Linc00511 Promotes Thyroid Cancer Through the miR-4739/RNF38 Pathway.

Objective: To analyze the effect of Linc00511 on thyroid cancer through the miR-4739/RNF38 pathway. Methods: A total of 78 patients in our hospital from July 2020 to July 2021 were collected, which were diagnosed with thyroid cancer after clinicopathological examination. Their cancer tissue samples were included in the thyroid cancer tissue group, and the fat 2 cm tissue samples were included in the para-cancer tissue group. Real-time quantitative PCR was used to detect the expression of Linc00511, miR-4739 and RNF38 in tissue samples from the two groups. Statistical analysis of data was performed using SPSS26.0. The correlation between Linc00511, miR-4739 and RNF38 were analyzed by Pearson's correlation coefficient. The expression of Linc00511 in thyroid cancer tissues with different clinicopathological characteristics were compared. Results: The expression levels of Linc00511 and RNF38 in thyroid cancer group were significantly higher than paracancer group, while miR-4739 levels were significantly lower (P < .05). Pearson correlation coefficient analysis showed that there was significant negative correlation between Linc00511 and miR-4739 expression and significant positive correlation between Linc00511 and RNF38 expression (P < .05). There was no significant difference in the expression of Linc00511 among different ages, sexes, and cancer types (P > .05). The expression of Linc00511 in patients with TNM stages I, II, and III were increased with the increase of TNM stage (P < .05). The expression of Linc00511 in patients with tumor diameter ≥1 cm was higher than that in patients with tumor diameter <1 cm and the difference was statistically significant (P < .05). Conclusion: Linc00511 and RNF38 were significantly overexpressed in thyroid cancer tissues, while miR-4739 was significantly underexpressed. In thyroid cancer, Linc00511 can promote the invasion and metastasis of thyroid cancer cells by targeting miR-4739 and RNF38, and its expression level may reflect the progression of thyroid cancer, which can provide target reference for the clinical treatment of thyroid cancer.

Addressing psychosomatic symptom distress with mindfulness-based cognitive therapy in somatic symptom disorder: mediating effects of self-compassion and alexithymia.

Objective: This study explored the association between self-compassion, alexithymia, and psychosomatic symptom distress in a clinical sample of somatic symptom disorder (SSD) patients participating in a mindfulness-based cognitive therapy (MBCT) program. Methods: One hundred sixteen SSD patients who had participated in an MBCT program and completed ≥4 intervention sessions were included in a retrospective study (76.7% women, mean age = 40.0, SD = 9.5). Psychometric measures of psychosomatic symptom distress [Brief Symptom Inventory-18 Global Severity Index (BSI-GSI)], self-compassion [Self-Compassion Scale (SCS)], and alexithymia [Toronto Alexithymia Scale (TAS)] were collected upon admission to the MBCT program and at 6-month follow-up following treatment inclusion. Results: Serial mediation analysis (MBCT→ΔSCS→ΔTAS→ΔBSI-GSI) suggested that changes in both self-compassion and alexithymia had significant indirect effects on improvement in psychosomatic distress [ΔSCS ß = -1.810, 95% bootstrap CI (-2.488, -1.160); ΔTAS ß = -1.615, bootstrap 95% CI (-2.413, -0.896); ΔSCS→ΔTAS ß = -0.621, bootstrap CI (-1.032, -0.315)]. Furthermore, a post-hoc analysis with a reverse sequence (MBCT→ΔTAS→ΔSCS→ΔBSI-GSI) revealed that reduction in alexithymia improved psychosomatic distress and that an increase in self-compassion was a subsequent outcome of alleviation of alexithymia [ΔTAS ß = -2.235, bootstrap 95% CI (-3.305, -1.270); ΔSCS ß = 0.013, 95% bootstrap CI (-0.600, 0.682); ΔTAS→ΔSCS ß = -1.823, bootstrap CI (-2.770, -1.047)]. Conclusion: Both alleviation of alexithymia and improvement in self-compassion play a mediating role in the reduction of psychosomatic distress in SSD patients following an MBCT program. Improvement in self-compassion might be a subsequent outcome of MBCT-related alleviation of alexithymia.

Decoupling Activation and Transport by Electron-Regulated Atomic-Bi Harnessed Surface-to-Pore Interface for Vanadium Redox Flow Battery.

