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Introduction. To investigate the predictive factors for successful repeat microdissection testicular sperm extraction attempts in patients with Klinefelter syndrome. Methods. A total of 28 azoospermic men with nonmosaic Klinefelter syndrome who have received microdissection testicular sperm extraction twice with successful initial microdissection testicular sperm extraction attempts in our institute were studied. Outcome variables (age, serum follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, and estradiol) of azoospermic men with nonmosaic Klinefelter syndrome and a successful 2nd surgical sperm retrieval attempt (group A) were compared to those with an unsuccessful 2nd sperm retrieval attempt (group B). Results. Twenty-one patients (75%) had successful sperm recovery at the 2nd microdissection testicular sperm extraction attempt. The mean testosterone level at baseline and before the 1st microdissection testicular sperm extraction attempt was higher in group A than in group B (2.7 vs. 0.9 ng/mL, p < 0.01 , and 3.9 vs. 1.1 ng/mL, p = 0.02 ). Receiver operating characteristic curve analysis identified the threshold baseline testosterone concentration (1.5 ng/mL) of patients with Klinefelter syndrome in predicting successful 2nd sperm retrieval attempts and revealed positive and negative predictive values of 94.44% and 60%, respectively. Conclusion. Azoospermic men with Klinefelter syndrome presenting with low testosterone levels and successful sperm recovery during the first microdissection testicular sperm extraction procedure are unlikely to retrieve sperm on the 2nd microdissection testicular sperm extraction attempt. Hence, these patients should be properly counseled before sperm retrieval.

Phytohormone signalling pathways have an important role in defence against pathogens mediated by cell-surface pattern recognition receptors and intracellular nucleotide-binding leucine-rich repeat class immune receptors

We found that in regenerative erythropoiesis, the erythroid progenitor landscape is reshaped, and a previously undescribed progenitor population with colony-forming unit-erythroid (CFU-E) activity (stress CFU-E [sCFU-E]) is expanded markedly to restore the erythron. sCFU-E cells are targets of erythropoietin (Epo), and sCFU-E expansion requires signaling from the Epo receptor (EpoR) cytoplasmic tyrosines. Molecularly, Epo promotes sCFU-E expansion via JAK2- and STAT5-dependent expression of IRS2, thus engaging the progrowth signaling from the IGF1 receptor (IGF1R). Inhibition of IGF1R and IRS2 signaling impairs sCFU-E cell growth, whereas exogenous IRS2 expression rescues cell growth in sCFU-E expressing truncated EpoR-lacking cytoplasmic tyrosines. This sCFU-E pathway is the major pathway involved in erythrocytosis driven by the oncogenic JAK2 mutant JAK2(V617F) in myeloproliferative neoplasm. Inability to expand sCFU-E cells by truncated EpoR protects against JAK2(V617F)-driven erythrocytosis. In samples from patients with myeloproliferative neoplasm, the number of sCFU-E-like cells increases, and inhibition of IGR1R and IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identified a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis.

Microdissection testicular sperm extraction (mTESE) is the mainstay of sperm retrieval in men with non-obstructive azoospermia (NOA). Some experts believe that a resting period of ≥6 months is required between procedures to ensure better sperm retrieval rates and fewer complications. However, no scientific studies have investigated how long patients should wait before arranging a second mTESE procedure. This retrospective study aimed to evaluate whether good success rates are still achieved when a repeat mTESE procedure is performed within 6 months.Total 146 patients with NOA who underwent mTESE twice from the same testis between May 2012 and September 2019 were retrospectively collected. These patients were categorized into three groups according to the time interval between the two mTESE surgeries, with 44, 60, and 42 patients undergoing a repeat mTESE after3 months (Group I), between 3 and 6 months (Group II), and6 months (Group III) after the first procedure, respectively.No significant differences were observed between groups in terms of patient characteristics and preoperative hormone profiles. Overall sperm retrieval rates did not differ among the three groups (93.2%, 90.0%, and 88.1% in groups I, II, and III, respectively (p=0.719)), nor did fertility outcomes, including rates of fertilization, biochemical pregnancy, clinical pregnancy, and cumulative live births.Sperm retrieval rates for repeat mTESE procedures were consistently high, even when the second procedure was performed within 6 months of the first. Repeat mTESE within 6 months is not a limitation for patients with NOA, if required clinically.

In patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), preoperative prediction of extraprostatic extension (EPE) can facilitate patient selection for nerve-sparing procedures. Since both multiparametric magnetic resonance imaging (mpMRI) and prostate health index (PHI) have shown promise for the diagnosis and prognostication of PCa, we investigated whether a combination of mpMRI and PHI evaluations can improve the prediction of EPE after RP.Patients diagnosed with PCa and treated with RP were prospectively enrolled between February 2017 and July 2019. Preoperative blood samples were analyzed for PHI (defined as [p2PSA/fPSA] × √tPSA), and mpMRI examinations were performed and interpreted by a single experienced uroradiologist retrospectively. The area under the receiver operating characteristic curve (ROC) was used to determine the performance of mpMRI, PHI, and their combination in predicting EPE after RP.A total of 163 patients were included for analysis. The pathological T stage was T3a or more in 59.5%. Overall staging accuracy of mpMRI for EPE was 72.4% (sensitivity and specificity: 73.2% and 71.2%, respectively). The area under the ROC of the combination of mpMRI and PHI in predicting EPE (0.785) was higher than those of mpMRI alone (0.717; p = 0.0007) and PHI alone (0.722; p = 0.0236). mpMRI showed false-negative non-EPE results in 26 patients (16%), and a PHI threshold of40 could avoid undiagnosed EPE before RP in 21 of these 26 patients.The combination of PHI and mpMRI may better predict the EPE preoperatively, facilitating preoperative counseling and tailoring the need for nerve-sparing RP.

In rodent models, Li-ESWT has been shown to negatively impact semen concentration after treatment on the penis, implying that the reproductive system in close proximity may be indirectly affected by this modality. We hypothesized that shock waves are detrimental to spermatogenesis, and the aim of this study was to evaluate the effect of shock waves on spermatogenesis after direct shockwave treatment on testes using different energy settings.Twenty-five male Sprague Dawley rats, 8 weeks old, were divided into five groups, including one control group and four treatment groups each treated using shock waves of different intensities. All rats in the treatment groups received 2000 shocks on the left testis twice a week for 4 weeks, with shock wave intensity and frequency varied by treatment group: 0.1 mJ/mm 2 at 4 Hz for Group A, 0.15 mJ/mm 2 at 4 Hz for Group B, 0.35 mJ/mm 2 at 4 Hz for Group C, and 0.55mJ/mm2 at 3 Hz for Group D. At the end of the experiment, sperm collected from the epididymis was evaluated for concentration and motility. Testicular spermatogenesis, the apoptotic index of germ cells, and the expression of a meiotic-specific gene were also analyzed.The treatment group receiving shock wave intensity at 0.55 mJ/mm2 showed a significant decrease in sperm concentration, motility, and Johnsen score as compared to other groups. The apoptotic index of spermatogenic cells increased as intensity of the shock wave treatment was escalated, and reach a statistically significant difference at 4 weeks post-treatment. Treating testes with intensity levels of 0.55 mJ/mm2 at 3 Hz interfere with the quality or quantity of spermatogenesis and also increases in spermatogenic cell apoptosis, whereas the expression of the SYCP3 gene significantly decreased after treatment with intensity levels of 0.10 mJ/mm2, 0.15 mJ/mm2, and 0.35 mJ/mm2 at 4 Hz.Treating testes with intensity levels of 0.55 mJ/mm2 at 3 Hz interfere with the quality or quantity of spermatogenesis and also increases in spermatogenic cell apoptosis, whereas the expression of the SYCP3 gene significantly decreased after treatment with intensity levels of 0.10 mJ/mm2, 0.15 mJ/mm2, and 0.35 mJ/mm2 at 4 Hz.

Recent years have witnessed an increasing trend in Chinese arbitration reform that emulates international norms and practices. This article examines some of these key reform measures and major challenges to their implementation. It explores in both legal and practical terms why most of these reform techniques may remain largely ineffective, showing that engaging in international norms and standards in China can be highly challenging due to their potential illegality, the general lack of institutional capacity to sustain them, and the conflicts of local ideas about the purposes of arbitration. It is thus doubtful whether commitment to satisfying the formal requirements prescribed by the legal reforms would often prevail. When it does, it is questionable whether this form of commitment would become prevalent and how it could proceed in a sustainable and coherent manner from a practical perspective.

To identify key predictors for successful sperm retrieval in men with AZFc microdeletion.Totally, 71 infertile men with confirmed AZFc microdeletion were studied. For each patient, the endocrine profile including serum follicle stimulating hormone (FSH), luteinizing hormone, total testosterone, prolactin, and estradiol was recorded, along with intratesticular testosterone levels (ITT), age, and testicular size. The factors were further analyzed to determine the key predictors for successful sperm retrieval.Of the 71 men with AZFc microdeletion, 52 (73.2%) were classified as having non-obstructive azoospermia (NOA), 7 (9.9%) as having cryptozoospermia, and 12 (15.8%) as having severe oligoasthenoteratozoospermia. Of the 52 men with azoospermia, 47 received microdissection testicular sperm retrieval, and sperm retrieval was successful in 35 of those cases (74.5%). A significantly lower serum FSH (p = 0.03) was found in those patients from whom sperm could be successfully retrieved. The area under the receiving operating characteristic curve for FSH was determined to be 0.721. Using an FSH cutoff point of 12.95 mIU/mL, the model for predicting successful sperm retrieval was found to have 51.4% sensitivity, 83.3% specificity, 90.0% positive predictive value, and 37.0% negative predictive value. ITT levels were obtained from 7 NOA patients, the mean ITT and the mean ITT/serum testosterone ratio was 1932.8 ng/ml and 567.2 in 6 men with successful sperm retrieval, whereas, in a patient with fail sperm retrieval, the levels were 2370 ng/ml and 393.0.Men exhibiting AZFc microdeletion with discernible spermatogenesis from whom sperm was successfully retrieved by mTESE generally presented with relatively lower FSH levels.

