Intratumor injected gold molecular clusters for NIR-II imaging and cancer therapy.

Surgical resections of solid tumors guided by visual inspection of tumor margins have been performed for over a century to treat cancer. Near-infrared (NIR) fluorescence labeling/imaging of tumor in the NIR-I (800 to 900 nm) range with systemically administrated fluorophore/tumor-targeting antibody conjugates have been introduced to improve tumor margin delineation, tumor removal accuracy, and patient survival. Here, we show Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC, ~2 nm in size) as a preclinical intratumorally injectable agent for NIR-II/SWIR (1,000 to 3,000 nm) fluorescence imaging-guided tumor resection. The AuPC clusters were found to be uniformly distributed in the 4T1 murine breast cancer tumor upon intratumor (i.t.) injection. The phosphocholine coating afforded highly stealth clusters, allowing a high percentage of AuPC to fill the tumor interstitial fluid space homogeneously. Intra-operative surgical navigation guided by imaging of the NIR-II fluorescence of AuPC allowed for complete and non-excessive tumor resection. The AuPC in tumors were also employed as a photothermal therapy (PTT) agent to uniformly heat up and eradicate tumors. Further, we performed in vivo NIR-IIb (1,500 to 1,700 nm) molecular imaging of the treated tumor using a quantum dot-Annexin V (QD-P3-Anx V) conjugate, revealing cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters combined with rapid renal excretion, high biocompatibility, and safety make them promising for clinical translation.

High hydrostatic pressure participates in atrial fibrosis through the p300/p53/Smad3 pathway.

As an independent risk factor of atrial fibrillation (AF), hypertension (HTN) can induce atrial fibrosis through cyclic stretch and hydrostatic pressure. The mechanism by which high hydrostatic pressure promotes atrial fibrosis is unclear yet. p300 and p53/Smad3 play important roles in the process of atrial fibrosis. This study investigated whether high hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway. Biochemical experiments were used to study the expression of p300/p53/Smad3 pathway in left atrial appendage (LAA) tissues of patients with sinus rhythm (SR), AF, AF + HTN, and C57/BL6 mice, hypertensive C57/BL6 mice and atrial fibroblasts of mice. To investigate the roles of p300 and p53 in the process of atrial fibrosis, p300 and p53 in mice atrial fibroblasts were knocked in or knocked down, respectively. The expression of p300/p53/Smad3 and fibrotic factors was higher in patients with AF and AF + HTN than those with SR only. The expressions of p300/p53/Smad3 and fibrotic factors increased in hypertensive mice. Curcumin (Cur) and knocking down of p300 reversed the expressions of these factors. 40 mmHg hydrostatic pressure/overexpression of p300 upregulated the expressions of p300/p53/Smad3 and fibrotic factors in mice LAA fibroblasts. While Cur or knocking down p300 reversed these changes. Knocking down/overexpression of p53, the expressions of p53/Smad3 and fibrotic factors also decreased/increased, correspondingly. High hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway, which further increases the susceptibility to AF.

High-entropy rare earth materials: synthesis, application and outlook.

Recently, high-entropy (HE) materials have attracted increasing interest in various fields due to their unique characteristics. Rare earth (RE) elements have a similar atomic radius and gradually occupied 4f orbitals, endowing them with abundant optical, electric, and magnetic properties. Furthermore, HE-RE materials exhibit good structural and thermal stability and various functional properties, emerging as an important class of HE materials, which are on the verge of rapid development. However, a comprehensive review focusing on the introduction and in-depth understanding of HE-RE materials has not been reported to date. Thus, this review endeavors to provide a comprehensive summary of the development and research status of HE-RE materials, including alloys and ceramics, ranging from their structure, synthesis, and properties to applications. In addition, some distinctive issues of HR-RE materials related to the special electronic structure of RE are also discussed. Finally, we put forward the current challenges and future development directions of HE-RE materials. We hope that this review will provide inspiration for new design ideas and valuable references in this emerging field in the future.

Biocompatible Silica-Coated Europium-Doped CsPbBr3 Nanoparticles with Luminescence in Water for Zebrafish Bioimaging.