Vanadium redox flow battery (VRFB) promises a route to low-cost and grid-scale electricity storage using renewable energy resources. However, the interplay of mass transport and activation processes of high-loading catalysts makes it challenging to drive high-performance density VRFB. Herein, a surface-to-pore interface design that unlocks the potential of atomic-Bi-exposed catalytic surface via decoupling activation and transport is reported. The functional interface accommodates electron-regulated atomic-Bi catalyst in an asymmetric Bi─O─Mn structure that expedites the V3+ /V2+ conversion, and a mesoporous Mn3 O4 sub-scaffold for rapid shuttling of redox-active species, whereby the site accessibility is maximized, contrary to conventional transport-limited catalysts. By in situ grafting this interface onto micron-porous carbon felt (Bi1 -sMn3 O4 -CF), a high-performance flow battery is achieved, yielding a record high energy efficiency of 76.72% even at a high current density of 400 mA cm-2 and a peak power density of 1.503 W cm-2 , outdoing the battery with sMn3 O4 -CF (62.60%, 0.978 W cm-2 ) without Bi catalyst. Moreover, this battery renders extraordinary durability of over 1500 cycles, bespeaking a crucial breakthrough toward sustainable redox flow batteries (RFBs).

Asymmetric Chemical Potential Activated Nanointerfacial Electric Field for Efficient Vanadium Redox Flow Batteries.

Constructing active sites with enhanced intrinsic activity and accessibility in a confined microenvironment is critical for simultaneously upgrading the round-trip efficiency and lifespan of all-vanadium redox flow battery (VRFB) yet remains under-explored. Here, we present nanointerfacial electric fields (E-fields) featuring outstanding intrinsic activity embodied by binary Mo2C-Mo2N sublattice. The asymmetric chemical potential on both sides of the reconstructed heterogeneous interface imposes the charge movement and accumulation near the atomic-scale N-Mo-C binding region, eliciting the configuration of an accelerator-like E-field from Mo2N to Mo2C sublattice. Supported with theoretical calculations and intrinsic activity tests, the improved vanadium ion adsorption behavior and charge-transfer process at the nanointerfacial sites were further substantiated, hence expediting the electrochemical kinetics. Accordingly, the pronounced promotion is achieved in the resultant flow battery, yielding an energy efficiency of 77.7% and an extended lifespan of 1000 cycles at 300 mA cm-2, outperforming flow cells with conventional single catalysts in most previous reports.

The effect of adverse pregnancy outcomes on vascular aging in young women: the Kailuan study.

Adverse pregnancy outcomes (APOs) are at increased future cardiovascular risk and require effective risk mitigation. However, data regarding appropriate postpartum screening for young women with APOs are lacking. We aimed to investigate the association between APOs and vascular aging by the determination of high pulse wave velocity (PWV) in young women. Women who gave birth from 1990 to 2020 and underwent brachial-ankle pulse wave velocity (baPWV) assessments in the postpartum period were recruited. We excluded women with age ≥50 years at the baPWV assessment or missing postpartum health examinations. The history of APOs including hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and low birth weight were assessed by medical records. High PWV was defined as baPWV above the 90th percentile for different age group. Multivariable Logistic regression was used to evaluate the association of APOs and high PWV. 3193 participants were included in the analysis, including 912 (28.6%) individuals with APOs. The prevalence of high PWV in the non-APO group and the APOs group were 7.19% (164) and 13.9% (127), respectively (P < 0.05). Compared with non-APO group, the OR (95% CI) of APOs group was 1.67 (1.29-2.16). The risks in the 20-29, 30-39, and 40-49 age groups were 2.51 (1.13-5.59), 1.83 (1.30-2.59), and 1.35 (0.82-2.21) (P for trend <0.05). We conclude that APOs are risk factors of vascular aging for young women and the risk decreased with increasing age. BaPWV should be an important indicator for preventive cardiovascular risk management in young women with APOs. Clinical trial registration: Registration number ChiCTR-TNRC-11001489, http://www.chictr.org.cn/showproj.aspx?proj=8050 .

Self-charging electrostatic face masks leveraging triboelectrification for prolonged air filtration.

