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Myosin-5a (Myo5a) is an actin-dependent molecular motor that recognizes a diverse range of cargo proteins through its tail domain, playing a crucial role in the transport and localization of various organelles within the cell. We have identified a new interaction between Myo5a and its cargo protein melanophilin (Mlph), i.e., the interaction between the middle tail domain of Myo5a (Myo5a-MTD) and the actin-binding domain of Mlph (Mlph-ABD), by GST pulldown assay. We then intend to obtain the dissociation constant between Myo5a-MTD and Mlph-ABD using isothermal titration calorimetry (ITC) or microscale thermophoresis (MST), both of which are two commonly used methods for determining quantitative data on protein interactions. The advantages of MST over ITC include less protein usage, shorter operation time, and higher sensitivity. In this protocol, we present a method for using MST to determine the dissociation constants of Myo5a-MTD and Mlph-ABD, which were purified through overexpression in bacteria using affinity chromatography. The dissociation constant values obtained directly reflect the binding strength between these two proteins and provide a foundation for the isolation and purification of the complex in the future.

The development of the new energy automobile industry has driven the development of the tire industry, and the development of the tire industry has put forward higher requirements for the handling and storage efficiency of tires. In this paper, through the discussion of the new tire synchronous fixture, the double parallel four-bar mechanism is introduced. The mechanism has the advantages of horizontal extension and contraction, and avoids the deviation in the vertical direction. In order to be better applied to the handling and storage of tires and further applied in other fields, this paper obtains the relationship between rod length and stroke through the kinematic analysis of double parallel four-bar mechanism, establishes a compact structure size table of common size, and carries out practical application simulation. The accuracy of size is verified by mechanical simulation. Through the relationship established in this paper and the compact structure size table, we can quickly and easily find the appropriate size of the double parallel four-bar mechanism according to the demand. Through the study of its structural characteristics, we can easily find the scene where it can be applied, so as to promote the universality of the application of the double parallel four-bar mechanism.

Residues of the pesticides chlorfenapyr (CFP) and emamectin benzoate (EMB) often coexist in the environment and can be accumulated in the body. To understand the impact of these two chemicals on health, we investigated their effect on the kidneys. In this study, rats were treated with CFP and/or EMB at low/medium/high doses of 1/3/9 mg/kg/day and 0.2/0.6/1.8 mg/kg/day, respectively, via oral gavage for 60 days. Kidneys and serum samples were collected and serum biochemistry and kidney histopathological changes were analyzed and examined. Kidney metabolome alterations were analyzed by using gas chromatography–mass spectrometry. The results showed that combined exposure to CFP and EMB elevated BUN levels and induced pathological damage, which presented as thinner renal tubular epithelial cells, an abnormal glomerular morphology, and an increased fibrotic area. CFP and/or EMB disrupted glutathione metabolism and carbohydrate metabolism, resulting in the alteration of kidney metabolomes and inducing oxidative stress in the cells of kidney tissues. In addition, CFP decreased ATP content and inhibited pyruvate PDH activity in the kidneys. These findings suggest that long-term exposure to CFP and EMB at environmentally relevant levels induce alterations in the renal metabolome, oxidative stress, and an insufficient energy supply, which may contribute to renal histopathological damage.

We present detailed evolutionary simulations of wide binary systems with high-mass (8–20 M _⊙ ) donor stars and a 1.4 M _⊙ neutron star. Mass transfer in such binaries is dynamically unstable, and common envelope (CE) evolution is followed. We use a recently developed prescription to deal with CE evolution and consider various CE ejection efficiencies varying in the range of 0.1–3.0. We focus on the evolutionary consequences of the binaries that survived CE evolution. We demonstrate that it is possible for the binaries to enter a CE decoupling phase (CEDP) when the donor stars are partially stripped, leaving a hydrogen envelope of ≲1.0–4.0 M _⊙ after CE evolution. This phase is expected to last ∼10 ^4 –10 ^5 yr, during which mass transfer occurs stably via Roche lobe overflow with super-Eddington rates. Identification of some X-ray binaries in a CEDP is important for the understanding of the physics of CE evolution itself, the origin of ultraluminous X-ray sources, and the recycling process of accreting pulsars. Also, we discuss the formation of double neutron stars and the occurrence of ultrastripped supernovae according to the results from our simulations. On the whole, the properties of post-CE binaries are sensitive to the options of CE ejection efficiencies.

