Early Time Research Articles

Transcriptomics identify the triggering of citrate export as the key event caused by manganese deficiency in Aspergillus niger.

Citric acid is produced on industrial scale by batch fermentation of the filamentous fungus Aspergillus niger. High-yield citric acid production requires a low (<5 ppb) manganese(II) ion concentration in the culture broth. However, the requirement for this deficiency has not been investigated on a functional genomics level. Here, we compared the transcriptome of a citric acid hyper-producer A. niger strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn2+ ion-deficient (5 ppb) and Mn2+ ion-sufficient (100 ppb) conditions at three early time points of cultivation. We observed that Mn2+ deficiency triggers an upregulation of the citrate exporter gene cexA and provides functional evidence that this event is responsible for citrate overflow. In addition to the industrial relevance, this is the first study that examined the role of Mn2+ ion deficiency in a heterotrophic eukaryotic cell on a genome-wide scale.

The HSV-1 encoded CCCTC-binding factor, CTRL2, impacts the nature of viral chromatin during HSV-1 lytic infection.

HSV-1 genomes are rapidly heterochromatinized following entry by host cells to limit viral gene expression. Efficient HSV-1 genome replication requires mechanisms that de-repress chromatin associated with the viral genome. CCCTC-binding factors, or CTCF insulators play both silencing and activating roles in cellular transcriptional regulation. Importantly, the HSV-1 genome encodes several CTCF insulators that flank IE genes, implying that individual HSV-1 encoded CTCF insulators regulate IE transcription during all stages of the HSV-1 life cycle. We previously reported that the HSV-1 encoded CTCF insulator located downstream of the LAT (CTRL2) controlled IE gene silencing during latency. To further characterize the role of this insulator during the lytic infection we leveraged a ΔCTRL2 recombinant virus to show that there was a genome replication defect that stemmed from decreased IE gene expression in fibroblasts and epithelial cells at early times following initiation of infection. Further experiments indicated that the defect in gene expression resulted from chromatin inaccessibility in the absence of the insulator. To elucidate how chromatin accessibility was altered in the absence of the CTRL2 insulator, we showed that enrichment of Alpha-thalassemia/mental retardation, X-linked chromatin remodeler (ATRX), and the histone variant H3.3, both of which are known for their roles in maintaining repressive histone markers on the HSV-1 viral genome were increased on IE regions of HSV-1. Finally, both H3K27me3 and H3K9me3 repressive histone marks remained enriched by 4 hours post infection in the absence of the CTRL2 insulator, confirming that the CTRL2 insulator is required for de-repression of IE genes of viral genomes. To our knowledge these are the first data that show that a specific CTCF insulator in the HSV-1 genome (CTRL2) regulates chromatin accessibility during the lytic infection.

A novel valve strategy for particulate matter reduction in a gasoline direct injection engine operated at cold conditions

In this study, we proposed a novel intake strategy to reduce Particulate matter (PM) emissions from gasoline direct-injection (GDI) engines during cold-start conditions emissions. This strategy is characterized by generating strong intake turbulence and low in-cylinder pressure during fuel injection through delayed intake valve opening, which theoretically promotes fuel atomization and fuel-air mixture, thereby suppressing PM formation during combustion. Experiments were conducted on a single-cylinder GDI research engine, operating at 1500 rpm, 3, 6, and 8 bar IMEP, and stoichiometric air-fuel ratio conditions with low coolant and lubricant temperatures to experimentally demonstrate the effectiveness of the proposed valve strategy in reducing PM emissions. Benchmark tests were performed using an intake camshaft with intake valve opening (IVO) at −13 °aTDC and intake valve closing (IVC) at 227 °aTDC. The novel strategy uses an intake camshaft with very late IVO at 66 °aTDC and IVC at 226 °aTDC. Two injection pressures (Pinj = 100/200 bar) were used to evaluate the pressure requirement for achieving low PM emissions with both strategies. Start of injection was swept and optimized to match the valve strategy. The results showed that the novel valve strategy leads to a 50%–90% reduction in particle number and mass emissions in cold-start conditions, and a lower injection pressure requirement to achieve comparable particle number and mass emissions compared with the normal one. For the novel valve strategy, the fuel impingement with early injection timings is largely mitigated, and thus an early injection timing shortly before the IVO is recommended.

