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Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) is an immediate early gene that plays a vital role in learning and memory. Arc protein has structural and functional properties similar to viral Group-specific antigen (Gag) protein and mediates the intercellular RNA transfer through virus-like capsids. However, the regulators and secretion pathway through which Arc capsids maneuver cargos are unclear. Here, we identified that phosphatidylinositol-3-phosphate (PI3P) mediates Arc capsid assembly and secretion through the endosomal-multivesicular body (MVB) pathway. Indeed, reconstituted Arc protein preferably binds to PI3P. In HEK293T cells, Arc forms puncta that colocalize with FYVE, an endosomal PI3P marker, as well as Rab5 and CD63, early endosomal and MVB markers, respectively. Superresolution imaging resolves Arc accumulates within the intraluminal vesicles of MVB. CRISPR double knockout of RalA and RalB, crucial GTPases for MVB biogenesis and exocytosis, severely reduces the Arc-mediated RNA transfer efficiency. RalA/B double knockdown in cultured rat cortical neurons increases the percentage of mature dendritic spines. Intake of extracellular vesicles purified from Arc-expressing wild-type, but not RalA/B double knockdown, cells in mouse cortical neurons reduces their surface GlutA1 levels. These results suggest that unlike the HIV Gag, whose membrane targeting requires interaction with plasma-membrane-specific phosphatidyl inositol (4,5) bisphosphate (PI(4,5)P2), the assembly of Arc capsids is mediated by PI3P at endocytic membranes. Understanding Arc's secretion pathway helps gain insights into its role in intercellular cargo transfer and highlights the commonality and distinction of trafficking mechanisms between structurally resembled capsid proteins., Competing Interests: Competing interests statement:The authors declare no competing interest.

Complex systems with many interacting nodes are inherently stochastic and best described by stochastic differential equations. Despite increasing observation data, inferring these equations from empirical data remains challenging. Here, we propose the Langevin graph network approach to learn the hidden stochastic differential equations of complex networked systems, outperforming five state-of-the-art methods. We apply our approach to two real systems: bird flock movement and tau pathology diffusion in brains. The inferred equation for bird flocks closely resembles the second-order Vicsek model, providing unprecedented evidence that the Vicsek model captures genuine flocking dynamics. Moreover, our approach uncovers the governing equation for the spread of abnormal tau proteins in mouse brains, enabling early prediction of tau occupation in each brain region and revealing distinct pathology dynamics in mutant mice. By learning interpretable stochastic dynamics of complex systems, our findings open new avenues for downstream applications such as control., (© 2024. The Author(s).)

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, enantioselective hydroboration of tetrasubstituted alkenes with high diastereo- and enantioselectivities continues as an unmet challenge since the 1950s due to its extremely low reactivity and the difficulties to simultaneously control the regio- and stereoselectivity of a tetrasubstituted alkene. Here, we report highly regio-, diastereo-, and enantioselective catalytic hydroboration of diverse acyclic tetrasubstituted alkenes. The delicate interplay of an electron-rich rhodium complex and coordination-assistance forms a highly adaptive catalyst that effectively overcomes the low reactivity and controls the stereoselectivity. The generality of the catalyst system is exemplified by its efficacy across various tetrasubstituted alkenes with diverse steric and electronic properties.

RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Rice husk, an agricultural waste from the rice industry, can cause serious environmental pollution if not properly managed. However, rice husk ash (RHA) has been found to have many positive properties, making it a potential replacement for non-renewable peat in soilless planting. Thus, this study investigated the impact of a RHA composite substrate on the growth, photosynthetic parameters, and fruit quality of cucumber (Yuyi longxiang variety) and melon (Yutian yangjiaomi variety). The RHA, peat, vermiculite, and perlite were blended in varying proportions, with the conventional seedling substrate (peat:vermiculite:perlite = 1:1:1 volume ratio) serving as the control (CK). All plants were cultivated in barrels filled with 10L of the mixed substrates. The results from this study found that RHA 40 (RHA:peat:vermiculite:perlite = 4:4:1:1 volume ratio) significantly enhanced substrate ventilation and positively influenced the stem diameter, root activity, seedling index, chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of cucumber and melon plants. Additionally, plant planted using RHA 40, the individual fruit weight of cucumber and melon found to increase by 34.62% and 21.67%, respectively, as compared to the control. Aside from that, both cucumber and melon fruits had significantly higher sucrose, total soluble sugar, vitamin C, and soluble protein levels. This subsequently improved the activity of sucrose synthase and sucrose phosphate synthase in both cucumber and melon. In conclusion, the RHA 40 found to best promote cucumber and melon plant growth, increase plant leaf photosynthesis, and improve cucumber and melon fruit quality, making it a suitable substrate formula for cucumber and melon cultivation in place of peat., (© 2024. The Author(s).)

Families can express high criticism, hostility and emotional over-involvement towards a person with or at risk of mental health problems. Perceiving such high expressed emotion (EE) can be a major psychological stressor for individuals, especially those at risk of mental health problems. To reveal the biological mechanisms underlying the effect of EE on health, this study investigated physiological response (salivary cortisol, frontal alpha asymmetry (FAA)) to verbal criticism and their relationship to anxiety and perceived EE. Using a repeated-measures design, healthy participants attended three testing sessions on non-consecutive days. On each day, participants listened to one of three types of auditory stimuli, namely criticism, neutral or praise, and Electroencephalography (EEG) and salivary cortisol were measured. Results showed a reduction in cortisol following criticism but there was no significant change in FAA. Post-criticism cortisol concentration negatively correlated with perceived EE after controlling for baseline mood. Our findings suggest that salivary cortisol change responds to criticism in non-clinical populations and this response might be largely driven by individual differences in the perception of criticism (e.g., arousal and relevance). Criticisms expressed by audio comments may not be explicitly perceived as an acute emotional stressor, and thus, physiological response to criticisms could be minimum., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Globally, gastric cancer (GC) is still a major leading cause of cancer-associated deaths. Downregulated desmocollin2 (DSC2) is considered to be closely related to tumor progression. However, the underlying mechanisms of DSC2 in GC progression require further exploration., Method: We initially constructed different GC cells based on DSC2 contents, established the mouse tumor xenografts, and subsequently performed clonal formation, MTT, Caspase-3 activity, and sperm DNA fragmentation assays to detect the functions of DSC2 in GC growth. Subsequently, we performed western blot, Co-IP, and immunofluorescence assays to investigate the underlying mechanisms through pretreatment with PI3K inhibitor, LY294002, and its activator, recombinant human insulin-like growth factor I (IGF1)., Result: DSC2 could significantly inhibit the viability of GC cells at both in vitro and in vivo levels. The underlying mechanism may be that DSC2 binds the γ-catenin to decrease its nuclear level, thereby downregulating the anti-apoptotic factor BCL-2 expression and upregulating the pro-apoptotic factor P53 expression, which adjusts the PTEN/PI3K/AKT signaling pathway to promote the cancer cell apoptosis., Conclusions: Our finding suggests that DSC2 might be a potential therapeutic target for the treatment of cancers, most especially GC.

