Clinical characteristics and prognosis of primary thymic adenocarcinoma: A single-center retrospective analysis.

BACKGROUND: Primary thymic adenocarcinoma (PTAC) is an extremely rare disease with a poor prognosis. In the present study, we sought to analyze the clinical characteristics and prognostic factors of patients with PTAC. METHODS: A total of 14 patients with PTAC treated at our center from January 2000 to January 2019 were included in this study. We retrospectively collected information on sex, age, history of smoking, family history of cancer, comorbidities, symptoms, imaging tests, serum tumor marker levels, tumor, node, metastasis (TNM) staging, and treatment records. Follow-up information was obtained by telephone interviews or outpatient clinic visit. Univariate and multivariate Cox regression analyses were performed to investigate the clinicopathological factors associated with survival. RESULTS: Among 14 patients with PTAC, there were five males and nine females, with an average age of 48.7 ± 9.3 years. A total of 23.1% of the patients had a history of smoking. The clinical symptoms of the patients were nonspecific and seven patients had elevated levels of serum tumor markers. Surgery was performed for nine patients, among which only four received R0 resection. The median survival time of the 14 patients was 16.0 months, and the 1-, 3- and 5-year survival rates were 57.1%, 35.7% and 21.4%, respectively. TNM stage was identified as an independent prognostic factor for PTAC patients (the median survival time of stage I-IIIA vs. stage IV was 44.0 months vs. 9.0 months, p = 0.002). CONCLUSIONS: PTAC is highly aggressive malignancy with poor prognosis. Surgical treatment is feasible, but R0 resection is challenging. TNM staging is significantly associated with patient survival.

NLR, MLR, and PLR are adverse prognostic variables for sleeve lobectomy within non-small cell lung cancer.

BACKGROUND: The goal of the research was to examine the value of peripheral blood indicators in forecasting survival and recurrence among people suffering central-type non-small cell lung cancer (NSCLC) undergoing sleeve lobectomy (SL). METHODS: Clinical information was gathered from 146 individuals suffering from NSCLC who had SL at our facility between January 2014 and May 2023. Peripheral blood neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR) levels were determined by receiver operating characteristic (ROC) curve to establish the threshold points. Kaplan-Meier survival analysis was employed to evaluate the prognostic value of different groupings, and both univariate and multivariate Cox proportional hazards model (referred to as COX) were performed. RESULTS: The disease-free survival (DFS) and overall survival (OS) cutoff values were carried out via ROC analysis. Kaplan-Meier survival analysis revealed notable differences in OS for NLR (≥2.196 vs. <2.196, p = 0.0009), MLR (≥0.2763 vs. <0.2763, p = 0.0018), and PLR (≥126.11 vs. <126.11, p = 0.0354). Similarly, significant differences in DFS were observed for NLR (≥3.010 vs. <3.010, p = 0.0005), MLR (≥0.2708 vs. <0.2708, p = 0.0046), and PLR (≥126.11 vs. <126.11, p = 0.0028). Univariate Cox analysis showed that NLR (hazard ratio [HR]: 2.469; 95% confidence interval [CI]: 1.416-4.306, p < 0.001), MLR (HR: 2.192, 95% CI: 1.319-3.643, p = 0.002) and PLR (HR: 1.696, 95% CI: 1.029-2.795, p = 0.038) were correlated alongside OS. Multivariate Cox analysis showed that NLR (HR: 2.036, 95% CI: 1.072-3.864, p = 0.030) was a separate OS risk variable. Additionally, the pN stage (HR: 3.163, 95% CI: 1.660-6.027, p < 0.001), NLR (HR: 2.530, 95% CI: 1.468-4.360, p < 0.001), MLR (HR: 2.229, 95% CI: 1.260-3.944, p = 0.006) and PLR (HR: 2.249, 95% CI: 1.300-3.889, p = 0.004) were connected to DFS. Multivariate Cox analysis showed that pN stage (HR: 3.098, 95% CI: 1.619-5.928, p < 0.001) was a separate DFS risk variable. CONCLUSION: The study demonstrates that NLR, MLR, and PLR play a convenient and cost-effective role in predicting survival and recurrence among individuals alongside central-type NSCLC having SL.

