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Alfalfa ( Medicago sativa L.) is one of the most important and widely cultivated forage crops. It is commonly used as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Based on Illumina, Nanopore and Hi-C data, we assembled a chromosome-scale assembly of Medicago sativa spp . caerulea (voucher PI464715), the direct diploid progenitor of autotetraploid alfalfa. The assembled genome comprises 793.2 Mb of genomic sequence and 47,202 annotated protein-coding genes. The contig N50 length is 3.86 Mb. This genome is almost twofold larger and contains more annotated protein-coding genes than that of its close relative, Medicago truncatula (420 Mb and 44,623 genes). The more expanded gene families compared with those in M. truncatula and the expansion of repetitive elements rather than whole-genome duplication (i.e., the two species share the ancestral Papilionoideae whole-genome duplication event) may have contributed to the large genome size of M. sativa spp . caerulea . Comparative and evolutionary analyses revealed that M. sativa spp . caerulea diverged from M. truncatula ~5.2 million years ago, and the chromosomal fissions and fusions detected between the two genomes occurred during the divergence of the two species. In addition, we identified 489 resistance ( R ) genes and 82 and 85 candidate genes involved in the lignin and cellulose biosynthesis pathways, respectively. The near-complete and accurate diploid alfalfa reference genome obtained herein serves as an important complement to the recently assembled autotetraploid alfalfa genome and will provide valuable genomic resources for investigating the genomic architecture of autotetraploid alfalfa as well as for improving breeding strategies in alfalfa.

A bstract The planar two-loop scalar Feynman integrals contributing to the massive NNLO QCD corrections for W -boson pair production via quark-antiquark annihilation can be classified into three family branches, each of which is reduced to a distinct set of master integrals (MIs), totaling 27, 45 and 15, respectively. These MIs are analytically calculated using the method of differential equations, with solutions expanded as Taylor series in the dimensional regulator ϵ . For the first two family branches, the differential systems can be successfully transformed into canonical form by adopting appropriate bases of MIs. This enables the MIs of these family branches to be expressed either as Goncharov polylogarithms (GPLs) or as one-fold integrals over GPLs, up to O ( ϵ 4 ). In contrast, the differential system for the third family branch can only be cast into a form linear in ϵ due to the presence of elliptic integrals. The solution to this linear-form differential system is expressed in an iterated form owing to the strictly lower-triangular structure of the coefficient matrices at ϵ = 0. Our analytic expressions for these MIs are verified with high accuracy against the numerical results from the AMFlow package.

A bstract The discrepancy between the CDF measurement and the Standard Model theoretical prediction for the W -boson mass underscores the importance of conducting high-precision studies on the W boson, which is one of the predominant objectives of proposed future e + e − colliders. We investigate in detail the production of W -boson pairs at e + e − colliders, and compute the next-to-next-to-leading order mixed QCD-EW corrections to both the integrated cross section and various kinematic distributions. By employing the method of differential equations, we analytically calculate the two-loop master integrals for the mixed QCD-EW virtual corrections to e + e − → W + W − . Utilizing the Magnus transformation, we derive a set of canonical master integrals for each integral family. This canonical basis satisfies a system of differential equations in which the dependence on the dimensional regulator is linearly factorized from the kinematics. We then express all these canonical master integrals as Taylor series in ϵ up to ϵ 4 , with coefficients articulated in terms of Goncharov polylogarithms up to weight four. Upon applying our analytic expressions of these master integrals to the phenomenological analysis of W -pair production, we observe that the O ( αα s ) corrections are significantly impactful in the α (0) scheme, particularly in certain phase-space regions. However, these mixed QCD-EW corrections can be heavily suppressed by adopting the G μ scheme.

