Favorable Characteristics Research Articles

Assessment of bioactive peptides derived from laminin-111 as prospective breast cancer-targeting agents

Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the α1, β1, and γ1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (131I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [131I]I-YIKVAV and [131I]I-YIGSR. Conversely, [131I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from − 2.12 to − 1.10. Serum protein binding assay for [131I]I-YIKVAV and [131I]I-YIGSR reached ≅ 48% and ≅ 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and β1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.

Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma.

Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8+ T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-α (TNF-α), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.

Integrated Waterflooding Effect Evaluation Methodology for Carbonate Fractured–Vuggy Reservoirs Based on the Unascertained Measure–Mahalanobis Distance Theory

The waterflooding effect evaluation of carbonate fractured–vuggy reservoirs constitutes a comprehensive multiple-information decision-making process involving quantitative unascertained measure theory. This paper establishes a novel comprehensive methodology to evaluate the waterflooding effects of carbonate fractured–vuggy reservoirs for the first time. A new evaluation grading criteria is proposed using the Mahalanobis distance method based on the multi-index comprehensive unascertained measure theory derived from a modified five-scale analytical hierarchy process–entropy weight method. The actual field data from the carbonate fractured–vuggy reservoirs and the nine evaluation indices are specifically applied to demonstrate the calculation process for the construction of the grading system model on the waterflooding effects and to verify the accuracy of the Mahalanobis distance method by comparing the calculation results with the Minkowski and Euclidean distance methods. The proposed methodology facilitates the effective evaluation of the waterflooding strategies implemented in carbonate fractured–vuggy reservoirs with three categories; the ones with outstanding performance usually demonstrated favorable index characteristics, with substantial contributions to the enhanced oil recovery, manifesting with complete well patterns, a balance in the injection–production dynamics, excellent waterflooding utilization, and control competence. In contrast, fractured–vuggy units with fair waterflooding performance revealed limitations in the enhanced oil recovery. It can also be inferred that the mediocre waterflooding performance of the fractured–vuggy units is associated with incomplete well patterns, an imbalance in the injection–production dynamics, low waterflooding utilization, and a negligible waterflooding effect. The results in this study show that this newly proposed integrated model can effectively assess the waterflooding effects quantitatively and provide a more precise scientific basis for evaluating the waterflooding effects in carbonate fractured–vuggy reservoirs, with potential applicability in other fields.

Design and Characterization of Compact, Programmable, Multistranded Nonimmunostimulatory Nucleic Acid Nanoparticles Suitable for Biomedical Applications.

We report a thorough investigation of the role of single-stranded thymidine (ssT) linkers in the stability and flexibility of minimal, multistranded DNA nanostructures. We systematically explore the impact of varying the number of ssTs in three-way junction motifs (3WJs) on their formation and properties. Through various UV melting experiments and molecular dynamics simulations, we demonstrate that while the number of ssTs minimally affects thermodynamic stability, the increasing ssT regions significantly enhance the structural flexibility of 3WJs. Utilizing this knowledge, we design triangular DNA nanoparticles with varying ssTs, all showing exceptional assembly efficiency except for the 0T triangle. All triangles demonstrate enhanced stability in blood serum and are nonimmunostimulatory and nontoxic in mammalian cell lines. The 4T 3WJ is chosen as the building block for constructing other polygons due to its enhanced flexibility and favorable physicochemical characteristics, making it a versatile choice for creating cost-effective, stable, and functional DNA nanostructures that can be stored in the dehydrated forms while retaining their structures. Our study provides valuable insights into the design and application of nucleic acid nanostructures, emphasizing the importance of understanding stability and flexibility in the realm of nucleic acid nanotechnology. Our findings suggest the intricate connection between these ssTs and the structural adaptability of DNA 3WJs, paving the way for more precise design and engineering of nucleic acid nanosystems suitable for broad biomedical applications.

GT-00AxIL15, a Novel Tumor-Targeted IL-15-Based Immunocytokine for the Treatment of TA-MUC1-Positive Solid Tumors: Preclinical In Vitro and In Vivo Pharmacodynamics and Biodistribution Studies.

