Mechanisms of electroacupuncture relieves uterine smooth muscle spasm in dysmenorrhea rats based on Rho/ROCK signaling pathway. / 基于Rho/ROCKä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆä»»è„‰ã€ç£è„‰ç»ç©´ç¼“è§£ç±»ç—›ç»æ¨¡åž‹å¤§é¼ å­å®«å¹³æ»‘è‚Œç—‰æŒ›çš„æœºåˆ¶.

OBJECTIVES: To investigate the effect of electroacupuncture (EA) on Rho/Rho-associated coiled-coil-forming kinases (ROCK) signaling pathway of uterus tissue in rats with dysmenorrhea, so as to explore the underlying mechanism of EA treating primary dysmenorrhea (PD) and uterine smooth muscle spasm, and to observe whether there is a difference in the effect of meridian acupoints in Conception Vessel (CV) and Governer Vessel (GV). METHODS: Sixty female SD rats were randomly divided into saline, model, CV, GV, and non-acupoint groups, with 12 rats in each group. The dysmenorrhea model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin (OT). EA (2 Hz) was applied to "Qihai" (CV6) and "Zhongji" (CV3) for CV group, "Mingmen" (GV4) and "Yaoshu" (GV2) for GV group, "non-acupoint 1" and "non-acupoint 3" on the left side for non-acupoint group, and manual acupuncture was applied to "Guanyuan" (CV4) for CV group, "Yaoyangguan" (GV3) for GV group, "non-acupoint 2" on the left side for non-acupoint group. The treatment was conducted for 20 min each time, once daily for 10 days. The writhing score was evaluated. The smooth myoelectric signals of rats' uterus in vivo were recorded by multi-channel physiological recorder. The uterine histopathological changes were observed by HE staining. The contents of prostaglandin F2α (PGF2α), OT and calcium ion (Ca2+) in uterine tissue of rats were detected by ELISA. The protein and mRNA expression levels of smooth muscle 22-α (SM22-α), RhoA and ROCKⅡ in uterine tissue were detected by Western blot and fluorescence quantitative PCR, respectively. RESULTS: Compared with the saline group, the writhing score of rats in the model group was increased (P<0.01), the amplitude voltage of uterine smooth muscle in vivo was elevated (P<0.01), the contents of PGF2α, OT and Ca2+, the protein and mRNA expression of SM22-α, RhoA and ROCK Ⅱ in uterine tissue were all increased (P<0.01). Compared with the model and the non-acupoint groups, the writhing scores of the CV and the GV groups were decreased (P<0.01, P<0.05), the amplitude voltage of uterine smooth muscle was decreased (P<0.01), the contents of PGF2α, OT and Ca2+ in uterine tissue were decreased (P<0.01, P<0.05), and the protein expression and mRNA expression of SM22-α, RhoA and ROCKⅡ in uterine tissue were decreased (P<0.01, P<0.05). HE staining showed extensive exfoliation of uterine intima with severe edema and increased glandular secretion in the model group, which was alleviated in the CV and GV groups. CONCLUSIONS: EA at acupoints of CV and GV can significantly reduce the writhing score, uterine smooth muscle amplitude voltage, pathological injury degree of uterus, and relieve spasm of uterine smooth muscle in dysmenorrhea rats, which may be related to its effect in regulating PGF2α and OT contents, inhibiting the Rho/ROCK signaling pathway, and reducing the SM22-α, RhoA, ROCKⅡ protein and mRNA expression, and Ca2+ content in uterine tissue.

The role of local non-tetragonal polar displacements in the temperature- and pressure-induced phase transitions in PbTiO3-BiMeO3 ferroelectrics.

In situ high-pressure/high-temperature Raman-scattering analyses on PbTiO 3 , 0.92PbTiO 3 - 0.08Bi(Zn 0.5 Ti 0.5 )O 3 and 0.83PbTiO 3 - 0.17Bi(Mg 0.5 Ti 0.5 )O 3 single crystals reveal an intensity transfer between the fine-structure components of the A 1 (TO) soft mode. The enhancement of the lowest-energy subpeak, which stems from intrinsic local non-tetragonal polar distortions, along with the suppression of the tetragonal A 1 (1TO) fundamental mode with increasing pressure and temperature indicates the key role of the local polarization fluctuations in transformation processes and emphasizes the significance of the order-disorder phenomena in both the pressure- and temperature-induced phase transitions of pure PbTiO 3 and its solid solutions with complex perovskites. Moreover, the temperature and pressure evolution of the fraction of the local non-tetragonal polar distortions is highly sensitive to the type of B-site substituent.

