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Defect identification for unintentionally induced defects and radiation‐implemented defects always attracts great attention in semiconductor materials. Recent advances in carbon‐implemented single‐photon emitters in silicon urgently require the accurate identification of defect structures to reveal transition mechanisms. Using hybrid functional with finite size correction, we investigate the charge and optical transitions of carbon‐related defects, including CSiCSi, VSiCSi, CSi, SiiCSiCSi, and Ci. Except for Ci, other defects present the negative‐U feature in the charge transition process. CSiCSi and VSiCSi tend to perform p‐type conductivity with the electron capture transition close to the valence band, of which transition level ε (0/−1) is 0.30 eV for CSiCSi and ε (+1/−2) is 0.34 eV for VSiCSi. CSi and SiiCSiCSi present a bipolar doping character, and CSi tends to capture holes with transition ε (0/+2) = 0.10 eV. The optical transitions that typically emit or absorb light in the telecom optical wavelength bands are identified in these defects in terms of band edge recombination. The zero‐phonon lines of optical transitions of ε (+2/+1) for VSiCSi and Ci are consistent with a previous experiment involving single‐photon emitters. The findings are helpful to understand the performance degradation of silicon devices and provide a reference for identifying the structure of carbon‐related defects in silicon. [ABSTRACT FROM AUTHOR]

Structural variations (SVs) are a feature of plant genomes that has been largely unexplored despite their significant impact on plant phenotypic traits and local adaptation to abiotic and biotic stress. In this study, we employed woolly grape (Vitis retordii), a species native to the tropical and subtropical regions of East Asia with both coastal and inland habitats, as a valuable model for examining the impact of SVs on local adaptation. We assembled a haplotype‐resolved chromosomal reference genome for woolly grape, and conducted population genetic analyses based on whole‐genome sequencing (WGS) data from coastal and inland populations. The demographic analyses revealed recent bottlenecks in all populations and asymmetric gene flow from the inland to the coastal population. In total, 1,035 genes associated with plant adaptive regulation for salt stress, radiation, and environmental adaptation were detected underlying local selection by SVs and SNPs in the coastal population, of which 37.29% and 65.26% were detected by SVs and SNPs, respectively. Candidate genes such as FSD2, RGA1, and AAP8 associated with salt tolerance were found to be highly differentiated and selected during the process of local adaptation to coastal habitats in SV regions. Our study highlights the importance of SVs in local adaptation; candidate genes related to salt stress and climatic adaptation to tropical and subtropical environments are important genomic resources for future breeding programs of grapevine and its rootstocks. [ABSTRACT FROM AUTHOR]

The assessment and diagnosis of controller performance for model‐based closed‐loop control systems has received considerable attention in recent years. A recognized factor dilapidating the controller performance is mismatching the true dynamical model of the plant and the mathematic model employed in the controller. In order to reduce the heavy effort to re‐identify the entire model, a large amount of recent works have been focusing on locating the mismatch. To further improve the mathematic model as well as controller performance, in this article, we provide a novel prediction‐based plant‐model mismatch quantification approach, which belongs to the class of moment match methodology. In particular, two cases of output prediction are considered: one‐step ahead prediction and multistep ahead prediction. Compared with existing efforts along the same line of mismatch quantification, when using the one‐step ahead prediction, our method shows an advantage of light computational complexity. On the other hand, when utilizing multistep predictions, it shows better convergence and robustness than the former, especially in the case of structural mismatches, and the long‐term prediction capability of the model is employed. With both predictions and consideration of the existence of unknown noise models in practice, we show that the plant‐model mismatch and unknown parameters of noise models can be quantified as the solution of a minimization issue that penalizes the discrepancy between the sample of plant outputs and the predictions calculated by considering the plant‐model mismatch and noise model parameters. Several examples are provided to demonstrate the effectiveness of the proposed methods, respectively. [ABSTRACT FROM AUTHOR]

