In Vivo NIR-II Fluorescence Lifetime Imaging of Whole-Body Vascular Using High Quantum Yield Lanthanide-Doped Nanoparticles.

Second near infrared (NIR-II, 1000-1700 nm) fluorescence lifetime imaging is a powerful tool for biosensing, anti-counterfeiting, and multiplex imaging. However, the low photoluminescence quantum yield (PLQY) of fluorescence probes in NIR-II region limits its data collecting efficiency and accuracy, especially in multiplex molecular imaging in vivo. To solve this problem, lanthanide-doped nanoparticles (NPs) ß-NaErF4 : 2%Ce@NaYbF4 @NaYF4 with high PLQY and tunable PL lifetime through multi-ion doping and core-shell structural design, are presented. The obtained internal PLQY can reach up to 50.1% in cyclohexane and 9.2% in water under excitation at 980 nm. Inspired by the above results, a fast NIR-II fluorescence lifetime imaging of whole-body vascular in mice is successfully performed by using the homebuilt fluorescence lifetime imaging system, which reveals a murine abdominal capillary network with low background. A further demonstration of fluorescence lifetime multiplex imaging is carried out in molecular imaging of atherosclerosis cells and different organs in vivo through NPs conjugating with specific peptides and different injection modalities, respectively. These results demonstrate that the high PLQY NPs combined with the homebuilt fluorescence lifetime imaging system can realize a fast and high signal-to-noise fluorescence lifetime imaging; thus, opening a road for multiplex molecular imaging of atherosclerosis.

Raw Pinelliae Rhizoma: examination of sedative and hypnotic effects in mice and chemical analysis.

PURPOSE: Raw "Pinelliae Rhizoma" (RPR) is widely used in Chinese clinics to treat insomnia. This study investigated its underlying sedative and hypnotic mechanisms and main active components. METHODS: A locomotor activity test was used to evaluate the sedative effects of RPR at three dosages (0.2 g/mL, 0.4 g/mL, and 0.8 g/mL) in mice. Polysomnography was used to assess its ability to improve sleep. Ultra-performance liquid chromatography/time of flight/mass spectrometry (UPLC-TOF-MS) analysis was used to identify the potential active components of RPR. RESULTS: Mice in the RPR groups were less active than mice in the vehicle group; this difference was greatest in the 0.8 g/mL RPR group. Compared with the vehicle, 0.8 g/mL RPR increased the duration of rapid eye movement (REM) sleep in the dark phase. In addition, the duration of wakefulness in the 0.8 g/mL RPR group decreased with increasing durations of nonrapid eye movement (NREM) and REM sleep. Compared with diazepam, 0.8 g/mL RPR increased REM sleep duration in both the light and dark phases and increased the number of transitions both from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 33 RPR constituents, including 15 alkaloids, were identified. CONCLUSION: The results preliminarily indicated that RPR exerts sedative and hypnotic effects in mice, mainly leading to improvements in REM sleep. These effects are possibly due to the alkaloid constituents of RPR.

Effect of Bone Marrow Stromal Cells Derived miR-26b on Chondrocytes of Osteoporosis Rats.

OBJECTIVE: Osteoporosis is a common bone disease. miR-26b regulates OA-induced osteogenesis and induces osteoporosis. miR-26b is elevated in bone marrow stromal cells (BMSCs) during bone formation; however, we haven't fully revealed whether it is directly involved in this process, which was the aim of this study. METHODS: An oophorectomized rat model of osteoporosis was used. BMSCs were detected by electron microscopy of exosomes, and mir-26b levels were detected by RT-PCR. The correlation between mir-26b and sirt2 was detected by bioinformatics and luciferase activity analysis. Bone microstructure and cartilage moisture content were also measured. The proliferation ability of mir-26b and sirt2 on chondrocytes was detected by cell viability test and flow cytometry. RESULTS: Western blotting further proved that the surface markers of isolated granular exosomes were positive for CD63 and CD81. Further analysis showed that exosomes' diameters ranged from 50 to 150 nm. Mir-26b is elevated in BMSC, and its mimics can promote proliferation. Luciferase showed that mir-26b targets sirt2 and the effect of elevated mir-26b on chondrocytes was completely reversed by silencing sirt2. The proliferation ability of C28/I2 chondrocytes in Mir MICs group was lower than other two groups, while that in Mir inhibition group had stronger proliferation ability than in the Mir NC group. mir-26b was highly expressed in BMSC, indicating that mir-26b comes from secretion of BMSC. CONCLUSION: Mir-26 is highly expressed in OP. mir-26b can therefore target sirt2 to promote proliferation and inhibit apoptosis of OP chondrocytes. It may offer a possibility of a treatment of OP in the future.

