MKK3 K329 Mutation Attenuates Diabetes-Associated Cognitive Dysfunction by Blocking the MKK3-RAGE Interaction and Inhibiting Neuroinflammation.

The receptor for advanced glycation end products (RAGE) contributes to diabetes-associated cognitive dysfunction (DACD) through the interaction of its C-terminal AAs 2-5 with mitogen-activated protein kinase kinase 3 (MKK3). However, the associated MKK3 binding site is unknown. Here, db/db mice were used as a model for type 2 diabetes. GST pull-down assays and AutoDock Vina simulations were conducted to identify the key RAGE binding site in MKK3. This binding site was mutated to investigate its effects on DACD and to elucidate the underlying mechanisms. The interaction of MKK3 and RAGE, the levels of inflammatory factors, and the activation of microglia and astrocytes were tested. Synaptic morphology and plasticity in hippocampal neurons were assessed via electrophysiological recordings and Golgi staining. Behavioral tests were used to assess cognitive function. In this study, MKK3 bound directly to RAGE via its lysine 329 (K329), leading to the activation of the nuclear factor-κB (NF-κB) signaling pathway, which in turn triggered neuroinflammation and synaptic dysfunction, and ultimately contributed to DACD. MKK3 mutation at K329 reversed synaptic dysfunction and cognitive deficits by downregulating the NF-κB signaling pathway and inhibiting neuroinflammation. These results confirm that neuroinflammation and synaptic dysfunction in the hippocampus rely on the direct binding of MKK3 and RAGE. We conclude that MKK3 K329 binding to C-terminal RAGE (ct-RAGE) is a key mechanism by which neuroinflammation and synaptic dysfunction are induced in the hippocampus. This study presents a novel mechanism for DACD and proposes a novel therapeutic avenue for neuroprotection in DACD.

Comparing three-dimensional and two-dimensional deep-learning, radiomics, and fusion models for predicting occult lymph node metastasis in laryngeal squamous cell carcinoma based on CT imaging: a multicentre, retrospective, diagnostic study.

Background: The occult lymph node metastasis (LNM) of laryngeal squamous cell carcinoma (LSCC) affects the treatment and prognosis of patients. This study aimed to comprehensively compare the performance of the three-dimensional and two-dimensional deep learning models, radiomics model, and the fusion models for predicting occult LNM in LSCC. Methods: In this retrospective diagnostic study, a total of 553 patients with clinical N0 stage LSCC, who underwent surgical treatment without distant metastasis and multiple primary cancers, were consecutively enrolled from four Chinese medical centres between January 01, 2016 and December 30, 2020. The participant data were manually retrieved from medical records, imaging databases, and pathology reports. The study cohort was divided into a training set (n = 300), an internal test set (n = 89), and two external test sets (n = 120 and 44, respectively). The three-dimensional deep learning (3D DL), two-dimensional deep learning (2D DL), and radiomics model were developed using CT images of the primary tumor. The clinical model was constructed based on clinical and radiological features. Two fusion strategies were utilized to develop the fusion model: the feature-based DLRad_FB model and the decision-based DLRad_DB model. The discriminative ability and correlation of 3D DL, 2D DL and radiomics features were analysed comprehensively. The performances of the predictive models were evaluated based on the pathological diagnosis. Findings: The 3D DL features had superior discriminative ability and lower internal redundancy compared to 2D DL and radiomics features. The DLRad_DB model achieved the highest AUC (0.89-0.90) among all the study sets, significantly outperforming the clinical model (AUC = 0.73-0.78, P = 0.0001-0.042, Delong test). Compared to the DLRad_DB model, the AUC values for the DLRad_FB, 3D DL, 2D DL, and radiomics models were 0.82-0.84 (P = 0.025-0.46), 0.86-0.89 (P = 0.75-0.97), 0.83-0.86 (P = 0.029-0.66), and 0.79-0.82 (P = 0.0072-0.10), respectively in the study sets. Additionally, the DLRad_DB model exhibited the best sensitivity (82-88%) and specificity (79-85%) in the test sets. Interpretation: The decision-based fusion model DLRad_DB, which combines 3D DL, 2D DL, radiomics, and clinical data, can be utilized to predict occult LNM in LSCC. This has the potential to minimize unnecessary lymph node dissection and prophylactic radiotherapy in patients with cN0 disease. Funding: National Natural Science Foundation of China, Natural Science Foundation of Shandong Province.