TAX1BP1 downregulation by STAT3 in cardiac fibroblasts contributes to diabetes-induced heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is now the most common form of HF and has been reported to be closely related to diabetes. Accumulating evidence suggests that HFpEF patients exhibit cardiac fibrosis. This study investigates whether direct targeted inhibition of the activation of cardiac fibroblasts (CFs), the main effector cells in cardiac fibrosis, improves diabetes-induced HFpEF and elucidates the underlying mechanisms. Twenty-week-old db/db mice exhibited HFpEF, as confirmed by echocardiography and hemodynamic measurements. Proteomics was performed on CFs isolated from the hearts of 20-week-old C57BL/6 and db/db mice. Bioinformatic prediction was used to identify target proteins. Experimental validation was performed in both high glucose (HG)-treated neonatal mouse CFs (NMCFs) and diabetic hearts. TAX1 binding protein 1 (TAX1BP1) was identified as the most significantly differentially expressed protein between 20-week-old C57BL/6 and db/db mice. TAX1BP1 mRNA and protein were markedly downregulated in CFs from diabetic hearts and HG-cultured NMCFs. Overexpression of TAX1BP1 profoundly inhibited HG/diabetes-induced NF-κB nuclear translocation and collagen synthesis in CFs, improved cardiac fibrosis, hypertrophy, inflammation and HFpEF in diabetic mice. Mechanistically, signal transducer and activator of transcription 3 (STAT3), which is phosphorylated and translocated from the cytoplasm into the nucleus under hyperglycemic conditions, bound to TAX1BP1 promoter and blocked TAX1BP1 transcriptional activity, consequently promoting NF-κB nuclear translocation and collagen synthesis in CFs, aggravating cardiac fibrosis, hypertrophy and inflammation, leading to HFpEF in db/db mice. Taken together, our findings demonstrate that targeting regulation of STAT3-TAX1BP1-NF-κB signaling in CFs may be a promising therapeutic approach for diabetes-induced HFpEF.

X-ray-induced piezoresponse during X-ray photon correlation spectroscopy of PbMg1/3Nb2/3O3.

X-ray photon correlation spectroscopy (XPCS) holds strong promise for observing atomic-scale dynamics in materials, both at equilibrium and during non-equilibrium transitions. Here an in situ XPCS study of the relaxor ferroelectric PbMg1/3Nb2/3O3 (PMN) is reported. A weak applied AC electric field generates strong response in the speckle of the diffuse scattering from the polar nanodomains, which is captured using the two-time correlation function. Correlated motions of the Bragg peak are also observed, which indicate dynamic tilting of the illuminated volume. This tilting quantitatively accounts for the observed two-time speckle correlations. The magnitude of the tilting would not be expected solely from the modest applied field, since PMN is an electrostrictive material with no linear strain response to the field. A model is developed based on non-uniform static charging of the illuminated surface spot by the incident micrometre-scale X-ray beam and the electrostrictive material response to the combination of static and dynamic fields. The model qualitatively explains the direction and magnitude of the observed tilting, and predicts that X-ray-induced piezoresponse could be an important factor in correctly interpreting results from XPCS and nanodiffraction studies of other insulating materials under applied AC field or varying X-ray illumination.

Knowledge mapping of acupoint sensitization and acupoint specificity: a bibliometric analysis.

