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ConspectusSynergistic catalysis is a powerful tool that involves two or more distinctive catalytic systems to activate reaction partners simultaneously, thereby expanding the reactivity space of individual catalysis. As an established catalytic strategy, organocatalysis has found numerous applications in enantioselective transformations under rather mild conditions. Recently, the introduction of other catalytic systems has significantly expanded the reaction space of typical organocatalysis. In this regard, aminocatalysis is a prototypical example of synergistic catalysis. The combination of aminocatalyst and transition metal could be traced back to the early days of organocatalysis and has now been well explored as an enabling catalytic strategy. Particularly, the acid-base properties of aminocatalysis can be significantly expanded to include usually electrophiles generated in situ via metal-catalyzed cycles. Later on, aminocatalyst has also been exploited in synergistically combining with photochemical and electrochemical processes to facilitate redox transformations. However, synergistically combining one type of aminocatalyst with many different catalytic systems remains a great challenge. One of the most daunting challenges is the compatibility of aminocatalysts in coexistence with other catalytic species. As nucleophilic species, aminocatalysts may also bind with metal, which leads to mutual inhibition or even quenching of the individual catalytic activity. In addition, oxidative stability of aminocatalyst is also a non-neglectable issue, which causes difficulties in exploring oxidative enamine transformations.In 2007, we developed a vicinal diamine type of chiral primary aminocatalysts. This class of primary aminocatalysts was developed and evolved as functional and mechanistic mimics to the natural aldolase and has been widely applied in a number of enamine/iminium ion-based transformations. By following a "1 + x" synergistic strategy, the chiral primary amine catalysts were found to work synergistically or cooperatively with a number of transition metal catalysts, such as Pd, Rh, Ag, Co, and Cu, or other organocatalysts, such as B(C6F5)3, ketone, selenium, and iodide. Photocatalysis and electrochemical processes can also be incorporated to work together with the chiral primary amine catalysts. The 1 + x catalytic strategy enabled us to execute unexploited transformations by fine-tuning the acid-base and redox properties of the enamine intermediates and to achieve effective reaction and stereocontrol beyond the reach individually. During these efforts, an unprecedented excited-state chemistry of enamine was uncovered to make possible an effective deracemization process. In this Account, we describe our recent efforts since 2015 in exploring synergistic chiral primary amine catalysis, and the content is categorized according to the type of synergistic partner such that in each section the developed synergistic catalysis, reaction scopes, and mechanistic features are presented and discussed.
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A full-quantum approach is used to study the quantum nonlinear properties of a compound Michelson-Sagnac interferometer optomechanical system. By deriving the effective Hamiltonian, we find that the reduced system exhibits a Kerr nonlinear term with a complex coefficient, entirely induced by the dissipative and dispersive couplings. Unexpectedly, the nonlinearities resulting from the dissipative coupling possess non-Hermitian Hamiltonian-like properties preserving the quantum nature of the dispersive coupling beyond the traditional system dissipation. This protective mechanism allows the system to exhibit strong quantum nonlinear effects when the detuning (the compound cavity detuning Δc and the auxiliary cavity detuning Δe) and the tunneling coupling strength (J) of two cavities satisfy the relation J2 = ΔcΔe. Moreover, the additive effects of dispersive and dissipative couplings can produce strong anti-bunching effects, which exist in both strong and weak coupling conditions. Our work may provide a new way to study and produce strong quantum nonlinear effects in dissipatively coupled optomechanical systems.
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Glioblastoma has been extensively studied due to its high mortality and short survival. The evolution mechanism of tumor-associated macrophages (TAMs) to Glioma-associated microglia and macrophages (GAMs) in the tumor microenvironment (TME) remains to be elucidated. The tumor cell-to-cell interaction patterns have not been well defined yet. The EF-Hand Domain Family Member D2 (EFHD2) has been reported to be differentially expressed as an immunomodulatory molecule in a variety of cancers. But large-scale clinical data from multiple ethnic communities have not been used to investigate the role of EFHD2 in glioma. RNA-seq data from 313 or 657 glioma patients from the Chinese Glioma Genome Atlas (CGGA) database and 603 glioma patients from the Cancer Genome Atlas (TCGA) database were analyzed retrospectively. Cell localization was performed using single-cell sequencing data from the CGGA database and the GSE131928 dataset. Mouse glioma cell lines and primary macrophages isolated from Efhd2 knockout mice were co-cultured to validate the immunomodulatory effects of EFHD2 on macrophages and the remodeling of TME of glioblastoma. EFHD2 is enriched in high-grade gliomas, isocitrate dehydrogenase wild-type, and 1p/19q non-co-deficient gliomas. It is a potential biomarker of glioma-proneuronal subtypes and an independent prognostic factor for overall survival in patients with malignant glioblastoma. EFHD2 regulates the monocyte-macrophage system function and positively correlates with immunosuppressive checkpoints. Further experimental data demonstrates that Efhd2 influences the polarization state of GAMs and inhibits the secretion of TGF-ß1. In vitro experiments have revealed that macrophages lacking Efhd2 suppress the vitality of two glioma cell lines and decelerate the growth of glioma xenografts. In conclusion, EFHD2 promises to be a key target for TME-related immunotherapy.
