Protection of Si Nanowires against Aß Toxicity by the Inhibition of Aß Aggregation.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid beta (Aß) plaques in the brain. Aß1-42 is the main component of Aß plaque, which is toxic to neuronal cells. Si nanowires (Si NWs) have the advantages of small particle size, high specific surface area, and good biocompatibility, and have potential application prospects in suppressing Aß aggregation. In this study, we employed the vapor-liquid-solid (VLS) growth mechanism to grow Si NWs using Au nanoparticles as catalysts in a plasma-enhanced chemical vapor deposition (PECVD) system. Subsequently, these Si NWs were transferred to a phosphoric acid buffer solution (PBS). We found that Si NWs significantly reduced cell death in PC12 cells (rat adrenal pheochromocytoma cells) induced by Aß1-42 oligomers via double staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and fluorescein diacetate/propyl iodide (FDA/PI). Most importantly, pre-incubated Si NWs largely prevented Aß1-42 oligomer-induced PC12 cell death, suggesting that Si NWs exerts an anti-Aß neuroprotective effect by inhibiting Aß aggregation. The analysis of Fourier Transform Infrared (FTIR) results demonstrates that Si NWs reduce the toxicity of fibrils and oligomers by intervening in the formation of ß-sheet structures, thereby protecting the viability of nerve cells. Our findings suggest that Si NWs may be a potential therapeutic agent for AD by protecting neuronal cells from the toxicity of Aß1-42.

Life-threatening gastrointestinal bleeding caused by cytomegalovirus-induced duodenal ulcer in a patient with AIDS: A case report.

Background: The reasons for gastrointestinal bleeding among patients with acquired immune deficiency syndrome (AIDS) were complex. Here we present an unusual case of life-threatening gastrointestinal bleeding caused by a cytomegalovirus-induced duodenal ulcer in an AIDS patient. Case presentation: A 31-year-old male with AIDS was admitted on July 18, 2023, complaining of abdominal pain for 38 days and intermittent hematochezia for 12 days. During his hospitalization, gastrointestinal endoscopy attributed gastrointestinal bleeding to a giant duodenal ulcer. Furthermore, cytomegalovirus(CMV) infection was confirmed as the reason for the ulcer through metagenomic next-generation sequencing (mNGs), hematoxylin-eosin(HE) staining, and immunohistochemistry (IHC) staining for the biopsy tissue. The patient's gastrointestinal bleeding was stopped by interventional embolization. Following a 4-week course of anti-CMV treatment, the giant duodenal ulcer was cured. Conclusions: For AIDS patients with gastrointestinal bleeding, the CMV-induced gastrointestinal ulcer should be considered. Comprehensive mothods (mNGs, HE staining and IHC staining for biopsy tissue) were benefit for confirmed diagnosis. Beside anti-CMV treatment, the interventional embolization is a choice for hemostasis.

Aspirin use and changes in circulating tumor DNA levels in patients with metastatic colorectal cancer.

The study aimed to investigate the effects of aspirin on patients with metastatic colorectal cancer, focusing on circulating tumor DNA levels and bone tissue. Two groups (A and B) of ten patients with osteoporosis were selected for the study. Bone tissue samples were obtained from the patients and cultured under sterile conditions. The aspirin group showed a significant decrease in circulating tumor DNA levels and an increase in bone tissue density compared to the control group. Additionally, osteoblast apoptosis was reduced, while proliferation was enhanced in the aspirin group. The protein pAkt related to the PI3K/Akt signaling pathway was upregulated in the aspirin group. These results indicate that aspirin can effectively lower circulating tumor DNA levels, promote bone tissue proliferation, inhibit apoptosis, and activate the PI3K/Akt signaling pathway, thereby influencing bone cell function. These findings provide a basis for aspirin's potential application in treating metastatic colorectal cancer and encourage further research on its mechanism and clinical use.

Parental experiences orchestrate locust egg hatching synchrony by regulating nuclear export of precursor miRNA.