Assessing the global burden of mesothelioma: trends, socioeconomic influences, and asbestos exposure: a retrospective cohort study.

INTRODUCTION: Mesothelioma is an uncommon type of cancer which has received little attention. This study aims to evaluate the global disease burden; trends of mesothelioma by age, sex, and geographic locations; and its risk factors on the population level. METHODS: The Global Cancer Observatory in 2022 and 2019 Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. Multivariable linear regression analyses was conducted to explore the associations between mesothelioma incidence and key predictors including Human Development Index (HDI), Gross Domestic Product (GDP) per capita, and occupational asbestos exposure, adjusting for age and sex across global regions. RESULTS: This study identified 30,870 global cases of mesothelioma in 2022, with a higher age-standardized incidence rate (ASR) in males (0.25 per 100,000) compared to females (0.39 per 100,000). Geographical analysis indicated the highest disease burden in Northern Europe, with particular prevalence in more developed regions. The incidence was also significantly associated with higher Human Development Index (HDI), with a beta coefficient of 0.133 overall, and Gross Domestic Product (GDP) per capita, with a beta coefficient of 0.101. These socioeconomic factors exhibited stronger associations in the elderly population, especially with HDI (ß=0.512) and GDP (ß=0.389), than in adults. Additionally, occupational exposure to asbestos remained a significant risk factor across all groups, except for the younger adult population, with an overall beta of 0.122 for incidence. The temporal trend analysis revealed a general decrease in mesothelioma incidence, particularly in the 15-49 years age group. CONCLUSIONS: The analysis indicates a higher mesothelioma incidence in males and in developed regions, with marked disparities noted particularly in Northern Europe. Significant correlations with socioeconomic indicators-HDI and GDP-and occupational asbestos exposure were identified, particularly affecting the elderly. Despite a decline in global incidence, especially among younger individuals, persistent cases in females highlight the need for continued public health measures addressing both occupational and environmental exposures.

Effects of Heating Treatment on the Physicochemical and Volatile Flavor Properties of Argentinian Shortfin Squid (Illex argentinus).

In this study, the effect of different heating temperatures (80, 90, 100, and 121 °C) on the physicochemical and volatile flavor properties of fried mantles (Argentinian shortfin) was investigated. The squid mantles were soaked in a maltose syrup solution (20% w/v) for 10 s and fried in soybean oil for 10 s (160 °C), vacuum-packed, and processed at different temperatures for 10 min. Then, the squid mantles were subjected to colorimetric analysis, sensory evaluation, free amino acid analysis, and texture profile analysis. In addition, the volatile organic compounds (VOCs) in the squid mantles were analyzed. The results revealed that lower treating temperatures (80 and 90 °C) improved the chromatic and textural properties, along with organoleptic perception. Additionally, the content of amino acid in the squid mantles treated at 121 °C was significantly lower than that of the samples treated at other temperatures (p < 0.05). Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was used to detect 41 VOCs, including their monomers and dimers. Among these detected VOCs, the contents of alcohols, ketones, and pyrazines were positively correlated with temperature. However, the content of aldehydes in the squid mantles gradually decreased as the heating temperature increased (p < 0.05). The combined HS-GC-IMS and E-nose results revealed that the lower temperatures (80 and 90 °C) were more suitable for flavor development and practical processing. This study provides valuable information for properly controlling the heating process of squid products, as well as flavor and practical applications for the aquatic industry.

Evaluating the effectiveness of dual dye combination of indocyanine green and carbon nanoparticles with parathyroid hormone test in preserving parathyroid gland during papillary thyroid cancer surgery: a single-center retrospective cohort study.

