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1.
Small ; 20(9): e2307179, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37857576

RESUMO

Rechargeable battery devices with high energy density are highly demanded by the modern society. The use of lithium (Li) anodes is extremely attractive for future rechargeable battery devices. However, the notorious Li dendritic and instability of solid electrolyte interface (SEI) issues pose series of challenge for metal anodes. Here, based on the inspiration of in situ photoelectrochemical engineering, it is showed that a tailor-made composite photoanodes with good photoelectrochemical properties (Li affinity property and photocatalytic property) can significantly improve the electrochemical deposition behavior of Li anodes. The light-assisted Li anode is accommodated in the tailor-made current collector without uncontrollable Li dendrites. The as-prepared light-assisted Li metal anode can achieve the in situ stabilization of SEI layer under illumination. The corresponding in situ formation mechanism and photocatalytic mechanism of composite photoanodes are systematically investigated via DFT theoretical calculation, ex situ UV-vis and ex situ XPS characterization. It is worth mentioning that the as-prepared composite photoanodes can adapt to the ultra-high current density of 15 mA cm-2 and the cycle capacity of 15 mAh cm-2 under light, showing no dendritic morphology and low hysteresis voltage. This work is of great significance for the commercialization of new generation Li metal batteries.

2.
Small ; : e2310584, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470191

RESUMO

Renewable energy is crucial for sustainable future, and Cu2 ZnSnS4 (CZTS) based solar cells shine as a beacon of hope. CZTS, composed of abundant, low-cost, and non-toxic elements, shares similarities with Cu(In,Ga)Se2 (CIGS). However, despite its promise and appealing properties for solar cells, CZTS-based solar cells faces performance challenges owing to inherent issues with CZTS material, and conventional substrate structure complexities. This review critically examines these roadblocks, explores ongoing efforts and breakthroughs, providing insight into the evolving landscape of CZTS-based solar cells research. Furthermore, as an optimistic turn in the field, the review first highlights the crucial need to transition to a superstrate structure for CZTS-based single junction devices, and summarizes the substantial progress made in this direction. Subsequently, dive into the discussion about the fascinating realm of CZTS-based tandem devices, providing an overview of the existing literature as well as outlining the possible potential strategies for enhancing the efficiency of such devices. Finally, the review provides a useful outlook that outlines the priorities for future research and suggesting where efforts should concentrate to shape the future of CZTS-based solar cells.

3.
Opt Express ; 32(10): 17657-17666, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858943

RESUMO

Tin diselenide (SnSe2), a layered transition metal dichalcogenide (TMDC), stands out among other TMDCs for its extraordinary photoactive ability and low thermal conductivity. Consequently, it has stimulated many influential researches on photodetectors, ultrafast pulse shaping, thermoelectric devices, etc. However, the carrier mobility in SnSe2, as determined experimentally, remains limited to tens of cm2V-1s-1. This limitation poses a challenge for achieving high-performance SnSe2-based devices. Theoretical calculations, on the other hand, predict that the carrier mobility in SnSe2 can reach hundreds of cm2V-1s-1, approximately one order of magnitude higher than experimental value. Interestingly, the carrier mobility could be underestimated significantly in long-range transportation measurements due to the presence of defects and boundary scattering effects. To address this discrepancy, we employ optic pump terahertz probe spectroscopy to access the photoinduced dynamical THz photoconductivity of SnSe2. Our findings reveal that the intrinsic carrier mobility in conventional SnSe2 single crystal is remarkably high, reaching 353.2 ± 37.7 cm2V-1s-1, consistent with the theoretical prediction. Additionally, dynamical THz photoconductivity measurements reveal that the SnSe2 crystal containing rich defects efficiently capture photoinduced conduction-band electrons and valence-band holes with time constants of ∼20 and ∼200 ps, respectively. Meanwhile, we observe an impulsively stimulated Raman scattering at 0.60 THz. Our study not only demonstrates ultrafast THz spectroscopy as a reliable method for determining intrinsic carrier mobility and detection of low frequency coherent Raman mode in materials but also provides valuable reference for the future application of high-performance SnSe2-based devices.

