared to nevus tissues, as well as remarkably increased in vitro in SK-MEL-28 and M14 melanoma cell lines compared to human melanocytes. In vivo, PLA2G6 was also elevated in nine melanoma tissues compared to adjacent tissues. To investigate the malignant behaviors of PLA2G6 in CMM, SK-MEL-28 and M14 cell lines with PLA2G6 stable knockdown by RNAi strategy were constructed. Through CCK8 and colony formation assays in vitro and xenograft tumor experiment in vivo, we found that knockdown of PLA2G6 dramatically inhibited cell proliferation. The results of scratch-wound and transwell assays suggested that the migration and invasion of melanoma cells were prominently suppressed after silencing PLA2G6. In addition, flow cytometry showed that the knockdown of PLA2G6 promoted the apoptosis rate of melanoma cells. To further explore the potential molecular mechanism, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomic and bioinformatics analysis. The GO and KEGG analysis suggested that the underlying mechanism of PLA2G6 in CMM might be associated with the ferroptosis pathway, and ferroptosis-related proteins were validated to be differentially expressed in PLA2G6 knockdown SK-MEL-28 and M14 cells. Together, these results suggested that PLA2G6 knockdown significantly inhibited cell proliferation, metastasis, and promoted apoptosis in melanoma. Our findings on the biological function of PLA2G6 and the underlying association between PLA2G6 and ferroptosis in melanoma may contribute to developing a potential therapeutic strategy for melanoma.

A case of pagetoid reticulosis treated with topical photodynamic therapy.

A 70-year-old male presented with reddish brown, keratotic plaque on his left leg which had grown slowly for ten years. The histopathological examination revealed acanthosis and bands of lymphocytes with significant epidermotropism. The intraepidermal lymphocytes showed large, pleomorphic and hyperchromatic nuclei with distinct nucleoli and perinuclear halos, positive for CD3, CD4 and CD30, negative for CD8, CD20 and high in Ki67 index. Accordingly, the diagnosis of Pagetoid reticulosis was made. The patient was then treated with topical photodynamic therapy once a week sequential to partial in-situ resection and preliminary skin dermabrasion and finally achieved complete remission without obvious scars or recurrence after four sessions.

Identification of the Role of Wnt/ß-Catenin Pathway Through Integrated Analyses and in vivo Experiments in Vitiligo.

PURPOSE: Vitiligo is an acquired depigmentation skin disease, which affects an average of 1% of the world's population. The purpose of this study is to identify the key genes and pathways responsible for vitiligo and find new therapeutic targets. METHODS: The datasets GSE65127, GSE53146, and GSE75819 were downloaded from the Gene Expression Omnibus (GEO) database. R language was used to identify the differentially expressed genes (DEGs) between lesional skin of vitiligo and non-lesional skin. Next, the key pathways were obtained by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein-protein interaction (PPI) networks were conducted by STRING database and Cytoscape software. Subsequently, module analysis was performed by Cytoscape. Among these results, the Wnt/ß-catenin pathway and melanogenesis pathway caught our attention. The expression level of ß-catenin, microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) was detected by immunofluorescence in vitiligo lesions and healthy skin. Moreover, zebrafish was treated with XAV-939, an inhibitor of the Wnt/ß-catenin pathway. After that, the area of melanin granules as a percentage of the head area was measured. The mRNA expression of ß-catenin, lymphoid-enhancing factor 1(lef1), tyr and mitf were detected by q-PCR (quantitative polymerase chain reaction) in zebrafish (Danio rerio). RESULTS: A total of 2442 DEGs were identified, including 1068 upregulated and 1374 downregulated DEGs. The key pathways were identified by GO and KEGG analyses, such as "NOD-like receptor signaling pathway", "Wnt signaling pathway", "Melanogenesis", "mTOR signaling pathway", "PI3K-Akt signaling pathway", "Calcium signaling pathway" and "Rap1 signaling pathway". The immunofluorescence results showed that the level of ß-catenin, MITF and TYR was significantly downregulated in vitiligo lesional skin. In zebrafish, the mean percentage area of melanin granules and the expression of ß-catenin, lef1, tyr and mitf were decreased after treated with XAV-939. CONCLUSION: The present study identified key genes and signaling pathways associated with the pathophysiology of vitiligo. Among them, the Wnt/ß-catenin pathway played an essential role in pigmentation and could be a breakthrough point in vitiligo treatment.

