Eight-year total, cognitive-affective, and somatic depressive symptoms trajectories and risks of cardiac events.

In this study, we analyzed pooled data from two prospective population-based cohorts-the Health Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA)-to explore the association between trajectories of depressive symptoms and the risk of cardiac events. Depressive symptoms were assessed using the 8-item CES-D scale and categorized into somatic and cognitive-affective subtypes. Trajectories were tracked for four surveys from baseline. Heart disease was identified based on self-reported physician-diagnosed conditions. Hazard ratios and 95% confidence intervals were calculated with Cox proportional risk models that adjusted for potential confounders. In total, 17,787 subjects (59.7% female, median age 63 years) were enrolled at baseline. During a 10-year follow-up, 2409 cases of heart disease were identified. Participants with fluctuating (HR = 1.13, 95% CI: 1.06-1.20), increasing (HR = 1.43, 95% CI: 1.25-1.64), and consistently high (HR = 1.64, 95% CI: 1.45-1.84) depressive symptom trajectories exhibited an increased risk of heart disease compared to those with consistently low depressive symptoms, while a decreasing (HR = 1.07, 95% CI: 0.96-1.19) depressive symptom trajectory did not significantly affect the risk of heart disease. Moreover, the association between heart disease and somatic depressive symptoms was found to be stronger than with cognitive-affective symptoms. These findings suggest a significant link between depressive symptom trajectories and heart disease, with particular emphasis on stronger associations with somatic symptoms. It is recommended that the identification and management of depressive symptoms be incorporated into heart disease prevention strategies.

EPDR1 promotes PD-L1 expression and tumor immune evasion by inhibiting TRIM21-dependent ubiquitylation of IkappaB kinase-ß.

While immune checkpoint blockade (ICB) has shown promise for clinical cancer therapy, its efficacy has only been observed in a limited subset of patients and the underlying mechanisms regulating innate and acquired resistance to ICB of tumor cells remain poorly understood. Here, we identified ependymin-related protein 1 (EPDR1) as an important tumor-intrinsic regulator of PD-L1 expression and tumor immune evasion. Aberrant expression of EPDR1 in hepatocellular carcinoma is associated with immunosuppression. Mechanistically, EPDR1 binds to E3 ligase TRIM21 and disrupts its interaction with IkappaB kinase-b, suppressing its ubiquitylation and autophagosomal degradation and enhancing NF-κB-mediated transcriptional activation of PD-L1. Further, we validated through a mouse liver cancer model that EPDR1 mediates exhaustion of CD8+ T cells and promotes tumor progression. In addition, we observed a positive correlation between EPDR1 and PD-L1 expression in both human and mouse liver cancer samples. Collectively, our study reveals a previously unappreciated role of EPDR1 in orchestrating tumor immune evasion and cancer progression.

Mechanistic Insights into Tanshinone IIA in the Amelioration of Post-Thyroidectomy Hypoparathyroidism.

BACKGROUND: Thyroidectomy causes impaired blood supply to the parathyroid glands, which leads to hypoparathyroidism. Tanshinone IIA (Tan IIA) is helpful in blood activation and cardiovascular protection. Therefore, the efficacy of Tan IIA in improving hypoparathyroidism was explored in this study. METHODS: New Zealand white rabbits were utilized to establish a unilateral parathyroid gland ischemia injury model. The model was created by selectively ligating the main blood supply vessel of one parathyroid gland, and the rabbits were then divided into three groups receiving 1, 5, and 10 mg/kg of Tan IIA. Serum calcium and parathyroid hormone (PTH) levels were measured using specialized assay kits. Immunohistochemistry was used to assess the microvessel density (MVD) in parathyroid glands. Western blotting (WB) was used to analyze protein expression related to the PI3K/AKT signaling pathway and the pathway-associated HIF-1α and VEGF. Moreover, MMP-2 and MMP-9 involved in angiogenesis were detected by WB. RESULTS: Tan IIA treatment effectively restored serum calcium and PTH levels in a dose-dependent manner. Notably, MVD in the parathyroid glands increased significantly, especially at higher doses. The Tan IIA treatment also elevated the p-PI3K/PI3K and p-AKT/AKT ratios, indicating that the PI3K/AKT pathway was reactivated. Moreover, Tan IIA significantly restored the decreased expression levels of VEGF and HIF-1α caused by parathyroid surgery. Additionally, Tan IIA increased MMP-2 and MMP-9 levels. CONCLUSION: Tan IIA activates the PI3K/AKT pathway, promotes angiogenesis by modulating VEGF, HIF-1α, MMP-2, and MMP-9, thereby further enhancing MVD within the parathyroid glands. This study demonstrates that Tan IIA improved post-thyroidectomy hypoparathyroidism.