Health promotion and prevention in early times of the COVID-19 pandemic: insights from a Delphi study in Switzerland.

COVID-19 pandemic and confinement measures had a major impact on the health and well-being of the population. Health promotion and prevention (HP&P) professionals had to rethink their practices to respond to the challenges raised by the pandemic context. This study aimed to build a professional consensus on the HP&P priorities (apart from the COVID-19 fight) in the early times of the pandemic in Switzerland and to identify the most relevant interventions to respond to these issues. HP&P experts from the three main linguistic regions of Switzerland reached a consensus through a two-round Delphi methodology with online questionnaires in June-July and October-November, 2020. Out of 282 experts contacted, 121 (43%) contributed in the first round and 99 (35%) in the second. A strong consensus emerged about the importance of tackling mental health problems, non-communicable diseases and their main risk factors, as well as multiple social determinants of health. Although they believed that HP&P priorities changed in this context, experts reported that professional practices had only partially adapted to this new context due to multiple constraints (political, strategic, financial). The experts noted the need to adapt the means of communication to reach the different target groups. They underlined the potential of communication via digital technologies, but also drew attention to the risk of widening social inequalities due to the unequal access to these resources. This study generated new insights and confirmed pre-established knowledge regarding the orientations the field of HP&P should follow. While stressing the need to consolidate the traditional missions of the field (i.e. the fight against non-communicable diseases and the actions on social determinants of health), experts surveyed in this study also revaluated health priorities and rethought the way of developing HP&P actions in this specific context of the early pandemic of COVID-19.

Acoustic behaviour and acoustic treatment strategies for the baroque church of Santuari del Miracle, Solsonès, Lleida

The church of Santuari del Miracle, located in the Catalan region of Solsonès, Lleida, is a unique barroque church in Catalonia that hosts Baroque music performances, like the festival Espurnes Barroques. However, according to the musicians and the audience, it is too reverberant to play this style of music. The objective of this work is to examine the current acoustic performance of the church and to propose acoustic treatment strategies that are respectful of this unique heritage building. Impulse response measurements are first performed following ISO 3382-1 standards, using Odeon software to assess reverberation time (T30), Early Decay Time (EDT), Clarity (C50), and Definition (D50). Simulations are next performed using Odeon. They are used to refine the smallest perceptible differences from the measured data and to examine potential treatment strategies. The proposed solution consists of elements based on variable acoustics that can be easily hidden or removed, thus preserving the original acoustics of this heritage building.

Allelic Variation of BnaFTA2 and BnaFTC6 Is Associated With Flowering Time and Seasonal Crop Type in Rapeseed (Brassica napus L.).

Different ecological types of rapeseed (Brassica napus L.), including winter, spring, and semi-winter cultivars, exhibit varying flowering times and cannot be planted in the same cultivation areas. FLOWERING LOCUS T (FT) plays a key role in regulating flowering. In allotetraploid B. napus six copies of FT (BnaFT) have been reported. However, there is uncertainty about how the translated products of each paralog, as well as cis-allelic variations at each locus, contribute functionally to flowering time and define specific crop types. In this study, we confirm that BnaFT exhibit distinct expression patterns in different crop types of rapeseed. Using the CRISPR/Cas9 gene editing system, we provide functional evidence that the mutants between Bnaft paralogues affects the regulation of flowering time. Furthermore, we identify a new haplotype of BnaFT.A2 that is associated with early flowering time, although this appears necessary but not sufficient to confer a spring type phenotype. Three haplotypes of BnaFT.C6 were further identified and associated with both flowering time and crop types. We speculate that variations in both BnaFT.A2 and BnaFT.C6 may have undergone diversifying selection during the divergence of seasonal crop types in rapeseed.