Cembranoids compounds are mainly distributed in higher plants of the Pinaceae and Solanaceae families, as well as soft corals, and serve as important aroma precursors. Their degradation products are widely used in various aspects of life, such as farnesal, which finds extensive applications in the pharmaceutical industry. In this study, a strain (Stenotrophomonas maltophilia H3-1) was isolated from soil, which can efficiently degrade α-cedriene-4,6-diol.Based on GC-MS detection of α-cembratriene-4,6-diol degradation efficiency of the H3-1 strain, it was determined that the optimal culture conditions for H3-1 are 40°C, pH 8, maltose concentration of 2 g/L, and ammonium sulfate concentration of 2 g/L. Under the optimum culture conditions, the degradation rate of 1 mg/mL α-cembratriene-4,6-diol by H3-1 strain within 36 h was as high as 85.86%. This indicates the strong biodegradation ability of the H3-1 strain towards α-cembratriene-4,6-diol. Through GC-MS analysis, we identified the biodegradation products of α-cembratriene-4,6-diol, including farnesal. This provides a theoretical basis and microbial resources for further study on the degradation products and applications of α-cembratriene-4,6-diol.

Background Previous studies have investigated the relationships between psychache or meaning in life and suicidal ideation based on sum score of corresponding scale. However, this practice has hampered the fine-grained understanding of their relationships. This network analysis study aimed to conduct a dimension-level analysis of these constructs and the relationships among them in a joint framework, and identify potential intervention targets to address suicidal ideation. Methods Suicidal ideation, psychache, and meaning in life were measured using self-rating scales among 738 adults. A network of suicidal ideation, psychache, and meaning in life was constructed to investigate the connections between dimensions and calculate the expected influence and bridge expected influence of each node. Results “Psychache” was positively linked to “sleep” and “despair”, while “presence of meaning in life” had negative associations with “psychache”, “despair”, and “pessimism”. The most important central nodes were “sleep” and “despair”, and the critical bridge nodes were “presence of meaning in life” and “psychache”. Conclusion These preliminary findings uncover the pathological pathways underlying the relationships between psychache, meaning in life, and suicidal ideation. The central nodes and bridge nodes identified may be potential targets for effectively preventing and intervening against the development and maintenance of suicidal ideation.

Spousal caregiving of head and neck cancer (HNC) patients challenges relationship quality and may negatively impact family function. Our purpose was to identify factors associated with family dysfunction in spousal caregivers (SCs) of HNC patients within the first 6 months after treatment. We explored whether patient or SC characteristics differ by level of family dysfunction.We conducted a cross-sectional study of HNC patient-SC dyads in Taiwan from July 2020 to January 2022 using patient-reported outcomes. Patients were assessed using a set of structured questionnaires to measure performance status, demographic and clinical characteristics, physical function, and social-emotional function. SCs were measured on their hardiness, coping styles, spousal relationship, quality of life, and family function.Of the 132 dyads surveyed, 62.1% of SCs reported a functional family, 34.8% reported a moderately dysfunctional family, and 3.0% reported a highly dysfunctional family. Patient factors associated with family dysfunction (highly dysfunctional or moderately dysfunctional) included lower family annual income and worse social-emotional function. Associated SC factors were lower hardiness, less use of active coping, and worse spousal relationships.Lower family annual income, less patient social-emotional function, less SC hardiness, less SC active coping, and worse SC perceived spousal relationship were associated with perceived family dysfunction. Providing patient-SC dyads with sufficient social resources and problem-solving training may help them positively cope with cancer and enhance family function.

Py-GC–MS Investigation of Pyrolysis Behaviors and Decomposition Products of α- and β-2,7,11-cembratriene-4,6-diols May 1, 2022 Shen Huang, Chen Yang, Ning Ma, Lifeng Zhou, Chunxiao Jia, Tao Wei, Duobin Mao LCGC North America, May 2022, Volume 40, Issue 5 Pages: 223–228 To study the thermal stability of cembratriene, α- and β-2, 7, 11-cembratriene-4, 6-diols (α- and β-CBT) were isolated from tobacco leaves. Thermogravimetric (TG) and differential thermogravimetric (DTG) analyses were used to evaluate the cleavage differences between the two compounds. The TGA results showed the peak temperatures (Tp) were 263.3 °C and 254.1 °C with the largest weight loss rate; the significant weight losses were 90.96% and 99.45%. Pyrolysis gas chromatography–mass spectrometry (Py-GC–MS) was employed for the pyrolysis products at different temperatures (300, 600, and 900 °C) under either N2 or an O2:N2 (10%:90%) mixture. The results showed that the major pyrolysates from α- and β-CBT were simple hydrocarbons, such as toluene, 1, 4-pentadiene, and p-xylene, as well as several important flavor compounds, such as 2-methylfuran, benzaldehyde, and 4-methylbenzaldehyde. More pyrolysis products were obtained at higher temperatures, and almost all of the harmful aromatic ingredients were produced at 900 °C. Importantly, solanone, a significant flavor component, was only obtained from the pyrolysis of α-CBT under 10% O2 in N2 at both 600 and 900 °C. The number of the pyrolysates changed with the change in pyrolysis temperature and the presence of oxygen. The study of the thermal behavior and pyrolysis products of these terpenoids could possibly suggest flavor precursors that could be used to provide specific flavors.