Self-Powered Autonomous Electrostatic Dust Removal for Solar Panels by an Electret Generator.

Solar panels often suffer from dust accumulation, significantly reducing their output, especially in desert regions where many of the world's largest solar plants are located. Here, an autonomous dust removal system for solar panels, powered by a wind-driven rotary electret generator is proposed. The generator applies a high voltage between one solar panel's output electrode and an upper mesh electrode to generate a strong electrostatic field. It is discovered that dust particles on the insulative glass cover of the panel can be charged under the high electrical field, assisted by adsorbed water, even in low-humidity environments. The charged particles are subsequently repelled from the solar panel with the significant Coulomb force. Two panels covered with sand dust are cleaned in only 6.6 min by a 15 cm diameter rotary electret generator at 1.6 m s-1 wind speed. Experimental results manifest that the system can work effectively in a wide range of environmental conditions, and doesn't impact the panel performance for long-term operation. This autonomous system, with its high dust removal efficiency, simplicity, and low cost, holds great potential in practical applications.

HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression.

Immune checkpoint blockade (ICB) has shown considerable promise for treating various malignancies, but only a subset of cancer patients benefit from immune checkpoint inhibitor therapy because of immune evasion and immune-related adverse events (irAEs). The mechanisms underlying how tumor cells regulate immune cell response remain largely unknown. Here we show that hexokinase domain component 1 (HKDC1) promotes tumor immune evasion in a CD8+ T cell-dependent manner by activating STAT1/PD-L1 in tumor cells. Mechanistically, HKDC1 binds to and presents cytosolic STAT1 to IFNGR1 on the plasma membrane following IFNγ-stimulation by associating with cytoskeleton protein ACTA2, resulting in STAT1 phosphorylation and nuclear translocation. HKDC1 inhibition in combination with anti-PD-1/PD-L1 enhances in vivo T cell antitumor response in liver cancer models in male mice. Clinical sample analysis indicates a correlation among HKDC1 expression, STAT1 phosphorylation, and survival in patients with hepatocellular carcinoma treated with atezolizumab (anti-PD-L1). These findings reveal a role for HKDC1 in regulating immune evasion by coupling cytoskeleton with STAT1 activation, providing a potential combination strategy to enhance antitumor immune responses.

Imaging microglia surveillance during sleep-wake cycles in freely behaving mice.

Microglia surveillance manifests itself as dynamic changes in cell morphology and functional remodeling. Whether and how microglia surveillance is coupled to brain state switches during natural sleep-wake cycles remains unclear. To address this question, we used miniature two-photon microscopy (mTPM) to acquire time-lapse high-resolution microglia images of the somatosensory cortex, along with EEG/EMG recordings and behavioral video, in freely-behaving mice. We uncovered fast and robust brain state-dependent changes in microglia surveillance, occurring in parallel with sleep dynamics and early-onset phagocytic microglial contraction during sleep deprivation stress. We also detected local norepinephrine fluctuation occurring in a sleep state-dependent manner. We showed that the locus coeruleus-norepinephrine system, which is crucial to sleep homeostasis, is required for both sleep state-dependent and stress-induced microglial responses and ß2-adrenergic receptor signaling plays a significant role in this process. These results provide direct evidence that microglial surveillance is exquisitely tuned to signals and stressors that regulate sleep dynamics and homeostasis so as to adjust its varied roles to complement those of neurons in the brain. In vivo imaging with mTPM in freely behaving animals, as demonstrated here, opens a new avenue for future investigation of microglia dynamics and sleep biology in freely behaving animals.

