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Pancreatic cancer remains the common cancer with the worst prognosis because of its late diagnosis and extensive metastasis. This study aimed to investigate the effects of GABRP on pancreatic cancer metastasis and the molecular mechanism. The expression of GABRP was measured using the quantitative real-time PCR and western blot. The biological behaviors of cancer cells were assessed using the cell counting kit-8, Transwell assay, and western blot. The regulation of GABRP on the MEK/ERK pathway was detected by western blot. The results indicated that GABRP was overexpressed in pancreatic cancer tissues and cells. Knockdown of GABRP suppressed cell viability, invasion, migration, and epithelial–mesenchymal transition (EMT), whereas GABRP overexpression facilitated these biological behaviors. Inactivation of the MEK/ERK pathway reversed the effects on cellular processes induced by GABRP. Moreover, silencing of GABRP inhibited tumor growth. In conclusion, GABRP promoted the progression of pancreatic cancer by facilitating cell metastasis and tumor growth via activating the MEK/ERK pathway. The findings suggest that GABRP has the potential to be a therapeutic target for the metastatic pancreatic cancer. [ABSTRACT FROM AUTHOR]

The application of clustered regularly interspaced short palindromic repeats-Cas (CRISPR-Cas9) technology in the genetic modification of Yarrowia lipolytica is challenged by low efficiency and low throughput. Here, a highly efficient CRISPR-iCas9 (with D147Y and P411T mutants) genetic manipulation tool was established for Y. lipolytica, which was further utilized to integrate carotene synthetic key genes and significantly improve the target product yield. First, CRISPR-iCas9 could shorten the time of genetic modification and enable the rapid knockout of nonsense suppressors. iCas9 can lead to more than 98% knockout efficiency for NHEJ-mediated repair after optimal target disruption of a single gene, 100% knockout efficiency for a single gene-guided version, and more than 80% knockout efficiency for multiple genes simultaneously in Y. lipolytica. Subsequently, this technology allowed for rapid one-step integration of large fragments (up to 9902-bp) of genes into chromosomes. Finally, YL-ABTG and YL-ABTG2Z were further constructed through CRISPR-iCas9 integration of key genes in a one-step process, resulting in a maximum β-carotene and zeaxanthin content of 3.12 mg/g and 2.33 mg/g dry cell weight, respectively. Therefore, CRISPR-iCas9 technology provides a feasible approach to genetic modification for efficient biosynthesis of biological compounds in Y. lipolytica. Key points: • iCas9 with D147Y and P411T mutants improved the CRISPR efficiency in Y. lipolytica. • CRISPR-iCas9 achieved efficient gene knockout and integration in Y. lipolytica. • CRISPR-iCas9 rapidly modified Y. lipolytica for carotenoid bioproduction. [ABSTRACT FROM AUTHOR]

In order to analyze the motion characteristics of the spring pendulum under the action of magnetic field force, the motion of the spring pendulum will be studied by applying a uniform magnetic field in the vertical direction. Firstly, a first-order approximate solution is given by studying the micro-vibration around its equilibrium point. And an approximate solution similar to the Foucault pendulum is also presented in the case of a soft spring with strong ductility. Then, according to the resonance conditions of mechanical vibration, the internal resonance phenomenon of magnetic spring pendulum is discovered, and then the conclusion that the energy of the system is cyclically transmitted between the three modes of breathing, oscillating and deflection is presented subsequently. Finally, the influence of magnetic field strength on the motion stability of the spring pendulum is explored, and not only the bifurcation phenomenon at its equilibrium point is found, but also the complex dynamic behavior including chaotic motion occurs. [ABSTRACT FROM AUTHOR]

