Simultaneous Regulation Research Articles

Improved volatile fatty acid production in anaerobic digestion via simultaneous temperature regulation and persulfate activation by biochar: Chemical and biological response mechanisms

Increasing volatile fatty acid (VFA) production via persulfate activation (i.e., chemical effect) in anaerobic digestion (AD) is an emerging resource utilization method. However, the reaction mechanisms responsible for improving VFA production in AD via simultaneous temperature regulation and persulfate activation by biochar remain unclear. In this study, three PB15 treatment systems of low temperature (15 °C), medium temperature (35 °C) and high temperature (55 °C) were set to explore the relationship between VFAs production and treatment temperature and the influence of temperature on the reaction mechanism. The results show that the improvement of hydrolysis and acidification efficiency of the system in the medium temperature system is the highest. The VFA yield and acid production rate in the treatment group at 35 °C were 2.49 and 5.22 times higher than those in the control group, respectively. The chemical effect effectively initiated the anaerobic acid production process and maintained the dominant role of the biological effect. The activity of persulfate is too low at low temperature, and its decomposition is too fast at high temperature. Plenty of free radicals lead to enhanced oxidation of the system, which may kill the fermentation bacteria. The NCM model indicates that microbial stability is reduced in high temperature systems. The SEM model showed that temperature change mainly affected substrate degradation by hydrolytic bacteria and indirectly affected acid production by acid-producing bacteria. This study provides a new strategy for realizing pollutant recycling and increasing VFAs production in cold area.

Static actuator-sharing algorithm for concurrent control of multiple plasma properties

Abstract Simultaneous regulation of multiple properties in next-generation tokamaks like ITER and Fusion Pilot Plant (FPP) may require the integration of different plasma control algorithms. Such integration requires the conversion of individual controller commands into physical actuator requests while accounting for the coupling between different plasma properties. This work proposes a tokamak and scenario-agnostic actuator-sharing algorithm (ASA) to perform the above-mentioned command-request conversion and, hence, integrate multiple plasma controllers. The proposed algorithm implicitly solves a quadratic programming (QP) problem formulated to account for the saturation limits and the relation between the controller commands and physical actuator requests. Since the constraints arising in the QP program are linear, the proposed ASA is highly computationally efficient and can be implemented in the tokamak plasma control system (PCS) in real time. Furthermore, the proposed algorithm is designed to handle real-time changes in the control objectives and actuators’ availability. Nonlinear simulations carried out using the Control Oriented Transport SIMulator (COTSIM) illustrate the effectiveness of the proposed algorithm in achieving multiple control objectives simultaneously.

Simultaneous regulation of solvation shell and ion migration in morpholine-crosslinked polyacrylamide hydrogel electrolytes for durable zinc metal batteries

Simultaneous regulation of solvation shell and ion migration in morpholine-crosslinked polyacrylamide hydrogel electrolytes for durable zinc metal batteries

A multi-energy inertia-based coordinated voltage and frequency regulation in isolated hybrid power system using PI-TISMC

This paper proposes novel multi-energy inertia support for simultaneous frequency and voltage control of an isolated hybrid power system (IHPS). Multi-energy storage (gas inertia – hydrogen storage, thermal inertia – solar thermal storage, hydro inertia – gravity hydro storage, chemical inertia – battery energy storage) supported by demand side management (DSM) for simultaneous voltage and frequency regulation and backed by biodiesel generators, are the essential elements of IHPS. A novel control strategy of concurrent virtual droop control, virtual damping control, virtual inertia control, and virtual negative inertia control is proposed to utilise multiple inertia sources and to improve LFC and AVR performance effectively. The effective coordination of inertia sources in eradicating oscillations in IHPS, is aided by a developed cascaded proportional integral-tilt-integral-sliding mode (PI-TISMC) controller. The performance of PI-TISMC is compared with PID, PI-PID, and PI-SMC controllers. A maiden attempt has been done by training five diverse classes of optimization techniques to optimize the parameters of controllers in the present work. The results are evaluated in MATLAB and it is evident from the results that the performance of frequency control is improved by 6.5%, 7.8% and 3.4 s (over shoot, undershoot, and settling time). The performance of frequency control is improved by 6.5%, 7.8% and 3.4 s (over shoot, undershoot, and settling time). Similarly, the performance of voltage control is improved by 6.7%, 4.8% and 2.3 s (over shoot, undershoot, and settling time) by employing developed PI-TISMC controller and proposed concurrent inertia control. The combination exhibits superior performance in minimizing oscillations in IHPS due to variations in loading and solar insolation.

