Biomechanical stress regulates mammalian tooth replacement via the integrin ß1-RUNX2-Wnt pathway.

Renewal of integumentary organs occurs cyclically throughout an organism's lifetime, but the mechanism that initiates each cycle remains largely unknown. In a miniature pig model of tooth development that resembles tooth development in humans, the permanent tooth did not begin transitioning from the resting to the initiation stage until the deciduous tooth began to erupt. This eruption released the accumulated mechanical stress inside the mandible. Mechanical stress prevented permanent tooth development by regulating expression and activity of the integrin ß1-ERK1-RUNX2 axis in the surrounding mesenchyme. We observed similar molecular expression patterns in human tooth germs. Importantly, the release of biomechanical stress induced downregulation of RUNX2-wingless/integrated (Wnt) signaling in the mesenchyme between the deciduous and permanent tooth and upregulation of Wnt signaling in the epithelium of the permanent tooth, triggering initiation of its development. Consequently, our findings identified biomechanical stress-associated Wnt modulation as a critical initiator of organ renewal, possibly shedding light on the mechanisms of integumentary organ regeneration.

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.

Low-acidity ALUMINUM-DEPENDENT MALATE TRANSPORTER4 genotype determines malate content in cultivated jujube.

Jujube (Ziziphus jujuba Mill.), the most economically important fruit tree in Rhamnaceae, was domesticated from sour jujube (Z. jujuba Mill. var. spinosa (Bunge) Hu ex H.F.Chow.). During domestication, fruit sweetness increased and acidity decreased. Reduction in organic acid content is crucial for the increase in sweetness of jujube fruit. In this study, the determination of malate content among 46 sour jujube and 35 cultivated jujube accessions revealed that malate content varied widely in sour jujube (0.90-13.31 mg g-1) but to a lesser extent in cultivated jujube (0.33-2.81 mg g-1). Transcriptome sequencing analysis showed that the expression level of Aluminum-Dependent Malate Transporter 4 (ZjALMT4) was substantially higher in sour jujube than in jujube. Correlation analysis of mRNA abundance and fruit malate content and transient gene overexpression showed that ZjALMT4 participates in malate accumulation. Further sequencing analyses revealed that three genotypes of the W-box in the promoter of ZjALMT4 in sour jujube associated with malate content were detected, and the genotype associated with low malate content was fixed in jujube. Yeast one-hybrid screening showed that ZjWRKY7 binds to the W-box region of the high-acidity genotype in sour jujube, whereas the binding ability was weakened in jujube. Transient dual-luciferase and overexpression analyses showed that ZjWRKY7 directly binds to the promoter of ZjALMT4, activating its transcription, and thereby promoting malate accumulation. These findings provide insights into the mechanism by which ZjALMT4 modulates malate accumulation in sour jujube and jujube. The results are of theoretical and practical importance for the exploitation and domestication of germplasm resources.

Propagation effects in polarization-gated attosecond soft-X-ray pulse generation.

Accurate estimation of the duration of soft-x-ray pulses from high-harmonic generation (HHG) remains challenging given their higher photon energies and broad spectral bandwidth. The carrier-envelope-phase (CEP) dependence of generated soft-x-ray spectra is indicative of attosecond pulse generation, but advanced simulations are needed to infer the pulse duration from such data. Here, we employ macroscopic propagation simulations to reproduce experimental polarization-gated CEP-dependent soft-x-ray spectra. The simulations indicate chirped pulses, which we theoretically find to be compressible in hydrogen plasmas, suggesting this as a viable compression scheme for broadband soft-x-rays from HHG.

Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study.

BACKGROUND: Diminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols. METHODS: A total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors. RESULTS: There were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted ß = 0.538 (0.221-0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted ß = 0.277 (0.031-0.523)] and transferable embryos [1.22 vs. 0.95, adjusted ß = 0.162 (-0.005-0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR. CONCLUSIONS: Dual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.

Risk factors for preoperative frailty in older patients with gastric cancer: a systematic review and meta-analysis.

