Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.

The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends generated during V(D)J recombination must be opened by the Artemis nuclease, together with autophosphorylated DNA-PK. Structures of DNA-PK bound to DNA before and after phosphorylation, and in complex with Artemis and a DNA hairpin, reveal an essential functional switch. When bound to open DNA ends in its protection mode, DNA-PK is inhibited for cis-autophosphorylation of the so-called ABCDE cluster but activated for phosphorylation of other targets. In contrast, DNA hairpin ends promote cis-autophosphorylation. Phosphorylation of four Thr residues in ABCDE leads to gross structural rearrangement of DNA-PK, widening the DNA binding groove for Artemis recruitment and hairpin cleavage. Meanwhile, Artemis locks DNA-PK into the kinase-inactive state. Kinase activity and autophosphorylation of DNA-PK are regulated by different DNA ends, feeding forward to coordinate NHEJ events.

Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.

Nucleotide excision repair removes DNA lesions caused by ultraviolet light, cisplatin-like compounds and bulky adducts1. After initial recognition by XPC in global genome repair or a stalled RNA polymerase in transcription-coupled repair, damaged DNA is transferred to the seven-subunit TFIIH core complex (Core7) for verification and dual incisions by the XPF and XPG nucleases2. Structures capturing lesion recognition by the yeast XPC homologue Rad4 and TFIIH in transcription initiation or DNA repair have been separately reported3-7. How two different lesion recognition pathways converge and how the XPB and XPD helicases of Core7 move the DNA lesion for verification are unclear. Here we report on structures revealing DNA lesion recognition by human XPC and DNA lesion hand-off from XPC to Core7 and XPA. XPA, which binds between XPB and XPD, kinks the DNA duplex and shifts XPC and the DNA lesion by nearly a helical turn relative to Core7. The DNA lesion is thus positioned outside of Core7, as would occur with RNA polymerase. XPB and XPD, which track the lesion-containing strand but translocate DNA in opposite directions, push and pull the lesion-containing strand into XPD for verification.

The large bat Helitron DNA transposase forms a compact monomeric assembly that buries and protects its covalently bound 5'-transposon end.

Helitrons are widespread eukaryotic DNA transposons that have significantly contributed to genome variability and evolution, in part because of their distinctive, replicative rolling-circle mechanism, which often mobilizes adjacent genes. Although most eukaryotic transposases form oligomers and use RNase H-like domains to break and rejoin double-stranded DNA (dsDNA), Helitron transposases contain a single-stranded DNA (ssDNA)-specific HUH endonuclease domain. Here, we report the cryo-electron microscopy structure of a Helitron transposase bound to the 5'-transposon end, providing insight into its multidomain architecture and function. The monomeric transposase forms a tightly packed assembly that buries the covalently attached cleaved end, protecting it until the second end becomes available. The structure reveals unexpected architectural similarity to TraI, a bacterial relaxase that also catalyzes ssDNA movement. The HUH active site suggests how two juxtaposed tyrosines, a feature of many replication initiators that use HUH nucleases, couple the conformational shift of an α-helix to control strand cleavage and ligation reactions.

Structure of an activated DNA-PK and its implications for NHEJ.

DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-PK, all existing structures represent inactive states with resolution limited to 4.3 Å at best. Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms at resolutions of 3.7 Å overall and 3.2 Å for FATKINs. These structures reveal the sequential transition of DNA-PK from inactive to activated forms. Most notably, activation of the kinase involves previously unknown stretching and twisting within individual solenoid segments and loosens DNA-end binding. This unprecedented structural plasticity of helical repeats may be a general regulatory mechanism of HEAT-repeat proteins.

Author Correction: Cryo-EM of the dynamin polymer assembled on lipid membrane.

In Figs. 2b and 3d of this Letter, the labels 'Dynamin 1' and 'Overlay' were inadvertently swapped. This has been corrected online.

Cryo-EM of the dynamin polymer assembled on lipid membrane.

