Discovery of a first-in-class degrader for the protein arginine methyltransferase 6 (PRMT6).

PRMT6 is a member of the protein arginine methyltransferase family, which participates in a variety of physical processes and plays an important role in the occurrence and development of tumors. Using small molecules to design and synthesize targeted protein degraders is a new strategy for drug development. Here, we report the first-in-class degrader SKLB-0124 for PRMT6 based on the hydrophobic tagging (HyT) method.Importantly, SKLB-0124 induced proteasome dependent degradation of PRMT6 and significantly inhibited the proliferation of HCC827 and MDA-MB-435 cells. Moreover, SKLB-0124 effectively induced apoptosis and cell cycle arrest in these two cell lines. Our data clarified that SKLB-0124 is a promising selective PRMT6 degrader for cancer therapy which is worthy of further evaluation.

[Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency]. / ç£·é ¸ç”˜éœ²ç³–å˜ä½é ¶2缺乏症的诊治进展.

Phosphomannomutase 2 deficiency is the most common form of N-glycosylation disorders and is also known as phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). It is an autosomal recessive disease with multi-system involvements and is caused by mutations in the PMM2 gene (OMIM: 601785), with varying severities in individuals. At present, there is still no specific therapy for PMM2-CDG, and early identification, early diagnosis, and early treatment can effectively prolong the life span of pediatric patients. This article reviews the advances in the diagnosis and treatment of PMM2-CDG.

Synthesis and Biological Evaluation of Novel 4-(4-Formamidophenylamino)-N-methylpicolinamide Derivatives as Potential Antitumor Agents.

A novel series of 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives were synthesized and evaluated against different tumor cell lines. Experiments in vitro showed that these derivatives could inhibit the proliferation of two kinds of human cancer cell lines (HepG2, HCT116) at low micromolar concentrations and the most potent analog 5q possessed broad-spectrum antiproliferative activity. Experiments in vivo demonstrated that 5q could effectively prolong the longevity of colon carcinoma-burdened mice and slow down the progression of cancer cells by suppression of angiogenesis and the induction of apoptosis and necrosis.

A novel fixed-dose combination treatment for chronic hepatitis C, based on NS5A inhibitor fopitasvir and NS5B inhibitor sofosbuvir.

Drug resistance caused by the extreme genetic variability of zhe hepatitis C virus has rendered effective combinations of drugs indispensable in the treatment of chronic hepatitis C (CHC). Herein, we developed a fixed-dose combination (FDC) treatment containing the NS5B inhibitor sofosbuvir (SOF) and the NS5A inhibitor fopitasvir (FOP). Then the dissolution behavior of FOP in FOP/SOF FDC was improved by co-micronizing FOP with lactose. The enhanced dissolution rate of FOP in the FDC was in good agreement with the behavior of the FOP singledrug tablet. In addition, pharmacokinetic studies showed that both FOP and SOF in the FDC exhibited similar characteristics (area under the curve, Cmax, Tmax, and T1/2) as those of tablets containing FOP or SOF alone. These results revealed that the FOP/SOF FDC represents a potential therapeutic option for the treatment of CHC.

Molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolates with focus on antimicrobial resistance.

BACKGROUND: The enhancing incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP)-mediated infections in Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017 is the motivation behind this investigation to study gene phenotypes and resistance-associated genes of emergence regarding the CRKP strains. In current study, seven inpatients are enrolled in the hospital with complete treatments. The carbapenem-resistant K. pneumoniae whole genome is sequenced using MiSeq short-read and Oxford Nanopore long-read sequencing technology. Prophages are identified to assess genetic diversity within CRKP genomes. RESULTS: The investigation encompassed eight CRKP strains that collected from the patients enrolled as well as the environment, which illustrate that blaKPC-2 is responsible for phenotypic resistance in six CRKP strains that K. pneumoniae sequence type (ST11) is informed. The plasmid with IncR, ColRNAI and pMLST type with IncF[F33:A-:B-] co-exist in all ST11 with KPC-2-producing CRKP strains. Along with carbapenemases, all K. pneumoniae strains harbor two or three extended spectrum ß-lactamase (ESBL)-producing genes. fosA gene is detected amongst all the CRKP strains. The single nucleotide polymorphisms (SNP) markers are indicated and validated among all CRKP strains, providing valuable clues for distinguishing carbapenem-resistant strains from conventional K. pneumoniae. CONCLUSIONS: ST11 is the main CRKP type, and blaKPC-2 is the dominant carbapenemase gene harbored by clinical CRKP isolates from current investigations. The SNP markers detected would be helpful for characterizing CRKP strain from general K. pneumoniae. The data provides insights into effective strategy developments for controlling CRKP and nosocomial infection reductions.