Key message: Chinese fir sprouting population lifespan is shortened and survivorship situation and biomass are also changed by bamboo expansion via declines in mother tree density and weakened physiological accommodation. Natural regeneration is a vital means of maintaining forest populations. Although bamboo expansion negatively affects population structures of neighboring communities, its influence on sprouting natural regeneration is still poorly understood. We compared the population structure and biomass allocation of Chinese fir regenerating sprouts in previous (CLS), middle (CPM) and late (PCM) periods of bamboo expansion. Life tables and survivorship curves were used to assess sprouting population structure and survival dynamics, and allometric analysis was conducted on biomass allocation. The results showed that bamboo expansion reduced the number and longevity (maximum age class shorted from X to VI) of the Chinese fir sprouting population and weakened its survival capacity. Survivorship curves indicated that the CLS population conformed more to a recession type (Deevey III) while CPM and PCM tended to be stable types (Deevey II). Highly mortality and survival risk in the early growing stage drove a population decrease. Meanwhile, sprouting component biomasses were decreased first and then increased by expansion effect, leaf and stem biomass had constant relationships with total biomass, and branch biomass had allometric relationships with total biomass. We considered that bamboo expansion changed sprouting population survival and growth mainly through affected Chinese fir mother tree density and growth. [ABSTRACT FROM AUTHOR]

Background and objective: Cervical spondylosis (CS) is often accompanied by persistent cervical pain, and psychological complications including depression and anxiety, which aggravate pain. Past studies have revealed brain alterations in chronic pain patients. However, the cortical mechanism for NSAID (non-steroidal anti-inflammatory drug) responders relative to non-responders is still lacking. Therefore, we aimed to investigate the brain functional differences between responders to NSAID relative to non-responders using amplitude of low-frequency fluctuation (ALFF) and dynamic functional connectivity variance (DFCV). To our knowledge, our study is the first to investigate the DFCV in CS patients. Materials and methods: We first explored the differences in psychological inventories in CS patients who respond to NSAID vs non-responders. The voxel-wise ALFF was calculated and compared between CS patients and healthy controls. The ALFF within the resultant clusters were extracted and compared between responders and non-responders. DFCV among the resulting clusters was compared in responders vs non-responders. Results: We found that (1) compared to responders, non-responders exhibited higher levels of anxiety and depression; (2) relative to healthy controls, CS patients exhibited altered ALFF within the middle cingulate cortice (MCC), cerebellum, and middle frontal gyrus (MFG); (3) moreover, compared with responders, non-responders exhibited lower ALFF within MCC; furthermore, non-responders also exhibited increased DFCV between MCC and cerebellum, and between MCC and MFG. Conclusion: Our data indicate that psychological comorbidities (e.g., anxiety) influence response to NSAID in CS patients. Relative to NSAID responders, non-responders had altered MCC function, which may be associated with anxiety in CS patients. [ABSTRACT FROM AUTHOR]

Purpose: To perform environmental sampling and molecular identification of Paragonimus in endemic regions, which may help in minimizing transmission among humans. Methods: Mountain crabs from the genus Potamiscus were collected and the encysted metacercariae were extracted and subjected to morphological identification, followed by animal inoculation in Sprague–Dawley (SD) rats. After 112 days of infection, animals were killed and adult worms were extracted from lungs and muscles. The morphology of adult worms was characterized by microscopy and molecular identification was done by polymerase chain reaction, followed by sequencing of cox1 and ITS2 genes. Phylogenetic analysis was done by maximum parsimony method. Results: A total of 447 crabs were captured from the streams of Tongchang Town, Jinping County, Yunnan Province, China. The infection rate was found to be 41% (186 out of 447 crabs). The metacercariae of Paragonimus skrjabini was identified by the characteristics round or spherical encysted form measuring 410 to 460 × 400 to 460 µm. After animal infection in SD rats, adults were presumptively confirmed to be P. skrjabini, which was also confirmed by gene amplification and sequence analysis of cox1 and ITS2 regions. Paragonimus skrjabini clustered with previously reported P. skrjabini from Yunnan and Vietnam. The confidence values of their branches were > 95%. Phylogenetic analysis of the ITS2 region revealed two distinct clusters with distinct geographical grouping. Phylogenetic analysis with the combined data sets reiterated the geographical grouping with P. skrjabini from Yunnan clustering with strains from Vietnam. Conclusion: Metacercariae of P. skrjabini was discovered in freshwater crabs in Yunnan province, China, and the strains were phylogenetically related to P. skrjabini from Vietnam. [ABSTRACT FROM AUTHOR]