Low Prognostic Nutritional Index Is Common and Associated with Poor Outcomes following Curative-Intent Resection for Gastro-Entero-Pancreatic Neuroendocrine Tumors.

INTRODUCTION: To investigate the impact of prognostic nutritional index (PNI) on short- and long-term outcomes of patients who underwent curative-intent resection for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). METHODS: Patients with GET-NETs who underwent curative-intent resection were identified from a multi-center database. The prognostic impact of clinicopathological factors including PNI on post-operative outcomes were evaluated. A novel nomogram was developed and externally validated. RESULTS: A total of 2,099 patients with GEP-NETs were included in the training cohort; 255 patients were in the external validation cohort. Median PNI (n = 973) was 47.4 (IQR 43.1-52.4). At the time of presentation, 1,299 (61.9%) patients presented with some type of clinical symptom. Low-PNI (≤42.2) was associated with gastrointestinal symptoms, as well as nodal metastasis and distant metastasis (all p < 0.05). Patients with a low PNI had a higher incidence of severe (≥Clavien-Dindo grade IIIa: low PNI 24.9% vs. high PNI 15.4%, p = 0.001) and multiple (≥3 types of complications: low PNI 14.5% vs. high PNI 9.2%, p = 0.024) complications, as well as a worse overall survival (OS)(5-year OS, low PNI 73.7% vs. high PNI 88.5%, p < 0.001), and RFS (5-year RFS, low PNI 68.5% vs. high PNI 79.8%, p = 0.008) versus patients with high PNI (>42.2). A nomogram based on PNI, tumor grade and metastatic disease demonstrated excellent discrimination and calibration to predict OS in both the training (C-index 0.748) and two external validation (C-index 0.827, 0.745) cohorts. CONCLUSIONS: Low PNI was common and associated with worse short- and long-term outcomes among patients with GEP-NETs.

Serum Copper/Zinc Ratio in Overweight and Obese Children: a Cross-Sectional Study.

To assess the association between serum copper/zinc ratio (CZR) and overweight/obesity in children. Sociodemographic and clinical data of children aged 8-18 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) database in this cross-sectional study. These associations were explored using weighted univariate and multivariate logistic regression analyses with the odds ratios (ORs) and 95% confidence intervals (CIs). High serum CZR level was related to higher odds of overweight (OR = 1.74), obesity (OR = 5.26), and central obesity (OR = 2.99). Subgroup analyses showed that high serum CZR levels were associated with high odds of overweight in children aged ≥ 12 years old (OR = 2.19) and females (OR = 2.02), while the increased odds of obesity and central obesity were found in children aged ≥ 12 years old and both male and female. Elevated serum CZR level was linked to high odds of childhood overweight, obesity, and central obesity, and this relationship was also found in children with different age and gender.

Research progress on the stress-strain index of Corvis ST / 国际眼科杂志(Guoji Yanke Zazhi)

Corneal visualization Scheimpflug technology(Corvis ST)is currently the most commonly used clinical device for assessing in vivo corneal biomechanics. The new parameter stress-strain index(SSI)has been a hot topic of clinical research in recent years, which not only directly reflect corneal biomaterial stiffness, but also closely correlates with the progression of certain diseases. SSI was generated based on the predictions of corneal behavior using finite element(FE)numerical modeling to simulate the effects of intraocular pressure and Corvis ST jets. The SSI algorithm does not change with central corneal thickness(CCT), intraocular pressure, or biomechanically corrected intraocular pressure(BIOP), but it is clearly associated with altered collagen fibres in the corneosclera. The principles of SSI, the relationship between age and SSI, the relationship between axial length and SSI, the relationship between myopia and SSI, and the application of SSI are summarized and concluded.

Maritime Infrared Small Target Detection Based on the Appearance Stable Isotropy Measure in Heavy Sea Clutter Environments.

