Omega-3 world map: 2024 update.

In 2016, the first worldwide n3 PUFA status map was published using the Omega-3 Index (O3I) as standard biomarker. The O3I is defined as the percentage of EPA + DHA in red blood cell (RBC) membrane FAs. The purpose of the present study was to update the 2016 map with new data. In order to be included, studies had to report O3I and/or blood EPA + DHA levels in metrics convertible into an estimated O3I, in samples drawn after 1999. To convert the non-RBC-based EPA + DHA metrics into RBC we used newly developed equations. Baseline data from clinical trials and observational studies were acceptable. A literature search identified 328 studies meeting inclusion criteria encompassing 342,864 subjects from 48 countries/regions. Weighted mean country O3I levels were categorized into very low ≤4%, low >4-6%, moderate >6-8%, and desirable >8%. We found that the O3I in most countries was low to very low. Notable differences between the current and 2016 map were 1) USA, Canada, Italy, Turkey, UK, Ireland and Greece (moving from the very low to low category); 2) France, Spain and New Zealand (low to moderate); and 3) Finland and Iceland (moderate to desirable). Countries such as Iran, Egypt, and India exhibited particularly poor O3I levels.

Dysbiosis and Staphylococcus species over representation in the exit site skin microbiota of hemodialysis patients carrying tunneled cuffed central venous catheter.

OBJECTIVES: Hemodialysis patients with end-stage renal disease (ESRD) are susceptible to infections and dysbiosis. Catheter-related infections are typically caused by opportunistic skin pathogens. This study aims to compare the skin microbiota changes around the exit site of tunneled cuffed catheters (peri-catheter group) and the contralateral site (control group). METHODS: ESRD patients on hemodialysis were recruited. The skin microbiota were collected with moist skin swabs and analyzed using high-throughput sequencing of the 16S rDNA V3-V4 region. After denoising, de-replication, and removal of chimeras, the reads were assigned to zero-radius operational taxonomic units (ZOTU). RESULTS: We found significantly reduced alpha diversity in the peri-catheter group compared to the control group, as indicated by the Shannon, Jost, and equitability indexes, but not by the Chao1 or richness indexes. Beta diversity analysis revealed significant deviation of the peri-catheter microbiota from its corresponding control group. There was an overrepresentation of Firmicutes and an underrepresentation of Actinobacteria, Proteobacteria, and Acidobacteria at the phylum level in the peri-catheter group. The most abundant ZOTU (Staphylococcus spp.) drastically increased, while Cutibacterium, a commensal bacterium, decreased in the peri-catheter group. Network analysis revealed that the skin microbiota demonstrated covariance with both local and biochemical factors. CONCLUSIONS: In conclusion, there was significant skin microbiota dysbiosis at the exit sites compared to the control sites in ESRD dialysis patients. Managing skin dysbiosis represents a promising target in the prevention of catheter-related bacterial infections.

A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

Correlation Between Messenger RNA Expression and Clinicopathological Features of Breast Cancer: A systematic review.

BACKGROUND: Meta analysis was adopted to investigate the correlation between messenger ribonucleic acid (mRNA) expression and clinicopathological features of breast cancer (BC). METHODS: English databases, PubMed, Web of Science, Embase, and The Cochrane Library, etc., were searched using a computer. The time range of retrieval was set to be from the establishment of the database to December 2023. The search terms were set as "mRNA", "Breast cancer", "Pathology", "Clinicopathological characteristics", etc. The literatures were screened in line with the inclusion and exclusion criteria, and the data was extracted for analysis by Revman5.3. RESULTS: Finally, 5 suitable included literatures were selected, including 969 patients. The analysis results were found to reveal a significant association between mRNA expression and BC grading (OR = 0.11, 95% CI = 0.04-0.30, Z = 4.26, P<0.0001); a significant correlation was observed between mRNA expression and BC staging (OR = 0.19, 95% CI = 0.05-0.65, Z = 2.65, P = 0.008<0.05); no correlation was found between mRNA expression and menstrual status of BC patients (OR = 0.63, 95% CI = 0.22-1.78, Z = 0.88, P = 0.38>0.05); a correlation was identified between mRNA expression and tumor size in BC (OR = 0.48, 95% CI = 0.24-0.99, Z = 2.00, P = 0.05). In the Discussion section, this study, comprising 10 research studies, aimed to explore the correlation between messenger ribonucleic acid and the clinical pathological features of BC. staging and grading of BC, a certain correlation with tumor size, and no correlation with the menstrual status of BC patients.