Electrostatic adsorption is an important complement to the mechanical filtration for high-efficiency air filtering. However, the electrostatic charge decays with time, especially in humid conditions. In this work, a self-charging air filter is presented to capture airborne particles in an efficient and long-lasting manner without the need of external power sources. Leveraging the triboelectric effect between the electrospun poly(vinylidene fluoride) nanofiber film and nylon fabric, the self-charging air filter-based mask excited by breathing can continuously replenish electrostatic charges. As a result, its effective lifespan is up to 60 hours (including 30 hours of wearing), with a minimum filtration efficiency of 95.8% for 0.3-µm particles. The filtration efficiency and lifespan are significantly higher than those of a commercial surgical mask. Furthermore, we uncover the quantitative relation between filtration efficiency and surface electrostatic potential. This work provides an effective strategy to significantly prolong the electrostatic adsorption efficacy for high-performance air-filtering masks.

Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPß and histone H3.

The clinical correlation between adiponectin (APN) signal and hypertrophic scar (HS) remains unclear. Here, we found significantly reduced expression of APN receptors (AdipoR1/2) in HS tissues and derived fibroblasts (HFs), suggesting that HS formation may be associated with APN/AdipoR1/2 decline. RNA sequencing and RT-PCR validation revealed that APN significantly elevated the expression of SIRT1. Both in vitro and in vivo experiments confirmed that SIRT1 plays important role in APN inhibiting the fibrotic phenotype transformation and proliferation of scar fibroblasts and improving skin fibrosis. Mechanistically, SIRT1 inhibited the acetylation of C/EBPß K39, histone H3K27, and H3K9, resulting in impaired transcription activity of C/EBPß and compact chromatin conformation, thus preventing C/EBPß from activating the transcription of YAP. Moreover, we found that YAP was critical for the transcriptional regulation of CTGF, CCND1, and CCNE1 by TEAD4. In conclusion, our study revealed the role of APN in antagonizing HS fibrosis by regulating the SIRT1/C/EBPß/YAP pathway.

Study of the Seawater Desalination Performance by Electrodialysis.

The global scarcity of freshwater resources has greatly contributed to the development of desalination technologies, in which electrodialysis desalination is one of the most widely used and highly regarded methods. In this work, the first step was to design and assemble a experiment module for electrodialysis desalination. The ion removal efficiency and single membrane mass transfer flux of electrodialysis desalination were investigated. The results show that the desalination performance of the module is improved by increasing the voltage gradient, increasing the concentration of seawater and electrolyte and decreasing the membrane surface flux and that the optimum operating conditions for the module at 24 V operating voltage are feedstock concentration of 35 g/L, electrolyte concentration of 1.42 g/L which and system flow rate of 15 L/h. The results of the study will help to better investigate electrodialysis desalination technology.

Investigating the quasi-liquid layer on ice surfaces: a comparison of order parameters.

Ice surfaces are characterized by pre-melted quasi-liquid layers (QLLs), which mediate both crystal growth processes and interactions with external agents. Understanding QLLs at the molecular level is necessary to unravel the mechanisms of ice crystal formation. Computational studies of the QLLs heavily rely on the accuracy of the methods employed for identifying the local molecular environment and arrangements, discriminating between solid-like and liquid-like water molecules. Here we compare the results obtained using different order parameters to characterize the QLLs on hexagonal ice (Ih) and cubic ice (Ic) model surfaces investigated with molecular dynamics (MD) simulations in a range of temperatures. For the classification task, in addition to the traditional Steinhardt order parameters in different flavours, we select an entropy fingerprint and a deep learning neural network approach (DeepIce), which are conceptually different methodologies. We find that all the analysis methods give qualitatively similar trends for the behaviours of the QLLs on ice surfaces with temperature, with some subtle differences in the classification sensitivity limited to the solid-liquid interface. The thickness of QLLs on the ice surface increases gradually as the temperature increases. The trends of the QLL size and of the values of the order parameters as a function of temperature for the different facets may be linked to surface growth rates which, in turn, affect crystal morphologies at lower vapour pressure. The choice of the order parameter can be therefore informed by computational convenience except in cases where a very accurate determination of the liquid-solid interface is important.

Level of systolic blood pressure within the normal range and risk of cardiovascular events in the absence of risk factors in Chinese.

