Endoplasmic reticulum stress: The underlying mechanism of chronic pain.

Chronic pain (CP) affects over 30 % of the global population, imposing significant financial burdens on individuals and society. However, existing treatments for CP offer limited efficacy and troublesome side effects, primarily owing to a lack of knowledge of its precise underlying mechanism. Pathological stimuli disrupt the intricate process of protein folding and endoplasmic reticulum (ER) homeostasis. This disruption leads to the accumulation of misfolded or unfolded proteins in the ER, generating a condition termed ER stress. Emerging data have indicated that ER stress, occurring in the peripheral and central nervous systems, contributes to the development and maintenance of CP. This review aimed to comprehensively explore the intersection of ER stress and CP within the lower and upper nervous systems and highlight the cell-specific contributions of the unfolded protein response in different CP types. We provide a comprehensive synthesis of evidence from animal models, examining neuronal and non-neuronal mechanisms and discuss the damaging ER stress-linked inflammation, autophagy, oxidative stress, and apoptosis, which collectively drive disease progression and contribute to a neurotoxic environment. However, the mechanisms through which ER stress influences the most advanced centre-of-pain projections in the brain remain unclear. Further investigation in this area is crucial to elucidate the relationship between ER stress and CP and facilitate the development of novel therapeutic drugs for this intractable dilemma.

Dynamic estimates of survival in patients with follicular thyroid cancer: a retrospective cohort study.

BACKGROUND: Few studies have been conducted on the dynamic survival rates of follicular thyroid cancer (FTC). This study aimed to ascertain how the survival probability of patients with FTC changes over time. METHODS: In this retrospective analysis, 10,617 patients diagnosed with FTC between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were included. Actuarial disease-specific survival (DSS) was estimated using the Kaplan-Meier method, and the log-rank test was used for comparisons. The annual hazard of mortality was determined using the hazard function, and the conditional survival (CS) was calculated using the life table method. RESULTS: A total of 459 (4.3%) patients died of FTC, and the 5-year and 10-year DSS rates were 96.6 ± 0.2% and 94.6 ± 0.3%, respectively. There was a statistically significant difference in the DSS rate between patients with different SEER combined summary stages (P < 0.001). The annual hazard curve for cancer mortality in the entire study cohort displayed a steep downward trend with a slight peak at 2.5 years after diagnosis, followed by a gradual decline. Patients with distant metastases exhibited a higher mortality hazard curve and more notable declining trend. CS demonstrated an upward trend across the entire study population, with the most pronounced trend in patients with distant metastases. CONCLUSION: Prognosis improved over time in a stage-dependent manner in patients with FTC after diagnosis. The most significant improvement was observed in the patients with distant metastases. Notably, dynamic survival estimations, such as death hazard and conditional survival analysis, provide more precise survival projections than traditional survival analysis for FTC survivors.

Fabrication of Highly Dispersed Ru Catalysts on CeO2 for Efficient C3H6 Oxidation.

Emissions of volatile organic compounds (VOCs) threaten both the environment and human health. To realize the elimination of VOCs, Ru/CeO2 catalysts have been intensively investigated and applied. Although it has been widely acknowledged that the catalytic performance of platinum group metal catalysts was highly determined by their dispersion and coordination environment, the most reactive structures on Ru/CeO2 catalysts for VOCs oxidation are still ambiguous. In this work, starting from Ce-BTC (BTC = 1,3,5-benzenetricarboxylic acid) materials, atomically dispersed Ru catalysts and agglomerated Ru catalysts were successfully created via one-step hydrothermal method (Ru-CeO2-BTC) and conventional incipient wetness impregnation method (Ru/CeO2-BTC), respectively. In a typical model reaction of C3H6 oxidation, atomically dispersed Ruδ+ species with the formation of abundant Ru-O-Ce linkages on Ru-CeO2-BTC were found to perform much better than agglomerated RuOx species on Ru/CeO2-BTC. Further characterizations and mechanism study disclosed that Ru-CeO2-BTC catalyst with atomically dispersed Ru ions and more superior low temperature redox performance compared to Ru/CeO2-BTC could better facilitate the adsorption/activation of C3H6 and the decomposition/desorption of intermediates, thus exhibiting superior C3H6 oxidation activity. This work elucidated the reactive sites on Ru/CeO2 catalysts in the C3H6 oxidation reaction and provided insightful guidance for designing efficient Ru/CeO2 catalysts to eliminate VOCs.