Infrared small target detection plays a crucial role in maritime security. However, detecting small targets within heavy sea clutter environments remains challenging. Existing methods often fail to deliver satisfactory performance in the presence of substantial clutter interference. This paper analyzes the spatial-temporal appearance characteristics of small targets and sea clutter. Based on this analysis, we propose a novel detection method based on the appearance stable isotropy measure (ASIM). First, the original images are processed using the Top-Hat transformation to obtain the salient regions. Next, a preliminary threshold operation is employed to extract the candidate targets from these salient regions, forming a candidate target array image. Third, to distinguish between small targets and sea clutter, we introduce two characteristics: the gradient histogram equalization measure (GHEM) and the local optical flow consistency measure (LOFCM). GHEM evaluates the isotropy of the candidate targets by examining their gradient histogram equalization, while LOFCM assesses their appearance stability based on local optical flow consistency. To effectively combine the complementary information provided by GHEM and LOFCM, we propose ASIM as a fusion characteristic, which can effectively enhance the real target. Finally, a threshold operation is applied to determine the final targets. Experimental results demonstrate that our proposed method exhibits superior comprehensive performance compared to baseline methods.

Characterization of the immune cell function landscape in head and neck squamous carcinoma to assist in prognosis prediction and immunotherapy.

BACKGROUND: The malignant characteristics of cancer depend not only on intrinsic properties of cancer cells but also on the functions of infiltrating immune cells. In this study, we aimed to investigate the functional landscape of immune cells in head and neck squamous cell carcinoma (HNSCC). METHODS: We employed single-sample gene set enrichment analysis to examine the immunophenotypes of HNSCC based on 29 immune cell functions (ICFs) in TCGA and GSE65858 datasets. We analyzed the clinical features, immune microenvironment, molecular profiles, and biological processes. Additionally, we developed and validated an ICF-based risk score for personalized prognosis prediction. We confirmed the value of the ICF score in our cohort using qRT-PCR and immunohistochemistry. Molecular docking was used to predict potential compounds for immunotherapy. RESULTS: Three immunophenotypes (Immune-L, Immune-M, and Immune-H) were identified in 769 HNSCC samples. The characteristics of Immune-H were consistent with a "Hot" tumor, Immune-L was similar to a "Cold" tumor, and Immune-M exhibited intermediate features. The ICF risk score was associated with immune checkpoints, infiltrating immune cells, tumor mutation burden, and sensitivities to targeted/chemotherapeutic agents. Gene set variation analysis implicated the involvement of metabolic reprogramming pathways in the high-risk group. The combination of "Tumor Immune Dysfunction and Exclusion" and "Immunophenoscore" algorithms indicated that the low-risk group had a higher likelihood of benefiting from immunotherapy. Finally, we identified Eltrombopag and other compounds that may be beneficial for HNSCC immunotherapy. CONCLUSION: Our study provides a novel perspective on the tumor microenvironment of HNSCC, aiding in the understanding of HNSCC heterogeneity and the development of personalized/precision medicine.

[Efficacy evaluation of transaxillary non-inflatable endoscopic surgery and open neck surgery in the treatment of PTC: a single center report of 342 cases].

Objective:To compare the clinical effect of transaxillary non-inflatable endoscopic surgery and traditional open thyroid surgery in the treatment of PTC. Methods:A retrospective analysis was performed on 342 patients with PTC treated in the Otorhinolaryngology Department of Qilu Hospital of Shandong University from December 2020 to December 2022. There were 73 males and 269 females, aged 16-72 years, who underwent unilateral non-inflatable transaxillary endoscopic thyroid surgery（endoscopic group） and unilateral traditional open thyroid surgery（open group）. There were 108 patients in the endoscopic group and 234 in the open group. Results:The endoscopic group was lower in age（37.1±9.4 vs 43.5±11.2） years and BMI（23.4±3.4 vs 25.7±3.8 ）kg/m² than that in the open group, and the difference was statistically significant（t was 5.53, 5.67 respectively, P<0.01）. There was no significant difference in hospitalization days between the two groups（P>0.05）. The logarithmic curve of the operation time showed a smooth downward trend, and the overall operation time of the endoscopic group was relatively consistent. There was no significant difference in intraoperative blood loss between the endoscopic group（13.3±3.2） mL and the open group（14.7±6.3） mL（P>0.05）, but the operation time（130.1±37.9） min was longer than that in the open group（57.4±13.7） min, and the difference was statistically significant（t=19.40, P<0.01）. There was no significant difference in complications such as temporary recurrent laryngeal nerve injury within 3 days after operation between the two groups（P>0.05）. The aesthetic satisfaction score of the surgical incision and the incision concealment effect score in the endoscopic group were higher than those in the open group, and the difference was statistically significant（P<0.05）. Conclusion:Compared with traditional open thyroidectomy, transaxillary non-inflatable endoscopic thyroidectomy has more advantages in the concealment and aesthetics of postoperative incision. Although the former has longer operation time and more drainage, it is still a safe and feasible surgical method with good postoperative clinical effect.

