Mesenchymal stem cells (MSCs) are derived from a wide range of sources and easily isolated and cultured. MSCs have the capacity for in vitro amplification and self-renewal, low immunogenicity and ...immunomodulatory properties, and under certain conditions, MSCs can be differentiated into a variety of cells. In the cardiovascular system, MSCs can protect the myocardium by reducing the level of inflammation, promoting the differentiation of myocardial cells around infarct areas and angiogenesis, increasing apoptosis resistance, and inhibiting fibrosis, which are ideal qualities for cardiovascular repair. Preclinical studies have shown that MSCs can be transplanted and improve cardiac repair, but challenges, such as their low rate of migration to the ischemic myocardium, low tissue retention, and low survival rate after transplantation, remain. This article reviews the potential and methods of MSC transplantation in the treatment of cardiovascular diseases (CVDs) and the challenges of the clinical use of MSCs.
Exploring the of regional tourism efficiency is of great significance in promoting high-quality development of regional tourism. However, there are not many studies that measure the quality ...development of tourism destinations from the perspective of inputs and output. Based on this, the data envelopment analysis model is used to measure the overall technical efficiency (TECRS), pure technical efficiency (TEVRS), and scale efficiency (SE) with the help of DEA-SOLVER software, taking the ten prefecture-level cities in Shaanxi Province as examples, to further analyze and evaluate the spatial differences of different tourism destinations and the reasons for the differences. The results of the study found that: the efficiency indicators explain the differences in the development quality of tourism destinations from different sides; the development quality of tourism destinations in Shaanxi as a whole is low, with excessive inputs and insufficient outputs; and the tourism destinations with relatively high development quality are distributed in the Guanzhong. On this basis, corresponding countermeasure suggestions are put forward to promote the improvement of governance efficiency of tourism destinations in Shaanxi Province, and then optimize the quality of development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Leaf senescence, a pivotal process in plants, directly influences both crop yield and nutritional quality. Foxtail millet (
) is a C
model crop renowned for its exceptional nutritional value and ...stress tolerance characteristics. However, there is a lack of research on the identification of senescence-associated genes (
s) and the underlying molecular regulatory mechanisms governing this process. In this study, a dark-induced senescence (DIS) experimental system was applied to investigate the extensive physiological and transcriptomic changes in two foxtail millet varieties with different degrees of leaf senescence. The physiological and biochemical indices revealed that the light senescence (LS) variety exhibited a delayed senescence phenotype, whereas the severe senescence (SS) variety exhibited an accelerated senescence phenotype. The most evident differences in gene expression profiles between these two varieties during DIS included photosynthesis, chlorophyll, and lipid metabolism. Comparative transcriptome analysis further revealed a significant up-regulation of genes related to polysaccharide and calcium ion binding, nitrogen utilization, defense response, and malate metabolism in LS. In contrast, the expression of genes associated with redox homeostasis, carbohydrate metabolism, lipid homeostasis, and hormone signaling was significantly altered in SS. Through WGCNA and RT-qPCR analyses, we identified three
s that exhibit potential negative regulation towards dark-induced leaf senescence in foxtail millet. This study establishes the foundation for a further comprehensive examination of the regulatory network governing leaf senescence and provides potential genetic resources for manipulating senescence in foxtail millet.
The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal ...cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA.
We used nationwide birth certificate data from the US National Vital Statistics System during 2016-2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking.
Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1-5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1-5, 6-10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22-1.41), 1.25 (1.17-1.33), and 1.35 (1.28-1.43), respectively. Corresponding values were 1.23 (1.14-1.33), 1.33 (1.24-1.42), 1.33 (1.23-1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21-1.44), 1.36 (1.26-1.47), and 1.38 (1.23-1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22-1.44), 1.35 (1.24-1.47), and 1.35 (1.19-1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73-0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05).
Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1-5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As a member of TALE family, Meis1 has been proven to regulate cell proliferation and differentiation during cell fate commitment; however, the mechanism is still not fully understood. The planarian, ...which has an abundance of stem cells (neoblasts) responsible for regenerating any organ after injury, is an ideal model for studying the mechanisms of tissue identity determination. Here, we characterized a planarian homolog of Meis1 from the planarian
. Importantly, we found that knockdown of
inhibits the differentiation of neoblasts into eye progenitor cells and results in an eyeless phenotype with normal central nervous system. Furthermore, we observed that
is required for the activation of Wnt signaling pathway by promoting the
expression during posterior regeneration. The silencing of
suppresses the expression of
and results in the inability to reconstruct posterior poles. In general, our findings indicated that
acts as a trigger for the activation of eye and tail regeneration by regulating the differentiation of eye progenitor cells and the formation of posterior poles, respectively.
In situ ceramic phase reinforced Ti-based composite coatings were successfully fabricated on Ti-6Al-4V alloys by laser cladding using Ti + Al + Si mixed powders with different NbC contents (0, 5, 10, ...15 wt.%). The effects of different NbC content on the microstructural evolution, hardness, and wear behaviors of the Ti-based composite coatings were studied. The results showed that the phase in the cladding layer was mainly consisted of Ti
3
Al, TiAl, and Ti
5
Si
3
before NbC was added. After NbC was added, the TiC and Ti
3
AlC
2
ceramic reinforcement phase was in suit synthesized. In addition, (Ti, Nb)C were also found. The in situ formed phases were proved beneficial to the improvement of the coating property. With the addition of NbC, the hardness of the coating is apparently increased. When the content of NbC is 15%, the maximum hardness of the coating is 1024 HV
0.2
, which is almost three times that of the substrate. The coefficient of friction of the coating without NbC was 0.591. With the addition of NbC, the coefficient of friction of S2, S3, and S4 was significantly decreased to 0.450, 0.388, and 0.375, respectively. Furthermore, the addition of NbC improves the worn surface of the coatings.
