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Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus, and there are currently no drugs to alleviate disease symptoms. LL-37 is a potent antimicrobial peptide with a wide range of immunoregulatory properties. In this study, we assessed the effect of LL-37 on DENV-2-induced responses in human monocyte-derived macrophages (MDMs). We show that simultaneous exposure of exogenous LL-37 and DENV-2 resulted in reduced replication of the virus in MDMs, while the addition of LL-37 postexposure to DENV-2 did not. Interestingly, the latter condition reduced the production of IL-6 and increased the expression of genes involved in virus sensing and antiviral response. Finally, we demonstrate that low endogenous levels and limited production of LL-37 in MDMs in response to DENV-2 infection can be increased by differentiating MDMs in the presence of Vitamin D (VitD3). Taken together, this study demonstrates that in addition to its antimicrobial properties, LL-37 has immunomodulatory properties in the curse of DENV infection and its production can be increased by VitD3.Acinic cell carcinoma (AcCC) of breast is a rare subtype of triple-negative breast carcinoma demonstrating a wide morphologic spectrum. In this study, we perform a detailed morphologic and immunohistochemical description of two cases of the rare entity and review the published relative literature. Histologically, the two cases both showed predominantly microglandular and solid structures overlapping with the histological features of microglandular adenosis (MGA), and one case presented spindle cell metaplastic carcinoma with chondromyxoid matrix as a minor morphologic pattern. In two cases, most of the cancer cells were positive for lysozyme and antitrypsin strongly and extensively, but negative for estrogen receptor (ER), progesterone receptor (PR), androgen receptors (AR) and human epidermal growth factor receptor 2 (HER2). The true relationship between breast AcCC and MGA or carcinoma arising in MGA(CAMGA) may remain unclear; re-excision is advised when the MGA-like content extends to the surgical margins in the setting of breast AcCC. More cases and further molecular investigations are required to elucidate the true histogenesis and give the patients appropriate treatment.We have recently described a novel family of compounds of reduced size and dual anti-HIV and anti-EV71 activity that encompasses tripodal and tetrapodal derivatives. The tripodal prototype, AL-470, has a nitro group at the focal point of the central scaffold and three attached tryptophan residues, each of which bearing an isophthaloyl moiety at the C2 position of the indole ring. A nitro to amino substitution has allowed us now to introduce a chemically addressable functionality to perform further structural modifications consisting of both direct and linker-mediated attachment of several aromatic groups, including the fluorescent dye Alexa Fluor 647 and the antibody-recruiting 2,4-dinitrophenyl motif. Some of the derivatives turned out to be more potent and selective than AL-470 against HIV-1, HIV-2 and EV-A71. The fluorescent probe demonstrated a specific tropism for intestines and lungs, two important niches for the human microbiome in health and disease.Current pain management is largely limited to opioids and non-steroidal anti-inflammatory drugs. Developing new analgesic drugs remains important to address the unmet medical needs of chronic pain patients. Calcium-activated chloride channel anoctamin-1 (ANO1) is a potential analgesic target. ANO1 is activated by noxious stimuli in peripheral sensory neurons and further induced neural depolarization. Downregulation of ANO1 reduced hyperalgesia and allodynia caused by inflammation and nerve injury. Here we developed a series of 4-arylthiophene-3-carboxylic acid derivatives for proof-of-concept studies of ANO1-targeted analgesia. These efforts led to the identification of the compound DFBTA, 4-(4-chlorophenyl)-2-(2,5-difluorobenzamido)thiophene-3-carboxylic acid, which displays dramatic ANO1 inhibition with IC50 of 24 nM. DFBTA displays very weak cytotoxicity, cardiotoxicity, and acute toxicity (HEK293 proliferation IC50 > 30 μM, hERG IC50 > 30 μM, mouse minimum lethal dosage, MLD>1000 mg/kg), as well as excellent pharmacokinetics properties with oral bioavailability >75% and little brain penetration ( less then 1.5% brain/plasma). Finally, the analgesic efficacy of ANO1 inhibitor was evaluated in animal models. DFBTA shown comparable efficacy to clinical drugs in all inflammatory pain models induced by complete Freund’s adjuvant, formalin, and capsaicin. These works provide a useful tool compound and promising results for ANO1-targenting analgesic development.Acetylation of histone lysine residues by histone acetyltransferase (HAT) p300 and its paralog CBP play important roles in gene regulation in health and diseases. The HAT domain of p300/CBP has been found to be a potential drug target for cancer. Compound screening followed by structure-activity relationship studies yielded a novel series of 1,4-pyrazine-containing inhibitors of p300/CBP HAT with their IC50s as low as 1.4 μM. Enzyme kinetics and other studies support the most potent compound 29 is a competitive inhibitor of p300 HAT against the substrate histone. It exhibited a high selectivity for p300 and CBP, with negligible activity on other classes of HATs in human. Compound 29 inhibited cellular acetylation of several histone lysine residues and showed strong activity against proliferation of a panel of solid and blood cancer cells. These results indicate it is a novel pharmacological lead for drug development targeting these cancers as well as a useful chemical probe for biological studies of p300/CBP.

