The shortage of good quantity and quality of water for irrigated agriculture is a major problem in arid and semiarid regions. To deal with this problem, deficit irrigation (DI) or arbuscular ...mycorrhizal fungi (AMF) inoculation have been proposed and adopted for many crops as a tool to save water, or to improve crop tolerance to drought stress. An experiment was conducted for two consecutive years to evaluate the effect of mycorrhizal inoculation on the physiological, morphological, yield, and quality characteristics of melon plants grown under deficit irrigation. Melon crop (Cucumis melo L. cv. Helios) was grown under field conditions adopting a split-plot design with four replications, where DI was the main factor and AMF inoculation was the secondary factor. DI treatments consisted of applying 60%, 80%, or 100% of crop evapotranspiration (ETc) on melon plants inoculated or not with a commercial biostimulant containing 50% of Rhizophagus irregularis, and 50% of Funneliformis mosseae. Moderate and severe deficit irrigation significantly reduced the relative water content, stomatal conductance, yield, nitrogen applied efficiency (NAE), and fruit firmness of the uninoculated plants, but significantly increased irrigation water use efficiency (IWUE) and the ascorbic acid content of the fruit. AMF had a positive effect on plant tolerance to moderate water stress, and on some fruit quality parameters (fruit length, firmness, and sugar content). The combined use of moderate deficit irrigation (80%) and soil inoculation with AMF on melon plants allows water savings without affecting fruit yield, and increases IWUE, NAE, and some fruit quality characteristics (firmness, SSC, and SSC/TA). Furthermore, the use of AMF plants could be worth it to reduce the yield loss and increase fruit quality, even with severe deficit irrigation (60%).
Ecklonia maxima and the commercial biostimulants produced from it contain various plant growth regulators that are responsible for the growth stimulation recorded in many crops. Auxins are one of the ...major plant growth regulators contained in E. maxima extracts. The aim of this research was to evaluate the growth-promoting effect of a seaweed extract from E. maxima on lettuce and tomato transplant production under nursery conditions, and to compare the effect of this extract with an equal concentration of synthetic auxin. Two doses of natural or synthetic exogenous auxins (50 or 100 μg L−1) were supplied to the substrate through the irrigation water with an ebb and flow system, 4, 11, and 18 days after sowing. A commercial biostimulant based on E. maxima extract was used as a source of natural auxin, while 1-naphthaleneacetic acid (NAA) was used as a synthetic auxin. Seedlings supplied only with water were used as a control. Tomato seedlings treated with 100 μg L−1 of natural auxins from E. maxima extract produced the tallest plants (+22%), with a higher leaf number (+12%), a wider leaf area (+44%), and a stronger stem (+12%), whereas lettuce seedling growth was promoted by all the treatments, but with a greater effect with increasing auxin supplementation and when using E. maxima extract, compared to NAA. The results showed that the supplementation of exogenous synthetic auxin (NAA), or an E. maxima extract containing natural auxins, can have a growth-promoting effect on lettuce and tomato seedlings. This effect was more evident on lettuce than tomato. The biostimulant produced from E. maxima extracts improved seedling quality and promoted shoot and root growth more than the NAA used as a synthetic source of auxins.
Maintenance of neuronal polarity and regulation of cytoskeletal dynamics are vital during development and to uphold synaptic activity in neuronal networks. Here we show that soluble β-amyloid (Aβ) ...disrupts actin and microtubule (MT) dynamics via activation of RhoA and inhibition of histone deacetylase 6 (HDAC6) in cultured hippocampal neurons. The contact of Aβ with the extracellular membrane promotes RhoA activation, leading to growth cone collapse and neurite retraction, which might be responsible for hampered neuronal pathfinding and migration in Alzheimer's disease (AD). The inhibition of HDAC6 by Aβ increases the level of heterodimeric acetylated tubulin and acetylated tau, both of which have been found altered in AD. We also find that the loss of HDAC6 activity perturbs the integrity of axon initial segment (AIS), resulting in mislocalization of ankyrin G and increased MT instability in the AIS concomitant with loss of polarized localization of tau and impairment of action potential firing.