Sea surface height (SSH) retrieval based on spaceborne Global Navigation Satellite System Reflectometry (GNSS-R) usually uses the GNSS-R geometric principle and delay-Doppler map (DDM). The traditional method condenses the DDM information into a single scalar measure and requires error model correction. In this article, the idea of using machine learning methods to retrieve SSH is proposed. Specifically, two widely-used methods, principal component analysis combined with support vector regression (PCA-SVR) and convolution neural network (CNN), are used for verification and comparative analysis based on the observation data provided by Techdemosat-1 (TDS-1). According to the DDM inversion method, ten features from TDS-1 Level 1 data are selected as inputs; The SSH verification model based on the Danmarks Tekniske Universitet (DTU) 15 ocean wide mean SSH model and the DTU global ocean tide model is used as output verification of SSH. For the hyperparameters in the machine learning model, a grid search strategy is used to find the optimal values. By analyzing the TDS-1 data from 31 GPS satellites, the mean absolute error (MAE), root-mean-square error (RMSE) and coefficient of determination (R2) of the PCA-SVR inversion model are 0.61 m, 1.72 m, and 99.56%, respectively; and the MAE, RMSE, and R2 of the CNN inversion model is 0.71 m, 1.27 m, and 99.76%, respectively. In addition, the time required to train the PCA-SVR and CNN inversion models is also analyzed. Overall, the technique proposed in this article can be confidently applied to SSH inversion based on TDS-1 data.

In this study, the employment of the aroma-boosting bacterium H8 (Klebsiella variicola) under optimal growth conditions significantly improved the content of aroma components in tobacco concentrate and reduced the content of nicotine. We performed a macro-genomic analysis of reconstituted tobacco leaf concentrate fermented by Klebsiella variicola to explain the enhanced aroma compound production and reduced harmful compound production. The results of macro-genomic analysis revealed following facts: (i) Genes related to carbohydrate degradation, amino acid degradation, and lipid degradation accounted for a large proportion of the concentrate microbiome, accounting for 16.1%, 21.8%, and 4.8%, respectively; (ii) Klebsiella variicola is significantly related to the decrease in water-soluble sugar and nicotine; (iii) changes in the contents of 2-acetylpyrrole,β-damascenone, benzyl alcohol, linalool, farnesyl acetone, and phenylethanol are significantly related to the genes abundance of glycoside hydrolases such as GH28, GH42, and GH13; (iv) changes in the contents of dihydrokiwifruit lactone, 2,4-di-t-butylphenol and megastigmatrienones are significantly and positively correlated with the genes abundance changes of Lactobacillus acidophilus, Lactobacillus Faraday and Klebsiella pneumonia; (v) the decrease in the number of aroma-enhancing bacteria during fermentation is due to the autophagy-related protein [ATG5]. This work may be helpful for improving fermentation product quality by regulating the microbial community and gaining insight into the microbial ecosystem.

Radiation is an integral part of cancer therapy. With the emergence of oncolytic vaccinia virus immunotherapy, it is important to study the combination of radiation and vaccinia virus in cancer therapy. In this study, we investigated the anti-tumor effect of and immune mechanisms underlying the combination of high-dose hypofractionated stereotactic body radiotherapy (SBRT) and oncolytic vaccinia virus in preclinical murine models. The combination enhanced the in vivo anti-tumor effect and increased the numbers of splenic CD4+Ki-67+ helper T lymphocytes and CD8+Ki-67+ cytotoxic T lymphocytes. Combinational therapy also increased tumor-infiltrating CD3+CD4+ helper T lymphocytes and CD3+CD8+ cytotoxic T lymphocytes, but decreased tumor-infiltrating regulatory T cells. In addition, SBRT combined with oncolytic vaccinia virus enhanced in vitro cell death, partly through necroptosis, and subsequent release of damage-associated molecular patterns (DAMPs), and shifted the macrophage M1/M2 ratio. We concluded that SBRT combined with oncolytic vaccinia virus can trigger tumor cell necroptosis and modify macrophages through the release of DAMPs, and then generate potent anti-tumor immunity and effects. Thus, combined therapy is potentially an important strategy for clinical cancer therapy.