Transport and localization of melanosome at the periphery region of melanocyte are depended on myosin-5a (Myo5a), which associates with melanosome by interacting with its adaptor protein melanophilin (Mlph). Mlph contains four functional regions, including Rab27a-binding domain, Myo5a GTD-binding motif (GTBM), Myo5a exon F-binding domain (EFBD), and actin-binding domain (ABD). The association of Myo5a with Mlph is known to be mediated by two specific interactions: the interaction between the exon-F-encoded region of Myo5a and Mlph-EFBD and that between Myo5a-GTD and Mlph-GTBM. Here, we identify a third interaction between Myo5a and Mlph, that is, the interaction between the exon-G-encoded region of Myo5a and Mlph-ABD. The exon-G/ABD interaction is independent from the exon-F/EFBD interaction and is required for the association of Myo5a with melanosome. Moreover, we demonstrate that Mlph-ABD interacts with either the exon-G or actin filament, but cannot interact with both of them simultaneously. Based on above findings, we propose a new model for the Mlph-mediated Myo5a transportation of melanosomes.

Tobacco (Nicotiana tabacum) is one of the major cash crops in China. Potato virus Y (PVY), a representative member of the genus Potyvirus, greatly reduces the quality and yield of tobacco leaves by inducing veinal necrosis. Mild strain-mediated cross-protection is an attractive method of controlling diseases caused by PVY. Currently, there is a lack of effective and stable attenuated PVY mutants. Potyviral helper component-protease (HC-Pro) is a likely target for the development of mild strains. Our previous studies showed that the residues lysine at positions 124 and 182 (K124 and K182) in HC-Pro were involved in PVY virulence, and the conserved KITC motif in HC-Pro was involved in aphid transmission. In this study, to improve the stability of PVY mild strains, K at position 50 (K50) in KITC motif, K124, and K182 were separately substituted with glutamic acid (E), leucine (L), and arginine (R), resulting in a triple-mutant PVY-HCELR. The mutant PVY-HCELR had attenuated virulence and did not induce leaf veinal necrosis symptoms in tobacco plants and could not be transmitted by Myzus persicae. Furthermore, PVY-HCELR mutant was genetically stable after six serial passages, and only caused mild mosaic symptoms in tobacco plants even at 90 days post inoculation. The tobacco plants cross-protected by PVY-HCELR mutant showed high resistance to the wild-type PVY. This study showed that PVY-HCELR mutant was a promising mild mutant for cross-protection to control PVY.

Abstract Background The common carp (Cyprinus carpio) might best represent the domesticated allopolyploid animals. Although subgenome divergence which is well-known to be a key to allopolyploid domestication has been comprehensively characterized in common carps, the link between genetic architecture underlying agronomic traits and subgenome divergence is unknown in the selective breeding of common carps globally. Results We utilized a comprehensive SNP dataset in 13 representative common carp strains worldwide to detect genome-wide genetic variations associated with scale reduction, vibrant skin color, and high growth rate in common carp domestication. We identified numerous novel candidate genes underlie the three agronomically most desirable traits in domesticated common carps, providing potential molecular targets for future genetic improvement in the selective breeding of common carps. We found that independently selective breeding of the same agronomic trait (e.g., fast growing) in common carp domestication could result from completely different genetic variations, indicating the potential advantage of allopolyploid in domestication. We observed that candidate genes associated with scale reduction, vibrant skin color, and/or high growth rate are repeatedly enriched in the immune system, suggesting that domestication of common carps was often accompanied by the disease resistance improvement. Conclusions In common carp domestication, asymmetric subgenome selection is prevalent, while parallel subgenome selection occurs in selective breeding of common carps. This observation is not due to asymmetric gene retention/loss between subgenomes but might be better explained by reduced pleiotropy through transposable element-mediated expression divergence between ohnologs. Our results demonstrate that domestication benefits from polyploidy not only in plants but also in animals.

Observations show that globular clusters (GCs) might be among the best places to find millisecond pulsars (MSPs). However, the GC Terzan 6 seems to be an exception without any pulsar discovered, although its high stellar encounter rate suggests that it harbors dozens of them. We report the discovery of the first radio pulsar, PSR J1750–3116A, likely associated with Terzan 6 in a search of C -band (4–8 GHz) data from the Robert C. Byrd Green Bank Telescope with a spin period of 5.33 ms and dispersion measure (DM) ≃ 383 pc cm ^−3 . The mean flux density of this pulsar is approximately 3 μ Jy. The DM agrees well with predictions from the Galactic free electron density model, assuming a distance of 6.7 kpc for Terzan 6. PSR J1750–3116A is likely an isolated MSP, potentially formed through dynamical interactions, considering the core-collapsed classification and the exceptionally high stellar encounter rate of Terzan 6. This is the highest radio frequency observation that has led to the discovery of a pulsar in a GC to date. While L -band (1–2 GHz) observations of this cluster are unlikely to yield significant returns due to propagation effects, we predict that further pulsar discoveries in Terzan 6 will be made by existing radio telescopes at higher frequencies.

