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Mycobacterium tuberculosis (MTB) is a pathogen that is known for its ability to persist in harsh environments and cause chronic infections. Understanding the regulatory networks of MTB is crucial for developing effective treatments. Small regulatory RNAs (sRNAs) play important roles in gene expression regulation in all kingdoms of life, and their classification based solely on genomic location can be imprecise due to the computational-based prediction of protein-coding genes in bacteria, which often neglects segments of mRNA such as 5’UTRs, 3’UTRs, and intercistronic regions of operons. To address this issue, our study simultaneously discovered genomic features such as TSSs, UTRs, and operons together with sRNAs in the M. tuberculosis H37Rv strain (ATCC 27294) across multiple stress conditions. Our analysis identified 1,376 sRNA candidates and 8,173 TSSs in MTB, providing valuable insights into its complex regulatory landscape. TSS mapping enabled us to classify these sRNAs into more specific categories, including promoter-associated sRNAs, 5’UTR-derived sRNAs, 3’UTR-derived sRNAs, true intergenic sRNAs, and antisense sRNAs. Three of these sRNA candidates were experimentally validated using 3’-RACE-PCR: predictedRNA_0240, predictedRNA_0325, and predictedRNA_0578. Future characterization and validation are necessary to fully elucidate the functions and roles of these sRNAs in MTB. Our study is the first to simultaneously unravel TSSs and sRNAs in MTB and demonstrate that the identification of other genomic features, such as TSSs, UTRs, and operons, allows for more accurate and specific classification of sRNAs. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OV) is a highly aggressive malignancy with poor prognosis due to recurrence and drug resistance. Therefore, it is imperative to investigate the key molecular mechanisms underlying OV progression in order to develop promising diagnostic and therapeutic interventions. Although the importance of hematological and neurological expressed 1 (HN1) protein in hemopoietic cell and neurological development has been well-established, its function in cancer, particularly in OV, remains uncertain. In this study, we compared the expression of HN1 in ovarian cancers and para-tumor tissues and predicted potential related signaling pathways through enrichment analysis. In order to confirm the role of HN1 in vitro and vivo, we carried out a variety of experiments including bioinformation analysis, colony formation, flow cytometry analysis, and subcutaneous tumor models. The results demonstrated that HN1 was upregulated in OV and was negatively associated with clinical prognosis. Moreover, we observed that HN1 enhances cell proliferation, migration, and drug resistance, while suppressing apoptosis in OV cells. Notably, we discovered that HN1 functions as a novel regulator of mTOR pathways. Our findings suggest that HN1-mediated mTOR regulation facilitates OV advancement and targeting HN1 could provide a promising therapeutic approach for clinical OV treatment. [ABSTRACT FROM AUTHOR]

This study delves into expressing primary emotions anger, happiness, sadness, and fear through drawings. Moving beyond the well-researched color-emotion link, it explores under-examined aspects like spatial concepts and drawing styles. Employing Python and OpenCV for objective analysis, we make a breakthrough by converting subjective perceptions into measurable data through 728 digital images from 182 university students. For the prominent color chosen for each emotion, the majority of participants chose red for anger (73.11%), yellow for happiness (17.8%), blue for sadness (51.1%), and black for fear (40.7%). Happiness led with the highest saturation (68.52%) and brightness (75.44%) percentages, while fear recorded the lowest in both categories (47.33% saturation, 48.78% brightness). Fear, however, topped in color fill percentage (35.49%), with happiness at the lowest (25.14%). Tangible imagery prevailed (71.43–83.52%), with abstract styles peaking in fear representations (28.57%). Facial expressions were a common element (41.76–49.45%). The study achieved an 81.3% predictive accuracy for anger, higher than the 71.3% overall average. Future research can build on these results by improving technological methods to quantify more aspects of drawing content. Investigating a more comprehensive array of emotions and examining factors influencing emotional drawing styles will further our understanding of visual-emotional communication. [ABSTRACT FROM AUTHOR]

This study explored the performance of electroplated grinding tools electroplated with single and dual-layer diamond particles (DPs). These tools were fabricated through a three-step electroplating process, involving Ni-undercoating, Ni-diamond co-electroplating, and Ni–B strengthen-electroplating, on AISI 440C steel rods. Grinding tool performance was assessed based on the maximum achievable ground length from slot-grinding Al2O3 plates. Dual-layer DP composite deposits with varying secondary Ni-undercoat thicknesses (0, 12, and 24 μm) all exhibited substantial improvements in tool's grinding performance due to their self-sharpening effect. As the secondary Ni-undercoat thickness increased, the maximum ground length increased significantly, reaching values of 2234, 5366, and 9632 mm, respectively. Raman spectroscopy revealed the transformation of outer DPs into graphite structures during grinding tests, indicating the formation and subsequent delamination of these DPs, leading to morphological changes. Tool failure was attributed to the fatigue rupture of the AISI 440C tool shaft. During slot grinding, the tool shaft experienced cyclic stress due to a consistent grinding speed of 2 mm/min and spindle rotation of 15,000 rpm. High-cycle fatigue fracture, characterized by the absent of plastic deformation and a nearly perpendicular crack to the tool shaft, occurred after over 107 stress cycles. [ABSTRACT FROM AUTHOR]

Background: Uptake of lung cancer screening (LCS) has been slow with less than 20% of eligible people who currently or formerly smoked reported to have undergone a screening CT. Objective: To determine individual-, health system-, and neighborhood-level factors associated with LCS uptake after a provider order for screening. Design and Subjects: We conducted an observational cohort study of screening-eligible patients within the Population-based Research to Optimize the Screening Process (PROSPR)–Lung Consortium who received a radiology referral/order for a baseline low-dose screening CT (LDCT) from a healthcare provider between January 1, 2015, and June 30, 2019. Main Measures: The primary outcome is screening uptake, defined as LCS-LDCT completion within 90 days of the screening order date. Key Results: During the study period, 18,294 patients received their first order for LCS-LDCT. Orders more than doubled from the beginning to the end of the study period. Overall, 60% of patients completed screening after receiving their first LCS-LDCT order. Across health systems, uptake varied from 41 to 87%. In both univariate and multivariable analyses, older age, male sex, former smoking status, COPD, and receiving care in a centralized LCS program were positively associated with completing LCS-LDCT. Unknown insurance status, other or unknown race, and lower neighborhood socioeconomic status, as measured by the Yost Index, were negatively associated with screening uptake. Conclusions: Overall, 40% of patients referred for LCS did not complete a LDCT within 90 days, highlighting a substantial gap in the lung screening care pathway, particularly in decentralized screening programs. [ABSTRACT FROM AUTHOR]