Mitochondria-localized cGAS suppresses ferroptosis to promote cancer progression.

A well-established role of cyclic GMP-AMP synthase (cGAS) is the recognition of cytosolic DNA, which is linked to the activation of host defense programs against pathogens via stimulator of interferon genes (STING)-dependent innate immune response. Recent advance has also revealed that cGAS may be involved in several noninfectious contexts by localizing to subcellular compartments other than the cytosol. However, the subcellular localization and function of cGAS in different biological conditions is unclear; in particular, its role in cancer progression remains poorly understood. Here we show that cGAS is localized to mitochondria and protects hepatocellular carcinoma cells from ferroptosis in vitro and in vivo. cGAS anchors to the outer mitochondrial membrane where it associates with dynamin-related protein 1 (DRP1) to facilitate its oligomerization. In the absence of cGAS or DRP1 oligomerization, mitochondrial ROS accumulation and ferroptosis increase, inhibiting tumor growth. Collectively, this previously unrecognized role for cGAS in orchestrating mitochondrial function and cancer progression suggests that cGAS interactions in mitochondria can serve as potential targets for new cancer interventions.

Efficacy of immune checkpoint inhibitors in EGFR-Mutant NSCLC patients with EGFR-TKI resistance: A systematic review and meta-analysis.

Background: Epidermal growth factor receptor (EGFR) mutations are common in patients with non-small-cell lung cancer (NSCLC), particularly in Asian populations. Tyrosine kinase inhibitors (TKIs) are a first-line treatment in patients with mutant EGFR, but their use is often accompanied by drug resistance, which leads to disease progression. Chemotherapy and immunotherapy are the main treatment options after progression. The efficacy of immune checkpoint inhibitors (ICIs) and their combination therapy in patients with EGFR-TKI resistant is not clear. It is thus necessary to evaluate the efficacy of ICIs and ICI-based combination therapies in patients with EGFR-TKI-resistant NSCLC. Methods: We searched for randomized controlled trials (RCTs) comparing ICI therapy alone or in combination versus other therapies using PubMed, the Cochrane Library, Web of Science, EMBASE, MEDLINE, ClinicalTrials.gov, and several international conference databases, from database inception to 10 March 2022. The hazard ratio (HR) and 95% confidence interval (95% CI) for median overall survival (OS) and median progression-free survival (PFS) were evaluated. Odds ratio (OR), risk ratio (RR), and 95% CI were used as effect indicators for objective response rate (ORR) and safety data. Results: Seven eligible RCTs were included in the present meta-analysis. The results showed that neither ICIs nor combination therapy prolonged median OS in EGFR-TKI resistant NSCLC patients (HR = 1.04, 95% CI: 0.84-1.29, p = 0.73). However, compared with the control group, the patients treated with ICI-based combination therapy had better PFS (HR = 0.62, 95% CI: 0.45-0.86, p = 0.004) and ORR (OR = 1.84, 95% CI: 1.28-2.66, p = 0.001). Conclusion: ICI monotherapy did not improve the OS or PFS of NSCLC patients previously treated with EGFR-TKIs, whereas patients treated with ICI-based combination therapy had better PFS compared with those receiving conventional chemotherapy, indicating that this therapy could be offered to patients with EGFR-mutant NSCLC after progression following TKI treatment. There was no significant difference in all-grade treatment-related adverse events (TRAEs) between the combination therapy group and the control group. However, a higher incidence of discontinuation due to TRAEs was observed; this requires attention in future studies. The results of this meta-analysis provide a reference for clinical practice and future trial design. PROSPERO registration number: CRD42021282207.

Effect of interparticle dipolar interaction on pore clogging during microfiltration.

