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ABSTRACT Background Cancer cachexia can impact prognosis, cause resistance to anticancer treatments and affect the tolerability of treatments. This study aims to identify hepatocellular carcinoma (HCC) with cachexia by characterizing longitudinal body composition (BC) trajectories. Methods This longitudinal, multicentre cohort study included unresectable HCC patients treated with first‐line programmed death‐(ligand)1 inhibitors plus anti‐vascular endothelial growth factor antibody/tyrosine kinase inhibitors between 01/2018–12/2022. BC measurements including skeletal muscle mass (SMM) and total adipose tissue area (TATA) were evaluated by computed tomography at the third lumbar vertebra at baseline and follow‐up imaging. Unsupervised latent class growth mixed models were applied to distinguish potential longitudinal SMM and TATA trajectories for identifying cachexia. The primary study endpoint was overall survival (OS), with secondary endpoints including progression‐free survival (PFS), objective response rate (ORR) and safety. Multiple Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) for survival. Results A total of 411 patients with 2138 time‐point measurements were included. The median age was 56 years, and 50 (12.2%) patients were female. Two distinct trajectories were identified for SMM and TATA: sharp‐falling and stable. SMM sharply declined in 58 patients (14.1%) and TATA in 71 of 406 patients (17.5%) with significant worse OS (for SMM, 17.0 vs. 24.9 months; p

Abstract Iodine, an essential trace element for the human body, plays a pivotal role in sustaining health. Malnutrition has emerged as a pressing public health concern, posing a significant threat to human well‐being. Iodine deficiency poses a substantial threat to the development of children, potentially leading to neurological developmental disorders and mental retardation. Conversely, excessive iodine intake can result in structural and functional abnormalities in the thyroid gland. In this study, we selected children aged 3–6 years through a stratified cluster sampling approach in six regions across China to explore the correlation between iodine nutrition and their physical growth. A total of 5920 preschool children participated in this study, with a median urinary iodine concentration (UIC) of 177.33 [107.06, 269.92] μg/L. Among these children, 250 (4.2%) exhibited stunting, 180 (3.0%) were underweight, 198 (3.3%) experienced wasting, 787 (3.3%) were overweight and 414 (7.0%) were classified as obese. The multivariate linear regression revealed that UIC exhibited a positive correlation with body mass index z‐Score (BMIZ) in overweight children (β = 0.038; 95% CI: 0.001, 0.075). In normally growing children, the associations between UIC and height‐for‐age z‐score, weight‐for‐age z‐score and BMIZ displayed nonlinear patterns. Our findings suggest that iodine nutrition is adequate for Chinese children aged 3–6 years. Furthermore, iodine nutrition is intricately linked to the growth and development of these children. Consequently, it is imperative to implement decisive measures to prevent both iodine deficiency and excess.

Summary: Sepsis-induced arrhythmia, linked to sudden cardiac death, is associated with gut microbiota, though the exact relationship is unclear. This study aimed to elucidate the relationship between Cronobacter sakazakii (C. sakazakii) and arrhythmia. The relative abundance of C. sakazakii was increased in cecal ligation and puncture (CLP)-induced septic mice. Live C. sakazakii, supernatant, and outer membrane vesicles (OMVs) resulted in premature ventricular beat (PVB), sinus arrhythmia (SA), and increased arrhythmia and mortality in sepsis model through dysregulated ion channel proteins. Moreover, short-chain fatty acids (SCFAs) showed antibacterial effects in vitro. We confirmed sodium acetate (C2) and sodium butyrate (C4) protect from C. sakazakii-induced arrhythmia, and C2 and C4 protected from septic arrhythmia by activating free fatty acid receptor 2 and 3 (FFAR2 and FFAR3) in mice. These findings point to how C. sakazakii’s OMVs trigger arrhythmia, and SCFAs may be a treatment for septic arrhythmia.

