Functional importance and divergence of plant apurinic/apyrimidinic endonucleases in somatic and meiotic DNA repair.

Apurinic/apyrimidinic (AP) sites are one of the most abundant DNA lesions and are mainly repaired by AP endonucleases (APEs). While most eukaryotic genomes encode two APEs, plants usually possess three APEs, namely APE1L, APE2, and ARP. To date, the biological relevance and functional divergence of plant APEs are unclear. Here, we show that the three plant APEs have ancient origins, with the APE1L clade being plant-specific. In Arabidopsis thaliana, simultaneously mutating APE1L and APE2, but not ARP alone or in combination with either APE1L or APE2, results in clear developmental defects linked to genotoxic stress. Genetic analyses indicated that the three plant APEs have different substrate preferences in vivo. ARP is mainly responsible for AP site repair, while APE1L and APE2 prefer to repair 3'-blocked single-stranded DNA breaks. We further determined that APEs play an important role in DNA repair and the maintenance of genomic integrity in meiotic cells. The ape1l ape2 double mutant exhibited a greatly enhanced frequency of sporulation 1 (SPO11-1)-dependent and SPO11-1-independent double-stranded DNA breaks. The DNA damage response (DDR) was activated in ape1l ape2 to trigger pollen abortion. Our findings suggest functional divergence of plant APEs and reveal important roles of plant APEs during vegetative and reproductive development.

The Arabidopsis ATR-SOG1 signaling module regulates pleiotropic developmental adjustments in response to 3'-blocked DNA repair intermediates.

Base excision repair and active DNA demethylation produce repair intermediates with DNA molecules blocked at the 3'-OH end by an aldehyde or phosphate group. However, both the physiological consequences of these accumulated single-strand DNAs break with 3'-blocked ends (DNA 3'-blocks) and the signaling pathways responding to unrepaired DNA 3'-blocks remain unclear in plants. Here, we investigated the effects of DNA 3'-blocks on plant development using the zinc finger DNA 3'-phosphoesterase (zdp) AP endonuclease2 (ape2) double mutant, in which 3'-blocking residues are poorly repaired. The accumulation of DNA 3'-blocked triggered diverse developmental defects that were dependent on the ATM and RAD3-related (ATR)-suppressor of gamma response 1 (SOG1) signaling module. SOG1 mutation rescued the developmental defects of zdp ape2 leaves by preventing cell endoreplication and promoting cell proliferation. However, SOG1 mutation caused intensive meristematic cell death in the radicle of zdp ape2 following germination, resulting in rapid termination of radicle growth. Notably, mutating FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE (FPG) in zdp ape2 sog1 partially recovered its radicle growth, demonstrating that DNA 3'-blocks generated by FPG caused the meristematic defects. Surprisingly, despite lacking a functional radicle, zdp ape2 sog1 mutants compensated the lack of root growth by generating anchor roots having low levels of DNA damage response. Our results reveal dual roles of SOG1 in regulating root establishment when seeds germinate with excess DNA 3'-blocks.

Intracellular infection by symbiotic bacteria requires the mitotic kinase AURORA1.

The subcellular events occurring in cells of legume plants as they form transcellular symbiotic-infection structures have been compared with those occurring in premitotic cells. Here, we demonstrate that Aurora kinase 1 (AUR1), a highly conserved mitotic regulator, is required for intracellular infection by rhizobia in Medicago truncatula. AUR1 interacts with microtubule-associated proteins of the TPXL and MAP65 families, which, respectively, activate and are phosphorylated by AUR1, and localizes with them within preinfection structures. MYB3R1, a rhizobia-induced mitotic transcription factor, directly regulates AUR1 through two closely spaced, mitosis-specific activator cis elements. Our data are consistent with a model in which the MYB3R1-AUR1 regulatory module serves to properly orient preinfection structures to direct the transcellular deposition of cell wall material for the growing infection thread, analogous to its role in cell plate formation. Our findings indicate that the eukaryotically conserved MYB3R1-TPXL-AUR1-MAP65 mitotic module was conscripted to support endosymbiotic infection in legumes.

Dietary restriction promote sperm remodeling in aged roosters based on transcriptome analysis.