NeuropsychopharmARCology: Shaping Neuroplasticity through Arc/Arg3.1 Modulation

Activity-regulated cytoskeletal associated protein (aka activity-regulated gene Arg3.1) belongs to the effector gene family of the immediate early genes. This family encodes effector proteins, which act directly on cellular homeostasis and function. Arc/Arg3.1 is localized at dendritic processes, allowing the protein local synthesis on demand, and it is considered a reliable index of activitydependent synaptic changes. Evidence also exists showing the critical role of Arc/Arg3.1 in memory processes. The high sensitivity to changes in neuronal activity, its specific localization as well as its involvement in long-term synaptic plasticity indeed make this effector gene a potential, critical target of the action of psychotropic drugs. In this review, we focus on antipsychotic and antidepressant drugs as well as on psychostimulants, which belong to the category of drugs of abuse but can also be used as drugs for specific disorders of the central nervous system (i.e., Attention Deficit Hyperactivity Disorder). It is demonstrated that psychotropic drugs with different mechanisms of action converge on Arc/Arg3.1, providing a means whereby Arc/Arg3.1 synaptic modulation may contribute to their therapeutic activity. The potential translational implications for different neuropsychiatric conditions are also discussed, recognizing that the treatment of these disorders is indeed complex and involves the simultaneous regulation of several dysfunctional mechanisms.

Potential antitumor effect of polysaccharides extracted from Polygonatum sibiricum on human prostate cancer PC‑3 cells.

Polygonatum sibiricum polysaccharides (PSP) are a traditional herbal medicine component with potential therapeutic effects on several diseases. The present study aimed to assess the role of PSP in the treatment of human prostate cancer using a PC-3 cell line by Cell CK-8, transwell and wound healing assays, then elucidate the potential underlying mechanisms by western blot and quantitative Real-time RT-PCR. Different concentrations of PSP were applied to PC-3 cells, and the proliferation, invasion and migration of PC-3 cells were demonstrated to be significantly inhibited with increasing concentrations of PSP. Additionally, cell apoptosis rate and expression of caspase-3 increased with higher PSP concentrations, and the cell cycle was arrested in the S phase. Furthermore, it was demonstrated that the expression of the multidrug resistance-1 gene and its encoded protein P-glycoprotein in PC-3 cells decreased following PSP treatment, suggesting that PSP may have the potential to reverse multidrug resistance in PC-3 cells. The present study also evaluated the possible mechanism of PSP action on PC-3 cells. The results revealed that phosphorylated P65, PI3K and AKT decreased in a concentration-dependent manner. As key molecules in the NF-κB and PI3K/Akt signaling pathways, this finding suggests that the potential mechanism of the effect of PSP on prostate cancer cells may involve simultaneous mediation of the PI3K/Akt and NF-κB signaling pathways. The present study demonstrated that PSP inhibit the proliferation, invasion and migration of PC-3 cells in vitro, as well as reverse MDR in these cells. The underlying mechanism may involve the simultaneous regulation of the PI3K/Akt and NF-κB signaling pathways.

GATA2 downregulation contributes to pro-inflammatory phenotype and defective phagocytosis of pulmonary macrophages in chronic obstructive pulmonary disease.

Pulmonary macrophages from COPD patients are characterized by lower phagocytic and bactericidal activity whereas there is hypersecretion of pro-inflammatory cytokines. The prominent decline of GATA2 expression in pulmonary macrophages from COPD patients inspired us to figure out its role during COPD development. The expression levels of GATA2 were decreased in alveolar macrophages isolated from cigarette smoke (CS)-induced COPD mice and cigarette smoke extract (CSE)-treated macrophages. In vitro, both CSE and GATA2 knockdown via siRNAs elevated pro-inflammatory cytokines expression whereas inhibiting phagocytosis in macrophages. Integrated analysis of transcriptomics of GATA2-knockdown macrophages and the results of ChIP sequencing of GATA2 together with dual-luciferase reporter assay identified Abca1 and Pacsin1 as functional target genes of GATA2. Mechanistically, ABCA1 mediates the pro-inflammatory secretion phenotype and the dysfunction in early stage of phagocytosis of macrophages through TLR4/MyD88 and MEGF10/GULP1 pathways, respectively. PACSIN1/SUNJ1 partially mediates the disruption effects of GATA2 downregulation on maturation of phagolysosomes in macrophages. Together, our study suggests that GATA2 influences multiple functions of pulmonary macrophages by simultaneous transcriptional regulation of several target genes, contributing to the dysfunctions of pulmonary macrophages in response to CS, which provides an impetus for further investigations of GATA2 or other underappreciated transcription factors as regulatory hubs in COPD pathogenesis.

