BrainDAS: Structure-aware domain adaptation network for multi-site brain network analysis.

In the medical field, datasets are mostly integrated across sites due to difficult data acquisition and insufficient data at a single site. The domain shift problem caused by the heterogeneous distribution among multi-site data makes autism spectrum disorder (ASD) hard to identify. Recently, domain adaptation has received considerable attention as a promising solution. However, domain adaptation on graph data like brain networks has not been fully studied. It faces two major challenges: (1) complex graph structure; and (2) multiple source domains. To overcome the issues, we propose an end-to-end structure-aware domain adaptation framework for brain network analysis (BrainDAS) using resting-state functional magnetic resonance imaging (rs-fMRI). The proposed approach contains two stages: supervision-guided multi-site graph domain adaptation with dynamic kernel generation and graph classification with attention-based graph pooling. We evaluate our BrainDAS on a public dataset provided by Autism Brain Imaging Data Exchange (ABIDE) which includes 871 subjects from 17 different sites, surpassing state-of-the-art algorithms in several different evaluation settings. Furthermore, our promising results demonstrate the interpretability and generalization of the proposed method. Our code is available at https://github.com/songruoxian/BrainDAS.

LOX-1 acts as an N6-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase.

The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.

Applied anatomy of female pelvic plexus for nerve-sparing radical hysterectomy(NSRH).

BACKGROUND: Nerve-sparing radical hysterectomy(NSRH)has the advantage of reducing postoperative complications and improving postoperative quality of life. The separation and protection of the pelvic plexus in NSRH is extremely important and challenging. METHODS: 24 female cadaveric hemipelves were dissected. Morphologic patterns and compositions of pelvic plexus as well as relationship of pelvic plexus to the surrounding structures were observed and documented. RESULTS: Two patterns of superior hypogastric plexus were observed, including fenestrated and cord-like shape. The origin of bilateral hypogastric nerves were inferiorly to upper margin of promontory about 1.6 ± 0.1 cm and parallel to the ureter in front of the sacrum. Pelvic splanchnic nerves(PSN)from the second sacral nerve, the third sacral nerve and the forth sacral nerve were observed combing with the hypogastric nerves within the lateral rectal ligament. The sacral sympathetic trunk can be identified anteriorly or medially to the anterior sacral foramen. We identified the boundaries of pelvic plexus as following: the upper margin is formed by the PSNs from the third sacral nerve, posterior margin by inferior rectal artery, and anteriorly by vesical venous plexus. The uterine branches from pelvic plexus were observed accompanying with uterine artery, while other branches were inferiorly to the artery. The PSNs were located beneath the deep uterine veins within the cardinal ligament. The upper margin of pelvic plexus was observed directly approach to urinary bladder within the vesico-vaginal ligament as a single trunk accompanying with ureter, between the middle and inferior vesical veins. CONCLUSIONS: Our study clarified the intricate arrangement, distribution and relationship of female pelvic plexus and the related structures to provide reference index for NSRH application. The innervation patterns of bladder and uterine were clarified, and by tracing these visceral branches of pelvic plexus, we suggest several new important land markers for NSRH.

Traditional Medicine Pien Tze Huang Suppresses Colorectal Tumorigenesis Through Restoring Gut Microbiota and Metabolites.