With the electrochemical performance of batteries approaching the bottleneck gradually, it is increasingly urgent to solve the safety issue. Herein, all‐in‐one strategy is ingeniously developed to design smart, safe, and simple (3S) practical pouch‐type LiNi0.8Co0.1Mn0.1O2||Graphite@SiO (NCM811||Gr@SiO) cell, taking full advantage of liquid and solid‐state electrolytes. Even under the harsh thermal abuse and high voltage condition (100 °C, 3–4.5 V), the pouch‐type 3S NCM811||Gr@SiO cell can present superior capacity retention of 84.6% after 250 cycles (based pouch cell: 47.8% after 250 cycles). More surprisingly, the designed 3S NCM811||Gr@SiO cell can efficiently improve self‐generated heat T1 by 45 °C, increase TR triggering temperature T2 by 40 °C, and decrease the TR highest T3 by 118 °C. These superior electrochemical and safety performances of practical 3S pouch‐type cells are attributed to the robust and stable anion‐induced electrode‐electrolyte interphases and local solid‐state electrolyte protection layer. All the fundamental findings break the conventional battery design guidelines and open up a new direction to develop practical high‐performance batteries. [ABSTRACT FROM AUTHOR]

This article studies the problem of prescribed‐time constrained tracking control for a class of 2×2$$ 2\times 2 $$ hyperbolic partial differential equation (PDE) systems with actuator dynamics, which are described by a set of nonlinear ordinary differential equations (ODEs). Since the control input only appears in the ODE subsystem rather than directly on the boundary of PDE subsystem, the control task becomes quite challenging. The most important is that for the control of such ODE controlled PDE systems we mainly make the following two contributions: (1) the controlled output of the PDE system tracks the reference signal within the prescribed time; (2) the controlled output and all the actuator states are constrained. It is the first time that such a prescribed‐time constrained tracking control problem is addressed for the PDE‐ODE coupled system considered in this article. Through rigorous theoretical proof, it is demonstrated that all the system states and control signals are bounded and sufficiently continuous by configuring appropriate design parameters. Finally, the performance is investigated via numerical simulation. [ABSTRACT FROM AUTHOR]

Family structure and characteristics are important factors that affect both economic development and CEOs' decision‐making. Corporate risk‐taking reflects the overall risk choices and preferences of decision‐makers in relation to various decisions. Using data for Chinese non‐state‐owned enterprises between the years 2000 and 2019, we examine the association between CEO offspring gender and corporate risk‐taking. We find that CEOs who have daughters are associated with a lower level of corporate risk‐taking than CEOs who have sons only. Raising daughters significantly stimulates cautious attitudes and behaviors in CEOs and reduces firm overinvestment, thereby lowering the level of corporate risk‐taking. Moreover, raising daughters has a more significant inhibitory effect on corporate risk‐taking for female CEOs and CEOs who were born in regions with a strong patriarchal culture. Our findings also show that CEOs with daughters can help companies effectively avoid financial crises. Focusing on both parenting behavior and corporate financial behavior, we suggest that the parent–child relationship extends far beyond the scope of the family, providing a broader perspective for understanding corporate decision‐making and financial behavior. [ABSTRACT FROM AUTHOR]

This work develops a network of adaptive boundary observers and studies the agreement between state and parameter estimates for a single target parabolic partial differential equation (PDE) system in the presence of structured and unstructured uncertainties. It is assumed that the unknown parameters take the form of either a structured uncertainty with unknown constant parameters or an unstructured uncertainty that can be neutralized by a radial basis function neural networks with unknown weights. The proposed adaptive observers consisting of m$$ m $$ agents in the network follow the structure of adaptive identifiers for the considered target PDE systems with the insertion of a penalty term in both the state and parameter estimates. Different from earlier efforts, the proposed adaptive laws include a penalty term of the mismatch between the parameter and state estimates generated by the other adjacent agents, which helps to accelerate the estimation of uncertainties. Additionally, the effects of these modifications on the agreement amongst the state and parameter estimates are investigated. Theoretical proofs are provided to show that the proposed approach guarantees the exponential convergence of estimation errors in the case of structured uncertainties and the ultimate boundedness of estimation errors in the case of unstructured uncertainties. Finally, numerical simulations are carried out to verify the effectiveness of the design methods. [ABSTRACT FROM AUTHOR]

