Reduction In Size Research Articles

Pembrolizumab in Japanese patients with primary mediastinal large B-cell lymphoma: results from the KEYNOTE-A33 study.

KEYNOTE-A33 (NCT04317066) is an open-label, single-arm, phase 1 trial designed to evaluate the safety and efficacy of pembrolizumab in Japanese patients with relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBCL). Patients received pembrolizumab 200mg every 3weeks for up to 35 cycles. The primary endpoints were safety and objective response rate (ORR) per International Working Group 2007 criteria by independent central review. The secondary endpoint was disease control rate (DCR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. Seven patients were enrolled and treated; the median age was 32years (range 26-43) and 86% were female. The median time from the first dose to data cutoff (April 12, 2022) was 5.6months (range 2.4-21.2). Grade 3-5 treatment-related adverse events (AEs) occurred in 2 patients (29%; 2 grade 4 neutropenia, 1 grade 3 febrile neutropenia); however, no patient discontinued pembrolizumab or died because of treatment-related AEs. The ORR was 43% [95% confidence interval (CI) 10-82]. DCR was 57% (95% CI 18-90). Median DOR was not reached (NR). Four (57%) patients had a reduction in target lesion size of ≥ 50%. The median PFS was 2.9months (95% CI 2.6-NR). The median OS was 17.5months (95% CI NE-NE), and the 12months OS rate was 100%. Overall, pembrolizumab had manageable safety and clinically meaningful antitumor activity in Japanese patients with R/R PMBCL, results that were consistent with those observed in prior global studies. Registry and the Registration No. of the study/trial: Clinicaltrials.gov: NCT04317066.

The Z isomer of pyridoxilidenerhodanine 5'-phosphate is an efficient inhibitor of human pyridoxine 5'-phosphate oxidase, a crucial enzyme in vitamin B6 salvage pathway and a potential chemotherapeutic target.

Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, acts as a cofactor in many metabolic processes. In humans, PLP is produced in the reactions catalysed by pyridox(am)ine 5'-phosphate oxidase (PNPO) and pyridoxal kinase (PDXK). Both PNPO and PDXK are involved in cancer progression of many tumours. The silencing of PNPO and PDXK encoding genes determines a strong reduction in tumour size and neoplastic cell invasiveness in models of acute myeloid leukaemia (in the case of PDXK) and ovarian and breast cancer (in the case of PNPO). In the present work, we demonstrate that pyridoxilidenerhodanine 5'-phosphate (PLP-R), a PLP analogue that has been tested by other authors on malignant cell lines reporting a reduction in proliferation, inhibits PNPO in vitro following a mixed competitive and allosteric mechanism. We also show that the unphosphorylated precursor of this inhibitor (PL-R), which has more favourable pharmacokinetic properties according to our predictions, is phosphorylated by PDXK and therefore transformed into PLP-R. On this ground, we propose the prototype of a novel prodrug-drug system as a useful starting point for the development of new, potential, antineoplastic agents.

Assessment of Clinical Outcomes in Patients with Oral Lichen Planus and Oral Lichenoid Lesions (OLP & OLL) Following Treatment with Topical Corticosteroids

Objective: To assess the clinical outcomes in patients with oral lichen planus and oral lichenoid lesions (OLP & OLL) following treatment with topical corticosteroids. Methodology: A total of 175 patients diagnosed with OLP and OLL were recruited from the outpatient department. This cross-sectional study was conducted at Institute of Dentistry (IOD) & CMH, Lahore from July 2023 to December 2023. Inclusion criteria included patients aged 18 years and above with clinically and histopathologically confirmed OLP or OLL lesions. All enrolled patients received topical corticosteroid therapy according to a standardized protocol. Patients were instructed on proper application techniques and advised to adhere to the prescribed treatment regimen. Clinical evaluation of the oral mucosal lesions was performed at baseline and at regular follow-up. Outcome measures included changes in lesion size, severity of symptoms (pain, burning sensation), and overall improvement in clinical appearance. Results: The mean age of the patients was 52.4 years (SD: 10.3). In terms of gender distribution, among the included patients 25 patients (28.57%) were male and 25 patients (71.42%) were female. Among the symptoms observed, Pain was reported by 95 patients (54.28%), Burning Sensation by 110 patients (62.85%), Discomfort by 75 patients (42.85%), and Other symptoms by 20 patients (11.42%). In the clinical outcomes observed with topical corticosteroids, reduction in lesion size was noted in 140 patients, accounting for 80.0%, complete resolution of lesions occurred in 60 patients, representing 34.3%, and reduction in symptoms was reported by 155 patients, constituting 88.6%. Oral candidiasis was noted in 7 patients (4.0%), Mucosal atrophy occurred in 13 patients (7.42%), whereas the majority. Conclusion: In conclusion, our study underscores the efficacy of topical corticosteroid therapy in managing oral lichen planus (OLP) and oral lichenoid lesions (OLL). With 80.0% of patients experiencing a reduction in lesion size, 34.3% achieving complete resolution of lesions, and 88.6% reporting a reduction in symptoms, our findings highlight the significant therapeutic benefits of topical corticosteroids.

