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Obesity-induced β cell dysfunction contributes to the onset of type 2 diabetes. Nevertheless, elucidating epigenetic mechanisms underlying islet dysfunction at single cell level remains challenging. Here we profile single-nuclei RNA along with enhancer marks H3K4me1 or H3K27ac in islets from lean or obese mice. Our study identifies distinct gene signatures and enhancer states correlating with β cell dysfunction trajectory. Intriguingly, while many metabolic stress-induced genes exhibit concordant changes in both H3K4me1 and H3K27ac at their enhancers, expression changes of specific subsets are solely attributable to either H3K4me1 or H3K27ac dynamics. Remarkably, a subset of H3K4me1 + H3K27ac - primed enhancers prevalent in lean β cells and occupied by FoxA2 are largely absent after metabolic stress. Lastly, cell-cell communication analysis identified the nerve growth factor (NGF) as protective paracrine signaling for β cells through repressing ER stress. In summary, our findings define the heterogeneous enhancer responses to metabolic challenges in individual β cells., (© 2024. The Author(s).)

Objective: To establish a practical risk stratification system (RSS) based on ultrasonography (US) and clinical characteristics for predicting soft tissue masses (STMs) malignancy., Methods: This retrospective multicenter study included patients with STMs who underwent US and pathological examinations between April 2018 and April 2023. Chi-square tests and multivariable logistic regression analyses were performed to assess the association of US and clinical characteristics with the malignancy of STMs in the training set. The RSS was constructed based on the scores of risk factors and validated externally., Results: The training and validation sets included 1027 STMs (mean age, 50.90 ± 16.64, 442 benign and 585 malignant) and 120 STMs (mean age, 51.93 ± 17.90, 69 benign and 51 malignant), respectively. The RSS was constructed based on three clinical characteristics (age, duration, and history of malignancy) and six US characteristics (size, shape, margin, echogenicity, bone invasion, and vascularity). STMs were assigned to six categories in the RSS, including no abnormal findings, benign, probably benign (fitted probabilities [FP] for malignancy: 0.001-0.008), low suspicion (FP: 0.008-0.365), moderate suspicion (FP: 0.189-0.911), and high suspicion (FP: 0.798-0.999) for malignancy. The RSS displayed good diagnostic performance in the training and validation sets with area under the receiver operating characteristic curve (AUC) values of 0.883 and 0.849, respectively., Conclusion: The practical RSS based on US and clinical characteristics could be useful for predicting STM malignancy, thereby providing the benefit of timely treatment strategy management to STM patients., Critical Relevance Statement: With the help of the RSS, better communication between radiologists and clinicians can be realized, thus facilitating tumor management., Key Points: There is no recognized grading system for STM management. A stratification system based on US and clinical features was built. The system realized great communication between radiologists and clinicians in tumor management., (© 2024. The Author(s).)

Among middle-aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle-aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007-2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake-related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non-osteoporosis group ( p  < .001). The lowest tertile category is then used to act as a reference category, and a higher dietary folic acid intake amount is observed to be positively related to lower odds for risk of osteoporosis. This trend is also not changed in adjustments for combinations of different covariates ( p all < .05). Based on this, a dietary folic acid intake of 475.5 μg/day is identified as an optimal cutoff value for revealing osteoporosis. Collectively, this nationwide population-based study reveals that a higher daily dietary folic acid intake has potential protective effects on osteoporosis in middle-aged and older people., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Osteoarthritis (OA) is a chronic inflammatory condition that affects the articular cartilage. Astragaloside IV (AS-IV) constitutes the primary active component of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV demonstrates anti-inflammatory and anti-apoptotic attributes, exhibiting therapeutic potential across various inflammatory and apoptosis-related disorders. Nevertheless, its pharmaceutical effects in OA are yet to be fully defined., Objectives: This study aimed to investigate the protective impact of AS-IV on rat chondrocytes treated with IL-1β and ascertain whether autophagy plays a role in this effect., Methods: Chondrocytes were isolated and cultivated from the knee joints of neonatal SD mice. The study included the blank control group, the model group, and the AS-IV concentration gradient group (50, 100, 200 μmol/L) to intervene with chondrocytes. The MTT assay was employed to assess cell viability at varying culture periods, enabling the determination of suitable concentration and duration. Subsequently, chondrocytes were treated with the optimal AS-IV concentration and divided into three groups: the model group replicated IL-1β-induced inflammatory chondrocyte injury, the AS-IV group received a co-culture of AS-IV and IL-1β, and a blank control group was established. Changes in cell morphology and structure were observed using ghost pen cyclic peptide staining. ELISA was used to measure TNF-α and GAG levels in cell supernatants. RT-qPCR assessed p62 and LC3 mRNA expression, while Western Blot evaluated p62 and LC3Ⅱ/Ⅰ protein expression., Results: AS-IV promoted chondrocyte proliferation and concurrently inhibited cell apoptosis. An optimal AS-IV dose of 200 μmol/L and a suitable reaction time of 48 h were identified. Ghost pen cyclic peptide staining indicated that the model group's cytoskeleton exhibited fusiform changes with reduced immunofluorescence intensity, as opposed to the blank control group. The AS-IV group displayed more polygonal cytoskeletal morphology with increased immunofluorescence intensity. AS-IV reduced TNF-α levels and elevated GAG levels in the culture supernatant. Additionally, AS-IV lowered p62 mRNA and protein expression while increasing LC3 mRNA expression in cultured chondrocytes., Conclusion: Our findings suggest that AS-IV mitigates inflammatory chondrocyte injury, safeguarding chondrocytes through a potential autophagy suppression mechanism. These results imply that AS-IV could offer preventive advantages for OA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate the effectiveness of contrast-enhanced ultrasound (CEUS) guided core needle biopsy (CNB) in diagnosing soft tissue tumors (STTs) and to identify the conventional ultrasonography (US) features of STTs that are recommended for CEUS-guided CNB., Materials and Methods: A retrospective study was conducted on 123 patients with surgically confirmed STTs. Before surgeries, all subjects underwent CNB under the guidance of US or CEUS. The histopathological results of surgical specimens were considered as the gold standards. A successful biopsy diagnosis was defined as the pathological subtypes obtained by biopsy consistent with the gold standard. The diagnostic yields were compared between the US and CEUS groups, and the diagnostic yields based on various conventional US features of STTs were also compared between the two groups., Results: Sixty-seven cases underwent US-guided CNB and fifty-six cases underwent CEUS-guided CNB. The clinical, biopsy, and conventional US characteristics revealed no significant difference between the two groups. The diagnostic yield of the CEUS group was statistically higher than that of the US group (p = 0.011). In the CEUS group, more STTs with the anechoic areas were identified after CEUS examination (p = 0.031). Furthermore, the diagnostic yields based on the conventional US features of STTs, including deep fascia layer (p = 0.010), a maximum diameter ≥5 cm (p = 0.037), rough margin (p = 0.016), heterogeneous echotexture (p = 0.017), and absence of anechoic area (p = 0.013), were significantly different between the two groups, and the CEUS group exhibited higher diagnostic yields., Conclusion: CEUS-guided CNB was found to be an efficient method for STTs diagnosis. It is particularly recommended for STTs with the following conventional US features, including location in deep fascia layer, a maximum diameter ≥5 cm, rough margin, heterogeneous echotexture, or absence of anechoic area., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As a rare and highly aggressive soft tissue sarcoma, the new immunophenotype, atypical FISH pattern and relevant molecular cytogenetics of synovial sarcoma (SS) remain less known, although it is characteristically represented by a pathognomonic chromosomal translocation t (X; 18) (p11.2; q11.2). Methodologically, the morphology was retrospectively analysed by using H&E staining, and immunohistochemical features were investigated by using markers that have been recently applied in other soft tissue tumors. Moreover, FISH signals for SS18 and EWSR-1 break-apart probes were examined. Finally, cytogenetic characteristics were analysed via RT-PCR and Sanger sequencing. Consequently, nine out of thirteen cases that were histologically highly suspected as SS were finally identified as SS via molecular analysis. Histologically, nine SS cases were divided into monophasic fibrous SS (4/9), biphasic SS (4/9) and poorly differentiated SS (1/9). Immunohistochemically, SOX-2 immunostaining was positive in eight cases (8/9) and PAX-7 immunostaining was diffusely positive in the epithelial component of biphasic SS (4/4). Nine cases showed negative immunostaining for NKX3.1 and reduced or absent immunostaining for INI-1. Eight cases showed typically positive FISH signalling for the SS18 break-apart probe, whereas one case exhibited an atypical FISH pattern (complete loss of green signalling, case 2). Furthermore, the SS18-SSX1 and SS18-SSX2 fusion genes were identified in seven cases and two cases, respectively. The fusion site in 8 out of 9 cases was common in the literature, whereas the fusion site in case 2 was involved in exon 10 codon 404 in SS18 and exon 7 codon 119 in SSX1 (which has not been previously reported), which notably corresponded to the complete loss of green signalling in the FISH pattern. Additionally, FISH analysis of the EWSR-1 gene in nine SS cases demonstrated aberrant signalling in three cases that were recognized as a monoallelic loss of EWSR-1 (1/9), an amplification of EWSR-1 (1/9) and a translocation of EWSR-1 (1/9). In conclusion, SS18-SSX fusion gene sequencing is obligatory for a precise diagnosis of SS when dealing with a confusing immunophenotype and atypical or aberrant FISH signalling for SS18 and EWSR-1 detection., (© 2023. The Author(s).)