4.
J Gen Virol ; 104(10)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37862073

RESUMO

Chikungunya virus (CHIKV) is an alphavirus, transmitted by Aedes species mosquitoes. The CHIKV single-stranded positive-sense RNA genome contains two open reading frames, coding for the non-structural (nsP) and structural proteins of the virus. The non-structural polyprotein precursor is proteolytically cleaved to generate nsP1-4. Intriguingly, most isolates of CHIKV (and other alphaviruses) possess an opal stop codon close to the 3' end of the nsP3 coding sequence and translational readthrough is necessary to produce full-length nsP3 and the nsP4 RNA polymerase. Here we investigate the role of this stop codon by replacing the arginine codon with each of the three stop codons in the context of both a subgenomic replicon and infectious CHIKV. Both opal and amber stop codons were tolerated in mammalian cells, but the ochre was not. In mosquito cells all three stop codons were tolerated. Using SHAPE analysis we interrogated the structure of a putative stem loop 3' of the stop codon and used mutagenesis to probe the importance of a short base-paired region at the base of this structure. Our data reveal that this stem is not required for stop codon translational readthrough, and we conclude that other factors must facilitate this process to permit productive CHIKV replication.


Assuntos
Aedes , Febre de Chikungunya , Vírus Chikungunya , Animais , Vírus Chikungunya/genética , Códon de Terminação/genética , Códon de Terminação/metabolismo , Febre de Chikungunya/genética , Proteínas não Estruturais Virais/genética , Replicação Viral/genética , Mamíferos/genética , Mamíferos/metabolismo
5.
Small ; 19(50): e2303745, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37616514

RESUMO

Rechargeable battery devices with high energy density are highly demanded by  our  modern society. The use of metal anodes is extremely attractive for future rechargeable battery devices. However, the notorious metal dendritic and instability of solid electrolyte interface issues pose a series of challenges for metal anodes. Recently, considering the indigestible dynamical behavior of metal anodes, photoelectrochemical engineering of light-assisted metal anodes have been rapidly developed since they efficiently utilize the integration and synergy of oriented crystal engineering and photocatalysis engineering, which provided a potential way to unlock the interface electrochemical mechanism and deposition reaction kinetics of metal anodes. This review starts with the fundamentals of photoelectrochemical engineering and follows with the state-of-art advance of photoelectrochemical engineering for light-assisted rechargeable metal batteries where photoelectrode materials, working principles, types, and practical applications are explained. The last section summarizes the major challenges and some invigorating perspectives for future research on light-assisted rechargeable metal batteries.

6.
Small ; 19(14): e2206848, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36604991

RESUMO

Great changes have occurred in the energy storage area in recent years as a result of rapid economic expansion. People have conducted substantial research on sustainable energy conversion and storage systems in order to mitigate the looming energy crisis. As a result, developing energy storage materials is critical. Materials with an open frame structure are known as Prussian blue analogs (PBAs). Anode materials for oxides, sulfides, selenides, phosphides, borides, and carbides have been extensively explored as anode materials in the field of energy conversion and storage in recent years. The advantages and disadvantages of oxides, sulfides, selenides, phosphides, borides, carbides, and other elements, as well as experimental methodologies and electrochemical properties, are discussed in this work. The findings reveal that employing oxides, sulfides, selenides, phosphides, borides, and other electrode materials to overcome the problems of low conductivity, excessive material loss, and low specific volume is ineffective. Therefore, this review intends to address the issues of diverse energy storage materials by combining multiple technologies to manufacture battery materials with low cost, large capacity, and extended service life.

7.
Small ; 19(47): e2304045, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37485629

RESUMO

The design of a novel photoelectric integrated system is considered to be an efficient way to utilize and store inexhaustible solar energy. However, the mechanism of photoelectrode under illuminate conditions is still unclear. Density functional theory (DFT) provides standardized analysis and becomes a powerful way to explain the photoelectrochemical mechanism. Herein, the feasibility of four metal oxide configurations as photoelectrode materials by using a high throughput calculation method based on DFT are investigated. According to the photoelectrochemical properties, band structure and density of states are calculated, and the intercalate/deintercalate simulation is performed with adsorption configuration. The calculation indicates that the band gap of Fe2 CoO4 (2.404 eV) is narrower than that of Co3 O4 (2.553 eV), as well as stronger adsorption energy (-3.293 eV). The relationship between the electronic structure and the photoelectrochemical performance is analyzed and verified according to the predicted DFT results by subsequent experiments. Results show that the Fe2 CoO4 photoelectrode samples exhibit higher coulombic efficiency (97.4%) than that under dark conditions (94.9%), which is consistent with the DFT results. This work provides a general method for the design of integrated photoelectrode materials and is expected to be enlightening for the adjustment of light-assisted properties of multifunctional materials.