Objective: The relationship between acupoint sensitization and acupoint specificity is a topic of significant interest in acupuncture research. Numerous clinical studies have demonstrated that needling pain sensitive acupoints yields superior therapeutic outcomes compared to traditional acupoints, particularly in the context of pain disorders. However, there is a lack of bibliometric analysis in acupuncture area. Therefore, the objective of this study is to offer a comprehensive overview of the knowledge structure and research hotspots pertaining to acupoint sensitization and acupoint specificity. Methods: The search for publications pertaining to acupoint sensitization and acupoint specificity was conducted in the Web of Science Core Collection (WoSCC) database from its inception until August 11, 2023. Subsequently, bibliometric analyses were carried out using VOSviewer, CiteSpace, R software (Bibliometrix package), and GraphPad Prism software. Results: This study includes 4,940 articles from 72 countries, with China and the United States being the leading countries. The number of publications related to acupoint sensitization and specificity has been increasing annually. Major research institutions involved in this field include the Shanghai University of Traditional Chinese Medicine, Kyung Hee University, Beijing University of Chinese Medicine, Chinese Academy of Chinese Medical Sciences, and China Medical University, among others. "Evidence-based Complementary and Alternative Medicine" is the most popular journal in acupuncture field, and "PAIN" is the most co-cited journal. Publications are contributed by 20,325 authors from all over the world, with Wu Huangan, Fang Jianqiao, Lin Yi-Wen, Liu Huirong, and Chen Rixin having published the most articles. Han Ji-Sheng is the most cited author in this research area. The main directions include the study of temperature specificity of acupoints, the diagnosis of acupoint sensitization diseases, and the study of the mechanism of acupoint sensitization. The most listed keywords in recent years are "TRPV1," "signaling pathway," and "diagnosis." Conclusion: This is the first bibliometric study to comprehensively summarize research trends and advances in acupoint sensitization and acupoint specificity, and the information highlights recent research preliminary and main directions that serve as a reference for acupoint sensitization and acupoint specificity research.

[The skin surface microcirculation of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea].

OBJECTIVE: To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea. METHODS: Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints. RESULTS: Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group (P>0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group (P<0.05, P<0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group (P<0.05). CONCLUSION: In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.

Structure, Antiferroelectricity and Energy-Storage Performance of Lead Hafnate in a Wide Temperature Range.

Lead hafnate (PbHfO3) has attracted a lot of renewed interest due to its potential as antiferroelectric (AFE) material for energy storage. However, its room temperature (RT) energy-storage performance has not been well established and no reports on the energy-storage feature of its high-temperature intermediate phase (IM) are available. In this work, high-quality PbHfO3 ceramics were prepared via the solid-state synthesis route. Based on high-temperature X-ray diffraction data, the IM of PbHfO3 was found to be orthorhombic, Imma space group, with antiparallel alignment of Pb2+ ions along the [001]cubic directions. The polarization-electric field (P-E) relation of PbHfO3 is displayed at RT as well as in the temperature range of the IM. A typical AFE loop revealed an optimal recoverable energy-storage density (Wrec) of 2.7 J/cm3, which is 286% higher than the reported data with an efficiency (η) of 65% at 235 kV/cm at RT. A relatively high Wrec value of 0.7 J/cm3 was found at 190 °C with an η of 89% at 65 kV/cm. These results demonstrate that PbHfO3 is a prototypical AFE from RT up to 200 °C, making it a suitable material for energy-storage applications in a wide temperature range.

Skin Temperature of Acupoints in Health and Primary Dysmenorrhea Patients: A Systematic Review and Meta-Analysis.

Objective: Dysmenorrhea is a common clinical condition and some studies shown that the skin temperature of some acupoints changes in primary dysmenorrhea (PD) patients. This study aimed to evaluate the changes in skin temperature at specific acupoints in PD patients and healthy subjects. Methods: The literature for assessing skin temperature at acupoints in PD patients and healthy subjects was searched in eight databases. The literatures obtained from the search was independently screened by two authors, and the quality of the included articles was evaluated using the consensus checklist of the Thermographic Imaging in Sports and Exercise Medicine (TISEM) and the Newcastle-Ottawa Scale (NOS) scale. The skin temperature of the relevant acupoints or the difference between the left and right acupoints of the same name was used as the outcome during any period of menstruation. Finally, the meta-analysis was performed using RevMan 5.4.1 software to evaluate the changes in skin temperature in the related acupoints. Results: Seven eligible studies were included, which included 328 patients with PD and 279 healthy subjects. The results of the meta-analysis revealed a significant difference in skin temperature around the Sanyinjiao (SP6)(MD: 0.04, 95% CI: 0.00, 0.08), Xuehai (SP 10)(MD: -0.07, 95% CI:-0.11, -0.02) and Taixi (KI 3)(MD: 0.06, 95% CI:0.01, 0.11) acupoints between PD and healthy subjects. PD patients also showed a difference in skin temperature at the Taixi (KI 3)(MD: 0.14, 95% CI:0.04, 0.24), Shuiquan (KI 5)(MD: 0.11, 95% CI: 0.03,0.19), Taichong (LR 3)(MD: -0.10, 95% CI: -0.19,-0.01), Diji (SP 8)(MD: -0.09, 95% CI: -0.16, -0.01), and Xuehai (SP 10)(MD: -0.14, 95% CI: -0.23, -0.06) acupoint areas at different times of menstruation compared to that of healthy subjects, as revealed by the subgroup analysis. Conclusion: Primary dysmenorrhea patients showed some differences in the skin temperature of the special acupoints are as Sanyinjiao (SP6), Diji (SP 8), Xuehai (SP 10), Shuiquan (KI 5), Taichong (LR 3), and Taixi (KI 3) compared with healthy subjects. Registration Number: CRD42022381387.