Synthesis of targeted doxorubicin-loaded gold nanorod −mesoporous manganese dioxide core–shell nanostructure for ferroptosis, chemo-photothermal therapy in vitro and in vivo

In the current study, a core–shell inorganic nanostructure comprising a gold nanorod core and −mesoporous manganese dioxide shell was synthesized. Then, the mesoporous manganese dioxide shell was loaded with doxorubicin (DOX) and then coated with pluronic F127 and pluronic F127-folic acid conjugate (1.5:1 wt ratio of pluronic F127: pluronic F127-folic acid conjugate) to prepare targeted final platform. In this design, mesoporous manganese dioxide acted as a reservoir for DOX loading, anti-hypoxia, and MRI contrast agent, while the gold nanorod core acted as a photothermal and CT scan imaging agent. DOX was encapsulated in the mesoporous manganese dioxide shell with a loading capacity and loading efficiency of 19.8 % ± 0.2 and 99.0 % ± 0.9, respectively. The in vitro release experiment showed the impact of glutathione (GSH), mildly acidic pH, and laser irradiating toward accelerated stimuli-responsive DOX release. The ·OH production of the prepared platform was verified by methylene blue (MB) decomposition reaction. Furthermore, thermal imaging exhibited the ability of the prepared platform to convert the NIR irradiation to heat. In vitro cytotoxicity tests on the folate receptor-positive 4 T1 cell line revealed the remarkable cytotoxicity of the targeted formulation compared to the nontargeted formulation (statistically significant). The MTT experiment demonstrated that exposure to laser 808 irradiation enhanced cytotoxicity of the targeted formulation (p < 0.0001). The production of ROS in 4 T1 cells following treatment with the targeted formulation was demonstrated by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Furthermore, in vivo investigations by implementing subcutaneous 4 T1 tumorized female BABL/c mice indicated that the prepared platform was an effective system in suppressing tumor growth by combining chemotherapy with PTT (photothermal therapy). Additionally, simultanous PTT and anti-hypoxic activity of this system showed potent tumor growth suppression impact. The percent of tumor size reduction in mice treated with FA-F127-DOX@Au-MnO2 + 808 nm laser compared to the control group was 99.7 %. The results of the biodistribution investigation showed tumor accumulation and modified pharmacokinetics of the targeted system. Lastly, 6 and 24 h post-intravenous injection, CT-scan and MR imagings capability of the prepared platform was verified in preclinical stage. The prepared multipurpose system introduces great opportunity to provide multiple treatment strategy along with multimodal imaging capability in a single platform for breast cancer treatment.

Abstract C028: Challenging PDAC adaptability: Uncovering therapeutic vulnerabilities in APE1 DNA repair mechanisms

