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Xiangyang Cheng,1,* Dejian Li,2,* Aiqi Lin,3 Jun Xu,1 Liang Wu,1 Huijie Gu,1 Zhongyue Huang,1 Jiangyi Liu,1 Yiming Zhang,1 Xiaofan Yin1 1Department of Orthopedics, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, China; 2Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201301, China; 3Department of Retired, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, China *These authors contributed equally to this work Introduction: For an ideal drug delivery system, the outstanding drug-loading capacity and specific control of the release of therapeutics at the desired lesions are crucial. In this work, we developed a triple-responsive nanoplatform based on copper sulfide (CuS)-capped yolk-shell-structured periodic mesoporous organosilica nanoparticles (YSPMOs) for synergetic chemo-photothermal therapy. Methods: Herein, the YSPMOs were employed as a drug carrier, which exhibited a high doxorubicin (DOX) loading capacity of 386 mg/g. In this controlled-release drug delivery system, CuS serves as a gatekeeper to modify YSPMOs with reduction-cleavable disulfide bond (YSPMOs@CuS). CuS could not only avoid premature leakage in the delivery process, but also endowed the excellent photothermal therapy (PTT) ability. Results: Upon entering into cancer cells, the CuS gatekeeper was opened with the breaking of disulfide bonds and the DOX release from YSPMOs(DOX)@CuS in response to the intracellular acidic environment and external laser irradiation. Such a precise control over drug release, combined with the photothermal effect of CuS nanoparticles, is possessed by synergistic chemo-photothermal therapy for cancer treatment. Both in vitro and in vivo experimental data indicated that the synergistic effect of YSPMOs(DOX)@CuS showed efficient antitumor effect. In addition, low systemic toxicity was observed in the pathologic examinations of liver, spleen, lungs, and kidneys. Conclusion: This versatile nanoplatform combination of PTT, chemotherapeutics, and gating components shows general potential for designing multifunctional drug delivery systems. Keywords: periodic mesoporous organosilica, CuS, triple-responsive release, chemo-photothermal therapy

The aim of this study was to investigate whether leisure screen time (LST) increases the risk of diabetic retinopathy (DR) using the Mendelian randomization (MR). This study employed a two-sample MR analysis, utilizing 63 single-nucleotide polymorphisms as instrumental variables (IVs) to assess the causal relationship between LST and the risk of Dr. To ensure the robustness of the results, a multi-effect test was conducted to evaluate the validity of the IVs. Additionally, heterogeneity tests were performed to explore differences among sub-samples. Sensitivity analyses were also conducted to further validate our findings. The impact of LST on the risk of DR was observed in both inverse variance weighted (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.04-1.43, P = 1.38 × 10-2) and weighted median (OR: 1.30, 95% CI: 1.05-1.61, P = 1.46 × 10-2) analyses. However, the MR-Egger method (OR: 0.66, 95% CI: 0.32-1.36, P = .273) did not find an increased risk of DR with increased LST. The pleiotropy test yielded a P-value of P = .09. Heterogeneity tests showed that the Q value for the inverse variance weighted method was 71.39 with a P-value of 0.17, indicating no significant heterogeneity. These results suggest that the IVs might be appropriate, and the analysis results could be robust. A large-scale MR analysis suggests a causal relationship between LST and the risk of Dr., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

With societal development and an ageing population, psychiatric disorders have become a common cause of severe and long-term disability and socioeconomic burdens worldwide. Semaphorin 3A (Sema-3A) is a secreted glycoprotein belonging to the semaphorin family. Sema-3A is well known as an axon guidance factor in the neuronal system and a potent immunoregulator at all stages of the immune response. It is reported to have various biological functions and is involved in many human diseases, including autoimmune diseases, angiocardiopathy, osteoporosis, and tumorigenesis. The signals of sema-3A involved in the pathogenesis of these conditions, are transduced through its cognate receptors and diverse downstream signalling pathways. An increasing number of studies show that sema-3A plays important roles in synaptic and dendritic development, which are closely associated with the pathophysiological mechanisms of psychiatric disorders, including schizophrenia, depression, and autism, suggesting the involvement of sema-3A in the pathogenesis of mental diseases. This indicates that mutations in sema-3A and alterations in its receptors and signalling may compromise neurodevelopment and predispose patients to these disorders. However, the role of sema-3A in psychiatric disorders, particularly in regulating neurodevelopment, remains elusive. In this review, we summarise the recent progress in understanding sema-3A in the pathogenesis of mental diseases and highlight sema-3A as a potential target for the prevention and treatment of these diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cumulative human exposure to the environmental toxin, bisphenol A (BPA), has raised important health concerns in recent decades. However, the direct genomic regulation of BPA in skeletal muscles and its clinical significance are poorly understood. Therefore, we conducted a genome-wide transcriptome analysis after daily oral administration of BPA at the lowest observed adverse-effect level (LOAEL, 50 mg/kg) in male mice for six weeks to explore the gene-expression regulations in skeletal muscle induced by BPA. The primary Gene Ontology terms linked to BPA-dependent, differentially expressed genes at LOAEL comprised adaptive-immune response, positive regulation of T cell activation, and immune system process. The gene-set enrichment analysis disclosed increased complement-associated genes [complement components 3 (C3) and 4B, complement factor D, complement receptor 2, and immunoglobulin lambda constant 2] in the group administered with BPA, with a false-discovery rate of <0.05. Subsequent validation analysis conducted in BPA-fed animal skeletal muscle tissue and in vitro experiments confirmed that BPA induced immune activation, as evidenced by increased levels of C3 and C4α proteins in mice, C2C12 myoblasts, and mouse skeletal muscle cells. In addition, BPA markedly upregulated the transcription of tumor necrosis factor-α (Tnfα) in C2C12 myoblasts and mouse skeletal muscle cells, which was substantially inhibited by 5z-7-oxozeanol and parthenolide, providing further evidence of BPA-induced inflammation in muscle cells. Our bioinformatics and subsequent animal and in vitro validations demonstrate that BPA can activate inflammation in skeletal muscle, which could be a risk factor underlying chronic muscle weakness and wastage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Capping protein regulatory factor and myosin 1 linker 1 is termed CARMIL1. CARMIL1 is involved in several physiological processes; it forms an actin filament network and plasma membrane-bound cellular projection tissues and positively regulates the cellular components and tissues. CARMIL1 exhibits important biological functions in cancer; nonetheless, these functions have not been completely explored. We aimed to investigate the novel functions of CARMIL1 in liver cancer, particularly in cell proliferation. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Component A experiments, and subcutaneous tumor formation model suggest that CARMIL1 is central to the proliferation of liver cancer cells both in vivo and in vitro. We extracted CARMIL1 samples from The Cancer Genome Atlas Program and analyzed its enrichment. CARMIL1 regulated the pathway activity by affecting the expression of star molecular proteins of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Moreover, it influenced the proliferation ability of liver cancer cells. Western blotting suggested that CARMIL1 downregulation could affect ERK and mTOR phosphorylation. Results of the co-immunoprecipitation demonstrated that CARMIL1 binds to tripartite motif (TRIM)27, which in turn binds to p53. Subsequently, CARMIL1 can regulate p53 stability and promote its degradation through TRIM27. Additionally, CARMIL1 inhibition enhanced the sensitivity of liver cancer cells to sorafenib. Tumor growth was significantly inhibited in the group treated with sorafenib and CARMIL1, compared with the group treated with CARMIL1 alone. Sorafenib is a first-line targeted chemotherapeutic drug for hepatocellular carcinoma treatment. It increases the long-term survival of hepatocellular carcinoma by 44%. In this study, downregulated CARMIL1 combined with sorafenib significantly reduced the tumor volume and weight of the mouse subcutaneous tumor model, indicating the potential possibility of combining CARMIL1 with sorafenib in hepatocellular carcinoma treatment. In summary, CARMIL1 promotes liver cancer cell proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS + T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8 + T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Recent evidence of gut microbiota dysbiosis in the context of psoriasis and the increased cooccurrence of inflammatory bowel disease and psoriasis suggest a close relationship between skin and gut immune responses. Using a mouse model of psoriasis induced by the Toll-like receptor (TLR) 7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by inflammatory changes in the small intestine associated with eosinophil degranulation, which impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were increased in mice prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells were treated with media containing eosinophil granule proteins and exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by the transfer of eosinophils. Imiquimod levels and the distribution of eosinophils were positively correlated in the intestine. TLR7-deficient mice did not exhibit intestinal eosinophil degranulation but did exhibit attenuated inflammation in the skin and small intestine following imiquimod administration. These results suggest that TLR7-dependent bidirectional skin-to-gut communication occurs in psoriatic inflammation and that inflammatory changes in the intestine can accelerate psoriasis., (© 2024. The Author(s).)