Auriculotherapy Modulates Macrophage Polarization to Reduce Inflammatory Response in a Rat Model of Acne.

Background: The inflammatory response is an important part of the pathogenesis of acne vulgaris. Auriculotherapy has been shown to have a good therapeutic effect on this disease. The aim of this study was to explore the mechanism underlying the anti-inflammatory effect of auriculotherapy in the treatment of acne vulgaris. Methods: Propionibacterium acnes was injected subcutaneously into the ears of rats to establish an animal model of acne. The auriculotherapy intervention in rats consisted of auricular bloodletting therapy (ABT), auricular point sticking (APS), or a combination of both (ABPS). The anti-inflammatory effects of auriculotherapy were evaluated by measuring changes in ear thickness, local body surface microcirculation in the ear, and serum inflammatory factors in rats. The polarization of macrophages was analyzed by flow cytometry, and the expression of TLR2/NF-κB signaling pathway in the target tissues was analyzed using western blot. Results: ABT, APS, and ABPS all reduced the erythema of ear acne, decreased microcirculation in localized ear acne, and decreased serum levels of TNF-α and IL-1ß in rats. Meanwhile, the three interventions reduced M1-type macrophages and increased M2-type macrophages; only APS could reduce the expression of TLR2/NF-κB signaling pathway. Conclusion: ABT, APS, and ABPS can improve the inflammatory symptoms of acne and reduce inflammatory cytokines. APS may exert anti-inflammatory effects by altering macrophage polarization and decreasing TLR2/NF-κB expression.

Tuning of Polar Domain Boundaries in Nonpolar Perovskite.

Domain boundaries in ferroic materials are found to have various physical properties not observed in the surrounding domains. Such differences can be enhanced and bring promising functionalities when centrosymmetric nonpolar materials encounter polar domain boundaries. In this work, a tunable polar domain boundary is discovered in an antiferroelectric single crystal. Under a small stress or electric field, the density, volume, and polarity of the boundaries are successfully controlled.

Highly heterogeneous epitaxy of flexoelectric BaTiO3-δ membrane on Ge.

The integration of complex oxides with a wide spectrum of functionalities on Si, Ge and flexible substrates is highly demanded for functional devices in information technology. We demonstrate the remote epitaxy of BaTiO3 (BTO) on Ge using a graphene intermediate layer, which forms a prototype of highly heterogeneous epitaxial systems. The Ge surface orientation dictates the outcome of remote epitaxy. Single crystalline epitaxial BTO3-δ films were grown on graphene/Ge (011), whereas graphene/Ge (001) led to textured films. The graphene plays an important role in surface passivation. The remote epitaxial deposition of BTO3-δ follows the Volmer-Weber growth mode, with the strain being partially relaxed at the very beginning of the growth. Such BTO3-δ films can be easily exfoliated and transferred to arbitrary substrates like Si and flexible polyimide. The transferred BTO3-δ films possess enhanced flexoelectric properties with a gauge factor of as high as 1127. These results not only expand the understanding of heteroepitaxy, but also open a pathway for the applications of devices based on complex oxides.

Strain-Induced Magnetoelectric Coupling in Fe3O4/BaTiO3 Nanopillar Composites.

Magnetoelectric coupling properties are limited to the substrate clamping effect in traditional ferroelectric/ferromagnetic heterostructures. Here, Fe3O4/BaTiO3 nanopillar composites are successfully constructed. The well-ordered BaTiO3 nanopillar arrays are prepared through template-assisted pulsed laser deposition. The Fe3O4 layer is coated on BaTiO3 nanopillar arrays by atomic layer deposition. The nanopillar arrays and heterostructure are confirmed by scanning electron microscopy and transmission electron microscopy. A large thermally driven magnetoelectric coupling coefficient of 395 Oe °C-1 near the phase transition of BaTiO3 (orthorhombic to rhombohedral) is obtained, indicating a strong strain-induced magnetoelectric coupling effect. The enhanced magnetoelectric coupling effect originated from the reduced substrate clamping effect and increased the interface area in nanopillar structures. This work opens a door toward cutting-edge potential applications in spintronic devices.

