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Owing to the greater absorption affinity for lipo-rich tissue than water, the 1210 nm laser is a promising candidate for transcutaneous lipolysis in the near-infrared band. However, fat reduction is limited because laser therapy may yield thermal injury of normal tissue. A new protocol to incorporate multipulsed cryogen spray cooling is beneficial to improve the lipolysis effect, and the parameters of laser and cooling can be optimized via skin histopathological analysis.A murine in vivo model of inguinal tissue of SD rats was established to test the effectivity of transcutaneous lipolysis protocol by R134a multipulsed spray cooling assisted 1210 nm laser irradiation. Tissue response of lipolysis with/without cooling 10 days post the treatment was evaluated by histopathological analysis of skin samples stained with hematoxylin-eosin (HE), through which safe and effective parameters for lipolysis were determined.From histopathological analysis of the inguinal tissue of SD rats irradiated by the 1210 nm laser alone, the optimal durations are respectively 7 and 3 s (seconds) for low-dosage (6 W) and high-dosage (9 W) therapy, with pronounced lipolysis effect and minimum injury of skin tissue. The multipulsed spray cooling by R134a with a pulse duration of 10 ms (milliseconds), a pulse delay of 2000 ms, and a pulse number of 5 can be introduced to assist the 1210 nm laser therapy with a power of 9 W and a duration of 7 s to achieve desirable fat liquefaction while keeping the complete structure of skin tissue as well as esthetic-related beneficial effects of hair removal and skin rejuvenation.Excellent lipolysis effect can be achieved via R134a multipulsed spray cooling assisted high-dosage 1210 nm laser irradiation with reasonably matched laser and cooling parameters. The protocol is as follows: Start MP-CSC for one cycle, and then fire the laser with specific power and duration, while keeping MP-CSC accordingly. This new protocol may promote the safe and effective clinical implement of transcutaneous laser lipolysis in body contouring.

Biofilms are communities of bacterial cells encased in a self-produced polymeric matrix and exhibit high tolerance towards environmental stress. Despite the plethora of research on biofilms, most biofilm models are produced using mono-interface culture in static flow conditions, and knowledge of the effects of interfaces and mechanical forces on biofilm development remains fragmentary. This study elucidated the effects of air-liquid (ALI) or liquid-liquid (LLI) interfaces and mechanical shear forces induced by airflow and hydrodynamic flow on biofilm growing using a custom-designed dual-channel microfluidic platform. Results from this study showed that comparing biofilms developed under continuous nutrient supply and shear stresses free condition to those developed with limited nutrient supply, ALI biofilms were four times thicker, 60% less permeable, and 100 times more resistant to antibiotics, while LLI biofilms were two times thicker, 20% less permeable, and 100 times more resistant to antibiotics. Subjecting the biofilms to mechanical shear stresses affected the biofilm structure across the biofilm thickness significantly, resulting in generally thinner and denser biofilm compared to their controlled biofilm cultured in the absence of shear stresses, and the ALI and LLI biofilm's morphology was vastly different. Biofilms developed under hydrodynamic shear stress also showed increased antibiotic resistance. These findings highlight the importance of investigating biofilm growth and its mechanisms in realistic environmental conditions and demonstrate a feasible approach to undertake this study using a novel platform.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.

To understand the morphological and structural characteristics of root nodules in Podocarpus macrophyllus and their development, this study prepared P. macrophyllus root nodule samples at the young, mature, and senescent stages. Optical microscopy and transmission electron microscopy (SEM) revealed that new nodules can be formed on roots and senescent nodules; new nodules formed on the roots are nearly spherical and have an internal structure similar to finite nodules; new nodules on senescent nodules are formed by extension and differentiation of the vascular cylinder of the original nodules; and these new nodules are nested at the base of the original nodules, which create growth space for new nodules by dissociating the cortical tissue; clusters of nodules are formed after extensive accumulation, and the growth pattern is similar to that of infinite nodules; the symbiotic bacteria of P. macrophyllus root nodules mainly invade from the epidermal intercellular space of the roots and migrate along the intercellular space of the nodule cortex; infected nodule cortex cells have a well-developed inner membrane system and enlarged and loose nuclei; and unique Frankia vesicles, and rhizobia cysts, and bacteriophages can all develop. Compared with common leguminous and nonleguminous plant nodules, P. macrophyllus root nodules are more complex in morphology, structure and composition. From the perspective of plant system evolution, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as P. macrophyllus. The conclusions of this study can provide a theoretical basis for the developmental biology of P. macrophyllus root nodules and the evolutionary pattern of plant symbionts.HighlightsWe discuss from the perspective of cell developmental biology, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as Podocarpus macrophyllus.

