Decoding transcriptional regulation via a human gene expression predictor

Transcription factors(TFs)regulate cellular activities by controlling gene expression,but a predictive model describing how TFs quantitatively modulate human transcriptomes is lacking.We construct a universal human gene expression predictor named EXPLICIT-Human and utilize it to decode transcriptional regulation.Using the expression of 1613 TFs,the predictor reconstitutes highly accurate transcriptomes for samples derived from a wide range of tissues and conditions.The broad applicability of the predictor indicates that it recapitulates the quantitative relationships between TFs and target genes ubiquitous across tissues.Significant interacting TF-target gene pairs are extracted from the predictor and enable downstream inference of TF regulators for diverse pathways involved in development,immunity,metabolism,and stress response.A detailed analysis of the hematopoiesis process reveals an atlas of key TFs regulating the development of different hematopoietic cell lineages,and a portion of these TFs are conserved between humans and mice.The results demonstrate that our method is capable of delineating the TFs responsible for fate determination.Compared to other existing tools,EXPLICIT-Human shows a better performance in recovering the correct TF regulators.

DSEMR: A database for special environment microorganisms resource and associating them with synthetic biological parts

Special environmental microorganisms are considered to be of great industrial application value because of their special genotypes,physiological functions and metabolites.The research and development of special environmental microorganisms will certainly bring about some innovations in biotechnology processes and change the face of bioengineering.The Special Environmental Microbial Database(DSEMR)is a comprehensive database that provides information on special environmental microbial resources and correlates them with synthetic biological parts.DSEMR aggregates information on specific environmental microbial genomes,physiological properties,culture media,biological parts,and metabolic pathways,and provides online tool analysis data,including 5268 strains from 620 genera,31 media,and 42,126 biological parts.In short,DSEMR will become an important resource for the study of microorganisms in special environments and actively promote the development of synthetic biology.

Relationship between corneal biomechanical parameters and corneal sublayer thickness measured by Corvis ST and UHR-OCT in keratoconus and normal eyes

Background:To explore the relationship between corneal biomechanical parameters and corneal sublayer thickness using corneal visualization Scheimpflug technology(Corvis ST)and ultrahigh-resolution optical coherence tomography(UHR-OCT)in clinical and suspected keratoconus and normal eyes.Methods:Cross-sectional prospective study.A total of 94 eyes of 70 participants were recruited.Twenty five eyes of 19 keratoconus patients,52 eyes of 34 patients showing high risk of developing keratoconus according to the Belin/Ambrosio Enhanced Ectasia Display,and each eye of 17 normal subjects were enrolled.All participants underwent Corvis ST,Pentacam,and UHR-OCT examinations at the same time.Stiffness parameter A1(SP-A1),deformation amplitude ratio(DA ratio),and other biomechanical parameters were recorded using Corvis ST.The vertical and horizontal thickness profiles of central 3mm corneal epithelium,Bowman’s layer,and stroma as measured by the perpendicular distance between the neighboring interfaces were generated using UHR-OCT.The flat keratometry and steep keratometry were obtained using Pentacam.Analysis of correlation was applied to explore the association between variables.Results:Most of the biomechanical parameters and corneal sublayer thickness profiles showed statistical differences among three groups.A statistically significant linear relationship was noted between SP-A1 and DA ratio in all three groups.SP-A1 was found to be positively correlated with epithelial and Bowman’s layer thickness in the keratoconus(KC)group,and with stromal thickness in all three groups.In the normal and suspected keratoconus(SKC)groups,only stromal thickness was included in the stepwise linear regression to predict SP-A1,whereas in the KC group,steep keratometry and Bowman’s layer thickness were included.Conclusions:Significant and different correlations were noted between corneal stiffness and corneal sublayer thickness in different groups,indicating that corneal sublayers may play different roles in maintaining corneal biomechanical stability between keratoconus and normal eyes.

scDPN for High-throughput Single-cell CNV Detection to Uncover Clonal Evolution During HCC Recurrence

Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution.Unfortunately,classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification.We developed a single-cell DNA library preparation method without preamplification in nanolitre scale(scDPN)to address these issues.The method achieved a throughput of up to 1800 cells per run for copy number variation(CNV)detection.Also,our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification(MDA)method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation.We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepatocellular carcinoma(HCC).We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome.Furthermore,we observed that a minor clone of the primary tumor containing additional alterations in chromosomes 1q,10q,and 14q developed into the dominant clone in the recurrent tumor,indicating clonal selection during recurrence in HCC.Overall,this approach provides a comprehensive and scalable solution to understand genome heterogeneity and evolution.