Psychiatric disorders are complex, multifactorial illnesses. It is challenging for us to understand the underlying mechanism of psychiatric disorders. In recent years, the morbidity of psychiatric disorders has increased yearly, causing huge economic losses to the society. Although some progress, such as psychotherapy drugs and electroconvulsive therapy, has been made in the treatment of psychiatric disorders, including depression, anxiety, bipolar disorder, obsessive-compulsive and autism spectrum disorders, antidepressants and psychotropic drugs have the characteristics of negative effects and high rate of relapse. Therefore, researchers continue to seek suitable interventions. cAMP response element binding protein (CREB) belongs to a protein family and is widely distributed in the majority of brain cells that function as a transcription factor. It has been demonstrated that CREB plays an important role in neurogenesis, synaptic plasticity, and neuronal growth. This review provides a 10-year update of the 2013 systematic review on the multidimensional roles of CREB-mediated transcriptional signaling in psychiatric disorders. We also summarize the classification of psychiatric disorders and elucidate the involvement of CREB and related downstream signalling pathways in psychiatric disorders. Importantly, we analyse the CREB-related signal pathways involving antidepressants and antipsychotics to relieve the pathological process of psychiatric disorders. This review emphasizes that CREB signalling may have a vast potential to treat psychiatric disorders like depression. Furthermore, it would be helpful for the development of potential medicine to make up for the imperfection of current antidepressants and antipsychotics.

Particulate matter (PM) generated by environmental and air pollution is known to have detrimental effects on human health. Among these, PM2.5 particles (diameter < 2.5 µm) can breach the alveolar-capillary barrier and disseminate to other organs, posing significant health risks. Numerous studies have shown that PMs can harm various organs, including the reproductive system. Therefore, this study aimed to investigate the harmful effects of PM2.5 on mouse GC-1 spermatogonia cells (GC-1 spg cells) and to verify the ameliorative effects of parthenolide (PTL) treatment on damaged GC-1 spg cells. We observed a significant dose-dependent reduction in cell proliferation after PM2.5 concentration of 2.5 μg/cm 2 . Additionally, treatment with 20 μg/cm 2 PM2.5 concentration significantly increased the expression of autophagy-related proteins ATG7, the ratio of LC3-II/LC3-I, and decreased phosphorylation of PI3K and AKT. Furthermore, PM2.5 exposure augmented inflammation mediator gene expressions, the phosphorylation of the inflammation-related transcription factor NF-κB p65 at Ser536, and ubiquitination. Treatment of PM2.5-exposed GC-1 spg cells with PTL significantly reduced NF-κB p65 phosphorylation and the expression of autophagy-related proteins ATG7 and LC3-II, leading to a statistically significant recovery in cell proliferation. Together, our findings elucidated the detrimental effects of PM2.5 exposure on male germ cells, and the restorative properties of PTL against air pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study investigated the effects of non-pharmacological interventions on sleep in older people through a systematic review and meta-analysis. We conducted a literature search using eight electronic databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Participant characteristics, the contents of the evaluated interventions, and the measured outcomes were systematically reviewed for 15 selected studies. We performed a meta-analysis to estimate the effect size for overall, aggregated sleep outcomes. Due to the small number of studies available for each intervention, only the overall effectiveness of non-pharmacological sleep interventions was evaluated. The evaluated interventions included exercise, aromatherapy, acupressure, cognitive behavior therapy, and meditation. Our results demonstrated that non-pharmacological interventions showed statistically significant effects on sleep (effect size = 1.00, 95% confidence interval: 0.16, 1.85, I 2 = 92%, p < 0.001). After confirming publication bias and removing outliers, we found no heterogeneity (I 2 = 17%, p = 0.298), with a decrease in effect size to 0.70 (95% confidence interval: 0.47, 0.93). Non-pharmacological interventions are effective for improving sleep in older adults. Future studies should continue to investigate sleep problems and interventions addressing these problems in this demographic, particularly in older women. Objective measures should be used to follow-up on the evaluated sleep interventions over the long term.

