Genome assembly of Polygala tenuifolia provides insights into its karyotype evolution and triterpenoid saponin biosynthesis

Polygala tenuifolia is a perennial medicinal plant that has been widely used in traditional Chinese medicine for treating mental diseases.However,the lack of genomic resources limits the insight into its evolutionary and biological characterization.In the present work,we reported the P.tenuifolia genome,the first genome assembly of the Polygalaceae family.We sequenced and assembled this genome by a combination of Illumnina,PacBio HiFi,and Hi-C mapping.The assembly includes 19 pseudochromosomes covering∼92.68%of the assembled genome(∼769.62 Mb).There are 36463 protein-coding genes annotated in this genome.Detailed comparative genome anal-ysis revealed that P.tenuifolia experienced two rounds of whole genome duplication that occurred∼39–44 and∼18–20 million years ago,respectively.Accordingly,we systematically reconstructed ancestral chromosomes of P.tenuifolia and inferred its chromosome evolution trajectories from the common ancestor of core eudicots to the present species.Based on the transcriptomics data,enzyme genes and transcription factors involved in the synthesis of triterpenoid saponin in P.tenuifolia were identified.Further analysis demonstrated that whole-genome duplications and tandem duplications play critical roles in the expansion of P450 and UGT gene families,which contributed to the synthesis of triterpenoid saponins.The genome and transcriptome data will not only provide valuable resources for comparative and functional genomic researches on Polygalaceae,but also shed light on the synthesis of triterpenoid saponin.

Inhibition of mTOR signaling by rapamycin protects photoreceptors from degeneration in rd1 mice

Retinitis pigmentosa(RP)is an inherited retinal degenerative disease that begins with defective rod photoreceptor function,followed by impaired cone function,and complete blindness in its late stage.To date,however,there is no effective treatment for RP.By carrying a nonsense mutation in the Pde6b gene,rd1 mice display elevated cGMP in conjunction with higher intracellular Ca2+in their rod photoreceptors,resulting in fast retinal degeneration.Ca2+has been linked to activation of the mammalian target of rapamycin(mTOR)pathway.The mTOR pathway integrates extracellular and intracellular signals to sense the supply of nutrients and plays a central role in regulating protein and lipid synthesis as well as apoptosis and autophagy.In the present study,we showed that mTOR and phosphorylated mTOR(p-mTOR,activated form of mTOR)are up-regulated in rd1 photoreceptors at postnatal day 10(P10),a pre-degenerative stage.Moreover,the downstream effectors of mTOR,such as pS6K and S6K,are also increased,suggesting activation of the mTOR signaling pathway.Intravitreal administration of rapamycin,a negative regulator of mTOR,inhibits the mTOR pathway in rd1 photoreceptors.Consequently,the progression of retinal degeneration is slower and retinal function is enhanced,possibly mediated by activation of autophagy in the photoreceptors.Taken together,these results highlight rapamycin as a potential therapeutic avenue for retinal degeneration.

A STUDY ON MECHANICAL PROPERTIES OF γ-RAY IRRADIATED HDPE FILLED WITH SERICITE-TRIDYMITE-CRISTOBALITE

The effect of γ-ray irradiation on the mechanical properties of high densitypolyethylene(HDPE) filled with sericite-tridymite-cristobalite(STC) was studied. The ex-perimental results show that γ-ray irradiation can improve the affinity between HDPE andSTC, and the dispersion of STC in HDPE matrix. Compared with HDPE/STC (80/20)blend, the yield stress and impact strength of irradiated HDPE (10kGy)/STC (80/20) blendare increased from 22.8 MPa and 70J/m to 28.5 MPa and 144J/m. The yield stress andimpact strength of HDPE/irradiated HDPE/STC (48/32/20) are 27.8MPa and 210J/m,respectively.

The prospects for bioprinting tumor models:recent advances in their applications

Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important characteristics with their in vivo tumor counterparts.Accordingly,their applications in tumor modeling,drug screening,and precision-targeted treatment are promising.However,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor microenvironment.Recently,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in vitro.Among the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor tissues.In this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model construction.The multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.