The stability and digestive properties of a dual-protein emulsion consisting of soy protein isolate (SPI) and whey protein isolate (WPI) have been systematically studied. The results showed that the particle size and viscosity of the dual-protein emulsion system decreased continuously with the increase in WPI, and this might be related to the large amount of electric charge on the surface of the emulsion droplets. Dual-protein emulsions with ratios of 3:7 and 5:5 showed the highest emulsion activity, while emulsion stability increased with the increase in WPI. The thicker adsorption layer formed at the interface might have contributed to this phenomenon. After in-vitro-simulated digestion, the emulsion droplet particle size increased substantially due to the weakened electrostatic repulsion on the droplet surface, especially for the intestinal digestion phase. Meanwhile, WPI accelerated the release of free fatty acids in the digestion process, which played a positive role in the nutritional value of the dual-protein emulsion. In accelerated oxidation experiments, WPI also improved the antioxidant properties of the dual-protein emulsion system. This study will provide a new insight and necessary theoretical basis for the preparation of dual-protein emulsions.

Background: Opsin-based optogenetics has emerged as a powerful biomedical tool using light to control protein conformation. Such capacity has been initially demonstrated to control ion flow across the cell membrane, enabling precise control of action potential in excitable cells such as neurons or muscle cells. Further advancement in optogenetics incorporates a greater variety of photoactivatable proteins and results in flexible control of biological processes, such as gene expression and signal transduction, with commonly employed light sources such as LEDs or lasers in optical microscopy. Blessed by the precise genetic targeting specificity and superior spatiotemporal resolution, optogenetics offers new biological insights into physiological and pathological mechanisms underlying health and diseases. Recently, its clinical potential has started to be capitalized, particularly for blindness treatment, due to the convenient light delivery into the eye., Aims and Methods: This work summarizes the progress of current clinical trials and provides a brief overview of basic structures and photophysics of commonly used photoactivable proteins. We highlight recent achievements such as optogenetic control of the chimeric antigen receptor, CRISPR-Cas system, gene expression, and organelle dynamics. We discuss conceptual innovation and technical challenges faced by current optogenetic research., Conclusion: In doing so, we provide a framework that showcases ever-growing applications of optogenetics in biomedical research and may inform novel precise medicine strategies based on this enabling technology., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Aims: Feathers are keratin-rich byproducts of poultry processing, but those are often frequently abandoned as garbage and thus polluting the environment. Therefore, the study focused on the efficient biodegradation, bioactivity, and high-value application of feather keratin., Methods and Results: Feather-degrading bacteria were identified, and the degradation properties were characterized. DPPH (1,1-Diphenyl-2-picrylhydrazyl radical) and ABTS (2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid))radical scavenging assays, cytotoxicity assays, intracellular reactive oxygen scavenging assays, and cell migration assays were used to examine the biological activities of the feather keratin hydrolysis peptides (FKHPs). The results showed that we screened a feather-degrading strain of Bacillus licheniformis 8-4, which achieved complete degradation of 2% (w/v) feathers within 48 h. Notably, the feather fermentation broth was particularly high in FKHPs, which exhibited good DPPH and ABTS radical scavenging ability. Further studies revealed that FKHPs had both the ability to scavenge H2O2-induced ROS from HaCat cells and the ability to promote HaCat cell migration, while remaining non-toxic., Conclusions: The effective feather-degrading ability of B. licheniformis 8-4 allowed for the fermentation of feather medium to yield active peptides that were both antioxidants and cell-migration enhancers., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Feather biodegradation is an important premise for efficient resource development and utilization, in which keratinase plays an important role. However, there are few keratinases that combine the high activity, thermal stability, and organic solvent tolerance required for industrialization. This paper reported an efficient feather-degrading Pseudomonas aeruginosa 4-3 isolated from slaughterhouses. After 48 h of fermentation by P. aeruginosa 4-3 in a feather medium at 40 °C, pH 8.0, keratinase was efficiently produced (295.28 ± 5.42 U/mL) with complete feather degradation (95.3 ± 1.5%). Moreover, the keratinase from P. aeruginosa 4-3 showed high optimal temperature (55 °C), good thermal stability, wide pH tolerance, and excellent organic solvent resistance. In addition, P. aeruginosa 4-3-derived aminopeptidases also exhibit excellent thermal stability and organic solvent tolerance. Encouragingly, the reaction of crude keratinase and aminopeptidase with feathers for 8 h resulted in a 78% degradation rate of feathers. These properties make P. aeruginosa 4-3 keratinase and aminopeptidase ideal proteases for potential applications in keratin degradation, as well as provide ideas for the synergistic degradation of keratin by multiple enzymes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this proof-of-concept study is to develop a predictive model based on deep learning algorithms to predict working alliances after the first therapeutic session and to provide a basis for clinical decisions., Methods: Using a sample of 325 patients and 32 psychotherapists from three university counseling centers, a deep learning algorithm known as fully connected neural networks (FCNNs) was adopted to construct data-driven predictive models. The performance differences between the model including only patient indicators and the model including both patient and therapist indicators were compared. The optimal model was further tested in a general hospital sample of 85 patients and 8 therapists., Results: The model incorporating both patient indicators and therapist-level indicators (R²: 0.30 ± 0.02) performed better than the model incorporating only patient indicators (R²: 0.11 ± 0.02). The performance of this model decreased when being transferred to the independent general hospital sample, but still retained some predictive value (R² = 0.11)., Conclusion: This study showed that the inclusion of therapist-level indicators can improve the performance of a predictive model in predicting working alliances. This model could assist clinical decisions on choosing psychotherapists for patients and may also initiate new possibilities for future research.

This study reported the cloning, expression, and characterization of a new salt-tolerant leucine dehydrogenase (PrLeuDH) from Pseudoalteromonas rubra DSM 6842. A codon-optimized 1038 bp gene encoding PrLeuDH was successfully expressed on pET-22b( +) in E. coli BL21(DE3). The purified recombinant PrLeuDH showed a single band of about 38.7 kDa on SDS-PAGE. It exhibited the maximum activity at 40 °C and pH 10.5, while kept high activities in the range of 25-45 °C and pH 9.5-12. The K m value and turnover number k cat for leucine of PrLeuDH were 2.23 ± 0.12 mM and 35.39 ± 0.05 s -1 , respectively, resulting in a catalytic efficiency k cat /K m of 15.87 s -1 /mM. Importantly, PrLeuDH remained 92.1 ± 2.67% active in the presence of 4.0 M NaCl. The study provides the first in-depth understanding of LeuDH from marine Pseudoalteromonas rubra, meanwhile the unique properties of high activity at low temperature and high salt tolerance make it a promising biocatalyst for the synthesis of non-protein amino acids and α-ketoacids under special conditions in pharmaceutical industry., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite 3-year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression-free survival at 3 years (3-year PFS) and overall survival (OS) among patients with ESCC., Methods: We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age- and sex-matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data., Results: The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3-year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5-year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9-17.5). Conversely, the SMR for patients who achieved 3-year PFS was 0.9 (95% CI, 0.6-1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88-0.90). The strongest correlation was observed between 3-year PFS and 5-year OS in RCTs and retrospective studies., Conclusions: Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3-year PFS had excellent outcomes. Our study supports 3-year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The study aimed to compare efficacy and safety of various immune checkpoint inhibitors for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC)., Methods: We searched Medline, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Clinical Trials.gov and several international conference databases from January 1, 2000 to December 19, 2021. We conducted Bayesian network meta-analysis to assess the relative effects among treatments. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate and adverse events., Results: Ten eligible trials with 5250 patients were included. Toripalimab and Camrelizumab plus chemotherapy were preferred to rank first on OS (probability, 61%) and PFS (probability, 37%) in the first-line setting, respectively. In refractory patients, Sintilimab and Camrlizumab were most likely to be ranked first on OS (probability, 37%) and PFS (probability, 94%). The toxicity related to immunotherapy was manageable in clinical trials. Camrelizumab and Nivolumab had the less adverse events of grade 3 or higher in the first and refractory setting, respectively., Conclusions: This study found that Toripalimab and Camrelizumab plus chemotherapy were likely to be the best option in terms of OS and PFS in the first-line setting for patients with advanced or metastatic ESCC respectively. Sintilimab and Camrelizumab were the preferred options for OS and PFS in refractory patients respectively. The toxicity of immunotherapy was different from conventional chemotherapy, but manageable in patients with ESCC., Trial Registration: PROSPERO registration number: (CRD 42021261554)., (© 2022. The Author(s).)