Strain-induced ferroelectric polarization reversal without undergoing geometric inversion in blue SiSe monolayer.

Ferroelectricity in two-dimensional (2D) systems generally arises from phonons and has been widely investigated. On the contrary, electronic ferroelectricity in 2D systems has been rarely studied. Using first-principles calculations, the ferroelectric behavior of the buckled blue SiSe monolayer under strain are explored. It is found that the direction of the out-of-plane ferroelectric polarization can be reversed by applying an in-plane strain. And such polarization switching is realized without undergoing geometric inversion. Besides, the strain-triggered polarization reversal emerges in both biaxial and uniaxial strain cases, indicating it is an intrinsic feature of such a system. Further analysis shows that the polarization switching is the result of the reversal of the magnitudes of the positive and negative charge center vectors. And the variation of buckling is found to play an important role, which results in the switch. Moreover, a non-monotonic variation of band gap with strain is revealed. Our findings throws light on the investigation of novel electronic ferroelectric systems.

Case report: Nutritionally supported perioperative chemo-immunotherapy for advanced gastric cancer with incomplete pyloric obstruction.

This case describes the benefits of perioperative chemo-immunotherapy for advanced gastric cancer and incomplete pyloric obstruction, supplemented with nutritional support. Early parenteral nutrition to stabilize nutritional status and mitigate nutrition impact symptoms, and in addition, throughout the chemo-immunotherapy perioperative period also maintained oral nutrition support and a tailored dietary plan. Above nutritional support maintained the patient's physical condition during immunotherapy. Eventually, this combination therapy plan leads to a partial response. On the other hand, a combination of therapies that focus more on immune checkpoint inhibitor may be able to mitigate the side effects of chemotherapy. Such findings may yield novel prospects for patients with advanced gastric cancer and incomplete pyloric obstruction, enabling them to achieve better outcomes.

Tetramethylpyrazine Antagonizes the Subchronic Cadmium Exposure-Induced Oxidative Damage in Mouse Livers via the Nrf2/HO-1 Pathway.

Hepatic oxidative stress is an important mechanism of Cd-induced hepatotoxicity, and it is ameliorated by TMP. However, this underlying mechanism remains to be elucidated. To investigate the mechanism of the protective effect of TMP on liver injuries in mice induced by subchronic cadmium exposure, 60 healthy male ICR mice were randomly divided into five groups of 12 mice each, namely, control (CON), Cd (2 mg/kg of CdCl2), Cd + 100 mg/kg of TMP, Cd + 150 mg/kg of TMP, and Cd + 200 mg/kg of TMP, and were acclimatized and fed for 7 d. The five groups of mice were gavaged for 28 consecutive days with a maximum dose of 0.2 mL/10 g/day. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study show that compared with the Cd group, TMP attenuated CdCl2-induced pathological changes in the liver and improved the ultrastructure of liver cells, and TMP significantly decreased the MDA level (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection show that TMP significantly increased the levels of Nrf2 in the liver compared with the Cd group as well as the HO-1 and mRNA expression levels in the liver (p < 0.05). In conclusion, TMP could inhibit oxidative stress and attenuate Cd group-induced liver injuries by activating the Nrf2 pathway.

NKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing.

BACKGROUND: Current approaches to profile the single-cell transcriptomics of human pancreatic endocrine cells almost exclusively rely on freshly isolated islets. However, human islets are limited in availability. Furthermore, the extensive processing steps during islet isolation and subsequent single cell dissolution might alter gene expressions. In this work, we report the development of a single-nucleus RNA sequencing (snRNA-seq) approach with targeted islet cell enrichment for endocrine-population focused transcriptomic profiling using frozen archival pancreatic tissues without islet isolation. RESULTS: We cross-compared five nuclei isolation protocols and selected the citric acid method as the best strategy to isolate nuclei with high RNA integrity and low cytoplasmic contamination from frozen archival human pancreata. We innovated fluorescence-activated nuclei sorting based on the positive signal of NKX2-2 antibody to enrich nuclei of the endocrine population from the entire nuclei pool of the pancreas. Our sample preparation procedure generated high-quality single-nucleus gene-expression libraries while preserving the endocrine population diversity. In comparison with single-cell RNA sequencing (scRNA-seq) library generated with live cells from freshly isolated human islets, the snRNA-seq library displayed comparable endocrine cellular composition and cell type signature gene expression. However, between these two types of libraries, differential enrichments of transcripts belonging to different functional classes could be observed. CONCLUSIONS: Our work fills a technological gap and helps to unleash frozen archival pancreatic tissues for molecular profiling targeting the endocrine population. This study opens doors to retrospective mappings of endocrine cell dynamics in pancreatic tissues of complex histopathology. We expect that our protocol is applicable to enrich nuclei for transcriptomics studies from various populations in different types of frozen archival tissues.