Fractional order slide mode droop control for simultaneous voltage and frequency regulation of AC microgrid

AbstractThis research proposes the application of fractional‐order sliding mode control (FOSMC) at the primary controller level to improve the stability of an islanded microgrid by adjusting its voltage and frequency. The control strategies used in the microgrid are performed in two levels (primary and secondary) in the islanded mode. Practically, most previous studies have worked to improve the primary controller. Droop control is one of the most commonly used methods at the primary level and is adopted in this study as well. The sliding mode control (SMC) strategy is normally used to control linear equations. Thus, the non‐linear microgrid equations were transformed into some linear ones using the input‐output feedback linearization technique. Further, a fractional sliding surface was acquainted. The sliding surface and FOSMC were designed to reject system uncertainties and organize the voltage and frequency. Design parameters were chosen using the Lyapunov stability theorem. The validation of the proposed method using Simulink‐MATLAB confirms its effectiveness in enhancing level power sharing, regulating frequency, and maintaining voltage stability across the system.

Sliding mode-based direct power control of unified power quality conditioner

The Unified Power Quality Conditioner (UPQC) is a promising solution for mitigating multiple Power Quality(PQ) issues in distribution systems, including harmonics, poor power factor, voltage sag/swell and voltage imbalance. The conventional Sliding Mode Controller (SMC) in UPQCs suffers from wide switching frequency variations, chattering problems, and inherent active and reactive power coupling. This study proposes a nonlinear control method, Sliding Mode-based Direct Power Control (SMC-DPC), for the simultaneous regulation of the shunt and series compensators in a UPQC. By optimizing voltage vector selection based on real-time power errors, the proposed method effectively mitigates chattering, and reduces switching frequency variations, and ensures precise tracking of instantaneous active and reactive powers even in the presence of coupling effects. The proposed approach simplifies the system design and improves steady state and dynamic power tracking. The simulation results in MATLAB Simulink® on a 20 kVA system demonstrate that the proposed method achieves a source current THD of 1.52%, compared to 2.31% for conventional SMC and 5.11% for linear controller. Furthermore, the method is robust to grid parameter variations and demonstrates satisfactory performance in both strong and weak grids. In weak grids, the proposed method reduces the line losses by 13.71% and 14.54% compared to SMC and linear controller respectively. The reported results comply with international standards such as IEEE-519 and IEC 61000-3-12, confirming effectiveness of SMC-DPC for enhancing PQ in distribution system.

Simultaneous Regulation of Organic and Inorganic Components in Interphase by Fiber Separator for High-Stable Sodium Metal Batteries.

Uncontrollable side reactions at the metal interface have been identified as the root cause of the formation of a fragile solid electrolyte interphase, leading to irreversible sodium loss in sodium metal batteries. Here, we proposed an interface engineering strategy that employed a carboxyl functionalized cellulose separator to provide strong dipole moments and induce the cleavage of P-F bond to construct a solid electrolyte interphase (SEI) rich in NaF. In addition, we employed nuclear magnetic resonance technology confirmed that the separator with strong dipole moments prevented the reduction of organic solvents by attracting electrons, thereby inhibiting the formation of organic oligomers. SEI with high NaF content and few oligomers is smooth and robust, obviously decreasing the interface impedance of the Na anode. The symmetric Na||Na cells, equipped with the functionalized separator, efficiently operated for 1400 hours with a stable 72 mV overpotential at 0.25 mA cm-2, exhibiting low energy barrier and fast ion transport kinetics. The Na||Na3V2(PO4)3 cell also showed stable cycling performance, with the capacity remaining at 94.83 % of the initial capacity after 1000 cycles at 1C. The proposed separator could control the formation and composition of SEI, paving the way for the development of long-life sodium metal batteries.

