Understanding the Relationship Between Vascular Smooth Muscle Cell Function and the Efficacy of Acupuncture in Treating Cerebral Ischemic Stroke: A Preclinical Meta-Analysis and Systematic Review.

Background: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models. Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD). Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=-3.75 [95% CI, -5.54 to -1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies. Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.

UCNPs-labeled electrospun scaffolds used to monitor in vivo degradation and bone tissue regeneration.

Biodegradable electrospun bone repair materials are effective means to treat bone defects. However, because the electrospun substrates are mostly organic polymer materials, there is a lack of real-time and intuitive monitoring methods for their degradation in vivo. Therefore, it is of great significance to develop in vivo traced electrospun bone repair materials for postoperative observation of their degradation. In this research, polycaprolactone/up-conversion nanoparticles/magnesium oxide (PCL/UCNPs/MgO) composite scaffolds were prepared by electrospun based on the luminescence characteristics of up-conversion nanoparticles (UCNPs) under near infrared excitation and the osteogenic ability of MgO. The in vivo and in vitro degradation results showed that with the increase of time, the electrospun scaffolds gradually degraded and its luminescence intensity decreased. The addition of UCNPs can effectively monitor the degradation of the scaffolds. In addition, the prepared electrospun scaffolds had great biocompatibility, among which PCL-1%UCNPs-1%MgO (P1U1M) electrospun scaffolds had obvious effect on promoting osteogenic differentiation of mouse embryonic osteoblasts cells (MC3T3-E1) in vitro. In conclusion, P1U1M electrospun scaffolds have the potential to induce bone regeneration at bone defect sites, and can monitor the degradation of electrospun scaffolds. It may be a potential candidate material for bone regeneration in defect area.

Understanding the mechanism of acupuncture in acute cerebral infraction through a proteomic analysis: protocol for a prospective randomized controlled trial.

Background: Acute cerebral infarction (ACI), being the predominant form of stroke, presents challenges in terms of the limited effectiveness of various treatments in improving the neurological function. Although acupuncture shows promise in addressing ACI, the availability of high-quality evidence regarding its efficacy, safety, and underlying mechanism remains insufficient. In this study, we design a multicenter, prospective, single-blind, randomized controlled trial with the aim of evaluating the efficacy and safety of acupuncture for ACI, making an attempt to unveil the molecular mechanisms by proteomic. Methods: A total of 132 patients involving four hospitals will be randomized at a 1:1:1 ratio in the acupuncture group, control group, and sham acupuncture group. All the patients will receive basic treatment, and the patients in the acupuncture and sham acupuncture groups will also receive either acupuncture or sham acupuncture treatment, respectively, at six sessions each week for a 2 weeks period, followed by 3 months of follow-up. The primary outcome will be the change in the National Institute of Health Stroke Scale (NIHSS) scores after treatment. The secondary outcomes will include the Fugl-Meyer Assessment (FMA) scale scores and the Barthel Index (BI). Adverse events that occur during the trial will be documented. To discover differentially expressed proteins (DEPs) and their roles between the ACI subjects and healthy controls, we will also perform 4D-DIA quantitative proteomics analysis, and the DEPs will be confirmed by enzyme-linked immunosorbent assay (ELISA). This study was approved by the institutional review board of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TYLL2023043). Written informed consent from patients is required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2300079204). Trial results will be published in a peer-reviewed academic journal. Discussion: The results of this study will determine the preliminary efficacy and safety of acupuncture in ACI patients and whether the mechanism of this form of non-pharmacologic stimulation is mediated by a novel therapeutic target for neurorehabilitation through our proteomic analysis. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2300079204.

Research status of indole-modified natural products.

Indole is a heterocyclic compound formed by the fusion of a benzene ring and pyrrole ring, which has rich biological activity. Many indole-containing compounds have been sold on the market due to their excellent pharmacological activity. For example, vincristine and reserpine have been widely used in clinical practice. The diverse structures and biological activities of natural products provide abundant resources for the development of new drugs. Therefore, this review classifies natural products by structure, and summarizes the research progress of indole-containing natural product derivatives, their biological activities, structure-activity relationship and research mechanism which has been studied in the past 13 years, so as to provide a basis for the development of new drug development.

Color-tunable luminescence based on the efficient energy transfer of a Tm-Dy system for optical thermometry and white LED lighting.