Vanillin is one of the most commonly used natural-occurring flavors in the world. This study successfully constructed an efficient whole-cell catalytic system for vanillin biosynthesis from ferulic acid by regulating feruloyl-CoA synthetase (FCS) and enoyl-CoA hydratase (ECH). First, we constructed an efficient cell-free catalytic system with FCS-Str (fcs from Streptomyces sp. V-1) and ECH-Str (ech from Streptomyces sp. V-1) combination at 1:1. The efficient cell-free catalytic system provided necessary strategies for optimizing the whole-cell catalytic system. Then, we constructed the recombinant Escherichia coli by heterologously expressing the fcs-Str and ech-Str combination. Moreover, E. coli JM109 was a better recombinant Escherichia coli than E. coli BL21 with higher vanillin production. Finally, we first adjusted the ratio of FCS and ECH in E. coli JM109 to 1:1 using two copies of fcs-Str. For higher vanillin production, we further optimized the induction conditions of E. coli JM109 to increase the amount of FCS and ECH. The optimized E. coli JM109-FE-F constructed in this study has the highest vanillin synthesis rate of converting 20 mM ferulic acid to 15 mM vanillin in 6 h among all of the E. coli catalytic systems. Our study made a significant contribution to the construction of the vanillin biosynthesis system and provided a valuable strategy for increasing vanillin production. Key points: • The efficient cell-free vanillin biosynthesis system was constructed by FCS-Str and ECH-Str combination at 1:1. • Escherichia coliJM109 was determined as a better recombinant Escherichia coli than E. coli BL21 with higher vanillin production. • Escherichia coliJM109-FE-F with two copies of fcs-Str and one copy of ech-Str has the highest catalytic efficiency for vanillin production. [ABSTRACT FROM AUTHOR]

The community species abundance and diversity declined with bamboo invasion had been widely reported worldwide. However, the physiological strategies used during root competition between native species and invasive bamboo are poorly understood. To clarify the mechanisms underlying such strategies, the stoichiometric dynamics and homeostasis of nitrogen, phosphorus, organic carbon in root orders of Phyllostachys edulis (I du [=I-Pe, years 1 and 2]; II du [=II-Pe, years 3 and 4]), Cunninghamia lanceolata in transition and pure forests were analyzed. With increasing intensity of bamboo invasion, N, P, and C content of C. lanceolata root orders declined, N and P content in P. edulis rhizome orders declined, while C increased, the stoichiometric ratios in mixed forest interface mainly increased, and the stoichiometric differences within native and invasive species root orders narrowed. Meanwhile, the stoichiometric homeostasis index (H) of elements in the same root order and even the same elements in different root orders were not consistent. H of most root orders (except some HP) was greater than 4, the H ranked order was I-Pe > Cl > II-Pe in mixed interfaces, and the N:P ratio of most species root orders was greater than 16, despite being affected by invasion. Our research concluded that the bamboo invasion narrows stoichiometric differences within root orders, and the juvenile bamboo rhizome has a stronger capacity for homeostatic regulation than in adult bamboo and C. lanceolata, which is a key determinant of bamboo invasion success. [ABSTRACT FROM AUTHOR]