Objective: To analyze the overweight and obesity status of students in the national pilot counties of the Nutrition Improvement Program for Rural Compulsory Education Students in 2019 and its associated factors. Methods: In 2019, a multi-stage cluster random sampling method was used to select about 40 students from each grade in primary and secondary schools in China's central and western regions where the Nutrition Improvement Program for Rural Compulsory Education Students was implemented . The height and weight of the children were measured using height or weight scales. The school questionnaire and county questionnaire were used to investigate the associated factors. A Chi-square test was used for comparison between groups. The logistic regression analysis was used to analyze the associated factors. Results: In 2019, the prevalence of overweight and obesity among rural primary and secondary school students aged 6-15 years in central and western China 2019 was 11.5%. It was higher for boys (13.1%) than that for girls (9.8%), higher in central (14.3%) than that in the west (9.9%) and higher for elementary school students (12.4%) than that for secondary school students (9.5%, all P <0.001). The logistic regression showed that boys ( OR =1.388), primary school students ( OR =1.271), students without other dietary subsidies( OR =1.037), schools in rural areas ( OR =1.133), schools with enterprise-based feeding mode ( OR =1.043), schools without the provision of lunch ( OR =1.143), schools without the provision of dinner ( OR =1.122), and schools without providing drinking water ( OR =1.015) were positively associated with overweight and obesity among students ( P <0.05). Schools with snack shops ( OR =0.952) were negatively associated with overweight and obesity among students ( P <0.001). Conclusion: A certain proportion of primary and secondary school students in rural areas of central and western China are overweight and obese. The prevalence is not only related to children's gender, school section and county area but also related to school meals, whether schools provide drinking water and other factors.

Background: Primary membranous nephropathy (MN) is a kidney-specific autoimmune disease. Human embryonic stem cells-derived immunity-and-matrix regulatory cells (hESC-IMRCs) have immunoregulatory functions. We hypothesized that hESC-IMRCs might have therapeutic effects on MN and be a potential treatment in clinical practice., Methods: Rats of Heymann nephritis were injected with sheep anti-rat Fx1A serum. hESC-IMRCs were intravenously administrated upon the detection of proteinuria, with 6 × 10 6 cells (high-dose) or 3 × 10 6 cells (low-dose) in 1 ml every other day. Splenocytes and IMRCs were co-cultured at different times and ratios. Cell types and cytokines were detected by flow cytometry and enzyme-linked immunosorbent assay., Results: The urinary protein of rats with Heymann nephritis was reduced remarkably to a level comparable to negative controls, in both low-dose (45.6 vs. 282.3 mg/d, P < 0.001) and high-dose (35.2 vs. 282.3 mg/d, P < 0.001) hESC-IMRC treatment groups. IgG and C3 deposit, glomerular basement membrane thickness and foot process effacement were alleviated and the reduced podocin was recovered in the kidneys. The proportions of CD4 + CD25 + T cells in circulation and spleen were increased, and the circulating level of IL-10 was increased, after IMRC interventions. IL-17 and TNF-α were reduced after IMRCs treatments. IL-10 increased remarkably in the co-culture supernatant of lymphocytes and IMRCs at 48 h with ratio 10:1., Conclusions: The intravenously delivered hESC-IMRCs alleviated proteinuria and kidney injuries of Heymann nephritis, by their immunosuppressive functions through regulatory T cells and IL-10. These pre-clinical results indicate that IMRCs worth careful consideration for human trials in the treatment of MN., (© 2022. The Author(s).)

Objective: To understand the growth retardation among primary and secondary school students in areas covered by the Nutrition Improvement Program for Rural Compulsory Education Students and its influencing factors to provide evidence for improving the nutrition status of rural students in China. Methods: The multi-stage cluster random sampling method selected 1 550 969 primary and secondary school students aged 6-15 years from China's central and western regions. The ratio of male and female students was balanced. The height was measured, and the growth retardation of students was determined according to the Screening Criteria for School-age Children and Adolescents malnutrition (WS/T 456-2014), from the school and county questionnaire survey related factors. The number of cases and percentages described the growth retardation of students, and the χ 2 test was used for comparison between groups. Binary logistic regression was used to analyze students' growth retardation factors. Results: In 2019, the growth retardation rate of primary and secondary school students in areas covered by the Nutrition Improvement Program for Rural Compulsory Education Students was 5.7% (88 631/1 550 969), the growth retardation rate in the western part (7.1%, 66 167/927 954) was higher than that in the central part (3.7%,19 511/533 973) with difference statistically significant ( P <0.001). The growth retardation rate of the boys (6.3%,50 665/803 851) were higher than that of girls (5.1%, 37 966/747 118), the difference was statistically significant ( P <0.001). The growth retardation rate of primary school students in central China was 3.9%(14 914/380 598), higher than that of junior middle school students (3.0%,4 597/153 375, P <0.001). In contrast, the growth retardation rate of the western junior high school students (7.2%, 21 494/297 217) were higher than that of elementary school students (7.1%, 44 673/630 737), with a difference statistically significant (all P =0.009). Multi-factor logistic regression results showed that, in high income area ( OR =0.829, 95% CI : 0.816-0.842, P <0.001), parents providing part of the meal cost ( OR =0.948, 95% CI : 0.931-0.965, P <0.001), enterprises providing meals ( OR =0.845, 95% CI : 0.805-0.887, P <0.001), schools providing milk ( OR =0.780, 95% CI : 0.767-0.793, P <0.001), health education courses ( OR =0.702, 95% CI : 0.682-0.723, P <0.001) and other local nutrition improvement efforts ( OR =0.739, 95% CI : 0.720-0.758, P <0.001) were negatively correlated with the occurrence of growth retardation, The growth retardation rate of the students was lower. Conclusions: There appeared significant regional, gender, and age differences in the growth retardation rate of primary and middle school students in areas covered by the Nutrition Improvement Program for Rural Compulsory Education Students. Appropriate food supply in schools, health education courses, and parental participation in nutritional improvement was related to children's lower growth retardation rate.