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As a natural satellite of the Earth, the moon is a prime target for planetary remote sensing exploration. However, lunar polarization studies are not popular in the planetary science community. Polarimetry of the lunar surface had not been carried out from a spacecraft until the Korean lunar exploration program was initiated. In previous polarization observations of the moon, images of different polarization states were obtained by a rotating linear polarizer. This method is not well suited for future polarization observations from space-based spacecraft. To this end, we present a new kind of polarized observation of the moon using a division of a focal-plane polarization camera and propose a pipeline on the processing method of the polarization observation of the moon. We obtain a map of the degree of white-light polarization on the nearside of the moon through polarization observation, data processing, and correction. The observation and data processing methods presented in this study have the potential to serve as a reference for analyzing polarization observation data from future orbiting spacecraft. These are expected to lead to new discoveries in the fields of astronomy and planetary science.
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PURPOSE: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. RESULTS: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). CONCLUSIONS: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.
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Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Humanos , Nefrolitotomía Percutánea/métodos , Dilatación , Riñón , Cálculos Renales/cirugía , Ultrasonografía Intervencional , Hemoglobinas , Nefrostomía Percutánea/métodos , Resultado del TratamientoRESUMEN
Catalytic asymmetric de Mayo reaction was achieved for the first time under visible light using asymmetric binary acid catalysis (ABC) involving zirconium chloride and chiral phosphoric acid (CPA). The chiral zirconium catalysis enables effective reactions over a broad range of 1,3-diketones and alkenes with up to >99% yield and 98% ee. The key chiral zirconium enolate was isolated and characterized to account for the observed catalysis and stereoselectivity.
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In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Animales , Humanos , Ratones , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/tratamiento farmacológico , Ratones Endogámicos C3H , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores Androgénicos/uso terapéutico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Quantum squeezing-assisted noise suppression is a promising field with wide applications. However, the limit of noise suppression induced by squeezing is still unknown. This paper discusses this issue by studying weak signal detection in an optomechanical system. By solving the system dynamics in the frequency domain, we analyze the output spectrum of the optical signal. The results show that the intensity of the noise depends on many factors, including the degree or direction of squeezing and the choice of the detection scheme. To measure the effectiveness of squeezing and to obtain the optimal squeezing value for a given set of parameters, we define an optimization factor. With the help of this definition, we find the optimal noise suppression scheme, which can only be achieved when the detection direction exactly matches the squeezing direction. The latter is not easy to adjust as it is susceptible to changes in dynamic evolution and sensitive to parameters. In addition, we find that the additional noise reaches a minimum when the cavity (mechanical) dissipation κ(γ) satisfies the relation κ = Nγ, which can be understood as the restrictive relationship between the two dissipation channels induced by the uncertainty relation. Furthermore, by taking into account the noise source of our system, we can realize high-level noise suppression without reducing the input signal, which means that the signal-to-noise ratio can be further improved.
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BACKGROUND: Cystinuria and xanthinuria are both rare genetic diseases involving urinary calculi. However, cases combining these two disorders have not yet been reported. CASE PRESENTATION: In this study, we report a case of cystinuria with xanthine stones and hyperuricemia. The 23-year-old male patient was diagnosed with kidney and ureteral stones, solitary functioning kidney and hyperuricemia after admission to the hospital. The stones were removed by surgery and found to be composed of xanthine. CONCLUSION: Genetic testing by next-generation sequencing technology showed that the patient carried the homozygous nonsense mutation c.1113 C> A (p.Tyr371*) in the SLC3A1 gene, which was judged to be a functionally pathogenic variant. Sanger sequencing revealed that the patient's parents carried this heterozygous mutation, which is a pathogenic variant that can cause cystinuria. The 24-h urine metabolism analysis showed that the cystine content was 644 mg (<320 mg/24 h), indicating that the patient had cystinuria, consistent with the genetic test results. This case shows that cystinuria and xanthine stones can occur simultaneously, and provides evidence of a possible connection between the two conditions. Furthermore, our findings demonstrate the potential value of genetic testing using next-generation sequencing to effectively assist in the clinical diagnosis and treatment of patients with urinary calculi.