Preserving the integrity of parathyroid glands is crucial in papillary thyroid cancer (PTC) surgery to avoid hypoparathyroidism. In recent years, two novel dyes, activated carbon nanoparticles (CNP) and indocyanine green (ICG), have been utilized to assist in parathyroid gland identification. However, the use of CNP or ICG alone can result in extravasation of dye or excessive fluorescence of non-parathyroid tissue, which can affect the accuracy of surgical outcomes by yielding false negative or false positive results. Therefore, it is important to further optimize the application of these two dyes in surgery. We analyzed case files of 124 PTC patients who underwent routine total or near-total thyroidectomy with bilateral lymph node dissection in the central region at the Affiliated People's Hospital of Ningbo University from January to November 2022. The patients were randomly divided into three groups based on the type of intraoperative dye used. The CNP group (n = 38) received an intra-thyroidal injection of CNP dye. The ICG group (n = 42) used the ICG near-infrared fluorescence endoscopy system to show parathyroid fluorescence. The group that received a combined approach of ICG and CNP (n = 44) leveraged the advantages of both methods that allow for positive development of ICG and negative development of CNP to identify and preserve the parathyroid gland during operation. The parathyroid hormone detection reagent (PTH test method) was employed to verify the highly suspected parathyroid tissue in all three groups. We analyzed intraoperative data pertaining to intraoperative parathyroid identification, misexcision, number of autotransplantation, and postoperative hypoparathyroidism among the three groups. Compared with the ICG group and the CNP group, the combined group demonstrated more prominent advantages in identifying average the number of lower parathyroid glands (1.93 ± 0.26, p = 0.015), reducing the average numberrate of misexcision (0.45 ± 0.5, p = 0.004), and reducing the incidence of postoperative temporary hypothyroidism (3/44, p = 0.015). The combined use of ICG and CNP dual-dye with PTH test method appears to be more effective in both identifying and protecting parathyroid glands during PTC surgery.

Competition between ocean thermal structure and tropical cyclone characteristics modulates ocean environmental responses in the Yellow and Bohai Seas.

To study the environmental responses of tropical cyclones (TCs) in continental shelf regions, TCs passing over the Yellow Sea and Bohai Sea (YBS) during 2002-2020 were investigated, with a special focus on how competition between ocean thermal structure and TC characteristics modulates ocean surface changes. The spatial distributions of the climatic mixed layer depth (MLD), accumulated wind forcing power index (WPi), accumulated sea surface temperature (SST) changes and accumulated chlorophyll (Chl-a) changes in the YBS were calculated. The linear regressions indicate that both the TC-induced SST cooling and TC-induced Chl-a increase are correlated with the TC wind speed rather than the translation speed, especially when the TC forcing depth (Zmixing) is greater than the MLD. Otherwise, both the changes in SST and Chl-a are correlated with the TC translation speed when Zmixing is shallower than the MLD. Further study has shown that whether TCs can break the MLD is also a key condition for oceanic responses. In the southern YBS, which has a deep-sea basin and MLD, the TC wind speed is the major factor affecting SST cooling and Chl-a increase, as TCs need more strength to reach the MLD. However, in the northern YBS, which has the shallowest sea basin and MLD, even weak TCs can easily break the MLD and reach the seabed; thus, ocean surface changes are associated mainly with the TC translation speed. The composite results reveal that both the maximum SST cooling center (1.64 °C) and the maximum Chl-a increasing center (0.14 log10(mg/m3)) are located on the right and behind the TC center, respectively. In addition, TC-induced SST cooling and Chl-a increase were initiated two days prior to TC passage and then reached their maximum values after 1 day. It takes approximately 7-8 days for the Chl-a concentration to recover, but it takes a much longer time (>15 days) for the SST to recover.

Entropy-Driven Phase Transition in Nanonucleation via Reciprocal Relations.

Depletion forces, commonly modeled with rigid body assumptions, inadequately describe nanoparticle behavior. This study introduces the roles of Soret and Dufour effects in nanoparticle systems, focusing on mass and energy gradient interchange. The Dufour effect drives energy flow through mass gradients, which implies the possibility of driving the energy flow near the nanoparticles to induce phase transitions via manipulating the monomer concentrations. Our experimental platform confirmed these theories, synthesizing HCP quantum dots from Au, Ag, Pd, and mixed halide perovskites under varied precursor concentrations. By analyzing energy flow and nucleation dynamics through the Dufour effect, we mapped phase transition thresholds, linking them to material entropy. This study provides insight into nanoparticle assembly and phase behavior, highlighting the significance of entropy in nucleation dynamics.