Oral squamous cell cancer (OSCC) is the most common type of oral cancer (about 80-90% of cases) and various research is being done to cure the disease. This paper aims to verify whether treatment with no-ozone cold plasma (NCP), which is designed for safe usage of the plasma on oral cavities, in combination with gold nanoparticles conjugated with p-FAK antibody (p-FAK/GNP) can trigger the selective and instant killing of SCC-25 cells both in vitro and in vivo. When SCC25 and HaCaT cells are exposed to p-FAK/GNP+NCP, the instant cell death was observed only in SCC25 cells. Such p-FAK/GNP+NCP-mediated cell death was observed only when NCP was directly treated on SCC25 harboring p-FAK/GNP. During NCP treatment, the removal of charged particles from NCP using grounded electric mesh radically decreased the p-FAK/GNP+NCP-mediated cell death. This p-FAK/GNP+NCP-mediated selective cell death of OSCC was also observed in mice xenograft models using SCC25 cells. The mere treatment of p-FAK/GNP and NCP on the xenograft tumor slowly decreased the size of the tumor, and only about 50% of the tumor remained at the end of the experiment. On the other hand, 1 week of p-FAK/GNP+NCP treatment was enough to reduce half of the tumor size, and most of tumor tissue had vanished at the end. An analysis of isolated tissues showed that in the case of individual treatment with p-FAK/GNP or NCP, the cancer cell population was reduced due to apoptotic cell death. However, in the case of p-FAK/GNP+NCP, apoptotic cell death was unobserved, and most tissues were composed of collagen. Thus, this paper suggests the possibility of p-FAK/GNP+NCP as a new method for treating OSCC.

Background: Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE)., Objectives: We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE., Methods: CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment., Results: The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells., Conclusions: Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

Although specialized pharmacists have been suggested to be essential members of antimicrobial stewardship programs (ASPs), not all hospitals in Korea operate ASPs with pharmacists involved. We aimed to evaluate the association of involvement of clinical pharmacists as team members of multidisciplinary ASPs with the incidence of antimicrobial-related adverse drug events (ADEs). Five tertiary teaching hospitals participated in this retrospective cohort study. At each participating hospital, we randomly selected 1000 participants among patients who had received systemic antimicrobial agents for more than one day during the first quarter of 2017. We investigated five categories of antimicrobial-related ADEs: allergic reactions, hematologic toxicity, nephrotoxicity, hepatotoxicity, and antimicrobial-related diarrhea. Multivariate logistic regression analysis was used to evaluate the potential impact of pharmacist involvement in ASPs on the incidence of ADEs. A total of 1195 antimicrobial-related ADEs occurred in 618 (12.4%) of the 4995 patients included in the analysis. The overall rate of ADE occurrence was 17.4 per 1000 patient days. Hospitals operating ASPs with pharmacists showed significantly lower AE incidence proportions than other hospitals (8.9% vs. 14.7%; p < 0.001). Multidisciplinary ASPs that included clinical pharmacists reduced the risk of antimicrobial-related ADEs by 38% (adjusted odds ratio 0.62; 95% confidence interval 0.50-0.77). Our results suggest that the active involvement of clinical pharmacists in multidisciplinary ASPs may contribute to reduce the incidence of antimicrobial-related ADEs in hospitalized patients.

Bacillus subtilis subsp. subtilis G7 was isolated from a deep-sea hydrothermal vent and is pathogenic to pathogenic to fish (Japanese flounder) and mice. G7 is able to survive in host sera and phagocytes. In this study, we investigated the underlying mechanism of G7 serum resistance. We found that (i) the remaining complement activity was very low in G7-incubated flounder serum but high in G7-incubated mouse serum; (ii) cleaved C3 and C5 components were detected on flounder serum-incubated G7 but not on mouse serum-incubated G7; (iii) abundant uncleaved C5 was localized in G7-incubated mouse, but not flounder, serum; (iv) G7-incubated flounder, but not mouse, serum exhibited strong chemotactic activity; (v) pre-treatment with low-dose lysozyme abolished the serum resistance of G7. Hence, G7 activates flounder complement but is protected from complement-mediated destruction by its cell wall structure, while G7 prevents the activation of mouse complement. These results indicate that G7 employs different mechanisms to avoid the complement killing of different hosts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The potential roles of solar ultraviolet radiation (UVR) as an environmental risk factor in inducing atopic dermatitis (AD) have not been well quantified. To determine the short-term associations between UVR and AD outpatient visits, we obtained daily outpatient visits of AD in Shanghai Skin Disease Hospital from 2013 to 2018. Data of hourly ground UVR were collected. We applied overdispersed generalized additive model to explore its associations. We found that daily exposure to UVR-A rather than UVR-B was positively associated with AD outpatient visits. The visits increased on the present day (lag 0 days) and decreased appreciably with longer lags and became insignificant at lag 4 days. For 10 w/m 2 increase in daytime mean and noontime mean exposure to overall UVR and UVR-A from lag 0 to 6 days, the cumulative relative risk of AD was 1.12/1.13 and 1.08/1.08, respectively. Stronger effects of UVR exposure on AD occurred in patients aged 0-7 and > 45 years and in the cold seasons. This study contributed to the few epidemiological evidences that acute exposure to solar UVR may elevate the risks of AD.

Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cathepsin K belongs to the family of cysteine cathepsins. It is well known that the cysteine cathepsins participate in various physiological processes and host immune defense in mammals. However, in teleost fish, the function of cathepsin K is very limited. In the present study, a cathepsin K homologue (SsCTSK) from the teleost black rockfish (Sebastes schlegelii) was identified and examined at expression and functional levels. In silico analysis showed that three domains, including signal peptide, cathepsin propeptide inhibitor I29 domain, and functional domain Pept&#95;C1, are existed in SsCTSK. SsCTSK also possesses a peptidase domain with three catalytically essential residues (Cys25, His162 and Asn183). Phylogenetic profiling indicated that SsCTSK was evolutionally close to the cathepsin K of other teleost fish. Expression of SsCTSK occurred in multiple tissues and was induced by bacterial infection. Purified recombinant SsCTSK (rSsCTSK) exhibited apparent maximal peptidase activity at 45 °C, and its enzymatic activity was remarkably declined in the presence of the cathepsin inhibitor E-64. Moreover, rSsCTSK possesses the ability to bind with PAMPs and bacteria. Finally, knockdown of SsCTSK expression facilitated bacterial invasion in black rockfish. Collectively, these results indicated that SsCTSK functions as a cysteine protease and may serves as a target for pathogen manipulation of host defense system., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by β-adrenergic receptors (β-ARs). However, α 1 -adrenergic receptors (α 1 -ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α 1 -AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α 1 -AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 μM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3 -/- mice compared with wild-type mice. In conclusion, α 1 -AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

Objective: To evaluate the effect of open reduction assisted by wrist arthroscopy in the treatment of Diepunch fracture of the distal radius., Methods: The clinical data of 50 patients with die punch fracture of distal radius from December 2015 to May 2017 were analyzed retrospectively, including 31 males and 19 females, aged 20 to 45 (34.12±2.56) years. All patients were treated with open reduction and internal fixation of volar plate through volar approach under the assistance of wrist arthroscope. The range of wrist movement and Cooney wrist function score before and after treatment were compared., Results: All patients were followed up with an average of 18 months. DR scan showed that all fractures healed and no shortening of radial axis. Three cases of incision infection occurred and disappeared after treatment. At 18 months after operation, the range of wrist movement was significantly larger than that before operation ( P <0.05) . At 18 months after operation, Cooney wrist function score was higher than that before operation ( P <0.05) , excellent in 33 cases, good in 13 cases, fair in 3 cases and poor in 1 case., Conclusion: The treatment of die punch fracture of the distal radius with open reduction assisted by arthroscopy can restore the flatness of the joint surface, promote the recovery of the function of the wrist joint quickly, and has high safety, which is worth popularizing.