OBJECTIVE: To investigate the clinical value of platelet and inflammatory factor activation in vascular endothelial injury in hypertension. METHODS: A total of 120 hypertension patients diagnosed in our hospital from December 2019 to June 2021 were enrolled as study objects (Hypertension group); besides, another cohort of 60 healthy people undergoing physical examination at the same period were recruited as the controls (Control group). Next, the baseline clinical characteristics of subjects in the two groups were recorded and compared. Specifically, a hematology analyzer was adopt for detecting the mean platelet volume (MPV), platelet distribution width (PDW) and platelet hematocrit (PCT); ELISA for the level of IL-6, IL-8 and TNF-α; PHILIPS EPIQ 7 C (a device assessing endothelial vasodilator function in a non-invasive fashion) for reactive hyperemia index (RHI); univariate and multivariate regression analysis for risk factors triggering endothelial dysfunction; and Spearman correlation analysis for the correlation of platelet activation indicators and inflammatory factor level with vascular endothelial function. RESULTS: Compared with the Control group, the patients in the Hypertension group exhibited higher levels of MPV, PDW, PCT, inflammatory factors (IL-6, IL-8 and TNF-α) and lower RHI. Moreover, Spearman correlation analysis showed a significant negative correlation of MPV, PDW, PCT, IL-6, IL-8 and TNF-α level with RHI level. In addition, univariate and multivariate regression analysis presented that MPV, PCT, IL-8 and TNF-α were risk factors for vascular endothelial dysfunction. CONCLUSION: The activation of platelet and inflammatory factor is closely related to vascular endothelial function injury in patients with hypertension. To be specifically, platelet and inflammatory factor activation can effectively reflect the vascular endothelial function injury in patients with hypertension and has high clinical value.

PURPOSE After suddenly stopping smoking after an initial oral cancer (OC) diagnosis, patients may restart smoking and nicotine dependence. This study sought to identify factors associated with high nicotine dependence in OC patients who restarted smoking post-treatment. DESIGN A cross-sectional study. METHODS A group of 220 OC patients who restarted smoking post-treatment were recruited from the outpatient radiation department of a single cancer center in northern Taiwan. Demographic and clinical characteristics were recorded, and patients were assessed for nicotine and smoking dependence, physical activity and function, socio-emotional function, social support, and depression. RESULTS Among patients who restarted smoking after treatment for OC, 75.9% reported low-to-moderate dependence on smoking, while 24.1% reported high nicotine dependence. Factors associated with high nicotine dependence included higher incidence of smoking per day, greater dependence on smoking, less physical activity per week, and poorer social-emotional function. Those highly dependent on nicotine were younger, unmarried, had less education, and had begun smoking earlier than those with low-to-moderate nicotine dependence. CONCLUSIONS The amount of smoking per day, greater smoking behavioral dependence, less physical activity per week, and worse social-emotional function affected high nicotine dependence. CLINICAL RELEVANCE Smoking cessation training and counseling for OC patients may help them better control their use of tobacco after treatment.

Angiopoietin-like protein 8 (Angptl8) is a new constituent of angiopoietin-related protein family. In the present study, Landrace × Yorkshire pigs, C57BL/6 J mice, and Wistar rat were used as experimental animals. Using normal PCR, T-A cloning, RACE, and other experimental techniques, full length of porcine Angptl8 gene was cloned. Through real-time PCR, Angptl8 expression was detected in assorted tissues (kidney, heart, spleen, liver, lung, abdominal fat, and back longest muscle) of different animals. The present result showed that the full-length of porcine Angptl8 was 875 bp. Its ORF region contained 597 bp, from 21 bp to 618 bp, it had high conservation. The protein of Angptl8 had 198 amino acids. Its relative molecular mass was 21,988.3 Da. Its theoretical isoelectric point was 6.35. There was a highly hydrophobic region near the 10th amino acid site of the Angptl8 gene, while 177th and 187th were highly hydrophilic. Angptl8 protein may be not a transmembrane protein. The first to the 19th amino acids on the N-terminal were signal peptides, and the first 18th–19th amino acid sites may be the signal peptide shear site. In addition, Angptl8 in healthy pigs was mainly expressed in the liver. Its expression in heart and adipose tissue was minimum. Angptl8 of both mouse and rat was enriched in the fat and liver; mouse and rat minimum Angptl8 expression was in muscle and spleen, respectively. The present results suggest that there may exist species difference in tissue-specific expression of Angptl8.