An overview of multi-omics technologies in rheumatoid arthritis: applications in biomarker and pathway discovery.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with a complex pathological mechanism involving autoimmune response, local inflammation and bone destruction. Metabolic pathways play an important role in immune-related diseases and their immune responses. The pathogenesis of rheumatoid arthritis may be related to its metabolic dysregulation. Moreover, histological techniques, including genomics, transcriptomics, proteomics and metabolomics, provide powerful tools for comprehensive analysis of molecular changes in biological systems. The present study explores the molecular and metabolic mechanisms of RA, emphasizing the central role of metabolic dysregulation in the RA disease process and highlighting the complexity of metabolic pathways, particularly metabolic remodeling in synovial tissues and its association with cytokine-mediated inflammation. This paper reveals the potential of histological techniques in identifying metabolically relevant therapeutic targets in RA; specifically, we summarize the genetic basis of RA and the dysregulated metabolic pathways, and explore their functional significance in the context of immune cell activation and differentiation. This study demonstrates the critical role of histological techniques in decoding the complex metabolic network of RA and discusses the integration of histological data with other types of biological data.

Sodium Assists Controlled Synthesis of Cubic Rare-Earth Oxyfluorides Nanocrystals for Information Encryption and Near-Infrared-IIb Bioimaging.

Rare-earth oxyfluoride (REOF) colloidal nanocrystals (NCs) suffer from a low photoluminescence efficiency due to their small size with poor crystallinity and a detrimental surface quenching effect. Herein, we introduce an innovative approach that involves doping sodium ions into REOF NCs to produce monodisperse, size-controllable, well-crystallized, and highly luminescent colloidal REOF core/shell NCs. The Na+ doping allows for successfully synthesizing the cubic REOF NCs with a tunable size from 6 to 30 nm. Further fabrication of the core/shell NCs doped with Na+ results in enhancements up to 1062 (Ho3+), 1140 (Er3+), and 2212 (Tm3+) folds in upconversion luminescence and 17.7 folds (Er3+) in downconversion luminescence compared to that of core/shell NCs without doping Na+ ions. These NCs were subsequently developed into multicolor luminescent inks, demonstrating significant potential application for information security, and used for near-infrared-IIb (NIR-IIb) (1500-1700 nm) in vivo imaging, which exhibits a high-resolution in vivo dynamic imaging capability with a signal-to-noise ratio of 5.28. These results present the way to the controlled synthesis of efficient luminescent cubic LuOF: RE3+/LuOF core/shell NCs, expanding the toolkit of rare-earth doped NCs in diverse applications such as advanced encoding encryption, varied fluorescence imaging, and biomedicine.

[Back arm flexion and extension combined with manipulation for the treatment of patient with adhesive scapulohumeral periarthritis].