Siamese based few-shot learning lightweight transformer model for coagulant and disinfectant dosage simultaneous regulation

Deep learning (DL) has emerged as a transformative and promising approach to address inefficient resource management due to imprecise chemical dosing in conventional manual-dependent drinking water treatment. However, the scarcity of high-quality data and limited computing resources of embedded devices hinder the development and deployment of state-of-the-art (SOTA) DL models. Herein, a novel lightweight Transformer (LighT) model integrated with the Siamese structure was proposed for simultaneous regulation of coagulant dosage (FeCl3 and PAC) and disinfectant dosage (NaClO) and compared with other attention-based DL models. The results demonstrate that LighT showed robust few-shot learning effectiveness and outperformed other models in multi-output prediction (R2 values of 0.99 and RMSE of 0.20 mg/L, 0.16 mg/L and 0.45 mg/L, respectively). The LighT model also exhibited enhanced cost-effectiveness with a 79.74 % compression in model parameters and a 36.14 % decrease in inference time. The LighT-based chemical dosage prediction program was sustained for one month of operation, which can save chemical dosage by 15.81 % while maintaining satisfactory product water quality, indicating the potential of LighT for economizing chemical dosing strategy in drinking water treatment.

A Methyl-Engineered DNAzyme for Endogenous Alkyltransferase Monitoring and Self-Sufficient Gene Regulation.

The on-demand gene regulation is crucial for extensively exploring specific gene functions and developing personalized gene therapeutics, which shows great promise in precision medicines. Although some nucleic acid-based gene regulatory tools (antisense oligonucleotides and small interfering RNAs) are devised for achieving on-demand activation, the introduction of chemical modifications may cause undesired side effects, thereby impairing the gene regulatory efficacy. Herein, a methyl-engineered DNAzyme (MeDz) is developed for the visualization of endogenous alkyltransferase (AGT) and the simultaneous self-sufficiently on-demand gene regulation. The catalytic activity of DNAzyme can be efficiently blocked by O6-methylguanine (O6MeG) modification and specifically restored via the AGT-mediated DNA-repairing pathway. This simply designed MeDz is demonstrated to reveal AGT of varying expression levels in different cells, opening the possibility to explore the AGT-related biological processes. Moreover, the AGT-guided MeDz exhibits cell-selective regulation on the human early growth response-1 (EGR-1) gene, with efficient gene repression in breast cancer cells and low effectiveness in normal cells. The proposed MeDz offers an attractive strategy for on-demand gene regulation, displaying great potential in biomedical applications.

Simultaneous regulation of nitrogen, sulfur and carbon using biochar during sewage sludge pyrolysis

Due to the complex nature of sewage sludge (SS), how to control the emission of precursor pollutants during its pyrolysis remains a challenge. In this work, the evolution of N, S and C during SS pyrolysis was investigated and biochars were employed to regulate their distribution in the resulting products. The release of N-containing products followed a descending order of NH3>HCN > NO > NO2 and the biochar addition resulted in a reduction of 40.7–54.3 % for these volatiles. The nitrile-N and pyrrolic-N species decreased, while the quaternary-N in residue increased significantly. The emission of S-containing products showed a descending order of COS > SO2>CH3SH > H2S > CS2 and the co-pyrolysis with biochar showed a reduction of 40.6–65.7 % for these products. The relative contents of thiophene-S and sulfoxide-S species increased, while the content of sulfone-S decreased. Biochar incorporation also resulted in a reduction of 67.2 % and 47.4 % for CO and CO2, respectively. Both Raman and XPS analysis indicated an increase in the graphitization degree and a decrease in structural defects.

IR Hidden Patterns for Security Labels.

Authentication of a product's originality by anticounterfeiting labels represents a crucial point toward protection against forgery. Fast and scalable fabrication methods of original labels with a high degree of protection are in high demand for the protection of valuable goods. Here, we propose a simple strategy for fabrication of hidden security tags with IR luminescent readout by the direct femtosecond laser patterning of silicon-erbium-silicon sandwiched thin films. The choice of laser processing parameters makes possible the creation of random or quasi-regular self-organized surface nanotextures. The controlled laser-driven oxidation accompanying this process provides simultaneous regulation of the film's optical properties and spontaneous emission yield of the embedded Er atoms. The regimes are detected when optically similar patterned areas demonstrate different Er emission intensities, allowing us to create hidden security tags with facile readout at the C-band telecommunication wavelengths. The obtained results take another step toward the application of IR-luminescent erbium-based anticounterfeiting labels for covert and/or forensic security levels.

