Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases:A retrospective,multicenter study

Background:Pulmonary embolism(PE)is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases(AIIRDs).Accurate prediction and timely intervention play a pivotal role in enhancing survival rates.However,there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods:In the training cohort,60 AIIRD with PE cases and 180 age-,gender-,and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022.Univariable logistic regression(LR)and least absolute shrinkage and selection operator(LASSO)were used to select the clinical features for further training with machine learning(ML)methods,including random forest(RF),support vector machines(SVM),neural network(NN),logistic regression(LR),gradient boosted decision tree(GBDT),classification and regression trees(CART),and C5.0 models.The performances of these models were subsequently validated using a multicenter validation cohort.Results:In the training cohort,24 and 13 clinical features were selected by univariable LR and LASSO strategies,respectively.The five ML models(RF,SVM,NN,LR,and GBDT)showed promising performances,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort.CART and C5.0 models achieved AUCs of 0.850 and 0.932,respectively,in the training cohort.Using D-dimer as a pre-screening index,the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort.These results markedly outperformed the use of D-dimer levels alone.Conclusion:ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration:Chictr.org.cn:ChiCTR2200059599.

The role of viral protein Ac34 in nuclear relocation of subunits of the actin-related protein 2/3 complex

The actin nucleator actin-related protein complex(Arp2/3) is composed of seven subunits: Arp2,Arp3, p40/ARPC1(P40), p34/ARPC2(P34), p21/ARPC3(P21), p20/ARPC4(P20), and p16/ARPC5(P16). Arp2/3 plays crucial roles in a variety of cellular activities through regulation of actin polymerization. Autographa californica multiple nucleopolyhedrovirus(Ac MNPV), one of the beststudied alphabaculoviruses, induces Arp2/3 nuclear relocation and mediates nuclear actin polymerization to assist in virus replication. We have demonstrated that Ac34, a viral late-gene product, induces translocation of the P40 subunit of Arp2/3 to the nucleus during Ac MNPV infection. However, it remains unknown whether Ac34 could relocate other Arp2/3 subunits to the nucleus. In this study, the effects of the viral protein Ac34 on the distribution of these subunits were studied by an immunofluorescence assay. Arp2, P34, P21, and P20 cloned from Spodoptera frugiperda(Sf9) cells showed mainly cytoplasmic localization and were relocated to the nucleus in the presence of Ac34. In addition, Arp3 was localized in the cytoplasm in both the presence and absence of Ac34, and P16 showed whole-cell localization. In contrast to Sf9 cells, all subunits of mammalian Arp2/3 showed no nuclear relocation in the presence of Ac34. Co-immunoprecipitation analysis of the interaction between Ac34 and Arp2/3 subunits revealed that Ac34 bound to P40,P34, and P20 of Sf9 cells. However, none of the subunits of mammalian Arp2/3 interacted with Ac34, indicating that protein-protein interaction is essential for Ac34 to relocate Arp2/3 subunits to the nucleus.

Dietary Zn proteinate with moderate chelation strength alleviates heat stress‑induced intestinal barrier function damage by promoting expression of tight junction proteins via the A20/NF‑κB p65/MMP‑2 pathway in the jejunum of broilers

Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

Lysine deficiency impaired growth performance and immune response and aggravated inflammatory response of the skin,spleen and head kidney in grown-up grass carp (Ctenopharyngodon idella)

