Exogenous Growth Research Articles

Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration.

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.

Pre-harvest exogenous application of growth regulators extends storability and maintains the seed potato quality

Preservation of potato tubers is essential not only for their general marketability but also for their potential use as seed potatoes. In subtropical areas, the small and marginal seed potato growers stored their produce at ambient temperature and thus prolonging storability through diverse seed storage techniques. Application of exogenous growth regulators is one the approaches which affect the quality of potato tubers positively. The present study assessed the impact of exogenous growth regulation on the storage and post-harvest quality of potato tubers. The seed potatoes crop was treated with growth regulators at 45 and 60 d after sowing to determine their effect on physiological losses and quality of tubers in storage at ambient temperature during 2019–20 and 2020–21. Application of GA200 reduced the total weight loss by 23.7 and 24.5% during 1st and 2nd year, respectively, compared to the untreated control. Among the auxin treatments, the minimum weight loss was recorded with IBA200. At 120 d of storage, GA200 resulted in a higher tuber dry-matter and total phenol content, compared to the untreated control. IBA200 pre-harvest application led to lower sprouting characteristics, followed by IBA100, NAA50, and NAA25. The Pearson correlation analysis revealed that post-harvest quality was negatively correlated with total weight loss and disease incidence (soft and dry rot). Among all the treatments, Ethrel50 was the more susceptible to soft and dry rot incidence. IBAs exhibited superior efficacy over NAAs in the suppression of storage diseases. In conclusion, a pre-harvest application of GA200 at 45 and 60 d after sowing can prolong the shelf life of seed potatoes at ambient temperature while maintaining or improving their post-harvest quality.

Exogenous growth hormone administration during total sleep deprivation changed the microRNA-9 and dopamine D2 receptor expressions followed by improvement in the hippocampal synaptic potential, spatial cognition, and inflammation in rats.

Disorders caused by total sleep deprivation can be modulated by the administration of growth hormone, which could affect the expression of microRNA-9 and dopamine D2 receptor expressions followed by improvement in the hippocampal synaptic potential, spatial cognition, and inflammation in rats. The present study aimed to elucidate the putative effects of exogenous growth hormone (GH) against total sleep deprivation (TSD)-induced learning and memory dysfunctions and possible involved mechanisms. To induce TSD, rats were housed in homemade special cages equipped with stainless steel wire conductors to induce general and inconsistent TSD. They received a mild repetitive electric shock to their paws every 10 min for 21 days. GH (1 mg/kg, sc) was administered to adult young male rats once daily for 21-day-duration induction of TSD. Spatial learning and memory performance, inflammatory status, microRNA-9 (miR-9) expression, dopamine D2 receptor (DRD2) protein level, and hippocampal histological changes were assayed at scheduled times after TSD. The results indicated that TSD impaired spatial cognition, increased TNF-α, decreased level of miR-9, and increased DRD2 levels. Treatment with exogenous GH improved spatial cognition, decreased TNF-α, increased level of miR-9, and decreased DRD2 levels after TSD. Our findings suggest that GH may play a key role in the modulation of learning and memory disorders as well as the ameliorating abnormal DRD2-related functional disorders associated with miR-9 in TSD.

Оцінка ефективності комбінованої терапії препаратами рекомбінантного гормона росту та вітаміну D дітей препубертатного віку із соматотропною недостатністю