BACKGROUND & AIMS: Pien Tze Huang (PZH) is a well-established traditional medicine with beneficial effects against inflammation and cancer. We aimed to explore the chemopreventive effect of PZH in colorectal cancer (CRC) through modulating gut microbiota. METHODS: CRC mouse models were established by azoxymethane plus dextran sulfate sodium treatment or in Apcmin/+ mice treated with or without PZH (270 mg/kg and 540 mg/kg). Gut barrier function was determined by means of intestinal permeability assays and transmission electron microscopy. Fecal microbiota and metabolites were analyzed by means of metagenomic sequencing and liquid chromatography mass spectrometry, respectively. Germ-free mice or antibiotic-treated mice were used as models of microbiota depletion. RESULTS: PZH inhibited colorectal tumorigenesis in azoxymethane plus dextran sulfate sodium-treated mice and in Apcmin/+ mice in a dose-dependent manner. PZH treatment altered the gut microbiota profile, with an increased abundance of probiotics Pseudobutyrivibrio xylanivorans and Eubacterium limosum, while pathogenic bacteria Aeromonas veronii, Campylobacter jejuni, Collinsella aerofaciens, and Peptoniphilus harei were depleted. In addition, PZH increased beneficial metabolites taurine and hypotaurine, bile acids, and unsaturated fatty acids, and significantly restored gut barrier function. Transcriptomic profiling revealed that PZH inhibited PI3K-Akt, interleukin-17, tumor necrosis factor, and cytokine-chemokine signaling. Notably, the chemopreventive effect of PZH involved both microbiota-dependent and -independent mechanisms. Fecal microbiota transplantation from PZH-treated mice to germ-free mice partly recapitulated the chemopreventive effects of PZH. PZH components ginsenoside-F2 and ginsenoside-Re demonstrated inhibitory effects on CRC cells and primary organoids, and PZH also inhibited tumorigenesis in azoxymethane plus dextran sulfate sodium-treated germ-free mice. CONCLUSIONS: PZH manipulated gut microbiota and metabolites toward a more favorable profile, improved gut barrier function, and suppressed oncogenic and pro-inflammatory pathways, thereby suppressing colorectal carcinogenesis.

Simulation of highly efficient GeSe-based solar cells with SCAPS-1D.

Recently GeSe has developed as a promising light harvesting material by enjoying to its optical and electrical features as well as earth-abundant and low-toxic constituent elements. Nevertheless, the power conversion efficiency of GeSe-based solar cells yet lags far behind the Shockley-Queisser limit. In this work, we systematically designed, simulated and analyzed the highly efficient GeSe thin-film solar cells by SCAPS-1D. The influence of thickness and defect density of light harvest material, GeSe/CdS interface defect density, electron transport layer (ETL), electrode work function and hole transport layer (HTL) on the device output are carefully analyzed. By optimizing the parameters (thickness, defect, concentration, work function, ETL and HTL), an impressive PCE of 17.98% is delivered along with Jsc of 37.11 mA/cm2, FF of 75.53%, Voc of 0.61 V. This work offers theoretical guidance for the design of highly efficient GeSe thin film solar cells.

Comparative study of pancreatic vessels and mesopancreas of rhesus monkeys and humans.

Introduction: With the introduction of the concept of mesopancreas defining the perineural structures that includes neurovascular bundle and lymph nodes extending from the posterior surface of the pancreatic head to behind the mesenteric vessels,Total Mesopancreas Excision (TMpE) based on this theory has facilitated the development of pancreatic cancer surgery in clinical practice in recent years. However, the existence of so called mesopancreas in the human body is still in debate and the comparative study of mesopancreas of rhesus monkey and human have not been well investigated. Purpose: The aim of our study is to compare the pancreatic vessels and fascia of human and rhesus monkeys in anatomical and embryological perspectives and to support the utilization of rhesus monkey as animal model. Methods: In this study, 20 rhesus monkey cadavers were dissected and their mesopancreas location, relationships and arterial distribution were analyzed. We compared the location and developmental patterns of mesopancreas in macaques and humans. Results: The results showed that the distribution of pancreatic arteries in rhesus monkeys was the same as that in humans, which is consistent with phylogenetic similarities. However, the morphological features of the mesopancreas and greater omentum is anatomically different from that of humans, including (1) the greater omentum is not connected to the transverse colon in monkeys. (2) The presence of the dorsal mesopancreas of the rhesus monkey suggests that it be an intraperitoneal organ. Comparative anatomical studies of mesopancreas and arteries in macaques and humans showed characteristic patterns of mesopancreas and similarities in pancreatic artery development in nonhuman primates, consistent with phylogenetic differentiation.

Microbial ecological responses of partial nitritation/anammox granular sludge to real water matrices and its potential application.