To explore the effects of maternal high-fat (HF) diet-induced obesity on fetal growth and the expression of placental nutrient transporters. Maternal obesity was established in rats by 8 weeks of pre-pregnancy fed HF diet, while rats in the control group were fed normal (CON) diet. Diet-induced obesity (DIO) rats and diet-induced obesity-resistant (DIR) rats were selected according to body weight gain over this period. After copulation, the CON rats were divided into two groups: switched to HF diet (CON-HF group) or maintained on the CON diet (CON-CON group). The DIO rats and DIR rats were maintained on the HF diet throughout pregnancy. Pregnant rats were euthanized at day 21 gestation, fetal and placental weights were recorded, and placental tissue was collected. Reverse transcription-polymerase chain reaction was used to determine mRNA expression of placental nutrient transporters. Protein expression was determined by Western blot. Average fetal weight of DIO dams was reduced by 6.9%, and the placentas of CON-HF and DIO dams were significantly heavier than the placentas of CON-CON and DIR dams at day 21 of gestation (p<0.05). The fetal/placental weight ratio of DIO dams was significantly reduced compared with the fetal/placental weight ratio of CON-CON dams (p<0.05). The mRNA expression of GLUT-1 and SNAT-2 were not significantly different between groups. The mRNA and protein expression levels of CD36, FATP-1, and FATP-4 in DIO dams were decreased significantly (p<0.05). Maternal obesity induced by a HF diet led to intrauterine growth retardation and down-regulated the expression of placental fatty acid transporters.

Self-intersecting energy band structures in momentum space can be induced by nonlinearity at the mean-field level, with the so-called nonlinear Dirac cones as one intriguing consequence. Using the Qi-Wu-Zhang model plus power law nonlinearity, we systematically study in this paper the Aharonov–Bohm (AB) phase associated with an adiabatic process in the momentum space, with two adiabatic paths circling around one nonlinear Dirac cone. Interestingly, for and only for Kerr nonlinearity, the AB phase experiences a jump of π at the critical nonlinearity at which the Dirac cone appears and disappears (thus yielding π-quantization of the AB phase so long as the nonlinear Dirac cone exists), whereas for all other powers of nonlinearity, the AB phase always changes continuously with the nonlinear strength. Our results may be useful for experimental measurement of power-law nonlinearity and shall motivate further fundamental interest in aspects of geometric phase and adiabatic following in nonlinear systems.

Foundering of mafic lower continental crust into underlying convecting mantle has been proposed as one means to explain the unusually evolved chemical composition of Earth's continental crust 1 , 2 , yet direct evidence of this process has been scarce. Here we report that Late Jurassic high-magnesium andesites, dacites and adakites (siliceous lavas with high strontium and low heavy-rare-earth element and yttrium contents) from the North China craton have chemical and petrographic features consistent with their origin as partial melts of eclogite that subsequently interacted with mantle peridotite. Similar features observed in adakites and some Archaean sodium-rich granitoids of the tonalite-trondhjemite-granodiorite series have been interpreted to result from interaction of slab melts with the mantle wedge. Unlike their arc-related counterparts, however, the Chinese magmas carry inherited Archaean zircons and have neodymium and strontium isotopic compositions overlapping those of eclogite xenoliths derived from the lower crust of the North China craton. Such features cannot be produced by crustal assimilation of slab melts, given the high Mg#, nickel and chromium contents of the lavas. We infer that the Chinese lavas derive from ancient mafic lower crust that foundered into the convecting mantle and subsequently melted and interacted with peridotite. We suggest that lower crustal foundering occurred within the North China craton during the Late Jurassic, and thus provides constraints on the timing of lithosphere removal beneath the North China craton.

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disorder characterized by a T helper 2 (Th2) immune response phenotype. Extracellular vesicles (EVs) are a heterogeneous family of cell-derived membranous structures, which transport cellular components such as DNA and proteins, and are involved in multiple physiological and pathological processes. Increasing evidence has shown that EVs secretion took part in the pathogenesis of AD. However, the proteomic studies of plasma-derived EVs in AD patients have not been reported. In this study, we investigated the diversity of plasma EVs collected from AD patients and healthy individuals and suggested that the candidates for uniquely or differentially expressed proteins in plasma EVs could be a diagnostic marker in AD. The plasma EVs were collected from 12 patients with moderate-to-severe AD and 13 healthy subjects. Proteomic analysis was performed by using a comprehensive nanoLC‑MS/MS method. Proteomic analysis revealed that a total of 1478 proteins in plasma EVs were found to be common proteins in AD, whereas a total of 1597 proteins in plasma EVs were found to be common proteins in HC. Eighty-six proteins in plasma EVs showed more than 2.5-fold up-regulation, while a total of 225 proteins in plasma EVs showed less than 1/2.5-fold down-regulation with a significant difference (p < 0.05) among AD compared with HC. The candidates for differentially expressed proteins in plasma EVs have been described as a connectivity PPI network related to several KEGG pathways, including pathways in platelet activation, complement, and so on. SLP-76 tyrosine phosphoprotein (SLP76) involved in platelet activation may significantly contribute to the pathogenesis of AD. We will further verify the role of SLP67 in AD via animal and cell experiments to provide a promising therapeutic or diagnostic target.

