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Abstract Background Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. Methods Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. Results CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. Conclusion A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases. Methods Based on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (DmdMu/+) mice were obtained after genotype identification. Male hemizygous DmdMu/+(DmdMu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting. An acute inflammation model was established in DmdMu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry. Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (DmdMu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of DmdMu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P

Background: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. Methods: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. Results: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. Conclusion: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients. [ABSTRACT FROM AUTHOR]

Background: Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. Methods: Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). Results: Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45–49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35–39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P < 0.001). Conclusions: The I-ELCAP guideline has the highest eligibility rate for both males and females. But its actual efficiency ratio for those deemed eligible by the guideline was the lowest. Whereas the NCCN guideline has the highest ERe value for those deemed eligible by the guideline. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the characteristics of the combined application of organic fertilizer and inorganic fertilizer using different tillage methods to delay the senescence of maize leaves. The yield and activities of GDH, CAT, APX, GR, and GSH enzymes in maize leaves were measured at different growth stages by using two tillage methods, three organic and inorganic combined applications (P1, P2, and P3), and four control treatments. (1) During the growth period, the R + S and R treatments were P1 treatments, with the highest enzyme activities noted for GDH, CAT, APX, GR, and GSH, which were 36.79–103.22% higher than those of CK. (2) The average yield of all R + S treatments was higher than that of R treatments, and the average yield of P1 treatment was the highest under R + S, which was 13,663.79 kg hm−2, which was 6.39%, 7.90%, and 14.67% higher than that of P2, P3, and CK, respectively, which was lower than that of R. The yield of P1 treatment was 2.53% higher. (3) There was a significant positive correlation between APX activity, CAT activity, GR activity, GDH activity, GSH activity, grain number per ear, ear length, and 100-grain weight of maize leaves at the grain filling stage, and a significant negative correlation between bald tip length and yield. The treatment details had the strongest enzyme activity and the highest yield when using the rotary tillage + subsoiling (R + S) P1 method, which was the most suitable tillage method and the best fertilizer ratio combination, which could be demonstrated and popularized in a large area in the dry farming area of spring maize in Shanxi Province. [ABSTRACT FROM AUTHOR]

2,6-Di-tert-butyl-4-methylphenol (BHT) is an excellent antioxidant that is easily oxidized to 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHTOOH). For the safety of BHT production and usage, it is meaningful to study the thermal stability and decomposition properties of BHT and BHTOOH. In this paper, the thermal decomposition properties of BHT and BHTOOH were compared by the mini closed pressure vessel test (MCPVT) and differential scanning calorimetry (DSC). Their kinetics of thermal decomposition were studied using thermogravimetric analysis (TGA). The thermal decomposition products of BHT and BHTOOH were analyzed by gas chromatography-mass spectrometry (GC–MS). The results show that there was no significant change in temperature pressure when BHT was warmed up under a nitrogen atmosphere, indicating that BHT was stable within 400 K. The thermal decomposition reaction of BHTOOH was rapid with an initial reaction temperature of 375.2 K. The initial exothermic temperature (Ti) and heat release (QDSC) of DSC were 384.9 K and 865.0 J g−1, respectively. The apparent activation energies (Ea) for the thermal decomposition reactions of BHT and BHTOOH calculated by the Kissinger method were 151.8 kJ mol−1 and 66.07 kJ mol−1, respectively. The main decomposition products of BHT were isobutene and 2-tert-butyl-4-methylphenol. The thermal decomposition products of BHTOOH included BHT, 2,6-di-tert-butyl-4-ethylphenol, 3,5-di-tert-butyl-4-hydroxybenzaldehyde, 4,4′-(1,2-ethanediyl) bis [2,6-bis (1,1-dimethylethyl) phenol, etc. Based on the thermal decomposition behavior and products, the reaction pathway has been described. These results indicate that BHT is a potential thermal hazard during production, storage and application. For the safety of the chemical industry, the oxidation of BHT should be avoided. [ABSTRACT FROM AUTHOR]

