Whole exome sequencing with a focus on cardiac disease-associated genes in families of sudden unexplained deaths in Yunnan, southwest of China.

OBJECTIVES: To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs.  METHODS: Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. RESULTS: In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. CONCLUSIONS: Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.

Engineered Cytokine-Primed Extracellular Vesicles with High PD-L1 Expression Ameliorate Type 1 Diabetes.

Type 1 diabetes (T1D), which is a chronic autoimmune disease, results from the destruction of insulin-producing ß cells targeted by autoreactive T cells. The recent discovery that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) function as therapeutic tools for autoimmune conditions has attracted substantial attention. However, the in vivo distribution and therapeutic effects of MSC-EVs potentiated by pro-inflammatory cytokines in the context of T1D have yet to be established. Here, it is reported that hexyl 5-aminolevulinate hydrochloride (HAL)-loaded engineered cytokine-primed MSC-EVs (H@TI-EVs) with high expression of immune checkpoint molecule programmed death-legend 1 (PD-L1) exert excellent inflammatory targeting and immunosuppressive effects for T1D imaging and therapy. The accumulated H@TI-EVs in injured pancreas not only enabled the fluorescence imaging and tracking of TI-EVs through the intermediate product protoporphyrin (PpIX) generated by HAL, but also promoted the proliferative and anti-apoptotic effects of islet ß cells. Further analysis revealed that H@TI-EVs exhibited an impressive ability to reduce CD4+ T cell density and activation through the PD-L1/PD-1 axis, and induced M1-to-M2 macrophage transition to reshape the immune microenvironment, exhibiting high therapeutic efficiency in mice with T1D. This work identifies a novel strategy for the imaging and treatment of T1D with great potential for clinical application.

Macrophage-Membrane-Camouflaged Nonviral Gene Vectors for the Treatment of Multidrug-Resistant Bacterial Sepsis.

Sepsis is a life-threatening disease caused by systemic bacterial infections, with high morbidity and mortality worldwide. As the standard treatment for sepsis, antibiotic therapy faces the challenge of impaired macrophages and drug-resistant bacteria. In this study, we developed a membrane-camouflaged metal-organic framework (MOF) system for plasmid DNA (pDNA) delivery to combat sepsis. The antimicrobial gene LL37 was efficiently encapsulated in the pH-sensitive MOF, and the nanoparticles were decorated with macrophage membranes in a compatible manner. Macrophage membrane coating allows targeted delivery of LL37 to macrophages and creates macrophage factories for the continuous generation of antimicrobial peptides. Compared to naked nanoparticles, primary bone marrow mesenchymal macrophage membrane-modified nanoparticles greatly improved the survival rate of immunodeficient septic mice through the synergistic effect of efficient gene therapy and inflammatory cytokine sequestration. This study demonstrates an effective membrane biomimetic strategy for efficiently delivering pDNA, offering an excellent option for overcoming sepsis.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS: The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Construction of an Interfacial Photocatalytic Mode Based on Carbonized Mushrooms to Enhance Infrared Light-Assisted Photocatalytic Water Splitting Performance.

To find a more efficient way to generate photocatalytic hydrogen, we developed the interfacial photocatalytic mode, in which the photocatalytic reaction can be transferred to a high-energy interfacial area. The new interfacial mode in this work is assembled with the help of carbonized mushrooms, which is an ideal water transporter as well as an excellent photothermal converter. The higher temperature from efficient light-to-heat conversion performance and thermal localization promote the efficiency of hydrogen evolution, and some effects peculiar to the interfacial mode can make the departure of hydrogen from the active sites of the photocatalyst smoother. As a result, the active sites can be exposed in a timely manner to allow the progress of the next cycle of the photocatalytic reaction to be smoother. The efficiency of interfacial photocatalytic hydrogen production can reach >10 times that of the corresponding sample in the traditional bulk water mode. This work has allowed further exploration of the construction of the interfacial photocatalytic mode, provided a reliable experimental basis for the development of the interfacial mode, and illuminated a new path for the development of photocatalytic water splitting.

Mesoporous N-P Codoped Carbon Nanosheets as Superior Cathodic Catalysts of Neutral Metal-Air Batteries.