How black holes are formed remains an open and fundamental question in astrophysics. Despite theoretical predictions, it lacks observations to understand whether the black hole formation experiences a supernova explosion. Here we report the discovery of an X-ray shell north of the Galactic microquasar SS 433 harboring a stellar-mass black hole spatially associated with radio continuum and polarization emissions and an H i cloud. Its spectrum can be reproduced by a 1 keV underionized plasma, from which the shell is inferred to have been created by a supernova explosion 20–30 kyr ago, and its properties constitute evidence for canonical supernova explosions to create some black holes. Our analysis precludes other possible origins including heated by jets or blown by disk winds. According to the lower mass limit of the compact object in SS 433, we roughly deduced that the progenitor should be more massive than 25 M _⊙ . The existence of such a young remnant in SS 433 can also lead to new insights into the supercritical accretion in young microquasars and the γ -ray emission of this system. The fallback ejecta may provide accretion materials within tens of thousands of years, while the shock of the supernova remnant may play a crucial role in the cosmic-ray (re)acceleration.

Abstract Tomato mottle mosaic virus (ToMMV) poses a threat to production and quality of tomato fruits. The Tm-2 2 gene confers resistance to some tobamoviruses by recognizing viral movement proteins. However, Tm-2 2 -mediated resistance against ToMMV is not well known. Here, we found that ToMMV could infect wild-type but not Tm-2 2 transgenic Nicotiana benthamiana plants and could also infect tomato cultivar Moneymaker but not resistant cultivar Jili with homozygous Tm-2 2 . Chimeric viral ToMMVToBRFV−MP with swapped ToMMV MP to MP of tomato brown rugose fruit virus could systemically infect Tm-2 2 transgenic N. benthamiana and tomato cultivars Jili plants. Further, transient expression of ToMMV MP in the leaves of Tm-2 2 transgenic N. benthamiana plants induced hypersensitive response-associated cell death, suggesting that the MP of ToMMV was the avirulent factor for the Tm-2 2 resistance gene. ToMMV could infect Tm-2 2 -containing cultivar Jinpeng 1 but not Chaobei. Sequence analysis revealed that cultivars Chaobei and Jinpeng 1 were heterozygous, where Chaobei consists of Tm-2 2 and Tm-2 genes, while Jinpeng 1 consists of Tm-2 2 and tm-2 genes. Transient co-expression assays showed that both Tm-2 2 and Tm-2 but not tm-2 could recognize ToMMV MP and induce hypersensitivity response-associated cell death in N. benthamiana leaves, suggesting that homozygous tomato harboring Tm-2 2 and heterozygous tomato containing Tm-2 2 and Tm-2 may exhibit more durable resistance to ToMMV than heterozygous tomato carrying Tm-2 2 and tm-2. Further, Tm-2 2 transgenic N. benthamiana and tomato cultivar Jili plants with silenced Tm-2 2 gene were susceptible to ToMMV. Also, silencing type-I J-domain MIP1 gene compromised Tm-2 2 -mediated resistance to ToMMV in Tm-2 2 transgenic N. benthamiana and tomato cultivar Jili. Moreover, we found that viral RNA could accumulate in the systemic leaves of Tm-2 2 transgenic N. benthamiana plants and tomato cultivar Jili at 35°C, but not at 20, 25, or 30°C. Altogether, our findings reveal that the Tm-2 2 confers resistance to ToMMV by recognizing MP, and the resistance is regulated by the allele combinations, accumulation levels of Tm-2 2 , MIP1, and the temperature.

Abstract The significance of 5-methylcytosine (m5C) methylation in human malignancies has become an increasing focus of investigation. Here, we show that m5C regulators including writers, readers and erasers, are predominantly upregulated in urothelial carcinoma of the bladder (UCB) derived from Sun Yat-sen University Cancer Center and The Cancer Genome Atlas cohort. In addition, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) as a methyltransferase and Aly/REF export factor (ALYREF) as a nuclear m5C reader, are frequently coexpressed in UCB. By applying patient-derived organoids model and orthotopic xenograft mice model, we demonstrate that ALYREF enhances proliferation and invasion of UCB cells in an m5C-dependent manner. Integration of tanscriptome-wide RNA bisulphite sequencing (BisSeq), RNA-sequencing (RNA-seq) and RNA Immunoprecipitation (RIP)-seq analysis revealed that ALYREF specifically binds to hypermethylated m5C site in RAB, member RAS oncogene family like 6 (RABL6) and thymidine kinase 1 (TK1) mRNA via its K171 domain. ALYREF controls UCB malignancies through promoting hypermethylated RABL6 and TK1 mRNA for splicing and stabilization. Moreover, ALYREF recognizes hypermethylated m5C site of NSUN2, resulting in NSUN2 upregulation in UCB. Clinically, the patients with high coexpression of ALYREF/RABL6/TK1 axis had the poorest overall survival. Our study unveils an m5C dependent cross-regulation between nuclear reader ALYREF and m5C writer NSUN2 in activation of hypermethylated m5C oncogenic RNA through promoting splicing and maintaining stabilization, consequently leading to tumor progression, which provides profound insights into therapeutic strategy for UCB.