The treatment of somatotropic insufficiency (SI) remains one of the most important problems in paediatric endocrinology. Since 1985, recombinant growth hormone (rGH) has been widely used to correct the growth of children with SI. Sufficient clinical experience has been gained in the use of rGH preparations, and the efficacy and safety of rGH therapy in children and adolescents with various forms of short stature has been proven. However, there are a number of factors that can have a significant impact on the achievement of final height in adulthood, including a wide range of sensitivity to exogenous growth hormone (GH), the degree of endogenous GH deficiency, patient compliance, and other uncertain factors. Patients with GH deficiency require long-term treatment, the effectiveness of which decreases significantly over time, prompting the search for optimal treatment options. Purpose - to evaluate the effectiveness of combined therapy of pre-pubertal children with SI with rGH and vitamin D drugs. Materials and methods. 23 pre-pubertal children with isolated SI were examined, who took monotherapy with rGH for 3 years. When the effectiveness of monotherapy decreases, vitamin D are added to the treatment complex. The level of 25(OH)D in blood serum is determined by the immunochemiluminescence method on microparticles (Abbott, USA). The levels of GH and insulin-like growth factor-1 were studied by solid-phase enzyme immunoassay using Immulite 2000 XPI kits. Results. At the end of the first year of rGH monotherapy, all patients showed a significant (p<0.05) increase in height. However, already after the second and third years of treatment, height velocity (HV) decreased in all patients. The increase in HV in the third year of treatment with rGH was significantly lower (p<0.05) than in the first year. Thanks to the addition of vitamin D, the further decrease in HV was stopped after the third year of monotherapy with rGH. The increase in HV during the first year of combined therapy was significantly (p<0.05) greater than during the third year of treatment with rGH monotherapy. The same trend was observed after the second year of combined therapy. Conclusions. In the presence of a decrease in the effectiveness of therapy with rGH after the first years of treatment, it is considered appropriate to use combined therapy of children with SI with rGH and vitamin D. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

The Attraction of Apple Rhizosphere Microorganisms and Changing Leaf Characteristics by Strigolactone

Apple leaf characteristics are the most important vegetative growth and development traits. The apple rhizosphere is also indirectly responsible for apple growth and development. It provides roots with elements and compounds that improve roots’ and shoots’ growth and development. The application of exogenous plant growth regulators such as strigolactones (SLs) has become one of the main trends for improving vegetative growth and enhancing the rhizosphere microbiome. This study aimed to investigate the effect of the exogenous SLs on some leaf characteristics, such as leaf area, angle, nitrogen content, chlorophyll content, and apical area diameter, in addition to the composition of the rhizosphere microbiome of apple M9 rootstock. The apple rootstocks were treated with various concentrations of GR24, an analog of SLs; the concentrations were 0, 1, 5, and 10 µM. The study found that the treatments of 5 µM increased the leaf–stem angles and leaf length while decreasing the apical diameter. The treatments of 1 and 5 µM increased leaf nitrogen content; however, this effect was not observed when using the higher concentration of 10 µM. The lower concentration (1 µM) led to a different abundance and diversity of microorganisms compared to the higher concentration (10 µm).

RWP-RK Domain 3 (OsRKD3) induces somatic embryogenesis in black rice

BackgroundPlants have the unique capability to form embryos from both gametes and somatic cells, with the latter process known as somatic embryogenesis. Somatic embryogenesis (SE) can be induced by exposing plant tissues to exogenous growth regulators or by the ectopic activation of embryogenic transcription factors. Recent studies have revealed that a discrete group of RWP-RK DOMAIN-CONTAINING PROTEIN (RKD) transcription factors act as key regulators of germ cell differentiation and embryo development in land plants. The ectopic overexpression of reproductive RKDs is associated with increased cellular proliferation and the formation of somatic embryo-like structures that bypass the need for exogenous growth regulators. However, the precise molecular mechanisms implicated in the induction of somatic embryogenesis by RKD transcription factors remains unknown.ResultsIn silico analyses have identified a rice RWP-RK transcription factor, named Oryza sativa RKD3 (OsRKD3), which is closely related to Arabidopsis thaliana RKD4 (AtRKD4) and Marchantia polymorpha RKD (MpRKD) proteins. Our study demonstrates that the ectopic overexpression of OsRKD3, which is expressed preferentially in reproductive tissues, can trigger the formation of somatic embryos in an Indonesian black rice landrace (Cempo Ireng) that is normally resistant to somatic embryogenesis. By analyzing the transcriptome of induced tissue, we identified 5,991 genes that exhibit differential expression in response to OsRKD3 induction. Among these genes, 50% were up-regulated while the other half were down-regulated. Notably, approximately 37.5% of the up-regulated genes contained a sequence motif in their promoter region, which was also observed in RKD targets from Arabidopsis. Furthermore, OsRKD3 was shown to mediate the transcriptional activation of a discrete gene network, which includes several transcription factors such as APETALA 2-like (AP2-like)/ETHYLENE RESPONSE FACTOR (ERF), MYB and CONSTANS-like (COL), and chromatin remodeling factors associated with hormone signal transduction, stress responses and post-embryonic pathways.ConclusionsOur data show that OsRKD3 modulates an extensive gene network and its activation is associated with the initiation of a somatic embryonic program that facilitates genetic transformation in black rice. These findings hold substantial promise for improving crop productivity and advancing agricultural practices in black rice.