8.
Small ; 18(25): e2201740, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35532321

RESUMO

Heteroatom doping can endow MXenes with various new or improved electromagnetic, physicochemical, optical, and structural properties. This greatly extends the arsenal of MXenes materials and their potential for a spectrum of applications. This article comprehensively and critically discusses the syntheses, properties, and emerging applications of the growing family of heteroatom-doped MXenes materials. First, the doping strategies, synthesis methods, and theoretical simulations of high-performance MXenes materials are summarized. In order to achieve high-performance MXenes materials, the mechanism of atomic element doping from three aspects of lattice optimization, functional substitution, and interface modification is analyzed and summarized, aiming to provide clues for developing new and controllable synthetic routes. The mechanisms underlying their advantageous uses for energy storage, catalysis, sensors, environmental purification and biomedicine are highlighted. Finally, future opportunities and challenges for the study and application of multifunctional high-performance MXenes are presented. This work could open up new prospects for the development of high-performance MXenes.


Assuntos
Catálise
9.
Small ; 18(31): e2203014, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35780491

RESUMO

As an emerging solar energy utilization technology, solar redox batteries (SPRBs) combine the superior advantages of photoelectrochemical (PEC) devices and redox batteries and are considered as alternative candidates for large-scale solar energy capture, conversion, and storage. In this review, a systematic summary from three aspects, including: dye sensitizers, PEC properties, and photoelectronic integrated systems, based on the characteristics of rechargeable batteries and the advantages of photovoltaic technology, is presented. The matching problem of high-performance dye sensitizers, strategies to improve the performance of photoelectrode PEC, and the working mechanism and structure design of multienergy photoelectronic integrated devices are mainly introduced and analyzed. In particular, the devices and improvement strategies of high-performance electrode materials are analyzed from the perspective of different photoelectronic integrated devices (liquid-based and solid-state-based). Finally, future perspectives are provided for further improving the performance of SPRBs. This work will open up new prospects for the development of high-efficiency photoelectronic integrated batteries.

10.
Small ; 18(9): e2105044, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34914176

RESUMO

The persistent double layer structure whereby two layers with different properties form at the front and rear of absorbers is a critical challenge in the field of kesterite thin-film solar cells, which imposes additional nonradiative recombination in the quasi-neutral region and potential limitation to the transport of hole carriers. Herein, an effective model for growing monolayer CZTSe thin-films based on metal precursors with large grains spanning the whole film is developed. Voids and fine grain layer are avoided successfully by suppressing the formation of a Sn-rich liquid metal phase near Mo back contact during alloying, while grain coarsening is greatly promoted by enhancing mass transfer during grain growth. The desired morphology exhibits several encouraging features, including significantly reduced recombination in the quasi-neutral region that contributes to the large increase of short-circuit current, and a quasi-Ohmic back contact which is a prerequisite for high fill factor. Though this growth mode may introduce more interfacial defects which require further modification, the strategies demonstrated remove a primary obstacle toward higher efficiency kesterite solar cells, and can be applicable to morphology control with other emerging chalcogenide thin films.

11.
Small ; 18(50): e2204392, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36319478

RESUMO

Small grain size and near-horizontal grain boundaries are known to be detrimental to the carrier collection efficiency and device performance of pure-sulfide Cu2 ZnSnS4 (CZTS) solar cells. However, forming large grains spanning the absorber layer while maintaining high electronic quality is challenging particularly for pure sulfide CZTS. Herein, a liquid-phase-assisted grain growth (LGG) model that enables the formation of large grains spanning across the CZTS absorber without compromising the electronic quality is demonstrated. By introducing a Ge-alloyed CZTS nanoparticle layer at the bottom of the sputtered precursor, a Cu-rich and Sn-rich liquid phase forms at the high temperature sulfurization stage, which can effectively remove the detrimental near-horizontal grain boundaries and promote grain growth, thus greatly improving the carrier collection efficiency and reducing nonradiative recombination. The remaining liquid phase layer at the rear interface shows a high work function, acting as an effective hole transport layer. The modified morphology greatly increases the short-circuit current density and fill factor, enabling 10.3% efficient green Cd-free CZTS devices. This work unlocks a grain growth mechanism, advancing the morphology control of sulfide-based kesterite solar cells.

