METTL3-mediated m6 A methylation of TRAF5 inhibits lung adenocarcinoma cell metastasis via activation of the PI3K/AKT/NF-κB signaling pathway.

Tumor necrosis factor receptor-associated factor 5 (TRAF5) has been implicated in the pathogenesis of human malignancies. This work aimed to clarify the role of TRAF5 in lung adenocarcinoma (LUAD) progression. Herein, we uncovered that TRAF5 level was reduced in LUAD tissues. Low TRAF5 expression correlated with dismal prognosis in LUAD patients. Moreover, upregulated TRAF5 impeded cell viability, migration, and invasion, induced apoptosis in vitro, as well as impaired tumorigenicity in vivo. However, depletion of TRAF5 revealed opposing results. Moreover, TRAF5 was identified as the downstream target of methyltransferase-like 3 (METTL3)-elicited N6 -methyladenosine (m6 A) modification. METTL3 stabilized TRAF5 mRNA and positively modulated TRAF5 level. Further, TRAF5 depletion relieved the repressive phenotype caused by METTL3 addition. In addition, it was manifested that the METTL3/TRAF5 axis served as an inhibitor in LUAD through the PI3K/AKT/Nuclear Factor-Kappa B (NF-κB) signaling. Collectively, we propose that METTL3-mediated TRAF5 m6 A modification exerted as a vital tumor inhibitory function in LUAD development. The METTL3/TRAF5 axis may be a critical effector of LUAD progression.

Estimation of life history traits and stock status for Scomber japonicus based on data-limited method.

The age-structure data is usually unavailable for most traditional fishery species in the East China Sea. The data-limited method is thus particularly important to understand life history and population dynamics of commercial fishes. At the offshore waters of southern Zhejiang, Chub mackerel (Scomber japonicus) is one of the dominant economic species. Based on fork length data from 2016 to 2020, we estimated its life history traits with the data-limited method, including the growth parameters and mortality coefficients. We further evaluated the status of Chub mackerel by the yield per recruitment (YPR) model. The results showed that the relationship between fork length (L) and body weight (W) based on 1606 samples was estimated to be W=4.18×10-3L3.28(R2=0.96). The asymptotic fork length L∞ of Chub mackerel was 28.34 cm, the growth rate was 0.36 a-1, and the initial theoretical age was -0.40 a. The total mortality was estimated as 1.67 a-1, and the estimated natural mortality (M) was 0.85 a-1. The fishing mortality (F) was 0.82 a-1, and the development rate was 0.49. The current capture age was estimated to be 1.78 a, while the capture fork length was 15.44 cm. The YPR model results showed YPR value showed a trend of increasing and then decreasing with the increases of F. The values of biological reference points F0.1 and Fmax were 0.97 a-1 and 4.55 a-1, respectively, which were higher than the value of current F. The sensitivity analysis showed that the uncertainty of M greatly influenced the estimation results of YPR and biological reference points. A decrease in M significantly increased the YPR value, but F0.1 and Fmax decreased. The status of Chub mackerel stock at the offshore waters of southern Zhejiang is in good condition. However, the miniaturization of catch is intensifying. It is recommended to extend the capture fork length to 20 cm (the impact point age) to improve the quality of the catch, which would sustainably use the Chub mackerel resources.

Monomeric C-reactive protein evokes TCR Signaling-dependent bystander activation of CD4+ T cells.

Bystander activation of T cells is defined as induction of effector responses by innate cytokines in the absence of cognate antigens and independent of T cell receptor (TCR) signaling. Here we show that C-reactive protein (CRP), a soluble pattern-recognition receptor assembled noncovalently by five identical subunits, can instead trigger bystander activation of CD4 + T cells by evoking allosteric activation and spontaneous signaling of TCR in the absence of cognate antigens. The actions of CRP depend on pattern ligand-binding induced conformational changes that result in the generation of monomeric CRP (mCRP). mCRP binds cholesterol in plasma membranes of CD4 + T cells, thereby shifting the conformational equilibrium of TCR to the cholesterol-unbound, primed state. The spontaneous signaling of primed TCR leads to productive effector responses manifested by upregulation of surface activation markers and release of IFN-γ. Our results thus identify a novel mode of bystander T cell activation triggered by allosteric TCR signaling, and reveal an interesting paradigm wherein innate immune recognition of CRP transforms it to a direct activator that evokes immediate adaptive immune responses.