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Sistemas de Transporte de Aminoácidos , Cistinuria , Humanos , Masculino , Adulto Joven , Cistinuria/genética , Sistemas de Transporte de Aminoácidos/genética , Xantina , Cálculos Renales , Hiperuricemia , Codón sin Sentido , Pruebas Genéticas , Linaje , FemeninoRESUMEN
INTRODUCTION: The aim of this study was to evaluate the association between recurrence-free survival (RFS) and perirenal fat thickness (PFT) in a cohort of Chinese population with unilateral nephrolithiasis. METHODS: We retrospectively reviewed the medical records of 81 patients with unilateral nephrolithiasis in our center from January 2019 to June 2019. PFT measured on computed tomography (CT) scans was evaluated. Kaplan-Meier curves and log-rank tests were used to assess significant differences in RSF between high-PFT and low-PFT groups within sexes. Univariable and multivariable Cox regression analyses were used to evaluate the potential risk factors for renal stone recurrence. RESULTS: High PFT was significantly associated with high BMI and hyperlipidemia (p = .003 and.047, respectively). The PFT of stone-bearing kidney was significantly greater than PFT of non-stone-bearing kidney (0.77 ± 0.60 cm vs. 0.67 ± 0.58 cm, p = .002) . During the follow-up periods (median 31 months), 21 (25.9%) patients experienced ipsilateral renal stone recurrence. In addition, Kaplan-Meier survival curves showed that patients with low PFT had a significant better RFS than those with high PFT (p = .012). In the univariable Cox analyses, male sex and high PFT were significantly associated with a poor RFS (p = .042 and .018, respectively). Moreover, both male sex and high PFT retained significance in the multivariable analyses (p = .045 and .020, respectively). CONCLUSIONS: Our findings suggested that PFT is a noninvasive and feasible parameter, which may help in the risk stratification of renal stone recurrence in the follow-up periods.
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Cálculos Renales , Nefrolitiasis , Humanos , Masculino , Pueblos del Este de Asia , Riñón , Cálculos Renales/diagnóstico por imagen , Cálculos Renales/epidemiología , Nefrolitiasis/diagnóstico por imagen , Nefrolitiasis/epidemiología , Obesidad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , ChinaRESUMEN
Nonreciprocity plays an indispensable role in quantum information transmission. We theoretically study the unidirectional amplification in the non-Markovian regime, in which a nanosphere surrounded by a structured bath is trapped in a single (dual)-mode cavity. The global mechanical response function of the nanosphere is markedly altered by the non-Markovian structured bath through shifting the effective frequency and magnifying the response function. Consequently, when there is a small difference in the transmission rate within the regime of Markovian, the unidirectional amplification is achieved in the super-Ohmic spectral environment. In the double-optomechanical coupling system, the phase difference between two optomechanical couplings can reverse the transmission direction. Meanwhile, the non-Markovian bath still can amplify the signal because of the XX-type coupling between nanosphere and its bath.
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Warming strongly stimulates soil nitrous oxide (N2O) emission, contributing to the global warming trend. Submerged paddy soils exhibit huge N2O emission potential; however, the N2O emission pathway and underlying mechanisms for warming are not clearly understood. We conducted an incubation experiment using 15N to investigate the dynamics of N2O emission at controlled temperatures (5, 15, 25, and 35°C) in 125% water-filled pore space. The community structures of nitrifiers and denitrifiers were determined via high-throughput sequencing of functional genes. Our results showed that elevated temperature sharply enhanced soil N2O emission from submerged paddy soil. Denitrification was the main contributor, accounting for more than 90% of total N2O emission at all treatment temperatures. N2O flux was coordinatively regulated by nirK-, nirS-, and nosZ-containing denitrifiers but not ammonia-oxidizing archaea or ammonia-oxidizing bacteria. The nirS-containing denitrifiers were more sensitive to temperature shifts, especially at a lower temperature range (5 to 25°C), and showed a stronger correlation with N2O flux than that of nirK-containing denitrifiers. In contrast, nosZ-containing denitrifiers exhibited substantial variation at higher temperatures (15 to 35°C), thereby playing an important role in N2O consumption. Certain taxa of nirS- and nosZ-containing denitrifiers regulated N2O flux, including nirS-containing denitrifiers affiliated with Rhodanobacter and Cupriavidus as well as nosZ-containing denitrifiers affiliated with Azoarcus and Azospirillum. Together, these findings suggest that elevated temperature can significantly increase N2O emission from denitrification in submerged paddy soils by shifting the overall community structures and enriching some indigenous taxa of nirS- and nosZ-containing denitrifiers. IMPORTANCE The interdependence between global warming and greenhouse gas N2O has always been the hot spot. However, information on factors contributing to N2O and temperature-dependent community structure changes is scarce. This study demonstrated high-temperature-induced N2O emission from submerged paddy soils, mainly via stimulating denitrification. Further, we speculate that key functional denitrifiers drive N2O emission. This study showed that denitrifiers were more sensitive to temperature rise than nitrifiers, and the temperature sensitivity differed among denitrifier communities. N2O-consuming denitrifiers (nosZ-containing denitrifiers) were more sensitive at a higher temperature range than N2O-producing denitrifiers (nirS-containing denitrifiers). This study's findings help predict N2O fluxes under different degrees of warming and develop strategies to mitigate N2O emissions from paddy fields based on microbial community regulation.