Membrane fission is a fundamental process in the regulation and remodelling of cell membranes. Dynamin, a large GTPase, mediates membrane fission by assembling around, constricting and cleaving the necks of budding vesicles1. Here we report a 3.75 Å resolution cryo-electron microscopy structure of the membrane-associated helical polymer of human dynamin-1 in the GMPPCP-bound state. The structure defines the helical symmetry of the dynamin polymer and the positions of its oligomeric interfaces, which were validated by cell-based endocytosis assays. Compared to the lipid-free tetramer form2, membrane-associated dynamin binds to the lipid bilayer with its pleckstrin homology domain (PHD) and self-assembles across the helical rungs via its guanine nucleotide-binding (GTPase) domain3. Notably, interaction with the membrane and helical assembly are accommodated by a severely bent bundle signalling element (BSE), which connects the GTPase domain to the rest of the protein. The BSE conformation is asymmetric across the inter-rung GTPase interface, and is unique compared to all known nucleotide-bound states of dynamin. The structure suggests that the BSE bends as a result of forces generated from the GTPase dimer interaction that are transferred across the stalk to the PHD and lipid membrane. Mutations that disrupted the BSE kink impaired endocytosis. We also report a 10.1 Å resolution cryo-electron microscopy map of a super-constricted dynamin polymer showing localized conformational changes at the BSE and GTPase domains, induced by GTP hydrolysis, that drive membrane constriction. Together, our results provide a structural basis for the mechanism of action of dynamin on the lipid membrane.

No-Touch Versus Conventional Vein Harvesting Techniques at 12 Months After Coronary Artery Bypass Grafting Surgery: Multicenter Randomized, Controlled Trial.

BACKGROUND: Vein graft occlusion is deemed a major challenge in coronary artery bypass grafting. Previous studies implied that the no-touch technique for vein graft harvesting could reduce occlusion rate compared with the conventional approach; however, evidence on the clinical benefit and generalizability of the no-touch technique is scare. METHODS: From April 2017 to June 2019, we randomly assigned 2655 patients undergoing coronary artery bypass grafting at 7 hospitals in a 1:1 ratio to receive no-touch technique or conventional approach for vein harvesting. The primary outcome was vein graft occlusion on computed tomography angiography at 3 months and the secondary outcomes included 12-month vein graft occlusion, recurrence of angina, and major adverse cardiac and cerebrovascular events. The generalized estimate equation model was used to account for the cluster effect of grafts from the same patient. RESULTS: During the follow-up, 2533 (96.0%) participants received computed tomography angiography at 3 months after coronary artery bypass grafting and 2434 (92.2%) received it at 12 months. The no-touch group had significantly lower rates of vein graft occlusion than the conventional group both at 3 months (2.8% versus 4.8%; odds ratio, 0.57 [95% CI, 0.41-0.80]; P<0.001) and 12 months (3.7% versus 6.5%; odds ratio, 0.56 [95% CI, 0.41-0.76]; P<0.001). Recurrence of angina was also less common in the no-touch group at 12 months (2.3% versus 4.1%; odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01). Rates of major adverse cardiac and cerebrovascular events were of no significant difference between the 2 groups. The no-touch technique was associated with higher rates of leg wound surgical interventions at 3-month follow-up (10.3% versus 4.3%; odds ratio, 2.55 [95% CI, 1.85-3.52]; P<0.001). CONCLUSIONS: Compared with the conventional vein harvesting approach in coronary artery bypass grafting, the no-touch technique significantly reduced the risk of vein graft occlusion and improved patient prognosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03126409.

Increasing contributions of airborne route in SARS-CoV-2 omicron variant transmission compared with the ancestral strain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant lineage worldwide. Experimental studies have shown that SARS-CoV-2 Omicron variant is more stable on various environmental surfaces than the ancestral strains of SARS-CoV-2. However, the influences on the role of the contact route in SARS-CoV-2 transmission are still unknown. In this study, we built a Markov chain model to simulate the transmission of the Omicron and ancestral strains of SARS-CoV-2 within a household over a 1-day period from multiple pathways; that is, airborne, droplet, and contact routes. We assumed that there were two adults and one child in the household, and that one of the adults was infected with SARS-CoV-2. We assumed two scenarios. (1) Asymptomatic/presymptomatic infection, and (2) symptomatic infection. During asymptomatic/presymptomatic infection, the contact route contributing the most (37%-45%), followed by the airborne (34%-38%) and droplet routes (21%-28%). During symptomatic infection, the droplet route was the dominant pathway (48%-71%), followed by the contact route (25%-42%), with the airborne route playing a negligible role (<10%). Compared to the ancestral strain, although the contribution of the contact route increased in Omicron variant transmission, the increase was slight, from 25%-41% to 30%-45%. With the growing concern about the increase in the proportion of asymptomatic/presymptomatic infection in Omicron strain transmissions, the airborne route, rather than the fomite route, should be of focus. Our findings suggest the importance of ventilation in the SARS-CoV-2 Omicron variant prevention in building environment.