Children’s exposures to environmental antibiotics are a major public health concern. However, limited data are available on the effects of environmental antibiotic exposures on childhood obesity. Our study aimed to explore this relationship. We conducted a cross-sectional case-control study nested in a population-based survey of primary school students, including 1855 obese and 1875 random selected control children. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression was used to assess the associations between environmental antibiotics exposures and childhood obesity. After adjusting for potential confounders, increased odds of obesity were observed in children exposed to tetracycline (OR = 1.31, 95% CI: 1.09–1.57) and sulfamonomethoxine (OR = 1.43, 95% CI: 1–2.05). Comparing none (

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

In this paper, an algorithm based on a fractional time-frequency spectrum feature is proposed to improve the accuracy of synthetic aperture radar (SAR) target detection. By extending the fractional Gabor transform (FrGT) into two dimensions, the fractional time-frequency spectrum feature of an image can be obtained. In the achievement process, we search for the optimal order and design the optimal window function to accomplish the two-dimensional optimal FrGT. Finally, the energy attenuation gradient (EAG) feature of the optimal time-frequency spectrum is extracted for high-frequency detection. The simulation results show that the proposed algorithm has a good performance in SAR target detection and lays the foundation for recognition.

Neural tract tracing is used to study neural pathways and evaluate neuronal regeneration following nerve injuries. However, it is not always clear which tracer should be used to yield optimal results. In this study, we examined the use of Alexa Fluor 488-conjugated cholera toxin subunit B (AF488-CTB). This was injected into the gastrocnemius muscle of rats, and it was found that motor, sensory, and sympathetic neurons were labeled in the spinal ventral horn, dorsal root ganglia, and sympathetic chain, respectively. Similar results were obtained when we injected AF594-CTB into the tibialis anterior muscle. The morphology and number of neurons were evaluated at different time points following the AF488-CTB injection. It was found that labeled motor and sensory neurons could be observed 12 hours post-injection. The intensity was found to increase over time, and the morphology appeared clear and complete 3–7 days post-injection, with clearly distinguishable motor neuron axons and dendrites. However, 14 days after the injection, the quality of the images decreased and the neurons appeared blurred and incomplete. Nissl and immunohistochemical staining showed that the AF488-CTB-labeled neurons retained normal neurochemical and morphological features, and the surrounding microglia were also found to be unaltered. Overall, these results imply that the cholera toxin subunit B, whether unconjugated or conjugated with Alexa Fluor, is effective for retrograde tracing in muscular tissues and that it would also be suitable for evaluating the regeneration or degeneration of injured nerves.

Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.44; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.

Background: In this study, we analyzed intestinal flora in an experimental mouse model of chronic kidney disease (CKD) and investigated whether oral supplementation with probiotic Lactobacillus rhamnosus GG could slow the decline in renal function and inflammatory status of mice with CKD. Methods: We surgically induced chronic kidney disease in C57BL/6J male mice aged 8–9 weeks. We used dual-stage 5/6 nephrectomy for this, while the mock group underwent a mock procedure. The experimental (CKD mice) and mock group were administered a daily dose of 10 × 109 colony forming unit (CFU) of probiotic L. rhamnosus GG or 2 g of maltodextrin as a placebo by oral gavage, respectively, for 5 weeks. At the end of the experiment, the fecal samples of the mice were collected and prepared for intestinal microbial diversity analysis. We examined the serum chemistry and renal histology of the mice. Results: Important serum and blood biomarkers were associated with the development of CKD, including increased serum concentrations of creatine, cystatin C, blood urea nitrogen (BUN), and a protein—interleukin-6 (denoted as IL-6), whereas decreased serum albumin concentration was also observed in the mice with CKD. The intestinal flora of the mice with CKD significantly declined in terms of diversity, richness, and homogeneity. The consumption of L. rhamnosus GG probiotic via oral gavage significantly decreased the serum concentration level present in creatinine and blood urea nitrogen. However, it increased albumin in the group with CKD. After probiotic treatment, serum IL-6 levels dropped considerably, and the kidney histopathology score in mice with CKD who were given L. rhamnosus GG improved. Moreover, supplementation with the probiotic significantly improved floral richness and lineage diversity in the mice with CKD.Conclusions: In this study, we found that probiotics significantly attenuated renal failure development, reduced serum levels of proinflammatory cytokine IL-6, and increased the abundance and lineage diversity of intestinal flora in mice with chronic kidney disease.

