Dried tea residue can alter the blood metabolism and the composition and functionality of the intestinal microbiota in Hu sheep

Ruminant animals face multiple challenges during the rearing process, including immune disorders and oxidative stress. Green tea by-products have gained widespread attention for their significant immunomodulatory and antioxidant effects, leading to their application in livestock production. In this study, we investigated the effects of Dried Tea Residue (DTR) as a feed additive on the growth performance, blood biochemical indicators, and hindgut microbial structure and function of Hu sheep. Sixteen Hu sheep were randomly divided into two groups and fed with 0 and 100 g/d of DTR, respectively. Data were recorded over a 56-day feeding period. Compared to the control group, there were no significant changes in the production performance of Hu sheep fed with DTR. However, the sheep fed with DTR showed a significant increase in IgA (p < 0.001), IgG (p = 0.005), IgM (p = 0.003), T-SOD (p = 0.013), GSH-Px (p = 0.005), and CAT (p < 0.001) in the blood, along with a significant decrease in albumin (p = 0.019), high density lipoprotein (p = 0.050), and triglyceride (p = 0.021). DTR supplementation enhanced the fiber digestion ability of hindgut microbiota, optimized the microbial community structure, and increased the abundance of carbohydrate-digesting enzymes. Therefore, DTR can be used as a natural feed additive in ruminant animal production to enhance their immune and antioxidant capabilities, thereby improving the health status of ruminant animals

A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition.

The type VII protein secretion system (T7SS) is conserved across Staphylococcus aureus strains and plays important roles in virulence and interbacterial competition. To date, only one T7SS substrate protein, encoded in a subset of S. aureus genomes, has been functionally characterized. Here, using an unbiased proteomic approach, we identify TspA as a further T7SS substrate. TspA is encoded distantly from the T7SS gene cluster and is found across all S. aureus strains as well as in Listeria and Enterococci. Heterologous expression of TspA from S. aureus strain RN6390 indicates its C-terminal domain is toxic when targeted to the Escherichia coli periplasm and that it depolarizes the cytoplasmic membrane. The membrane-depolarizing activity is alleviated by coproduction of the membrane-bound TsaI immunity protein, which is encoded adjacent to tspA on the S. aureus chromosome. Using a zebrafish hindbrain ventricle infection model, we demonstrate that the T7SS of strain RN6390 promotes bacterial replication in vivo, and deletion of tspA leads to increased bacterial clearance. The toxin domain of TspA is highly polymorphic and S. aureus strains encode multiple tsaI homologs at the tspA locus, suggestive of additional roles in intraspecies competition. In agreement, we demonstrate TspA-dependent growth inhibition of RN6390 by strain COL in the zebrafish infection model that is alleviated by the presence of TsaI homologs

Triggering MSR1 promotes JNK-mediated inflammation in IL-4 activated macrophages

Alternatively activated M2 macrophages play an important role in maintenance of tissue homeostasis by scavenging dead cells, cell debris and lipoprotein aggregates via phagocytosis. Using proteomics, we investigated how alternative activation, driven by IL-4, modulated the phagosomal proteome to control macrophage function. Our data indicate that alternative activation enhances homeostatic functions such as proteolysis, lipolysis and nutrient transport. Intriguingly, we identified the enhanced recruitment of the TAK1/MKK7/JNK signalling complex to phagosomes of IL-4-activated macrophages. The recruitment of this signalling complex was mediated through K63 polyubiquitylation of the macrophage scavenger receptor 1 (MSR1). Triggering of MSR1 in IL-4-activated macrophages leads to enhanced JNK activation, thereby promoting a phenotypic switch from an anti-inflammatory to a pro-inflammatory state, which was abolished upon MSR1 deletion or JNK inhibition. Moreover, MSR1 K63 polyubiquitylation correlated with the activation of JNK signalling in ovarian cancer tissue from human patients, suggesting that it may be relevant for macrophage phenotypic shift in vivo Altogether, we identified that MSR1 signals through JNK via K63 polyubiquitylation and provides evidence for the receptor's involvement in macrophage polarization

Weight self-misperception and Obesity-related Knowledge, Attitudes, Lifestyle Behaviors and Cardio-metabolic Markers among Chinese School-aged Children and Adolescents

