The renal apical sodium-dependent bile acid transporter expression rescue attenuates renal damage in diabetic nephropathy via farnesoid X receptor activation.

AIM: Bile acids (BA) function as signalling molecules regulating glucose-lipid homeostasis and energy expenditure. However, the expression of the apical sodium-dependent bile acid transporter (ASBT) in the kidney, responsible for renal BA reabsorption, is downregulated in patients with diabetic kidney disease (DKD). Using the db/db mouse model of DKD, this study aimed to investigate the effects of rescuing ASBT expression via adeno-associated virus-mediated delivery of ASBT (AAVASBT) on kidney protection. METHODS: Six-week-old male db/db mice received an intraparenchymal injection of AAVASBT at a dose of 1 × 1011 viral genomes (vg)/animal and were subsequently fed a chow diet for 2 weeks. Male db/m mice served as controls. For drug treatment, daily intraperitoneal (i.p.) injections of the farnesoid X receptor (FXR) antagonist guggulsterone (GS, 10 mg/kg) were administered one day after initiating the experiment. RESULTS: AAVASBT treatment rescued renal ASBT expression and reduced the urinary BA output in db/db mice. AAVASBT treatment activated kidney mitochondrial biogenesis and ameliorated renal impairment associated with diabetes by activating FXR. In addition, the injection of FXR antagonist GS in DKD mice would reverse these beneficial effects by AAVASBT treatment. CONCLUSION: Our work indicated that restoring renal ASBT expression slowed the course of DKD via activating FXR. FXR activation stimulates mitochondrial biogenesis while reducing renal oxidative stress and lipid build up, indicating FXR activation's crucial role in preventing DKD. These findings further suggest that the maintenance of renal BA reabsorption could be a viable treatment for DKD.

Clinical features, immune profile and induction chemotherapy options for blastic plasmacytoid dendritic cell neoplasm: a systematic review and meta-analysis.

Aim: Blastic plasmacytoid dendritic cell neoplasm is a rarely occurring hematologic malignancy with a dismal prognosis. Methods: We conducted a meta-analysis for a total of 1312 patients from 24 retrospective studies. Results: The complete remission (CR) rate of acute lymphoblastic leukemia-like induction chemotherapy was 82%, and the overall survival (OS) was 15.75 months; the CR rate of acute myeloid leukemia-like chemotherapy was 51%, and the OS was 7.18 months; and the CR rate of cyclophosphamide, doxorubicin, vincristine and prednisone-like chemotherapy was 50%, and the OS was 12.06 months. Conclusion: Acute lymphoblastic leukemia-like induction chemotherapy has the best CR rate and OS.

Penicillium fungi mediate behavioral responses of the yellow peach moth, Conogethes punctiferalis (Guenée) to apple fruits via altering the emissions of host plant VOCs.

Plant-associated microbes have been reported as important but overlooked drivers of plant-herbivorous insect interactions. Influence of plant-associated microbes on plant-insect interactions is diverse, including beneficial, detrimental, and neutral. Here, we determined the effects of three Penicillium fungi, including Penicillium citrinum, Penicillium sumatrense, and Penicillium digitatum, on the oviposition selection and behavior of the yellow peach moth (YPM), Conogethes punctiferalis (Guenée). Compared with fungi noninfected apples (NIA), mechanically damaged apples (MDA), and P. citrinum in potato dextrose agar medium (PC), the oviposition selection and four-arm olfactometer experiments both showed that mated YPM females preferred to P. citrinum-infected apples (PCA). For P. sumatrense or P. digitatum, we also found that mated YPM females preferred to P. sumatrense-infected apples (PSA) or P. digitatum-infected apples (PDA), respectively. Among three Penicillium fungi-infected apples, the selection rates including oviposition and olfactometer behavior of mated YPM females on PDA were both higher than those on PSA and PCA. Further analyses of host plant volatile organic compounds (VOCs) by GC-MS showed that the absolute contents of ethyl hexanoate and (Z, E)-α-farnesene in PCA, PSA, and PDA were all higher than those in NIA, and a total of 16 novel VOCs were detected in fungi-infected apples (PCA, PSA, and PDA), indicating that fungi infection changed the components and proportions of apple VOCs. Taken together, three Penicillium fungi play significant roles in mediating the host selection of YPMs via altering the emissions of VOCs. These findings will be beneficial for developing formulations for field trapping of YPMs in the future.