The integration of solar‐driven interfacial evaporation and electricity co‐generation is considered a promising approach to simultaneously alleviate freshwater scarcity and the energy crisis. However, affected by intermittent solar irradiation/uncontrollable weather, the overall performance of solar‐driven evaporation in the real world is greatly reduced. Herein, inspired by antifreeze proteins in beetles that survive in extreme climates, all‐weather solar‐driven interfacial evaporators with a sandwich structure are designed. The top and bottom layers composed of MnO2‐modified cotton cloth are used for photothermal conversion and water transport, meanwhile, the middle layer made of a phase change microcapsule/hydrogel composite serves for heat storage and release. Under 1 kW m−2 irradiation, the evaporator exhibits a high evaporation rate of 2.67 kg m−2 h−1 and an efficiency of 89.5%. In the dark, the heat released from the phase change layer supports an evaporation rate of 0.43 kg m−2 h−1, 3.6 times that of pure water. Additionally, assembled with a thermoelectric module, the hybrid device achieves a stable output electricity power of 0.42 W m−2 under 1‐sun illumination and a prolonged output for 30 min in the dark. This work provides a novel approach for full‐time solar‐powered steam‐electricity co‐generation and a proof of concept for biomimetic steam generation/heat management integration. [ABSTRACT FROM AUTHOR]

T cells play an important role in the development of focal segmental glomerulosclerosis (FSGS). The mechanism underlying such T cell‐based kidney disease, however, remains elusive. Here the authors report that activated CD8 T cells elicit renal inflammation and tissue injury via releasing miR‐186‐5p‐enriched exosomes. Continuing the cohort study identifying the correlation of plasma level of miR‐186‐5p with proteinuria in FSGS patients, it is demonstrated that circulating miR‐186‐5p is mainly derived from activated CD8 T cell exosomes. Renal miR‐186‐5p, which is markedly increased in FSGS patients and mice with adriamycin‐induced renal injury, is mainly delivered by CD8 T cell exosomes. Depleting miR‐186‐5p strongly attenuates adriamycin‐induced mouse renal injury. Supporting the function of exosomal miR‐186‐5p as a key circulating pathogenic factor, intravenous injection of miR‐186‐5p or miR‐186‐5p‐containing T cell exosomes results in mouse renal inflammation and tissue injury. Tracing the injected T cell exosomes shows their preferential distribution in mouse renal tubules, not glomerulus. Mechanistically, miR‐186‐5p directly activates renal tubular TLR7/8 signal and initiates tubular cell apoptosis. Mutating the TLR7‐binding sequence on miR‐186‐5p or deleting mouse TLR7 largely abolishes renal tubular injuries induced by miR‐186‐5p or adriamycin. These findings reveal a causative role of exosomal miR‐186‐5p in T cell‐mediated renal dysfunction. [ABSTRACT FROM AUTHOR]