While there are over a dozen known neutron star (NS) symbiotic X-ray binaries (SyXBs) in the Galaxy, no SyXBs containing a black hole (BH) have been detected. We address this problem by incorporating binary population synthesis and the accretion properties of BHs fed by the wind from red giant companions. We investigate the impact of different supernova mechanisms, kick velocity distributions, and wind velocities on the formation of both NS and BH SyXBs. Our simulations show that the number of BH SyXBs is at most one-sixth of that of NS SyXBs in the Galaxy provided that the common envelope efficiency parameter α ∼ 0.3–5, and less than ∼10 BH SyXBs could be detectable in X-ray, considering their low radiation efficiencies. These findings indicate a scarcity of BH SyXBs in the Galaxy.

The discrepancies between observations and theoretical predictions of cataclysmic variables (CVs) suggest that there exists unknown angular-momentum-loss mechanism(s) besides magnetic braking and gravitational radiation. Mass loss due to nova eruptions belongs to the most likely candidates. While standard theory assumes that mass is lost in the form of radiation-driven, optically thick wind (fast wind), recent numerical simulations indicate that most of the mass loss is initiated and shaped by binary interaction. We explore the effect of this binary-driven mass loss (BDML) on the CV evolutions assuming a major fraction of the lost mass leaves the system from the outer Lagrangian point. Different from the traditional continuous wind picture, we consider the mass loss process to be instantaneous because the duration of nova eruptions is much shorter than the binary evolutionary timescale. Our detailed binary evolution calculations reveal the following results. (1) BDML seems able to provide extra angular momentum loss below the period gap. The mass transfer rates at a given orbital period occupy a large range, in agreement with the observed secular mass transfer rate distribution in CVs. (2) The enhanced mass transfer rates do not lead to a runaway mass transfer process and allow the white dwarfs to grow mass ≲0.1 M _☉ . (3) BDML can cause both positive and negative variations in the orbital period induced by nova eruptions, in line with observations, and can potentially explain the properties of some peculiar supersoft X-ray sources likely CAL 87, 1E 0035.4−7230, and RX J0537.7−7034.

The existence of a population of low-accretion-rate symbiotic stars (SySts), consisting of a giant star and a compact companion (usually a white dwarf), has been proposed recently. However, their population has not been fully understood. In this work, we present an investigation on SySts candidates consisting of asymptotic giant branch stars (AGBs) by cross-correlating the Gaia DR3, the Galaxy Evolution Explorer All-Sky Imaging Survey, and the 4XMM DR13 catalogs. We first build a sample of AGBs within 500 pc based on their locations in the Gaia color–absolute magnitude diagram. We then explore the UV and X-ray properties of the sampled AGBs and compare them to known SySts and candidates. We find 10 SySts candidates based on the far-ultraviolet excess. The typical UV luminosity of the candidates is 10 ^31 erg s ^−1 , which corresponds to a typical accretion rate of 10 ^−12 –10 ^−11 M _⊙ yr ^−1 , which is more than 1 order of magnitude lower than known SySts. Based on these findings, the total number of SySts within 500 pc is estimated to be 18. The number of AGBs with X-ray flux above 10 ^−14 erg s ^−1 cm ^−2 within 500 pc is estimated to be 37. Our finding implies that a large number of low-accretion-rate SySts are yet to be detected, which provides a base for a complete understanding of their population.

The detection of gravitational wave events has stimulated theoretical modeling of the formation and evolution of double compact objects (DCOs). However, even for the most studied isolated binary evolution channel, there exist large uncertainties in the input parameters and treatments of the binary evolution process. So far, double neutron stars (DNSs) are the only DCOs for which direct observations are available through traditional electromagnetic astronomy. In this work, we adopt a population synthesis method to investigate the formation and evolution of Galactic DNSs. We construct 324 models for the formation of Galactic DNSs, taking into account various possible combinations of critical input parameters and processes such as mass transfer efficiency, supernova type, common envelope efficiency, neutron star kick velocity, and pulsar selection effect. We employ Bayesian analysis to evaluate the adopted models by comparing with observations. We also compare the expected DNS merger rate in the galaxy with that inferred from the known Galactic population of pulsar-neutron star systems. Based on these analyses we derive the favorable range of the aforementioned key parameters.