BACKGROUND: The breeder rooster has played a pivotal role in poultry production by providing high-quality semen. Typically, fertility peaks between 30 and 40 weeks of age and then declines rapidly from 45 to 55 weeks of age. Research into improving fertility in aging roosters is essential to extend their productive life. While progress has been made, enhancing fertility in aging roosters remains a significant challenge. METHODS: To identify the genes related to promoting sperm remodeling in aged Houdan roosters, we combined changes in testis and semen quality with transcriptome sequencing (RNA-seq) to analyze the synchrony of semen quality and testis development. In this study, 350-day-old Houdan breeder roosters were selected for RNA-seq analysis in testis tissues from induced molting roosters (D group) and non-induced molting roosters (47DG group). All analyses of differentially expressed genes (DEGs) and functional enrichment were performed. Finally, we selected six DEGs to verify the accuracy of the sequencing by qPCR. RESULTS: Compared with the 47DG group, sperm motility (P < 0.05), sperm density (P < 0.01), and testis weight (P < 0.05) were significantly increased in roosters in the D group. Further RNA-seq analysis of the testis between the D group and 47DG group identified 61 DEGs, with 21 up-regulated and 40 down-regulated. Functional enrichment analysis showed that the DEGs were primarily enriched in the cytokine-cytokine receptor interaction, Wnt signaling pathway, MAPK signaling pathway, TGF-ß signaling pathway, and focal adhesion pathway. The qRT-PCR results showed that the expression trend of these genes was consistent with the sequencing results. WNT5A, FGFR3, AGTR2, TGFß2, ROMO1, and SLC26A7 may play a role in testis development and spermatogenesis. This study provides fundamental data to enhance the reproductive value of aging roosters.

Unraveling the rhizobial infection thread.

Most legumes can form an endosymbiotic association with soil bacteria called rhizobia, which colonize specialized root structures called nodules where they fix nitrogen. To colonize nodule cells, rhizobia must first traverse the epidermis and outer cortical cell layers of the root. In most legumes, this involves formation of the infection thread, an intracellular structure that becomes colonized by rhizobia, guiding their passage through the outer cell layers of the root and into the newly formed nodule cells. In this brief review, we recount the early research milestones relating to the rhizobial infection thread and highlight two relatively recent advances in the symbiotic infection mechanism, the eukaryotically conserved 'MYB-AUR1-MAP' mitotic module, which links cytokinesis mechanisms to intracellular infection, and the discovery of the 'infectosome' complex, which guides infection thread growth. We also discuss the potential intertwining of the two modules and the hypothesis that cytokinesis served as a foundation for intracellular infection of symbiotic microbes.

Au(I)/Sc(III)-co-catalyzed tandem spiroannulation/cycloisomerization of 3-(2-ethynylaryl)-N-tosylaziridines with indoles to access 5H-benzo[b]carbazoles.

An unusual spiroannulation/cycloisomerization cascade of 3-(2-ethynylaryl)-N-tosylaziridines with indoles enabled by cooperative gold/scandium catalysis is presented, which facilitates the synthesis of 5H-benzo[b]carbazoles in moderate to excellent yields. This protocol features a broad substrate scope and good functional-group compatibility. Additionally, the resulting 5H-benzo[b]carbazoles exhibit good fluorescence properties, demonstrating the synthetic practicality of this method. Moreover, control experiments were performed to illustrate the reaction mechanism.

miR-128-3p inhibits intramuscular adipocytes differentiation in chickens by downregulating FDPS.

BACKGROUND: Intramuscular fat (IMF) content is the major indicator for evaluating chicken meat quality due to its positive correlation with tenderness, juiciness, and flavor. An increasing number of studies are focusing on the functions of microRNAs (miRNAs) in intramuscular adipocyte differentiation. However, little is known about the association of miR-128-3p with intramuscular adipocyte differentiation. Our previous RNA-seq results indicated that miR-128-3p was differentially expressed at different periods in chicken intramuscular adipocytes, revealing a possible association with intramuscular adipogenesis. The purpose of this research was to investigate the biological functions and regulatory mechanism of miR-128-3p in chicken intramuscular adipogenesis. RESULTS: The results of a series of assays confirmed that miR-128-3p could promote the proliferation and inhibit the differentiation of intramuscular adipocytes. A total of 223 and 1,050 differentially expressed genes (DEGs) were identified in the mimic treatment group and inhibitor treatment group, respectively, compared with the control group. Functional enrichment analysis revealed that the DEGs were involved in lipid metabolism-related pathways, such as the MAPK and TGF-ß signaling pathways. Furthermore, target gene prediction analysis showed that miR-128-3p can target many of the DEGs, such as FDPS, GGT5, TMEM37, and ASL2. The luciferase assay results showed that miR-128-3p targeted the 3' UTR of FDPS. The results of subsequent functional assays demonstrated that miR-128-3p acted as an inhibitor of intramuscular adipocyte differentiation by targeting FDPS. CONCLUSION: miR-128-3p inhibits chicken intramuscular adipocyte differentiation by downregulating FDPS. Our findings provide a theoretical basis for the study of lipid metabolism and reveal a potential target for molecular breeding to improve meat quality.