The availability of empirical data that capture the structure and behaviour of complex networked systems has been greatly increased in recent years; however, a versatile computational toolbox for unveiling a complex system's nodal and interaction dynamics from data remains elusive. Here we develop a two-phase approach for the autonomous inference of complex network dynamics, and its effectiveness is demonstrated by the tests of inferring neuronal, genetic, social and coupled oscillator dynamics on various synthetic and real networks. Importantly, the approach is robust to incompleteness and noises, including low resolution, observational and dynamical noises, missing and spurious links, and dynamical heterogeneity. We apply the two-phase approach to infer the early spreading dynamics of influenza A flu on the worldwide airline network, and the inferred dynamical equation can also capture the spread of severe acute respiratory syndrome and coronavirus disease 2019. These findings together offer an avenue to discover the hidden microscopic mechanisms of a broad array of real networked systems., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

A healthy plant microbiome is diverse, taxonomically-structured, and gives its plant host moderate advantages in growth, development, stress tolerance, and disease resistance. The plant microbiome varies with ecological niches and is influenced by variables that are complex and difficult to separate from each other, such as the plant species, soil, and environmental factors. To explore the composition, diversity, and functions of the bacterial community of Korean pine forests, we used high-throughput sequencing to study five areas with different forest ages from June to October 2017 in northeast China. We obtained 3,247 operational taxonomic units (OTUs) based on 16S rRNA gene sequencing via an Illumina Hi-seq platform. A total of 36 phyla and 159 known genera were classified. The Shannon index of the bacterial community from the rhizospheric soil was significantly higher ( p  < 0.01, n  = 10) than that of the root tips. Beta-diversity analysis confirmed that the bacterial community of the rhizospheric soil was significantly different ( p  < 0.001) from the root tips. Nine bacterial phyla were dominant (relative richness > 1%) in the rhizospheric soil, but there were six dominant phyla in the root tips. Proteobacteria was the core flora in the root tips with a relative abundance of more than 50%. It is known that the formation of bacterial communities in the rhizospheric soil or the root is mainly caused by the processes of selection, and we found a relatively high abundance of a few dominant species. We further analyzed the correlations between the bacterial community from the rhizospheric soil with that of the root tips, as well as the correlations of the bacterial community with soil physicochemical properties and climate factors. We used Functional Annotation of the Prokaryotic Tax (FAPROTAX) to predict the functions of the bacterial community in the rhizospheric soil and root tips. Five related phototrophic functions, nine nitrogen cycle functions, two related chemoheterotrophic functions, and two others were predicted. The abundance of the bacteria phyla performing relevant functions was different in the rhizospheric soil than in the root tips. These functions were significantly influenced by the contents of nitrogen, phosphorus, and potassium in the soil habitat. The bacterial composition and functions in the rhizospheric soil and root tips of Korean pine were analyzed, and the results demonstrated the importance of soil and plant species on the bacterial community in the below ground plant microbiome., Competing Interests: The authors declare there are no competing interests., (©2022 Ji et al.)

This study investigated the feasibility and preliminary effectiveness of a concurrent mindfulness program (MYmind) on Chinese adolescents with autism spectrum disorder and their parents in Hong Kong, China using a randomized controlled trial with a waitlist control group. Results showed the study had 80% compliance rate, 0% dropout rate, and 89% response rate. Between-group comparisons showed mindfulness had trend effects on parent's rumination (g = 1.16), mindful parenting (d = 0.6), parenting style (d = 0.59), and parenting stress (d = 0.5). The study demonstrated the feasibility of the MYmind program in the Chinese context. A larger trial with longer follow-up period is suggested to better examine the effect of mindfulness on adolescents with ASD and their parents., (© 2021. The Author(s).)

Chiral tertiary boronic esters are important precursors to bioactive compounds and versatile synthetic intermediates to molecules containing quaternary stereocenters. The development of conjugate boryl addition to α,β-unsaturated amide has been hampered by the intrinsic low electrophilicity of the amide group. Here we show the catalytic asymmetric synthesis of enantioenriched tertiary boronic esters through hydroboration of β,β-disubstituted α,β-unsaturated amides. The Rh-catalyzed hydroboration occurs with previously unattainable selectivity to provide tertiary boronic esters in high enantioselectivity. This strategy opens a door for the hydroboration of inert Michael acceptors with high stereocontrol and may provide future applications in the synthesis of biologically active molecules.

Dengue virus (DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV for virus replication in which lipid droplets (LDs) play a key role during the virus lifecycle. In this study, we reveal a novel role for phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in LDs-mediated DENV infection. We demonstrate that PTEN expression is downregulated upon DENV infection through post-transcriptional regulation and, in turn, PTEN overexpression enhances DENV replication. PTEN lipid phosphatase activity was found to decrease cellular LDs area and number through Akt/FoxO1/Maf1 signaling, which, together with autophagy, enhanced DENV replication and virus production. We therefore provide mechanistic insight into the interaction between lipid metabolism and the DENV replication cycle.

Background: Depression is one of the most common forms of mental illness and also a leading cause of disability worldwide. Developing novel antidepressant targets beyond the monoaminergic systems is now popular and necessary. LIM kinases, including LIM domain kinase 1 and 2 (LIMK1/2), play a key role in actin and microtubule dynamics through phosphorylating cofilin. Since depression is associated with atrophy of neurons and reduced connectivity, here we speculate that LIMK1/2 may play a role in the pathogenesis of depression., Methods: In this study, the chronic unpredictable mild stress (CUMS), chronic restraint stress (CRS), and chronic social defeat stress (CSDS) models of depression, various behavioral tests, stereotactic injection, western blotting, and immunofluorescence methods were adopted., Results: CUMS, CRS, and CSDS all significantly enhanced the phosphorylation levels of LIMK1 and LIMK2 in the medial prefrontal cortex (mPFC) but not the hippocampus of mice. Administration of fluoxetine, the most commonly used selective serotonin reuptake inhibitor in clinical practice, fully reversed the effects of CUMS, CRS, and CSDS on LIMK1 and LIMK2 in the mPFC. Moreover, pharmacological inhibition of LIMK1 and LIMK2 in the mPFC by LIMKi 3 infusions notably prevented the pro-depressant effects of CUMS, CRS, and CSDS in mice., Conclusions: In summary, these results suggest that LIMK1/2 in the mPFC has a role in chronic stress-induced depressive-like effects in mice and could be a novel pharmacological target for developing antidepressants., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

Many bacteria belonging to Paenibacillus polymyxa are plant growth-promoting rhizobacteria (PGPR) with the potential to promote plant growth and suppress phytopathogens and have been used as biological control agents (BCAs). However, the growth promotion and biocontrol mechanisms of P. polymyxa have not been thoroughly elucidated thus far. In this investigation, the genome sequences of two P. polymyxa strains, ZF129 and ZF197, with broad anti-pathogen activities and potential for growth promotion were comparatively studied. Comparative and functional analyses of the two sequenced P. polymyxa genomes showed that the ZF129 genome consists of one 5,703,931 bp circular chromosome and two 79,020 bp and 37,602 bp plasmids, designated pAP1 and pAP2, respectively. The complete genome sequence of ZF197 consists of one 5,507,169 bp circular chromosome and one 32,065 bp plasmid, designated pAP197. Phylogenetic analysis revealed that ZF129 is highly similar to two P. polymyxa strains, HY96-2 and SQR-21, while ZF197 is highly similar to P. polymyxa strain J. The genes responsible for secondary metabolite synthesis, plant growth-promoting traits, and systemic resistance inducer production were compared between strains ZF129 and ZF197 as well as other P. polymyxa strains. The results indicated that the variation of the corresponding genes or gene clusters between strains ZF129 and ZF197 may lead to different antagonistic activities of their volatiles or cell-free supernatants against Fusarium oxysporum . This work indicates that plant growth promotion by P. polymyxa is largely mediated by phytohormone production, increased nutrient availability and biocontrol mechanisms. This study provides an in-depth understanding of the genome architecture of P. polymyxa , revealing great potential for the application of this bacterium in the fields of agriculture and horticulture as a PGPR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Li, Gao and Wang.)

