Boosting External Quantum Efficiency to 12.0 % of an Ultraviolet OLED by Engineering the Horizontal Dipole Orientation of a Hot Exciton Emitter.

Currently, much research effort has been devoted to improving the exciton utilization efficiency and narrowing the emission spectra of ultraviolet (UV) fluorophores for organic light-emitting diode (OLED) applications, while almost no attention has been paid to optimizing their light out-coupling efficiency. Here, we developed a linear donor-acceptor-donor (D-A-D) triad, namely CDFDB, which possesses high-lying reverse intersystem crossing (hRISC) property. Thanks to its integrated narrowband UV photoluminescence (PL) (λPL: 397 nm; FWHM: 48 nm), moderate PL quantum yield (ϕPL: 72 %, Tol), good triplet hot exciton (HE) conversion capability, and large horizontal dipole ratio (Θ//: 92 %), the OLEDs based on CDFDB not only can emit UV electroluminescence with relatively good color purity (λEL: 398 nm; CIEx,y: 0.161, 0.040), but also show a record maximum external quantum efficiency (EQEmax) of 12.0 %. This study highlights the important role of horizontal dipole orientation engineering in the molecular design of HE UV-OLED fluorophores.

HMGB1 Positive Feedback Loop Between Cancer Cells and Tumor-Associated Macrophages Promotes Osteosarcoma Migration and Invasion.

Numerous studies have demonstrated the key roles of tumor-associated macrophages (TAMs) in osteosarcoma metastasis. Higher levels of high mobility group box 1 (HMGB1) promote osteosarcoma progression. However, whether HMGB1 is involved in the polarization of M2 macrophages into M1 macrophages in osteosarcoma remains largely unknown. Here, HMGB1 and CD206 mRNA expression levels were measured by a quantitative reverse transcription-polymerase chain reaction in osteosarcoma tissues and cells. HMGB1 and receptor for advanced glycation end products (RAGE) protein expression levels were measured by western blotting. Osteosarcoma migration was measured using transwell and wound-healing assays, while a transwell assay determined osteosarcoma invasion. Macrophage subtypes were detected using flow cytometry. HMGB1 expression levels were aberrantly enhanced in osteosarcoma tissues compared with normal tissues and were positively correlated with AJCC III and IV stages, lymph node metastasis, and distant metastasis. Silencing HMGB1 inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. Furthermore, reduced HMGB1 expression levels in conditioned media derived from osteosarcoma cells induced the polarization of M2 TAMs to M1 TAMs. In addition, silencing HMGB1 inhibited the liver and lung metastasis of tumors and reduced the expression levels of HMGB1, CD163, and CD206 in vivo. HMGB1 was found to regulate macrophage polarization through RAGE. Polarized M2 macrophages induced osteosarcoma migration and invasion, activating HMGB1 expression in osteosarcoma cells to form a positive feedback loop. In conclusion, HMGB1 and M2 macrophages enhanced osteosarcoma migration, invasion, and EMT through positive feedback regulation. These findings reveal the significance of tumor cell and TAM interactions in the metastatic microenvironment.

A Feasible Strategy for a Highly Efficient Thermally Activated Delayed Fluorescence Emitter Over 900 nm Based on Phenalenone Derivatives.

Near-infrared (NIR) organic light-emitting diodes (OLEDs) suffer from the low external electroluminescence (EL) quantum efficiency (EQE), which is a critical obstacle for potential applications. Herein, 1-oxo-1-phenalene-2,3-dicarbonitrile (OPDC) is employed as an electron-withdrawing aromatic ring, and by incorporating with triphenylamine (TPA) and biphenylphenylamine (BBPA) donors, two novel NIR emitters with thermally activated delayed fluorescence (TADF) characteristics, namely OPDC-DTPA and OPDC-DBBPA, are first developed and compared in parallel. Intense NIR emission peaks at 962 and 1003 nm are observed in their pure films, respectively. Contributed by the local excited (LE) characteristics in the triplet (T1 ) state in synergy with the charge transfer (CT) characteristics for the singlet (S1 ) state to activate TADF emission, the solution processable doped NIR OLEDs based on OPDC-DTPA and OPDC-DBBPA yield EL peaks at 834 and 906 nm, accompanied with maximum EQEs of 0.457 and 0.103 %, respectively, representing the state-of-the-art EL performances in the TADF emitter-based NIR-OLEDs in the similar EL emission regions so far. This work manifests a simple and effective strategy for the development of NIR TADF emitters with long wavelength and efficiency synchronously.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

Cancer Cell enters reversible quiescence through Intracellular Acidification to resist Paclitaxel Cytotoxicity.