Clinical and Imaging Characteristics of Metastatic Orbital Tumours in North China.

Purpose: This study was designed to review the primary sites, clinical manifestations, imaging features, treatments, and outcomes of 36 patients with orbital metastasis in North China. Methods: This was a retrospective review of 36 patients with orbital metastasis at Tianjin Eye Hospital between January 2010 and December 2020 in North China as well as a review of the literature. Results: Thirty-six patients were included in the study; 17 were male, and 19 were female, with an age range of 1-82 years (average 54.9 ± 19.8 years). All the tumours were unilateral. The mean duration from the onset of orbital signs to presentation at the hospital was 2.4 months (range 1-10 months). Breast carcinoma, gastrointestinal tract carcinoma, and lung carcinoma were the most common histological types. Proptosis, ocular pain, and diplopia were the most common clinical manifestations. The superior orbit was the most common quadrant involved. All patients received comprehensive therapy, including surgery, radiotherapy, or chemotherapy. The average follow-up time was 2.45 years (range 7 months to 5.5 years). Ten patients in this study died as a result of disseminated metastasis from the primary tumour. Conclusions: In North China, the most common primary cancer that metastasizes to the orbit is breast cancer, followed by gastrointestinal tract carcinoma and lung cancer. The increasing trend of orbital gastrointestinal tract metastases in North China in recent years is noteworthy. The survival rate of patients with orbital metastasis of neuroblastoma is low.

Investigation of the Alternations in Lipid Oxidation and Lipase Activity in Air-Dried Hairtail (Trichiurus lepturus) during Chilled Storage.

The effects of water content and water activity on the lipid stability of air-dried hairtail (Trichiurus haumela) were investigated during chilled storage. Air-dried hairtail samples with high and low water contents were comparatively analyzed over 8 days of storage at 4 °C. The results indicated that the decreases in water activity and increases in the NaCl content significantly inhibited lipid oxidation in the air-dried hairtail samples. The peroxidation value (PV), conjugated diene value (CD), thiobarbituric acid reactive substance (TBARS) value, and p-anisidine value (p-AnV) of the air-dried hairtail significantly increased with the extension of storage time. The low water content significantly inhibited the activity of neutral and alkaline lipase, in addition to lipoxygenase, and retarded the rapid increases in the non-esterified fatty acid (NEFA) content in the hairtail samples. The correlation analysis results showed that the TBARS, p-AnV, and lipase activity were positively correlated in the air-dried hairtail samples, and the lower water content significantly inhibited the progress of lipid oxidation. This study offers a theoretical framework for the industrial processing and storage of air-dried hairtail products.

Effect of Preheating Whey Protein Concentrate on the Stability of Purple Sweet Potato Anthocyanins.

Anthocyanins (ANs) have strong antioxidant activities and can inhibit chronic diseases, but the instability of ANs limits their applications. The conservation of preheating whey protein concentrate (WPC) on the stability of purple sweet potato ANs was investigated. The retention of ANs in WPC-ANs was 85.88% after storage at 25 °C for 5 h. WPC-ANs had higher retention of ANs in heating treatment. The retention rates of ANs in WPC-ANs exposed to light and UV lamps for 6 h were 78.72% and 85.76%, respectively. When the concentration of H2O2 was 0.50%, the retention rate of ANs in the complexes was 62.04%. WPC-ANs' stability and antioxidant activity were improved in simulated digestive juice. The WPC-ANs connection was static quenching, and the binding force between them was a hydrophobic interaction at one binding site, according to the fluorescence quenching spectroscopy. UV-visible absorption spectroscopy and Fourier transform infrared spectroscopy (FTIR) analysis further indicated that the secondary structure and microenvironment of amino acid residues in WPC can be impacted by the preheating temperature and preheating times of WPC. In conclusion, preheating WPC can successfully preserve the stability of purple sweet potato ANs by binding to them through a non-covalent interaction.