Development of high-efficiency oxygen reduction reaction (ORR) catalysts under neutral conditions has made little research progress. In this work, we synthesized a three-dimensional porous N/P codoped carbon nanosheet composites (CNP@PNS) by high-temperature thermal treatment of dicyandiamide, starch, and triphenylphosphine and subsequent porous structure-making treatment using the NaCl molten salt template. In the neutral solution, the electrocatalytic performance of the CNP@PNS-4 catalyst exhibits an onset potential of 0.98 V (vs reversible hydrogen electrode) and a half-wave potential of 0.91 V for ORR, which greatly surpasses commercial Pt/C (40%). Three kinds of neutral metal-air batteries (Zn-air, Al-air, and Fe-air) using the prepared samples as cathodic catalysts were constructed, corresponding to the maximum power density of 120.2, 78.3, and 18.9 mW·cm-2, respectively. Also, they reveal outstanding discharge stability under different current densities. The density functional theory calculation depicts the reduction of the free energy of the determining step and subsequent decline of the overpotential for ORR.

The efficacy of a new high-intensity focused ultrasound therapy for metastatic pancreatic cancer.

PURPOSE: To compare the survival benefit, pain control and safety of low-power cumulative and traditional high-intensity focused ultrasound (HIFU) for metastatic pancreatic cancer. METHOD: We retrospectively analyzed 55 patients with metastatic pancreatic cancer who received HIFU treatment between January 2008 and April 2014 in our department. 23 patients received low-power cumulative HIFU treatment (L group), 32 received the traditional HIFU treatment (T group). Performance status, cancer-related pain and serum biochemistry results were assessed before and after treatment. All patients were followed up until death. The survival rate and adverse events of the two groups were compared. RESULTS: The baseline characteristics of the two groups were generally well balanced (p > 0.05). The average KPS score after treatment was significantly improved in both groups compared with the baseline score. 36 patients exhibited tumor-related pain at baseline. The pain response rate was significantly higher in the L group (92.3%) than in the T group (52.2%) (p = 0.025). The median overall survival (OS) for the L group was 7.0 months, which was significantly longer than that of the T group (p = 0.000). The 3-month and 6-month survival rates were higher in the L group. The adverse events in both groups included abdominal pain, elevated C-reactive protein (CRP) and elevated amylase. The incidence was lower in the L group than in the T group. CONCLUSION: Compared with traditional HIFU treatment, low-power cumulative HIFU treatment showed a significantly higher pain relief rate and survival benefit with a better safety profile in patients with metastatic pancreatic cancer.

Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy.

BACKGROUND: Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). RESULTS: In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4ß1 and αLß2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. CONCLUSION: This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.

Impacts of Local Effects and Surface Loads on the Common Mode Error Filtering in Continuous GPS Measurements in the Northwest of Yunnan Province, China.

While seasonal hydrological mass loading, derived from Gravity Recovery and Climate Experiment (GRACE) measurements, shows coherent spatial patterns and is an important source for the common mode error (CME) in continuous global positioning system (cGPS) measurements in Yunnan, it is a challenge to quantify local effects and detailed changes in daily GPS measurements by using GRACE data due to its low time and spatial resolutions. In this study, we computed and compared two groups of CMEs for nine cGPS sites in the northwest Yunnan province; rCMEs were computed with the residual cGPS time series having high inter-station correlations, while oCMEs were computed with all the GPS time series. The rCMEs-filtered time series had smaller variances and larger root mean square (RMS) reductions than those that were oCMEs-filtered, and when the stations local effects were not removed, spurious transient-like signals occurred. Compared with hydrological mass loading (HYDL), its combination with non-tidal atmosphere pressure and ocean mass reached a better agreement with the CME in the vertical component, with the Nash-Sutcliffe efficiency (NSE) increasing from 0.28 to 0.55 and the RMS reduction increasing from 15.19% to 33.4%, respectively. Our results suggest that it is necessary to evaluate the inter-station correlation and remove the possible noisy stations before conducting CME filtering, and that one should carefully choose surface loading models to correct the raw cGPS time series if CME filtering is not conducted.