PURPOSE: To summarize the available evidence on risk factors for preoperative frailty in older gastric cancer patients. METHODS: We comprehensively searched the CNKI, Wanfang, VIP, CBM, PubMed, Embase, The Cochrane Library, Web of Science, and CINAHL databases for preoperative articles on risk factors for frailty in older gastric cancer patients. The search was conducted from the time of construction of the library to January 27, 2024, with no language restrictions. The quality of the included studies was rated by the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality tool. RESULTS: A total of 20 studies were included, including 16 cohort studies and 4 cross-sectional studies, with a total sample size of 51,717 individuals. The results of the meta-analysis showed that age, albumin, hemoglobin, cancer stage III-IV, Charlson Comorbidity Index score ≥ 3, Eastern Cooperative Oncology Group score > 2, American Society of Anesthesiologists score > 2, smoking, nutritional risk, high school degree or above, and sleep disorders are the main influencing factors for the occurrence of preoperative frailty in older gastric cancer patients. Among them, high school degree or above was a protective factor. CONCLUSIONS: Our study provides valid evidence of risk factors for preoperative frailty in older patients with gastric cancer and informs clinical healthcare professionals to make targeted interventions.

Quality of working life and adaptability of returning to work in nurse cancer survivors: a cross-sectional study.

OBJECTIVE: To explore the relationship between quality of working life (QWL) and adaptability of returning to work (RTW) among nurse cancer survivors (NCSs). METHOD: We conducted a cross-sectional study on nurses previously diagnosed with cancer. QWL was quantified using the Quality of Working Life Scale (QWL7-32), and the level of RTW adaptability was assessed using the Adaptability of Returning to Work for Cancer Survivors (ARTW-CS) scale. Multiple linear regression analysis was used to control for confounding factors, and a simple effect analysis was performed on the interaction term. RESULTS: After controlling for sociodemographic, work-related, and health-related factors, the findings indicated a significant correlation between "adaptation and planning" and QWL score (p < 0.05). Further analysis revealed that "RTW gradualness" and "support seeking" had an interaction effect (p = 0.021). The simple effect analysis demonstrated that when the "RTW gradualness" score was ≥ 16 points, nurses with a high "support seeking" score (≥ 7 points) exhibited a significantly better QWL than those with a low "support seeking" score (< 7 points) (p < 0.001). CONCLUSION: The interaction between "RTW gradualness" and "support seeking" in the ARTW-CS scale significantly impacted the QWL of the NCSs, underscoring the importance of implementing a gradual career plan and seeking support to enhance QWL.

Translation, cultural adaptation, and validation of the Chinese standardized outcomes in nephrology-hemodialysis fatigue (C-SONG-HD fatigue) scale: a study of Chinese patients undergoing hemodialysis.

OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.

Rapamycin alleviates irradiation-induced parotid injury by enhancing the whole gland homeostasis.

OBJECTIVES: Salivary gland injury is one of the most common complications of radiotherapy in head-and-neck cancers. This study investigated the mechanism by which rapamycin prevents irradiation (IR)-induced injury in the parotid glands. MATERIALS AND METHODS: Miniature pigs either received (a) no treatment (NT), (b) IR in the right parotid gland for 5 consecutive days (IR), or intraperitoneal administration of rapamycin (Rap) 1 h prior to IR (IR + Rap). Tissues were collected at three distinct time points (24 h, 4 weeks, and 16 weeks) after IR. Histological analyses, western blot, and real-time reverse transcriptase-polymerase chain reaction were performed to explore the mechanisms of IR-induced injury in the parotid gland. RESULTS: Rapamycin treatment maintained parotid salivary flow 16 weeks post-IR, preserved the number of acinar cells, and reduced parotid tissue fibrosis, as well as reduced apoptosis levels, decreased cleaved caspase-3 expression, and increased the Bcl-2/Bax ratio in the parotid glands. Autophagy marker LC3B was upregulated by rapamycin after IR, while P62 expression was downregulated. Rapamycin reduced the expression of pro-inflammatory factors and the mesenchymal tissue fibrosis following IR. CONCLUSIONS: Rapamycin maintains gland homeostasis after IR by decreasing apoptosis, reducing the expression of pro-inflammatory factors, and enhancing autophagy.

AKT from dental epithelium to papilla promotes odontoblast differentiation.