The Influence of Grain Size on Microstructure Evolution in CeO2 under Xenon Ion Irradiation.

Large-grained UO2 is considered a potential accident-tolerant fuel (ATF) due to its superior fission gas retention capabilities. Irradiation experiments for cerium dioxide (CeO2), used as a surrogate fuel, is a common approach for evaluating the performance of UO2. In this work, spark plasma sintered CeO2 pellets with varying grain sizes (145 nm, 353 nm, and 101 µm) and a relative density greater than 93.83% were irradiated with 4 MeV Xe ions at a fluence of 2 × 1015 ions/cm2 at room temperature, followed by annealing at 600 °C for 3 h. Microstructure, including dislocation loops and bubble morphology of the irradiated samples, has been characterized. The average size of dislocation loops increases with increasing grain size. Large-sized dislocation loops are absent near the grain boundary because the boundary absorbs surrounding defects and prevents the dislocation loops from coalescing and expanding. The distribution of bubbles within the grain is uniform, whereas the large-sized and irregularly shaped xenon bubbles observed in the small grain exhibit pipe diffusion along the grain boundaries. The bubble diameter in the large-grained pellet is the smallest. As the grain size increases, the volumetric swelling of the irradiated pellets decreases while the areal density of Xe bubbles increases. Elemental segregation, which tends to occur at dislocation loops and grain boundaries, has been analyzed. Large-grained CeO2 pellet with lower-density grain boundaries exhibits better resistance to volumetric swelling and elemental segregation, suggesting that large-grained UO2 pellets could serve as a potential ATF.

Application of a dual-modality colorimetric analysis method to inkjet printing lateral flow detection of Salmonella typhimurium.

Lateral flow assay (LFA) color signal quantification methods were developed by utilizing both International Commission on Illumination (CIE) LAB (CIELAB) color space and grayscale intensity differences. The CIELAB image processing procedure included calibration, test, control band detection, and color difference calculation, which can minimize the noise from the background. The LFA platform showcases its ability to accurately discern relevant colorimetric signals. The rising occurrence of infectious outbreaks from foodborne pathogens like Salmonella typhimurium presents significant economic, healthcare, and public health risks. The study introduces an aptamer-based lateral flow (ABLF) platform by using inkjet printing for specially detecting S. typhimurium. The ABLF utilized gold-decorated polystyrene microparticles, functionalized with specific S. typhimurium aptamers (Ps-AuNPs-ssDNA). The platform demonstrates a detection limit of 102 CFU mL-1 in buffer solutions and 103 CFU mL-1 in romaine lettuce tests. Furthermore, it sustained performance for over 8 weeks at room temperature. The ABLF platform and analysis methods are expected to effectively resolve the low-sensitivity problems of the former LFA systems and to bridge the gap between lab-scale platforms to market-ready solutions by offering a simple, cost-effective, and consistent approach to detecting foodborne pathogens in real samples.

Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with leptomeningeal metastases harboring targetable mutations.

Background: Driver gene-positive non-small cell lung cancer (NSCLC) patients are prone to develop leptomeningeal metastasis (LM), leading to an extremely high mortality. The objective of this study was to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) treatments for patients with NSCLC and LM harboring targetable mutations. Methods: We retrospectively collected records of patients with NSCLC harboring targetable mutations and prescribed ICIs following the diagnosis of LM at Huashan Hospital, Fudan University. In addition, we reviewed relevant literature and enrolled patients who met the inclusion criteria. Clinical characteristics were statistically analyzed, and the Kaplan-Meier method and log-rank test were employed to assess the median progression-free survival (mPFS) and median overall survival (mOS). Results: A total of 37 patients with NSCLC harboring targetable mutations who received ICIs after LM diagnosis were included. The median age of the enrolled patients was 54 years (range, 33-70 years), and 62.2% were female. Following ICI administration, the intracranial objective response rate (iORR) and intracranial disease control rate (iDCR) for all enrolled patients were 18.9% and 62.2%, respectively. The mPFS of all patients was 2.5 months [95% confidence interval (CI): 2.166-2.834 months] and the mOS was 5.8 months (95% CI: 5.087-6.513 months). Both univariate and multivariate analyses revealed a significant increase in mOS or individuals who had previously undergone cranial radiation therapy compared to those who had not. Furthermore, different histology molecular types were found to be potentially associated with survival time. Conclusions: Some patients with NSCLC harboring targetable gene mutations following LM diagnosis may benefit from ICI treatment with relatively good tolerance. However, further screening of the most suitable patient populations for ICIs is required.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

SOX12 Facilitates Hepatocellular Carcinoma Progression and Metastasis through Promoting Regulatory T-Cells Infiltration and Immunosuppression.