Objective: β-Carotene has been widely used in the food and feed industry and has significant commercial value. This study aimed to increase the β-carotene production in engineered Yarrowia lipolytica by optimizing the host metabolic network. The DID2 gene, a subunit of the endosomal sorting complex required for transport (ESCRT), was integrated into a β-carotene producing strain. Results: The β-carotene production was increased by 260%, and the biomass increased by 10% for engineered Y. lipolytica. Meanwhile, DID2 elevated the mRNA level and protein level of the genes in the β-carotene synthesis pathway, then increased precursors (FPP, Lycopene) utilization. DID2 also increased the mRNA level of the genes in the glucose pathway, pentose phosphate pathway, and tricarboxylic acid cycle and promoted glucose utilization and cofactors consumption. Conclusion: The ESCRT protein complex subunit, DID2, improved β-carotene production in engineered Y. lipolytica and beneficial to glucose utilization and cofactors consumption. This study provided new finding of the DID2 gene's function and it mostly could be used for many other natural product productions. [ABSTRACT FROM AUTHOR]

Sterols attract increasing attention due to their important bioactivities. The oleaginous yeast Yarrowia lipolytica has large lipid droplets, which provide storage for the accumulated steroid compounds. In this study, we have successfully constructed a campesterol biosynthetic pathway by modifying the synthetic pathway of ergosterol in Y. lipolytica with different capacity of lipid synthesis. The results showed that the maximal campesterol production was produced in the engineered strain YL-D+M−E−, as the optimal lipid content. Furthermore, we found that campesterol mainly exists in the lipid droplets. The campesterol production was further accumulated through the overexpression of two copies of dhcr7. Finally, the maximal campesterol production of 837 mg/L was obtained using a 5-L bioreactor in the engineered YL-D+D+M−E−, exhibiting a 3.7-fold increase compared with the initial strain YL-D+E−. Our results demonstrate that the proper promotion of lipid content plays an important role in campesterol biosynthesis in Y. lipolytica, and what we found provides an effective strategy for the production of hydrophobic compounds. Key Points • Campesterol was biosynthesized by deleting erg5 and introducing heterologous dhcr7. • Campesterol production elevated via promotion of lipid content. • Campesterol was mainly found in lipid droplets. • Promotion of lipid content is an effective strategy to produce hydrophobic compounds. [ABSTRACT FROM AUTHOR]

To explain the anomalous anisotropy in thermal expansion properties reported in rhodochrosite (MnCO3) previously Rao and Murthy (J Mater Sci 5: 82, 1970), Li et al. (High Temp High Press, 2019), the evaluation of crystal structure is thought to be indispensable as an important aspect in mineralogy. In this spirit, single crystals of impurity-free rhodochrosite, up to 100 μm in size, were synthesized under high-pressure–temperature (P–T) conditions. The standard crystal structure, without the impurities common to natural samples, was investigated by means of single-crystal X-ray diffraction (XRD). The unit cell parameters obtained for the R 3 ¯ c symmetry were a = 4.7754(5) Å and c = 15.6484(18) Å, with a final R value of 0.0162. The (MnO6) octahedron exhibits an anomalous bond angle that tends more toward 90° of a regular octahedron, which is totally different from those of MgCO3, FeCO3, and CaCO3. Using the single-crystal XRD from 100 to 370 K, the thermal expansion coefficients were quantified as αa = 5.08 × 10−6 K−1 and αc = 18.06 × 10–6 K−1, as well as αVunit cell = 28.49 × 10–6 K−1. The geometry of (MnO6) octahedron as function of temperature was also determined as αMn–O = 12.14 × 10−6 K−1 and αO–Mn–O ≈ 0.05°/100 K. The anisotropy of MnCO3 (αa/αc = 3.55), similar to that of MgCO3 (~ 3.0, Markgraf and Reeder, Am Mineral, 70: 590–600, 1985), indicates that the difference in bond angle has no significant effect on the thermal expansion properties. According to the standard crystal structures of end members (MgCO3, FeCO3, MnCO3, and CaCO3), the cation substitution in calcite-type structures is proven to agree with the rigid body model and the linear solid solution relationship is highly consistent with those of natural carbonates. [ABSTRACT FROM AUTHOR]