Cationic liposomes (CLs) composed of 3β-N-(N′,N′-dimethylaminoethane) carbamoyl cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) (DC-Chol/DOPE liposomes) have been classified as one ...of the most efficient gene delivery systems. Our study aims to examine the effect of the molar ratio of DC-Chol/DOPE, PEGylation and serum on the pDNA (plasmid pDNA) and siRNA (small interfering RNA) transfection of DC-Chol/DOPE liposomes. The results showed that the most efficient DC-Chol/DOPE liposomes for pDNA or siRNA delivery were at a 1:2 or 1:1 molar ratio of DC-Chol/DOPE, respectively. The transfection efficiency of DC-Chol/DOPE liposomes increased along with increased weight ratio of DC-Chol/siRNA. However, the pDNA transfection efficiency decreased along with increased weight ratio of DC-Chol/pDNA from 3/1. As expected, PEGylation decreased siRNA and pDNA transfection efficiency of DC-Chol/DOPE liposomes. In PEGylated DC-Chol/DOPE liposomes, increased weight ratio of DC-Chol/pDNA from 3/1 did not lead to higher pDNA transfection efficiency, whereas increased weight ratio of DC-Chol/siRNA resulted in increased siRNA transfection efficiency. Furthermore, the serum did not significantly inhibit the pDNA and siRNA transfection efficiency of DC-Chol/DOPE liposomes. In conclusion, our results elucidated the influence factors of DC-Chol/DOPE liposome transfection and would reveal that siRNA and pDNA transfection mechanisms were different in DC-Chol/DOPE liposomes.
There is an urgent need for improved therapy for advanced ovarian carcinoma, which may be met by administering immune-modulatory monoclonal antibodies (mAbs) to generate a tumor-destructive immune ...response. Using the ID8 mouse ovarian cancer model, we investigated the therapeutic efficacy of various mAb combinations in mice with intraperitoneal (i.p.) tumor established by transplanting 3 × 10(6) ID8 cells 10 days previously. While most of the tested mAbs were ineffective when given individually or together, the data confirm our previous finding that 2 i.p. injections of a combination of anti-CD137 with anti-PD-1 mAbs doubles overall survival. Mice treated with this mAb combination have a significantly increased frequency and total number of CD8(+) T cells both in the peritoneal lavage and spleens, and these cells are functional as demonstrated by antigen-specific cytolytic activity and IFN-γ production. While administration of anti-CD137 mAb as a single agent similarly increases CD8(+) T cells, these have no functional activity, which may be attributed to up-regulation of co-inhibitory PD-1 and TIM-3 molecules induced by CD137. Addition of the anti-cancer drug cisplatin to the 2 mAb combination increased overall survival >90 days (and was probably curative) by a mechanism which included a systemic CD8(+) T cell response with tumor specificity and immunological memory. Strikingly, combined treatment of cisplatin and CD137/PD-1 mAb also gave rise to the long-term survival of mice with established TC1 lung tumors. A similar combination of the 2 mAbs and cisplatin should be considered for clinical 'translation'.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuroepithelial transforming gene 1 (NET1) is a RhoA subfamily guanine nucleotide exchange factor that governs a wide array of biological processes. However, its roles in meiotic oocyte remain ...unclear. We herein demonstrated that the NET1-HACE1-RAC1 pathway mediates meiotic defects in the progression of oocyte maturation.
NET1 was reduced using a specific small interfering RNA in mouse oocytes. Spindle assembly, chromosomal alignment, the actin cap, and chromosomal spreads were visualized by immunostaining and analyzed under confocal microscopy. We also applied mass spectroscopy, and western blot analysis for this investigation.
Our results revealed that NET1 was localized to the nucleus at the GV stage, and that after GVBD, NET1 was localized to the cytoplasm and predominantly distributed around the chromosomes, commensurate with meiotic progression. NET1 resided in the cytoplasm and significantly accumulated on the spindle at the MI and MII stages. Mouse oocytes depleted of Net1 exhibited aberrant first polar body extrusion and asymmetric division defects. We also determined that Net1 depletion resulted in reduced RAC1 protein expression in mouse oocytes, and that NET1 protected RAC1 from degradation by HACE1, and it was essential for actin dynamics and meiotic spindle formation. Importantly, exogenous RAC1 expression in Net1-depleted oocytes significantly rescued these defects.
Our results suggest that NET1 exhibits multiple roles in spindle stability and actin dynamics during mouse oocyte meiosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A flow field analysis was performed in this research using the ANSYS Fluent module, and a dynamic heat source employing UDF was constructed using the DEFINE_PROFILE macro. A VOF model was developed ...to track the volume fraction of each fluid throughout the computational domain as well as the steady-state or transient condition of the liquid–gas interface in the free liquid surface area. To determine the distribution state and regularity of the molten pool flow field, the flow field velocity was calculated iteratively by linking the Simple algorithm with the horizontal set method. The molten pool was concave, indicating that the key hole was distributed narrowly. Inserting cross-sections at different depths yielded the vector distribution of the molten pool flow velocity along the depth direction. We set up monitoring sites along the molten pool’s depth direction and watched the flow change over time. We investigated the effects of the process parameters on the flow field’s vector distribution.
PDF