Design, synthesis and biological evaluation of 3,5-dimethylisoxazole and pyridone derivatives as BRD4 inhibitors.

Bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal (BET) family, has been recognized as an attractive candidate target for the treatment targeting gene transcription in several types of cancers. In this study, two types of novel compounds were designed, synthesized and evaluated as BRD4 inhibitors. Therein, pyridone derivatives were more effective against BRD4 protein and human leukemia cell lines MV4-11. Among them, compounds 11d, 11e and 11f were the most potential ones with IC50 values of 0.55 µM, 0.86 µM and 0.80 µM against BRD4, and exhibited remarkable antiproliferative activities against MV4-11 cells with IC50 values of 0.19 µM, 0.32 µM and 0.12 µM, respectively. Moreover, in western blot assay, compound 11e induced down-regulation of C-Myc, which is a significant downstream gene of BRD4. Cell cycle analysis assay also showed that compound 11e could block MV4-11 cells at G0/G1 phase. Taken together, our results suggested that compound 11e and its derivatives were a class of novel structural potential BRD4 inhibitors and could serve as lead compounds for further exploration.

The effects of LSD1 inhibition on self-renewal and differentiation of human induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) are capable of unlimited self-renewal and can generate nearly all cells in the body. Changes induced by different LSD1 activities on the regulation of hiPSC self-renewal and differentiation and the mechanism underlying such changes were determined. We used two different LSD1 inhibitors (phenelzine sulfate and tranylcypromine) and RNAi technique to inhibit LSD1 activity, and we obtained hiPSCs showing 71.3%, 53.28%, and 31.33% of the LSD1 activity in normal hiPSCs. The cells still maintained satisfactory self-renewal capacity when LSD1 activity was at 71.3%. The growth rate of hiPSCs decreased and cells differentiated when LSD1 activity was at approximately 53.28%. The hiPSCs were mainly arrested in the G0/G1 phase and simultaneously differentiated into endodermal tissue when LSD1 activity was at 31.33%. Teratoma experiments showed that the downregulation of LSD1 resulted in low teratoma volume. When LSD1 activity was below 50%, pluripotency of hiPSCs was impaired, and the teratomas mainly comprised endodermal and mesodermal tissues. This phenomenon was achieved by regulating the critical balance between histone methylation and demethylation at regulatory regions of several key pluripotent and developmental genes.

Sp1 and c-Myc modulate drug resistance of leukemia stem cells by regulating survivin expression through the ERK-MSK MAPK signaling pathway.

BACKGROUND: Acute myeloid leukemia (AML) is initiated and maintained by a subset of self-renewing leukemia stem cells (LSCs), which contribute to the progression, recurrence and therapeutic resistance of leukemia. However, the mechanisms underlying the maintenance of LSCs drug resistance have not been fully defined. In this study, we attempted to elucidate the mechanisms of LSCs drug resistance. METHODS: We performed reverse phase protein arrays to analyze the expression of anti-apoptotic proteins in the LSC-enriched leukemia cell line KG-1a. Immuno-blotting, cell viability and clinical AML samples were evaluated to verify the micro-assay results. The characteristics and transcriptional regulation of survivin were analyzed with the relative luciferase reporter assay, mutant constructs, chromatin immuno-precipitation (ChIP), quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and western blotting. The levels of Sp1, c-Myc, phospho-extracellular signal-regulated kinase (p-ERK), phospho-mitogen and stress-activated protein kinase (p-MSK) were investigated in paired CD34+ and CD34- AML patient samples. RESULTS: Survivin was highly over-expressed in CD34 + CD38- KG-1a cells and paired CD34+ AML patients compared with their differentiated counterparts. Functionally, survivin contributes to the drug resistance of LSCs, and Sp1 and c-Myc concurrently regulate levels of survivin transcription. Clinically, Sp1 and c-Myc were significantly up-regulated and positively correlated with survivin in CD34+ AML patients. Moreover, Sp1 and c-Myc were further activated by the ERK/MSK mitogen-activated protein kinase (MAPK) signaling pathway, modulating survivin levels. CONCLUSION: Our findings demonstrated that ERK/MSK/Sp1/c-Myc axis functioned as a critical regulator of survivin expression in LSCs, offering a potential new therapeutic strategy for LSCs therapy.