Abstract Objective: The relationships between childhood weight self-misperception and obesity-related factors particularly health markers have not been extensively discussed. This study aims to examine the associations between weight self-misperception and obesity-related knowledge, attitudes, lifestyles and cardio-metabolic markers among Chinese pediatric population. Design: Cross-sectional study. Setting: Data sourced from a national survey in Chinese seven provinces in 2013. Participants: Children and adolescents aged 5-19 years. Results: Of the total 14079 participants, there were 14.5% and 2.2% participants over-estimated and under-perceived their weight, respectively. Multi-variable logistic regression was applied to calculate odds ratio (OR) and 95% confidence interval (95% Cl) of obesity-related behaviors and cardio-metabolic markers by actual and perceived weight status. Individuals who perceived themselves as overweight/obese were more likely to have prolonged screen time, insufficient dairy intake, and over sugar-sweetened beverages consumption (all P<0.05), regardless of their weight. Furthermore, actual overweight/obese individuals had higher odds of abnormal cardio-metabolic markers, but a smaller magnitude of association was found among weight under-estimators. Among non-overweight/obese individuals, weight over-estimation was positively associated with abdominal obesity (OR: 10.49, 95% CI: 7.45, 14.76), elevated blood pressure (OR: 1.30, 95% CI: 1.12, 1.51), and dyslipidemia (OR: 1.43, 95% CI: 1.29, 1.58). Conclusions: Weight over-perception was more prevalent than under-estimation, particularly in girls. Weight over-estimators tended to master better knowledge but behave more unhealthily, both weight over-perception and actual overweight/obesity status were associated with poorer cardio-metabolic markers. Future obesity intervention programs should additionally pay attention to the population with inaccurate estimation of weight who were easily overlooked

A holin and an endopeptidase are essential for chitinolytic protein secretion in <i>Serratia marcescens</i>

Pathogenic bacteria adapt to their environment and manipulate the biochemistry of hosts by secretion of effector molecules. Serratia marcescens is an opportunistic pathogen associated with healthcare-acquired infections and is a prolific secretor of proteins, including three chitinases (ChiA, ChiB, and ChiC) and a chitin binding protein (Cbp21). In this work, genetic, biochemical, and proteomic approaches identified genes that were required for secretion of all three chitinases and Cbp21. A genetic screen identified a holin-like protein (ChiW) and a putative l-alanyl-d-glutamate endopeptidase (ChiX), and subsequent biochemical analyses established that both were required for nonlytic secretion of the entire chitinolytic machinery, with chitinase secretion being blocked at a late stage in the mutants. In addition, live-cell imaging experiments demonstrated bimodal and coordinated expression of chiX and chiA and revealed that cells expressing chiA remained viable. It is proposed that ChiW and ChiX operate in tandem as components of a protein secretion system used by gram-negative bacteria

Age-specific reference values for low psoas muscle index at the L3 vertebra level in healthy populations: A multicenter study

Background and aimsThe progressive and generalized loss of skeletal muscle mass, strength and physical function is defined as sarcopenia. Sarcopenia is closely related to the prognosis of patients. Accurate diagnosis and adequate management of sarcopenia are crucial. The psoas muscle mass index taken at the third lumbar vertebra (L3-PMI, cm2/m2) is one of the established methods for evaluating skeletal muscle mass. However, the cutoff values of L3-PMI for diagnosis of sarcopenia are not yet to be clarified in Asian populations. We attempted to establish reference values for low L3-PMI that would be suitable for defining sarcopenia in the Northern Chinese population.MethodsThis was a retrospective, multicenter cross-sectional study. A search of abdominal CT imaging reports was conducted in four representative cities in northern China. Transverse CT images were measured using the analysis software Slice-O-Matic. Low psoas muscle index was defined as the 5th percentile or mean-2SD of the study group.Results1,787 healthy individuals in the study were grouped by age. The sex and number of people in each group were similar. L3-PMI had a negative linear correlation with age, and a strong correlation with the skeletal muscle index taken at the third lumbar vertebrae (L3-SMI, cm2/m2). The L3-PMI reference values in males were 5.41 cm2/m2 for 20–29 years, 4.71 cm2/m2 for 30–39 years, 4.65 cm2/m2 for 40–49 years, 4.10 cm2/m2 for 50–59 years and 3.68 cm2/m2 for over 60 years by using 5th percentile threshold. Similarly, the reference values in females were 3.32, 3.40, 3.18, 2.91, and 2.62 cm2/m2. When using mean-2SD as the reference, the values for each age group were 4.57, 4.16, 4.03, 3.37, and 2.87 cm2/m2 for males and 2.79, 2.70, 2.50, 2.30, and 2.26 cm2/m2 for females, respectively.ConclusionWe defined the reference values of age-specific low skeletal muscle mass when simply evaluated by L3-PMI. Further studies about the association of sarcopenia using these reference values with certain clinical outcomes or diseases are needed

VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System

The Type VI secretion system (T6SS) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells. The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing device based on a tube of Hcp topped with a VgrG spike, which can be extended by a final tip from a PAAR domain-containing protein. Effector proteins are believed to be delivered by specifically associating with particular Hcp, VgrG or PAAR proteins, either covalently ('specialised') or non-covalently ('cargo' effectors). Here we used the T6SS of the opportunistic pathogen Serratia marcescens, together with integratecd genetic, proteomic and biochemical approaches, to elucidate the role of specific VgrG and PAAR homologues in T6SS function and effector specificity, revealing new aspects and unexpected subtleties in effector delivery by the T6SS. We identified effectors, both cargo and specialised, absolutely dependent on a particular VgrG for delivery to target cells, and discovered that other cargo effectors can show a preference for a particular VgrG. The presence of at least one PAAR protein was found to be essential for T6SS function, consistent with designation as a 'core' T6SS component. We showed that specific VgrG-PAAR combinations are required to assemble a functional T6SS and that the three distinct VgrG-PAAR assemblies in S. marcescens exhibit distinct effector specificity and efficiency. Unexpectedly, we discovered that two different PAAR-containing Rhs proteins can functionally pair with the same VgrG protein. Showing that accessory EagR proteins are involved in these interactions, native VgrG-Rhs-EagR complexes were isolated and specific interactions between EagR and cognate Rhs proteins identified. This study defines an essential yet flexible role for PAAR proteins in the T6SS and highlights the existence of distinct versions of the machinery with differential effector specificity and efficiency of target cell delivery

Exploring the processes and mechanisms by which nonprofit organizations orchestrate global innovation networks: A case study of the COVAX program

In cocreating value with other organizations, nonprofit organizations may face multiple management challenges, posed by multistakeholder global innovation networks. Since these have not yet been systematically studied by academics, this study explores how nonprofit organizations can promote the cocreation of value in multistakeholder global innovation networks. Adopting a longitudinal single-case study approach from the perspective of network orchestration theory, this work deeply analyzes how nonprofit organizations can promote the evolution of the global innovation network of the COVID-19 vaccine under the COVAX program. The results show that nonprofits need to successively address the dilemmas of legitimacy, direction, and heterogeneity in constructing global innovation networks and that to solve these stage dilemmas, orchestrators must successively function as network architects, liaisons, and leaders to direct the implementation of network actions using trusted, leveraged, and adapted orchestration logics. This paper further proposes a model of the orchestration process and mechanisms by which nonprofit organizations facilitate multistakeholder global innovation networks. Theoretically, this study therefore extends network orchestration theory by summarizing the mechanisms and orchestration logics by which NPOs construct and develop networks when they act as orchestrators. From a practical perspective, this study also provides guidance for future unexpected global public health crises, improving the global community's ability to combat them

Internationalization of emerging economies: Empirical investigation of cross-border mergers &amp; acquisitions and greenfield investment by Chinese firms

This study incorporates the eclectic paradigm and institutional theory to examine the key determinants of Chinese firms’ cross-border mergers and acquisitions (M&As) and greenfield (GF) investment in advanced economies (AEs) and developing economies (DEs) during the period 2003–2016. It uses a negative binomial regression model. In terms of M&As, our findings are consistent with the growing theoretical literature on emerging market multinational enterprises (EM MNEs). However, Chinese firms’ GF investments in AEs and DEs show results that are inconsistent with predictions, which means that research on GF investment requires more scrutiny and in-depth analysis. Although both economic and institutional factors affect Chinese firms’ location strategies, institutions tend to play a more dynamic role in shaping the location decisions for Chinese GF investments, implying that institutional context has a greater moderating effect on the link between investment motives and GF activity. In a nutshell, one should be cautious in generalizing Chinese cross-border M&A deals to GF investments or other entry modes