Abstract Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire “competence” for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.

Mussel is an economically and ecologically important species widely distributed throughout the world. The mussel adheres to the attachment substrate by secreting byssus external to the body. Various environmental and biological factors influence the process of byssus secretion, and the present study investigated the effect of starvation on byssal secretion in the hard-shelled mussel Mytilus coruscus. Histological changes in mussel foot secretory glands and gene expression of mussel foot proteins were also determined. The experimental setup consisted of starvation treatments for 7, 14 and 21 days, and the control groups. The results showed that the number of produced byssus was higher in the starvation group compared to the control (CTR) group, and the starvation group had a significantly higher of byssal shedding number from 6 days of starvation treatment onwards (p < 0.05). The byssal thread diameter was significantly reduced in all starvation treatment groups (p < 0.05). However, starvation treatment had no effect on the length of the byssal thread (p > 0.05). After 21 days of starvation treatment, the byssal thread volume was significantly lower than that of the CTR group (p < 0.05). A significant decrease in the breaking force of the byssal thread was observed after 14 and 21 days of starvation treatment (p < 0.05), along with an upward shift in the breakpoints. Starvation treatment significantly reduced the percentage of foot secretory glands area to total tissue (p < 0.05). The expression of the mussel foot protein genes (Mcfp-1P and Mcfp-1T) was significantly up-regulated at 7 days of starvation treatment (p < 0.05). These findings reveal that starvation weakens byssal thread performance by influencing mussel foot secretory glands, which increases the dislodgment risks of suspended-cultured mussels.

As carriers containing abundant biological information, exosomes could deliver the property of donor cells to recipient cells. Emerging studies have shown that tumor cells could secrete a mass of exosomes into the microenvironment to regulate bystander cells. However, the underlying mechanisms of such a phenomenon remain largely unexplored. In this research, we purified and identified the exosomes of A549 cells and found that A549-cell-derived exosomes promoted BEAS-2B cells migration, invasion, and epithelial–mesenchymal transition (EMT). Importantly, we observed that let-7c-5p and miR-181b-5p were attenuated in A549-cell-derived exosomes compared to BEAS-2B-cell-derived exosomes. The analysis of miRNA expression level in BEAS-2B cells indicated that incubation with A549-cell-derived exosomes reduced the expression levels of let-7c-5p and miR-181b-5p. In transient transfections assay, we found that downregulation of let-7c-5p and miR-181b-5p simultaneously showed stronger promotion of BEAS-2B cells migration and invasion than individually. Moreover, exosomes secreted from A549 cells with upregulated expression of let-7c-5p and miR-181b-5p significantly reduce their regulatory effect on BEAS-2B cells. Bioinformatics analyses revealed that let-7c-5p and miR-181b-5p inhibit the EMT process mainly by regulating focal adhesion and mitogen-activated protein kinase (MAPK) signaling pathway. Thus, our data demonstrated that A549-cell-derived exosomal let-7c-5p and miR-181b-5p could induce migration, invasion, and EMT in BEAS-2B cells, which might be regulated through focal adhesion and MAPK signaling pathway. The expression level of let-7c-5p and miR-181b-5p may show great significance for the early diagnosis of lung cancer.

The metamorphosis process is a critical life-changing event for marine invertebrate planktonic larvae to transform into benthic adults, which is crucial for the shellfish bed’s ecosystem stability and seed production in aquaculture. The mechanism of neuroendocrine regulation in the larval metamorphosis of bivalves remains ambiguous. In the present study, the expression of two deiodinase genes, McDx and McDy, was analyzed by whole-mount in situ hybridization at four larval stages in the hard-shelled mussel Mytilus coruscus. The McDx and McDy localized in visceral tissues, nervous system, mantle, and velum, indicating that two deiodinase genes are essential for larval development in M. coruscus. Knockdown of the McDx and McDy in the pediveliger larvae of M. coruscus using electroporation of siRNA significantly (p < 0.001) reduced McDx and McDy expression. McDx and McDy knockdown reduced larval metamorphosis in 45% and 49% of the pediveliger larvae induced by epinephrine (EPI). It is hypothesised that the knockdown effects of McDx and McDy repress metamorphic induction rather than larval viability, which does not elicit a lethal effect. The present study corroborates a synergistic action of the adrenergic and thyroid hormones signalling pathway in M. coruscus, and suggests the role of McDx and McDy in larval development and metamorphic transition.