The risk of cardiovascular disease (CVD) at currently defined normal systolic blood pressure (SBP) levels in individuals without CVD risk factors is not well examined. We evaluated whether higher systolic blood pressure within the range considered normal is associated with a higher CVD risk in Chinese without traditional CVD risk factors. The community-based study included 25,529 individuals (mean age:47.3 ± 12.3 years;range:18-95 years) with a baseline SBP of 90-129 mmHg, who were free of CVD and traditional CVD risk factors, and who were re-examined in biennial intervals. During a mean follow-up of 10.6 ± 1.49 years (maximum. 11.5 years), 847 CVD events occurred. CVD incidence per 1000 person-years increased with higher baseline SBP levels (SBP,90-99 mmHg:1.45;100-109 mmHg:2.15;110-119 mmHg:3.06; and 120-129 mmHg:3.80). After adjusting for CVD risk factors, the categorical Cox regression suggested that the CVD risk was not statistically significant for study participants with a baseline SBP level of 100-109 mmHg, 110-119 mmHg, and 120-129 mmHg compared with those with a baseline SBP level of 90-99 mmHg. If CVD risk factors including blood pressure categories which developed during follow-up were included in a time-dependent Cox regression analysis, the normal baseline SBP was still not associated with incident CVDs. A SBP between 90 and 129 mmHg was not associated with an increased CVD risk in a healthy population.

Advances on Graphene-Based Nanomaterials and Mesenchymal Stem Cell-Derived Exosomes Applied in Cutaneous Wound Healing.

Graphene is a new type of carbon nanomaterial discovered after fullerene and carbon nanotube. Due to the excellent biological properties such as biocompatibility, cell proliferation stimulating, and antibacterial properties, graphene and its derivatives have become emerging candidates for the development of novel cutaneous wound dressings and composite scaffolds. On the other hand, pre-clinical research on exosomes derived from mesenchymal stem cells (MSC-Exos) has been intensified for cell-free treatment in wound healing and cutaneous regeneration, via ameliorating the damaged microenvironment of the wound site. Here, we provide a comprehensive understanding of the latest studies and observations on the various effects of graphene-based nanomaterials (GBNs) and MSC-Exos during the cutaneous wound repair process, as well as the putative mechanisms thereof. In addition, we propose the possible forward directions of GBNs and MSC-Exos applications, expecting to promote the clinical transformation.

Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis.

BACKGROUND: Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties. METHODS: ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson's trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice. RESULTS: The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs. CONCLUSIONS: This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.

IL-10 alleviates lipopolysaccharide-induced skin scarring via IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts.

Hypertrophic scar (HS) is a severe fibrotic skin disease. It has always been a major problem in clinical treatment, mainly because its pathogenesis has not been well understood. The roles of bacterial contamination and prolonged wound inflammation were considered significant. IL-10 is a potent anti-inflammatory cytokine and plays a pivotal role in wound healing and scar formation. Here, we investigate whether IL-10 alleviates lipopolysaccharide (LPS)-induced inflammatory response and skin scarring and explore the possible mechanism of scar formation. Our results showed that the expression of TLR4 and pp65 was higher in HS and HS-derived fibroblasts (HSFs) than their counterpart normal skin (NS) and NS-derived fibroblasts (NSFs). LPS could up-regulate the expression of TLR4, pp65, Col I, Col III and α-SMA in NSFs, but IL-10 could down-regulate their expression in both HSFs and LPS-induced NSFs. Blocking IL-10 receptor (IL-10R) or the phosphorylation of STAT3, their expression was up-regulated. In addition, in vitro and in vivo models results showed that IL-10 could alleviate LPS-induced fibroblast-populated collagen lattice (FPCL) contraction and scar formation. Therefore, IL-10 alleviates LPS-induced skin scarring via IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts by reducing ECM proteins deposition and the conversion of fibroblasts to myofibroblasts. Our results indicate that IL-10 can alleviate the LPS-induced harmful effect on wound healing, reduce scar contracture, scar formation and skin fibrosis. Therefore, the down-regulation of inflammation may lead to a suitable scar outcome and be a better option for improving scar quality.

Isolated diastolic hypertension as defined by the 2017 American College of Cardiology/American Heart Association blood pressure guideline and incident cardiovascular events in Chinese.

