Stochastic linear quadratic optimal control problem with terminal state constraints

This paper addresses the stochastic linear quadratic (LQ) control problem with first- and second-order moment constraints on the terminal state. The problem is a modified version of the optimal covariance control problem, where the terminal state is steered to a given probability distribution. Studying a multiplicative-noise stochastic system rather than an additive-noise system is a salient feature. Unlike the existing ideas in the optimal steering, by using the Lagrange multipliers method and establishing the stochastic maximum principle, our problem is converted into solving forward–backward stochastic difference equations (FBSDEs), which is a special stochastic two-point boundary-value problem (TPBVP). We provide the optimal closed-loop controller and necessary and sufficient solvability conditions by developing a nonhomogeneous relationship between the optimal state and costate in FBSDEs. Finally, numerical examples are given to demonstrate our results.     

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1^−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2^−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.     

Development of a Multi-Criteria Decision-Making Approach for Evaluating the Comprehensive Application of Herbaceous Peony at Low Latitudes

The growing region of herbaceous peony (Paeonia lactiflora) has been severely constrained due to the intensification of global warming and extreme weather events, especially at low latitudes. Assessing and selecting stress-tolerant and high-quality peony germplasm is essential for maintaining the normal growth and application of peonies under adverse conditions. This study proposed a modified multi-criteria decision-making (MCDM) model for assessing peonies adapted to low-latitude climates based on our previous study. This model is low-cost, timesaving and suitable for screening the adapted peony germplasm under hot and humid climates. The evaluation was conducted through the analytic hierarchy process (AHP), three major criteria, including adaptability-related, ornamental feature-related and growth habits-related criteria, and eighteen sub-criteria were proposed and constructed in this study. The model was validated on fifteen herbaceous peonies cultivars from different latitudes. The results showed that ‘Meiju’, ‘Hang Baishao’, ‘Hongpan Tuojin’ and ‘Bo Baishao’ were assessed as Level I, which have strong growth adaptability and high ornamental values, and were recommended for promotion and application at low latitudes. The reliability and stability of the MCDM model were further confirmed by measuring the chlorophyll fluorescence of the selected adaptive cultivars ‘Meiju’ and ‘Hang Baishao’ and one maladaptive cultivar ‘Zhuguang’. This study could provide a reference for the introduction, breeding and application of perennials under everchanging unfavorable climatic conditions.     

Fascaplysin Induces Apoptosis and Ferroptosis,and Enhances Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) by Promoting PD-L1 Expression

Fascaplysin is a natural product isolated from sponges with a wide range of anticancer activities. However, the mechanism of fascaplysin against NSCLC has not been clearly studied. In this study, fascaplysin was found to inhibit migration by regulating the wnt/β-catenin signaling pathway and reversing the epithelial–mesenchymal transition phenotype. Further research showed that the anti-NSCLC effect of fascaplysin was mainly through the induction of ferroptosis and apoptosis. Fascaplysin-induced ferroptosis in lung cancer cells, evidenced by increased levels of ROS and Fe²⁺ and downregulation of ferroptosis-associated protein and endoplasmic reticulum stress, was involved in fascaplysin-induced ferroptosis. In addition, ROS was found to mediate fascaplysin-induced apoptosis. Fascaplysin significantly upregulated the expression of PD-L1 in lung cancer cells, and enhanced anti-PD-1 antitumor efficacy in a syngeneic mouse model. Therefore, these results suggest that fascaplysin exerts anticancer effects by inducing apoptosis and ferroptosis in vitro, and improving the sensitivity of anti-PD-1 immunotherapy in vivo. Fascaplysin is a promising compound for the treatment of NSCLC.     

The Role of Circular RNAs in the Physiology and Pathology of the Mammalian Ovary

Circular RNAs (circRNAs) are an abundant class of endogenous non-coding RNAs (ncRNAs) generated from exonic, intronic, or untranslated regions of protein-coding genes or intergenic regions. The diverse, stable, and specific expression patterns of circRNAs and their possible functions through cis/trans regulation and protein-coding mechanisms make circRNA a research hotspot in various biological and pathological processes. It also shows practical value as biomarkers, diagnostic indicators, and therapeutic targets. This review summarized the characteristics, classification, biogenesis and elimination, detection and confirmation, and functions of circRNAs. We focused on research advances circRNAs in the mammalian ovary under conditions including ovarian cancer, polycystic ovarian syndrome (PCOS), and maternal aging, as well as during reproductive status, including ovarian follicle development and atresia. The roles of circRNAs in high reproductive traits in domestic animals were also summarized. Finally, we outlined some obstructive factors and prospects to work with circRNA, aiming to provide insights into the functional research interests of circRNAs in the reproduction and gynecology areas.     

Nicotinamide Mononucleotide Supplementation Improves Mitochondrial Dysfunction and Rescues Cellular Senescence by NAD+/Sirt3 Pathway in Mesenchymal Stem Cells

In vitro expansion-mediated replicative senescence has severely limited the clinical applications of mesenchymal stem cells (MSCs). Accumulating studies manifested that nicotinamide adenine dinucleotide (NAD⁺) depletion is closely related to stem cell senescence and mitochondrial metabolism disorder. Promoting NAD⁺ level is considered as an effective way to delay aging. Previously, we have confirmed that nicotinamide mononucleotide (NMN), a precursor of NAD⁺, can alleviate NAD⁺ deficiency-induced MSC senescence. However, whether NMN can attenuate MSC senescence and its underlying mechanisms are still incompletely clear. The present study herein showed that late passage (LP) MSCs displayed lower NAD⁺ content, reduced Sirt3 expression and mitochondrial dysfunction. NMN supplementation leads to significant increase in intracellular NAD⁺ level, NAD⁺/ NADH ratio, Sirt3 expression, as well as ameliorated mitochondrial function and rescued senescent MSCs. Additionally, Sirt3 over-expression relieved mitochondrial dysfunction, and retrieved senescence-associated phenotypic features in LP MSCs. Conversely, inhibition of Sirt3 activity via a selective Sirt3 inhibitor 3-TYP in early passage (EP) MSCs resulted in aggravated cellular senescence and abnormal mitochondrial function. Furthermore, NMN administration also improves 3-TYP-induced disordered mitochondrial function and cellular senescence in EP MSCs. Collectively, NMN replenishment alleviates mitochondrial dysfunction and rescues MSC senescence through mediating NAD⁺/Sirt3 pathway, possibly providing a novel mechanism for MSC senescence and a promising strategy for anti-aging pharmaceuticals.     

