Trim21 modulates endoplasmic reticulum-associated degradation and sensitizes cancer cells to ER stress-induced apoptosis by inhibiting VCP/Npl4/UFD1 assembly.

Endoplasmic reticulum-associated degradation (ERAD) serves as a crucial quality and quantity control system that removes misfolded or unassembled proteins from the Endoplasmic Reticulum (ER) through the cytoplasmic ubiquitin-proteasome system (UPS), which is critical for cell fate decision. ER stress arises when misfolded proteins accumulated within the ER lumen, potentially leading to cell death via proapoptotic unfolded protein response (UPR). UFD1 in associated with VCP-Npl4, is recognized as a key regulator of protein homeostasis in ERAD. However, the factors that control VCP complex assembly remain unclear. The study elucidates the function of Trim21, an E3 ubiquitin ligase, through its interaction with UFD1, facilitating K27-linkage ubiquitination of UFD1 and inhibiting its incorporation into the VCP complex. This results in the suppression of ERAD substrates degradation and the activation of a proapoptotic unfolded protein response in cancer cells. Additionally, Trim21 over-expression enhances ER stress response and promotes apoptosis upon expose to the ER inducer Tunicamycin. Notably, elevated Trim21 expression correlates with improved overall survival in various tumor types. Overall, the findings highlight the critical role of Trim21 in regulating ERAD progression and cell fate determination in cancer cells through modulation of VCP/Npl4/UFD1 complex assembly.

Impact of surface ultraviolet radiation intensity on hospital admissions for ischemic and hemorrhagic stroke: A large-scale database study using distributed lag nonlinear analysis, 2015-2022, in Harbin, China.

OBJECTIVES: Our aim is to evaluate the impact of surface ultraviolet radiation intensity on hospital admissions for stroke and to compare the correlation and differences among different subtypes of strokes. MATERIALS AND METHODS: We collected daily data on surface ultraviolet radiation intensity, temperature, air pollution, and hospital admissions for stroke in Harbin from 2015 to 2022. Using a distributed lag non-linear model, we determined the correlation between daily surface ultraviolet radiation intensity and the stroke admission rate. Relative risks (RR) with 95% confidence intervals (CI) and attributable fractions (AF) with 95% CI were calculated based on stroke subtypes, gender, and age groups. RESULTS: A total of 132,952 hospitalized stroke cases (including hemorrhagic and ischemic strokes) were included in the study. We assessed the non-linear effects of ultraviolet intensity on hospitalized patients with ischemic and hemorrhagic strokes. Compared to the maximum morbidity benchmark ultraviolet intensity (19.2 × 10^5 for ischemic stroke and 20.25 for hemorrhagic stroke), over the 0-10 day lag period, the RR for extreme low radiation (1st percentile) was 0.86 (95% CI: 0.77, 0.96), and the RR for extreme high radiation (99th percentile) was 0.86 (95% CI: 0.77, 0.96). In summary, -4.842% (95% CI: -7.721%, -2.167%) and -1.668% (95% CI: -3.061%, -0.33%) of ischemic strokes were attributed to extreme low radiation intensity with a lag of 0 to 10 days and extreme high radiation intensity with a lag of 0 to 5 days, respectively. The reduction in stroke hospitalization rates due to low or high ultraviolet intensity was more pronounced in females and younger individuals compared to males and older individuals. None of the mentioned ultraviolet intensity intensities and lag days had a statistically significant impact on hemorrhagic stroke. CONCLUSIONS: Our study fundamentally suggests that both lower and higher levels of surface ultraviolet radiation intensity in Harbin, China, contribute to a reduced incidence of ischemic stroke, with this effect lasting approximately 10 days. This finding holds significant potential for public health and clinical relevance.

Advances in noncoding RNA in children allergic rhinitis.

BACKGROUND: A chronic condition that significantly reduces a child's quality of life is allergic rhinitis (AR). The environment and allergens that the body is regularly exposed to can cause inflammatory and immunological reactions, which can change the expression of certain genes Epigenetic changes are closely linked to the onset and severity of allergy disorders according to mounting amounts of data. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. METHODS: Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. RESULTS: Recent findings indicate that various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. CONCLUSION: This article demonstrates the significance and progress of ncRNAs in children's AR. The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore.

Delta-like noncanonical notch ligand 2 regulates the proliferation and differentiation of sheep myoblasts through the Wnt/ß-catenin signaling pathway.