Stratified structure of membrane clogs observed in full scale cross-flow tubular ultrafiltration (UF) system: Fouling characterization and a proposed two-stage formation mechanism.

Membrane fouling remains a significant challenge in wastewater treatment, hindering both efficiency and lifespan. This study reports a distinct phenomenon of stratified membrane clogging observed in a full-scale cross-flow tubular ultrafiltration (UF) system treating sludge anaerobic digestion (AD) reject water. The distinct stratified structure, comprising inner and outer layers within the cake layer, has not been previously described. This research involved characterizing the filtration performance, analyzing membrane clog composition, and proposing a two-stage formation mechanism for the stratified clogs. It was revealed that higher inorganic and lower organic content in the outer layer compared to the inner layer. Acid and alkali treatments demonstrated the effectiveness of combined cleaning strategies. A mathematical model was developed to determine the critical conditions for stratified clog formation, influenced by membrane flux and cross-flow velocity (CFV). It is proposed that outer layer forms through long-term selective deposition, while the inner layer results from short-term dewatering within limited tubular space. High CFV (>2.5 m/s) prevents inner layer formation. Critical conditions for stratification occur at a flux of 18 L/m2/h with a CFV of 0.1 m/s or 65 L/m2/h with a CFV of 0.35 m/s. This study contributes a novel understanding of stratified membrane clogging, proposing a two-stage formation mechanism and identifying critical conditions, which provides insights for effective fouling control strategies and maintenance of operational efficiency for membrane systems.

PGC-1α repression dysregulates lipid metabolism and induces lipid droplet accumulation in retinal pigment epithelium.

Drusen, the yellow deposits under the retina, are composed of lipids and proteins, and represent a hallmark of age-related macular degeneration (AMD). Lipid droplets are also reported in the retinal pigment epithelium (RPE) from AMD donor eyes. However, the mechanisms underlying these disease phenotypes remain elusive. Previously, we showed that Pgc-1α repression, combined with a high-fat diet (HFD), induce drastic AMD-like phenotypes in mice. We also reported increased PGC-1α acetylation and subsequent deactivation in the RPE derived from AMD donor eyes. Here, through a series of in vivo and in vitro experiments, we sought to investigate the molecular mechanisms by which PGC-1α repression could influence RPE and retinal function. We show that PGC-1α plays an important role in RPE and retinal lipid metabolism and function. In mice, repression of Pgc-1α alone induced RPE and retinal degeneration and drusen-like deposits. In vitro inhibition of PGC1A by CRISPR-Cas9 gene editing in human RPE (ARPE19- PGC1A KO) affected the expression of genes responsible for lipid metabolism, fatty acid ß-oxidation (FAO), fatty acid transport, low-density lipoprotein (LDL) uptake, cholesterol esterification, cholesterol biosynthesis, and cholesterol efflux. Moreover, inhibition of PGC1A in RPE cells caused lipid droplet accumulation and lipid peroxidation. ARPE19-PGC1A KO cells also showed reduced mitochondrial biosynthesis, impaired mitochondrial dynamics and activity, reduced antioxidant enzymes, decreased mitochondrial membrane potential, loss of cardiolipin, and increased susceptibility to oxidative stress. Our data demonstrate the crucial role of PGC-1α in regulating lipid metabolism. They provide new insights into the mechanisms involved in lipid and drusen accumulation in the RPE and retina during aging and AMD, which may pave the way for developing novel therapeutic strategies targeting PGC-1α.

Targeting type I PRMTs as promising targets for the treatment of pulmonary disorders: Asthma, COPD, lung cancer, PF, and PH.

