Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion.

The association of p120 catenin (p120) with the juxtamembrane domain (JMD) of the cadherin cytoplasmic tail is critical for the surface stability of cadherin-catenin cell-cell adhesion complexes. Here, we present the crystal structure of p120 isoform 4A in complex with the JMD core region (JMD(core)) of E-cadherin. The p120 armadillo repeat domain contains modular binding pockets that are complementary to electrostatic and hydrophobic properties of the JMD(core). Single-residue mutations within the JMD(core)-binding site of p120 abolished its interaction with E- and N-cadherins in vitro and in cultured cells. These mutations of p120 enabled us to clearly differentiate between N-cadherin-dependent and -independent steps of neuronal dendritic spine morphogenesis crucial for synapse development. NMR studies revealed that p120 regulates the stability of cadherin-mediated cell-cell adhesion by associating with the majority of the JMD, including residues implicated in clathrin-mediated endocytosis and Hakai-dependent ubiquitination of E-cadherin, through its discrete "dynamic" and "static" binding sites.

Advances in experimental models of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent articular inflammation and joint damage. RA was first described over 200 years ago; however, its etiology and pathophysiology remain insufficiently understood. The current treatment of RA is mainly empirical or based on the current understanding of etiology with limited efficacy and/or substantial side effects. Thus, the development of safer and more potent therapeutics, validated and optimized in experimental models, is urgently required. To improve the transition from bench to bedside, researchers must carefully select the appropriate experimental models as well as draw the right conclusions. Here, we summarize the establishment, pathological features, potential mechanisms, advantages, and limitations of the currently available RA models. The aim of the review is to help researchers better understand available RA models; discuss future trends in RA model development, which can help highlight new translational and human-based avenues in RA research.

Molecular determinants of olfactory receptor activation: Comparative analysis of Olfr205 and Olfr740 family member responses to indole.

Indole is widely present in nature and contributes significantly to the smell of flowers and animal excretion. However, the odor perception mechanism for indole is unclear, despite previous reports suggesting that it activates the Olfr740 family of receptors. In this study, we successfully identified another receptor, Olfr205, that is responsive to indole. Molecular model construction and binding pocket analysis predicted that the A202 residue in transmembrane helix 5 of Olfr205 forms a crucial hydrogen bond with indole, facilitating receptor activation. Additionally, G112 in transmembrane helix 3 of the Olfr740 family is involved in indole activation of receptors. Finally, our mutant function assay showed that substitution of A202 in Olfr205 and G112 in Olfr740 with other amino acids significantly decreased the receptor response to indole, which provides robust evidence to confirm the docking results. In summary, our study is the first to reveal that Olfr205 is an olfactory receptor distinct from those in the Olfr740 family that is activated by indole. Moreover, these receptors display different indole-binding mechanisms. This study sheds light on molecular binding mechanisms and contributes to a deeper understanding of indole perception.

Unsymmetrical Benzothieno-Fused BODIPYs as Efficient NIR Heavy-Atom-Free Photosensitizers.

Heavy-atom-free photosensitizers are potentially suitable for use in photodynamic therapy (PDT). In this contribution, a new family of unsymmetrical benzothieno-fused BODIPYs with reactive oxygen efficiency up to 50% in air-saturated toluene was reported. Their efficient intersystem crossing (ISC) resulted in the generation of both 1O2 and O2-• under irradiation. More importantly, the PDT efficacy of a respective 4-methoxystyryl-modified benzothieno-fused BODIPY in living cells exhibited an extremely high phototoxicity with an ultralow IC50 value of 2.78 nM. The results revealed that the incorporation of an electron-donating group at the α-position of the unsymmetrical benzothieno-fused BODIPY platform might be an effective approach for developing long-wavelength absorbing heavy-atom-free photosensitizers for precision cancer therapy.

Protection of schisantherin A against dictamnine-induced hepatotoxicity: Pharmacokinetic insights.