Epithelial-mesenchymal interactions occur during tooth development. The dental epithelium (DE) is regarded as the signal center that regulates tooth morphology. However, the mechanism by which DE regulates the differentiation of mesenchyme-derived dental papilla (DP) into odontoblasts remains unclear. Using miniature pigs as a model, we analyzed the expression profiles of the DE and DP during odontoblast differentiation using high-throughput RNA sequencing. The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is one of the most enriched pathways in both DE and DP. The PI3K/AKT pathway was first activated in the inner enamel epithelium but not in the DP on embryonic day 50. This pathway was then activated in the odontoblast layer on embryonic day 60. We showed that AKT activation promoted odontoblast differentiation of DP cells. We further demonstrated that activation of PI3K/AKT signaling in the DE effectively increased the expression levels of AKT and dentin sialophosphoprotein in DP cells. Additionally, we found that DE cells secreted collagen type IV alpha 6 chain (COL4A6) downstream of epithelial AKT signaling to positively regulate mesenchymal AKT levels. Therefore, our data suggest that PI3K/AKT signaling from the DE to the DP promotes odontoblast differentiation via COL4A6 secretion.

Analysis of Distribution of Intracranial and Extracranial Atherosclerotic Lesions and Risk Factors for Recurrence in First-Ever and Recurrent Ischemic Stroke Patients in Northeast China.

Objective: The purpose of this study is to analyze the distribution characteristics of atherosclerotic lesions and the risk factors of recurrence in patients with ischemic stroke. Methods: A total of 505 patients diagnosed with ischemic stroke from October 2016 to October 2022 were included. Divide 505 patients with ischemic stroke into old stroke group and new stroke group. Patients without old cerebral infarction were included in the first ischemic stroke group (first group), while patients with old cerebral infarction were included in the recurrent ischemic stroke group (recurrence group).Carotid artery color Doppler ultrasonography and transcranial Doppler ultrasonography were performed on all patients. Results: We compared the distribution and risk factors of atherosclerotic lesions between the first and recurrent groups (378 cases) (127 cases). Mild, moderate, and severe stenosis of the middle cerebral artery (MCA) and occlusion of the intracranial vertebral artery (VA) were the most common in both groups. Intracranial artery stenosis is significantly higher than extracranial artery stenosis, and the anterior circulation artery is more affected than the posterior circulation artery. In the initial and recurrent groups, the proportion of patients with intracranial artery stenosis was significantly higher than that of patients with extracranial artery stenosis (43.4% vs. 22.5% and 53.4% vs. 22.5%), and the number of patients with anterior circulation stenosis was higher than that of other groups. Compared with the first group, the recurrence group had a higher incidence of hypertension, dyslipidemia, and insufficient physical exercise. There is a significant difference in the levels of triglycerides (TG) and platelets (PLT) between the two groups in biochemical indicators. In the first group, infarction was most common in 284 cases (75.1%) of the frontal lobe, followed by 232 cases (61.4%) of the basal ganglia, and 147 cases (38.9%) of the parietal lobe. In the recurrence group, the proportion of frontal lobe infarction [284 (74.0%)], basal ganglia infarction [232 (70.1%)], and parietal lobe infarction [147 (37.0%)] was the highest. It can be observed that the recurrence group had a higher incidence of basal ganglia infarction (70.1% vs. 61.4%), but a lower incidence of occipital lobe infarction (0.8% vs. 4.2%). Conclusions: Our study found no significant difference in the distribution of intracranial and extracranial atherosclerotic lesions between first-ever and recurrent ischemic stroke patients in China. Notably, hypertension, years of dyslipidemia, insufficient physical exercise, elevated triglyceride (TG) levels, and increased platelet (PLT) counts were identified as significant risk factors for stroke recurrence. These findings may have implications for the management and prevention of recurrent ischemic strokes in clinical practice.

Effects of coffee and tea on postprandial cardiometabolic risk factors in healthy individuals: a randomized crossover trial.

BACKGROUND AND OBJECTIVES: The effect of different coffee and tea consumption on postprandial glucose and lipid metabolism has never been reported previously. The aim of the present study was to investigate the effect of different coffee or tea consumption at breakfast on postprandial cardiometabolic risk factors in healthy individuals. METHODS AND STUDY DESIGN: Eighteen healthy young subjects completed the trial. After 8-hour overnight fast, volunteers either ingested water, freeze-dried coffee, spray-dried coffee, green tea, black tea or oolong tea together with a breakfast consisting of an egg and 180g deep-fried dough sticks. Blood was drawn at 0h, 0.5h, 1h, 2h, and 3h. RESULTS: The differences in triglyceride (TG) values relative to the baseline levels at 2h and 3h of green tea was significantly decreased compared with black tea and oolong tea (p<0.05). Compared with black tea, green tea and oolong tea significantly reduced postprandial total cholesterol (TC) levels (p<0.05, p<0.01), respectively. Furthermore, the serum concentrations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were substantially decreased after oolong tea consumption compared with black tea (p<0.05, p<0.01). CONCLUSIONS: Green tea ingestion can lower the elevation of serum TG and TC levels after high-fat or high-cholesterol diets. Our findings have far-reaching implications given the widespread use of coffee and tea and the current concern over cardiometabolic risk factors.