Chaperonin GroEL accelerates protofibril formation and decorates fibrils of the Het-s prion protein.

We have studied the interaction of the prototypical chaperonin GroEL with the prion domain of the Het-s protein using solution and solid-state NMR, electron and atomic force microscopies, and EPR. While GroEL accelerates Het-s protofibril formation by several orders of magnitude, the rate of appearance of fibrils is reduced. GroEL remains bound to Het-s throughout the aggregation process and densely decorates the fibrils at a regular spacing of ∼200 Å. GroEL binds to the Het-s fibrils via its apical domain located at the top of the large open ring. Thus, apo GroEL and bullet-shaped GroEL/GroES complexes in which only a single ring is capped by GroES interact with the Het-s fibrils; no evidence is seen for any interaction with football-shaped GroEL/GroES complexes in which both rings are capped by GroES. EPR spectroscopy shows that rotational motion of a nitroxide spin label, placed at the N-terminal end of the first ß-strand of Het-s fibrils, is significantly reduced in both Het-s/GroEL aggregates and Het-s fibrils, but virtually completely eliminated in Het-s/GroEL fibrils, suggesting that in the latter, GroEL may come into close proximity to the nitroxide label. Solid-state NMR measurements indicate that GroEL binds to the mobile regions of the Het-s fibril comprising the N-terminal tail and a loop connecting ß-strands 4 and 5, consistent with interactions involving GroEL binding consensus sequences located therein.

Bioinformatics analysis on differentially expressed genes of alveolar macrophage in IPF.

Objective: This study aimed to explore the differentially expressed genes (DEGs) of pulmonary macrophages in human idiopathic pulmonary fibrosis (IPF) by bioinformatics, and elaborate on IPF on the gene level. Methods: The gene expression profile GSE49072 was downloaded from the gene expression omnibus (GEO) database. Genes of alveolar macrophages between normal volunteers and patients diagnosed as IPF were analyzed by GEO2R tools. Gene ontology (GO) and pathway enrichment analyses of genes were performed in the database for annotation, visualization and integrated discovery (DAVID) database, followed by functional annotation and protein-protein interaction (PPI) network construction in String website. Finally, the results were analyzed in a comprehensive way. Results: A total of 551 DEGs, including 205 down-regulated and 346 up-regulated were identified. The expression of 209875_s_at (secreted phosphoprotein 1, SPP1) and 214146_s_at (pro-platelet basic protein, PPBP) genes are the most significant in upregulated genes. DEGs in the MAPK（mitogen-activated protein kinase） signaling pathway and chemokine signaling pathway play important roles in the development of IPF. Conclusions: The up-regulation of genes such as SPP1 and PPBP affect the secretion of alveolar macrophages, thereby speeding up the process of fibrosis.

A study of blockchain-based liquidity cross-chain model.

Blockchain cross-chaining is about interconnectivity and interoperability between chains and involves both physical to virtual digital aspects and cross-chaining between digital networks. During the process, the liquidity transfer of information or assets can increase the use of items with other chains, so it is worth noting that the enhancement of cross-chain liquidity is of great practical importance to cross-chain technology. In this model, Layerzero is used as the primary secure cross-chain facility to build a full-chain identity by unifying NFT-distributed autonomous cross-chain identity IDs; applying super-contract pairs to enhance cross-chain liquidity; and initiating a dynamic transaction node creditworthiness model to increase the security of the cross-chain model and its risk management. Finally, by verifying three important property metrics timeliness is improved by at least 18%, robustness is increased by at least 50.9%, and radius of convergence is reduced by at least 25%. It is verified that the liquidity cross-chain model can eliminate the authentication transition between hierarchies while saving the cross-chain time cost, as a way to truly realize the liquid interoperability between multiple chains of blockchain.

HIV-1 Integrase Assembles Multiple Species of Stable Synaptic Complex Intasomes That Are Active for Concerted DNA Integration In vitro.