Increased gut permeability is implicated in the initiation and extent of the cytokine inflammatory response associated with exertional heat stroke (EHS). The primary objective of this study was to determine if a five amino acid oral rehydration solution (5AAS), specifically designed for the protection of the gastrointestinal lining, would prolong time to EHS, maintain gut function and dampen the systemic inflammatory response (SIR) measured during EHS recovery. Male C57/BL6J mice instrumented with radiotelemetry were gavaged with 150 μL of 5AAS or H2O, and ≈12 h later were either exposed to an EHS protocol where mice exercised in a 37.5°C environmental chamber to a self‐limiting maximum core temperature (Tc,max) or performed the exercise control (EXC) protocol (25°C). 5AAS pretreatment attenuated hypothermia depth and length (p < 0.005), which are indicators of EHS severity during recovery, without any effect on physical performance or thermoregulatory responses in the heat as determined by percent body weight lost (≈9%), max speed (≈6 m/min), distance (≈700 m), time to Tc,max (≈160 min), thermal area (≈550°C∙min), and Tc,max (42.2°C). EHS groups treated with 5AAS showed a significant decrease in gut transepithelial conductance, decreased paracellular permeability, increased villus height, increased electrolyte absorption and changes in tight junction protein expression pattern suggestive of improved barrier integrity (p < 0.05). No differences were witnessed between EHS groups in acute phase response markers of liver, circulating SIR markers, or indicators of organ damage during recovery. These results suggest that a 5AAS improves Tc regulation during EHS recovery through maintaining mucosal function and integrity. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders caused by a misdirected immune response against self‐antigens expressed in the central nervous system. The thymus is a central organ in the immune system and thymic tumors are thought to be possible initiators of many neurological disorders. Recently, there is growing evidence that thymomas are associated with autoimmune encephalitis. Aims: Our study initially explored the characteristics of patients with autoimmune encephalitis combined with thymoma. Methods: We used patient data from January 1, 2011 to October 1, 2021 from the PubMed, Web of Science, Ovid, and CNKI platforms to analyze overall demographics, frequency of symptoms and associations, and treatment prognosis outcomes. Results: A total of 68 patients were included. There were 39 female cases (57.4%). The mean age was 50 years (IQR 40–66 years). All had acute and subacute onset. The clinical manifestations were mostly cognitive changes (70.6%), mental disorders (57.4%), and epilepsy (50.0%). The most common neuronal antibody was alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). Magnetic resonance imaging (MRI) abnormalities were present in 81.0% of patients, mostly in the hippocampus, temporal lobe, and some in cortical and subcortical areas. Abnormalities in the electroencephalogram (EEG) in 69.8% of patients. Treatment involved immunotherapy and thymoma treatment, with 79.7% of patients improving after treatment. While 20.3% of patients had a poor prognosis. Further, 14.8% of patients relapsed. Mental disorders, autonomic dysfunction, sleep disturbances, anti‐Ma2, and thymoma untreated were more frequent in patients with poor prognosis. Conclusion: Thymoma‐associated autoimmune encephalitis is a unique disease entity. Long‐term follow‐up of chest CT findings is recommended for patients with autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Biodegradable polymeric materials with high strength and outstanding toughness are necessary for real‐world applications in the fields of electronics, electrics, and packaging. Unfortunately, such performance portfolios in polymers remain challenging to achieve due to their different governing mechanisms. Inspired by the hydrogen‐bond (H‐bond) cross‐linking structure of spider silk, herein, strong and tough poly(vinyl alcohol) (PVA) composites with β‐cyclodextrin as a cross‐linker are developed. Benefiting from the H‐bond cross‐linking effect, the addition of 1.0 wt% of β‐cyclodextrin enables PVA to achieve a high tensile strength of 136.5 MPa, and a high elastic modulus of 3.0 GPa, in combination with a good toughness of 82.1 MJ m−3. In addition, the presence of β‐cyclodextrin improves the biodegradability of PVA composite by decreasing its crystalline size. Furthermore, PVA/β‐cyclodextrin composite combined with MXene has great potential as a sensor material for humidity and strain detection. This proof‐of‐concept opens numerous opportunities to create strong, tough, and biodegradable polymers for packing and sensing applications. [ABSTRACT FROM AUTHOR]

The study investigates the role of public and private capital investment and globalization in the economic growth of 34 Asian economies along with investment risk and demographic pressure. By applying the two‐step system generalized method of moment, results show that private capital investment in Asian emerging‐economies has been a substantial positive impact on regional economic growth and is significantly influenced by low‐investment risks and demographic conditions as compared to low‐income and advance‐economies from 2001 to 2019. It further states that economic globalization accelerates the economic growth in Asian emerging, developing, and low‐income economies compared to advanced‐economies. This study contributes to the existing literature by analyzing Asian economies in two ways (separately public and private investment and economic globalization index to economic growth), which has been scarce in this regard. The study also suggests that private capital investment should be backed with low‐risk investment policies that create more private investment, enhance the institutional capacity, productivity, and attract foreign investors. This study's findings highlight that, for the development of the economies, private‐investment inclusion with public‐investment is the backbone that can accelerate economic growth by controlling external pressures and business risk in the country with effective public policies. [ABSTRACT FROM AUTHOR]