12.
Photochem Photobiol Sci ; 21(12): 2115-2126, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35933640

RESUMO

Photoreforming has been shown to accelerate the H2 evolution rate compared to water splitting due to thermodynamically favorable organic oxidation. In addition, the potential to simultaneously produce solar fuel and value-added chemicals is a significant benefit of photoreforming. To achieve an efficient and economically viable photoreforming process, the selection and design of an appropriate photocatalyst is essential. Carbon nitride is promising as a metal-free photocatalyst with visible light activity, high stability, and low fabrication cost. However, it typically exhibits poor photogenerated charge carrier dynamics, thereby resulting in low photocatalytic performance. Herein, we demonstrate improved carrier dynamics in urea-functionalized carbon nitride with in situ photodeposited Ni cocatalyst (Ni/Urea-CN) for ethanol photoreforming. In the presence of 1 mM Ni2+ precursor, an H2 evolution rate of 760.5 µmol h-1 g-1 and an acetaldehyde production rate of 888.2 µmol h-1 g-1 were obtained for Ni/Urea-CN. The enhanced activity is ascribed to the significantly improved carrier dynamics in Urea-CN. The ability of oxygen moieties in the urea group to attract electrons and to increase the hole mobility via a positive shift in the valence band promotes an improvement in the overall carrier dynamics. In addition, high crystallinity and specific surface area of the Urea-CN contributed to accelerating charge separation and transfer. As a result, the electrons were efficiently transferred from Urea-CN to the Ni cocatalyst for H2 evolution while the holes were consumed during ethanol oxidation. The work demonstrates a means by which carrier dynamics can be tuned by engineering carbon nitride via edge functionalization.


Assuntos
Níquel , Ureia , Etanol , Acetaldeído
13.
Small ; 17(31): e2100496, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34173332

RESUMO

Copper-based chalcogenides have been considered as potential photocathode materials for photoelectrochemical (PEC) CO2 reduction due to their excellent photovoltaic performance and favorable conduction band alignment with the CO2 reduction potential. However, they suffer from low PEC efficiency due to the sluggish charge transfer kinetics and poor selectivity, resulting from random CO2 reduction reaction pathways. Herein, a facile heat treatment (HT) of a Cu2 ZnSnS4 (CZTS)/CdS photocathode is demonstrated to enable significant improvement in the photocurrent density (-0.75 mA cm-2 at -0.6 V vs RHE), tripling that of pristine CZTS, as a result of the enhanced charge transfer and promoted band alignment originating from the elemental inter-diffusion at the CZTS/CdS interface. In addition, rationally regulated CO2 reduction selectivity toward CO or alcohols can be obtained by tailoring the surficial sulfur vacancies by HT in different atmospheres (air and nitrogen). Sulfur vacancies replenished by O-doping is shown to favor CO adsorption and the CC coupling pathway, and thereby produce methanol and ethanol, whilst the CdS surface with more S vacancies promotes CO desorption capability with higher selectivity toward CO. The strategy in this work rationalizes the interface charge transfer optimization and surface vacancy engineering simultaneously, providing a new insight into PEC CO2 reduction photocathode design.

14.
Environ Microbiol ; 22(9): 3772-3783, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32618113

RESUMO

Thraustochytrium is a unicellular marine protist for the commercial production of very long-chain polyunsaturated fatty acids (VLCPUFAs). Biosynthesis of these VLCPUFAs in the protist is catalysed by a PUFA synthase comprising three subunits, each with multiple catalytic domains. Among these domains, two tandem FabA-like dehydratase domains (DH1 and DH2) in subunit-C together are responsible for introducing double bonds in VLCPUFAs. Domain swapping analysis in yeast showed that the defective phenotype of a Scfas1 mutant could be complemented by expressing an engineered ScFAS1 gene in which the DH domain was replaced by a single DH1 or mutated DH2 of the two. Heterologous expression of the PUFA synthase in E. coli showed that the mutation of DH1 of the two or deletion of DH1 or substitution of DH1 with DH2 resulted in the complete loss of activity in the biosynthesis of VLCPUFAs. Mutation of DH2 of the two or deletion of the DH2 domain produced a small amount of DPA, but not docosahexaenoic acid (DHA). These results indicate that each of the two FabA-like domains of the PUFA synthase possesses distinct function. DH1 domain is essential for the biosynthesis of VLCPUFAs, but DH2 domain is required for the biosynthesis of DHA.