Cesium lead halide (CsPbX3, X = Br, Cl, and I) nanocrystals (NCs) are widely concerned and applied in many fields due to the excellent photoelectric performance. However, the toxicity of Pb and the loss of luminescence in water limit its application in vivo. A stable perovskite nanomaterial with good bioimaging properties is developed by incorporating europium (Eu) in CsPbX3 NCs followed with the surface coating of silica (SiO2) shell (CsPbX3:Eu@SiO2). Through the surface coating of SiO2, the luminescence stability of CsPbBr3 in water is improved and the leakage of Pb2+ is significantly reduced. In particular, Eu doping inhibits the photoluminescence quantum yield reduction of CsPbBr3 caused by SiO2 coating, and further reduces the release of Pb2+. CsPbBr3:Eu@SiO2 nanoparticles (NPs) show efficient luminescence in water and good biocompatibility to achieve cell imaging. More importantly, CsPb(ClBr)3:Eu@SiO2 NPs are obtained by adjusting the halogen components, and green light and blue light are realized in zebrafish imaging, showing good imaging effect and biosafety. The work provides a strategy for advanced perovskite nanomaterials toward biological practical application.

Hirschsprung's disease: m6A methylase VIRMA suppresses cell migration and proliferation by regulating GSK3ß.

BACKGROUND: N6-methyladenosine (m6A) is the most abundant mRNA modification in mammals, participating in various biological processes. VIRMA is a key methyltransferase involved in m6A modification. However, the role of VIRMA in Hirschsprung's disease (HSCR) remains unclear. This study aims to investigate the function of VIRMA in HSCR and identify its corresponding regulatory mechanisms. METHODS: The expression of VIRMA and GSK3ß in colon tissues of HSCR was examined using RT-qPCR, Western blot, and Immunohistochemistry. Immunofluorescence detected localization of VIRMA and GSK3ß. Cell proliferation was measured by CCK8 and EdU assays, and cell migration was evaluated via cell migration and wound healing assays. The stability of GSK3ß mRNA was assessed using the actinomycin D assay and the overall level of m6A in cells was assessed by colorimetric assay. RESULTS: VIRMA was significantly downregulated in narrow-segment colon tissue. Silencing of VIRMA inhibited cell proliferation and migration. VIRMA can inhibit the degradation of GSK3ß mRNA and increase the expression of GSK3ß. GSK3ß was significantly upregulated in narrow-segment colon tissues. Accordingly, our findings showed that GSK3ß mediated the VIRMA-driven cell migration and proliferation. CONCLUSION: VIRMA can inhibit cell migration and proliferation by upregulating the expression of GSK3ß, contributing to the onset of HSCR. IMPACT: The expressions of VIRMA were significantly reduced in HSCR, while GSK3ß expression was increased in HSCR, and can be used as a molecular marker. VIRMA overexpression promoted the proliferation and migration of SH-SY5Y and HEK-293T cells. VIRMA can inhibit the degradation of GSK3ß mRNA and increase the expression of GSK3ß.

Induced transparency by interference or polarization.

Polarization of optical fields is a crucial degree of freedom in the all-optical analogue of electromagnetically induced transparency (EIT). However, the physical origins of EIT and polarization-induced phenomena have not been well distinguished, which can lead to confusion in associated applications such as slow light and optical/quantum storage. Here we study the polarization effects in various optical EIT systems. We find that a polarization mismatch between whispering gallery modes in two indirectly coupled resonators can induce a narrow transparency window in the transmission spectrum resembling the EIT lineshape. However, such polarization-induced transparency (PIT) is distinct from EIT: It originates from strong polarization rotation effects and shows a unidirectional feature. The coexistence of PIT and EIT provides additional routes for the manipulation of light flow in optical resonator systems.

Optimized Protocols for Duplex Quantum Transduction.

Quantum transducers convert quantum signals through hybrid interfaces of physical platforms in quantum networks. Modeled as quantum communication channels, performance of unidirectional quantum transduction can be measured by the quantum channel capacity. However, characterizing performance of quantum transducers used for duplex quantum transduction where signals are converted bidirectionally remains an open question. Here, we propose rate regions to characterize the performance of duplex quantum transduction. Using this tool, we find that quantum transducers optimized for simultaneous duplex transduction can outperform strategies based on the standard protocol of time-shared unidirectional transduction. Integrated over the frequency domain, we demonstrate that the rate region can also characterize quantum transducers with finite bandwidth.