Understanding population genetic structures is crucial for planning and implementing conservation programmes to preserve species’ adaptive and evolutionary potential and thus ensure their long-term persistence. The grey mullet (Mugil cephalus) is a globally distributed coastal fish. Its populations in waters surrounding Taiwan on the western Pacific fringe are divided into at least two stocks (migratory and residential), but questions remain regarding their genetic divergence and gene flow. To cast more light on this, allozyme variations at 21 presumptive gene loci of 1,217 adult grey mullets from 15 localities in Japan, Taiwan and mainland China, and four gene loci from 1,470 juveniles from three localities in Taiwan were used to investigate patterns of genetic variation. The mean expected heterozygosity (He) was 0.128—ranging from 0.031 (Matsu) to 0.442 (Kaoping)—and the mean observed heterozygosity (Ho) was 0.086—ranging from 0.017 (Kaohsiung) to 0.215 (Kaoping). Both AMOVA and the high overall mean FST of 0.252 indicated enormous genetic differentiation among populations and the positive mean value of FIS was 0.328, indicating a deficiency of heterozygotes. PCA analysis indicated that the samples of M. cephalus could be split into four groups and STRUCTURE analysis showed that all individuals were grouped into three genetic clusters. Results of mutation-drift equilibrium tests did not suggest that the populations experienced any recent genetic bottleneck. Results from all localities in the present investigation showed that significant change in the GPI-A genotype frequencies with latitudes—e.g., an increase in GPI-A * 135/135 homozygote frequencies and GPI- A * 100/100 frequencies were highly correlated with latitudinal cline. T All migratory populations with the GPI-A genotype were almost exclusively the GPI-A * 100/100 homozygote. During the life history of M. cephalus, the GPI-A * 100/135 heterozygote frequency significantly decreases with age. Based on these data, we suggested that each GPI-A genotype represents trait combinations of higher fitness in some portions of the environment. Furthermore, the genotypic frequencies change in accordance with life stages, suggesting that selection occurs throughout the life span.

The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that it may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we find that centrosomes are highly accessible to soluble molecules with a Stokes radius of less than 5.8 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of this barrier is tightly regulated by branched actin filaments outside of centrosomes and it decreases during anaphase when branched actin temporally increases. The actin-based diffusion barrier gates microtubule nucleation by interfering with γ-tubulin ring complex recruitment. We propose that actin filaments spatiotemporally constrain protein complexes at centrosomes in a size-dependent manner.

Radiation-induced liver disease (RILD) is the major complication for cancer patients after radiation therapy. We investigated the protective effects of BPC 157 peptide in reducing RILD.Mice were irradiated with a single dose of 12 Gy to induce acute liver injury with or without oral BPC 157. Plasma levels of AST and ALT were determined. In vitro rat liver clone 9 cells and in vivo liver tissues were harvested for MTT assay, TUNEL assay, lipid staining, polypoid cell counts, Western blotting of caspase-3, PCNA, KLF-4 and HIF-2α, and immunocytochemistry for PCNA, KLF-4 and HIF-2α. SiRNAs were used to knockdown KLF-4.BPC 157 was firstly demonstrated to reduce RILD by decreasing plasma levels of AST and ALT, and inhibiting hydropic degeneration of liver. BPC 157 significantly decreased radiation-induced cell apoptosis, increased PCNA expression, promoted the expression of KLF4, decreased the radiation-induced hepatic lipid accumulation and HIF-2α expression both in mice liver and in clone 9 liver cells. The knockdown of KLF4 abolished the protective effect of BPC 157 on radiation-induced apoptosis and lipid accumulation in clone 9 liver cells, indicating that the protective effect of BPC 157 was mediated by KLF4 in liver cells.The present study provided a good model for molecular mechanism underlying the acute RILD. BPC 157, as a stable pentadecapeptide that can be chemically synthesized and purified easily for research, together with its in vivo markedly protective effect made it worth of being investigated for future clinical application for RILD.

People have wishes and sometimes share their wishes in social media, hoping to receive supports or to find partners with the same wishes. By collecting and analyzing those wishes, we may find out not only the trend of common wishes, but also the needs of individuals. This paper presents a preliminary study of Chinese wish detection. We provide analysis on the data from Linkwish, which is a micro social network for wish sharing with users mainly from Taiwan, Hong Kong, and Macao. Then, we use SVM with various types of features to classify these messages as wish or not. Our experimental results show that some features can achieve average areas under precision-recall curves higher than 0:95 in 10-fold cross validation.