Nocturnal hypertension and riser pattern are associated with heart failure rehospitalization in patients with heart failure with preserved ejection fraction

BACKGROUND Nocturnal hypertension is reported as a risk factor for cardiovascular disease.This study aimed to explore the potential association between nocturnal hypertension and heart failure(HF)rehospitalization in patients with HF with preserved ejection fraction(HFpEF).METHODS A total of 538 patients with HFpEF from May 2018 to December 2021 were consequently recruited in this study and followed up until they were readmitted for HF or the end of this study.Cox regression analysis was used to reveal the potential association between nighttime blood pressure(BP)levels,nocturnal hypertension and nocturnal BP patterns and HF rehospitalization.Kaplan-Meier curve was used to assess the cumulative event-free survival rate between groups.RESULTS There were 537 patients with HFpEF were included in the final analysis.The mean age of the study population was 77.14±8.68 years,and 41.2% of patients were men.After a median follow-up duration of 10.93(4.19–21.13)months,176 patients(32.7%)with HFpEF were readmitted for HF.Cox regression analysis had revealed that nighttime systolic BP level[hazards ratio(HR)=1.018,95%CI:1.008–1.028,P=0.001],nighttime diastolic BP level(HR=1.024,95%CI:1.007–1.042,P=0.007),nocturnal hypertension(HR=1.688,95%CI:1.229–2.317,P=0.001)were associated with HF rehospitalization.Kaplan-Meier analysis had demonstrated that patients with nocturnal hypertension had significantly lower event-free survival rate(log-rank P<0.001).Furthermore,patients with a riser pattern had a higher risk of HF rehospitalization(HR=1.828,95%CI:1.055–3.166,P=0.031)and lower eventfree survival rate(log-rank P=0.003)than those with a dipper pattern.These findings were also confirmed in patients with HFpEF and hyperuricemia.CONCLUSIONS Nighttime BP levels,nocturnal hypertension and a riser pattern are independently associated with HF rehospitalization in patients with HFpEF,and prominently in patients with HFpEF and hyperuricemia.Well controlled nighttime BP levels should be emphasized and considered in patients with HFpEF.

Bioinspired super-hydrophilic zwitterionic polymer armor combats thrombosis and infection of vascular catheters

Thrombosis and infection are two major complications associated with central venous catheters(CVCs),which significantly contribute to morbidity and mortality.Antifouling coating strategies currently represent an efficient approach for addressing such complications.However,existing antifouling coatings have limitations in terms of both duration and effectiveness.Herein,we propose a durable zwitterionic polymer armor for catheters.This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization,followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine(pMPC)via in-situ radical polymerization.The resulting pMPC coating armor exhibits super-hydrophilicity,thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro.In practical applications,the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model,as well as inhibited thrombus formation in a rabbit jugular vein model.Overall,our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.

Acupuncture Ameliorates AIDS Symptoms in 36 Cases

Acquired immunodeficiency syndrome(AIDS)is caused by the human immunodeficiency virus(HIV).At present,there is no specific treatmentavailable.To explore a method of treatment,weapplied acupuncture in 36 HIV infected cases in amilitary hospital in Zambia,from May 1995 to May1996.The results are reported as follows.

Inorganic-organic Composite Membranes with Novel Microstructure for High Temperature Proton Exchange Membrane Fuel Cells

Nowadays,more and more fossil fuels are consumed and air pollution has become a threat to the survival of people.Therefore,we need some other power sources to provide energy without damaging the environment.Proton exchange membrane fuel cells(PEMFCs)have received wide attention due to their advantages such as high energy density and zero emission.Particularly,direct methanol fuel cells (DMFCs)were considered as the most suitable energy sources for electric vehicles(EVs)and portable electronics.

