Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

[Spatial Differentiation Characteristics and Influencing Factors of Surface Soil Cd in Karst Plateau Area of Guiyang City].

In order to explore the spatial differentiation characteristics and variation law of soil Cd content in a high geological background area, 14 421 topsoil samples were collected from topsoil in the karst area of Guiyang City. Global Moran's I index, cold hot spot analysis, semi-variance function, and Kriging interpolation were used to reveal the spatial structure and distribution law of soil Cd content. The influence of environmental factors on soil Cd content and its main controlling factors were analyzed through analysis of variance and geographic detector. The results showed that： ① The Cd content of karst surface soil in Guiyang varied from 0.03 to 1.36 mg·kg-1, with an average of 0.440 mg·kg-1, which was 1.77 times and 5.95 times the Guizhou soil Cd background value and Chinese soil Cd background value, respectively. The over-standard rate of soil Cd was 30%, which was 4.29 times that of 7% of soil Cd in China. ② There was a significant spatial positive correlation of soil Cd content, showing an aggregation trend in the global space, whereas in the local region, the northeast and southwest were hot spots, and the north was a cold spot. The nugget coefficient of soil Cd content was 10.37%, indicating that soil Cd was mainly affected by structural factors. ③ In terms of spatial distribution, soil Cd showed different accumulation trends. In some massive soils, such as Xifeng County, Xiuwen County, Qingzhen City, Huaxi District, and Nanming District, the soil ω（Cd）was less than 0.3 mg·kg-1. The soil ω（Cd）was between 0.3 and 0.6 mg·kg-1,and soil Cd in Baiyun District, Wudang District, Guanshan Lake area, and Yunyan area as a whole lied within this range. The soil ω（Cd）between 0.6 and 0.9 mg·kg-1 was concentrated in the southwest of Qingzhen City, the south of Huaxi District, and the north of Kaiyang County, whereas soil ω（Cd） between 0.9 and 1.2 mg·kg-1 was mainly concentrated in the southwest of Qingzhen City. The extreme value of soil Cd content （ > 1.2 mg·kg-1） was mostly distributed in Kaiyang County, Xiuwen County, Qingzhen City, and Huaxi District. ④ The results of analysis of variance and geo-detector showed that different environmental factors had significant effects on the spatial differentiation of soil Cd, but their explanatory power on soil Cd content varied： stratum （0.176 5） > soil type （0.026 0） > organic matter （0.025 1） > altitude （0.010 5） > parent rock （0.007 3） > land use （0.006 4） > pH （0.001 3）, and the interaction between stratum and arbitrary environmental factors was the greatest. Therefore, stratum was the main factor affecting the spatial differentiation of soil Cd content.

Robotic pancreaticoduodenectomy in patients with overweight or obesity: a meta-analysis protocol.

INTRODUCTION: The prevalence of overweight or obesity among patients undergoing pancreaticoduodenectomy is on the rise. The utilisation of robotic assistance has the potential to enhance the feasibility of performing minimally invasive pancreaticoduodenectomy in this particular group of patients who are at a higher risk. The objective of this meta-analysis is to assess the safety and effectiveness of robotic pancreaticoduodenectomy in individuals with overweight or obesity. METHODS AND ANALYSIS: This investigation will systematically search for randomised controlled trials (RCTs) and non-randomised comparative studies that compare robotic pancreaticoduodenectomy with open or laparoscopic pancreaticoduodenectomy in patients with overweight or obesity, using PubMed, Embase and the Cochrane Library databases. The methodological quality of studies will be evaluated using the Cochrane risk of bias tool for RCTs and the Newcastle-Ottawa Scale for observational studies. RevMan software (V.5.4.1) will be used for statistical analysis. The OR and weighted mean differences will be calculated separately for dichotomous and continuous data. The selection of a fixed-effects or random-effects model will depend on the level of heterogeneity observed among the included studies. ETHICS AND DISSEMINATION: This study will be conducted based on data in the published literature from publicly available databases. Therefore, ethics approval is not applicable. The results will be disseminated in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023462321.

Mechanism of Preventing Recurrence of Stage II-III Colorectal Cancer Metastasis with Immuno-inflammatory and Hypoxic Microenvironment by a Four Ingredients Chinese Herbal Formula: A Bioinformatics and Network Pharmacology Analysis.

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.