Time-course characterization of whole-transcriptome dynamics of HepG2/C3A spheroids and its toxicological implications

Physiologically relevant in vitro models are a priority in predictive toxicology to replace and/or reduce animal experiments. The compromised toxicant metabolism of many immortalized human liver cell lines grown as monolayers as compared to in vivo metabolism limits their physiological relevance. However, recent efforts to culture liver cells in a 3D environment, such as spheroids, to better mimic the in vivo conditions, may enhance the toxicant metabolism of human liver cell lines. In this study, we characterized the dynamic changes in the transcriptome of HepG2/C3A hepatocarcinoma cell spheroids maintained in a clinostat system (CelVivo) to gain insight into the metabolic capacity of this model as a function of spheroid size and culture time. We assessed morphological changes (size, necrotic core), cell health, and proliferation rate from initial spheroid seeding to 35 days of continuous culture in conjunction with a time-course (0, 3, 7, 10, 14, 21, 28 days) of the transcriptome (TempO-Seq, BioSpyder). The phenotypic characteristics of HepG2/C3A growing in spheroids were comparable to monolayer growth until ∼Day 12 (Day 10–14) when a significant decrease in cell doubling rate was noted which was concurrent with down-regulation of cell proliferation and cell cycle pathways over this time period. Principal component analysis of the transcriptome data suggests that the Day 3, 7, and 10 spheroids are pronouncedly different from the Day 14, 21, and 28 spheroids in support of a biological transition time point during the long-term 3D spheroid cultures. The expression of genes encoding cellular components involved in toxicant metabolism and transport rapidly increased during the early time points of spheroids to peak at Day 7 or Day 10 as compared to monolayer cultures with a gradual decrease in expression with further culture, suggesting the most metabolically responsive time window for exposure studies. Overall, we provide baseline information on the cellular and molecular characterization, with a particular focus on toxicant metabolic capacity dynamics and cell growth, of HepG2/C3A 3D spheroid cultures over time.

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in Early and Late Time Windows.

This study aimed to compare outcomes of low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) patients with stroke who underwent mechanical thrombectomy (MT) within 6 hours or 6 to 24 hours after stroke onset. A retrospective cohort study was conducted using data from a large multicenter international registry from 2013 to 2023. Patients with low ASPECTS (2-5) who underwent MT for anterior circulation intracranial large vessel occlusion were included. A propensity matching analysis was conducted for patients presented in the early (<6 hours) vs late (6-24 hours) time window after symptom onset or last known normal. Among the 10 229 patients who underwent MT, 274 met the inclusion criteria. 122 (44.5%) patients were treated in the late window. Early window patients were older (median age, 74 years [IQR, 63-80] vs 66.5 years [IQR, 54-77]; P < .001), had lower proportion of female patients (40.1% vs 54.1%; P = .029), higher median admission National Institutes of Health Stroke Scale score (20 [IQR, 16-24] vs 19 [IQR, 14-22]; P = .004), and a higher prevalence of atrial fibrillation (46.1% vs 27.3; P = .002). Propensity matching yielded a well-matched cohort of 84 patients in each group. Comparing the matched cohorts showed there was no significant difference in acceptable outcomes at 90 days between the 2 groups (odds ratio = 0.90 [95% CI = 0.47-1.71]; P = .70). However, the rate of symptomatic ICH was significantly higher in the early window group compared with the late window group (odds ratio = 2.44 [95% CI = 1.06-6.02]; P = .04). Among patients with anterior circulation large vessel occlusion and low ASPECTS, MT seems to provide a similar benefit to functional outcome for patients presenting <6 hours or 6 to 24 hours after onset.

Carbon envelopes around merging galaxies at z ∼ 4.5

Context. Galaxies evolve through a dynamic exchange of material with their immediate surrounding environment, the so-called circumgalactic medium (CGM). Understanding the physics of gas flows and the nature of the CGM is fundamental to studying galaxy evolution, especially at 4 ≤ z ≤ 6 (i.e., after the Epoch of Reionization) when galaxies rapidly assembled their masses and reached their chemical maturity. Galactic outflows are predicted to enrich the CGM with metals, although it has also been suggested that gas stripping in systems undergoing a major merger may play a role. Aims. In this work, we explore the metal enrichment of the medium around merging galaxies at z ∼ 4.5, observed by the ALMA Large Program to INvestigate [CII] at Early times (ALPINE). To do so, we study the nature of the [CII] 158 μm emission in the CGM around these systems, using simulations to help disentangle the mechanisms contributing to the CGM metal pollution. Methods. By adopting an updated classification of major merger systems in the ALPINE survey, we selected and analyzed merging galaxies whose components can be spatially and/or spectrally resolved in a robust way. This makes it possible to distinguish between the [CII] emission coming from the single components of the system and that coming from the system as a whole. We also made use of the dustyGadget cosmological simulation to select synthetic analogs of observed galaxies and guide the interpretation of the observational results. Results. We find a large diffuse [CII] envelope (≳20 kpc) embedding all the merging systems, with at least 25% of the total [CII] emission coming from the medium between the galaxies. Using predictions from dustyGadget, we suggest that this emission has a multi-fold nature, with dynamical interactions between galaxies playing a major role in stripping the gas and enriching the medium with heavy elements.

Shock-driven three-fluid mixing with various chevron interface configurations

When a shock wave crosses a density interface, the Richtmyer–Meshkov instability causes perturbations to grow. Richtmyer–Meshkov instabilities arise from the deposition of vorticity from the misaligned density and pressure gradients at the shock front. In many engineering applications, microscopic surface roughness will grow into multi-mode perturbations, inducing mixing between the fluid on either side of an initial interface. Applications often have multiple interfaces, some of which are close enough to interact in the later stages of instability growth. In this study, we numerically investigate the mixing of a three-layer system with periodic zigzag (or chevron) interfaces, calculating the dependence of the width and mass of mixed material on properties such as the shock timing, chevron amplitude, multi-mode perturbation spectrum, density ratio, and shock mach number. The multi-mode case is also compared with a single-mode perturbation. The Flash hydrodynamic code is used to solve the Euler equations in three dimensions with adaptive grid refinement. Key results include a significant increase in mixed mass when changing from a single-mode to a multi-mode perturbation on one of the interfaces. The mixed width is mainly sensitive to the density ratio and chevron amplitude, whereas the mixed mass also depends on the multi-mode spectrum. Steeper initial perturbation spectra have lower mixed mass at early times but a greater mixed mass after the reflected shock transits back across the layer.

Receptivity of Rayleigh-Taylor instability to acoustic pulses: Theoretical explanation of pulse propagation

Direct numerical simulation (DNS) of Rayleigh-Taylor instability (RTI) has been reported in “Three-dimensional (3D) DNS of RTI triggered by acoustic excitation - Sengupta, et al. Phys. Fluids 34(5), 054108 (2022)” using more than 4 billion points with initial time steps of 7.69 ×10−8s. The set-up consists of quiescent heavy (cold) fluid atop lighter (hot) fluid initially separated by an insulated partition. Removal of this partition creates acoustic pulses in the directions normal to the interface, which provides the receptivity route of RTI to transient acoustic pulses spread over several mega-Hz frequencies, far in excess of ultrasonic frequencies. The DNS and its analysis reveal the pulses to be severely attenuated, which cannot be explained by the classical wave equation. In the present research, after demonstrating the features of the DNS results, we report in detail, the theoretical development of a wave equation incorporating losses based on the Navier-Stokes equation without Stokes' hypothesis for a quiescent ambience. Apart from the physical properties of this altered wave equation, the numerical solution of the same is obtained. The governing partial differential equation (PDE) for the propagation of disturbances in the spectral plane, provides the dispersion relation between wavenumber and circular frequency in the dissipative medium accounting for viscous losses. The presented analysis provides physical properties using the global spectral analysis (GSA). This shows the far-field perturbation to propagate either as attenuated waves or strictly in a diffusive manner depending upon the wavenumber. The PDE is solved numerically by a high-accuracy compact scheme and the four-stage, Runge-Kutta scheme for time advancement. The computed solution is shown to match not only with the developed theoretical analysis but also explains the DNS results for RTI at early times when the computed flow field truly represents the quiescent ambience.

Comparing sharp and smooth transitions of the second slow-roll parameter in single-field inflation

In single-field inflation, violation of the slow-roll approximation can lead to growth of curvature perturbation outside the horizon. This violation is characterized by a period with a large negative value of the second slow-roll parameter. At an early time, inflation must satisfy the slow-roll approximation, so the large-scale curvature perturbation can explain the cosmic microwave background fluctuations. At intermediate time, it is viable to have a theory that violates the slow-roll approximation, which implies amplification of the curvature perturbation on small scales. Specifically, we consider ultraslow-roll inflation as the intermediate period. At late time, inflation should go back to the slow roll period so that it can end. This means that there are two transitions of the second slow-roll parameter. In this paper, we compare two different possibilities for the second transition: sharp and smooth transitions. Focusing on effects generated by the relevant cubic self-interaction of the curvature perturbation, we find that the bispectrum and one-loop correction to the power spectrum due to the change of the second slow-roll parameter vanish if and only if theMukhanov-Sasaki equation for perturbation satisfies a specific condition called Wands duality.We also find in the case of sharp transition that, even though this duality is satisfied in the ultraslow-roll and slow-roll phases, it is severely violated at the transition so that the resultant one-loop correction is extremely large inversely proportional to the duration of the transition.

The Time Evolution of Fast Flavor Crossings in Postmerger Disks around a Black Hole Remnant

We postprocess a three-dimensional, general relativistic, full transport neutrino radiation magnetohydrodynamics simulation of the black-hole-accretion disk-wind system thought to be a potential outcome of the GW170817 merger to investigate the presence of electron lepton number (ELN-XLN) crossings in the neutrino angular distribution. Neutrinos are evolved with an explicit Monte Carlo method and can interact with matter via emission, absorption, or scattering. Within the postprocessing framework, we find ubiquitous occurrence of ELN-XLN crossings at early times (∼11 ms), but this does not hold for later times in the simulation. At postmerger times of ∼60 ms and beyond, ELN-XLN crossings are only present near the equator. We provide a detailed analysis of the neutrino radiation field to investigate the origin and time evolution of these crossings. Previous reports have suggested ubiquitous flavor crossings persisting throughout the simulation lifetime, albeit for different sets of conditions for the merger remnant, the treatment of hydrodynamics, and neutrino transport. Even though we do not perform a direct comparison with other published works, we qualitatively assess the reasons for the difference with our results. The geometric structure and evolution of the ELN-XLN crossings found in our analysis, and by extension, fast flavor instabilities, have important implications for heavy element nucleosynthesis in neutron star mergers.

Pre-peak Emission in Tidal Disruption Events

The rising part of a tidal disruption event light curve provides unique insight into early emission and the onset of accretion. Various mechanisms are proposed to explain the pre-peak emission, including shocks from debris interaction and reprocessing of disk emission. We study the pre-peak emission and its influence on the gas circularization by a series of gray radiation hydrodynamic simulations with varying black hole mass. We find that, given a super-Eddington fallback rate of 10ṀEdd , the stream–stream collision can occur multiple times and drive strong outflows of up to 9ṀEdd . By dispersing gas to ≳100r s , the outflow can delay gas circularization and leads to sub-Eddington accretion rates during the first few stream–stream collisions. The stream–stream collision shock and circularization shock can sustain a luminosity of ∼1044 erg s−1 for days. The luminosity is generally sub-Eddington and shows a weak correlation with accretion rate at early times. The outflow is optically thick, yielding a reprocessing layer with a size of ∼1014 cm and photospheric temperature of ∼4 × 104 K.

Efficacy of timing‑dependent infusion of nivolumab in patients with advanced gastric cancer.

Although an association exists between the timing of immune checkpoint inhibitor (ICI) administration and therapeutic efficacy in several types of cancer, to the best of our knowledge, no reports exist regarding this relationship in gastric cancer (GC). The present study aimed to evaluate the optimal timing of ICI (nivolumab) administration in patients with advanced GC. A total of 58 consecutive patients with advanced GC who received nivolumab monotherapy after ≥2 chemotherapy regimens were retrospectively evaluated. These patients were divided into two groups according to the median time of nivolumab administration: i) Early-timing and (ii) late-timing groups, and the efficacy was assessed in both groups. The early-timing group had significantly longer overall survival (OS) than the late-timing group [median OS 8.2 months; 95% confidence interval (CI), 4.2-12.9 vs. median OS 5.4 months; 95% CI, 3.6-6.1]. Moreover, patients in the early-timing group had significantly longer progression-free survival (PFS) than those in the late-timing group (median PFS 2.6 months; 95% CI, 1.3-3.9 months vs. median PFS 1.6 months; 95% CI, 0.9-2.1 months). Furthermore, univariate analysis showed that early timing, immune-related adverse events and nonsteroidal anti-inflammatory drug administration were associated with longer OS and PFS. Cutoff Finder analysis revealed that the optimal timing of nivolumab administration for achieving better outcomes was before 12:06 p.m. Nivolumab administration in the morning, especially before 12:06 p.m., had a better clinical impact on patients with advanced GC.

Assessment of clinical efficacy and safety of ICL implantation in patients with relatively shallow anterior chamber depth in early and midterm postoperative time

ObjectiveTo investigate the clinical effect and safety of ICL implantation in myopic patients with relatively shallow anterior chamber depth ( ACD ). MethodsRetrospective analysis,comparative, non-interventional case series. Patients with myopia who underwent ICL implantation were included in the study and were categorized into two groups: one with a relatively shallow ACD ( 2.60 mm ≤ ACD ＜ 2.80 mm ) and the other with a normal ACD ( ACD ≥ 2.80 mm ). Each group comprised 51 eyes and were reviewed for at least 6 months. To evaluate preoperative and postoperative visual acuity, intraocular pressure ( IOP ), central vault, ACD, endothelial cell density ( ECD ) and anterior chamber angle parameters( trabecular iris angle ( TIA ), angle opening distance at 500 μm and 750 μm ( AOD500, AOD750 ), trabecular iris space area at 500 μm and 750 μm ( TISA500, TISA750 ). Analyze the trend of postoperative data changes of 1 week, 1 month, 3 months, and at least 6 months. Patients in relatively shallow ACD with vault <100 μm or >1000 μm were performed detailed follow-up. ResultThe postoperative uncorrected distance visual acuity ( UDVA ) and best corrected visual acuity ( BCVA ) surpassed the preoperative BCVA in two groups. The group differences of effectiveness index ( EI ) was p=0.409 and of safety index ( SI ) was p=0.563. The EI were 1.07 and 1.09, SI were1.10 and 1.21. Postoperative vision and refractive error were effectively corrected. The preoperative and postoperative IOP and ECD values of the two groups were within the normal range, and the preoperative and postoperative differences and the group differences of IOP and ECD were p=0.649, p=0.501, p=0.222, p=0.276. The ACD in two groups were reduced by approximately 25% and 26%, the nasal and temporal TIA were reduced to 45% and 50% approximately. The nasal and temporal AOD500, AOD750, TISA500, and TISA750 in the relatively shallow ACD group were reduced 40% approximately and in the normal ACD group were reduced to 30% approximately. All the preoperative and postoperative differences and the group differences of anterior segment parameters were statistically significant ( all p<0.01 ), with more significant anterior segment changes in normal ACD group.The postoperative data in two groups showed that when the follow-up time was prolonged, the central vault was decreasing, and the postoperative ACD was increasing, the postoperative TIA increased slowly in relatively shallow ACD group and decreased slowly in normal ACD group, temporal TIA were greater than nasal TIA, with no significant variation. There were four eyes in the relatively shallow ACD group in the remarkable abnormal postoperative central vault. Three eyes had second operation: one eye had an ICL alignment, and two eyes had ICL replacement. ConclusionPatients with relatively shallow ACD who underwent ICL implantation had fine postoperative clinical efficacy and safety.

Intravenous thrombolysis versus dual antiplatelet therapy in minor ischemic stroke within the thrombolytic window (TAMIS): a multicenter cohort study.

Intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT) have been widely used in minor ischemic stroke (MIS) treatment. However, the clinical outcomes and safety of these two treatments have not been compared within the early thrombolytic time window. Here, we conducted a multicenter, ambispective cohort study involving patients with MIS presenting within 4.5 h of symptom onset at 3 affiliated hospitals of Jinan University from 2018-2022. The patients were divided into the IVT group and DAPT group. The primary outcome was a 90-day excellent outcome (mRS ≤ 1). A total of 1,026 patients were enrolled, of whom 492 were assigned to the IVT group and 534 were assigned to the DAPT group. The IVT group had better 90-day excellent outcomes (mRS ≤ 1) than the DAPT group (OR 1.69, 95% CI 1.14-2.52, P = 0.010). Among the 623 patients with nondisabling stroke, the proportion of mRS ≤ 1 in the IVT group was higher than the DAPT group (P = 0.009). In the subtypes of MIS with large vessel occlusion/stenosis and with isolated symptoms, the 90-day outcomes of the IVT group and DAPT group were not different (P > 0.05). In conclusion, compared with DAPT, IVT was associated with better 90-day clinical outcomes in patients with MIS (in particular, for those with mRS > 1), including earlier clinical improvement.IVT also benefited the early neurological improvement of patients with severe stenosis/occlusion of intracranial large vessels, nondisabling mild stroke, nondisabling mild stroke with isolated symptoms.

Widespread coastal upwelling along the marginal Yangtze Platform (South China) during the early Cambrian: Implications for hyper-enrichment of organic matter

Early Cambrian Earth history witnessed significant changes in marine environments and biological evolution contemporaneous with extensive accumulation of organic-rich shale. However, major factors controlling hyper-enrichment of organic matter (OM) of lower Cambrian shale deposits remain controversial. Black shale of the lower Cambrian Niutitang Formation (NTT) of the Marginal Yangtze Platform (South China) deposited during the Cambrian middle Age 2 are especially organic-rich, with total organic carbon (TOC) concentrations of as much as 13.0 wt%. Geochemical evidence suggests that cool, dry paleo-climatic conditions that prevailed on the Yangtze Platform during the Cambrian Fortunian-late Age 2, induced vigorous coastal upwelling. Paleo-productivity level assessments indicate that the magnitude of primary productivity contemporaneous with deposition of the NTT shale deposits exceeded that of modern upwelling systems (e.g., Peruvian Margin). The widespread occurrence of phosphate nodules within these deposits and decreased Co-EF × Mn-EF values of associated lower Cambrian black shale successions deposited along the margin of the Yangtze carbonate platform suggest extensive coastal upwelling. Widespread and strong coastal upwelling in tandem with elevated surface water primary productivity and anoxic (even euxinic) bottom water conditions are manifested by deposition of OM hyper-enriched black shale during Cambrian Fortunian to middle Age 2 time. However, weakened seasonal upwelling that appears to have prevailed during the late Cambrian Age 2 was accompanied by accumulation of NTT shale deposits of diminished TOC content. In summary, this study provides robust evidence of extensive coastal upwelling along the Marginal Yangtze Platform during early Cambrian time that favored accumulation of OM hyper-enriched shale. These results help to elucidate the distribution of high-quality lower Cambrian natural gas source rocks in South China.

