Review on the Significant Interactions between Ultrafine Gas Bubbles and Biological Systems.

Having sizes comparable with living cells and high abundance, ultrafine bubbles (UBs) are prone to inevitable interactions with different types of cells and facilitate alterations in physiological properties. The interactions of four typical cell types (e.g., bacterial, fungal, plant, and mammalian cells) with UBs have been studied over recent years. For bacterial cells, UBs have been utilized in creating the capillary force to tear down biofilms. The release of high amounts of heat, pressure, and free radicals during bubble rupture is also found to affect bacterial cell growth. Similarly, the bubble gas core identity plays an important role in the development of fungal cells. By the proposed mechanism of attachment of UBs on hydrophobin proteins in the fungal cell wall, oxygen and ozone gas-filled ultrafine bubbles can either promote or hinder the cell growth rate. On the other hand, reactive oxygen species (ROS) formation and mass transfer facilitation are two means of indirect interactions between UBs and plant cells. Likewise, the use of different gas cores in generating bubbles can produce different physical effects on these cells, for example, hydrogen gas for antioxidation against infections and oxygen for oxidation of toxic metal ions. For mammalian cells, the importance of investigating their interactions with UBs lies in the bubbles' action on cell viability as membrane poration for drug delivery can greatly affect cells' survival. UBs have been utilized and tested in forming the pores by different methods, ranging from bubble oscillation and microstream generation through acoustic cavitation to bubble implosion.

Factors Influencing Mobility During the COVID-19 Pandemic in Community-Dwelling Older Adults.

OBJECTIVE: To describe and identify factors influencing mobility among older adults during the first 5 months of the COVID-19 pandemic. DESIGN: A cross-sectional telesurvey. SETTING: Community dwelling older adults, situated within the first 5 months of the COVID-19 pandemic, in Hamilton, Canada. PARTICIPANTS: A random sample of 2343 older adults were approached to be in the study, of which 247 completed the survey (N=247). Eligible participants were aged ≥65 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mobility was measured using global rating of change items and the Late Life Function Instrument (LLFI). Multivariate linear regression models were used to examine the association between mobility and related factors based on Webber's model. RESULTS: 247 older adults (29% male, mean age 78±7.3 years) completed surveys between May and August 2020. Respectively, 26%, 10%, and 9%, rated their ability to engage in physical activity, housework, and move around their home as worse compared with the start of the pandemic. The mean LLFI score was 60.9±13.4. In the model, walking volume (ß=0.03 95% confidence interval 0.013, 0.047), fall history (ß=-0.04, 95% confidence interval -0.08, -0.04), male sex (ß=0.06, 95% confidence interval 0.02, 0.09), unpleasant neighborhood (ß=-0.06, 95% confidence interval -0.11, -0.02), musculoskeletal pain (ß=-0.07, 95% confidence interval -0.11, -0.03), and self-reported health (ß=0.08, 95% confidence interval 0.03, 0.13) had the strongest associations with LLFI scores and explained 64% of the variance in the LLFI score. CONCLUSIONS: Physical and environmental factors may help explain poorer mobility during lockdowns. Future research should examine these associations longitudinally to see if factors remain consistent over time and could be targeted for rehabilitation.

Method validation for the recovery of the porcine respiratory and reproductive syndrome virus, a potential SARS-CoV-2 surrogate, from stainless steel.

Virus survival on fomites may represent a vehicle for transmission to humans. This study was conducted to optimize and validate a recovery method for the porcine respiratory and reproductive syndrome virus (PRRSV), a potential SARS-CoV-2 surrogate, from stainless steel. Coupons (1.5 × 1.5 cm) inoculated with ca. 7 logs TCID50 of PRRSV were dried for 15 min at room temperature, followed by incubation at 4°C and 35% relative humidity. After 1 h and 24 h, the coupons were processed by four different methods: vortex in DMEM media, vortex in DMEM media with beads, vortex in elution buffer, and shake in elution buffer. The rinsates were processed for titration using the TCID50 method in the MARC-145 cell line. All four methods were equally effective to recover the virus from the soiled SS surfaces (> 79% recovery). The amount of infectious virus recovered after 24 h was similar (P > 0.05) to that recovered after 1 h, indicating that the virus was stable at 4°C for up to 24 h. Using an elution buffer followed by shaking was the least labor-intensive and most economical method. Therefore, this method will be used for future experiments on PRRSV survival and transfer from food-contact surfaces.

