Potential distribution and ecological impacts of Acmella radicans (Jacquin) R.K. Jansen (a new Yunnan invasive species record) in China.

BACKGROUND ACMELLA RADICANS: (Jacquin) R.K. Jansen is a new invasive species record for Yunnan Province, China. Native to Central America, it has also been recently recorded invading other parts of Asia. To prevent this weed from becoming a serious issue, an assessment of its ecological impacts and potential distribution is needed. We predicted the potential distribution of A. radicans in China using the MaxEnt model and its ecological impacts on local plant communities and soil nutrients were explored. RESULTS: Simulated training using model parameters produced an area under curve value of 0.974, providing a high degree of confidence in model predictions. Environmental variables with the greatest predictive power were precipitation of wettest month, isothermality, topsoil TEB (total exchangeable bases), and precipitation seasonality, with a cumulative contribution of more than 72.70% and a cumulative permutation importance of more than 69.20%. The predicted potential suitable area of A. radicans in China is concentrated in the southern region. Projected areas of A. radicans ranked as high and moderately suitable comprised 5425 and 26,338 km2, accounting for 0.06 and 0.27% of the Chinese mainland area, respectively. Over the 5 years of monitoring, the population density of A. radicans increased while at the same time the population density and importance values of most other plant species declined markedly. Community species richness, diversity, and evenness values significantly declined. Soil organic matter, total N, total P, available N, and available P concentrations decreased significantly with increasing plant cover of A. radicans, whereas pH, total K and available K increased. CONCLUSION: Our study was the first to show that A. radicans is predicted to expand its range in China and may profoundly affect plant communities, species diversity, and the soil environment. Early warning and monitoring of A. radicans must be pursued with greater vigilance in southern China to prevent its further spread.

COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

Serum proteome and metabolome uncover novel biomarkers for the assessment of disease activity and diagnosing of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting thousands of people. There are still no effective biomarkers for SLE diagnosis and disease activity assessment. We performed proteomics and metabolomics analyses of serum from 121 SLE patients and 106 healthy individuals, and identified 90 proteins and 76 metabolites significantly changed. Several apolipoproteins and the metabolite arachidonic acid were significantly associated with disease activity. Apolipoprotein A-IV (APOA4), LysoPC(16:0), punicic acid and stearidonic acid were correlated with renal function. Random forest model using the significantly changed molecules identified 3 proteins including ATRN, THBS1 and SERPINC1, and 5 metabolites including cholesterol, palmitoleoylethanolamide, octadecanamide, palmitamide and linoleoylethanolamide, as potential biomarkers for SLE diagnosis. Those biomarkers were further validated in an independent cohort with high accuracy (AUC = 0.862 and 0.898 for protein and metabolite biomarkers respectively). This unbiased screening has led to the discovery of novel molecules for SLE disease activity assessment and SLE classification.

Spatial proteomics landscape and immune signature analysis of renal sample of lupus nephritis based on laser-captured microsection.

OBJECTIVE: We aimed to reveal a spatial proteomic and immune signature of kidney function regions in lupus nephritis (LN). MATERIAL AND METHODS: The laser capture microdissection (LCM) was used to isolate the glomerulus, tubules, and interstitial of the kidney from paraffin samples. The data-independent acquisition (DIA) method was used to collect proteomics data. The bioinformatic analysis was performed. RESULTS: A total of 49,658 peptides and 4056 proteins were quantitated. Our results first showed that a high proportion of activated NK cells, naive B cells, and neutrophils in the glomerulus, activated NK cells in interstitial, and resting NK cells were accumulated in tubules in LN. The immune-related function analysis of differential expression proteins in different regions indicated that the glomerulus and interstitial were major sites of immune disturbance and regulation connected with immune response activation. Furthermore, we identified 7, 8, and 9 hub genes in LN's glomerulus, renal interstitial, and tubules. These hub genes were significantly correlated with the infiltration of immune cell subsets. We screened out ALB, CTSB, LCN2, A2M, CDC42, VIM, LTF, and CD14, which show higher performance as candidate biomarkers after correlation analysis with clinical indexes. The function within three regions of the kidney was analyzed. The differential expression proteins (DEGs) between interstitial and glomerulus were significantly enriched in the immune-related biological processes, and myeloid leukocyte-mediated immunity and cellular response to hormone stimulus. The DEGs between tubules and glomerulus were significantly enriched in cell activation and leukocyte-mediated immunity. While the DEGs between tubules and interstitial were enriched in response to lipid, antigen processing, and presentation of peptide antigen response to oxygen-containing compound, the results indicated a different function within kidney regions. CONCLUSIONS: Collectively, we revealed spatial proteomics and immune signature of LN kidney regions by combined using LCM and DIA.