Dictamnine (DIC), as the most abundant furoquinoline alkaloid ingredient of the herbal medicine Cortex Dictamni (CD), can induce severe liver injury. A previous study found that DIC-induced liver injury was initiated by cytochrome P4503A (CYP3A)-mediated metabolic activation and subsequent formation of adducts with cellular proteins. Schisantherin A (SchA) is the major lignan component of the herbal medicine Schisandra chinensis (SC). SC is frequently combined with CD used in numerous Chinese medicinal formulas for the treatment of eczema and urticaria. Furthermore, SC could protect against CD-induced hepatotoxicity. The objective of the study was to investigate the protective effect of SchA on DIC-induced hepatotoxicity based on pharmacokinetic interactions. The studies found that SchA exerted a protective effect on DIC-induced hepatotoxicity in a dose-dependent manner. Pharmacokinetic studies showed that pretreatment with SchA enhanced the area under concentration-time curve (AUC) and maximal concentration (Cmax ) values of DIC in the serum and liver tissue of mice, indicating that SchA could augment the accumulation of DIC in the circulation. In vitro metabolism assays with mouse liver microsomes (MLMs) showed that SchA reduced the production of DIC-glutathione (GSH) conjugate. In addition, SchA significantly reduced the excretion of DIC-GSH conjugate in the urine of mice and relieved hepatic GSH depletion induced by DIC. These results suggested that SchA could inhibit the metabolic activation of DIC in vitro and in vivo. In summary, our findings showed that the observed pharmacokinetic interactions might be attributable to the inhibition of the metabolism of DIC by SchA, which might be responsible for the protection of SchA against DIC-induced hepatotoxicity. Therefore, the development of a standardized combination of DIC and SchA may protect patients from DIC-induced liver injury.

Laparoscopic treatment of a patient with multiple organ dysfunction syndrome induced by necrotising fasciitis.

Necrotising fasciitis (NF) is an uncommon surgical emergency that threatens the life and health of patients. We report the treatment of a 76-year-old female patient with NF. The patient developed NF due to chronic poor glycaemic control, which further progressed to multiple organ dysfunction syndrome due to the severity of the hyperglycaemia. After resuscitation at the intensive care unit, surgical treatment was recommended and the patient underwent laparoscopic surgery. She had an uneventful post-operative recovery with aggressive anti-inflammatory therapy, glycaemic control and systemic nutritional support. There were no recurrences during the next 6 months of follow-up. NF should be diagnosed and treated as early as possible to gain valuable treatment time for the patient. Laparoscopic surgery is a treatment option.

A feedback loop between NONHSAT024276 and PTBP1 inhibits tumor progression and glycolysis in HCC by increasing the PKM1/PKM2 ratio.

Hepatocellular carcinoma (HCC) is one of the most common malignancies with a hallmark of aberrant metabolism. The mechanism of long noncoding RNAs (lncRNAs) underlying the aggressive behaviors and glycolysis of HCC is poorly understood. In this study, we identified, via microarray, novel lncRNA NONHSAT024276 as a potential tumor suppressor in HCC. The downregulation of NONHSAT024276 closely correlated with larger tumor volume and higher aspartate transaminase levels. Functional experiments were performed to verify the role of NONHSAT024276 in HCC progression, and the negative effects of NONHSAT024276 expression on cell proliferation and migration were identified. Mechanistically, NONHSAT024276 directly bound to polypyrimidine tract-binding protein 1 (PTBP1), downregulating it and forming a feedback loop. Furthermore, NONHSAT024276 increased the ratio of M1 and M2 isoforms of pyruvate kinase (PKM1/PKM2) and also obstructed the PTBP1/PKM-mediated glycolysis. Finally, the rescue assays confirmed that NONHSAT024276 functioned in HCC via downregulating PTBP1 to increase the PKM1/PKM2 ratio. Hence, this study supported a model in which NONHSAT024276 downregulated PTBP1 and formed a feedback loop to increase the PKM1/PKM2 ratio to inhibit glycolysis and progression of HCC, opening new prospects for preventing or treating HCC.

The Efficacy and Frequency of Self-monitoring of Blood Glucose in Non-insulin-Treated T2D Patients: a Systematic Review and Meta-analysis.