Intestinal Cathelicidin Antimicrobial Peptide Shapes a Protective Neonatal Gut Microbiota Against Pancreatic Autoimmunity.

BACKGROUND & AIMS: Alteration of the gut microbiota is implicated in the development of autoimmune type 1 diabetes (T1D), as shown in humans and the nonobese diabetic (NOD) mouse model. However, how gut dysbiosis arises and promotes the autoimmune response remains an open question. We investigated whether early events affecting the intestinal homeostasis in newborn NOD mice may explain the development of the autoimmune response in the adult pancreas. METHODS: We profiled the transcriptome and the microbiota in the colon between newborn NOD mice and nonautoimmune strains. We identified a seminal defect in the intestinal homeostasis of newborn NOD mice and deciphered the mechanism linking this defect to the diabetogenic response in the adult. RESULTS: We determined that the cathelicidin-related antimicrobial peptide (CRAMP) expression was defective in the colon of newborn NOD mice, allowing inducing dysbiosis. Dysbiosis stimulated the colonic epithelial cells to produce type I interferons that pathologically imprinted the local neonatal immune system. This pathological immune imprinting later promoted the pancreatic autoimmune response in the adult and the development of diabetes. Increasing colonic CRAMP expression in newborn NOD mice by means of local CRAMP treatment or CRAMP-expressing probiotic restored colonic homeostasis and halted the diabetogenic response, preventing autoimmune diabetes. CONCLUSIONS: We identified whether a defective colonic expression in the CRAMP antimicrobial peptide induces dysbiosis, contributing to autoimmunity in the pancreas. Hence, the manipulation of intestinal antimicrobial peptides may be considered a relevant therapeutic approach to prevent autoimmune diabetes in at-risk children.

Identification of Toxicity Forcing Agents from Individual Aliphatic and Aromatic Disinfection Byproducts Formed in Drinking Water: Implications and Limitations.

Recently, a study found that aromatic DBP fractions dominate the overall toxicity of chlorinated drinking water. However, key toxicity drivers have not been reported via comprehensive evaluation based on the formation of aliphatic and aromatic DBPs in drinking water. In this study, the occurrence of 37 aliphatic and 19 aromatic DBPs in drinking samples with different water characteristics collected in a Chinese megacity was explored. According to the individual DBP concentrations and cytotoxicity potencies as well as the "TIC-Tox" method, haloacetonitriles and halonitrophenols were found to be the toxicity drivers among the measured aliphatic and aromatic DBPs, respectively. However, when aromatic and aliphatic DBPs are taken into consideration together, aliphatic DBPs were calculated to present higher toxicity contribution than aromatic DBPs, which is inconsistent with the previous study. TOX showed significant positive correlations with most aliphatic DBPs but no aromatic DBPs, and the overall toxicity of the water sample concentrates is significantly related to the total calculated cytotoxicity and aliphatic DBPs, suggesting that current selected aromatic DBPs are insufficient to represent the overall aromatic DBPs. UV254 and DOC rather than SUVA are better surrogates for predicting DBP formation potential for DOM with a lower humification degree as indicated by fluorescence results.

Depth estimation from a single-shot fringe pattern based on DD-Inceptionv2-UNet.

The quick and accurate retrieval of an object's depth from a single-shot fringe pattern in fringe projection profilometry has been a topic of ongoing research. In recent years, with the development of deep learning, a deep learning technique to FPP for single-shot 3D measurement is being used. To improve the accuracy of depth estimation from a single-shot fringe pattern, we propose the depthwise separable Dilation Inceptionv2-UNet (DD-Inceptionv2-UNet) by adjusting the depth and width of the network model simultaneously. And we evaluate the model on both simulated and experimental datasets. The experimental results show that the error between the depth map predicted by the proposed method and the label is smaller, and the depth curve map is closer to the ground truth. And on the simulated dataset, the MAE of the proposed method decreased by 35.22%, compared to UNet. On the experimental dataset, the MAE of the proposed method decreased by 34.62%, compared to UNet. The proposed method is relatively outstanding in both quantitative and qualitative evaluations, effectively improving the accuracy of 3D measurement results from a single-shot fringe pattern.

