Treatment of chronic wounds such as diabetic wounds with large volumes of biofluids is a significant clinical challenge due to ischemia caused by localized edema. To alleviate edema and stimulate ...angiogenesis, a four‐layer composite dressing is designed with a micropore array modified Janus membrane for self‐pumping and bioactive ion backflow, a superabsorbent layer for high capacity water absorption, and a bioactive layer containing bioglass for stimulating angiogenesis. The modified Janus membrane not only allows wound exudates transport from wound bed to the dressing, but also enables controlled backflow of bioactive ion containing fluid to the wound bed for stimulating angiogenesis. The in vivo experiment confirms the function of composite dressing in reducing wound edema, stimulating blood vessel formation and promoting diabetic wound healing. These results demonstrate that the novel composite dressing is a promising wound healing biomaterial for promoting chronic wound healing, and the unique characteristics of the micropore arrayed Janus membrane may extend its applications in biomedicine.
The designed micropore array Janus membrane changes the unidirectional water transport properties of traditional Janus membranes to a controllable bi‐directional water transport characteristic. A four‐layer wound dressing with the micropore array Janus membrane is further constructed, which effectively absorbs wound exudates, stimulates blood vessel formation, and enhances diabetic wound healing.
Golden 2-Like (G2-like) transcription factors play an important role in plant development. However, the roles of these G2-like regulatory genes in response to abiotic stresses in tomato are not well ...understood.
In this study, we identified 66 putative G2-like genes in tomato (Solanum lycopersicum) and classified them into 5 groups (I to V) according to gene structure, motif composition and phylogenetic analysis. The G2-like genes were unevenly distributed across all 12 chromosomes. There were nine pairs of duplicated gene segments and four tandem duplicated SlGlk genes. Analysis of the cis-regulatory elements (CREs) showed that the promoter regions of SlGlks contain many kinds of stress- and hormone-related CREs. Based on RNA-seq, SlGlks were expressed in response to three abiotic stresses. Thirty-six differentially expressed SlGlks were identified; these genes have multiple functions according to Gene Ontology (GO) analysis and are enriched mainly in the zeatin biosynthesis pathway. Further studies exhibited that silencing SlGlk16 in tomato would reduce drought stress tolerance by earlier wilted, lower superoxide dismutase (SOD), peroxidase (POD) activities, less Pro contents and more MDA contents.
Overall, the results of this study provide comprehensive information on G2-like transcription factors and G2-like genes that may be expressed in response to abiotic stresses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Much of the current understanding of thermal effects in biological systems is based on macroscopic measurements. There is little knowledge about the local thermostability or heat tolerance of ...subcellular components at the nanoscale. Herein, we show that gold nanorod–fluorescent nanodiamond (GNR‐FND) hybrids are useful as a combined nanoheater/nanothermometer in living cells. With the use of a 594 nm laser for both heating and probing, we measure the temperature changes by recording the spectral shifts of the zero‐phonon lines of negatively charged nitrogen‐vacancy centers in FNDs. The technique allows us to determine the rupture temperatures of individual membrane nanotubes in human embryonic kidney cells, as well as to generate high temperature gradients on the cell membrane for photoporation and optically controlled hyperthermia. Our results demonstrate a new paradigm for hyperthermia research and application.
Heating up: Gold nanorod–fluorescent nanodiamond (GNR‐FND) hybrids are shown to be useful as a combined nanoheater/nanothermometer in living cells. A temperature difference of up to 10 °C in the damage threshold between local and global heating of intercellular membrane nanotubes was found. These hybrid devices open new opportunities in hyperthermia research.
Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the ...over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.
Deregulation of protein translation control is a hallmark of cancers. Eukaryotic initiation factor 4A2 (EIF4A2) is required for mRNA binding to ribosome and plays an important role in translation ...initiation. However, little is known about its functions in colorectal cancer (CRC).
Analysis of CRC transcriptome data from TCGA identified that EIF4A2 was associated with poor prognosis. Immunohistochemistry study of EIF4A2 was carried out in 297 paired colorectal tumor and adjacent normal tissue samples. In vitro and in vivo cell-biological assays were performed to study the biological functions of EIF4A2 on experimental metastasis and sensitivity to oxaliplatin treatment. Bioinformatic prediction, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay were carried out to unveil the transcription factor of EIF4A2 regulation.