Histone proteins are not only structurally important for chromosomal DNA packaging but also involved in the regulation of gene expression and the immune response of host against pathogens. Japanese flounder (Paralichthys olivaceus) as one of the most important marine flatfish, suffered from widespread outbreaks of diseases, and its immunological functioning remained to be elucidated. In the present study, we reported the expression patterns of four histones (H1, H2A, H3, and H3.3) and functional characterization of the histone H3.3 from flounder. Quantitative real time RT-PCR (RT-qPCR) analysis showed that expression of the four histones occurred in multiple tissues, but their levels of expression were relatively high in immune organs, and inducible in response to pathogens infection. Infection with extracellular and intracellular bacterial pathogens and viral pathogen regulated the expression of histones in a manner that depended on tissue type, pathogen, and infection stage. Specifically, H1 expression was highly induced by intracellular viral pathogens; H2AX and H3 expressions were highly induced by intracellular bacterial pathogen; dissimilarly, H3.3 expression was slightly induced by extracellular bacterial pathogen, but was inhibited by intracellular bacterial and viral pathogens. To further investigate H3.3 function, recombinant H3.3 (rH3.3) was obtained, and in vitro experiments showed rH3.3 possessed the capability of binding to both Gram-negative and Gram-positive bacteria and inhibiting the growth of some target bacteria. Consistently, In vivo results showed that overexpression of H3.3 promoted the host defense against invading pathogenic microorganism and regulated the expressions of several cytokines. These results suggested that flounder histones exhibit different expression patterns in response to the infection of different microbial pathogens, and H3.3 serves as an immune-related protein and plays an important role in antimicrobial immunity of Japanese flounder. Taken together, this study is the first report about the expression profile of different histones upon different kind of pathogens and anti-infectious immunity of H3.3 in teleost, which offered new insights into the immunological function of histones in teleost., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations. In rachidial ridges, epidermal progenitors generate cortex and medullary keratinocytes, guided by Bmp and transforming growth factor β (TGF-β) signaling that convert rachides into adaptable bilayer composite beams. In barb ridges, epidermal progenitors generate cylindrical, plate-, or hooklet-shaped barbule cells that form fluffy branches or pennaceous vanes, mediated by asymmetric cell junction and keratin expression. Transcriptome analyses and functional studies show anterior-posterior Wnt2b signaling within the dermal papilla controls barbule cell fates with spatiotemporal collinearity. Quantitative bio-physical analyses of feathers from birds with different flight characteristics and feathers in Burmese amber reveal how multi-dimensional functionality can be achieved and may inspire future composite material designs. VIDEO ABSTRACT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The Bacillus cereus group is frequently isolated from soil, plants, food, and other environments. In this study, we report the first isolation and characterization of a B. cereus group member, Bacillus wiedmannii SR52, from the hydrothermal field in the Iheya Ridge of Okinawa Trough. SR52 was isolated from the gills of shrimp Alvinocaris longirostris , an invertebrate species found abundantly in the ecosystems of the hydrothermal vents, and is most closely related to B. wiedmannii FSL W8-0169. SR52 is aerobic, motile, and able to form endospores. SR52 can grow in NaCl concentrations up to 9%. SR52 has a circular chromosome of 5,448,361 bp and a plasmid of 137,592 bp, encoding 5,709 and 189 genes, respectively. The chromosome contains 297 putative virulence genes, including those encoding enterotoxins and hemolysins. Fourteen rRNA operons, 107 tRNAs, and 5 sRNAs are present in the chromosome, and 7 tRNAs are present in the plasmid. SR52 possesses 13 genomic islands (GIs), all on the chromosome. Comparing to FSL W8-0169, SR52 exhibits several streaking features in its genome, notably an exceedingly large number of non-coding RNAs and GIs. In vivo studies showed that following intramuscular injection into fish, SR52 was able to disseminate in tissues and cause mortality; when inoculated into mice, SR52 induced acute mortality and disseminated transiently in tissues. In vitro studies showed that SR52 possessed hemolytic activity, and the extracellular product of SR52 exhibited a strong cytotoxic effect. These results provided the first insight into the cytotoxicity and genomic feature of B. wiedmannii from the deep-sea hydrothermal environment., (Copyright © 2019 Zhao, Chen, Gu, Zhang and Sun.)

Objective: Hepatopulmonary syndrome (HPS) is a kind of pulmonary microvascular disease and occurs in 15%-30% cirrhosis. This study aimed to investigate the effects of pulmonary CX3CR1 on angiogenesis and associated mechanisms in HPS animal models., Materials and Methods: CX3CR1GFP/GFP mice were constructed by replacing CX3CR1 with GFP. Common bile duct ligation (CBDL) mouse model was established with surgery. Release of nitric oxide (NO) was evaluated. Hematoxylin-eosin (HE) staining was employed to examine the inflammation of lung tissues. CD31 expression was detected with immunohistochemistry assay. Western blotting was used to evaluate the expression of CX3CL1, CX3CR1, phosphorylated-AKT (p-AKT), phosphorylated-ERK (p-ERK). Quantitative Real Time-PCR (qRT-PCR) assay was used to examine VEGF, PDGF, iNOS, eNOS, and HO-1 expression., Results: CX3CR1-deficiency (CX3CR1GFP/GFP-sham or CX3CR1GFP/GFP-CBDL mice) significantly reduced NO release compared to wide type (WT)-mice or WT-CBDL mice (p<0.05). CX3CR1-deficiency significantly alleviated inflammation compared to wide type (WT)-mice or WT-CBDL mice (p<0.05). CX3CR1-deficiency significantly reduced CD31 expression compared to WT-sham and WT-CBDL mice, respectively (p<0.05). CX3CR1 also participated in anti-angiogenesis efficacy of Bevacizumab. CX3CR1-deficiency significantly down-regulated the ratio of p-AKT/AKT and p-ERK/ERK and inhibited the secretion of VEGF and PDGF compared to WT-mice (p<0.05). CX3CR1-deficiency significantly reduced iNOS, eNOS, and HO-1 expression compared to WT-mice (p<0.05)., Conclusions: CX3CR1 deficiency reduced VEGF and PDGF production, inhibited p-AKT, and p-ERK activation and down-regulated iNOS, eNOS, and HO-1 expression. Therefore, CX3CR1 participates in pulmonary angiogenesis in the experimental HPS mice via inhibiting AKT/ERK signaling pathway and regulating NO/NOS release. These findings would provide a potential insight for clarifying the pathological mechanisms of HPS.