[Safety Analysis of Perioperative Period in Non-Small Cell Lung Cancer Patients with Comorbid Pneumoconiosis].

Objective: To explore the surgical safety of patients with comorbid non-small cell lung cancer (NSCLC) and pneumoconiosis. Methods: In this study, the clinical data of 165 NSCLC patients treated at West China Fourth Hospital, Sichuan University from August 2019 to May 2021 were collected. Among them, 21 patients with comorbid pneumoconiosis were included in the pneumoconiosis group, and the remaining 144 patients were included in the general group. Radical resection for lung cancer was performed in both groups. The perioperative clinical data, including preoperative, intraoperative and postoperative indicators, of the two groups were compared and analyzed. Results: There was no perioperative death in either group. The proportions of male patients and patients with smoking history in the pneumoconiosis group were significantly higher than those in the general group ( P<0.05). The body mass index (BMI), pulmonary ventilation function and diffusion function in the pneumoconiosis group were significantly lower than those in the general group ( P<0.05). There was no significant difference in the median operative time and the median volume of intraoperative blood loss between the pneumoconiosis group and the general group. In the pneumoconiosis group, the proportion of advanced tumors (stage Ⅱ/Ⅲ), incidence of postoperative complications, median duration of postoperative intubation, and postoperative length of hospital stay were higher/longer than those of the normal group ( P<0.05). Compared with the general group, the incidences of lymph node calcification, dense pleural adhesion and surgical method alteration (switching from thoracoscopic surgery to open surgery or video-assisted thoracoscopy) were also significantly higher in the pneumoconiosis group ( P<0.05). Univariate analysis showed that age, smoking history, pneumoconiosis, pulmonary ventilation dysfunction, lymph node calcification, dense pleural adhesion and the volume of intraoperative blood loss were the risk factors for postoperative complications. Further multivariate regression analysis demonstrated that smoking history ( OR=1.37, P<0.05), lymph node calcification ( OR=2.36, P<0.05) and pulmonary ventilation dysfunction ( OR=5.21, P<0.05) were independent risk factors for postoperative complications. Conclusion: NSCLC patients with comorbid pneumoconiosis face relatively greater risks during the perioperative period when they undergo radical resection for lung cancer. Therefore, the close attention of surgeons and the nursing staff should be raised accordingly.

Adjuvant radiotherapy shows benefit in selected stage I uterine sarcoma: A risk scoring system based on a population analysis.

BACKGROUND: The potential therapeutic benefit of adjuvant radiotherapy for patients with stage I uterine sarcoma has not been clear. In this study, we aimed to develop a risk scoring model to select the subgroup of patients with stage I uterine sarcoma who might benefit from adjuvant radiotherapy. METHODS: Patients with stage I uterine sarcoma from the Surveillance, Epidemiology, and End Results program from 2010 to 2014 were retrospectively included in this analysis. Cox proportional hazards models were performed to identify risk factors. RESULTS: A total of 947 stage I uterine sarcoma patients were included. The 5-year disease-specific survival (DSS) of the overall cohort was 75.81%. Multivariate analysis identified stage (p = 0.013), tumor grade (p <0.001) and histology (p = 0.043) as independent prognostic factors for DSS, and these factors were used to generate the risk scoring model. The low-risk group presented a better DSS than the high-risk group (95.51% vs. 49.88%, p < 0.001). The addition of radiotherapy to surgery significantly increased the DSS in the high-risk group compared with surgery alone (78.06% vs. 46.88%, p = 0.022), but no significant survival benefit was observed in the low-risk group (98.36% vs. 100%, p = 0.766). CONCLUSIONS: Our risk scoring model based on stage, tumor grade, and histology predicted the outcome of patients with stage I uterine sarcoma cancer. This system may help to select stage I uterine sarcoma cancer patients who might benefit from adjuvant radiotherapy.