The development of phosphors with color-tunable luminescence including white emission is at the forefront of lighting and display technologies. Herein, Dy3+,Tm3+ single-doped or co-doped K3Y(PO4)2 phosphors are synthesized through the solid-state reaction method. By properly adjusting the ratio of Dy3+,Tm3+ co-doping concentrations, color-tunable luminescence from blue to yellow, including white luminescence, is realized under 359 nm excitation. The mechanism of energy transfer between Tm3+ and Dy3+ is further investigated via measuring the luminescence decay curve. Based on efficient energy transfer from Tm3+ to Dy3+, the emission of Dy3+ exhibits an abnormal thermal enhancement phenomenon as the temperature increases. The optical thermometry behaviors of various emission combinations for the Dy3+,Tm3+ co-doped system are analyzed. The maximum sensitivity can be obtained as a constant of 4.8 × 10-3 K-1, which is conducive to improve the measurement accuracy of optical temperature sensing at high temperatures. Furthermore, we also demonstrate the applicability of K3Y(PO4)2:Tm3+,Dy3+ phosphors in white LEDs, providing proof-of-concept for the lighting and display fields.

Differences of oribatid mite community and trophic structure between karst caves and surface different moss habitats.

In order to reveal the community characteristics and trophic structure of oribatid mites in different moss habitats in karst caves, the oribatid mites in the moss habitats of ground (GD), understory (US), cave wall (CW), surface shrub (SB) and farmland (FL) outside the cave were collected in October 2021. Through the identification and data analysis of oribatid mites, 2352 oribatid mites were found, belonging to 45 families and 72 genera, most of which were Gymnonota. The family number, genus number, individual number, individual density, dominant genus composition, community diversity, community similarity, MGP (Analysis methods for ecological groups of oribatid mites) ecological group of oribatid mites and trophic structure of oribatid mites in different moss were analyzed. The results showed that: (1) The number of families, genera, individuals, and individual density of SB and FL are higher than those of the other three habitats; (2) Platyliodes, Oppiella, Tectocepheus, Scutovertex, Scheloribates and Trichogalumna are the dominant genera of the oribatid mites in the cave moss habitat, among them, Tectocepheus and Trichogaluna have the most obvious advantages; (3) The diversity index of shrub (SB) was higher than that of other four habitats; Similarity between ground and cave wall, shrub and farmland is high; (4) The MGP ecological group of oribatid mites in different habitats is dominated by O type (Overall type belongs to MGP analysis results, 20%≤M,G,P≤50%), and a total of 42 genera of oribatid mites preliminarily constitute the trophic structure of oribatid mites in the cave moss habitat. Based on the above results, it can be concluded that there are differences in the community structure of oribatid mites in different moss habitats in the study area, and the use of dominant genera of mites can preliminarily indicate the environmental conditions of different moss habitats. This study enriches the study of mites in karst cave mosses, and can provide theoretical significance for the protection of cave biodiversity in karst areas.

Winning color-tunable upconversion luminescence and high-sensitive optical thermometry in K3Gd(PO4)2:Yb3+,Er3+,Tm3.

A series of Yb3+, Er3+, Tm3+ co-doped K3Gd(PO4)2 are prepared via the solid-state reaction method. Upon 980 nm excitation, the synthesized samples present color-tunable upconversion luminescence ranging from yellow to blue with the increment of Tm3+ doping contents. The upconversion mechanisms of Yb3+, Er3+, Tm3+ co-doped system are systematically investigated in detail. Varying contents of Tm3+ can appropriately alter the upconversion emissions of blue, green and red via possible energy transfer processes. Furthermore, the thermometric performances of phosphors associated with upconversion luminescence are analyzed in the temperature region of 300-675 K. By employing non-thermally coupled energy levels (2H11/2/4F9/2 of Er3+), the maximum relative and absolute sensitivity reaches 0.78 % K-1 and 0.168 K-1. Combining the sensitivity characteristic and repeatability of thermometer, the luminescence intensity ratio technology based on non-thermally coupled energy levels may be a more effective choice for optical thermometry. These excellent results will pave an avenue to K3Gd(PO4)2:Yb3+,Er3+,Tm3+ phosphors for the fields of color-tunable luminescence and non-contact temperature sensing.