Mechanism of acacetin regulating hepatic stellate cell apoptosis based on network pharmacology and experimental verification.

Background: Hepatic fibrosis is caused by various liver diseases and eventually develops into liver cancer. There is no specific drug approved for the treatment of hepatic fibrosis in the world. Acacetin (AC), a natural flavonoid, is widely present in nature in various plants, such as black locust, Damiana, Silver birch. It has been reported that acacetin can inhibit the proliferation of cancer cells and induce apoptosis. Purpose: In this study, we investigated the effect of acacetin on hepatic stellate cell apoptosis, thereby improving hepatic fibrosis, and combined experimental validation and molecular docking to reveal the underlying mechanism. Result: First, we discovered that acacetin inhibited hepatic stellate cell proliferation as well as the expression of fibrosis-related proteins α-smooth muscle actin (α-SMA) and collagen type I 1 gene (COL1A1) in LX2 cells. Acacetin was then found to promote apoptosis of hepatic stellate cells through the caspase cascade pathway. Network pharmacology screening showed that TP53, CASP3, CASP8, BCL2, PARP1, and BAX were the most important targets related to apoptosis in the PPI network. GO and KEGG analyses of these six important targets were performed, and the top 10 enriched biological processes and related signaling pathways were revealed. Further network pharmacology analysis proved that apoptosis was involved in the biological process of acacetin's action against hepatic stellate cells. Finally, molecular docking revealed that acacetin binds to the active sites of six apoptotic targets. In vitro experiments further confirmed that acacetin could promote the apoptosis of LX2 cells by inducing the activation of P53, thereby improving hepatic fibrosis. Conclusion: acacetin induces P53 activation and promotes apoptosis of hepatic stellate cells thereby ameliorating hepatic fibrosis.

The efficacy of antiviral treatment in chronic hepatitis B patients with hepatic steatosis.

Background & aims: With a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. Methods: CHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. Results: In total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245-0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. Conclusions: Among CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Differences and Correlations of Morphological and Hemodynamic Parameters between Anterior Circulation Bifurcation and Side-wall Aneurysms.

OBJECTIVE: The objective of this research was to explore the difference and correlation of the morphological and hemodynamic features between sidewall and bifurcation aneurysms in anterior circulation arteries, utilizing computational fluid dynamics as a tool for analysis. METHODS: In line with the designated inclusion criteria, this study covered 160 aneurysms identified in 131 patients who received treatment at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, China, from January 2021 to September 2022. Utilizing follow-up digital subtraction angiography (DSA) data, these cases were classified into two distinct groups: the sidewall aneurysm group and the bifurcation aneurysm group. Morphological and hemodynamic parameters in the immediate preoperative period were meticulously calculated and examined in both groups using a three-dimensional DSA reconstruction model. RESULTS: No significant differences were found in the morphological or hemodynamic parameters of bifurcation aneurysms at varied locations within the anterior circulation. However, pronounced differences were identified between sidewall and bifurcation aneurysms in terms of morphological parameters such as the diameter of the parent vessel (Dvessel), inflow angle (θF), and size ratio (SR), as well as the hemodynamic parameter of inflow concentration index (ICI) (P<0.001). Notably, only the SR exhibited a significant correlation with multiple hemodynamic parameters (P<0.001), while the ICI was closely related to several morphological parameters (R>0.5, P<0.001). CONCLUSIONS: The significant differences in certain morphological and hemodynamic parameters between sidewall and bifurcation aneurysms emphasize the importance to contemplate variances in threshold values for these parameters when evaluating the risk of rupture in anterior circulation aneurysms. Whether it is a bifurcation or sidewall aneurysm, these disparities should be considered. The morphological parameter SR has the potential to be a valuable clinical tool for promptly distinguishing the distinct rupture risks associated with sidewall and bifurcation aneurysms.