This dissertation was primarily focused on the immune response,inflammatory response and molecular mechanisms in the skin,head kidney and spleen of grown-up grass carp(Ctenopharyngodon idella).Six iso-nitrogen diets differing in lysine concentrations(5.6,8.5,11.6,14.4,17.5 and 20.7 g/kg)were fed to 540 grass carp(164.85±0.79 g)for 60 d.After that,grass carp were challenged by Aeromonas hydrophila for 6 d.This study revealed that lysine deficiency(1)suppressed the growth performa,nce of the fish and decreased their ability to resist skin lesion morbidity,(2)impaired the immune organ s immune response by decreasing the gene expressions of mucin,liver-expressed antimicrobial peptide(LEAP)-2B,β-defensin-1 and LEAP-2A and the production of antibacterial compounds of grown-up grass carp,and(3)aggravated the inflammatory response of immune organs in the fish by increasing the gene expressions of pro-inflammatory cytokines(interferon y2[IFN-γ2],tumor necrosis factorα[TNF-α],interleukin[IL]-15,IL-17D,IL-12p40,IL-6 and IL-8)and down-regulating anti-inflammatory cytokines(IL-11,transforming growth factorβ1[TGF-β1],IL-10 and IL-4/13A),which were tightly correlated with signal transducer and activator of transcription(STAT)1 and STAT3 signaling pathway,respectively.The different phenomenon in the skin,spleen and head kidney of fish may be correlated with the difference in gene subtype.In addition,using quadratic regression analysis of percent weight gain(PWG),skin lesion morbidity,and the lysozyme activities in the spleen and head kidney,the dietary lysine requirements for grown-up grass carp were estimated to be 13.58,13.51,14.56 and 14.18 g/kg,respectively.

Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion

Hepatitis B virus(HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration(FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC_(50) of4.321 lmol/L and 2.910 lmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells,with an EC_(50) of 2.349 lmol/L. These findings provide new ideas for screening and research related to HBV agents.

METAGENOMICS COMBINED WITH HIGHTHROUGHPUT SEQUENCING REVEALS THE METHANOGENIC POTENTIAL OF FRESH CORN STRAW UNDER THERMOPHILIC AND HIGH OLR

Dry corn straw(DCS)is usually used in anaerobic digestion(AD),but fresh corn straw(FCS)has been given less consideration.In this study,the thermophilic AD of single-substrate(FCS and DCS)and co-digestion(straw with cattle manure)were investigated.The results show that when FCS was used as the single-substrate for AD,the methane production was 144 mL·g^(−1)·VS^(−1),which was 7.5%and 19.6%higher than that of single DCS and FCS with cattle manure,respectively.In addition,the structure of FCS was loose and coarse,which was easier to be degraded than DCS.At the hydrolysis and acidification stages,Clostridium_sensu_stricto_1,Clostridium_sensu_stricto_7 and Sporosarcina promoted the decomposition of organic matter,leading to volatile fatty acids(VFAs)accumulation.Methanosarcina(54.4%)activated multifunctional methanogenic pathways to avoid the VFAs inhibition,which was important at the CH_(4) production stage.The main pathway was hydrogenotrophic methanogenesis,with genes encoding formylmethanofuran dehydrogenase(K00200-K00203)and tetrahydromethanopterin Smethyltransferase(K00577-K00584).Methanosarcina also activated acetotrophic and methylotrophic methanogenesis pathways,with genes encoding acetyl phosphate(K13788)and methyl-coenzyme M reductase(K04480,K14080 and K14081),respectively.In the co-digestion,the methanogenic potential of FCS was also confirmed.This provides a scientific basis for regulating AD of crop straw.

Are public‒private partnerships still an answer for social infrastructure?A systematic literature review

Social infrastructure has become an important element for measuring national economic development and social benefits that are usually financed in the form of government grants,private investment,and public‒private partnerships(PPPs).However,social infrastructure PPPs have attracted considerable public debate due to their low profitability and complex operational demands.This study aims to answer the question,“are PPPs still an answer for social infrastructure?”,from the perspectives of the body of knowledge,application status,and prospects.Initially,an iterative search and review procedure and a scientometric analysis were performed to systematically screen the literature and to structure the body of knowledge of the social infrastructure PPPs literature.Furthermore,the application status and trends were analyzed to further explore the studied countries/regions,application sectors,and research topics.Results show that PPPs still have valuable application potential for delivering social infrastructure despite their mixed results across different topics.Six main research themes and the corresponding research trends were also identified,namely,financing and economics viability,risk management,performance management,contract and relationship management,governance and regulation,and facilitating and hindering factors.These findings offer practitioners and researchers a comprehensive overview and constructive guidance on social infrastructure PPPs.