Clinical Observation of Infarct Volume ≥150 mL in Endovascular Thrombectomy Treatment.

OBJECTIVES: Whether patients with infarct volume ≥150 mL could benefit from endovascular thrombectomy (EVT) remains unclear. METHODS: Patients (n=104) with anterior circulation Alberta Stroke Program Early Computed Tomography Score <6 were screened for infarct volume ≥150 mL using the Pullicino formula × (1-22%). The following were compared with the baseline at 90 days: the modified Rankin scale score (mRS) ≤3, mortality rate, symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours, and modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b between the EVT and drug therapy (DT) groups. RESULTS: In patients with infarct volumes ≥150 mL, mRS≤3 at 90 days was higher in the EVT group than in the DT group [adjusted odds risk (aOR), 5.52; 95% CI: 1.10-28.24, P=0.04), and mTICI ≥2b at 82.8%. Intracranial hemorrhage within 48 hours occurred in 7 (24.1%) patients in the EVT group and 5 (14.7%) in the DT group (aOR, 0.75; 95% CI: 0.16-3.46; P=0.71). Older age (aOR, 0.94; 95% CI: 0.90-0.99, P=0.01), EVT treatment (aOR, 4.51; 95% CI: 1.60-12.78, P=0.01), and infarct volume ≥150 mL (aOR, 0.11; 95% CI: 0.04-0.31, P<0.01) were significantly associated with patient prognosis. CONCLUSIONS: Patients with infarct volume ≥150 mL who received EVT had a higher proportion of mRS≤3 compared with those who received DT. However, there was no statistically significant difference in intracranial hemorrhage and death between the groups. EVT, smaller infarct volume, and younger age were associated with a good prognosis. The findings require large sample data verification.

Exosomal miR-196a-5p contributes to esophageal squamous cell carcinoma malignant progression by inhibiting ITM2B.

Exosomes from cancer cells function as carriers to spread or transport specific microRNAs (miRNAs) to distant sites to exert their effects, but the mechanism of exosomal miRNA action in esophageal squamous cell carcinoma (ESCC) has not been fully explained. Therefore, in this study, we were interested in the impact of exosomal miR-196a-5p in ESCC progression. We found that miR-196a-5p was expressed enriched in clinical tissues, ESCC cells, and exosomes. Functionally, depletion of miR-196a-5p impeded ESCC cell growth, migration, and invasion, whereas overexpression of miR-196a-5p produced the opposite results. Moreover, enhancement of exosomal miR-196a-5p in recipient ESCC cells triggered more intense proliferation and migration. Mechanistically, we identified integral membrane protein 2B (ITM2B) as a direct target of miR-196a-5p. Silencing of ITM2B partially counteracted the inhibitory effect of miR-196a-5p inhibitors on the malignant phenotype of ESCC. Furthermore, in vivo, lower miR-196a-5p levels triggered by the introduction of antagomiR-196a-5p resulted in the generation of smaller volume and weight xenograft tumors. Thus, our results demonstrated novel mechanisms of exosomal and intracellular miR-196a-5p-mediated ESCC growth and migration and identify the interaction of miR-196a-5p with ITM2B. These works might provide new targets and basis for the development of clinical treatment options for ESCC.

PLK3 is linked with higher tumor stage and unfavorable prognosis in patients with colorectal cancer.

Objective: This study intended to explore the relationship of PLK3 with prognosis in patients with colorectal cancer (CRC). Methods: PLK3 positivity was detected by immunohistochemistry in 160 patients with CRC receiving surgical resection. Results: The median tumor PLK3-positive rate was 26.5%. Tumor PLK3-positive rate was related to increased lymph node stage (p = 0.002) and tumor-node-metastasis stage (p < 0.001) of CRC. Tumor PLK3-positive rate ≥30% was related to shortened disease-free survival (p = 0.009) and overall survival (p = 0.003); tumor PLK3-positive rate ≥50% showed a stronger correlation with them (both p = 0.001), which was validated by multivariate Cox regression analyses (both p < 0.05). Conclusion: Tumor PLK3-positive rate ≥50% relates to increased tumor stage and unfavorable survival in patients with CRC.

[Box: see text].

Application of imaging modalities for endovascular thrombectomy of large core infarcts in clinical practice.