OBJECTIVE: To observe clinical efficacy of back arm flexion and extension combined with manipulation in treating adhesive scapulohumeral periarthritis. METHODS: From March 2016 to April 2018, 53 patients with adhesive scapulohumeral periarthritis were treated with back arm flexion and extension combined with manipulation, the main symptoms were shoulder pain and limited activity. There were 22 males and 31 females aged from 45 to 71 years old with an average of (51.63±5.79) years;the courses of disease ranged from 3 to 24 months with an average of (8.62±3.73) months. Manipulation treatment was carried out once a week, and back arm flexion and extension were performed for 3 times a day with15 movements each time, totally 4 weeks for a single course. Visual analogue scale (VAS) and Constant-Murley shoulder function score were observed and compared before treatment and one week, one and three months after treatment. RESULTS: All patients were followed up from 3 to 12 months, with an average of (5.91±3.55) months. VAS score before treatment was 4.02±1.46, and was improved to 3.15±1.54, 1.98±1.37, 1.12±0.86 respectively at one week, one and three months after treatment. Constant-Murley score before treatment was 42.70 ±5.72, and improved to 54.25 ±6.34, 67.45 ±6.84, 82.40 ±6.63 at one week, one and three months after treatment respectively;19 patients got excellent result, 22 good, 9 fair and 3 poor. CONCLUSION: Back arm flexion combined with manipulation for the treatment of adhesive scapulohumeral periarthritis could effectively relieve pain, improve shoulder function, which is a simple effective treatment strategy.

[Acupuncture combined with Jingtong granule for nerve-root type cervical spondylosis and its effects on IL-6、TNF-α、IL-1ß and hemorheological indexes].

OBJECTIVE: To explore the clinical efficacy of acupuncture combined with Jingtong granule for nerve-root type cervical spondylosis and its effects on serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and hemorheological indexes. METHODS: A total of 114 patients with nerve-root type cervical spondylosis were randomly divided into an observation group and a control group, 57 cases in each group. The patients in both groups were treated with traction. The patients in the control group were treated with oral administration of Jingtong granule, 4 g each time, 3 times a day, while based on the treatment of control group, the patients in the observation group were treated with acupuncture at Dazhui (GV 14), Tianzhu (BL 10), Houxi (SI 3), cervical Jiaji (EX-B 2), Quchi (LI 11), Hegu (LI 4) and Waiguan (TE 5), once a day. Both groups were treated for 4 weeks. The simplified McGill pain questionnaire (MPQ), neck disability index (NDI), numbness score, levels of IL-6, TNF-α, IL-1ß in serum and hemorheological indexes were observed before and after treatment, and the clinical efficacy was compared between the two groups. RESULTS: The total effective rate was 91.2% (52/57) in the observation group, which was higher than 71.9% (41/57) in the control group (P<0.05). Compared before treatment, the scores of MPQ, NDI and numbness in the two groups were reduced after treatment (P<0.05). After treatment, the scores of MPQ, NDI and numbness in the observation group were lower than those in the control group (P<0.05). After treatment, the serum levels of IL-6, TNF-α and IL-1ß in the two groups were reduced (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, the plasma viscosity, fibrinogen, low shear rate of whole blood viscosity and high shear rate of whole blood viscosity in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). CONCLUSION: Acupuncture combined with Jingtong granule have significant clinical efficacy for nerve-root type cervical spondylosis, which could reduce the serum levels of IL-6, TNF-α and IL-1ß and improve hemorheology.

Abnormal intrinsic functional hubs in alcohol dependence: evidence from a voxelwise degree centrality analysis.

OBJECTIVE: To explore the abnormal intrinsic functional hubs in alcohol dependence using voxelwise degree centrality analysis approach, and their relationships with clinical features. MATERIALS AND METHODS: Twenty-four male alcohol dependence subjects free of medicine (mean age, 50.21±9.62 years) and 24 age- and education-matched male healthy controls (mean age, 50.29±8.92 years) were recruited. The alcohol use disorders identification test and the severity of alcohol dependence questionnaire (SADQ) were administered to assess the severity of alcohol craving. Voxelwise degree centrality approach was used to assess the abnormal intrinsic functional hubs features in alcohol dependence. Simple linear regression analysis was performed to investigate the relationships between the clinical features and abnormal intrinsic functional hubs. RESULTS: Compared with healthy controls, alcohol dependence subjects exhibited significantly different degree centrality values in widespread left lateralization brain areas, including higher degree centrality values in the left precentral gyrus (BA 6), right hippocampus (BA 35, 36), and left orbitofrontal cortex (BA 11) and lower degree centrality values in the left cerebellum posterior lobe, bilateral secondary visual network (BA 18), and left precuneus (BA 7, 19). SADQ revealed a negative linear correlation with the degree centrality value in the left precentral gyrus (R2=0.296, P=0.006). CONCLUSION: The specific abnormal intrinsic functional hubs appear to be disrupted by alcohol intoxication, which implicates at least three principal neural systems: including cerebellar, executive control, and visual cortex, which may further affect the normal motor behavior such as an explicit type of impaired driving behavior. These findings expand our understanding of the functional characteristics of alcohol dependence and may provide a new insight into the understanding of the dysfunction and pathophysiology of alcohol dependence.