Abstract 2569: Investigation of the effect of chronic IL-1 exposure on breast cancer cell line response to external signaling factors

Abstract As part of our immune response, the body produces anti-tumorigenic inflammatory proteins to kill cancer cells. However, cancer cells can usurp chronic inflammation for their own survival. Interleukin-1 (IL-1) is an inflammatory protein found in breast cancer (BCa) tumors that is elevated in the BCa patient tumors and serum and promotes metastasis, indicating IL-1 is clinically relevant. But the molecular mechanisms underlying the effect of chronic IL-1 on BCa progression remain unknown. We previously discovered that acute exposure to IL-1 represses essential hormone receptors in cancers cells, but concomitantly upregulates other compensatory pro-survival proteins that contribute to tumor progression. To determine if chronic IL-1 inflammation has the same effect, we generated cell subline models using the human breast cancer cell line, T47D, by exposing T47D cells chronically to IL-1 for several months. Notably, we found that the T47D chronic IL-1 sublines stably evolve insensitivity to exogenous IL-1. This result suggests that chronic IL-1 causes stable molecular changes that may affect cancer cell response to exogenous factors.Therapeutic strategies include blocking exogenous hormone or growth factor signals in the tumor microenvironment to attenuate cancer cell growth, proliferation, and survival. Therefore, we grew T47D parental and chronic IL-1 sublines in the absence of serum to determine the effect of chronic IL-1 exposure on BCa cell response to hormone and growth factor inhibition. Preliminarily, we do not observe differences in parental versus subline response to serum starvation, suggesting that differential response to exogenous factors is specific to IL-1 signaling. To better understand how chronic IL-1 -induced molecular changes effect BCa cell response to the tumor microenvironment, we will perform sequencing and bioinformatics analysis to identify IL-1 -dependent and/or independent signaling pathways stably altered in the chronic IL-1 sublines. Citation Format: Roopal Dhar, Ola M. Olaleye, Rana Tarig Abdelaziz, Jyotsna Tera Reddy, Nikki Delk. Investigation of the effect of chronic IL-1 exposure on breast cancer cell line response to external signaling factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2569.

Sustainable per capita consumption under population growth

We establish two investment rules for maximal constant per capita consumption under exogenous population growth, one in terms of total capital stocks and the other in terms of per capita capital stocks. Both rules show the importance of the development of future population growth. The investment rules are illustrated in the one-sector model of capital accumulation, the DHSS model of capital accumulation and resource depletion, and the Stollery–d’Autume–Schubert model in which natural capital provides amenities. Application to recent empirical evidence indicates that actual genuine savings might be insufficient to sustain per capita consumption, when future population growth is combined with a large per capita consumption-wage gap.

Maturation of Nephrons by Implanting hPSC-derived Kidney Progenitors Under Kidney Capsules of Unilaterally Nephrectomized Mice.

Human pluripotent stem cell (hPSC)-derived kidney organoids may contribute to disease modeling and the generation of kidney replacement tissues. However, the realization of such applications requires the induction of hPSCs into functional mature organoids. One of the key questions for this process is whether a specific vascular system exists for nephrogenesis. Our previous study showed that short-term (2 weeks) implantation of hPSC-derived organoids below the kidney capsules of unilaterally nephrectomized and immunodeficient mice resulted in the enlargement of organoids and production of vascular cells, although signs of maturation were lacking. Organoids were induced for 15 days in vitro and then grafted below kidney capsules of the same unilaterally nephrectomized immunodeficient mouse model to examine whether medium-term (4 weeks) implantation could improve organoid maturation and vascularization, as evaluated by immunofluorescence and transmission electron microscopy. We demonstrated that after 2-4 weeks of implantation, renal organoids formed host-derived vascularization and matured without any exogenous vascular endothelial growth factor. Glomerular filtration barrier maturation was evidenced by glomerular basement membrane deposition, perforated glomerular endothelial cell development, and apical, basal podocyte polarization. A polarized monolayer epithelium and extensive brush border were also observed for tubular epithelial cells. Our results indicate that the in vivo microenvironment is important for the maturation of human kidney organoids. Stromal expansion and a reduction of nephron structures were observed following longer-term (12 weeks) implantation, suggesting effects on off-target cells during the induction process. Accordingly, induction efficiency and transplantation models should be improved in the future.