GT-00AxIL15 is a novel interleukin-15-based immunocytokine targeting a tumor-specific, glycosylated epitope of MUC1 (TA-MUC1). We characterized mode of action, pharmacokinetic (PK) and pharmacodynamic (PD) properties and investigated the relevance of TA-MUC1 binding for the concept of delivering IL-15 to solid tumors. In vitro pharmacology was analyzed in binding and cell-based assays. The in vivo PK profile and IL-15-mediated PD effects of GT-00AxIL15 were investigated in tumor-free mice. Tumor accumulation, immune infiltration and anti-tumor activity were assessed in TA-MUC1+ syngeneic and xenogeneic murine tumor models. GT-00AxIL15 was shown to specifically bind TA-MUC1 on tumor cells via its mAb moiety, to IL-15 receptors on immune cells via its IL-15 fusion modules and to FcγRs via its functional Fc-part. In vitro, NK, NKT and CD8+ T cells were activated and proliferated, leading to anti-tumor cytotoxicity and synergism with antibody-dependent cellular cytotoxicity (ADCC)-mediating mAbs. In vivo, GT-00AxIL15 exhibited favorable PK characteristics with a serum half-life of 13 days and specifically accumulated in TA-MUC1+ tumors. In the tumor microenvironment, GT-00AxIL15 induced robust immune activation and expansion and mediated anti-metastatic and anti-tumor effects in syngeneic and xenograft tumor models. These results support the rationale to improve PK and anti-tumor efficacy of IL-15 by increasing local concentrations at the tumor site via conjugation to a TA-MUC1 binding mAb. The tumor-selective expression pattern of TA-MUC1, powerful immune activation and anti-tumor cytotoxicity, long serum half-life and tumor targeting properties, render GT-00AxIL15 a promising candidate for treatment of solid tumors with high medical need, e.g., ovarian, lung and breast cancer.

P979 Diet, disease activity and extraintestinal symptoms in IBD outpatients

Abstract Background Patients with inflammatory bowel disease (IBD) show higher rates of fatigue and symptoms of depression and anxiety. Growing evidence reports a beneficial influence of plant- based diets on IBD as well as psychological disorders. The Mediterranean diet shows favorable characteristics in this regard and is simple to implement. We aimed to examine adherence to a Mediterranean diet as well as its associations with disease activity, quality of life and fatigue or affective symptoms in outpatients with IBD. Methods We delivered questionnaires to IBD outpatients, assessing adherence to the Mediterranean diet (MEDAS), symptoms of depression and anxiety (HADS), as well as fatigue (FACIT-F) and quality of life (SHS). Disease activity was measured with HBI or pMS, respectively. Associations between the parameters were determined using spearman correlation. Results We collected data of n=281 patients. Adherence to the Mediterranean diet was generally low in our sample with a median MEDAS score of 6 (0-13). The greatest deficit was observed in the regular consumption of fish (10 %) and fruit (16.6 %). However, we found a very high adherence for olive oil as the main source of fat (81.9 %), as well as a preference for white meat over red meat and processed meats (63.7 %). The prevalence of depressive symptoms (HADS-D ≥ 8) was 22.4 %, while symptoms of anxiety (HADS-A ≥ 8) were found in 35.9 % of the participants. Severe fatigue (FACIT < 30) was present in 33.8 % of the patients. Patients with clinically active disease were more likely to experience fatigue (ρ=-.231, p=<.001), symptoms of anxiety (ρ=.132, p=.010), depressive symptoms (ρ=.216 p=<.001), and reduced quality of life (ρ=.359, p<.001), all Figure 1a. There were no significant associations between the MEDAS score and disease activity (ρ=.033, p=.522), fatigue (ρ=-.009, p=.831), anxiety symptoms (ρ=.049, p=.294), or depressive symptoms (ρ=-.035, p=.461). Women showed significantly higher adherence to Mediterranean diet (mean MEDAS score 5.2 vs. 6, p=.003). We found a negative correlation between adherence to Mediterranean diet and level of calprotectin (ρ=-.146, p=.023, Figure 1b). Conclusion The preliminary analysis of our sample suggests low levels of adherence to the Mediterranean diet in our patient population. Contrary to our expectation, there were no statistically significant associations between diet and disease activity, quality of life, or psychological complaints. However, the inverse correlation between adherence to Mediterranean diet and level of calprotectin can support the anti-inflammatory characteristics this diet. It remains unclear, to which intent an anti-inflammatory diet can impact the course of disease and clinical symptoms in patients with IBD.