Ligand-binding specificities of four odorant-binding proteins in Conogethes punctiferalis.

Odorant-binding proteins (OBPs) play essential roles in lepidopteran insects' perception of host volatiles by binding and transporting hydrophobic ligands. The yellow peach moth (YPM), Conogethes punctiferalis (Guenée), is a serious agricultural pest, with broad host range and cryptic feeding habits. However, few studies about YPM perceiving pheromones and host plant odorants have been reported. In this study, four OBP genes (CpunOBP8, CpunOBP9, CpunABP, and CpunGOBP2) were cloned from the antennae of YPM. The recombinant proteins were expressed and purified by prokaryotic expression system, with their binding affinities to 26 ligands being tested. Four CpunOBPs all had six conserved cysteine residues, which were typical structural characteristics of classical OBPs. The fluorescence competitive binding assay indicated that CpunOBP8 and CpunABP could not only exhibit high binding affinities to female sex pheromones, but also to host plant odorants. For example, CpunOBP8 bound strongly with cis-10-hexadecenal, hexadecanal, and so forth, whereas CpunABP bound with cis-10-hexadecenal, camphene, and 3-carene. Comparatively, CpunOBP9 and CpunGOBP2 could only bind with host plant odorants, with CpunOBP9 binding strongly to 3-methyl-1-butanol, hexyl acetate, and so forth, while CpunGOBP2 displaying the widest binding spectra and correlating with 3-carene, pentyl acetate, and so forth. The results indicated that on the one hand, each of the four CpunOBPs had its specific binding spectra when binding and transporting olfactory ligands; on the other hand, the same ligand might be bound to more than one CpunOBPs, which would provide information for the potential application of semiochemicals in controlling YPM.

A Polar Robust Kalman Filter Algorithm for DVL-Aided SINSs Based on the Ellipsoidal Earth Model.

Autonomous underwater vehicles (AUVs) play an increasingly essential role in the field of polar ocean exploration, and the Doppler velocity log (DVL)-aided strapdown inertial navigation system (SINS) is widely used for it. Due to the rapid convergence of the meridians, traditional inertial navigation mechanisms fail in the polar region. To tackle this problem, a transverse inertial navigation mechanism based on the earth ellipsoidal model is designed in this paper. Influenced by the harsh environment of the polar regions, unknown and time-varying outlier noise appears in the output of DVL, which makes the performance of the standard Kalman filter degrade. To address this issue, a robust Kalman filter algorithm based on Mahalanobis distance is used to adaptively estimate measurement noise covariance; thus, the Kalman filter gain can be modified to weight the measurement. A trial ship experiment and semi-physical simulation experiment were carried out to verify the effectiveness of the proposed algorithm. The results demonstrate that the proposed algorithm can effectively resist the influence of DVL outliers and improve positioning accuracy.

Inhibition of histamine receptor H3 suppresses the growth and metastasis of human non-small cell lung cancer cells via inhibiting PI3K/Akt/mTOR and MEK/ERK signaling pathways and blocking EMT.

Recent evidence shows that the expression levels of histamine receptor H3 (Hrh3) are upregulated in several types of cancer. However, the role of Hrh3 in non-small cell lung cancer (NSCLC) has not been elucidated. In the present study, we showed that the expression levels of Hrh3 were significantly increased in NSCLC samples, and high levels of Hrh3 were associated with poor overall survival (OS) in NSCLC patients. In five human NSCLC cell lines tested, Hrh3 was significantly upregulated. In NSCLC cell lines H1975, H460, and A549, Hrh3 antagonist ciproxifan (CPX, 10-80 µM) exerted moderate and concentration-dependent inhibition on the cell growth and induced apoptosis, whereas its agonist RAMH (80 µM) reversed these effects. Furthermore, inhibition of Hrh3 by CPX or siRNA retarded the migration and invasion of NSCLC cells through inhibiting epithelial-mesenchymal transition (EMT) progression via reducing the phosphorylation of PI3K/Akt/mTOR and MEK/ERK signaling pathways. In nude mice bearing H1975 cell xenograft or A549 cell xenograft, administration of CPX (3 mg/kg every other day, intraperitoneal) significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue. In conclusion, this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC; it might be a potential therapeutic target against the lung cancer.