This study delved into the role of delta-like noncanonical notch ligand 2 (DLK2) in the cell cycle, proliferation, apoptosis, and differentiation of myoblasts, as well as its interaction with the classical Wnt/ß-catenin signaling pathway in regulating myoblast function. The research revealed that upregulation of DLK2 in myoblasts during the proliferation phase enhanced myoblast proliferation, facilitated cell cycle progression, and reduced apoptosis. Conversely, downregulation of DLK2 expression using siRNA during the differentiation phase promoted myoblast hypertrophy and fusion, suppressed the expression of muscle fiber degradation factors, and expedited the differentiation process. DLK2 regulates myoblasts function by influencing the expression of various factors associated with the Wnt/ß-catenin signaling pathway, including CTNNB1, FZD1, FZD6, RSPO1, RSPO4, WNT4, WNT5A, and adenomatous polyposis coli. In essence, DLK2, with the involvement of the Wnt/ß-catenin signaling pathway, plays a crucial regulatory role in the cell cycle, proliferation, apoptosis, and differentiation of myoblasts.

A two-center randomized controlled trial of a repairing mask as an adjunctive treatment for mild to moderate rosacea.

OBJECTIVE: To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea. METHODS: Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score. RESULTS: A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants. CONCLUSION: The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use.

Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-ß-carboline derivatives as potential antibacterial agents.

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.

New Clerodane Diterpenoids from Tinospora Capillipes with Antibacterial and Anti-Inflammatory Properties.

Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4-64 µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.

Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review.

Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.

Novel cancer-fighting role of ticagrelor inhibits GTSE1-induced EMT by regulating PI3K/Akt/NF-κB signaling pathway in malignant glioma.

Background: Glioma is the most common malignant brain tumor of the central nervous system. Despite of the improvement of therapeutic strategy, the prognosis of malignant glioma patients underwent by STUPP strategy is still unexpected. Previous studies have suggested that ticagrelor exerted chemotherapeutic effects by inhibition of epithelial-mesenchymal transition (EMT) in various diseases including tumors. However, whether ticagrelor can exhibit the antitumor efficiency in glioma by affecting the EMT process is still unclear. In this study, we investigated the cancer-fighting role of ticagrelor and demonstrated its chemotherapeutic mechanism in glioma. Materials and methods: The MTT assay was performed to detect the cytotoxicity of ticagrelor in glioma cells. We evaluated the expression of Ki67 in glioma cells by immunofluorescence assay after ticagrelor treatment. We conducted wound healing assay and transwell assay to determine the effects of ticagrelor on the migration and invasion of glioma cells. RNA-seq analysis was conducted to examine potential target genes and alternative signaling pathways for ticagrelor treatment. The expression levels of key EMT -related proteins were examined by Western blot experiment. Results: Ticagrelor inhibited the proliferation, migration and invasion of glioma cells with a favorable toxicity profile in vitro. Ticagrelor downregulated the expression of GTSE1 in glioma cells. RNA-seq analysis explored that GTSE1 acted as the potential target gene for ticagrelor treatment. Upregulation of GTSE1 antagonized the inhibitory effect of ticagrelor on the invasion of glioma and EMT progression by regulation of PI3K/Akt/NF-κB signaling pathway. And ticagrelor also exhibited the similar chemotherapeutic effect of glioma in vivo. Conclusions: Ticagrelor as a potential chemotherapeutic option induced the inhibition of the GTSE1-induced EMT progression by regulation of PI3K/AKT/NF-κB signaling pathway.

Novel a-linolenic acid emulsions stabilized by octenyl succinylated starch -soy protein-epigallocatechin-3-gallate complexes: Characterization and antioxidant analysis.

In this study, octenyl succinylated starch (OSAS)-soy protein (SP)-epigallocatechin-3-gallate (EGCG) complexes were designed to enhance the physical and oxidative stability of α-linolenic acid emulsions. Formations of OSAS-SP-EGCG complexes were confirmed via particle size, ξ-potential, together with fourier transform infrared (FTIR). A mixing ratio of 1:2 for OSAS to SP-EGCG resulted in ternary complexes with the highest contact angle (59.69°), indicating the hydrophobicity. Furthermore, the characteristics of α-linolenic acid emulsions (oil phase volume fractions (φ) of 10% and 20%) stabilized by OSAS-SP-EGCG complexes were investigated, including particle size, ξ-potential, emulsion stability, oxidative stability, and microstructure. These results revealed exceptional physical stability together with enhanced oxidative stability for these emulsions. Particularly, emulsions utilizing complexes having a 1:2 OSAS to SP-EGCG ratio exhibited superior emulsion stability. These findings provide theoretical support to the development of emulsions containing high levels of α-linolenic acid and for the broader application of α-linolenic acid in food products.