Spring viraemia of carp (SVC) caused by spring viraemia of carp virus (SVCV) can infect almost all fish of cyprinids, which bring huge economic losses to aquaculture. Glycoprotein (G), as the most important antigenic determinant protein of SVCV, is widely considered as an effective method against SVCV. In our previous study, we found that G3 (131 aa) is the potential dominant antigen epitope that induces strong immune responses similar to G protein (510 aa). Here, in order to further improve the immune effect, we reported a subunit vaccine (PEG-G3) constructed by PEG-modified dominant epitope protein (G3). The results of serum antibody production, enzyme activities and immune-related genes expression showed that PEG-G3 induces significantly stronger immune protective responses against SVCV than G3. PEG modification significantly increased the serum antibody level of the vaccine, which increased significantly after immunization and reached the peak at 21 day post-vaccination. T-AOC and AKP activities in the lowest concentration group (5 μg) of PEG-G3 were significantly higher than those in the highest concentration group (20 μg) of G3. In PEG-G3 group, the expression of almost all genes increased at least 4 times compared with the control group. After 14-day challenge, the RPS (relative percentage survival) of the highest concentration of PEG-G3 group was 53.6%, while that of G3 group is 38.9%. Therefore, this work shows that PEG modification and dominant epitope screening may be effective methods to improve the immune protective effect of vaccines and to resist the infection of aquatic animal viral diseases.

Despite advances in stent technology for vascular interventions, in-stent restenosis (ISR) remains a main complication. The corrosion of cobalt-chromium (CoCr) alloy coronary stents has been identified to be associated with ISR, whereas its role in ISR has not been elucidated. In the current work, CoCr nanoparticles, simulated corrosion products of CoCr alloy, were used to investigate their effect on the endothelial cells. It has been demonstrated that the cell viability declines and the cell membrane is damaged, indicating the cytotoxicity of CoCr nanoparticles. The expression of GRP78, CHOP, and cleaved-caspase12 proteins has increased when exposed to CoCr nanoparticles, suggesting that CoCr nanoparticles induced cell apoptosis through endoplasmic reticulum (ER) stress-mediated apoptotic pathway. An increased release of adhesion and inflammatory mediators was also induced by CoCr nanoparticles, including ICAM-1, VCAM-1, IL-1β, IL-6, and TNF-α. Our results demonstrated that CoCr nanoparticles could trigger apoptosis, adhesion, and inflammation. These findings indicated potential damaging effects of CoCr nanoparticles on the vascular endothelium, which suggested corrosion of CoCr alloy may promote the progression and development of ISR.

Solid polymer electrolytes with relatively low ionic conductivity at room temperature and poor mechanical strength greatly restrict their practical applications. Herein, we design semi-interpenetrating network polymer (SNP) electrolyte composed of an ultraviolet-crosslinked polymer network (ethoxylated trimethylolpropane triacrylate), linear polymer chains (polyvinylidene fluoride-co-hexafluoropropylene) and lithium salt solution to satisfy the demand of high ionic conductivity, good mechanical flexibility, and electrochemical stability for lithium metal batteries. The semi-interpenetrating network has a pivotal effect in improving chain relaxation, facilitating the local segmental motion of polymer chains and reducing the polymer crystallinity. Thanks to these advantages, the SNP electrolyte shows a high ionic conductivity (1.12 mS cm-1 at 30 °C), wide electrochemical stability window (4.6 V vs. Li+ /Li), good bendability and shape versatility. The promoted ion transport combined with suppressed impedance growth during cycling contribute to good cell performance. The assembled quasi-solid-state lithium metal batteries (LiFePO4 /SNP/Li) exhibit good cycling stability and rate capability at room temperature.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from Jan 2008 to Aug 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation. This article is protected by copyright. All rights reserved.

INTRODUCTION: Stroke, especially ischemic stroke's (IS) link with Alzheimer's disease (AD) remains unclear. METHODS: This prospective cohort study included 2459 AD- and cerebrovascular disease-free older adults at baseline (mean age 71.9 ± 10.3 years, Stockholm, Sweden). Using Cox regressions, shared risk factors (SRFs) and shared protective factors (SPFs) between AD and IS were recognized when their hazard ratios in both AD and IS models were significant and in the same direction. RESULTS: During the follow-up period of up to 15 years, 132 AD and 260 IS mutually exclusive cases were identified. SRFs were low education, sedentary lifestyle, and heart diseases. High levels of psychological well-being, actively engaging in leisure activities, and a rich social network were SPFs. Having ≥1 SPF reduced 47% of AD and 28% of IS risk among people with a low risk profile (