Parental experiences can affect the phenotypic plasticity of offspring. In locusts, the population density that adults experience regulates the number and hatching synchrony of their eggs, contributing to locust outbreaks. However, the pathway of signal transmission from parents to offspring remains unclear. Here, we find that transcription factor Forkhead box protein N1 (FOXN1) responds to high population density and activates the polypyrimidine tract-binding protein 1 (Ptbp1) in locusts. FOXN1-PTBP1 serves as an upstream regulator of miR-276, a miRNA to control egg-hatching synchrony. PTBP1 boosts the nucleo-cytoplasmic transport of pre-miR-276 in a "CU motif"-dependent manner, by collaborating with the primary exportin protein exportin 5 (XPO5). Enhanced nuclear export of pre-miR-276 elevates miR-276 expression in terminal oocytes, where FOXN1 activates Ptbp1 and leads to egg-hatching synchrony in response to high population density. Additionally, PTBP1-prompted nuclear export of pre-miR-276 is conserved in insects, implying a ubiquitous mechanism to mediate transgenerational effects.

Network pharmacology integrated with experimental validation to elucidate the mechanisms of action of the Guizhi-Gancao Decoction in the treatment of phenylephrine-induced cardiac hypertrophy.

CONTEXT: The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown. OBJECTIVE: This study explores the mechanisms of GGD against cardiac hypertrophy. MATERIALS AND METHODS: Network pharmacology analysis was carried out to identify the potential targets of GGD. In vivo experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). In vitro experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10-5 g/mL) and GGD (10-5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested via real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis. RESULTS: Network pharmacology identified ADORs among those of the core targets of GGD. In vitro experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC50 of 5.484 × 10-6 g/mL). In vivo data shown that GGD attenuated PE-induced ventricular wall thickening. In vitro and in vivo data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD. DISCUSSION AND CONCLUSIONS: Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.

Analysis of hepatitis B virus infection in 1424 patients with different pathological types of lymphoma (2018-2022): A real-world, retrospective study.

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.

Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

KIAA1429 regulates lung adenocarcinoma proliferation and metastasis through the PI3K/AKT pathway by modulating ARHGAP30 expression.

BACKGROUND: Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6-methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD. METHODS: This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP-seq), as well as RNA stability tests to ascertain the half-life and stability of the target genes. RESULTS: The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP-seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis. CONCLUSION: This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular-based interventions for LUAD.

The clinical effectiveness and safety of Zone III REBOA for resection of sacropelvic tumors in patients older than 70 years.

BACKGROUND: REBOA is a method used to manage bleeding during surgery involving sacropelvic tumors. Nevertheless, studies on the use of REBOA among elderly people are lacking. The aim of this research was to investigate the efficacy and safety of Zone III REBOA in patients aged more than 70 years. METHODS: A comparative study was conducted using case-control methods. A group of patients, referred to as Group A, who were younger than 70 years was identified and paired with a comparable group of patients, known as Group B, who were older than 70 years. Continuous monitoring of physiological parameters was conducted, and blood samples were collected at consistent intervals. RESULTS: Totally, 188 participants were enrolled and received REBOA. Among the 188 patients, seventeen were aged more than 70 years. By implementing REBOA, the average amount of blood loss was only 1427 ml. Experiments were also conducted to compare Group A and Group B. No notable differences were observed in terms of demographic variables, systolic blood pressure (SBP), arterial pH, lactate levels, blood creatinine levels, potassium levels, or calcium levels at baseline. Additionally, after the deflation of the REBOA, laboratory test results, which included arterial pH, lactate, potassium concentration, calcium concentration, and blood creatinine concentration, were not significantly different (P > 0.05). CONCLUSION: This study indicated that in selected patients aged more than 70 years can achieve satisfactory hemodynamic and metabolic stability with Zone III REBOA. LEVEL OF EVIDENCE: Therapeutic study, Level III.

Nasal filter reveal exposure risks of inhalable particulates and heavy metals in urban women.