[Advances of spatial omics in the individualized diagnosis and treatment of head and neck cancer].

Spatialomics is another research hotspot of biotechnology after single-cell sequencing technology, which can make up for the defect that single-cell sequencing technology can not obtain cell spatial distribution information. Spatialomics mainly studies the relative position of cells in tissue samples to reveal the effect of cell spatial distribution on diseases. In recent years, spatialomics has made new progress in the pathogenesis, target exploration, drug development and many other aspects of head and neck tumors. This paper summarizes the latest progress of spatialomics in the diagnosis and treatment of head and neck cancer.

Recognition of refractory Mycoplasma pneumoniae pneumonia among Myocoplasma pneumoniae pneumonia in hospitalized children: development and validation of a predictive nomogram model.

BACKGROUD: The current diagnostic criteria for refractory Mycoplasma pneumoniae pneumonia (RMPP) among Mycoplasma pneumoniae Pneumonia (MPP) are insufficient for early identification, and potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP. METHODS: A total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA). RESULTS: Multivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08-1.33, P = 0.038), fever duration (HR 1.34, 95%CI 1.20-1.50, P < 0.001), lymphocyte count (HR 0.45, 95%CI 0.23-0.89, P = 0.021), serum D-dimer (D-d) level (HR 1.70, 95%CI 1.16-2.49, P = 0.006), and pulmonary imaging score (HR 5.16, 95%CI 2.38-11.21, P < 0.001). The area under the ROC curve was 90.7% for the development cohort and 96.36% for the validation cohort. The internal and external verification calibration curves were almost linear with slopes of 1, and the DCA curve revealed a net benefit with the final predictive nomogram. CONCLUSION: This study proposes a predictive nomogram only based on five variables. The nomogram can be used for early identification of RMPP among pediatric patients with MPP, thereby facilitating more timely and effective intervention.

Low T3 syndrome predicts more adverse events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM. METHODS: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis. RESULTS: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively). CONCLUSIONS: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population.

CYP4F12 is a potential biomarker and inhibits cell migration of head and neck squamous cell carcinoma via EMT pathway.

Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor of head and neck. Due to the insidious nature of HNSC and the lack of effective early diagnostic indicators, the development of novel biomarkers to improve patient prognosis is particularly urgent. In this study, we explored and validated the correlation between cytochrome P450 family 4 subfamily F member 12 (CYP4F12) expression levels and HNSC progression using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets and collected patient samples. We analyzed the association of CYP4F12 expression with clinicopathological features, immune correlation and prognosis. Finally, we analyzed the correlation between CYP4F12 and pathways, and verified by experiments. The results showed that CYP4F12 was low expressed in tumor tissues, participated in a variety of phenotypic changes of HNSC and affected immune cell infiltration. Pathway analysis indicated that CYP4F12 may play a key role in tumor cell migration and apoptosis. Experimental results showed that over-expression of CYP4F12 inhibited cell migration and enhanced the adhesion between cells and matrix by inhibiting epithelial-mesenchymal transition (EMT) pathway in HNSC cells. In conclusion, our study provided insights into the role of CYP4F12 in HNSC and revealed that CYP4F12 may be a potential therapeutic target for HNSC.

Effects of Deep Hyperthermia Combined with Intraperitoneal Chemotherapy on Liver-Kidney Function, Immune Function, and Long-Term Survival in Patients with Abdominal Metastases.