A SiO2 Hybrid Enzyme-Based Biosensor with Enhanced Electrochemical Stability for Accuracy Detection of Glucose.

A novel enzyme-based biosensor for glucose detection is successfully developed using layer-by-layer assembly technology. The introduction of commercially available SiO2 was found to be a facile way to improve overall electrochemical stability. After 30 CV cycles, the proposed biosensor could retain 95% of its original current. The biosensor presents good detection stability and reproducibility with the detection concentration range of 1.96 × 10-9 to 7.24 × 10-7 M. This study demonstrated that the hybridization of cheap inorganic nanoparticles was a useful method in preparing high-performance biosensors with a much lower cost.

Comparison of physicochemical and volatile flavor properties of neon flying squid (Ommastrephes bartramii), jumbo squid (Dosidicus gigas), and Argentine shortfin squid (Illex argentinus) during chilled storage.

The difference and similarities in the physicochemical and volatile flavor properties were determined in neon flying squid (OB), jumbo squid (DG), and Argentine squid (IA) mantles during 8 days of chilled storage. Physicochemical analysis indicated the chilled conditions induced rapid increases in pH value, total volatile basic nitrogen (TVBN), and carbonyl and malondialdehyde (MDA) content of the three squid species. In addition, myofibrillar protein (MP) content decreased and springiness in the OB, DG, and IA mantle samples declined with the extension of storage time. Importantly, OB mantles presented less chemical stability than the other two squid samples during 8 days of chilled storage. In addition, histological observations suggest DG mantle tissues presented more compact structures than those of the other two samples. Volatile flavor analysis showed propionaldehyde, 3-pentanone, trimethylamine, 3-furanmethanol, 2-methyl butyric acid, and 2-butanone were highly abundant in the squid mantles after storage, likely resulting from decomposition, oxidation, and degradation of proteins and lipids in the squid mantle, which varied with different squid species. The findings provide insight into the performance of three squid species during chilled storage.

Predictors of impaired effectiveness of carbon nanoparticle-based central lymph node tracing in patients who underwent surgery for papillary thyroid cancer: A retrospective cohort study.

Carbon nanoparticles (CNs) are used in papillary thyroid cancer (PTC) surgery to facilitate central lymph node dissection (CLND) and protect the parathyroid glands (PGs). However, some cases develop hypoparathyroidism after using CNs. This cohort study was undertaken to explore the predictors of the reduced effectiveness of CNs. Data on patients with PTC who underwent surgery wherein CNs were used during CLND were reviewed retrospectively. Patients who did not develop hypoparathyroidism and developed hypoparathyroidism were classified into Group A and B, respectively. Demographic and clinical characteristics were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed on related variables. The receiver operating characteristic curve was used to evaluate the predictors of the binary logistic model and the cutoff value of each predictor was obtained. A total of 265 patients were included. Compared with Group A, the patients in Group B had a higher body mass index (BMI) (P = .003), were more frequently associated with Hashimoto thyroiditis (HT) (P = .001), and tumors were larger in size (P = .026). Multivariate logistic regression analyses were performed on these variables and showed that HT (P = .001) and tumor size (P = .001) predicted the impaired role of CNs. CNs are not always useful in protecting PG function in patients who undergo CLND for PTC. In patients with coexisting HT (blood thyroid peroxidase antibody [TPOAb] level higher than 44.0 IU/mL or blood anti-thyroglobulin antibody [ATG] level higher than 125.0 IU/mL) or a tumor size exceeding 1.1 cm in diameter, the protective role of CNs may be impaired.

One-pot self-assembly fabrication of chitosan coated hollow sphere for pH/ glutathione dual responsive drug delivery.