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a therapeutically challenging malignancy notorious for its resilience to therapeutic strategies and ability to thrive under extreme conditions. The cancer's inherent ability to adaptively resist treatments underscores the need for novel and combinatorial therapeutic approaches. Our research focuses on elucidating the role of Apurinic-apyrimidinic endonuclease/Redox effector factor 1 (APE1/Ref-1), a critical multifunctional protein in PDAC pathobiology. APE1 serves two essential functions: as the principal endonuclease in the base excision repair (BER) pathway for DNA repair and as a redox regulator of transcription factors essential for cancer cell proliferation. While the therapeutic targeting of APE1’s redox function has been effective and continues to yield significant advances, the development of treatments aimed at its DNA repair function has proven more challenging with comparatively limited progress. Since standard PDAC treatment regimens involve DNA damaging agents potentially repaired via BER and APE1, we engineered three mutant cell lines with knock-in mutations resulting in a reduction of APE1’s BER activity while maintaining full redox activity. Biochemical evaluations confirmed the effects of the mutation, revealing a 30-fold reduction in DNA repair capacity. Surprisingly, with respect to growth and proliferation, the mutant and wild-type cell lines behaved similarly. Analyses of cytotoxic vulnerabilities revealed similar findings with the mutant lines exhibiting minimal phenotypic differences in sensitivity when challenged with cytotoxic and DNA damaging agents in proliferation-based assays. These findings led us to posit that the mutant cell lines were relying on compensatory DNA repair pathways which were providing sufficient compensation for the decrease in APE1 activity. We further hypothesized that the cell lines may still have hidden, long-term deficiencies in DNA damage processing which are not apparent during the initial stress response. Subsequent colony formation assays revealed that the mutant cell lines do exhibit poor long-term survival even after only short-term exposure to DNA damage. In vivo orthotopic mouse model experiments further corroborated these findings, showing a significant reduction in tumor size and decreased metastasis to the lungs and liver in mutant cell lines compared to wild-type controls. While APE1 is the primary endonuclease in the BER pathway, studies have demonstrated APE1-independent BER in rare, specific contexts. We are probing the hypothesis that these APE1-independent BER pathways function as the compensatory mechanism safeguarding these cells in short-term stress situations. Identifying and characterizing these backup pathways will not only offer a better understanding of APE1’s DNA repair capabilities within PDAC but will also provide a better understanding of how DNA repair mechanisms can be therapeutically targeted for novel therapeutic options or combinations. This opens the path to enhance standard of care treatments such as FOLFIRINOX. Citation Format: Eyram K Kpenu, Randall Wireman, Mahmut Mijiti, Silpa Gampala, Melissa L Fishel, Mark R Kelley. Challenging PDAC adaptability: Uncovering therapeutic vulnerabilities in APE1 DNA repair mechanisms [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C028.

Abstract B049: Oncolytic virotherapy as an effective tool to synergistically enhance therapeutic efficacy of standard systemic treatments for pancreatic cancer

Abstract Background: Standard therapies provide marginal benefits in overall survival and leading immunologic agents have proven ineffective in the immunologically cold environment of pancreatic ductal adenocarcinoma (PDAC). Current standard of care chemotherapies experience demonstrable resistance in the clinical setting with primary and secondary resistance frequently leading to poor outcomes. Oncolytic virus (OV) therapies are emerging as an avenue of therapeutic potential with vesicular stomatitis virus (VSV) providing an onco- selective platform with potential for rapid replication and minimal outside virulence. The aim of this project is to determine if the addition of OV to the standard systemic treatments would result in a synergistic improvement of the therapeutic efficacy, and investigate the potential mechanisms involved. Methods: A VSV variant containing the Morreton G protein inserted into a wild-type VSV backbone (VMG)was propagated and purified for in vitro and in vivo studies. In vitro studies investigating oncolytic potential and viral kinetics of VSV in combination with FOLFIRINOX (FFX) and Gemcitabine Paclitaxel (GP) therapies were compared to monotherapy in multiple cell culture formats including 2D Monolayer, 3D Spheroid, and ongoing investigation into patient derived organoids. Proteomics analysis of monotherapies along with combination therapy was performed on in vitro cultures. Ongoing in vivo studies are investigating the therapeutic potential of concurrent treatments. Results: Cytotoxicity assay studies of equivalent multiplicities of infection (MOI) demonstrated increased cytotoxicity of combination therapy (Percent viable 10.2% ± 1.3%) compared to virus alone (30.7% ± 1.9%) or FFX alone (84.4% ± 6.6%) in Hs766T PDAC cell lineAsPC-1 cell line demonstrated similar effects with minimal cytotoxicity from FFX alone (100% ± 5%) with comparable resistance to virus alone (69.9% ± 1.8%) in comparison to combination therapy (40.3% ± 1.0%). Additional cell lines including Panc-01 and MiaPaCa2 provided similar results. Treatment of formed spheroids with combination therapy resulted in reduction in overall size of spheroid along with increased Viral GFP marker fluorescence, in combination group, compared to monotherapy with each treatment. Proteomic analysis investigating concomitant treatment with both standards of care produced unique expression profiles. Multiple pathways including cell cycle regulation, apoptosis, MAPK signaling, PI3K-Akt signaling, ErbB signaling showed significant regulatory changes in protein expression across all treatment groups. Conclusion: VSV oncolytic virus in conjunction with standard of care therapy demonstrates a potentially effective approach for synergistic enhancement of the therapeutic efficacy against PDAC. Ongoing research is investigating the immunomodulatory and metabolic effects of both monotherapies in conjunction with combination therapy to further determine the synergistic mechanisms involved and how they can be further utilized to overcome treatment resistance in PDAC. Citation Format: Conner Hartupee, Amirsalar Mansouri, Joycelynn Coleman-Barnett, Dana Adamcova, Dorota Wyczechowska, Bolni Marius Nagalo, Mulu Tesfay, Jovanny Zabaleta, Luis Del Valle, John West, Jiri Adamec, Omeed Moaven. Oncolytic virotherapy as an effective tool to synergistically enhance therapeutic efficacy of standard systemic treatments for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B049.