Retroviral DNA integration is mediated by nucleoprotein complexes (intasomes) in which a pair of viral DNA ends are bridged by a multimer of integrase (IN). Most of the high-resolution structures of HIV-1 intasomes are based on an HIV-1 IN with an Sso7d protein domain fused to the N-terminus. Sso7d-IN aggregates much less than wild-type IN and has been critical for structural studies of HIV-1 intasomes. Unexpectedly, these structures revealed that the common core architecture that mediates catalysis could be assembled in various ways, giving rise to both tetrameric and dodecameric intasomes, together with other less well-characterized species. This differs from related retroviruses that assemble unique multimeric intasomes, although the number of protomers in the intasome varies between viruses. The question of whether the additional Sso7d domain contributes to the heterogeneity of HIV-1 intasomes is therefore raised. We have addressed this by biochemical and structural studies of intasomes assembled with wild-type HIV-1 IN. Negative stain and cryo-EM reveal a similar range of multimeric intasome species as with Sso7d-IN with the same common core architecture. Stacks of intasomes resulting from domain swapping are also seen with both wild-type and Sso7d-IN intasomes. The propensity to assemble multimeric intasome species is, therefore, an intrinsic property of HIV-1 IN and is not conferred by the presence of the Sso7d domain. The recently solved intasome structures of different retroviral species, which have been reported to be tetrameric, octameric, dodecameric, and hexadecameric, highlight how a common intasome core architecture can be assembled in different ways for catalysis.

Cryo-EM structures of membrane-bound dynamin in a post-hydrolysis state primed for membrane fission.

Dynamin assembles as a helical polymer at the neck of budding endocytic vesicles, constricting the underlying membrane as it progresses through the GTPase cycle to sever vesicles from the plasma membrane. Although atomic models of the dynamin helical polymer bound to guanosine triphosphate (GTP) analogs define earlier stages of membrane constriction, there are no atomic models of the assembled state post-GTP hydrolysis. Here, we used cryo-EM methods to determine atomic structures of the dynamin helical polymer assembled on lipid tubules, akin to necks of budding endocytic vesicles, in a guanosine diphosphate (GDP)-bound, super-constricted state. In this state, dynamin is assembled as a 2-start helix with an inner lumen of 3.4 nm, primed for spontaneous fission. Additionally, by cryo-electron tomography, we trapped dynamin helical assemblies within HeLa cells using the GTPase-defective dynamin K44A mutant and observed diverse dynamin helices, demonstrating that dynamin can accommodate a range of assembled complexes in cells that likely precede membrane fission.

Ox-LDL promotes migration and adhesion of bone marrow-derived mesenchymal stem cells via regulation of MCP-1 expression.

Bone marrow-derived mesenchymal stem cells (bmMSCs) are the most important cell source for stem cell transplant therapy. The migration capacity of MSCs is one of the determinants of the efficiency of MSC-based transplant therapy. Our recent study has shown that low concentrations of oxidized low-density lipoprotein (ox-LDL) can stimulate proliferation of bmMSCs. In this study, we investigated the effects of ox-LDL on bmMSC migration and adhesion, as well as the related mechanisms. Our results show that transmigration rates of bmMSCs and cell-cell adhesion between bmMSCs and monocytes are significantly increased by treatments with ox-LDL in a dose- and time-dependent manner. Expressions of ICAM-1, PECAM-1, and VCAM-1 as well as the levels of intracellular Ca(2+) are also markedly increased by ox-LDL in a dose-dependent manner. Cytoskeleton analysis shows that ox-LDL treatment benefits to spreading of bmMSCs and organization of F-actin fibers after being plated for 6 hours. More interestingly, treatments with ox-LDL also markedly increase expressions of LOX-1, MCP-1, and TGF- ß ; however, LOX-1 antibody and MCP-1 shRNA markedly inhibit ox-LDL-induced migration and adhesion of bmMSCs, which suggests that ox-LDL-induced bmMSC migration and adhesion are dependent on LOX-1 activation and MCP-1 expression.

Tandem MutSß binding to long extruded DNA trinucleotide repeats underpins pathogenic expansions.