Towards highly efficient NIR II response up-conversion phosphor enabled by long lifetimes of Er3.

The second near-infrared (NIR II) response photon up-conversion (UC) materials show great application prospects in the fields of biology and optical communication. However, it is still an enormous challenge to obtain efficient NIR II response materials. Herein, we develop a series of Er3+ doped ternary sulfides phosphors with highly efficient UC emissions under 1532 nm irradiation. ß-NaYS2:Er3+ achieves a visible UC efficiency as high as 2.6%, along with high brightness, spectral stability of lights illumination and temperature. Such efficient UC is dominated by excited state absorption, accompanied by the advantage of long lifetimes (4I9/2, 9.24 ms; 4I13/2, 30.27 ms) of excited state levels of Er3+, instead of the well-recognized energy transfer UC between sensitizer and activator. NaYS2:Er3+ phosphors are further developed for high-performance underwater communication and narrowband NIR photodetectors. Our findings suggest a novel approach for developing NIR II response UC materials, and simulate new applications, eg., simultaneous NIR and visible optical communication.

Synthesis of core-shell nanoparticles based on interfacial energy transfer for red emission and highly sensitive temperature sensing.

Red up-conversion luminescence with both emission and excitation peaks within the "tissue transparency window" makes for ideal fluorescent labels for deep tissue penetration and low-background biological imaging. In this work, an efficient strategy is proposed to realize bright red up-conversion luminescence based on interfacial energy transfer (IET), and the luminescence centers (Er3+ and Tm3+) and sensitizers (Yb3+) are doped in separate layers to avoid deleterious cross-relaxation. The IET process between Yb3+ and Er3+ can enable bright red photon up-conversion under 980 nm excitation via fine control and manipulation of the lanthanide ion concentration and shell thickness. By appropriately employing the fluorescence intensity ratio technique, an optical thermometer based on non-thermally coupled energy levels demonstrates a superior relative sensitivity of 2.02% K-1 across the whole temperature region. NaYF4:Er3+,Tm3+@NaYF4:Yb3+ with strong red UC luminescence and highly sensitive performance exhibits potential for application in the field of non-contact temperature sensing.

High-sensitive temperature sensing based on thermal-enhanced emission and non-thermally coupled energy levels of white upconversion luminescence system.

Na3Y(VO4)2:Nd3+,Yb3+,Ho3+,Tm3+ phosphors present significantly improved sensitivity of optical temperature sensing based on thermal-enhanced upconversion luminescence and non-thermally coupled energy levels. Under 808 nm excitation, white upconversion luminescence is successfully achieved in Nd3+-sensitized system. In addition, the emissions intensities originated from 4G5/2→4I9/2 transition of Nd3+ and 3F2,3→3H6 transition of Tm3+ gradually increase with elevating temperature owning to the thermal population effects, as opposed to the blue (1G4→3H6 transition of Tm3+), green (5S2,5F4→5I8 transition of Ho3+) and red (5F5→5I8 transition of Ho3+) emissions intensities show continuous decreasing trend. The temperature sensing behaviors are investigated by employing multiple non-thermally coupled energy levels. Based on non-thermally coupled energy levels of 4G5/2 (Nd3+)/1G4 (Tm3+), the absolute and relative sensitivities are obtained to be 0.433 K-1 and 2.81 % K-1. These results demonstrate that the Na3Y(VO4)2:Nd3+,Yb3+,Ho3+,Tm3+ phosphors with superior optical thermometry performance and white luminescence within a relatively wide temperature range can achieve optical applications in many fields.

Near-infrared-emitting upconverting BiVO4 nanoprobes for in vivo fluorescent imaging.