Efficacy of auricular acupressure on lung function among chronic obstructive pulmonary disease: A meta-analysis of randomised controlled trials.

OBJECTIVES: To systematically evaluate the efficacy of auricular acupressure on lung function, sleep quality and quality of life in chronic obstructive pulmonary disease patients. BACKGROUND: Auricular acupressure has been increasingly used in chronic obstructive pulmonary disease patients, such as lung function and sleep quality, but the efficacy has not yet been unified. DESIGN: A meta-analysis of randomised controlled trials. METHODS: Randomised controlled trials comparing auricular acupressure intervention with non-auricular acupressure intervention in chronic obstructive pulmonary disease patients were included. We searched English databases and Chinese databases from the inception to 26 December 2022. The risk of bias was assessed by the Cochrane risk of bias tool. The PRISMA statement was used to report a meta-analysis. RESULTS: A total of 12 randomised controlled trials with 987 chronic obstructive pulmonary disease patients were included. The meta-analysis showed that auricular acupressure had significant differences in improving lung function, including FEV1 (MD = 0.29, 95% CI: 0.21 to 0.37, p < .0001), FVC (MD = 0.24, 95% CI: 0.14 to 0.34, p < .0001) and FEV1/FVC (MD = 4.70, 95% CI: 3.63 to 5.78, p < .0001). There was also a positive effect on sleep quality (MD = -0.71, 95% CI: -0.89 to -0.53, p < .0001) and quality of life (MD = -3.20, 95% CI: -3.92 to -2.49, p < .0001). CONCLUSIONS: The results indicated auricular acupressure had a positive efficacy in chronic obstructive pulmonary disease patients to improve lung function, sleep quality and quality of life, but these results should be treated with caution due to the low quality of included studies. Future researchers need to conduct more high-quality randomised controlled trials to provide a solid basis to demonstrate the efficacy of auricular acupressure in chronic obstructive pulmonary disease patients. RELEVANT TO CLINICAL PRACTICE: Auricular acupressure has the advantages of being non-invasive, convenient and without significant side effects. This review suggested auricular acupressure could be considered a non-pharmacological intervention for patients. Clinical nurses can teach chronic obstructive pulmonary disease patients to perform auricular acupressure to help self-manage complications. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Alterations in CX3CL1 Levels and Its Role in Viral Pathogenesis.

CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases.

Efficient Integration of Rate-Adaptive Reconciliation with Syndrome-Based Error Estimation and Subblock Confirmation for Quantum Key Distribution.

An effective post-processing algorithm is essential for achieving high rates of secret key generation in quantum key distribution. This work introduces an approach to quantum key distribution post-processing by integrating the three main steps into a unified procedure: syndrome-based error estimation, rate-adaptive reconciliation, and subblock confirmation. The proposed scheme employs low-density parity-check codes to estimate the quantum bit error rate using the syndrome information, and to optimize the channel coding rates based on the Slepian-Wolf coding scheme for the rate-adaptive method. Additionally, this scheme incorporates polynomial-based hash verification in the subblock confirmation process. The numerical results show that the syndrome-based estimation significantly enhances the accuracy and consistency of the estimated quantum bit error rate, enabling effective code rate optimization for rate-adaptive reconciliation. The unified approach, which integrates rate-adaptive reconciliation with syndrome-based estimation and subblock confirmation, exhibits superior efficiency, minimizes practical information leakage, reduces communication rounds, and guarantees convergence to the identical key. Furthermore, the simulations indicate that the secret key throughput of this approach achieves the theoretical limit in the context of a BB84 quantum key distribution system.

Meta-analysis of peripheral blood eosinophils in clinical testing of chronic obstructive pulmonary disease patients.

