Pinin (PNN) is a desmosome-associated protein that reinforces the organization of keratin intermediate filaments and stabilizes the anchoring of the cytoskeleton network to the lateral surface of the plasma membrane. The aberrant expression of PNN affects the strength of cell adhesion as well as modifies the intracellular signal transduction pathways leading to the onset of CRC. In our previous studies, we characterized the role of miR-195-5p in the regulation of desmosome junctions and in CRC progression. Here, with the aim of investigating additional mechanisms related to the desmosome complex, we identified PNN as a miR-195-5p putative target. Using a public data repository, we found that PNN was a negative prognostic factor and was overexpressed in colon cancer tissues from stage 1 of the disease. Then, we assessed PNN expression in CRC tissue specimens, confirming the overexpression of PNN in tumor sections. The increase in intracellular levels of miR-195-5p revealed a significant decrease in PNN at the mRNA and protein levels. As a consequence of PNN regulation by miR-195-5p, the expression of KRT8 and KRT19, closely connected to PNN, was affected. Finally, we investigated the in vivo effect of miR-195-5p on PNN expression in the colon of AOM/DSS-treated mice. In conclusion, we have revealed a new mechanism driven by miR-195-5p in the regulation of desmosome components, suggesting a potential pharmacological target for CRC therapy.

BACKGROUND: Chronic rhinitis is when the nasal passages become inflamed and irritated, causing symptoms like nasal congestion, runny nose, sneezing, and postnasal drip that last for at least 12 weeks. While various medical treatments are available for chronic rhinitis, studies have shown that patients often do not comply with the treatment or report that it is ineffective. Cryotherapy for the nasal mucosa is a surgical option that has shown promise for these patients, with acceptable side effects.
OBJECTIVE: Our goal is to evaluate the existing literature regarding the effectiveness and safety of cryotherapy as a treatment for chronic rhinitis.
METHODS: We searched four electronic databases for relevant studies. Data were extracted from the included studies after screening procedures. Using the random effect model, we calculated the pooled mean difference (MD) for our continuous outcomes and pooled proportions for categorical outcomes. The I2 test was used to detect heterogenicity. Randomized controlled trials (RCTs) were assessed for methodological quality using the Cochrane risk of bias assessment tool 2, while observational studies and single-arm studies were assessed using the National Institutes of Health\'s tools.
RESULTS: Our study comprised 21 studies; eighteen were eligible for analysis, with 1663 patients with chronic rhinitis. All of our assessed outcomes showed improvement with cryotherapy from their baseline status. Our pooled MDs for Total Nasal Symptom Score (rTNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Nasal Obstruction Symptom Evaluation (NOSE) scores were as follows: ( - 3.58, 95% CI [ - 3.80,  - 3.37], p < 0.001), ( - 1.48, 95% CI [ - 1.68,  - 1.27], p < 0.001), and ( - 26.65, 95% CI [ - 33.98,  - 19.31], p < 0.001), respectively. Regarding nasal obstruction and rhinorrhea, cryotherapy showed effectiveness in 61% and 52% of patients in the complete relief subgroup and 26% and 34% in the < 50%-relief subgroup, respectively.
CONCLUSIONS: We observed significant improvement in our measured outcomes as rTNSS, RQLQ, and NOSE scores compared to the baseline state, demonstrating the cryotherapy\'s efficacy. This improvement was consistent in all subsequent follow-up periods. However, we need more high-quality RCTs for stronger evidence to be generalized.

The brain\'s extracellular matrix (ECM) regulates neuronal plasticity and animal behavior. ECM staining shows an aggregated pattern in a net-like structure around a subset of neurons and diffuse staining in the interstitial matrix. However, understanding the structural features of ECM deposition across various neuronal types and subcellular compartments remains limited. To visualize the organization pattern and assembly process of the hyaluronan-scaffolded ECM in the brain, we fused a HaloTag to HAPLN1, which links hyaluronan and proteoglycans. Expression or application of the probe enables us to identify spatial and temporal regulation of ECM deposition and heterogeneity in ECM aggregation among neuronal populations. Dual-color birthdating shows the ECM assembly process in culture and in vivo. Sparse expression in vivo reveals novel forms of ECM architecture around excitatory neurons and developmentally regulated dendritic ECM. Overall, our study uncovers extensive structural features of the brain\' ECM, suggesting diverse roles in regulating neuronal plasticity.