Reconstruction of Large Anterior Skull Base Defects After Resection of Sinonasal Tumors With Intracranial Extension by Using Pedicled Double Flap Techniques.

INTRODUCTION: The use of surgical resection for large anterior skull base (ASB) tumors and sinonasal malignancies with intracranial extension will result in a large skull base defect. Reconstruction of large ASB defects using traditional techniques is high risk and may lead to postoperative cerebral spinal fluid (CSF) leakage, meningitis, and an increase in mortality rate. The use of a pedicled double flap technique to reconstruct the ASB defect may decrease complications. This study presents the clinical outcomes of patients who underwent double flap reconstruction techniques after resection of their sinonasal malignancies with significant intracranial extension at Cho Ray hospital in Vietnam. METHODS: The case series study was conducted at Cho Ray hospital from September 2010 to September 2020. All patients with large sinonasal malignancies that invaded intracranially underwent transnasal endoscopic surgery and subfrontal craniotomy. Reconstruction of large skull base defects (>2 cm) were followed up by using the pedicled double flaps technique. This study was performed in line with the principles of the Declaration of Helsinki. Approval of the study was granted by the Independent Ethics Committee of Cho Ray Hospital (Date: March 3, 2014/No: 11/BVCRHDDD). RESULTS: During September 2010 to September 2020, there were 75 patients who underwent a modified multilayer, double flap reconstruction technique after the resection of their ASB tumor. Skull base defects were commonly seen along the horizontal plate of the ethmoid bone and the ethmoid roof (98.6%). Large skull base defects (>2 cm) accounted for 81.3% of cases. Overall, the risk of postoperative CSF leakage and meningitis after double flap repair was considerably low. Of all participants, only 1 experienced postoperative CSF leakage and 1 experienced postoperative meningitis. Despite the complications, these patients improved significantly and remained stable. CONCLUSION: The use of double vascularized pedicled flaps may decrease the incidence of postoperative CSF leakage and meningitis. This technique is an effective method for the reconstruction of ASB tumors with large defects.

Head-to-head comparison between MEFIB, MAST, and FAST for detecting stage 2 fibrosis or higher among patients with NAFLD.

BACKGROUND & AIMS: Patients with non-alcoholic fatty liver disease (NAFLD) and significant fibrosis (fibrosis stage ≥2) are candidates for pharmacological trials. The aim of this study was to perform a head-to-head comparison of the diagnostic test characteristics of three non-invasive stiffness-based models including MEFIB (magnetic resonance elastography [MRE] plus FIB-4), MAST (magnetic resonance imaging [MRI]-aspartate aminotransferase [AST]), and FAST (FibroScan-AST) for detecting significant fibrosis. METHODS: This prospective study included 563 patients with biopsy-proven NAFLD undergoing contemporaneous MRE, MRI proton density fat fraction (MRI-PDFF) and FibroScan from two prospective cohorts derived from Southern California and Japan. Diagnostic performances of models were evaluated by area under the receiver-operating characteristic curve (AUC). RESULTS: The mean age of the cohort was 56.5 years (51% were women). Significant fibrosis was observed in 51.2%. To detect significant fibrosis, MEFIB outperformed both MAST and FAST (both p <0.001); AUCs for MEFIB, MAST, and FAST were 0.901 (95% CI 0.875-0.928), 0.770 (95% CI 0.730-0.810), and 0.725 (95% CI 0.683-0.767), respectively. Using rule-in criteria, the positive predictive value of MEFIB (95.3%) was significantly higher than that of FAST (83.5%, p = 0.001) and numerically but not statistically greater than that of MAST (90.0%, p = 0.056). Notably, MEFIB's rule-in criteria covered more of the study population than MAST (34.1% vs. 26.6%; p = 0.006). Using rule-out criteria, the negative predictive value of MEFIB (90.1%) was significantly higher than that of either MAST (69.6%) or FAST (71.8%) (both p <0.001). Furthermore, to diagnose "at risk" non-alcoholic steatohepatitis defined as NAFLD activity score ≥4 and fibrosis stage ≥2, MEFIB outperformed both MAST and FAST (both p <0.05); AUCs for MEFIB, MAST, and FAST were 0.768 (95% CI 0.728-0.808), 0.719 (95% CI 0.671-0.766), and 0.687 (95% CI 0.640-0.733), respectively. CONCLUSIONS: MEFIB was better than MAST and FAST for detection of significant fibrosis as well as "at risk" NASH. All three models provide utility for the risk stratification of NAFLD. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) affects over 25% of the general population worldwide and is one of the main causes of chronic liver disease. Because so many individuals have NAFLD, it is not practical to perform liver biopsies to identify those with more severe disease who may require pharmacological interventions. Therefore, accurate non-invasive tests are crucial. Herein, we compared three such tests and found that a test called MEFIB was the best at detecting patients who might require treatment.

