Gas Sensing Properties of PLD Grown 2D SnS Film: Effect of Film Thickness, Metal Nanoparticle Decoration, and In Situ KPFM Investigation.

This study employs novel growth methodologies and surface sensitization with metal nanoparticles to enhance and manipulate gas sensing behavior of two-dimensional (2D)SnS film. Growth of SnS films is optimized by varying substrate temperature and laser pulses during pulsed laser deposition (PLD). Thereafter, palladium (Pd), gold (Au), and silver (Ag) nanoparticles are decorated on as-grown film using gas-phase synthesis techniques. X-ray diffraction (XRD), Raman spectroscopy, and Field-emission scanning electron microscopy (FESEM) elucidate the growth evolution of SnS and the effect of nanoparticle decoration. X-ray photoelectron spectroscopy (XPS) analyses the chemical state and composition. Pristine SnS, Ag, and Au decorated SnS films are sensitive and selective toward NO2 at room temperature (RT). Ag nanoparticle increases the response of pristine SnS from 48 to 138% toward 2 ppm NO2, which indicates electronic and chemical sensitization effect of Ag. Pd decoration on SnS tunes its selectivity toward H2 gas with a response of 55% toward 70 ppm H2 and limit of detection (LOD) < 1 ppm. In situ Kelvin probe force microscopy (KPFM) maps the work function changes, revealing catalytic effect of Ag toward NO2 in Ag-decorated SnS and direct charge transfer between Pd and SnS during H2 exposure in Pd-decorated SnS.

Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Neoadjuvant Chemotherapy or Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chemotherapy and chemoradiation have become essential adjuncts to improve the survival of patients with resectable esophageal squamous cell carcinoma (ESCC) in the perioperative period. Although preoperative treatment plus surgery is commonly used, controversy remains regarding the optimal treatment strategy for patients with locally advanced ESCC. METHODS: A retrospective review of clinical stage II and III ESCC patients who underwent esophagectomy at Henan Cancer Hospital between October 2014 and October 2017 was performed. The patients were divided into a neoadjuvant chemotherapy (NAC) group and an adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was used to exclude confounders. Survival was estimated using Kaplan‒Meier analysis and compared by the log-rank test. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses. RESULTS: A total of 684 patients were enrolled, including 365 (53.4%) patients in the NAC group. After PSM, 294 pairs of patients were left. NAC prolonged the OS (not reached versus 57.3 months, P = 0.002) and DFS (57.2 vs. 36.4 months, P = 0.010) and decreased the total rate of recurrence (50.1% vs. 59.2%, P = 0.025) and local recurrence (27.9% vs. 36.7%, P = 0.022) compared with AC. The multivariable analyses showed that NAC plus surgery modality was an independent predictor for improved OS (HR: 0.582, 95% CI: 0.467-0.786, P = 0.001). CONCLUSION: NAC plus surgery prolonged OS and DFS, and significantly decreased the total rate of recurrence compared with surgery plus AC in patients with clinical stage II and III ESCC.

NLRP3/miR-223-3p axis attenuates neuroinflammation induced by chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is mainly characterized by chronic intermittent hypoxia (CIH) with multiple brain injuries. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining inflammation. However, the role of NLRP3 and its underlying mechanism in CIH-elicited neuroinflammation remains unclear. We constructed an OSA-related CIH in vivo model and assessed the rats' cognitive behavior in the Morris water maze. The combination of miR-223-3p and NLRP3 was confirmed by the TargetScan database, double luciferase reporter gene experiment, and RNA immunoprecipitation (RIP) experiment. Western blot and ELISA assay were used to analyze the effects of miR-223-3p targeting NLRP3 on the expression of pyroptotic or inflammatory factors in vivo in CIH rats. Severe cognitive impairment was observed in rats at week 6 post-treatment, with increased inflammatory factors in the blood and hippocampus, heightened NLRP3 expression, and low miR-223-3p levels. And the good binding activity of the two was confirmed by dual luciferase reporter and RIP experiments. Next, we found that silencing NLRP3 or overexpression of miR-223-3p in the CIH model could improve cognitive deficits and reduce the level of proinflammatory factors and pyroptosis factors in rats. Finally, based on silencing NLRP3 or overexpression miR-223-3p, we confirmed that there was a regulatory relationship between miR-223-3p and NLRP3. Our results suggested that the NLRP3/ miR-223-3p axis played a role in attenuating CIH-induced neuroinflammation.