Over the last decades, epidemiology and functional studies have started to reveal a pivotal role of vitamin D in both type 1 and type 2 diabetes pathogenesis. Acting through the vitamin D receptor (VDR), vitamin D regulates insulin secretion in pancreatic islets and insulin sensitivity in multiple peripheral metabolic organs. In vitro studies and both T1D and T2D animal models showed that vitamin D can improve glucose homeostasis by enhancing insulin secretion, reducing inflammation, reducing autoimmunity, preserving beta cell mass, and sensitizing insulin action. Conversely, vitamin D deficiency has been shown relevant in increasing T1D and T2D incidence. While clinical trials testing the hypothesis that vitamin D improves glycemia in T2D have shown conflicting results, subgroup and meta-analyses support the idea that raising serum vitamin D levels may reduce the progression from prediabetes to T2D. In this review, we summarize current knowledge on the molecular mechanisms of vitamin D in insulin secretion, insulin sensitivity, and immunity, as well as the observational and interventional human studies investigating the use of vitamin D as a treatment for diabetes.

The size of particles determines the adsorption reaction. In this study, three different particle sizes of biochar (0.25-1 mm, 0.075-0.25 mm, <0.075 mm) were produced from rapeseed straw (SBC) and chicken manure (MBC). The biochar was mixed with high phosphorus (P) soil and low P soil and then incubated for 30 days. We conducted isothermal P sorption and desorption experiments to evaluate the effects of biochar particle size on sorption-desorption characteristics of soil P, and analyzed soil properties associated with P sorption. The results showed that P sorption capacity of SBC and MBC in the water system was highest for the smallest particle size (<0.075 mm) (SBC: 43125 mg·kg -1 , MBC: 20083 mg·kg -1 ), followed by the intermediate particle size (0.075-0.25 mm) (SBC: 37376 mg·kg -1 , MBC: 13199 mg·kg -1 ) and the largest particle size (0.25-1 mm) (SBC: 27749 mg·kg -1 , MBC: 12251 mg·kg -1 ). However, there was little difference in soil P sorption between the three particle sizes of the same biochar in the soil system. In comparison with no biochar treatment, the addition of SBC increased the Langmuir P sorption maximum ( S max ) by 236.8%-755.7%, and decreased soil P desorption rate. The addition of MBC increased S max , but the enhancement was less than that of SBC. Soil P desorption rate was increased by 7.2%-295.9%. Both SBC and MBC significantly increased the contents of soil total P, available P, and exchangeable calcium (Ca) and magnesium (Mg). The increases in Ca and Mg contents due to biochar addition was 64.0%-257.1% (SBC) and 39.1%-205.3% (MBC), respectively. The contents of soil exchangeable Ca and Mg were positively correlated with S max . These results suggested that biochar particle size had little effect on soil P sorption, but the enrichment of Ca and Mg due to biochar addition played a critical role in regulating soil P sorption. The rapeseed straw biochar had a high adsorption capacity for soil P, making it suitable for improving the P fixation capacity of soil rich in P and reducing the loss of excess P. Chicken manure biochar could be used to improve the P availability of low P soils and increase the contents of available P.

The authors demonstrate the enhanced light output from 275-nm AlGaN-based deep ultraviolet (DUV) light-emitting diode (LED) structures via the in-plane modulation of shallow photonic crystal (PC) patterns that were fabricated on the p-AlGaN contact layer surface. The employed PC lattice constants are in the range of 270-780 nm, much larger than the fundamental Bragg order lattice constant (∼95 nm). As compared to the unpatterned sample, the intensity of the top (or bottom) emission can be enhanced by up to 331% (or 246%), attributed to the high-order coherent diffraction of the internal trapped light and also the Purcell enhancement of spontaneous emission. The findings in this Letter suggest an easier way for the realization of more energy-efficient DUV LEDs which offer the advantage of high emission for various applications in disinfection and sterilization.