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Contaminantes Atmosféricos/análisis , Desnitrificación , Óxido Nitroso/análisis , Microbiología del Suelo , Contaminantes del Suelo/análisis , Calentamiento Global , Concentración de Iones de Hidrógeno , Nitrificación , Oryza , Suelo/química , TemperaturaRESUMEN
Electroorganic synthesis has recently become a rapidly blossoming research area within the organic synthesis community. It should be noted that electrochemical reaction is always a balanced reaction system with two half-cell reactions-oxidation and reduction. Most electrochemical strategies, however, typically focus on one of the two sides for the desired transformations. Paired electrolysis has two desirable half reactions running simultaneously, thus maximizing the overall margin of atom and energy economy. Meanwhile, the spatial separation between oxidation and reduction is the essential feature of electrochemistry, offering unique opportunities for the development of redox-neutral reactions that would otherwise be challenging to accomplish in a conventional reaction flask setting. This review discusses the most recent illustrative examples of paired electrolysis with special emphasis on sequential and convergent processes.
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BACKGROUND: To provide participants with a more real and immersive intervening experience, virtual reality (VR) and/or augmented reality (AR) technologies have been integrated into some bystander intervention training programs and studies measuring bystander behaviors. OBJECTIVE: We focused on whether VR or AR can be used as a tool to enhance training bystanders. We reviewed the evidence from empirical studies that used VR and/or AR as a tool for examining bystander behaviors in the domain of interpersonal violence research. METHODS: Two librarians searched for articles in databases, including APA PsycInfo (Ovid), Criminal Justice Abstracts (EBSCO), Medline (Ovid), Applied Social Sciences Index & Abstracts (ProQuest), Sociological Abstracts (ProQuest), and Scopus till April 15, 2020. Studies focusing on bystander behaviors in conflict situations were included. All study types (except reviews) written in English in any discipline were included. RESULTS: The search resulted in 12,972 articles from six databases, and the articles were imported into Covidence. Eleven studies met the inclusion and exclusion criteria. All 11 articles examined the use of VR as a tool for studying bystander behaviors. Most of the studies were conducted in US young adults. The types of interpersonal violence were school bullying, dating violence, sexual violence/assault, and soccer-associated violence. VR technology was used as an observational measure and bystander intervention program. We evaluated the different uses of VR for bystander behaviors and noted a lack of empirical evidence for AR as a tool. We also discuss the empirical evidence regarding the design, effectiveness, and limitations of implementing VR as a tool in the reviewed studies. CONCLUSIONS: The reviewed results have implications and recommendations for future research in designing and implementing VR/AR technology in the area of interpersonal violence. Future studies in this area may further contribute to the use of VR as an observational measure and explore the potential use of AR to study bystander behaviors.
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Realidad Aumentada , Efecto Espectador/fisiología , Psicoterapia Interpersonal/métodos , Violencia/psicología , Realidad Virtual , Femenino , Humanos , MasculinoRESUMEN
We propose a scheme to generate the macroscopic entangled Schrödinger cat state of two mechanical resonators in a hybrid optomechanical system by introducing modulated photon-hopping interaction between two cavities. We show that the obtained entangled cat state possesses large average phonon number and the two base vectors of which are nearly orthogonal, thus causing the high degree of entanglement. To justify the robust of the scheme, the dissipation of the system and the noise from the environment are considered. It shows that the high fidelity between the obtained state and the target state can be achieved in the presence of dissipation and thermal noise within our parameter regions, which suggests that our state-generation proposal is feasible.