Cancer cells can enter quiescent or dormant state to resist anticancer agents while maintaining the potential of reactivation. However, the molecular mechanism underlying quiescence entry and reactivation remains largely unknown. In this paper, cancer cells eventually entered a reversible quiescent state to resist long-term paclitaxel (PTX) stress. The quiescent cells were characterized with Na+/H+ exchanger 1 (NHE1) downregulation and showed acidic intracellular pH (pHi). Accordingly, decreasing pHi by NHE1 inhibitor could induce cell enter quiescence. Further, acidic pHi could activate the ubiquitin-proteasome system and inhibiting proteasome activity by MG132 prevented cells entering quiescence. In addition, we show that after partial release, the key G1-S transcription factor E2F1 protein level was not recovered, while MCM7 protein returned to normal level in the reactivated cells. More importantly, MCM7 knockdown inhibited G1/S genes transcription and inhibited the reactivated proliferation. Taken together, this study demonstrates a regulatory function of intracellular acidification and subsequent protein ubiquitination on quiescence entry, and reveals a supportive effect of MCM7 on the quiescence-reactivated proliferation.

Huge myxoid chondrosarcoma expanded into the thoracic cavity with spinal involvement.

PURPOSE: En bloc resection is the treatment of choice of myxoid chondrosarcoma. These tumors can produce huge masses. Anatomical constraints limit the possibility to perform en bloc resection in the spine. METHODS: A very huge myxoid chondrosarcoma (14.2 × 10.8 × 11.4 cm) arising from T2 to T5 and invading the whole higher left pleural cavity was observed. Surgical planning according to WBB staging system was performed. RESULTS: The tumor was successfully submitted to en bloc resection achieving a tumor-free margin as demonstrated by the pathologist's report. CONCLUSIONS: A careful planning and a multidisciplinary collaboration make possible to perform en bloc resection even in apparently impossible cases.

PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2.

The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome has been linked to sterile inflammation, which is involved in ischemic injury in myocardial cells. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein with many biological activities, such as anti-inflammatory, antioxidant and anti-angiogenic properties. However, it is not known whether and how PEDF acts to regulate the activation of the NLRP3 inflammasome in cardiomyocytes. In the present study, we used the neonatal cardiomyocytes models of ischemia-like conditions to evaluate the mitochondrial fission and the activation of the NLRP3 inflammasome. We also determined the mechanism by which PEDF inhibits hypoxia-induced activation of the NLRP3 inflammasome. We found that PEDF decreased the activation of the NLRP3 inflammasome in neonatal cardiomyocytes through pigment epithelial-derived factor receptor/calcium-independent phospholipase A2 (PEDFR/iPLA2). Meanwhile, PEDF reduced Drp1-induced mitochondrial fission and mitochondrial fission-induced mitochondrial DNA (mtDNA), as well as mitochondrial reactive oxygen species (mtROS) release into cytosol through PEDFR/iPLA2. We also found that PEDF inhibited mitochondrial fission-induced NLRP3 inflammasome activation. Furthermore, previous research has found that endogenous cytosolic mtDNA and mtROS can serve as activators of NLRP3 inflammasome activity. Therefore, we hypothesized that PEDF can protect against hypoxia-induced activation of the NLRP3 inflammasome by inhibiting mitochondrial fission though PEDFR/iPLA2.

Polyhexamethylene guanidine hydrochloride shows bactericidal advantages over chlorhexidine digluconate against ESKAPE bacteria.

More information regarding the bactericidal properties of polyhexamethylene guanidine hydrochloride (PHMG) against clinically important antibiotic-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens needs to be provided for its uses in infection control. The bactericidal properties of PHMG and chlorhexidine digluconate (CHG) were compared based on their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations, and time-course-killing curves against clinically important antibiotic-susceptible and antibiotic-resistant ESKAPE pathogens. Results showed that PHMG exhibited significantly higher bactericidal activities against methicillin-resistant Staphylococcus aureus, carbapenem-resistant Klebsiella pneumoniae, and ceftazidime-resistant Enterobacter spp. than CHG. A slight bactericidal advantage over CHG was obtained against vancomycin-resistant Enterococcus faecium, ciprofloxacin- and levofloxacin-resistant Acinetobacter spp., and multidrug-resistant Pseudomonas aeruginosa. In previous reports, PHMG had higher antimicrobial activity against almost all tested Gram-negative bacteria and several Gram-positive bacteria than CHG using MIC test. These studies support the further development of covalently bound PHMG in sterile-surface materials and the incorporation of PHMG in novel disinfectant formulas.