The massive use and the persistence of per- and polyfluoroalkyl substances (PFAS) have led to their frequent detection in aquatic environments, which may further threaten drinking water safety. So far, our knowledge about the occurrence of PFAS in drinking water system is still very limited. Here we investigated the occurrence and removal of PFAS in a drinking water system using non-target, suspect and target screening strategies. Sampling was performed in three seasons in the drinking water system including a water source, two drinking water treatment plants, and tap water in five households. The results showed detection of 17 homologous series with 51 homologues in non-target screening and 50 potential PFAS detected in suspect screening. Probable structures were proposed for 15 PFAS with high confidence levels (the first three of the five levels), with seven of them being reported for the first time in drinking water system. Semi-quantification was performed on seven homologous series based on target PFAS, the estimated total concentrations for non-target PFAS ranged between 4.10 and 17.6 ng/L. Nine out of 50 target PFAS were found and precisely quantified (

In this work, we propose an unsupervised multiple parametric-margin support vector clustering (MPMSVC) for noisy clustering tasks. The main idea of MPMSVC is to find a parametric-margin center hyperplane for each cluster in a manner that gathers the within-cluster instances around the corresponding center hyperplane, and keeps the between-cluster instances far away. Specifically, our MPMSVC owns the following attractive merits: i) The primal of MPMSVC is enhanced in the least squares sense, which enjoys an effective learning procedure. ii) The utilization of the linear $L_{1}$ -norm loss makes MPMSVC be more robust to noisy clustering tasks. iii) An efficient iterative algorithm is presented to optimize the non-smooth problem in MPMSVC, which only involves a set of linear equations. Also, the convergence of the proposed algorithm is guaranteed theoretically. iv) The nonlinear extension is further derived via kernel technique to deal with more complex clustering tasks. Finally, the feasibility and effectiveness of MPMSVC is validated by extensive experiments on both synthetic and real-world datasets.

In order to investigate the inhibitory eff ects of oyster enzymatic hydrolysate (OEH) on the metastasis of Lewis lung cancer and to evaluate its mechanism, daily gavage of low(LOEH), medium(MOEH) and high (HOEH) doses of OEH for 5 weeks was administered based on the subcutaneous Lewis lung cancer model in C57BL/6J male mice, the volume and weight of subcutaneous tumor were measured, the lung metastatic nodules were counted, the number of tumor-associated-macrophages (TAMs; CD11b+F4/80+), the expression of E-cadherin, Vimentin, microRNA-21 and microRNA-218 in subcutaneous tumor were measured. It was found that OEH treatment significantly decreased the subcutaneous tumor weight for the MOEH and HOEH groups (P=0.013, P=0.007) and significantly inhibited lung metastasis in a dose-dependent manner (χ2=13.16, P=0.004). The expression of E-cadherin showed a statistical increase at high dose, while the expression of Vimentin and the number of TAMs in subcutaneous tumor was significantly decreased at all OEH doses (P

Melon (Cucumismelo L.) is an important vegetable crop that has been subjected to domestication and improvement. Several varieties of melons with diverse phenotypes have been produced. In this study, we constructed a melon pan-genome based on 297 accessions comprising 168 Mb novel sequences and 4,325 novel genes. Based on the results, there were abundant genetic variations among different melon groups, including 364 unfavorable genes in the IMP_A vs. LDR_A group, 46 favorable genes, and 295 unfavorable genes in the IMP_M vs. LDR_M group. The distribution of 709 resistance gene analogs (RGAs) was also characterized across 297 melon lines, of which 603 were core genes. Further, 106 genes were found to be variable, 55 of which were absent in the reference melon genome. Using gene presence/absence variation (PAV)-based genome-wide association analysis (GWAS), 13 gene PAVs associated with fruit length, fruit shape, and fruit width were identified, four of which were located in pan-genome additional contigs.