OBJECTIVE: The new arterial hypertension guidelines by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) changed the definition of isolated diastolic hypertension (IDH). We assessed and compared in a Chinese population the IDH prevalence, newly defined by the 2017 ACC/AHA guidelines versus the former definition by the Joint National Committee 7 (JNC7) criteria, and examined longitudinal associations of IDH with cardiovascular disease (CVD) outcomes. METHODS: The prospective community-based Kailuan Study included participants aged 18-98 years who underwent a detailed medical examination at baseline in 2006/2007 and who were biennially re-examined till 2017. History of antihypertensive medication at baseline was an exclusion criterion. RESULTS: The study population consisted of 87 346 individuals (mean age: 50.9 years; range: 18-98 years). Prevalence of IDH was 7.79% [95% confidence interval (CI): 7.62, 7.97] by JNC7 guidelines and 24.72% (95% CI: 24.43, 25.01) by 2017 ACC/AHA criteria [difference: 19.93% (95% CI: 16.81, 17.04)]. Applying the 2017 ACC/AHA guidelines, the prevalence of IDH-recommended antihypertensive therapy was 7.73% (95% CI: 7.55, 7.90). In multivariable analysis, IDH by JNC7 criteria was significantly associated with incident myocardial infarction [n = 93 events; hazard ratio: 1.30 (95 CI: 1.02, 1.66)], cerebral hemorrhage [n = 73 events; hazard ratio: 1.79 (95% CI: 1.35, 2.38)], and total CVD [n = 373 events; hazard ratio: 1.15 (95% CI: 1.02, 1.30)], when compared with normotension. IDH based on 2017 ACC/AHA guidelines was associated with incident cerebral hemorrhage [n = 129 events; hazard ratio: 1.47 (95% CI: 1.12, 1.94)] and total CVD [n = 828 events; hazard ratio: 1.13 (95% CI: 1.02, 1.26)]. CONCLUSION: In this adult Chinese community, 2017 ACC/AHA-defined IDH was associated with the incidence of cerebral hemorrhage and total CVD, and as compared with JNC7-defined IDH, it was more prevalent.

Micro triboelectric ultrasonic device for acoustic energy transfer and signal communication.

As a promising energy converter, the requirement for miniaturization and high-accuracy of triboelectric nanogenerators always remains urgent. In this work, a micro triboelectric ultrasonic device was developed by integrating a triboelectric nanogenerator and micro-electro-mechanical systems technology. To date, it sets a world record for the smallest triboelectric device, with a 50 µm-sized diaphragm, and enables the working frequency to be brought to megahertz. This dramatically improves the miniaturization and chip integration of the triboelectric nanogenerator. With 63 kPa@1 MHz ultrasound input, the micro triboelectric ultrasonic device can generate the voltage signal of 16.8 mV and 12.7 mV through oil and sound-attenuation medium, respectively. It also achieved the signal-to-ratio of 20.54 dB and exhibited the practical potential for signal communication by modulating the incident ultrasound. Finally, detailed optimization approaches have also been proposed to further improve the output power of the micro triboelectric ultrasonic device.

Baseline CHADS2 Score and Risk of Cardiovascular Events in the Population Without Atrial Fibrillation.

The association between CHADS2 score and stroke has been confirmed in patients with atrial fibrillation. But the majority of cardiovascular events occurred primarily in population without atrial fibrillation. Therefore, we performed this cohort study to evaluate the association between baseline CHADS2 score and cardiovascular events in the population without atrial fibrillation. A total of 99,755 Chinese adults with complete baseline data were followed for up to 10 years. The primary outcomes were cardiovascular event (a composite endpoint of myocardial infarction, cerebral infarction, and cerebral hemorrhage) and all-cause death. The area under the receiver operating characteristic curve was calculated for each kind of outcome. The adjusted cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. The results showed the incidence of cardiovascular events and all-cause death increased with CHADS2 score. The area under the receiver operating characteristic curve for myocardial infarction, cerebral infarction, cerebral hemorrhage, cardiovascular events and all-cause death was 0.66, 0.67, 0.66, 0.67, and 0.69, respectively in participants without atrial fibrillation. Each 1 point increase in CHADS2 score was associated with the risk of all the outcomes in participants without atrial fibrillation after adjusting for age, sex, and other conventional cardiovascular confounders, the hazard ratio (95% confidence interval) for cardiovascular event and all-cause death was 1.17 (1.13 to 1.22) and 1.12 (1.08 to 1.15), respectively. In conclusion, baseline CHADS2 score is an independent risk factor for cardiovascular events and all-cause death in the population without atrial fibrillation.