Despite the success of immunotherapy in treating hepatocellular carcinoma (HCC), HCC remains a severe threat to health. Here, a crucial transcription factor, SOX12, is revealed that induces the immunosuppression of liver tumor microenvironment. Overexpressing SOX12 in HCC syngeneic models increases intratumoral regulatory T-cell (Treg) infiltration, decreases CD8+T-cell infiltration, and hastens HCC metastasis. Hepatocyte-specific SOX12 knockout attenuates DEN/CCl4-induced HCC progression and metastasis, whereas hepatocyte-specific SOX12 knock-in accelerates these effects. Mechanistically, SOX12 transcriptionally activates C-C motif chemokine ligand 22 (CCL22) expression to promote the recruitment and suppressive activity of Tregs. Moreover, SOX12 transcriptionally upregulates CD274 expression to suppress CD8+T-cell infiltration. Either knockdown of CCL22 or PD-L1 dampens SOX12-mediated HCC metastasis. Blocking of CC chemokine receptor 4 (CCR4), a receptor for CCL22, by inhibitor C-021 or Treg-specific knockout of CCR4 inhibits SOX12-mediated HCC metastasis. Transforming growth factor-ß1 (TGF-ß1)/TGFßR1-Smad2/3/4 is identified as a key upstream signaling for SOX12 overexpression in HCC cells. Combining C-021 or TGFßR1 inhibitor galunisertib with anti-PD-L1 exhibits an enhanced antitumor effect in two HCC models. Collectively, the findings demonstrate that SOX12 contributes to HCC immunosuppression through the CCL22/CCR4-Treg and PD-L1-CD8+T axes. Blocking of CCR4 or TGFßR1 improves the efficacy of anti-PD-L1 in SOX12-mediated HCC.

Microsurgical Management of Pineal Region Tumors.

BACKGROUND: Pineal tumors are rare, and the pineal region is a challenging surgical location for neurosurgeons. The present study aimed to investigate the effects of microsurgical management in patients with pineal region tumors and explore probable factors associated with preoperative hydrocephalus, postoperative hydrocephalus remission, and prolonged hospital length of stay (LoS). METHODS: A retrospective study of patients with pineal region tumors who underwent microsurgical management at the First Affiliated Hospital of Soochow University (Jiangsu, China) between 1 January 2010 and 31 October 2022 was conducted. RESULTS: Data from 36 patients were included in this study. The top 5 common symptoms included headache (58%), dizziness (44%), double vision (22%), vomiting (19%), and nausea (14%). Patients with a lower Karnofsky Performance Score (KPS), younger age, and larger maximum tumor diameters were more vulnerable to preoperative hydrocephalus. Preoperative hydrocephalus also led to a prolonged postoperative LoS (P = 0.021). Patients with a lower KPS score (P = 0.020) or larger maximum tumor diameters (P = 0.045) were more likely to achieve postoperative remission of hydrocephalus. Most postoperative complications led to increased hospital LoS. CONCLUSIONS: Microsurgical resection of pineal tumors yielded favorable long-term outcomes. Patients with a lower KPS score, younger age, and larger maximum tumor diameters were more vulnerable to preoperative hydrocephalus and prolonged LoS. Patients with a lower KPS score or larger tumor diameter were likely to achieve significant remission of hydrocephalus after tumor resection.