Quantitative proteomics analysis of lysine 2-hydroxyisobutyrylation in IgA nephropathy.

BACKGROUND: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. METHODS: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. CONCLUSIONS: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.

A single-cell map for the transcriptomic signatures of peripheral blood mononuclear cells in end-stage renal disease.

BACKGROUND: Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. METHODS: We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. RESULTS: We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. CONCLUSIONS: We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD.

Comprehensive analysis of lysine crotonylation modification in patients with chronic renal failure.

BACKGROUND: Post-translational modifications (PTMs) are at the heart of many cellular signaling events, which changes the function of protein. Crotonylation, one of the most important and common PTMs, plays a crucial role in the regulation of various biological processes. However, no study has evaluated the role of lysine crotonylation modification in chronic renal failure (CRF) patients. METHODS: Here, we comparatively evaluated the crotonylation proteome of normal controls and chronic renal failure patients using liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with highly sensitive immune-affinity purification. RESULTS: A total of 1109 lysine modification sites were identified, of which 772 sites were up-regulated and 69 sites were down-regulated. This suggested that crotonylation modification maintains high levels in the patients with chronic renal failure. Gene ontology(GO) enrichment analysis showed that the crotonylated proteins were significantly enriched in the platelet alpha granule lumen, platelet degradulation, and cell adhesion molecule binding. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG)-based functional enrichment analysis in the Kyoto encyclopedia showed that crotonylated protein was enriched in CD36, which is closely linked to renal failure. CONCLUSIONS: This is the first report of the global crotonylation proteome in chronic renal failure patients. Crotonylation of histone and non-histone may play important roles in delaying the continuous deterioration of renal function in patients with chronic renal failure.

The potential role of tRNAs and small RNAs derived from tRNAs in the occurrence and development of systemic lupus erythematosus.

BACKGROUND: Emerging evidence has shown the involvement of dysregulated transfer RNAs (tRNAs) and small RNAs derived from transfer RNAs (tsRNAs) in the pathophysiology of human diseases. The role of tRNAs and tsRNAs in systemic lupus erythematosus (SLE) remains unclear. Therefore, this study aims to investigate the possible regulatory roles of tRNAs and tsRNAs in the pathological mechanism of SLE. METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 20 SLE patients and 20 normal controls (NCs) to obtain tRNAs and tsRNAs, followed by tRNA and tsRNA expression profiling by the NextSeq system. Target genes were predicted by informatics analysis. Subsequently, to explore the function of messenger RNA (mRNA) in these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database, and Cytoscape software. RESULTS: A total of 101 tRNAs and 355 tsRNAs were found to be differentially expressed in SLE patients versus NCs by RNA microarray. GO analysis revealed that the altered target genes of the selected tRNAs and tsRNAs were most enriched similarly in immune response and the immune system process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tRNAs were most enriched in systemic lupus erythematosus, while the altered target genes of tsRNAs were most enriched in the T cell receptor signalling pathway, Th1 and Th2 cell differentiation and primary immunodeficiency. These pathways may be related to the initiation of SLE. CONCLUSION: Our results provide a novel perspective for studying the tRNA-related and tsRNA-related pathogenesis of SLE.

Controversial treatments: An updated understanding of the coronavirus disease 2019.

An outbreak of severe acute respiratory syndrome-related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case-fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.

Endoscopic Variceal Sequential Ligation Does Not Increase Risk of Gastroesophageal Reflux Disease in Cirrhosis Patients.