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Solution blow spinning (SBS) has emerged as a rapid and scalable technique for the production of polymeric and ceramic materials into micro-/nanofibers. Here, SBS was employed to produce submicrometer fibers of regenerated silk fibroin (RSF) from Bombyx mori (silkworm) cocoons based on formic acid or aqueous systems. Spinning in the presence of vapor permitted the production of fibers from aqueous solutions, and high alignment could be obtained by modifying the SBS setup to give a concentrated channeled airflow. The combination of SBS and a thermally induced phase separation technique (TIPS) resulted in the production of macro-/microporous fibers with 3D interconnected pores. Furthermore, a coaxial SBS system enabled a pH gradient and kosmotropic salts to be applied at the point of fiber formation, mimicking some of the aspects of the natural spinning process, fostering fiber formation by self-assembly of the spinning dope. This scalable and fast production of various types of silk-based fibrous scaffolds could be suitable for a myriad of biomedical applications.
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Biomimética , Fibroínas/química , Soluciones/química , Animales , Bombyx/química , Transición de Fase , Porosidad , Agua/químicaRESUMEN
Based on photon-phonon nonlinear interaction, a scheme of controllable photon-phonon converters is proposed at single-quantum level in a composed quadratically coupled optomechanical system. With the assistance of the mechanical oscillator, the Kerr nonlinear effect between photon and phonon is enhanced so that the single-photon state can be converted into the phonon state with high fidelity even under the current experimental condition that the single-photon coupling rate is much smaller than mechanical frequency (g ⪠ωm). The state transfer protocols and their transfer fidelity are discussed analytically and numerically. A multi-path photon-phonon converter is designed by combining the optomechanical system with low frequency resonators, which can be controlled by experimentally adjustable parameters. This work provides us a potential platform for quantum state transfer and quantum information.
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A dual activation strategy integrating primary amine catalysis and Lewis base activation has been developed for an asymmetric α-benzylation reaction. Enamines derived from ß-ketocarbonyls could react effectively with in situ generated ortho-quinone methides under Lewis base activation in asymmetric α-benzylation of ß-ketocarbonyls and α-branched aldehydes. The approach enables the creation of acyclic all-carbon quaternary stereocenters with excellent enantioselectivities and good activity.
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The design and development of wound dressings with excellent procoagulant and antibacterial activity to achieve high wound healing effectiveness are highly desirable in clinical applications. In this work, we develop a calcium-copper zeolite gauze (CaCu-ZG) by a two-step process involving calcium and copper ion exchange in a zeolite gauze. The CaCu-ZG exhibits remarkable procoagulant and antibacterial abilities, as well as good biocompatibility. Compared with the medical gauze, the blood clotting time of CaCu-ZG significantly decreases and the antibacterial activity increases in both in vivo and in vitro experiments. The remarkable ability of wound healing has been verified using a mouse dorsal skin-infected wound model, demonstrating its great potential for wound treatment in clinical applications.
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EFHD2 (EF-hand domain family, member D2) has been identified as a calcium-binding protein with immunomodulatory effects. In this study, we characterized the phenotype of Efhd2-deficient mice in sepsis and examined the biological functions of EFHD2 in peripheral T cell activation and T helper (Th) cell differentiation. Increased levels of EFHD2 expression accompanied peripheral CD4+ T cell activation in the early stages of sepsis. Transcriptomic analysis indicated that immune response activation was impaired in Efhd2-deficient CD4+ T cells. Further, Efhd2-deficient CD4+ T cells isolated from the spleen of septic mice showed impaired T cell receptor (TCR)-induced Th differentiation, especially Th1 and Th17 differentiation. In vitro data also showed that Efhd2-deficient CD4+ T cells exhibit impaired Th1 and Th17 differentiation. In the CD4+ T cells and macrophages co-culture model for antigen presentation, the deficiency of Efhd2 in CD4+ T cells resulted in impaired formation of immunological synapses. In addition, Efhd2-deficient CD4+ T cells exhibited reduced levels of phospho-LCK and phospho-ZAP70, and downstream transcription factors including Nfat, Nfκb and Nur77 following TCR engagement. In summary, EFHD2 may promote TCR-mediated T cell activation subsequent Th1 and Th17 differentiation in the early stages of sepsis by regulating the intensity of TCR complex formation.