Pulmonary disorders, including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), pulmonary hypertension (PH), and lung cancer, seriously impair the quality of lives of patients. A deeper understanding of the occurrence and development of the above diseases may inspire new strategies to remedy the scarcity of treatments. Type I protein arginine methyltransferases (PRMTs) can affect processes of inflammation, airway remodeling, fibroblast proliferation, mitochondrial mass, and epithelial dysfunction through substrate methylation and non-enzymatic activity, thus affecting the occurrence and development of asthma, COPD, lung cancer, PF, and PH. As potential therapeutic targets, inhibitors of type I PRMTs are developed, moreover, representative compounds such as GSK3368715 and MS023 have also been used for early research. Here, we collated structures of type I PRMTs inhibitors and compared their activity. Finally, we highlighted the physiological and pathological associations of type I PRMTs with asthma, COPD, lung cancer, PF, and PH. The developing of type I PRMTs modulators will be beneficial for the treatment of these diseases.

A two-stage partial nitritation-denitritation/anammox (PN-DN/A) process to treat high-solid anaerobic digestion (HSAD) reject water: Verification based on pilot-scale and full-scale projects.

High-solid anaerobic digestion (HSAD) reject water, distinguished by elevated levels of chemical oxygen demand (COD), NH4+-N and an imbalanced COD/TIN, presents a significant challenge for treatment through conventional partial nitritation/ anammox (PN/A) process. This study introduced a revised two-stage PN/A process, namely partial nitritation/denitritation-anammox (PN-DN/A) process. Its effectiveness was investigated through both pilot-scale (12 t/d) and full-scale (400 t/d) operations, showcasing stable operation with an impressive total removal rate of over 90 % for total inorganic nitrogen (TIN) and exceeding 60 % for COD. Notably, 30 % of TIN was eliminated through heterotrophic denitritation in partial nitritation-denitritation (PN-DN) stage, while approximately 55 % of TIN removal occurred in the anammox stage with anaerobic ammonium oxidizing bacteria (AnAOB) enrichment (Candidatus Kuenenia, 25.9 % and 26.6 % relative abundance for pilot and full scale). In the PN-DN stage, aerobic-anaerobic alternation promoted organics elimination (around 50 % COD) and balanced nitrogen species. Microbial and metagenomic analysis verified the coupling between autotrophic and heterotrophic denitritation and demonstrated that PN-DN stage acted as a protective buffer for anammox stage. This comprehensive study highlights the PN-DN/A process's efficacy in stably treating HSAD reject water.

Spatial and temporal dynamics of sewage sludge phosphorus recovery potential in the cities of Yangtze River Zone in China: Implications for regional recycling policies.

Sewage sludge phosphorus (P) recovery presents opportunities to sustainably recycle P from cities to agriculture and alleviate global P scarcity. However, limited research explores sustainable recovery targets considering spatial-temporal variations in sludge generation and implications based on city-level local P demand. This study analyzed sludge production over 2009-2021 across 130 cities in China's Yangtze River Zone, which increased by almost 35 % from 2009 to 2021. Per capita gross domestic product (GDP), influent chemical oxygen demand (COD), and per capita drainage infrastructure were identified as main significant influencing factors. City-level analysis revealed pronounced spatial-temporal disparities, with yearly sludge generation spanning five orders of magnitude (62-5.4 × 105 t/a). An indicator, "Potential of P recovery to local P demand", was defined, indicating the average city-level P recycle contribution increased from 5.3 % to 18.9 % during 2009-2021. A novel frame paradigm based on supply-demand characteristics classified cities into "P recycling supply cities" with surplus recoverable P versus "P recycling self-sufficient cities". City-specific dynamics and possibilities of broader "city clusters" to match supply and demand should be considered for policies implement. Recovering P from livestock manure and kitchen waste alongside sludge can further strengthen urban P cycles. This study provides novel city-scale analysis and strategic considerations for regional sludge P recycling policies in China and beyond.

Understanding the amylose biosynthesis and regulation mechanisms in Tartary buckwheat by the endosperm transcriptome.