Near-infrared (NIR) emitting BiVO4:Yb3+,Tm3+ nanoparticles are synthesized by a new solvothermal strategy using solvents of oleic acid and methanol. The obtained BiVO4:Yb3+,Tm3+ samples show an average particle size of ≈164 nm and exhibit an asymmetry monoclinic crystal structure of BiVO4. At NIR excitation of 980 nm, the BiVO4:Yb3+,Tm3+ sample exhibits a nearly single NIR emission at ≈796 nm with extremely weak blue emissions from Tm3+ ions. These high-energy visible emissions are absorbed by the semiconducting host of BiVO4 that possesses a bandgap of ≈2.2 eV. Therefore, the NIR excitation to a single intense NIR emission fluorescent BiVO4 materials could be a potential ideal probe for deep-tissue high-resolution bioimaging. To validate the ability of BiVO4 materials for bio-applications, we conduct the cytotoxicity experiments. The results show that the cytotoxicity of HeLa cells is negligible at a concentration of 0.2 mg/ml of BiVO4:Yb3+,Tm3+ , and the cell viability approaches 90% at a high dosage of 0.5 mg/ml. The Daphnia magna and Zebrafish treated with nanoparticles (0.5 mg/ml) display bright NIR emission without any background, indicating the excellent in vivo fluorescent imaging capacity of BiVO4:Yb3+,Tm3+ nanoparticles. Our findings offer an environment-friendly strategy to synthesize BiVO4 UCL nanophosphors and provide a promising new class of fluorescent probes for biological applications.

Exploiting D2 receptor ß-arrestin2-biased signalling to suppress tumour growth of pituitary adenomas.

BACKGROUND AND PURPOSE: Dopamine agonists targeting D2 receptor have been used for decades in treating pituitary adenomas. There has been little clear evidence implicating the canonical G protein signalling as the mechanism by which D2 receptor suppresses the growth of pituitary tumours. We hypothesize that ß-arrestin2-dependent signalling is the molecular mechanism dictating D2 receptor inhibitory effects on pituitary tumour growth. EXPERIMENTAL APPROACH: The involvement of G protein and ß-arrestin2 in bromocriptine-mediated growth suppression in rat MMQ and GH3 tumour cells was assessed. The anti-growth effect of a ß-arrestin2-biased agonist, UNC9994, was tested in cultured cells, tumour-bearing nude mice and primary cultured human pituitary adenomas. The effect of G protein signalling on tumour growth was also analysed by using a G protein-biased agonist, MLS1547, and a Gßγ inhibitor, gallein, in vitro. KEY RESULTS: ß-arrestin2 signalling but not G protein pathways mediated the suppressive effect of bromocriptine on pituitary tumour growth. UNC9994 inhibited pituitary tumour cell growth in vitro and in vivo. The suppressive function of UNC9994 was obtained by inducing intracellular reactive oxygen species generation through downregulating mitochondrial complex I subunit NDUFA1. The effects of Gαi/o signalling and Gßγ signalling via D2 receptor on pituitary tumour growth were cell-type-dependent. CONCLUSION AND IMPLICATIONS: Given the very low expression of Gαi/o proteins in pituitary tumours and the complexity of the responses of pituitary tumours to G protein signalling pathways, our study reveals D2 receptor ß-arrestin2-biased ligand may be a more promising choice to treat pituitary tumours with improved therapeutic selectivity.

Potential α-glucosidase inhibitor from Hylotelephium erythrostictum.

In light of the adequate sources for Hylotelephium erythrostictum, its active components have aroused research interest. 2-(3',4'-dihydroxyphenyl)-2,3-dihydro-4,6-dihydroxy-2-(methoxy)- 3-benzofuranone(1), apigenin(2), diosmetin(3), kaempferol(4), kaempferide(5), rhamnocitrin(6), quercetin(7), and gallic acid(8) were isolated from H. erythrostictum. Rarely occurring naturally, 1 is 2-methoxybenzofuranone type compound against α-glucosidase and exhibits a potential inhibitory effect on α-glucosidase(IC50 = 1.8 µM), with a Ki value of 709 nM. In silico molecular docking was performed for the investigation of the inhibition mechanism. H. erythrostictum is a potential source of antidiabetic agent. This information is useful in finding more potent antidiabetic candidates from medicinal plants for the clinical development of therapeutics.

Three primary color emissions from single multilayered nanocrystals.

The achievement of three-primary-color luminescence in a single material will lead to revolutionary developments of many advanced applications such as dynamic display with ultra-high resolution, and complex anti-counterfeiting. Here we report the realization of steady-state three-primary-color emission in single multilayered NaYF4 upconversion (UC) nanoparticles. In this core-shell structure, a novel design of a tri-sensitizer, i.e., Nd3+, Yb3+ and Er3+ ions, is utilized, which effectively absorbs the excitation photons of 808, 980 and 1550 nm, and then exhibits blue, red and green emissions, respectively. By simply combining the three primary color emissions, tunable full-color luminescence was achieved in this single material. These nanoparticles have demonstrated promising potential applications in dynamic display and multiple anti-counterfeiting.