[Effect and complication among different kinds of spinal endoscopic surgery for lumbar disc herniation].

OBJECTIVE: To compare clinical efficacy and complication rate of percutaneous endoscopic transforaminal discectomy(PETD),percutaneous endoscopic interlaminar discectomy (PEID) and unilateral biportal endoscopic (UBE) in treating single-segment lumbar disc herniation(LDH). METHODS: From October 2019 to August 2021,121 LDH patients with single-segment treated by spinal endoscopy were retrospectively analyzed and divided into three groups. In PETD group,there were 48 patients,including 19 males and 29 females,aged from 18 to 72 years old with an average of (44.0±13.9) years old;3 patients with L3,4 segments,27 patients with L4,5 segments,and 18 patients with L5S1 segments. In PEID group,there were 43 patients,including 23 males and 20 females,aged from 20 to 69 years old with an average of (40.1±12.1) years old;1 patient with L3,4 segments,15 patients with L4,5 segments,and 27 patients with L5S1 segments. In UBE group,there were 30 patients,including 12 males and 18 females,aged from 29 to 72 years old with an average of (41.2±15.0) years old;1 patient with L3,4 segments,18 patients with L4,5 segments,and 11 patients with L5S1 segments. Operation time,blood loss,fluoroscopy times and complications among three groups were observed and compared. Before opertaion,3 months after operation and at the latest follow-up,visual analogue scale (VAS) was used to evaluate low back pain and lower extremity pain,Oswestry disfunction index (ODI) was used to evaluate lumbar function,and modified MacNab was used to evaluate clinical efficacy at the latest follow-up. RESULTS: All patients were performed endoscopic spinal surgery completly and were followed up for at least 12 months. One patient occurred dural sac rupture both in PETD and PEID group,and dural sac rupture was small,and there was no obvious discomfort after operation. Two patients were occurred intraoperative rupture of dural sac in UBE group. One patient was occurred cerebrospinal fluid leakage after operation,and was improved after rest in supine position and fluid rehydration. One patient without no significant postoperative discomfort. (1)There were no significant difference in operating time,blood loss and hospital stay between PETD and PEID group (P>0.05),while UBE group was higher than those of PETD and PEID group (P<0.05). There was no statistical significance in fluoroscopy times between PEID and UBE group (P>0.05),but PETD group was higher than that of PEID and UBE group (P<0.05). (2)VAS of low back pain at 3 months after operation in UBE group was higher than that in PETD and PEID group (P<0.05),but there was no significant difference between PETD and PEID group (P>0.05). At the latest follow-up,there was no significant difference in VAS of low back pain among three groups (P>0.05). (3)Lower extremity pain of VAS and ODI among 3 groups after operation were significantly improved at all time points compared with those before opertaion(P<0.05),and there were no statistical significance between groups (P>0.05),and there were no statistical significance in interaction between different time points and operation groups (P>0.05). (4) At the latest follow-up,according to the modified MacNab standard,the results of PETD group were excellent in 27 patients,good in 16 patients,moderate in 4 patients,poor in 1 patient;in PEID group,27 patients got excellent result,12 good,3 moderate,and 1 poor;in UBE group,16 patients got excellent,10 good,2 moderate,and 2 poor. There was no significant difference among three groups (χ2=0.308,P>0.05). Recurrence of lumbar disc herniation occurred in 1 patient among each three groups,symptoms were improved in 2 patients after symptomatic treatment,and 1 patient was treated in other hospitals. CONCLUSION: PETD,PEID and UBE techniques could achieve good early clinical effects in treating lumbar disc herniation with similar complication rates. Both of PETD and PEID are single-channel minimally invasive surgery,with mild intraoperative tissue damage and quick postoperative recovery; while intraoperative fluoroscopy of PETD was relatively more frequent, and PEID was more suitable for L5S1 segment;UBE is a two-channel surgery,in which the intraoperative soft tissue damage is more severe,but exposure is broad,which is more suitable for complex cases.

Effect of biophysical properties of tumor extracellular matrix on intratumoral fate of nanoparticles: Implications on the design of nanomedicine.