Chitosan-coated poly (methacrylic acid) (PMAA) hollow spheres with 64 ± 3% drug loading capacity and low drug leakage (7 ± 2%, 54 h) were prepared through a novel one-pot two-step self-assembly process. Site-specific doxorubicin (DOX) loading and chitosan coating were achieved by electrostatic interaction to fulfill efficient drug loading and well-controlled drug release behavior. In vitro drug release profile revealed the pH and glutathione (GSH) dual responsive fast triggered drug release behavior, reaching 62 ± 3% during the first 10 h. And completely drug release could be achieved in 54 h. The high drug content and sensitive tumor microenvironment responsibility lead to similar anti-cancer efficiency with free doxorubicin in in vitro MTT assay. This self-assembly guided one-pot two-step fabrication process was proved to be an effective and convenient way to prepare the well-defined multi-layer structure and might be further employed in fabricating high-performance drug delivery systems.

Fluorescence determination of chloramphenicol in milk powder using carbon dot decorated silver metal-organic frameworks.

Carbon dot decorated silver metal-organic frameworks (CD-MOFs) were successfully synthesized at room temperature by adding CDs during the formation of Ag-MOFs. The CD-MOFs have excellent optical property, stability, and good fluorescence intensity in water compared with other solvents. The fluorescence intensity of CD-MOFs was relatively stable in the range of pH 5-9. It was used to construct a sensitive and reliable fluorescent sensor for the determination of chloramphenicol (CAP). When the CAP was introduced into the CD-MOFs, the fluorescence at 427 nm was quenched at the excitation wavelength of 332 nm. Wide linear relationships were established for CAP with a limit of detection of 44 nM. The fluorescent sensor has been applied to determine CAP in milk powder sample with satisfied recoveries (104 to 109%) and good precision (< 4%). The photoinduced electron-transfer is the most important mechanism contributing to the fluorescence quenching. The synthesized CD-MOFs provide a new orientation for fluorescence determination of chloramphenicol in real samples.

Clinical characteristics, surgical treatments, prognosis, and prognostic factors of primary tracheal cancer patients: 20-year data of the National Cancer Center, China.

Background: Tracheal cancer is a rare malignancy of which previous reports are mostly case reports or small series. Herein, we sought to evaluate the clinical characteristics, surgical treatments, and prognosis of surgically treated primary tracheal cancer patients. Methods: Patients with primary tracheal cancer who had received surgery in our center between January 2000 and December 2020 were enrolled. Clinical and surgical features were collected by retrospective review of medical records and follow-up was done by telephone interview. The statistical tests were two-sided. Results: A total of 128 patients were included in the study, 49.2% of whom were male, and the average age was 49.4±13.6 years. The most common histological subtype was adenoid cystic carcinoma (ACC; 78/128, 60.9%) followed by squamous cell carcinoma (SCC; 24/128, 18.8%). The percentage of tumors located in the cervical trachea, thoracic trachea, and carina were 50%, 41.4%, and 8.6%, respectively. Among those analyzed, 32.0% of the primary tumors had invaded adjacent organs (E2 disease) and 7.8% of patients had lymph node involvement. Tracheal resection plus reconstruction (with or without thyroidectomy) was the predominant surgical procedure, followed by carinal resection with neocarina. Radical resection (R0) was performed on 61.7% of patients and 63 (49.2%) patients received adjuvant therapy. Compared to ACC, SCC patients had significantly higher risk of tumor of the carina, nodal metastasis, and complications. The 5-year overall survival (OS) for the entire cohort was 84.5% and factors associated with poor prognosis included carinal tumor [hazard ratio (HR) =10.206; P<0.001], E2 disease (HR =8.870; P=0.001), lymph node metastasis (HR =15.197; P<0.001), and postoperative complications (HR =12.497; P=0.001). Conclusions: The two major subtypes of tracheal cancer are ACC and SCC. Tumor location, extension, lymph node metastasis and complication are survival related factors for surgically treated patients.

Regulation of drug release performance using mixed doxorubicin-doxorubicin dimer nanoparticles as a pH-triggered drug self-delivery system.