The perineuronal net (PNN) is a highly latticed extracellular matrix in the central nervous system, which is composed of hyaluronic acid, proteoglycan, hyaluronan and proteoglycan link protein (Hapln), and tenascin. PNN is predominantly distributed in GABAergic interneurons expressing Parvalbumin (PV) and plays a critical role in synaptic function, learning and memory, oxidative stress, and inflammation. In addition, PNN\'s structure and function are also modulated by a variety of factors, including protein tyrosine phosphatase σ (PTPσ), orthodenticle homeo-box 2 (Otx2), and erb-b2 receptor tyrosine kinase 4 (ErbB4). Glycosaminoglycan (GAG), a component of proteoglycan, also influences PNN through its sulfate mode. PNN undergoes abnormal changes during aging and in various neurological diseases, such as Alzheimer\'s disease, Parkinson\'s disease, schizophrenia, autism spectrum disorder, and multiple sclerosis. Nevertheless, there is limited report on the relationship between PNN and aging or age-related neurological diseases. This review elaborates on the mechanisms governing PNN regulation and summarizes how PNN abnormalities contribute to aging and neurological diseases, offering insights for potential treatments.

BACKGROUND: Endoscopic vidian neurectomy is expected to provide good therapeutic relief in patients with allergic rhinitis (AR) being refractory to medication therapy or conservative surgery. However, the evidence bases for its benefit remain debatable. In this study, we conducted a systematic review and meta-analysis to clarify the therapeutic role of various forms of vidian neurectomy in refractory AR.
METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct a systematic review of primary studies that reported original patient data for endoscopic vidian neurectomy (EVN) and vidian-branch neurectomy, which includes selective vidian neurectomy (SVN) and posterior nasal neurectomy (PNN). The primary outcome was patient-reported outcome measures (PROMs), including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Visual Analog Scale (VAS), to assess an improvement in nasal symptom severity and quality of patient\'s life. The incidence of surgical complications and other objective outcomes were considered secondary outcomes.
RESULTS: This review included 24 clinical studies involving 1677 patients with refractory AR, of which 510 patients in six studies had combined chronic rhinosinusitis with nasal polyps (CRSwNP) and 95 patients in one study had combined asthma. Postoperative PROMs were significantly better than preoperatively in almost all patients who underwent vidianp (RQLQ: standardized mean difference [SMD] = 2.66, 95% confidence interval [CI] = 2.40-2.92, p < 0.001; VAS: SMD = 5.15, 95% CI = 4.29-6.02, p < 0.001) or vidian-branch neurectomy (RQLQ in PNN: SMD = 3.29, 95% CI = 2.45-4.13, p < 0.001; VAS in PNN: SMD = 4.38, 95% CI = 3.41-5.34, p < 0.001), and were generally better than in the conservative treatment group. Dividing with 18 months as the cutoff point, a subgroup analysis of the follow-up period was conducted, and the results showed that both long-term and short-term postoperative patients had considerably reduced symptoms compared to the preoperative period. The two surgical procedures, SVN and PNN, attributed to vidian-branch neurectomy have extremely few complications. However, EVN is more likely to cause dry eyes and palatal numbness, with no other serious complications. In patients with AR and CRSwNP, vidian or selective vidian neurectomy combined with functional endoscopic sinus surgery (FESS) is more effective than conventional FESS (RQLQ: SMD = 2.17, 95% CI = 1.66-2.69, p < 0.001; VAS: SMD = 6.42, 95% CI = 4.78-8.06, p < 0.001). For patients who have both AR and asthma, SVN with pharyngeal branch excision is a potential treatment option.
CONCLUSIONS: EVN and vidian-branch neurectomy (including SVN and PNN) are effective treatments, but the former has a higher risk of complications. Additionally, vidian-branch neurectomy with FESS is beneficial for patients with mixed CRSwNP. SVN is a potential approach for patients with coexisting AR and asthma.