BACKGROUND: Endoscopic variceal sequential ligation (EVSL) is currently endorsed in our hospital, as the preferred endoscopic treatment for prevention of variceal rebleeding and achieving adequate hemostasis. There is currently a lack of consensus surrounding EVSL-induced changes in esophageal motor function and abnormal reflux. AIMS: To explore alterations in esophageal motor function and risk of abnormal gastroesophageal reflux in liver cirrhosis patients with esophageal varices, after EVSL. METHODS: Twenty-one liver cirrhosis patients with esophageal varices were studied using manometry and 24-h pH monitoring 1 day prior to and 1 month following EVSL. The EVSL consisted of performing esophageal variceal ligation using a multi-band ligator, which was repeated every 4 weeks until the varices were eradicated. RESULTS: The amplitude and duration of peristaltic contraction waves and the percentage of abnormal esophageal contraction waveforms were unaltered in both the proximal (P > 0.05) and the distal (P > 0.05) esophagus after EVSL. However, the lower esophageal sphincter pressure was decreased following EVSL (16.1 ± 7.9 mmHg vs 21.1 ± 6.3 mmHg (P < 0.05)). Various quantitative parameters including percentage of total monitoring time with pH < 4.0, total number of reflux episodes, number of reflux episodes > 5 min, and DeMeester scores were not increased in post-EVSL patients. Abnormal reflux monitored by 24-h pH monitoring occurred in ten (47.6%) pre-EVSL patients and 11 (52.4%) post-EVSL patients. CONCLUSIONS: Although EVSL affects esophageal motility by relatively decreasing LES pressure, it does not induce substantial motor abnormalities nor increase risk of abnormal gastroesophageal reflux disease in cirrhosis patients.

Single-Cell Sequencing Reveals the Relationship between Phenotypes and Genotypes of Klinefelter Syndrome.

Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified. Here, we report a 47,XXY Chinese male with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) with regard to a Chinese male and a female control with normal karyotype by single-cell sequencing. A total of 24,439 cells were analyzed and divided into 5 immune cell types (including B cells, T cells, macrophage cells, dendritic cells, and natural killer cells) according to marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between the KS patient and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system and type I diabetes mellitus. Based on our data, we identified several candidate genes which may be implicated in regulating the phenotype of KS. Overall, this analysis provides a comprehensive map of the cell types of PBMCs in a KS patient at the single-cell level, which will contribute to the prevention of comorbidity and improvement of the life quality of KS patients.

ß-Arrestin1 alleviates acute pancreatitis via repression of NF-κBp65 activation.

BACKGROUND AND AIM: ß-Arrestins (ß-arrs) are regulators and mediators of G protein-coupled receptor signaling that are functionally involved in inflammation. Nuclear factor-κB p65 (NF-κBp65) activation has been observed early in the onset of pancreatitis. However, the effect of ß-arrs in acute pancreatitis (AP) is unclear. The aim of this study is to investigate whether ß-arrs are involved in AP through activation of NF-κBp65. METHODS: Acute pancreatitis was induced by either caerulein injection or choline-deficient supplemented with ethionine diet (CDE). ß-arr1 wild-type and ß-arr1 knockout mice were used in the experiment. The survival rate was calculated in the CDE model mice. Histological and western blot analyses were performed in the caerulein model. Inflammatory mediators were detected by real-time polymerase chain reaction in the caerulein-induced AP mice. Furthermore, AR42J and PANC-1 cell lines were used to further study the effects of ß-arr1 in caerulein-induced pancreatic cells. RESULTS: ß-Arr1 but not ß-arr2 is significantly downregulated in caerulein-induced AP in mice. Targeted deletion of ß-arr1 notably upregulated expression of the pancreatic inflammatory mediators including tumor necrosis factor α and interleukin 1ß as well as interleukin 6 and aggravated AP in caerulein-induced mice. ß-Arr1 deficiency increased mortality in mice with CDE-induced AP. Further, ß-arr1 deficiency enhanced caerulein-induced phosphorylation of NF-κBp65 both in vivo and in vitro. CONCLUSION: ß-Arr1 alleviates AP via repression of NF-κBp65 activation, and it is a potentially therapeutic target for AP.

Insulin-Like Growth Factor-1 Contributes to Mucosal Repair by ß-Arrestin2-Mediated Extracellular Signal-Related Kinase Signaling in Experimental Colitis.