We present numerical investigations on the clogging of adhesive particles carrying electric dipoles at pore scale using an adhesive discrete element method (DEM). Based on the simulation results, the long-range dipolar interaction is reported to promote the clogging process, which is quantified by the bulk permeability, the penetrating particle number, and the particle capture efficiency. A clogging phase diagram is constructed in terms of the Stokes number (St) and the adhesion parameter (Ad) for both neutral and polarized particles. The influence of the dipolar interaction on the clogging-nonclogging transition is then described by the shifted boundary on the diagram. Also, the cake structure is characterized by different mathematical descriptions. A looser structure is formed with the increase of both the short-range adhesion and the long-range dipolar interaction. More ordered structures, such as particle chains, are observed in the presence of the stronger dipolar interaction. Furthermore, fluid stress is found to be essential in the compression and restructuring of the cake structure. Finally, a schematic representation of the cake structure is established, which provides a general physical picture showing the relationship between the cake structure and the particle-scale interactions.

A Novel Pyroptosis-Related Gene Signature for Prognostic Prediction of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous malignant cancer with poor prognosis. Pyroptosis is defined as a novel inflammation-dependent programmed cell death. However, the pyroptosis-associated gene expression in HNSCC and their relationship with prognosis are still indistinct. MATERIAL AND METHODS: We acquired the mRNA expression information of HNSCC patients from publicly available TCGA and GEO databases. We compared the tumor issues and adjacent normal tissues in terms of the gene expression for the purpose of identifying differentially expressed genes (DEGs). Based on these genes, we established a risk signature by the LASSO Cox regression in the TCGA cohort and validated the results in a GEO cohort. We also verified the levels of relevant mRNA expression in the model by RT-qPCR analysis. Eventually, functional enrichment approach was carried out to explore the potential mechanisms. RESULTS: Our team found a total of 18 differentially expressed genes (DEGs) between the HNSCC and healthy samples, and 4 DEGs displayed a remarkable association with the overall survival (OS) (P < 0.05). A 4-gene signature was constructed, presenting beneficial forecast power in both TCGA and GEO cohorts. Our team categorized patients into a group with high risk and another group with low risk as per the average risk value of the 4-gene feature. The individuals in the low risk group displayed a notably greater OS compared with the high risk one (P < 0.01). The Cox regression study demonstrated the independent forecast capability of the risk score. The receiver operating characteristic approach facilitated the verification of the forecast function of the gene signature. Posterior to verification, 4 genes were aberrantly expressed in the HNSCC and healthy samples. Functional study displayed that these groups presented diverse immunity conditions. CONCLUSION: Pyroptosis-associated genes are pivotal for the prognosis of HNSCC and can serve as potential therapeutic targets.

Hypertension Induced by Combination Therapy of Cancer: A Systematic Review and Meta-Analysis of Global Clinical Trials.

Background: Nowadays, due to the limitation of single therapy, combination therapy for cancer treatments has become important strategy. With the advancement of research on cardiotoxicities induced by anti-cancer treatment, among which cancer treatment-induced hypertension is the most frequent case. However, due to the small sample size and the absence of comparison (single-arm study alone), these studies have limitations to produce a feasible conclusion. Therefore, it is necessary to carry out a meta-analysis focusing on hypertension caused by cancer combination therapy. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and CNKI, from database inception to November 31, 2020, with randomized controlled trials (RCTs) associated with hypertension induced by cancer combination drugs. The main endpoint of which was to assess the difference in the incidence of hypertension in cancer patients with monotherapy or combination therapy. We calculated the corresponding 95% confidence interval (95% CIs) according to the random effect model and evaluated the heterogeneity between different groups. Results: According to the preset specific inclusion and exclusion criteria, a total of 23 eligible RCTs have been included in the present meta-analysis, including 6,241 patients (Among them, 2872 patients were the control group and 3369 patients were the experimental group). The results showed that cancer patients with combination therapy led to a higher risk of hypertension (All-grade: RR 2.85, 95% CI 2.52∼3.22; 1∼2 grade: RR 2.43, 95% CI 2.10∼2.81; 3∼4 grade: RR 4.37, 95% CI 3.33∼5.72). Furthermore, compared with the control group who received or did not receive a placebo, there was a higher risk of grade 3-4 hypertension caused by cancer combination treatment. Conclusion: The present meta-analysis carries out a comprehensive analysis on the risk of patients suffering from hypertension in the process of multiple cancer combination therapies. Findings in our study support that the risk of hypertension may increase significantly in cancer patients with multiple cancer combination therapies. The outcomes of this meta-analysis may provide a reference value for clinical practice and may supply insights in reducing the incidence of hypertension caused by cancer combined treatment.