Pronounced Linewidth Narrowing of Vertical Metallic Split-Ring Resonators via Strong Coupling with Metal Surface.

We theoretically study the plasmonic coupling between magnetic plasmon resonances (MPRs) and propagating surface plasmon polaritons (SPPs) in a three-dimensional (3D) metamaterial consisting of vertical Au split-ring resonators (VSRRs) array on Au substrate. By placing the VSRRs directly onto the Au substrate to remove the dielectric substrates effect, the interaction between MPRs of VSRRs and the SPP mode on the Au substrate can generate an ultranarrow-band hybrid mode with full width at half maximum (FWHM) of 2.2 nm and significantly enhanced magnetic fields, compared to that of VSRRs on dielectric substrates. Owing to the strong coupling, an anti-crossing effect similar to Rabi splitting in atomic physics is also obtained. Our proposed 3D metamaterial on a metal substrate shows high sensitivity (S = 830 nm/RIU) and figure of merit (FOM = 377), which could pave way for the label-free biomedical sensing.

Clinicopathological analysis of primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder: a retrospective study of 22 patients.

BACKGROUND: Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder has been defined as a type of lymphoproliferative disorder with indolent clinical course and excellent prognosis, yet a precise diagnosis is still hard to reach. METHODS: A retrospective analysis of 22 patients including 16 females and six males was performed. RESULTS: The age of patients ranged from 5 to 79 years. The average age of all patients was 43.5, and the median age of all patients was 44.5. Two patients had multiple lesions, and others were presented with a solitary asymptomatic lesion. Besides general features, folliculotropism was observed in four cases. In addition to express CD3 and CD4, CD30 were positive to some extent. Some reactive cells could express CD8 and CD20. For follicular helper T-cell markers, although CXCL-13 was negative in the stained cases (18/18), the expression of PD-1 (12/17), BCL-6 (12/16) and CD10 (11/15) was observed in most cases. In addition, we performed T-cell receptor (TCR) rearrangement on five patients, and all of them showed monoclonality. Nearly all patients had excellent prognosis. CONCLUSIONS: Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder is complex. Some features like folliculotropism should also be noted. Besides, the expression of follicular helper T-cell markers is not invariable. Moreover, CD8 positivity, Ki-67 index, and lesion number were perhaps not absolute prognostic indicators. To reach a diagnosis of this rare entity, putting all the pieces together is important.

Mining Database for the Clinical Significance and Prognostic Value of ESRP1 in Cutaneous Malignant Melanoma.

BACKGROUND: Epithelial splicing regulatory protein 1 (ESRP1) has been described as an RNA-binding protein involved in cancer development. However, the expression and regulatory network of ESRP1 in cutaneous malignant melanoma (CMM) remain unclear. METHODS: From the sequencing data of 103 CMM samples in The Cancer Genome Atlas database, the expression level of ESRP1 and its correlation with the clinicopathological characteristics were analyzed using the Oncomine 4.5, Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN tools, while LinkedOmics was used to identify differential gene expression with ESRP1 and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Gene enrichment analysis examined target networks of kinases, miRNAs, and transcription factors. Finally, TIMER was used to analyze the relationship between ESRP1 and tumor immune cell infiltration. RESULTS: We found that ESRP1 was lowly expressed in CMM tissues, and a low level of ESRP1 expression correlated with better overall survival. Expression of this gene was linked to functional networks involving the condensed chromosomes, epidermal development, and translation initiation. Functional network analysis suggested that ESRP1 regulated ribosome metabolism, drug metabolism, and chemical carcinogenesis via pathways involving several cancer-related kinases, miRNAs, and transcription factors. Furthermore, our results suggested that ESRP1 played an important role in regulating tumor-associated macrophage polarization, dendritic cell infiltration, Treg cells, and T cell exhaustion. CONCLUSION: Our study demonstrates ESRP1 expression, prognostic value, and potential regulatory networks in CMM, thereby shedding light on the clinical significance of ESRP1, and provides a novel biomarker for determining prognosis and immune infiltration in CMM.

Anomalous energy diffusion in two-dimensional nonlinear lattices.