Label-Free Optical Technologies for Middle-Ear Diseases.

Medical applications of optical technology have increased tremendously in recent decades. Label-free techniques have the unique advantage of investigating biological samples in vivo without introducing exogenous agents. This is especially beneficial for a rapid clinical translation as it reduces the need for toxicity studies and regulatory approval for exogenous labels. Emerging applications have utilized label-free optical technology for screening, diagnosis, and surgical guidance. Advancements in detection technology and rapid improvements in artificial intelligence have expedited the clinical implementation of some optical technologies. Among numerous biomedical application areas, middle-ear disease is a unique space where label-free technology has great potential. The middle ear has a unique anatomical location that can be accessed through a dark channel, the external auditory canal; it can be sampled through a tympanic membrane of approximately 100 microns in thickness. The tympanic membrane is the only membrane in the body that is surrounded by air on both sides, under normal conditions. Despite these favorable characteristics, current examination modalities for middle-ear space utilize century-old technology such as white-light otoscopy. This paper reviews existing label-free imaging technologies and their current progress in visualizing middle-ear diseases. We discuss potential opportunities, barriers, and practical considerations when transitioning label-free technology to clinical applications.

90Y]Yttria Alumino Silicate Glass Microspheres: A Biosimilar Formulation to "TheraSphere" for Cost-Effective Treatment of Liver Cancer.

Background: Selective internal radiation therapy (SIRT) using a suitable β--emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 (90Y) [T1/2 = 64.2 h, Eβ(max) = 2.28 MeV, no detectable γ-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics. Objective: The present study describes indigenous development and evaluation of intrinsically radiolabeled [90Y]yttria alumino silicate ([90Y]YAS) glass microsphere, a formulation biosimilar to "TheraSphere" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients. Methods: YAS glass microspheres of composition 40Y2O3-20Al2O3-40SiO2 (w/w) and diameter ranging between 20 and 36 μm were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [90Y]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to in vitro evaluations and in vivo studies in healthy Wistar rats, customized doses of [90Y]YAS glass microspheres were administered in human patients. Results: [90Y]YAS glass microspheres were produced with 137.7 ± 8.6 MBq/mg YAS glass (∼6800 Bq per microsphere) specific activity and 99.94% ± 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent in vitro stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [90Y]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe. Conclusions: The study confirmed the suitability of indigenously prepared [90Y]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma.

PEGylated porcine-human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications.

The growing prevalence of hyperuricemia necessitates the urgent development of more potent treatments. This study aimed to develop, optimize, and evaluate the safety and efficacy of porcine-human recombinant uricase (PHRU) both in vitro and in vivo. The study employed gene editing of PHRU through site-directed mutagenesis, with recombinant proteins expressed in vitro utilizing Escherichia coli. The polyethylene glycol (PEG) approach was employed to augment uricase stability and diminish immunogenicity. The pharmacokinetics and pharmacodynamics of PHRU were tested in vitro and in Sprague Dawley rats. Successful expression of the fusion protein in E. coli and the development of the PEGylated drug were achieved. In vitro experiments confirmed the efficacy of PEG-PHRU in degrading uric acid, with PEGylation not markedly affecting the biological activity of PHRU. Animal studies revealed that PEG-PHRU significantly lowered plasma uric acid levels and mitigated hyperuricemia-induced renal damage in rats. Both drug metabolism and pharmacokinetics exhibited favorable characteristics without observable adverse effects in experimental animals. This novel fusion protein shows the potential for ameliorating hyperuricemia and related renal complications, highlighting it as a promising drug candidate with substantial market applications.

Clinical application of 99mTc‐labeled peptides for tumor imaging: Current status and future directions

AbstractTargeting receptors overexpressed on cancer cells with radiolabeled peptides has become a crucial aspect of molecular imaging in oncology. Small peptides offer favorable characteristics for tumor targeting with minimal side effects and toxicity owing to their small size and simple radiolabeling protocols. Among them, somatostatin analogs have received regulatory approval for the diagnosis and treatment of neuroendocrine tumors. Cyclic RGD (Arg‐Gly‐Asp) peptides, bombesin analogs, and glucagon‐like peptide‐1 analogs are currently under development and/or undergoing clinical trials. The most used radionuclides for tumor imaging include 99mTc and 111In for single‐photon emission computed tomography, 68Ga and 18F for positron emission tomography. This review highlights the clinical potential and future prospects of 99mTc‐labeled peptides for tumor imaging.