Electroconvulsive seizure therapy is often used in both treatment-resistant and geriatric depression. However, preclinical studies identifying targets of chronic electroconvulsive seizure (ECS) are predominantly focused on animal models in young adulthood. Given that putative transcriptional, neurogenic, and neuroplastic mechanisms implicated in the behavioral effects of chronic ECS themselves exhibit age-dependent modulation, it remains unknown whether the molecular and cellular targets of chronic ECS vary with age.
We subjected young adult (2-3 months) and middle-aged (12-13 months), male Sprague Dawley rats to sham or chronic ECS and assessed for despair-like behavior, hippocampal gene expression, hippocampal neurogenesis, and neuroplastic changes in the extracellular matrix, reelin, and perineuronal net numbers.
Chronic ECS reduced despair-like behavior at both ages, accompanied by overlapping and unique changes in activity-dependent and trophic factor gene expression. Although chronic ECS had a similar impact on quiescent neural progenitor numbers at both ages, the eventual increase in hippocampal progenitor proliferation was substantially higher in young adulthood. We noted a decline in reelin⁺ cell numbers following chronic ECS only in young adulthood. In contrast, an age-invariant, robust dissolution of perineuronal net numbers that encapsulate parvalbumin⁺ neurons in the hippocampus were observed following chronic ECS.
Our findings indicate that age is a key variable in determining the nature of chronic ECS-evoked molecular and cellular changes in the hippocampus. This raises the intriguing possibility that chronic ECS may recruit distinct, as well as overlapping, mechanisms to drive antidepressant-like behavioral changes in an age-dependent manner.

Prostate cancer (PCa) is the most common malignancy. New biomarkers are in demand to facilitate the management. The role of the pinin protein (encoded by PNN gene) in PCa has not been thoroughly explored yet. Using The Cancer Genome Atlas (TCGA-PCa) dataset validated with Gene Expression Omnibus (GEO) and protein expression data retrieved from the Human Protein Atlas, the prognostic and diagnostic values of PNN were studied. Highly co-expressed genes with PNN (HCEG) were constructed for pathway enrichment analysis and drug prediction. A prognostic signature based on methylation status using HCEG was constructed. Gene set enrichment analysis (GSEA) and the TISIDB database were utilised to analyse the associations between PNN and tumour-infiltrating immune cells. The upregulated PNN expression in PCa at both transcription and protein levels suggests its potential as an independent prognostic factor of PCa. Analyses of the PNN\'s co-expression network indicated that PNN plays a role in RNA splicing and spliceosomes. The prognostic methylation signature demonstrated good performance for progression-free survival. Finally, our results showed that the PNN gene was involved in splicing-related pathways in PCa and identified as a potential biomarker for PCa.

Modulation recognition is the indispensable part of signal interception analysis, which has always been the research hotspot in the field of radio communication. With the increasing complexity of the electromagnetic spectrum environment, interference in signal propagation becomes more and more serious. This paper proposes a modulation recognition scheme based on multimodal feature fusion, which attempts to improve the performance of modulation recognition under different channels. Firstly, different time- and frequency-domain features are extracted as the network input in the signal preprocessing stage. The residual shrinkage building unit with channel-wise thresholds (RSBU-CW) was used to construct deep convolutional neural networks to extract spatial features, which interact with time features extracted by LSTM in pairs to increase the diversity of the features. Finally, the PNN model was adapted to make the features extracted from the network cross-fused to enhance the complementarity between features. The simulation results indicated that the proposed scheme has better recognition performance than the existing feature fusion schemes, and it can also achieve good recognition performance in multipath fading channels. The test results of the public dataset, RadioML2018.01A, showed that recognition accuracy exceeds 95% when the signal-to-noise ratio (SNR) reaches 8dB.