Single crystals of norsethite-type carbonate BaMn(CO3)2 up to 200 μm in size were synthesized in a closed cavity under high pressure–temperature (P–T) conditions. Electron microprobe analyses revealed the composition of 49.00–49.09 wt% BaO and 22.66–22.74 wt% MnO, which correspond well to the ideal formula of Ba1.0Mn1.0(CO3)2. Accurate crystalline structural data were determined from single crystal X-ray diffraction (XRD). The R 3 ¯ c space-group with a doubled c-axis and R 3 ¯ m space-group were used to refine the crystal structure of BaMn(CO3)2. It is proved that R 3 ¯ m is the most probable space-group for the BaMn(CO3)2 crystal structure because no superstructure reflections were observed in the X-ray images. The unit cell parameters were identified to be a = 5.0827(2) Å and c = 17.2797(10) Å in the rhombohedral symmetry of the R 3 ¯ m space-group with a final R-value of 0.0184. High-pressure Raman spectroscopy was performed up to 10 GPa at room temperature, and Raman band shifts ( d ν i d P ) were quantified. Each Raman vibration underwent resolvable splitting and the corresponding d ν i d P showed a pronounced jump as the pressure reached 3.8 GPa arising from a pressure-induced transition. [ABSTRACT FROM AUTHOR]

The parasitic mite Varroa destructor is a major threat to the European honey bee Apis mellifera. Beekeepers apply the miticide thymol directly within the hives to kill this parasitic mite. Thymol is repellent to bees and causes them to ventilate the hive, yet its impact on bee hygienic behaviours that prevent the spread of diseases has never been studied. We measured the efficiency of colonies at removing dead adult bees, uncapping dead pupal cells and removing dead brood in two miticide-free Australian environments where the mite is absent. Thymol increased the uncapping and removal of dead brood by 24 to 36% after 48 h at both locations but had no effect on the removal of dead adult bees. The increased removal of brood could enhance the effect of thymol on V. destructor, especially if bees preferentially remove cells infected with the mite. [ABSTRACT FROM AUTHOR]

The lipopeptide and its homologues are a kind of the five major biosurfactants with prominent interfacial and biological activities. A suite of mutagenesis method was adopted to expose a wild lipopeptide-producing strain Bacillus subtilis HSO121 to improve lipopeptide yield, and a stable mutant named R2-104 with a 2.0-fold production of lipopeptide was obtained. Compared to that of the wild strain HSO121, the lipopeptide produced by R2-104 showed a similar surface activity, but the course profiles of lipopeptide production during cultivation were different, with the peak yield of 500 mg at about 9 h by R2-104, and 400 mg at about 5 h by HSO121. The constituent abundance of the lipopeptide homologues produced by R2-104 was also different from that by HSO121. Combined methods of ESI-MS, GC-MS and MS-MS were applied for structural characterization of lipopeptide homologues, and it showed that the lipopeptides produced by R2-104 and HSO121 were attributed to a surfactin family with different constituents. The dominant constituent of the surfactin family produced by R2-104 was anteiso C-surfactin with a relative content of 43.8 %, while the dominant one produced by HSO121was iso C-surfactin with a relative content of 33.1 %. [ABSTRACT FROM AUTHOR]

This paper investigates a locally coupled neural oscillator autonomous system qualitatively. By applying an approximation method, we give a set of parameter values with which an asymptotically stable limit cycle exists, and the sufficient conditions on the coupling parameters that guarantee asymptotically global synchronization are established under the same external input. A gradational classifier is introduced to detect synchronization, and the network model based on the analytical results is applied to image segmentation. The performance is comparable to the results from other segmentation methods. [ABSTRACT FROM AUTHOR]