EIF4A2 Expression is significantly higher in colorectal tumors. Multivariate analysis suggests EIF4A2 as an independent predictor of overall, disease-free and progression-free survival. Dysfunction of EIF4A2 by genetic knock-down or small-molecule inhibitor silvestrol dramatically inhibited CRC invasion and migration, sphere formation and enhanced sensitivity to oxaliplatin treatment in vitro and in vivo. Notably, EIF4A2 knock-down also suppressed lung metastasis in vivo. qRT-PCR and immunoblotting analyses identified c-Myc as a downstream target and effector of EIF4A2. ChIP and dual-luciferase reporter assays validated the bioinformatical prediction of ZNF143 as a specific transcription factor of EIF4A2.
EIF4A2 promotes experimental metastasis and oxaliplatin resistance in CRC. Silvestrol inhibits tumor growth and has synergistic effects with oxaliplatin to induce apoptosis in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models.
•The LCF performances of Ni-based single-crystal superalloy plates with film cooling holes were studied.•The LCF lifetime prediction model of plates with film cooling holes was established.•The model ...was based on rate dependent crystal plasticity theory and the theory of critical distances.•The model employed the damage parameter of resolved shear stress/strain of slip systems.•The damage parameter in the model could describe the multi-holes interference effect well.
Considering the effects of the numbers and diameters of film cooling holes, the Low Cycle Fatigue (LCF) performances of Ni-based single-crystal superalloy plate specimens were studied. The investigation found that the low cycle fatigue lifetimes of the single hole specimens were significantly longer than those of multi-holes specimens because of the multi-holes interference effect. Combined with the rate dependent Crystal Plasticity (CP) theory and the Theory of Critical Distances (TCD), the LCF lifetime prediction models of specimens with close packed film cooling holes were established. Instead of the SWT parameter, the models used the damage parameter of maximum resolved shear stress/strain, which can describe the multi-holes interference effect well. The damage model was defined based on the rate dependent CP framework. Combined with the Manson – Coffin formula, the concrete process of predicting LCF lifetimes of the specimen with close packed film cooling holes was given. Both the predicted and tested LCF lifetimes of the specimens were in the double error band.
Abstract
Background
Previous studies have reported that vitamin D supplement could improve fracture healing, but evidence regarding the role of vitamin D supplements in spinal fusion was limited. ...Thus, this study aimed to evaluate the effectiveness of oral vitamin D supplements on fusion outcomes in patients undergoing lumbar spinal fusion.
Methods
This randomized, double-blind, parallel-designed, active-control trial included the patients who planned for elective lumbar spinal fusion. Eligible patients were randomly assigned to receive either daily vitamin D3 (cholecalciferol) 800 IU and daily calcium citrate 600 mg (experimental group) or only daily calcium citrate 600 mg (control group). All supplements were given from postoperative day 1 and lasted for 3 months. Primary outcome was postoperative 1-year fusion rate, and secondary outcomes included time to fusion, Oswestry Disability Index (ODI), and visual analogue scale (VAS) for pain.
Results
Among the included 34 patients (21 in the experimental group and 13 in the control group), baseline 25-hydroxyvitamin D (25OHVitD) level was 26.7 (10.4) ng/ml. Preoperative prevalence of vitamin D deficiency and insufficiency were 23.5% and 47.1%, respectively. Postoperative 1-year fusion rate was not significantly different between the two groups (95.2% vs. 84.6%,
P
= 0.544). The experimental group had significantly shorter time to fusion (Kaplan–Meier estimated: 169 days vs. 185 days interquartile range: 88–182 days vs. 176–324 days, log-rank test:
P
= 0.028), lower postoperative 6-month ODI (
P
< 0.001), and lower postoperative 6-month VAS (
P
< 0.001) than the control group. Time to fusion was significantly and negatively correlated with preoperative, postoperative 3-month, and 6-month 25(OH)VitD levels (all
P
< 0.01).
