Dissecting the manipulation of lufenuron on chitin synthesis in Helicoverpa armigera.

Lufenuron, a benzoylurea chitin synthesis inhibitor, is effective against many insect pests. However, the insecticidal activity of lufenuron has not been completely elucidated, nor has its disturbing effect on chitin synthesis genes. In this study, bioassay results demonstrated an outstanding toxicity of lufenuron against Helicoverpa armigera larvae. The treated larvae died from abortive molting and metamorphosis defects, and severe separation of epidermis and subcutaneous tissues was observed. Treatment of 3rd- and 4th-instar larvae with LC25 lufenuron significantly extended the duration of larval and pupal stage, reduced the rates of pupation and emergence, and adversely affected pupal weight. Besides, lufenuron can severely reduce chitin content in larval integument, and the lufenuron-treated larvae showed reduced trehalose content in their hemolymph. Further analysis using RNA sequencing revealed that five chitin synthesis genes were down-regulated, whereas the expressions of two chitin degradation genes were significantly enhanced. Knockdown of chitin synthase 1 (HaCHS1), uridine diphosphate-N-acetylglucosamine-pyrophosphorylase (HaUAP), phosphoacetyl glucosamine mutase (HaPGM), and glucosamine 6-phosphate N-acetyl-transferase (HaGNPAT) in H. armigera led to significant increase in larval susceptibilities to LC25 lufenuron by 75.48%, 65.00%, 68.42% and 28.00%, respectively. Our findings therefore revealed the adverse effects of sublethal doses of lufenuron on the development of H. armigera larvae, elucidated the perturbations on chitin metabolism, and proved that the combination of RNAi and lufenuron would improve the control effect of this pest.

ATP protects anti-PD-1/radiation-induced cardiac dysfunction by inhibiting anti-PD-1 exacerbated cardiomyocyte apoptosis, and improving autophagic flux.

The synergy between radiotherapy and immunotherapy in treating thoracic cancers presents a potent therapeutic advantage, yet it also carries potential risks. The extent and nature of cumulative cardiac toxicity remain uncertain, prompting the need to discern its mechanisms and devise effective mitigation strategies. Radiation alone or in combination with an anti- Programmed cell death protein1 (PD-1) antibody significantly reduced cardiac function in C57BL/6J mice, and this pathologic effect was aggravated by anti-PD-1 (anti-PD-1 + radiation). To examine the cellular mechanism that causes the detrimental effect of anti-PD-1 upon cardiac function after radiation, AC16 human cardiomyocytes were used to study cardiac apoptosis and cardiac autophagy. Radiation-induced cardiomyocyte apoptosis was significantly promoted by anti-PD-1 treatment, while anti-PD-1 combined radiation administration blocked the cardiac autophagic flux. Adenosine 5'-triphosphate (ATP) (a molecule that promotes lysosomal acidification) not only improved autophagic flux in AC16 human cardiomyocytes, but also attenuated apoptosis induced by radiation and anti-PD-1 treatment. Finally, ATP administration in vivo significantly reduced radiation-induced and anti-PD-1-exacerbated cardiac dysfunction. We demonstrated for the first time that anti-PD-1 can aggravate radiation-induced cardiac dysfunction via promoting cardiomyocyte apoptosis without affecting radiation-arrested autophagic flux. ATP enhanced cardiomyocyte autophagic flux and inhibited apoptosis, improving cardiac function in anti-PD-1/radiation combination-treated animals.

Neohesperidin dihydrochalbazone protects against septic acute kidney injury in mice.