Background: Recent studies have suggested the role of mammalian target of rapamycin complex 1 (mTORC1) in the pathophysiology of depression. Although venlafaxine was thought to be a serotonin and norepinephrine reuptake inhibitor (SNRI), its pharmacological mechanism remain elusive. In this study, the effects of venlafaxine on the mTORC1 system were studied in both chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models., Method: First, we examined whether repeated venlafaxine treatment reversed the effects of CUMS and CSDS on the mTORC1 signaling cascade in both the hippocampus and medial prefrontal cortex (mPFC). Second, several selective pharmacological inhibitors of the mTORC1 system, including rapamycin, LY294002 and U0126, were used together to determine whether the protective effects of venlafaxine against the CUMS and CSDS models were prevented by mTORC1 system blockade. Finally, genetic knockdown of mTORC1 by mTORC1-shRNA was further adopted to test whether mTORC1 was necessary for the anti-stress effects of venlafaxine in mice., Result: Our results showed that the decreasing effects of CUMS and CSDS on the mTORC1 signaling cascade in the hippocampus and mPFC were restored by venlafaxine, and the use of rapamycin, LY294002, U0126 and mTORC1-shRNA fully abolished the anti-stress actions of venlafaxine in mice., Conclusion: The mTORC1 system is involved in the pharmacological mechanism of venlafaxine., (Copyright © 2020. Published by Elsevier B.V.)

Recent studies have suggested that CREB-regulated transcription coactivator 1 (CRTC1) plays a role in the pathophysiology of depression. Although imipramine is thought to prevent the reuptake of synaptic serotonin and norepinephrine, its antidepressant-like mechanisms remain elusive. In this study, the effects of imipramine on CRTC1 were studied in several models of depression, including the chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models. We examined whether repeated imipramine administration can reverse the effects of CRS, CUMS and CSDS on CRTC1 expression in both the hippocampus and medial prefrontal cortex (mPFC). Furthermore, genetic knockdown of CRTC1 by CRTC1-shRNA was used to determine whether CRTC1 is necessary for the antidepressant-like effects of imipramine in mice. Our results showed that imipramine reversed the down-regulating effects of CRS, CUMS and CSDS on CRTC1 expression in the mPFC but not the hippocampus, and that CRTC1-shRNA fully abolished the antidepressant-like actions of imipramine in mice. In conclusion, CRTC1 in the mPFC is involved in the antidepressant mechanism of imipramine., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Migraine is a complex and disabling neurological disorder, the exact neurological mechanisms of which remain unclear. The thalamus is considered to be the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes., Methods: A total of 48 migraineurs without aura (MWoAs) during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized masked independent component analysis and seed-based functional connectivity (FC) to investigate whether MWoAs exhibited abnormal FC between subregions in the thalamus and the cortex regions., Results: The MWoAs showed significantly weaker FC between the anterior dorsal thalamic nucleus and left precuneus. Additionally, MWoAs exhibited significantly reduced FC between the ventral posterior nucleus (VPN) and left precuneus, right inferior parietal lobule (R-IPL) and right middle frontal gyrus. Furthermore, the FC Z-scores between the VPN and R-IPL were negatively correlated with pain intensity in MWoAs. The disease duration of patients was negatively correlated with the FC Z-scores between the VPN and R-IPL., Conclusion: These altered thalamocortical connectivity patterns may contribute to multisensory integration abnormalities, deficits in pain attention, cognitive evaluation and pain modulation. Pain sensitivity and disease duration are closely tied to abnormal FC between the VPN and R-IPL. Remarkably, recurrent headache attacks might contribute to this maladaptive functional plasticity closely related to pain intensity., (© 2020 European Academy of Neurology.)

Gephyromycin C (GC), a natural compound isolated from a marine-derived actinomycete Streptomyces sp. SS13I, which exerts anti-proliferative effect on PC3 cells. However, its underlying mechanism of the anti-cancer effect remains unknown. The results of SRB assays showed that GC inhibited the proliferation of PC3 cells with an IC 50 value of 1.79 ± 0.28 μM. GC also induced G2/M cell cycle arrest which was accompanied by declining levels of cyclin proteins. Possible mechanisms were investigated and it was found that GC bound to Hsp90 and caused the degradation of Hsp90 client proteins (AKT, CHK1, P53, CDK4, Raf-b, and Raf-1). The fluorescent polarization assay with FITC-labeled geldanamycin (FITC-GA) demonstrated that GC was able to compete with FITC-GA in binding to wild type Hsp90 with an IC 50 of 2.15 μM. Results of a docking study also suggested that GC interacted with the N-terminal domain of Hsp90. Our results showed that GC could bind to Hsp90, which resulted in down-regulation of Hsp90 client proteins and G2/M arrest in PC3 cells. Since the antitumor effects of this kind of angucycline via targeting Hsp90 has not been reported before, our results indicate that GC is a novel inhibitor of Hsp90 from marine resources and worthy of further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Depression is a serious and worldwide neuropsychiatric disesase, and developing novel antidepressant targets beyond the monoaminergic systems is now popular and necessary. Bone morphogenetic protein (BMP) signals modulate numerous developmental, physiological, and homeostatic processes. The functions of BMPs are also regulated by secreted extracellular antagonists such as chordin and noggin. Chordin has abundant expression in adult brain, and may play critical role in the central nervous system. In this study, the chronic social defeat stress (CSDS) model of depression, various behavioral tests, western blotting, quantitative real-time reverse transcription PCR, immunohistochemistry, recombinant mouse chordin protein and AAV-Chordin-EGFP were together used to explore the role of chordin in the pathogenesis of depression. It was found that CSDS significantly decreased the expression of chordin in the hippocampus but not other related brain regions. Moreover, both pharmacological and genetic overexpression of hippocampal chordin fully protected against the CSDS-induced depressive-like effects in mice. Collectively, hippocampal chordin could be a novel antidepressant target, and this study further highlights the importance of the hippocampal BMP system in the pathophysiology of depression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ventilator‑associated lung injury (VALI) remains a significant medical problem in intensive care units. The present study aimed to investigate the role of sphingosine kinase 1 (SPHK1) in VALI using a two‑hit model and explore the potential underlying molecular mechanism. Mice were divided into five groups: i) Non‑ventilated group; ii) non‑ventilated + lipopolysaccharide (LPS) group; iii) ventilated group; iv) ventilated + LPS group; and v) ventilated + LPS + SPHK1 inhibitor group. Mice were administered LPS (1 mg/kg) via an intraperitoneal injection. After 12 h, the mice were anesthetized and connected to a ventilator (10 ml/kg at 150 breaths/min) for 4 h. SPHK1 inhibitor (50 mg/kg) was injected intraperitoneally 1 h prior to ventilation. Mouse lung vascular endothelial cells were treated with LPS and SPHK1 inhibitor, and then subjected to cyclic stretch for 4 h. The present results suggested that the expression of SPHK1 and sphingosine 1 phosphate was upregulated in the two‑hit model of VALI; SPHK1 inhibitor could attenuate VALI in the two‑hit model as observed by hematoxylin and eosin staining, and affected the cell count and the protein content levels in the bronchoalveolar lavage fluid. In addition, treatment with SPHK1 inhibitor reduced the wet‑to‑dry ratio of the lungs and suppressed Evans blue dye leakage into the lung tissue. Furthermore, SPHK1 inhibitor exhibited protective effects on the two‑hit model of VALI by inhibiting the Ras homolog family member a‑mediated phosphorylation of myosin phosphatase target subunit 1 (MYPT‑1) and endothelial hyperpermeability. Additionally, mice were divided into five additional groups: i) Non‑ventilated group; ii) non‑ventilated + LPS group; iii) ventilated group; iv) ventilated + LPS group; and v) ventilated + LPS + Rho‑associated coiled‑coil forming protein kinase (ROCK)1 inhibitor group. ROCK1 inhibitor (10 mg/kg) was injected intraperitoneally 1 h prior to ventilation. The present results suggested that ROCK1 inhibitor could attenuate mechanical stretch‑induced lung endothelial injury and the phosphorylation of MYPT‑1 in vivo and in vitro. Collectively, the present findings indicated that upregulation of SPHK1 may contribute to VALI in a two‑hit model.