Lycium barbarum polysaccharide increases thermogenesis and energy metabolism through modulation of the gut microbiota to confer resistance to cold temperatures.

Traditional Chinese medical literature contains numerous records of many traditional Chinese herbal medicines that exhibit efficacy in enhancing resistance to cold, yet there is a lack of scientific explanation. Lycium barbarum is among the herbal medicines that are explicitly documented to enhance resistance to cold in the "Ben Cao Gang Mu (Compendium of Materia Medica)". Herein, we investigated L. barbarum polysaccharide (LBP)-induced browning of inguinal white adipose tissue (iWAT), energy expenditure and thermogenic function in a long-term (4 months) treatment mouse model. LBP supplementation resulted in a significant reduction in weight and adipocyte size in iWAT, along with increased gut microbiota diversity. Specifically, the levels of Lachnospiraceae, Ruminococcaceae and Bacteroidaceae (short-chain fatty acid-producing bacteria) were elevated, leading to a higher level of short-chain fatty acids (SCFAs) in the caecal content. These effects subsequently triggered the release of glucagon-like peptide-1 (GLP-1) and activated the CREB/PGC1α signaling pathway in iWAT, thereby increasing energy expenditure and enhancing thermogenic function. The antibiotic treatment experiments confirmed that the LBP-mediated gut microbiota participated in the process of iWAT browning. In summary, our findings provide the first scientific explanation and mechanistic insights into the cold resistance of L. barbarum and identify potentially safe natural product supplements for individuals in alpine areas.

Abstract B031: Alternate pain management strategies: targeting pancreatic cancer-related pain with Flavonoid