Study on the Evaluation Method of Sound Phase Cloud Maps Based on an Improved YOLOv4 Algorithm.

Most sound imaging instruments are currently used as measurement tools which can provide quantitative data, however, a uniform method to directly and comprehensively evaluate the results of combining acoustic and optical images is not available. Therefore, in this study, we define a localization error index for sound imaging instruments, and propose an acoustic phase cloud map evaluation method based on an improved YOLOv4 algorithm to directly and objectively evaluate the sound source localization results of a sound imaging instrument. The evaluation method begins with the image augmentation of acoustic phase cloud maps obtained from the different tests of a sound imaging instrument to produce the dataset required for training the convolutional network. Subsequently, we combine DenseNet with existing clustering algorithms to improve the YOLOv4 algorithm to train the neural network for easier feature extraction. The trained neural network is then used to localize the target sound source and its pseudo-color map in the acoustic phase cloud map to obtain a pixel-level localization error. Finally, a standard chessboard grid is used to obtain the proportional relationship between the size of the acoustic phase cloud map and the actual physical space distance; then, the true lateral and longitudinal positioning error of sound imaging instrument can be obtained. Experimental results show that the mean average precision of the improved YOLOv4 algorithm in acoustic phase cloud map detection is 96.3%, the F1-score is 95.2%, and detection speed is up to 34.6 fps. The improved algorithm can rapidly and accurately determine the positioning error of sound imaging instrument, which can be used to analyze and evaluate the positioning performance of sound imaging instrument.

Stat3 activation is critical for pluripotency maintenance.

Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic transcription with many important functions, including regulation of cell proliferation, differentiation, survival, angiogenesis, and immune response. Besides, it plays critical roles in regulating the pluripotency. With the ability of self-renewal and differentiation, embryonic stem (ES) cells provide an unlimited source for cell transplantation. ES cells can maintain its undifferentiated state with leukemia inhibitory factor, the role which is achieved by the activation of the Stat3 pathway. Moreover, Stat3 activation is necessary for the naïve state maintenance of the ES cells and somatic stem cells reprogramming. This study presents an overview of the critical roles of Stat3 activation in the pluripotency maintenance of ES cells, somatic cell reprogramming, and naïve-primed pluripotent states conversion of ES cells.

Postmortem Analysis of 4 Mutation Hotspots of KCNQ1, KCNH2, and SCN5A Genes in Sudden Unexplained Death in Southwest of China.

Long QT syndrome (LQTS) is known to be involved in some sudden unexplained death (SUD) cases. To make clear whether the pathogenic genes of LQTS are involved in SUD in Yunnan province, southwest of China, we examined 4 mutation hotspot segments of KCNQ1, KCNH2, and SCN5A genes in 83 SUD cases using polymerase chain reaction and direct DNA sequencing. Genomic DNA was extracted from paraffin-embedded tissues in 83 cases of sudden cardiac death. One novel homozygous missense variant was identified in exon 3 of KCNQ1, c. 575G>T (p.R192L) in one case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1789T>A (p.Y597N) in 1 case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1800C>A (p.S600R) in 9 cases. In addition, 18 individuals were found to have heterozygous missense variant in exon 7 of KCNH2, c.1801G>A (p.G601S). Our study suggests that some SUDs in Yunnan province may be related with the pathogenic genes of LQTS.

Differential effects of tumor necrosis factor-α on matrix metalloproteinase-2 expression in human myometrial and uterine leiomyoma smooth muscle cells.