Mechanism of [CO2] Enrichment Alleviated Drought Stress in the Roots of Cucumber Seedlings Revealed via Proteomic and Biochemical Analysis

Cucumber is one of the most widely cultivated greenhouse vegetables, and its quality and yield are threatened by drought stress. Studies have shown that carbon dioxide concentration ([CO₂]) enrichment can alleviate drought stress in cucumber seedlings; however the mechanism of this [CO₂] enrichment effect on root drought stress is not clear. In this study, the effects of different drought stresses (simulated with 0, 5% and 10% PEG 6000, i.e., no, moderate, and severe drought stress) and [CO₂] (400 μmol·mol⁻¹ and 800 ± 40 μmol·mol⁻¹) on the cucumber seedling root proteome were analyzed using the tandem mass tag (TMT) quantitative proteomics method. The results showed that after [CO₂] enrichment, 346 differentially accumulating proteins (DAPs) were found only under moderate drought stress, 27 DAPs only under severe drought stress, and 34 DAPs under both moderate and severe drought stress. [CO₂] enrichment promoted energy metabolism, amino acid metabolism, and secondary metabolism, induced the expression of proteins related to root cell wall and cytoskeleton metabolism, effectively maintained the balance of protein processing and degradation, and enhanced the cell wall regulation ability. However, the extent to which [CO₂] enrichment alleviated drought stress in cucumber seedling roots was limited under severe drought stress, which may be due to excessive damage to the seedlings.     

A Novel L-Phenylalanine Dipeptide Inhibits the Growth and Metastasis of Prostate Cancer Cells via Targeting DUSP1 and TNFSF9

Prostate cancer (PCa) is a common malignant cancer of the urinary system. Drug therapy, chemotherapy, and radical prostatectomy are the primary treatment methods, but drug resistance and postoperative recurrence often occur. Therefore, seeking novel anti-tumor compounds with high efficiency and low toxicity from natural products can produce a new tumor treatment method. Matijin-Su [N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol, MTS] is a phenylalanine dipeptide monomer compound that is isolated from the Chinese ethnic medicine Matijin (Dichondra repens Forst.). Its derivatives exhibit various pharmacological activities, especially anti-tumor. Among them, the novel MTS derivative HXL131 has a significant inhibitory effect against prostate tumor growth and metastasis. This study is designed to investigate the effects of HXL131 on the growth and metastasis of human PCa cell lines PC3 and its molecular mechanism through in vitro experiments combined with proteomics, molecular docking, and gene silencing. The in vitro results showed that HXL131 concentration dependently inhibited PC3 cell proliferation, induced apoptosis, arrested cell cycle at the G2/M phase, and inhibited cell migration capacity. A proteomic analysis and a Western blot showed that HXL131 up-regulated the expression of proliferation, apoptosis, cell cycle, and migration-related proteins CYR61, TIMP1, SOD2, IL6, SERPINE2, DUSP1, TNFSF9, OSMR, TNFRSF10D, and TNFRSF12A. Molecular docking, a cellular thermal shift assay (CETSA), and gene silencing showed that HXL131 had a strong binding affinity with DUSP1 and TNFSF9, which are important target genes for inhibiting the growth and metastasis of PC3 cells. This study demonstrates that HXL131 exhibited excellent anti-prostate cancer activity and inhibited the growth and metastasis of prostate cancer cells by regulating the expression of DUSP1 and TNFSF9.     

Rice β-Glucosidase 4 (Os1βGlu4) Regulates the Hull Pigmentation via Accumulation of Salicylic Acid

Salicylic acid (SA) is a stress hormone synthesized in phenylalanine ammonia-lyase (PAL) and the branching acid pathway. SA has two interconvertible forms in plants: SAG (SA O-β-glucoside) and SA (free form). The molecular mechanism of conversion of SA to SAG had been reported previously. However, which genes regulate SAG to SA remained unknown. Here, we report a cytoplasmic β-glucosidase (β-Glu) which participates in the SA pathway and is involved in the brown hull pigmentation in rice grain. In the current study, an EMS-generated mutant brown hull 1 (bh1) displayed decreased contents of SA in hulls, a lower photosynthesis rate, and high-temperature sensitivity compared to the wild type (WT). A plaque-like phenotype (brown pigmentation) was present on the hulls of bh1, which causes a significant decrease in the seed setting rate. Genetic analysis revealed a mutation in LOC_Os01g67220, which encodes a cytoplasmic Os1βGlu4. The knock-out lines displayed the phenotype of brown pigmentation on hulls and decreased seed setting rate comparable with bh1. Overexpression and complementation lines of Os1βGlu4 restored the phenotype of hulls and normal seed setting rate comparable with WT. Subcellular localization revealed that the protein of Os1βGlu4 was localized in the cytoplasm. In contrast to WT, bh1 could not hydrolyze SAG into SA in vivo. Together, our results revealed the novel role of Os1βGlu4 in the accumulation of flavonoids in hulls by regulating the level of free SA in the cellular pool.