Abstract Purpose For up to 90% of cancer patients, pain is a substantial symptom, contributing to morbidity and, possibly, mortality. In this study we sought to test the hypothesis that a flavonoid, derived from Cannabis, and previously shown to suppress cancer cell growth in vitro and tumor progression in mice in vivo, could also reduce the pain caused by pancreatic tumors in vivo. Methods A subcutaneous tumor in the dorsum of C57BL/6 mouse was generated by sub- dermal injection of KPC mouse pancreatic cancer cell line (ATCC). All the mice were video recorded to observe and analyze their spontaneous pain-related behaviors, including facial washing, dorsal hunching, dorsal skin twitch, licking of dorsal skin and overall locomotion around the cage. Two five minute recording sessions were analyzed by a blinded observer during times before the cancer cell injection (Baseline), after tumor growth, to about 8mm diameter (30d and 37d post-injection) and just before and then 24h after intra-tumor injection of the flavonoid ( Group A: FBL-03G, 1 nmole in 100µL) or Vehicle(100µL; Group B). Pain-related behavioral changes were averaged from the two recording sessions and analyzed from Baseline, just before FBL-03G and 24h after and compared between test compound-and vehicle injected groups (n=7 in each), using non-parametric statistics. Results Facial washing (events/5min) was: reduced to 87% of Baseline in tumor-bearing mice, then increased by 150% at 24h post-injection in Group A (FBL-03G); reduced to 65% of Baseline in tumor-bearing mice of Group B, then reduced a further 9% by Vehicle. Dorsal hunching, which events occur only after tumor growth (Baseline =0), was reduced at 24h by 62% in Group A but increased by 75% in Group B. Dorsal twitch, also absent before tumor growth, was reduced by 64% in Group A, but increased by 19% in Group B. Dorsal skin licking was reduced from Baseline by 33% in tumor-bearing mice of Group A, then increased by 76% after FBL-03g injection whereas licking, reduced by 22% by tumors in Group B and then by an additional 4% by vehicle (Group B). Tumors reduced locomotion by 58% in Group A, which was reversed by 32% after FBL-03g (Group A); vehicle injection resulted in a 38% reduction in locomotion (Group B). Thus, in 4 of the 5 pain-related behaviors from tumors quantitated symptoms were reversed by FBL-03G and oppositely affected, or not at all, by Vehicle. Conclusions These results indicate a substantial relief of spontaneous pain-related pain in this mouse model of pancreatic cancer. Such an acute effect occurs much more rapidly than the previously published in vitro suppression of KPC cell growth (assayed after 9-12d of treatment) or the reduction of tumor size (1-7 weeks) in vivo and suggest that the anti-hyperalgesic affect is due to mechanisms that do not involve reduction in tumor mass. The findings, using a single dose and a small number of mice, appear promising for further studies that examine a range of doses or FBL-03G and its actions in intra-pancreatic tumors. Citation Format: Sayeda Yasmin-Karim, Suheera Haq, Mike Makrigiorgos, Gary Strichartz, Geraud Richards, Natasha Rayman. Alternate pain management strategies: targeting pancreatic cancer-related pain with Flavonoid [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B031.

Techno-Economic Feasibility Study of Tractor Pto Operated Shredder Cum Pulverizer

India's agricultural sector faces a challenge of widespread crop residue burning. An estimated 90-140 million tonnes of crop residues are burned annually by farmers across the country. The shredder cum pulverizer focuses on the shredding and pulverizing of coconut husks and fronds (Cocos nucifera), corn stalks (Zea mays L.) and subabul branches (Leucaena leucocephala). This shredded and pulverized crop residue is used to prepare the vermin compost, biomass production and various other purposes. The experiment was conducted at the IGKV, Raipur (C.G.). The detailed specifications parameters were optimized for each unit of the shredder cum pulverier. This study was conducted with four levels of feed rate varies with four levels of different speeds of operation at four moisture content) as the independent parameters. Their effects were studied on dependent parameters. The detailed data were analyzed statistically by SPD (Split Plot Design) with the three replications. The various performance parameters were also calculated. The result of the experiments showed that the shredding capacity and size of reduction of the shredder cum pulverizer with different feed rates of crop residues of coconut husks, coconut fronds, corn stalks, and subabul branches at different feed rates are 79.65 kg/h, 86.98 kg/h, 82.65 kg/h, and 94.64 kg/h, respectively, and the resultant size reductions of crop residues are 1.26mm, 2.66mm, 1.73mm, and 2.57mm, respectively. The result showed that the maximum shredding capacity 94.64kg/h was found on subabul branches were observed at 400kg/h feed rate, 40m/s speed of operation and 24% moisture content and the maximum size of reduction 1.26mm was found on coconut husks were observed at 600kg/h feed rate, 70m/s speed of operation and 24% moisture content. The cost of operation of shredder cum pulverizer was observed to be 983.25 Rs/h.

Exploring macroalgae biorefinery: Extraction of bioactive compounds and production of volatile fatty acids