To report our institutional experience and the medium-term outcomes of utilizing robotic-assisted laparoscopic surgery (RALS) in patients with Wilms' tumor (WT). The robotic surgical interventions include nephron-sparing surgery (RAL-NSS), radical nephrectomy (RAL-RN), and nephrectomy with inferior vena cava thrombectomy (RAL-N-IVCT). We retrospectively collected medical records of WT patients who underwent RALS in our center between August 2019 and February 2022. Patients' baseline demographics, preoperative parameters, and perioperative/postoperative data were recorded and analyzed. Follow-up results were collected to evaluate the oncological outcomes. A total of 12 patients (13 sides) with a median age of 30 (IQR: 19.5–45.5) months were included. All operations were successfully completed without conversion. Seven patients received preoperative chemotherapy. Distribution of surgical interventions was as follows: five patients underwent RAL-RN, five received RAL-NSS, one with bilateral WT underwent concurrent RAL-RN and RAL-NSS, and one received RAL-RN-IVCT post preoperative chemotherapy. Postoperative chemotherapy was conducted in ten patients. The estimated intraoperative blood loss was 27 ± 4.0 ml for the RAL-NSS group, 41.67 ± 12.13 ml for the RAL-RN group, and 350 ml for the RAL-RN-IVCT groups, respectively. The median perioperative serum creatinine levels were 32.5 (IQR: 30.75–39.5) μmol/l preoperatively and 35 (IQR: 31.75–38.5) μmol/l postoperatively, which showed no significant difference. No positive lymph nodes were detected. Postoperative chemotherapy was performed according to the tumor volume and pathological findings. The median follow-up time was 17.5 (15.8–22.3) months. During this interval, neither distant metastasis nor recurrence was identified. Based on our medium-term follow-up observations, RAL-NSS, RAL-RN, and RAL-RN-IVCT exhibit promising feasibility and safety profiles in the therapeutic landscape of WT. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), a chronic degenerative disease characterized mainly by damage to the articular cartilage, is increasingly relevant to the pathological processes of senescence, apoptosis, autophagy, proliferation, and differentiation of chondrocytes. Clinical strategies for osteoarthritis can only improve symptoms and even along with side effects due to age, sex, disease, and other factors. Therefore, there is an urgent need to identify new ideas and targets for current clinical treatment. The tumor suppressor gene p53, which has been identified as a potential target for tumor therapeutic intervention, is responsible for the direct induction of the pathological processes involved in OA modulation. Consequently, deciphering the characteristics of p53 in chondrocytes is essential for investigating OA pathogenesis due to p53 regulation in an array of signaling pathways. This review highlights the effects of p53 on senescence, apoptosis, and autophagy of chondrocytes and its role in the development of OA. It also elucidates the underlying mechanism of p53 regulation in OA, which may help provide a novel strategies for the clinical treatment of OA. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) plays a crucial role in the development and functional homeostasis of the central nervous system. The fat mass and obesity-associated (FTO) gene, which is highly expressed in the hypothalamus, is closely related to female pubertal development. In this study, we found that m6A methylation decreased in the hypothalamus gradually with puberty and decreased in female rats with precocious puberty. FTO expression was increased at the same time. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed that the m6A methylation of PLCβ3, a key enzyme of the Ca2+ signalling pathway, was decreased significantly in the hypothalamus in precocious rats. Upregulating FTO increased PLCβ3 expression and activated the Ca2+ signalling pathway, which promoted GnRH expression. Dual-luciferase reporter and MeRIP-qPCR assays confirmed that FTO regulated m6A demethylation of PLCβ3 and promoted PLCβ3 expression. Upon overexpressing FTO in the hypothalamic arcuate nucleus (ARC) in female rats, we observed advanced puberty onset. Meanwhile, PLCβ3 and GnRH expression in the hypothalamus increased significantly, and the Ca2+ signalling pathway was activated. Our study demonstrates that FTO enhances GnRH expression, which promotes puberty onset, by regulating m6A demethylation of PLCβ3 and activating the Ca2+ signalling pathway. A study based on in vivo and in vitro experiments suggests that FTO enhances GnRH expression, which promotes puberty onset, by regulating m6A demethylation of PLCβ3 and activating the Ca2+ signalling pathway. [ABSTRACT FROM AUTHOR]

As important atmospheric circulation patterns in Northern Hemisphere (NH), the North Atlantic Oscillation (NAO) and the Western Pacific teleconnection (WP) affect the winter climate in Eurasia. In order to explore the combined effects of NAO and WP on East Asian (EA) temperature, the NAO and WP indices are divided into four phases from 1980–2021: the positive NAO and WP phase (NAO+/WP+), the negative NAO and WP phase (NAO−/WP−), the positive NAO and negative WP phase (NAO+/WP−), the negative NAO and positive WP phase (NAO−/WP+). In the phase of NAO+/WP+, the low geopotential height (GH) stays in north of EA at 50°–80°N; the surface air temperature anomaly (SATA) is 0.8–1 °C lower than Southern Asian. In the phase of NAO−/WP−, the center of high temperature and GH locate in the northeast of EA; the cold air spreads to Southern Asia, causing the SATA decreases 1–1.5 °C. In the phase of NAO+/WP−, the high GH belt is formed at 55°–80°N. Meanwhile, the center of high SATA locates in the north of Asia that increases 0.8–1.1 °C. The cold airflow causes temperature dropping 0.5–1 °C in the south of EA. The SATA improves 0.5–1.5 °C in south of EA in the phase of NAO−/WP+. The belt of high GH is formed at 25°–50°N, and blocks the cold air which from Siberia. The NAO and WP generate two warped plate pressure structures in NH, and affect the temperature by different pressure configurations. NAO and WP form different GH, and GH acts to block and push airflow by affecting the air pressure, then causes the temperature to be different from the north and south of EA. Finally, the multiple linear regression result shows that NAO and WP are weakened by each other such as the phase of NAO+/WP+ and NAO−/WP−. [ABSTRACT FROM AUTHOR]

The activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been reported to importantly contribute to glomerular inflammation and injury under different pathological conditions such as obesity. However, the mechanism mediating NLRP3 inflammasome activation in podocytes and subsequent glomerular injury remains poorly understood. Given that the ceramide signaling pathway has been reported to be implicated in obesity-related glomerulopathy (ORG), the present study was designed to test whether the ceramide-producing enzyme, acid sphingomyelinase (ASM), determines NLRP3 inflammasome activation and inflammatory exosome release in podocytes leading to glomerular inflammation and injury during ORG. In Smpd1trg/Podocre mice, podocyte-specific overexpression of Smpd1 gene which encodes ASM significantly exaggerated high-fat diet (HFD)-induced NLRP3 inflammasome activation in podocytes and immune cell infiltration in glomeruli compared to WT/WT mice. Smpd1 gene deletion, however, blocked these pathological changes induced by HFD in Smpd1−/− mice. Accompanied with NLRP3 inflammasome activation and glomerular inflammation, urinary excretion of exosomes containing podocyte marker and NLRP3 inflammasome products (IL-1β and IL-18) in Smpd1trg/Podocre mice on the HFD was much higher than that in WT/WT mice. In contrast, Smpd1−/− mice on the HDF had significantly lower urinary exosome excretion than WT/WT mice. Correspondingly, HFD-induced podocyte injury, glomerular sclerosis, and proteinuria were more severe in Smpd1trg/Podocre mice, but milder in Smpd1−/− mice compared to WT/WT mice. Using podocytes isolated from these mice, we demonstrated that visfatin, a prototype pro-inflammatory adipokine, induced NLRP3 inflammasome activation and enrichment of multivesicular bodies (MVBs) containing IL-1β in podocytes, which was much stronger in podocytes from Smpd1trg/Podocre mice, but weaker in those from Smpd1−/− mice than WT/WT podocytes. By quantitative analysis of exosomes, it was found that upon visfatin stimulation, podocytes from Smpd1trg/Podocre mice released much more exosomes containing NLRP3 inflammasome products, but podocytes from Smpd1−/− mice released much less exosomes compared to WT/WT podocytes. Super-resolution microscopy demonstrated that visfatin inhibited lysosome-MVB interaction in podocytes, indicating impaired MVB degradation by lysosome. The inhibition of lysosome-MVB interaction by visfatin was amplified by Smpd1 gene overexpression but attenuated by Smpd1 gene deletion. Taken together, our results suggest that ASM in podocytes is a crucial regulator of NLRP3 inflammasome activation and inflammatory exosome release that instigate glomerular inflammation and injury during obesity. [ABSTRACT FROM AUTHOR]

To study the numerical relationship between the pull-out force and indentation depth of aviation wire crimp terminal, the crimping process between electrical contacts and stranded conductors and the tensile process of crimping assembly were simulated by the explicit dynamic finite element method. Regarding the variation trend of the tension of the crimping assembly with the tensile displacement during the tensile process and the failure mode, the numerical results and the experimental results showed a high degree of fit, and the relative error of the pull-out force was only 2.6%, which verified the reliability of the established numerical model. This model obtained the pull-out force curve of the crimp terminal that changes with the indentation depth. The authors suggest selecting the interval where the pull-out force is not less than 95% of the peak value, and the depth is less than the corresponding value at the peak value as the best value range of the indentation depth. [ABSTRACT FROM AUTHOR]

In this work, nanosized Co3O4 particles with nanosheet and octahedron morphologies were prepared through one-step hydrothermal method and template-free process. The morphology can be easily regulated through the precursor concentration and reaction time. The binder-free carbon cloth @Co3O4 octahedral electrodes delivered a reversible capacity of 507 mAh g−1 after 100 cycles at a current density of 300 mA g−1 and also exhibited superior rate performance. The kinetic behavior of CC@ Co3O4 octahedral electrodes was investigated and the results implied the capacitive process played the main role at higher cycle rates. The unique octahedral morphology with a greater area of (111) planes and high surface area may contribute to the superior electrochemical performance. [ABSTRACT FROM AUTHOR]

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40–59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756–0.797; validation AUC 0.766, 0.741–0.790). The validation cohort was stratified as low-risk (score 0–8), intermediate-risk (score 9–13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the mid–short-term risk factors for chronic renal failure (CRF) in children with posterior urethral valve (PUV) after valve ablation. Materials and methods: A retrospective study of 143 patients with PUV who underwent operation was performed. Patients were divided into CRF group (n = 39) and non-CRF group (n = 104). Clinical data of both groups such as the first resection age, last resection age, number of operations, the maximal detrusor pressure (Pdetmax), and vesicoureteral reflux (VUR) were collected and analyzed. Results: The first resection age, last resection age, and the Pdetmax of patients in the CRF group were higher than those of patients in the non-CRF group (P < 0.05). Multiple regression analysis showed that the indicators related to chronic renal failure were last resection age (β = 1.034, P < 0.05) and Pdetmax (β = 1.068, P < 0.05). The cut-off value of last resection age was 35.5 months, Pdetmax was 41.65 cmH2O. There was positive correlation of final blood creatinine with last resection age and Pdetmax. Conclusion: The last resection age and Pdetmax are the risk factors of chronic renal failure in children with PUV. A Pdetmax of lower than 41.65 cmH2O indicates a good prognosis of renal function in patients with PUV. [ABSTRACT FROM AUTHOR]