Metal-Free Annulation of 2-Nitrobenzyl Alcohols and Tetrahydroisoquinolines toward the Divergent Synthesis of Quinazolinones and Quinazolinethiones.

A simple metal-free method for the synthesis of quinazolinones from commercially available 2-nitrobenzyl alcohols and tetrahydroisoquinolines is developed. The reaction conditions were tolerant of an array of functionalities such as halogen, tertiary amine, protected alcohol, and ester groups. Under nearly identical conditions, quinazolinethiones were obtained in the presence of elemental sulfur and suitable mediators.

Combined Nasal Endoscopic and Subfrontal Craniotomy for Resection Tumors of Anterior Skull Base.

OBJECTIVE: Sinonasal tumors invading anterior skull base is difficult to treat in Otorhinolaryngology and Neurosurgery. Treatment requires the collaboration of ear, nose and throat (ENT) and neurosurgeon to remove the tumor completely. This study was to evaluate the outcome of combined technique nasal endoscopic and subfrontal approach in case of sinonasal tumors involving anterior skull base. METHODS: Retrospective cross-sectional study. RESULTS: The study was a cross-sectional study that had taken place at Otorhinolaryngology and Neurosurgery Department of Cho Ray Hospital, Vietnam. All 45 patients were enrolled and underwent the surgery. 71.1% of these cases were malignant tumors. The ratio of sinonasal malignant tumor is squamous cell carcinoma and esthesioneuroblastoma were 24.4% and 11.1%, respectively. All the cases were diagnosed as sinonasal tumor invading anterior skull base and successfully removed by combining nasal endoscopic approach with subfrontal craniotomy. CONCLUSIONS: The combined nasal endoscopic with subfrontal craniotomy for resection nasoethmoid tumor invading the brain show a good result. This technique is an important adjunct that contribute to the treatment of anterior skull base tumor involving the brain.

Internal Mammary Lymph Node Biopsy during Microsurgical Breast Reconstruction: A Prospective Study.

BACKGROUND: Accurate assessment of regional lymph node basins is critical for oncological management of breast cancer. The internal mammary lymph node (IMLN) basin directly drains the medial pole of the breast, but biopsy is not commonly performed. While the axillary sentinel lymph node sample remains the standard of care, the majority of patients who have been found to have a positive IMLN biopsy have simultaneously had negative axillary sentinel lymph nodes. This study prospectively examines routine IMLN biopsy during microsurgical breast reconstruction. METHODS: An IRB-approved study of routine IMLN biopsies in 270 consecutive patients who underwent microsurgical breast reconstruction was performed from July 1, 2018, to June 1, 2021. Recorded data included unilateral or bilateral breast reconstruction, unilateral or bilateral IMLN sampling, patient demographics, disease stage, and pathologic findings of IMLN. RESULTS: The majority of patients, 240 of 270 patients (88.9%), had bilateral reconstruction. Overall, 5 out of 270 (1.9%) patients had positive IMLN; one of these patients had positive axillary sentinel lymph nodes. The IMLN biopsy results in two of the five patients affected the clinical course as they were upstaged and required chemoradiation. CONCLUSION: Direct visualization of the internal mammary lymph nodes during dissection of the recipient vessels for microsurgical breast reconstruction allows for convenient sampling, with minimal donor site morbidity and enhances the therapeutic management of patients in whom nodal involvement is present. As such, the authors recommend IMLN sampling.

Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study.