Exceptional Entanglement Phenomena: Non-Hermiticity Meeting Nonclassicality.

Non-Hermitian (NH) extension of quantum-mechanical Hamiltonians represents one of the most significant advancements in physics. During the past two decades, numerous captivating NH phenomena have been revealed and demonstrated, but all of which can appear in both quantum and classical systems. This leads to the fundamental question: what NH signature presents a radical departure from classical physics? The solution of this problem is indispensable for exploring genuine NH quantum mechanics, but remains experimentally untouched so far. Here, we resolve this basic issue by unveiling distinct exceptional entanglement phenomena, exemplified by an entanglement transition, occurring at the exceptional point of NH interacting quantum systems. We illustrate and demonstrate such purely quantum-mechanical NH effects with a naturally dissipative light-matter system, engineered in a circuit quantum electrodynamics architecture. Our results lay the foundation for studies of genuinely quantum-mechanical NH physics, signified by exceptional-point-enabled entanglement behaviors.

Contribution of calcium dysregulation to impaired coronary artery contraction in Zucker diabetic fatty rats.

Diabetic coronary artery injury is closely associated with Ca2+ dysregulation, although the underlying mechanism remains unclear. This study explored the role and mechanism of Ca2+ handling in coronary artery dysfunction in type 2 diabetic rats. Zucker diabetic fatty (ZDF) rats were used as the type 2 diabetes mellitus model. The contractility of coronary artery rings induced by KCl, CaCl2 , 5-HT and U46619 was significantly lower in ZDF rats than in Zucker lean rats. Vasoconstriction induced by 5-HT and U46619 was greatly inhibited by nifedipine. However, in the presence of 1 µM nifedipine or in the Ca2+ -free KH solution containing 1 µM nifedipine, there was no difference in the vasoconstriction between Zucker lean and ZDF rats. Store-operated calcium channels (SOCs) were not involved in coronary vasoconstriction. The downregulation of contractile proteins and the upregulation of synthesized proteins were in coronary artery smooth muscle cells (CASMCs) from ZDF rats. Metformin reversed the reduction of vasoconstriction in ZDF rats. Taken together, L-type calcium channel is important for regulating the excitation-contraction coupling of VSMCs in coronary arteries, and dysregulation of this channel contributes to the decreased contractility of coronary arteries in T2DM.

Hexafluoropropylene oxide tetramer acid (HFPO-TeA)-induced developmental toxicities in chicken embryo: Peroxisome proliferator-activated receptor Alpha (PPARα) is involved.

Hexafluoropropylene oxide tetramer acid (HFPO-TeA) is an emerging environmental contaminant, with environmental presence but limited toxicological information. To investigate its potential developmental toxicities, various doses of HFPO-TeA exposure were achieved in chicken embryos via air cell injection, and the exposed embryos were incubated until hatch. Within 24 h of hatch, the hatchling chickens were assessed with electrocardiography and histopathology for toxicological evaluation. For mechanistic investigation, in ovo silencing of PPARα was achieved via lentivirus microinjection, then the morphological/functional endpoints along with protein expression levels of PPARα-regulated genes were assessed. HFPO-TeA exposure in chicken embryo resulted in developmental cardiotoxicity and hepatotoxicity. Specifically, decreased right ventricular wall thickness, increased heart rate and hepatic steatosis were observed, whereas silencing of PPARα resulted in alleviation of observed toxicities. Western blotting for EHHADH and FABPs suggested that developmental exposure to HFPO-TeA effectively increased the expression levels of both targets in hatchling chicken heart and liver tissue samples, while PPARα silencing prevented such changes, suggesting that PPARα and its downstream genes are playing critical roles in HFPO-TeA induced developmental toxicities.

In Vitro Antifungal Activity of Azoles and Other Antifungal Agents Against Pathogenic Yeasts from Vulvovaginal Candidiasis in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. OBJECTIVE: Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. METHODS: Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. RESULTS: 543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). CONCLUSIONS: C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.