Introduction: Meta-analysis was used to investigate the relationship between peripheral blood eosinophil (EOS) levels, clinical characteristics, and prognosis in chronic obstructive pulmonary disease (COPD)patients in previous literature. Aim: To analyse the correlation between peripheral blood EOS levels and clinical characteristics and prognosis of patients with COPD using meta-analysis. Material and methods: In databases such as PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wan Fang Data, literature related to the clinical characteristics or prognosis of COPD patients with high-level EOS published before July 2023 was searched for meta-analysis. Results: Through computer search and screening, 29 articles were ultimately included. The meta-analysis results showed that compared to conventional EOS levels, COPD patients with high EOS levels had a lower proportion of GOLD III-IV grade patients (OR = 00.78, 95% CI (0.68, 0.88), p < 0.001), lower CAT scores (OR = -1.01, 95% CI (-1.75, -0.28), p = 0.007), shorter hospital stay (OR = -1.33, 95% CI (-1.52, -1.14), p < 0.001), and lower mortality rate (OR = 0.53, 95% CI (0.42, 0.66), p < 0.001). The readmission rate was low (OR = 0.40, 95% CI (0.33, 0.48), p < 0.001), and there was no statistically significant difference in FEV1%pred (OR = -0.55, 95% CI (-1.33, 0.23), p = 0.17), higher FEV1/FVC values (OR = -0.45, 95% CI (-1.08, 0.18), p = 0.160), and mechanical ventilation usage rate (OR = 0.89, 95% CI (0.65, 1.21), p = 0.450) among COPD patients with different EOS levels. Conclusions: The levels of peripheral blood EOS in COPD patients are related to lung function, respiratory symptoms, etc.; Moreover, COPD patients with high-level EOS have shorter hospital stays, lower mortality and readmission rates. Therefore, ESO can be used as an auxiliary indicator for clinical symptom diagnosis of COPD patients and as an auxiliary indicator for predicting prognosis.

Anti-inflammatory effects of steroidal alkaloids of Solanum lyratum Thunb.

Solanum lyratum Thunb., a traditional Chinese herbal medicine, has a promising background. However, the anti-inflammatory effects of its component steroid alkaloid have not been explored. In this study, animal and cell experiments were performed to investigate the anti-inflammatory effects and mechanism of action of Solanum lyratum Thunb steroid alkaloid (SLTSA), in order to provide evidence for its potential utilization. SLTSA effectively inhibited ear swelling and acute abdominal inflammation of mice. We observed concentration-dependent inhibition of pro-inflammatory cytokines by SLTSA, as confirmed by the ELISA and RT-qPCR results. Flow cytometry, immunofluorescence and RT-qPCR analyses revealed that SLTSA suppressed TLR4 expression. Western blot results indicated that SLTSA inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway. Our study demonstrated that SLTSA possesses anti-inflammatory properties.

HTNV infection induces activation and deficiency of CD8+MAIT cells in HFRS patients.

Hantaan virus (HTNV) infection causes an epidemic of hemorrhagic fever with renal syndrome (HFRS) mainly in Asia. Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes known to play an important role in innate host defense during virus infection. However, their roles and phenotypes during HTNV infection have not yet been explored. We characterized CD8+MAIT cells from HFRS patients based on scRNA-seq data combined with flow cytometry data. We showed that HTNV infection caused the loss and activation of CD8+MAIT cells in the peripheral blood, which were correlated with disease severity. The production of granzyme B and IFN-γ from CD8+MAIT cells and the limitation of HTNV replication in endothelia cells indicated the anti-viral property of CD8+MAIT cells. In addition, in vitro infection of MAIT cells by HTNV or HTNV-exposed monocytes showed that the activation of MAIT cells was IL-18 mediated. In conclusion, this study identified, for the first time, gene expression profiles of MAIT cells, provided underlying molecular mechanisms for activation of MAIT cells during HTNV infection, and suggested a potential anti-viral role of MAIT cells in HFRS.

LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network.

BACKGROUND: Extracellular vesicles (EVs) transport biologically active molecules, and represent a recently identified way of intercellular communication. Recent evidence has also reported that EVs shed by cancer stem cells (CSCs) make a significant contribution to carcinogenesis and metastasis. Here, this study aims to explore the possible molecular mechanism of CSCs-EVs in gastric cancer (GC) by mediating intratumor communication network. METHODS: CSCs and non-stem cancer cells (NSCCs) were sorted from GC cells, and EVs were isolated from CSCs. H19 was knocked down in CSCs, and CSCs-EVs or CSCs-EVs containing shRNA-H19 (CSCs-EVs-sh-H19) were co-cultured with NSCCs, followed by evaluation of the malignant behaviors and stemness of NSCCs. Mouse models of GC were established and injected with CSCs-EVs from sh-H19-treated NSCCs in vivo. RESULTS: CSCs had notable self-renewal and tumorigenic capacity compared with NSCCs. CSCs promoted the malignant behaviors of NSCCs and expression of stemness marker proteins through secretion of EVs. Inhibited secretion of CSCs-EVs curtailed the tumorigenicity and metastasis of NSCCs in vivo. H19 could be delivered by CSCs-EVs into NSCCs. H19 promoted the malignant behaviors of NSCCs and stemness marker protein expression in vitro along with tumorigenicity and liver metastasis in vivo, which was mechanistically associated with activation of the YAP/CDX2 signaling axis. CONCLUSION: Taken together, the present study points to the importance of a novel regulatory axis H19/YAP/CDX2 in carcinogenic and metastatic potential of CSCs-EVs in GC, which may be potential targets for anticancer therapy.