Urban populations, especially women, are vunerable to exposure to airborne pollution, particularly inhalable particulates (PM10). Thus, more accurate measurement of PM10 levels and evaluating their health effects is critical for guiding policy to improve human health. Previous studies obtained personal PM10 with time-weighted average by air filter-based sampling (AFS), which ignores individual differences and behavioral patterns. Here, we used nasal filters instead of AFS to obtain actual inhaled PM10 under short-term exposure for urban dwelling women during a severe haze event in Beijing in 2016. The levels of six heavy metals such as As, Cd, Ni, Cr, Pb, and Co in PM10 were investigated, and carcinogenic and non-carcinogenic risks evaluated based on an adjusted US EPA health risk assessment model. The health endpoints for urban dwelling women were further assessed through an exposure-reponse model. We found that the hourly inhaled dose of PM10 obtained through the nasal filter was about 2.5-17.6 times that obtained by AFS, which also resulted in 4.41-11.30 times more morbidity than estimated by AFS (p < 0.05). Proximity to traffic emissions resulted in greater exposure to particulate matter (>18.8 µg/kg·h) and heavy metals (>2.2 ng/kg·h), and these populations are therefore at greatest risk of developing non-cancer (HI = 4.16) and cancer (Rt = 7.8 × 10-3) related morbities.

Construction of a Cancer Stem Cell related Histone Acetylation Regulatory Genes Prognostic Model for Hepatocellular Carcinoma via Bioinformatics Analysis: Implications for Tumor Chemotherapy and Immunity.

BACKGROUND: Cancer stem cells (CSC) play an important role in the development of Liver Hepatocellular Carcinoma (LIHC). However, the regulatory mechanisms between acetylation- associated genes (HAGs) and liver cancer stem cells remain unclear. OBJECTIVE: To identify a set of histone acetylation genes (HAGs) with close associations to liver cancer stem cells (LCSCs), and to construct a prognostic model that facilitates more accurate prognosis assessments for LIHC patients. METHODS: LIHC expression data were downloaded from the public databases. Using mRNA expression- based stemness indices (mRNAsi) inferred by One-Class Logistic Regression (OCLR), Differentially Expressed Genes (DEGs) (mRNAsi-High VS. mRNAsi-Low groups) were intersected with DEGs (LIHC VS. normal samples), as well as histone acetylation-associated genes (HAGs), to obtain mRNAsi-HAGs. A risk model was constructed employing the prognostic genes, which were acquired through univariate Cox and Least Shrinkage and Selection Operator (LASSO) regression analyses. Subsequently, independent prognostic factors were identified via univariate and multivariate Cox regression analyses and then a nomogram for prediction of LIHC survival was developed. Additionally, immune infiltration and drug sensitivity analysis were performed to explore the relationships between prognostic genes and immune cells. Finally, the expressions of selected mRNAsi-HAGs were validated in the LIHC tumor sphere by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) assay and western blot analysis. RESULTS: Among 13 identified mRNAsi-HAGs, 3 prognostic genes (HDAC1, HDAC11, and HAT1) were selected to construct a risk model (mRNAsi-HAGs risk score = 0.02 * HDAC1 + 0.09 * HAT1 + 0.05 * HDAC11). T-stage, mRNAsi, and mRNAsi-HAGs risk scores were identified as independent prognostic factors to construct the nomogram, which was proved to predict the survival probability of LIHC patients effectively. We subsequently observed strongly positive correlations between mRNAsi-HAGs risk score and tumor-infiltrating T cells, B cells and macrophages/monocytes. Moreover, we found 8 drugs (Mitomycin C, IPA 3, FTI 277, Bleomycin, Tipifarnib, GSK 650394, AICAR and EHT 1864) had significant correlations with mRNAsi-HAGs risk scores. The expression of HDAC1 and HDAC11 was higher in CSC-like cells in the tumor sphere. CONCLUSION: This study constructed a mRNAsi and HAGs-related prognostic model, which has implications for potential immunotherapy and drug treatment of LIHC.