BACKGROUND: Anti-PD-1 therapy (hereafter referred to as anti-PD-1) induces long-term disease control in approximately 30% of patients with metastatic melanoma; however, two-thirds of patients are resistant and will require further treatment. We aimed to determine the efficacy and safety of ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab) compared with ipilimumab monotherapy in patients who are resistant to anti-PD-(L)1 therapy (hereafter referred to as anti-PD-[L]1). METHODS: This multicentre, retrospective, cohort study, was done at 15 melanoma centres in Australia, Europe, and the USA. We included adult patients (aged ≥18 years) with metastatic melanoma (unresectable stage III and IV), who were resistant to anti-PD-(L)1 (innate or acquired resistance) and who then received either ipilimumab monotherapy or ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab), based on availability of therapies or clinical factors determined by the physician, or both. Tumour response was assessed as per standard of care (CT or PET-CT scans every 3 months). The study endpoints were objective response rate, progression-free survival, overall survival, and safety of ipilimumab compared with ipilimumab plus anti-PD-1. FINDINGS: We included 355 patients with metastatic melanoma, resistant to anti-PD-(L)1 (nivolumab, pembrolizumab, or atezolizumab), who had been treated with ipilimumab monotherapy (n=162 [46%]) or ipilimumab plus anti-PD-1 (n=193 [54%]) between Feb 1, 2011, and Feb 6, 2020. At a median follow-up of 22·1 months (IQR 9·5-30·9), the objective response rate was higher with ipilimumab plus anti-PD-1 (60 [31%] of 193 patients) than with ipilimumab monotherapy (21 [13%] of 162 patients; p<0·0001). Overall survival was longer in the ipilimumab plus anti-PD-1 group (median overall survival 20·4 months [95% CI 12·7-34·8]) than with ipilimumab monotherapy (8·8 months [6·1-11·3]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). Progression-free survival was also longer with ipilimumab plus anti-PD-1 (median 3·0 months [95% CI 2·6-3·6]) than with ipilimumab (2·6 months [2·4-2·9]; HR 0·69, 95% CI 0·55-0·87; p=0·0019). Similar proportions of patients reported grade 3-5 adverse events in both groups (59 [31%] of 193 patients in the ipilimumab plus anti-PD-1 group vs 54 [33%] of 162 patients in the ipilimumab group). The most common grade 3-5 adverse events were diarrhoea or colitis (23 [12%] of 193 patients in the ipilimumab plus anti-PD-1 group vs 33 [20%] of 162 patients in the ipilimumab group) and increased alanine aminotransferase or aspartate aminotransferase (24 [12%] vs 15 [9%]). One death occurred with ipilimumab 26 days after the last treatment: a colon perforation due to immune-related pancolitis. INTERPRETATION: In patients who are resistant to anti-PD-(L)1, ipilimumab plus anti-PD-1 seemed to yield higher efficacy than ipilimumab with a higher objective response rate, longer progression-free, and longer overall survival, with a similar rate of grade 3-5 toxicity. Ipilimumab plus anti-PD-1 should be favoured over ipilimumab alone as a second-line immunotherapy for these patients with advanced melanoma. FUNDING: None.

A Multicenter Analysis of Immune Checkpoint Inhibitors as Adjuvant Therapy Following Treatment of Isolated Brain Metastasis.

BACKGROUND: The objective of this work was to characterize outcomes of patients with isolated brain metastases managed with local therapy followed by immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: Patients from four medical centers were included if they presented with isolated brain metastases treated with local therapy and received adjuvant treatment with ICIs. RESULTS: Eleven patients with median size of largest brain metastasis of 3.9 cm, treated with surgical resection (n = 8) and/or stereotactic radiosurgery (SRS; n = 6), were included. Ipilimumab/nivolumab was the adjuvant ICI used in four patients, of whom one recurred (25%) and none died, compared with three of seven (43%) who recurred and two of seven (29%) who died following adjuvant treatment with ICI monotherapy. All recurrences were intracranial. CONCLUSION: Patients with isolated brain metastases treated with surgery or SRS appeared to benefit from adjuvant ICI therapy, particularly with combination therapy. Recurrences in this setting appear to largely occur intracranially.

Copper-catalyzed synthesis of pyrido-fused quinazolinones from 2-aminoarylmethanols and isoquinolines or tetrahydroisoquinolines.