The persistence of leukemia stem cells (LSCs) is one of the leading causes of chemoresistance in acute myeloid leukemia (AML). To explore the factors important in LSC-mediated resistance, we use mass spectrometry to screen the factors related to LSC chemoresistance and defined IFN-γ-inducible lysosomal thiol reductase (GILT) as a candidate. We found that the GILT expression was upregulated in chemoresistant CD34+ AML cells. Loss of function studies demonstrated that silencing of GILT in AML cells sensitized them to Ara-C treatment both in vitro and in vivo. Further mechanistic findings revealed that the ROS-mediated mitochondrial damage plays a pivotal role in inducing apoptosis of GILT-inhibited AML cells after Ara-C treatment. The inactivation of PI3K/Akt/ nuclear factor erythroid 2-related factor 2 (NRF2) pathway, causing reduced generation of antioxidants such as SOD2 and leading to a shifted ratio of GSH/GSSG to the oxidized form, contributed to the over-physiological oxidative status in the absence of GILT. The prognostic value of GILT was also validated in AML patients. Taken together, our work demonstrated that the inhibition of GILT increases AML chemo-sensitivity through elevating ROS level and induce oxidative mitochondrial damage-mediated apoptosis, and inhibition of the PI3K/Akt/NRF2 pathway enhances the intracellular oxidative state by disrupting redox homeostasis, providing a potentially effective way to overcome chemoresistance of AML.

AIM: To investigate the curative effect of intravitreal injection of ranibizumab combined with trabeculectomy on neovascular glaucoma(NVG).METHODS: The clinical data of 52 patients(52 affected eyes)with NVG who were admitted to the hospital between September 2015 and April 2017 were collected and retrospectively analyzed. The patients were divided into group A(intravitreal injection of ranibizumab combined with trabeculectomy, 31 affected eyes)and group B(intravitreal injection of ranibizumab combined with Ahmed glaucoma valve implantation, 21 affected eyes)according to the surgical method. They were followed up for 6mo after surgery. The intraocular pressure before surgery and after surgery, eyesight, visual field and complications after surgery were compared between two groups. The clinical curative effect was assessed. RESULTS: The intraocular pressure of both groups decreased gradually after surgery. The intraocular pressure of group A was lower than that of group B at 7d, 1mo and 3mo after surgery(PP>0.05). The total effective rate of treatment in group A at 6mo after surgery was obviously higher than that in group B(97% vs 71%, P=0.013). The incidence rates of corneal edema and hyphema in group A were lower than those in group B(PCONCLUSION: Intravitreal injection of ranibizumab combined with trabeculectomy for treating NVG can effectively decrease and maintain intraocular pressure and reduce the incidence of postoperative complications, with marked curative effect.

SARS-CoV-2 infection has become an urgent public health concern worldwide, severely affecting our society and economy due to the long incubation time and high prevalence. People spare no effort on the rapid development of vaccine and treatment all over the world. Amongst the numerous ways of tackling this pandemic, some approaches using extracellular vesicles (EVs) are emerging. In this review, we summarize current prevalence and pathogenesis of COVID-19, involving the combination of SARS-CoV-2 and virus receptor ACE2, endothelial dysfunction and micro thrombosis, together with cytokine storm. We also discuss the ongoing EVs-based strategies for the treatment of COVID-19, including mesenchymal stem cell (MSC)-EVs, drug-EVs, vaccine-EVs, platelet-EVs, and others. This manuscript provides the foundation for the development of targeted drugs and vaccines for SARS-CoV-2 infections.