Four randomized controlled trials of large infarct core volume (LICV) included three imaging modalities: non-contrast CT (NCCT)-Alberta Stroke Program Early CT Score (ASPECTS), diffusion-weighted imaging (DWI)-ASPECTS, and NCCT-ASPECTS combined with CTP (CT perfusion). However, there is no clear consensus on the optimal imaging modality for endovascular thrombectomy (EVT) trials of large core infarcts. The variety and complexity of imaging modalities make it difficult to apply them in clinical practice. By familiarizing ourselves with these imaging modalities, we can better apply them in the clinic and correctly screen patients with large core infarcts in the anterior circulation who can benefit from EVT therapy.

Current and future perspectives in unresectable locally advanced esophageal squamous cell cancer (Review).

Definitive concurrent chemoradiotherapy has been the main standard treatment method for unresectable locally advanced esophageal squamous cell cancer (ESCC) since 1999. However, several disadvantages continue to be associated with this type of treatment, including a high local failure rate (reaching ~50% within 3 years) and a median overall survival (OS) time of 16.9 months. In addition, the 5­year overall survival rate of patients remains relatively low, at only ~21% for patients with ESCC with TNM stage T1­3N0­1M0. Burgeoning clinical trials and continually updating treatment modalities are currently in the process of being developed for the treatment of unresectable locally advanced ESCC. Compared with definitive concurrent chemoradiotherapy alone, clinical trials that have examined the efficacy of induction therapy, consolidation therapy, immunotherapy and targeted therapy have observed a prolonged median progression­free survival and OS. Salvage surgery can also bring benefits to some patients. Therefore, the present review aimed to provide a comprehensive overview on the latest progress that is being made in the development of treatment strategies for unresectable locally advanced ESCC, taking into account the several new challenges that need to be overcome.

Synthesis of Benzofuro[3,2-b]indol-3-one Derivatives via Dearomative (3 + 2) Cycloaddition of 2-Nitrobenzofurans and para-Quinamines.

An efficient dearomative (3 + 2) cycloaddition of para-quinamines and 2-nitrobenzofurans has been developed. This reaction proceeds smoothly under mild conditions and affords a series of benzofuro[3,2-b]indol-3-one derivatives in good to excellent yields (up to 98%) with perfect diastereoselectivities (all cases > 20:1 dr). The scale-up synthesis and versatile derivatizations demonstrate the potential synthetic application of the protocol. A plausible reaction mechanism is also proposed to account for the observed reaction process. This work represents the first instance of the N-triggered dearomative (3 + 2) cycloaddition of 2-nitrobenzofurans.

Human UDP-glucuronosyltransferase 1As catalyze aristolochic acid D O-glucuronidation to form a lesser nephrotoxic glucuronide.

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochic acids (AAs) are naturally occurring nitro phenanthrene carboxylic acids primarily found in plants of the Aristolochiaceae family. Aristolochic acid D (AAD) is a major constituent in the roots and rhizomes of the Chinese herb Xixin (the roots and rhizomes of Asarum heterotropoides F. Schmidt), which is a key material for preparing a suite of marketed Chinese medicines. Structurally, AAD is nearly identical to the nephrotoxic aristolochic acid I (AAI), with an additional phenolic group at the C-6 site. Although the nephrotoxicity and metabolic pathways of AAI have been well-investigated, the metabolic pathway(s) of AAD in humans and the influence of AAD metabolism on its nephrotoxicity has not been investigated yet. AIM OF THE STUDY: To identify the major metabolites of AAD in human tissues and to characterize AAD O-glucuronidation kinetics in different enzyme sources, as well as to explore the influence of AAD O-glucuronidation on its nephrotoxicity. MATERIALS AND METHODS: The O-glucuronide of AAD was biosynthesized and its chemical structure was fully characterized by both 1H-NMR and 13C-NMR. Reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses were conducted to assess the crucial enzymes involved in AAD O-glucuronidation in humans. Docking simulations were performed to mimic the catalytic conformations of AAD in human UDP-glucuronosyltransferases (UGTs), while the predicted binding energies and distances between the deprotonated C-6 phenolic group of AAD and the glucuronyl moiety of UDPGA in each tested human UGT isoenzyme were measured. The mitochondrial membrane potentials (MMP) and reactive oxygen species (ROS) levels in HK-2 cells treated with either AAI, or AAD, or AAD O-glucuronide were tested, to elucidate the impact of O-glucuronidation on the nephrotoxicity of AAD. RESULTS: AAD could be rapidly metabolized in human liver and intestinal microsomes (HLM and HIM, respectively) to form a mono-glucuronide, which was purified and fully characterized as AAD-6-O-ß-D-glucuronide (AADG) by NMR. UGT1A1 was the predominant enzyme responsible for AAD-6-O-glucuronidation, while UGT1A9 contributed to a lesser extent. AAD-6-O-glucuronidation in HLM, HIM, UGT1A1 and UGT1A9 followed Michaelis-Menten kinetics, with the Km values of 4.27 µM, 9.05 µM, 3.87 µM, and 7.00 µM, respectively. Docking simulations suggested that AAD was accessible to the catalytic cavity of UGT1A1 or UGT1A9 and formed catalytic conformations. Further investigations showed that both AAI and AAD could trigger the elevated intracellular ROS levels and induce mitochondrial dysfunction and in HK-2 cells, but AADG was hardly to trigger ROS accumulation and mitochondrial dysfunction. CONCLUSION: Collectively, UGT1A-catalyzed AAD 6-O-glucuronidation represents a crucial detoxification pathway of this naturally occurring AAI analogs in humans, which is very different from that of AAI.