Pyrido-fused quinazolinones were synthesized via copper-catalyzed cascade C(sp2)-H amination and annulation of 2-aminoarylmethanols with isoquinolines or pyridines. The transformation proceeded readily in the presence of a commercially available CuCl2 catalyst with molecular oxygen as a green oxidant. Moreover, the dehydrogenative cross-coupling of 2-aminoarylmethanols with tetrahydroisoquinolines was explored, in which CuBr exhibited higher catalytic activity than CuCl2. Broad substrate scope with good tolerance of functionalities was observed under the optimized reaction conditions. The bioactive naturally occurring alkaloid rutaecarpine could be obtained by this strategy. The remarkable feature of this protocol is that complicated heterocyclic structures are readily achieved in a single synthetic step from easily accessible reactants and catalysts. This pathway to pyrido-fused quinazolinones would be complementary to existing protocols.

Evaluation of internal mammary lymph node biopsy during microsurgical breast reconstruction: An analysis of 230 consecutive patients.

INTRODUCTION: Clinical significance of internal mammary (IM) lymph node biopsy during microvascular free flap breast reconstruction remains controversial. Some microsurgeons may choose to biopsy an IM lymph node during routine IM vessel dissection. The authors reviewed the results of IM lymph node biopsy during autologous breast reconstruction. METHODS: A retrospective chart review of patients who underwent autologous breast reconstruction during a seven-year period (January 2010 to January 2017) was performed. Patient demographic data, disease staging, flap details, pathology reports, and adjuvant treatment were evaluated. RESULTS: A total of 230 patients with a mean age of 52.1 (SD 9.3) underwent IM lymph node biopsy (n = 297). Single IM lymph node was removed in 169 patients, 2 nodes were removed in 56 patients, 3 nodes in 4 patients, and 4 nodes in a single patient. Histopathologic analysis demonstrated presence of IM lymph node metastasis in 16 patients (7.0%). Thirteen patients were found to have metastatic IM lymph nodes in the setting of immediate reconstruction. Three patients were found to have metastatic IM lymph nodes in the setting of delayed. Five out of 16 patients (31.3%) had negative axillary sentinel lymph node biopsy and IM lymph nodes were the only site of nodal metastases. All five of these patients were upstaged accordingly and received adjuvant therapy based on the discussion at the multidisciplinary breast tumor conference. CONCLUSIONS: Opportunistic internal mammary lymph node sampling during autologous breast reconstruction can be performed with minimal morbidity and has significant impact on the disease staging and adjuvant treatment.

Magnetic Ni-Doped TiO2 Photocatalysts for Disinfection of Escherichia coli Bacteria.

Ni-doped TiO2 nanoparticles have been synthesized by a modified sol-gel method. The crystal phase composition, particle size, and magnetic and optical properties of the samples were comprehensively examined using x-ray diffraction analysis, transmission electron microscopy, Brunauer-Emmett-Teller surface area analysis, Raman spectroscopy, magnetization measurements, and ultraviolet-visible (UV-Vis) absorption techniques. The results showed that the prepared Ni-doped TiO2 samples sintered at 400°C crystallized completely in anatase phase with average particle size in the range from 8 nm to 10 nm and presented broad visible absorption. The bactericidal efficiency of TiO2 was effectively enhanced by Ni doping, with an optimum Ni doping concentration of 6% (x = 0.06), at which 95% of Escherichia coli were killed after just 90 min of irradiation. Density functional theory (DFT) calculations revealed good agreement with the experimental data. Moreover, the Ni dopant induced magnetic properties in TiO2, facilitating its retrieval using a magnetic field after use, which is an important feature for photocatalytic applications.

Calosides A-F, Cardenolides from Calotropis gigantea and Their Cytotoxic Activity.

Phytochemical analysis of the roots of Calotropis gigantea led to the isolation of six new cardenolide glycosides, calosides A-F (1-6), and five known cardenolides (7-11). The structures of 1-6 were elucidated based on NMR and ECD spectroscopic data interpretation. Caloside D (4) is the first naturally occurring example of a cardenolide containing a C-8/C-19 oxygen bridge. In turn, calosides E (5) and F (6) represent the first naturally occurring 3-epi-cannogenol diglycosides having potent cytotoxicity against the PANC-1 cell line (IC50, 0.081 and 0.070 µM, respectively) and HeLa (IC50, both 0.17 µM) cells, under normoglycemic conditions.

Retiform Purpura as a Sign of Necrotizing Cellulitis in an Immunocompetent Boy.