Autophagy is a highly conserved degradative process that conveys dysfunctional proteins, lipids, and organelles to lysosomes for degradation. The post-mitotic nature, complex and highly polarized ...morphology, and high degree of specialization of neurons make an efficient autophagy essential for their homeostasis and survival. Dysfunctional autophagy occurs in aging and neurodegenerative diseases, and autophagy at synaptic sites seems to play a crucial role in neurodegeneration. Moreover, a role of autophagy is emerging for neural development, synaptogenesis, and the establishment of a correct connectivity. Thus, it is not surprising that defective autophagy has been demonstrated in a spectrum of neurodevelopmental disorders, often associated with early-onset epilepsy. Here, we discuss the multiple roles of autophagy in neurons and the recent experimental evidence linking neurodevelopmental disorders with epilepsy to genes coding for autophagic/lysosomal system-related proteins and envisage possible pathophysiological mechanisms ranging from synaptic dysfunction to neuronal death.
Introduction
Postoperative pancreatic fistula (POPF) is common after distal pancreatectomy (DP). Whilst extensive investigation into potential predictors has been carried out, there is little ...evidence regarding POPF healing time.
Methods
This is a retrospective analysis of all consecutive DPs performed at the Department of General and Pancreatic Surgery, University of Verona Hospital Trust, from 2015 to 2019. Perioperative variables were analyzed identifying possible predictors of POPF healing time defined as days between surgery and last drain removal due to POPF.
Results
A total of 496 patients were included. POPF rate was 28.2% and median POPF healing time was 30 days (95% CI 28‐31). Independent predictors of POPF were body mass index (BMI) (OR 1.073, 95% CI 1.010‐1.147, p = 0.040), operative time (OR 95% CI 1.002–1.009, P = .003), and postoperative acute pancreatitis (OR 3.793, 95% CI, 1.852–7.767, P < .001). Independent predictors of POPF healing time were female sex (HR 1.323, 95% CI 1.093–1.998, P = .042), preoperative pancreatic enzyme replacement therapy (HR 2.319, 95% CI 1.195–4.498, P = .013), ASA score 3 (HR 0.278, 95% CI 0.119–0.646, P = .003), pancreatic transection with ultrasonic dissector (HR 0.605, 95% CI 0.404–0.907, P = .015), and positive drain cultures (HR 0.635, 95% CI 0.443–0.910, P = .013).
Conclusion
POPF healing after DP is a slow process since only half of patients recover within 30 days of surgery. A longer healing time can be predicted early in the postoperative period with significant implications in therapeutic choices.
Highlight
Andrianello and colleagues analyzed the healing time of pancreatic fistula after distal pancreatectomy. Fistula closure is a slow process as only half of patients recover within 30 days of surgery. ASA score, pancreatic transection with an ultrasonic dissector and positive drain cultures were found to be associated with slower healing.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction:
Postoperative pancreatic fistula (POPF) is the most dreaded complication after distal pancreatectomy (DP). This multicenter randomized trial evaluated the efficacy, safety, and ...tolerance of Hemopatch in preventing clinically relevant (grades B/C according to the ISGPS classification) POPF after DP.
Material and methods:
After stump closure, patients were randomized to affix Hemopatch to the stump or not. Statistical significance was set at 0.025. Clinical significance was defined as the number of patients needed to treat (NNT) to avoid 1 B/C POPF.
Results:
Of 631 eligible patients, 360 were randomized and 315 analyzed per protocol (155 in the standard closure group; 160 in the Hemopatch group). The rates of B/C POPF (the primary endpoint) were 23.2% and 16.3% (
P
= 0.120), while the number of patients with 1 or more complications (including patients with B/C POPF) was 34.8% and 24.4% (
P
= 0.049) in the standard and Hemopatch groups, respectively. In patients with hand-sewn stump and main duct closure, the rates were 26.2% versus 10.0% (
P
= 0.014) and 23.3% versus 7.7% (
P
= 0.015) in the standard and Hemopatch groups, respectively. The NNT in these 2 subgroups was 6 and 6.4, respectively.
Conclusion:
The results of the first randomized trial evaluating Hemopatch-reinforced pancreatic stump after DP to prevent type B/C POPF do not allow us to conclude that the risk of B/C POPF was lower. Based on the NNT, however, routine use of Hemopatch after DP may result in fewer complications (including POPF) overall, especially in cases with hand-sewn closure of the pancreatic stump or main pancreatic duct.