Corncob hydrolysate, an efficient substrate for Monascus pigment production through submerged fermentation.

Monascus pigment has traditionally been produced by the fermentation of Monascus using rice powder or glucose as a culture substrate. Submerged fermentation can produce stable Monascus pigment yield and control the accumulation of the by-product, citrinin, which can then be more easily removed. To reduce the cost of Monascus submerged fermentation, the feasibility of corncob hydrolysate as an alternative substrate was investigated. Results showed that, when compared with a conventional glucose medium, the corncob hydrolysate medium produced an equivalent pigment yield without stimulating citrinin accumulation. Furthermore, the corncob hydrolysate medium and cultivation conditions were optimized to enhance pigment production and decrease citrinin synthesis. When Monascus sp. was cultured under dark conditions in the presence of caprylic acid, pigment production was increased to 25.8 ± 0.8 UA500 /mL, which was higher than that achieved in a glucose medium (24.0 ± 0.9 UA500 /mL), and those obtained in previously reported Monascus submerged fermentations using the same yield unit; on the other hand, citrinin accumulation was decreased to 26.2 ± 1.9 µg/L, which was significantly lower than that generated in the glucose control (44.3 ± 2.2 µg/L) and in those previously reported fermentations. Thus, corncob hydrolysate was proved to be an efficient alternative substrate for Monascus pigment production through submerged fermentation, which showed significant advantages over a conventional glucose substrate.

Screening of Ganoderma strains with high polysaccharides and ganoderic acid contents and optimization of the fermentation medium by statistical methods.

Polysaccharides and ganoderic acids (GAs) are the major bioactive constituents of Ganoderma species. However, the commercialization of their production was limited by low yield in the submerged culture of Ganoderma despite improvement made in recent years. In this work, twelve Ganoderma strains were screened to efficiently produce polysaccharides and GAs, and Ganoderma lucidum 5.26 (GL 5.26) that had been never reported in fermentation process was found to be most efficient among the tested stains. Then, the fermentation medium was optimized for GL 5.26 by statistical method. Firstly, glucose and yeast extract were found to be the optimum carbon source and nitrogen source according to the single-factor tests. Ferric sulfate was found to have significant effect on GL 5.26 biomass production according to the results of Plackett-Burman design. The concentrations of glucose, yeast extract and ferric sulfate were further optimized by response surface methodology. The optimum medium composition was 55 g/L of glucose, 14 g/L of yeast extract, 0.3 g/L of ferric acid, with other medium components unchanged. The optimized medium was testified in the 10-L bioreactor, and the production of biomass, IPS, total GAs and GA-T enhanced by 85, 27, 49 and 93 %, respectively, compared to the initial medium. The fermentation process was scaled up to 300-L bioreactor; it showed good IPS (3.6 g/L) and GAs (670 mg/L) production. The biomass was 23.9 g/L in 300-L bioreactor, which was the highest biomass production in pilot scale. According to this study, the strain GL 5.26 showed good fermentation property by optimizing the medium. It might be a candidate industrial strain by further process optimization and scale-up study.

Intervention effects of fructooligosaccharide and astragalus polysaccharide, as typical antibiotic alternatives, on antibiotic resistance genes in feces of layer breeding: advantages and defects.

Although antibiotic alternatives are widely used in livestock and poultry breeding industry after in-feed antibiotics ban, their intervention effects on antibiotic resistance genes (ARGs) in these food animals' feces remain poorly understood. Here effects of fructooligosaccharide (FOS) and astragalus polysaccharide (APS), as typical antibiotic alternatives in China, on ARGs in layer feces were estimated by performing metagenomic sequencings and fluorescence quantitative PCR. Fructooligosaccharide significantly reduced sum abundance of ARGs and mobile genetic elements (MGEs) by increasing Lactobacillus clones and reducing Escherichia clones which had relatively higher abundances of ARG subtypes and MGE subtypes in layer feces. However, at least parts of core ARGs and MGEs categories were not reduced by FOS, such as aminoglycosides- and tetracyclines-resistant genes, Tn916, Integrase, and so on. MGEs and microbiome, especially Escherichia genus and Lactobacillus genus, were the key factors affecting ARGs' sum abundance. MGEs had a higher correlation coefficient with ARGs' sum abundance than Escherichia genus and Lactobacillus genus. These findings firstly reveal the defects of antibiotic alternatives in controlling bacterial resistance in livestock and poultry breeding after in-feed antibiotics ban, and more strategies are needed to control pollutions and risks of core ARGs and MGEs in food animals' feces under a special environment.