STUDY QUESTION: Does tumor necrosis factor-α (TNF-α) differentially regulate matrix metalloproteinase-2 (MMP-2) expression in leiomyomas compared with normal myometrium? SUMMARY ANSWER: TNF-α up-regulates MMP-2 expression and stimulates cell migration through the activation of extracellular signal-regulated kinase (ERK) signaling pathway in leiomyoma smooth muscle cells (SMCs), but not in normal myometrial SMCs. WHAT IS KNOWN ALREADY: Uterine leiomyoma, the benign smooth muscle cell tumor, is the single most common indication for hysterectomy. High expression of MMPs or TNF-α has been reported in uterine leiomyomas; however, the molecular mechanism underlying these observations remains unknown. STUDY DESIGN, SIZE, DURATION: Samples were obtained between 2009 and 2013 from 12 women of reproductive age at the proliferative phase of the menstrual cycle by hysterectomy. Leiomyomas and matched normal myometrium from each woman were analyzed in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS: Western blot, RT-qPCR and a wound-healing assay were used to investigate the effects of TNF-α on MMP-2 expression and intracellular signal transduction in cultured SMCs from leiomyomas and matched myometrium. MAIN RESULTS AND THE ROLE OF CHANCE: Western blot and RT-qPCR analyses using tissues from clinical patients showed that the levels of MMP-2 protein (P = 0.008) and mRNA (P = 0.009) were significantly higher in uterine leiomyomas compared with their matched myometrium. Treatment with TNF-α significantly up-regulated the protein (P = 0.039) and mRNA (P = 0.037) levels of MMP-2 in cultured leiomyoma SMCs but not in matched myometrial SMCs. The extracellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways were activated by TNF-α in leiomyoma SMCs. Specific inhibitors of the ERK or NF-κB pathway (PD98059 or Bay11-7082) suppressed TNF-α-induced MMP-2 expression in leiomyoma SMCs. The wound-healing assay revealed that TNF-α promoted the migration of cultured leiomyoma SMCs (P = 0.036); however, PD98059 compromised the cell migration triggered by TNF-α. LIMITATIONS, REASONS FOR CAUTION: This study is descriptive and although we observed clear differential regulation of MMP-2 by TNF-α at mRNA and protein levels in leiomyoma, future studies are needed to identify why the difference in TNF-α response exists between human leiomyoma tissue and normal myometrium. Including some of the experiments such as transfection studies for TNF-α and MMP-2 promoter mapping could have added more insight as to why this difference exists. In addition, further studies in vivo are needed to verify the results obtained from primary cultured SMCs. WIDER IMPLICATIONS OF THE FINDINGS: Considering the positive effect of TNF-α on leiomyoma SMC migration, strategies targeting TNF-α, in parallel with the production of more specific inhibitors of MMPs, may provide alternative therapeutic approaches for the treatment of leiomyoma. STUDY FUNDING/COMPETING INTERESTS: This work was partially supported by grants from the Program for New Century Excellent Talents in University (NCET-12-0282), National Natural Science Foundation of China (81371620) and Tianjin Natural Science Foundation (12JCZDJC24900). The authors have no conflicts of interest to declare.

Differential expression of caveolin-1 in human myometrial and uterine leiomyoma smooth muscle.

OBJECTIVE: Uterine leiomyomas, the most common neoplasms of the female genital tract, are benign tumors of the uterus arising from the smooth muscle cells (SMCs) of the myometrium with an involvement of estrogen. Caveolin-1 (Cav-1), a major protein component in caveolae membrane lipid rafts, is down-regulated in several estrogen-related cancer cells, and overexpression of Cav-1 inhibits proliferation of cancer cells and vascular SMCs as well. Therefore, we hypothesize that Cav-1 is down-regulated in human uterine leiomyoma. RESULTS: Western blot using tissues from clinical patients showed that Cav-1 expression was significantly lower or undetectable in uterine leiomyoma compared with their matched myometrium (P < .001). This finding was confirmed by immunohistochemistry and confocal microscopy. The cav-1 mRNA level in uterine leiomyomas was also significantly lower as detected by reverse transcription-quantitative polymerase chain reaction analysis (P = .001). To further study the underlying mechanism, we performed primary cell culture, and found that the expression of Cav-1 remained low in cultured leiomyoma SMCs (P = .009). Serum withdrawal did not change Cav-1 expression in leiomyoma SMCs, but increased expression in myometrial SMCs (P = .006). 17-ß estradiol inhibited the expression of Cav-1 protein (P = .047) and mRNA (P = .007) in leiomyoma SMCs, whereas it stimulated expression in myometrial SMCs (P = .043). 17-ß estradiol, although activating the mitogen-activated protein kinase pathway in both SMCs, did not stimulate their proliferation. CONCLUSION: We conclude that human uterine leiomyomas in vitro express low levels of Cav-1, which may result from estrogen inhibition. This effect of estrogen may contribute to the pathogenesis of uterine leiomyoma. Further studies in vivo are needed to verify these results.