LncRNA LINP1 regulates acute myeloid leukemia progression via HNF4α/AMPK/WNT5A signaling pathway.

LncRNAs play critical roles in various pathophysiological and biological processes, such as protein translation, RNA splicing, and epigenetic modification. Indeed, abundant evidences demonstrated that lncRNA act as competing endogenous RNAs (ceRNAs) to participate in tumorigenesis. However, little is known about the underlying function of lncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1) in pediatric and adolescent acute myeloid leukemia (AML). The expression of LINP1 was examined in AML patient samples by qRT-PCR. Cell proliferation was examined by CCK-8 and Edu assays. ß-Galactosidase senescence assay, mGlucose uptake assay, lactate production assay, and Gene Ontology (GO) analysis were performed for functional analysis. We found that LINP1 was significantly overexpressed in AML patients at diagnosis, whereas downregulated after complete remission (CR). Furthermore, knockdown of LINP1 expression remarkably suppressed glucose uptake and AML cell maintenance. Mechanistically, LINP1 was found to inhibit the glucose metabolism by suppressing the expression of HNF4a. Both LINP1 and HNF4a knockdown reduced the expression levels of AMPK phosphorylation and WNT5A, indicating for the first time that LINP1 strengthened the HNF4a-AMPK/WNT5A signaling pathway involved in cell glucose metabolism modulation and AML cell survival. Taken together, our results indicated that LINP1 promotes the malignant phenotype of AML cells and stimulates glucose metabolism, which can be regarded as a potential prognostic marker and therapeutic target for AML.

[Effects of cysteinyl leukotrienes receptor antagonists on chronic brain injury after global cerebral ischemia/reperfusion].

OBJECTIVE: : To investigate the effects of cysteinyl leukotrienes receptor (CysLTR) antagonists on global cerebral ischemia/reperfusion (CI/R) injury in gerbils, and to explore its mechanism. METHODS: : Totally 40 gerbils weighting 45-65 g were randomized into sham, saline, Pranlukast and HAMI 3379 groups with 10 animals in each. The CI/R model was established in gerbils by bilateral common carotid occlusion for 10 min followed by reperfusion. After ischemia, the CysLTR antagonists Pranlukast (0.1 mg/kg) and HAMI 3379 (0.1 mg/kg) were injected intraperitoneally for 5 consecutive days in the last two groups,while the former two groups were injected with saline only (10 mL/kg). After 24 h or 14 d reperfusion, neurological deficit score was evaluated and the behavioral dysfunction was assessed, respectively. And 14 d after reperfusion, the neuron morphology of cerebral cortex was observed in brain sections stained with Cresyl violet. In addition, the Iba-1 (microgila) and GFAP (astrocyte) positive cells in cerebral cortex were observed by using immunohistochemitry method. RESULTS: : CI/R models were successfully established in 21 out of 30 gerbils with 7 in saline group, 6 in Pranlukast group, and 8 in HAMI 3379 group. Compared with saline group, Pranlukast and HAMI 3379 significantly attenuated neurological deficits, improved the behavioral function 24 h after reperfusion(all P<0.01); Pranlukast and HAMI 3379 also significantly improved the behavioral function 14 days after reperfusion(P<0.05 or P<0.01). Compared with saline group, the neurological symptom scores in Pranlukast and HAMI 3379 groups presented a trend of amelioration 14 d after reperfusion, but it was not significant(P>0.05). In addition, Pranlukast and HAMI 3379 also inhibited the neuron loss and injury, suppressed microgila and astrocyte activation 14 d after reperfusion(all P<0.01). CONCLUSIONS: : CysLTR antagonists Pranlukast and HAMI 3379 have long-term neuroprotective effect on chronic brain injury induced by global cerebral ischemia/reperfusion in gerbils.

Consequences of orthodontic treatment in malocclusion patients: clinical and microbial effects in adults and children.