Background: Human epidermal growth factor receptor 2 (ERBB2) mutation is a known oncogenic driver mutation in a small proportion of non-small cell lung cancers (NSCLCs). Many targeted therapies are being developed and investigated for the treatment of ERBB2-mutated NSCLC, however none of these agents have yet been approved as a front-line treatment. Thus, platinum-based chemotherapy with or without immunotherapy remains the preferred first-line therapy for ERBB2-mutated NSCLC. Objective: We aimed to study the activity of chemotherapy in combination with pembrolizumab as first-line treatment in patients with stage IV ERBB2-mutated NSCLC. Patients and Methods: We retrospectively identified five patients with ERBB2-mutated NSCLC treated with carboplatin, pemetrexed and pembrolizumab as first-line therapy between 2018 and 2020. Overall survival (OS), progression-free survival (PFS), and time to next therapy (TTNT) were summarized by Kaplan–Meier methodology using R 4.0.5 with median time to event. Response rates defined by partial response (PR) or PR + stable disease (SD) and 95% Clopper–Pearson confidence interval (CI) were calculated. Results: The median age of these five patients was 60 years and all five patients' tumors had ERBB2 mutations—4 had exon 20 mutation and 1 had exon 23 mutation. With a median follow-up of 32 months, the median OS was 24 months, the median PFS was 9 months, and the median TTNT was 9 months. The response rate was 0.6 for PR (Clopper–Pearson exact 95% CI 0.147–0.947) and 0.8 for PR and SD (Clopper–Pearson exact 95% CI 0.284–0.995). No unexpected toxicities were observed. Conclusion: In a small number of patients, chemotherapy and pembrolizumab as first-line therapy in ERBB2-mutated NSCLC patients demonstrated activity similar to previous reports with this regimen. Future clinical trials are needed to determine the role of chemotherapy and immunotherapy for this patient population in the context of emerging targeted agents. [ABSTRACT FROM AUTHOR]

In this study, the relationship between the tensile strength and the indentation depth was studied by analysing the deformation mechanism of the crimping assembly of the aviation wiring harness end. Tensile strength tests were performed on samples of crimping assemblies with different indentation depths. The results showed that the experimental and theoretical values were in good agreement, verifying the validity of the established mathematical model for tensile strength. Based on this model, a reasonable design range for the indentation depth corresponding to the specific combination of contacts and strands was determined. [ABSTRACT FROM AUTHOR]

Background: Cancer survivors often experience physical and psychological symptoms that may affect their daily activities and quality of life. A mindfulness-based psychoeducation for cancer survivors, (MindCAN) program, has been established to help cancer survivors manage their physical and psychological symptoms. This study aimed to explore perceptions of participants who attended the MindCAN program. Methods: A descriptive qualitative study was conducted at a tertiary hospital in Singapore. Purposive sampling was used to recruit adult cancer survivors. They attended the MindCAN program that was conducted once a week for 8 weeks, comprising education and mindfulness practice. Two focus group interviews were conducted to elicit the participants' perceptions of the program. The interviews were audio-recorded and transcribed verbatim. A thematic analysis was performed to identify essential themes and subthemes. Trustworthiness, including creditability, confirmability, dependability, and transferability were ascertained. Results: A total of 13 participants were recruited. Most of whom were Chinese, female, and single. The participants' perceptions were documented in five major themes: heightened awareness of the self, enriching body experiences through mindfulness practice, cultivating powerful minds and positive emotions, integrating mindfulness to daily life, and embracing interpersonal mindfulness. Conclusion: Overall, the MindCAN program received positive comments from cancer survivors. They reported increased self-awareness, pleasant body experiences, positive thinking and emotions, and relaxation. Future research is required to test the effectiveness of the program. [ABSTRACT FROM AUTHOR]

The current generation of coupled ocean–atmosphere climate models, which are widely used for studying the dynamics of the climate system and to make projections of future climate, suffers from erroneously warm (exceeding 5 °C) sea surface temperature (SST) simulation in the eastern boundary upwelling systems (EBUS) in the Atlantic and Pacific oceans. While recent improvements in the horizontal resolution of coupled model components helped to alleviate this issue in the North and South Pacific and North Atlantic oceans, the warm bias in the Southeast Tropical Atlantic (SETA) region still remains above 5 °C. Recent studies have highlighted the importance of inaccuracies in the near-coastal winds, especially in the Benguela low-level coastal jet (BLLCJ), in the formation of this warm SST bias. In addition, unique ocean circulation features like the poleward flowing coastal current and the presence of a strong coastal SST front were argued to contribute to the complexity in simulating realistic SST in the SETA region. In this study, we investigate how ocean model resolution and the spatial structure and strength of the BLLCJ affect the SST warm bias in the SETA. We conducted a suite of ocean model experiments with varying horizontal resolutions (81–3 km) and different atmospheric forcing products. We found that the accuracy in the magnitude of BLLCJ's alongshore component and in the spatial structure of BLLCJ are the primary factors in reducing the warm SST bias in SETA and the ocean model horizontal resolution is of only secondary importance. A weaker alongshore component of the BLLCJ leads to a weaker upwelling through Ekman transport and fails to generate a downwind equatorward surface jet in the ocean. When the core of the BLLCJ is too far offshore, the broad wind stress curl zone gives rise to anomalous poleward depth integrated flow through Sverdrup balance and weakens the wind stress curl induced Ekman pumping near the coast. Both the presence of a poleward current, which can transport warm equatorial waters farther south, and the absence of the equatorward surface jet contributes to the warm SST bias. Heat budget analysis shows that the contribution from the anomalous poleward flow is a bigger contributor to the warm bias than the weak upwelling. With more realistic, high-resolution winds, an ocean model resolution increase from 27 to 9 km slightly reduces the extent and magnitude of SST bias. However, no such improvement occurs with coarse resolution less realistic winds. Sensitivity experiments using atmospheric forcing fields from different sources confirm that the major contribution to the warm SST bias is in fact from the erroneous winds rather than other atmospheric forcing fields like net shortwave and downward longwave radiation. Further studies are needed to understand whether eddy heat advection or mean flow heat advection primarily cause the warm SST bias. [ABSTRACT FROM AUTHOR]