Purpose: To evaluate the diagnostic yield of ultrasonography (US)-guided core needle biopsy (CNB) in the diagnosis of soft tissue tumors (STTs) and to analyze the failure factors., Methods: 139 patients with STTs that underwent both US-guided CNB and surgical resection were collected retrospectively. Compared with the histopathological results of surgical resection, the biopsy failure was defined as the following conditions: indefinitive diagnosis, including insufficient samples and unknown subtypes with correct biological potential classification; wrong diagnosis, including wrong biological potential classification and wrong subtypes with correct biological potential classification. Univariate and multivariate analyses from the perspectives of histopathological, demographic and US features together with biopsy procedures were performed to determine risk factors for diagnostic failure., Results: The diagnostic yield of US-guided CNB for STTs in our study was 78.4%, but when only considering the correct biological potential classification of STTs, the diagnostic yield was 80.6%. The multivariate analysis showed that adipocytic tumors (odds ratio (OR) = 10.195, 95% confidence interval (CI): 1.062 - 97.861, p  = 0.044), vascular tumors (OR = 41.710, 95% CI: 3.126 - 556.581, p  = 0.005) and indeterminate US diagnosis (OR = 8.641, 95% CI: 1.852 - 40.303, p  = 0.006) were correlated with the diagnostic failure. The grade III vascular density (OR = 0.019, 95% CI: 0.001 - 0.273, p  = 0.007) enabled a higher diagnostic accuracy., Conclusion: US-guided CNB can be an effective modality for the diagnosis of STTs. The diagnostic yield can be increased when the tumor vascular density was grade III in Color Doppler US, but can be decreased in adipocytic tumors, vascular tumors and masses with indeterminate US diagnosis., Competing Interests: The authors declare that they have no known competing financial or personal relationships that could be viewed as influencing the work reported in this paper., (© 2023 The Author(s).)

By precisely managing fiber-optic nonlinearity with anomalous dispersion, we have demonstrated the control of generating plural few-optical-cycle pulses based on a 24-MHz Chromium:forsterite laser, allowing multicolor two-photon tissue imaging by wavelength mixing. The formation of high-order soliton and its efficient coupling to dispersive wave generation leads to phase-matched spectral broadening, and we have obtained a broadband continuum ranging from 830 nm to 1200 nm, delivering 5-nJ pulses with a pulse width of 10.5 fs using a piece of large-mode-area fiber. We locate the spectral enhancement at around 920 nm for the two-photon excitation of green fluorophores, and we can easily compress the resulting pulse close to its limited duration without the need for active pulse shaping. To optimize the wavelength mixing for sum-frequency excitation, we have realized the management of the power ratio and group delay between the soliton and dispersive wave by varying the initial pulse energy without additional delay control. We have thus demonstrated simultaneous three-color two-photon tissue imaging with contrast management between different signals. Our source optimization leads to efficient two-photon excitation reaching a 500-µm imaging depth under a low 14-mW illumination power. We believe our source development leads to an efficient and compact approach for driving multicolor two-photon fluorescence microscopy and other ultrafast investigations, such as strong-field-driven applications.

Objective: Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer, but not in normal tissues except for testis. This study aimed to investigate the expression and functional role of FMR1NB in glioma., Methods: The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry, respectively, in glioma specimens from 83 patients at follow-up. The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines A172 and U251., Results: FMR1NB mRNA and protein expression was detected in 58.8% (77/131) and 46.34% (57/123) of glioma tissues, respectively. FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome. Knockdown of FMR1NB induced apoptosis and suppressed proliferation, adhesion, migration, and invasion by modulating the expression of cyclin A, CDK2, caspase-3, E-cadherin, and N-cadherin in A172 and U251 cells., Conclusion: Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma., (© 2022. Huazhong University of Science and Technology.)

The possibility of accomplishing sustainable objectives is largely connected to the management and flourishing of an organizational system which keeps human capital engaged and committed. Our study investigated the association of inspirational leadership and innovative communication with employee engagement and commitment under the lens of leader member exchange theory. Specifically, we emphasized the mediating role of mutual trust in connection to social sustainability facets. A survey of data from employees in the manufacturing sector of Yunnan, China was utilized to test the hypothesized model. The study findings reported a significant association and came to the conclusion that a leader's inspirational behavior coupled with innovative communication is a significant predictor of engagement and commitment in socially sustainable organizations. Moreover, mutual trust significantly mediated the relationship of innovative communication and inspirational leadership with employee engagement and commitment reaching the social perspective of sustainability. The current study added to the literature of sustainable organization by pointing out the social dimensions of sustainability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Toseef, Kiran, Zhuo, Jahangir, Riaz, Wei, Ghauri, Ullah and Ahmad.)

Pancreatic β cells secrete insulin in response to glucose, a process that is regulated at multiple levels, including a network of input signals from other organ systems. Impaired islet function contributes to the pathogenesis of type 2 diabetes mellitus (T2DM), and targeting inter-organ communications, such as GLP-1 signalling, to enhance β-cell function has been proven to be a successful therapeutic strategy in the last decade. In this review, we will discuss recent advances in inter-organ communication from the metabolic, immune and neural system to pancreatic islets, their biological implication in normal pancreas endocrine function and their role in the (mal)adaptive responses of islet to nutrition-induced stress., (© 2022 Federation of European Biochemical Societies.)

