Tissue optical clearing enhances efficacy of vascular targeted photodynamic therapy of mouse dorsal skin

Vascular-targeted photodynamic therapy(V-PDT)is an effective treatment for port wine stains(PWS).However,repeated treatment is usually needed to achieve optimal treatment outcomes,possibly due to the limited treatment light penetration depth in the PWS lesion.The optical clearing technique can increase light penetration in depth by reducing light scattering.This study aimed to investigate the V-PDT in combination with an optical clearing agent(OCA)for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model.Vascular responses were closely monitored with laser speckle contrast imaging(LSCI),optical coherence tomography angiography,and stereo microscope before,during,and after the treatment.We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature.The combination of OCA and V-PDT resulted in significant vascular damage,including vasoconstriction and the reduction of blood flow.Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases,including PWS.

A Simple One-Step System Enhances the Availability of High-Quality Sperm for Assisted Reproductive Procedures

Over the last forty years, in vitro fertilization, which has expanded to assisted reproductive technologies (ART), has gone from an experimental procedure to the mainstay of infertility treatment. A technique that once made news with each birth is now responsible for 2% - 3% of the babies born in several nations of the world. This has happened due to significant advances in hormone therapies, culture techniques, and the specialization of equipment designed to support oocytes and embryos. However, for all the advances made to support female fertility, little has changed in male treatment since the advent of intracytoplasmic sperm injection in the early 1990’s. Recently, a number of authors have documented problems with sperm preparation techniques. Some report DNA damage, others membrane and organelle issues, all of which potentially hamper fertilization rates and possibly take-home baby rates. Further, as the clinical workload of ART has increased and staffing shortages have become critical, all labs are looking for simpler, more efficient ways to perform job functions. This study describes a simple, one-step method for preparing semen samples for ART. This new technique minimizes excessive manipulation of the sample compared to current standards and is less likely to cause cell damage. Preliminary results suggest a significant enhancement in recovered sample motility and an optimal sample for ART procedures with minimal sample manipulation.

DNA N^6-methyladenine demethylase ALKBH1 enhances osteogenic differentiation of human MSCs

ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells （MSCs） was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.

Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model

Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus （DMM） to induce OA in two mouse models with reduced EGFR activity, one with genetic modification （, was/＋ mice） and the other one with pharmacological inhibition （gefitinib treatment）. Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 （MMP13）, the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α （HIF2α）, a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation.

Ketamine enhances structural plasticity in human dopaminergic neurons:possible relevance for treatment-resistant depression

Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.

TLR signaling that induces weak inflammatory response and SHIP1 enhances osteogenic functions

Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 （P3C） and Escherichia coli lipopolysaccharide （EcLPS） were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism （Pg1690） or TLR4 antagonism （Pg1449） and mutant E. coli LPS （LPxE/LPxF/WSK） were used. IL-lp, SH2-containing inositol phosphatase-1 （SHIP1） that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane （3AC） was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 （with SHIP1 activity） and mutant TLR4 ligands could enhance osteogenesis.

Valproic Acid Enhances the Anti-tumor Effect of(-)-gossypol to Burkitt Lymphoma Namalwa Cells

Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and （-）-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years.

TRAF7 enhances degradation of ubiquitinated KLF4 to promote hepatocellular carcinoma progression

Objective:The tumor necrosis factor receptor-associated factor 7(TRAF7)is one of the components of the tumor necrosis factor alpha(TNF-α)/nuclear factor kappa B(NF-κB)pathway and a putative E3-ubiquitin ligase.This study aims to explore the biologic effects and the molecular mechanisms of deregulated TRAF7 signaling in hepatocellular carcinoma(HCC)progression.