Objectives: To analyze the effects of deep hyperthermia combined with intraperitoneal chemotherapy on liver-kidney function, immune function, and long-term survival in patients with abdominal metastases. Methods: A total of 88 patients with abdominal metastases confirmed in the hospital were enrolled as the research objects between August 2018 and August 2021. They were randomly divided into control group (n = 44) and observation group (n = 44). The control group was treated with intraperitoneal chemotherapy, while observation group was additionally treated with deep hyperthermia. The general clinical data of patients were recorded. The short-term and long-term curative effects were evaluated. The occurrence of side effects in both groups was recorded. Before and after treatment, levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected by full-automatic biochemical analyzer. The level of blood urea nitrogen (BUN) was detected by the urease electrode method. The level of serum creatinine (Scr) was detected by the picric acid method. The levels of CD3 +, CD4 +, CD8 +, and NK cells were detected by BD FACSCalibur flow cytometer. Results: There was no significant difference in clinical data between the two groups (P > 0.05). In the observation group, ORR was significantly higher than that in the control group (54.55% vs 29.55%) (P < 0.05), OS was significantly longer than that in the control group (P < 0.05), and median survival time and mPFS were longer than those in the control group. After treatment, the levels of ALT, AST, BUN, and Scr were significantly increased in the control group (P < 0.05), but there was no significant difference in peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio or count of NK cells before and after treatment (P > 0.05). Before and after treatment, there was no significant difference in the levels of ALT, AST, BUN, and Scr in the observation group (P > 0.05). After treatment, peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio and count of NK cells were all increased in the observation group, significantly higher than those in the control group (P < 0.05). The incidence of chemotherapy side effects in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion: The short-term and long-term curative effects of deep hyperthermia combined with intraperitoneal chemotherapy are good on patients with intraperitoneal metastases, with less damage to liver-kidney function. It is beneficial to enhance immune function of patients, with mild side effects.

Glycemic dispersion: a new index for screening high glycemic variability.

OBJECTIVE: For patients with diabetes, high-frequency and -amplitude glycemic variability may be more harmful than continuous hyperglycemia; however, there is still a lack of screening indicators that can quickly and easily assess the level of glycemic variability. The aim of this study was to investigate whether the glycemic dispersion index is effective for screening high glycemic variability. METHODS: A total of 170 diabetes patients hospitalized in the Sixth Affiliated Hospital of Kunming Medical University were included in this study. After admission, the fasting plasma glucose, 2-hour postprandial plasma glucose, and glycosylated hemoglobin A1c were measured. The peripheral capillary blood glucose was measured seven times in 24 h, before and after each of three meals and before bedtime. The standard deviation of the seven peripheral blood glucose values was calculated, and a standard deviation of > 2.0 was used as the threshold of high glycemic variability. The glycemic dispersion index was calculated and its diagnostic efficacy for high glycemic variability was determined by the Mann-Whitney U test, receiver operating characteristic (ROC) curve and, Pearson correlation analysis. RESULTS: The glycemic dispersion index of patients with high glycemic variability was significantly higher than that of those with low glycemic variability (p < 0.01). The best cutoff value of the glycemic dispersion index for screening high glycemic variability was 4.21. The area under the curve (AUC) was 0.901 (95% CI: 0.856-0.945) and had a sensitivity of 0.781 and specificity of 0.905. It was correlated with the standard deviation of blood glucose values (r = 0.813, p < 0.01). CONCLUSIONS: The glycemic dispersion index had good sensitivity and specificity for screening high glycemic variability. It was significantly associated with the standard deviation of blood glucose concentration and is simple and easy to calculate. It was an effective screening indicator of high glycemic variability.

Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Delineating the twin role of autophagy in lung cancer.