Assuntos
Ácido Graxo Sintases/química , Ácido Graxo Sintases/metabolismo , Ácidos Graxos Insaturados/biossíntese , Domínio Catalítico , Ácidos Docosa-Hexaenoicos/biossíntese , Escherichia coli/genética , Ácido Graxo Sintases/genética , Hidroliases/química , Mutação , Subunidades Proteicas , Saccharomyces cerevisiae/genética , Estramenópilas/enzimologia , Estramenópilas/genética
15.
Biochem Biophys Res Commun ; 527(4): 935-940, 2020 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-32430181

RESUMO

Circadian clock controls plant behaviors to anticipate day-night switch and keeps plant fitness. Here, we reported that plant response to auxin is also strictly governed by clock. The amplitude of auxin-responsive gene expressions gradually declined from morning to the dusk, and then enhanced from dusk to dawn. Plants with defects in both CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and its closest homologue LATE ELONGATED HYPOCOTYL (LHY) (cca1 lhy) showed comparable responses to auxin at different time points in consecutive days, suggesting that CCA1 and LHY were required for gating auxin responses. Moreover, CCA1/LHY physically interacted with the core transcriptional repressors (Aux/IAA proteins), which might further modulate plant sensitivity to auxin. Taken together, we demonstrate that the central morning phased circadian oscillator CCA1 plays a pivotal role in gating auxin response.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Mapas de Interação de Proteínas , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética
16.
New Phytol ; 221(1): 341-355, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30019753

RESUMO

Group A protein phosphatase 2Cs (PP2Cs) are abscisic acid (ABA) co-receptors that negatively regulate the ABA signaling pathway by inhibiting the downstream SnRK2 protein kinases. It has long been observed that exogenous ABA treatments dramatically induce the expression of group A PP2C genes, but the underlying molecular mechanisms and the biological significance remain largely unknown. Here, by using GUS reporter transgenic lines in which various lengths of ABI1 and ABI2 promoters were used to drive GUS gene expression, we defined the promoter fragments that confer ABA inducibility to ABI1 and ABI2. We further showed that ABRE-binding factors (ABFs), the bZIP family transcription factors, directly bind to the promoters of group A PP2C genes, and mediate rapid induction of their expression on exogenous ABA treatments. Moreover, our data indicated that ABA dramatically induces the expression of ABF genes and the accumulation of endogenous ABF proteins, and that ABFs themselves are involved in this induction, thus providing another layer of ABA regulation towards ABF proteins in addition to the well-characterized ABA-induced phosphorylation by SnRK2 protein kinases. Together, our data demonstrate that ABFs mediate rapid ABA induction of group A PP2C genes, thus playing a role in the negative feedback regulation of ABA signaling.


Assuntos
Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Ácido Abscísico/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Sítios de Ligação , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Retroalimentação Fisiológica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Front Endocrinol (Lausanne) ; 15: 1343704, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586461

RESUMO

Background: To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing. Methods: A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value. Results: The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older. Conclusion: Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age.


Assuntos
Captopril , População do Leste Asiático , Hiperaldosteronismo , Humanos , Adulto , Pessoa de Meia-Idade , Hiperaldosteronismo/diagnóstico , Aldosterona , Hipertensão Essencial/diagnóstico , China/epidemiologia
19.
J Am Heart Assoc ; 13(4): e030427, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38348775