New Medium-Bandgap Nonfused Ring Guest Acceptor with a Higher-Lying LUMO Level Enables High-Performance Ternary Organic Solar Cells.

Adding another constituent into a binary system, known as a ternary strategy, represents a simple and effective approach to boosting the power conversion efficiency (PCE) of organic solar cells (OSCs). Herein, we have prepared a new nonfused ring small-molecule acceptor with a medium bandgap, named DFTQA-2FIC, which possesses a high-lying lowest unoccupied molecular orbital energy level and a strong intramolecular charge-transfer effect. We elaborately utilized it as a third component in a typical PM6:Y6 blend to obtain high-performance ternary OSCs. The resulting ternary blend film exhibited superior and balanced hole/electron mobility, enhanced favorable aggregation morphology, and reduced charge carrier recombination. Consequently, an optimized ternary OSC presented a distinctly increased PCE of 17.29%, accompanied by synchronous enhancements in crucial parameters, representing a 7.46% improvement over the binary OSC based on PM6:Y6 with a PCE of 16.09%. This study highlights that incorporating DFTQA-2FIC as a third component in a binary system is suitable for optimizing photovoltaic performance.

Comparative Lipidomics and Metabolomics Reveal the Underlying Mechanisms of Taurine in the Alleviation of Nonalcoholic Fatty Liver Disease Using the Aged Laying Hen Model.

SCOPE: Aged laying hen is recently suggested as a more attractive animal model than rodent for studying nonalcoholic fatty liver disease (NAFLD) of humans. This study aims to reveal effects and metabolic regulation mechanisms of taurine alleviating NAFLD by using the aged laying hen model. METHODS AND RESULTS: Liver histomorphology and biochemical indices show 0.02% taurine effectively alleviated fat deposition and liver damage. Comparative liver lipidomics and gene expressions analyses reveal taurine promoted lipolysis, fatty acids oxidation, lipids transport, and reduced oxidative stress in liver. Furthermore, comparative serum metabolomics screen six core metabolites negatively correlated with NAFLD, including linoleic acid, gamma-linolenic acid, pantothenate, L-methionine, 2-methylbutyroylcarnitine, L-carnitine; and two core metabolites positively correlated with NAFLD, including lysophosphatidylcholine (14:0/0:0) and lysophosphatidylcholine (16:0/0:0). Metabolic pathway analysis reveals taurine mainly regulated linoleic acid metabolism, cysteine and methionine metabolism, carnitine metabolism, pantothenic acid and coenzyme A biosynthesis metabolism, and glycerophospholipid metabolism to up-adjust levels of six negatively correlated metabolites and down-adjust two positively correlated metabolites for alleviating NAFLD of aged hens. CONCLUSION: This study firstly reveals underlying metabolic mechanisms of taurine alleviating NAFLD using the aged hen model, thereby laying the foundation for taurine's application in the prevention of NAFLD in both human and poultry.

Feasibility and safety of guidewire-balloon entrapment technique for recanalization of thoracic central vein occlusion in hemodialysis patients.

OBJECTIVE: To explore the feasibility and safety of Guidewire-Balloon Entrapment Technique (GBET) for the recanalization of thoracic central vein occlusions (TCVOs) in hemodialysis patients. METHODS: A retrospective observational study was conducted using data from 28 patients who required the establishment or maintenance of hemodialysis access and were treated with GBET for the recanalization of right-sided TCVOs from January 2017 to April 2021. Of the patients, 27 required tunneled cuffed catheter (TCC) placement or exchange, and 1 had an outflow tract occlusion of the Brescia-Cimino radio cephalic arteriovenous fistula (AVF). RESULTS: A total of 26 patients successfully underwent TCC exchange and placement using GBET; 1 patient underwent successful recanalization of an occlusion of the outflow tract of the right Brescia-Cimino AVF; and 1 patient underwent successful TCC placement in the left internal jugular vein (LIJV) after the failure of TCC placement in the right internal jugular vein (RIJV). The success rate for GBET was 27/28 (96.43%), and there were no major complications. CONCLUSION: GBET is a safe and effective method for the recanalization of right-sided TCVOs, especially for TCC exchange and placement, and can be used as a safe and easy approach for TCVO recanalization.