Autophagy represents an intracellular defense mechanism equipped within each eukaryotic cells to enable them to cope with variety of physical, chemical, and biological stresses. This mechanism helps to restore the homeostasis and preserve the cellular integrity and function of the cells. In these conditions, such as hypoxia, nutrient deprivation, inhibition of protein synthesis or microbial attack, the process of autophagy is upregulated to maintain cellular homeostasis. The role of autophagy in cancer is an intriguing topic which needs further exploration. This process of autophagy has been many times referred as a double-edged sword in the process of tumorigenesis. In the initial stages, it may act as a tumor suppressor and enable to quench the damaged organelles and harmful molecules generated. In more advanced stages, autophagy has been shown to act as a tumor-promoting system as it may help the cancer cells to cope better with stressful microenvironments. Besides this, autophagy has been associated with development of resistance to anticancer drugs as well as promoting the immune evasion in cancer cells, representing a serious obstacle in cancer treatment and its outcome. Also, autophagy is associated with hallmarks of cancer that may lead to activation of invasion and metastasis. The information on this twin role needs further exploration and deeper understanding of the pathways involved. In this review, we discuss the various aspects of autophagy during tumor development, from early to late stages of tumor growth. Both the protective role of autophagy in preventing tumor growth and the underlying mechanisms adopted with evidence from past studies have been detailed. Further, the role of autophagy in conferring resistance to distinct lung cancer treatment and immune shielding properties has also been discussed. This is essential for further improving on treatment outcome and success rates.

Dietary bamboo leaf flavonoids improve quality and microstructure of broiler meat by changing untargeted metabolome.

BACKGROUND: Dietary bamboo leaf flavonoids (BLFs) are rarely used in poultry production, and it is unknown whether they influence meat texture profile, perceived color, or microstructure. RESULTS: A total of 720 one-day-old Arbor Acres broilers were supplemented with a basal diet with 20 mg bacitracin/kg, 50 mg BLFs/kg, or 250 mg BLFs/kg or without additions. Data showed that the dietary BLFs significantly (P < 0.05) changed growth performance and the texture profile. In particular, BLFs increased birds' average daily gain and average daily feed intake, decreased the feed:gain ratio and mortality rate, improved elasticity of breast meat, enhanced the gumminess of breast and leg meat, and decreased the hardness of breast meat. Moreover, a significant (P < 0.05) increase in redness (a*) and chroma (c*) of breast meat and c* and water-holding capacity of leg meat was found in BLF-supplemented broilers compared with control broilers. In addition, BLFs supplementation significantly decreased (P < 0.05) the ß-sheet ratio and serum malondialdehyde and increased the ß-turn ratio of protein secondary structure, superoxide dismutase, and glutathione peroxidase of breast meat and total antioxidant capacity and catalase of serum. Based on the analysis of untargeted metabolome, BLFs treatment considerably altered 14 metabolites of the breast meat, including flavonoids, amino acids, and organic acids, as well as phenolic and aromatic compounds. CONCLUSIONS: Dietary BLFs supplementation could play a beneficial role in improving meat quality and sensory color in the poultry industry by changing protein secondary structures and modulating metabolites.

[Expression of HSP27 and BAX/BCL-2 apoptosis factor in silicosis rat model of fibrosis].

OBJECTIVE: To study the expression of heat shock protein 27(HSP27), BAX and BCL-2 apoptosis in silicosis rat model, and to explore the correlation between HSP27 and BAX and BCL-2 apoptosis. METHODS: Silicosis model was established by the oropharyngeal and endotracheal intubation. Forty SPF healthy adult Wistar male rats were randomly divided into 4 groups, with 10 rats in each group. Silicosis group for 6 weeks(feeding for 6 weeks), silicosis group for 8 weeks(feeding for 8 weeks): oropharyngeal and tracheal perfusion of 50 mg/mL SiO_2 suspension 1.0 mL/mouse; Model control group for 6 weeks and model control group for 8 weeks: 1.0 mL saline was infused into the oropharynx and trachea. Immunohistochemical staining was used to detect the expression of HSP27, BAX and BCL-2 in the right lower lung of silicosis model group at 6 and 8 weeks and model control group at 6 and 8 weeks. Western blot was used to detect the protein expression of HSP27, BAX and BCL-2 in the left lower lobe lung tissue of silicosis model group at 6 and 8 weeks and model control group at 6 and 8 weeks, respectively. Immunofluorescence staining was used to detect the colocalization of HSP27 with pro-apoptotic factor BAX and HSP27 with anti-apoptotic factor BCL-2. RESULTS: Compared with the model control group at 6 weeks and 8 weeks, the expression of HSP27 and pro-apoptotic factor BAX in fibrotic region increased, and the expression of anti-apoptotic factor BCL-2 decreased in silicosis model group at 6 weeks and 8 weeks(P<0.05). Immunofluorescence staining showed that there was colocalization of HSP27 and pro-apoptotic factor BAX in the fibrotic region. Correlation analysis showed that the correlation coefficient between HSP27 and pro-apoptotic factor BAX was r=0.94, indicating a positive correlation between them, while the correlation coefficient between HSP27 and anti-apoptotic factor BCL-2 was r=-0.81, indicating a negative correlation between them. CONCLUSION: High expression of HSP27 and pro-apoptotic factor BAX and low expression of anti-apoptotic factor BCL-2 exist in silicosis rats, and their expression is correlated.