P75 pan-neurotrophin receptor (p75NTR) is an important receptor for the role of neurotrophins in survival and death of neurons during development and after nerve injury. Our previous research found that the precursor of brain-derived neurotrophic factor (proBDNF) regulates pain as an inflammatory mediator. The current understanding of the role of proBDNF/p75NTR signaling pathway in inflammatory arthritis pain and rheumatoid arthritis (RA) is unclear. We recruited 20 RA patients, 20 healthy donors (HDs), and 10 osteoarthritis (OA) patients. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of proBDNF and p75NTR in synovial membrane were performed and evaluated. We next examined the mRNA and protein expression of proBDNF/p75NTR signaling pathway in peripheral blood mononuclear cells (PBMCs) and synovial tissue. ELISA and flow cytometry were assessed between the blood of RA patients and HD. To induce RA, collagen-induced arthritis (CIA) were induced in mice. We found over-synovitis of RA synovial membrane compared to OA controls in histologic sections. P75NTR and sortilin mRNA, and proBDNF protein level were significantly increased in PBMCs of RA patients compared with the HD. Consistently, ELISA showed that p75NTR, sortilin, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels in the serum of RA patients were increased compared with HD and p75NTR, sortilin were positively correlated with Disease Activity Score in 28 joints (DAS28). In addition, using flow cytometry we showed that the increased levels of proBDNF and p75NTR characterized in CD4 + and CD8 + T cells of RA patients were subsequently reversed with methotrexate (MTX) treatment. Furthermore, we found pathological changes, inflammatory pain, upregulation of the mRNA and protein expression of proBDNF/p75NTR signaling pathway, and upregulation of inflammatory cytokines in spinal cord using a well-established CIA mouse model. We showed intravenous treatment of recombinant p75ECD-Fc that biologically blocked all inflammatory responses and relieved inflammatory pain of animals with CIA. Our findings showed the involvement of proBDNF/p75NTR pathway in the RA inflammatory response and how blocking it with p75ECD-Fc may be a promising therapeutic treatment for RA., (© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Macrophages induce a number of inflammatory response genes in response to stimulation with microbial ligands. In response to endotoxin Lipid A, a gene-activation cascade of primary followed by secondary-response genes is induced. Epigenetic state is an important regulator of the kinetics, specificity, and mechanism of gene activation of these two classes. In particular, SWI/SNF chromatin-remodeling complexes are required for the induction of secondary-response genes, but not primary-response genes, which generally exhibit open chromatin. Here, we show that a recently discovered variant of the SWI/SNF complex, the noncanonical BAF complex (ncBAF), regulates secondary-response genes in the interferon (IFN) response pathway. Inhibition of bromodomain-containing protein 9 (BRD9), a subunit of the ncBAF complex, with BRD9 bromodomain inhibitors (BRD9i) or a degrader (dBRD9) led to reduction in a number of interferon-stimulated genes (ISGs) following stimulation with endotoxin lipid A. BRD9-dependent genes overlapped highly with a subset of genes differentially regulated by BET protein inhibition with JQ1 following endotoxin stimulation. We find that the BET protein BRD4 is cobound with BRD9 in unstimulated macrophages and corecruited upon stimulation to ISG promoters along with STAT1, STAT2, and IRF9, components of the ISGF3 complex activated downstream of IFN-alpha receptor stimulation. In the presence of BRD9i or dBRD9, STAT1-, STAT2-, and IRF9-binding is reduced, in some cases with reduced binding of BRD4. These results demonstrate a specific role for BRD9 and the ncBAF complex in ISG activation and identify an activity for BRD9 inhibitors and degraders in dampening endotoxin- and IFN-dependent gene expression., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

THIS ARTICLE WAS WITHDRAWN BY THE PUBLISHER IN MAY 2021

β cell dysfunction and failure are driving forces of type 2 diabetes mellitus (T2DM) pathogenesis. Investigating the underlying mechanisms of β cell dysfunction may provide novel targets for the development of next generation therapy for T2DM. Epigenetics is the study of gene expression changes that do not involve DNA sequence changes, including DNA methylation, histone modification, and non-coding RNAs. Specific epigenetic signatures at all levels, including DNA methylation, chromatin accessibility, histone modification, and non-coding RNA, define β cell identity during embryonic development, postnatal maturation, and maintain β cell function at homeostatic states. During progression of T2DM, overnutrition, inflammation, and other types of stress collaboratively disrupt the homeostatic epigenetic signatures in β cells. Dysregulated epigenetic signatures, and the associating transcriptional outputs, lead to the dysfunction and eventual loss of β cells. In this review, we will summarize recent discoveries of the establishment and disruption of β cell-specific epigenetic signatures, and discuss the potential implication in therapeutic development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sun, Wang, Obayomi and Wei.)

In macrophages, homeostatic and immune signals induce distinct sets of transcriptional responses, defining cellular identity and functional states. The activity of lineage-specific and signal-induced transcription factors are regulated by chromatin accessibility and other epigenetic modulators. Glucocorticoids are potent antiinflammatory drugs; however, the mechanisms by which they selectively attenuate inflammatory genes are not yet understood. Acting through the glucocorticoid receptor (GR), glucocorticoids directly repress inflammatory responses at transcriptional and epigenetic levels in macrophages. A major unanswered question relates to the sequence of events that result in the formation of repressive regions. In this study, we identify bromodomain containing 9 (BRD9), a component of SWI/SNF chromatin remodeling complex, as a modulator of glucocorticoid responses in macrophages. Inhibition, degradation, or genetic depletion of BRD9 in bone marrow-derived macrophages significantly attenuated their responses to both liposaccharides and interferon inflammatory stimuli. Notably, BRD9-regulated genes extensively overlap with those regulated by the synthetic glucocorticoid dexamethasone. Pharmacologic inhibition of BRD9 potentiated the antiinflammatory responses of dexamethasone, while the genetic deletion of BRD9 in macrophages reduced high-fat diet-induced adipose inflammation. Mechanistically, BRD9 colocalized at a subset of GR genomic binding sites, and depletion of BRD9 enhanced GR occupancy primarily at inflammatory-related genes to potentiate GR-induced repression. Collectively, these findings establish BRD9 as a genomic antagonist of GR at inflammatory-related genes in macrophages, and reveal a potential for BRD9 inhibitors to increase the therapeutic efficacies of glucocorticoids., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Objective: To compare the clinical effects of cervical decompression first, lumbar decompression first, or simultaneous decompression of both lesions in the treatment of tandem spinal stenosis (TSS)., Methods: This is a retrospective analysis. From January 2013 to December 2018, 51 TSS patients underwent our surgery and postoperative investigation. Among the 51 subjects, 27 females and 24 males, aged 49-77 years with an average age of 66.3 ± 6.8, were selected. According to the different operation sequences, all patients were divided into three groups. In simultaneous operation group, five patients underwent cervical and lumbar vertebrae surgery at the same time. In first cervical surgery group, 28 patients underwent cervical vertebra surgery first, followed by lumbar spine surgery after a period of recovery. And in first lumbar surgery group, 18 patients underwent lumbar vertebrae surgery first. The choice for neck surgery is posterior cervical single-door vertebroplasty, the surgery of lumber is plate excision and decompression needle-rod system internal fixation. The outcome measures are visual analogue scale (VAS), Japanese Orthopaedic Association cervical (JOA-C) and lumbar (JOA-L) scores, which were assessed at 3 months and 1 year after the operation by telephone interview. In addition, operative time, estimated blood loss, and hospital stay were also recorded., Results: All the patients in the study had surgery performed successfully by the same group of orthopaedic surgeons. The preoperative VAS scores of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 8.00 ± 1.00, 8.36 ± 0.68, and 8.17 ± 0.71 (P > 0.05). The preoperative JOA-C scores were 7.00 ± 2.35, 6.54 ± 1.53, and 7.83 ± 1.04 (P < 0.05). And the preoperative JOA-L scores were 7.20 ± 2.17, 4.64 ± 2.36, and 5.78 ± 1.22 respectively (P < 0.05). During the final 1-year follow-up, the JOA-C improvement rates of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 85.68% ± 5.44%, 84.27% ± 5.02%, and 83.34% ± 10.25%, respectively (P > 0.05), and the JOA-L improvement rates were 80.04% ± 3.35%, 81.65% ± 3.74%, and 80.21% ± 4.76% (P > 0.05). The difference among them was not statistically significant. In addition, operation time (OP), blood loss (BL), and hospital stay (HS) in the simultaneous operation group were 245.00 ± 5.00 min, 480.00 ± 27.39 mL, and 16.60 ± 0.55 days, respectively. While those parameters in the first cervical surgery group were 342.50 ± 18.18 min, 528.21 ± 43.97 mL, and 22.75 ± 2.15 days, and in the first lumbar surgery group they were 346.11 ± 24.77 min, 519.44 ± 43.99 mL, and 22.89 ± 1.64 days. The average blood loss in simultaneous operation group was less (P > 0.05); meanwhile, the operation time and hospital stay time were significantly shorter in the simultaneous operation group than in the first cervical surgery group and first lumbar surgery group (P < 0.05). Only one case of fat liquefaction occurred in first cervical surgery group, which healed spontaneously after a regular change of dressing for 1 month., Conclusions: Under the condition of ensuring the surgical effect, the choice of staged surgery or concurrent surgery according to the patients' own symptoms of cervical and lumbar symptoms could both obtain satisfactory results, and the damage of simultaneous surgery was less than that of staged surgery., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Renal fibrosis, the leading cause of end-stage renal disease and in which epithelial-mesenchymal transition (EMT) plays a central role, has a complex pathogenesis that is not fully understood. Therefore, we investigated the role of the long noncoding RNA LUCAT1 in the EMT of renal tubular epithelial cells under high-glucose (HG) conditions and the underlying mechanism involved. In this study, we established HG and normal glucose groups of HK-2 cells by treating HK-2 cells 30.0 or 5.5 mmol/L glucose, respectively. To investigate the roles of LUCAT1 and miR-199a-5p in HG-induced EMT, we transfected the HG group with negative control small interfering RNA (siRNA), siRNA targeting LUCAT1, negative control microRNA, or an miR-199a-5p mimic. The results of the quantitative reverse transcription PCR indicated that the LUCAT1 level in the HG group was increased, whereas the miR-199a-5p level was decreased. The EMT in the cells was induced by treatment with HG but was weakened by LUCAT1 knockdown or miR-199a-5p overexpression, which both also inhibited the HG-induced phosphorylation of SMAD3. Moreover, LUCAT1 and ZEB1 mRNA comprised the same microRNA response elements of miR-199a-5p. LUCAT1 knockdown had no effect on the miR-199a-5p level but decreased the HG-induced upregulation of ZEB1. In conclusion, HG conditions induced the upregulation of LUCAT1, and LUCAT1 knockdown inhibited the EMT in HG-treated HK-2 cells. LUCAT1 likely promotes HG-induced EMT through ZEB1 by sponging miR-199a-5p., Competing Interests: The authors do not have any conflicts of interest to declare., (Copyright © 2020 Li-Cai Zhang et al.)