BACKGROUND: Neohesperidin dihydrochalbazone (NHDC) shows a range of pharmacological actions, however, in septic acute kidney injury (AKI), the effect of NHDC is little known. PURPOSE: To assess the role of NHDC against AKI and the possible mechanisms. METHODS: In vivo, we used different concentration of NHDC (50, 100, and 200 mg/kg) treated septic AKI model of mice. Moreover, in vitro, in HK-2 cells, a lipopolysaccharide (LPS) induced cell model was treated with 10, 20, and 30 µM NHDC. Next, kidney tissue pathologic change, marker of renal injury, apoptosis, and inflammatory factors were assessed using hematoxylin and eosin staining, enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase dUTP nick end labeling, and western blot. HK-2 cell apoptosis and viability were assessed via flow cytometry and cell counting kit-8. In HK-2 cells and tissues, NLRP3, caspase 1, ASC, and P38/ERK 1/2/JNK pathway related protein levels were tested using western blot. RESULTS: NHDC (100 and 200 mg/kg) significantly attenuated kidney injury in caecal ligation and puncture (CLP)-treated mice. In CLP-treated mice, the level of BUN, Scr, KIM-1, and NAGL was reduced by 100 and 200 mg/kg NHDC. Furthermore, 100 and 200 mg/kg NHDC inhibited inflammation by reducing the production of IL-6, TNF-α, and IL-1ß, and inhibited oxidative stress by regulating the change of MDA, SOD, GSH, and CAT. NHDC (100 and 200 mg/kg) inhibited renal cell apoptosis by increasing Bcl2 protein expression and inhibiting Bax and cleaved caspase-3 protein expression. Additionally, NHDC (100 and 200 mg/kg) inhibited the protein levels of phosphorylated (p)-P38, p-JNK, p-ERK 1/2, NLRP3, caspase 1, ASC. In vitro, in LPS-stimulated HK-2 cells, NHDC (20 and 30 µM) increased cell viability, reduced cell apoptosis, restrained inflammation by reducing the content of IL-6, TNF-α, and IL-1ß, and inhibited the protein expression of caspase 1, NLRP3, ASC, p-P38, p-JNK, and p-ERK1/2. Importantly, the promotive effect of NHDC on HK-2 cell viability was reversed by DHR (an activator of P38 MAPK signaling pathway), and DHR reversed the inhibitive effects of NHDC on HK-2 cell apoptosis and inflammation. CONCLUSION: For the first time, NHDC was found to inhibit oxidative stress, inflammation, and apoptosis in AKI model, which was related to the inhibition of P38 MAPK pathways. Our findings provided the theoretical basis for NHDC on the prevention of AKI.

miR-21 inhibition reverses doxorubicin-resistance and inhibits PC3 human prostate cancer cells proliferation.

Many approaches have been examined to reversing multidrug resistance (MDR), but sub-optimal target-based strategies have limited their efficacy. Herein, we investigate microRNA (miR-21) suppression on the doxorubicin (DOX)-sensitisation of the DOX-resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR-21, P-glycoprotein (P-gp), MDR-1 and PTEN evaluated in PC3/DOX cancer cells by qRT-PCR and western blot analyses. The cytotoxic effects of transfected of miR-21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P-gp. Apoptosis was detected by Flow cytometry. As expected, miR-21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA-21 suppression considerably hindered PC3/DOX cell viability. miR-21 suppression dramatically downregulated P-gp expression and activity in DOX-resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P-gp cascade, which miR-21 suppression led to the upregulation of PTEN and sequentially lower-expression of P-gp that reversed MDR. Also, miR-21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR-21 in MDR-reversing in PCa.

A Study on the Preparation of Regular Multiple Micro-Electrolysis Filler and the Application in Pretreatment of Oil Refinery Wastewater.

Through a variety of material screening experiments, Al was selected as the added metal and constituted a multiple micro-electrolysis system of Fe/C/Al. The metal proportion of alloy-structured filler was also analyzed with the best Fe/C/Al ratio of 3:1:1. The regular Fe/C/Al multiple micro-electrolysis fillers were prepared using a high-temperature anaerobic roasting method. The optimum conditions for oil refinery wastewater treated by Fe/C/Al multiple micro-electrolysis were determined to be an initial pH value of 3, reaction time of 80 min, and 0.05 mol/L Na2SO4 additive concentration. The reaction mechanism of the treatment of oil refinery wastewater by Fe/C/Al micro-electrolysis was investigated. The process of the treatment of oil refinery wastewater with multiple micro-electrolysis conforms to the third-order reaction kinetics. The gas chromatography-mass spectrometry (GC-MS) used to analyze the organic compounds of the oil refinery wastewater before and after treatment and the Ultraviolet-visible spectroscopy (UV-VIS) absorption spectrum analyzed the degradation process of organic compounds in oil refinery wastewater. The treatment effect of Fe/C/Al multiple micro-electrolysis was examined in the continuous experiment under the optimum conditions, which showed high organic compound removal and stable treatment efficiency.

[Dieulafoy disease of the bronchus: 3 cases report with literature review].