Luminescence property tuning of Yb3+-Er3+ doped oxysulfide using multiple-band co-excitation.

Lanthanide ions have abundant excited-state channels which result in a radiation relaxation process generally accompanied by a non-radiation relaxation process. However, non-radiation relaxation processes will consume the activation energy and reduce the luminescence efficiency of the phosphor. Two lasers with an excitation energy which matched the ground state absorption and excited state absorption of ions were used to excite the phosphors to avoid the non-radiation relaxation process. This approach can achieve the purpose of populating specific states of the lanthanide ions, and furthermore effectively tunes the luminescence intensity and color output of the sample. Results show that the red emission intensity of the sample is significantly improved and this is caused by populating the 4F9/2 level under simultaneous 1510 nm and 980 nm excitation. Then when the 1510 nm and 808 nm co-operate to excite the sample, the green emission obtained increased sharply because the 2H11/2/4S3/2 states were efficiently populated. As a proof-of-concept experiment, this new approach has potential in the applications of solar cells.

Correction: Luminescence property tuning of Yb3+-Er3+ doped oxysulfide using multiple-band co-excitation.

[This corrects the article DOI: 10.1039/C8RA02503G.].

Investigation on the thermal effects of NaYF4:Er under 1550 nm irradiation.

The thermal effects of NaYF4:Er microcrystals under 1550 nm laser diode irradiation were investigated using an infrared thermal imaging method. The results revealed that the temperature of the LD irradiation beam area was non-uniform. The NaYF4:Er sample exhibits a rapid temperature increase within 5-10 s, and the heating process reaches its steady state after 60 s of irradiation when exposed to 1550 nm LD. The response time, temperature increase, and emission intensity of the samples depend on the excitation power density and concentration of doped Er3+ ions. Low excitation power density is required to avoid the influence of thermal effects on the up-conversion emission spectra measurement. Rapid scanning in up-conversion emission spectra measurement is not effective in preventing the heating effect under high excitation power pumping. In addition, a relative deviation of temperature, existing in fluorescence intensity ratio technique, decreased with the increasing irradiation time.

Synthesis and Positive Inotropic Activity of [1,2,4]Triazolo[4,3-a] Quinoxaline Derivatives Bearing Substituted Benzylpiperazine and Benzoylpiperazine Moieties.

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07%) at 3 × 10-5 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.

A retrospective comparison of dexmedetomidine versus midazolam for pediatric patients with congenital heart disease requiring postoperative sedation.

We hypothesized that postoperative sedation with dexmedetomidine/fentanyl would be effective in infants and neonates with congenital heart disease and pulmonary arterial hypertension (PAH). Children who were <36 months of age, had congenital heart disease with PAH, and had been treated at our hospital between October 2011 and April 2013 (n = 187) were included in this retrospective study. Either dexmedetomidine/fentanyl (Group Dex) or midazolam/fentanyl (Group Mid) was used for postoperative sedation. The main outcome variables included delirium scores, supplemental sedative/analgesic drugs, ventilator use, and sedation time. Baseline demographics and clinical characteristics were similar between the two groups. The Pediatric Anesthesia Emergence Delirium scale (5.2 ± 5.3 vs. 7.1 ± 5.2 in the Dex and Mid groups, respectively; P = 0.016) and the incidence of delirium (18.2 vs. 32.0 % in the Dex and Mid groups, respectively; P = 0.039) were significantly lower in the Dex group than in the Mid group. Total sufentanil, midazolam, and propofol doses given during the operation did not differ between the two groups. Group Dex patients required significantly lower doses of adjunctive sedative/analgesic drugs than group Mid patients in the cardiac intensive care unit (CICU; midazolam, P = 0.007; morphine, P < 0.001). In conclusion, we found no differences between dexmedetomidine/fentanyl and midazolam/fentanyl in terms of the duration of sedation, mechanical ventilator use, and CICU stay in children with PAH. However, patients in the Dex group required a lower additional sedative/analgesic drugs and had a lower incidence of delirium than patients in the Mid group.