Some Electrical Stimulation Methods for Articular Cartilage Regeneration

Bioelectrical signals can regulate a wide range of cellular activities in living organisms, including division, differentiation, etc. The physiological properties of stem cell cells are regulated by artificial input of electrical stimuli, including electric and electromagnetic fields, to promote cartilage repair by inducing stem cell cellular differentiation toward cartilage. Electrical stimulation (ES) stimulates cartilage regeneration at the cellular level through three mechanisms: intricate interactions of the physical environment, growth factors (GFs), and signal transduction cascades. The relevant ways in which bioelectrical stimulation regulates cellular function are the subject of this review. The non-invasive nature of this and the fact that it is not dependent on exogenous growth factors offer great promise for the clinical application of ES. However, the precise mechanisms underlying how ES interacts with cells are not well understood and need a lot more investigation. Similarly, there is a certain variability in the means and parameters of ES in in vivo and in vitro experiments, which poses a great challenge for clinical applications. Here some feasible means of ES and specific ES parameters to provide ideas for subsequent clinical applications are reviewed.

Rat bone marrow mesenchymal stem cells induced by rrPDGF-BB promotes bone regeneration during distraction osteogenesis.

Background: In the clinical treatment of large bone defects, distraction osteogenesis can be used. However, some patients may suffer from poor bone regeneration, or even delayed healing or non-union. Problems with the aggregation and proliferation of primary osteoblasts, or problems with the differentiation of primary osteoblasts will lead to poor bone regeneration. Therefore, supplementing exogenous primary osteoblasts and growth factors when using distraction osteogenesis may be a treatment plan with great potential. Methods: Bone marrow mesenchymal stem cells (BMSCs) were extracted from rats and cultured. Subsequently, Recombinant Rat Platelet-derived Growth Factor BB (rrPDGF-BB) was used to induce bone marrow mesenchymal stem cells. At the same time, male adult rats were selected to make the right femoral distraction osteogenesis model. During the mineralization period, phosphate buffer salt solution (control group), non-induction bone marrow mesenchymal stem cells (group 1) and recombinant rat platelet-derived growth factor BB intervened bone marrow mesenchymal stem cells (group 2) were injected into the distraction areas of each group. Then, the experimental results were evaluated with imaging and histology. Statistical analysis of the data showed that the difference was statistically significant if p < 0.05. Results: After intervention with recombinant rat platelet-derived growth factor BB on bone marrow mesenchymal stem cells, the cell morphology changed into a thin strip. After the cells were injected in the mineralization period, the samples showed that the callus in group 2 had greater hardness and the color close to the normal bone tissue; X-ray examination showed that there were more new callus in the distraction space of group 2; Micro-CT examination showed that there were more new bone tissues in group 2; Micro-CT data at week eight showed that the tissue volume, bone volume, percent bone volume, bone trabecular thickness, bone trabecular number and bone mineral density in group 2 were the largest, and the bone trabecular separation in group 2 was the smallest. There was a statistical difference between the groups (p < 0.05); HE staining confirmed that group 2 formed more blood vessels and chondrocytes earlier than the control group. At 8weeks, the bone marrow cavity of group 2 was obvious, and some of them had been fused. Conclusion: The study confirmed that injecting bone marrow mesenchymal stem cellsBB into the distraction space of rats can promote the formation of new bone in the distraction area and promote the healing of distraction osteogenesis.

Bioinspired Piezoelectric Periosteum to Augment Bone Regeneration via Synergistic Immunomodulation and Osteogenesis.