The role of hyperbaric oxygen in idiopathic sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss is an unexplained sudden loss of sensorineural hearing, with no specific pathogenesis, and is difficult to treat. The most common therapeutic strategy for idiopathic sudden sensorineural hearing loss is the use of steroids combined with neurotrophic drugs, as other treatments have shown limited efficacy. However, in recent years, hyperbaric oxygen therapy has emerged as a promising treatment option. Studies have shown that hyperbaric oxygen therapy, in combination with conventional treatments, can effectively alleviate inner ear edema, improve blood circulation, and suppress inflammation. Therefore, hyperbaric oxygen therapy plays an important role in the treatment of idiopathic sudden sensorineural hearing loss. In this review, we aim to assess existing studies and summarize the clinical effects and mechanisms of hyperbaric oxygen therapy in idiopathic sudden sensorineural hearing loss, providing a basis for further research on the clinical treatment of this disorder.

Risk factors for cervical lymph node metastasis of papillary thyroid cancer in elderly patients aged 65 and older.

Objective: To assess the risk factors of cervical lymph node metastasis in elderly patients aged 65 years and older diagnosed with papillary thyroid cancer (PTC). Design and method: In this retrospective analysis, we included a total of 328 elderly patients aged 65 years and older diagnosed with PTC. We thoroughly examined clinical features from these patients. Utilizing univariate and multivariate logistic regression analyses, we aimed to identify factors contributing to the risk of central and lateral lymph node metastasis (CLNM/LLNM) in this specific population of PTC patients aged 65 years and older. Results: In the univariate analysis, CLNM was significantly associated with tumor size, multifocality, bilaterality, and microcalcification, while only tumor size ≥ 1cm (OR = 0.530, P = 0.019, 95% CI = 0.311 - 0.900) and multifocality (OR = 0.291, P < 0.001, 95% CI = 0.148 - 0.574) remained as risk factors in the multivariate analysis. LLNM was confirmed to be associated with male (OR = 0.454, P < 0.020, 95% CI = 0.233 - 0.884), tumor size ≥ 1cm (OR = 0.471, P = 0.030, 95% CI = 0.239 - 0.928), age ≥ 70 (OR = 0.489, P = 0.032, 95% CI = 0.254 - 0.941), and microcalcification (OR = 0.384, P = 0.008, 95% CI = 0.189 - 0.781) in the multivariate analysis. In elderly PTC patients with CLNM, male gender (OR = 0.350, P = 0.021, 95% CI = 0.143 - 0.855), age ≥ 70 (OR = 0.339, P = 0.015, 95% CI = 0.142 - 0.810), and bilaterality (OR = 0.320, P = 0.012, 95% CI = 0.131 - 0.779) were closely associated with concomitant LLNM in both univariate and multivariate analyses. Conclusion: For elderly PTC patients aged 65 and older, tumor size ≥ 1cm and multifocality are significant risk factors for CLNM. Meanwhile, male, tumor size ≥ 1cm, age ≥ 70, and microcalcification are crucial predictors for LLNM. In patients already diagnosed with CLNM, male, age ≥ 70, and bilaterality increase the risk of LLNM.

Quercetin regulates dendritic cell activation by targeting STAT4 in the treatment of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU.

Berberine inhibits intracellular Ca2+ signals in mouse pancreatic acinar cells through M3 muscarinic receptors: Novel target, mechanism, and implication.

Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects, but the pharmacological targets and mechanisms remain elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced intracellular Ca2+ oscillations, mediated through an inhibition of the muscarinic subtype 3 (M3) receptor. Patch-clamp recordings and confocal Ca2+ imaging were applied to acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca2+ oscillations. Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca2+ oscillations in a concentration-dependent manner, and this inhibition also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl-) channels, and store-operated Ca2+ channels. Together, the results demonstrate that berberine directly inhibits the muscarinic M3 receptors, further confirmed by evidence of the interaction between berberine and M3 receptors in pancreatic acinar cells.

Interactions between LAMP3+ dendritic cells and T-cell subpopulations promote immune evasion in papillary thyroid carcinoma.

BACKGROUND: The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets. METHODS: This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples. RESULTS: A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3+) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3+ DCs promote CD8+ T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3+ DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion. CONCLUSION: Our findings expound valuable insights into the role of the interaction between LAMP3+ DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.

A Comprehensive Review of Licorice: The Preparation, Chemical Composition, Bioactivities and Its Applications.