What is the central question of this study? What is the role of pinin (PNN) in the malignant phenotype of colon adenocarcinoma cells and the underlying mechanism? What is the main finding and its importance? PNN mRNA can be stabilized and upregulated by methyltransferase like 3 (METTL3), which promotes glycolysis in colon adenocarcinoma and augments cell proliferation, migration and invasiveness. METTL3 and PNN might serve as potential targets for the treatment of colon adenocarcinoma.
Colon adenocarcinoma (COAD) is a fatal malignancy with high morbidity and mortality rates globally. Pinin (PNN), a desmosome associated protein, has been revealed as a tumour driver in several malignancies. This study aims to probe the expression and role of PNN in COAD and the underlying mechanism. PNN was expressed at high levels in clinically collected COAD tumours and was linked to poor prognosis of patients. Downregulation of PNN reduced glucose uptake, lactate production and ATP levels in COAD cells and suppressed cell proliferation, migration and invasiveness. Methyltransferase like 3 (METTL3) was positively associated with PNN levels in COAD tumour tissues. RNA immunoprecipitation and N6 -methyladenosine (m6 A) quantification assays indicated that METTL3 enhanced PNN mRNA stability and expression in COAD through m6 A modification with the involvement of the m6 A \'reader\' protein YT521-B homology domain family member 1. Downregulation of METTL3 reduced COAD cell glycolysis and proliferation in vitro and suppressed growth and metastasis of xenograft tumours in vivo, but further overexpression of PNN restored malignant behaviours of COAD cells and tumour growth. In summary, this study demonstrates that METTL3 promotes PNN mRNA stability and expression in COAD through m6 A modification, which augments glycolysis and proliferation of COAD cells and leads to the resultant tumour progression.

BACKGROUND: Nonallergic rhinitis (NAR) is characterized by rhinorrhea, nasal obstruction, and sneezing, in the absence of systemic sensitization to allergens. For cases refractory to medical therapy and conservative surgical interventions, more targeted procedures, such as endoscopic vidian neurectomy (EVN) and posterior nasal neurectomy (PNN), including surgical (SPNN) and cryoablative (CPNN) methods, may reduce symptoms of NAR.
OBJECTIVE: The purpose of this study was to compare the efficacy, side effect profile, and complication rate between EVN and PNN for NAR.
METHODS: A systematic review of primary articles that reported original patient data for either EVN or PNN was conducted using Embase, Medline, PubMed, and Cochrane databases since 2006, according to PRISMA guidelines. The primary outcome of the study was an improvement in NAR symptom severity. Secondary outcomes included the incidence of postoperative side effects or complications.
RESULTS: In total, 58 articles met the search criteria with a total of 9 studies (including 2 RCTs) eligible for inclusion. There was a pooled sample of 229 NAR patients that underwent EVN (n = 65; 28.4%), SPNN (n = 50; 21.8%), or CPNN (n = 114; 49.8%). For all 3 techniques, there was a statistically significant improvement in nasal symptoms, particularly rhinorrhea, nasal congestion, and obstruction along with quality of life. Heterogeneity in outcome reporting prevented meta-analysis and direct comparison of efficacy. The pooled incidence of postoperative complications for EVN (n = 65), SPNN (n = 50), and CPNN (n = 70) was 30.8% versus 0% versus 2.9% for dry eye, 16.9% versus 0% versus 1.4% for palatal/cheek numbness, and 0% versus 6% versus 4.3% for bleeding.
CONCLUSIONS: EVN, SPNN, and CPNN are similarly efficacious for patients with NAR refractory to medical management. SPNN and CPNN are associated with lower rates of complications (dry eye and palatal/cheek numbness) compared with EVN.