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Cryptosporidium spp. are significant opportunistic pathogens causing diarrhoea in humans and animals. Pigs are one of the most important potential hosts for Cryptosporidium. We evaluated the prevalence of Cryptosporidium in pigs globally using published information and a random-effects model. In total, 131 datasets from 36 countries were included in the final quantitative analysis. The global prevalence of Cryptosporidium in pigs was 16.3% (8560/64 809; 95% confidence interval [CI] 15.0–17.6%). The highest prevalence of Cryptosporidium in pigs was 40.8% (478/1271) in Africa. Post-weaned pigs had a significantly higher prevalence (25.8%; 2739/11 824) than pre-weaned, fattening and adult pigs. The prevalence of Cryptosporidium was higher in pigs with no diarrhoea (12.2%; 371/3501) than in pigs that had diarrhoea (8.0%; 348/4874). Seven Cryptosporidium species (Cryptosporidium scrofarum, Cryptosporidium suis, Cryptosporidium parvum, Cryptosporidium muris, Cryptosporidium tyzzeri, Cryptosporidium andersoni and Cryptosporidium struthioni) were detected in pigs globally. The proportion of C. scrofarum was 34.3% (1491/4351); the proportion of C. suis was 31.8% (1385/4351) and the proportion of C. parvum was 2.3% (98/4351). The influence of different geographic factors (latitude, longitude, mean yearly temperature, mean yearly relative humidity and mean yearly precipitation) on the infection rate of Cryptosporidium in pigs was also analysed. The results indicate that C. suis is the dominant species in pre-weaned pigs, while C. scrofarum is the dominant species in fattening and adult pigs. The findings highlight the role of pigs as possible potential hosts of zoonotic cryptosporidiosis and the need for additional studies on the prevalence, transmission and control of Cryptosporidium in pigs.

Targeting bromodomain and extra-terminal domain (BET) proteins has shown a promising therapeutic effect on melanoma. The development of strategies to better kill melanoma cells with BET inhibitor treatment may provide new clinical applications. Here, we used a drug synergy screening approach to combine JQ1 with 240 antitumor drugs from the Food and Drug Administration (FDA)-approved drug library and found that sunitinib synergizes with BET inhibitors in melanoma cells. We further demonstrated that BET inhibitors synergize with sunitinib in melanoma by inducing apoptosis and cell cycle arrest. Mechanistically, BET inhibitors sensitize melanoma cells to sunitinib by inhibiting GDF15 expression. Strikingly, GDF15 is transcriptionally regulated directly by BRD4 or indirectly by the BRD4/IL6/STAT3 axis. Xenograft assays revealed that the combination of BET inhibitors with sunitinib causes melanoma suppression in vivo. Altogether, these findings suggest that BET inhibitor-mediated GDF15 inhibition plays a critical role in enhancing sunitinib sensitivity in melanoma, indicating that BET inhibitors synergize with sunitinib in melanoma.

The diagnosis cycle of schizophrenia is long, there is no objective diagnostic basis. The over-energy entropy product of the speech fluency rectangular parameter is designed in the paper, the fuzzy clustering is used to double locate speech pause areas and to assist in the diagnosis of schizophrenia. The pause area of speech is located based on the low speech fluency and flat energy in schizophrenia patients, an extraction algorithm is given for speech fluency quantification parameters, support vector machine (SVM) classifier is used in the approach. The fluency acoustic features of speech are taken from 28 schizophrenia patients and 28 normal controls, these are used to verify the effect of the method in schizophrenia recognition, there is a correct rate of over 85%. The automatic schizophrenia identification based on energy entropy product and fuzzy clustering can provide objective, effective and non-invasive auxiliary for clinical diagnosis of schizophrenia.