Recovery of injured corticospinal tracts after late recanalisation of basilar artery occlusion

In this study,we performed emergency stent angioplasty in a patient with basilar artery occlusion(BAO)at 21 hours after onset.Serial diffusion tensor tract imaging revealed that the ischaemic corticospinal tracts(CSTs),which passed through pontine infarct,rapidly recovered to normal level even after delayed reperfusion.This case provided in vivo evidences that ischaemic white matter was still salvageable even after prolonged ischaemia.It also provided a new method(diffusion tensor tract imaging)and a novel therapeutic target(white matter)in the evaluation and treatment of acute BAO.

Research and development of a novel subunit vaccine for the currently circulating pseudorabies virus variant in China

Pseudorabies(PR)is a devastating viral disease which leads to fatal encephalitis and respiratory disorders in pigs.Commercial gE-deleted live pseudorabies virus(PRV)vaccine has been widely used to control this disease in China.However,the new-emerging variants of PRV compromises the protection provided by current vaccines and lead to the outbreak of PR in vaccinated pig herds.Several killed and live vaccine candidates based on current PRV variants have been reported to be effective to control the disease.A subunit vaccine based on gB protein,one major PRV glycoprotein which elicits strong humoral and cellular immune responses,however,was never evaluated for protection against the current circulating PRV variants.In this study,full-length PRV gB protein was successfully expressed in baculovirus/insect cells in the soluble format and was tested on 3-week-old piglets as a subunit vaccine.Compared with unvaccinated pigs,the gB-vaccinated pigs developed specific antibody-mediated responses and were protected from the virulent PRV HN1201 challenge.All vaccinated pigs survived without showing any PRV-specific respiratory and neurological signs,but all unvaccinated pigs died within 7 days after HN1201 challenge.Hence,this novel gB-based vaccine could be applied as an effective subunit vaccine to control PRV variant in China.

Effect of environmental factors on the complexation of iron and humic acid

A method of size exclusion chromatography coupled with ultraviolet spectrophotometry and off-line graphite furnace atomic absorption spectrometry was developed to assess the complexation properties of iron（Fe） and humic acid（HA） in a water environment. The factors affecting the complexation of Fe and HA, such as ionic strength, pH, temperature and UV radiation, were investigated. The Fe–HA complex residence time was also studied. Experimental results showed that pH could influence the deprotonation of HA and hydrolysis of Fe, and thus affected the complexation of Fe and HA. The complexation was greatly disrupted by the presence of NaCl. Temperature had some influence on the complexation. The yield of Fe–HA complexes showed a small decrease at high levels of UV radiation, but the effect of UV radiation on Fe–HA complex formation at natural levels could be neglected. It took about 10 hr for the complexation to reach equilibrium, and the Fe–HA complex residence time was about 20 hr.Complexation of Fe and HA reached a maximum level under the conditions of pH 6, very low ionic strength, in the dark and at a water temperature of about 25°C, for 10 hr. It was suggested that the Fe–HA complex could form mainly in freshwater bodies and reach high levels in the warm season with mild sunlight radiation. With changing environmental parameters, such as at lower temperature in winter or higher pH and ionic strength in an estuary, the concentration of the Fe–HA complex would decrease.

Chest-scale self-compensated epidermal electronics for standard 6-precordial-lead ECG

Six chest leads are the standardized clinical devices of diagnosing cardiac diseases.Emerging epidermal electronics technology shift the dangling wires and bulky devices to imperceptible wearing,achieving both comfortable experience and high-fidelity measuring.Extending small areas of current epidermal electronics to the chest scale requires eliminating interference from long epidermal interconnects and rendering the data acquisition(DAQ)portable.Herein,we developed a chest-scale epidermal electronic system(EES)for standard precordial-lead ECG and hydration monitoring,including the onlyμm-thick substrate-free epidermal sensing module and the soft wireless DAQ module.An electrical compensation strategy using double channels within the DAQ module and epidermal compensated branches(ECB)is proposed to eliminate unwanted signals from the long epidermal interconnects and to achieve the desired ECG.In this way,the EES works stably and precisely under different levels of exercise.Patients with sinus arrhythmias have been tested,demonstrating the prospect of EES in cardiac diseases.