Islets derived from stem cells hold promise as a therapy for insulin-dependent diabetes, but there remain challenges towards achieving this goal 1-6 . Here we generate human islet-like organoids (HILOs) from induced pluripotent stem cells and show that non-canonical WNT4 signalling drives the metabolic maturation necessary for robust ex vivo glucose-stimulated insulin secretion. These functionally mature HILOs contain endocrine-like cell types that, upon transplantation, rapidly re-establish glucose homeostasis in diabetic NOD/SCID mice. Overexpression of the immune checkpoint protein programmed death-ligand 1 (PD-L1) protected HILO xenografts such that they were able to restore glucose homeostasis in immune-competent diabetic mice for 50 days. Furthermore, ex vivo stimulation with interferon-γ induced endogenous PD-L1 expression and restricted T cell activation and graft rejection. The generation of glucose-responsive islet-like organoids that are able to avoid immune detection provides a promising alternative to cadaveric and device-dependent therapies in the treatment of diabetes.

This study evaluates the efficacy and safety of bevacizumab (BEV) in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BM) by performing meta-analyses of response and survival indices. Seventeen studies were included. BEV treatment was associated with a lower new BM incidence (hazard ratio: 0.30 [95% confidence interval (CI): 0.14, 0.46]) during follow-up. Disease control rate (DCR) of BEV-treated patients with BM was 91% [95% CI: 85, 95]. However, intracranial DCR was relatively higher (94% [95% CI: 87, 98]) than extracranial DCR (86% [95% CI: 74, 96]). DCR of NSCLC patients with BM was significantly better with BEV than with control therapies (odds ratio: 2.71 [95% CI: 1.26, 5.86], P = 0.01). Progression-free survival (PFS) of BEV-treated patients with and without BM was 7.1 months [95% CI: 6.2, 8.0] and 7.4 months [95% CI: 6.3, 8.4], respectively. Intracranial PFS of BEV-treated patients with BM was 8.0 months [95% CI: 6.0, 10.0]. Overall survival of BEV-treated NSCLC patients with and without BM was 13.5 months [95% CI: 11.4, 15.6] and 12.5 months [95% CI: 10.2, 14.8], respectively. The incidence of bleeding/hemorrhage in the central nervous system was 1% with BEV treatment., Competing Interests: Conflict of interest: All authors declare that they have no competing interests., (© 2020 Ping Liang et al., published by De Gruyter.)

It is a longstanding debate on the absence of threshold for susceptible-infected-susceptible (SIS) model on networks with finite second order moment of degree distribution. The eigenvector localization of the adjacency matrix for a network gives rise to the inactive Griffiths phase featuring slow decay of the activity localized around highly connected nodes due to the dynamical fluctuation. We show how it dramatically changes our understanding of the SIS model, opening up new possibilities for the debate. We derive the critical condition for Griffiths to active phase transition: on average, an infected node can further infect another one in the characteristic lifespan of the star subgraph composed of the node and its nearest neighbors. The system approaches the critical point of avoiding the irreversible dynamical fluctuation and the trap of absorbing state. As a signature of the phase transition, the infection density of a node is not only proportional to its degree, but also proportional to the exponentially growing lifespan of the star. And the divergence of the average lifespan of the stars is responsible for the vanishing threshold in the thermodynamic limit. The eigenvector localization exponentially reinforces the infection of highly connected nodes, while it inversely suppresses the infection of small-degree nodes.