Tumor necrosis factor-α regulates matrix metalloproteinase-2 expression and cell migration via ERK pathway in rat glomerular mesangial cells.

Mesangial cells (MCs), vascular smooth muscle-derived cells, contribute to glomerular injury by generating a number of cytokines such as tumor necrosis factor-α (TNF-α). Matrix metalloproteinases (MMPs), regulated by various stimuli, are important in remodeling of glomerular ECM, which leads to a number of renal diseases. We investigated whether TNF-α participated in the regulation of MMPs and explored signal pathways involved in TNF-α-induced MMPs expression in rat glomerular MCs. Western blot and RT-qPCR results showed that treatment with TNF-α significantly increased the expression of MMP-2, but not MMP-9 at both protein and mRNA levels in rat glomerular MCs. The extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-κB) signal pathways were activated by TNF-α. Moreover, the activation of NF-κB pathway in rat MCs was effectively inhibited by PD98059, specific inhibitor of ERK, suggesting a role for ERK in regulating NF-κB function. PD98059 or NF-κB signal pathway selective inhibitor Bay 11-7082 effectively blocked TNF-α-induced expression of MMP-2 in rat MCs, as determined by gene and protein expression. C-jun N-terminal kinase (JNK) signal pathway had no effect on TNF-α-induced expression of MMP-2, even though it was also activated by TNF-α in rat MCs. Furthermore, TNF-α could induce the cell migration of rat MCs, whereas ERK signal pathway specific inhibitor PD98059 compromised the cell migration triggered by TNF-α. Thus, TNF-α upregulates the expression of MMP-2 via activation of ERK-dependent NF-κB pathway in rat MCs, which may contribute to the cell migration of rat MCs.

Drug Treatment Attenuates Retinal Ganglion Cell Death by Inhibiting Collapsin Response Mediator Protein 2 Phosphorylation in Mouse Models of Normal Tension Glaucoma.

Normal tension glaucoma (NTG) is a progressive neurodegenerative disease in glaucoma families. Typical glaucoma develops because of increased intraocular pressure (IOP), whereas NTG develops despite normal IOP. As a subtype of open-angle glaucoma, NTG is characterized by retinal ganglion cell (RGC) degeneration, gradual loss of axons, and injury to the optic nerve. The relationship between glutamate excitotoxicity and oxidative stress has elicited great interest in NTG studies. We recently reported that suppressing collapsin response mediator protein 2 (CRMP2) phosphorylation in S522A CRMP2 mutant (CRMP2 KIKI) mice inhibited RGC death in NTG mouse models. This study evaluated the impact of the natural compounds huperzine A (HupA) and naringenin (NAR), which have therapeutic effects against glutamate excitotoxicity and oxidative stress, on inhibiting CMRP2 phosphorylation in mice intravitreally injected with N-methyl-D-aspartate (NMDA) and GLAST mutant mice. Results of the study demonstrated that HupA and NAR significantly reduced RGC degeneration and thinning of the inner retinal layer, and inhibited the elevated CRMP2 phosphorylation. These treatments protected against glutamate excitotoxicity and suppressed oxidative stress, which could provide insight into developing new effective therapeutic strategies for NTG.

Childhood maltreatment and engaging in NSSI for automatic-negative reinforcement: The mediating role of alexithymia and moderating role of help-seeking attitudes.