Expression of long non-coding RNA LUCAT1 in patients with chronic obstructive pulmonary disease and its potential functions in regulating cigarette smoke extract-induced 16HBE cell proliferation and apoptosis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), characterized by persistent airflow limitation, was a disease mediated by a combination of inflammatory factors, immune cells, and immune mediators. COPD was an inflammatory and autoimmune disease involving T-lymphocytes triggered by cigarette smoke and other factors that progressively affected the bronchi, lung parenchyma, and pulmonary blood vessels. LncRNAs were reported to be implicated in COPD pathogenesis and development. METHODS: Non-smokers, smokers (non-COPD), and COPD patients were randomly selected in an established COPD surveillance cohort. Demographic and clinical information of all subjects were collected. Pulmonary function was measured by post-bronchodilator testing. qRT-PCR and ELISA assays were performed to detect the expression levels of lncRNA LUCAT1, miR-181a-5p, and inflammatory cytokines. An in vitro exposure model was constructed using cigarette smoke extract (CSE)-induced human bronchial epithelial (16HBE) cells. The dual-luciferase reporter and RNA pull-down assays were used to detect the binding relationship between lncRNA LUCAT1 and miR-181a-5p; meanwhile, Spearman's correlation assay was used to verify the correlation between lncRNA LUCAT1 and miR-181a-5p. Afterward, the lncRNA LUCAT1 silencing plasmid was constructed and co-transfected with a miR-181a-5p inhibitor to evaluate the effects on CSE-induced 16HBE cell proliferation and apoptosis. Finally, a Western blot assay was utilized to determine the mechanism of lncRNA LUCAT1/miR-181a-5p/Wnt/ß-catenin axis in COPD. RESULTS: LncRNA LUCAT1 was upregulated in the serums of COPD patients. Correlation analysis further confirmed the strong correlation between LUCAT1 expression and inflammatory cytokines IL-1ß, IL-6, and TNF-α. Receiver operating characteristic (ROC) analysis verified the potential of LUCAT1 in COPD diagnosis. After treatment with CSE, LUCAT1 was significantly increased while its target miR-181a-5p was decreased in 16HBE cells. Cell proliferation and apoptosis assays showed that LUCAT1 silencing alleviated CSE's effects on 16HBE cell proliferation and apoptosis. Mechanically, rescue assays demonstrated that miR-181a-5p inhibition could partially counteract the impact of LUCAT1 on COPD progression through the Wnt/ß-catenin pathway. CONCLUSIONS: LncRNA LUCAT1 may be a valuable indicator for differentiating COPD. Moreover, LncRNA LUCAT1/miR-181-5p/Wnt/ß-catenin axis behaved as a critical role in COPD development, shedding new sights for clinical treatment.