OBJECTIVES: To improve the understanding of bronchial Dieulafoy disease by summarizing the clinical and literature reported cases. METHODS: The clinical data of 3 patients with bronchial Dieulafoy disease diagnosed by pathology from January 1, 2007 to May 31, 2012 in our hospital was collected and summarized. The data of 19 cases from literature case report regarding bronchial Dieulafoy disease both in Chinese and English were also reviewed through databases including Wanfang Data, National Knowledge Infrastructure, National Center for Biotechnology Information and Ovid Technologics from January 1, 2005 to May 31, 2012. The clinical characteristics, diagnosis and treatment of all the 22 cases were summarized and analyzed. RESULTS: The average age of the 22 cases with bronchial Dieulafoy disease was (47 ± 15) years, and the preponderance was in male adults (16/22). Right lung (16/22) was more commonly involved than the left lung (4/22), and rarely in both lungs (2/22). Eight cases had smoking history, and 10 cases had underlying diseases such as tuberculosis.Sudden onset of massive hemoptysis was a common manifestation. Massive or lethal hemorrhage was often caused by biopsy injury. The abnormality of bronchial Dieulafoy disease was usually demonstrated as nodular lesions within the lumen of the bronchus.However, It was unable to determine their originating of the anomalous arteries in half of the cases(11/22). Most anomalous arteries confirmed by pathology were branched from bronchial artery (9/22), and rarely from pulmonary artery (2/22). The definitive diagnosis was made by pathological examination.Selective bronchial artery embolization and pulmonary lobectomy were the major therapeutic strategies, but bleeding may relapse after bronchial artery embolization, and lobectomy of the lung was a cure approach. CONCLUSIONS: Bronchial Dieulafoy disease should be differentiated in patients with massive and unexplained hemoptysis.It takes a very high risk for biopsy, which rarely needs to be implemented. Bronchial arteriography and selective bronchial artery embolization should be promptly carried out to avoid life-threatening hemoptysis.Lobectomy could be an alternative choice for a cure.

[Evaluation of chronic obstructive pulmonary disease screening in a high risk population].

OBJECTIVE: To investigate the results of spirometry testing used in the screening of COPD from at risk populations. METHODS: A survey of the population aged over 40 years with any of chronic cough and sputum, dyspnea, heavy tobacco smoke was performed, using a questionnaire on clinical characteristics of COPD. Spirometry and chest X ray examination were performed. Different screening methods were compared for sensitivity and specificity for COPD diagnosis. RESULTS: Of 241 surveyed persons, 156 were diagnosed as having COPD, among whom 126 cases were firstly diagnosed. Among all surveyed persons, 87 (36. 1%) cases had mild and moderate COPD, while 69 (28. 6%) had severe and very severe disease. The sensitivity and specificity for diagnosis of COPD of shortness of breath were 61.5% and 61.2% respectively. Combination of respiratory symptoms and risk factors improved the screening power. More than 40 years of age combined with any of heavy smoking, chronic cough and sputum, or shortness of breath, improved the sensitivity to more than 90 percent. CONCLUSIONS: Spirometry test screening of the at risk population can effectively improve early diagnosis of COPD.

[Study on matrix metalloproteinase 1, 9, 12 polymorphisms and susceptibility to chronic obstructive pulmonary disease among Han nationality in northern China].

OBJECTIVE: To study the association between the functional polymorphism of matrix metalloproteinases (MMPs) and the development of chronic obstructive pulmonary disease (COPD). METHODS: 147 COPD patients and 120 healthy smoking controls were selected. Spirometry and chest X-rays had been taken. Questionnaires including sex, age, smoking history, occupational exposure were completed. MMP-9 (-1562 C/T), MMP-1(-1607 1G/2G), MMP-12 (-82 A/G), MMP-12(-357 Asn/ Ser) alleles were determined using PCR-RFLP method. Independent samples T test analysis was carried out to compare patients' age, smoking index, FEV1 /FVC, FEV1 % pred with that of healthy controlled group. The frequencies of genotypes and alleles between groups were analyzed by chi-square tests and multilogistic regression. RESULTS: MMP12 Asn/Asn, CT/AsnAsn were risk factors for smoking-induced COPD. The ORs were 2.361 (95% CI: 1.369-4.017) and 2.433(95% CI: 1.159-5.342) respectively while CC/1G1G/ SerSer seemed to be a protective factor for smoking-induced COPD, with OR as 0.457 and 95% CI as 0.231-0.911. CONCLUSION: Asn/Asn, CT/AsnAsn might be susceptible genotypes while CC/GG/SerSer might serve as protective genotype.