Starch serves as a crucial energy source for both plants and humans, predominantly synthesized and stored in endosperms, tubers, rhizomes, and cotyledons. Given the significant role of amylose in determining the quality of starchy crops, optimizing its content has become a key objective in current crop breeding efforts. Tartary buckwheat, a dicotyledonous plant, notably accumulates high levels of amylose in its endosperm, surpassing common cereals like rice and maize. However, the mechanisms underlying amylose accumulation, distribution, and regulation in Tartary buckwheat remain unclear. Here, amylose content was determined across various tissues and organs of Tartary buckwheat, identifying with the endosperm as the primary site for its biosynthesis and accumulation. RNA sequencing analysis of endosperms from different developmental stages identified 35 genes potentially involved in starch biosynthesis, with 13 genes showing high endosperm-specific expression, suggesting crucial roles in starch biosynthesis. Additionally, the transcription factor FtNF-YB2, which was specifically highly expressed in the endosperm, was discovered to enhance amylose synthesis. Moreover, promoters with potential endosperm-specific activity were identified, advancing our understanding of amylose regulation. Additionally, this study also demonstrates that brassinosteroids (BR) positively influence amylose biosynthesis in Tartary buckwheat endosperm. These findings provide essential insights into the mechanisms of understanding amylose biosynthesis, accumulation and regulation in Tartary buckwheat, offering significant implications for future breeding strategies.

A Dataset of Distribution and Characterization of Underground Wastewater Treatment Plants in China.

Underground wastewater treatment plants (U-WWTPs) have emerged as a novel paradigm for urban wastewater pollutants management, offering benefits such as alleviating the Not-in-my-backyard (NIMBY) effect and utilizing land resources efficiently. China stands at the forefront, witnessing swift advancements in U-WWTP technology and deployment. However, the absence of a thorough understanding of their geographical distribution and operational characteristics could lead to misaligned planning and construction, resulting in inefficient resource allocation and treatment capacities for urban wastewater treatment. This dataset provides an up-to-date overview of the spatial distribution, process selection, and discharge standards for all U-WWTPs in China (with a total number of 201) constructed since 1995. To enhance comparative analysis, the dataset has been supplemented with information on conventional aboveground wastewater treatment plants (A-WWTPs), comprising a total of 2464 records, which enriches a more comprehensive evaluation of different wastewater treatment approaches. Utilizing this dataset can provide essential data support for the strategic management of urban wastewater systems and serve as a valuable reference for the paradigmatic renovation of existing wastewater treatment plants.

O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer.

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors. Mechanistically, O-GlcNAcylation of MITF at Serine 49 enhances its interaction with importin α/ß, thus promoting its translocation to nuclei, where it suppresses palbociclib-induced senescence. Inhibition of MITF or its O-GlcNAcylation re-sensitizes resistant cells to palbociclib. Moreover, clinical studies confirm the activation of MITF in tumors from patients who are palbociclib-resistant or undergoing palbociclib treatment. Collectively, our studies shed light on the mechanism regulating palbociclib resistance and present clinical evidence for developing therapeutic approaches to treat CDK4/6i-resistant breast cancer patients.

Role of histone deacetylase inhibitors in the aging of human umbilical cord mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are self-renewing cells that exhibit differentiation capacity and immune regulation ability. These versatile cells have a wide range of potential applications. However, the spontaneous differentiation and aging of MSCs during long-term culturing restrict the amount of cells available for therapies and tissue engineering. Thus, maintaining the biological characteristics of MSCs during long-term culturing is crucial. Chromatic modification via epigenetic regulatory mechanisms (e.g., histone acetylation, deacetylation, and methylation) is crucial in stem cell pluripotency. We investigated the effects of largazole or trichostatin A (TSA), a novel histone deacetylase inhibitor (HDACi), against human umbilical cord (hUC)-MSCs aging. Results show that low concentrations of largazole or TSA can significantly improve hUC-MSCs proliferation and delay hUC-MSCs aging. Largazole can better improve MSCs proliferation than TSA. HDAC is modulate histone H3 acetylation and methylation in the telomerase reverse-transcriptase, octamer-binding transcription factor 4, Nanog, C-X-C chemokine receptor 4, alkaline phosphatase, and osteopontin genes. HDACis can promote hUC-MSCs proliferation and suppress hUC-MSCs spontaneous osteogenic differentiation. HDACis can affect histone H3 lysine 9 or 14 acetylation and histone H3 lysine 4 dimethylation, thus increasing the mRNA expression of pluripotent and proliferative genes and suppressing the spontaneous differentiation of hUC-MSCs.