Voacangine mitigates oxidative stress and neuroinflammation in middle cerebral artery occlusion-induced cerebral ischemia/reperfusion injury by averting the NF-κBp65/MAPK signaling pathways in rats.

Ischemic stroke is a leading cause of human mortality. Cerebral ischemia-reperfusion injury (CI/RI) is a primary cause of stroke. Ischemia-reperfusion (I/R) resulting in oxidative stress and inflammatory events may lead to severe neuronal impairments. Thus, anti-oxidative and anti-inflammatory mediators that can alleviate post-I/R neuronal injuries are required for the treatment of CI/RI. An alkaloid, voacangine (VCG) is a recognized antioxidant, anti-inflammatory, and anticancer agent. Hence, the current study intended to explore the neuroprotective potential and the principal mechanisms of VCG in CI/RI. The experimental rats were divided into four sets: control, I/R-induced, I/R + VCG (2.5 mg/kg), I/R + VCG (5 mg/kg). CI/RI was induced by implanting a thread into the middle cerebral artery occlusion (MCAO) model. Brain damages were assessed on the basis of brain edema, brain infarct volume, neurological deficit score, histopathology, oxidative stress, and neuroinflammation. Results revealed that VCG inhibited the triggering of NLRP3 inflammasome, pro-inflammatory cytokines, lipid peroxidation, but enhanced the antioxidant status in MCAO rats. Furthermore, VCG treatment averted brain damage by I/R, neuroinflammation, and oxidative stress by suppressing NF-κBp65/MAPK pathways. The results of the study provide pertinent insights pertaining to the role of VCG as a potential neuroprotective agent against ischemic stroke.

Effects of Cu2O nanoparticles on the kinetic characteristics of rapid chlorophyll fluorescence induction and related genes in wheat seedlings.

Metal nanoparticles could be accumulated in soils, which threatens the ecological stability of crops. Investigating the effects of cuprous oxide nanoparticles (Cu2O-NPs) on photosystem Ⅱ (PSⅡ) of wheat seedling leaves holds considerable importance in comprehending the implications of Cu2O-NPs on crop photosynthesis. Following the hydroponic method, we investigated the effects of 0, 10, 50, 100, and 200 mg·L-1 Cu2O-NPs on chlorophyll fluorescence induction kinetics and photosynthetic-related genes in wheat seedlings of "Zhoumai 18". The results showed that, with the increases of Cu2O-NPs concentrations, chlorophyll contents in wheat leaves decreased, and the standardization of the OJIP curve showed a clearly K-phase (ΔK＞0). Cu2O-NPs stress increased the parameters of active PSⅡ reaction centers, including the absorption flux per active RC (ABS/RC), the trapping flux per active RC (TRo/RC), the electron transport flux per active RC (ETo/RC), and the dissipation flux per active RC (DIo/RC). Cu2O-NPs stress decreased the parameters of PSⅡ energy distribution ratio including the maximum quantum yield of PSⅡ (φPo), the quantum yield of electron transport from QA (φEo), and the probability that a trapped exciton moved an electron further than QA (Ψo), while increased the quantum ratio for heat dissipation (φDo). Moreover, there was a decrease in photosynthetic quantum yield Y(Ⅱ), photochemical quenching coefficient (qP), net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) of leaves with the increases of Cu2O-NPs concentration. Under Cu2O-NPs stress, the expression levels of genes which included PSⅡ genes (PsbD, PsbP, Lhcb1), Rubisco large subunit genes (RbcL), cytochrome b6/f complex genes (PetD, Rieske), and ATP synthase genes (AtpA, AtpB, AtpE, AtpI) were downregulated. These results indicated that Cu2O-NPs stress altered the activity and structure of PSⅡ in wheat seedlings, affected the activity of PSⅡ reaction centers, performance parameters of PSⅡ donor and acceptor sides. PSⅡ related genes were downregulated and exhibited significant concentration effects.