Integrins are the adhesion molecules and receptors of extracellular matrix (ECM). They mediate the interactions between cells-cells and cells-ECM. The crosstalk between cancer cells and their microenvironment triggers a variety of critical signaling cues and promotes the malignant phenotype of cancer. As a type of transmembrane protein, integrin-mediated cell adhesion is essential in regulating various biological functions of cancer cells. Recent evidence has shown that integrins present on tumor cells or tumor-associated stromal cells are involved in ECM remodeling, and as mechanotransducers sensing changes in the biophysical properties of the ECM, which contribute to cancer metastasis, stemness and drug resistance. In this review, we outline the mechanism of integrin-mediated effects on biological changes of cancers and highlight the current status of clinical treatments by targeting integrins.

Human cytomegalovirus (HCMV), a ubiquitous beta-herpesvirus, is able to establish lifelong latency after initial infection. Periodical reactivation occurs after immunosuppression, remaining a major cause of death in immunocompromised patients. HCMV has to reach a structural and functional balance with the host at its earliest entry. Virion-carried mediators are considered to play pivotal roles in viral adaptation into a new cellular environment upon entry. Additionally, one clear difference between primary infection and reactivation is the idea that virion-packaged factors are already formed such that those molecules can be used swiftly by the virus. In contrast, virion-carried mediators have to be transcribed and translated; thus, they are not readily available during reactivation. Hence, understanding virion-carried molecules helps to elucidate HCMV reactivation. In this article, the impact of virion-packaged molecules on viral structure, biological behavior, and viral life cycle will be reviewed.

Background: Recrossing the compromised side branch (SB) with a balloon is sometimes technically challenging. The aim of this study was to evaluate whether in-stent anchoring (ISA) is safe and effective to facilitate SB balloon delivery for final kissing. Methods: One hundred and fifty-nine consecutive patients were included (166 bifurcation lesions) in this prospective, single-center registry. ISA was used as a bailout method after unsuccessful SB crossing using conventional techniques, including low-profile balloons. Technique success was defined as SB balloon delivery and final kissing. Results: Kissing-balloon delivery was successfully performed with conventional strategies in 149 of 166 lesions (89.8%). In the remaining 17 lesions (10.2%), recrossing of the main vessel stent strut was not successful; therefore, ISA was attempted. The balloon successfully crossed the stent struts, and final kissing was achieved in 15 of 17 lesions (88.2%). Total final kissing was achieved in 164 of 166 lesions (98.8%), with success rates of 100% in the single-stent group and 97.6% in the two-stent group. Two cases without balloon delivery had complex bifurcation lesions with severe calcification. There was no vessel dissection in the anchoring zone. Conclusions: ISA is safe and effective for recrossing stent struts when conventional low-profile balloons have failed. However, large-scale trials are warranted for further evaluation.

AIM:To detect the protective effect of curcumin for retinal ganglion cells(RGCs)in adult rabbits with acute intraocular hypertension.METHODS: Twenty-four adult rabbits were divided randomly into normal control group, model group and curcumin group. Except normal control group, the rabbit model with acute ocular hypertension was established by increasing intraocular pressure through anterior chamber infusion. After the establishment of the model, rabbits in curcumin group were injected intravitreally with curcumin(0.1mg/0.1mL)for 7d. Rabbits in mdodel group were injected with physiological saline replaced of the same volume curcumin. The oculars in normal control group without any treatments were acquired directly. The levels of Thy-1 in RGCs were detected by immunohistochemistry. The density of RGCs was counted too.RESULTS: Thy-1 expressed in the RGCs in normal control group and curcumin group had no significant difference(P>0.05).While the difference between model group and normal control group on Thy-1 expression was statistically significant(PCONCLUSION: In this study on curcumin in adult rabbits with acute ocular hypertension, curcumin can increase the expression of Thy-1, which shows that it can partly reduce the injury of RGCs in rabbits with acute intraocular hypertension and curcumin may be able to protect the retina under certain situation.