A new ferroptosis-related gene model for prognostic prediction of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a highly heterogeneous malignancy with diverse prognoses. Ferroptosis is a new type of cell death dependent on iron. Nevertheless, the predictive ability of ferroptosis-related genes for PTC is unclear. Based on the mRNA expression information from The Cancer Genome Atlas, we compared tumor and normal tissues in terms of the gene expression, for identifying differentially expressed genes (DEGs). Then, the risk score of a 5-gene signature was calculated and a prognostic model was established to test the predictive value of this gene signature by virtue of the LASSO Cox regression. The 5 genes were validated in PTC tissues by RT-qPCR.At last, functional analysis was implemented to investigate the underlying mechanisms. We found a total of 45 ferroptosis-related genes expressed differentially between tumor and normal tissues. 6 DEGs exhibited a significant relevance to the overall survival (OS) (P< 0.05). We classified patients into group with high risk and group with low risk based on the median risk score of a 5-gene signature. Patients in the group with low risk presented a remarkably higher OS relative to the group with high risk (P< 0.01). The Cox regression analysis displayed the independent predictive ability of the risk score. The receiver operating characteristic analysis helped to validate the predictive power owned by the gene signature. After validation, the 5 genes were abnormally expressed between PTC and normal tissues. Functional analysis showed two groups had different immune status. A new ferroptosis-related gene signature can predict the outcomes of PTC patients.

Application of Carbon Nanoparticle Tracers in the Lateral Neck Lymph Nodes of CN1bx Patients with Papillary Thyroid Carcinoma.

This study aimed to investigate the applicability of carbon nanoparticle tracers in the lateral neck lymph nodes of CN1bx patients with papillary thyroid carcinoma surgery. 73 patients with papillary thyroid carcinoma at our hospital between January 2019 to December 2019 were suspected metastasis in the lateral neck lymph node before surgical treatment. During the operation, carbon nanoparticle tracers were used as black staining tracers for the lateral neck lymph nodes to detect metastasis in each Compartment of the neck. The lateral Compartment is defined as level ll-V The black-stained lymph nodes, dyed by Carbon nanoparticle tracers, and non-dyed lymph nodes were compared. Post-surgery paraffin pathology was adopted as the gold standard to calculate the predictive performance of the carbon nanoparticle tracers in detecting lymph node biopsy metastasis. 59 of the patients (80.8%) had lateral neck metastasis. The black-stained lymph nodes, dyed by Carbon nanoparticle tracers, in Compartment IV exhibited the highest proportions in the case number submitted for detection and in lymph nodes metastasis, followed by Compartment III. The metastasis rate of the dyed lymph nodes in areas III and IV was significantly higher than that of non-dyed lymph nodes (P < 0.05). The sensitivity and accuracy of the dyed lymph node biopsy in Compartments III-IV were 90% and 93.2%, respectively. This predictive performance was similar to that Compartments ll-V combined. In conclusion, when carbon nanoparticle tracers are used for lymph node biopsy, high sensitivity and accuracy are obtained in lateral neck compartments III-IV, making these compartments ideal for lymph node biopsy.

A prospective study of Salvia miltiorrhiza and Rhizoma chuanxiong preparation in the treatment of hypoparathyroidism after total thyroidectomy.

This study aimed to investigate the clinical efficacy of Salvia miltiorrhiza and Rhizoma chuanxiong preparation on hypoparathyroidism. A total of 100 patients with hypoparathyroidism after total thyroidectomy were erolled, they were divided into the observation group (n=50), Salvia miltiorrhiza and Rhizoma chuanxiong preparation were added on the basis of traditional treatment. The control group (n=50), were treated with traditional treatment. To analyze the therapeutic effect of Salvia miltiorrhiza and Rhizoma chuanxiong preparation on hypoparathyroidism. After follow-up, the recovery time of parathyroid function in the observation group was significantly shorter than the control (P<0.05). No permanent hypoparathyroidism in the observation group and 4 cases in the control, which was statistically significant (P<0.05). The serum PTH in the observation group was significantly higher than the control on the 7th, 30th day, 3rd and 6th month. The level of serum calcium in the observation group was significantly higher than the control on the 3rd, 7th and 30th day (P<0.05). Salvia miltiorrhiza and Rhizoma chuanxiong preparation has obvious effects on the treatment of hypoparathyroidism and has low adverse reactions, which is worthy of clinical application.

Polymeric Immunoglobulin Receptor Mediates Immune Excretion of Mucosal IgM-Antigen Complexes Across Intestinal Epithelium in Flounder (Paralichthys olivaceus).