Ideal periosteum materials are required to participate in a sequence of bone repair-related physiological events, including the initial immune response, endogenous stem cell recruitment, angiogenesis, and osteogenesis. However, conventional tissue-engineered periosteal materials have difficulty achieving these functions by simply mimicking the periosteum via structural design or by loading exogenous stem cells, cytokines, or growth factors. Herein, we present a novel biomimetic periosteum preparation strategy to comprehensively enhance the bone regeneration effect using functionalized piezoelectric materials. The resulting biomimetic periosteum possessing an excellent piezoelectric effect and improved physicochemical properties was prepared using a biocompatible and biodegradable poly(3-hydroxybutyric acid-co-3-hydrovaleric acid) (PHBV) polymer matrix, antioxidized polydopamine-modified hydroxyapatite (PHA), and barium titanate (PBT), which were further incorporated into the polymer matrix to fabricate a multifunctional piezoelectric periosteum by a simple one-step spin-coating method. The addition of PHA and PBT dramatically enhanced the physicochemical properties and biological functions of the piezoelectric periosteum, resulting in improved surface hydrophilicity and roughness, enhanced mechanical performance, tunable degradation behavior, and stable and desired endogenous electrical stimulations, which is conducive to accelerating bone regeneration. Benefiting from endogenous piezoelectric stimulation and bioactive components, the as-fabricated biomimetic periosteum demonstrated favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro, which not only promoted adhesion, proliferation, and spreading as well as osteogenesis of mesenchymal stem cells (MSCs) but also effectively induced M2 macrophage polarization, thereby suppressing reactive oxygen species (ROS)-induced inflammatory reactions. Through in vivo experiments, the biomimetic periosteum with endogenous piezoelectric stimulation synergistically accelerated the formation of new bone in a rat critical-sized cranial defect model. The whole defect was almost completely covered by new bone at 8 weeks post treatment, with a thickness close to that of the host bone. Collectively, with its favorable immunomodulatory and osteogenic properties, the biomimetic periosteum developed here represents a novel method to rapidly regenerate bone tissue using piezoelectric stimulation.

Heparin-based sericin hydrogel–encapsulated basic fibroblast growth factor for in vitro and in vivo skin repair

The treatment of full-thickness cutaneous wounds remains a significant challenge in clinical therapeutics. Exogenous growth factor (GF) has been applied in clinics to promote wound healing. However, the retention of GF on the wound bed after its direct application to the wound surface is difficult. Moreover, growth factors (GFs) are always inactivated in the complex wound healing microenvironment due to various factors, which significantly decrease the therapeutic effect. Sericin hydrogel (S) can be used as an effective carrier for GFs owing to its low immunogenicity, good biocompatibility, and good healing-promoting ability. Here, we designed a heparin-based sericin hydrogel (HS) -encapsulated basic fibroblast growth factor (bFGF-HS) to facilitate wound healing and skin regeneration. The hydrogel exhibited a three-dimensional (3D) microporous structure, excellent biodegradability, good adhesiveness, and low cytotoxicity. In vitro release of bFGF from bFGF-HS coacervates revealed that bFGF-HS might control the release of bFGF within 25 days through heparin regulation. bFGF-HS significantly promoted vascularization and re-epithelialization and improved collagen deposition, ultimately accelerating wound healing in vivo in mice. bFGF-HS treated wounds were also found to have more hair follicles and milder inflammatory reactions. Overall, this study provides a new therapeutic approach for full-thickness skin defect wounds using bFGF-HS.