It is well known that there exist great differences in human brain anatomy and functions between males and females. With the development of noninvasive neuroimaging techniques, the sex differences in adult human brain have been well studied in some researches. However, the sexual dimorphism of human brain anatomy and functions has not been sufficiently described during the developmental period of early childhood brain when the sex differences emerge in behavior. This study was to identify specific patterns of the sexual dimorphism in developing brain structure of early childhood using multimodal brain image analysis. We have performed a multivariate and data-driven analysis by combining multiple neuroimaging technologies including the 3D T1-weighted structural MR images (sMRI) and diffusion tensor imaging (DTI) in a prospective cohort of 188 children (128 males and 60 females) between the ages of 0 and 15. First, the brain images were segmented into 90 regions of interest (ROIs) based on the AAL template to extract the ROI volume and connectivity features. Then, the individual multimodal imaging biomarkers were identified associated with the sex differences. Finally, the selected features from multi-modality neuroimages were combined using multi-kernel support vector machine for classifications of male or female. The method achieved sex classification accuracy 72% for the children between the ages of 0 and 15. And the volumes of right precuneus and right postcentral were more related to sexual dimorphism of developing brain structure than those of other regions in sMRI (p < 0.002). In DTI, the connections between right middle occipital gyrus and right inferior occipital gyrus, between left superior marginal gyrus and left middle temporal gyrus, and between right triangle inferior frontal gyrus and right putamen are also more relevant to the sexual dimorphism than others (p < 0.005). The brain regions and connections related to the sexual differences were identified with sMRI and DTI in early developing brain structure by using the multimodal image analysis. And these sexually dimorphic patterns of brain may be related to the observed sex differences in developing childhood brain structure and connectivity. [ABSTRACT FROM AUTHOR]

In mammals, mature miR-122 is 22 nucleotides long and can be involved in regulating a variety of physiological and biological pathways. In this study, the expression profile and effects of grouper Epinephelus coioides miR-122 response to Singapore grouper iridovirus (SGIV) infection were investigated. The sequences of mature microRNAs (miRNAs) from different organisms are highly conserved, and miR-122 from E. coioides exhibits high similarity to that from mammals and other fish. The expression of miR-122 was up-regulated during SGIV infection. Up-regulation of miR-122 could significantly enhance the cytopathic effects (CPE) induced by SGIV, the transcription levels of viral genes (MCP, VP19, LITAF and ICP18), and viral replication; reduce the expression of inflammatory factors (TNF-a, IL-6, and IL-8), and the activity of AP-1 and NF-κB, and miR-122 can bind the target gene p38α MAPK to regulate the SGIV-induced cell apoptosis and the protease activity of caspase-3. The results indicated that SGIV infection can up-regulate the expression of E. coioides miR-122, and up-regulation of miR-122 can affect the activation of inflammatory factors, the activity of AP-1 and NF-κB, and cell apoptosis to regulate viral replication and proliferation. [ABSTRACT FROM AUTHOR]

Unfortunately, cSCC is not reportable in SEER apart from special cutaneous sites of the lip and external genitals, severely limiting the number and variety of cSCC cases for inclusion [[2]]. (1) Their cohort only included 916 metastatic cSCC cases over an 18 year period, whereas conservative estimates predict at least 5600 U.S. patients develop cSCC metastasis annually [[3]]. Given that the authors' study is limited to metastatic cSCC from external genitalia and lip, including non-cSCC cases, we cannot endorse using this nomogram to evaluate cSCC-specific survival. [Extracted from the article]

Endothelial cell (EC) metabolism is thought to be one of the driving forces for angiogenesis. Here we report the identification of the hexosamine D-mannosamine (ManN) as an EC mitogen and survival factor for bovine and human microvascular EC, with an additivity with VEGF. ManN inhibits glycosylation in ECs and induces significant changes in N-glycan and O-glycan profiles. We further demonstrate that ManN and two N-glycosylation inhibitors stimulate EC proliferation via both JNK activation and the unfolded protein response caused by ER stress. ManN results in enhanced angiogenesis in a mouse skin injury model. ManN also promotes angiogenesis in a mouse hindlimb ischemia model, with accelerated limb blood flow recovery compared to controls. In addition, intraocular injection of ManN induces retinal neovascularization. Therefore, activation of stress pathways following inhibition of protein glycosylation can promote EC proliferation and angiogenesis and may represent a therapeutic strategy for treatment of ischemic disorders. Therapeutic angiogenesis has the potential of inducing and maintaining new blood vessels and thus improving outcomes in patients with ischemic disorders. Mannosamine functions as an endothelial cell mitogen/survival factor through activation of stress pathways and might be useful to protect and regenerate the vascular endothelium in a variety of disorders. [ABSTRACT FROM AUTHOR]

The androgen insensitivity syndrome (AIS) is a congenital disease characterized by androgen resistance due to androgen receptor (AR) gene mutations, resulting in disorders of sex differentiation in 46,XY individuals. However, the underlying mechanisms in the majority of AR variants and the phenotype–genotype correlations are unclear. Here, we identified a p.Y764H variant of the AR gene that results in different phenotypes in a family. Structural analyses revealed that amino acid substitution affected protein properties and spatial conformation, and in vitro, functional studies showed impaired nuclear translocation ability of the mutated protein. Moreover, the extent to which this variant reduced nuclear translocation depends on the dihydrotestosterone (DHT) concentrations. Our results, for the first time, demonstrated a pathogenesis of the p.Y764H mutations in AR resulting in AIS phenotype, and indicated that AIS patients with p.Y764H mutation and preserved gonad might have residual AR activity at high androgen levels, putting patients at risk for pubertal virilization in the future. We provide an in-depth insight into the pathogenesis in AIS based on the amino acid substitution, which may help aid its precise diagnosis, personalized treatment, and organized follow-up to avoid gender dysphoria. [ABSTRACT FROM AUTHOR]

Arterial medial calcification (AMC) involves an increased small extracellular vesicle (sEV) secretion and apatite calcium precipitation in the arterial wall. The mechanisms mediating AMC remain poorly understood. In the present study, smooth muscle-specific acid ceramidase (Ac) gene knockout mice (Asah1fl/fl/SMCre) were used to demonstrate the role of lysosomal ceramide signaling pathway in AMC. Asah1fl/fl/SMCre mice were found to have more severe AMC in both aorta and coronary arteries compared to their littermates (Asah1fl/fl/SMwt and WT/WT mice) after receiving a high dose vitamin D. These mice also had pronounced upregulation of osteopontin and RUNX2 (osteogenic markers), CD63, AnX2 (sEV markers) and ALP expression (mineralization marker) in the arterial media. In cultured coronary arterial smooth muscle cells (CASMCs) from Asah1fl/fl/SMCre mice, high dose of Pi led to a significantly increased calcium deposition, phenotypic change and sEV secretion compared to WT CASMCs, which was associated with reduced lysosome-multivesicular body (MVB) interaction. Also, GW4869, sEV release inhibitor decreased sEV secretion and calcification in these cells. Lysosomal transient receptor potential mucolipin 1 (TRPML1) channels regulating lysosome interaction with MVBs were found remarkably inhibited in Asah1fl/fl/SMCre CASMCs as shown by GCaMP3 Ca2+ imaging and Port-a-Patch patch clamping of lysosomes. Lysosomal Ac in SMCs controls sEV release by regulating lysosomal TRPML1 channel activity and lysosome-MVB interaction, which importantly contributes to phenotypic transition and AMC. [ABSTRACT FROM AUTHOR]