UV-A Coexposure Enhances the Toxicity of AromaticHydrocarbons, Munitions, and Metals to Photobacterium phosphoreum

Johnson et al. (1993) showed that coexposure to UV-A between 300-400 nm enhanced the toxicity of nitrotoluenes to Phoiobacterium phosphoreum, a marine bioluminescent bacteria used in the Microtox test (Microbics Inc.). This paper reports that UV-A photoenhanced the toxicity of polynuclear aromatic hydrocarbons, other types of organic compounds, and some transition metals to P. phosphoreum. Coexposure to 400 μw/cm2 for 15 min increased the toxicity of psoralen, α-terthienyl, anthracene, acridine, fluoranthene,TNT, Cu2+, As3+, Ni2, and Cd2+. Phenanthrene was photoenhanced after 30 min coexposure at 400 μw/cm2+, and Mn2+ at 800 μw/cm2 aftef 15 min. Naphthalene was not enhanced at 800 μw/cm2 for 30 min

Retinoic acid enhances expression of neural specific genes in Sca-1^+ cells of mouse fetal liver through activating protein kinase C

BACKGROUND： Interstitial stem cell is charactenzed by multiple differentiations, and retinoic acid （RA） can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal transduction pathway should be discussed to trigger differentiation. OBJECTIVE ： To study the effect of RA on expression of neural specific gene and its signal transduction in fetal liver of mice.DESIGN ： Paired controlled study on the basis of cell.SETTING ： Institute of Hematology, Medical College of Jinan University.MATERIALS： The experiment was completed in the Institute of Hematology, Medical College of Jinan University from April to December 2005. C57BL/6 mice, of clean grade, aged 8-10 weeks, weighting 20-35 g, 10 females and 4 males, were selected in this study.METHODS： Sca-1^＋ cells in fetal liver were prepared with MACS kit and cultured with DMEM ＋ 10% fetal bovine serum （FBS）. On the fourth day, it was added with or without protein kinase C （PKC） inhibitor chelerythrine chloride （3μmol/L） and 5×10^-7 mol/L RA for 24 hours, and then incubated in serum-free medium for 5 days. Expressions of genes were assayed by Westem blotting and semi-quantitative RT-PCR.MAIN OUTCOME MEASURES ： Expression of neural specific gene NF-L, NF-H, BF-1 and TH.RESULTS： Expression of neural specific gene NF-L, NF-H, BF-1 and TH was significantly increased after treatment with RA and they were increased 5.06, 5.15, 4.63 and 3.33 times, respectively. However, chelerythrine chloride could inhibit expression of neural specific gene NF-L, NF-H, BF-1 and TH induced by RA.CONCLUSION ： RA can promote the expression of neural specific genes in Sca-1^＋ cells of fetal liver, and its pathway may be related to PKC.

ZTE Enhances 3G Mobile TV Experience at Beijing 2008 Olympic Games

ZTE Corporation enhanced 3G mobile TV viewing experience during the Beijing 2008 Olympic Games as it officially rolled out U728

3-67 MiR-449a Overexpression Enhances the Radiosensitivity in Prostate Cancer Cells

Multiple links between miRNA activity and cancer have been established. Several miRNAs have been describedas oncogenes while others act as tumour suppressors[1]. MiR-449a is a member of miR-34 family which locates onhuman chromosome 5q11.2, a region identified as a susceptibility locus in a variety of malignancies, includingprostate cancer[2]. In line with the tumor-suppressive role of miR-34, miR-449a was shown to be significantly downregulatedin prostate cancer cell lines and tissue relative to normal tissues and plays a critical role in growth ofprostate cancer cells [3;4].

3-68 Loss of Nrf2 Enhances the Radiosensitivity in Human Lung Cancer Cells

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor regulating the expression ofantioxidant genes. Under oxidative stress conditions or other stimulus, Nrf2 translocating from the cytoplasminto the nucleus, binds to antioxidant response elements, and increases the expression of antioxidant enzymes[1;2].Constitutive Nrf2 activation in many tumors enhances cell survival and resistance. For instance, high level of Nrf2 isobserved in non-small cell lung cancer A549 cells[3;4]. The gain of Nrf2 function has been implicated in the resistanceof cancer cells to radiation therapy.

3-69 MiR-449a Enhances Radiosensitivity by Downregulation of c-Myc in Prostate Cancer Cells

c-Myc was one of the first oncogenes to be identified and its overexpression at the RNA and protein levels has subsequently been linked to a wide variety of human cancers[1]. Overexpression of the c-Myc protein or c-Myc gene has been shown in 80% of breast cancers, 70% of colon cancers, 90% of gynecological cancers, 50% of hepatocellular carcinomas and a variety of hematological tumors.