Synergistic integration of electrical stimulation, reactive oxygen species regulation, and pro-angiogenic for accelerated wound healing

Wound healing involves a complex series of coordinated events throughout the inflammatory, proliferative, and maturation phases of tissue repair. Current treatment modalities lack a device catering to all wound healing stages for tissue recovery, angiogenesis and epithelialization. Herein, we developed an integrated wound healing system with multiple functions of self-electrical stimulation (ES), reactive oxygen species (ROS) regulation, and bioactive metal-releasing patch (ERMP) to address all wound healing stages including hemostasis, inflammation, proliferation, and remodeling. The multiple functions of ERMP are ES, generated by the movement of the mice, for tissue regeneration, magnesium (Mg) ion release via iontophoresis triggered by ES for pro-angiogenic effects, and simultaneous regulation of ROS. This system employs self-generating ES utilizing the movements of the individuals to trigger triboelectric nanogenerators (TENGs), which consequently transfer ES through Mg microneedles while effectively delivering enhanced Mg ions with an iontophoresis via ES to the wound site. Specially, Prussian blue (PB) was utilized to not only enhance output performance on TENG as charge trap, but also regulate excessive ROS via modified PB with carbon–nitrogen vacancies in the wound site. The synergistic effects of ES, ROS regulation, and enhanced Mg ions releases led to a nine-fold recovery rates in wound healing compared to the control group in vivo tests. This approach addresses the inherent limitations of conventional wound healing methods and provides a viable treatment for various severe wound types.

Harnessing the potential of the NALT and BALT as targets for immunomodulation using engineering strategies to enhance mucosal uptake.

Mucosal barrier tissues and their mucosal associated lymphoid tissues (MALT) are attractive targets for vaccines and immunotherapies due to their roles in both priming and regulating adaptive immune responses. The upper and lower respiratory mucosae, in particular, possess unique properties: a vast surface area responsible for frontline protection against inhaled pathogens but also simultaneous tight regulation of homeostasis against a continuous backdrop of non-pathogenic antigen exposure. Within the upper and lower respiratory tract, the nasal and bronchial associated lymphoid tissues (NALT and BALT, respectively) are key sites where antigen-specific immune responses are orchestrated against inhaled antigens, serving as critical training grounds for adaptive immunity. Many infectious diseases are transmitted via respiratory mucosal sites, highlighting the need for vaccines that can activate resident frontline immune protection in these tissues to block infection. While traditional parenteral vaccines that are injected tend to elicit weak immunity in mucosal tissues, mucosal vaccines (i.e., that are administered intranasally) are capable of eliciting both systemic and mucosal immunity in tandem by initiating immune responses in the MALT. In contrast, administering antigen to mucosal tissues in the absence of adjuvant or costimulatory signals can instead induce antigen-specific tolerance by exploiting regulatory mechanisms inherent to MALT, holding potential for mucosal immunotherapies to treat autoimmunity. Yet despite being well motivated by mucosal biology, development of both mucosal subunit vaccines and immunotherapies has historically been plagued by poor drug delivery across mucosal barriers, resulting in weak efficacy, short-lived responses, and to-date a lack of clinical translation. Development of engineering strategies that can overcome barriers to mucosal delivery are thus critical for translation of mucosal subunit vaccines and immunotherapies. This review covers engineering strategies to enhance mucosal uptake via active targeting and passive transport mechanisms, with a parallel focus on mechanisms of immune activation and regulation in the respiratory mucosa. By combining engineering strategies for enhanced mucosal delivery with a better understanding of immune mechanisms in the NALT and BALT, we hope to illustrate the potential of these mucosal sites as targets for immunomodulation.

Facilitating charge transport by phenyl-substitution and sulfate-intercalation on carbon nitride tubes for highly efficient photocatalytic hydrogen evolution

Despite challenges still remain, simultaneous regulation of light absorption, carrier separation and efficient exposed active sites of carbon nitride for the photocatalytic production of hydrogen (H2) are essential to help alleviate the energy crisis and achieve carbon neutrality. Using in-plane phenyl groups doping and interlayer sulfate groups modification, we demonstrated an eco-friendly and facile method for excogitating porous tubular graphitic carbon nitride (PhSO-TCN2.5). The PhSO-TCN2.5 has hollow tubular morphology with ultrathin pore walls, which offers more exposed active sites, shortened charge diffusion path and readily available diffusion channels. More importantly, the in-plane phenyl groups doping and interlayer sulfate groups modification enabled significant intense the visible light absorption, accelerated carrier transfer due to the electron transport channel between the interlayers. Meanwhile, PhSO-TCN2.5 possesses exceptionally adjusted band gap structure and more negative conduction band potential. Accordingly, the above synergistic effects contribute to the efficient photocatalytic efficiency in H2 evolution to 8709.29 μmol g−1 h−1. In addition to the apparent quantum yield of 12.0% at 420 nm, that far exceeds the reported tubular and functional group-modified carbon nitride photocatalysts. This document offers guidance on designing and producing photocatalysts with high efficiency.