In utero exposure to the Great Chinese Famine and risk of intracerebral hemorrhage in midlife.

OBJECTIVE: To investigate whether in utero exposure to the Great Chinese Famine in 1959 to 1961 was associated with risk of intracerebral hemorrhage (ICH) in adulthood. METHODS: In this cohort analysis, we included 97,399 participants of the Kailuan Study who were free of cardiovascular disease and cancer at baseline (2006). Cases of incident ICH were confirmed by medical record review. We used the Cox proportional hazards model to calculate the hazard ratio (HR) and 95% confidence interval (CI) for ICH according to in utero famine exposure status. RESULTS: Among 97,399 participants in the current analyses, 6.3% (n = 6,160) had been prenatally exposed to the Great Chinese Famine. During a median 9.0 years of follow-up (2006-2015), we identified 724 cases of incident ICH. After adjustment for potential confounders, the HR of ICH was 1.99 (95% CI 1.39-2.85) for in utero famine-exposed individuals vs individuals who were not exposed to the famine. When exposure to famine and severity of famine were examined jointly, the adjusted HR was 2.99 (95% CI 1.21-7.39) for in utero exposure to severe famine and 1.94 (95% CI 1.32-2.84) for in utero exposure to less severe famine relative to those without exposure to famine. CONCLUSIONS: Individuals with in utero exposure to famine, especially those exposed to severe famine, were more likely to have ICH in midlife, highlighting the role of nutritional factors in susceptibility to this severe cerebral condition.

New Progress of Adipose-derived Stem Cells in the Therapy of Hypertrophic Scars.

Burns are a global public health issue of great concern. The formation of scars after burns and physical dysfunction of patients remain major challenges in the treatment of scars. Regenerative medicine based on cell therapy has become a hot topic in this century. Adipose-derived stem cells (ADSCs) play an important role in cellular therapy and have become a promising source of regenerative medicine and wound repair transplantation. However, the anti-scarring mechanism of ADSCs is still unclear yet. With the widespread application of ADSCs in medical, we firmly believe that it will bring great benefits to patients with hypertrophic scars.

Wnt4 negatively regulates the TGF-ß1-induced human dermal fibroblast-to-myofibroblast transition via targeting Smad3 and ERK.

Abnormal activation of Wnt signaling has been demonstrated in the wound healing process and the pathogenesis of fibrotic disorders, with Wnt4 specifically identified as having a key role in the pathogenesis of renal, pulmonary and liver fibrosis. Wnt4 also was found to be upregulated by transforming growth factor-ß1 (TGF-ß1) in fetal and postnatal murine fibroblasts and bone marrow mesenchymal cells, suggesting an underlying cooperation between Wnt4 and TGF-ß1 in fibrosis. However, the specific roles of Wnt4 in TGF-ß1-induced skin myofibroblast transition and hypertrophic scar formation remain unclear. In the present study, we first observed reduced Wnt4 expression in hypertrophic scar tissue compared with that in normal skin tissue. Following upregulation by TGF-ß1, Wnt4 inhibited the TGF-ß1-induced transdifferentiation of fibroblasts into myofibroblasts. Using fibroblast-populated collagen lattice contraction assays, we showed that the increased contractility induced by TGF-ß1 was significantly blocked by exogenous Wnt4 and the α-smooth muscle actin (α-SMA) expression was decreased in fibroblasts in the collagen lattices. In addition, knockdown of Wnt4 resulted in further increases in α-SMA and collagen I expressions. Further investigation showed that Wnt4 could inhibit the autocrine effect of TGF-ß1 as well as block the phosphorylation of Smad3 and ERK but not of AKT or JNK. Lastly, using hypertrophic scar-derived fibroblasts, we showed that the elevated α-SMA and collagen I levels were markedly reduced after treatment with Wnt4. Taken together, our results suggest that Wnt4 negatively regulates TGF-ß1-induced fibroblast activation, which may represent a novel therapeutic strategy for the treatment and prevention of hypertrophic scars.