Background: Ovarian stimulation with clomiphene (CC) or progestin has been applied for patients with diminished ovarian reserve (DOR). However, it remains unclear which treatment confers greater benefits. This study aimed to compare the outcomes of progestin-primed ovarian stimulation (PPOS) protocol vs CC-primed ovarian stimulation (CPOS) in infertile women with DOR., Methods: A before-and-after self-controlled study was conducted to retrospectively investigate the data from 50 infertile women with DOR, who failed to conceive in their first in vitro fertilization/intracytoplasmic sperm injection-frozen embryo transfer cycle when stimulated with CPOS, and switched to PPOS, in the Reproductive Medicine Center of Changzhou Maternal and Child Health Care Hospital., Results: Our results showed that PPOS significantly suppressed the luteinizing hormone (LH) surge and yielded more satisfactory results in patients with DOR, including increased number of retrieved oocytes, MII mature oocytes, normal fertilized oocytes, cleaved embryos, high-grade embryos, cryopreserved embryos, pregnancy rate, live-birth rate, and decreased miscarriage rates., Conclusion: Our study demonstrated that compared with CPOS protocol, PPOS protocol could not only suppress the LH surge but also improved the quantity, particularly the quality of oocytes in patients with DOR, suggesting that PPOS treatment is more effective than CPOS for patients with DOR.

Exercise training (ExT) is beneficial for cardiovascular health, yet the central mechanism by which aerobic ExT attenuates the hypertensive responses remains unclear. Activation of pro-inflammatory cytokines (PICs) in the hypothalamic paraventricular nucleus (PVN) is important for the sympathoexcitation and hypertensive response. We thus hypothesized that aerobic ExT can decrease the blood pressure of hypertensive rats by reducing the levels of PICs through TLR4/MyD88/NF-κB signaling within the PVN. To examine this hypothesis, two-kidney-one-clip (2K1C) renovascular hypertensive rats were assigned to two groups: sedentary or exercise training and examined for 8 weeks. At the same time, bilateral PVN infusion of vehicle or TAK242, a TLR4 inhibitor, was performed on both groups. As a result, the systolic blood pressure (SBP), renal sympathetic nerve activity (RSNA) and plasma levels of norepinephrine (NE), epinephrine (EPI) were found significantly increased in 2K1C hypertensive rats. These rats also had higher levels of Fra-like activity, NF-κB p65 activity, TLR4, MyD88, IL-1β and TNF-α in the PVN than SHAM rats. Eight weeks of ExT attenuated the RSNA and SBP, repressed the NF-κB p65 activity, and reduced the increase of plasma levels of NE, EPI, and the expression of Fra-like, TLR4, MyD88, IL-1β and TNF-α in the PVN of 2K1C rats. These findings are highly similar to the results in 2K1C rats with bilateral PVN infusions of TLR4 inhibitor (TAK242). This suggests that 8 weeks of aerobic ExT may decrease blood pressure in hypertensive rats by reducing the PICs activation through TLR4/MyD88/NF-κB signaling within the PVN, and thus delays the progression of 2K1C renovascular hypertension., (Copyright © 2019 Qi, Yu, Fu, Liu, Gao, Tu, Kang, Shi, Li, Li and Kang.)

Background: Major depressive disorder is a worldwide neuropsychiatric disorder associated with various symptoms, but current antidepressants used in clinical practice have various side effects and high failure rates. Andrographolide is the main bioactive ingredient of Andrographis paniculata and exhibits numerous pharmacological actions. This study aimed to evaluate the antidepressant-like effects of andrographolide in male C57BL/6J mice., Methods: The antidepressant-like effects of andrographolide in mice were explored in a forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression. Western blotting and immunofluorescence were further performed to assess the effects of chronic unpredictable mild stress and andrographolide on the brain-derived neurotrophic factor signalling cascade and hippocampal neurogenesis. Moreover, a pharmacological inhibitor (K252a) and a lentiviral-short hairpin RNA (LV-TrkB-shRNA) were used to clarify the antidepressant-like mechanism of andrographolide., Results: Andrographolide exhibited antidepressant-like potential in the forced swim test and tail suspension test without influencing the locomotor activity of mice. Repeated andrographolide treatment not only produced significant antidepressant-like effects in the chronic unpredictable mild stress model but also prevented the decreasing effects of chronic unpredictable mild stress on hippocampal brain-derived neurotrophic factor signalling and neurogenesis in mice. Importantly, blockade of the hippocampal brain-derived neurotrophic factor system by K252a and TrkB-shRNA fully abolished the antidepressant-like effects of andrographolide in mice., Conclusions: Andrographolide exerts antidepressant-like effects in mice via promoting the hippocampal brain-derived neurotrophic factor signalling cascade., (© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.)

While it is known that spermatogonial stem cells (SSCs) initiate the production of male germ cells, the mechanisms of SSC self-renewal, proliferation, and differentiation remain poorly understood. We have previously identified Strawberry Notch 1 (SBNO1), a vertebrate strawberry notch family protein, in the proteome profile for mouse SSC maturation and differentiation, revealing SBNO1 is associated with neonatal testicular development. To explore further the location and function of SBNO1 in the testes, we performed Sbno1 gene knockdown in mice to study the effects of SBNO1 on neonatal testicular and SSC development. Our results revealed that SBNO1 is required for neonatal testicular and SSC development in mice. Particularly, in vitro Sbno1 gene knockdown with morpholino oligonucleotides caused a reduction of SSCs and inactivation of the noncanonical Wnt pathway, through Jun N-terminal kinases. Our study suggests SBNO1 maintains SSCs by promoting the noncanonical Wnt pathway.

