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In this article, a robust adaptive dynamic position-control problem is addressed for full-actuated surface vessels under coupled uncertainties from unmodeled hydrodynamic effects and time-varying external disturbances. To obtain a high-performance dynamic position controller, a reinforcement learning (RL) weights law involving actor and critic networks is designed without knowledge of the model dynamics and the disturbance parameters. This can enhance the robustness of the closed-loop control system. Furthermore, dynamic surface control is integrated to diminish the design complexity resulting from the derivative of the kinematics, while ensuring semi-global uniformly ultimately bounded (SGUUB) stability through Lyapunov-based synthesis. Simulations are carried out to evaluate the superiority and feasibility of the proposed algorithm.

A novel extended-gate field-effect transistor (FET) photoelectrochemical (EGFET PEC) sensor was designed for highly sensitive detection of L-cysteine (L-Cys). TiO 2 was initially modified on the ITO electrode by the sol–gel dip-coating method and calcined to produce TiO 2 /ITO. Then, CdS was synthesized on the TiO 2 surface by hydrothermal method to obtain the CdS–TiO 2 heterojunction material. CdS/TiO 2 /ITO was connected to the gate of the FET to obtain an EGFET PEC sensor. Under the irradiation of a xenon lamp simulating visible light, the CdS/TiO 2 heterojunction composite absorbs light energy to produce photogenerated electron–hole pairs, which have strong photocatalytic oxidation activity and oxidize L-Cys covalently identified by Cd(II) through CdS covalent. These pairs generate a photovoltage that controls the current between the source and the drain to detect L-Cys. Under the optimized experimental conditions, the optical drain current ( I D ) of the sensor exhibited a good linear relationship with the logarithm of L-Cys in the range of 5.0 × 10 −9 –1.0 × 10 −6 mol/L, and the detection limit was 1.3 × 10 −9 mol/L (S/N = 3), which is lower than the values reported by other detection methods. Results showed that the CdS/TiO 2 /ITO EGFET PEC sensor revealed high sensitivity and good selectivity. The sensor has been used to determine L-Cys in urine samples. Graphical abstract

Atrazine (ATZ) is used extensively, resulting in residues in food and the environment, posing a serious threat to human health. Herein, Cd 0.5 Zn 0.5 S/Ti 3 C 2 photoelectric material was synthesized and immobilized on a FTO electrode as a photoanode. A photoelectrochemical (PEC) aptamer sensor was constructed for the highly sensitive and selective determination of ATZ based on signal amplification via cascade catalysis of CRISPR/Cas12a and G-quadruplex/hemin DNAzyme (G4/hemin DNAzyme). G4/hemin DNAzyme catalyses the oxidation reaction between H 2 O 2 and dopamine (DA) to form polydopamine (PDA) deposit. This process, in turn, inhibits the photocurrent at the photoanode, leading to a decrease in photocurrent. Concurrently, the depletion of DA as an electron donor for the PEC reaction at the photoelectrode further contributes to the decrease in photocurrent. ATZ can hybridize with ATZ aptamer (Apt) in Apt/cDNA to release activation strand (cDNA), which activates the activity of CRISPR/Cas12a and triggers cleavage of G4, causing the cleaving of G4/hemin DNAzyme immobilized on the electrode surface. This process leads to a decrease of G4/hemin DNAzymes amount on the electrode, consequently reducing both the PDA generation and the DA consumption. As a result, the photocurrent is restored. The cascade catalysis of CRISPR/Cas12a and G4/hemin DNAzyme has been demonstrated to result in photocurrent amplification. The photocurrent change was linear with the logarithmic value of ATZ concentration in the range 1.00 × 10 –12 to 1.00 × 10 –5  mol/L. The limit of detection was 3.47 × 10 –13  mol/L. The sensor has been successfully applied to the determination of trace ATZ in environmental and food samples. Graphical abstract

A novel extended-gate field-effect transistor (FET) photoelectrochemical (EGFET PEC) sensor was designed for highly sensitive detection of L-cysteine (L-Cys). TiO.sub.2 was initially modified on the ITO electrode by the sol-gel dip-coating method and calcined to produce TiO.sub.2/ITO. Then, CdS was synthesized on the TiO.sub.2 surface by hydrothermal method to obtain the CdS-TiO.sub.2 heterojunction material. CdS/TiO.sub.2/ITO was connected to the gate of the FET to obtain an EGFET PEC sensor. Under the irradiation of a xenon lamp simulating visible light, the CdS/TiO.sub.2 heterojunction composite absorbs light energy to produce photogenerated electron-hole pairs, which have strong photocatalytic oxidation activity and oxidize L-Cys covalently identified by Cd(II) through CdS covalent. These pairs generate a photovoltage that controls the current between the source and the drain to detect L-Cys. Under the optimized experimental conditions, the optical drain current (I.sub.D) of the sensor exhibited a good linear relationship with the logarithm of L-Cys in the range of 5.0 x 10.sup.-9-1.0 x 10.sup.-6 mol/L, and the detection limit was 1.3 x 10.sup.-9 mol/L (S/N = 3), which is lower than the values reported by other detection methods. Results showed that the CdS/TiO.sub.2/ITO EGFET PEC sensor revealed high sensitivity and good selectivity. The sensor has been used to determine L-Cys in urine samples. Graphical abstract