Self-Assembled Epitaxial Ferroelectric Oxide Nanospring with Super-Scalability.

Oxide nanosprings have attracted many research interests because of their anticorrosion, high-temperature tolerance, oxidation resistance, and enhanced-mechanic-response from unique helix structures, enabling various applications like nanomanipulators, nanomotors, nanoswitches, sensors, and energy harvesters. However, preparing oxide nanosprings is a challenge for their intrinsic lack of elasticity. Here, an approach for preparing self-assembled, epitaxial, ferroelectric nanosprings with built-in strain due to the lattice mismatch in freestanding La0.7 Sr0.3 MnO3 /BaTiO3 (LSMO/BTO) bilayer heterostructures is developed. It is found that these LSMO/BTO nanosprings can be extensively pulled or pushed up to their geometrical limits back and forth without breaking, exhibiting super-scalability with full recovery capability. The phase-field simulations reveal that the excellent scalability originates from the continuous ferroelastic domain structures, resulting from twisting under co-existing axial and shear strains. In addition, the oxide heterostructural springs exhibit strong resilience due to the limited plastic deformation nature and the built-in strain between the bilayers. This discovery provides an alternative way for preparing and operating functional oxide nanosprings that can be applied to various technologies.

Effects of Composition Segregation in PMN-PT Crystals on Ultrasound Transducer Performance.

This study investigates the relationship between the composition segregation in lead magnesium niobate-lead titanate (PMN-PT; PMN-29%PT, PMN-29.5%PT, PMN-30%PT, PMN-30.5%PT, and PMN-31%PT) single crystals within morphotropic phase boundary (MPB) and the corresponding ultrasonic transducer performance through PiezoCAD modeling and real transducer testing. For five crystals with compositions distributed across the main body of a crystal ingot, the piezoelectric coefficient and free relative permittivity values were measured to vary by over 30%, whereas the transducer bandwidth and center frequency values were modeled to change by less than 10%. For the single-element ultrasonic transducers fabricated using those crystals without matching layers, the variations of -6-dB bandwidth, insertion loss, receiver-free field voltage response, and center frequency were measured to be 9.61%, -15.23%, 9.76%, and 1.41%, respectively, confirming the modeling results. Using the Mason and Krimholtz, Leedom, and Matthaei (KLM) models, it is found that the relatively stable transducer performance can be attributed to the relatively consistent electromechanical coupling coefficient, acoustic impedance, and clamped relative permittivity originated from the stable elastic compliance properties among the crystals of various compositions. It is expected that the relatively stable performance could be extended to multielement transducers with matching layers for the same contributing mechanisms. Our results suggest that it is possible to use crystal plates of different compositions within the MPB region, obtained from one and the same ingot, to fabricate a batch of ultrasonic transducers that will exhibit a similar performance, significantly reducing the cost of materials.

Acupuncture and related therapies for the anxiety and depression in irritable bowel syndrome with diarrhea (IBS-D): A network meta-analysis of randomized controlled trials.