Tectono-geochemical samples were systematically collected from 5 drillcores along the No. 304 exploration line and at the −310 m level under the pit in the mining area, totalling 705 samples from the metamorphic rocks, granites, altered rocks and orebodies, and were determined for their contents of 20 kinds of elements including Au, Ag, As, Sb, Hg, Cu,-Pb, Zn, Sn, Bi, Mo, Co, Ni, Mn, Cr, V, Ti, Ba, Rb, Sr, etc. By using the Surfer software the geochemical exploration line profile maps for the 20 kinds of elements and the curves for the element geochemical contents of individual ore vein groups were established. In conbination with the geochemical map analytical method and Gregorian's zoning index calculation method, the vertical, longitudinal and lateral zonation sequences of the elements were ascertained and the geochemical three-dimentional zonation model of the primary halos was established on the basis of the analysis of metallogenic structures and alteration zonation. Coupled with the results of analysis of the geology and geochemistry data, it may be concluded that the process of alteration of granites in the mining area is also accompanied with the process of gold enrichment and mineralization. With the intensification of alteration of granites from granite →potash feldspathization granite →sericite-quartz alteration granite, sericite-quartz rocks →beresitized granite, pyrite sericite-quartz rock, silicified granite →gold ore, the contents of thiophile ore-forming elements such as Au, Ag, As, Cu, Bi, Mo, Pb, Sb, Hg, and Sn tended to increase. Factor analysis of trace elements indicated: factor F2 (Au, Ag, Cu, Sn, As) represents the element association brought in at the main stage of hydrothermal metallogenesis; factor F4 (Bi, Sb) and factor F5 (Pb, Zn) represent the ore-forming element association supperposed during the late stage of Au-bearing sulfides. By using the Gregorian's zoning index and map analysis method we have ascertained the primary halo axial zonation sequence (form frontal halo →tail halo): Pb, Zn, Mn, Ba, Sr, Rb, As, Sb, Ag, Cu, Sn, Mo, Au, Bi, Hg, Ti, Cr, V, Ni, and Co. The geochemical anomalies in the mining area display a tendency of lateral plunging to WS, which is consistent with the lateral plunging of orebodies and mineralization alteration zone. Comprehensive analysis of the results of investigations on ore-controlling structures, mineralization-alteration zonation and geochemical zonation of the primary halos indicates that the gold orebodies in this area are still of greater extension. [ABSTRACT FROM AUTHOR]

Baihua meta-igneous complex consists mainly of pyroxenite-gabbro(diorite)-diorite-quartz diorite. They form a complete comagmatic evolutionary series. The geochemical characteristics of basic-intermediate basic igneous rocks indicate that they belong to a tholeiite suite. The REE distribution pattern is nearly flat type and LREE is slightly enriched type, and their primitive mantle-normalized and MORB-normalized trace element spider diagrams are generally similar; the LIL elements (LILE) Cs, Ba, Sr, Th and U are enriched, but Rb, K and the HFSEs Nb, P, Zr, Sm, Ti and Y are relatively depleted. All these show comagmatic evolution and origin characteristics. The tectonics environment discrimination of trace element reveals that these igneous complexes formed in an island-arc setting. The LA-ICP-MS single-zircons U-Pb age of Baihua basic igneous complex is 434.6±1.5 Ma (MSWD = 1.3), which proves that the formation time of the island-arc type magmatite in the northern zone of West Qinling is Late Ordovician or Early Silurian, also reveals that the timing of subduction of paleo-ocean basin represented by the Guanzizhen ophiolite and resulting island-arc-type magmatic activities is probably Middle-Late Ordovician to Early Silurian. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the role of the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase Akt signaling pathway in mediating interactions between angiotensin II (Ang II) and insulin-like growth factor-1 (IGF-1) in regulation of inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells (VSMCs). Exposure to 100 n MIGF-1 for 10 min resulted in increased insulin-receptor substrate-1 associated PI3K activity and Akt kinase activity, whereas 100 n M Ang II pretreatment for 5 min strikingly decreased these IGF-1 effects. NOS activity was also increased in VSMCs following exposure to IGF-1 (10 min up to 24 h). Pretreatment with Ang II for 5 min reduced IGF-1-induced NOS activity. IGF-1 treatment for 24 hr increased iNOS gene transcription, and Ang II pretreatment reduced this stimulation of iNOS gene expression by attenuating PI3K/Akt signaling. These results implicate PI3K/Akt pathways in Ang II/IGF-1 regulation of iNOS in VSMCs. [ABSTRACT FROM AUTHOR]

Presents research which showed that mice lacking the Mxi1 protein exhibit progressive, multisystem abnormalities. Mxi1 an antagonist of Myc oncoproteins; Possibility that Mxi1 is a tumor-suppressor gene; Chromosomal location of gene; Traits of mice; Proliferative ability of Mxi1-deficient cell types; Role of Mxi1.