Macroalgae have gained significant attention in recent research owing to their potential as novel food source and their noteworthy nutritional properties. However, a substantial amount of these macroalgae accumulates along the coast without being utilized, highlighting the need for proper treatment and disposal methods to mitigate secondary pollution effects. Previous studies on macroalgae have primarily focused on extracting bioactive compounds or anaerobic digestion processes to produce methane or volatile fatty acids (VFA), with observed improvements following different pre-treatments. In this study, three biorefinery options for macroalgae have been compared. Additionally, the extraction of bioactive compounds followed by VFA production is proposed as a promising new valorization strategy. Milled macroalgae exhibited a low methane production yield (138 ± 17 NmL CH4·g volatile solid−1), corresponding to 31 ± 4 % biodegradability, while the acidification percentage was higher (45 ± 1%). Among the three solvents applied (water, ethanol and acetone), ethanol (80%) at 25 °C was the most effective in recovering bioactive compounds, such as chlorophylls, sugars, and phenolic compounds with antioxidant activity. The extraction of chlorophylls and phenolic compounds was not influenced by particle size reduction. However, a more efficient extraction of sugars was observed with lower particle size. Moreover, ethanol treatment demonstrated the good efficiency in VFA production, reaching up to 3.6 ± 0.2 g VFA-(chemical oxygen demand, COD)·L−1, with a VFA spectrum (in COD basis) consisting of 51% acetic acid, 29% propionic acid, 5% i-butyric acid, 7% butyric acid, and 7% i-valeric acid. These findings highlight the potential of ethanol for efficient compound recovery and VFA production from macroalgae.

448 Interactive effects of extrusion and particle size reduction of corn on metabolizable energy by weanling pigs

Abstract The objective was to test the hypothesis that there are interactive effects of extrusion and reduction of the particle size of corn on apparent total tract digestibility (ATTD) of gross energy (GE) and digestible energy (DE) and metabolizable energy (ME) when fed to weanling pigs. Six corn-based diets were arranged in a 3 × 2 factorial with 3 particle sizes of corn (i.e., 700, 500, or 300 μm) and two forms (i.e., meal or extruded corn). The daily feed allowance was limited to 3.0 times the energy requirement for maintenance and pigs had free access to water. Pigs [n = 48; initial body weight (BW) = 12.8 kg; SD = 1.32) were housed in metabolism crates and allotted to the 6 diets using a randomized complete block design with two blocks. Fecal and urine samples were quantitatively collected for 4 d following 5 d of adaptation. The statistical model included diet as fixed effect and block as random effect. Contrast coefficients were used to determine effects of extrusion, linear effects of particle size, and the interaction. Results indicated that the ATTD of GE and DE and ME in corn increased by reducing the particle size of corn only if corn was in a meal form, but that was not the case for extruded corn (interaction; P &amp;lt; 0.001; Table 1). Regardless of particle size, the ATTD of GE and DE and ME in corn were increased (P &amp;lt; 0.001) by extrusion. In conclusion, reducing particle size of corn had a positive impact on energy digestibility in non-extruded corn. Regardless of particle size, extrusion of corn increased energy digestibility and DE and ME, which is likely a result of starch gelatinization in extruded corn. However, the effects of reducing particle size and extrusion were not additive, which indicates that it is not necessary to grind corn to 500 or 300 μm before extrusion.

A rare case of pancreatic pseudocyst-portal vein fistula in a patient with chronic pancreatitis.

A 60-year-old female with chronic pancreatitis and a history of splenectomy presented with epigastric pain, vomiting, and asthenia. Elevated pancreatic enzymes and CT imaging revealed a pseudocyst in the pancreatic head with suspected communication to the portal vein, confirmed by MR Cholangiopancreatography and endoscopic ultrasound (EUS). EUS-guided puncture revealed high amylase levels. Given her manageable symptoms, a conservative approach was adopted, leading to symptomatic relief and pseudocyst size reduction. Pancreatic pseudocyst-portal vein fistula is a rare pancreatitis complication, challenging to diagnose, with no gold-standard treatment. Endoscopic stenting offers a promising alternative to surgery for severe cases.

Cost-effective task offloading and trajectory optimization in UAV assisted edge networks with DDPG

Purpose Unmanned aerial vehicles (UAVs), known for their exceptional flexibility and maneuverability, have become an integral part of mobile edge computing systems in edge networks. This paper aims to minimize system costs within a communication cycle. To this end, this paper has developed a model for task offloading in UAV-assisted edge networks under dynamic channel conditions. This study seeks to efficiently execute task offloading while satisfying UAV energy constraints, and validates the effectiveness of the proposed method through performance comparisons with other similar algorithms. Design/methodology/approach To address this issue, this paper proposes a task offloading and trajectory optimization algorithm using deep deterministic policy gradient, which jointly optimizes Internet of Things (IoT) device scheduling, power distribution, task offloading and UAV flight trajectory to minimize system costs. Findings The analysis of simulation results indicates that this algorithm achieves lower redundancy compared to others, along with reductions in task size by 22.8%, flight time by 34.5%, number of IoT devices by 11.8%, UAV computing power by 25.35% and the required cycle for per-bit tasks by 33.6%. Originality/value A multi-objective optimization problem is established under dynamic channel conditions, and the effectiveness of this approach is validated.