Bacillus subtilis is the best studied Gram-positive bacterium, primarily as a model of cell differentiation and industrial exploitation. To date, little is known about the virulence of B. subtilis . In this study, we examined the virulence potential of a B. subtilis strain (G7) isolated from the Iheya North hydrothermal field of Okinawa Trough. G7 is aerobic, motile, endospore-forming, and requires NaCl for growth. The genome of G7 is composed of one circular chromosome of 4,216,133 base pairs with an average GC content of 43.72%. G7 contains 4,416 coding genes, 27.5% of which could not be annotated, and the remaining 72.5% were annotated with known or predicted functions in 25 different COG categories. Ten sets of 23S, 5S, and 16S ribosomal RNA operons, 86 tRNA and 14 sRNA genes, 50 tandem repeats, 41 mini-satellites, one microsatellite, and 42 transposons were identified in G7. Comparing to the genome of the B. subtilis wild type strain NCIB 3610 T , G7 genome contains many genomic translocations, inversions, and insertions, and twice the amount of genomic Islands (GIs), with 42.5% of GI genes encoding hypothetical proteins. G7 possesses abundant putative virulence genes associated with adhesion, invasion, dissemination, anti-phagocytosis, and intracellular survival. Experimental studies showed that G7 was able to cause mortality in fish and mice following intramuscular/intraperitoneal injection, resist the killing effect of serum complement, and replicate in mouse macrophages and fish peripheral blood leukocytes. Taken together, our study indicates that G7 is a B. subtilis isolate with unique genetic features and can be lethal to vertebrate animals once being introduced into the animals by artificial means. These results provide the first insight into the potential harmfulness of deep-sea B. subtilis .

Accumulating data have indicated a fundamental role of eosinophils in regulating adipose tissue homeostasis. Here, we performed whole-genome RNA sequencing of the small intestinal tract, which suggested the presence of impaired lipid metabolism in eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice fed a high-fat diet (HFD) showed reduced body fat mass, impaired enlargement of adipocytes, decreased expression of adipogenic genes, and developed glucose intolerance. HFD induced accumulation of eosinophils in the perigonadal white adipose tissue. Concordantly, adipocyte-differentiated 3T3-L1 cells promoted the migration of eosinophils through the expression of CCL11 (eotaxin-1) and likely promoted their survival through the expression of interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor. HFD-fed ΔdblGATA mice showed increased infiltration of macrophages, CD4 + T-cells, and B-cells, increased expression of interferon-γ, and decreased expression of IL-4 and IL-13 in white adipose tissue. Interferon-γ treatment significantly decreased lipid deposition in adipocyte-differentiated 3T3-L1 cells, while IL-4 treatment promoted lipid accumulation. Notably, HFD-fed ΔdblGATA mice showed increased lipid storage in the liver as compared with wild-type mice. We propose that obesity promotes the infiltration of eosinophils into adipose tissue that subsequently contribute to the metabolic homeostasis by promoting adipocyte maturation.

Anti-lipopolysaccharide factor (ALF) is a type of antimicrobial peptides (AMPs) with a vital role in antimicrobial defense. Although a large amount of ALFs have been identified from neritic and fresh water crustacean species, no functional investigation of ALFs from deep-sea animals have been documented. In the present study, we characterized the immune function of an ALF molecule (named RspALF1) from the shrimp Rimicaris sp. residing in the deep-sea hydrothermal vent in Desmos, Manus Basin. RspALF1 shares 51.5%-62.4% overall sequence identities with known shrimp ALFs and contains the conserved LPS binding domain (LBD). Both recombinant RspALF1 (rRspALF1) and the LBD-derived peptide (ALF1P1) bound to the cell wall components of Gram-negative and Gram-positive bacteria and killed a wide range of bacteria, especially those from deep-sea hydrothermal field, by damaging bacterial cellular structures. The bactericidal activities of rRspALF1 and ALF1P1 were optimal and stably maintained from 4 °C to 37 °C, which is comparable to the ambient temperature range of the habitat of Rimicaris sp. In addition to bacteria, rRspALF1 and ALF1P1 also exhibited anti-fungal activity. rRspALF1 and ALF1P1 exhibited high killing efficiencies, which, in terms of MIC values, were ranged between 0.25 μM and 4 μM for bacteria and 4 μM-8 μM for fungi. When introduced in vivo, both rRspALF1 and ALF1P1 effectively inhibited bacterial infection in shrimp and reduced the dissemination of bacterial and viral pathogens in fish. Together, these results provide the first insight into the biological property of deep-sea ALF and indicate that RspALF1 very likely plays a significant role in immune defense by functioning as a highly effective antimicrobial with a broad target range., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Osteosarcoma (OS) is a fatal form of musculoskeletal tumor that commonly leads to pulmonary metastatic disease. Traditional therapies such as surgery and chemotherapy are not effective treatment modalities in certain patients with OS; therefore, identifying the molecular mechanism of OS is imperative for the development of novel therapeutics. Previous studies have reported that focal adhesion kinase (FAK) is associated with numerous types of human malignancies. Therefore, in order to investigate the biological function of FAK in OS, the present study examined the expression levels of FAK in OS cell lines, OS tissues and paired normal tissue specimens by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). FAK expression in vitro was blocked using small interfering RNA (siRNA) to observe the invasion, proliferation and apoptosis trends of OS cells. Phosphoinositide-dependent kinase-1 (PDK1), AKT and BRAF protein levels were also evaluated by western blotting to analyze the effects of FAK depletion on the AKT and mitogen-activated protein kinase (MAPK) signaling pathways. A significantly reduced level of FAK mRNA was identified in paired normal tissues compared with OS tissues and cell lines. The invasive capability and proliferative potential of OS cells were suppressed due to the transient in vitro transfection of FAK siRNA. It was also demonstrated that decreased FAK expression facilitated the apoptosis of OS cells, as demonstrated by flow cytometric and western blotting analyses. Decreased FAK expression resulted in the downregulation of phosphorylated (p)-AKT, p-PDK1 and p-BRAF protein levels. Higher FAK expression levels are positively associated with clinicopathological characteristics of advanced Enneking stages (P<0.001) and recurrence (P=0.041) in patients with OS. Collectively, these data demonstrated that FAK is an important diagnostic biomarker for OS, and FAK siRNA therapy may be a potentially promising approach for the treatment of OS.

Avian influenza A(H7N9) virus has caused 5 epidemic waves in China since its emergence in 2013. We investigated the dynamic changes of antibody response to this virus over 1 year postinfection in 25 patients in Suzhou City, Jiangsu Province, China, who had laboratory-confirmed infections during the fifth epidemic wave, October 1, 2016-February 14, 2017. Most survivors had relatively robust antibody responses that decreased but remained detectable at 1 year. Antibody response was variable; several survivors had low or undetectable antibody titers. Hemagglutination inhibition titer was >1:40 for <40% of the survivors. Measured in vitro in infected mice, hemagglutination inhibition titer predicted serum protective ability. Our findings provide a helpful serologic guideline for identifying subclinical infections and for developing effective vaccines and therapeutics to counter H7N9 virus infections.