Study on the association between estrogen receptor gene (ESR) and reproduction traits in Landrace pigs.

To study the potential use of estrogen receptor gene (ESR) as a genetic marker to improve the reproductive traits of pigs, the genotypes of the ESR PCR product digested by Pvu II were determined in 2,239 litters from 612 Landrace sows. The data of the first, second, and later parities were separately evaluated. Although the frequency of the B allele was much lower than that of the A allele, likelihood ratio test showed that the gene frequencies were in Hardy-Weinberg equilibrium. The effects of ESR of different parities were not equal. In summary, the sows with the BB genotype showed better performance for total number of piglets born (TNB) and number of piglets born alive (NBA), but had a lower average piglet weight at birth (AWB). It was concluded that ESR could be used as a marker for the selection of litter size in the Landrace population.

Influence of embryo handling and transfer method on pig cloning efficiency.

The somatic cell nuclear transfer (SCNT) technique could be used to produce genetically superior or genetically engineered cloned pigs that have wide application in agriculture and bioscience research. However, the efficiency of porcine SCNT currently is very low. Embryo transfer (ET) is a key step for the success of SCNT. In this study, the effects of several ET-related factors, including cloned embryo culture time, recipient's ovulation status, co-transferred helper embryos and ET position, on the success rate of pig cloning were investigated. The results indicated that transfer of cloned embryos cultured for a longer time (22-24h vs. 4-6h) into pre-ovulatory sows decreased recipient's pregnancy rate and farrowing rate, and use of pre-ovulatory and post-ovulatory sows as recipients for SCNT embryos cultured for 22-24h resulted in a similar porcine SCNT efficiency. Use of insemination-produced in vivo fertilized, parthenogenetically activated and in vitro fertilized embryos as helper embryos to establish and/or maintain pregnancy of SCNT embryos recipients could not improve the success rate of porcine SCNT. Transfer of cloned embryos into double oviducts of surrogates significantly increased pregnancy rate as well as farrowing rate of recipients, and the developmental rate of transferred cloned embryos, as compared to unilateral oviduct transfer. This study provided useful information for optimization of the embryo handling and transfer protocol, which will help to improve the ability to generate cloned pigs.

[Using VCE4.0 package to estimate genetic parameters on growth traits in Landrace].

It is an accurate and quick methods to apply VCE4.0 to estimating genetic parameter. It makes full use of all information, analyzing selection and culling effects. The Genetic parameters for the age to 30kg(AGE30), age to 100kg (AGE100), and average daily gain from 30kg to 100kg (ADG) and backfat thickness at 100kg(probed,FAT) are estimated using VCE4.0 applied to REML with a multivariate individual animal model in Landrace pigs. Estimates of heritabilities for AGE30, AGE100,ADG and FAT are 0.207,0.396,0.304 and 0.493, respectively. Genetic correlations for FAT/ADG, FAT/AGE100, ADG/AGE100, ADG /AGE30 and AGE30/AGE100 are -0.343,0.180,-0.941,-0.48,and 0.745, respectively, its phenotypic correlations are -0.139,0.138,-0.82,-0.026, and 0.565, respectively. The common litter environment effects for AGE30,AGE100, ADG and FAT are 0.194,0.156,0.157 and 0.043, respectively.