Dynamics of parainfluenza virus among hospitalized children with acute respiratory tract infection under two-child policy and COVID-19 pandemic in Hubei Province, China, 2014-2022.

To analyze changes in the detection of parainfluenza virus (PIV) in children hospitalized with acute respiratory tract infection (ARTI) during 2014-2022 in Hubei Province, and explore the impact of the universal two-child policy and the public health measures against COVID-19 epidemic on the prevalence of PIV in China. The study was conducted at the Maternal and Child Health Hospital of Hubei Province. Children aged <18 years with ARTI admitted from January 2014 to June 2022 were enrolled. The infection of PIV was confirmed by the direct immunofluorescence method in nasopharyngeal specimens. Adjusted logistic regression models were used to analyze the influence of the universal two-child policy implementation and public health measurements against COVID-19 on PIV detection. Totally 75 128 inpatients meeting the criteria were enrolled in this study from January 2014 to June 2022 with an overall PIV positive rate of 5.5%. The epidemic seasons of PIV prevalence lagged substantially in 2020. A statistically significant higher positive rate of PIV was observed in 2017-2019 compared to that in 2014-2015 (6.12% vs 2.89%, risk ratio = 2.12, p < 0.001) after the implementation of the universal two-child policy in 2016. A steep decline occurred in PIV positive rate during the COVID-19 epidemic in 2020 (0.92% vs 6.92%, p < 0.001) and it rebounded during the regular epidemic prevention and control period in 2021-2022 (6.35%, p = 0.104). In Hubei Province, the implementation of the universal two-child policy might have led to an increase of PIV prevalence, and public health measures during the COVID-19 epidemic might have influenced the fluctuation in PIV detection since 2020.

Patterns and Influence of Lymph Nodal Metastases After Neoadjuvant Chemotherapy and Surgery for Thoracic Esophageal Squamous Cell Carcinoma.

PURPOSE: The purpose of this retrospective study was to define the pattern of lymph nodal metastases in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy (NCT) followed by esophagectomy and to evaluate its influence on prognosis. METHODS: A total of 398 patients with clinical stage T3N0 or T1-3N+ ESCC who underwent NCT and radical esophagectomy with two-field lymphadenectomy were included. The distribution and frequency of metastases were counted separately for each lymph node station. The ypN stage, number of positive lymph node stations and lymph node stations with a metastasis rate greater than 5% were analyzed by using univariate Cox regression, followed by separate multivariable Cox regression analyses after adjusting for various clinical factors. RESULTS: Lymph node metastases were most frequently observed in the right upper paratracheal (16.8%) and left gastric artery (13.1%) stations. Multivariable models controlling for clinical factors showed that ypN stage remained a significant independent predictor of survival (N1 vs. N0: hazard ratio [HR], 2.30, 95% confidence interval [CI] 1.38-3.83, P < 0.001; N2 vs. N0: HR, 3.76, 95% CI 2.21-6.38, P < 0.001; N3 vs. N0: HR, 7.14, 95% CI 3.78-13.48, P < 0.001). The model from the multivariable analysis with the highest c-index score, indicating superior discriminatory preference, was ypN stage (c-index, 0.72). CONCLUSIONS: The pattern and influence of lymph node metastases after NCT will provide guidance on the extent of lymphadenectomy. Common positive lymph node stations for thoracic ESCC after NCT include the paratracheal, subcarinal, paraesophageal, paracardial, and left gastric artery stations.

Preparation of multiphoton high-dimensional GHZ states.

The physics associated with multipartite high-dimensional entanglement is different from that of multipartite two-dimensional entanglement. Therefore, preparing multipartite high-dimensional entanglements with linear optics is challenging. This study proposes a preparation protocol of multiphoton GHZ state with arbitrary dimensions for optical systems. Auxiliary entanglements realize a high-dimensional entanglement gate to connect the high-dimensional entangled pairs to a multipartite high-dimensional GHZ state. Specifically, we use the path degrees of freedom of photons to prepare a four-partite, three-dimensional GHZ state. Our method can be extended to other degrees of freedom to generate arbitrary GHZ entanglements in any dimension.

Development and evaluation of serological screening based on one dried plasma spot for HIV, syphilis, and HCV.