Heat transport in one-dimensional (1D) momentum-conserved lattices is generally assumed to be anomalous, thus yielding a power-law divergence of thermal conductivity with system length. However, whether heat transport in a two-dimensional (2D) system is anomalous or not is still up for debate because of the difficulties involved in experimental measurements or due to the insufficiently large simulation cell size. Here we simulate energy and momentum diffusion in the 2D nonlinear lattices using the method of fluctuation correlation functions. Our simulations confirm that energy diffusion in the 2D momentum-conserved lattices is anomalous and can be well described by the Lévy-stable distribution. As is expected, we verify that 2D nonlinear lattices with on-site potentials exhibit normal energy diffusion, independent of the dimension. Contrary to the hypothesis of a 1D system, we further clarify that anomalous heat transport in the 2D momentum-conserved system cannot be corroborated by the momentum superdiffusion any longer. Our findings offer some valuable insights into mechanisms of thermal transport in 2D system.

miR-128 targets the CC chemokine ligand 18 gene (CCL18) in cutaneous malignant melanoma progression.

BACKGROUND: The CC chemokine ligand 18 (CCL18) has a higher expression in some tumors, while the CCL18 level can be a marker of tumor progression and prognosis. We previously reported that the expression of CCL18 gene was dramatically up-regulated in cutaneous malignant melanoma (CMM) and its expression levels were correlated with tumor thickness. OBJECTIVE: To investigate miRNAs which could target the CCL18 gene so as to mediate CMM development and improvement. METHODS: The expression of miR-128 and CCL18 in CMM were measured by qRT-PCR. The interaction of miR-128 with CCL18 3'UTR was verified by Luciferase reporter gene assay. The changes in expression of CCL18 after miR-128 mimic transfection of A375 melanoma cells were determined by both qRT-PCR and Western-bloting. Cell viability was accessed by CCK8-assay. Flow cytometry was employed to detect the incidence of apoptosis. Clonogenic assay was used to detect the ability of colony formation. Cell migration was evaluated by Transwell migration study. The protein levels of epithelial-mesenchymal transition (EMT), such as E-cadherin, N-cadherin and ß-catenin were analyzed by Western-bloting. RESULTS: The expression of miR-128 had negative relevance with CCL18 in CMM. miR-128 could interact with CCL18 3'UTR. Transfected miR-128 mimic significantly reduced CCL18 expression and this impairment of CCL18 gene promoted apoptosis, inhibited migration and colony formation of A375 melanoma cells. Furthermore, the relative expression of N-cadherin was decreased. CONCLUSION: CCL18 is a target gene of miR-128. Overexpression of miR-128 inhibits the oncogenic effect of CCL18.

Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

The HIV-1 nucleocapsid 7 (NCp7) plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3) recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.

Ovostatin 2 knockdown significantly inhibits the growth, migration, and tumorigenicity of cutaneous malignant melanoma cells.

BACKGROUND: We previously identified ovostatin 2 (OVOS2) as a new candidate gene for cutaneous malignant melanoma (CMM) in a Chinese population. In this study, we aimed to investigate the exact role of OVOS2 in cell proliferation, invasion, and tumorigenesis of melanoma A375 cells. METHODS: The downregulation of OVOS2 expression was performed using lentiviral vectors with specific shRNA. The effects of OVOS2 expression on cell proliferation, cell cycle, cell migration, cell invasion, and potential of tumorigenesis were further investigated. RESULTS: The downregulation of OVOS2 significantly suppressed the proliferation of A375 cells and led to a G2/M phase block. The transwell cell migration assay showed that the reduced expression of OVOS2 also significantly inhibited the transmigration of A375 cells. The western blot results showed downregulated expression of p-FAK, p-AKT, and p-ERK. This was accompanied by the upregulated epithelial phenotypes E-cadherin and ß-catenin, and downregulated expression of mesenchymal phenotype N-cadherin after OVOS2 knockdown. The transplantation tumor experiment in BALB/C nude mouse showed that after an observation period of 32 days, the growth speed and weight of the transplanted tumors were significantly suppressed in the BALB/c nude mice subcutaneously injected with OVOS2 knocked-down A375 cells. CONCLUSION: The inhibition of OVOS2 had significant suppressive effects on the proliferation, motility, and migration capabilities of A375 cells, suggesting a crucial promotive role of OVOS2 in the pathogenesis and progression of CMM. The involved mechanisms are at least partly associated with the overactivation of FAK/MAPK/ERK and FAK/PI3K/AKT signals.