BACKGROUND: Malocclusion is a common disease of oral and maxillofacial region. The study was aimed to investigate levels changes of periodontal pathogens in malocclusion patients before, during and after orthodontic treatments, and to confirm the difference between adults and children. METHOD: One hundred and eight malocclusion patients (46 adults and 62 children at the school-age) were randomly selected and received orthodontic treatment with fixed orthodontic appliances. Subgingival plaques were Porphyromonas gingivalis (P.gingivalis), Fusobacterium nucleatum (F. nucleatum), Prevotella intermedia (P. intermedia) and Tannerella forsythensis (T. forsythensis) collected from the observed regions before and after treatment. Clinical indexes, including plaque index (PLI), gingival index (GI), sulcus bleeding index (SBI), probing depth (PD) and attachment loss (AL) of observed teeth were examined. RESULTS: The detection rates of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis increased from baseline to the third month without significant difference, and then returned to pretreatment levels 12 month after applying fixed orthodontic appliances. Adults' percentage contents of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis were significantly higher than those of children at baseline and the first month, but not obvious at the third month. PLI and SBI were increased from baseline to the first and to the third month both in adults and children groups. Besides, PD were increased from baseline to first month, followed by a downward trend in the third month; however, all patients were failed to detect with AL. CONCLUSIONS: Periodontal and microbiological statuses of malocclusion patients may be influenced by fixed orthodontic appliances in both adults and children, more significant in children than in adults. Some microbiological indexes have synchronous trend with the clinical indexes. Long-term efficacy of fixed orthodontic appliances for malocclusion should be confirmed by future researches.

PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling.

Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies.

Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma.

Germinal center lymphoma is a heterogeneous human lymphoma entity. Here we report that constitutive activity of SHP2 (PTPN11) and its downstream kinase ERK is essential for the viability of germinal center lymphoma cells and disease progression. Mechanistically, SHP2/ERK inhibition impedes c-Myc transcriptional activity, which results in the repression of proliferative phenotype signatures of germinal center lymphoma. Furthermore, SHP2/ERK signaling is required to maintain the CD19/c-Myc loop, which preferentially promotes survival of a distinct subtype of germinal center lymphoma cells carrying the MYC/IGH translocation. These findings demonstrate a critical function for SHP2/ERK signaling upstream of c-Myc in germinal center lymphoma cells and provide a rationale for targeting SHP2 in the therapy of germinal center lymphoma.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury.

The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1ß, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Screening of a Prognostic Gene Signature for Relapsed/Refractory Acute Myeloid Leukemia Based on Altered Circulating CircRNA Profiles.

Background: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined. Methods: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs. Results: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis. Conclusion: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.

Establishment and application of a loop-mediated isothermal amplification-lateral flow dipstick (LAMP-LFD) method for detecting Clostridium piliforme.

BACKGROUND: Clostridium piliforme (causative agent of Tyzzer disease) infects various animals, including primates, and hence a threat to animal and human health worldwide. At present, it is detected using traditional methods, such as path morphology, polymerase chain reaction and enzyme-linked immunosorbent assay. Therefore, it is necessary to develop convenient, efficient visual molecular biological methods for detecting C. piliforme. OBJECTIVES: To establish a method with good specificity, high sensitivity and simple operation for the detection of C. piliforme. METHODS: In this study, we designed internal and external primers based on the conserved 23S rRNA region of C. piliforme to develop a biotin-labelled diarrhoea-suffered loop-mediated isothermal amplification (LAMP) system for detecting of C. piliforme and assessed the specificity, sensitivity and repeatability of the LAMP system. RESULTS: The LAMP system did not exhibit cross-reactivity with 24 other common pathogenic species, indicating that it had good specificity. The minimum concentration of sensitivity was 1 × 10-7  ng/µL. Mouse models (Meriones unguiculatus) of Tyzzer disease were established and a LAMP-lateral flow dipstick (LAMP-LFD) was developed for detecting C. piliforme. The detection rate of C. piliforme was 5.08% in clean-grade animals and 9.96% in specific-pathogen-free-grade animals from Jiangsu, Zhejiang and Shanghai. In addition, the detection rates of C. piliforme were 10.1%, 8.6% and 20%, in animals from Hangzhou, Wenzhou and Shaoxing, respectively. The detection rate of C. piliforme was higher in experimental animals used in schools than in those used in companies and research institutes. CONCLUSIONS: The LAMP-LFD method established in this study can be used to detect C. piliforme in animals handled in laboratory facilities of universities, pharmaceutical enterprises and research and development institutions.

Prolonged oral intake of green tea polyphenols attenuates delirium-like behaviors in mice induced by anesthesia/surgery.

Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.