Severe group A streptococcus (GAS) infections, particularly necrotizing soft tissue infections (NSTIs), have been associated with the development of streptococcal toxic-shock syndrome (STSS), a systemic illness caused by GAS-derived toxins. Traditional physical examination findings in NSTIs include skin necrosis, crepitus, and hemorrhagic bullae. However, these findings are limited in sensitivity and additional clinical markers may aid in making an early diagnosis of NSTI. We present a case of a superficial infection, specifically GAS necrotizing cellulitis, complicated by STSS in a healthy boy with an associated skin finding of retiform purpura that aided in early diagnosis of a NSTI.

Violaceous nodules in an HIV-positive man.

Plasmablastic lymphoma (PBL) is a rare and aggressive malignancy associated with immunosuppression and the oncogenic effects of the Epstein-Barr virus (EBV). We present an HIV-positive man with PBL that presented as ulcers and violaceous exophytic nodules on the legs. The clinical features, histologic appearance, and differential diagnosis of this malignancy are briefly reviewed.

Revisiting Nasal Reconstruction After Mohs Surgery: A Simplified Approach Based on the Liberal Application of Local Flaps.

INTRODUCTION: Nasal reconstruction after oncologic resection often constitutes a technically demanding task. The aim of this study was to investigate our experience with nasal reconstruction after Mohs micrographic surgery using the following 3 well-established, versatile, and reliable techniques: the bilobed flap, nasolabial flap, and forehead flap. METHODS: A single-surgeon retrospective chart review of all patients undergone a bilobed, nasolabial, or forehead flap for nasal reconstruction after Mohs micrographic surgery from 2003 to 2017 was conducted. Data collected for analysis included demographics and defect characteristics. Revisions and complications were analyzed. RESULTS: A total of 83 patients were included in the study; 52 patients underwent bilobed, 17 patients nasolabial, and 14 patients forehead flaps. All defects involved the middle and lower nasal zones. There was a significant difference in the defect size between the 3 groups (P < 0.001). The mean diameters were as follows: 1.37 cm for the bilobed, 2.22 cm for the nasolabial, and 3.46 cm for the forehead flap groups. Liberal utilization of the bilobed and nasolabial flaps achieved reconstruction of defects larger than typically described in the literature. Reconstruction of all defects, including support for successful restoration of mucosal lining and cartilage when indicated, was achieved. An algorithm dealing with defects larger than 0.5 cm in the middle and distal nasal zones was devised. CONCLUSIONS: In this study, the liberal application of the 3 flaps was described based on an individualized treatment approach. The algorithm provides a simplified approach for larger nasal defects in the middle and lower thirds.

Validation of the MCNP6 code for SFR shielding design analysis.

In this paper, the uncertainty of the Monte Carlo code MCNP6 for the sodium-cooled fast reactor (SFR) shielding design is studied. Shielding analysis, which ensures the radiation safety of the core design, is challenging for the Monte Carlo modeling because it is associated with large uncertainties. In order to evaluate the performance of the MCNP6 relative to the shielding design of the SFR, four SFR shielding benchmarks from the Shielding Integral Benchmark Archive Database benchmark suite, i.e. JANUS Phase VIII, SDT12, EURAC_Na and HARMO_Na were selected and analysed. In this research, the weight window variance-reduction technique and the neutron data library ENDF/B-VII.1 were used in the modeling of the benchmark problems. The results and the validation of the MCNP6 models with the available measurement data are presented in this paper. These results contribute to the assessment of radiological protection and shielding design of the Korean Prototype Gen-IV Sodium-cooled Fast Reactor.

Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea.

A new lignan, 9'-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4-12) have been isolated from the active fractions, CHCl3 (IC50, 0.32µgmL-1) and EtOAc (IC50, 0.55µgmL-1) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC50 values of 3.7 and 3.3µM, respectively. 9'-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner.

Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses.

BACKGROUND: Human polyomavirus (HPyV)6 and HPyV7 are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. OBJECTIVE: We determined whether biopsy specimens showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. METHODS: We screened biopsy specimens showing "peacock plumage" histology by polymerase chain reaction for HPyVs. Cases positive for HPyV6 or HPyV7 were then analyzed by immunohistochemistry, electron microscopy, immunofluorescence, quantitative polymerase chain reaction, and complete sequencing, including unbiased, next-generation sequencing. RESULTS: We identified 3 additional cases of HPyV6 or HPyV7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared with normal-appearing skin and the identification of intact virions by both electron microscopy and next-generation sequencing support a role for active viral infections in these skin diseases. LIMITATION: This was a small case series of archived materials. CONCLUSION: We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a distinctive histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatoses."