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.

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.

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.

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.

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%.

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.

Effect of the Current on the Fire Characteristics of Overloaded Polyvinyl Chloride Copper Wires.

In this study, the fire behavior variation of unenergized polyvinyl chloride (PVC) copper wires subjected to overload with different currents was investigated by a cone calorimeter. Overload currents were selected from 1 times safe-rated current (Ie) to 3.5 times Ie to obtain tested sample wires. The mass fraction, time to ignition (TTI), heat release rate (HRR), gas emission, and residue were measured. If the current flowing through the wire increased up to 3.5 times Ie, the TTI of this unenergized wire increased drastically and the peak HRR (pHRR) decreased notably so that the flame growing index (FGI) reduced considerably. When the wire carried less than three times Ie, the FGI remained stable. For all overloaded PVC copper wires, the increase in the heat flux resulted in a higher pHRR and a lower burning duration. However, regardless of the external heat flux exposure, the FGI of copper wires overloaded at 3.5 times Ie was lower than that of copper wires carrying less than other times Ie. Moreover, the consumption of O2 and generation of CO2 as the heat flux varied were consistent with that of the HRR. Opposed to expectation, the flame propagation of unenergized PVC copper wires would decline in a fire, if the wire has been damaged by overload with some currents.

lncRNA HAGLR modulates myocardial ischemia-reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis.

Acute myocardial infarction is one of the leading causes of morbidity worldwide, but the underlying mechanism responsible for myocardial ischemia-reperfusion (I/R) injury remains elusive. lncRNA plays roles in inflammatory response, cell apoptosis and regulation of myocardial ischemia. However, whether lncRNA HAGLR could regulate myocardial I/R injury and the molecular mechanism need to be further investigated. lncRNA has been shown to bind to miRNAs and compete with endogenous RNAs. miR-133a-3p has been shown to regulate cardiomyocyte apoptosis and ischemic myocardial injury. In this work, it has shown that knockdown of HAGLR could suppress inflammatory response and cell apoptosis induced by I/R and, thus, alleviate myocardial I/R injury. HAGLR promoted myocardial I/R injury by inhibiting miR-133a-3p to promote MAPK1 expression.

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.

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.

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.

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.

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.

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.

Static and dynamic failure mechanisms of circular granite under the condition of water-heat cycles.

Based on the engineering environment where rocks surrounding wellbores in energy storage areas are influenced by high temperature, cool and hot water, thermal stress etc. in the exploitation of hydrothermally geothermal energy, the experimental study on mechanical properties of ring granite under the static and dynamic loads in the water-heat condition was performed. The experimental results showed that when the ring granite was influenced by the inner diameters, heating temperatures, curing temperatures and heat recovery cycle times, the impact load-strain curves were nonlinear. However, the concave stages, platform stages and cliff-like drop stages appeared in the load-strain curves under the static loads. The radical peak loads decreased exponentially with the growth of the damage factors and the dynamic peak loads were far greater than the static peak loads. By analyzing the damage cracks and broken fragments, it was found that under the static and dynamic radical loads, the cracks generated in the ring specimens were tensile cracks and the failure mode was tensile failure. However, the dynamic failure was more aggressive than the static failure. Then, the apparent deformation modulus was defined to describe the deformation characteristics of ring granite before the radical peak loads. And it is found that the variation law of dynamic apparent deformation modulus is more dispersed than the changes of static apparent deformation modulus. Finally, based on the deformation and failure characteristics of ring granite obtained from the tests, the static and dynamic failure criteria considering whether the cracks along the loading direction were generated in the inner ring wall were deduced and verified by the corresponding tests.

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.

Study on the dynamic characteristics of rock surrounding a wellbore in energy storage areas during deep geothermal energy mining.

Based on the engineering background in which the rock surrounding a wellbore is affected by a thermal shock, impact disturbances from drilling vibration, cyclic heat extraction and high temperature during hydrothermal geothermal energy mining, the environmental conditions in the shaft wall rock are simulated by means of high temperature, cooling, immersing granite in water with different curing temperatures and applying impact loads. Additionally, an experimental study on the mechanical characteristics of circular granite specimens under radial impact loads and in the heat treatment and water curing conditions is carried out. The results show that the inner diameters of the rings, heating temperatures, curing water temperatures and cycle heating times are less affected than other parameters by the impact load-strain curves of circular granite, which can generally be divided into three sections, i.e., the initial straight stage, nonlinear ascent yield stage and post-peak nonlinear decline stage. The factors in the test weaken the capacity of the circular granite to resist the impact, but the sizes of the inner diameters of the rings play a leading role. Dynamic tensile strain is generated in the inner wall along the impact direction during the impact, while compressive strain is produced on the inner wall in the vertical impact loading direction. By analysing the crack propagation and final failure mode of circular granite, it is found that dynamic tensile failures are generated, crack initiation starts from the inner wall along the impact loading direction, and the outer circle in the vertical direction lags behind. The crack starts early and develops quickly on one side of the transmission bar. Finally, the failure criterion is established on the basis of some assumptions and circular-granite deformation failure characteristics, and the parameters, measured by the Brazilian disk test, are reasonably verified via substitution into the failure criterion equation.

A comparative analysis on thermal runaway behavior of Li (NixCoyMnz) O2 battery with different nickel contents at cell and module level.

The problem of thermal runaway (TR) propagation challenges the safety design of battery packs, because it aggravates the thermal hazards to accidents. There are many unsolved scientific questions in understanding the mechanisms of TR and its propagation behavior for large format lithium-ion batteries (LIBs). LiNixCoyMnzO2(NCM) is considered as one of the most promising cathode materials for lithium-ion batteries LIBs, given its higher energy design and lower cost. However, higher Nickel (Ni) content of cathode material worsens the thermal stability of LIBs. This paper provides a comparative analysis on the TR propagation behavior of NCM battery with different Ni ratios. Results have shown that when the characteristic temperatures of TR {T1, T2, T3}and the specific electrochemical energy of the cell are similar, TR propagation behavior will be similar, no matter what kinds of chemistry the cell has. Observation suggests that the average propagation time within a large format cell is 7-10 s in module tests. Besides, the internal temperature of the cell has an order of NCM622 ≥ NCM523 ≥ NCM111,whereas the mass is ordered by NCM622 > NCM523 > NCM111.This work firstly reports the TR feature in large format LIBs with different Ni ratios, both at cell and module level, providing the guidelines for engineering practice and further theoretical researches.

Cutting antiparallel DNA strands in a single active site.

A single enzyme active site that catalyzes multiple reactions is a well-established biochemical theme, but how one nuclease site cleaves both DNA strands of a double helix has not been well understood. In analyzing site-specific DNA cleavage by the mammalian RAG1-RAG2 recombinase, which initiates V(D)J recombination, we find that the active site is reconfigured for the two consecutive reactions and the DNA double helix adopts drastically different structures. For initial nicking of the DNA, a locally unwound and unpaired DNA duplex forms a zipper via alternating interstrand base stacking, rather than melting as generally thought. The second strand cleavage and formation of a hairpin-DNA product requires a global scissor-like movement of protein and DNA, delivering the scissile phosphate into the rearranged active site.