Engineering mussel-inspired multifunctional nanocomposite hydrogels to orchestrate osteoimmune microenvironment and promote bone healing

The reconstruction of large bone defects by bioactive materials without exogenous cells, cytokines or growth factors remains a substantial clinical challenge. Herein, we present the rational design of injectable and adhesive (GMAD/LP) hydrogels composed of gelatin-methacryloyl (GelMA), dopamine-grafted alginate (AD), and polydopamine-functionalized Laponite (Lap@PDA) nanosheets that can act as osteoimmune regulators to engineer the pro-regenerative microenvironment for personalized bone regeneration. The as-fabricated GMAD/LP hydrogel with excellent tissue adhesion, self-healing, injectability, and improved mechanical strength can fill irregular bone defects in a minimally invasive manner. Moreover, the hydrogel exhibited outstanding osteogenic potential and osteoimmunomodulatory functions in vitro, significantly promoting the adhesion, proliferation, spreading, and osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by hydrogel-induced macrophage M2-phenotype polarization and effective M2 macrophage-BMSC crosstalk. In vivo experiments in a cranial defect model demonstrated that the GMAD/LP hydrogel induced a reparative microenvironment similar to that in normal cranium, as characterized by an increased percentage of anti-inflammatory M2 macrophages and endogenous stem cells and high-level neovascularization, consequently accelerating bone healing. This strategy not only achieves a bioactive hydrogel for bone defect reconstruction but also provides a feasible methodology to recover injured bone tissue through integrated design with diverse functions.

Foliar Application of Carnosine and Chitosan Improving Drought Tolerance in Bermudagrass

Drought stress is one of the crucial factors affecting plant growth and development in turfgrass species, especially during the summer season. Exogenous plant growth regulators are an effective and convenient approach to mitigating the adverse effects of drought stress on plant growth. The objectives of this study were to reveal the effects of exogenous carnosine or chitosan on turf performance and physiological indexes in bermudagrass (Cynodon transvaalensis × C. dactylon) in response to drought stress. Bermudagrass was foliar sprayed with carnosine or chitosan, and dose-dependent effects on turf quality were observed under drought stress. Under drought stress, foliar application of either carnosine (0.03%) or chitosan (10 mg L−1) significantly increased turf quality, chlorophyll content, leaf relative water content, and decreased electrolyte leakage, malonaldehyde, and hydrogen peroxide content in comparison with untreated control in bermudagrass. Moreover, exogenous carnosine treatment significantly enhanced the activities of both catalase and peroxidase, but chitosan application only increased catalase activity. The results of this experiment were beneficial to the development of new plant growth regulators and would provide helpful insights for turf management under drought-stressed conditions.

Exogenous Growth Regulators and Water Stress Enhance Long-Term Storage Quality Characteristics of Onion

Exogenous growth regulators (GRs) play a crucial role in alleviating water stress and sustaining crop yields in water-stressed areas. However, their effects on onions post-harvest quality, particularly post-monsoon onion—often preferred for long-term storage—were never studied. Therefore, this led us to investigate the interaction between water stress and GRs on the physiochemical and functional quality attributes of onions during long-term storage (9 months, at 25 ± 1 °C and 65 ± 5% RH). Onion crop was raised under four water stress levels i.e., 1.00–0.85, 0.84–0.70, 0.69–0.40, and 0.39–0.10 IW: CPE, designated as no, low, medium, and severe water stress, respectively, using a line source sprinkler system (LSS). GR treatments include potassium nitrate (PN, 15 g L−1), sodium benzoate (SB, 100 mg L−1), thio-urea (TU, 450 ppm), and gibberellic acid (GA, 25 ppm). Results reveal that the significant temporal changes in the dry matter, rehydration ratio, total soluble sugar (TSS), protein, and total phenolics content (TP) of the onion bulbs during storage, indicate the cumulative impact of the treatments on overall physicochemical status. Water stress increased onion biochemical attributes, especially pyruvic acid content, superoxide dismutase (SOD), and peroxidase (POD) activity. Storage quality of onions progressively decreased with the increase in storage period. Stressed onions, especially those produced under severe water stress condition, showed high weight losses, presenting poor keeping quality. However, application of GRs, especially SB, TU, and PN, reduced bulb weight losses together with maintaining slightly better bulb physicochemical properties, thereby improving the overall storage quality, particularly with a moderate level of water stress (0.69–0.40 IW:CPE). The exogenous application of GRs with moderate water stress is suggested as a key strategy in improving the keeping quality of onion bulbs and ensuring its availability during the lean season.