VOCs from fungi-infected apples attract and increase the oviposition of yellow peach moth Conogethes punctiferalis.

BACKGROUND: Plant volatile organic compounds (VOCs) modified by plant-associated microbes can attract or repel the oviposition of herbivores. Here, we explored the effects of three different fungi on apples' VOCs and the cascading impacts on the oviposition preference of yellow peach moth [YPM, Conogethes punctiferalis (Guenée)]. RESULTS: Among Penicillium crustosum-infected apples (PCA), Rhizopus oryzae-infected apples (ROA), Colletotrichum gloeosporioides-infected apples (CGA) and healthy apples (HA), mated YPM females preferred to oviposit eggs on ROA and CGA, and showed significant attractiveness to VOCs from PCA, ROA, and CGA under laboratory conditions. The VOCs analyses showed that there were significant differences between fungi-infected apples (ROA, CGA) and control treatments (mechanically damaged apples (MDA), HA) in terms of the relative contents of 13 VOCs. The relative contents of ethyl 2-methylbutyrate, ethyl caprylate, estragole, ethyl hexanoate in ROA and CGA were higher than those in MDA. The relative content of isopropyl 2-methylbutyrate in ROA was significantly higher than those in HA and CGA. The relative contents of 2-methylbutyl acetate, butyl 2-methylbutyrate, hexyl 2-methylbutyrate, amyl hexanoate, hexyl hexanoate, (E, E)-α-farnesene in ROA and CGA were lower than those in HA. The relative content of hexyl acetate in ROA and CGA was significantly higher than that in MDA, but lower than that in HA. Additionally, 10 fungi-induced VOCs were detected in ROA and/or CGA. When 20 VOCs from ROA and/or CGA were tested as individuals or mixed blends in Y-tube olfactometer assays, mated YPM females preferred amyl 2-methylbutyrate, isoamyl 2-methylbutyrate, isopropyl 2-methylbutyrate, hexyl propionate (common VOCs in ROA, CGA, and HA), and heptacosane (a fungi-induced VOC in ROA), but no significant preferences were observed between individual compounds and mixed blends, except for hexyl propionate. CONCLUSION: Different fungi infection increased the relative contents of common VOCs from healthy and fungi-infected apples, which ultimately resulted in the significant attractiveness for the oviposition of mated YPM females. This study clarified why fungi-infected apples were more attractive to YPMs than healthy apples and screened out the crucial VOCs for YPM oviposition. © 2023 Society of Chemical Industry.

Epidemiological characteristics of adult SCIWORA in Tianjin, China: a preliminary study.

INTRODUCTION: The epidemiology of spinal cord injury without radiographic abnormality (SCIWORA) is less frequently reported in adults as compared with children. The annual incidence of SCIWORA was approximately 5.74% per million in Tianjin from 2004 to 2008. Importantly, the epidemiological characteristics of adult SCIWORA may be different from that in children. The aim of this study was to evaluate the radiological-clinical data of patients with adult SCIWORA, and to relatively analyze the epidemiological features. MATERIALS AND METHODS: Inpatients with cervical SCIWORA who were 16 and above in Tianjin were admitted in municipal hospitals in Tianjin from 2004 to 2008; all the patients received MRI scanning in sagittal and axial views. Epidemiological characteristics, such as injury origin, injury level or severity, neurological scale and MRI feature were acquired. RESULTS: In total, 203 patients were enrolled. The average age among the adult groups was 55.9 years (men 55.8 years, women 53.6 years). SCIWORA occurred more commonly in adults in the 46-60 age group, and falls were the leading cause of injury (52.2%), followed by vehicular injury (28.6%). The most predominantly affected level was C4/5 (48.7%), followed by C5/6 (30.5%) and C3/4 (12.8%), respectively. The occurrence of central cord syndrome (50.2%) with posterior longitudinal ligament tear (43.8%) was relatively higher than other injury patterns. CONCLUSION: It is clear that adult cervical SCIWORA is different from that in the pediatric group. Our study highlights the epidemiological properties of adult SCIWORA in Tianjin, China. Differing from other reports, particularly epidemiology study, we represent the first report regarding adult SCIWORA from China. As the geriatric population increases, it is very important to set up an individualized evaluation system based on a nationally scaled epidemiological database. The results from our study will be useful in assisting in the creation of such a database.