Conclusion
The patient with vitamin D supplements had shorter time to fusion, better spinal function and less pain after elective spinal fusion. Further research is warranted to identify the patients who can benefit the most from vitamin D supplements and the appropriate dose of vitamin D supplements.
Trial registration
ClinicalTrials.gov, NCT05023122. Registered 20 August 2021. Retrospectively registered,
http://clinicaltrials.gov/ct2/show/NCT03793530
.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The potential role of Tai Chi in improving sarcopenia and frailty has been shown in randomized controlled trials (RCTs). This systematic review and meta-analysis aimed to examine the effect of Tai ...Chi on muscle mass, muscle strength, physical function, and other geriatric syndromes in elderly individuals with sarcopenia and frailty.
Systematic searches of the PubMed, Cochrane Library, PEDro, EMBASE, Web of Science, CINAHL, and Medline databases for RCTs published between 1989 and 2022 were conducted; the database searchers were supplemented with manual reference searches. The inclusion criteria were as follows: (1) the study was designed as a RCT; (2) Tai Chi was one of the intervention arms; (3) the participants had a minimum age of ≥ 60 years and were diagnosed with frailty or sarcopenia, and the diagnostic guidelines or criteria were mentioned; (4) the number of participants in each arm was ≥ 10; and (5) the outcome reports included ≥ 1 item from the following primary or secondary outcomes. The exclusion criteria were as follows: (1) non-RCT studies; (2) nonhuman subjects; (3) participants aged < 60 years; (4) no description of the diagnostic guidelines or criteria for frailty or sarcopenia in the text; and (5) reported outcomes not among the following primary or secondary outcomes. The primary outcomes were muscle mass, grip strength and muscle performance (gait speed, 30-second chair stand test (30CST), sit-to-stand test (SST), Timed up and go test (TUGT), balance, and the Short Physical Performance Battery (SPPB)). The secondary outcomes included the number of falls and fear of falling (FOF), diastolic blood pressure (DBP), Mini-Mental State Examination (MMSE) score, and depression and quality of life (QOL) assessments.
Eleven RCTs were conducted from 1996 to 2022 in 5 countries that investigated 1676 sarcopenic or frail elderly individuals were included in the review. There were 804 participants in the Tai Chi exercise cohort and 872 participants in the control cohort (nonexercised (n = 5)/ exercise (n = 8)). The mean age of participants was 70–89.5 years and the numbers of participants from each arm in each study were 10–158. The majority of the participants practiced Yang-style Tai Chi (n = 9), and the numbers of movement ranged from 6 to 24. The prescriptions of training were 8–48 weeks, 2–7 sessions per weeks, and 30–90 min per session. Most studies used Tai Chi expert as instructor (n = 8). The lengths of follow-up period were 8–48 weeks. The results from our meta-analysis revealed significant improvements for Tai Chi compared to control group (nonexercise/ exercise) on measures of the 30CST (weighted mean difference (WMD): 2.36, 95% confidence interval (CI) 1.50–3.21, p < 0.00001, I2 = 87%), the TUGT (WMD: −0.72, 95% CI −1.10 to −0.34, p = 0.0002, I2 =0%), numbers of fall (WMD: −0.41, 95% CI −0.64 to −0.17, p = 0.0006, I2 =0%) and FOF (standardized MD (SMD): −0.50, 95% CI −0.79 to −0.22, p = 0.0006, I2 = 57%); and for Tai Chi compared to ‘nonexercise’ controls on measures of SST (WMD: −2.20, 95% CI −2.22 to −2.18, p < 0.00001), balance (SMD: 9.85, 95% CI 8.88–10.82, p < 0.00001), DBP (WMD: −7.00, 95% CI −7.35 to −6.65, p < 0.00001), MMSE (WMD: 1.91, 95% CI 1.73–2.09, p < 0.00001, I2 =0%), depression (SMD: −1.37, 95% CI −1.91 to −0.83, p < 0.00001) and QOL (SMD: 10.72, 95% CI 9.38–12.07, p < 0.00001). There were no significant differences between Tai Chi and control groups on any of the remaining 4 comparisons: body muscle mass (WMD: 0.53, 95% CI −0.18 to 1.24; P = 0.14; I2 =0%), grip strength (WMD: −0.06, 95% CI −1.98 to 1.86; P = 0.95; I2 =0%), gait speed (WMD: 0.05, 95% CI −0.11 to 0.20; P = 0.55; I2 =99%), and SPPB (WMD: 0.55, 95% CI −0.04 to 1.14; P = 0.07). The variables of bias summary, Tai Chi instructor, Tai Chi movements, and Tai Chi training duration without significant association with the 30CST or the TUGT through meta-regression analyses.