BACKGROUND: Self-monitoring of blood glucose (SMBG) is a useful tool in diabetes management, but its efficacy and optimal application in type 2 diabetes (T2D) patients treated without insulin have been controversial. We aimed to evaluate the efficacy of SMBG in controlling blood glucose levels in non-insulin-treated T2D patients and to determine the optimal frequency and the most appropriate population to benefit from SMBG. METHODS: Eligible publications from January 2000 to April 2022 were retrieved from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. Randomized controlled trials comparing SMBG with no SMBG or structured SMBG (S-SMBG, SMBG with defined timing and frequency of glucose measurements) were included. Meta-analyses and sub-analyses were performed to assess the efficacy, optimal frequency, and most appropriate population for SMBG. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases. RESULTS: Twenty-two studies involving 6204 participants were identified, including 17 comparing SMBG with no SMBG and 4 comparing SMBG with S-SMBG. SMBG reduced HbA1c (MD -0.30%, 95% CI -0.42 to -0.17) compared with no SMBG, and S-SMBG performed better than SMBG (MD -0.23%, 95% CI -0.38 to -0.07). Subgroup analyses showed that HbA1c control was better with SMBG at 8-11 times weekly (MD -0.35%, 95% CI -0.51 to -0.20) compared with other frequencies and with lifestyle adjustments (MD -0.37%, 95% CI -0.50 to -0.23) than with no adjustments. No significant differences in HbA1c were observed between baseline HbA1c subgroups (≤ 8% and > 8%, P = 0.63) and between diabetes duration subgroups (≤ 6 years and > 6 years, P = 0.72), respectively. DISCUSSION: SMBG was effective for controlling HbA1c in non-insulin-treated T2D patients, although lacking detailed monitoring design. Better outcomes were seen with SMBG at 8-11 times weekly and lifestyle adjustment based on SMBG results. TRIAL REGISTRATION: PROSPERO (CRD42021285604).

Expression profiles of circular RNAs in spermatozoa from aging men.

BACKGROUND: Advanced paternal age (APA) is associated with decreased fertility, but the mechanism underlying APA remains unknown. CircRNAs have been reported to be ideal candidate biomarkers for diagnostic and therapeutic applications in many diseases and are also involved in spermatogenesis. Hence, we aimed to assess the circRNA expression profile of spermatozoa from aging men. METHODS AND RESULTS: We recruited 6 subjects, including 3 in the younger group (men age < 40) and 3 in the APA group (men age ≥ 40). RNA sequencing was exploited to identify the expression profiles of circRNAs between the two groups. The expression levels of circRNAs were validated using real-time quantitative polymerase chain reaction (RT-qPCR). Kyoto Encyclopedia of Genes and Genomes biological pathway analysis and Gene Ontology analysis were performed to evaluate the functions of differentially expressed circRNAs (DE-circRNAs) between the two groups. In total, 18,787 circRNAs were sequenced in the spermatozoa of two groups. Our analysis revealed that there were 1056 downregulated circRNAs and 1228 upregulated circRNAs between the two groups, and KEGG analysis showed they were mainly involved in pathways including the DNA repair signaling pathway, meiotic recombination signaling pathway, and PI3K/AKT signaling pathway. CONCLUSIONS: In conclusion, our study suggested that circRNAs play a vital role in spermatozoa from aging men and provided a fresh perspective on the specific regulatory mechanism of spermatozoa from aging men.

Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry.

Stromal interaction molecule-1 (STIM1) activates store-operated Ca2+ entry (SOCE) in response to diminished luminal Ca2+ levels. Here, we present the atomic structure of the Ca2+-sensing region of STIM1 consisting of the EF-hand and sterile alpha motif (SAM) domains (EF-SAM). The canonical EF-hand is paired with a previously unidentified EF-hand. Together, the EF-hand pair mediates mutually indispensable hydrophobic interactions between the EF-hand and SAM domains. Structurally critical mutations in the canonical EF-hand, "hidden" EF-hand, or SAM domain disrupt Ca2+ sensitivity in oligomerization via destabilization of the entire EF-SAM entity. In mammalian cells, EF-SAM destabilization mutations within full-length STIM1 induce punctae formation and activate SOCE independent of luminal Ca2+. We provide atomic resolution insight into the molecular basis for STIM1-mediated SOCE initiation and show that the folded/unfolded state of the Ca2+-sensing region of STIM is crucial to SOCE regulation.

Point-wise spatial network for identifying carcinoma at the upper digestive and respiratory tract.

PROBLEM: Artificial intelligence has been widely investigated for diagnosis and treatment strategy design, with some models proposed for detecting oral pharyngeal, nasopharyngeal, or laryngeal carcinoma. However, no comprehensive model has been established for these regions. AIM: Our hypothesis was that a common pattern in the cancerous appearance of these regions could be recognized and integrated into a single model, thus improving the efficacy of deep learning models. METHODS: We utilized a point-wise spatial attention network model to perform semantic segmentation in these regions. RESULTS: Our study demonstrated an excellent outcome, with an average mIoU of 86.3%, and an average pixel accuracy of 96.3%. CONCLUSION: The research confirmed that the mucosa of oral pharyngeal, nasopharyngeal, and laryngeal regions may share a common appearance, including the appearance of tumors, which can be recognized by a single artificial intelligence model. Therefore, a deep learning model could be constructed to effectively recognize these tumors.