AIM:To investigate the changes of retinal histology and oxidative stress in diabetic retinopathy and its reversal by pyruvate in diabetic rats. METHODS:Eighty Wistar rats were divided into 3 groups: control group(20 rats), model group(30 rats)and treatment group(30 rats). After streptozotocin(STZ)induced diabetes mellitus in the model group and the treatment group, the treatment group received 2% pyruvate in diet and drinking. The changes of body weight and blood glucose were observed and the changes of glutathione peroxidase(GSH-PX), malonie dialdehyde(MDA), and Na+-K+-ATPase levels of retinal tissue and retinal ultrastructure were investigated in three groups at 12wk after occurrence of diabetes. RESULTS:Compared with control group, the body weight of the model group were significantly decreased, the activities of GSH-PX and ATP in the retina of diabetic rats were significantly lower, the MDA was signigicantly higher and significant changes occurred in retinal ultrastructure. Compared with model group, the blood glucose of the treatment group had no significant changes. However, the activities of GSH and ATP in the retina of diabetic rats were higher, the MDA was lower and the retinal ultrastructure was comparatively mild. CONCLUSION:Pyruvate can alleviate oxidatie stress reaction, improve the energy metabolism of retina, and delay the development of retinopathy.

To investigate the prevalence of common viruses and Mycoplasma pneumoniae (MP) in hospitalized infants with acute bronchiolitis and study the relationship between bronchiolitis and meteorological conditions. Methods: A 2-year prospective study was conducted on infants with a first episode of bronchiolitis admitted to Respiratory Department of Suzhou Children's Hospital. Demographic and clinical characteristics and meteorological conditions were obtained and analyzed. Results: Pathogens were identified in 59.6% of 998 cases analyzed. The most frequent pathogen identified was respiratory syncytial virus (28.7%), followed by human bocavirus (11.6%), MP (9.0%), human parainfluenza virus-3 (7.8%), human metapneumovirus (6.6%), influenza A (3.5%), adenovirus (1.0%), and human parainfluenza virus-1 (0.3%). The clinical scores in children with MP or human metapneumovirus single infections, based on the assessment of severity of acute bronchiolitis, were significantly lower than in children with respiratory syncytial virus single infections. Respiratory syncytial virus had the strongest inverse correlation with mean temperature, followed by influenza A and human metapneumovirus. In addition, MP and human parainfluenza virus-3 showed positive correlations with mean temperature. Conclusion: Although respiratory syncytial virus was the most frequent pathogen in patients in whom bronchiolitis was diagnosed, other pathogens, including newly identified viruses and MP, also play important roles in infants with bronchiolitis. Different respiratory pathogens have different traits in response to certain meteorological conditions.

Abstract.: This study aims to evaluate the protective effects of Yi-Qi-Fu-Mai sterile powder (YQFM) on myocardial oxidative damage and tries to identify the active components responsible for its pharmacological benefits. YQFM and the n-butanol extract of YQFM (YQFM-Bu) were administered to ISO-induced myocardial injury mice. Left ventricle weight index and histopathological analyses were conducted. Serum enzymatic activities of lactate dehydrogenase (LDH), creatine kinase (CK) and superoxide dismutase (SOD), myeloperoxidase (MPO), and the levels of malondialdehyde (MDA) were also measured. Our results demonstrated that both YQFM and YQFM-Bu significantly restored the abnormal activities of CK, LDH, MPO, SOD, and the levels of MDA in ISO-induced myocardial injury mice, and these biochemical results were further supported by histopathological data. Our in vitro findings also confirmed that both YQFM and YQFM-Bu exhibit significant radical scavenging activity. Furthermore, the major active fractions of YQFM were identified by UPLC–MS/MS. Twenty-five ginsenosides and three lignans were identified from YQFM-Bu. These findings suggested YQFM-Bu is the major active fraction of YQFM with the ginsenosides and lignans as potential active components responsible for its protective effect against myocardial injury, and YQFM exerted its beneficial effects on myocardial injury mainly through inhibiting oxidative damage and maintaining the functional integrity of myocardial tissue. Keywords:: myocardial oxidative damage, Traditional Chinese Medicine, Yi-Qi-Fu-Mai sterile powder, active ingredient, cardioprotection