This study aimed to develop and examine the psychometric properties of validity and reliability of the Core Competence in Fundamental Nursing Practicum Scale.

Fundamental nursing practicum is an initial practicum required for nursing students; however, no measurement tool is available to assess students’ core competence during their first practicum.

Cross-sectional design.

Nursing students from six nursing colleges in Southern Taiwan who completed their fundamental nursing practicum within 1 month were recruited. The initial 39-item Core Competence in Fundamental Nursing Practicum Scale was drafted and examined for its content, face and factorial validity. The data were randomly assigned into two subgroups and analyzed using exploratory and confirmatory factor analyses. Exploratory factor analysis was performed using principal-axis factoring and direct oblimin rotation and numbers of factors were extracted on the basis of eigenvalues >1 and a scree plot. The exploratory factor analysis derived struticum Scale was 0.94.

The 25-item Core Competence in Fundamental Nursing Practicum Scale reliably and validly measures nursing students’ core competence during their fundamental nursing practicum. Instructors can use the scale to identify students’ weak core competencies and refine their courses for novice nurses.

The 25-item Core Competence in Fundamental Nursing Practicum Scale reliably and validly measures nursing students’ core competence during their fundamental nursing practicum. Instructors can use the scale to identify students’ weak core competencies and refine their courses for novice nurses.

The increasing administration of belimumab has demonstrated its biological benefits. Prior meta-analyses have examined the overall adverse events (AEs) associated with belimumab, but such knowledge needs to be updated with a high volume of new trials. However, little is known about the occurrence of AEs associated with different underlying diseases. This study aimed to address the safety of the intravenous (IV) administration of belimumab combined with standard of care (SoC) therapy in Systemic lupus erythematosus (SLE) patients.

We used PubMed, Embase, and the Cochrane Library to systematically search for randomised controlled trials (RCTs) reporting AEs and specific AEs in SLE patients receiving belimumab and SoC therapy before 30 November 2021. We extracted the data of the eligible studies and calculated pooled risk ratios (RRs) and their 95% confidence intervals (CIs) in SLE patients receiving belimumab and SoC therapy and experiencing various AEs. The main outcomes were as follows (1) any AEs, any seRR=1.05, 95% CI 0.85-1.30, P=0.63; depression RR=1.42, 95% CI 0.92-2.20, P=0.11; serious depression RR=2.60, 95% CI 0.85-7.93, P=0.09; suicide or self-injury RR=0.97, 95% CI 0.48-1.96, P=0.92; serious suicide or self-injury RR=1.26, 95% CI 0.59-2.70, P=0.56).

According to the results of the meta-analysis, SLE patients did not have significantly increased risk of experiencing any type of AEs when receiving SoC therapy. Special caution should be exercised during close follow-ups and individual clinical management before drug prescription.

According to the results of the meta-analysis, SLE patients did not have significantly increased risk of experiencing any type of AEs when receiving SoC therapy. Special caution should be exercised during close follow-ups and individual clinical management before drug prescription.Like a rocket being propelled into space, evolution has engineered flies to launch into adulthood via multiple stages. Flies develop and deploy two distinct bodies, linked by the transformative process of metamorphosis. The fly larva is a soft hydraulic tube that can crawl to find food and avoid predators. The adult fly has a stiff exoskeleton with articulated limbs that enable long-distance navigation and rich social interactions. Because the larval and adult forms are so distinct in structure, they require distinct strategies for sensing and moving the body. The metamorphic divide thus presents an opportunity for comparative analysis of neural circuits. Here, we review recent progress toward understanding the neural mechanisms of proprioception and motor control in larval and adult Drosophila. We highlight commonalities that point toward general principles of sensorimotor control and differences that may reflect unique constraints imposed by biomechanics. EGFR inhibitor Finally, we discuss emerging opportunities for comparative analysis of neural circuit architecture in the fly and other animal species.Most chemotherapy agents have serious side effects due to lack of tumor targeting, which affects their clinical application. In addition, as an essential characteristic of malignant tumor, hypoxia is attracting exclusive research focus regarding its non-invasive real-time tracing in novel targeting delivery system. Herein, we designed a mixed micelle with tumor targeting and hypoxia responsiveness for tumor therapy and imaging. In particular, the dual-modified mix micelles were self-assembled by folic acid (FA) and 2-(2-nitroimidazole) ethylamine (NI) conjugated polymers, in which paclitaxel (PTX) and quantum dots (QDs) were co-loaded into the hydrophobic core. The drug loaded micelles showed satisfactory drug encapsulation, good storage stability, and sustained release properties. In vitro cell experiments showed that the mixed micelles exhibited enhanced cytotoxic effect and improved the cellular uptake, especially under hypoxic conditions, which was due to the FA mediated active targeting effect and NI induced hypoxic responsive release.