Computational exploration of microsomal cytochrome P450 3A1 enzyme modulation by phytochemicals of Cichorium intybus L.: Insights into drug metabolism.

Drug metabolism plays a crucial role in drug fate, including therapeutic inactivation or activation, as well as the formation of toxic compounds. This underscores the importance of understanding drug metabolism in drug discovery and development. Considering the substantial costs associated with traditional drug development methods, computational approaches have emerged as valuable tools for predicting the metabolic fate of drug candidates. With this in mind, the present study aimed to investigate the potential mechanisms underlying the modulation of microsomal cytochrome P450 3A1 (CYP3A1) enzyme activity by various phytochemicals found in Cichorium intybus L., commonly known as chicory. To achieve this goal, several in silico methods, including molecular docking and molecular dynamics (MD) simulation, were employed to explore computationally the microsomal CYP3A1 enzyme. Schrodinger software was utilized for the molecular docking study, which involved the interaction analysis between CYP3A1 and 28 phytoconstituents of Cichorium intybus. Virtual screening of 28 compounds from chicory led to the identification of the top five ranked compounds. These compounds were evaluated for drug-likeness properties, pharmacokinetic profiles, and predicted binding affinities to CYP3A1. Caffeoylshikimic acid and cichoric acid emerged as promising candidates due to their favorable characteristics, including good oral bioavailability and high binding affinities to CYP3A1. Molecular dynamics simulations were conducted to assess the stability of caffeoylshikimic acid within the CYP3A1 binding pocket. The results demonstrated that caffeoylshikimic acid maintained stable interactions with the enzyme throughout the simulation, suggesting its potential as an effective modulator of CYP3A1 activity. The findings of this study have the potential to provide valuable insights into the complex molecular mechanisms by which Cichorium intybus L. acts on hepatocytes and modulates CYP3A1 enzyme expression or activity. By elucidating the impact of these phytochemicals on drug metabolism, this research contributes to our understanding of how chicory may interact with drugs and influence their efficacy and safety profiles.

OME[formula omitted]/air mixtures: The structure and propagation mechanism of their laminar premixed flames

Oxymethylene dimethyl ethers (CH3O(CH2O)xCH3 or OMEx) are synthetic substitutes of diesel and jet fuel. They can achieve soot-less combustion and have been shown to exhibit favourable ignition characteristics. With the aim to explore their combustion physics, the structure of their flames is analysed using the algorithmic tools of the Computational Singular Perturbation (CSP) method. It is demonstrated that the flame structure and the mechanism for its propagation is encapsulated in the fastest explosive mode, introduced by chemical dynamics in a narrow region of the flame front. This narrow region extends around the point where the maximum heat release rate (MHRR) is recorded. CSP diagnostics identify (i) reactions H + O2→ O + OH and CO + OH → CO2 + H beyond MHRR as initiating an upstream diffusion of heat and H radicals, both of which are generated by the exothermic reaction H2 + OH → H2O + H, (ii) a downstream convective motion that ensues and (iii) chemical activity that is initiated ahead of MHRR and sustained by the convective transport of fuel and oxygen. CSP also identifies differences in the action of the upstream diffusion of heat and H radicals and of the downstream transport of fuel and oxidiser. It is also shown that the fastest explosive mode far from the neighbourhood of MHRR has no influence on the structure and propagation of the flame front. Although OME2−4/air mixtures exhibit drastically different dynamics in the context of homogeneous autoignition, very small differences are recorded in terms of flame structure and propagation. The findings suggests that, since practically all major processes driving the flame front propagation are similar to those of hydrocarbons, OMEx fuels can be used as “drop-in” fuels in currently employed burners.

Patterns of surgery and adjuvant therapy in pancreatic carcinoid tumor: An NCDB analysis.

