Insight into the Feasibility of Fatty Acyl Chlorides with 10-18 Carbons for the Ball-Milling Synthesis of Thermoplastic Cellulose Esters.

Fatty acid cellulose esters (FACE) are common cellulose-based thermoplastics, and their thermoplasticity is determined by both the contents and the lengths of the side chains. Herein, various FACE were synthesized by the ball-milling esterification of cellulose and fatty acyl chlorides containing 10-18 carbons, and their structures and thermoplasticity were thoroughly studied. The results showed that FACE with high degrees of substitution (DS) and low melting flow temperatures (Tf) were achieved as the chain lengths of the fatty acyl chlorides were reduced. In particular, a cellulose decanoate with a DS of 1.85 and a Tf of 186 °C was achieved by feeding 3 mol of decanoyl chloride per mole anhydroglucose units of cellulose. However, cellulose stearate (DS = 1.53) synthesized by the same protocols cannot melt even at 250 °C. More interestingly, the fatty acyl chlorides with 10 and 12 carbons resulted in FACE with superior toughness (elongation at break up to 94.4%). In contrast, due to their potential crystallization of the fatty acyl groups with 14-18 carbons, the corresponding FACE showed higher tensile strength and Young's modulus than the others. This study provides some theoretical basis for the mechanochemical synthesis of thermoplastic FACE with designated properties.

Autophagy is involved in the replication of H9N2 influenza virus via the regulation of oxidative stress in alveolar epithelial cells.

BACKGROUND: Oxidative stress is an important pathogenic factor in influenza A virus infection. It has been found that reactive oxygen species induced by the H9N2 influenza virus is associated with viral replication. However, the mechanisms involved remain to be elucidated. METHODS: In this study, the role of autophagy was investigated in H9N2 influenza virus-induced oxidative stress and viral replication in A549 cells. Autophagy induced by H9N2 was inhibited by an autophagy inhibitor or RNA interference, the autophagy level, viral replication and the presence of oxidative stress were detected by western blot, TCID50 assay, and Real-time PCR. Then autophagy and oxidative stress were regulated, and viral replication was determined. At last, the Akt/TSC2/mTOR signaling pathways was detected by western blot. RESULTS: Autophagy was induced by the H9N2 influenza virus and the inhibition of autophagy reduced the viral titer and the expression of nucleoprotein and matrix protein. The blockage of autophagy suppressed the H9N2 virus-induced increase in the presence of oxidative stress, as evidenced by decreased reactive oxygen species production and malonaldehyde generation, and increased superoxide dismutase 1 levels. The changes in the viral titer and NP mRNA level caused by the antioxidant, N-acetyl-cysteine (NAC), and the oxidizing agent, H2O2, confirmed the involvement of oxidative stress in the control of viral replication. NAC plus transfection with Atg5 siRNA significantly reduced the viral titer and oxidative stress compared with NAC treatment alone, which confirmed that autophagy was involved in the replication of H9N2 influenza virus by regulating oxidative stress. Our data also revealed that autophagy was induced by the H9N2 influenza virus through the Akt/TSC2/mTOR pathway. The activation of Akt or the inhibition of TSC2 suppressed the H9N2 virus-induced increase in the level of LC3-II, restored the decrease in the expression of phospho-pAkt, phospho-mTOR and phospho-pS6 caused by H9N2 infection, suppressed the H9N2-induced increase in the presence of oxidative stress, and resulted in a decrease in the viral titer. CONCLUSION: Autophagy is involved in H9N2 virus replication by regulating oxidative stress via the Akt/TSC2/mTOR signaling pathway. Thus, autophagy maybe a target which may be used to improve antiviral therapeutics.

Helicase POLQ-like (HELQ) as a novel indicator of platinum-based chemoresistance for epithelial ovarian cancer.

OBJECTIVE: To investigate the role of HELQ in chemo-resistance of epithelial ovarian carcinoma (EOC), which is a critical factor of patients' prognosis. METHODS: Immunohistochemistry, survival analysis of our 87 EOC patients and bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets (Nature, 2011) disclosed the clinical importance of HELQ expression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western Blot analyses of EOC tissue were used to confirm it. Ectopic overexpression and RNA interference knockdown of HELQ were carried out in OVCAR3 and A2780 cell lines, respectively, to determine the effect of altered HELQ expression on cellular response to cisplatin by CCK8 assay. The DNA repair capacity of these cells was evaluated by using host-cell reactivation assay. Western Blot analyses were carried out to determine the effect of HLEQ on the DNA repair genes by using cells with altered HELQ expression. RESULTS: HELQ expression associates with response of EOC patients to platinum-based chemotherapy and their overall survival (OS), disease free survival (DFS). HELQ overexpression or knockdown, respectively, increased and decreased the cellular resistance to cisplatin, DNA repair activity, and expression of DNA repair proteins of Nucleotide excision repair (NER) pathway. CONCLUSIONS: HELQ plays an important role in regulating the expression of DNA repair proteins NER pathway which, in turn, contributes to cellular response to cisplatin and patients' response to platinum-based chemotherapy. Our results demonstrated that HELQ could serve as a novel indicator for chemo-resistance of EOC, which can predict the prognosis of the disease.