The gravitational bending of light in the framework of conformal gravity is considered where an exact solution for null geodesics in the Mannheim-Kazanas is obtained. The linear coefficient γ characteristic to conformal gravity is shown to contribute enhanced deflection compared to the angle predicted by General Relativity for small γ. We also briefly consider gravitational lensing in covariant emergent gravity.

Background The Warburg effect demonstrates the importance of glycolysis in the development of primary and metastatic cancers. We aimed to explore the role of monocarboxylate transporter 1 (MCT1) and MCT4, two essential transporters of lactate, in renal cancer progression during cancer-endothelial cell co-culturing. Methods Renal cancer cells (786-O) and human vascular endothelial cells (HUVECs) were single-cultured or co-cultured in transwell membranes in the presence or absence of a MCT-1/MCT-4 specific blocker, 7ACC1. Cell proliferation was evaluated with the CCK-8 kit, while cell migration, after a scratch and invasion in transwell chambers, was evaluated under a microscope. Real-time qPCR and western blot were employed to determine the mRNA and protein levels of MCT1 and MCT4, respectively. The concentration of lactic acid in the culture medium was quantified with an l -Lactic Acid Assay Kit. Results 786-O cells and HUVECs in the co-culturing mode exhibited significantly enhanced proliferation and migration ability, compared with the cells in the single-culturing mode. The expression of MCT1 and MCT4 was increased in both 786-O cells and HUVECs in the co-culturing mode. Co-culturing promoted the invasive ability of 786-O cells, and markedly increased extracellular lactate. Treatments with 7ACC1 attenuated cell proliferation, migration, and invasion, and down-regulated the levels of MCT1/MCT4 expression and extracellular lactate. Conclusions The Warburg effect accompanied with high MCT1/MCT4 expression in the cancer-endothelial microenvironments contributed significantly to renal cancer progression, which sheds new light on targeting MCT1/MCT4 and glycolytic metabolism in order to effectively treat patients with renal cancers.

This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus sintilimab and bevacizumab biosimilar as first-line therapy for intermediate-advanced hepatocellular carcinoma (HCC). A total of 253 patients with HCC who received either TACE plus sintilimab and bevacizumab biosimilar (combination group, n=74) or TACE alone (monotherapy group, n=179) were included retrospectively. Propensity score matching (PSM) analysis was used to match patients. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety of two groups were compared. After propensity score matching (1:2), 65 patients in the combination group were matched to 100 patients in the monotherapy group. The ORR (63.1% vs. 40.0%,  = 0.004) was better in the combination group than those in monotherapy group. The combination group had higher median PFS (13.3 vs. 7.1 months; hazard ratio [HR] = 0.63, 95% confidence interval [CI], 0.41-0.87;  = 0.017) and OS (20.1 vs. 14.6 months; HR = 0.53, 95% CI, 0.35-0.81;  = 0.010) than those in the monotherapy group. Multivariate analysis confirmed that BCLC stage B, ECOG PS of 0, and combination therapy were associated with higher PFS and OS. Grade 3/4 TRAEs occurred in 21.5% of the patients in the combination group, and 14.0% of the patients in the monotherapy group. Compared to TACE monotherapy, TACE plus sintilimab and bevacizumab biosimilar showed significantly better ORR, PFS, and OS for intermediate-advanced HCC.