Nanomedicine has a profound impact on various research domains including drug delivery, diagnostics, theranostics, and regenerative medicine. Nevertheless, the clinical translation of nanomedicines for solid cancer remains limited due to the abundant physiological and pathological barriers in tumor that hinder the intratumoral penetration and distribution of these nanomedicines. In this article, we review the dynamic remodeling of tumor extracellular matrix during the tumor progression, discuss the impact of biophysical obstacles within tumors on the penetration and distribution of nanomedicines within the solid tumor and collect innovative approaches to surmount these obstacles for improving the penetration and accumulation of nanomedicines in tumor. Furthermore, we dissect the challenges and opportunities of the respective approaches, and propose potential avenues for future investigations. The purpose of this review is to provide a perspective guideline on how to effectively enhance the penetration of nanomedicines within tumors using promising methods.

ß-Cyclodextrin based Pickering emulsions for α-tocopherol delivery: Antioxidation stability and bioaccessibility.

ß-Cyclodextrin (ß-CD) Pickering emulsion and cinnamaldehyde/ß-cyclodextrin (CIN/ß-CD) Pickering emulsion were prepared and the influences of oxidation and digestion were investigated. CIN/ß-CD composite was better dispersed at the oil-water interface than ß-CD. Hydrophobic group of CIN anchored in the oil phase and Hydrophilic hydroxyl group of ß-CD extended into the aqueous phase, which allowed CIN/ß-CD composite to be oriented at the oil-water interface and formed a more stable oil-water interface layer. ß-CD Pickering emulsion was more susceptible to oxidative deterioration than CIN/ß-CD Pickering emulsion, its malondialdehyde (MDA) value was as high as 509.41 ± 9.37 nmol/L. Digestion experiment indicated that CIN/ß-CD Pickering emulsion was released inner oil phase in the small intestine and free fatty acid (FFA) release rate was 44.32 ± 1.08%. Pharmacokinetic parameters manifested that α-tocopherol peak concentration (Cmax) was 64.32 ± 6.45 mg/L and the peak time (Tmax) appeared at 5 h after administration of CIN/ß-CD Pickering emulsion.

Structural insights into the role of N-terminal integrity in PhoSL for core-fucosylated N-glycan recognition.

PhoSL (Pholiota squarrosa Lectin) has an exceptional binding affinity for biomolecules with core-fucosylated N-glycans. This modification involves the addition of fucose to the inner N-acetylglucosamine within the N-glycan structure and is known to influence many physiological processes. Nevertheless, the molecular interactions underlying high-affinity binding of native PhoSL to core-fucosylated N-glycans remain largely unknown. In this study, we devised a strategy to produce PhoSL with the essential structural characteristics of the native protein (n-PhoSL). To do so, a fusion protein was expressed in E. coli and purified. Then, enzymatic cleavage and incubation with glutathione were utilized to recapitulate the native primary structure and disulfide bonding pattern. Subsequently, we identified the residues crucial for n-PhoSL binding to core-fucosylated chitobiose (N2F) via NMR spectroscopy. Additionally, crystal structures were solved for both apo n-PhoSL and its N2F complex. These analyses suggested a pivotal role of the N-terminal amine in maintaining the integrity of the binding pocket and actively contributing to core-fucose recognition. In support of this idea, the inclusion of additional residues at the N-terminus considerably reduced binding affinity and PhoSL cytotoxicity toward breast cancer cells. Taken together, these findings can facilitate the utilization of PhoSL in basic research, diagnostics and therapeutic strategies.

AZD7762 induces CRBN dependent BAG3 degradation through ubiquitin-proteasome pathway.

Protein degraders are currently under rapid development as a promising modality for drug discovery. They are compounds that orchestrate interactions between a target protein and an E3 ubiquitin ligase, prompting intracellular protein degradation through proteasomal pathway. More protein degraders identification will greatly promote the development of this field. BAG3 is widely recognized as an excellent therapeutic target in cancer treatments. Exploring protein degraders that target BAG3 degradation has profound implications. Herein, molecular docking was applied to assess binding energy between 81 clinical phase I kinase inhibitors and BAG3. BAG3 protein and mRNA level were detected by western blot and quantitative real-time PCR. CCK8 assay and colony formation assay were applied to detect the cell viability and proliferation rate. Cell death was accessed using flow cytometry combined with PI and Annexin V double staining. AZD7762, a Chk1 kinase inhibitor, was identified to induce BAG3 degradation in a ubiquitin-proteasome pathway. AZD7762-induced BAG3 degradation was not dependent on Chk1 expression or activity. CRBN, an E3 ligase, was identified to bind to BAG3 and mediated BAG3 ubiquitination in the presence of AZD7762. By targeting Chk1 and BAG3, two ideal therapeutic targets in cancer treatment, AZD7762 would be a powerful chemotherapy agent in the future.