3-70 Capsazepine, a TRPV1 Antagonist, Enhances Radiation Sensitivity in Human Hepatocellular Carcinoma HepG2 Cells

Transient receptor potential vanilloid 1(TRPVl) that is known as capsaicin receptor is a non-selective cationion channel[1]. TRPV1 can regulate Ca2+ influx, participate in a variety of physiological and pathological processof tumor[2]. One such agent is Capsazepine (CPZ) that is now widely used as a selective vanilloid type 1 receptor(TRPV1) antagonist. CPZ can be directly actived on the capsaicin receptor, blocked its biological effects, and abolishedosteosarcoma-induced hyperalgesia when administered subcutaneously at doses ranging from 3 to 10 mg/kg,blocked calcium channels[3]. However, the mechanisms underlying the anticancer effects of CPZ have not fully beenunderstood. Whether CPZ can induce apoptosis of human hepatocellular carcinoma cell line HepG2 is not known.Therefore, the objective of the study reported here was to determine whether CPZ can enhance radiation sensitivityin HepG2 cell, and impact on cell proliferation.

Festival of China Enhances China-Nepal Ties

From October 10 to 17,the Festival of China 2009 was held in Kathmandu,capital of Nepal.This one-week biennial celebration,initiated in 2003,aims to"promote

Enhanced recovery after surgery protocol enhances early postoperative recovery after pancreaticoduodenectomy

Background: Enhanced recovery after surgery(ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy(PD). Methods: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube(NGT) was removed on postoperative day(POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula(POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications(defined as per the ISGPS definitions). Results: NGT was removed on POD1 in 45(90%) patients, abdominal drain removed by POD4 in 41(82%) and 43(86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three(6%) patients had delayed gastric emptying(DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay(LOS) with age( P < 0.05) and a marginal relation between LOS and postoperative albumin( P = 0.05). Conclusions: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.

A Fragment of Cadherin-Like Protein Enhances Bacillus thuringiensis Cry1B and Cry1C Toxicity to Spodoptera exigua(Lepidoptera:Noctuidae)

Cry toxins produced by Bacillus thuringiensis（Bt） are effective biological insecticides against certain insect species.In this study,bioassay results indicated that Cry1B and Cry1C were toxic to Spodoptera exigua.We also identified a cadherin-like gene in S.exigua that could enhance the toxicity of Cry1B and Cry1C.The cadherin-like gene identified from the larvae midgut tissue was cloned by reverse transcription polymerase chain reaction（RT-PCR） and rapid amplification of cDNA ends（RACE）.The full-length cDNA of the gene consisted of 5 220 bp encoding 1 740 amino acid with a predicted molecular mass of 196 kD.BLAST search analysis showed that the predicted amino acid sequence had a high sequence identity to the published sequences of cadherin-like proteins from other Lepidoptera insects.Spatial expression of the cadherin-like gene detected by qRT-PCR analysis revealed that the cadherin-like gene was mainly present in the gut of 4th instar larvae and during different life stages.The results suggested that the commercial development of this synergist has the potential to enhance Cry1B and Cry1C toxicity against Lepidoptera insects.

Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells.Herein,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)models.Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen secretion.Besides,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating them.As a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

Advances in All-Solid-State Lithium-Sulfur Batteries for Commercialization

Solid-state batteries are commonly acknowledged as the forthcoming evolution in energy storage technologies.Recent development progress for these rechargeable batteries has notably accelerated their trajectory toward achieving commercial feasibility.In particular,all-solid-state lithium-sulfur batteries(ASSLSBs)that rely on lithium-sulfur reversible redox processes exhibit immense potential as an energy storage system,surpassing conventional lithium-ion batteries.This can be attributed predominantly to their exceptional energy density,extended operational lifespan,and heightened safety attributes.Despite these advantages,the adoption of ASSLSBs in the commercial sector has been sluggish.To expedite research and development in this particular area,this article provides a thorough review of the current state of ASSLSBs.We delve into an in-depth analysis of the rationale behind transitioning to ASSLSBs,explore the fundamental scientific principles involved,and provide a comprehensive evaluation of the main challenges faced by ASSLSBs.We suggest that future research in this field should prioritize plummeting the presence of inactive substances,adopting electrodes with optimum performance,minimizing interfacial resistance,and designing a scalable fabrication approach to facilitate the commercialization of ASSLSBs.