Increasing evidence has revealed a close association between intestinal bacterial communities and human health. However, given that host phylogeny shapes the composition of intestinal microbiota, it is unclear whether changes in intestinal microbiota structure in relation to shrimp health status. In this study, we collected shrimp and seawater samples from ponds with healthy and diseased shrimps to understand variations in bacterial communities among habitats (water and intestine) and/or health status. The bacterial communities were clustered according to the original habitat and health status. Habitat and health status constrained 14.6 and 7.7 % of the variation in bacterial communities, respectively. Changes in shrimp intestinal bacterial communities occurred in parallel with changes in disease severity, reflecting the transition from a healthy to a diseased state. This pattern was further evidenced by 38 bacterial families that were significantly different in abundance between healthy and diseased shrimps; moderate changes were observed in shrimps with sub-optimal health. In addition, within a given bacterial family, the patterns of enrichment or decrease were consistent with the known functions of those bacteria. Furthermore, the identified 119 indicator taxa exhibited a discriminative pattern similar to the variation in the community as a whole. Overall, this study suggests that changes in intestinal bacterial communities are closely associated with the severity of shrimp disease and that indicator taxa can be used to evaluate shrimp health status.

The association of Fcgamma receptor (FcgammaR) polymorphisms with systemic lupus erythematosus (SLE) has been demonstrated in various populations; however, the results have been inconsistent. We recently identified a single-nucleotide polymorphism encoding a non-synonymous substitution, Ile232Thr (I232T), of FCGR2B and its association with SLE in Japanese and in Thais. Multiple functional FcgammaR genes with polymorphisms (FCGR2A, FCGR2B, FCGR3A, and FCGR3B) cluster in 1q23, and some of them are in linkage disequilibrium (LD). To differentiate contributions from multiple-linked loci, comparison of different populations may provide useful information. In this study, we analyzed the above four FCGR polymorphisms of the Chinese patients and controls for the association with SLE. FCGR2A-H131R, FCGR2B-I232T, FCGR3A-F176V, and FCGR3B genotypes were determined in 167 Chinese patients with SLE and 129 healthy controls. Association was examined using case-control analysis. Allele frequencies of FCGR2B-232T and FCGR3A-176F were significantly increased in SLE [odds ratio (OR) = 1.67 and OR = 1.41, respectively]. Interestingly, while these alleles had a tendency of positive LD in the controls, FCGR2B-232T was in positive association with FCGR3A-176V in SLE, suggesting that these two alleles were associated with SLE in an independent manner. Comparison between SLE with and without nephritis indicated significant association of FCGR2B-232T with nephritis (OR = 2.65). When the present results were combined with our previous data on the Japanese and the Thais using meta-analytic methods, highly significant and independent association was observed for FCGR2B and FCGR3A genotypes. These results strongly suggested that FCGR2B is a common susceptibility factor to SLE in the Asians.

The underlying mechanisms of microbial community assembly in connective coastal environments are unclear. The coastal water area of northern Zhejiang, East China Sea, is a complex marine ecosystem with multiple environmental gradients, where the distributions and determinants of bacterioplankton communities remain unclear. We collected surface water samples from 95 sites across eight zones in this area for investigating bacterial community with 16S rRNA gene high-throughput sequencing. Bacterial alphadiversity exhibits strong associations with water chemical parameters and latitude, with 75.5% of variation explained by suspended particle. The composition of dominant phyla can group the sampling sites into four bacterial provinces, and most key discriminant phyla and families/genera of each province strongly associate with specific environmental features, suggesting that local environmental conditions shape the biogeographic provincialism of bacterial taxa. At a broader and finer phylogenetic scale, bacterial beta-diversity is dominantly explained by the shared variation of environmental and spatial factors (63.3%); meanwhile, the environmental determinants of bacterial β-diversity generally exhibit spatially structured patterns, suggesting that bacterial assembly in surface water is highly controlled by spatially structured environmental gradients in this area. This study provides evidence for the unique biogeographic pattern of bacterioplankton communities at an entire scale of this marine ecosystem.