Comparative genomic analysis of thermophilic fungi reveals convergent evolutionary adaptations and gene losses

Thermophily is a trait scattered across the fungal tree of life, with its highest prevalence within three fungal families (Chaetomiaceae, Thermoascaceae, and Trichocomaceae), as well as some members of the phylum Mucoromycota. We examined 37 thermophilic and thermotolerant species and 42 mesophilic species for this study and identified thermophily as the ancestral state of all three prominent families of thermophilic fungi. Thermophilic fungal genomes were found to encode various thermostable enzymes, including carbohydrate-active enzymes such as endoxylanases, which are useful for many industrial applications. At the same time, the overall gene counts, especially in gene families responsible for microbial defense such as secondary metabolism, are reduced in thermophiles compared to mesophiles. We also found a reduction in the core genome size of thermophiles in both the Chaetomiaceae family and the Eurotiomycetes class. The Gene Ontology terms lost in thermophilic fungi include primary metabolism, transporters, UV response, and O-methyltransferases. Comparative genomics analysis also revealed higher GC content in the third base of codons (GC3) and a lower effective number of codons in fungal thermophiles than in both thermotolerant and mesophilic fungi. Furthermore, using the Support Vector Machine classifier, we identified several Pfam domains capable of discriminating between genomes of thermophiles and mesophiles with 94% accuracy. Using AlphaFold2 to predict protein structures of endoxylanases (GH10), we built a similarity network based on the structures. We found that the number of disulfide bonds appears important for protein structure, and the network clusters based on protein structures correlate with the optimal activity temperature. Thus, comparative genomics offers new insights into the biology, adaptation, and evolutionary history of thermophilic fungi while providing a parts list for bioengineering applications.

Pluronic F127-Complexed PEGylated Poly(glutamic acid)-Cisplatin Nanomedicine for Enhanced Glioblastoma Therapy.

Glioblastoma is one of the most aggressive and treatment-resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127-complexed PEGylated poly(glutamic acid)-cisplatin (PLG-PEG/PF127-CDDP). PLG-PEG/PF127-CDDP demonstrated an optimal size of 133.97±12.60nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half-maximal (50%) inhibitory concentration (IC50) of 12.61µgmL-1 at 48h and a 72.53%±1.89% reduction in cell invasion. Furthermore, PLG-PEG/PF127-CDDP prolonged the circulation half-life of cisplatin to 9.75h in vivo, leading to a more than 50% reduction in tumor size on day 16 post-treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG-PEG/PF127-CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer-based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications.

Osmotic energy harvesting using acrylic acid hydrogel PET membrane

In this study, we investigated the osmotic energy harvesting using a cation-selective membrane. The cation-selective membrane was synthesized by the incorporation of acrylic acid hydrogel in a porous support membrane. FTIR analysis and SEM images confirmed the presence of the acrylic acid hydrogel rods inside the porous support material. The exposure of the acrylic acid hydrogel PET (AP) membrane to a concentration gradient culminated in the generation of electric power. The AP membrane was evaluated in regard to the following parameters: EDiff, Io, Pmax and t+. The maximum power obtained with the membrane was 1.10 μW at the 40-fold concentration gradient (test area∽ 100 mm2). Increasing the concentration gradient increased the power output. However, a decrease in power output was observed after a certain value of the concentration gradient. An enhancement in power output was noted as the fraction of acrylic acid within the membrane was augmented. Additionally, the cation transference number also increased owing to a high charge density and a reduction in the mesh size. The AP membrane was also investigated in acidic and basic media. The time-dependent study revealed the superior chemical stability of the AP membrane.

Transduced Olfactory Mucosa Cells Expressing Nerve Growth Factor for the Therapy of Experimental Spinal Cord Cysts.

A new gene-cell construct expressing nerve growth factor (NGF) has been developed. After obtaining engineered adenovectors Ad5-RGD-CAG-NGF and Ad5-RGD-CAG-EGFP, transduction efficiency and transgene expression were studied and multiplicity of infection was determined. The efficacy of transduced human olfactory ensheathing cells expressing NGF in restoring motor activity in rats has been shown in a limited period of time. Improved rat hindlimb mobility and cyst size reduction after gene-cell construct transplantation were more likely due to the cellular component of the construct.