En bloc resection of huge primary tumors with epidural involvement in the mobile spine using the "rotation-reversion" technique: Feasibility, safety, and clinical outcome of 11 cases.

Background: En bloc resection of spinal tumors provides better local control and survival outcomes than intralesional resection. Safe margins during en bloc resection of primary spinal tumors with epidural involvement are required for improved outcomes. The present study describes a "rotation-reversion" technique that has been used for en bloc resection of huge primary tumors in the mobile spine with epidural involvement and reported the clinical outcomes in these patients. Methods: All patients with primary spinal tumors who were treated with the rotation-reversion technique at our institution between 2015 and 2021 were evaluated retrospectively. Of the patients identified, those with both huge extraosseous soft-tissue masses and epidural involvement were selected for a case review. Clinical and radiological characteristics, pathologic findings, operative procedures, complications, and oncological and functional outcomes of these patients were reviewed. Results: Of the 86 patients identified with primary spinal tumors who underwent en bloc resection using the rotation-reversion technique between 2015 and 2021, 11 had huge extraosseous soft-tissue masses with epidural involvement in the mobile spine. The average maximum size of these 11 tumors was 8.1 × 7.5 × 9.7 cm. Median follow-up time was 28.1 months, mean operation time was 849.1 min (range 465-1,340 min), and mean blood loss was 6,972.7 ml (range 2,500-17,700 ml), with 10 (91%) of the 11 patients experiencing perioperative complications. The negative margin rate was 91%, with only one patient (9%) experiencing local recurrence. Ten patients were able to walk normally or with a crutch at the last follow-up, whereas one was completely paralyzed preoperatively. Conclusion: The rotation-reversion technique is an effective procedure for the en bloc resection of huge primary spinal tumors, with the extension of invasion in selected patients including not only the vertebral body but also the pedicle and part of the posterior arch.

Process-Aid Solid Engineering Triggers Delicately Modulation of Y-Series Non-Fullerene Acceptor for Efficient Organic Solar Cells.

Volatile solids with symmetric π-backbone are intensively implemented on manipulating the nanomorphology for improving the operability and stability of organic solar cells. However, due to the isotropic stacking, the announced solids with symmetric geometry cannot modify the microscopic phase separation and component distribution collaboratively, which will constrain the promotion of exciton splitting and charge collection efficiency. Inspired by the superiorities of asymmetric configuration, a novel process-aid solid (PAS) engineering is proposed. By coupling with BTP core unit in Y-series molecule, an asymmetric, volatile 1,3-dibromo-5-chlorobenzene solid can induce the anisotropic dipole direction, elevated dipole moment, and interlaminar interaction spontaneously. Due to the synergetic effects on the favorable phase separation and desired component distribution, the PAS-treated devices feature the evident improvement of exciton splitting, charge transport, and collection, accompanied by the suppressed trap-assisted recombination. Consequently, an impressive fill factor of 80.2% with maximum power conversion efficiency (PCE) of 18.5% in the PAS-treated device is achieved. More strikingly, the PAS-treated devices demonstrate a promising thickness-tolerance character, where a record PCE of 17.0% is yielded in PAS devices with a 300 nm thickness photoactive layer, which represents the highest PCE for thick-film organic solar cells.

Interactions of biocidal guanidine hydrochloride polymer analogs with model membranes: a comparative biophysical study.

Four synthesized biocidal guanidine hydrochloride polymers with different alkyl chain length, including polyhexamethylene guanidine hydrochloride and its three new analogs, were used to investigate their interactions with phospholipids vesicles mimicking bacterial membrane. Characterization was conducted by using fluorescence dye leakage, isothermal titration calorimetry, and differential scanning calorimetry. The results showed that the gradually lengthened alkyl chain of the polymer increased the biocidal activity, accompanied with the increased dye leakage rate and the increased binding constant and energy change value of polymer-membrane interaction. The polymer-membrane interaction induced the change of pretransition and main phase transition (decreased temperature and increased width) of phospholipids vesicles, suggesting the conformational change in the phospholipids headgroups and disordering in the hydrophobic regions of lipid membranes. The above information revealed that the membrane disruption actions of guanidine hydrochloride polymers are the results of the polymer's strong binding to the phospholipids membrane and the subsequent perturbations of the polar headgroups and hydrophobic core region of the phospholipids membrane. The alkyl chain structure significantly affects the binding constant and energy change value of the polymer-membrane interactions and the perturbation extent of the phospholipids membrane, which lead to the different biocidal activity of the polymer analogs. This work provides important information about the membrane disruption action mechanism of biocidal guanidine hydrochloride polymers.

