Robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) for the treatment of gastric gastrointestinal stromal tumors in challenging anatomical locations: single-center experience

BackgroundGastric gastrointestinal stromal tumors in challenging anatomical locations are difficult to remove.MethodsThis study retrospectively analyzed the clinical data of 12 patients with gastric GISTs in challenging anatomical locations who underwent robot-assisted laparoscopic combined with endoscopic partial gastrectomy (RALE-PG) and manual suturing of the gastric wall.ResultsThis study included 12 patients with a mean age of 56.8 ± 9.8 years and a mean BMI of 23.9 ± 1.9 kg/m2. Tumors were located in the GEJ (n = 3), lesser curvature (n = 3), posterior gastric wall (n = 3) and antrum (n = 3). The cardia and pylorus were successfully preserved in all patients regardless of the tumor location. The mean tumor size was 4.5 ± 1.4 cm. The mitotic-count/50 mm2 was less than 5 in all patients (100%). There was no intraoperative tumor rupture (0%) and no conversion to open surgery (0%). The median operation time was 122 (97–240) min, and the median blood loss volume was 10 (5–30) ml. The median postoperative VAS score was 2 (2–4). The median time to first flatus was 2 (2–3) days. The median time to first fluid intake was 2 (2–3) days. The median time to first ambulation after the operation was 3 (2–4) days. No cases of anastomotic stenosis or leakage were found. The median time to drain removal for 6 patients was 5 (4–7) days. The median time to nasogastric tube removal for all patients was 2 (1–5) days. The median postoperative hospital stay was 5 (4–8) days. One patient (female/41 year) developed moderate anemia (Clavien-Dindo grade II complication). There was no unplanned readmission within 30 days after the operation. The median distance from the tumor to the resection margin was 1 (1–2) cm. R0 resection was achieved in all patients. The median follow-up period was 19 (10–25) months, and all patients survived with no recurrence or metastasis.ConclusionsRALE-PG is a safe, feasible and advantageous technique for treating GISTs in challenging anatomical locations. It can be used to accurately remove the tumor while preserving gastric function to the greatest extent, but long-term oncologic outcomes need to be evaluated in a study with a larger sample size and longer follow-up period

Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age.

BACKGROUND: Atrial fibrillation (AF), often associated with structural, fibrotic change in cardiac tissues involving regulatory signaling mediators, becomes increasingly common with age. In the present study, we explored the role of mitogen-activated protein kinase kinase 4 (Mkk4), a critical component of the stress-activated mitogen-activated protein kinase family, in age-associated AF. METHODS AND RESULTS: We developed a novel mouse model with a selective inactivation of atrial cardiomyocyte Mkk4 (Mkk4(ACKO)). We characterized and compared electrophysiological, histological, and molecular features of young (3- to 4-month), adult (6-month), and old (1-year) Mkk4(ACKO) mice with age-matched control littermates (Mkk4(F/F)). Aging Mkk4(ACKO) mice were more susceptible to atrial tachyarrhythmias than the corresponding Mkk4(F/F) mice, showing characteristic slow and dispersed atrial conduction, for which modeling studies demonstrated potential arrhythmic effects. These differences paralleled increased interstitial fibrosis, upregulated transforming growth factor beta 1 (TGF-β1) signaling and dysregulation of matrix metalloproteinases in Mkk4(ACKO), compared to Mkk4(F/F), atria. Mkk4 inactivation increased the sensitivity of cultured cardiomyocytes to angiotensin II-induced activation of TGF-β1 signaling. This, in turn, enhanced expression of profibrotic molecules in cultured cardiac fibroblasts, suggesting cross-talk between these two cell types in profibrotic signaling. Finally, human atrial tissues in AF showed a Mkk4 downregulation associated with increased production of profibrotic molecules, compared to findings in tissue from control subjects in sinus rhythm. CONCLUSIONS: These findings together demonstrate, for the first time, that Mkk4 is a negative regulator of the TGF-β1 signaling associated with atrial remodeling and arrhythmogenesis with age, establishing Mkk4 as a new potential therapeutic target for treating AF

A Novel High-Throughput Vaccinia Virus Neutralization Assay and Preexisting Immunity in Populations from Different Geographic Regions in China

Background: Pre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China. Methodology/Principal Findings: A new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, crosssectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30–55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significan

Vertical Distribution of Soil Denitrifying Communities in a Wet Sclerophyll Forest under Long-Term Repeated Burning