631 Background: Pancreatic Carcinoid Tumor (PCT) is a neuroendocrine tumor (NET) of the gastrointestinal (GI) tract composed of Argentaffin cells. Of the primary pancreatic cancers, NETs are exceedingly rare in comparison to pancreatic adenocarcinoma, accounting for less than 2% of pancreatic cancer diagnoses. PCTs constitute for only a subset of these and hold a better prognosis than adenocarcinoma (What Is a Pancreatic Neuroendocrine Tumor? | American Cancer Society, n.d.). GI carcinoid tumors classically originate in the appendix, ileum, or rectum, and are seldom a primary neoplasm of the pancreas. PCTs generate secretory products with Serotonin being the most frequently isolated. Some cases may produce a carcinoid syndrome with characteristic diarrhea, cutaneous flushing, and bronchospasm (Ha & Tan, 2012). Surgical resection is the hallmark of treatment, though other modalities of management are available. Due to the rarity of PCT, no significant study exists in the literature analyzing the association of survival with receipt of surgery or predictors of receipt of surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PCT from 2004 to 2019 using the histology codes 8240 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, Binary Logistic Regression and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α = 0.05. Results: 2237 patients with PCT formed the final sample, with an average age of 61 years of age. 724 patients (32.3%) underwent surgery of the primary site, 72 (3.2%) received adjuvant chemotherapy, and 9 (0.4%) received adjuvant radiation. Surgery alone was associated with the longest median survival ( 198.5 months) compared to the other treatments ( Adjuvant chemotherapy=155.3 months, Adjuvant radiation=122.7 months, No surgery=73.95 months; p<0.05). After controlling for covariates, receipt of surgery was independently associated with decreased overall mortality ( HR=.380; p<0.05). Decreased age, lower grade tumors, and fewer positive regional lymph nodes were significantly associated with increased odds of receiving surgery. Additionally, treatment at an academic facility and private insurance status was associated with significantly higher rates of surgery. Patients who did not receive surgery were significantly older, had later stage disease, higher co-morbidity scores, and larger tumor size. Income level and race had no effect on treatment selection. Conclusions: This study found that surgery alone without adjuvant therapy is independently associated with improved survival. Favorable clinical characteristics may be contributing to this discrepancy in survival. Further exploration of treatment strategies in PCT may benefit patients through the creation of definitive treatment guidelines to manage this disease.

Registration of ‘CLL17’ rice

Abstract‘CLL17’ (Reg. no. CV‐160; PI 693941), a high‐yielding long‐grain rice (Oryza sativa L.) cultivar, was developed by the Louisiana State University Agricultural Center at the H. Rouse Caffey Rice Research Station near Crowley, LA, and approved for release in 2020. CLL17 contains the herbicide‐resistant gene for use in the Clearfield rice production system. The Clearfield rice production system is defined as the brand of rice cultivars that are tolerant to imidazolinone herbicides. CLL17 was derived from the cross ‘CL131’/‘Trenasse’. It showed good yield potential and favorable agronomic characteristics in the 2015 Clearfield Preliminary Yield Trial. In 2016, it was evaluated in the uniform regional rice nursery trial across four southern states. From 2017 to 2022, CLL17 was evaluated in 50 replicated trials across 10 locations in Louisiana. Three high‐yielding commercial cultivars were included as checks: ‘Cheniere’, ‘CL153’, and ‘CL111’. The grain yield of CLL17 was 9.0 t ha−1 compared with 8.9 t ha−1 for CL153, 8.3 t ha−1 for CL111, and 8.2 t ha−1 for Cheniere across 25 commercial advanced trials from 2017 to 2020. CLL17 had a similar plant height to CL111, 2‐cm taller than CL153, and 5‐cm taller than Cheniere. It exhibits typical US long‐grain rice cooking quality with intermediate amylose and gel temperature. CLL17 is susceptible to sheath blight [caused by Rhizoctonia solani Kuhn ], resistant to Cercospora spp., leaf blast [caused by Magnaporthe grisea (T.T. Hebert)], and neck blast, and moderately susceptible to bacterial panicle blight (caused by Burkholderia glumae).

