Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT.

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

Allelopathic Toxicity of Cyanamide Could Control Amaranth (Amaranthus retroflexus L.) in Alfalfa (Medicago sativa L.) Field.

The inclination toward natural products has led to the onset of the discovery of new bioactive metabolites that could be targeted for specific therapeutic or agronomic applications. Despite increasing knowledge coming to light of allelochemicals as leads for new herbicides, relatively little is known about the mode of action of allelochemical-based herbicides on herbicide-resistant weeds. Cyanamide is an allelochemical produced by hairy vetch (Vicia villosa Roth.). This study aimed to detect the toxicity of cyanamide to alfalfa and amaranth. Seed germination experiments were carried out by the filter paper culture, and the seedling growth inhibition experiment was carried out by spraying alfalfa (Medicago sativa L.) and amaranth (Amaranthus retroflexus L.) seedlings with cyanamide. The results showed that when the concentration of cyanamide was 0.1 g·L-1, the germination of amaranth seeds could be completely inhibited without affecting the germination of alfalfa seeds. At the concentration of 0.5 g·L-1, cyanamide could significantly inhibit the growth of the root and stem of amaranth seedlings but did not affect the growth of alfalfa. This effect was associated with the induction of oxidative stress. The ascorbate peroxidase (APX) and catalase (CAT) activity of amaranth decreased by 6.828 U/g FW and 290.784 U/g FW, respectively. The malondialdehyde (MDA) content, peroxidase (POD), and superoxide dismutase (SOD) activity of amaranth firstly increased and then decreased with the increasing concentration of CA. These enzyme activities of amaranth changed more than that of alfalfa. Activities of the antioxidant enzymes APX, CAT, POD, and SOD and the content of MDA varied dramatically, thereby demonstrating the great influence of reactive oxygen species upon identified allelochemical exposure. In addition, cyanamide can also inhibit the production of chlorophyll, thereby affecting the growth of plants. From the above experiments, we know that cyanamide can inhibit the growth of amaranth in alfalfa fields. Thus, the changes caused by cyanamide described herein can contribute to a better understanding of the actions of allelochemical and the potential use of cyanamide in the production of bioherbicides.

Pretreatment with high oxygen controlled atmosphere enhanced fresh-cut white mushroom (Agaricus bisporus) quality via activating wounding stress defenses.

BACKGROUND: High oxygen treatment has been proven to be effective in fresh-cut white mushroom preservation, however, the preservation effect and possible mechanisms in high oxygen controlled atmosphere pretreatment (HOCAP) on wounding stress are incompletely understood. RESULTS: In this study, based on the time chosen of HOCAP research, whole white mushrooms treated with 3 h HOCAP (80% O2 + 20% CO2 ) and the wounding resistant responses of their slices were mainly investigated through phenylpropane pathway, reactive oxygen species (ROS) scavenging system, and ascorbate-glutathione (AsA-GSH) cycle. Results showed that 3 h HOCAP can induce the production of hydrogen peroxide (H2 O2 ) and superoxide anion (O2 -• ) in the early stage, as well as the NADPH oxidase activity. Enzymes and endogenous antioxidants involved in ROS scavenging were enhanced by HOCAP during the whole storage. Besides, HOCAP maintained high level of phenylalanine ammonia-lyase (PAL) activity, enhanced the content of total phenolic and lignin, accelerated the AsA-GSH cycle. CONCLUSION: The results demonstrated that HOCAP induced defense responses by increasing the ROS in the early stage which stimulated the activities of ROS scavenging enzymes, along with the capability of increasing for wounding stress defense and resistance. This study provides a theoretical pretreatment technology for fresh-cut white mushroom preservation. © 2021 Society of Chemical Industry.

Preparation of Wood Ear Medicinal Mushroom, Auricularia auricula-judae (Agaricomycetes), Melanin and Its Antioxidant Properties: Evaluation In Vitro and In Vivo.

This study investigated the extraction method of Auricularia auricula-judae melanin, focusing on the tough cell wall of the fruiting body and its free radical scavenging ability and antioxidant effects on Caenorhabditis elegans. The biological enzymatic method was performed to break the cell wall and prepare melanin extract. Further, extraction conditions were optimized using the Box-Behnken design. The in vitro free radical scavenging ability of melanin and its antioxidant effects on C. elegans were also studied. The results showed that A. auricula-judae melanin had strong absorption at a wavelength of 192 nm, with a absorbance-concentration equation of y = 0.7042x + 0.2114. Enzyme extraction under the following conditions yielded melanin of 2.21% ± 0.03%: 150 min, enzyme-to-substrate ratio of 1.1%, pH 4.4, 50°C, and 52 min. Free radical scavenging ability of A. auricula-judae melanin to superoxide anion-, ABTS+., and OH· radicals was concentration dependent. For example, at a concentration of 1 mg/mL, the scavenging rate of these free radicals was 85.71% ± 0.02%, 91.34% ± 0.01%, and 91.81% ± 0.01%, respectively. A. auricula-judae melanin could significantly prolong the lifespan of C. elegans (P < 0.05), and enhance locomotion behavior of C. elegans compared with the worms in the vehicle group (P < 0.05).