The role of the BTLA-HVEM complex in the pathogenesis of breast cancer.

Breast cancer (BC) is widely recognized as a prevalent contributor to cancer mortality and ranks as the second most prevalent form of cancer among women across the globe. Hence, the development of innovative therapeutic strategies is imperative to effectively manage BC. The B- and T-lymphocyte attenuator (BTLA)-Herpesvirus entry mediator (HVEM) complex has garnered significant scientific interest as a crucial regulator in various immune contexts. The interaction between BTLA-HVEM ligand on the surface of T cells results in reduced cellular activation, cytokine synthesis, and proliferation. The BTLA-HVEM complex has been investigated in various cancers, yet its specific mechanisms in BC remain indeterminate. In this study, we aim to examine the function of BTLA-HVEM and provide a comprehensive overview of the existing evidence in relation to BC. The obstruction or augmentation of these pathways may potentially enhance the efficacy of BC treatment.

Effects of short- and long-term plant functional group loss on alpine meadow community structure and soil nutrients.

The rapid loss of global biodiversity can greatly affect the normal functioning of ecosystems. However, how biodiversity losses affect plant community structure and soil nutrients is unclear. We conducted a field experiment to examine the short- and long-term effects of removing plant functional groups (Gramineae, Cyperaceae, legumes, and forbs) on the interrelationships among the species diversity, productivity, community structure, and soil nutrients in an alpine meadow ecosystem at Menyuan County, Qinghai Province. The variations in the species richness, above- and belowground biomass of the community gradually decreased over time. Species richness and productivity were positively correlated, and this correlation tended to be increasingly significant over time. Removal of the Cyperaceae, legumes, and other forbs resulted in fewer Gramineae species in the community. Soil total nitrogen, phosphorus, organic matter, and moisture contents increased significantly in the legume removal treatment. The removal of other forbs led to the lowest negative cohesion values, suggesting that this community may have difficulty recovering its previous equilibrium state within a short time. The effects of species removal on the ecosystem were likely influenced by the species structure and composition within the community. Changes in the number of Gramineae species indicated that they were more sensitive and less resistant to plant functional group removal. Legume removal may also indirectly cause distinct community responses through starvation and compensation effects. In summary, species loss at the community level led to extensive species niche shifts, which caused community resource redistribution and significant changes in community structure.

In Situ Growth Reaction on Photoelectrodes of Single-Atom Fe Incorporated Bi4O5I2: A General Photoelectrochemical Immunoassay Toward Sensitive Protein Analysis.

As one of the interesting signaling mechanisms, the in situ growth reaction on a photoelectrode has proven its powerful potential in photoelectrochemical (PEC) bioanalysis. However, the specific interaction between the signaling species with the photoactive materials limits the general application of the signal mechanism. Herein, on the basis of an in situ growth reaction on a photoelectrode of single-atom-based photoactive material, a general PEC immunoassay was developed in a split-type mode consisting of the immunoreaction and PEC detection procedure. Specifically, a single-atom photoactive material that incorporates Fe atoms into layered Bi4O5I2 (Bi4O5I2-Fe SAs) was used as a photoelectrode for PEC detection. The sandwich immunoreaction was performed in a well of a 96-well plate using Ag nanoparticles (Ag NPs) as signal tracers. In the PEC detection procedure, the Ag+ converted from Ag NPs were transferred onto the surface of the Bi4O5I2-Fe SAs photoelectrode and thereafter AgI was generated on the Bi4O5I2-Fe SAs in situ to form a heterojunction through the reaction of Ag+ with Bi4O5I2-Fe SAs. The formation of heterojunction greatly promoted the electro-hole separation, boosting the photocurrent response. Exemplified by myoglobin (Myo) as the analyte, the immunosensor achieved a wide linear range from 1.0 × 10-11 to 5.0 × 10-8 g mL-1 with a detection limit of 3.5 × 10-12 g mL-1. This strategy provides a general PEC immunoassay for disease-related proteins, as well as extends the application scope of in situ growth reaction in PEC analysis.