Objective: To compare the clinical effects of arthroscopic debridement versus open debridement on controlling and treatment of infection after total knee replacement., Methods: From October 2009 to September 2016 in three hospitals, 11 patients with 11 joints which were infected after total knee replacement were randomly divided into two groups:5 cases in arthroscopy group and 6 cases in routine group. Patients in arthroscopy group were treated with arthroscopic debridement to remove the necrotic tissues, then closed-type irrigation with sensitive antibiotics by using two sebific ducts were performed continuously for 2 or 3 weeks until the flushing fluid became clear for 3 or 5 days;other 6 patients in routine group were treated with open surgical debridement and the following procedures in keeping with those in the arthroscopy group. Operation time, blood loss and incision length were recorded during the operation, and pain scores were recorded on the 1st, 3rd and 7th day after the operation. The curative effects were evaluated according to the Hospital for Special Surgery score system., Results: The local and general symptoms of the 11 patients disappeared, and the test outcomes of biochemistry, blood and synovial fluid were normal. All patients were followed up, and the duration ranged from 6 to 18 months. Infection recurrences were observed in 1 case of arthroscopy group and 2 cases of routine group 3 months later after operation, and all these patients who underwent the second time operation with arthroscopic debridement were cured. According to the Hospital for Special Surgery score system, 3 cases obtained excellent result, 2 good, no poor and bad cases in arthroscopy group;3 cases obtained excellent result, 1 good, 1 poor and 1 bad in routine group., Conclusions: If the sensitive antibiotics can be found for the infected joints without obvious destruction of bone and no prosthesis loosening, it has a better therapeutic effect by using arthroscopic debridement combined with continuous drainage and irrigation. The method has a better curative effect with smaller trauma., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

A 25-year-old tea plantation in a typical red soil region was selected for an in situ simulated acid rain experiment treated by pH 4.5, 3.5, 2.5 and water (control, CK). Roots with different functions, leaves and twigs with different ages were collected to measure nitrogen (N) and phosphorus (P) contents in the third year after simulated acid rain treatment. The N/P and acid rain sensitivity coefficient of tea plant organs were also calculated. The results indicated that with the increase of acid rain intensity, the soil pH, NO 3 - -N and available P decreased, while the absorption root N content increased. Compared with the control, the N content in absorption root was increased by 32.9% under the treatment of pH 2.5. The P content in storage root significantly decreased with enhanced acid rain intensity, and the acid rain treatment significantly enhanced N/P of absorption root. Young and mature leaf N, P contents were not sensitive to different intensities of acid rain, but the mature leaf N/P was significantly increased under pH 3.5 treatment compared with the control. The effects of acid rain treatments differed with tea twig ages. Compared with the control, low intensity acid treatment (pH 4.5) significantly increased young twig N content and N/P, while no signi-ficant differences in old twig N content and N/P were observed among four acid rain treatments. Acid rain sensitivity coefficients of absorption root, young leaf and twig N contents were higher than that of storage root, old leaf and twig, respectively. And the storage root and leaf P had higher acid rain sensitivity coefficient than other tea organs. In sum, tea organs N content was sensitive to acid rain treatment, and moderate acid rain could increase young organ N content and N/P, and change the cycle and balance of N and P in tea plantation.

Objective: To compare the ability of leak compensation in 6 medical ventilators during non-invasive ventilation. Methods: Six medical ventilators were selected, including 3 non-invasive ventilators (V60, Flexo and Stellar150), and 3 invasive ventilators(Avea, Servo I and BellaVist). Using a lung simulator, the ability of leak compensation was evaluated during triggering and cycling in 2 respiratory mechanics conditions (high airway resistance condition and high elastance resistance condition), and each condition was performed under 2 PEEP levels (4, and 8 cmH(2)O, 1 mmHg=0.098 kPa) at 4 air leak level conditions (L0: 2-3 L/min, L1: 8-10 L/min, L2: 22-27 L/min, L3: 35-40 L/min). Results: In the high elastance resistance condition (L2, L3)with different leak levels, the number of auto-triggering and miss-triggering of the non-invasive ventilator Flexo was significantly less than those of the others (L2: 1, 1; L3: 1.67, 1.33, P <0.01), and had better synchronization (L2: 2.33, 2.33; L3: 3.33, 3.33, P <0.01). In the high airway resistance condition with PEEP 4 cmH(2)O, V60 had less number of auto-triggering than other ventilators ( P <0.01), while in the high airway resistance condition with PEEP 8 cmH(2)O, Stellar150 had less number of miss-triggering than other ventilators (1, 0.67, 0, P <0.01). Flexo had a shorter trigger delay time than other ventilators in both high airway resistance and high elastance resistance conditions with L0 and L1 leak levels and PEEP levels [ARDS, PEEP=4: (109.8±1.8) ms, (112.0±0.6) ms; ARDS, PEEP=8: (103.1±0.7) ms, (109.7±0.7) ms; COPD, PEEP=4: (207.3±1.1) ms, (220.8±1.1) ms; COPD, PEEP=8: (195.6±6.7) ms, (200.0±1.2) ms , P <0.01]. Stellar150 had the shortest trigger delay time in high airway resistance condition with PEEP 4 cmH(2)O and high leak level L3[(262.8±0.8) ms , P <0.01]. V60 had a good performance on trigger delay time in high elastance resistance condition with PEEP 4 and 8 cmH(2)O, and also was most stable in increasing leak levels. Conclusion: In high airway resistance and high elastance resistance conditions with different PEEP levels and leak levels, V60, Stellar150, Flexo and BellaVista ventilators could be synchronized, among which V60, Stellar150 and Flexo presented a good performance features in specific conditions.