Human chimeric antigen receptor macrophages for cancer immunotherapy.

Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging1-4. Given the unique effector functions of macrophages and their capacity to penetrate tumors5, we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype. CAR macrophages (CAR-Ms) demonstrated antigen-specific phagocytosis and tumor clearance in vitro. In two solid tumor xenograft mouse models, a single infusion of human CAR-Ms decreased tumor burden and prolonged overall survival. Characterization of CAR-M activity showed that CAR-Ms expressed pro-inflammatory cytokines and chemokines, converted bystander M2 macrophages to M1, upregulated antigen presentation machinery, recruited and presented antigen to T cells and resisted the effects of immunosuppressive cytokines. In humanized mouse models, CAR-Ms were further shown to induce a pro-inflammatory tumor microenvironment and boost anti-tumor T cell activity.

Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia.

PURPOSE: To describe long-term outcomes of anti-CD19 chimeric antigen receptor T (CART) cells in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). METHODS: Between January 2013 and June 2016, 42 patients with relapsed or refractory CLL were enrolled in this study and 38 were infused with anti-CD19 CART cells (CART-19). Of these, 28 patients were initially randomly assigned to receive a low (5 × 107) or high (5 × 108) dose of CART-19, and 24 were evaluable for response assessment. After an interim analysis, 10 additional patients received the selected (high) dose and of these, eight were evaluable for response. Patients were followed for a median 31.5 months (range, 2 to 75 months). RESULTS: At 4 weeks, the complete and overall responses for the 32 evaluable patients were 28% (90% CI, 16% to 44%) and 44% (90% CI, 29% to 60%), respectively. The median overall survival (OS) for all patients was 64 months; there was no statistically significant difference between low- and high-dose groups (P = .84). Regardless of dose, prolonged survival was observed in patients who achieved a CR versus those who did not (P = .035), with median OS not reached in patients with CR versus 64 months in those without CR. The median progression-free survival was 40.2 months in patients with CR and 1 month in those without a CR (P < .0001). Toxicity was comparable in both dose groups. CONCLUSION: In patients with advanced CLL, a 5 × 108 dose of CART-19 may be more effective than 5 × 107 CART-19 at inducing CR without excessive toxicity. Attainment of a CR after CART-19 infusion, regardless of cell dose, is associated with longer OS and progression-free survival in patients with relapsed CLL.

Genetic Inactivation of CD33 in Hematopoietic Stem Cells to Enable CAR T Cell Immunotherapy for Acute Myeloid Leukemia.

The absence of cancer-restricted surface markers is a major impediment to antigen-specific immunotherapy using chimeric antigen receptor (CAR) T cells. For example, targeting the canonical myeloid marker CD33 in acute myeloid leukemia (AML) results in toxicity from destruction of normal myeloid cells. We hypothesized that a leukemia-specific antigen could be created by deleting CD33 from normal hematopoietic stem and progenitor cells (HSPCs), thereby generating a hematopoietic system resistant to CD33-targeted therapy and enabling specific targeting of AML with CAR T cells. We generated CD33-deficient human HSPCs and demonstrated normal engraftment and differentiation in immunodeficient mice. Autologous CD33 KO HSPC transplantation in rhesus macaques demonstrated long-term multilineage engraftment of gene-edited cells with normal myeloid function. CD33-deficient cells were impervious to CD33-targeting CAR T cells, allowing for efficient elimination of leukemia without myelotoxicity. These studies illuminate a novel approach to antigen-specific immunotherapy by genetically engineering the host to avoid on-target, off-tumor toxicity.

Quasi-type II CuInS2/CdS core/shell quantum dots.

Ternary chalcopyrite CuInS2 quantum dots (QDs) have been extensively studied in recent years as an alternative to conventional QDs for solar energy conversion applications. However, compared with the well-established photophysics in prototypical CdSe QDs, much less is known about the excited properties of CuInS2 QDs. In this work, using ultrafast spectroscopy, we showed that both conduction band (CB) edge electrons and copper vacancy (VCu) localized holes were susceptible to surface trappings in CuInS2 QDs. These trap states could be effectively passivated by forming quasi-type II CuInS2/CdS core/shell QDs, leading to a single-exciton (with electrons delocalized among CuInS2/CdS CB and holes localized in VCu) half lifetime of as long as 450 ns. Because of reduced electron-hole overlap in quasi-type II QDs, Auger recombination of multiple excitons was also suppressed and the bi-exciton lifetime was prolonged to 42 ps in CuInS2/CdS QDs from 10 ps in CuInS2 QDs. These demonstrated advantages, including passivated trap states, long single and multiple exciton lifetimes, suggest that quasi-type II CuInS2/CdS QDs are promising materials for photovoltaic and photocatalytic applications.