Alike but also different: a spatiotemporal analysis of the older populations in Zhejiang and Jilin provinces, China.

According to the 7th National Population Census, China is experiencing rapid growth of its ageing population, with large spatial disparities in the distribution of older folks in different regions. And yet, scant comparative research has been conducted on the two regions of Zhejiang and Jilin in particular, which differ considerably in economic development but witness nearly the same ageing trend. In response, this article compares Zhejiang, an advanced economic province, with Jilin, with its relatively low level of economic development, to explore the ageing issue and analyse the spatial correlation between older populations and socioeconomic factors. Using the spatiotemporal data analysis and geographical detector approaches, we obtain three significant findings: 1. both provinces have maintained steady rates of increase in ageing; 2. the older populations in Zhejiang and Jilin are mostly concentrated in the provincial capitals and nearby cities with reasonably established economies; and 3. the factors, including local fiscal expenditures, beds in hospitals and nursing homes, and coverage of social security, show a highly similar spatial pattern between older populations in Zhejiang and Jilin. The q-values of all the selected socioeconomic factors in Jilin showed a growth trend, indicating that the spatial correlation between these factors and ageing is strengthening year on year, that is, the resources gained from the socioeconomic development of Jilin have shifted steadily toward old-age services. As a consequence, a vicious circle of the slowing down of the economic growth drives away working forces and quickens the pace of population ageing, is present. From a policy perspective, Jilin province is strongly dependent on state-owned enterprises characterised by institutional rigidity, an inflexible market economy and an under-developed private sector, all of which are profoundly influenced by ageing. The consequence is large population outflows of young people. In contrast, the economy of Zhejiang province is partially decoupled from the ageing trend, so the gap in level of development between its counties has been narrowing. The policy implication here is that Zhejiang represents an active private economy that has coped successfully with ageing by attracting young migrants and developing new forms of development, such as the digital economy.

Sex-specific bone and muscular morphological features in ischiofemoral impingement: A three-dimensional study.

The study aimed to investigate how hip bone and muscular morphology features differ between ischiofemoral impingement (IFI) patients and healthy subjects among males and females. Three-dimensional models were reconstructed based on magnetic resonance imaging images from IFI patients and healthy subjects of different sexes. Bone morphological parameters and the cross-sectional area of the hip abductors were measured. The diameter and angle of the pelvis were compared between patients and healthy subjects. Bone parameters of the hip and cross-sectional area of the hip abductors were compared between affected and healthy hips. The comparison results of some parameters were significant for females but not males. For females, the comparison results of pelvis parameters showed that the anteroposterior diameter of the pelvic inlet (p = 0.001) and intertuberous distance (p < 0.001) were both larger in IFI patients than in healthy subjects. Additionally, the comparison results of hip parameters showed that the neck shaft angle (p < 0.001) and the cross-sectional area of the gluteus medius (p < 0.001) and gluteus minimus (p = 0.005) were smaller, while the cross-sectional area of the tensor fasciae latae (p < 0.001) was significantly larger in affected hips. Morphological changes in IFI patients demonstrated sexual dimorphism, including bone and muscular morphology. Differences in the anteroposterior diameter of the pelvic inlet, intertuberous distance, neck shaft angle, gluteus medius, and gluteus minimus may explain why females are more susceptible to IFI.

Deciphering the synergistic and redundant roles of CG and non-CG DNA methylation in plant development and transposable element silencing.

DNA methylation plays key roles in transposable element (TE) silencing and gene expression regulation. DNA methylation occurs at CG, CHG and CHH sequence contexts in plants. However, the synergistic and redundant roles of CG and non-CG methylation are poorly understood. By introducing CRISPR/Cas9-induced met1 mutation into the ddcc (drm1 drm2 cmt2 cmt3) mutant, we attempted to knock out all five DNA methyltransferases in Arabidopsis and then investigate the synergistic and redundant roles of CG and non-CG DNA methylation. We found that the homozygous ddcc met1 quintuple mutants are embryonically lethal, although met1 and ddcc mutants only display some developmental abnormalities. Unexpectedly, the ddcc met1 quintuple mutations only reduce transmission through the male gametophytes. The ddcc met1+/- mutants show apparent size divergence, which is not associated with difference in DNA methylation patterns, but associated with the difference in the levels of DNA damage. Finally, we show that a group of TEs are specifically activated in the ddcc met1+/- mutants. This work reveals that CG and non-CG DNA methylation synergistically and redundantly regulate plant reproductive development, vegetative development and TE silencing in Arabidopsis. Our findings provide insights into the roles of DNA methylation in plant development.