A novel extended-gate field-effect transistor (FET) photoelectrochemical (EGFET PEC) sensor was designed for highly sensitive detection of L-cysteine (L-Cys). TiO was initially modified on the ITO electrode by the sol-gel dip-coating method and calcined to produce TiO /ITO. Then, CdS was synthesized on the TiO surface by hydrothermal method to obtain the CdS-TiO heterojunction material. CdS/TiO /ITO was connected to the gate of the FET to obtain an EGFET PEC sensor. Under the irradiation of a xenon lamp simulating visible light, the CdS/TiO heterojunction composite absorbs light energy to produce photogenerated electron-hole pairs, which have strong photocatalytic oxidation activity and oxidize L-Cys covalently identified by Cd(II) through CdS covalent. These pairs generate a photovoltage that controls the current between the source and the drain to detect L-Cys. Under the optimized experimental conditions, the optical drain current (I ) of the sensor exhibited a good linear relationship with the logarithm of L-Cys in the range of 5.0 × 10 -1.0 × 10 mol/L, and the detection limit was 1.3 × 10 mol/L (S/N = 3), which is lower than the values reported by other detection methods. Results showed that the CdS/TiO /ITO EGFET PEC sensor revealed high sensitivity and good selectivity. The sensor has been used to determine L-Cys in urine samples.

The function of the fibrinolytic system was first identified to dissolve fibrin to maintain vascular patency. Connections between the fibrinolytic system and many other physiological and pathological processes have been well established. Dysregulation of the fibrinolytic system is closely associated with multiple pathological conditions, including thrombosis, inflammation, cancer progression, and neuropathies. Thus, molecules in the fibrinolytic system are potent therapeutic and diagnostic targets. This review summarizes the currently used agents targeting this system and the development of novel therapeutic strategies in experimental studies. Future directions for the development of modulators of the fibrinolytic system are also discussed.Fibirinolytic system: an old system as new therapeutic targetsThe fibrinolytic system was originally identified to dissolve blood clots, and is shown to have important roles in other pathological processes, including cancer progression, inflammation, and thrombosis. Molecules or therapeutics targeting fibrinolytic system have been successfully used in the clinical treatments of cancer and thrombotic diseases. The clinical studies and experimental models targeting fibrinolytic system are reviewed by Haili Lin at Sanming First Hosipital, Mingdong Huang at Fuzhou University in China, and Peng Xu at A*STAR in Singapore to demonstrate fibrinolytic system as novel therapeutic targets. As an example, the inhibition of fibrinolytic system protein can be used to suppress cancer prolifieration and metastasis. This review also discusses the potential therapeutic effects of inhibitiors of fibrinolytic system on inflammatory disorders.

An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity. Importantly, Agrin overhauls cytoskeletal architecture via enhancing actomyosin cables upon sensing geometric stress and force following an injury. Moreover, we identify Matrix Metalloproteinase-12 (MMP12) as a downstream effector of Agrin’s mechanoperception. We also reveal a promising potential of a recombinant Agrin fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing. Together, we propose that Agrin-MMP12 pathway integrates a broad range of mechanical stimuli to coordinate a competent skin wound healing niche. Replenishing key extracellular matrix (ECM) proteins facilitate wound healing through unclear mechanisms. Here the authors report that injury-triggered Agrin, an ECM proteoglycan, tunes a mechanocompetent niche by engaging MMP-12, thereby enforcing efficient skin wound healing.

This study examines whether penalties issued to Chinese listed companies by securities regulators for violations of corporate law affect the cost of debt, and the moderating role of corporate social responsibility (CSR) fulfillment on this relationship. Our sample consists of firms listed on Shanghai and Shenzhen stock exchanges from 2011 to 2017 and the data are collected from the announcements of China Securities Regulatory Commission. The findings are as follows: (1) punishment announcements by regulatory authorities increase the cost of debt; and (2) the effect of punishment announcements on the cost of debt is partially offset by prior CSR performance. These findings are shown to be robust. The reputation insurance effect of CSR is more pronounced in state-owned enterprises and in an institutional environment with low marketization, a weak legal environment, and low information transparency. The findings support the reputation insurance hypothesis of CSR and employ the cost of debt as a governance mechanism.

Dysregulation of Hippo pathway leads to hyperactivation of YAP-TEAD transcriptional complex in various cancers, including colorectal cancer (CRC). In this study, we observed that HHEX (Hematopoietically expressed homeobox) may enhance transcription activity of the YAP-TEAD complex. HHEX associates with and stabilizes the YAP-TEAD complex on the regulatory genomic loci to coregulate the expression of a group of YAP/TEAD target genes. Also, HHEX may indirectly regulate these target genes by controlling YAP/TAZ expression. Importantly, HHEX is required for the pro-tumorigenic effects of YAP during CRC progression. In response to serum stimulation, CK2 (Casein Kinase 2) phosphorylates HHEX and enhances its interaction with TEAD4. A CK2 inhibitor CX-4945 diminishes the interaction between HHEX and TEAD4, leading to decreased expression of YAP/TEAD target genes. CX-4945 synergizes the antitumor activity of YAP-TEAD inhibitors verteporfin and Super-TDU. Elevated expression of HHEX is correlated with hyperactivation of YAP/TEAD and associated with poor prognosis of CRC patients. Overall, our study identifies HHEX as a positive modulator of YAP/TEAD to promote colorectal tumorigenesis, providing a new therapeutic strategy for targeting YAP/TEAD in CRC. Hippo signalling is often deregulated in cancers. Here the authors show that CK2 enhances the cooperation of HHEX with YAP-TEAD complex to promote colorectal tumorigenesis.

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways 1 . Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development 2 , 3 . However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients’ peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts. A dominantly inherited human autoinflammatory disease caused by mutations in RIPK1 is identified, and RIPK1 mutations that prevent caspase-8 cleavage sensitize cells to apoptosis, necroptosis and inflammation.