Pregnancy-Specific Beta-1-Glycoprotein 1 Increases HTR-8/SVneo Cell Migration through the Orai1/Akt Signaling Pathway.

The impaired invasion ability of trophoblast cells is related to the occurrence of preeclampsia (PE). We previously found that pregnancy-specific beta-1-glycoprotein 1 (PSG1) levels were decreased in the serum of individuals with early-onset preeclampsia (EOPE). This study investigated the effect of PSG1 on Orai1-mediated store-operated calcium entry (SOCE) and the Akt signaling pathway in human trophoblast cell migration. An enzyme-linked immunosorbent assay (ELISA) was used to determine the level of PSG1 in the serum of pregnant women with EOPE. The effects of PSG1 on trophoblast proliferation and migration were examined using cell counting kit-8 (CCK8) and wound healing experiments, respectively. The expression levels of Orai1, Akt, and phosphorylated Akt (p-Akt) were determined through Western blotting. The results confirmed that the serum PSG1 levels were lower in EOPE women than in healthy pregnant women. The PSG1 treatment upregulated the protein expression of Orai1 and p-Akt. The selective inhibitor of Orai1 (MRS1845) weakened the migration-promoting effect mediated by PSG1 via suppressing the Akt signaling pathway. Our findings revealed one of the mechanisms possibly involved in EOPE pathophysiology, which was that downregulated PSG1 may reduce the Orai1/Akt signaling pathway, thereby inhibiting trophoblast migration. PSG1 may serve as a potential target for the treatment and diagnosis of EOPE.

A novel MPPT technology based on dung beetle optimization algorithm for PV systems under complex partial shade conditions.

Solar power is a renewable energy source, and its efficient development and utilization are important for achieving global carbon neutrality. However, partial shading conditions cause the output of PV systems to exhibit nonlinear and multipeak characteristics, resulting in a loss of output power. In this paper, we propose a novel Maximum Power Point Tracking (MPPT) technique for PV systems based on the Dung Beetle Optimization Algorithm (DBO) to maximize the output power of PV systems under various weather conditions. We performed a performance comparison analysis of the DBO technique with existing renowned MPPT techniques such as Squirrel Search Algorithm, Cuckoo search Optimization, Horse Herd Optimization Algorithm, Particle Swarm Optimization, Adaptive Factorized Particle Swarm Algorithm and Gray Wolf Optimization Hybrid Nelder-mead. The experimental validation is carried out on the HIL + RCP physical platform, which fully demonstrates the advantages of the DBO technique in terms of tracking speed and accuracy. The results show that the proposed DBO achieves 99.99% global maximum power point (GMPP) tracking efficiency, as well as a maximum improvement of 80% in convergence rate stabilization rate, and a maximum improvement of 8% in average power. A faster, more efficient and robust GMPP tracking performance is a significant contribution of the DBO controller.

Longitudinal association of spirituality with depressive symptom trajectories among older adults in mainland China.

OBJECTIVES: The relationship between spirituality and depressive symptoms among the Chinese elderly is not well known. The current study explores this relationship using longitudinal data and trajectory modeling of depressive symptoms. METHODS: A longitudinal study design was used to measure depressive symptoms repeatedly from 2012 to 2021 using the Geriatric Depression Scale (GDS). Group-based trajectory modeling analysis was conducted to determine the trajectories of depressive symptoms, and multiple logistic regression was used to explore the association between spirituality and depressive symptom trajectories. RESULTS: A total of 2333 participants completed at least two GDS measures, and these were included in the Group-based trajectory modeling analysis. An optimal model of three trajectories was derived: no depressive symptoms group (75.2%), new-onset depressive symptoms group (14.4%), and persistent depressive symptoms group (10.4%). Logistic regression modeling revealed that higher spirituality was associated with a lower risk of both new-onset depressive symptoms (OR = 0.68, 95% CI = 0.49-0.93) and persistent depressive symptoms (OR = 0.32, 95% CI = 0.23-0.45). CONCLUSIONS: Spirituality predicts a lower risk of new-onset depressive symptoms and persistent symptoms among older adults in mainland China.

Exploring the interplay between methylation patterns and non-coding RNAs in non-small cell lung cancer: Implications for pathogenesis and therapeutic targets.