Recovery of responses to cutaneous stimuli in the area 3b hand cortex of monkeys after dorsal column lesions (DCLs) in the cervical spinal cord relies on neural rewiring in the cuneate nucleus (Cu) over time. To examine whether the corticocuneate projections are modified during recoveries after the DCL, we injected cholera toxin subunit B (CTB) into the hand representation in Cu to label the cortical neurons after various recovery times, and related results to the recovery of neural responses in the affected area 3b hand cortex. In normal New World monkeys, labeled neurons were predominately distributed in the hand regions of contralateral areas 3b, 3a, 1 and 2, parietal ventral (PV), secondary somatosensory cortex (S2), and primary motor cortex (M1), with similar distributions in the ipsilateral cortex in significantly smaller numbers. In monkeys with short-term recoveries, the area 3b hand neurons were unresponsive or responded weakly to touch on the hand, while the cortical labeling pattern was largely unchanged. After longer recoveries, the area 3b hand neurons remained unresponsive, or responded to touch on the hand or somatotopically abnormal parts, depending on the lesion extent. The distributions of cortical labeled neurons were much more widespread than the normal pattern in both hemispheres, especially when lesions were incomplete. The proportion of labeled neurons in the contralateral area 3b hand cortex was not correlated with the functional reactivation in the area 3b hand cortex. Overall, our findings indicated that corticocuneate inputs increase during the functional recovery, but this functional role is uncertain.

BACKGROUND The Work Support Profile (WSP) is a brief assessment instrument that enables staff supporting adults with disabilities to provide calibrated and individualized support for specific work tasks. This paper sought to examine the psychometric properties of WSP for people with disabilities. METHOD A pilot study was conducted with 239 sheltered workshop employees diagnosed mainly with intellectual disability to explore the structure of this assessment tool, and provide initial evidence of its psychometric properties. Subsequently, a larger-scale study captured a nationwide profile of 761 sheltered workshop employees with intellectual disability. RESULTS Across both studies, factor analyses yielded a conceptually acceptable 5-factor structure with 33 items accounting for approximately 65% of the variance. Furthermore, the reliability, convergent and discriminant validity of WSP can be considered adequate. CONCLUSION Results provide preliminary evidence that WSP is a psychometrically adequate tool for assessing the work support needs of adults with disabilities on given work tasks.

Aortic dissection (AD) is the rupture of the aortic intima, causing the blood in the cavity to enter the middle of the arterial wall. Without urgent and proper treatment, the mortality rate increases to 50% within 48 hours. Most patients present with acute onset of symptoms, including sudden severe pain and complex and variable clinical manifestations, which can be easily misdiagnosed. Despite this, the molecular mechanisms underlying AD are still unknown. Recently, non‐coding RNAs have emerged as novel regulators of gene expression. Previous studies have proven that ncRNAs can regulate several cardiovascular diseases; therefore, their potential as clinical biomarkers and novel therapeutic targets for AD has aroused widespread interest. To date, several studies have reported that microRNAs are crucially involved in AD progression. Additionally, several long non‐coding RNAs and circular RNAs have been found to be differentially expressed in AD samples, suggesting their potential roles in vascular physiology and disease. In this review, we discuss the functions of ncRNAs in AD pathophysiology and highlight their potential as biomarkers and therapeutic targets for AD. Meanwhile, we present the animal models previously used for AD research, as well as the specific methods for constructing mouse or rat AD models.

Objective We investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein e4 (APOE-e4), a well-known genetic risk factor for dementia. Methods We followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE-e4 was assessed on multiplicative and additive scales. Results After an average of 6.3 years (range = 2.1-10.7) of follow-up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE-e4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE-e4 carriers with low cognitive reserve, e4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13-0.59). The magnitude of risk reduction was similar in e4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15-0.40). Interpretation Lifelong engagement in reserve-enhancing activities attenuates the risk of dementia attributable to APOE-e4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019.

Adipose‐derived stem cells (ASCs) are highly attractive for cell‐based therapies in tissue repair and regeneration because they have multilineage differentiation capacity and are immunosuppressive. However, the detailed epigenetic mechanisms of their immunoregulatory capacity are not fully defined. In this study, we found that Mysm1 was induced in ASCs treated with inflammatory cytokines. Adipose‐derived stem cells with Mysm1 knockdown exhibited attenuated immunosuppressive capacity, evidenced by less inhibition of T cell proliferation, more pro‐inflammatory factor secretion and less nitric oxide (NO) production in vitro. Mysm1‐deficient ASCs exacerbated inflammatory bowel diseases but inhibited tumour growth in vivo. Mysm1‐deficient ASCs also showed depressed miR‐150 expression. When transduced with Mysm1 overexpression lentivirus, ASCs exhibited enhanced miR‐150 expression. Furthermore, Mysm1‐deficient cells transduced with lentivirus containing miR‐150 mimics produced less pro‐inflammatory factors and more NO. Our study reveals a new role of Mysm1 in regulating the immunomodulatory activities of ASCs by targeting miR‐150. These novel insights into the mechanisms through which ASCs regulate immune reactions may lead to better clinical utility of these cells.