Background: Tuberculosis (TB) is now the leading cause of death from infectious disease. Rapid screening and diagnostic methods for TB are urgently required. Rapid development of metagenomics next-generation sequencing (mNGS) in recent years showed promising and satisfying application of mNGS in several kinds of infectious diseases. However, research directly evaluating the ability of mNGS in TB infection is still scarce.Methods: We conducted an adult prospective study in mainland China to evaluate the diagnostic performance of mNGS for detection of Mycobacterium tuberculosis complex (MTB) in multiple forms of direct clinical samples compared with GeneXpert MTB/RIF assay (Xpert), traditional diagnostic methods, and the clinical final diagnosis.Results: Of 123 patients presenting with suspected active TB infection between June 1, 2017, and May 21, 2018, 105 patients underwent synchronous tuberculous testing with culture, Xpert, and mNGS on direct clinical samples including sputum, cerebrospinal fluids, pus, etc. During follow-up, 45 of 105 participants had clinical final diagnosis of active TB infection, including 13 pulmonary TB cases and 32 extrapulmonary TB cases. Compared to clinical final diagnosis, mNGS produced a sensitivity of 44% for all active TB cases, which was similar to Xpert (42%) but much higher than conventional methods (29%). With only one false-positive result, mNGS had a specificity of 98% in our study. mNGS yielded significantly much higher sensitivity in pre-treatment samples (76%) than post-treatment ones (31%) (P = 0.005), which was also true for Xpert and conventional methods. Combining Xpert and mNGS together, the study identified 27 of 45 active TB cases (60%), including all 13 conventional method-identified cases, and the result reached statistical significance compared to conventional methods (McNemar-test P < 0.001).Conclusions: mNGS had a similar diagnostic ability of MTB compared with Xpert and showed potential for a variety of clinical samples. Combined mNGS and Xpert showed an overall superior advantage over conventional methods and significantly improved the etiology diagnosis of both MTB and other pathogens. The result that anti-TB treatment significantly reduced diagnostic efficacy of culture, Xpert, and mNGS highlighted the importance of collecting samples before empirical treatment.

Tissue replenishment from stem cells follows a precise cascade of events, during which stem cell daughters first proliferate by mitotic transit amplifying divisions and then enter terminal differentiation. Here we address how stem cell daughters are guided through the early steps of development. In Drosophila testes, somatic cyst cells enclose the proliferating and differentiating germline cells and the units of germline and surrounding cyst cells are commonly referred to as cysts. By characterizing flies with reduced or increased Epidermal Growth Factor (EGF) signaling we show that EGF triggers different responses in the cysts dependent on its dose. In addition to the previously reported requirement for EGF signaling in cyst formation, a low dose of EGF signaling is required for the progression of the germline cells through transit amplifying divisions, and a high dose of EGF signaling promotes terminal differentiation. Terminal differentiation was promoted in testes expressing a constitutively active EGF Receptor (EGFR) and in testes expressing both a secreted EGF and the EGFR in the cyst cells, but not in testes expressing either only EGF or only EGFR. We propose that as the cysts develop, a temporal signature of EGF signaling is created by the coordinated increase of both the production of active ligands by the germline cells and the amount of available receptor molecules on the cyst cells.

Facile construction of ordered macroporous polyoxometalate-based metal–organic frameworks (POM@MOFs) to break the intrinsic microporous restriction is significant but remains challenging. On one hand, the POMs introduced improve the structural stability and modify the pores of MOFs, e.g., introducing functional catalytic and adsorptive units. Meanwhile, the acidic POMs severely affect the nucleation and growth of the POM@MOFs, resulting in complicated synthesis and difficult assembly control. Herein, a general approach has been developed to fabricate ordered macroporous POM@MOF single crystals, involving close-packed polystyrene (PS) nanosphere templates. The artificially selected polar solvents exerting strong solvent effect with POMs weaken the affinity between POMs and metal ions, thereby effectively stabilizing the precursors from assembly before filling into the PS template interstices. The weak alkaline carboxylate used regulates the in situ nucleation and growth of POM@MOFs through deprotonation of the ligands as well as coordinating modulation, affording a series of hierarchically cuboctahedral POM@MOF single crystals with ordered macropores (ca. 180 nm) and intrinsic micropores after template removal. The ordered macroporous structure and thinned microporous skeleton markedly improve mass diffusion properties, while the integral single-crystal lattice retains superior stability.