Eurotium cristatum Fermented Loose Dark Tea Ameliorates Cigarette Smoke-Induced Lung Injury by MAPK Pathway and Enhances Hepatic Metabolic Detoxification by PXR/AhR Pathway in Mice.

Cigarette smoke- (CS-) induced oxidative stress and inflammation in the lung are serious health problems. Primary and reprocessed tea products contain multiple antioxidants that have been reported to protect the lung against CS-induced injury. However, the beneficial effects of Eurotium cristatum fermented loose dark tea (ECT) and Eurotium cristatum particle metabolites (ECP) on CS-induced lung injury and its potential hepatic metabolic detoxification are still unclear. Therefore, sixty mice were randomly divided into six equal groups. CS-exposed mice were prevented or treated with ECP or ECT infusions for 12 or 8 weeks to determine the antioxidative stress, anti-inflammatory and potential metabolic detoxification of ECT and ECP. Thirty-six mice were randomly divided into six equal groups to observe the effects on hepatic metabolic detoxification by replacing daily drinking water with ECT. Results showed that CS significantly decreased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and upregulated the expressions of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-1ß in serum. These adverse effects were modulated by ECP and ECT. In addition, ECT upregulated the mRNA expression of pregnane X receptor (PXR) and cytochrome P450 (CYP450) in the liver on daily free drinking ECT mice group. Western blot analysis further revealed that in CS-exposed mice, ECP and ECT significantly decreased the phosphorylation of mitogen-activated protein kinase (MAPK) in the lung but upregulated the protein expressions of PXR and aryl hydrocarbon receptor (AhR) in the liver. Overall, our findings demonstrated that ECT and ECP protected against lung injury induced by CS via MAPK pathway and enhanced hepatic metabolic detoxification via PXR and AhR pathways. Therefore, daily intake of ECT and ECP can potentially protect against CS-induced oxidative and inflammatory injuries.

Liquiritin (LT) exhibits suppressive effects against the growth of human cervical cancer cells through activating Caspase-3 in vitro and xenograft mice in vivo.

Cervical cancer is one of the most common female malignancies worldwide. Liquiritin (LT), a major constituent of Glycyrrhiza Radix, possesses a variety of pharmacological activities, including anti-cancer, anti-oxidative, anti-inflammatory and neuro-protective effects. However, its role in human cervical cancer remains to be elusive. In our study, we found that LT suppressed cervical cancer cell migration, invasion and cloning ability with little cytotoxicity to human normal cells. In addition, apoptosis was induced by LT in cervical cancer cells through activation of Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage. LT-triggered apoptosis was dependent on extrinsic and intrinsic pathways, which were relied on Fas-associated protein with death domain (FADD)- and Bcl-2/Bax-regulated pathways, leading to Caspase-8 and Caspase-9 cleavage, respectively. LT was found to increase FADD expression, while reduce Bcl-2 expression, contributing to Caspase-3 cleavage. And tumor suppressors, p21 and p53, were enhanced after LT treatment, inhibiting the growth of cervical cancer cells in vitro. Significantly, in vivo study suggested that tumor growth was impeded by LT in a dose-dependent manner through enhancing apoptosis. Together, the data here revealed that LT was an effective and promising candidate for preventing human cervical cancer progression via apoptosis enhancement.

[Impacts of drought stress on leaf osmotic adjustment and chloroplast ultrastructure of stay-green sorghum].

