The noscapinoid substantially damaged cellular microtubule network and induced cell death, facilitated by elevated levels of ROS.
 
  9-PAN exerts its antiproliferative effect by targeting tubulin and elevating ROS level in the cells.
 9-PAN exerts its antiproliferative effect by targeting tubulin and elevating ROS level in the cells.
  Multiple strategies have been used to evaluate the minimal important change (MIC) of the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD). The meaningfulness of these MICs is not well established across all severities of atopic dermatitis (AD).
 
  To determine the MIC of percentage and absolute improvement of EASI and SCORAD scores in adults and children with AD.
 
  We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n=826). An anchor-based approach was used to determine thresholds for the percentage and absolute MICs of EASI, SCORAD and objective SCORAD (O-SCORAD) at follow-up from baseline.
 
  One-grade improvements of Physician's Global Assessment (PGA) and validated Investigator Global Assessment scale for AD (vIGA-AD) were associated with 50%, 35% and 35% decreases of EASI, SCORAD and O-SCORAD, respectively. The thresholds for percentage MIC of EASI (Kruskal-Wallis test, P=0·61), SCORAD (P=0·07) and O-SCORAD (P=0·09) were similar across baseline AD severities. One-grade improvements of PGA and vIGA-AD were associated with 14·0- and 14·9-point decreases of EASI, 19·9- and 14·9-point decreases of SCORAD, and 15·5- and 17·4-point decreases of O-SCORAD. The thresholds for the absolute MIC of EASI (P<0·001), SCORAD (P<0·001) and O-SCORAD (P<0·001) significantly differed by baseline AD severity. Percentage and absolute MICs for EASI and SCORAD were associated with improvements of AD symptoms and quality of life.
 
  EASI 50, SCORAD 35 and O-SCORAD 35 were meaningful percentage MICs regardless of baseline AD severity. The absolute MICs for EASI, SCORAD and O-SCORAD varied by baseline AD severity.
 EASI 50, SCORAD 35 and O-SCORAD 35 were meaningful percentage MICs regardless of baseline AD severity. The absolute MICs for EASI, SCORAD and O-SCORAD varied by baseline AD severity.
  The transient receptor potential vanilloid 4 (TRPV4) cation channel participates in multiple physiological processes and is also at the core of different diseases, making this channel an interesting pharmacological target with therapeutic potential. However, little is known about the structural elements governing its inhibition.
 
  We have now combined in silico drug discovery and molecular dynamics simulation based on Xenopus tropicalis xTRPV4 structure with functional studies measuring cell Ca
  influx mediated by human TRPV4 channel to characterize the binding site of known TRPV4 inhibitors and to identify novel small molecule channel modulators.
 
  We have found that the inhibitor HC067047 binds to a pocket conformed by residues from S2-S3 linker (xTRPV4-D542), S4 (xTRPV4-M583 and Y587 and S5 (xTRPV4-D609 and F613). This pocket was also used for structure-based virtual screening in the search of novel channel modulators. Forty potential hits were selected based on the lower docking scores (from ~250,000 compounds) and their effect upon TRPV4 functionally tested. Three were further analysed for stability using molecular dynamics simulation and functionally tested on TRPV4 channels carrying mutations in the binding pocket. Compound NSC151066, shown to require residue xTRPV4-M583 for its inhibitory effect, presented an IC
  of 145 nM and demonstrated to be an effective antiviral against Zika virus with a potency similar to HC067047.
 
  Together, we propose structural insights into the inhibition of TRPV4 and how this information can be used for the design of novel channel modulators.
 Together, we propose structural insights into the inhibition of TRPV4 and how this information can be used for the design of novel channel modulators.
  The current coronavirus disease 19 (COVID-19) pandemic has affected most countries. Infection, Prevention, and Control training is important in mitigating the spread of COVID-19. The closure of universities by the Nigerian government has hampered academic activities of dental students. Our objectives were to assess the knowledge, perception, and attitude of undergraduate dental students in Nigeria to the COVID-19 pandemic and infection control practices.
 
  This was a cross-sectional study of undergraduate clinical dental students from the dental schools in Nigeria. Self-administered questionnaires were distributed to participants using an online data collection platform. Correct responses to the 45-item questionnaire on COVID-19 knowledge were scored to determine their knowledge level. A Likert scale of 1-5 was used to assess the 13-item perception and attitude questions. The level of significance was set at P values ≤ 0.05.
 
  A total of 102 undergraduate clinical dental students participated in the study. tice.
  Depicting past epidemics currently relies on DNA-based detection of pathogens, an approach limited to pathogens with well-preserved DNA sequences. We used paleoserology as a complementary approach detecting specific antibodies under a mini line-blot format including positive and negative control antigens.
 
  Mini line blot assay incorporated skim milk as negative control, Staphylococcus aureus as positive control, and antigens prepared from lice-borne pathogens Rickettsia prowazekii, Borrelia recurrentis, Bartonella quintana, and Yersinia pestis. Paleoserums were extracted from rehydrated dental pulp recovered from buried individuals. Mini line blots observed with the naked eye, were quantified using a scanner and appropriate software. Paleoserology was applied to the indirect detection of lice-borne pathogens in seven skeletons exhumed from a 16th-17th century suspected military burial site (Auxi-le-Château); and 14 civils exhumed from a 5th-13th century burial site (Saint-Mont). Direct detection of pathogecentury military garrison, missed by real-time PCR.  https://www.selleckchem.com/products/l-arginine-l-glutamate.html  Paleoserology offers a new tool for investigating past epidemics, in complement to DNA sequence-based approaches.