Sustained release of a human PD-L1 single-domain antibody using peptide-based hydrogels

Monoclonal antibodies (mAbs) targeting the immune checkpoint axis, which contains the programmed cell death protein-1 (PD-1) and its ligand PD-L1, revolutionized the field of oncology. Unfortunately, the large size of mAbs and the presence of an Fc fraction limit their tumor penetrative capacities and support off-target effects, potentially resulting in unresponsive patients and immune-related adverse events (irAEs) respectively. Single-domain antibodies (sdAbs) are ten times smaller than conventional mAbs and represent an emerging antibody subclass that has been proposed as next generation immune checkpoint inhibitor (ICI) therapeutics. They demonstrate favorable characteristics, such as an excellent stability, high antigen-binding affinity and an enhanced tumor penetration. Because sdAbs have a short half-life, methods to prolong their presence in the circulation and at the target site might be necessary in some cases to unfold their full therapeutic potential. In this study, we investigated a peptide-based hydrogel as an injectable biomaterial depot formulation for the sustained release of the human PD-L1 sdAb K2. We showed that a hydrogel composed of the amphipathic hexapeptide hydrogelator H-FQFQFK-NH2 prolonged the in vivo release of K2 after subcutaneous (s.c.) injection, up to at least 72 h, as monitored by SPECT/CT and fluorescence imaging. Additionally, after encapsulation in the hydrogel and s.c. administration, a significantly extended systemic presence and tumor uptake of K2 was observed in mice bearing a melanoma tumor expressing human PD-L1. Altogether, this study describes how peptide hydrogels can be exploited to provide the sustained release of sdAbs, thereby potentially enhancing its clinical and therapeutic effects.

Adaptive Optimization Method for Prediction and Compensation of Thin-Walled Parts Machining Deformation Based on On-Machine Measurement.

Thin-walled aluminum alloy parts are widely used in the aerospace field because of their favorable characteristics that cater to various applications. However, they are easily deformed during milling, leading to a low pass rate of workpieces. On the basis of on-machine measurement (OMM) and surrogate stiffness models (SSMs), we developed an iterative optimization compensation method in this study to overcome the machining deformation of thin-walled parts. In the error compensation process, the time-varying factors of workpiece stiffness and the impact of prediction model errors were considered. First, we performed machining deformation simulation and information extraction on the key nodes of the machined surface, and an SSM containing the stiffness information of discrete nodes of each cutting layer was established. Subsequently, the machining errors were monitored through intermittent OMM to suppress the adverse impact of prediction model errors. Further, an interlayer correction coefficient was introduced in the compensation process to iteratively correct the prediction model error of each node in the SSM along the depth direction, and a correction coefficient between parts was introduced to realize the iterative correction of the prediction model for the same node position between different parts. Finally, the feasibility of the proposed method was verified through multiple sets of actual machining experiments on thin-walled parts with added pads.

Cellulose nanocrystals-gelatin composite hydrocolloids: Application to controllable responsive deformation during 3D printing

Three-dimensional (3D) food printing is an effective technology for creating food designs with complex appearances and customized nutritional profiles. However, controlling the deformation of 3D printed foods during processing remains a challenge. Here, a food hydrocolloid with customizable designs during heating and dehydration was designed using cellulose nanocrystals (CNC) and gelatin (G). The resultant cellulose nanocrystals-gelatin (CNC-G) hydrocolloid exhibited favorable rheological characteristics for three-dimensional (3D) printing. 3D printing allows the controlled oriented alignment of the CNC particles within the hydrocolloid along the printing direction, endowing the CNC-G hydrocolloid with highly anisotropic structures. This anisotropic property can cause a strain mismatch during dehydrated food processing, leading to a specific deformation of the hydrocolloid. By adjusting the 3D printing parameters and intentionally designing of the 3D printed structures, the alignment degree of CNCs within the hydrocolloid can be controlled, and thus, its deformation can be programmed. The customizable deformation of CNC-G hydrocolloid during food processing was deliberately designed through printing, and its adaptability and flexibility are demonstrated through the "flapping" of a butterfly and the "blooming" of a four-leaf clover. The flexibility and customizability of CNC-G hydrocolloid in 3D printing provide a new strategy to achieve deformation and precise control of 3D printed foods during processing.