Circadian clock protein CRY1 prevents paclitaxel­induced senescence of bladder cancer cells by promoting p53 degradation.

Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first­line treatment is cisplatin­based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy­induced senescence can act as a 'back­up' response to chemotherapy in cancer types that are resistant to apoptosis­based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)­induced senescence in cisplatin­resistant bladder cancer cells. Cisplatin­resistant bladder cancer cells were established via long­term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA­ß­Gal staining, but this was not observed in the cisplatin­resistant cells. The cisplatin­resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin­resistant cells, and that CRY1 knockdown restored PTX­induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto­oncogene. These data suggested that the accumulated CRY1 in cisplatin­resistant cells could prevent PTX­induced senescence by promoting p53 degradation.

Untargeted metabolomics revealed therapeutic mechanisms of icariin on low bone mineral density in older caged laying hens.

Osteoporosis is a common chronic disease in the elderly population and in some domestic animals. Caged layer osteoporosis (CLO) is a common bone metabolism disease that was recently recommended as an ideal animal model for osteoporosis. This study aimed to investigate the therapeutic effect and mechanism of dietary icariin (ICA), the main bioactive component of the Chinese herb Epimedium, on low bone mineral density (BMD) in older caged laying hens. A total of 216, 54-week-old Lohmann pink-shell laying hens were allocated to three groups, comprising one control group and two treatment groups that were additionally supplied with 0.5 or 2.0 g kg-1 ICA. The results showed that dietary ICA significantly increased the femur BMD by 49.3% and the tibia BMD by 38.9%, improved the microstructure of bone tissue, decreased levels of the bone metabolism index, enhanced serum antioxidant capacity and regulated messenger RNA expression of bone-related genes. ICA-induced differential metabolites were clarified by using untargeted metabolomics assays. Furthermore, correlation analysis between differential metabolites and BMD indicated that eight differential metabolites correlated highly with both femur and tibia BMD, including uridine, taurine, palmitic acid, adrenic acid, fexofenadine, lysoPC(18 : 1), lysoPE(20 : 3/0 : 0) and 3-acetyl-11-keto-beta-boswellic acid. ICA mainly perturbed pyrimidine metabolism, taurine metabolism and lipid metabolism, which led to increased BMD in older caged laying hens. These findings revealed underlying therapeutic mechanisms of dietary ICA on low BMD, and provided reference metabolites for the early diagnosis of osteoporosis.

miR-632 Promotes Laryngeal Carcinoma Cell Proliferation, Migration, and Invasion Through Negative Regulation of GSK3ß.

Laryngeal cancer, one of the most common head and neck malignancies, is an aggressive neoplasm. Increasing evidence has demonstrated that microRNAs (miRNAs) exert important roles in oncogenesis and progression of diverse types of human cancers. miR-632, a tumor-related miRNA, has been reported to be dysregulated and implicated in human malignancies; however, its biological role in laryngeal carcinoma remains to be elucidated. The present study aimed at exploring the role of miR-632 in laryngeal cancer and clarifying the potential molecular mechanisms involved. In the current study, miR-632 was found to be significantly upregulated both in laryngeal cancer tissues and laryngeal cancer cell lines. Functional studies demonstrated that miR-632 accelerated cell proliferation and colony formation, facilitated cell migration and invasion, and enhanced the expression of cell proliferation-associated proteins, cyclin D1 and c-myc. Notably, miR-632 could directly bind to the 3'-untranslated region (3'-UTR) of glycogen synthase kinase 3ß (GSK3ß) to suppress its expression in laryngeal cancer cells. Mechanical studies revealed that miR-632 promoted laryngeal cancer cell proliferation, migration, and invasion through negative modulation of GSK3ß. Pearson's correlation analysis revealed that miR-632 expression was inversely correlated with GSK3ß mRNA expression in laryngeal cancer tissues. Taken together, our findings suggest that miR-632 functions as an oncogene in laryngeal cancer and may be used as a novel therapeutic target for laryngeal cancer.