Anti-scattering light focusing with full-polarization digital optical phase conjugation based on digital micromirror devices.

The high resolution of optical imaging and optogenetic stimulation in the deep tissue requires focusing light against strong scattering with high contrast. Digital optical phase conjugation (DOPC) has emerged recently as a promising solution for this requirement, because of its short latency. A digital micromirror device (DMD) in the implementation of DOPC enables a large number of modulation modes and a high speed of modulation both of which are important when dealing with a highly dynamic scattering medium. Here, we propose full-polarization DOPC (fpDOPC) in which two DMDs simultaneously modulate the two orthogonally polarized components of the optical field, respectively, to mitigate the effect of depolarization caused by strong scattering. We designed a simple system to overcome the difficulty of alignment encountered when modulating two polarized components independently. Our simulation and experiment showed that fpDOPC could generate a high-contrast focal spot, even though the polarization of light had been highly randomized by scattering. In comparison with the conventional method of modulating the polarization along a particular direction, fpDOPC can improve the peak to background ratio of the focal spot by a factor of two. This new technique has good potential in applications such as high-contrast light focusing in vivo.

Classification prediction of pancreatic cystic neoplasms based on radiomics deep learning models.

BACKGROUND: Preoperative prediction of pancreatic cystic neoplasm (PCN) differentiation has significant value for the implementation of personalized diagnosis and treatment plans. This study aimed to build radiomics deep learning (DL) models using computed tomography (CT) data for the preoperative differential diagnosis of common cystic tumors of the pancreas. METHODS: Clinical and CT data of 193 patients with PCN were collected for this study. Among these patients, 99 were pathologically diagnosed with pancreatic serous cystadenoma (SCA), 55 were diagnosed with mucinous cystadenoma (MCA) and 39 were diagnosed with intraductal papillary mucinous neoplasm (IPMN). The regions of interest (ROIs) were obtained based on manual image segmentation of CT slices. The radiomics and radiomics-DL models were constructed using support vector machines (SVMs). Moreover, based on the fusion of clinical and radiological features, the best combined feature set was obtained according to the Akaike information criterion (AIC) analysis. Then the fused model was constructed using logistic regression. RESULTS: For the SCA differential diagnosis, the fused model performed the best and obtained an average area under the curve (AUC) of 0.916. It had a best feature set including position, polycystic features (≥6), cystic wall calcification, pancreatic duct dilatation and radiomics-DL score. For the MCA and IPMN differential diagnosis, the fused model with AUC of 0.973 had a best feature set including age, communication with the pancreatic duct and radiomics score. CONCLUSIONS: The radiomics, radiomics-DL and fused models based on CT images have a favorable differential diagnostic performance for SCA, MCA and IPMN. These findings may be beneficial for the exploration of individualized management strategies.

Nitrogen starvation induces genome-wide activation of transposable elements in Arabidopsis.

Nitrogen (N) availability is a major limiting factor for plant growth and agricultural productivity. Although the gene regulation network in response to N starvation has been extensively studied, it remains unknown whether N starvation has an impact on the activity of transposable elements (TEs). Here, we report that TEs can be transcriptionally activated in Arabidopsis under N starvation conditions. Through genetic screening of idm1-14 suppressors, we cloned GLU1, which encodes a glutamate synthase that catalyzes the synthesis of glutamate in the primary N assimilation pathway. We found that glutamate synthase 1 (GLU1) and its functional homologs GLU2 and glutamate transport 1 (GLT1) are redundantly required for TE silencing, suggesting that N metabolism can regulate TE activity. Transcriptome and methylome analyses revealed that N starvation results in genome-wide TE activation without inducing obvious alteration of DNA methylation. Genetic analysis indicated that N starvation-induced TE activation is also independent of other well-established epigenetic mechanisms, including histone methylation and heterochromatin decondensation. Our results provide new insights into the regulation of TE activity under stressful environments in planta.

APURINIC/APYRIMIDINIC ENDONUCLEASE2 and ZINC FINGER DNA 3'-PHOSPHOESTERASE Play Overlapping Roles in the Maintenance of Epigenome and Genome Stability.