Enhancing Sodium-Ion Transport by Hollow Nanotube Structure Design of a V5S8@C Anode for Sodium-Ion Batteries.

V5S8 has received extensive attention in the field of sodium-ion batteries (SIBs) due to its two-dimensional (2D) layered structure, and weak van der Waals forces between V-S accelerate the transport of sodium ions. However, the long-term cycling of V5S8 still suffers from volume expansion and low conductivity. Herein, a hollow nanotube V5S8@C (H-V5S8@C) with improved conductivity was synthesized by a solvothermal method to alleviate cracking caused by volume expansion. Benefiting from the large specific surface area of the hollow nanotube structure and uniform carbon coating, H-V5S8@C exhibits a more active site and enhanced conductivity. Meanwhile, the heterojunction formed by a few residual MoS2 and the outer layer of V5S8 stabilizes the structure and reduces the ion migration barrier with fast Na+ transport. Specifically, the H-V5S8@C anode provides an enhanced rate performance of 270.1 mAh g-1 at 15 A g-1 and high cycling stability of 291.7 mAh g-1 with a retention rate of 90.98% after 300 cycles at 5 A g-1. This work provides a feasible approach for the structural design of 2D layered materials, which can promote the practical application of fast-charging sodium-ion batteries.

Adjusting Crystal Orientation to Promote Sodium-Ion Transport in V5 S8 @Graphene Anode Materials for High-Performance Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have inspired the potential for widespread use in energy storage owing to the advantages of abundant resources and low cost. Benefiting from the layered structure, 2D-layered materials enable fast interlayer transport of sodium ions and thus are considered promising candidates as anodes for SIBs. Herein, a strategy of adjusting crystal orientation is proposed via a solvothermal method to improve sodium-ion transport at the edge of the interlayers in 2D-layered materials. By introducing surfactants and templates, the 2D-layered V5 S8 nanosheets are controlled to align the interlayer diffusion channels vertically to the surface, which promotes the fast transport of Na+ at the edge of the interlayers as revealed by experimental methods and ab initio calculations. Benefiting from the aligned crystal orientation and rGO coating, the vertical-V5 S8 @rGO hybrid delivers a high initial discharge capacity of 350.6 mAh g-1 at a high current density of 15 A g-1 . This work provides a strategy for the structural design of 2D-layered anode materials by adjusting crystal orientation, which demonstrates the promise for applications in fast-charging alkaline-ion batteries.

Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.

Efficacy and safety of non-insulated fractional microneedle radiofrequency for treating difficult-to-treat rosacea: a 48-week, prospective, observational study.

Rosacea is a common chronic facial inflammatory skin disease. However, treatment for "difficult-to-treat rosacea" cases has not been established. This 48-week, prospective, observational study analyzed patients who underwent three non-insulated fractional microneedle radiofrequency (NFMRF) sessions at 2-month intervals. Therapy efficacy, epidermal barrier function, and side effects were evaluated. 34 subjects completed the trial. NFMRF resulted in CEA score reduction from 2.65 ± 0.59 to 1.56 ± 0.50 (P < 0.001) and mean DLQI reduction from 16.70 ± 3.55 to 10.48 ± 2.92 (P < 0.001). The successes of CEA (44.12 vs. 2.94%), IGA (91.67 vs. 25.00%), and flushing (58.82 vs. 26.47%) were observed. Among 34 patients, 22 reported "excellent" or "good" improvement and 30 were "very" or "relatively" satisfied. Skin barrier results revealed that hemoglobin content significantly decreased from 376.47 ± 71.29 at visit 0 to 161.32 ± 52.86 at visit 3. 2 of 30 patients followed-up at 6 months had a relapse at 18 and 20 weeks, respectively. No serious side effects were observed. NFMRF alone results in visible improvement and has great efficacy for difficult-to-treat rosacea without compromising patient safety or damaging the skin barrier.

Recent Advances on Heterojunction-Type Anode Materials for Lithium-/Sodium-Ion Batteries.

Rechargeable batteries are key in the field of electrochemical energy storage, and the development of advanced electrode materials is essential to meet the increasing demand of electrochemical energy storage devices with higher density of energy and power. Anode materials are the key components of batteries. However, the anode materials still suffer from several challenges such as low rate capability and poor cycling stability, limiting the development of high-energy and high-power batteries. In recent years, heterojunctions have received increasing attention from researchers as an emerging material, because the constructed heterostructures can significantly improve the rate capability and cycling stability of the materials. Although many research progress has been made in this field, it still lacks review articles that summarize this field in detail. Herein, this review presents the recent research progress of heterojunction-type anode materials, focusing on the application of various types of heterojunctions in lithium/sodium-ion batteries. Finally, the heterojunctions introduced in this review are summarized, and their future development is anticipated.

LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

[Association of human microRNA related genetic variations with cancer].

microRNAs (miRNAs) are a highly conserved class of small noncoding RNAs that regulate gene expression by post-transcriptional degradation or translational repression. miRNAs are involved in the regulation of cell apoptosis, proliferation, differentiation and other physiological processes, and are closely related with the development of cancer. More recently, it has been proposed that the presence of genetic variations (e.g., single nucleotide polymorphism and copy number variation) in microRNA genes, their biogenesis pathway and target binding sites affect the miRNA processing machinery and targeting, and have a significant genetic effect. In this review, we focus on the miRNA-related genetic variations and cancer susceptibility and progression.

Incidence, predictors, and prognosis of thrombocytopenia among patients undergoing intra-aortic balloon pumping in the intensive care unit: a propensity score analysis.

OBJECTIVE: To explore the incidence, predictors, and prognosis of intra-aortic balloon pumping (IABP)-related thrombocytopenia in critically ill patients. METHODS: This multi-center study used the eICU Collaborative Research Database V1.2, comprising data on > 130,000 patients from multiple intensive care units (ICUs) in America between 2014 and 2015. A total of 710 patients undergoing IABP were included. Thrombocytopenia was defined as a drop in platelet count > 50% from baseline. From the cohort, 167 patients who developed thrombocytopenia were matched 1:1 with 167 patients who did not, after propensity score (PS) matching. The associations between IABP-related thrombocytopenia and clinical outcomes were examined by multivariable logistic regression. RESULTS: Among 710 patients undergoing IABP, 249 patients (35.07%) developed thrombocytopenia. The APACHE IVa score was a predictor of thrombocytopenia [adjusted odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.02-1.15]. After 1:1 PS matching, in-hospital mortality (adjusted OR = 0.76, 95% CI: 0.37-1.56) and in-ICU mortality (adjusted OR = 0.74, 95% CI: 0.34-1.63) were similar between the thrombocytopenia and non-thrombocytopenia groups. However, major bleeding occurred more frequently in the thrombocytopenia group (adjusted OR = 2.54, 95% CI: 1.54-4.17). In-hospital length of stay (LOS) and in-ICU LOS were significantly longer in patients who developed thrombocytopenia than in those who did not (9.71vs. 7.36, P < 0.001; 5.13 vs. 2.83, P < 0.001). CONCLUSIONS: Among patients undergoing IABP in the ICUs, thrombocytopenia was not associated with a difference in in-hospital mortality or in-ICU mortality; however, thrombocytopenia was significantly associated with a greater risk of major bleeding and increased in-ICU and in-hospital LOS.

CEP55 promotes cilia disassembly through stabilizing Aurora A kinase.

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55-/- mice display clinical manifestations of Meckel-Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55-/- mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel-Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.

Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.

Molecular characterization and pathogenesis of H9N2 avian influenza virus isolated from a racing pigeon.

H9N2 avian influenza viruses (AIVs) can cross species barriers and expand from birds tomammals and humans. It usually leads to economic loss for breeding farms and poses a serious threat to human health.This study investigated the molecular characteristics of H9N2 AIV isolated from a racing pigeon and its pathogenesis in BALB/c mice and pigeons. Phylogenetic analysis indicated that the H9N2 virus belonged to the Ck/BJ/94-like lineage, and acquired multiple specific amino acid substitutions that might contribute to viral transmission from birds to mammals and humans. A pathogenesis study showed that both mice and pigeons infected with H9N2 virus showed clinical signs and mortality. The H9N2 viruses efficiently replicated in mice and pigeons. In our study, high levels of viral shedding were detected in pigeons, but the infection was not transmitted to co-housed pigeons. Histopathological examination revealed the presence of inflammatory responses in the infected mice and pigeons. Immunohistochemical analysis showed the presence of H9N2 virus in multiple organs of the infected mice and pigeons. Moreover, the infected mice and pigeons demonstrated significant cytokine/chemokine production. Our results showed that the H9N2 virus can infect mice and pigeons, and can not be transmitted between pigeons through direct contact.

Autophagy is involved in the acute lung injury induced by H9N2 influenza virus.