Granular sludges are commonly microbial aggregates used to apply partial nitritation/anammox (PN/A) processes during efficient biological nitrogen removal from ammonium-rich wastewater. Considering keystone taxa of anammox bacteria (AnAOB) in granules and their sensitivity to unfavorable environments, it is essential to investigate microbial responses of autotrophic PN/A granules to real water matrices containing organic and inorganic pollutants. In this study, tap water, surface water, and biotreated wastewater effluents were fed into a series of continuous PN/A granular reactors, respectively, and the differentiation in functional activity, sludge morphology, microbial community structure, and nitrogen metabolic pathways was analyzed by integrating kinetic batch testing, size characterization, and metagenomic sequencing. The results showed that feeding of biotreated wastewater effluents causes significant decreases in nitrogen removal activity and washout of AnAOB (dominated by Candidatus Kuenenia) from autotrophic PN/A granules due to the accumulation of heavy metals and formation of cavities. Microbial co-occurrence networks and nitrogen cycle-related genes provided evidence for the high dependence of symbiotic heterotrophs (such as Proteobacteria, Chloroflexi, and Bacteroidetes) on anammox metabolism. The enhancement of Nitrosomonas nitritation in the granules would be considered as an important contributor to greenhouse gas (N2O) emissions from real water matrices. In a novel view on the application of microbial responses, we suggest a bioassay of PN/A granules by size characterization of red-color cores in ecological risk assessment of water environments.

Kynurenine pathway metabolites modulated the comorbidity of IBD and depressive symptoms through the immune response.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is defined as chronic inflammation in the gastrointestinal tract. Notably, more than 20% of people with IBD experience depressive symptoms. Understanding the immunological mechanism of chronic intestinal inflammation on cognitive behavior has become a key research focus. Previous studies have shown that a dysregulated immune response contributes to chronic inflammation and depressive symptoms. The tolerant phenotype exhibited by immune cells regulates the course of chronic inflammation in distinct ways. In addition, neuroglia, such as microglia and astrocytes specific to the brain, are also influenced by deregulated inflammation to mediate the development of depressive symptoms. The kynurenine pathway (KP), a significant tryptophan metabolic pathway, transforms tryptophan into a series of KP metabolites that modulate chronic inflammation and depressive symptoms. In particular, indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in the KP, is activated by chronic inflammation and leads to the production of kynurenine. In addition, disruption of the brain-gut axis induced by IBD allows kynurenine to cross the blood-brain barrier (BBB) and form a series of neuroactive kynurenine metabolites in glial cells. Among them, quinolinic acid continuously accumulates in the brain, indicating depression. Thus, KP metabolites are critical for driving the comorbidity of IBD and depressive symptoms. In this review, the pathological mechanism of KP metabolite-mediated chronic intestinal inflammation and depressive symptoms by regulating the immune response is summarized according to the latest reports.

3'untranslated regions of tumor suppressor genes evolved specific features to favor cancer resistance.

Cancer-related genes have evolved specific genetic and genomic features to favor tumor suppression. Previously we reported that tumor suppressor genes (TSGs) acquired high promoter CpG dinucleotide frequencies during evolution to maintain high expression in normal tissues and resist cancer-specific downregulation. In this study, we investigated whether 3'untranslated regions (3'UTRs) of TSGs have evolved specific features to carry out similar functions. We found that 3'UTRs of TSGs, especially those involved in multiple histological types and pediatric cancers, are longer than those of non-cancer genes. 3'UTRs of TSGs also exhibit higher density of binding sites for RNA-binding proteins (RBPs), particularly those having high affinities to C-rich motifs. Both longer 3'UTR length and RBP binding sites enrichment are correlated with higher gene expression in normal tissues across tissue types. Moreover, both features together with the correlated N6-methyladenosine modification and the extent of protein-protein interactions are positively associated with the ability of TSGs to resist cancer-specific downregulation. These results were successfully validated with independent datasets. Collectively, these findings indicate that TSGs have evolved longer 3'UTR with increased propensity to RBP binding, N6-methyladenosine modification and protein-protein interactions for optimizing their tumor-suppressing functions.

[Characterization of Sludge Morphology and Bacterial Community Evolution in the Rapid Activation of Freeze-stored PN/A Granular Sludge].