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

Implementing selective-area p-type doping through ion implantation is the most attractive choice for the fabrication of GaN-based bipolar power and related devices. However, the low activation efficiency of magnesium (Mg) ions and the inevitable surface decomposition during high-temperature activation annealing process still limit the use of this technology for GaN-based devices. In this work, we demonstrate successful p-type doping of GaN using protective coatings during a Mg ion implantation and thermal activation process. The p-type conduction of GaN is evidenced by the positive Seebeck coefficient obtained during thermopower characterization. On this basis, a GaN p-i-n diode is fabricated, exhibiting distinct rectifying characteristics with a turn-on voltage of 3 V with an acceptable reverse breakdown voltage of 300 V. Electron beam induced current (EBIC) and electroluminescent (EL) results further confirm the formation of p-type region due to Mg ion implantation and subsequent thermal activation. This repeatable and uniform manufacturing process can be implemented in mass production of GaN devices for versatile power and optoelectronic applications.

Covering a network with minimum number of boxes is critical for using the renormalization technique to explore the network configuration space in a multiscale fashion. Here, we propose a versatile methodology composed of flexible representation and sampling of boxes, which have so far received scant attention, and the strategy of selecting boxes to cover the network. It is exemplified via random box sampling strategies and greedy methods to select boxes. We show that the key to substantially reduce the number of boxes is to give the selection priority to those boxes containing nodes that are not included in boxes bigger than themselves. Our algorithm achieves the improvement of diminishing the number of boxes amounting to nearly 25% compared with these well known algorithms.

Semiconductor nanowire (NW) lasers have attracted considerable research effort given their excellent promise for nanoscale photonic sources. However, NW lasers currently exhibit poor directionality and high threshold gain, issues critically limiting their prospects for on-chip light sources with extremely reduced footprint and efficient power consumption. Here, we propose a new design and experimentally demonstrate a vertically emitting indium phosphide (InP) NW laser structure showing high emission directionality and reduced energy requirements for operation. The structure of the laser combines an InP NW integrated in a cat's eye (CE) antenna. Thanks to the antenna guidance with broken asymmetry, strong focusing ability, and high Q-factor, the designed InP CE-NW lasers exhibit a higher degree of polarization, narrower emission angle, enhanced internal quantum efficiency, and reduced lasing threshold. Hence, this NW laser-antenna system provides a very promising approach toward the achievement of high-performance nanoscale lasers, with excellent prospects for use as highly localized light sources in present and future integrated nanophotonics systems for applications in advanced sensing, high-resolution imaging, and quantum communications.

Objective: To investigate the efficiency of inducing CIK from peripheral blood mononuclear cells(PBMNC) by using immune cell serum replacement(immune cell SR), so as to provide a new strategy for the industrialized production of immune cells., Methods: The PBMNC of healthy volunteers were collected, and these cells were thawed after short-term cryopreservation and cultured to induce CIK cells. The cells viability was measured by trypan blue exclusion, the phenotypes were analyzed by flow cytometry, and the cytotoxicity was determined by Calcein-AM/PI double staining., Results: In cryopreserved PBMNC, the control group cells failed to normally proliferate. Cell proliferation ratio was low in 2% SR group in comparison with the fresh group, and the difference was significant (P<0.05), however, differences were not statistically significant between 5% SR and fresh group or between 10% AP and fresh group. CD3 + , CD3 + CD8 + and CD3 + CD56 + cell subsets were not significantly different before and after cryopreservation (P>0.05). After being cultured, CD3 + , CD3 + CD4 + , CD3 + CD8 + , CD3 + CD56 + and CD3 - CD56 + subsets and the cytotoxicity in vitro were not significantly different among all group(P>0.05)., Conclusion: 5% SR without the protein of animal origin can be safely used as a substitute for autologous plasma in CIK induced from cryopreserved PBMNC by culture, thus providing a basis for the application of cryopreservation technique of immune cells to cell therapy.

A primary cause of disease progression in type 2 diabetes (T2D) is β cell dysfunction due to inflammatory stress and insulin resistance. However, preventing β cell exhaustion under diabetic conditions is a major therapeutic challenge. Here, we identify the vitamin D receptor (VDR) as a key modulator of inflammation and β cell survival. Alternative recognition of an acetylated lysine in VDR by bromodomain proteins BRD7 and BRD9 directs association to PBAF and BAF chromatin remodeling complexes, respectively. Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Devising effective strategies for hindering the propagation of viruses and protecting the population against epidemics is critical for public security and health. Despite a number of studies based on the susceptible-infected-susceptible (SIS) model devoted to this topic, we still lack a general framework to compare different immunization strategies in completely random networks. Here, we address this problem by suggesting a novel method based on heterogeneous mean-field theory for the SIS model. Our method builds the relationship between the thresholds and different immunization strategies in completely random networks. Besides, we provide an analytical argument that the targeted large-degree strategy achieves the best performance in random networks with arbitrary degree distribution. Moreover, the experimental results demonstrate the effectiveness of the proposed method in both artificial and real-world networks.

The aim of the present study was to evaluate the clinical importance of melanoma-associated antigen D4 (MAGE-D4) expression in glioma, and to identify it as a valuable prognostic biomarker and therapeutic target. To achieve this, the expression of MAGE-D4 protein in 124 tumor tissues from patients with glioma was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC), and the associations between MAGE-D4expression and clinicopathological factors were evaluated. The survival analysis demonstrated the significant prognostic value of MAGE-D4 in glioma using follow-up data. RT-qPCR and IHC analysis confirmed that MAGE-D4 mRNA and protein expression levels were significantly increased in glioma tissues compared with those in normal brain tissues. The present study demonstrated that the percentage of glioma tissues with high expression of MAGE-D4 mRNA was 67.74%, and the percentage positive for MAGE-D4 protein expression was 78.23%. All patients with high MAGE-D4 expression in cancerous tissues experienced significantly reduced median overall survival (OS; 18.00 vs. 33.29 months; P<0.001) and recurrence-free survival (RFS; 12.7 vs. 28.3 months; P<0.001) times compared with those with low MAGE-D4 expression. In the patients with lower grade glioma [World Health Organization (WHO), I-II], similar results were obtained for the OS (26.11 vs. 57.85 months; P=0.013) and RFS (22.7 vs. 55.3 months; P=0.010) times; however, in patients with high-grade glioma (WHO, III-IV), there were no significant differences between high and low MAGE-D4 expression levels with regard to OS and RFS times (P>0.05). Multivariate analysis indicated that high MAGE-D4 protein expression was an important independent prognostic factor for patients with glioma (hazard ratio, 2.384; P=0.005), and was significantly associated with higher grade glioma (P<0.001). These results indicated that MAGE-D4 may be a potential biomarker for glioma and an important prognostic factor for patients with new or recurring glioma.