Cathodic Deposition-Assisted Synthesis of Thin Glass MOF Films for High-Performance Gas Separations.

Glass metal-organic framework (MOF) films can be fabricated from their crystalline counterparts through a melt-quenching process and are prospective candidates for gas separation because of the elimination of the grain boundaries in crystalline MOF films. However, current techniques are limited to producing glass MOF films with a thickness of tens of micrometers, which leads to ultralow gas permeances. Here, we report a novel cathodic deposition-assisted synthesis of glass ZIF-62 films with a thickness as low as ~1 µm. Electrochemical analyses and deposition experiments suggest that the cathodic deposition can lead to pure crystalline ZIF-62 films with a controllable thickness of ~2 µm to ~15 µm. Accordingly, glass ZIF-62 films with a thickness of ~1 µm to ~10 µm can be obtained after a thermal treatment. The fabricated defect-free glass ZIF-62 film measuring 2 µm in thickness shows a remarkable CO2/N2 and CO2/CH4 selectivity of 31.4 and 33.4, respectively, with a CO2 permeance which is over 30 times higher than the best-performing glass ZIF-62 films in literature.

g-C3N4 as ballistic electron transport "Tunnel" in CsPbBr3-based ternary photocatalyst for gas phase CO2 reduction.

Perovskite CsPbBr3 quantum dot shows great potential in artificial photosynthesis, attributed to its outstanding optoelectronic properties. Nevertheless, its photocatalytic activity is hindered by insufficient catalytic active sites and severe charge recombination. In this work, a CsPbBr3@Ag-C3N4 ternary heterojunction photocatalyst is designed and synthesized for high-efficiency CO2 reduction. The CsPbBr3 quantum dots and Ag nanoparticles are chemically anchored on the surface of g-C3N4 sheets, forming an electron transfer tunnel from CsPbBr3 quantum dots to Ag nanoparticles via g-C3N4 sheets. The resulting CsPbBr3@Ag-C3N4 ternary photocatalyst, with spatial separation of photogenerated carriers, achieves a remarkable conversion rate of 19.49 µmol·g-1·h-1 with almost 100 % CO selectivity, a 3.13-fold enhancement in photocatalytic activity as compared to CsPbBr3 quantum dots. Density functional theory calculations reveal the rapid CO2 adsorption/activation and the decreased free energy (0.66 eV) of *COOH formation at the interface of Ag nanoparticles and g-C3N4 in contrast to the g-C3N4, leading to the excellent photocatalytic activity, while the thermodynamically favored CO desorption contributes to the high CO selectivity. This work presents an innovative strategy of constructing perovskite-based photocatalyst by modulating catalyst structure and offers profound insights for efficient CO2 conversion.

Direct contact between tumor cells and platelets initiates a FAK-dependent F3/TGF-ß positive feedback loop that promotes tumor progression and EMT in osteosarcoma.

Platelets have received growing attention for their roles in hematogenous tumor metastasis. However, the tumor-platelet interaction in osteosarcoma (OS) remains poorly understood. Here, using platelet-specific focal adhesion kinase (FAK)-deficient mice, we uncover a FAK-dependent F3/TGF-ß positive feedback loop in OS. Disruption of the feedback loop by inhibition of F3, TGF-ß, or FAK significantly suppresses OS progression. We demonstrate that OS F3 initiated the feedback loop by increasing platelet TGF-ß secretion, and platelet-derived TGF-ß promoted OS F3 expression in turn and modulated OS EMT process. Immunofluorescence results indicate platelet infiltration in OS niche and we verified it was mediated by platelet FAK. In addition, platelet FAK was proved to mediate platelet adhesion to OS cells, which was vital for the initiation of F3/TGF-ß feedback loop. Collectively, these findings provide a rationale for novel therapeutic strategies targeting tumor-platelet interplay in metastatic OS.

Safety and Efficacy Analysis of Radical Surgery for 403 Patients with Colon Cancer over 80 Years Old.