RESUMO

BACKGROUND: This case-control study aimed to determine whether there were differences between patients with essential hypertension with accessory renal arteries (ARAs) and those without ARAs. METHODS AND RESULTS: The enrolled patients with essential hypertension were divided into the ARA group (n=200) and control group without ARAs (n=238). After propensity matching, 394 patients (197 in each of the 2 groups), were included. The 24-hour BP (4.33/2.43 mm Hg) and daytime BP (4.48/2.61 mm Hg) of patients in the ARA group were significantly higher than those of the control group (P<0.05). The flow-mediated dilation was lower in the ARA group (5.98±2.70 versus 5.18±2.66; P<0.05). In correlation analysis, the horizontal plasma aldosterone concentration had the highest correlation with 24-hour, daytime, and nighttime systolic BP (r=0.263, 0.247, and 0.243, respectively; P<0.05) and diastolic BP (r=0.325, 0.298, and 0.317, respectively; P<0.05). As for multivariate regression analysis, plasma aldosterone concentration was a significant risk factor for elevated 24-hour, daytime, and nighttime systolic BP (ß=0.249 [95% CI, 0.150-0.349], 0.228 [95% CI, 0.128-0.329], and 0.282 [95% CI, 0.187-0.377], respectively; P<0.05) and elevated diastolic BP (ß=0.289 [95% CI, 0.192-0.385], 0.256 [95% CI, 0.158-0.353], and 0.335 [95% CI, 0.243-0.427], respectively; P<0.05). Direct renin concentration was also a risk factor for 24-hour and daytime BPs, whereas heart rate was a risk factor correlated with 24-hour, daytime, and nighttime diastolic BP (all P<0.05). For the mixed-effects model for repeated measures, the results were similar to results of the multivariate regression analysis (all P<0.05). CONCLUSIONS: ARAs could contribute a higher BP of patients with essential hypertension and might promote the development of essential hypertension. The mechanism might be related to overactivation of the renin-angiotensin-aldosterone system and sympathetic nervous system.


Assuntos
Hipertensão , Humanos , Aldosterona , Estudos de Casos e Controles , Artéria Renal , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Hipertensão Essencial/diagnóstico
20.
Front Immunol ; 15: 1410457, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765013

RESUMO

Introduction: CM313 is currently under clinical investigation for treatments of multiple myeloma, systemic lupus erythematosus, and immune thrombocytopenia. We aimed to report the preclinical profile of the novel therapeutic anti-CD38 monoclonal antibody (mAb) CM313, with an emphasis on the difference with other CD38-targeting mAb. Methods: The binding of CM313 to CD38 recombinant protein across species was assessed using ELISA. The binding of CM313 to CD38-positive (CD38+) cells was detected using flow cytometry assays. CM313-induced complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and apoptosis on different CD38+ cells were assessed by LDH release assays or flow cytometry assays. The effect of CM313 on CD38 enzymatic activity was measured using fluorescence spectroscopy. CM313 immunotoxicity in human blood was assessed using flow cytometry assays, ELISA, and LDH release assays. Anti-tumor activity of CM313 was assessed in multiple mouse xenograft models. Safety profile of CM313 were evaluated in cynomolgus monkeys and human CD38 transgenic (B-hCD38) mice. Results: There exist unique sequences at complementarity-determining regions (CDR) of CM313, which facilitates its affinity to CD38 is consistently higher across a spectrum of CD38+ cell lines than daratumumab. In vitro studies showed that CM313 induces comparable killing activity than daratumumab, including ADCC, CDC, ADCP, apoptosis induced by Fc-mediated cross-linking, and effectively inhibited the enzymatic activity of CD38. However, CM313 showed more potent CDC than isatuximab. In vivo, CM313 dose-dependently inhibited xenograft tumor growth, both as a monotherapy and in combination with dexamethasone or lenalidomide. Furthermore, CM313 was well tolerated with no drug-related clinical signs or off-target risks, as evidenced by 4-week repeat-dose toxicology studies in cynomolgus monkeys and B-hCD38 mice, with the later study showing no observed adverse effect level (NOAEL) of 300mg/kg once weekly. Discussion: CM313 is a novel investigational humanized mAb with a distinct CDR sequence, showing comparable killing effects with daratumumab and stronger CDC activity than isatuximab, which supports its clinical development.


Assuntos
ADP-Ribosil Ciclase 1 , Anticorpos Monoclonais , Citotoxicidade Celular Dependente de Anticorpos , Macaca fascicularis , Animais , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Humanos , Camundongos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/imunologia , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino , Camundongos Transgênicos , Apoptose/efeitos dos fármacos , Antineoplásicos Imunológicos/farmacologia , Glicoproteínas de Membrana
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