Registration of ‘PVL03’ rice

Abstract‘PVL03’ (Reg. no. CV‐159, PI 699656), a Provisia (BASF) long‐grain rice (Oryza sativa L.) cultivar, was developed by the Louisiana State University Agricultural Center at the H. Rouse Caffey Rice Research Station near Crowley, LA, and approved for release in 2020. PVL03 is the third rice cultivar released as part of the Provisia Rice System with resistance to Provisia herbicide, containing the active ingredient quizalofop‐p‐ethyl, an AACase (group 1) herbicide. PVL03 was derived from the cross ‘PVL01’/‘Catahoula’. Testing in the Provisia preliminary yield trial in 2018 and the multi‐location trial in 2019 indicated good yield potential and favorable agronomic characteristics. In 2020, PVL03 was evaluated in commercial advanced replicated trials across six locations in Louisiana. Four high‐yielding commercial cultivars were included as checks: ‘PVL02’, PVL01, ‘CL153’, and ‘Cheniere’. The average grain yield of PVL03 was 9.6 t ha−1 compared with 8.0 t ha−1 for PVL02, 8.1 t ha−1 for PVL01, 9.8 t ha−1 for CL153, and 9.1 t ha−1 for Cheniere. PVL03 was shorter than the previous Provisia cultivar, PVL02. The milled grain length was longer than that of PVL02, with a length‐to‐width ratio of 3.0. It has a typical US long‐grain rice cooking quality with intermediate amylose and gelatinization temperature. PVL03 is moderately susceptible to sheath blight and moderately resistant to leaf blast and bacterial panicle blight.

Enhancement in the Electrocatalytic and Optoelectronic Performance of Cost-Effective Counter Electrode VO2 for Dye-Sensitized Solar Cell (DSSC)

Dye-sensitized solar cells (DSSCs) have garnered significant attention in the scientific community for more than two decades due to their cost-effectiveness, convenient manufacturability, little toxicity, and straightforward preparation methodology. In this study, we present a cost-effective alternative to the platinum electrode for DSSCs, which serves as the counter electrode. The utilization of vanadium oxide nanoparticles as counter electrodes (CEs) in DSSCs has been the subject of research due to its enhanced stability, cost-effectiveness, and favorable photovoltaic characteristics. The device has been fabricated in configuration of fluorine-doped tin oxide (FTO)||TiO2||ruthenium (II) dye (N719)||iodide—triiodide electrolyte||VO2 (counter electrode)||FTO and investigate their photovoltaic performance. The utilization of X-ray diffraction (XRD) analysis has provided insights into the crystalline properties of VO2, indicating that it exists in a crystalline phase with a crystalline size measuring 43.19 nm and a lattice strain of 1.68 × 10−3. The utilization of a field emission scanning electron microscope (FESEM) that is equipped with an energy dispersive X-ray spectrum reveals a dense microstructure characterized by a uniform distribution of vanadium (V) and oxygen (O) across the whole surface. The Raman spectroscopic examination of VO2 reveals the existence of many Raman bands, thereby confirming the presence of the monoclinic phase. Cyclic voltammetry measurements were employed to investigate the catalytic activity of the CE toward the electrolyte. The photovoltaic performance of the manufactured device was examined by I–V measurement, revealing a notable open circuit voltage (Voc) and efficient power conversion efficiency when compared to the other materials that were evaluated.

Steady-State Temperature-Sensitive Electrical Parameters’ Characteristics of GaN HEMT Power Devices

Gallium nitride high-electron-mobility transistor (GaN HEMT) power devices are favored in various scenarios due to their high-power density and efficiency. However, with the significant increase in the heat flux density, the junction temperature of GaN HEMT has become a crucial factor in device reliability. Since the junction temperature monitoring technology for GaN HEMT based on temperature-sensitive electrical parameters (TSEPs) is still in the exploratory stage, the TSEPs’ characteristics of GaN HEMT have not been definitively established. In this paper, for the common steady-state TSEPs of GaN HEMT, the variation rules of the saturation voltage with low current injection, threshold voltage, and body-like diode voltage drop with temperature are investigated. The influences on the three TSEPs’ characteristics are considered, and their stability is discussed. Through experimental comparison, it is found that the saturation voltage with low current injection retains favorable temperature-sensitive characteristics, which has potential application value in junction temperature measurement. However, the threshold voltage as a TSEP for certain GaN HEMT is not ideal in terms of linearity and stability.