Base excision repair (BER) is essential for active DNA demethylation and DNA damage repair in mammals and plants. Here, we provide genetic and biochemical evidence that APURINIC/APYRIMIDINIC ENDONUCLEASE2 (APE2) plays overlapping roles with ZINC FINGER DNA 3'-PHOSPHOESTERASE (ZDP) in active DNA demethylation and DNA damage repair in Arabidopsis thaliana Simultaneous mutation of APE2 and ZDP causes DNA hypermethylation at more than 2000 loci, most of which are not hypermethylated in ape2 or zdp single mutants. The zdp and ape2 single mutants exhibit normal development, but the zdp ape2 double mutants display pleiotropic developmental defects and are supersensitive to the DNA alkylating reagent methyl methanesulfonate. The gradual accumulation of DNA lesions in the zdp ape2 seedlings is accompanied by constitutive activation of the DNA damage response and alteration of the cell cycle. Interestingly, knockout of the key DNA demethylase REPRESSOR OF SILENCING1 reduces the magnitude of DNA lesion accumulation and the DNA damage response in the zdp ape2 mutants, suggesting that a proportion of the DNA damage in the zdp ape2 mutants arises from incomplete active DNA demethylation. Lastly, we find that APE2 has 3'-phosphatase activity and strong 3'-5' exonuclease activity in vitro. Together, our results suggest that APE2 and ZDP, two BER proteins, play overlapping roles in the maintenance of epigenome and genome stability in plants.

A novel danshensu derivative ameliorates experimental colitis by modulating NADPH oxidase 4-dependent NLRP3 inflammasome activation.

We have previously reported a novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from danshensu, exhibits cytoprotective activities in vitro. Here, we investigated the effects and underlying mechanisms of DSC on dextran sodium sulphate (DSS)-induced experimental colitis. We found that DSC treatment afforded significant protection against the development of colitis, evidencing by suppressed inflammatory responses and enhanced barrier integrity. Intriguingly, DSC specifically down-regulated DSS-induced colonic NADPH oxidase 4 (Nox4) expression, accompanied by a balanced redox status, suppressed nuclear factor-κB (NF-κB) and NLRP3 inflammasome activation and up-regulated nuclear factor (erythroid-derived 2)-like 2 and haeme oxygenase-1 expression. In vitro study also demonstrated DSC also markedly decreased Nox4 expression and activity associated with inhibiting reactive oxygen species generation, NF-κB activation and NLRP3 inflammasome activation in bone marrow-derived macrophages. Either lentiviral Nox4 shRNA-mediated Nox4 knockdown or Nox4-specific small-interfering RNA mimicked effects of DSC by suppressing NLPR3 inflammasome activation to alleviate experimental colitis or inflammatory macrophage response. Collectively, our results provide the first evidence that DSC ameliorates experimental colitis partly through modulating Nox4-mediated NLRP3 inflammasome activation.

[Dynamic changes of chest CT imaging in patients with COVID-19].

OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare,the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.

Ghrelin attenuates sepsis-induced acute lung injury by inhibiting the NF-κB, iNOS, and Akt signaling in alveolar macrophages.

Ghrelin has proven to be protective against sepsis-induced acute lung injury (ALI) via anti-inflammatory effects. However, its mechanisms remain poorly understood. Alveolar macrophages (AMs) play a key role in mediating inflammatory responses during sepsis-induced ALI by secretion of cytokines and chemokines. This study was undertaken to investigate whether ghrelin suppresses inflammatory effects of AMs and therefore may help to attenuate sepsis-induced ALI. A sepsis model in rats was achieved using cecal ligation and puncture. Ghrelin treatment markedly improved histopathological changes in the lungs and reduced pulmonary inflammation in septic rats. NF-κB translocation and p-Akt and inducible nitric oxide synthase (iNOS) activities in AMs from septic rats were suppressed by ghrelin. In vitro data indicated that ghrelin decreased the levels of LPS-induced IL-1ß, TNF-α, and IL-6, NF-κB translocation, and iNOS and Akt activities of AMs. Furthermore, the NF-κB/iNOS pathway or Akt signaling was positively correlated with LPS-induced inflammatory production of AMs in vitro. In conclusion, ghrelin exerts a protective role against sepsis-induced ALI probably by reducing the production of inflammatory cytokines from AMs via inhibition of the NF-κB/iNOS pathway or Akt signaling.