Inoculating granular sludge is an alternative method for the quick start-up of a high-performance autotrophic nitrogen removal reactor. In order to establish the response relationship between sludge activation and reactor performance, the freeze-stored granular sludge was inoculated into a continuous-flow reactor, and a control strategy of the high loading rate and high hydraulic selective pressure was carried out in this study. As a result, a one-stage partial nitritation/ANAMMOX process was started up in 34 days, and the removal efficiency of total nitrogen was over 83%, with a removal loading rate of total nitrogen of 1.67 kg·(m3·d)-1. During this period, the Image pro-plus software was employed to analyze the evolution of the characteristic dimensions of particles. A good linear positive correlation (R2=0.988) between the projected area of the erythrine zone in the inner layer and the specific nitrogen removal rate of granules was found, which provide a simple method to estimate the activity of the PN/A granules. The results of MiSeq high-throughput sequencing showed that the enrichment of aerobic ammonia-oxidizing bacteria (Nitrosomonas) and the wash-out of heterotrophic bacteria (such as Denitratisoma and Haliangium, etc.) were achieved in the start-up of the reactor. Meanwhile, the improvement in granular compactness was in favor of activating anaerobic ammonia oxidizing bacteria (Candidatus_Kuenenia, abundance>30%) that colonized the inner layer of the granules.

SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1.

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1ß/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

A two-layer nested heterogeneous ensemble learning predictive method for COVID-19 mortality.

The COVID-19 epidemic has had a great adverse impact on the world, having taken a heavy toll, killing hundreds of thousands of people. In order to help the world better combat COVID-19 and reduce its death toll, this study focuses on the COVID-19 mortality. First, using the multiple stepwise regression analysis method, the factors from eight aspects (economy, society, climate etc.) that may affect the mortality rates of COVID-19 in various countries is examined. In addition, a two-layer nested heterogeneous ensemble learning-based prediction method that combines linear regression (LR), support vector machine (SVM), and extreme learning machine (ELM) is developed to predict the development trends of COVID-19 mortality in various countries. Based on data from 79 countries, the experiment proves that age structure (proportion of the population over 70 years old) and medical resources (number of beds) are the main factors affecting the mortality of COVID-19 in each country. In addition, it is found that the number of nucleic acid tests and climatic factors are correlated with COVID-19 mortality. At the same time, when predicting COVID-19 mortality, the proposed heterogeneous ensemble learning-based prediction method shows better prediction ability than state-of-the-art machine learning methods such as LR, SVM, ELM, random forest (RF), long short-term memory (LSTM) etc.

Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance.

Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.

Bioinformatic analyses hinted at augmented T helper 17 cell differentiation and cytokine response as the central mechanism of COVID-19-associated Guillain-Barré syndrome.

OBJECTIVES: Guillain-Barré syndrome (GBS) results from autoimmune attack on the peripheral nerves, causing sensory, motor and autonomic abnormalities. Emerging evidence suggests that there might be an association between COVID-19 and GBS. Nevertheless, the underlying pathophysiological mechanism remains unclear. MATERIALS AND METHODS: We performed bioinformatic analyses to delineate the potential genetic crosstalk between COVID-19 and GBS. RESULTS: COVID-19 and GBS were associated with a similar subset of immune/inflammation regulatory genes, including TNF, CSF2, IL2RA, IL1B, IL4, IL6 and IL10. Protein-protein interaction network analysis revealed that the combined gene set showed an increased connectivity as compared to COVID-19 or GBS alone, particularly the potentiated interactions with CD86, IL23A, IL27, ISG20, PTGS2, HLA-DRB1, HLA-DQB1 and ITGAM, and these genes are related to Th17 cell differentiation. Transcriptome analysis of peripheral blood mononuclear cells from patients with COVID-19 and GBS further demonstrated the activation of interleukin-17 signalling in both conditions. CONCLUSIONS: Augmented Th17 cell differentiation and cytokine response was identified in both COVID-19 and GBS. PBMC transcriptome analysis also suggested the pivotal involvement of Th17 signalling pathway. In conclusion, our data suggested aberrant Th17 cell differentiation as a possible mechanism by which COVID-19 can increase the risk of GBS.

Ultrasensitive visual detection of Hg2+ ions via the Tyndall effect of gold nanoparticles.

This work reports a new methodology for naked-eye nanosensing of Hg2+ where the Tyndall effect of gold nanoparticles (GNPs) acts as a light scattering signalling readout. Its utility is demonstrated with ultrasensitive detection of the target with a limit down to 0.13 nM (∼5461-fold sensitivity improvement over conventional GNP-based methods with surface plasmon resonance signalling).

Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19.

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, causing significant mortality. There is a mechanistic relationship between intracellular coronavirus replication and deregulated autophagosome-lysosome system. We performed transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and identified the aberrant upregulation of genes in the lysosome pathway. We further determined the capability of two circulating markers, namely microtubule-associated proteins 1A/1B light chain 3B (LC3B) and (p62/SQSTM1) p62, both of which depend on lysosome for degradation, in predicting the emergence of moderate-to-severe disease in COVID-19 patients requiring hospitalization for supplemental oxygen therapy. Logistic regression analyses showed that LC3B was associated with moderate-to-severe COVID-19, independent of age, sex and clinical risk score. A decrease in LC3B concentration <5.5 ng/ml increased the risk of oxygen and ventilatory requirement (adjusted odds ratio: 4.6; 95% CI: 1.1-22.0; P = 0.04). Serum concentrations of p62 in the moderate-to-severe group were significantly lower in patients aged 50 or below. In conclusion, lysosome function is deregulated in PBMCs isolated from COVID-19 patients, and the related biomarker LC3B may serve as a novel tool for stratifying patients with moderate-to-severe COVID-19 from those with asymptomatic or mild disease. COVID-19 patients with a decrease in LC3B concentration <5.5 ng/ml will require early hospital admission for supplemental oxygen therapy and other respiratory support.

Conversion of full nitritation to partial nitritation/anammox in a continuous granular reactor for low-strength ammonium wastewater treatment at 20 °C.

The feasibility of converting full nitritation to partial nitritation/anammox (PN/A) at ambient temperature (20 °C) was investigated in a continuous granular reactor. The process was conducted without anammox bacteria inoculation for the treatment of 70 mg L-1 of low-strength ammonium nitrogen wastewater. Following the stepwise increase of the nitrogen loading rate from 0.84 to 1.30 kg N m-3 d-1 in 320 days of operation, the removal efficiency of total inorganic nitrogen (TIN) exceeded 80% under oxygen-limiting conditions. The mature PN/A granules, which had a compact structure and abundant biomass, exhibited a specific TIN removal rate of 0.11 g N g-1 VSS d-1 and a settling velocity of 70.2 m h-1. This was comparable with that obtained at above 30 °C in previous reports. High-throughput pyrosequencing results revealed that the co-enrichment of aerobic and anaerobic ammonium-oxidizing bacteria identified as genera Nitrosomonas and Candidatus Kuenenia, which prompted a hybrid competition for oxygen and nitrite with nitrite-oxidizing bacteria (NOB). However, the overgrowth of novel NOB Candidatus Nitrotoga adapted to low temperatures and low nitrite concentration could potentially deteriorate the one-stage PN/A process by exhausting residual bulk ammonium under long-term excessive aeration.

The draft genome of mandrill (Mandrillus sphinx): An Old World monkey.

Mandrill (Mandrillus sphinx) is a primate species, which belongs to the Old World monkey (Cercopithecidae) family. It is closely related to human, serving as a model for human health related research. However, the genetic studies on and genomic resources of mandrill are limited, especially in comparison to other primate species. Here we produced 284 Gb data, providing 96-fold coverage (considering the estimated genome size of 2.9 Gb), to construct a reference genome for the mandrill. The assembled draft genome was 2.79 Gb with contig N50 of 20.48 Kb and scaffold N50 of 3.56 Mb. We annotated the mandrill genome to find 43.83% repeat elements, as well as 21,906 protein-coding genes. The draft genome was of good quality with 98% gene annotation coverage by Benchmarking Universal Single-Copy Orthologs (BUSCO). Based on comparative genomic analyses of  the Major Histocompatibility Complex (MHC) of the immune system in mandrill and human, we found that 17 genes in the mandrill that have been associated with disease phenotypes in human such as Lung cancer, cranial volume and asthma, barbored amino acids changing mutations. Gene family analyses revealed expansion of several genes, and several genes associated with stress environmental adaptation and innate immunity responses exhibited signatures of positive selection. In summary, we established the first draft genome of  the mandrill of value for studies on evolution and human health.