Methylated ZNF582 as a triage marker for occult cervical cancer and advanced cervical intraepithelial neoplasia.

Aim: To explore the appropriate triage methods for women infected with high-risk human papillomavirus (hrHPV). Materials & methods: A total of 424 out of 872 hrHPV-infected women were divided into cervicitis (n = 123), cervical intraepithelial neoplasia grade 1 (CIN1; n = 89), CIN2 (n = 72), CIN3 (n = 87) and cervical cancer (n = 53) groups. Results: The sensitivity/specificity of ZNF582m, PAX1m and liquid-based cytology (LBC) for hrHPV-infected women with transformation zone 3 CIN3+ was 83.9/93.1, 77.4/90.6 and 80.6/58.5%, respectively. The ZNF582m/PAX1m test had a higher specificity than LBC (p < 0.001) and similar sensitivity to that observed for LBC (p > 0.05). ZNF582m/PAX1m improved the positive predictive value of CIN3+ (64.7/60.0%) in low-grade LBC (negative predictive value: 91.7/88.7%). Conclusion: ZNF582m was superior to PAX1m and LBC tests in detecting CIN3+ in hrHPV-infected women.

Human papillomavirus (HPV) testing is the main method for cervical cancer screening. Although most HPV infections are transient and can be cleared by the body, persistent infection with HPV can lead to cervical cancer. In this study, 424 HPV-infected women were divided into normal, cervical intraepithelial neoplasia grade 1 (CIN1), CIN2, CIN3 and cervical cancer groups according to the grade of cervical lesion (low to high). Women with CIN3 or cervical cancer need treatment. ZNF582^m, PAX1^m and liquid-based cytology detected 83.9, 77.4 and 80.6% of women with CIN3+ and 93.1, 90.6 and 58.5% of women without CIN3+. However, the ZNF582^m test was superior to the PAX1^m and liquid-based cytology tests.

Management of patients with positive margin after conization for high-grade cervical intraepithelial lesions.

BACKGROUND AND OBJECTIVE: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of patients with positive margin in comparison to regular follow-up, and a repeat cervical conization. MATERIALS AND METHODS: A retrospective analysis was conducted using 83 patients with pathologically confirmed high-grade cervical intraepithelial neoplasia (CIN) with a positive margin after conization. The management methods and patient prognosis were analyzed and compared. RESULTS: Thirty-five, 33, and 15 patients were treated for regular follow-up, ALA-PDT, and a repeat cervical conization, respectively. About 33.3% (5/15) patients had residual lesions of low-grade CIN and above after recognization. The clinical characteristics of patients in the three groups were similar. The residual lesion rates of patients selected for follow-up, ALA-PDT, and recognization were 34.3% (12/35), 9.1% (3/33), and 0% (0/15), respectively, at 6-month follow-up (p = 0.004). The HPV clearance rates were 31.3%, 66.7%, and 84.6%, respectively (p = 0.01). Further analysis showed that a positive margin in the inscribed margin of the cervical canal (p = 0.022) and persistent HR-HPV positive tests after initial conization (p = 0.003) significantly increased the risk of residual disease. At 2-year follow-up, the recurrence rates of lesions were 3.3% and 26.1% in the ALA-PDT and follow-up groups, respectively (p = 0.021). Notably, the recurrence rates were not significantly different between the ALA-PDT and recognization groups (3.3% vs. 6.7%) (p = 0.561). CONCLUSION: ALA-PDT is an effective treatment for patients with a positive margin after cervical conization for high-grade CIN. Compared with regular follow-up, ALA-PDT can reduce residual and recurrence rate. Moreover, there was no significant difference in the efficacy between AlA-PDT and recognization.

Research Status and Prospects of Non-Traumatic Fat Embolism in Forensic Medicine.