Magnetars and central compact objects (CCOs) are subgroups of neutron stars that show a number of properties distinguished from canonical radio pulsars. We performed radio observations of three magnetars, SGR 0418+5729, 1E 2259+586, and 4U 0142+61, and a CCO, PSR J1852+0040, with the Five-hundred-meter Aperture Spherical radio Telescope at 1.25 GHz, aiming to search for radio pulsations in their quiescent states. During two observation epochs, no radio pulses have been detected toward any target above a significance of signal-to-noise ratio = 7 from either the direct folding or blind search. We provided the most stringent upper limit of radio flux (≲2–4 μ Jy) for the magnetars and the CCO. For the magnetars with long periods, the real upper limits are likely 1 order of magnitude larger due to the red noise. The deep radio observations suggest that these magnetars and the CCO are indeed radio-quiet sources or unfavorably beamed.

The fallback disk model is widely accepted to explain long-period neutron stars (NSs) that cannot be simulated by magnetic dipole radiation. However, there was no confirmed detection of disks from the newly discovered long-period pulsars GLEAM-X 162759.5-523504.3 and GPM J1839-10 and the slowest known isolated NS 1E 161348-5055. This might be because the disks have either been in a noninteracting/inactive state where their emission is too weak to be detected or have been disrupted. In this work, we conduct simulations to examine the lifetime of supernova fallback disks around isolated NSs. We assume that the disks' mass varies in a self-similar way, and their interaction with the NS occurs only in an interacting/active state. Our results reveal that nearly all the interacting lifetimes for the disks are shorter than 10 ^5 yr, while the existence lifetimes are considerably longer.

Magnetic braking (MB) plays an important role in the evolution of close low-mass X-ray binaries (LMXBs). It is also essential to the formation of ultracompact X-ray binaries (UCXBs). There have been lively investigations on the MB mechanism(s) in both single stars and close binaries including cataclysmic variables and neutron star (NS) LMXBs but with diverse conclusions. In this paper we explore the effect of MB on the black hole (BH) LMXB evolution. We combine binary population synthesis with detailed binary evolution to obtain the expected properties of the Galactic BH LMXB population. The simulated results are compared with the observational data including the BH mass, companion mass, companion temperature, orbital period, and mean accretion rate. Our results reveal that the MB laws with relatively low efficiency (i.e., RM12 and RVJ83) exhibit better agreement with observations, contrary to what was found for NS LMXBs. This raises the interesting question about whether MB really follows the same unified law in different types of binaries. We also predict that only a very small fraction (≲2.5%) of BH LMXBs can evolve to be UCXBs. This explains why no BH UCXB has been discovered so far.

IC 10 X-1 is one of the close X-ray binaries containing a Wolf–Rayet donor, which can provide an evolutionary link between high-mass X-ray binaries and gravitational wave sources. It is still unclear about the precise nature of the accreting compact object in IC 10 X-1, although it looks more like a black hole (BH) than a neutron star. In this work, we use a binary population synthesis method to simulate the formation of IC 10 X-1–like binaries by assuming different common-envelope ejection efficiencies. This work represents a big step forward over previous studies since we adopt new criteria for mass-transfer stability. These criteria allow the formation of IC 10 X-1–like systems without experiencing common envelope evolution. Based on our calculations, we propose that the compact object in IC 10 X-1 is a BH with a mass of ∼10–30 M _⊙ and the progenitor evolution of this binary probably just experienced stable mass transfer.

Swift J1858.6−0814 (hereafter J1858) is a transient neutron star (NS) low-mass X-ray binary (LMXB). There is controversy regarding its donor mass derived from observations and theoretical calculations. In this paper, we adopt seven magnetic braking (MB) prescriptions suggested in the literature and different metallicity Z to simulate the evolution of the LMXB. Our results show that, employing the MB model proposed by A. Reiners & S. Mohanty (“rm12”), the convection- and rotation-boosted (“carb”) model, and the intermediate (“inter”) and convection-boosted (“cboost”) models in K. X. Van et al. can match (part of) the observational parameters of J1858 well. We then apply our method to other observed LMXBs and find that the “rm12” and “inter” MB laws are most promising in explaining transient LMXBs. In comparison, the simulations with the “cboost” and “carb” MB laws are more inclined to reproduce persistent LMXBs and ultracompact X-ray binaries, respectively. Our results, though subject to computational and/or observational bias, show that it is challenging to find a unified MB law that applies to the NS LMXB subpopulations simultaneously, indicating our lack of understanding of the true MB law. In addition, we explore the influence of various MB laws on the magnitude of the bifurcation periods in LMXBs.