Investigation, Analysis, and Management Application of Mental Resilience and Psychosomatic State of the Medical Team Against COVID-19.

Objective: In the initial stages of the COVID-19 epidemic, frontline medical staff faced numerous psychological pressures, such as shortages of medical supplies, lack of treatment experience, and high risk of infection. This study plans to understand the mental resilience and psychosomatic status of first-line anti-epidemic medical team members to provide a reference for managing their mental health status and the improvement of mental resilience. Methods: From March 3 to March 5, 2020 a medical team serving as a first-line medical rescue group in Wuhan was chosen as the research subject, with 160 cases. The staff status questionnaire and the Chinese Version of the mental resilience scale were used simultaneously in a mobile phone questionnaire survey on the selected subjects using a cluster sampling method, which refers to the sampling strategy considering an independent cluster as a unit. (Chinese Version of the CD-RISC). Results: The participants were frontline medical staff against COVID-19. A total of 156 samples were effective, with a 97.5% effective sample rate. The 156 cases investigated included 77 males (49.4%) and 79 females (51.6%), with an average age of 36.50±8.50. There were 22 (14.1%) cases with a junior college diploma or less, 97 (62.2%) cases with a bachelor's degree, and 37 (23.7%) cases with a master's degree or higher. Conversely, men were more tenacious than women (Cohen's d = 0.319, t = 1.997, P = .048). In terms of the psychosomatic state influence score, women had a greater psychosomatic influence than men (F = 3.076, P = .006). Conclusion: The anti-epidemic task significantly impacts the psychosomatic state of first-line medical personnel, who may require improved social and psychological support. Women experience more stress than men. Frontline medical personnel should seek social support and learn positive stress management techniques. When facing medical emergencies, medical decision-makers also need to pay attention to strengthening the psychosocial support of frontline personnel.

Auxin response factors (ARFs) differentially regulate rice antiviral immune response against rice dwarf virus.

There are 25 auxin response factors (ARFs) in the rice genome, which play critical roles in regulating myriad aspects of plant development, but their role (s) in host antiviral immune defense and the underneath mechanism remain largely unknown. By using the rice-rice dwarf virus (RDV) model system, here we report that auxin signaling enhances rice defense against RDV infection. In turn, RDV infection triggers increased auxin biosynthesis and accumulation in rice, and that treatment with exogenous auxin reduces OsIAA10 protein level, thereby unleashing a group of OsIAA10-interacting OsARFs to mediate downstream antiviral responses. Strikingly, our genetic data showed that loss-of-function mutants of osarf12 or osarf16 exhibit reduced resistance whereas osarf11 mutants display enhanced resistance to RDV. In turn, OsARF12 activates the down-stream OsWRKY13 expression through direct binding to its promoter, loss-of-function mutants of oswrky13 exhibit reduced resistance. These results demonstrated that OsARF 11, 12 and 16 differentially regulate rice antiviral defense. Together with our previous discovery that the viral P2 protein stabilizes OsIAA10 protein via thwarting its interaction with OsTIR1 to enhance viral infection and pathogenesis, our results reveal a novel auxin-IAA10-ARFs-mediated signaling mechanism employed by rice and RDV for defense and counter defense responses.

A fungal microRNA-like RNA subverts host immunity and facilitates pathogen infection by silencing two host receptor-like kinase genes.

Small RNAs (sRNAs) play important roles in various biological processes by silencing their corresponding target genes in most eukaryotes. However, cross-kingdom regulation mediated by fungal microRNA-like RNAs (milRNAs) in plant-pathogen interactions is still largely unknown. Using molecular, genetic, histological, and biochemical approaches, we found that the apple tree Valsa canker pathogen Valsa mali milRNA Vm-milR1 could suppress the host immunity by silencing two host receptor-like kinase genes, MdRLKT1 and MdRLKT2. Vm-milR1 was highly induced during V. mali infection. Deletion of Vm-milR1 precursor abolished the generation of Vm-milR1 and reduced the virulence of V. mali. Inoculation of Vm-milR1 deletion mutants induced the host defence responses, including reactive oxygen species (ROS) accumulation, callose deposition, and high expression of defence-related genes. Furthermore, Vm-milR1 was confirmed to be able to suppress the expression of MdRLKT1 and MdRLKT2 in a sequence-specific manner. Moreover, overexpression of either MdRLKT1 or MdRLKT2 enhanced apple resistance to V. mali by activating the host defence responses. Furthermore, knockdown of MdRLKT1 or MdRLKT2 compromised the host resistance to V. mali. Our study revealed that V. mali was equipped with Vm-milR1 as an sRNA effector to silence host receptor-like kinase genes, suppress the host defence responses, and facilitate pathogen infection.