In the practice of forensic pathology, fat embolism is one of the common causes of death, which can be divided into two categories: traumatic and non-traumatic. Non-traumatic fat embolism refers to the blockage of small blood vessels by fat droplets in the circulatory blood flow caused by non-traumatic factors such as underlying diseases, stress, poisoning and lipid metabolism disorders. At present, it is believed that the production of non-traumatic fat embolism is related to the disturbance of lipid metabolism, C-reactive protein-related cascade reaction, the agglutination of chylomicron and very low-density lipoprotein. The forensic identification of the cause of death of non-traumatic fat embolism is mainly based on the case, systematic autopsy, HE staining and fat staining, but it is often missed or misdiagnosed by forensic examiners because of its unknown risk factors, hidden onset, the difficulty of HE staining observation and irregular implementation of fat staining. In view of the lack of attention to non-traumatic fat embolism in forensic identification, this paper reviews the concepts, pathophysiological mechanism, research progress, existing problems and countermeasures of non-traumatic fat embolism, providing reference for forensic scholars.

Photoinduced Copper-Catalyzed Asymmetric C(sp3 )-H Alkynylation of Cyclic Amines by Intramolecular 1,5-Hydrogen Atom Transfer.

The development of a mild and general method for C(sp3 )-H functionalization of cyclic amines has been an ongoing challenge. In this work, we describe the copper-catalyzed enantioselective C(sp3 )-H alkynylation of unactivated cyclic 2-iodo-benzamide under photo-irradiation by intramolecular 1,5-hydrogen atom transfer (HAT). The employment of a new bisoxazoline diphenylamine ligand, in conjunction with 1,1'-bi-2-naphthol, which significantly improved the reduction potential of the copper complex, was the key to success of this chemistry. Mechanistic and computational studies supported that the new copper complex served the dual role as a photoredox and coupling catalyst, the reaction went through a radical process, and the intramolecular 1,5-HAT process was involved in the rate-limiting step. Apart from the broad substrate scope including unprecedented benzocyclic amines, this method also showed excellent diastereoselectivity in 2-monosubstituted cyclic amines via substrate control.

When rare earth meets carbon nanodots: mechanisms, applications and outlook.

Rare earth (RE) elements are widely used in the luminescence and magnetic fields by virtue of their abundant 4f electron configurations. However, the overall performance and aqueous stability of single-component RE materials need to be urgently improved to satisfy the requirements for multifunctional applications. Carbon nanodots (CNDs) are excellent nanocarriers with abundant functional surface groups, excellent hydrophilicity, unique photoluminescence (PL) and tunable features. Accordingly, RE-CND hybrids combine the merits of both RE and CNDs, which dramatically enhance their overall properties such as luminescent and magnetic-optical imaging performances, leading to highly promising practical applications in the future. Nevertheless, a comprehensive review focusing on the introduction and in-depth understanding of RE-CND hybrid materials has not been reported to date. This review endeavors to summarize the recent advances of RE-CNDs, including their interaction mechanisms, general synthetic strategies and applications in fluorescence, biosensing and multi-modal biomedical imaging. Finally, we present the current challenges and the possible application perspectives of newly developed RE-CND materials. We hope this review will inspire new design ideas and valuable references in this promising field in the future.

High hydrostatic pressure induces atrial electrical remodeling through angiotensin upregulation mediating FAK/Src pathway activation.

Hypertension is an independent risk factor for atrial fibrillation (AF), although its specific mechanisms remain unclear. Previous research has been focused on cyclic stretch, ignoring the role of high hydrostatic pressure. The present study aimed to explore the effect of high hydrostatic pressure stimulation on electrical remodeling in atrial myocytes and its potential signaling pathways. Experiments were performed on left atrial appendages from patients with chronic AF or sinus rhythm, spontaneously hypertensive rats (SHRs) treated with or without valsartan (10 mg/kg/day) and HL-1 cells were exposed to high hydrostatic pressure using a self-developed device. Whole-cell patch-clamp recordings and western blots demonstrated that the amplitudes of ICa,L, Ito, and IKur were reduced in AF patients with corresponding changes in protein expression. Angiotensin protein levels increased and Ang1-7 decreased, while focal adhesion kinase (FAK) and Src kinase were enhanced in atrial tissue from AF patients and SHRs. After rapid atrial pacing, AF inducibility in SHR was significantly higher, accompanied by a decrease in ICa,L, upregulation of Ito and IKur, and a shortened action potential duration. Angiotensin upregulation and FAK/Src activation in SHR were inhibited by angiotensin type 1 receptor inhibitor valsartan, thus, preventing electrical remodeling and reducing AF susceptibility. These results were verified in HL-1 cells treated with high hydrostatic pressure, and demonstrated that electrical remodeling regulated by the FAK-Src pathway could be modulated by valsartan. The present study indicated that high hydrostatic pressure stimulation increases AF susceptibility by activating the renin-angiotensin system and FAK-Src pathway in atrial myocytes.