The DO-stat fed-batch fermentation was carried out to explore the volumetric productivity of β-carotene in engineered Yarrowia lipolytica C11 strain. Using DO-stat fed-batch fermentation, we achieved 94 g/L biomass and 2.01 g/L β-carotene. Both biomass and β-carotene were about 1.28-fold higher than that in fed-batch fermentation. The ATP, NADP+/NADPH, and gene expression levels of tHMG, GGS1, carRA, and carB were promoted as compared to that in fed-batch fermentation. As for as the kinetic parameters in DO-stat fed-batch fermentation, μm′, Yx/s′, and Yp/s′ was 0.527, 0.353, and 0.158, respectively. The μm′ was elevated 4.66-fold than that in fed-batch fermentation. These data illustrate that more dissolved oxygen increased the biomass. The Yx/s′ and Yp/s′ were increased 1.15 and 22.57-fold, which suggest that the DO-stat fed-batch fermentation reduced the Crabtree effect and improved the utilization rate of glucose. Therefore, DO-stat fed-batch fermentation is a promising strategy in the industrialized production of β-carotene. [ABSTRACT FROM AUTHOR]

No previous study reports the effect of age on cardiac performance, motor function and quality of life (QoL) in Chinese chronic heart failure (CHF) patients. This single-center, prospective study enrolled CHF patients with resting heart rate (RHR) > 80 bpm, who were treated with metoprolol and were followed up at 1, 3, 6, and 12 months. Changes in cardiac, motor, and QoL parameters between patients aged ≥60 years and those aged <60 years were compared at all time points. P < 0.05 was considered significant. A total of 154 patients were enrolled (median age: 66.39 years; 116 aged ≥60 years, 38 aged <60 years; 95% New York Heart Association class III-IV). RHR decreased significantly in both patient groups (P < 0.0001 for both groups). Patients aged ≥60 years had a significant improvement in both ejection fraction (EF) at 6 and 12 months and in cardiac index (CI) at 3, 6, and 12 months. However, no major difference was observed in motor function in both groups. Significantly higher SF-8 scores showed greater improvement in QoL in the <60 age group at 12 months (P = 0.0008). Metoprolol demonstrated improvement in cardiac performance, motor function, QoL, and anxiety with increase in depression and burnout in both genders; however, the findings were independent of age. [ABSTRACT FROM AUTHOR]

This study aims to investigate the repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model. BMSCs were separated from rat bone marrow. LTR-CMVpro-RFP and LTR-CMVpro-GFP were transfected into the BMSCs for in vitro and in vivo tracking. BMSCs-RFP and BMSCs-GFP were induced into endothelial progenitor cells (EPCs) and osteoblasts (OBs). Rats were divided into five groups: Group A: in vitro prefabrication with EPCs-RFP + in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Group B: in vitro prefabrication with EPCs-RFP + secondary OBs-GFP implantation; Group C: in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Group D: implantation of EPCs-RFP + implantation of with arteriovenous vascular bundle + simultaneous OBs-GFP implantation; Group E: demineralized bone matrix (DBM) grafts (blank control). Among five groups, Group A had the fastest bone regeneration and repair, and the regenerated bone highly resembled normal bone tissues; Group D also had fast bone repair, but the repair was slightly slower than Group A. Therefore, in vitro prefabrication with EPCs-RFP plus in vivo prefabrication with arteriovenous vascular bundle and secondary OBs-GFP implantation could be the best treatment for bone defect. [ABSTRACT FROM AUTHOR]