We performed a meta-analysis in an effort to systematically explore the association between apolipoprotein E (ApoE) epsilon2/epsilon3/epsilon4 polymorphisms and hypertension. We searched for case-control studies in English-language publications performed with human subjects using MEDLINE and included appropriate studies that had been published as of 6 May 2009. Fixed-effects models were used to pool data when between-study heterogeneity was absent, and random-effects models were used otherwise. Data and study quality were assessed in duplicate. Publication bias was assessed by calculating the fail-safe number. From six heterogeneous studies that included a total of 1812 patients with hypertension and 1762 controls, we found that the ApoE epsilon4 allele was significantly associated with hypertension using a random-effects model (odds ratio (OR)=1.79; 95% confidence interval (CI): 1.04 to 1.19; P=0.04). With regard to ApoE genotypes, we observed that the association with hypertension was more prominent when ApoE4/4 was compared with E3/3, with a nearly twofold increased risk identified for the ApoE4/4 genotype using a random-effects model (OR=1.97; 95% CI: 1.11 to 3.52; P=0.02). Furthermore, after restricting our analysis to Asian populations, the contrasts between the risk of hypertension among individuals possessing ApoE epsilon4 vs. epsilon3 and ApoE4/4 vs. ApoE3/3 were positively reinforced, with ORs of 1.97 (95% CI, 0.93 to 4.15; P=0.08) and 2.27 (95% CI, 1.03 to 4.98; P=0.04), respectively. The fail-safe number supported these significant associations at a significance level of 0.05. Taken together, our meta-analysis expands the data available regarding genetic risk factors for hypertension by illustrating that the presence of the ApoE epsilon4 allele is associated with an increased risk of developing hypertension and that it appears to be recessive. Of note, this effect was more pronounced in Asians.

Pulmonary infections are among the most common and important infectious diseases due to their high morbidity and mortality, especially in older and immunocompromised individuals. However, due to the limitations in sensitivity and the long turn-around time (TAT) of conventional diagnostic methods, pathogen detection and identification methods for pulmonary infection with greater diagnostic efficiency are urgently needed. In recent years, unbiased metagenomic next generation sequencing (mNGS) has been widely used to detect different types of infectious pathogens, and is especially useful for the detection of rare and newly emergent pathogens, showing better diagnostic performance than traditional methods. There has been limited research exploring the application of mNGS for the diagnosis of pulmonary infections. In this study we evaluated the diagnostic efficiency and clinical impact of mNGS on pulmonary infections. A total of 100 respiratory samples were collected from patients diagnosed with pulmonary infection in Shanghai, China. Conventional methods, including culture and standard polymerase chain reaction (PCR) panel analysis for respiratory tract viruses, and mNGS were used for the pathogen detection in respiratory samples. The difference in the diagnostic yield between conventional methods and mNGS demonstrated that mNGS had higher sensitivity than traditional culture for the detection of pathogenic bacteria and fungi (95% vs 54%; p&lt;0.001). Although mNGS had lower sensitivity than PCR for diagnosing viral infections, it identified 14 viral species that were not detected using conventional methods, including multiple subtypes of human herpesvirus. mNGS detected viruses with a genome coverage &gt;95% and a sequencing depth &gt;100× and provided reliable phylogenetic and epidemiological information. mNGS offered extra benefits, including a shorter TAT. As a complementary approach to conventional methods, mNGS could help improving the identification of respiratory infection agents. We recommend the timely use of mNGS when infection of mixed or rare pathogens is suspected, especially in immunocompromised individuals and or individuals with severe conditions that require urgent treatment.