Using research papers of WoS database as the data source, the present paper adopts the method of Documents Co-citation Analysis, and employs the tool of CiteSpace to analyze the theme, evolution and research trend of Library and Information Science (LIS) research in the recent 30 years from 1989 to 2018. The findings demonstrate that (1) research on LIS develops along the path from the ordering of information to the digging and application of information value. And in this process, the factor of "people" and the network information resources have been receiving more and more attentions; (2) over the past 30 years, research on LIS has mainly focused on areas such as information retrieval, social media, information system, information behavior, bibliometrics and webometrics, scientific evaluation and knowledge management; and (3) in the future, LIS research will mainly focus on six theme areas: metrology research, open government, scientific evaluation, big data, social media and information system. These six areas are all significantly affected by social media. [ABSTRACT FROM AUTHOR]

The permeability of broken coal is not only mainly controlled by coal structure, but also unavoidably influenced by variations of stress, particle size, moisture content, and temperature. In this paper, a self-designed experimental device was utilized to investigate the permeability evolution of seven coal samples with different particle size ratios during the loading processes under the condition of temperature, water content, and pore pressure. The results show that both the permeability and the porosity are negative exponential functions of axial stress. Under the same stress, the porosity and the permeability decrease with the increase of the particle size and the particle size range of the coal samples; in the process of compaction, the larger the particle size and the particle size range of the coal samples, the higher the change rate of the porosity and the permeability. Under the same stress, any increase of temperature, water content, or pore pressure would cause the decrease of the permeability of the coal samples, i.e., they are negatively correlated. With the establishment of the permeability calculation model of the coal samples under different temperatures, water contents, and pore pressures during the loading processes, the permeability of different locations in different environments can be speculated. Based on the estimated data, the air leakage in different areas can be obtained to determine the spontaneous combustion zone in goaf, which is crucial for fire prevention and control in goaf. [ABSTRACT FROM AUTHOR]

Many feature weighting methods have been proposed to evaluate feature saliencies in recent years. Neural-network (NN) feature weighting, as a supervised method, is founded upon the mapping from input features to output decisions, and implemented by evaluating the sensitivity of network outputs to its inputs. Through training on sample data, NN implicitly embodies the saliencies of input features. The partial derivatives of the outputs with respect to the inputs in the trained NN are calculated to measure their sensitivities to input features, which means that implicit feature weighting of the NN is transformed into explicit feature weighting. The purpose of this paper is to further probe into the principle of NN feature weighting, and evaluate its performance through a comparative study between NN feature weighting method and state-of-art weighting methods in the same working conditions. The motivation of this study is inspired by the lack of direct and comprehensive comparison studies of NN feature weighting method. Experiments in UCI repository data sets, face data sets and self-built data sets show that NN feature weighting method achieves superior performance in different conditions and has promising prospects. Compared with the other existing methods, NN feature weighting method can be used in more complex conditions, provided that NN can work in those conditions. As decision data, output data can be labels, reals or integers. Especially, feature weights can be calculated without the discretization of outputs in the condition of continuous outputs. [ABSTRACT FROM AUTHOR]

Background and purpose: We evaluated whether dose-intensified chemoradiation alters patterns of failure and is associated with favorable survival in the temozolomide era. Materials and methods: Between 2003 and 2015, 82 patients with newly diagnosed glioblastoma were treated with 66–81 Gy in 30 fractions using conventional magnetic resonance imaging. Progression-free (PFS) and overall survival (OS) were calculated using Kaplan–Meier methods. Factors associated with improved PFS, OS, and time to progression were assessed using multivariate Cox model and linear regression. Results: Median follow-up was 23 months (95% CI 4–124 months). Sixty-one percent of patients underwent subtotal resection or biopsy, and 38% (10/26) of patients with available data had MGMT promoter methylation. Median PFS was 8.4 months (95% CI 7.3–11.0) and OS was 18.7 months (95% CI 13.1–25.3). Only 30 patients (44%) experienced central recurrence, 6 (9%) in-field, 16 (23.5%) marginal and 16 (23.5%) distant. On multivariate analysis, younger age (HR 0.95, 95% CI 0.93–0.97, p = 0.0001), higher performance status (HR 0.39, 95% CI 0.16–0.95, p = 0.04), gross total resection (GTR) versus biopsy (HR 0.37, 95% CI 0.16–0.85, p = 0.02) and MGMT methylation (HR 0.25, 95% CI 0.09–0.71, p = 0.009) were associated with improved OS. Only distant versus central recurrence (p = 0.03) and GTR (p = 0.02) were associated with longer time to progression. Late grade 3 neurologic toxicity was rare (6%) in patients experiencing long-term survival. Conclusion: Dose-escalated chemoRT resulted in lower rates of central recurrence and prolonged time to progression compared to historical controls, although a significant number of central recurrences were still observed. Advanced imaging and correlative molecular studies may enable targeted treatment advances that reduce rates of in- and out-of-field progression. [ABSTRACT FROM AUTHOR]