Novel processing strategies to enhance the bioaccessibility and bioavailability of functional components in wheat bran.

Dietary fiber, polysaccharides and phenols are the representative functional components in wheat bran, which have important nutritional properties and pharmacological effects. However, the most functional components in wheat bran exist in bound form with low bioaccessibility. This paper reviews these functional components, analyzes modification methods, and focuses on novel solid-state fermentation (SSF) strategies in the release of functional components. Mining efficient microbial resources from traditional fermented foods, exploring the law of material exchange between cell populations, and building a stable self-regulation co-culture system are expected to strengthen the SSF process. In addition, emerging biotechnology such as synthetic biology and genome editing are used to transform the mixed fermentation system. Furthermore, combined with the emerging physical-field pretreatment coupled with SSF strategies applied to the modification of wheat bran, which provides a theoretical basis for the high-value utilization of wheat bran and the development of related functional foods and drugs.

Prognostic Role of DNA Damage Response Genes Mutations and their Association With the Sensitivity of Olaparib in Prostate Cancer Patients.

OBJECTIVE: Evidence shows that gene mutation is a significant proportion of genetic factors associated with prostate cancer. The DNA damage response (DDR) is a signal cascade network that aims to maintain genomic integrity in cells. This comprehensive study was performed to determine the link between different DNA damage response gene mutations and prostate cancer. MATERIALS AND METHODS: A systematic literature search was performed using PubMed, Web of Science, and Embase. Papers published up to February 1, 2022 were retrieved. The DDR gene mutations associated with prostate cancer were identified by referring to relevant research and review articles. Data of prostate cancer patients from multiple PCa cohorts were obtained from cBioPortal. The OR or HR and 95% CIs were calculated using both fixed-effects models (FEMs) and random-effects models (REMs). RESULTS: Seventy-four studies were included in this research, and the frequency of 13 DDR genes was examined. Through the analysis of 33 articles that focused on the risk estimates of DDR genes between normal people and PCa patients, DDR genes were found to be more common in prostate cancer patients (OR = 3.6293 95% CI [2.4992; 5.2705]). Also, patients in the mutated group had a worse OS and DFS outcome than those in the unmutated group (P < .05). Of the 13 DDR genes, the frequency of 9 DDR genes in prostate cancer was less than 1%, and despite differences in race, BRCA2 was the potential gene with the highest frequency (REM Frequency = .0400, 95% CI .0324 - .0541). The findings suggest that mutations in genes such as ATR, BLM, and MLH1 in PCa patients may increase the sensitivity of Olaparib, a PARP inhibitor. CONCLUSION: These results demonstrate that mutation in any DDR pathway results in a poor prognosis for PCa patients. Furthermore, mutations in ATR, BLM, and MLH1 or the expression of POLR2L, PMS1, FANCE, and other genes significantly influence Olaparib sensitivity, which may be underlying therapeutic targets in the future.

Irisin Protects Cerebral Neurons from Hypoxia/Reoxygenation via Suppression of Apoptosis and Expression of Pro-Inflammatory Cytokines.

BACKGROUND: Ischemic stroke is a major health issue that causes high incidents of morbidity and mortality worldwide. Irisin is an excise-induced protein that has exhibited pleiotropic properties. Accumulating evidence reveals its critical roles in the regulation of various cellular functions, including nervous system functions. This study aims to disclose the effect of irisin on rat cerebral neurons suffering from hypoxia/reoxygenation (H/R) treatment and to explore the potential underlying molecular mechanisms. METHODS: The percentage of rat cerebral neuron cell death was determined by flow cytometry analysis and MTT assay. The expression levels of target genes were measured by western blotting and real-time quantitative reverse transcription PCR assay. RESULTS: Our results demonstrated that irisin treatment substantially reduced H/R-induced apoptosis of rat cerebral neurons. Further investigation revealed that irisin treatment markedly decreased mitogen-activated protein kinase (MAPK) signaling pathway activation and suppressed pro-informatory cytokine expression in cerebral neurons with H/R challenge. Finally, we showed that the neuroprotective effect and anti-inflammatory effect of irisin were comparable with three MAPK signaling inhibitors. CONCLUSION: Irisin exerts profound neuroprotective and anti-inflammatory effects on H/R-stimulated cerebral neurons by inhibiting the MAPK signaling activation. Therefore, irisin may serve as a potential drug for the treatment of patients with ischemic stroke.