The highly pathogenic avian influenza (HPAI) H5N1 virus has caused several outbreaks in domestic poultry. Despite great efforts to control the spread of this virus, it continues to evolve and poses a substantial threat to public health because of a high mortality rate. In this study, we sequenced whole genomes of eight H5N1 avian influenza viruses isolated from domestic poultry in eastern China and compared them with those of typical influenza virus strains. Phylogenetic analyses showed that all eight genomes belonged to clade 2.3.2.1 and clade 7.2, the two main circulating clades in China. Viruses that clustered in clade 2.3.2.1 shared a high degree of homology with H5N1 isolates located in eastern Asian. Isolates that clustered in clade 7.2 were found to circulate throughout China, with an east-to-west density gradient. Pathogenicity studies in mice showed that these isolates replicate in the lungs, and clade 2.3.2.1 viruses exhibit a notably higher degree of virulence compared to clade 7.2 viruses. Our results contribute to the elucidation of the biological characterization and pathogenicity of HPAI H5N1 viruses., (Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Human Lasiodiplodia theobromae infection has not been reported frequently. We report the first case of invasive L. theobromae nasal and neck infection. A 66-year-old male visited our hospital with anemia and general weakness. He showed pancytopenia, and his bone marrow examination revealed markedly decreased hematopoietic cells. The patient was presumed to have iatrogenic aplastic anemia due to mushroom toxicity. He began treatment for multiple organ infections with broad-spectrum antibiotics and antifungal agents. During hospitalization, he complained of nasal obstruction and left neck lymph node enlargement. A mass-like lesion was observed, and a nasal mass biopsy was performed. The mass was identified as a fungal ball. He underwent surgical excision for the nasal mass and the neck lymph node. The pathologic examination indicated an invasive fungal infection, and the lymph node revealed chronic granulomatous inflammation with fungal infection. 18s rRNA sequencing revealed that the sequence shared 99 % identity with L. theobromae. The nasal mass fungus was identified by internal transcribed spacer region sequencing from pathologic paraffin sections. The obtained sequence corresponded to Lasiodiplodia or Macrophoma. The sequence corresponded to the neck discharge sequence results. Hence, the patient was diagnosed with invasive fungal sinusitis with neck lymph node involvement caused by L. theobromae. To our knowledge, this is the first report of L. theobromae infection in Korea and the first report of invasive L. theobromae fungal sinusitis in the literature. We should include more precise evaluations of additional novel fungal species as possible candidates.

Dialister pneumosintes and Slackia exigua are both obligatory anaerobe and known to be associated with periodontal diseases and other oral infection. We report a case of blood stream infection caused by D. pneumosintes and S. exigua. This occurred in a 78-year-old female patient that presented with general weakness and fever. We revealed that she had a periapical abscess. The blood culture was positive for D. pneumosintes and S. exigua; however, identifying them was challenging. Ultimately, 16S rRNA sequencing was used to identify the organisms. The patient recovered after being treated with ceftriaxone and clindamycin. To the best of our knowledge, this is the first report of bacteremia caused by mixed infection of D. pneumosintes and S. exigua., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has been reported to be able to reduce body fat. In this study, we investigated the antidiabetic effect of fermented milk (FM) containing CLA on type II diabetes db/db mice. Mice were treated with 0.2% low FM, 0.6% high FM, or Glimepiride (GLM) for 6 wk. Our results revealed that the body weight and the levels of fasting blood glucose, serum insulin, and leptin were significantly decreased in FM fed mice compared to db/db mice. Oral glucose tolerance and insulin tolerance were significantly ameliorated in FM fed mice compared to db/db mice. Consistent with these results, the concentrations of serum total cholesterol, triglycerides, and LDL cholesterol were also significantly decreased in FM fed mice compared to db/db mice. However, the concentration of HDL cholesterol was significantly higher in FM fed mice compared to db/db mice. These results were similar to those of GLM, a commercial anti-diabetic drug. Therefore, our results suggest that FM has anti-diabetic effect as a functional food to treat type II diabetes mellitus.

Objective: To investigate clinical effects of minimally invasive fixation and bone grafting througn medial side for the treatment of Schatzker III tibial plateau fracture., Methods: From April 2009 to August 2011, 18 patients with Schatzker III tibial plateau fracture were treated with minimally invasive fixation and bone grafting through medial side. There were 15 males and 3 females ranging in age from 64 to 73 years, with an average of (69.75 ± 1.22) years. Sixteen patients were caused by falling down, 2 cases were caused by traffic accident. Operative time and length of incision were be recorded. Clinical and radiological follow-up was performed after operation. Hospital for Special Surgery (HSS) score and Kellgren-Lawrence score were used to evaluate clinical effects., Results: The mean operative time was (45.32 ± 1.58) min, and the mean length of incision was (5.21 ± 0.65) cm. Postoperative X-ray showed excellent reduction. Eighteen patients were followed up for 10 to 13 months with an average of (11.5 ± 1.35) months. The mean HSS score was 86.51 ± 2.71, 12 cases got excellent results,4 good and 2 fair. Three patients were developed mild osteoarthritis according to the Kellgren-Lawrence system., Conclusion: Minimally invasive fixation and bone grafting through medial side, not only could reduce surgical invasive, but also guarantee early function activities. It has advantages of keeping well after reduction. So it has the favorable future in clinic.

Zn(2+) is an essential component of metalloproteinases, and is required for their activity in cartilage; however, the effect of Zn(2+) on nucleus pulposus (NP) cells has not been widely investigated. The aim of this paper was to investigate the effect of intracellular Zn(2+) concentration ([Zn(2+)]i) in hypoxia-induced regulation of metalloproteinases (MMPs) and extracellular matrix (ECM) production in NP cells. NP cells from Sprague-Dawley (SD) rats were cultured as monolayers or in alginate beads. [Zn(2+)]i was assayed by FluoZin-3 AM staining. Alcian Blue staining, immunochemistry, 1,9-dimethylmethylene blue (DMMB) assay, and real-time PCR were used to assay collagen II, proteoglycan, and COL2A1, MMP-13, and ADAMTS-5 mRNA expression. ZIP8, a main Zn(2+) transporter in chondrocytes, was assayed by immunochemistry and in Western blotting. Interleukin (IL)-1β- and ZnCl2-induced increases of [Zn(2+)]i were significantly inhibited by hypoxia. Hypoxia did not reverse a decline of ECM expression caused by IL-1β and ZnCl2 in monolayer cultures, but did significantly attenuate the decreases of proteoglycan, glycosaminoglycan (GAG), and COL2A1 mRNA expression following IL-1β and ZnCl2 treatment in alginate bead cultures. However, ZnCl2 inhibited the protective effect of hypoxia. Both an intracellular Zn(2+) chelator and hypoxia prevented the increase in MMP-13 mRNA expression. IL-1β and ZnCl2 treatment increased ZIP8 expression in NP cells, and hypoxia inhibited ZIP8 expression. In conclusion, decrease of Zn(2+) influx mediates the protective role of hypoxia on ECM and MMP-13 expression. Consequently, changes in intracellular Zn(2+) concentration maybe involved in intervertebral disc degeneration.