Polymeric immunoglobulin receptor (pIgR) is one important player of mucosal defenses, but very little is known on pIgR-mediated immune excretion of the antigens that penetrate mucosal surface in fish. Previously, we cloned the pIgR of flounder (Paralichthys olivaceus) and developed anti-pIgR antibody. In this study, the flounders were immunized intraperitoneally with the chicken ovalbumin (OVA) and the control protein bovine serum albumin (BSA) to elicit mucosal IgM antibody and pIgR response, and then challenged with OVA via caudal vein injection after the immunized OVA was absent from fish body at the fourth week after immunization. After OVA challenge, strong OVA-positive fluorescence signals were observed in lamina propria (LP) submucosa and epithelial cells of the hindgut at 30 min, increased proceeding toward the distal portion of intestinal folds, reached a peak at 2-3 h, and then weakened and disappeared at 12 h, indicating that the OVA rapidly diffused from bloodstream into LP submucosa and excreted across intestinal epithelium. Whereas in BSA-immunized and OVA-challenged control fish, the OVA was detected in LP submucosa but not in intestinal epithelium due to the lack of OVA-specific antibody. Accordingly, in intestinal epithelium, the transepithelial transport of OVA was confirmed by immunogold electron microscopy, and co-localization of OVA, IgM, and pIgR was illuminated by multiple-label immunofluorescence confocal microscopy and analyzed using Image J software. Furthermore, in gut mucus but not in serum, an ~800-kDa protein band showed IgM-positive, OVA-positive, and pIgR-positive simultaneously, and the OVA, together with IgM and secretory component (SC) of pIgR, could be immunoprecipitated by anti-OVA antibody, demonstrating the existence of SC-polymeric IgM-OVA complexes. All these results collectively revealed that the pIgR could transport mucosal IgM-OVA complexes from LP across intestinal epithelium into gut mucus via the transcytosis in flounder. These new findings provided direct evidences for pIgR-mediated immune excretion of IgM-antigen complexes, and better understanding the role of pIgR in mucosal immunity in teleost fish.

Characterization of the roles of suppressor of cytokine signaling-3 in prostate cancer development and progression.

As negative feedback regulators of cytokine signaling, suppressor of cytokine signaling proteins are induced by interleukins and various peptide hormones and may prevent sustained activation of signaling pathways. In particular, suppressor of cytokine signaling-3 (SOCS-3) plays pivotal roles in the development and progression of various cancers and exerts pleiotropic effects on cell proliferation and apoptosis. In recent years, abnormal expression of SOCS-3 and its multiple functions have been extensively investigated in human carcinomas, particularly in prostate cancer. SOCS-3 can act as an oncogene or a tumor suppressor depending on the cellular context. In this review, we focus on the role of SOCS-3 in prostate cancer development and prognosis, as well as the potential of SOCS-3 as a therapeutic target and diagnostic marker.

[Efficacies of neoadjuvant chemotherapy plus nutritional support in advanced gastric cancer complicated with pylori obstruction].

OBJECTIVE: To explore the efficacies of neoadjuvant chemotherapy plus nutritional supports for gastric cancer complicated with pyloric obstruction. METHODS: Retrospective analyses were performed for a total of 116 patients of gastric cancer complicated with pyloric obstruction undergoing exploratory laparotomy from January 2004 to June 2013. RESULTS: Sixty-two patients (group A) received neoadjuvant chemotherapy (regimen of FOLFOX) plus preoperative nutritional support. And parenteral (PN, n = 30) and enteral (EN, n = 32) nutritional supports were provided. Another 54 patients (group B) underwent exploratory laparotomy alone. The serum level of albumin and score of quality of life in group A at the last preoperative day improved significantly. And EN was better than PN. The rate of excision/radical excision of group A (85.5%, 45.2%) was much higher than group B (64.8%, 18.5%) (both P < 0.05). CONCLUSION: Nutritional support, especially EN, can improve the nutritional status and quality of life in patients with gastric cancer complicated with pyloric obstruction. And nutritional support plus neoadjuvant chemotherapy increase the rate of tumor excision.