Several pulsars with unusually long periods were discovered recently, comprising a potential population of ultralong period pulsars (ULPPs). The origin of their long periodicity is not well understood, but may be related to magnetars spun down by surrounding fallback disks. While there are few systematic investigations on the fallback-disk-assisted evolution of magnetars, instability in the disk has received little attention, which determines the lifetime of the disk. In this work we simulate the evolution of the magnetic field, spin period, and magnetic inclination angle of magnetars with a supernova fallback disk. We find that a thermal viscous instability in the disk could significantly affect the formation of ULPPs. Our simulation results also reveal that a large fraction of ULPPs seem to be nearly aligned and orthogonal rotators. This might help place ULPPs above the death line in the pulse period–period derivative plane. However, some extra mechanisms seem to be required to account for the radio emission of ULPPs.

The Galactic magnetar SGR J1935+2154 has undergone another outburst since 2022 October 10. We present the results of searching for an optical/near-infrared (NIR) counterpart of SGR J1935+2154 before and during this outburst. No counterpart was detected at the magnetar’s position in $r^{\prime} $ and $z^{\prime} $ bands, providing stringent upper limits of $r^{\prime} \gtrsim 28.65$ and $z^{\prime} \gtrsim 26.27$ . Using archival X-ray data from NICER, we investigated the properties of the bursts and the spectral evolution of persistent emission. The burst flux F showed a power-law distribution of N ∝ F ^−0.76±0.10 for flux ≳2.6 × 10 ^−9 erg cm ^−2 s ^−1 , while the temperature and radius followed a log-normal distribution with ${kT}={1.63}_{-0.50}^{+0.73}\ \mathrm{keV}$ and ${R}_{\mathrm{bb}}={4.35}_{-1.35}^{+1.95}\ \mathrm{km}$ , respectively. The persistent flux evolution experienced a quick decay and an enhancement ∼27 days after the Burst Alert Telescope trigger. Using the NIR and X-ray emission, together with the Gran Telescopio Canarias optical/NIR upper limits, we discussed the origin of the NIR emission from the magnetar based on the fallback disk model and magnetosphere model. We found that either model cannot be ruled out with currently available data. Further mid-infrared observations are needed to find out the mechanism for producing the NIR emission from SGR J1935+2154.

Abstract Background Threats of antimicrobial resistance (AMR) to human health are on the rise worldwide. Airborne fine particulate matter (PM2.5), especially those emitted from hospitals, could serve as a substantial yet lesser-known environmental medium of inhalable antibiotic resistomes. A genome-centric understanding of the hosting bacterial taxa, mobility potential, and consequent risks of the resistomes is needed to reveal the health relevance of PM2.5-associated AMR from clinical settings. Results Compared to urban ambient air PM2.5, the hospital samples harbored nearly twice the abundance of antibiotic resistantance genes (ARGs, ~ 0.2 log10(ARGs/16S rRNA gene)) in the summer and winter sampled. The profiled resistome was closely correlated with the human-source-influenced (~ 30% of the contribution) bacterial community (Procrustes test, P < 0.001), reflecting the potential antibiotic-resistant bacteria (PARB), such as the human commensals Staphylococcus spp. and Corynebacterium spp. Despite the reduced abundance and diversity of the assembled metagenomes from summer to winter, the high horizontal transfer potential of ARGs, such as the clinically relevant bla OXA and bacA, in the human virulent PARB remained unaffected in the hospital air PM samples. The occurring patterns of β-lactam resistance genes and their hosting genomes in the studied hospital-emitting PM2.5 were closely related to the in-ward β-lactam-resistant infections (SEM, std = 0.62, P < 0.01). Featured with more abundant potentially virulent PARB (2.89 genome copies/m3-air), the hospital samples had significantly higher resistome risk index scores than the urban ambient air samples, indicating that daily human exposure to virulent PARB via the inhalation of PM2.5 was ten times greater than from the ingestion of drinking water. Conclusions The significance of AMR in the studied hospital-emitting PM2.5 was highlighted by the greater abundance of ARGs, the prevalence of potentially virulent PARB, and the close association with hospital in-ward β-lactam infections. A larger-scale multi-source comparison of genome-resolved antibiotic resistomes is needed to provide a more holistic understanding to evaluate the importance of airborne AMR from the “One-Health” perspective. Video Abstract