Aim: To investigate the safety and efficacy of radical surgery in colon cancer patients over 80 years old. Methods: Data from colon cancer patients aged ≥80 years who underwent radical surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences and affiliated Heji Hospital of Changzhi Medical College from January 2011 to December 2022 were retrospectively analysed. Data on clinical characteristics, pathological features, perioperative data, and long-term prognosis were collected. Severe complications were classified as grade III-V. Logistic regression models were used to identify the risk factors for severe postoperative complications, and a Cox regression model was used to determine prognostic variables. Results: A total of 403 eligible patients were included in the study. A total of 118 (29.3%) patients developed postoperative complications, of which 51 (12.7%) experienced grade 3-5 severe complications. Two (0.5%) patients died of pulmonary embolism and myocardial infarction during the perioperative period. The multivariate logistic regression analysis showed that preoperative albumin levels <35 g/L and right colon cancer were independent risk factors for grade 3-5 postoperative complications. In terms of prognosis, multivariate analysis revealed that overall survival was significantly affected by TNM stage III and grade 3-4 postoperative complications. In addition, TNM stage III and perineural invasion were the independent prognostic factors for disease-free survival. Conclusion: Radical surgery can be performed safely in elderly colon cancer patients aged over 80 years, with an acceptable morbidity and mortality. Patients with preoperative albumin levels <35 g/L or tumors in the right colon should be alerted to the development of severe postoperative complications. In addition, the occurrence of severe complications can significantly affect the prognosis of elderly colon cancer patients.

circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

A high-throughput differential scanning fluorimetry method for rapid detection of thermal stability and iron saturation in lactoferrin.

Thermal stability and iron saturation of lactoferrin (LF) are of great significance not only for the evaluation of the biological activities of LF but also for the optimization of the isolation and drying process parameters. Differential scanning calorimetry (DSC) is a well-established and efficient method for thermal stability and iron saturation detection in LF. However, multiple DSC measurements are typically performed sequentially, thus time-consuming and low throughput. Herein, we introduced the differential scanning fluorimetry (DSF) approach to overcome such limitations. The DSF can monitor LF thermal unfolding with a commonly available real-time PCR instrument and a fluorescent dye (SYPRO orange or Glomelt), and the measured melting temperature of LF is consistent with that determined by DSC. On the basis of that, a new quantification method was established for determination of iron saturation levels using the linear correlation of the degree of ion saturation of LF with DSF measurements. Such DSF method is simple, inexpensive, rapid (<15 min), and high throughput (>96 samples per experiment), and provides a valuable alternative tool for thermal stability detection of LF and other whey proteins.

PD-1/PD-L1 axis is involved in the interaction between microglial polarization and glioma.

The tumor microenvironment plays a vital role in glioblastoma growth and invasion. PD-1 and PD-L1 modulate the immunity in the brain tumor microenvironment. However, the underlying mechanisms remain unclear. In the present study, in vivo and in vitro experiments were conducted to reveal the effects of PD-1/PD-L1 on the crosstalk between microglia and glioma. Results showed that glioma cells secreted PD-L1 to the peritumoral areas, particularly microglia containing highly expressed PD-1. In the early stages of glioma, microglia mainly polarized into the pro-inflammatory subtype (M1). Subsequently, the secreted PD-L1 accumulated and bound to PD-1 on microglia, facilitating their polarization toward the microglial anti-inflammatory (M2) subtype primarily via the STAT3 signaling pathway. The role of PD-1/PD-L1 in M2 polarization of microglia was partially due to PD-1/PD-L1 depletion or application of BMS-1166, a novel inhibitor of PD-1/PD-L1. Consistently, co-culturing with microglia promoted glioma cell growth and invasion, and blocking PD-1/PD-L1 significantly suppressed these processes. Our findings reveal that the PD-1/PD-L1 axis engages in the microglial M2 polarization in the glioma microenvironment and promotes tumor growth and invasion.