A mixed drug self-delivery system (DSDS) with high drug content (>50%) was developed to regulate pH-triggered drug release, based on two doxorubicin (DOX)-DOX dimmers: D-DOXADH and D-DOXcar conjugated with acid-labile dynamic covalent bonds (hydrazone and carbamate, respectively) and stabilized with PEGylated D-DOXADH (D-DOXADH-PEG). Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them, pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS. Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios. The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates. The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.

27-hydroxycholesterol linked high cholesterol diet to lung adenocarcinoma metastasis.

Dietary cholesterol has been implicated to promote lung cancer. Lung adenocarcinoma (LAC) is a main type of lung cancer, whereas the functional mechanism of cholesterol in LAC remained largely unknown. In the present study, we evidenced that cholesterol promoted cell proliferation and invasion of LAC in vitro as well as LAC metastasis in vivo. Cyp27A1 knockdown reduced the cholesterol-induced LAC cells proliferation and invasion. In contrast, Cyp7B1 knockdown enhanced the effect of cholesterol on LAC cells proliferation and invasion. Furthermore, Cyp27A1 deficiency remarkably reduced high cholesterol-induced LAC metastasis in vivo. Mechanism investigation demonstrated that exposure of LAC cells to 27-hydroxycholesterol induced the phosphorylation of AKT and NFκB p65, and promoted the expression of peptidylprolyl isomerase B (PPIB), especially in the coculture with THP1-derived macrophage. Meanwhile, 27-hydroxycholesterol induced the secretion of FGF2 and IL-6, which contributed to the expression of snail and vimentin. Luciferase report assay and ChIP assay confirmed that NFκB p65 controlled the transcription of PPIB. Inhibiting NFκB p65 activation reduced PPIB expression. PPIB inhibition reduced 27-hydroxycholesterol-induced expression of snail and vimentin. These results indicated that 27-hydroxycholesterol linked high cholesterol and LAC metastasis by regulating NFκB/PPIB axis and the secretion of FGF2 and IL-6.

The combination of novel immune checkpoints HHLA2 and ICOSLG: A new system to predict survival and immune features in esophageal squamous cell carcinoma.

Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma (ESCC) have shown promising results. However, a comprehensive understanding of B7-CD28 family members in ESCC is still limited. This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC. We collected 179 cases from our previously published microarray data and 86 cases with qPCR data. Specifically, 119 microarray data (GSE53624) were used as a training set, whereas the remaining 60 microarray data (GSE53622), all 179 microarray data (GSE53625) and an independent cohort with 86 qPCR data were used for validation. The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence. We examined 13 well-defined B7-CD28 family members and identified 2 genes (ICSOLG and HHLA2) with the greatest prognostic value. A system based on the combination HHLA2 and ICOSLG (B7-CD28 signature) was constructed to distinguish patients as high- or low-risk of an unfavorable outcome, which was further confirmed as an independent prognostic factor. As expected, the signature was well validated in the entire cohort and in the independent cohort, as well as in different clinical subgroups. The signature was found to be closely related to immune-specific biological processes and pathways. Additionally, high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels. Collectively, we built the first, practical B7-CD28 signature for ESCC that could independently identify high-risk patients. Such information may help inform immunotherapy-based treatment decisions for patients with ESCC.

Authentic Intelligent Machine for Scaling Driven Discovery: A Case for Chiral Quantum Dots.

The scaling laws have long been used as evidence of science where many fundamental physics laws emerge. As emerging nanomaterials, quantum dots are also sensitive to scaling because of their strong size effect. In this work, we developed the chiral dielectric theory based on the exciton absorption mechanism to explain the increment of the dielectric constant from chirality via its dimensionality. To help researchers discover and develop scaling relevant theories, the Authentic Intelligent Machine (AIM) protocol was developed to generate and interpret experimental data in an analytical and scaling-oriented manner. We show how the AIM protocol interprets spectra such as transient absorption data of chiral quantum dots with theories, where discrepancies concerning the dielectric constant were discovered. Examples for applying the AIM protocol on other spectra, such as absorption spectra and photoluminescence spectra, are also given.