Influenza A virus usually leads to economic loss to breeding farms and pose a serious threat to human health. Virus infecting tissues directly and influenza virus-induced excessive production of inflammatory factors play the key role in pathogenesis of the disease, but the mechanism is not well clarified. Here, the role of autophagy was investigated in H9N2 influenza virus-triggered inflammation. The results showed that autophagy was induced by H9N2 virus in A549 cells and in mice. Inhibiting autophagy by an autophagy inhibitor (3-methyladenine, 3-MA) or knockdown of Atg5(autophagy-related gene) by Atg5 siRNA significantly suppressed H9N2 virus replication, H9N2 virus-triggered inflammatory cytokines and chemokines, including IL-1ß, TNF-α, IL-8, and CCL5 in vitro and in vivo, and suppressed H9N2 virus-triggered acute lung injury as indicated as accumulative mortality of mice, inflammatory cellular infiltrate and interstitial edema, thickening of the alveolar walls in mice lung tissues, increased inflammatory cytokines and chemokines, increased W/D ratio in mice. Moreover, autophagy mediated inflammatory responses through Akt-mTOR, NF-κB and MAPKs signaling pathways. Our data showed that autophagy was essential in H9N2 influenza virus-triggered inflammatory responses, and autophagy could be target to treat influenza virus-caused lung inflammation.

Epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor and effectively alleviates acute lung injury induced by H9N2 swine influenza virus.

Epigallocatechin-3-gallate (EGCG) was found to inhibit the Toll-like receptor 4 (TLR4) pathway involved in influenza virus pathogenesis. Here, the effect of EGCG on TLR4 in an H9N2 virus-induced acute lung injury mouse model was investigated. BALB/c mice were inoculated intranasally with A/Swine/Hebei/108/2002 (H9N2) virus or noninfectious allantoic fluid, and treated with EGCG and E5564 or normal saline orally for 5 consecutive days. PMVECs were treated with EGCG or anti-67kDa laminin receptor (LR). Lung physiopathology, inflammation, oxidative stress, viral replication, and TLR4/NF-κB/Toll-interacting protein (Tollip) pathway in lung tissue and/or PMVECs were investigated. EGCG attenuated lung histological lesions, decreased lung W/D ratio, cytokines levels, and inhibited MPO activity and prolonged mouse survival. EGCG treatment also markedly downregulated TLR4 and NF-κB protein levels but Tollip expression was upregulated compared with that in untreated H9N2-infected mice (P<0.05). In PMVECs, anti-67LR antibody treatment significantly downregulated Tollip levels; however, the TLR4 and NF-κB protein levels dramatically increased compared with that in the EGCG-treated group (P<0.05). EGCG remarkably downregulated TLR4 protein levels through 67LR/Tollip, decreased MPO activity and inflammatory cytokine levels, supporting EGCG as a potential therapeutic agent for managing acute lung injury induced by H9N2 SIV.

[Establishment of heat acclimatization model in rabbits and its pathophysiological characteristics].

OBJECTIVE: To establish an effective and stable rabbit heat acclimatization model for the experiment of heat acclimatization mechanisms. METHODS: Sixteen healthy male rabbits were divided into heat acclimatization group and control group randomly (n = 8). Heat acclimatization (HA) group was kept in simulation chamber with dry bulb temperature of (36 +/- 1) degrees C, wet bulb temperature of (29 +/- 0.5) degrees C, black-bulb temperature of (40 +/- 1.0) degrees C, 100 min/day for 21 days. Control group was kept in the room with temperature of 20 degrees C and relative humidity < 60% during 20 days, then removed into simulation chamber on day 21 to estimate and monitor the rectal temperature together with the heat acclimatization group. Venous blood of control and heat acclimatization group before and after heat exposure on the 1st day, 11th day and 21st day were collected to detect levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and heat shock protein 70 (HSP70) by ELISA analysis. RESULTS: (1) Rectal temperature: There was no significant change in control group during 21 days. In heat acclimatization group, it increased (2.07 +/- 0.43) degrees C after the 1st exposure, and increased (1.78 +/- 0.37) degrees C after the 11th exposure, the range of increasing decreased (0.29 +/- 0.09) degrees C. After the 21st exposure, it increased (1.52 +/- 0.29) degrees C, which was (0.55 +/- 0.14) degrees C lower than that of the 1st (P < 0.05),and (0.53 +/- 0.14) degrees C lower to that of the control group under 1st heat stress (P < 0.05); (2) The level of TNF-alpha after the 1st exposure increased significantly (P < 0.05), but didn't raise along with the exposure times. And fell back to the original level after the 11th and 21st exposure. Compared with control group, the level of IL-6 increased after the 1st, 11th and 21st exposure (P < 0.05), and maintained highly after the 11th and 21st exposure. Compared with the control group, the level of HSP70 increased dramatically with the heat exposure times. Significant increasing of (HSP70) could be detected after the 11th and 21st exposure (P < 0.05), but there was no difference to that of the 1st exposure. CONCLUSION: Prolonged or repeated exposure to heat stressful environmental conditions can reduce the physiological strain, improve heat tolerance, elicits heat acclimatization.