BACKGROUND: There is evidence indicating that childhood maltreatment is linked to the occurrence of non-suicidal self-injury (NSSI). Nevertheless, the association between childhood maltreatment and the automatic-negative reinforcement aspect of NSSI remains understudied. Chapman's (2006) experiential avoidance model posits that the main factor in sustaining NSSI is negative reinforcement, specifically through the avoidance or escape from distressful emotional experiences. The current study examines a conceptual framework based on this theory and the available literature that explores the potential mediation role of alexithymia in the relation between childhood maltreatment and the automatic-negative reinforcement of NSSI. Additionally, this study investigates how this process may be influenced by individuals' attitudes toward seeking professional help. METHODS: 3657 adolescents (1616 females) completed questionnaires regarding childhood maltreatment, alexithymia, help-seeking attitudes, the NSSI, and its functions. RESULTS: The findings of the study exposed a positive link between childhood maltreatment and the automatic-negative reinforcement of NSSI, with the mediating role of alexithymia. Interestingly, it was unexpected to discover that individuals with high help-seeking attitudes experienced an intensification of the relationship between childhood maltreatment and both alexithymia and the automatic-negative reinforcement of NSSI. LIMITATION: The study's cross-sectional design hindered the inference of causality. CONCLUSION: The present study demonstrated that it is crucial to consider the impact of both alexithymia and help-seeking attitudes in adolescents who have experienced maltreatment. These findings hold implications for preventive interventions that target the reduction of NSSI behaviors driven by automatic-negative reinforcement.

The phenotypic fate of bone marrow-derived stem cells in acute kidney injury.

BACKGROUND: Despite increasing attention on the role of bone marrow derived stem cells in repair or rejuvenation of tissues and organs, cellular mechanisms of such cell-based therapy remain poorly understood. METHODS: We reconstituted hematopoiesis in recipient C57BL/6J mice by transplanting syngeneic GFP(+) bone marrow (BM) cells. Subsequently, the recipients received subcutaneous injection of granulocyte-colony stimulating factor (G-CSF) and were subjected to acute renal ischemic injury. Flow cytometry and immunostaining were performed at various time points to assess engraftment and phenotype of BM derived stem cells. RESULTS: Administration of G-CSF increased the release of BM derived stem cells into circulation and enhanced the ensuing recruitment of BM derived stem cells into injured kidney. During the second month post injury, migrated BM derived stem cells lost hematopoietic phenotype (CD45) but maintained the expression of other markers (Sca-1, CD133 and CD44), suggesting their potential of transdifferentiation into renal stem cells. Moreover, G-CSF treatment enhanced the phenotypic conversion. CONCLUSION: Our work depicted a time-course dependent transition of phenotypic characteristics of BM derived stem cells, demonstrated the existence of BM derived stem cells in damaged kidney and revealed the effects of G-CSF on cell transdifferentiation.

A comparison of two methods for phase response calibration of hydrophones in the frequency range 10-400 kHz.

A comparison is made of two methods for determining the phase response of hydrophones in the kilohertz frequency range: The three-transducer spherical-wave reciprocity method and the method of optical interferometry. The implementation of the methods and the corresponding experimental systems are described. To facilitate a comparison, the methods are used to determine the phase response of three commercially available measuring hydrophones over the frequency range from 10 to 400 kHz. The results are compared, showing agreement within the estimated uncertainties of the methods. An investigation is conducted into the sources of uncertainties in the methods which increase with frequency. The major sources of uncertainty are residual positioning errors giving rise to phase uncertainties; a significant problem for the reciprocity method is that it requires one hydrophone to be rotated during the measurement procedure. An additional source of uncertainty at higher frequencies may be present if the position of the sensing element is not central within the outer hydrophone boot.

A novel fault classification feature extraction method for rolling bearing based on multi-sensor fusion technology and EB-1D-TP encoding algorithm.

To improve the accuracy of bearing fault diagnosis in a multisensor monitoring environment, it is necessary to obtain more accurate and effective fault classification features for bearings. Accordingly, a bearing fault classification feature extraction method based on multisensor fusion technology and an enhanced binary one-dimensional ternary pattern (EB-1D-TP) algorithm were proposed in this study. First, an optimal equalization weighting algorithm was established to realize high-precision fusion of bearing signals by introducing an optimal equalization factor and determining the theoretical optimal equalization factor value. Second, an enhanced binary encoding method similar to balanced ternary encoding was developed, which increases the difference between the different fault features of the bearing. Finally, the new sequence obtained after encoding was used as the input to a support vector machine to classify and diagnose the faults of the rolling bearing. The experimental results show that the algorithm can significantly improve the accuracy and speed of rolling-bearing fault classification. Combining fusion-encoding features with other intelligent classification methods, the classification results were improved.