Expansion of trinucleotide repeats causes Huntington's disease, Fragile X syndrome and over twenty other monogenic disorders1. How mismatch repair protein MutSß and large repeats of CNG (N=A, T, C or G) cooperate to drive the expansion is poorly understood. Contrary to expectations, we find that MutSß prefers to bind the stem of an extruded (CNG) hairpin rather than the hairpin end or hairpin-duplex junction. Structural analyses reveal that in the presence of MutSß, CNG repeats with N:N mismatches adopt a B form-like pseudo-duplex, with one or two CNG repeats slipped out forming uneven bubbles that partly mimic insertion-deletion loops of mismatched DNA2. When the extruded hairpin exceeds 40-45 repeats, it can be bound by three or more MutSß molecules, which are resistant to ATP-dependent dissociation. We envision that such MutSß-CNG complexes recruit MutLγ endonuclease to nick DNA and initiate the repeat expansion process3,4. To develop drugs against the expansion diseases, we have identified lead compounds that prevent MutSß binding to CNG repeats but not to mismatched DNA.

Detailed characterization of particle emissions due to thermal failure of batteries with different cathodes.

Sufficient levels of thermal, electrical, mechanical, or electrochemical abuse can cause thermal runaway in lithium-ion batteries, leading to the release of electrolyte vapor, combustible gas mixtures, and high-temperature particles. Particle emissions due to thermal failure of batteries may cause serious pollution of the atmosphere, water sources, and soil as well as enter the human biological chain through crops, posing a potential threat to human health. Furthermore, high-temperature particle emissions may ignite the flammable gas mixtures produced during the thermal runaway process, resulting in combustion and explosions. This research focused on determining the particle size distribution, elemental composition, morphology, and crystal structure of particles released from different cathode batteries after thermal runaway. Accelerated adiabatic calorimetry tests were performed on a fully charged Li(Ni0.3Co0.3Mn0.3)O2 battery (NCM111), Li(Ni0.5Co0.2Mn0.3)O2 battery (NCM523), and Li(Ni0.6Co0.2Mn0.2)O2 battery (NCM622). Results of all three batteries indicate that particles with a diameter less than or equal to 0.85 mm exhibit an increase in volume distribution followed by a decrease in volume distribution as the diameter increases. F, S, P, Cr, Ge, and Ge were detected in particle emissions with mass percentages ranging from 6.5% to 43.3%, 0.76-1.20%, 2.41-4.83%,1.8-3.7%, and 0-0.14%, respectively. When present in high concentrations, these may have negative impacts on human health and the environment. In addition, the diffraction patterns of the particle emissions were approximately the same for NC111, NCM523, and NCM622, with emissions primarily composed of Ni/Co elemental, graphite, Li2CO3, NiO, LiF, MnO, and LiNiO2. This study can provide important insights into the potential environmental and health risks associated with particle emissions from thermal runaway in lithium-ion batteries.

Predicting the Glycemic Index of Biscuits Using Static In Vitro Digestion Protocols.

In vitro digestion methods that can accurately predict the estimated GI (eGI) values of complex carbohydrate foods, including biscuits, are worth exploring. In the current study, standard commercial biscuits with varied clinical GI values between 9~30 were digested using both the INFOGEST and single-enzyme digestion protocols. The digestion kinetic parameters were acquired through mathematical fitting by mathematical kinetics models. The results showed that compared with the INFOGEST protocol, the AUR180 deduced from digesting using either porcine pancreatin or α-amylase showed the best potential in predicting the eGI values. Accordingly, mathematical equations were established based on the relations between the AUR180 and the GI values. When digesting using porcine pancreatin, GI= 1.834 + 0.009 ×AUCR180 (R2= 0.952), and when digesting using only α-amylase, GI= 6.101 + 0.009 ×AUCR180 (R2=0.902). The AUR180 represents the area under the curve of the reducing-sugar content normalized to the total carbohydrates versus the digestion time in 180 min. The in vitro method presented enabled the rapid and accurate prediction of the eGI values of biscuits, and the validity of the formula was verified by another batch of biscuits with a known GI, and the error rate of most samples was less than 30%.

Prediction of Male Coronary Artery Bypass Grafting Outcomes Using Body Surface Area Weighted Left Ventricular End-diastolic Diameter: Multicenter Retrospective Cohort Study.