While linear ubiquitin plays critical roles in multiple cell signaling pathways, few substrates have been identified. Global profiling of linear ubiquitin substrates represents a significant challenge because of the low endogenous level of linear ubiquitination and the background interference arising from highly abundant ubiquitin linkages (e.g. K48- and K63-) and from the non-specific attachment of interfering proteins to the linear polyubiquitin chain. We developed a bio-orthogonal linear ubiquitin probe by site-specific encoding of a norbornene amino acid on ubiquitin (NAEK-Ub). This probe facilitates covalent labeling of linear ubiquitin substrates in live cells and enables selective enrichment and identification of linear ubiquitin-modified proteins. Given the fact that the frequent overexpression of the linear linkage-specific deubiquitinase OTULIN correlates with poor prognosis in glioblastoma, we demonstrated the feasibility of the NAEK-Ub strategy by identifying and validating substrates of linear ubiquitination in patient-derived glioblastoma stem-like cells (GSCs). We identified STAT3 as a bona fide substrate of linear ubiquitin, and showed that linear ubiquitination negatively regulates STAT3 activity by recruitment of the phosphatase TC-PTP to STAT3. Furthermore, we demonstrated that preferential expression of OTULIN in GSCs restricts linear ubiquitination on STAT3 and drives persistent STAT3 signaling, and thereby maintains the stemness and self-renewal of GSCs.

A phase I open-label study assessed the effect of multiple oral doses of a potent CYP3A4 inhibitor (itraconazole) and inducer (rifampicin) on the pharmacokinetic profile of a single oral dose of senaparib, a novel, highly potent poly-(ADP-ribose) polymerase 1/2 inhibitor and CYP3A4 substrate, in Chinese healthy male volunteers (HMV).Adult HMV were enrolled to the itraconazole or rifampicin group (n = 16 each). In Period 1, all participants received a single oral dose of senaparib 40 mg (itraconazole group) or 100 mg (rifampicin group). In Period 2, the same dose was coadministered with itraconazole (200 mg) and rifampicin (600 mg), respectively. The primary endpoints were senaparib exposure parameters.Coadministration with itraconazole significantly increased exposure of senaparib and decreased that of its major metabolites M9 and M14. Maximum plasma senaparib concentration (CIn Chinese HMV, the exposure of senaparib was significantly increased when coadministered with itraconazole and significantly decreased when coadministered with rifampicin. It is recommended to avoid concomitant use of senaparib and strong inhibitors or inducers of CYP3A4.

LPI-CVD growth not only avoids the use of solid powders, but also enables the uniform distribution of precursors on the substrate, which are favorable for the monolayer synthesis, substitution doping and corresponding heterostructures of 2D TMDs.

Xinxin Zhu,1,* Shiyun Huang,1,* Yuxuan Tang,1,* Zhonglan Wu,2,* Yue Sun,1 Huiyan Ren,1 Hongmei Lu,1 Tingting Yin,1 Qing Zuo,1,* Zhiping Ge,1,* Ziyan Jiang1,* 1Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ziyan Jiang, Department of Obstetrics, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-13512534017, Email zyjiangchm@163.comBackground: Grade III meconium stained amniotic fluid (MSAF) is a common obstetric disease, and has the greatest impact on poor maternal and neonatal outcomes.Question or Hypothesis or Aim: There is no consensus on treatment, especially on the timing of delivery.Methods: We collected the medical records of 345 women who gave birth with grade III MSAF and analyzed the difference in baseline characteristics and maternal and neonatal outcomes relative to different labor stage, observation times in the first stage of labor, and the presence or absence of abnormal fetal heart rate (FHR) or thick amniotic fluid.Findings: Higher rate of cesarean section was observed when grade III MSAF was found in active labor. Intervention occurred at an observation time of 90– 120 min, but there were no significant differences in maternal or neonatal outcomes shown when the observation time was greater than 3 or 4 hours. However, a higher rate of admission to the neonatal intensive care unit was demonstrated in cases with grade III MSAF with abnormal FHR either in the first or second stage of labor or in cases with thick MSAF in the second stage of labor.Discussion: Higher rate of composite adverse neonatal outcomes was found when secondary MSAF (a transition from clear AF to MSAF) was diagnosed > 3 h before delivery.Conclusion: In the first stage of labor, an observation time of greater than 4 hours might be possible after grade III MSAF is found if the labor has progressed and is without abnormal FHR.Keywords: MSAF, grade III MSAF, observation time, abnormal FHR, thick AF