Objective: A growing number of clinical studies have suggested the value of acupuncture-related therapies for patients with irritable bowel syndrome with diarrhea (IBS-D), and the patient's mental state plays an important role, but there are many types of acupuncture-related therapies involved. This study aimed to evaluate the mental status, efficacy and safety of the different acupuncture-related therapies for IBS-D patients. Methods: We searched seven databases to collect randomized controlled trials of acupuncture-related therapies for IBS-D. After independent literature screening and data extraction, the quality of the final included literature was evaluated. Hamilton anxiety rating scale (HAMA), hamilton depression rating scale (HAMD), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) was used as the primary outcome indicator. And the network meta-analysis (NMA) was performed by using Revman 5.4, Stata 15.0 and WinBUGS 1.4.3 software, and the surface under the cumulative ranking curve was conducted to rank the included interventions. Results: We analyzed 24 eligible studies with 1,885 patients, involving eight types of acupuncture and related therapies along with comprehensive therapies. The NMA result shows that: for SAS scores, combined therapies were more efficacious than anti-diarrheal or antispasmodic (western medicine, WM) (SMD: -8.92; 95% CI: -15.30, -2.47); for SDS scores, combined therapies were more efficacious than WM (SMD: -8.45; 95% CI: -15.50, -1.41). For HAMA scores, moxibustion (MOX) was more efficacious than placebo (SMD: -8.66; 95% CI: -16.64, -0.38). For HAMD scores, MOX was more efficacious than all other included interventions. For response rate, MOX was more efficacious than the following interventions: acupuncture (ACU) (SMD:0.29; 95% CI:0.08,0.93), Chinese herb medicine (CH) (SMD:0.09; 95% CI:0.02,0.36), combined therapies (SMD:0.23; 95% CI:0.06, 0.85), electroacupuncture (EA) (SMD:0.06; 95% CI:0.01,0.33), warm acupuncture (WA) (SMD:22.16; 95% CI:3.53,148.10), WM (SMD:15.59; 95% CI:4.68,61.21), and placebo (SMD:9.80; 95% CI:2.90,45.51). Combined therapies were more efficacious than the following interventions: CH (SMD:0.39; 95% CI:0.19,0.80), WA (SMD:4.96; 95% CI:1.30,21.62), and WM (SMD:3.62; 95% CI:2.35,5.66). The comprehensive ranking results show that MOX, ACU, combined therapies, and EA had high SUCRA rankings involving different outcome indicators. Conclusion: MOX, ACU, combined therapies, and EA better alleviate anxiety and depression among IBS-D patients, and with a higher safety level, may be the optimal therapies. In addition, combining acupuncture-related treatments and other therapies also delivers a higher global benefit level. Systematic review registration: [https://www.crd.york.ac.uk/], identifier [CRD42022364560].

Single-Cell RNA Sequencing of the Rat Carotid Arteries Uncovers Potential Cellular Targets of Neointimal Hyperplasia.

Aims: In-stent restenosis (ISR) remains an Achilles heel of drug-eluting stents despite technical advances in devices and procedural techniques. Neointimal hyperplasia (NIH) is the most important pathophysiological process of ISR. The present study mapped normal arteries and stenotic arteries to uncover potential cellular targets of neointimal hyperplasia. Methods and Results: By comparing the left (control) and right (balloon injury) carotid arteries of rats, we mapped 11 clusters in normal arteries and 11 mutual clusters in both the control and experimental groups. Different clusters were categorized into 6 cell types, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), macrophages, unknown cells and others. An abnormal cell type expressing both VSMC and fibroblast markers at the same time was termed a transitional cell via pseudotime analysis. Due to the high proportion of VSMCs, we divided them into 6 clusters and analyzed their relationship with VSMC phenotype switching. Moreover, N-myristoyltransferase 1 (NMT1) was verified as a credible VSMC synthetic phenotype marker. Finally, we proposed several novel target genes by disease susceptibility gene analysis, such as Cyp7a1 and Cdk4, which should be validated in future studies. Conclusion: Maps of the heterogeneous cellular landscape in the carotid artery were defined by single-cell RNA sequencing and revealed several cell types with their internal relations in the ISR model. This study highlights the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia and provides clues regarding the underlying mechanism of NIH.

Ferroelectric phase-transition frustration near a tricritical composition point.

Phase transition describes a mutational behavior of matter states at a critical transition temperature or external field. Despite the phase-transition orders are well sorted by classic thermodynamic theory, ambiguous situations interposed between the first- and second-order transitions were exposed one after another. Here, we report discovery of phase-transition frustration near a tricritical composition point in ferroelectric Pb(Zr1-xTix)O3. Our multi-scale transmission electron microscopy characterization reveals a number of geometrically frustrated microstructure features such as self-assembled hierarchical domain structure, degeneracy of mesoscale domain tetragonality and decoupled polarization-strain relationship. Associated with deviation from the classic mean-field theory, dielectric critical exponent anomalies and temperature dependent birefringence data unveil that the frustrated transition order stems from intricate competition of short-range polar orders and their decoupling to long-range lattice deformation. With supports from effective Hamiltonian Monte Carlo simulations, our findings point out a potentially universal mechanism to comprehend the abnormal critical phenomena occurring in phase-transition materials.

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract.