Rapid increase of nitrogen (N) deposition could alter nutrient availability, leading to changes in soil microbial processes and ecosystem carbon and nutrient cycling. However, the effects of N deposition on soil microbes remain elusive in the tropical rainforests in Asia. Here, we conducted a 3-year N addition experiment with four treatments (0, 20, 50, and 100 kg N ha−1 year−1) in a primary and secondary tropical montane forest in Hainan Island, China, to explore the effects of elevated N availability on soil microbial community composition. We also conducted a phosphorus (P) treatment (50 kg P ha−1 year−1) and a N + P treatment (50 kg N ha−1 year−1 + 50 kg P ha−1 year−1) to examine potential P limitation driven by N deposition in highly weathered tropical soils, using a bar-coded pyrosequencing technique. The composition of soil bacterial communities differed dramatically between the primary and secondary forests, but not significant dissimilarity among the fertilization treatments. The community composition, phylogenetic diversity and phylotype richness were significantly correlated with soil pH, total organic C (TOC), and total N (TN), respectively. There were significant differences between the primary and secondary forest in pH, TOC, and TN, but not among the fertilization treatments. These results suggest that differences in soil nutrient status between the primary and secondary forests due to different successional stages rather than chronic N fertilization may be the major factor affecting soil bacterial composition in the tropical montane rainforests. [ABSTRACT FROM AUTHOR]

In recent years, the dual stego-image reversible data embedding methods have been developed rapidly, e.g., exploiting modification direction, magic matrix, least significant bit matching, and center folding strategy. The kind of method can effectively embed secret data into two stego-images and maintain excellent image quality and enhance the security. In 2015, Lu et al. proposed a center folding strategy that can effectively encode messages as the smaller digits. The encoding procedure reduces the modification level of pixels, thereby maintaining good image quality. However, their strategy does not use the relationship between the adjacent digits to reduce the number of the largest digits. Inspired by joint neighboring coding, we proposed a dynamic encoding strategy to improve the center folding strategy. The encoding strategy can reduce the secret digits and decrease the occurrence frequency of the maximum digits, thereby substantially reducing the modification level of pixels. The advantage makes that the proposed method can achieve a higher PSNR value than previous methods under the same embedding rate. [ABSTRACT FROM AUTHOR]

Reversible data hiding methods can embed secret data into multimedia to prevent attacks from hackers. Reversible data hiding methods based on multiple stego-images have been proposed extensively in recent years. This type of method can embed large amounts of secret bits into several stego-images. However, data embedding may cause serious distortion of stego-images. To solve this problem, Lu et al. proposed a center-folding strategy to reduce secret digits to narrow down the distance between the original pixel and the stego pixel in 2015. Although the center-folding strategy works well, it can still be improved. In their proposed scheme, the maximum secret digit seriously damages the image quality of the stego-image. If the maximum secret digit occurs often, then the visual quality of the stego-image decreases quickly. In this paper, we propose a frequency-based encoding method to solve this problem. The secret digit that occurs most frequently is encoded as the minimum absolute digit, thereby decreasing the frequency and level of modification. Experimental results showed that the proposed method can achieve a greater peak signal-to-noise ratio value than previous methods, thereby confirming that the proposed method is effective. [ABSTRACT FROM AUTHOR]

A variational wavefunction including the breather, dipole and scissor modes simultaneously is constructed to investigate the collective-excitation dynamics of spin-1 $$^{87}\mathrm{Rb}$$ condensates driven by a space- and time-dependent magnetic field. When the Dirac point never enters the condensate, it is shown that the dipole, breather and scissor modes will be all excited driven by the sinusoidal oscillation of the Dirac point, due to the coupling of different collective modes from the inhomogeneity of the magnetic field. A resonance-driving phenomenon is observed. If the Dirac point passes through the condensate, our numerical results agree with most experimental observations (Ray et al. in Nature 505:657, 2014) and find that the center of mass of the condensate does not follow the zero point of the magnetic field. Hopefully, our method can be extended to study the similar dynamics for the other spinor condensates. [ABSTRACT FROM AUTHOR]

Objective: Patient-controlled epidural analgesia (PCEA), used to relieve pain during delivery, delays labor but the mechanism is unknown. The aim was to investigate the effects of PCEA on uterine and abdominal muscles electromyographic (EMG) activity during the second stage of labor. Methods: This study included 45 nulliparous pregnant women without PCEA, 42 women with standard PCEA treatment given during the first stage of labor and stopped near the end of the first stage, and 22 women with standard PCEA treatment with continued use throughout the first and second stages of labor. The EMG signals were recorded from the abdominal surface using PowerLab hardware and LabChart software (ADInstruments, New South Wales, Australia) and filtered to separate uterine and abdominal EMG. Various EMG burst parameters were obtained. Results: There are no differences (P > .05) in the age, body mass index, fetal weight, and Apgar scores between the patients from the various groups. PCEA (both stopped and continued) inhibits (P < .05) duration, number of bursts, and root mean square of uterine EMG. PCEA also produces statistically significant (P < .001) reductions in abdominal EMG. The decrease in EMG activity is accompanied by a significant (P < .001) prolongation of the second stage duration (PCEA continued = 95.08 ± 8.60 minutes, PCEA stopped = 79.39 ± 6.25 minutes, no PCEA = 61.00 ± 7.23 minutes). Conclusion: PCEA suppresses uterine and abdominal muscle EMG during the second stage of labor but inhibition depends upon the treatment schedule. PCEA prolongs the duration of labor by inhibition of uterine and abdominal muscle and neural activity [ABSTRACT FROM AUTHOR]

Objective: To record and characterize electromyography (EMG) from the uterus and abdominal muscles during the nonlabor to first and second stages of labor and to define relationships to contractions. Methods: Nulliparous patients without any treatments were used (n = 12 nonlabor stage, 48 during first stage and 33 during second stage). Electromyography of both uterine and abdominal muscles was simultaneously recorded from electrodes placed on patients’ abdominal surface using filters to separate uterine and abdominal EMG. Contractions of muscles were also recorded using tocodynamometry. Electromyography was characterized by analysis of various parameters. Results: During the first stage of labor, when abdominal EMG is absent, uterine EMG bursts temporally correspond to contractions. In the second stage, uterine EMG bursts usually occur at same frequency as groups of abdominal bursts and precede abdominal bursts, whereas abdominal EMG bursts correspond to contractions and are accompanied by feelings of “urge to push.” Uterine EMG increases progressively from nonlabor to second stage of labor. Conclusions: (1) Uterine EMG activity can be separated from abdominal EMG events by filtering. (2) Uterine EMG gradually evolves from the antepartum stage to the first and second stages of labor. (3) Uterine and abdominal EMG reflect electrical activity of the muscles during labor and are valuable to assess uterine and abdominal muscle events that control labor. (4) During the first stage of labor uterine, EMG is responsible for contractions, and during the second stage, both uterine and abdominal muscle participate in labor. [ABSTRACT FROM AUTHOR]