Objectives: The objective of this study was to evaluate bone formation/osseointegration following surgical treatment of experimental peri-implantitis at dental implants with different surface characteristics exposed to ligature-induced breakdown conditions., Methods: Ten turned (control), 10 sandblasted/acid-etched (SA), and 10 SA/hydroxyapatite nanocoated (HA) implants were installed into the edentulated posterior mandible in five Beagle dogs and allowed to osseointegrate for 12 weeks. Ligature-induced breakdown defects were then induced over 23 weeks using stainless steel wire ligatures. The ligatures were removed and soft tissues were allowed to heal for 3 weeks. Next, exposed implant surfaces were decontaminated followed by guided bone regeneration using a collagen membrane and submerged wound healing. The animals were euthanized for histometric analysis at 12 weeks post-surgery., Results: The radiographic analysis showed vertical bone loss following ligature-induced breakdown without statistically significant differences among implant technologies. The histometric analysis showed significantly enhanced bone formation (height) at SA and SA/HA compared with turned implants (p = 0.028) following reconstructive surgery. Bone formation area was greater at SA/HA compared with turned implants, however the difference did not reach statistical significance., Conclusions: While ligature-induced defect progression does not appear implant surface dependent in this animal model, bone formation at the decontaminated implant surfaces appears more favourable at SA and SA/HA over turned implants following reconstructive surgery., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The surface structures, CO adsorption, and oxidation-reaction properties of CuO1-x(111) with different reduction degree have been investigated by using density functional theory including on-site Coulomb corrections (DFT + U). Results indicate that the reduction of Cu has a great influence on the adsorption of CO. Electron localization caused by the reduction turns Cu(2+) to Cu(+), which interacts much stronger with CO, and the adsorption strength of CO is related to the electronic interaction with the substrate as well as the structural relaxation. In particular, the electronic interaction is proved to be the decisive factor. The surfaces of CuO1-x(111) with different reduction degree all have good adsorption to CO. With the expansion of the surface reduction degree, the amount of CO that is stably adsorbed on the surface increases, while the number of surface active lattice O decreases. In general, the activity of CO oxidation first rises and then declines.

Objective: To compare clinical efficacy for the treatment of proximal humeurs fractures in elderly patients between the minimally invasive plate osteosynthesis (MIPO) with less invasive stabilization system (LISS) and the open reduction and internal fixation (ORIF) with locking compression plate (LCP)., Methods: From June 2008 to June 2011, 40 elderly patients suffering from proximal humeurs fractures were divided into two groups: 20 cases in minimally invasive group and 20 cases in routine group. Mini-incision approach from the lateral shoulder (minimally invasive group) and LISS can be chosen. It was short for MIPO. The antero-medial incision was used in routine group, LCP can be chosen in the method of ORIF. The operation time, the blood loss, the incision length, soreness at 1st, 3rd and 7th days after operation were recorded. The postoperative Neer score, the healing time of bone were recorded. The curative effects were compared according to Neer score system., Results: The mean operation times were (133.60 +/- 8.90) min and (132.70 +/- 8.41) min in minimally invasive group and routine group (P > 0.05). The blood losses were (155.20 +/- 19.07) ml and (324.05 +/- 48.32) ml (P < 0.05). The incision lengths were (8.15 +/- 1.89) cm and (13.05 +/- 1.95) cm (P < 0.05). The pain scores on the 1st,3rd and 7th days after operation were (6.20 +/- 2.39) and (8.33 +/- 3.01) (P < 0.05), (3.83 +/- 2.09) and (5.31 +/- 2.22) (P < 0.05), (1.22 +/- 0.89) and (3.13 +/- 1.75) (P < 0.05). The postoperative Neer scores were 93.16 +/- 2.55 and 80.31+/- 2.22 (P < 0.05) and the healing times of bone were (6.60 +/- 2.33) months and (8.93 +/- 3.41) months (P < 0.05). There were statistially differences in the blood losses, incision lengths, postoperative pain scores, postoperative Neer scores and the healing times of bone between two groups (P < 0.05). The operation time between the two groups had no statistically different (P > 0.05). According to Neer score system, 13 patients obtained an excellent results, 2 good, 5 fair in minimally invasive group; 6 patients obtained an excellent results, 5 good, 9 fair in routine group., Conclusion: To compare with the routine group of ORIF, MIPO with LISS has the advantages of small incision, easier operation, less blood loss and improved postoperative shoulder joint function recovery for treatment of proximal humeurs fracture in elderly patients. It is another better method of internal fixation.

Experimental gene engineering is a laboratory course focusing on the molecular structure, expression pattern and biological function of genes. Providing our students with a solid knowledge base and correct ways to conduct research is very important for high-quality education of genetic engineering. Inspired by recent progresses in this field, we improved the experimental gene engineering course by adding more updated knowledge and technologies and emphasizing on the combination of teaching and research, with the aim of offering our students a good start in their scientific careers.

Objective: Left ventricular remodeling (LVR) following myocardial infarction (MI) is a key pathophysiological process in which MI develops into heart failure. The exact mechanism of LVR remains unclear. We performed differential proteomic analysis on the myocardia of rats with LVR after MI, to explore the mechanism of ventricular remodeling after MI., Methods: In the LVR group (n = 12), after the anterior descending coronary artery was ligated, the rats were fed for four weeks before the LVR models were established. Rats in the sham-operated group (n = 11) underwent thread-drawing without ligation. The hemodynamic parameters, pathological findings, and proteomics were compared between the two groups., Results: In the LVR group, the left ventricular end-diastolic pressure increased, the maximal left ventricular pressure increase/decrease ratio decreased significantly, and the left ventricular systolic pressure decreased. H-E staining and Masson staining of cardiac muscle tissues of the LVR group showed myocytolysis, disarray, and collagen proliferation. Twenty-one differentially expressed proteins were detected by proteomic analysis. We validated two proteins using western blot analysis. The differentially expressed proteins could be divided into six categories: energy metabolism-related proteins, cytoskeletal proteins, protein synthesis-related proteins, channel proteins, anti-oxidation- related proteins, and immune-related proteins., Conclusion: These differentially expressed proteins might play key roles in LVR following MI., (Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.)

Purpose: This study was done to identify effects of fatigue and postpartum depression on quality of life in early postpartum mothers., Methods: The data were collected from 130 mothers at four general hospitals in J and M metropolitan cities. Instruments used to collect the data for the study were the Fatigue Scale developed by Pugh (1993); Postpartum Depression Scale developed by Cox, Holden & Sagovsky (1987), and the Quality of Life Scale developed by Hill, Aldag, Hekel, Riner, G., & Bloomfield (2006)., Results: Results showed that the mean for fatigue was 56.74, the mean for postpartum depression was 8.00+/-4.37 and mean for quality of life was 19.78. The quality of life variable showed statistically significant differences for the variable: age (F=3.20, p=.026). The relationship between fatigue and quality of life showed a significant negative correlation (r=-.44, p<.001). The relationship between postpartum depression and quality of life also showed a negative correlation (r=-.42, p<.001). The relationship between postpartum depression and fatigue showed a positive correlation (r=.59, p<.001). These factors explained 23% of the variance in quality of life., Conclusion: The results indicate that it is necessary to develop nursing intervention programs to improve quality of life in for early postpartum mothers.