Arthritis is a common condition that causes pain and inflammation in a joint. Previously, we reported that the mixture extract (ME) from Agrimonia pilosa Ledeb. (AP) and Salvia miltiorrhiza Bunge (SM) could ameliorate gout arthritis. In the present study, we aimed to investigate the potential anti-inflammatory and antinociceptive effects of ME and characterize the mechanism. We compared the anti-inflammatory and antinociceptive effects of a positive control, Perna canaliculus powder (PC). The results showed that one-off and one-week treatment of ME reduced the pain threshold in a dose-dependent manner (from 10 to 100 mg/kg) in the mono-iodoacetate (MIA)-induced osteoarthritis (OA) model. ME also reduced the plasma TNF-α, IL-6, and CRP levels. In LPS-stimulated RAW 264.7 cells, ME inhibited the release of NO, PGE2, LTB4, and IL-6, increased the phosphorylation of PPAR-γ protein, and downregulated TNF-α and MAPKs proteins expression in a concentration-dependent (from 1 to 100 µg/mL) manner. Furthermore, ME ameliorated the progression of ear edema in mice. In most of the experiments, ME-induced effects were almost equal to, or were higher than, PC-induced effects. Conclusions: The data presented here suggest that ME shows anti-inflammatory and antinociceptive activities, indicating ME may be a potential therapeutic for arthritis treatment.

Hybrid System Combining Two-Dimensional Materials and Ferroelectrics and Its Application in Photodetection.

Photodetectors are one of the most important components for a future "Internet-of-Things" information society. Compared to the mainstream semiconductor-based photodetectors, emerging devices based on two-dimensional (2D) materials and ferroelectrics as well as their hybrid systems have been extensively studied in recent decades due to their outstanding performances and related interesting physical, electrical, and optoelectronic phenomena. In this paper, we review the photodetection based on 2D materials and ferroelectric hybrid systems. The fundamentals of 2D and ferroelectric materials as well as the interaction in the hybrid system will be introduced. Ferroelectricity modulated optoelectronic properties in the hybrid system will be discussed in detail. After the basics and figures of merit of photodetectors are summarized, the 2D-ferroelectrics devices with different structures including p-n diodes, Schottky diodes, and field-effect transistors will be reviewed and compared. The polarization of ferroelectrics offers the possibility of the modulation and enhancement of the photodetection in the hybrid detectors, which will be discussed in depth. Finally, the challenges and perspectives of the photodetectors based on 2D ferroelectrics will be proposed. This Review outlines the important aspects of the recent development of the hybrid system of 2D and ferroelectric materials, which could interact with each other and thus lead to photodetectors with higher performances. Such a Review will be helpful for the research of emerging physical phenomena and for the design of multifunctional nanoscale electronic and optoelectronic devices.

Plasma Small Extracellular Vesicle-Carried miRNA-501-5p Promotes Vascular Smooth Muscle Cell Phenotypic Modulation-Mediated In-Stent Restenosis.

Vascular smooth muscle cell (VSMC) phenotypic modulation plays an important role in the occurrence and development of in-stent restenosis (ISR), the underlying mechanism of which remains a key issue needing to be urgently addressed. This study is designed to investigate the role of plasma small extracellular vesicles (sEV) in VSMC phenotypic modulation. sEV were isolated from the plasma of patients with ISR (ISR-sEV) or not (Ctl-sEV) 1 year after coronary stent implantation using differential ultracentrifugation. Plasma sEV in ISR patients are elevated markedly and decrease the expression of VSMC contractile markers α-SMA and calponin and increase VSMC proliferation. miRNA sequencing and qRT-PCR validation identified that miRNA-501-5p was the highest expressed miRNA in the plasma ISR-sEV compared with Ctl-sEV. Then, we found that sEV-carried miRNA-501-5p level was significantly higher in ISR patients, and the level of plasma sEV-carried miRNA-501-5p linearly correlated with the degree of restenosis (R 2 = 0.62). Moreover, miRNA-501-5p inhibition significantly increased the expression of VSMC contractile markers α-SMA and calponin and suppressed VSMC proliferation and migration; in vivo inhibition of miRNA-501-5p could also blunt carotid artery balloon injury induced VSMC phenotypic modulation in rats. Mechanically, miRNA-501-5p promoted plasma sEV-induced VSMC proliferation by targeting Smad3. Notably, endothelial cells might be the major origins of miRNA-501-5p. Collectively, these findings showed that plasma sEV-carried miRNA-501-5p promotes VSMC phenotypic modulation-mediated ISR through targeting Smad3.