Tomato mottle mosaic virus (ToMMV), an economically important species of the genus Tobamovirus, causes significant loss in yield and quality of tomato fruits. Here, we identified the Shandong isolate of ToMMV (ToMMV-SD) collected from symptomatic tomato fruits in Weifang, Shandong Province of China. ToMMV-SD caused symptoms such as severe mosaic, mottling, and necrosis of tomato leaves, yellow spot and necrotic lesions on tomato fruits. The obtained full genome of ToMMV-SD was 6 399 nucleotides (accession number MW373515) and had the highest identity of 99.5% with that of isolate SC13-051 from the United States of America at the genomic level. The infectious clone of ToMMV-SD was constructed and induced clear mosaic and necrotic symptoms onto Nicotiana benthamiana leaves. Several commercial tomato cultivars, harboring Tm-22 resistance gene, and pepper cultivars, containing L resistance gene, were susceptible to ToMMV-SD. Plants of Solanum melongena (eggplant) and Brassica pekinensis (napa cabbage) showed mottling symptoms, while N. tabacum cv. Zhongyan 100 displayed latent infection. ToMMV-SD did not infect plants of N. tabacum cv. Xanthi NN, Brassica rapa ssp. chinensis (bok choy), Raphanus sativus (radish), Vigna unguiculata cv. Yuanzhong 28-2 (cowpea), or Tm-22 transgenic N. benthamiana. A quintuplex RT-PCR system differentiated ToMMV from tomato mosaic virus, tomato brown rugose fruit virus, tobacco mosaic virus, and tomato spotted wilt virus, with the threshold amount of 0.02 pg. These results highlight the threat posed by ToMMV to tomato and pepper cultivation and offer an efficient detection system for the simultaneous detection of four tobamoviruses and tomato spotted wilt virus infecting tomato plants in the field.

Potyviruses move to neighboring cells in the form of virus particles or a coat protein (CP)-containing ribonucleoprotein complex. However, the precise roles of RNA-binding residues in potyviral CP in viral cell-to-cell movement remain to be elucidated. In this study, we predicted the three-dimensional model of tobacco vein banding mosaic virus (TVBMV)-encoded CP and found nine residues presumably located in the CP RNA-binding pocket. Substitutions of the two basic residues at positions 192 and 225 (R(^192) and K(^225)) with either alanine, cysteine, or glutamic acid abolished TVBMV cell-to-cell and systemic movement in Nicotiana benthamiana plants. These substitutions also reduced the replication of the mutant viruses. Results from the electrophoretic mobility shift assay showed that the RNA-binding activity of mutant CPs derived from R(^192) or K(^225) substitutions was significantly lower than that of wild-type CP. Analysis of purified virus particles showed that mutant viruses with R(^192) or K(^225) substitutions formed RNA-free virus-like particles. Mutations of R(^192) and K(^225) did not change the CP plasmodesmata localization. The wild-type TVBMV CP could rescue the deficient cell-to-cell movement of mutant viruses. Moreover, deletion of any of the other seven residues also abolished TVBMV cell-to-cell movement and reduced the CP RNA-binding activity. The corresponding nine residues in watermelon mosaic virus CP were also found to play essential roles in virus cell-to-cell movement. In conclusion, residues R(^192) and K(^225) in the CP RNA-binding pocket are critical for viral RNA binding and affect both virus replication and cell-to-cell movement.

Tomato brown rugose fruit virus (ToBRFV) is a novel tobamovirus firstly reported in 2015 and poses a severe threat to the tomato industry. So far, it has spread to 10 countries in America, Asia, and Europe. In 2019, ToBRFV was identified in Shandong Province (ToBRFV-SD), China. In this study, it was shown that ToBRFV-SD induced mild to severe mosaic and blistering on leaves, necrosis on sepals and pedicles, and deformation, yellow spots, and brown rugose necrotic lesions on fruits. ToBRFV-SD induced distinct symptoms on plants of tomato, Capsicum annumm, and Nicotiana benthamiana, and caused latent infection on plants of Solanum tuberosum, Solanum melongena, and N. tabacum cv. Zhongyan 102. All the 50 tomato cultivars tested were highly sensitive to ToBRFV-SD. The complete genomic sequence of ToBRFV-SD shared the highest nucleotide and amino acid identities with isolate IL from Israel. In the phylogenetic tree constructed with the complete genomic sequence, all the ToBRFV isolates were clustered together and formed a sister branch with tobacco mosaic virus (TMV). Furthermore, a quadruplex RT-PCR system was developed that could differentiate ToBRFV from other economically important viruses affecting tomatoes, such as TMV, tomato mosaic virus, and tomato spotted wilt virus. The findings of this study enhance our understanding of the biological and molecular characteristics of ToBRFV and provide an efficient and effective detection method for multiple infections, which is helpful in the management of ToBRFV.