Recent studies indicate that inflammasomes serve as intracellular machinery to initiate classical cytokine-mediated inflammatory responses and play a crucial role in the pathogenesis of cardiovascular diseases. However, whether or not the activation of endothelial inflammasomes directly causes cell dysfunction or tissue injury without recruitment of inflammatory cells is unknown. We explored the role of endothelial cell inflammasome activation in mediating tight junction disruption, a hallmark event of endothelial barrier dysfunction leading to endothelial hyperpermeability in diabetes. We used confocal microscopy to study the formation and activation of NOD-like receptor family pyrin domain containing-3 (Nlrp3) inflammasomes and expression of tight junction proteins in coronary arteries of streptozotocin-treated diabetic wild type and Nlrp3 gene-deleted mice. We found that Nlrp3 ablation prevented inflammasome activation and tight junction disassembly in the coronary arterial endothelium of diabetic mice. Similarly, Nlrp3 gene silencing prevented high glucose-induced down-regulation of tight junction proteins in cultured mouse vascular endothelial cells (MVECs). The high glucose-induced tight junction disruption and consequent endothelial permeability were attributed to increased release of the high mobility group box protein-1 (HMGB1), which is dependent on enhanced Nlrp3 inflammasome activity. Mechanistically, reducing reactive oxygen species (ROS) production abolished high glucose-induced inflammasome activation, tight junction disruption, and endothelial hyperpermeability in MVECs. Collectively, the ROS-dependent activation of endothelial Nlrp3 inflammasomes by hyperglycemia may be an important initiating mechanism to cause endothelial dysfunction. These effects could contribute to the early onset of endothelial injury in diabetes. Key message: [ABSTRACT FROM AUTHOR]

Because of great polar differences and poor compatibility, polyethylene (PE) and polyamide 66 (PA66) cannot be welded by laser transmission welding (LTW), even though they are widely used in our daily life. In this paper, using grafting modification technology to improve the welding performance between PE and PA66 is researched. First of all, two ways of the graft modified polyethylene (TGMPE) that the strong polar and reactive maleic anhydride (MAH) and glycidyl methacrylate (GMA) are grafted to PE respectively are introduced. Also, the mechanical and thermal performances of TGMPE are tested which show that the grafting modification has small influence on them. After TGMPE and PA66 are welded by laser, the high welding strength is found and the mechanism of the weldability between them is researched, which reveals that two reasons account for the high welding strength. For one thing, by observing the welding region micro morphology, it is not difficult to find that the grafting modification makes low interfacial tension, good compatibility, and strong interfacial adhesion between PE and PA66. At the same time, the good compatibility makes them easy to diffuse mutually, which causes some locking structures formed in the welding region. For another, the X-ray photoelectron spectrometer proves that chemical reactions are involved between TGMPE and PA66, which make the welding performance better. Afterward, the tensile failure forms of the welding are researched. At last, the welding strength of the MAH modified polyethylene and PA66 is compared to the GMA modified polyethylene and PA66. [ABSTRACT FROM AUTHOR]

Pulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus-induced sepsis and an important cause of human pathology and death. We investigated the role of the mammalian acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm reduced lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of superoxide, resulting in degradation of tight junction proteins followed by lung edema. Treatment of infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from lung edema caused by S. aureus, but did not reduce systemic bacterial numbers. In turn, treatment with antibiotics reduced bacterial numbers but did not protect mice from lung edema. In contrast, only the combination of antibiotics and amitriptyline inhibited both pulmonary edema and bacteremia protecting mice from lethal sepsis and lung dysfunction suggesting the combination of both drugs as novel treatment option for sepsis. Key messages: [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate incidence trend of childhood type 1 diabetes in Shanghai, a megalopolis in east China. We established a population-based retrospective registry for the disease in the city's registered population during 1997-2011 and collected 622 incident type 1 diabetes in children aged 0-14 years. Standardized incidence rates and 95 % CI were estimated by applying the capture-recapture method and assuming Poisson distribution. Incidence trend was analyzed using the Poisson regression model. The mean annual incidence of childhood type 1 diabetes was 3.1 per 100,000 person-years. We did not observe significant difference in incidence between boys and girls. The incidence is unstable and had a mean annual increase 14.2 % per year during the studied period. A faster annual increase was observed in boys, warmer seasons, and in the outer regions of the city. If present trends continue, the number of new type 1 diabetes cases will double from 2016 to 2020, and prevalent cases will sextuple by 2025. Our results showed the incidence of childhood type 1 diabetes was rising rapidly in Shanghai. More studies are needed to analyze incidence changes in other regions of China for appropriate allocation of healthcare resources. [ABSTRACT FROM AUTHOR]

Adult stem cell deficiency has been implicated in the pathogenic mechanism for various diseases. Renal medullary dysfunction is one of the major mechanisms for the development of hypertension in Dahl salt-sensitive (S) rats. The present study first detected a stem cell deficiency in the renal medulla in Dahl S rats and then tested the hypothesis that transplantation of mesenchymal stem cells (MSCs) into the renal medulla improves salt-sensitive hypertension in Dahl S rats. Immunohistochemistry and flowcytometry analyses showed a significantly reduced number of stem cell marker CD133+ cells in the renal medulla from Dahl S rats compared with controls, suggesting a stem cell deficiency. Rat MSCs or control cells were transplanted into the renal medulla in uninephrectomized Dahl S rats, which were then treated with a low- or high-salt diet for 20 days. High-salt-induced sodium retention and hypertension was significantly attenuated in MSC-treated rats compared with control cell-treated rats. Meanwhile, high-salt-induced increases of proinflammatory factors, monocyte chemoattractant protein-1, and interleukin-1β, in the renal medulla were blocked by MSC treatment. Furthermore, immunostaining showed that high-salt-induced immune cell infiltration into the renal medulla was substantially inhibited by MSC treatment. These results suggested that stem cell defect in the renal medulla may contribute to the hypertension in Dahl S rats and that correction of this stem cell defect by MSCs attenuated hypertension in Dahl S rats through anti-inflammation. Key message: [ABSTRACT FROM AUTHOR]