Integrative metabolome and transcriptome analyses reveal the coloration mechanism in Camellia oleifera petals with different color.

BACKGROUND: Camellia olelfera petals are colorful, and have high ornamental value. However, the color formation mechanism of C. olelfera petals with different color is still unclear. In our study, WGCNA method was applied to integrate metabolites and transcriptomes to investigate the coloration mechanism of four C. olelfera cultivars with different petal colors. RESULTS: Here, a total of 372 flavonoids were identified (including 27 anthocyanins), and 13 anthocyanins were significantly differentially accumulated in C. olelfera petals. Among them, cyanidin-3-O-(6''-O-p-Coumaroyl) glucoside was the main color constituent in pink petals, cyanidin-3-O-glucoside, cyanidin-3-O-galactoside, cyanidin-3-O-rutinoside, and cyanidin-3-O-(6''-O-malonyl) glucoside were the main contributors to candy pink petals, and peonidin-3-O-glucoside was the important color substance responsible for the red petals of C. oleifera. Furthermore, six structural genes (Co4CL1, CoF3H1, CoF3'H, CoANS, CoUGT75C1-4, and CoUGT75C1-5), three MYBs (CoMYB1, CoMYB4, and CoMYB44-3), three bHLHs (CobHLH30, CobHLH 77, and CobHLH 79-1), and two WRKYs (CoWRKY7 and CoWRKY22) could be identified candidate genes related to anthocyanins biosynthesis and accumulation, and lead to the pink and red phenotypes. The regulatory network of differentially accumulated anthocyanins and the anthocyanins related genes in C. olelfera petals were established. CONCLUSIONS: These findings elucidate the molecular basis of the coloration mechanisms of pink and red color in C. olelfera petals, and provided valuable target genes for future improvement of petals color in C. olelfera.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

Treatment options for neoadjuvant strategies of esophageal squamous cell carcinoma (Review).

Compared with postoperative adjuvant therapy, neoadjuvant therapy has more potential advantages, such as decreasing tumor stage, killing micrometastatic cells. Because of these advantages, neoadjuvant therapy is recommended for numerous types of tumor, such as breast, lung and rectal cancer. To determine the role of neoadjuvant therapy on overall survival and adverse for patients with resectable esophageal carcinoma. we summarized clinical studies on 7 types of neoadjuvant therapies in this review. Currently, patients with esophageal cancer (EC) in China mainly receive postoperative treatment with <30% of patients receiving neoadjuvant therapy. One reason for the limited use of neoadjuvant therapy in China is inaccurate staging based on imaging and neoadjuvant treatment may increase difficulties in surgery. After neoadjuvant therapy, there may be tissue edema, blurry surgical field of view and unclear tissue gaps, resulting in greater difficulty in surgical procedures. However, oncologists are interested in neoadjuvant treatment, especially neoadjuvant immunotherapy to treat EC. Concurrent chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) is the most common neoadjuvant treatment regimen and increases the pathological complete response (pCR) and 5- and 10-year survival rates. Preoperative induction chemotherapy and sequential concurrent chemoradiotherapy are currently the most widely treatments used in clinical practice in China. However, this treatment strategy does not yield long-term survival. The pCR rate of neoadjuvant immunotherapy is greater than that of concurrent chemoradiotherapy but, to the best of our knowledge, no evidence of long-term survival benefit has been found in phase I and II clinical trials. Neoadjuvant treatment should be considered for patients with locally advanced ESCC.