Comprehensive analysis reveals CCDC60 as a potential biomarker correlated with prognosis and immune infiltration of head and neck squamous cell carcinoma.

Background: Coiled-coil domain containing 60 (CCDC60) is a member of the CCDC family, which participates in the progression of many types of cancer. However, the prognostic value of CCDC60 in head and neck squamous cell carcinoma (HNSC) and its function in tumor immunity remain unclear. Methods: CCDC60 expression and its prognostic potential in HNSC were evaluated by bioinformatics approaches, which was validated in human HNSC samples. Genetic alteration analysis of CCDC60 and the underlying biological function of CCDC60 related co-expressed genes in HNSC were analyzed. The impact of CCDC60 on the regulation of immune infiltration in HNSC was comprehensively investigated. In vitro, a series of functional assays on CCDC60 were performed in HNSC cells. Results: Our study has indicated that compared with the adjacent normal tissues, CCDC60 expression was considerably downregulated in HNSC tissues. High CCDC60 expression was connected with favorable outcome of HNSC patients, and its prognostic significance was examined by distinct clinical characteristics. We identified the CCDC60-related co-expression genes, which were mainly enriched in the NOD-like receptor signaling pathway associated with the inhibition of tumor growth, leading to a better prognosis of HNSC patients. In vitro, CCDC60 overexpression significantly inhibited the growth, migration and invasiveness but regulated cell cycle progression, and promoted cell adhesion of Fadu and Cal27 cells. Additionally, high CCDC60 expression had strong connections with the infiltrating levels of immune cells, immune marker sets, immunomodulators and chemokines in HNSC, suggesting that targeting CCDC60 could be a promising strategy to enhance the efficacy of immunotherapy for HNSC patients. Conclusion: Tumor suppressor CCDC60 may be identified as a prognostic and immune-related indicator in HNSC, which had the potential functions in regulating the immune infiltration of HNSC and improving the response to immunotherapy for HNSC patients.

Design, Synthesis, and Biological Activities of Novel 2-Cyanoacrylate Compounds Containing Substituted Pyrazolyl or 1,2,3-Triazolyl Moiety.

To develop novel 2-cyanoacrylate derivatives with potential bioactivity, a number of 2-cyanoacrylate compounds, including substituted pyrazole or 1,2,3-triazole ring, were designed, prepared, and structurally detected by 1H NMR, 13C NMR, and elemental analysis. The biological assessment displayed that some designed compounds had significant herbicidal activities against Brassica juncea, Chenopodium serotinum, Rumex acetosa, Alopecurus aequalis, Polypogon fugax, and Poa annua at a dosage of 1500 g/ha. Furthermore, some derivatives still expressed satisfactory herbicidal activities against Brassica juncea, Chenopodium serotinum, and Rumex acetosa when the dosage was lowered to 150 g/ha, especially the inhibitory effects of compounds 9a, 9d, 9f, 9i, 10a, 10b, 10e, and 10n against Brassica juncea were all over 80%, compounds 9d, 9f, 9g, 9h, 9i, 10h, 10i, 10m, 10n, and 10o possessed more than 70% inhibition rates against Chenopodium serotinum, and compound 9d indicated 70% herbicidal activity against Rumex acetosa. These results provided an important basis for further design and discovery of biologically active 2-cyanoacrylate compounds.