The BnaBPs gene regulates flowering time and leaf angle in Brassica napus.

The flowering time and plant architecture of Brassica napus were significantly associated with yield. In this study, we found that the BREVIPEDICELLUS/KNAT1(BP) gene regulated the flowering time and plant architecture of B. napus. However, the precise regulatory mechanism remains unclear. We cloned two homologous BP genes, BnaBPA03 and BnaBPC03, from B. napus Xiaoyun. The protein sequence analysis showed two proteins containing conserved domains KNOX I, KNOX II, ELK, and HOX of the KONX protein family. The CRISPR/Cas9 knockout lines exhibited early budding and flowering time, coupled with floral organ abscission earlier and a larger leaf angle. On the contrary, overexpression plants displayed a phenotype that was the inverse of these characteristics. Furthermore, we observed upregulation of gibberellin and ethylene biosynthesis genes, as well as floral integrator genes in knocked-out plants. The results revealed that BnaBPs play a role in flowering time, floral organ abscission, and leaf angle as well as germination processes mediated. Additionally, BnaBPs exerted an impact on the biosynthesis pathways of ethylene and GA.

Was Grand Duchy of Lithuania a Federation?

According to received wisdom in the historiography of the Grand Duchy of Lithuania (GDL), going back to M. Dovnar-Zapolski, M. Liubavski, O. Halecki, the territorial form of government in the GDL was federal in the late XV-early XVI century. The paper critically reviews the arguments advanced in favor of this thesis and argues that the concept of empire describes the territorial organization of GDL in a more accurate way. The criticism of the federalist theory is grounded in the conceptual analysis of the state forms provided by the distinguished Lithuanian historian and law theorist Mykolas Rėimeris (1880-1945). In his analysis, M. Rėimeris draws the distinction between a unitary state and three types of state compounds: federation, confederation, and empire. While federation and empire share the principle of subordination as the mode of organization, in the empire this is the subordination to a privileged metropole territory and cultural-ethnic group, while in federation all territories are subordinated to the federal center on parity grounds, all participating in federal government. Supplementing M. Rėimeris' ideas with those from the contemporary comparative sociological research on empires and imperialism (S. Eisenstadt, M. Doyle, A. Motyl, Ch. Tilly), the author argues that GDL was an empire because relations between Lithuania in the strict sense (including also some Russian lands annexed by the early XV century) and Polotsk, Vitebsk, Smolensk, Volynia, Kiev, Samogitia, etc. were those of subordination of the periphery to the imperial metropole. The proponents of the federalist thesis mistake as federalism what in reality was a system of indirect rule characteristic for premodern empires. The historiographical tradition was blind to imperial features of GDL because it implicitly or explicitly compared GDL with the Moscow state, considering it as a paradigmatic case of empires. However, the Moscow empire represents only one specific type of empire - Westphalian empire, distinguished by the early application of direct rule. While most medieval polities were transformed into sovereign territorial states and Westphalian empires in the early modern time, GDL was unique in following the path of federalization. However, GDL was transformed into a federation only on the eve of the Lublin Union in 1569, while in the XIV-first half of the XVI century it was a traditional empire, including metropolitan military agrarian domains and indirectly ruled peripheral areas shading into areas of mere hegemony.