Insulin-like growth factor-1 (IGF-1) possesses the ability to attenuate intestinal damage and promote mucosal repair of colitis. ß-Arrestins, as the scaffolding proteins of G protein-coupled receptors or non-G protein-coupled receptors signaling, can be involved in IGF-1-mediated signaling pathways. However, the interaction of IGF-1 and ß-arrestin2 in the mucosal repair of experimental colitis remains unexplored. Ulcerative colitis was induced in ß-arrestin2 wild-type mice and ß-arrestin2 knockout littermates by using 3% dextran sulfate sodium for 5 days, followed by regular water consumption for 1, 2, 3, and 4 weeks to analyze the mucosal repair from experimental colitis. Disease activity index and histologic score analyses were performed. Apoptosis and proliferation were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Ki-67 staining, respectively. The expressions of ß-arrestin2, phospho (p)-IGF-1R, and p-extracellular signal-regulated kinase (ERK)1/2 were examined. Furthermore, ß-arrestin2 was overexpressed or altered in HCT116 cells by transfection before IGF-1 treatment in vitro. IGF-1 and ß-arrestin2 expression was up-regulated in the repairing phase of experimental colitis. Targeted deletion of ß-arrestin2 delayed the repair of colitis by inhibiting cell proliferation without affecting the levels of IGF-1 and p-IGF-1R. The ß-arrestin2/ERK signaling pathway was involved in IGF-1-mediated mucosal repair through promoting epithelial cell and goblet cell regeneration from experimental colitis. These results indicate that IGF-1 contributes to the mucosal repair by ß-arrestin2-mediated ERK signaling in experimental colitis.

Role of ACSL4 in modulating farnesoid X receptor expression and M2 macrophage polarization in HBV-induced hepatocellular carcinoma.

The intricate relationship between bile acid (BA) metabolism, M2 macrophage polarization, and hepatitis B virus-hepatocellular carcinoma (HBV-HCC) necessitates a thorough investigation of ACSL4's (acyl-CoA synthetase long-chain family member 4) role. This study combines advanced bioinformatics and experimental methods to elucidate ACSL4's significance in HBV-HCC development. Using bioinformatics, we identified differentially expressed genes in HBV-HCC. STRING and gene set enrichment analysis analyses were employed to pinpoint critical genes and pathways. Immunoinfiltration analysis, along with in vitro and in vivo experiments, assessed M2 macrophage polarization and related factors. ACSL4 emerged as a pivotal gene influencing HBV-HCC. In HBV-HCC liver tissues, ACSL4 exhibited upregulation, along with increased levels of M2 macrophage markers and BA. Silencing ACSL4 led to heightened farnesoid X receptor (FXR) expression, reduced BA levels, and hindered M2 macrophage polarization, thereby improving HBV-HCC conditions. This study underscores ACSL4's significant role in HBV-HCC progression. ACSL4 modulates BA-mediated M2 macrophage polarization and FXR expression, shedding light on potential therapeutic targets and novel insights into HBV-HCC pathogenesis.

Effects of Acmella radicans Invasion on Soil Seed Bank Community Characteristics in Different Habitats.

To examine the effects of the recent Acmella radicans invasion on plant community and diversity in invaded habitats, the composition, density, species richness, diversity indices, and evenness index of the soil seed bank community of two different habitats (wasteland and cultivated land) in Yunnan Province, China, were analyzed through field sampling and greenhouse germination tests. A total of 28 species of plants belonging to 15 families and 28 genera, all annual herbs, were found in the soil seed bank. Seed densities and species number in the seed bank tended to be greater in April than in October; cultivated land also featured higher seed densities and species numbers compared to wasteland. With increased A. radicans cover, the seed bank population of A. radicans also significantly increased, but the seed bank populations of many other dominant species (e.g., Ageratum conyzoides and Gamochaeta pensylvanica) and native species (e.g., Laggera crispata and Poa annua) clearly declined. The germination of A. radicans seeds was concentrated during the period from the 4th to the 5th weeks. Vertically, the seed number of A. radicans was significantly different among the 0-5 cm, 5-10 cm and 10-20 cm layers that accounted for 80.7-90.6%, 9.4-16.1% and 0.0-3.2% of the total seed density in wasteland, respectively; and in cultivated land, A. radicans accounted for 56.8-64.9%, 26.7-31.8% and 8.1-13.5% of the total seed density, respectively. With reduced A. radicans cover, the species richness, Simpson index, Shannon-Wiener index, and Pielou indices of the weed community generally increased, and most diversity indices of weed communities in cultivated land were lower than in wasteland under the same cover of A. radicans. The results indicate that the invasion of A. radicans has negatively affected local weed community composition and reduced weed community diversity, and that these negative impacts in cultivated land may be enhanced by human disturbance. Our study was the first to elucidate the influence of A. radicans invasion on soil seed bank community characteristics in invaded habitats, providing a better understanding of its invasion and spread mechanisms in order to aid in developing a scientific basis for the prevention and control of this invader.

Unraveling the proteomic landscape of fibrosis in lupus nephritis through CI-based analysis.