Abnormal Ca2+ handling contributes to the impairment of aortic smooth muscle contractility in Zucker diabetic fatty rats.

Vascular dysfunction is a common pathological basis for complications in individuals affected by diabetes. Previous studies have established that endothelial dysfunction is the primary contributor to vascular complications in type 2 diabetes (T2DM). However, the role of vascular smooth muscle cells (VSMCs) in vascular complications associated with T2DM is still not completely understood. The aim of this study is to explore the potential mechanisms associated with Ca2+ handling dysfunction and how this dysfunction contributes to diabetic vascular smooth muscle impairment. The results indicated that endothelium-dependent vasodilation was impaired in diabetic aortae, but endothelium-independent vasodilation was not altered. Various vasoconstrictors such as phenylephrine, U46619 and 5-HT could induce vasoconstriction in a concentration-dependent manner, such that the dose-response curve was parallel shifted to the right in diabetic aortae, compared to the control. Vasoconstrictions mediated by L-type calcium (Cav1.2) channels were attenuated in diabetic aortae, but effects mediated by store-operated calcium (SOC) channels were enhanced. Intracellular Ca2+ concentration ([Ca2+]i) in VSMCs was detected by Fluo-4 calcium fluorescent probes, and demonstrated that SOC-mediated Ca2+ entry was increased in diabetic VSMCs. VSMC-specific knockout of STIM1 genes decreased SOC-mediated and phenylephrine-induced vasoconstrictive response in mice aortae. Additionally, Orai1 expression was up-regulated, Cav1.2 expression was downregulated, and the phenotypic transformation of diabetic VSMCs was determined in diabetic aortae. The overexpression of Orai1 markedly promoted the OPN expression of VSMCs, whereas SKF96365 (SOC channel blocker) reversed the phenotypic transformation of diabetic VSMCs. Our results demonstrated that the vasoconstriction response of aortic smooth muscle was weakened in type 2 diabetic rats, which was related to the downregulation of the Cav1.2 channel and the up-regulation of the SOC channel signaling pathway.

Path-Independent Quantum Gates with Noisy Ancilla.

Ancilla systems are often indispensable to universal control of a nearly isolated quantum system. However, ancilla systems are typically more vulnerable to environmental noise, which limits the performance of such ancilla-assisted quantum control. To address this challenge of ancilla-induced decoherence, we propose a general framework that integrates quantum control and quantum error correction, so that we can achieve robust quantum gates resilient to ancilla noise. We introduce the path independence criterion for fault-tolerant quantum gates against ancilla errors. As an example, a path-independent gate is provided for superconducting circuits with a hardware-efficient design.

Proposal for Heralded Generation and Detection of Entangled Microwave-Optical-Photon Pairs.

Quantum state transfer between microwave and optical frequencies is essential for connecting superconducting quantum circuits to optical systems and extending microwave quantum networks over long distances. However, establishing such a quantum interface is extremely challenging because the standard direct quantum transduction requires both high coupling efficiency and small added noise. We propose an entanglement-based scheme-generating microwave-optical entanglement and using it to transfer quantum states via quantum teleportation-which can bypass the stringent requirements in direct quantum transduction and is robust against loss errors. In addition, we propose and analyze a counterintuitive design-suppress the added noise by placing the device at a higher temperature environment-which can improve both the device quality factor and power handling capability. We systematically analyze the generation and verification of entangled microwave-optical-photon pairs. The parameter for entanglement verification favors the regime of cooperativity mismatch and can tolerate certain thermal noises. Our scheme is feasible given the latest advances on electro-optomechanics, and can be generalized to various physical systems.