Summary: Global warming has profound impact on growth and development, and plants constantly adjust their internal circadian clock to cope with external environment. However, how clock‐associated genes fine‐tune thermoresponsive growth in plants is little understood.We found that loss‐of‐function mutation of REVEILLE5 (RVE5) reduces the expression of circadian gene EARLY FLOWERING 4 (ELF4) in Arabidopsis, and confers accelerated hypocotyl growth under warm‐temperature conditions.Both RVE5 and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) accumulate at warm temperatures and bind to the same EE cis‐element presented on ELF4 promoter, but the transcriptional repression activity of RVE5 is weaker than that of CCA1. The binding of CCA1 to ELF4 promoter is enhanced in the rve5‐2 mutant at warm temperatures, and overexpression of ELF4 in the rve5‐2 mutant background suppresses the rve5‐2 mutant phenotype at warm temperatures.Therefore, the transcriptional repressor RVE5 finetunes ELF4 expression via competing at a cis‐element with the stronger transcriptional repressor CCA1 at warm temperatures. Such a competition–attenuation mechanism provides a balancing system for modulating the level of ELF4 and thermoresponsive hypocotyl growth under warm‐temperature conditions. See also the Commentary on this article by Balcerowicz, 237: 9–11. [ABSTRACT FROM AUTHOR]

Ho‐doped sesquioxide is one of the most important laser gain media for 2 micron wavelength band laser applications. It is hard to be transparent by sintering because of its high melting point. Herein, the structural and spectral properties of 0.5 at% Ho:(Y1−xScx)2O3 (x = 0, 0.3, 0.5, 0.7, 1.0) ceramics fabricated by vacuum pressureless sintering are studied. Then, 0.5 at% Ho:(Y0.7Sc0.3)2O3 transparent ceramics with 1.0 at% ZrO2 as a sintering aid are prepared by vacuum pressureless presintering (1680 °C for 4 h) combined with hot isostatic pressing sintering treatment (1600 °C/190 MPa for 3 h). The transmittance of Ho:(Y0.7Sc0.3)2O3 ceramic reaches 80.8% at 1100 nm (6 mm in thickness), which is close to its theoretic value. The addition of ZrO2 has no significant influence on spectroscopic properties of 0.5 at% Ho:(Y0.7Sc0.3)2O3 ceramics. [ABSTRACT FROM AUTHOR]

Endogenous circadian clock integrates cyclic signals of environment and daily and seasonal behaviors of organisms to achieve spatiotemporal synchronization, which greatly improves genetic diversity and fitness of species. This review addresses recent studies on the plant circadian system in the field of chronobiology, covering topics on molecular mechanisms, internal and external Zeitgebers, and hierarchical regulation of physiological outputs. The architecture of the circadian clock involves the autoregulatory transcriptional feedback loops, post‐translational modifications of core oscillators, and epigenetic modifications of DNA and histones. Here, light, temperature, humidity, and internal elemental nutrients are summarized to illustrate the sensitivity of the circadian clock to timing cues. In addition, the circadian clock runs cell‐autonomously, driving independent circadian rhythms in various tissues. The core oscillators responds to each other with biochemical factors including calcium ions, mineral nutrients, photosynthetic products, and hormones. We describe clock components sequentially expressed during a 24‐h day that regulate rhythmic growth, aging, immune response, and resistance to biotic and abiotic stresses. Notably, more data have suggested the circadian clock links chrono‐culture to key agronomic traits in crops. [ABSTRACT FROM AUTHOR]

The bulk photovoltaic effect shift current (SC), a constant photocurrent generated by irradiating polar homogeneous non‐centrosymmetric materials has lately emerged as a possible option for next‐generation photovoltaic systems that may potentially overcome the Shockley–Queisser limits. The current work predicts gigantic and anisotropic SC with multiple peaks across a wide range of frequencies in pristine 2D monolayer α‐AsP and α‐NP based on first‐principle calculations. The dominant SC tensors components hosted by 2D monolayer α‐AsP and α‐NP are the in‐plane, and reaches peaks of −154 µАV−2, and 87 µАV−2, respectively, in the UV region. The SC magnitudes of the α‐AsP are not significantly affected by the spin‐orbital coupling, while in α‐NP, no such effect occurs. This study recommends new photovoltaic materials with strong SC peaks spread across the electromagnetic spectrum, largely within the UV region. [ABSTRACT FROM AUTHOR]