Background: Developing novel pharmacological targets beyond monoaminergic systems is now a popular strategy for finding new ways to treat depression. Salt-inducible kinase (SIK) is a kinase that regulates the nuclear translocation of cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator (CRTC) by phosphorylation. Here, we hypothesize that dysfunction of the central SIK-CRTC system may contribute to the pathogenesis of depression., Methods: Chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, viral-mediated gene transfer, Western blotting, coimmunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immunohistochemistry were used in this study (for in vivo studies, n = 10; for in vitro studies, n = 5)., Results: Both CSDS and CUMS markedly increased the expression of hippocampal SIK2, which reduced CRTC1 nuclear translocation and binding of CRTC1 and CREB in the hippocampus. Genetic overexpression of hippocampal SIK2 in naïve mice simulated chronic stress, inducing depressive-like behaviors in the forced swim test, tail suspension test, sucrose preference test, and social interaction test, as well as decreasing the brain-derived neurotrophic factor signaling cascade and neurogenesis in the hippocampus. In contrast, genetic knockdown and knockout of hippocampal SIK2 protected against CSDS and CUMS, exerting significant antidepressant-like effects that were mediated via the downstream CRTC1-CREB-brain-derived neurotrophic factor pathway. Moreover, fluoxetine, venlafaxine, and mirtazapine all significantly restored the effects of CSDS and CUMS on the hippocampal SIK2-CRTC1 pathway, which was necessary for their antidepressant actions., Conclusions: The hippocampal SIK2-CRTC1 pathway is involved in the pathogenesis of depression, and hippocampal SIK2 could be a novel target for the development of antidepressants., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Interleukin-12 receptor β2 (IL-12Rβ2) is a signaling subunit of heterodimeric receptors for IL-12 and IL-35. It plays important regulatory functions in the development of Th1 cells and in the expression of inflammatory cytokines in mammals and other higher vertebrates. However, little is known about IL-12Rβ2 in teleost fish. In this work, we have cloned and characterized IL-12Rβ2 from grass carp (Ctenopharyngodon idella). The full-length cDNA of grass carp IL-12Rβ2 is 2875 bp, which encodes a mature protein with 741 amino acids. This mature protein contains three fibronectin type III domains, a transmembrane helix, and CXW and WSXWS-like motifs that are characteristic of the type I cytokine receptor family. Phylogenetic analysis revealed that cyprinid fish IL-12Rβ2 formed a single branch, clearly separated from those of other vertebrates. We expressed and purified a recombinant grass carp IL-12Rβ2 protein containing major antigenic regions, which was used to raise a polyclonal antibody. The specificity of the antibody was assessed by Western blotting analysis of whole cell lysates from Escherichia coli cells expressing the recombinant IL-12Rβ2, grass carp intestinal intraepithelial lymphocytes, and cultured C. idella kidney cells. To explore the potential regulatory role of IL-12Rβ2 in inflammation, we generated an intestinal inflammation model by anal intubation of fish with Aeromonas hydrophila. Immunohistochemical staining of the inflamed intestines revealed that IL-12Rβ2 expression is consistent with inflammatory cell recruitment during intestinal inflammation. Real-time quantitative PCR revealed that IL-12Rβ2 is widely expressed in normal tissues and is up-regulated in most tissues after infecting with A. hydrophila. We found that IL-12Rβ2, IL-12p35, and interferon-γ were expressed in similar patterns in the intestines during inflammation. Taken together, our results suggest that IL-12Rβ2 is involved in the regulation of intestinal inflammation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The control of chemo-, regio-, diastereo-, and enantioselectivity is a central theme in organic synthesis. The capability to obtain the full set of stereoisomers of a molecule would significantly enhance the efficiency for the synthesis of natural product analogues and creation of chiral compound libraries for drug discovery. Despite the tremendous progress achieved in the field of asymmetric synthesis in the past decades, the precise control of both relative and absolute configurations in catalyst-controlled reactions that create multiple stereocenters remains a significant synthetic challenge. We report here the development of a catalyst-controlled hydroboration with hitherto unattainable selectivity. The Rh-catalyzed hydroboration of α, β-unsaturated carbonyl compounds with pinacolborane proceeds with high levels of regio-, diastereo-, and enantioselectivities to provide a hydroboration product with two vicinal stereocenters. Through the appropriate choice of substrate geometry ( E or Z) and ligand enantiomer ( S or R), all the possible diastereoisomers are readily accessible. The boron-containing products underwent many stereospecific transformations, thus providing a strategy for collective stereodivergent synthesis of diverse valuable chiral building blocks.

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is a serine-threonine mitogen-activated protein kinase that is highly expressed in many types of human cancer. Due to its important role in cancer progression, TOPK is becoming an attractive target in chemotherapeutic drug design. In this study, a series of 1-phenyl phenanthridin-6(5H)-one derivatives have been identified as a novel chemical class of TOPK inhibitors. Some of them displayed very potent anti-cancer activity with IC 50 s less than 100 nM, superior than reference compound OTS964. The most potent compound, 9g suppressed the growth of cancer cells by apoptosis and specifically inhibited the activities of TOPK. Oral administration of 9g effectively suppressed tumor growth with TGI >79.7% in colorectal cancer xenograft models, demonstrating superior efficacy compared to OTS964. Pharmacokinetic studies reveal its good oral bioavailability. Our findings therefore show that 9g is a specific inhibitor of TOPK both in vitro and in vivo that may be further developed as a potential therapeutic agent against colorectal cancer., (Copyright © 2018 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

A number of clinical trials demonstrated that tigecycline was effective and well tolerated in the treatment of patients with various bacterial infections, but few literatures had shown the coagulopathy induced by tigecycline. To address this concern, we performed a retrospective analysis to assess the impact of tigecycline treatment on coagulation parameters in 50 patients with bacterial infections in our hospital (Shandong Provincial Hospital, China). These patients were treated with tigecycline at Shandong Provincial Hospital in 2015-2016 at either a recommended (50 mg q12h) or a higher dose (100 mg q12h). Coagulation parameters, including Fibrinogen (FIB) levels, prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count (PLT) and D-dimer, were evaluated in order to assess the impact of tigecycline treatment in these severely infected patients. What we found was that the plasma fibrinogen (FIB) level was 4.63 ± 1.56 g/L before tigecycline treatment, and decreased to 2.92 ± 1.23 g/L during treatment, which was statistically significant (p < 0.001). The mean values of aPTT and PT were significantly increased from 39.58 ± 8.72 to 44.05 ± 10.45 s (p = 0.002), and from 15.37 ± 1.53 to 16.37 ± 2.64 s (p = 0.004), respectively. This study demonstrates that treatment of tigecycline could reduce FIB, prolong aPTT and PT. In conclusion, we advise that it is necessary for practitioners routinely monitor coagulation level in at-rick patient populations treated with tigecycline.