BACKGROUND: The presence of a high left ventricular end-diastolic diameter (LVEDD) has been linked to a less favorable outcome in patients undergoing coronary artery bypass grafting (CABG) procedures. However, by taking into consideration the reference of left ventricular size and volume measurements relative to the patient's body surface area (BSA), it has been suggested that the accuracy of the predicting outcomes may be improved. OBJECTIVE: We propose that BSA weighted LVEDD (bLVEDD) is a more accurate predictor of outcomes in patients undergoing CABG compared to simply using LVEDD alone. METHODS: This study was a comprehensive retrospective cohort study that was conducted across multiple medical centers. The inclusion criteria for this study were patients who were admitted for treatment between October 2016 and May 2021. Only elective surgery patients were included in the study, while those undergoing emergency surgery were not considered. All participants in the study received standard care, and their clinical data were collected through the institutional registry in accordance with the guidelines set forth by the Society of Thoracic Surgeons National Adult Cardiac Database. bLVEDD was defined as LVEDD divided by BSA. The primary outcome was in-hospital all-cause mortality (30 days), and the secondary outcomes were postoperative severe adverse events, including use of extracorporeal membrane oxygenation, multiorgan failure, use of intra-aortic balloon pump, postoperative stroke, and postoperative myocardial infarction. RESULTS: In total, 9474 patients from 5 centers under the Chinese Cardiac Surgery Registry were eligible for analysis. We found that a high LVEDD was a negative factor for male patients' mortality (odds ratio 1.44, P<.001) and secondary outcomes. For female patients, LVEDD was associated with secondary outcomes but did not reach statistical differences for morality. bLVEDD showed a strong association with postsurgery mortality (odds ratio 2.70, P<.001), and secondary outcomes changed in parallel with bLVEDD in male patients. However, bLVEDD did not reach statistical differences when fitting either mortality or severer outcomes in female patients. In male patients, the categorical bLVEDD showed high power to predict mortality (area under the curve [AUC] 0.71, P<.001) while BSA (AUC 0.62) and LVEDD (AUC 0.64) both contributed to the risk of mortality but were not as significant as bLVEDD (P<.001). CONCLUSIONS: bLVEDD is an important predictor for male mortality in CABG, removing the bias of BSA and showing a strong capability to accurately predict mortality outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400125; https://clinicaltrials.gov/ct2/show/NCT02400125.

Comprehensive bioinformation analysis of differentially expressed genes in recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) occurs frequently, and its causes are complex. The aetiology of nearly 50% of RPL cases is still unknown. This study aimed to ascertain differentially expressed genes (DEGs) and pathways by comprehensive bioinformatics analysis. We downloaded the gene expression microarray of GSE165004 from the Gene Expression Omnibus (GEO). Gene ontology (GO) analysis and Kyoto Encyclopaedia of Gene and Genome (KEGG) pathway enrichment analyses were performed on selected genes by using the R Programming Language. A protein-protein interaction (PPI) network was constructed with the Retrieval of Interacting Genes (STRING). Our analysis revealed that 1,869 genes were differentially expressed in RPL and control groups. GO analysis revealed that the interferon type 1 and the glycoprotein-related biological processes played irreplaceable roles, meanwhile KEGG enrichment analysis also revealed that the cAMP signalling pathway and the prolactin signalling pathway played important roles. In the following study, we found that there were many DEGs in the RPL group that were closely related to endometrial decidualization, such as IL17RD, IL16, SOX4, CREBBP, and POFUT1 as well as Notch1 and RBPJ in the Notch signalling pathway family were down-regulated in the RPL group. The results provided valuable information on the pathogenesis of RPL.

Addition of amino acids modulates the in vitro digestibility of corn starch.

The addition of amino acids (AAs) including glycine (Gly), lysine (Lys) and glutamic acid (Glu) with different concentrations on starch morphological, physicochemical and in vitro digestion properties were studied. While AAs showed no effects on neither morphology nor crystalline characters, they all significantly influenced the starch relative crystallinity and swelling capacity in an order of Glu > Lys > Gly. For all samples, both fastly- and slowly- digestible starch fractions (SF and SS) were observed. While Glu and Gly increased SF content with a faster digestion rate, they reduced SS content with a slower digestion rate. On contrary, Lys reduced SF content and the digestion rate of SS. The inhibitory effects of AAs on starch retrogradation and enzyme activities, the acidic environment and Maillard reaction between starch phosphate monoester and Lys are responsible for altered starch digestibility. This study betters our understanding concerning how AAs interactions affect starch functional properties.