Objective: A method for determining the residues of 30 antiparasitic drugs in animal-derived food using ultrahigh- performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established. Methods: The samples were extracted with acetonitrile and 1% ammonia acetic ether and purified by QuEChERS. After purification, Waters ACQUITY UPLCTM BEH C18 column was used for separation, and a gradient elution of 10 mmol/L ammonium formate (containing 0.1% formic acid) aqueous solution, acetonitrile:methanol (50:50, v:v) was performed as the mobile phase. Detection was carried out using electrospray ionization (ESI) in both positive and negative ion modes using multiple reaction monitoring (MRM). Matrix-matched external standard quantification was used. Results: Under the optimized conditions, the 30 antiparasitic drugs showed good linearity within their respective linear ranges, with coefficient of determination (r2) greater than 0.99. The recoveries ranged from 70.1% to 111%, and the relative standard deviations were between 0.10% and 9.1% (n=6). The method detection limit ranged from 0.001 to 0.3 μg/kg, and the method quantification limit ranged from 0.004 to 1 μg/kg. Conclusion: The method is sensitive, accurate, and exhibits good repeatability and stability, making it suitable for detecting various antiparasitic drug residues in animal-derived food. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of cancer‐related deaths worldwide. Recent studies have identified pyroptosis, a type of programmed cell death, as a critical process in the development and progression of lung cancer. In this study, we investigated the effect of EEBR, a new compound synthesized by our team, on pyroptosis in non‐small cell lung cancer cells (NSCLC) and the underlying molecular mechanisms. Our results demonstrated that EEBR significantly reduced the proliferation and metastasis of NSCLC cells in vitro. Moreover, EEBR‐induced pyroptosis in NSCLC cells, as evidenced by cell membrane rupture, the release of cytokines such as interleukin‐18 and interleukin‐1 beta and the promotion of Gasdermin D cleavage in a Caspase‐1‐dependent manner. Furthermore, EEBR promoted the nuclear translocation of NF‐κB and upregulated the protein level of NLRP3. Subsequent studies revealed that EEBR‐induced pyroptosis was suppressed by the inhibition of NF‐κB. Finally, EEBR effectively suppressed the growth of lung cancer xenograft tumours by promoting NSCLC pyroptosis in animal models. Taken together, our findings suggest that EEBR induces Caspase‐1‐dependent pyroptosis through the NF‐κB/NLRP3 signalling cascade in NSCLC, highlighting its potential as a candidate drug for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Insufficient immune cell infiltration into the tumor microenvironment (TME) greatly compromises the clinical application of immune‐checkpoint inhibitors (ICIs)‐based immunotherapy. Recent findings have shown that activation of the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway can enhance natural immunity and increase lymphocyte infiltration into the TME, which presents a promising strategy for cancer immunotherapy. In this study, we constructed hydroxyapatite nanoparticles co‐loaded with curcumin and L‐oxaliplatin (Cur/L‐OHP@HAP NPs). We analyzed the particle‐size distribution, zeta potential, spectral characteristics (Fourier‐transform infrared spectroscopy, X‐ray photoelectron spectroscopy, ultraviolet–visible spectroscopy), and drug‐release properties of the Cur/L‐OHP@HAP NPs. The cellular uptake of the Cur/L‐OHP@HAP NPs detected by flow cytometry and confocal laser‐scanning microscopy. We comprehensively evaluated the anti‐tumor properties and immune‐activating effects of the NPs, both in vitro and in vivo. Physicochemical characterizations demonstrated that the Cur/L‐OHP@HAP NPs were successfully synthesized and were capable of pH‐dependent drug release. Notably, the Cur/L‐OHP@HAP NPs efficiently entered cancer cells, after which the released L‐OHP induced nuclear DNA (nDNA) damage to some extent. HAP promoted the release of intracellular Ca2+ stores in cancer cells, and curcumin inhibited Ca2+ efflux, resulting in intracellular Ca2+ overload and the release of mitochondrial DNA (mtDNA). Damage to both nDNA and mtDNA greatly stimulated the cGAS‐STING pathway, thereby activating natural immunity, accompanied by immune cell recruitment to the TME. In summary, the Cur/L‐OHP@HAP NPs show good prospects for improving cancer immunotherapy. [ABSTRACT FROM AUTHOR]