Simultaneous regulation of the solvation shell and electrode interface via a multifunctional and low-cost additive enabling long-life aqueous Zn metal batteries

Zinc metal batteries have great potential for energy storage applications in smart grids. However, the Zn metal anode presents significant challenges, such as the irrepressible growth of zinc dendrites on the anode’s surface, the accumulation of inert products, and the hydrogen evolution reaction. These issues can lead to the decreased cycling stability of the anode. To solve these problems, we developed a method of adding sodium p-toluenesulfonate to the electrolyte to protect the zinc metal anode. Density functional theory calculations show that the −SO3 functional group in sodium p-toluenesulfonate can alter the solvation structure of Zn2+ and adsorb onto the surface of the Zn metal anode. Thus, the Zn||Zn symmetric cell could be cycled stably for over 2000 h, whereas the Zn||Cu half-cell could be cycled stably for over 5000 cycles, with an average Coulombic efficiency of 99.87 %. The Zn||I2 full cell could be cycled stably for 10,000 cycles under test conditions of 1A/g, and the capacity retention rate was 95.49 %. This study provides insights into the use of additives in the electrolytes of zinc metal batteries.

NIR-II-Responsive Hybrid System Achieves Cascade-Augmented Antitumor Immunity via Genetic Engineering of Both Bacteria and Tumor Cells.

The combination of nanoparticles and tumor-targeting bacteria for cancer immunotherapy can overcome the shortcomings of poor nanoparticle accumulation, limited penetration, and restricted distribution. However, it remains a great challenge for the hybrid system to improve therapeutic efficacy through the simultaneous and controllable regulation of immune cells and tumor cells. Herein, a hybrid therapeutic platform is rationally designed to achieve immune cascade-augmented cancer immunotherapy. To construct the hybrids, photothermal nanoparticles responsive to light in the second near-infrared (NIR-II) region are conjugated onto the surface of engineered bacteria through pH-responsive Schiff base bonds. Taking advantage of the hypoxia targeting and deep penetration characteristics of the bacteria, the hybrids can accumulate at tumor sites. Then nanoparticles detach from the bacteria to realize genetic engineering of tumor cells, which induces tumor cell apoptosis and down-regulate the expression of programmed cell death ligand 1 to alleviate immunosuppressive tumor microenvironment. The mild photothermal heating can not only induce tumor-associated antigen release, but also trigger sustainable expression of cytokine interleukin-2. Notably, a synergistic antitumor effect is achieved between the process of p53 transfection and NIR-II light-activated genetic engineering of bacteria. This work proposes a facile strategy for the construction of hybrid system to achieve cascade-augmented cancer immunotherapy.

Discovery and Optimization of Hsp110 and sGC Dual-Target Regulators for the Treatment of Pulmonary Arterial Hypertension.

Currently, bifunctional agents with vasodilation and ameliorated vascular remodeling effects provide more advantages for the treatment of pulmonary arterial hypertension (PAH). In this study, we first screened the hit 1 with heat shock protein 110 (Hsp110) inhibition effect from our in-house compound library with soluble guanylate cyclase (sGC) activity. Subsequently, a series of novel bisamide derivatives were designed and synthesized as Hsp110/sGC dual-target regulators based on hit 1. Among them, 17i exhibited optimal Hsp110 and sGC molecular activities as well as remarkable cell malignant phenotypes inhibitory and vasodilatory effects in vitro. Moreover, compared to riociguat, 17i showed superior efficacy in attenuating pulmonary vascular remodeling and right ventricular hypertrophy via Hsp110 suppression in hypoxia-induced PAH rat models (i.g.). Notably, our study successfully demonstrated that the simultaneous regulation of Hsp110 and sGC dual targets was a novel and feasible strategy for PAH therapy, providing a promising lead compound for anti-PAH drug discovery.