Temporal trends in incidence and mortality of cervical cancer in China from 1990 to 2019 and predictions for 2034.

OBJECTIVE: This study aimed to analyze long-term trends of cervical cancer (CC) burden in China based on the GBD 2019 data and provide information and data support for formulating corresponding policies to control CC. METHODS: Incidence and mortality rate data of CC in China were described using GBD 2019 data. The Joinpoint regression analysis and age-period-cohort model were implemented to describe temporal trends of CC in China over the past 30 years. ARIMA model was used to predict trends of disease burden of CC in China for the next 15 years. RESULTS: From 1990 to 2019, the relative percentage change in age-standardized incidence rate (ASIR) of CC in Chinese women was 30.91 (95% UI: -50.13 to 96.78), and the relative percentage change in age-standardized mortality rate (ASMR) was -12.37 (95% UI: -63.54 to 28.52). The age-period-cohort model had different impacts on incidence and mortality rates. Overall annual percentage change (APC) (net drift) in incidence risk was 1.22 (95% CI: 0.87-1.57), and the overall APC (net drift) in mortality risk was -0.143 (95% CI: -0.38 to 0.09). The ARIMA model predicted ASIR and ASMR trends of CC for the next 15 years. CONCLUSION: From 1990 to 2019, the overall incidence risk of CC in Chinese has shown an upward trend, with an earlier occurrence in the high-incidence age groups, while mortality risk showed a downward trend. It is anticipated that over the next 15 years, the incidence rate will decrease, while the mortality rate will initially rise before decreasing.

Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis.

BACKGROUND: Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. METHODS: An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. RESULTS: Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. CONCLUSIONS: Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.

Multivalent iron-based magnetic porous biochar from peach gum polysaccharide as a heterogeneous Fenton catalyst for degradation of dye pollutants.

Water contamination caused by organic dyes has become a significant concern, and catalytic degradation of dye pollutants is an effective solution. However, developing an affordable, easy-to-prepare, high-catalytic-activity, and renewable catalyst has proved challenging. The current study addresses this issue by introducing an efficient heterogeneous Fenton catalyst, known as multivalent iron-based magnetic porous biochar (mFe-MPB). This catalyst comprises multiple iron species, such as Fe3O4, γ-Fe2O3, zero-valent Fe (Fe0), and Fe3C. The mFe-MPB was easily prepared by utilizing a straightforward crosslinking-pyrolysis strategy with natural peach gum polysaccharide (PGP), which has a unique structure and composition that facilitates the creation of multivalent iron species. The mFe-MPB demonstrates high catalytic activity in the degradation of an array of dyes, including cationic dyes such as methylene blue (MB) and methyl violet (MV), as well as anionic new coccine (NC) dye. Its mass standardized rate constant value for catalytic degradation of MB can reach as high as 1.65 L min-1 g-1. Additionally, the catalyst can be easily recovered through magnetic separation and possesses remarkable structural stability, enabling several reuses without compromising its efficiency. Therefore, this study offers a viable strategy to fabricate low-cost, efficient and sustainable Fenton catalyst for removal of dye pollutants from water.

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells.