Chieh-Min Liu,1 Bing-Shen Huang,2,3 Yi-Hao Yen,4 Yu-Ming Wang,1,5,6 Eng-Yen Huang,1,5,6 Hsuan-Chih Hsu,1 Tzu-Ting Huang,1 Yao-Hsu Yang,5,7,8 Jen-Yu Cheng1 1Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 3Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan, Taiwan; 4Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; 6Department of Radiation Oncology, Xiamen Chang Gung Hospital, Fujian, People’s Republic of China; 7Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 8Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, TaiwanCorrespondence: Jen-Yu ChengDepartment of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, TaiwanTel +886-9-10722590Email york480@cgmh.org.twPurpose: Evidence is lacking concerning the benefit of the combination of sorafenib and radiotherapy to treat advanced hepatocellular carcinoma (HCC). To date, no publication has reported the outcomes of radiotherapy alone versus concurrent therapy. We aimed to compare the effectiveness of radiotherapy alone versus concurrent radiotherapy and sorafenib for locally advanced hepatocellular carcinoma.Materials and Methods: We conducted a propensity score matching (PSM) cohort study comparing the effectiveness of the concurrent use of sorafenib and external beam radiotherapy versus radiotherapy alone in Barcelona Clinic Liver Cancer (BCLC) stage B or C, nonsurgically managed, nonmetastatic patients with HCC. Two subpopulations were matched based on baseline characteristics. Stratified analysis was also performed to assess the heterogeneous effects of the two arms. Overall survival (OS) was compared. Radiation-induced liver disease (RILD) and overt gastrointestinal (GI) bleeding events were also recorded.Results: Seven hundred thirty-one BCLC stage B or C nonmetastatic HCC patients were identified from 2007 to 2017. Of these, 347 patients met the inclusion criteria (Radiotherapy alone: 269 patients; concurrent therapy: 78 patients). Propensity score matching yielded 73 patients each in the radiotherapy and concurrent groups. The median OS was 9.6 months in the radiotherapy-alone group and 9.9 months in the concurrent group (hazard ratio (HR): 1.12; 95% CI=0.78– 1.62; p=0.544). Posttreatment toxicities, including radiation-induced liver disease and overt gastrointestinal bleeding, showed no significant differences between the groups.Conclusion: In our study, the concurrent use of sorafenib and conventional external beam radiotherapy shows no survival benefit over radiotherapy alone for locally advanced hepatocellular carcinoma.Keywords: radiotherapy, sorafenib, hepatocellular carcinoma

Summary Plants use intracellular nucleotide‐binding leucine‐rich repeat immune receptors (NLRs) to recognize pathogen‐encoded effectors and initiate immune responses. Tomato spotted wilt virus (TSWV), which has been found to infect >1000 plant species, is among the most destructive plant viruses worldwide. The Sw‐5b is the most effective and widely used resistance gene in tomato breeding to control TSWV. However, broad application of tomato cultivars carrying Sw‐5b has resulted in an emergence of resistance‐breaking (RB) TSWV. Therefore, new effective genes are urgently needed to prevent further RB TSWV outbreaks. In this study, we conducted artificial evolution to select Sw‐5b mutants that could extend the resistance spectrum against TSWV RB isolates. Unlike regular NLRs, Sw‐5b detects viral elicitor NSm using both the N‐terminal Solanaceae‐specific domain (SD) and the C‐terminal LRR domain in a two‐step recognition process. Our attempts to select gain‐of‐function mutants by random mutagenesis involving either the SD or the LRR of Sw‐5b failed; therefore, we adopted a stepwise strategy, first introducing a NSmRB‐responsive mutation at the R927 residue in the LRR, followed by random mutagenesis involving the Sw‐5b SD domain. Using this strategy, we obtained Sw‐5bL33P/K319E/R927A and Sw‐5bL33P/K319E/R927Q mutants, which are effective against TSWV RB carrying the NSmC118Y or NSmT120N mutation, and against other American‐type tospoviruses. Thus, we were able to extend the resistance spectrum of Sw‐5b; the selected Sw‐5b mutants will provide new gene resources to control RB TSWV.

In this work, the impact of positive bias stress (PBS) on an all copper(Cu)-electrode a-InGaZnO TFT is discussed. Commonly, Cu diffusion from the source/drain electrode after negative bias stress (NBS) leads to degradations in the on-state current and subthreshold swing. However, this study finds that diffusion in the gate insulator layer from the gate electrode suffers from more serious degradation. Eventually, this phenomenon causes a serious breakdown of the gate insulator such that it loses the transistor function. Results indicate that after 2000s of PBS, accumulation of Cu ions forms a filament which dominates the leakage path. During the stress duration, the gate leakage current is monitored and current fittings are adopted to confirm the phenomena. Furthermore, temperature dependencies have verified the results of hopping and Ohmic conduction at different stages of deterioration. Compared to previous literature that focus on the impacts of source/drain electrodes, this work suggests that gate engineering for thin film transistors is more urgent for high-quality display applications.

Most fast synaptic inhibitions in the mammalian brain are mediated by GABA

Head and neck cancer (HNC) patients who are unable to return to work after completing treatment might face financial loss and reduced self-esteem. The aim of this study was to identify factors influencing a return to work in HNC cancer patients in the first 6 months after treatment. This cross-sectional study examined HNC patients who completed treatment from the outpatient radiation department of a single cancer center in northern Taiwan. Patients were assessed according to psychological distress, patient-perceived health status, barriers to returning to work, and facilitators of returning to work. Of the 106 HNC patients surveyed, 54.7% successfully returned to work. Barriers to returning to work included poor self-perception of health, greater psychological distress, and age ≥50 years. Patients who had higher psychological distress, returned to work after start of the pandemic, or received reconstruction surgery were less likely to experience a positive environment facilitating a return to work.