The performance of lithium–sulfur (Li–S) battery is strongly dependent on the sulfur electrodes materials. Due to the chemical interaction between electrodes and intermediates produced in charging and discharging process, the Janus‐polar two dimensional (2D) electrode materials can enhance the electrochemical performance of Li–S battery by overcoming shuttle effect and increasing diffusion rates. Here, it is explored the structural, electronic, and dynamic characteristics of Li ion, S8 cluster, and lithium polysulfides adsorbed over Janus Phosphorus Nitride monolayer with blue phosphorene phase (b‐PN) by using first‐principles calculations. The reported findings highlight potential of the b‐PN monolayer as a good host material, given that the large absorption energies of different clusters vary from −0.47 to −3.78 eV, which can suppress shuttle effect effectively. These strong adsorptions are origin from the chemical interaction between nitrogen atoms of the b‐PN and Li atoms in lithium polysulfides in present work. Particularly, it is predicted that b‐PN monolayer has extremely small diffusion barriers for Li ion and Li2S8 clusters of 0.10 and 0.03 eV, which leading to a higher battery charge and discharge rate than reported graphene and MoS2. It is hoped that this efficient strategy for promising host materials of sulfur‐electrode guides the development of next‐generation lithium–sulfur batteries. [ABSTRACT FROM AUTHOR]

The influence of the strength of the pillar on the bearing characteristics of the backfill‐pillar system (BPS) based on the mechanism of backfill. Quantitative synergy relationships between backfill and pillar were defined and pointed out. There are four kinds of quantitative synergy relationships in the bearing process of the system. To verify the relationship, systems with different strengths of the pillar were selected to carry out numerical simulation experiments, and a mathematical calculation method to quantify synergy relationship in the BPS was designed. The results show that the system under the low strength of the pillar presents the overall increase in bearing characteristics, while the system under the high strength of the pillar presents "N"‐type bearing features. Four kinds of quantitative synergy relationships able to characterise the action mechanism between backfill and pillar in each stage of the bearing of the system. Through analysis and discussion, it was concluded that the essential reason for the difference in bearing characteristics is that the effect of displacement restraint, joint support, and passive compressive weaken with the increase of the strength of pillar. The effect of pillar strength on the internal synergy of BPS is well verified by numerical simulation test. [ABSTRACT FROM AUTHOR]

The baculovirus expression vector system (BEVS) is an attractive manufacturing platform for recombinant protein production in insect cells. However, baculovirus infection commonly induces host apoptosis in 3–4 days which would subsequently terminate the protein expression. Previous studies have proved that protein production by BEVS can be elevated in apoptosis‐suppressed insect cells. We also developed a baculovirus vector in our previous report to inhibit the apoptosis and improve protein production in Sf9 cells. In this study, we designed five short hairpin RNA (shRNA) expression cassettes targeting a conserved region in Spodoptera frugiperda caspase‐1 (Sf‐caspase‐1) and Trichoplusia ni caspase‐1 (Tn‐caspase‐1), and found that introduction of C to T mutations within the stem region of the expression cassette was beneficial for the heterologous protein expression. One of the improved shRNA expression cassettes was knocked into a bacmid with the deletion of several nonessential genes. The novel baculovirus vector demonstrated the ability to suppress cell apoptosis in both Sf9 and High Five cells, and exhibited superior recombinant protein productivity of intracellularly expressed GFP and firefly luciferase and secreted glycoprotein OD‐Fc. The antiapoptotic baculovirus vector developed in this study could serve as a useful tool for the protein production in scientific research and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