BACKGROUND: In the effort to prevent and control HIV/AIDS, China has established a national sentinel surveillance system. However, some sentinel sites face limitations in environmental resources and accessibility, prompting the exploration of alternative sample strategies. Dried plasma spots (DPS) samples are viewed as promising alternatives to traditional plasma samples due to their advantages, including sample stability, easy storage, and convenient transport. This study aims to develop a method for screening HIV, Treponema pallidum (TP), and Hepatitis C Virus (HCV) using DPS samples and assess their performance. METHODS: Based on existing commercial assay kits, a detection method was established through the optimization of experimental parameters, including the amount of plasma on filter paper, the volume of elution solution applied to dried plasma spots, the size of dried plasma spots, elution solution volume, elution solution components, elution temperature, and elution time. A series of laboratory evaluation panels were constructed for laboratory assessments, including the laboratory basic panel, laboratory interference panel, and laboratory precision panel. Additionally, clinical samples were used for evaluation. RESULTS: Optimal conditions for DPS sample extraction were: plasma volume, 100 µL; DPS size, whole spot; eluent volume, 500 µL; eluent, PBS with 1‰ Tween20; elution time, 2 h; elution temperature, room temperature. A total of 619 paired plasma/DPS samples were tested by both methods. The DPS-based ELISA method exhibited 100% sensitivity/specificity for HIV, 98.6%/100% for TP, and 99.6%/100% for HCV. Kappa values between the plasma samples and DPS samples were 100% for HIV, 99% for TP, and 100% for HCV. The DPS-based ELISA method failed to detect 1 HCV mono-infected sample and TP in 1 HIV/HCV/TP co-infected sample. For the HIV/HCV/TP co-infected sample, the S/CO in the plasma sample was 2.143 and in the DPS sample was 0.5. For HCV, the S/CO (sample OD/cut-off) was 3.049 in the plasma sample and 0.878 in the DPS sample. CONCLUSIONS: A single DPS, following one-time standardized processing, can be used to detect HIV, HCV, and TP. Researching and establishing laboratory testing methods better suited for China's sentinel surveillance have significant practical applications in improving HIV testing in resource-constrained environments.

Epidemiological change of influenza virus in hospitalized children with acute respiratory tract infection during 2014-2022 in Hubei Province, China.

PURPOSE: Influenza virus (IFV) causes acute respiratory tract infection (ARTI) and leads to high morbidity and mortality annually. This study explored the epidemiological change of IFV after the implementation of the universal two-child policy and evaluated the impact of coronavirus disease 2019 (COVID-19) pandemic on the detection of IFV. METHODS: Hospitalized children under 18 years with ARTI were recruited from Hubei Maternal and Child Healthcare Hospital of Hubei Province from January 2014 to June 2022. The positive rates of IFV were compared among different periods by the implementation of the universal two-child policy and public health measures against COVID-19 pandemic. RESULTS: Among 75,128 hospitalized children with ARTI, the positive rate of IFV was 1.98% (1486/75128, 95% CI 1.88-2.01). Children aged 6-17 years had the highest positive rate of IFV (166/5504, 3.02%, 95% CI 2.58-3.50). The positive rate of IFV dropped to the lowest in 2015, then increased constantly and peaked in 2019. After the universal two-child policy implementation, the positive rate of IFV among all the hospitalized children increased from 0.40% during 2014-2015 to 2.70% during 2017-2019 (RR 6.72, 95% CI 4.94-9.13, P < 0.001), particularly children under one year shown a violent increasing trend from 0.20 to 2.01% (RR 10.26, 95% CI 5.47-19.23, P < 0.001). During the initial outbreak of COVID-19, the positive rate of IFV decreased sharply compared to that before COVID-19 (0.35% vs. 3.37%, RR 0.10, 95% CI 0.04-0.28, P < 0.001), and then rebounded to 0.91%, lower than the level before COVID-19 (RR 0.26, 95% CI 0.20-0.36, P < 0.001). CONCLUSION: IFV epidemiological pattern has changed after the implementation of the universal two-child policy. More attention should be emphasized to comprehend the health benefits generated by COVID-19 restrictions on IFV transmission in future.

Organocatalytic Aza-Michael/Mannich Cascade Reaction: Synthesis of Enantioenriched 3,3'-Spirooxindole γ-Lactams.