Licorice (Glycyrrhiza) is a medicinal and food homologue of perennial plants derived from the dried roots and rhizomes of the genus Glycyrrhiza in the legume family. In recent years, the comprehensive utilization of licorice resources has attracted people's attention. It is widely utilized to treat diseases, health food products, food production, and other industrial applications. Furthermore, numerous bioactive components of licorice are found using advanced extraction processes, which mainly include polyphenols (flavonoids, dihydrostilbenes, benzofurans, and coumarin), triterpenoids, polysaccharides, alkaloids, and volatile oils, all of which have been reported to possess a variety of pharmacological characteristics, including anti-oxidant, anti-inflammatory, antibacterial, antiviral, anticancer, neuroprotective, antidepressive, antidiabetic, antiparasitic, antisex hormone, skin effects, anticariogenic, antitussive, and expectorant activities. Thereby, all of these compounds promote the development of novel and more effective licorice-derived products. This paper reviews the progress of research on extraction techniques, chemical composition, bioactivities, and applications of licorice to provide a reference for further development and application of licorice in different areas.

Electrophysiological Phenotypes of Hippocampal Synaptic and Network Functions in Cannabinoid Receptor 2 Knockout Mice.

Background: The cannabinoid receptor 2 (CB2R), a cannabinoid receptor primarily expressed in immune cells, has been found in the brain, particularly in the hippocampus, where it plays crucial roles in modulating various neural functions, including synaptic plasticity, neuroprotection, neurogenesis, anxiety and stress responses, and neuroinflammation. Despite this growing understanding, the intricate electrophysiological characteristics of hippocampal neurons in CB2R knockout (CB2R KO) mice remain elusive. Aim and Methods: This study aimed to comprehensively assess the electrophysiological traits of hippocampal synaptic and network functions in CB2R KO mice. The focus was on aspects such as synaptic transmission, short- and long-term synaptic plasticity, and neural network synchrony (theta oscillations). Results: Our findings unveiled multiple functional traits in these CB2R KO mice, notably elevated synaptic transmission in hippocampal CA1 neurons, decreased both synaptic short-term plasticity (paired-pulse facilitation) and long-term potentiation (LTP), and impaired neural network synchronization. Conclusion: In essence, this study yields insightful revelations about the influence of CB2Rs on hippocampal neural functions. By illuminating the electrophysiological modifications in CB2R KO mice, our research enriches the comprehension of CB2R involvement in hippocampal function. Such insights could hold implications for advancing our understanding of the neural mechanisms under the influence of CB2Rs within the brain.

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis.

Background: Anoikis presents a significant barrier in the metastasis of cancer. As the most aggressive type of thyroid cancer, anaplastic thyroid cancer (ATC) exhibits a high risk of metastasis and is characterized by high mortality. Therefore, investigating the molecular mechanisms of anoikis resistance in ATC is important for devising therapeutic targets in clinical research. Methods: Differentially Expressed Genes were screened in ATC cells under attached and detached culture conditions with RNA-seq. Investigate the impact of enolase 2 (ENO2) on apoptosis and spheroid formation by gain and loss of function. Changes of reactive oxygen species (ROS), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were detected to assess redox balance. The transcriptional regulatory role of signal transducer and activator of transcription 1 (STAT1) on ENO2 was validated through Dual-Luciferase Reporter Gene Assay. Explore the impact of ENO2 expression on the formation of lung metastases in nude mice. Results: We found that the glycolysis process was activated in detached ATC cells. Several genes in the glycolysis process, particularly ENO2, a member of the enolase superfamily was upregulated in ATC cells cultured in suspension. The upregulation of ENO2 enabled the maintenance of redox balance by supplying GSH and NADPH, thereby preventing cells from undergoing anoikis. In terms of mechanism, the expression of STAT1 was enhanced in anoikis resistance cells, which in turn positively regulated the expression of ENO2. In vivo, ENO2-suppressed ATC cells resulted in a significantly lower rate of lung colonization compared to control ATC cells. Conclusions: Stable expression of ENO2 and the maintenance of redox balance played a pivotal role in facilitating anoikis resistance of ATC.

Effect of degraded flaxseed meals on the growth performance, nutrient digestibility, and health status of broilers.