A histone deacetylase inhibitor, largazole, decreases liver fibrosis and angiogenesis by inhibiting transforming growth factor-ß and vascular endothelial growth factor signalling.

BACKGROUND & AIMS: Largazole is a novel histone deacetylase (HDAC) inhibitor. This study investigated the effects of largazole against liver fibrosis. METHODS: The in vitro effects of largazole were examined using hepatic stellate cells (HSCs). In vivo effects of largazole were studied using a mouse liver fibrotic model induced by CCl4 . RESULTS: Largazole augmented acetylation of histone H3 (H3) and histone H4 (H4) in HSCs. It directly inhibited the activation of HSCs owing to HDAC inhibitory activity as the antifibrotic effect of largazole was significantly decreased in cells with HDAC1, HDAC2 and HDAC3 knockdown. Largazole also induced apoptosis of HSCs. Largazole not only inhibited the expression of TGFßR2, but also reduced phosphorylation of Smad2 and Akt induced by TGF-ß1. Largazole also inhibited the expression of vascular endothelial growth factor (VEGF) and its receptor. VEGF-induced proliferation of HSCs and activation of Akt and p38MAPK were also suppressed by largazole. In vivo, largazole reduced the expression of collagen I, α-smooth muscle actin and tissue inhibitor of metalloproteinase-1 in CCl4 -induced fibrosis, and these antifibrotic effects were associated with increased acetylation of H3 and H4. Largazole also induced HSCs to undergo apoptosis in vivo, which was correlated with downregulation of bcl-2 and bcl-xL. Furthermore, largazole inhibited angiogenesis in vivo as evidenced by reduced expression of CD34, VEGF and VEGFR. In addition to its antifibrotic activity, the drug reduced inflammatory activity in CCl4 -induced liver fibrosis. CONCLUSIONS: Our findings revealed a novel role of largazole in the treatment of liver fibrosis. Through multiple mechanisms, largazole could be a potentially effective antifibrotic agent.

Event-Triggered Practical Prescribed Time Output Feedback Neuroadaptive Tracking Control Under Saturated Actuation.

This work focuses on the issue of event-triggered practical prescribed time tracking control for a type of uncertain nonlinear systems subject to actuator saturation and unmeasurable states as well as time-varying unknown control coefficients. First, a state observer with simple structure is constructed by means of neural network technology to estimate the unmeasurable system states under time-varying control coefficients. Then, with the help of one-to-one nonlinear mapping of the tracking error, an event-triggered output feedback control scheme is developed to steer the tracking error into a residual set of predefined accuracy within a preassigned settling time. Unlike existing related control methods, there is no need to involve finite-time state observer or fractional power feedback of system states, and thus, the control solution presented here is less complex and more acceptable. The key technique in control design lies in the establishment of an alternative first-order auxiliary system for dealing with the impact arisen from the input saturation. In our proposed approach, a new bounded function related to auxiliary variable and new dynamics of the auxiliary system are skillfully utilized such that the upper bound of the difference between actual input and designed input signal is not involved in implementation of the controller.

Prescribed Performance Tracking Control Under Uncertain Initial Conditions: A Neuroadaptive Output Feedback Approach.

This work is concerned with the prescribed performance tracking control for a family of nonlinear nontriangular structure systems under uncertain initial conditions and partial measurable states. By combining neural network and variable separation technique, a state observer with a simple structure is constructed for output-based finite-time tracking control, wherein the issue of algebraic loop arising from a nontriangular structure is circumvented. Meanwhile, by using an error transformation, the developed control scheme is able to ensure tracking with a prescribed accuracy within a pregiven time at a preassigned convergence rate under any bounded initial condition, eliminating the long-standing initial condition dependence issue inherited with conventional prescribed performance control methods, and guaranteeing the predeterminability of convergence time simultaneously. Two simulation examples also demonstrate the effectiveness of the presented control strategy.