Introduction: Mindfulness is one of the potential alternative interventions for children with attention-deficit hyperactivity disorder (ADHD). Some evidence suggests that mindfulness is related to changes in brain regions associated with ADHD. The potential benefits of mindfulness on children with ADHD, as well as the feasibility of this intervention approach, are warranted through prior local and foreign studies. This study aims to evaluate the effect of mindfulness-based group intervention for children with ADHD and their respective parents through a robust research design., Methods and Analysis: This study will adopt a randomised controlled trial design including 140 children aged 8-12 years with ADHD together with one of their parents (n=140). These families will be randomised into intervention group (n=70) who will be offered the MYmind programme delivered by trained healthcare professionals, and an active control group (n=70) who will be offered the CBT programme. The intervention includes 8 weekly 90 min group sessions for children with ADHD (aged 8-12 years) and their respective parents. The primary and secondary outcomes will include children's attention, ADHD-related symptoms, behaviours, executive function and mindfulness levels measured by validated objective measures and parent's reported instruments. Parents' parental stress, parenting styles, ADHD related symptoms, well-being, rumination level and mindfulness levels will also be measured. Analysis is by intention to treat. The effects of intervention will be evaluated by comparing outcomes between the two arms, as well as comparing outcomes within subject through comparing measurements at baseline (T0), immediately after the 8 week intervention (T1) and at 3 (T2) and 6 (T3) months postintervention., Ethics and Dissemination: Ethics approval has been granted by the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (The Joint CUHK-NTEC CREC). Participants will be required to sign informed consent form from both parents and children. Findings will be reported in conferences and peer-reviewed publications in accordance with recommendations of Consolidated Standards of Reporting Trials., Trial Registration Number: ChiCTR1800014741; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A catalytic macrolactonization through oxidative cyclization of alkynyl alcohol by synergistic transition-metal and Lewis-acid catalysis was developed. Because the alkynyl alcohol substrates involved in this method are different from the seco acids that are used in conventional macrolactonization methods, the current method provides a strategically distinct entry to macrolactones. In addition to the operational simplicity, this macrolactonization protocol proceeds at relatively high concentration, precluding the need for high dilution or slow addition procedures.

Background: Malnutrition is a common and critical problem that influences outcome in cancer patients. Body composition reflects a patient's metabolic profile and physiologic reserves, which might be the true determinant of prognosis. In the present study, which aimed to identify valuable new prognostic indicators, we investigated the association between computed tomography-quantified body composition and short-term outcomes after gastrectomy for gastric cancer., Methods: Skeletal muscle index, mean muscle attenuation, and ratio of visceral-to-subcutaneous adipose tissue area (vsr) were calculated from preoperative computed tomography images. Low skeletal muscle index, low mean muscle attenuation, and high vsr were respectively termed "sarcopenia," "myosteatosis," and "visceral obesity." The association of body composition with postoperative complications and serum markers of nutrition and inflammation after radical gastrectomy were analyzed., Results: The overall complication rate was significantly higher in the sarcopenia (62.5% vs. 27.3%, p = 0.001) and myosteatosis groups (38.2% vs. 4%, p = 0.002). Patients with visceral obesity had a higher incidence of inflammatory complications (20.3% vs. 6.5%, p = 0.01). Multivariate logistic regression analysis demonstrated that sarcopenia ( p = 0.013), myosteatosis ( p = 0.017), and low serum retinol-binding protein ( p = 0.019) were independent risk factors for overall complications. Compared with control subjects, patients with sarcopenia had lower postoperative levels of serum retinol-binding protein ( p = 0.007), and patients with visceral obesity had higher levels of C-reactive protein ( p = 0.026)., Conclusions: Sarcopenia, myosteatosis, and visceral obesity were significantly associated with increased rates of postoperative complications and affected the postoperative nutrition and inflammation status of patients with gastric cancer., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

New psychoactive substances (NPS) are emerging continuously, as the crackdown against traditional drugs becomes stricter. Metabolites of NPSs and the unchanged drugs enter wastewater through urine and are collected and treated by wastewater treatment plants before being discharged into the aquatic environment. Based on previous research, solid phase extraction (SPE) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) were used and the detection method of 11 NPSs was optimized. Influences of wastewater pretreatment procedures, including SPE columns; pH values of water samples; and processes of flushing and redissolving on NPS recoveries were compared. It was shown that the best recovery was achieved when Oasis MCX columns were used and the pH value of wastewater samples was adjusted to 2. A flushing process with 2 mL water at pH=2 followed by 2 mL methanol was needed. Redissolution of the residue after evaporation was best achieved with 400 μL of a 20% methanol water solution. It was indicated by retention times, recoveries, matrix effects, limits of detection, limits of quantification, as well as precision that C18-UPLC-MS/MS and the optimized method are efficient and valid. Influent and effluent samples from 11 municipal wastewater treatment plants in Beijing were analyzed using the optimized method for validation. The validated method can be used as an important reference for monitoring NPSs via wastewater-based epidemiology and for assessing the risk of NPS abuse in China.

yhcZ and yhcY genes constitute a two-component system in Bacillus subtilis and B. cereus that regulates bacterial growth. However, the exact biological function of yhcZ gene in B. thuringiensis has not been fully elucidated. In this study, we proved that HD73&#95;5824 is an yhcZ gene in B. thuringiensis subsp. kurstaki HD73 strain by combining gene functional annotation, analysis of upstream and downstream genes arrangement, and amino acid sequence alignment. This yhcZ gene may co-regulate bacterial growth with HD73&#95;5825 gene (yhcY gene) by constituting a two-component system. Homologous recombination technology was employed to knock out yhcZ gene of HD73, resulting in a mutant strain HD (ΔyhcZ). The HD (ΔyhcZ) strain grew slower than wild-type strain HD73 in both LB and SSM medium. Re-introduction of yhcZ gene in HD (ΔyhcZ) strain can partially restore the growth, indicating that the deletion of yhcZ gene impacts the cell growth of HD73 strain. HD (ΔyhcZ) strain grew faster than HD73 strain in M9 medium with 0.4% glucose as the sole carbon source, implying that the yhcZ gene plays an important role in glucose utilization by HD73 strain. The results of biolog assay showed that HD (ΔyhcZ) exhibits a lower average well color development compared to HD73. HD(ΔyhcZ) cells also demonstrated a decreased capacity for absorbing and utilizing D/L-serine, formic acid, D-gluconic acid, L-histamine, D-methyl lactate, and citric acid, indicating that yhcZ gene could dramatically influence carbon source utilization of HD73 strains. Additionally, HD (ΔyhcZ) was less resistant to 8% NaCl, suggesting that yhcZ gene may be involved in the expression and regulation of genes related to high-salt stress response in bacterial cells. The results above show that the yhcZ gene significantly promotes glucose and other carbon sources utilization of HD73 strain during growth. Our findings will lay a foundation not only for analyzing the regulatory mechanisms of glucose and carbon sources utilization by yhcZ gene, but also providing a reference for the further research on bacterial growth and fermentation.

A palladium catalyzed synthesis of N-H phenanthridinones was developed via C-H arylation. The protocol gives phenanthridinones regioselectively by one-pot reaction without deprotection. It exhibits broad substrate scope and affords targets in up to 95% yields. Importantly, it could be applied for the less reactive o -chlorobenzamides., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)