OBJECTIVE: The present study evaluated the effect of flaxseed meal degraded by a protease, Lactobacillus plantarum, or both on the growth performance, nutrient digestibility, and health status of broilers. METHODS: There were four diets containing flaxseed meals in its non-degraded form (control, CON), degraded with 3,000 U/kg of protease (enzymatic, ELM), 1.0×109 CFU/kg of Lactobacillus plantarum (fermented, FLM), or both (dual-degraded, DLM). Each form of flaxseed meals was added at 15% of diet. A total of 480 yellow-feathered broilers at 22 d of age were distributed into 4 groups with 6 replicates of 20 chickens each. The feeding trial lasted for 42 d. Growth performance, apparent fecal digestibility (dry matter, energy, crude protein, and ash), and serum immunoglobins and antioxidases were determined at 42 and 63 d of age. RESULTS: Results showed that ELM, FLM, and DLM increased (p<0.001) the contents of peptides and decreased (p<0.001) cyanogenic glycosides, compared to CON. The diets with degraded flaxseed meals increased (p<0.05) feed intake and body weight gain throughout the feeding trial, and the digestibility of energy, crude protein, and ash at the end of feeding trial. Furthermore, all degraded groups enhanced (p<0.05) broiler health status by increasing serum immunoglobulins A and G. Additinally, DLM showed more pronounced effects (p<0.05) on these parameters than ELM or FLM. CONCLUSION: Flaxseed meals degraded by enzymolysis, fermentation, or both had improved nutrition and application in broilers.

Modified basalt fibers boost performance of constructed wetlands: Comparison between surface coating and chemical grafting.

Modified basalt fiber (MBF) is a potential material that has been applied in wastewater treatment fields. In this study, superior performances of MBFs by calcium (Ca-MBF) and polyethyleneimine modification (PEI-MBF) were compared in constructed wetlands (CWs). Via chemical grafting, higher biofilm contents were observed on the surface of PEI-MBF, compared to Ca-MBF. Moreover, MBF increased key enzyme activities particularly in lower substrate layer, contributing to positive responses of microbial community in CWs. For instance, PEI-MBF boosted microbial richness and diversity and improved the abundances of denitrifying functional bacteria and biomarkers like Thauera, Vulcanibacillus, and Maritimimonas, probably promoting nitrate removal compared with Ca-MBF group. By contrast, Ca-MBF enriched more functional genera involved in nutrients removal, with the highest removal of ammonium (43.9 %), total nitrogen (66.2 %), and total phosphorus (37.1 %). Overall, this work provided new findings on improved performance of CWs with MBF.

Formamidinium Lead Iodide-Based Inverted Perovskite Solar Cells with Efficiency over 25 % Enabled by An Amphiphilic Molecular Hole-Transporter.

Formamidinium lead iodide (FAPbI3) represents an optimal absorber material in perovskite solar cells (PSCs), while the application of FAPbI3 in inverted-structured PSCs has yet to be successful, mainly owing to its inferior film-forming on hydrophobic or defective hole-transporting substrates. Herein, we report a substantial improvement of FAPbI3-based inverted PSCs, which is realized by a multifunctional amphiphilic molecular hole-transporter, (2-(4-(10H-phenothiazin-10-yl)phenyl)-1-cyanovinyl)phosphonic acid (PTZ-CPA). The phenothiazine (PTZ) based PTZ-CPA, carrying a cyanovinyl phosphonic acid (CPA) group, forms a superwetting hole-selective underlayer that enables facile deposition of high-quality FAPbI3 thin films. Compared to a previously established carbazole-based hole-selective material (2-(3,6-dimethoxy-9H-carbazol-9-yl)ethyl)phosphonic acid (MeO-2PACz), the crystallinity of FAPbI3 is enhanced and the electronic defects are passivated by the PTZ-CPA more effectively, resulting in remarkable increases in photoluminescence quantum yield (four-fold) and Shockley-Read-Hall lifetime (eight-fold). Moreover, the PTZ-CPA shows a larger molecular dipole moment and improved energy level alignment with FAPbI3, benefiting the interfacial hole-collection. Consequently, FAPbI3-based inverted PSCs achieve an unprecedented efficiency of 25.35 % under simulated air mass 1.5 (AM1.5) sunlight. The PTZ-CPA based device shows commendable long-term stability, maintaining over 90 % of its initial efficiency after continuous operation at 40 °C for 2000 hours.