Reversible Controlling the Supramolecular Chirality of Side Chain Azobenzene Polymers: Chiral Induction and Modulation.

Chirality represents a fundamental structure in nature and the induction and reversible modulation of supramolecular chirality with feasible techniques is of great value in the design of new chiroptical smart materials. Herein, two kinds of azobenzene side-chain polymers (without spacer: Azo-PMA0; with 6 spacers: Azo-PMA6) are synthesized, the length of spacer and azobenzene chromophores play a vital role in chirality transfer and modulation. The supramolecular chiral arrangement of Azo-PMA0 (amorphous phase) can be completely controlled and reversibly modulated over multiple cycles by 450 nm circularly polarized light driven by the supramolecular interaction between azo groups of polymer chains, with an absorption dissymmetry factor (g) value of 0.0019. The chiroptical properties of Azo-PMA6 (liquid crystal state) can also be reversibly modulated by UV light and thermal annealing treatment during trans-cis isomerization of azo chromophore, with the g-value changes from 0-0.038. The successful construction of reversible chiral induction and modulation based on side chain azobenzene polymers may pave the way for designing photo-switchable functional materials.

Delayed Endoscopic Management of Esophageal Sharp-Pointed Food Impaction: An Analysis of 829 Cases in China.

BACKGROUND: Esophageal foreign body impaction is the most common cause of endoscopic emergency. However, there are limited available data on delayed endoscopic management of esophageal sharp-pointed food impaction. AIMS: To investigate cases of esophageal sharp-pointed food impaction with endoscopic removal findings. METHODS: This single-center retrospective study collected medical records to identify patients with esophageal sharp-pointed food impaction who underwent endoscopic removal between April 2018 and April 2020. The patients were divided into the early (endoscopic removal <12 h) and delayed intervention (>12 h) cohorts. RESULTS: Overall, 133 and 696 patients received early and delayed intervention, respectively. The success rate of endoscopic foreign body removal was 96.45%. The most common foreign body was fish bone (66.90%), and the most common shape was "I" (56.26%). Patients from the delayed intervention cohort received general anesthesia with a higher risk for perforation, and no foreign body was identified. The duration of endoscopy, distance between the foreign body/wound and the incisor, and longest diameter of the foreign body were not different between the groups. In multivariate analysis, male sex (odds ratio = 1.792 [1.159, 2.771]; P = 0.009), longer duration of impaction (odds ratio = 2.212 [1.121, 4.365]; P = 0.022) and endoscopy (odds ratio = 1.502 [1.253, 1.800]; P < 0.001), and longest diameter of the foreign body (odds ratio = 1.632 [1.329, 2.003]; P < 0.001) were associated with a higher incidence of perforation in patients with foreign body impaction. CONCLUSIONS: Endoscopic removal is a safe and effective treatment method for sharp-pointed food impaction. Delayed endoscopic removal can increase the risk of esophageal perforation.

Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL.

Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant diseases worldwide. LSCC patients suffer from a severe decline in life quality, due to the essential roles of the larynx in basic functions in the human body. The overarching goal of the present study is to explore whether exosome from M2 macrophages promotes LSCC by targeting glycolysis. In the current study, the expression of PDLIM2, an E3 ubiquitin ligase, in clinical samples was monitored by quantitative PCR and immunohistochemical examination. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by the Seahorse machine. Cell proliferation was measured by using Cell Counting Kit-8. A luciferase assay was performed to verify the regulation of miRNA on its target gene. The results showed that PDLIM2 exhibited downregulation in LSCC clinical samples and was associated with stage and differentiation of tumors in patients. In FaDu cell line, PDLIM2 inhibited cell proliferation and glycolysis but promoted the ubiquitination of PFKL. Exosomes from M2-type macrophages delivered miR-222-3p into LSCC cells to suppress PDLIM2 expression, leading to the elevated expression of PFKL and enhanced glycolysis which accelerated the proliferation of FaDu cells. The findings from cultured cells were supported by a subcutaneous tumor growth model in nude mice. Collectively, our data provided a snapshot of the miR-222-3p/PDLIM2/PFKL axis in LSCC tumorigenesis, and in concert with the importance of TAM exosomes and glycolysis, could be potentially translated to LSCC clinics.