BACKGROUND: Airway basal stem cells (ABSCs) have self-renewal and differentiation abilities. Although an abnormal mechanical environment related to chronic airway disease (CAD) can cause ABSC dysfunction, it remains unclear how mechanical stretch regulates the behavior and structure of ABSCs. Here, we explored the effect of mechanical stretch on primary human ABSCs. METHODS: Primary human ABSCs were isolated from healthy volunteers. A Flexcell FX-5000 Tension system was used to mimic the pathological airway mechanical stretch conditions of patients with CAD. ABSCs were stretched for 12, 24, or 48 h with 20% elongation. We first performed bulk RNA sequencing to identify the most predominantly changed genes and pathways. Next, apoptosis of stretched ABSCs was detected with Annexin V-FITC/PI staining and a caspase 3 activity assay. Proliferation of stretched ABSCs was assessed by measuring MKI67 mRNA expression and cell cycle dynamics. Immunofluorescence and hematoxylin-eosin staining were used to demonstrate the differentiation state of ABSCs at the air-liquid interface. RESULTS: Compared with unstretched control cells, apoptosis and caspase 3 activation of ABSCs stretched for 48 h were significantly increased (p < 0.0001; p < 0.0001, respectively), and MKI67 mRNA levels were decreased (p < 0.0001). In addition, a significant increase in the G0/G1 population (20.2%, p < 0.001) and a significant decrease in S-phase cells (21.1%, p < 0.0001) were observed. The ratio of Krt5+ ABSCs was significantly higher (32.38% vs. 48.71%, p = 0.0037) following stretching, while the ratio of Ac-tub+ cells was significantly lower (37.64% vs. 21.29%, p < 0.001). Moreover, compared with the control, the expression of NKX2-1 was upregulated significantly after stretching (14.06% vs. 39.51%, p < 0.0001). RNA sequencing showed 285 differentially expressed genes, among which 140 were upregulated and 145 were downregulated, revealing that DDIAS, BIRC5, TGFBI, and NKX2-1 may be involved in the function of primary human ABSCs during mechanical stretch. There was no apparent difference between stretching ABSCs for 24 and 48 h compared with the control. CONCLUSIONS: Pathological stretching induces apoptosis of ABSCs, inhibits their proliferation, and disrupts cilia cell differentiation. These features may be related to abnormal regeneration and repair observed after airway epithelium injury in patients with CAD.

Autophagy suppression facilitates macrophage M2 polarization via increased instability of NF-κB pathway in hepatocellular carcinoma.

The tumor microenvironment is a highly heterogeneous circumstance composed of multiple components, while tumor-associated macrophages (TAMs) are major innate immune cells with highly plastic and are always educated by tumor cells to structure an advantageous pro-tumor immune microenvironment. Despite emerging evidence focalizing the role of autophagy in other immune cells, the regulatory mechanism of autophagy in macrophage polarization remains poorly understood. Herein, we demonstrated that hepatocellular carcinoma (HCC) cells educated macrophages toward M2-like phenotype polarization under the condition of coculture. Moreover, we observed that inhibition of macrophage autophagy promoted M2-like macrophage polarization, while the tendency was impeded when autophagy was motivated. Mechanistically, macrophage autophagy inhibition inactivates the NF-κB pathway by increasing the instability of TAB3 via ubiquitination degradation, which leads to the M2-like phenotype polarization of macrophages. Both immunohistochemistry staining using human HCC tissues and experiment in vivo verified autophagy inhibition is correlated with M2 macrophage polarization. Altogether, we illustrated that macrophage autophagy was involved in the process of HCC cells domesticating M2 macrophage polarization via the NF-κB pathway. These results provide a new target to interfere with the polarization of macrophages to M2-like phenotype during HCC progression.

Multi-environment evaluations across ecological regions reveal climate and soil effects on amides contents in Chinese prickly ash peels (Zanthoxylum bungeanum Maxim.).

BACKGROUND: Environmental factors difference is the key factor for the difference in the production, transformation and accumulation of effective components in plants. UPLC-MS/MS and multivariate statistical methods were applied to describe the region difference of amides compounds in Chinese prickly ash peels from different regions and their correlation with climatic factors and soil factors. RESULTS: Amides compounds contents were significantly higher in high altitude areas, with obvious altitude change trend. Two ecotypes were classified based on the amides compounds contents, one was the high altitude-cool type from Qinghai, Gansu, Sichuan and western Shaanxi province, and the other one was low altitude-warm type from eastern Shaanxi, Shanxi, Henan, Hebei and Shandong province. Amides compounds content were negatively correlated with annual mean temperature, max temperature of warmest month, mean temperature of wettest quarter and mean temperature of warmest quarter (P < 0.01). Except for hydroxy-γ-sanshool and ZP-amide A, the residual amides contents were significantly positively correlated with organic carbon, available nitrogen, phosphorus and potassium in soil and negatively correlated with soil bulk density. Low temperature, low precipitation and high organic carbon in soil were conducive to amides accumulation. CONCLUSIONS: This study aided in site specific exploration of high amides contents yielding samples, enriched the environment factors effects on amides compounds, and provided scientific foundation for the improvement of Chinese prickly ash peels quality and the location of high-quality production areas.