This manuscript develops a robust output regulator for the column froth flotation process in the presence of unknown disturbance. In particular, motivated by relevant physical modeling setting, all information (including magnitude, phase, bias, and frequency) of the disturbance is unavailable. The system considered is consisting of froth and collection zones and is governed by a set of conservative heterodirectional transport hyperbolic partial differential equations (PDEs). Moreover, the transport related time delay between the froth and the collection region is considered, and is associated with the boundary conditions of the PDEs. The velocity of the feed is considered the input and the concentration of the solid particle with air phase at the top of froth region as the output. We propose a disturbance frequency identifier and formulate a robust controller according to the internal model principle such that the output tracks the desired concentration despite the model uncertainties and unknown disturbance. [ABSTRACT FROM AUTHOR]

R6106 --> 875.18 --> Objective: Chloride and bicarbonate transport across the apical membrane via CFTR is critical for homeostasis of airway surface liquid and mucociliary clearance. Cystic fibrosis (CF) is caused by mutations in the CFTR gene resulting in mucus buildup, bacterial colonization, inflammation and respiratory insufficiency. F508del and nonsense mutations are the most common mutations characterized by defective protein processing and trafficking (F508del) or early termination of CFTR synthesis (G542X, R1162X). A combination of CFTR modulators (VX445/661/770; VX) has largely improved CFTR function in patients with F508del but is ineffective in nonsense mutations. We have shown that select amino acids (SAA) can modulate trafficking and activity of CFTR and alternative anion‐secretory pathways, and thus could improve clinical outcomes in CF patients. Hypothesis: SAA can stimulate anion secretion in primary HBEC with F508del/F508del, F508del/R1162X and G542X/G542X mutation. Methods: Transepithelial short‐circuit current (Isc) was measured in differentiated HBEC treated with DMSO or VX for 24h and bathed in vehicle or SAA in Ussing chambers. After blocking ENaC with benzamil, benzamil‐insensitive (anion) Isc was either continuously recorded for 90min, or sequentially blocked with CFTRinh172, CaCCinhA01 and bumetanide in 15min intervals. Isotope (36Cl) flux studies and whole‐cell patch clamp technique were used to confirm chloride movements, and CFTR and alternative anion‐secretory channel expression was analyzed by immunofluorescence. Results: Anion Isc increased in all mutations and was more sustained when exposed to SAA compared to vehicle (F508del: 15.4±0.5 vs 1.4±0.2; R1162X: 19.4±0.3 vs 2.3±0.3; G542X: 17.2±0.5 vs 1.6±0.2 µA.cm‐2; P<0.001). SAA recovered 48.7, 57.3 and 40.9% of normal Isc (21.9±0.5 µA.cm‐2). Treatment with VX increased anion Isc in F508del and R1162X (11.4±0.7 and 5.7±0.4 µA.cm‐2; P<0.001) but not in G542X (1.7±0.2 µA.cm‐2). In F508del, the CFTR response increased from 20.7% (non‐treated cells) to 32.9 and 85.5% of the anion Isc when treated with SAA or VX, and in R542X from 3.7% to 46.3 and 16.0%, respectively. Both, SAA and VX did not affect CaCC, but SAA increased the bumetanide‐sensitive Isc from 31.0 to 50.5% in F508del, and from 33.3 to 56.3% in R1162X, while VX reduced the bumetanide response to 5.4 and 4.5%. Isotope flux studies showed that SAA (‐0.21±0.08 μEq.h‐1.cm‐2) and VX (‐0.19±0.02 μEq.h‐1.cm‐2) increased net Cl‐ secretion in F508del when compared to vehicle (‐0.03±0.01 μEq.h‐1.cm‐2; P<0.05). SAA, but not VX increased Cl‐ secretion in G542X (‐0.21 0.07 vs ‐0.08±0.02 μEq.h‐1.cm‐2). In patch clamp recordings, SAA and VX resulted in a significant reduction in CFTRinh172 whole cell current in F508del. Immunofluorescence imaging demonstrated increased CFTR and alternative anion‐secretory channel expression along the apical membrane in SAA cells while VX showed increased expression of only CFTR. Conclusions: These studies demonstrate that SAA stimulates anion current and increases Cl‐ secretion via CFTR and alternative secretory pathways in different mutations, and could be beneficial in nonsense mutations but needs further investigation. [ABSTRACT FROM AUTHOR]