INTRODUCTION: The underlying mechanism by which lupus nephritis (LN) progresses to chronic kidney disease remains elusive. Fibrosis is a hallmark feature of chronic kidney disease, including LN. The chronicity index (CI) score, which incorporates glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis, summarizes the extent of kidney tissue fibrosis. METHOD: In this study, we employed label-free quantitative proteomics based on mass spectrometry to generate kidney protein profiles with varying CI scores. RESULTS: A total of 98 proteins exhibiting linear correlation with CI scores were initially screened out by linear model (CI linearly related proteins), and subsequently, 12 key proteins were derived based on the CI linearly related proteins using Cytohubba. LN patients were stratified into two subtypes based on CI scores and epithelial-mesenchymal transition (EMT) characteristics. These subtypes exhibited significant disparities in immune infiltration and molecular pathways. The high EMT group exhibited heightened activation of immune cells, such as memory B cells, gamma delta T cells, and resting mast cells. Gene Set Enrichment Analysis (GSEA) uncovered substantial dysregulation in critical biological processes and signaling pathways, including NF-κB, JNK, PI3K/AKT/mTOR signaling pathway, lipoprotein biosynthetic process, and endocytosis, in both subgroups. CONCLUSION: In conclusion, this study establishes molecular subgroups based on the CI score, providing novel insights into the molecular mechanisms governing chronicity in the kidneys of diverse LN patients. Key Points • Fibrosis is a fundamental and characteristic pathological process underlying the NIH-CI in LN. • Different EMT status presented variant clinical characteristics, immune features in LN.

Diabetes Mellitus Inhibits Hair Follicle Regeneration by Inducing Macrophage Reprogramming-Mediated Pyroptosis.

Background: Diabetes mellitus (DM) is known to inhibit skin self-renewal and hair follicle stem cell (HFSC) activation, which may be key in the formation of chronic diabetic wounds. This study aimed to investigate the reasons behind the suppression of HFSC activation in DM mice. Methods: Type 1 DM (T1DM) was induced in 6-week-old mice via streptozotocin, and hair follicle growth was subsequently monitored. RNA sequencing, bioinformatics analyses, qRT‒PCR, immunostaining, and cellular experiments were carried out to investigate the underlying mechanisms involved. Results: T1DM inhibited HFSC activation, which correlated with an increase in caspase-dependent programmed cell death. Additionally, T1DM triggered apoptosis and pyroptosis, predominantly in HFSCs and epidermal regions, with pyroptosis being more pronounced in the inner root sheath of hair follicles. Notably, significant cutaneous immune imbalances were observed, particularly in macrophages. Cellular experiments demonstrated that M1 macrophages inhibited HaCaT cell proliferation and induced cell death, whereas high-glucose environments alone did not have the same effect. Conclusion: T1DM inhibits HFSC activation via macrophage reprogramming-mediated caspase-dependent pyroptosis, and there is a significant regional characterization of cell death. Moreover, T1DM-induced programmed cell death in the skin may be more closely related to immune homeostasis imbalance than to hyperglycemia itself. These findings shed light on the pathogenesis of diabetic ulcers and provide a theoretical basis for the use of hair follicle grafts in wound repair.

High Expression of F-Box Protein 43 Is Associated With Poor Prognosis and Adjuvant Chemotherapy Resistance in Colorectal Cancer.

Background: The F-box protein 43 (FBXO43), also referred to as endogenous meiotic inhibitor 2 (EMI2), has been linked to the advancement of various types of cancer, such as hepatocellular carcinoma, breast cancer, cholangiocarcinoma, and gastric cancer. Nevertheless, the precise function of FBXO43 in colorectal cancer (CRC) remains unclear. This study employed data from The Cancer Genome Atlas (TCGA) and clinical specimens to analyze the expression, prognostic value, and chemotherapeutic advantages of FBXO43 in CRC. Methods: Level 3 RNA sequencing data pertaining to 631 cases of colon and rectal adenocarcinomas (COAD-READ) were downloaded from TCGA. The data were utilized to analyze the expression, prognosis, and related signal pathways of FBXO43. The expression of FBXO43 in clinical samples was subsequently confirmed through the use of real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Lastly, a tissue microarray (TMA) consisting of 120 cases of CRC and corresponding normal tissues was established to investigate the relationship between FBXO43 and survival outcomes. Results: Results from both the TCGA analysis and clinical samples indicated that FBXO43 was significantly upregulated in CRC tissues in comparison to normal tissues. Moreover, high level of FBXO43 was found to be relevant to malignant clinical features, such as differentiation, lymph node metastasis, and pathological stage, as well as unfavorable prognosis in CRC patients. Subgroup analysis further demonstrated that FBXO43 could be an effective parameter for stratifying low-risk CRC patients. Notably, survival analysis showed that patients with high level of FBXO43 had worse overall survival (OS) and disease-free survival (DFS) following adjuvant chemotherapy, and FBXO43 was distinctly upregulated in chemotherapy-resistant patients' primary CRC tissues. Conclusions: FBXO43 was upregulated and associated with poor prognosis of CRC; patients with high expression of FBXO43 may not be benefit from adjuvant chemotherapy.