PGC1α is a pleiotropic co-factor that affects angiogenesis, mitochondrial biogenesis, and oxidative muscle remodeling via its association with multiple transcription factors, including the master oxidative nuclear receptor ERRγ. To decipher their epistatic relationship, we explored ERRγ gain of function in muscle-specific PGC1α/β double-knockout (PKO) mice. ERRγ-driven transcriptional reprogramming largely rescues muscle damage and improves muscle function in PKO mice, inducing mitochondrial biogenesis, antioxidant defense, angiogenesis, and a glycolytic-to-oxidative fiber-type transformation independent of PGC1α/β. Furthermore, in combination with voluntary exercise, ERRγ gain of function largely restores mitochondrial energetic deficits in PKO muscle, resulting in a 5-fold increase in running performance. Thus, while PGC1s can interact with multiple transcription factors, these findings implicate ERRs as the major molecular target through which PGC1α/β regulates both innate and adaptive energy metabolism., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Total knee arthroplasty (TKA) is one of the most common joint replacement surgeries in the United States. Postoperative pain is still a major complication after TKA. Electroacupuncture (EA) has been commonly used in clinical practice for pain after TKA, but its effects and safety remain uncertain. This protocol is described for a systematic review to investigate the beneficial effects and safety of EA for postoperative pain after TKA., Methods: Randomized controlled trials (RCTs) related to EA treatment of pain after TKA will be collected from 3 databases of English literature, namely PubMed, Embase, and Cochrane Library, and 4 databases of Chinese literatures, namely CBM, CNKI, VIP and Wanfang database. The retrieved trials will be those published from the time when the respective databases were built to January 2018. The therapeutic effects according to the change from baseline in the amount of pain measured by the visual analogue scale (VAS) or numerical rating scale, will be accepted as the primary outcomes. We will use RevMan V.5.3 software as well to compute the data synthesis carefully when a meta-analysis is allowed., Results: This systematic review and meta-analysis will provide a high-quality synthesis of current evidence of EA for pain after TKA., Conclusion: The conclusion of our systematic review will provide evidence to judge whether EA is an effective intervention for patient with postoperative pain after TKA., Prospero Registration Number: PROSPERO CRD 42018082407.

In this study, a novel method to treat the persulfate-ZVI dewatered WAS by producing a magnetic biochar as an environmentally friendly biosorbent (nZVI-WSBC) to remove heavy metals (HMs) from wastewaters was proposed. The nZVI-WSBC exhibited good adsorption property of Pb 2+ and the adsorption isotherm data were fitted well to Langmuir isotherm. Corresponding reaction kinetics fitted well with the pseudo second-order adsorption model. Notably, nZVI-WSBC was successfully used for efficient removal of HMs from real. This study comprehensively demonstrates the mechanisms between Pb 2+ and nZVI-WSBC surfaces, providing a breakthrough in making a sustainable biosorbent from the dewatered iron-containing WAS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bimetallic oxide CuFeO 2 as a new heterogeneous catalyst has shown much higher catalytic ability for activating peroxide than single-metal oxides. The present work demonstrated a synergistic microwave (MW) enhanced Fenton-like process with CuFeO 2 for rapid decolorization of azo dye Orange G (OG). The MW irradiation dramatically enhanced the OG degradation efficiency, achieving 99.9% decolorization within 15min at pH5. The XRD analysis of reused CuFeO 2 , together with metal leaching tests, indicated merits of recycling for CuFeO 2 . The subsequent surface element analysis by XPS for fresh and used CuFeO 2 showed a complex network for reactions between copper-iron redox pairs and surface hydroxyl groups, leading to a synergistic Fenton-like system accelerated by MW irradiation. In the CuFeO 2 initiated Fenton-like reactions, several oxidant species (i.e., OH, O 2 - , electron hole, and Fe IV O) responsible to the OG oxidation were identified by quenching experiments, showing the MW generated high temperature and "hot spots" enhanced the yield of OH by generation of electron-hole pairs. Further, the 26 detected degradation products confirmed the OH dominant oxidation of OG. This study shows that the MW-enhanced Fenton-like reaction using CuFeO 2 has potential applications for rapid decolorization of dye effluent., (Copyright © 2016 Elsevier B.V. All rights reserved.)

An ultrasonic image speckle noise removal method by using total least squares model is proposed and applied onto images of cardiovascular structures such as the carotid artery. On the basis of the least squares principle, the related principle of minimum square method is applied to cardiac ultrasound image speckle noise removal process to establish the model of total least squares, orthogonal projection transformation processing is utilized for the output of the model, and the denoising processing for the cardiac ultrasound image speckle noise is realized. Experimental results show that the improved algorithm can greatly improve the resolution of the image, and meet the needs of clinical medical diagnosis and treatment of the cardiovascular system for the head and neck. Furthermore, the success in imaging of carotid arteries has strong implications in neurological complications such as stroke.

Some real-world networks are shown to be fractal or self-similar. It is widespread that such a phenomenon originates from the repulsion between hubs or disassortativity. Here we show that this common belief fails to capture the causality. Our key insight to address it is to pinpoint links critical to fractality. Those links with small edge betweenness centrality (BC) constitute a special architecture called fractal reference system, which gives birth to the fractal structure of those reported networks. In contrast, a small amount of links with high BC enable small-world effects, hiding the intrinsic fractality. With enough of such links removed, fractal scaling spontaneously arises from nonfractal networks. Our results provide a multiple-scale view on the structure and dynamics and place fractality as a generic organizing principle of complex networks on a firmer ground.

Searching for new regulators of autophagy involved in selective dopaminergic (DA) neuron loss is a hallmark in the pathogenesis of Parkinson disease (PD). We here report that an endoplasmic reticulum (ER)-associated transmembrane protein SLC35D3 is selectively expressed in subsets of midbrain DA neurons in about 10% TH (tyrosine hydroxylase)-positive neurons in the substantia nigra pars compacta (SNc) and in about 22% TH-positive neurons in the ventral tegmental area (VTA). Loss of SLC35D3 in ros (roswell mutant) mice showed a reduction of 11.9% DA neurons in the SNc and 15.5% DA neuron loss in the VTA with impaired autophagy. We determined that SLC35D3 enhanced the formation of the BECN1-ATG14-PIK3C3 complex to induce autophagy. These results suggest that SLC35D3 is a new regulator of tissue-specific autophagy and plays an important role in the increased autophagic activity required for the survival of subsets of DA neurons.