PCMT1 regulates the migration, invasion, and apoptosis of prostate cancer through modulating the PI3K/AKT/GSK-3ß pathway.

Protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is a repair enzyme that catalyzes the conversion of isomerized aspartic acid (iso-Asp) residues into their normal structure, thereby restoring the configuration and function of proteins. Studies have shown that PCMT1 is overexpressed in several tumors and affects patients' prognosis. However, there are few reports on the role of PCMT1 in prostate cancer (PCa). In the present research, with the assistance of The Cancer Genome Atlas Program (TCGA) database, we found that PCMT1 was overexpressed in PCa tissues. The results of quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry staining also showed that PCMT1 expression was significantly increased in PCa tissues and cell lines. In PCa clinical samples, PCMT1 expression was closely related to Gleason score, clinical stage, lymph node metastasis and bone metastasis. The experiments of overexpression and knockdown of PCMT1 in vitro or in vivo showed that PCMT1 can significantly promote the proliferation, migration and invasion of PCa cells, inhibit cell apoptosis, and promote the growth of PCa. We furthermore confirmed that PCMT1 regulated the migration, invasion and apoptosis of PCa cells by modulating the phosphatidylinositol 3-kinase/AKT kinase/glycogen-synthase kinase-3ß (PI3K/AKT/GSK-3ß) signaling pathway. Collectively, PCMT1 plays a cancer-facilitative role in PCa by promoting the proliferation, migration and invasion of PCa cells, and inhibiting apoptosis. Therefore, PCMT1 is considered to represent a novel target for treating PCa.

Effect on the Skin Microbiota of Oral Minocycline for Rosacea.

In the rosacea an unstable skin microbiota is significant for disease progression. However, data on the influence on the skin microbiota of treatment with systemic antibiotics are limited. This single-arm trial recruited patients with rosacea. Oral minocycline 50 mg was administered twice daily for 6 weeks. The lesions on the cheek and nose were sampled for 16S rRNA amplicon sequencing and metagenomic sequencing at baseline, 3 weeks and 6 weeks of treatment. Physiological parameters were detected using non-invasive instruments. After treatment, distribution of the Investigator Global Assessment scores changed significantly. For the skin microbiota, a notable increase in α-diversity and a shift of structure were observed after treatment. Treatment was accompanied by a reduction in the relative abundance of Cutibacterium and Staphylococcus, indicating negative correlations with increased bacterial metabolic pathways, such as butyrate synthesis and L-tryptophan degradation. The increased butyrate and tryptophan metabolites would be conducive to inhibiting skin inflammation and promoting skin barrier repair. In addition, the abundance of skin bacterial genes related to tetracycline resistance and multidrug resistance increased notably after antibiotic treatment.

Proteome Analysis of Alpine Merino Sheep Skin Reveals New Insights into the Mechanisms Involved in Regulating Wool Fiber Diameter.

Wool fiber is a textile material that is highly valued based on its diameter, which is crucial in determining its economic value. To analyze the molecular mechanisms regulating wool fiber diameter, we used a Data-independent acquisition-based quantitative proteomics approach to analyze the skin proteome of Alpine Merino sheep with four fiber diameter ranges. From three contrasts of defined groups, we identified 275, 229, and 190 differentially expressed proteins (DEPs). Further analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that pathways associated with cyclic adenosine monophosphate and peroxisome proliferator-activated receptor signaling are relevant to wool fiber diameter. Using the K-means method, we investigated the DEP expression patterns across wool diameter ranges. Using weighted gene co-expression network analysis, we identified seven key proteins (CIDEA, CRYM, MLX, TPST2, GPD1, GOPC, and CAMK2G) that may be involved in regulating wool fiber diameter. Our findings provide a theoretical foundation for identifying DEPs and pathways associated with wool fiber diameter in Alpine Merino sheep to enable a better understanding of the molecular mechanisms underlying the genetic regulation of wool fiber quality.