Dewatering promoting of carbon-rich coal gasification coarse slag by size reduction with surface modification

ABSTRACT Coal gasification coarse slag (CGCS) has become a bulk coal-based solid waste that threatens the ecological environment. The high moisture content of carbon-rich coal coarse gasification slag (CR-CGCS) seriously limits its utilization. In this study, a pore water releasing method was proposed to promote the dewatering of CR-CGCS through size reduction with surface modification. Hexadecyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and kerosene were added during the grinding process, respectively. The results showed that kerosene can significantly improve the dewatering efficiency of CR-CGCS more than CTAB and SDS. The final moisture content of the CR-CGCS could be reduced from 47.50% to 33.01%. The SEM and FTIR results illustrated that kerosene could effectively reduce the content of oxygen-containing functional groups on the surface of CR-CGCS more than CTAB and SDS. Meanwhile, the PVM results showed that CR-CGCS modified by kerosene tended to form hydrophobic agglomerates. The LF-NMR results indicated that only the water in the macropores of CR-CGCS could be released in grinding process, but the water in micropores could be reduced when kerosene, CTAB, or SDS was added in grinding. This study provides new insight into enhancing the dewatering of CR-CGCS and theoretical support for the efficient utilization of CR-CGCS.

A 96-position platform for magnetic sorbent-based dispersive microextraction: Application to the determination of tetrahydrocannabinol and cannabidiol in saliva of cannabis smokers

BackgroundIn order to obtain sustainable analytical methods, it is essential to develop kinetically efficient sample preparation strategies in which equilibria are reached faster, as dispersive extraction techniques. In addition, the higher the reduction in size, the higher number of extraction vessels can be located and thus the higher number of samples can be simultaneously treated. All this increases sample throughput, and contributes to the reduction of chemical waste, and energy and sample consumption. In this sense, multiposition extraction platforms are smart strategies to achieve these goals, but they are scarcely developed for dispersive extraction techniques. ResultsTaking miniaturized stir bar sorptive dispersive microextraction (mSBSDME) as a starting point, a 96-position extraction platform has been developed using a 96-position stirring plate and a tailor-designed 3D-printed support for locating the miniaturized extraction vessels, achieving a high-throughput miniaturized sample preparation strategy. In order to show the applicability of this novel platform, the determination of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in human saliva has been carried out and applied to samples collected after the consumption of marijuana and legal CBD-rich cannabis. Only 100 μL of saliva were needed for the analysis and good analytical features in terms of linearity (at least up to 500 ng mL−1), limits of detection (0.7 and 2.8 ng mL−1 for THC and CBD, respectively), and precision (RSD ≤ 14 %) were achieved. SignificanceThe miniaturization of the vessel allows the use of small volumes of sample (i.e., a few microliters) and the treatment of 96 samples in parallel, being the first proposal for carrying out dispersive sorbent-based microextraction under the concept of 96-well format. Additionally, this new workflow contributes to the development of analytical methods that meet the three pillars of sustainability, i.e., greenness and easily affordable in terms of economics and applicability.

The influence of nano structuring and combined doping (Ag and Sb) on the thermoelectric properties of PbTe thin films

Nanocrystalline PbTe and Ag & Sb co-doped PbTe thin films are prepared using an integrated physical-chemical approach by evaporating chemically synthesized PbTe and Ag & Sb co-doped PbTe nanopowders on glass substrates. The X-Ray Diffractogram (XRD) reveals that all samples are NaCl-type structure and the structural parameters such as crystallite size D, dislocation density δ, strain ε, lattice constant, volume of the cell and number of crystallites are calculated and reported the results. The crystallite size of the films is around 24 nm. The absolute value of the Seebeck coefficient of nanocrystalline PbTe and Ag and Sb co-doped PbTe thin films is 1.069 mV/K and 0.569 mV/K respectively and the positive values indicate their p-type conductivity of the film. The values of Seebeck coefficient and power factor are higher than that of bulk which implies an enhancement in the thermoelectric properties with a reduction in the particle size and co doping.