Transcription factor LHX9 (LIM Homeobox 9) enhances pyruvate kinase PKM2 activity to induce glycolytic metabolic reprogramming in cancer stem cells, promoting gastric cancer progression.

BACKGROUND: Glycolytic metabolic reprogramming is a phenomenon in which cells undergo altered metabolic patterns during malignant transformation, mainly involving various aspects of glycolysis, electron transport chain, oxidative phosphorylation, and pentose phosphate pathway. This reprogramming phenomenon can be used as one of the markers of tumorigenesis and development. Pyruvate kinase is the third rate-limiting enzyme in the sugar metabolism process by specifically catalyzing the irreversible conversion of PEP to pyruvate. PURPOSE: This study aimed to reveal the critical mediator(s) that regulate glycolytic metabolism reprogramming in gastric cancer and their underlying molecular mechanism and then explore the molecular mechanisms by which LHX9 may be involved in regulating gastric cancer (GC) progression. METHODS: Firstly, we downloaded the GC and glycolysis-related microarray datasets from TCGA and MSigDB databases and took the intersection to screen out the transcription factor LHX9 that regulates GC glycolytic metabolic reprogramming. Software packages were used for differential analysis, single gene predictive analysis, and Venn diagram. In addition, an enrichment analysis of the glycolytic pathway was performed. Immunohistochemical staining was performed for LHX9 and PKM2 protein expression in 90 GC patients, and the association between their expressions was evaluated by Spearman's correlation coefficient method. Three human GC cell lines (AGS, NCI-N87, HGC-27) were selected for in vitro experimental validation. Flow cytometry was utilized to determine the stem cell marker CD44 expression status in GCSCs. A sphere formation assay was performed to evaluate the sphere-forming capabilities of GCSCs. In addition, RT-qPCR and Western blot experiments were employed to investigate the tumor stem cell markers OCT4 and SOX2 expression levels in GCSCs. Furthermore, a lentiviral expression vector was constructed to assess the impact of downregulating LHX9 or PKM2 on the glycolytic metabolic reprogramming of GCSCs. The proliferation, migration, and invasion of GCSCs were then detected by CCK-8, EdU, and Transwell assays. Subsequently, the mutual binding of LHX9 and PKM2 was verified using chromatin immunoprecipitation and dual luciferase reporter genes. In vivo experiments were verified by establishing a subcutaneous transplantation tumor model in nude mice, observing the size and volume of tumors in vivo in nude mice, and obtaining fresh tissues for subsequent experiments. RESULTS: Bioinformatics analysis revealed that LHX9 might be involved in the occurrence and development of GC through regulating glycolytic metabolism. High LHX9 expression could be used as a reference marker for prognosis prediction of GC patients. Clinical tissue assays revealed that LHX9 and PKM2 were highly expressed in GC tissues. Meanwhile, GC tissues also highly expressed glycolysis-associated protein GLUT1 and tumor cell stemness marker CD44. In vitro cellular assays showed that LHX9 could enhance its activity and induce glycolytic metabolic reprogramming in GCSCs through direct binding to PKM2. In addition, the knockdown of LHX9 inhibited PKM2 activity and glycolytic metabolic reprogramming and suppressed the proliferation, migration, and invasive ability of GCSCs. In vivo animal experiments further confirmed that the knockdown of LHX9 could reduce the tumorigenic ability of GCSCs in nude mice by inhibiting PKM2 activity and glycolytic metabolic reprogramming. CONCLUSION: The findings suggest that both LHX9 and PKM2 are highly expressed in GCs, and LHX9 may induce the reprogramming of glycolytic metabolism through transcriptional activation of PKM2, enhancing the malignant biological properties of GCSCs and ultimately promoting GC progression.