Taking stay-green sorghum (B35) and non-stay green sorghum (Sanchisan) as test materials, a pot experiment was conducted to study their leaf osmotic adjustment and chloroplast ultrastructure at flowering and filling stages under impacts of drought stress (45% -50% of maximum field capacity). For the two sorghum lines, drought stress caused the reduction of their leaf free water content and relative water content, and increased the leaf bound water content, water saturation deficit, and electrical conductivity, with the increment or dement being larger for Sanchisan than for B35. Drought stress increased the leaf soluble sugar content and proline content, with the increment of the soluble sugar content being larger for Sanchisan and the increment of the proline content being larger for B35, while decreased the leaf soluble protein content, with the decrement being larger for Sanchisan than for B35. The chloroplast ultrastructure of both B35 and Sanchisan under drought stress was damaged to some extent, but the damaged degree was obviously lower for B35 than for Sanchisan. The findings indicated that stay-green sorghum had a greater adaptation to drought stress through stronger osmotic adjustment.

[Isolation and characterization of an alkaline xylanasefrom a newly isolated Bacillus sp. QH14].

Twenty-fivealkaline xylanase producing strains were isolated from Qinghai Lake side soil samples. Among these strains, QH14 produced 648.79 U/mLxylanase, and the enzymatic specific activity was 1148.56 U/mg after purification. This alkaline xylanase producing strain belongs to genus Bacillus based on16S rDNA sequencing analysis and then was designated as Bacillus sp. QH14. The alkalinexylanaseencoding gene, XynQH14, was cloned from Bacillus sp. QH14 and expressed in Escherichiacoli BL21 (DE3). The specific activity of the recombinant xylanase XynQH14 was 700.47 Umg-1 after purification by Ni-NTA affinity chromatography. The optimal temperature and pH of XynQH14 were 60℃ and pH9.2, respectively. Its activity was 50% of initial activity after incubation at 55 ℃ for 1h, 80% at pH7-11 at 37 ℃ for 24 h, and 31.02% at pH11 at 50℃ after 24 h, indicating that XynQH14 isthermostable and alkali-stable. These properties ofXynQH14 suggest its favorable potential applications in pulp and paper industries.

[Modeling of forest landscape change in Xiaoxinganling mountains under different planting proportions of coniferous and broadleaved species].

With spatially explicit landscape model (LANDIS), the dynamic change of forest landscape in Youhao Forest Bureau in Xiaoxinganling Mountains from 2001-2201 under 5 planting proportions of coniferous and broadleaved species, i.e., 100% broadleaved species, 70% broadleaved and 30% coniferous species, 50% broadleaved and 50% coniferous species, 30% broadleaved and 70% coniferous species, and 100% coniferous species, was studied, taking the forest under natural regeneration after harvesting as the control. The results showed that afforestation effectively promoted the recovery of forest resources, but single planting of coniferous species would lead to the area percent of broadleaved species lower than the control. When broadleaved species were planted only, the area percent of coniferous species was lower than the control. The area percent and aggregation index of Pinus koraiensis and Larix gmelini increased with increasing planting proportion of coniferous species, and those of Quercus mongolica increased with increasing planting proportion of broad-leaved species. Afforestation decreased the area percent of Betula phatyphylla, but had no significant effects on its aggregation index. Different afforestation strategies not only altered the species area percent, but also affected the species spatial pattern.

[Effects of different forest management alternatives on Sciurus vulgaris habitat].

A spatially explicit landscape model LANDIS was applied to simulate the forest landscape changes under four management alternatives (no cutting, clear cutting, selective cutting I and II) in Youhao Forestry Bureau located in Small Xing' an Mountain from 2000 to 2200. The outcomes from LANDIS were combined with a landscape-level habitat suitability index (HSI) model in a GIS environment to assess Sciurus vulgaris habitat quality. The results showed that the increase of suitable habitat area and the decrease of marginally suitable area were the fastest under no cutting scenario, and the slowest under clear cutting scenario. Suitable habitat area increased faster while marginally suitable area decreased more slowly under selective cutting I scenario than under selective cutting II. Overall, the optimal management alternative of S. vulgaris habitat was in the sequence of no cutting, selective cutting I, selective cutting II, and clear cutting.