Lung cancer is a global public health issue, with non-small cell lung cancer (NSCLC) accounting for 80-85 % of cases. With over two million new diagnoses annually, understanding the complex evolution of this disease is crucial. The development of lung cancer involves a complex interplay of genetic, epigenetic, and environmental factors, leading the key oncogenes and tumor suppressor genes to disorder, and activating the cancer related signaling pathway. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNA (circRNAs) are unique RNA transcripts with diverse biological functions. These ncRNAs are generated through genome transcription and play essential roles in cellular processes. Epigenetic modifications such as DNA methylation, N6-methyladenosine (m6A) modification, and histone methylation have gained significant attention in NSCLC research. The complexity of the interactions among these methylation modifications and ncRNAs contribute to the precise regulation of NSCLC development. This review comprehensively summarizes the associations between ncRNAs and different methylation modifications and discusses their effects on NSCLC. By elucidating these relationships, we aim to advance our understanding of NSCLC pathogenesis and identify potential therapeutic targets for this devastating disease.

The GRHL3-regulated long non-coding RNA lnc-DC modulates keratinocytes differentiation by interacting with IGF2BP2 and up-regulating ZNF750.

BACKGROUND: Aberrant keratinocytes differentiation has been demonstrated to be associated with a number of skin diseases. The roles of lncRNAs in keratinocytes differentiation remain to be largely unknown. OBJECTIVE: Here we aim to investigate the role of lnc-DC in regulating epidermal keratinocytes differentiation. METHODS: Expression of lnc-DC in the skin was queried in AnnoLnc and verified by FISH. The lncRNA expression profiles during keratinocytes differentiation were reanalyzed and verified by qPCR and FISH. Gene knock-down and over-expression were used to explore the role of lnc-DC in keratinocytes differentiation. The downstream target of lnc-DC was screened by whole transcriptome sequencing. CUT&RUN assay and siRNAs transfection was used to reveal the regulatory effect of GRHL3 on lnc-DC. The mechanism of lnc-DC regulating ZNF750 was revealed by RIP assay and RNA stability assay. RESULTS: Lnc-DC was biasedly expressed in skin and up-regulated during epidermal keratinocytes differentiation. Knockdown lnc-DC repressed epidermal keratinocytes differentiation while over-express lnc-DC showed the opposite effect. GRHL3, a well-known transcription factor regulating keratinocytes differentiation, could bind to the promoter of lnc-DC and regulate its expression. By whole transcriptome sequencing, we identified that ZNF750 was a downstream target of lnc-DC during keratinocytes differentiation. Mechanistically, lnc-DC interacted with RNA binding protein IGF2BP2 to stabilize ZNF750 mRNA and up- regulated its downstream targets TINCR and KLF4. CONCLUSION: Our study revealed the novel role of GRHL3/lnc-DC/ZNF750 axis in regulating epidermal keratinocytes differentiation, which may provide new therapeutic targets of aberrant keratinocytes differentiation related skin diseases.

Photobiomodulation Increases M2-Type Polarization of Macrophages by Inhibiting Versican Production After Spinal Cord Injury.

Spinal cord injury (SCI) is a catastrophic accidence with little effective treatment, and inflammation played an important role in that. Previous studies showed photobiomodulation (PBM) could effectively downregulate the process of inflammation with modification of macrophage polarization after SCI; however, the potential mechanism behind that is still unclear. In the presented study, we aimed to investigate the effect of PBM on the expression level of versican, a matrix molecular believed to be associated with inflammation, and tried to find the mechanism on how that could regulate the inflammation process. Using immunofluorescence technique and western blot, we found the expression level of versican is increased after injury and markedly downregulated by irradiation treatment. Using virus intrathecal injection, we found the knock-down of versican could produce the effect similar to that of PBM and might have an effect on inflammation and macrophage polarization after SCI. To further verify the deduction, we peptide the supernatant of astrocytes to induce M0, M1, and M2 macrophages. We found that the versican produced by astrocytes might have a role on the promotion of M2 macrophages to inflammatory polarization. Finally, we investigated the potential pathway in the regulation of M2 polarization with the induction of versican. This study tried to give an interpretation on the mechanism of inflammation inhibition for PBM in the perspective of matrix regulation. Our results might provide light on the inflammation regulation after SCI.