Soil biogeochemical cycles are largely mediated by microorganisms, while fire significantly modifies biogeochemical cycles mainly via altering microbial community and substrate availability. Majority of studies on fire effects have focused on the surface soil; therefore, our understanding of the vertical distribution of microbial communities and the impacts of fire on nitrogen (N) dynamics in the soil profile is limited. Here, we examined the changes of soil denitrification capacity (DNC) and denitrifying communities with depth under different burning regimes, and their interaction with environmental gradients along the soil profile. Results showed that soil depth had a more pronounced impact than the burning treatment on the bacterial community size. The abundance of 16S rRNA and denitrification genes (narG, nirK, and nirS) declined exponentially with soil depth. Surprisingly, the nosZ-harboring denitrifiers were enriched in the deeper soil layers, which was likely to indicate that the nosZ-harboring denitrifiers could better adapt to the stress conditions (i.e., oxygen deficiency, nutrient limitation, etc.) than other denitrifiers. Soil nutrients, including dissolved organic carbon (DOC), total soluble N (TSN), ammonium (NH4 +), and nitrate (NO3 −), declined significantly with soil depth, which probably contributed to the vertical distribution of denitrifying communities. Soil DNC decreased significantly with soil depth, which was negligible in the depths below 20 cm. These findings have provided new insights into niche separation of the N-cycling functional guilds along the soil profile, under a varied fire disturbance regime

Vertical Distribution of Soil Denitrifying Communities in a Wet Sclerophyll Forest under Long-Term Repeated Burning

Soil biogeochemical cycles are largely mediated by microorganisms, while fire significantly modifies biogeochemical cycles mainly via altering microbial community and substrate availability. Majority of studies on fire effects have focused on the surface soil; therefore, our understanding of the vertical distribution of microbial communities and the impacts of fire on nitrogen (N) dynamics in the soil profile is limited. Here, we examined the changes of soil denitrification capacity (DNC) and denitrifying communities with depth under different burning regimes, and their interaction with environmental gradients along the soil profile. Results showed that soil depth had a more pronounced impact than the burning treatment on the bacterial community size. The abundance of 16S rRNA and denitrification genes (narG, nirK, and nirS) declined exponentially with soil depth. Surprisingly, the nosZ-harboring denitrifiers were enriched in the deeper soil layers, which was likely to indicate that the nosZ-harboring denitrifiers could better adapt to the stress conditions (i.e., oxygen deficiency, nutrient limitation, etc.) than other denitrifiers. Soil nutrients, including dissolved organic carbon (DOC), total soluble N (TSN), ammonium (NH4 +), and nitrate (NO3 −), declined significantly with soil depth, which probably contributed to the vertical distribution of denitrifying communities. Soil DNC decreased significantly with soil depth, which was negligible in the depths below 20 cm. These findings have provided new insights into niche separation of the N-cycling functional guilds along the soil profile, under a varied fire disturbance regime

Regioselective Fluorination of Imidazo[1,2‑<i>a</i>]pyridines with Selectfluor in Aqueous Condition

A regioselective synthesis of 3-fluorinated imidazo­[1,2-<i>a</i>]­pyridines using 1-chloromethyl-4-fluoro-1,4-diazoniabi cyclo[2.2.2]­octane bis­(tetrafluoroborate) (Selectfluor) as the fluorinating reagent in aqueous condition is described. In the presence of DMAP, the reaction mainly gave monofluorinated product via electrophilic fluorinated process in moderate to good yields

In-plane coherent control of plasmon resonances for plasmonic switching and encoding

Considerable attention has been paid recently to coherent control of plasmon resonances in metadevices for potential applications in all-optical light-with-light signal modulation and image processing. Previous reports based on out-of-plane coherent control of plasmon resonances were established by modulating the position of a metadevice in standing waves. Here we show that destructive and constructive absorption can be realized in metallic nano-antennas through in-plane coherent control of plasmon resonances, which is determined by the distribution rule of electrical-field components of nano-antennas. We provide proof-of-principle demonstrations of plasmonic switching effects in a gold nanodisk monomer and dimer, and propose a plasmonic encoding strategy in a gold nanodisk chain. In-plane coherent control of plasmon resonances may open a new avenue toward promising applications in optical spectral enhancement, imaging, nanolasing, and optical communication in nanocircuits.MOE (Min. of Education, S’pore)Published versio

Additional file 3: of Comparative transcriptomic analyses of normal and malformed flowers in sugar apple (Annona squamosa L.) to identify the differential expressed genes between normal and malformed flowers

KEGG classifications of unigenes. (XLSX 13 kb