Highly enantioselective synthesis of 3,3'-spirooxindole γ-lactams with three contiguous stereocenters (two quaternary) was achieved. The aza-Michael/Mannich cascade reaction of α-imine-ß-oxobutanamides and methyleneindolinones catalyzed by a bifunctional diaminocyclohexane-derived thiourea catalyst gave the desired products in moderate to good yields (up to 78%), moderate to good diastereoselectivities (up to 10:1 dr), and good to excellent enantioselectivities (up to >99% ee). A gram-scale synthesis and some transformations of 3,3'-spirooxindole γ-lactams were also carried out.

A multicenter randomized, controlled clinical trial of adjuvant sintilimab for esophageal squamous cell carcinoma.

No adjuvant treatment has been established for patients who remain at high risk of recurrence and incidental pathologic lymph node metastasis for esophageal squamous cell carcinoma (ESCC). In this open-label, multicenter, phase III, randomized controlled trial, ESCC patients who did not achieve pathologic complete response after neoadjuvant chemotherapy plus surgery and clinical T1-2 N0 patients with incidental pathologic lymph node metastasis following initial surgery were randomized at a 2:1 ratio to receive either a sintilimab regimen or observational management (NCT05495152). The primary end point was disease-free survival for all randomized patients. The results of this randomized controlled trial addressed controversy regarding the survival benefits of adjuvant sintilimab treatment for patients with resected locally advanced ESCC. Clinical Trial Registration: NCT05495152 (ClinicalTrials.gov).

Survival impact of the number of lymph nodes dissection in patients receiving neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

This study aimed to investigate the survival impact of the number of lymph nodes dissection (LND) in patients receiving neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed the clinical pathological data and survival of 407 ESCC patients who underwent esophagectomy after NCT between January 2015 and December 2016. The relationship between the number of LNDs and 5-year overall survival (OS) or disease-free survival (DFS) was plotted by using restricted cubic spline analysis. A Cox proportional hazards regression model was used to identify prognostic factors of OS and DFS. We observed an obvious non-linear relationship between LND and the hazard ratios (HRs) for OS (P = 0.0015) and DFS (P < 0.001) of all the patients. In the multivariate analysis of OS and DFS, the number of LNDs (greater than 28 and less than 46) had a significant protective effect on survival (OS: HR: 0.61, 95% CI: 0.42-0.88, P = 0.007; DFS: HR: 0.50, 95% CI: 0.36-0.70, P < 0.001). For patients with nodal metastases, it was also an independent prognostic factor for OS (HR, 0.56, 95% CI, 0.35-0.90, P = 0.017) and DFS (HR, 0.42, 95% CI, 0.28-0.65, P < 0.001). Some degree of lymphadenectomy after NCT was beneficial in improving 5-year OS and DFS for ESCC patients with nodal metastases. For patients with nodal negativity, more extended lymphadenectomy did not improve patient survival.

Predictive performance of renal resistive index, semiquantitative power Doppler ultrasound score and renal venous Doppler waveform pattern for acute kidney injury in critically ill patients and prediction model establishment: a prospective observational study.

BACKGROUND: This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score and renal venous Doppler waveform (RVDW) pattern in predicting acute kidney injury (AKI) in critically ill patients and establish prediction models. METHODS: This prospective observational study included 234 critically ill patients. Renal ultrasound was measured within 24 h after intensive care unit admission. The main outcome was the highest AKI stage within 5 days after admission according to the Kidney Disease Improving Global Outcomes criteria. RESULTS: Patients in the AKI stage 3 group had significantly higher RRI, RVDW pattern and lower PDU score (p < 0.05). Only lactate, urine volume, serum creatinine (SCr) on admission, PDU score and RVDW pattern were statistically significant predictors (p < 0.05). Model 1 based on these five variables (area under the curve [AUC] = 0.938, 95% confidence interval [CI] 0.899-0.965, p < 0.05) showed the best performance in predicting AKI stage 3, and difference in AUC between it and the clinical model including lactate, urine volume and SCr (AUC = 0.901, 95% CI 0.855-0.936, p < 0.05) was statistically significant (z statistic = 2.224, p = 0.0261). The optimal cut-off point for a nomogram based on Model 1 was ≤127.67 (sensitivity: 95.8%, specificity: 82.3%, Youden's index: 0.781). CONCLUSIONS: The nomogram model including SCr, urine volume, lactate, PDU score and RVDW pattern upon admission exhibited a significantly stronger capability for AKI stage 3 than each single indicator and clinical model including SCr, urine volume and lactate.

Analysis of Intestinal Metabolites in SR-B1 Knockout Mice via Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry.

Scavenger receptor class B type 1 (SR-B1), a multiligand membrane receptor, is expressed in a gradient along the gastrocolic axis. SR-B1 deficiency enhances lymphocyte proliferation and elevates inflammatory cytokine production in macrophages. However, whether SR-B1 affects intestinal metabolites is unclear. In this study, we detected metabolite changes in the intestinal tissue of SR-B1-/- mice, including amino acids and neurotransmitters, by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and HPLC. We found that SR-B1-/- mice exhibited changes in intestinal lipid metabolites and metabolic pathways, including the glycerophospholipid, sphingolipid, linoleic acid, taurine, and hypotaurine metabolic pathways. SR-B1 deficiency influenced the contents of amino acids and neurotransmitters in all parts of the intestine; the contents of leucine (LEU), phenylalanine (PHE), tryptophan (TRP), and tyrosine (TYR) were affected in all parts of the intestine; and the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were significantly decreased in both the colon and rectum. In summary, SR-B1 deficiency regulated intestinal lipids, amino acids, and neurotransmitter metabolism in mice.

High-Dimensional Bell Test without Detection Loophole.

Violation of Bell's inequalities shows strong conflict between quantum mechanics and local realism. Loophole-free Bell tests not only deepen understanding of quantum mechanics, but are also important foundations for device-independent (DI) tasks in quantum information. High-dimensional quantum systems offer a significant advantage over qubits for closing the detection loophole. In the symmetric scenario, a detection efficiency as low as 61.8% can be tolerated using four-dimensional states and a four-setting Bell inequality [Phys. Rev. Lett. 104, 060401 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.060401]. For the first time, we show that four-dimensional entangled photons violate a Bell inequality while closing the detection loophole in experiment. The detection efficiency of the four-dimensional entangled source is about 71.7%, and the fidelity of the state is 0.995±0.001. Combining the technique of multicore fibers, the realization of loophole-free high-dimensional Bell tests and high-dimensional quantum DI technologies are promising.

Base-controlled dearomative [3 + 2] cycloadditions between 3-nitro-indoles and fumaric acid amide esters.

The base-controlled dearomative [3 + 2] cycloaddition reaction between 3-nitroindoles and fumaric acid amide esters has been disclosed by using the dearomatization and aromatization strategy. Three kinds of diverse functionalized pyrrolo[2,3-b]indole derivatives were obtained respectively with excellent chemoselectivities and good diastereoselectivities using different bases.

Intra-articular opening wedge osteotomy for varus ankle arthritis with computer-assisted planning and patient-specific surgical guides: a retrospective case series.

BACKGROUND: Computer-assisted preoperative planning, combined with PSI has become an effective technique for treating complex limb deformities. The purpose of this study was to evaluate the efficacy and safety of the novel technique in corrective osteotomy for intra-articular varus ankle deformities associated with osteoarthritis and ankle instability. METHODS: Nineteen patients with intra-articular varus ankle arthritis were reviewed between April 2017 and June 2019, including ten men and nine women with a mean age of 58.3 ± 9.9 years (range, 38 to 76 years). All patients underwent intra-articular opening wedge osteotomy assisted by 3D virtual planning and PSI. Weight-bearing radiographs were used to assess the radiographic results, including TAS angle, TT angle, TMM angle, TC angle, TLS angle, opening-wedge angle, and wedge height. Functional outcomes were assessed by the AOFAS score, VAS score, and ROM of the ankle. RESULTS: The average follow-up time was 32.2 ± 9.0 months (range, 22 to 47 months). The average union time was 4.4 ± 0.9 months (range, 3.0 to 6.5 months). The TAS angle significantly changed from 84.1 ± 4.6° preoperatively to 87.7 ± 3.1° at the 1-year follow-up and 86.2 ± 2.6° at the latest follow-up. Similarly, the TT angle, TMM angle and TC angle changed significantly at the 1-year follow-up compared with the preoperative assessment and remained stable until the last follow-up. However, the TLS was not corrected significantly. The postoperative obtained opening-wedge angle, and wedge height showed no significant change with preoperative planning. The overall complication rate was 15.8%. The mean VAS score improved from 5.3 ± 0.6 to 2.7 ± 0.7. The mean AOFAS score improved from 56.2 ± 7.6 to 80.6 ± 4.6. However, the ROM showed no significant change. CONCLUSIONS: Accurate correction and satisfactory functional recovery were attained with computer-assisted planning and PSI in the corrective osteotomy of intra-articular varus ankle deformities.

Three new tyrosol derivatives from Huangjing wine.

Phytochemical investigation on the concentrate of Huangjing wine, resulted in the isolation of three new tyrosol derivatives 4'''-hydroxyphenethyl 2-(R)-hydroxy-3-phenylpropionate (1), 4'''-hydroxyphenethyl(4'-hydroxy-3'-methoxyphenyl)propionate (2) and 4''-hydroxyphenethyl ethyl succinate (3), together with 5 known compounds, ferulic acid (4), L-phenyllactic acid (5), hydroxytyrosol (6), dihydroferulic acid (7), cyclo(L-Pro-D-Tyr) (8). Their structures were elucidated using spectroscopic analysis and by comparison with the literature data. All compounds displayed antioxidant effect in the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. Among them, the new compound 2 exhibited obvious antioxidant effect, and new compounds 1 and 3 exhibited medium antioxidant effect.

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis.

Doxorubicin (DXB) is one of the most commonly used anticancer agents for treating solid and hematological malignancies; however, DXB-induced cardiorenal toxicity presents a limiting factor to its clinical usefulness in cancer patients. Costunolide (COST) is a naturally occurring sesquiterpene lactone with excellent anti-inflammatory, antioxidant and antiapoptotic properties. This study evaluated the effect of COST on DXB-induced cardiorenal toxicity in rats. Rats were orally treated with COST for 4 weeks and received weekly 5 mg/kg doses of DXB for three weeks. Cardiorenal biochemical biomarkers, lipid profile, oxidative stress, inflammatory cytokines, histological and immunohistochemical analyses were evaluated. DXB-treated rats displayed significantly increased levels of lipid profiles, markers of cardiorenal dysfunction (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin T, blood urea nitrogen, uric acid and creatinine). In addition, DXB markedly upregulated cardiorenal malondialdehyde, tumor necrosis factor-α, interleukin-1ß, interleukin-6 levels and decreased glutathione, superoxide dismutase and catalase activities. COST treatment significantly attenuated the aforementioned alterations induced by DXB. Furthermore, histopathological and immunohistochemical analyses revealed that COST ameliorated the histopathological features and reduced p53 and myeloperoxidase expression in the treated rats. These results suggest that COST exhibits cardiorenal protective effects against DXB-induced injury presumably via suppression of oxidative stress, inflammation and apoptosis.

CircRNA CircZMYM4 inhibits the growth and metastasis of lung adenocarcinoma via the miR-587/ODAM pathway.

Circular RNAs (circRNAs) are known to regulate tumorigenesis. In this study, circRNAs microarray was used to analyze the circRNA expression in lung adenocarcinoma (LUAD) tissues, and CircRNA zinc finger MYM-type containing 4(circZMYM4) was selected for further analysis. In this study, we detected circZMYM4 expression in LUAD specimens and cell lines using RT-PCR. The expression of circZMYM4 was further verified in the GEO datasets and TCGA datasets. Gain-of-function and loss-of-function experiments were used to analyze the effects of circZMYM4 on LUAD in vivo and in vitro. The relationship between miR-587 and circZMYM4 or ODAM was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assays and RNA-pull down. We found that circZMYM4 was distinctly down-regulated in LUAD tissues and cell lines. Functional assays revealed that circZMYM4 overexpression suppressed LUAD cell proliferation, metastasis and suppressed apoptosis, while miR-587 overexpression could weaken these effects. Importantly, circZMYM4 upregulated ODAM expression via sponging miR-587 to suppress LUAD progression. ODAM knockdown could reverse the repressive effect of circZMYM4 overexpression on cell proliferation, migration and invasion abilities. Overall, circZMYM4 regulates the miR-587/ODAM axis to suppress LUAD progression, which may become a potential biomarker and therapeutic target.