We find that in regenerative erythropoiesis, the erythroid progenitor landscape is reshaped, and a previously undescribed progenitor population with CFU-E activity (stress CFU-E/sCFU-E) is markedly expanded to restore the erythron. sCFU-E are targets of erythropoietin (Epo) and sCFU-E expansion requires signaling from the Epo receptor (EpoR) cytoplasmic tyrosines. Molecularly, Epo promotes sCFU-E expansion via JAK2/STAT5-dependent expression of IRS2, thus engaging the pro-growth signaling from the IGF1 receptor (IGF1R). Inhibition of IGF1R/IRS2 signaling impairs sCFU-E cell growth, whereas exogenous IRS2 expression rescues cell growth in sCFU-E expressing truncated EpoR lacking cytoplasmic tyrosines. This sCFU-E pathway is the major pathway involved in erythrocytosis driven by the oncogenic JAK2 mutant, JAK2(V617F), in myeloproliferative neoplasm. Inability to expand sCFU-E cells by truncated EpoR protects against JAK2(V617F)-driven erythrocytosis. In myeloproliferative neoplasm patient samples, the number of sCFU-E like cells increases, and inhibition of IGR1R/IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identify a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis.Key PointsEpo-induced IRS2 allows engagement of IGF1R signaling to expand a previously unrecognized progenitor population in erythropoietic stress.Truncated EpoR does not support stress CFU-E expansion and protects against JAK2(V617F)-driven erythrocytosis in MPN.

As antibiotics and heavy metals are often mixed in animal feed, their excretion through animal feces would cause bacteria to produce antibiotic resistance genes and heavy metal resistance genes. The pollution of antibiotics resistance gene and heavy metal resistance gene has become a major threat to human health and ecological environment. From the perspective of bacterial evolution, we proposed the importance of bacterial long-term evolution experiments about antibiotics and heavy metals. There is a complex co-selection resistance between antibiotic resistance genes and heavy metal resistance genes, which interact with each other and collectively determine the environmental behavior of bacteria. Horizontal transfer of resistance gene increases its variability in the environment. Mobile genetic elements play an important role in horizontal transfer of resistance gene. As for resistance gene pollution control, advanced oxidation technology has a good resistance gene removal effect. The UV/TiO动物饲料中常混有抗生素和重金属,导致外排的动物粪便中携带有抗生素和重金属,引发细菌产生耐药性和重金属抗性,继而产生抗生素抗性基因和重金属抗性基因。抗生素和重金属抗性基因污染已成为威胁人类身体健康及破坏生态环境的重大问题。本文从细菌进化的角度,明确了细菌的抗生素和重金属长期进化试验对抗性机制研究的重要性;抗生素抗性基因与重金属抗性基因间存在复杂的协同选择抗性,两者间相互影响,共同决定着细菌环境行为;抗性基因的水平转移增加了细菌在环境中的可变性,可移动遗传元件在抗性基因水平转移中发挥着重要作用。在抗性基因污染控制方面,高级氧化技术具有很好的抗性基因去除效果,尤其是UV/TiO

Most fast synaptic inhibitions in the mammalian brain are mediated by GABAA receptors (GABAARs). An appropriate level of GABAAR expression at the cell surface is essential for neurodevelopment and the efficacy of GABAergic synaptic transmission. We previously reported that brefeldin A-inhibited GDP/GTP exchange factor 1 (BIG1), a binding partner of GABAARs, plays an important role in trafficking GABAARs to the cell surface. However, its regulatory mechanisms remain unknown. In the present study, we identified a new cellular protein, 14-3-3ζ, which can interact with the β subunit of GABAARs and BIG1 both in vitro and in vivo and colocalizes in the soma, dendrites and axons of hippocampal neurons. Overexpression of 14-3-3ζ-WT increased the surface expression of BIG1 in dendrites and axons, as well as the binding of BIG1 with GABAAR. Depleted 14-3-3ζ with efficacious siRNA attenuated the interaction between BIG1 and GABAARs and resulted in significant decreases in the surface expression levels of BIG1 and GABAAR. GABAAR agonist treatment increased the expression levels of BIG1 and 14-3-3ζ on the surface, indicating that 14-3-3ζ is involved in regulating BIG1-mediated GABAAR surface expression. Depletion of BIG1 or 14-3-3ζ significantly decreased GABAAR expression at the cell surface and suppressed the GABA-gated influx of chloride ions. These data indicate that the combination of 14-3-3ζ and BIG1 is required for GABAAR membrane expression. Our results provide a potential promising therapeutic target for neurological disorders involving GABAergic synaptic transmission.

In this work, the time-dependent behaviors of dual-channel amorphous InGaZnO (a-IGZO) thin-film transistors (TFTs) under negative bias illumination stress (NBIS) are systematically discussed. The dual-channel comprised two different IGZO layers fabricated by tuning the oxygen flow during deposition. The presence of heterojunctions enhanced field-effect mobility by 1.5× owing to the confinement of carriers in buried channels because of an energy barrier. However, after long periods of NBIS stress, the degradation of a-IGZO TFTs resulted in the entrapment of photo-generated electron–hole pairs at interface defects. The conduction path migrated to the surface channel. Results from extracting the hysteresis window and utilizing capacitance–voltage measurements have indicated a channel migration phenomenon due to the entrapment of electrons and holes at the surface and buried channel interfaces.