Our results demonstrated that patients with frailty or sarcopenia who practiced Tai Chi exhibited improved physical performance in the 30-second chair stand test, the Timed up and go test, number of falls and fear of falling. However, there was no difference in muscle mass, grip strength, gait speed, or Short Physical Performance Battery score between the Tai Chi and control groups. Improvements in the sit-to-stand test, balance, diastolic blood pressure, Mini-Mental State Examination score, and depression and quality of life assessments were found when comparing the Tai Chi cohort to the nonexercise control cohort rather than the exercise control cohort. To explore the effectiveness of Tai Chi in sarcopenic and frail elderly individuals more comprehensively, a standardized Tai Chi training prescription and a detailed description of the study design are suggested for future studies.
•Tai Chi practice could improve the 30CST, TUGT, number of falls and FOF in the sarcopenic and frail elderly individual.•The sarcopenic and frail elderly individual has improved DBP, MMSE score, depression and QOL after Tai Chi training.•The advantage from Tai Chi exercise on the muscle mass, grip strength, or SPPB score was not obvious.
Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association ...study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49–1.99; p = 4.07 × 10−11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20–1.74; p = 1.23 × 10−4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (−) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (−) subtype.
•Hepatocytes secrete Gal-9 to attenuate intrahepatic production of Th1 cytokines in AIH.•Gal-9 suppresses intrahepatic T cell activation through Tim-3 during AIH induction.•Gal-9 promotes Foxp3 ...expression and Treg function through TL1A but not TGF-β in AIH.•Gal-9 hinders the increase of activated T cells in liver in a Tim-3-independent way.•TLR2/4 ligands attenuate the effects of Gal-9 by increasing intrahepatic IL-6 and IL-12.
Hepatocytes are the targets in autoimmune hepatitis (AIH) that results in T cell-dependent liver injury. However, hepatocytes may also affect the hepatic T cells in AIH, but the underlying mechanisms are not fully understood. Here we report that hepatocytes could secrete galectin-9 (Gal-9) to suppress the intrahepatic production of Th1 cytokine IFN-γ and restrict AIH development, but hepatocyte damage resulted in opposite effects due to release of TLR2/4 ligands that promoted the intrahepatic production of IL-1β, IL-6, and IL-12. Through Tim-3, Gal-9 could efficiently suppress the intrahepatic T cell activation despite presence of TLR2/4 ligands, thus attenuating Th1 response in AIH. Intriguingly, intrahepatic IL-6/IL-12 suppressed the effect of TGF-β on Treg cells. Therefore, in AIH, Gal-9 promoted Foxp3 expression and function of hepatic Treg cells through TL1A signaling, although Treg function was still impaired, compared with that in naive state. Due to its promoting effect on Treg function, together with its effect on T effector cells in a Tim-3-independent way, Gal-9 could attenuate intrahepatic IFN-γ production by hindering the increase of hepatic CD4+CD43+ T cells resulting from extrahepatic T cell activation. TLR2/4 ligands attenuated the effects of Gal-9 on Treg cells and CD4+CD43+ T cells by increasing intrahepatic IL-6 and IL-12. Blocking TLR2/4 ligands could efficiently suppress intrahepatic IFN-γ production, liver injury, and hepatic fibrosis. These findings suggest that hepatocytes paradoxically affect Th1 response in AIH due to Gal-9 expression and TLR2/4 ligands release, and that targeting TLR2/4 signaling may provide an important approach in the therapeutic strategy for AIH.
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