BRCA2 controls RAD51 recombinase during homologous DNA recombination (HDR) through eight evolutionarily conserved BRC repeats, which individually engage RAD51 via the motif Phe-x-x-Ala. Using ...structure-guided molecular design, templated on a monomeric thermostable chimera between human RAD51 and archaeal RadA, we identify CAM833, a 529 Da orthosteric inhibitor of RAD51:BRC with a Kd of 366 nM. The quinoline of CAM833 occupies a hotspot, the Phe-binding pocket on RAD51 and the methyl of the substituted α-methylbenzyl group occupies the Ala-binding pocket. In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionizing radiation, augmenting 4N cell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. Thus, chemical inhibition of the protein-protein interaction between BRCA2 and RAD51 disrupts HDR and potentiates DNA damage-induced cell death, with implications for cancer therapy.
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•CAM833 inhibits the protein-protein interaction between RAD51 and BRCA2•Crystal structure shows CAM833 binds RAD51 at the same site as the BRCA2 FxxA motif•CAM833 blocks formation of RAD51 foci and filaments, preventing DNA repair•CAM833 potentiates cytotoxicity by IR and synergises with PARP1 inhibitors
Scott et al. describe CAM833, an inhibitor of DNA recombinase RAD51, that binds at the site normally occupied by the BRC repeats of the BRCA2 protein. Through blocking this protein-protein interaction, CAM833 is able to prevent RAD51-mediated homologous recombination and thus potentiate cancer cells to damage by radiation or PARP1 inhibition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Label-free SERS is a powerful bio-analytical technique in which molecular fingerprinting is combined with localized surface plasmons (LSPs) on metal surfaces to achieve high sensitivity. Silver and ...gold colloids are among the most common nanostructured substrates used in SERS, but since protein-rich samples such as serum or plasma can hinder the SERS effect due to protein-substrate interactions, they often require a deproteinization step. Moreover, SERS methods based on metal colloids often suffer from a poor reproducibility. Here, we propose a paper-based SERS sampling method in which unprocessed human serum samples are first soaked on paper strips (0.4 × 2 cm
), and then mixed with colloidal silver nanoparticles by centrifugation to obtain a Centrifugal Silver Plasmonic Paper (CSPP). The CSPP methodology has the potential to become a promising tool in bioanalytical SERS applications: it uses common colloidal substrates but without the need for sample deproteinization, while having a good reproducibility both in terms of overall spectral shape (r > 0.96) and absolute intensity (RSD < 10%). Moreover, this methodology allows SERS analysis more than one month after serum collection on the paper strip, facilitating storage and handling of clinical samples (including shipping from clinical sites to labs).
Background
Pancreatic surgery is still a challenge even in high‐volume centers. Clinically relevant postoperative pancreatic fistula (CR‐POPF) represents the greatest contributor to major morbidity ...and mortality, especially following pancreatic distal resection. In this study, we compared robotic distal pancreatectomy (RDP) to open distal pancreatectomy (ODP) in terms of CR‐POPF development and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC).
Methods
We collected data from five high‐volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long‐term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA (American Society of Anesthesiologists) score, body mass index (BMI), final pathology, and TNM (Tumour, Node, Metastasis) staging system VIII ed.
Results
Two hundred and forty‐six patients who underwent 82 RDPs and 164 ODPs were included. No differences were found in the incidence of CR‐POPF. In the PDAC group, median DFS and OS were 10.8 months and 14.8 months in the ODP group and 10.4 months and 15 months in the RDP group, respectively.
Conclusions
Robotic distal pancreatectomy is a safe surgical strategy for PDAC and incidence of CR‐POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high‐volume and proficient centers.
Highlight
In this multicenter matched comparison analysis, Magistri and colleagues revealed that robotic distal pancreatectomy significantly reduced postoperative hospital stay, with equivalent incidence of clinically relevant pancreatic fistula, and similar survival rates in the adenocarcinoma subgroup, compared with open distal pancreatectomy. Robotic distal pancreatectomy is safe in patients with left‐sided pancreatic neoplasms.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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