The circRNA-miRNA-mRNA regulatory network in plasma and peripheral blood mononuclear cells and the potential associations with the pathogenesis of systemic lupus erythematosus.

OBJECTIVES: This study aimed to explore the possible role of plasma and peripheral blood mononuclear cells (PBMCs) circular RNA (circRNA) in systemic lupus erythematosus (SLE). METHOD: Total RNA was extracted from blood plasma samples obtained from 10 patients with SLE and 10 healthy controls and subjected to microarray analysis to define the profile of circRNA expression. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) amplification was conducted. The overlapped circRNA between PBMCs and plasma was performed, the interactions with microRNAs were predicted, the miRNA target mRNA was predicted, and the GEO database was used. The Gene ontology and pathway analysis was performed. RESULTS: One hundred thirty-one upregulated and 314 significantly downregulated circRNAs were identified in the plasma of patients with SLE by the Fold change criteria (≥ 2.0) and P < 0.05. The qRT-PCR results showed that the expression of has-circRNA-102531, has-circRNA-103984, and has-circRNA-104262 was increased in plasma of SLE, and the expression of has-circRNA-102972, has-circRNA-102006, has-circRNA-104313 was decreased in plasma of SLE. Twenty-eight upregulated circRNAs and 119 downregulated circRNAs were overlapped from PBMCs and plasma, and ubiquitination was enriched. Furthermore, the circRNA-miRNA-mRNA network was constructed in SLE after analyzing dataset GSE61635 from GEO. The circRNA-miRNA-mRNA network comprises 54 circRNAs, 41 miRNAs, and 580 mRNAs. In addition, the TNF signaling pathway and the MAPK pathway were enriched from the mRNA of the miRNA target. CONCLUSION: We first revealed the differentially expressed circRNAs in plasma and PBMCs, and then the circRNA-miRNA-mRNA network was constructed. The network's circRNAs could be a potential diagnostic biomarker and potentially play an important role in the pathogenesis and development of SLE. Key Points • This study analyzed the circRNAs expression profiles combined with the plasma and PBMCs, which provided a comprehensive overview of circRNAs expression patterns in SLE. • The network of the circRNA-miRNA-mRNA in SLE was constructed, which contributes to a better understanding of the pathogenesis and development of SLE.

Global-feature of autoimmune glomerulonephritis using proteomic analysis of laser capture microdissected glomeruli.

Background: IgA nephropathy (IgAN), (LN), membranous nephropathy (MN), and minimal change nephropathy (MCN) are all belonged to autoimmune glomerulonephritis. This study aimed to identify the specific proteomic characteristics of the four GNs diseases in order to provide frameworks for developing the appropriate drug for patients diagnosed with GNs disease. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized to investigate proteomic features of glomerular tissues obtained by laser capture microdissection (LCM). 8 normal control cases, 11 IgAN cases, 19 LN cases, 5 MN cases, and 3 MCN cases in this study were selected for bioinformatics analyses. Results: The shared overlapping proteins among the top 100 DEPs of each GNs type were mostly downregulated, in which only FLII was significantly downregulated in the four GNs diseases. A2M was significantly upregulated in MN, IgAN, and LN subgroups. The pathway of complement and coagulation cascades was notably activated with NES value ranging 2.77 to 3.39 among MCN, MN, IgAN, and LN diseases, but the pattern of protein expression level were significantly different. In LN patients, the increased activity of complement and coagulation cascades was contributed by the high expression of multiple complements (C1QB, C3, C4A, C4B, C6, C8B, C8G, C9). Meanwhile, both C1QC and C4B were remarkably upregulated in MN patients. On the contrary, complement-regulating proteins (CD59) was substantially decreased in MCN and IgAN subgroup. Conclusions: The integrative proteomics analysis of the four GNs diseases provide insights into unique characteristics of GNs diseases and further serve as frameworks for precision medicine diagnosis and provide novel targets for drug development.