Pancreatic β cells undergo postnatal maturation to achieve maximal glucose-responsive insulin secretion, an energy intensive process. We identify estrogen-related receptor γ (ERRγ) expression as a hallmark of adult, but not neonatal β cells. Postnatal induction of ERRγ drives a transcriptional network activating mitochondrial oxidative phosphorylation, the electron transport chain, and ATP production needed to drive glucose-responsive insulin secretion. Mice deficient in β cell-specific ERRγ expression are glucose intolerant and fail to secrete insulin in response to a glucose challenge. Notably, forced expression of ERRγ in iPSC-derived β-like cells enables glucose-responsive secretion of human insulin in vitro, obviating in vivo maturation to achieve functionality. Moreover, these cells rapidly rescue diabetes when transplanted into β cell-deficient mice. These results identify a key role for ERRγ in β cell metabolic maturation, and offer a reproducible, quantifiable, and scalable approach for in vitro generation of functional human β cell therapeutics., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Engineering metamaterials with tunable resonances are of great importance for improving the functionality and flexibility of terahertz (THz) systems. An ongoing challenge in THz science and technology is to create large-area active metamaterials as building blocks to enable efficient and precise control of THz signals. Here, an active metamaterial device based on enhancement-mode transparent amorphous oxide thin-film transistor arrays for THz modulation is demonstrated. Analytical modelling based on full-wave techniques and multipole theory exhibits excellent consistent with the experimental observations and reveals that the intrinsic resonance mode at 0.75 THz is dominated by an electric response. The resonant behavior can be effectively tuned by controlling the channel conductivity through an external bias. Such metal/oxide thin-film transistor based controllable metamaterials are energy saving, low cost, large area and ready for mass-production, which are expected to be widely used in future THz imaging, sensing, communications and other applications.

We are only beginning to understand the higher-order chromatin structure of pluripotent stem cells and its relevance to cell fate. Three recent studies used different approaches to reconstruct the 3D chromatin landscape of naive and primed pluripotent cells, unveiling common features as well as differences between these two states., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Laparoscopic ultrasound (LUS) has been widely utilized as a surgical aide in general, urological, and gynecological applications. Our study summarizes the clinical applications of laparoscopic ultrasonography in laparoscopic gynecologic surgery. Retrospective analyses were performed on 42 women subjects using laparoscopic surgery during laparoscopic extirpation and excision of gynecological tumors in our hospital from August 2011 to August 2013. Specifically, the Esaote 7.5 × 10 MHz laparoscopic transducer was used to detect small residual lesions, as well as to assess, locate and guide in removing the lesions during laparoscopic operations. The findings of LUS were compared with those of preoperative trans-vaginal ultrasound, postoperative, and pathohistological examinations. In addition, a novel method for lesion segmentation was proposed in order to facilitate the laparoscopic gynecologic surgery. In our experiment, laparoscopic operation was performed using a higher frequency and more close to pelvic organs via laparoscopic access. LUS facilitates the ability of gynaecologists to find small residual lesions under laparoscopic visualization and their accurate diagnosis. LUS also helps to locate residual lesions precisely and provides guidance for the removal of residual tumor and eliminate its recurrence effectively. Our experiment provides a safer and more valuable assistance for clinical applications in laparoscopic gynecological surgery that are superior to trans-abdominal ultrasound and trans-vaginal ultrasound.

In laparoscopic gynecologic surgery, ultrasound has been typically implemented to diagnose urological and gynecological conditions. We applied laparoscopic ultrasonography (using Esaote 7.5~10MHz laparoscopic transducer) on the retrospective analyses of 42 women subjects during laparoscopic extirpation and excision of gynecological tumors in our hospital from August 2011 to August 2013. The objective of our research is to develop robust segmentation technique for isolation and identification of the uterus from the ultrasound images, so as to assess, locate and guide in removing the lesions during laparoscopic operations. Our method enables segmentation of the uterus by the active contour algorithm. We evaluated 42 in-vivo laparoscopic images acquired from the 42 patients (age 39.1 ± 7.2 years old) and selected images pertaining to 4 cases of congenital uterine malformations and 2 cases of pelvic adhesions masses. These cases (n = 6) were used for our uterus segmentation experiments. Based on them, the active contour method was compared with the manual segmentation method by a medical expert using linear regression and the Bland-Altman analysis (used to measure the correlation and the agreement). Then, the Dice and Jaccard indices are computed for measuring the similarity of uterus segmented between computational and manual methods. Good correlation was achieved whereby 84%-92% results fall within the 95% confidence interval in the Student t-test) and we demonstrate that the proposed segmentation method of uterus using laparoscopic images is effective.

Aim: To investigate the effects of salvianolic acid B (Sal B) on the morphological characteristics and functions of liver mitochondria of rats with nonalcoholic steatohepatitis (NASH)., Methods: A total of 60 male Sprague-Dawley rats were randomly divided into three groups: (1) a normal group fed a normal diet; (2) an NASH model group; and (3) a Sal B-treated group fed a high-fat diet. Two rats from each group were executed at the end of the 12th week to detect pathological changes. The rats in the Sal B-treated group were gavaged with 20 mL/kg Sal B (1 mg/mL) daily. The model group received an equal volume of distilled water as a control. At the end of the 24th weekend, the remaining rats were executed. Serum biochemical parameters and liver histological characteristics were observed. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver were determined. Protein expression of CytC and caspase-3 was determined by immunohistochemistry. The mRNA transcripts of mitofusin-2 (Mfn2) and NF-κB in the liver tissue were detected by real-time PCR. Mitochondrial membrane potential was detected using a fluorescence spectrophotometer. Mitochondrial respiratory function was detected using a Clark oxygen electrode., Results: The model group showed significantly higher ALT, AST, TG, TC and MDA but significantly lower SOD than the normal group. In the model group, the histological characteristics of inflammation and steatosis were also evident; mitochondrial swelling and crest were shortened or even disappeared. CytC (18.46 ± 1.21 vs 60.01 ± 3.43, P < 0.01) and caspase-3 protein expression (30.26 ± 2.56 vs 83.31 ± 5.12, P < 0.01) increased significantly. The mRNA expression of NF-κB increased (0.81 ± 0.02 vs 0.91 ± 0.03, P < 0.05), whereas the mRNA expression of Mfn2 decreased (1.65 ± 0.31 vs 0.83 ± 0.16, P < 0.05). Mitochondrial membrane potential also decreased and breathing of rats was weakened. Steatosis and inflammation degrees in the treatment group were significantly alleviated compared with those of the model group. In the treatment group, mitochondrial swelling was alleviated. CytC (60.01 ± 3.43 vs 30.52 ± 2.01, P < 0.01) and caspase-3 protein expression (83.31 ± 5.12 vs 40.15 ± 3.26, P < 0.01) significantly decreased. The mRNA expression of NF-κB also decreased (0.91 ± 0.03 vs 0.74 ± 0.02, P < 0.01), whereas the mRNA expression of Mfn2 increased (0.83 ± 0.16 vs 1.35 ± 0.23, P < 0.01). Mitochondrial membrane potential increased and respiratory function was enhanced., Conclusion: Sal B can treat NASH by protecting the morphological characteristics and functions of liver mitochondria, regulating lipid metabolism, controlling oxidative stress and lipid peroxidation and inhibiting apoptosis.