Highly Sensitive Colorimetric Detection of a Variety of Analytes via the Tyndall Effect.

This work initially reports the use of a quite familiar optical phenomenon of colloidal solutions, namely, the Tyndall Effect (TE) as signal readout for highly sensitive colorimetric chemical and biological analysis. Taking gold nanoparticles (GNPs) as a model colloid, the TE-inspired assay (TEA) is developed based on the conversion of a specific recognition event (e.g., the aptamer-analyte binding) into the aggregation of GNPs, leading to a significant TE enhancement. In the TEA, a cheap laser pointer pen is used as a hand-held light source, while a smartphone serves as a portable quantitative reader. The results show that the TE signaling strategy achieves a ∼1000-fold sensitivity improvement compared with the most common surface plasmon resonance signaling method using GNPs. The utility of the TEA is well demonstrated with the inexpensive, rapid, and portable detection of trace levels of analytes ranging from an important small-molecule drug (cocaine, ∼1.5 pM detection limit) to a protein biomarker (interferon-γ, ∼2.2 fM detection limit) and a toxic metal ion (Ag+, ∼1.4 nM detection limit). In addition, as the TE enhancement simply stems from the aggregation of either bare (unmodified) or modified GNPs, the TEA is universally applicable to almost all of the existing GNP-based liquid-phase colorimetric assays. The TEA method developed herein lights a new way for equipment-free point-of-care analysis in various fields including medical diagnosis, food safety evaluation, and environmental monitoring, especially in the resource-poor areas of the world.

Genomic variants identified from whole-genome resequencing of indicine cattle breeds from Pakistan.

The primary goal of cattle genomics is the identification of genome-wide polymorphism associated with economically important traits. The bovine genome sequencing project was completed in 2009. Since then, using massively parallel sequencing technologies, a large number of Bos taurus cattle breeds have been resequenced and scanned for genome-wide polymorphisms. As a result, a substantial number of single nucleotide polymorphisms (SNPs) have been discovered across European Bos taurus genomes, whereas extremely less number of SNPs are cataloged for Bos indicus breeds. In this study, we performed whole-genome resequencing, reference-based mapping, functional annotation and gene enrichment analysis of 20 sires representing eleven important Bos indicus (indicine) breeds of Pakistan. The breeds sequenced here include: Sahiwal, Red Sindhi, Tharparkar and Cholistani (tropically adapted dairy and dual purpose breeds), Achai, Bhagnari, Dajal and Lohani (high altitude adapted dual and drought purpose breeds); Dhanni, Hisar Haryana and Gabrali (dairy and light drought purpose breeds). A total of 17.4 billion QC passed reads were produced using BGISEQ-500 next generation sequencing platform to generate 9 to 27-fold genome coverage (average ~16×) for each of the 20 sequenced sires. A total of 67,303,469 SNPs were identified, of which 3,850,365 were found novel and 1,083,842 insertions-deletions (InDels) were detected across the whole sequenced genomes (491,247 novel). Comparative analysis using coding region SNPs revealed a close relationship between the best milking indicine breeds; Red Sindhi and Sahiwal. On the other hand, Bhagnari and Tharparkar being popular for their adaptation to dry and extremely hot climates were found to share the highest number of SNPs. Functional annotation identified a total of 3,194 high-impact (disruptive) SNPs and 745 disruptive InDels (in 275 genes) that may possibly affect economically important dairy and beef traits. Functional enrichment analysis was performed and revealed that high or moderate impact variants in wingless-related integration site (Wnt) and vascular smooth muscle contraction (VSMC) signaling pathways were significantly over-represented in tropically adapted heat tolerant Pakistani-indicine breeds. On the other hand, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) signaling pathways were found over-represented in highland adapted Pakistani-indicine breeds. Similarly, the ECM-receptor interaction and Jak-STAT signaling pathway were significantly enriched in dairy and beef purpose Pakistani-indicine cattle breeds. The Toll-like receptor signaling pathway was significantly enriched in most of the Pakistani-indicine cattle. Therefore, this study provides baseline data for further research to investigate the molecular mechanisms of major traits and to develop potential genomic markers associated with economically important breeding traits, particularly in indicine cattle.