Objective To investigate the role of tyrosine 23 (Tyr23) phosphorylation of Annexin A2 (Anxa2) in regulating the proliferation and invasion of human breast cancer SK-BR-3 cells.Methods A panel of lentivirus plasmids expressing Anxa2-wide type (Ana2-WT), Anxa2-Y23A, and Anxa2-Y23D was generated and infected with SK-BR-3 cells. The monoclonal strains were screened. The expression of Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D was determined by Western blot analysis. The ability of the cells to proliferate was detected through an MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. Boyden chamber assays were employed to examine migration and invasion abilities. The interaction between Anxa2 and Stat3 was analyzed by immunoprecipitation analyses. Nucleoprotein and cytosolic protein were extracted from SK-BR-3, Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D cells to analyze the expression and localization of Stat3 phosphorylation.Results The monoclonal strains constitutively expressing Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D were screened. Both Anxa2-WT and Anxa2-Y23D enhanced the proliferation, migration and invasion abilities of SK-BR-3 cells (PConclusions Tyr23 phosphorylation of Anxa2 promotes the proliferation and invasion of human breast cancer SK-BR-3 cells and the phosphorylation of Stat3 in the nucleus.

G-quadruplexes are four-stranded nucleic acid secondary structures that are formed in guanine-rich sequences. G-quadruplexes are widely distributed in functional regions of the human genome and transcriptome, such as human telomeres, oncogene promoter regions, replication initiation sites, and untranslated regions. Many G-quadruplex-forming sequences are found to be associated with cancer, and thus, these non-canonical nucleic acid structures are considered to be attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this mini review, we summarize recent advances made by our lab in the study of G-quadruplex-targeted natural alkaloids and their derivatives toward the development of potential anticancer agents.

The effect of pulsating jet on the unsteady film cooling performance was studied by experimental and numerical simulation. The FLIR thermal infrared thermal camera was used the measure the adiabatic temperature of the surface. The large eddy simulation was conducted for analyzing the adiabatic film cooling effectiveness at four different jet non-dimensionalized pulsated frequency of St = 0, 0.1, 0.2, and 0.3. The analysis of the dynamic model decomposition of both the velocity and temperature fields obtained by numerical calculation was performed to obtain the coupling relationship between the flow and heat transfer. Results show that the cooling effectiveness of steady film cooling (St = 0) decreases with the increase of blowing ratio. At low blowing ratio (M = 0.65), the cooling efficiency of the pulsating jet is significantly lower than the steady-state jet. At the blowing ratio of 1.0 and 1.5, the cooling efficiency of the low frequency pulsating jet (St = 0.1) is a little higher than the steady-state jet, indicating that the low frequency pulsation under the high blowing ratio can improve the coverage of the cooling air. At high pulsating frequency (St = 0.3), the cooling effectiveness is obviously declined. [ABSTRACT FROM AUTHOR]

Red macroalga Pyropia yezoensis is a high valuable cultivated marine crop. Its acclimation to cold stress is especially important for long cultivation period across winter in coasts of warm temperate zone in East Asia. In this study, the response of P. yezoensis thalli to low temperature was analyzed on physiology and transcriptome level, to explore its acclimation mechanism to cold stress. The results showed that the practical photosynthesis activity (indicated by FPSII and qP) was depressed and pigment allophycocyanin content was decreased during the cold stress of 48 h. However, the Fv/Fm and non-photochemical quenching increased significantly after 24 h, and the average growth rate of thalli also rebounded from 24 to 48 h, indicating a certain extent of acclimation to cold stress. On transcriptionally, the low temperature promoted the expression of differentially expressed genes (DEGs) related to carbohydrate metabolism and energy metabolism, while genes related to photosynthetic system were depressed. The increased expression of DEGs involved in ribosomal biogenesis and lipid metabolism which could accelerate protein synthesis and enhance the degree of fatty acid unsaturation, might help P. yezoensis thallus cells to cope with cold stress. Further co-expression network analysis revealed differential expression trends along with stress time, and corresponding hub genes play important roles in the systemic acquired acclimation to cold stress. This study provides basic mechanisms of P. yezoensis acclimation to cold temperature and may aid in exploration of functional genes for genetic breeding of economic macroalgae. [ABSTRACT FROM AUTHOR]