Dynamic time-varying evaluation on enterprise technological innovation

This paper describes a dynamic time-varying evaluation system based on set-valued statistics to eliminate the interference of subjective factors of multiple experts in evaluating enterprise technological innovation.This method is applied to evaluating three enterprises in the same industry but at a different phase regarding the status of technological innovation,using four evaluation indexes,namely talents,environment,capability and achievements of technological innovation.The obtained reasonable evaluation results deomstrate the viability of this method.

Emergency Logistics and Standardization

Emergency logistics are complex systems engineering operations.Standardizationis the solution to establishing a successful emergency logistics framework.Standardized systems of emergency logistics can be used to tackle sudden events anddisasters,to minimize disaster loss and to promote a healthy development of emergencylogistics in China.

Design and Implement an Novel File Access Prediction Model in Linux

So far, file access prediction models is mainly based on either the file access frequency or the historical record of the latest access. In this paper, a new file access prediction model called frequency- and recency-based successor (FRS) is presented which combines the advantages of the file frequency with the historical record. FRS model has the capability of rapid response to workload changes and can predict future events with greater accuracy than most of other prediction models. To evaluate the performance of FRS mode, the Linux kernel is modified to predict and prefetch upcoming accesses. The experiment shows that FRS can accurately predict approximately 80% of all file access events, while maintaining an immediate successor queue (ISQ) per-file which only requires regular dynamic updates.

Engineering anti-thrombogenic and anti-infective catheters through a stepwise metal-catechol-(amine)surface engineering strategy

Thrombosis and infection are pivotal clinical complications associated with interventional blood-contacting devices,leading to significant morbidity and mortality.To address these issues,we present a stepwise metal-catechol-(amine)(MCA)surface engineering strategy that efficiently integrates therapeutic nitric oxide(NO)gas and antibacterial peptide(ABP)onto catheters,ensuring balanced anti-thrombotic and anti-infective properties.First,copper ions were controllably incorporated with norepinephrine and hexanediamine through a one-step molecular/ion co-assembly process,creating a NO-generating and amine-rich MCA surface coating.Subsequently,azide-polyethylene glycol 4-N-hydroxysuccinimidyl and dibenzylcyclooctyne modified ABP were sequentially immobilized on the surface via amide coupling and bioorthogonal click chemistry,ensuring the dense grafting of ABP while maintaining the catalytic efficacy for NO.This efficient integration of ABP and NO-generating ability on the catheter surface provides potent antibacterial properties and ability to resist adhesion and activation of platelets,thus synergistically preventing infection and thrombosis.We anticipate that this synergistic modification strategy will offer an effective solution for advancing surface engineering and enhancing the clinical performance of biomedical devices.

ERRATUM TO:Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival

Erratum to:SCIENCE CHINA Life Sciences,Volume 66,Issue 2:211-225(2022),https://doi.org/10.1007/s11427-021-2126-2 This paper contains an error in Figure 4C,where the representative images of filipin staining of retinal sections from 6-month-old mice were misused.We provide the correct picture for Figure 4C as follows.The statistical result in Figure 4D was corrected as well.This new Figure 4 does not affect the conclusion of this article.

Detection of serum IgM and IgG for COVID-19 diagnosis

Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 remains ongoing and was linked to more than 80,000 infected patients and more than 3,000 deaths in China as of March 7,2020(Holshue et al.,2020).

Exploring the R-ISS stage-specific regular networks in the progression of multiple myeloma at single-cell resolution

The Revised International Staging System(R-ISS)is a simple and powerful prognostic tool for multiple myeloma(MM).However,heterogeneity in R-ISS stage is still poorly characterised,hampering improvement of treatments.We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS.Plasma cells were clustered into nine groups(P1–P9)based on gene expression,where P1–P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1was enriched in P1,and they were validated to be upregulated in the MM cell line and in 22 other patients’myeloma cells.Furthermore,in progression,PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation,while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway.Finally,a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3.A few ligand-receptor pairs(CCL3/CCL5/CCL3L1-CCR1)were obviously active in monocyte-plasma communications in stage III.Herein,this study identified novel molecules,networks and crosstalk pairs in different R-ISS stages of MM,providing significant insight for its prognosis and treatment.