The Rise of Specialized and Innovative Little Giant Enterprises under China’s ‘Dual Circulation’ Development Pattern: An Analysis of Spatial Patterns and Determinants

As potential ‘hidden champion’ companies originating from Germany, specialized and innovative ‘little giant’ enterprises (LGEs) have become role models for small and medium-sized enterprises (SMEs) in China and have been considered important actors in the strategy of ‘strengthening and supplementing national supply chains’. Based on the exogenous growth theory of the firm, this article takes the perspective of the ‘dual circulation’ new development pattern of China and analyses the spatial patterns and their determinants of LGEs using the data of national-level LGEs from 2019 to 2021 and the geographical weighted regression method. The following results were obtained: (1) the national-level LGEs show the spatial distribution pattern of ‘east–central–west’ decline and are highly concentrated in the high administrative levels of the cities, especially in the Beijing–Tianjin–Hebei, Yangtze River Delta, Cross–Strait urban agglomeration. (2) The domestic and international circulations jointly affect the spatial distribution of LGEs. Local institutional thickness has the largest and widest impact, followed by local industrial synergy. The impact of global linkage is relatively stable. (3) The impacts of the main determinants have spatial heterogeneity. The positive impact of local government support shows a decreasing differentiation law from east to west, and local industrial synergy is mainly significant in the east area of Northeast China, Bohai Rim, Shandong Peninsula, and Huang-Huai-hai Plain. The spatial heterogeneity of the effect of international circulation comes from the difference in marginal effects among regions and the influence of the Belt and Road Initiative. The positive impact of FDI is mainly concentrated in the northeast and southwest regions. This article highlights the importance of the domestic value chain in the strategy of Innovative China, and proves that varying global-local nexus of cities creates ‘soils’ with varying fertility in which LGEs thrives as well.

Strategies for indica rice adapted to high-temperature stress in the middle and lower reaches of the Yangtze River.

High temperatures caused by climate warming severely affect the grain yield and quality of rice. In this study, the rice cultivars Longliangyou Huazhan (LLYHZ) and Quanliangyou 2118 (QLY2118) were selected as the experimental materials for investigation of an optimal cultivation system under high-temperature treatment. In addition, the heat-resistant cultivar Huanghuazhan (HHZ) and heat-sensitive cultivar Huiliangyou 858 (HLY858) were chosen as the experimental materials to study the effects of exogenous plant growth regulators on heat stress responses under high-temperature treatment. The results showed that mechanical transplanting of carpet seedlings and delayed sowing effectively increased the leaf area index and reduced the canopy temperature of LLYHZ and QLY2118. Furthermore, carpet seedling mechanical transplantation and delayed sowing improved grain yield and quality. Spray application of five plant growth regulators revealed that brassinolide and salicylic acid had the strongest effects on significantly improving antioxidant enzyme activities in the panicle, which would reduce the damage caused by the accumulation of reactive oxygen species and enhance plant tolerance of high-temperature stress. In addition, brassinolide and salicylic acid enhanced the percentage of anther dehiscence and percentage seed set. In this study, a set of simplified eco-friendly cultivation techniques for single-season indica rice adaptation to high-temperature stress was established. These results will be of great importance in alleviating the effects of high-temperature stress on rice production.

Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers.

Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)-overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen. Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription-quantitative polymerase chain reaction. We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment. The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Understanding why degrowth is absent from mitigation scenarios

The range of climate change mitigation scenarios in the IPCC reports frames the futures and policies that we deem possible. In the mitigation pathways produced by Integrated Assessment Models (IAM), economic growth is sustained throughout the century, as we show by surveying the GDP trajectories considered in the IPCC AR5 scenario database and in the more recent IAM literature. We unpack the reasons for IAM’s commitment to GDP growth, and seek to understand the quasi-absence of no-growth and degrowth scenarios. An overview of the current organisation of IAM research highlights the internal dynamics within the IAM community and the resulting coordination of choices. We then analyse the representation of economic growth in two IAMs, GCAM (exogenous growth) and WITCH (endogenous growth). From a technical point of view, degrowth scenarios could be considered, but the modelling teams have coordinated their work around growth scenarios. Ultimately, the absence of degrowth/no growth scenarios stems from the fact that, economic growth is largely conceived of and computed as a “natural” driver in IAM research, and not as an intervention point.