Upregulated mitosis-associated genes CENPE, CENPF, and DLGAP5 predict poor prognosis and chemotherapy resistance of Acute Myeloid Leukemia.

BACKGROUND: Mitosis-associated genes are dysregulated in many types of cancers and play important roles in disease progression and chemotherapy resistance. However, their expression and functions in chemotherapy-resistant Acute Myeloid Leukemia (AML) are still largely undetermined. OBJECTIVE: This study aims to explore the roles of spindle assembly checkpoint (SAC) genes CENPE, CENPF, and DLGAP5 in chemotherapy-resistant AML. METHODS: RNA-sequencing (RNA-seq) was performed in patients with chemotherapy-resistant AML and chemotherapy-sensitive AML. AML mRNA data from 151 patients with recurrence were downloaded from TCGA. Integrated analysis of the differentially expressed genes (DEGs), GO and KEGG pathways. CENPE, CENPF, or DLGAP5 knockdown cell lines were used to analyse proliferation, apoptosis and cell cycle alterations. RESULTS: A total of 87 DEGs (48 upregulated and 39 downregulated) were obtained through gene analysis of R/R-AML and a total of 329 DEGs (202 upregulated and 127 downregulated) were obtained in refractory S-AML. Upregulated DEGs were mainly enriched in cell cycle (GO: 0007049, hsa04110) and mitotic cell cycle (GO: 0000278) processes and pathway. Venn diagram analysis identified the most upregulated DEGs (including CENPE, CENPF, and DLGAP5) in chemoresistant AML. The expression of CENPE, CENPF and DLGAP5 in R-AML (TCGA) was significantly higher than that of primary AML (GEO). The proliferation of K562 cells after CENPE and DLGAP5 knockdown was significantly decreased (P= 0.0001 and P= 0.0006). In THP-1 cells, the CCK-8 values after CENPE, CENPF and DLGAP5 knockdown were significantly decreased (P= 0.01, P= 0.0395 and P= 0.0362). Knockdown of CENPE, CENPF and DLGAP5 significantly increased cell apoptosis by regulating Caspase-9, BAX, TP-53 and bcl-2, and induced cell cycle arrested by regulating CDK1, CDK2, CDKN1A, and CyclinD1. CONCLUSIONS: In conclusion, the mitotic cell cycle-associated genes CENPE, CENPF, and DLGAP5 were upregulated in chemotherapy-resistant AML patients and might be useful for predicting poor prognosis.

Mdivi-1 improves postoperative neurocognitive disorders in aged rats undergoing splenectomy by inhibiting dynamin-related protein-1.

Background: The regulatory role of mitochondria in the inflammatory response of the nervous system postoperatively remains unclear. This study explored the relationship between mitochondria and postoperative neurocognitive dysfunction (PNCD) by regulating mitochondrial function in aged rats undergoing splenectomy. Methods: A total of 120 aged rats were randomly divided into five groups (n=24) as follows: Control group (not subjected to any form of treatment), Sham group (subjected only to sham-splenectomized operation after anesthesia), Splenectomy group (only underwent splenectomy after anesthesia), Synonyms Mitochondrial division inhibitor 1 (Mdivi-1) group [treated with Mdivi-1, a dynamin-relatedprotein 1 (Drp1) inhibitor], and Dimethyl Sulfoxide (DMSO) group (treated with DMSO, a solvent). Inflammatory markers, namely interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), were measured in the plasma and brains of the rats. Cognitive function was assessed using the Morris water maze test. Results: During the perioperative period, the physiological parameters did not differ among the five groups (P>0.05). The results of the Morris water maze experiments showed that the memory of the rats was significantly impaired after splenectomy, which was alleviated by Mdivi-1 administration (P=0.04). Postoperatively, the proinflammatory cytokine levels in the serum and hippocampus tissue were upregulated, while Mdivi-1 administration reduced this increase. The electron microscopy and hematoxylin-eosin (HE) staining results indicated that the structure of neurons and mitochondria was minimally impaired in the Mdivi-1 group. Conclusions: Aged rats that underwent splenectomy exhibited significant postoperative cognitive impairments. The selective inhibitor of Drp1, Mdivi-1, exerted protective effects against PNCD by ameliorating mitochondrial dysfunction and reducing the inflammatory response.

Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice.

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.