General Solutions to Some Types of Solitons in the Atmosphere

In terms of the Bargmann potential technique the problem of solutions to atmospheric solitary waves is investigated with the derivation of the solutions and their dispersion relations of such solitary waves as of inertial, internal gravity and Rossby modes, and some further appreciation and significant outcome have been achieved.

Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival

Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells(RGCs) by using an artificial intelligence(AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing(scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/-retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/-mice using atorvastatin reduced the cholesterol level in the retina,thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/-retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.

Age-related macular degeneration: Epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy

Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macula and it is classified as early stage to late stage (advanced AMD). The advanced AMD is classified into the nonexudative or atrophic form (dry AMD) and the exudative or neovascular form (wet AMD). More severe vision loss is typically associated with the wet form. Multiple genetic factors, lipid metabolism, oxidative stress and aging, play a role in the etiology of AMD. Dysregulation in genetic to AMD is established to 46%–71% of disease contribution, with CFH and ARMS2/HTRA1 to be the two most notable risk loci among the 103 identified AMD associated loci so far. Chronic cigarette smoking is the most proven consistently risk living habits for AMD. Deep learning algorithm has been developed based on image recognition to distinguish wet AMD and normal macula with high accuracy. Currently, anti-vascular endothelial growth factor (VEGF) therapy is highly effective at treating wet AMD. Several new generation AMD drugs and iPSC-derived RPE cell therapy are in the clinical trial stage and are promising to improve AMD treatment in the near future.

Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population

Intraocular pressure(IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues for therapeutic intervention. We performed a genome-wide association study and replication analysis of 8,552 Chinese participants. In the genome-wide association study, we identified 51 loci that surpassed the significance of P<9×10^(-7), and we formally replicated these loci. A combined discovery and replication meta-analysis identified 21 genome-wide loci that surpassed the genome-wide significance of P<5×10^(-8), including 4 previously reported loci: rs145063132(7 p21.2, ETV1/DGKB), rs548030386(7 q31.2, ST7 near CAV1/CAV2), rs7047871(9 p24.2, GLIS3), and rs2472494(9 q31.1, ABCA1/SLC44 A1). Of the 17 newly identified loci, five were reported to have ocular related phenotypes: PTCH2(rs7525308 in 1 p34.1), LRIF1/DRAM2(rs1282146 in 1 p13.3), COLEC11(rs201143466 in 2 p25.3),SPTBN1(rs4514918 in 2 p16.2), and CRK(rs11078446 in 17 p13.3). The genetic loci identified in this study not only increase our understanding of the genes involved in intraocular pressure but also provide important genetic markers to improve future genetic screening and drug discovery for intraocular pressure disorders.

The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis

The endoplasmic reticulum(ER) membrane protein complex(EMC) regulates the synthesis and quality control of membrane proteins with multiple transmembrane domains. One of the membrane spanning subunits, EMC3, is a core member of the EMC complex that provides essential hydrophilic vestibule for substrate insertion. Here, we show that the EMC subunit Emc3 plays critical roles in the retinal vascular angiogenesis by regulating Norrin/Wnt signaling. Postnatal endothelial cell(EC)-specific deletion of Emc3 led to retarded retinal vascular development with a hyperpruned vascular network, the appearance of bluntended, aneurysm-like tip endothelial cells(ECs) with reduced numbers of filopodia and leakage of erythrocytes at the vascular front. Diminished tube formation and cell proliferation were also observed in EMC3 depleted human retinal endothelial cells(HRECs). We then discovered a critical role for EMC3 in expression of FZD4 receptor of β-catenin signaling using RNA sequencing, real-time quantitative PCR(RT-q PCR) and luciferase reporter assay. Moreover, augmentation of Wnt activity via lithium chloride(Li Cl) treatment remarkably enhanced β-catenin signaling and cell proliferation of HRECs. Additionally, Li Cl partially reversed the angiogenesis defects in Emc3-c KO mice. Our data reveal that Emc3 plays essential roles in angiogenesis through direct control of FZD4 expression and Norrin/β-catenin signaling.