Abstract Coat protein (CP) is required for potyviruses to move and establish a systemic infection in plants. π-stackings formed by aromatic residues play critical roles in maintaining protein stability and functions. As we know, many aromatic residues located in the core region of potyvirus CPs are conserved. However, their roles in potyvirus infection remain largely unknown. Here, through analysis of the three-dimensional model of the tobacco vein banding mosaic virus (TVBMV; genus Potyvirus) CP, 16 aromatic residues were predicated to form π-stackings. The results of transient expression experiments demonstrated that deletion of any of these 16 aromatic residues reduced CP accumulation. Infectivity assays showed that deletion of any of these aromatic residues in the TVBMV infectious clone abolished cell-to-cell movement and reduced replication of the virus. Substitution of Y105 and Y147 individually with non-aromatic residues alanine or glycine reduced CP accumulation, virus replication, and abolished the ability of TVBMV to move intercellularly, while substitution of these two residues individually with aromatic residues phenylalanine or tryptophan, had no or little effect on CP accumulation and TVBMV systemic movement and replication. Similar results were obtained from the CP mutants of watermelon mosaic virus (WMV, genus Potyvirus). Taken together, our results demonstrate that multiple aromatic residues in CP are involved in potyvirus movement by forming π-stackings to maintain CP accumulation.

Job’s tears, also known as adlay, is a valuable plant that has commonly been used in traditional Chinese medicine, as well as an edible food. Due to the lack of knowledge of its genetics and gaps in its evolutionary analysis, breeding of adlay has been hindered. Here, we report five complete chloroplast genomes of various species and varieties in the genus by Illumina sequencing, while their genome structure, comparative analysis, and phylogenetic relationships were conducted. Genome sizes ranged from 140,860 to 140,864 bp in length, GC contents were 38.43%, and genome architecture was of a typical quadripartite structure. We annotated 82～83 protein-coding genes and 46～47 non-coding RNA genes in each genome and they functionally associated with self-replication, photosynthesis, cytochrome synthesis and other unknown functions. Three codons that encoded tryptophan, arginine and leucine were used frequently at rates of 41.42, 37.98, and 32.28% respectively. The preferred codons consistently ended with A or T. A total of 146 simple sequence repeats (SSR), 9 insertions and deletions (InDels) and 143 single nucleotide polymorphisms (SNPs) were observed among genomes. The InDel and SNP variations were mostly distributed in intergenic regions. It confirmed that Coix, Sorghum, Saccharum, Zea, Tripsacum and Saccharum were closely genera and the genetic distance of Sorghum to Coix was closer than Zea to Coix. These results give us more insight into the evolution of Coix in a wide range of evolutionary studies.

Smut is a serious disease in Job's tears, also known as adlay, and contributes to the reduction of crop yield in agricultural fields. In this study, the key pathogenic fungi in adlay smut disease were first identified by internal transcribed spacer region (ITS) high-throughput sequencing and then used to elucidate the composition and diversity of the fungal community in adlay smut. Results indicate that an abundance of operational taxonomic units (OTUs) were detected in the infected involucres of flowering plants and the OTUs were classified to nine phyla, 20 classes, 45 orders, 90 families and 119 genera. A total of 4 986 OTUs clustered together, sharing six core OTUs in all samples, while 145 OTUs were shared among four geographical groups. The Shannon and Simpson indices ranged from 0.137–1.629 and 0.357–0.970, respectively. Community diversity ranked as Anshun (AS)>Qinglong (QL)>Xingren (XR)>Xingyi (XY) among the four geographical groups by Shannon and Simpson indices, exhibiting complex community diversities among accessions and geographical groups. The richness and diversity data imply a weak relationship between the accession community richness and geographical origins of samples. Two closely related fungal genera, Sporisorium and Ustilago, were implicated as causes of smut disease. The genus Sporisorium appears to be more commonly found among accessions and thus is more likely to be the fungal pathogen causing smut in adlay. This work can facilitate strategies to control and prevent smut infection to improve adlay yield.

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.

Sugarcane mosaic virus (SCMV; genus Potyvirus) induces maize dwarf mosaic disease that has caused serious yield losses of maize in China. Cross-protection is one of the efficient strategies to fight against severe virus strains. Although many mild strains have been identified, the spontaneous mutation is one of the challenging problems affecting their application in cross-protection. In this study, we found that the substitution of cysteine (C) at positions 57 or 60 in the zinc finger-like motif of HC-Pro with alanine (A; C57A or C60A) significantly reduced its RNA silencing suppression activity and SCMV virulence. To reduce the risk of mild strains mutating to virulent ones by reverse or complementary mutations, we obtained attenuated SCMV mutants with double-mutations in the zinc finger-like and FRNK motifs of HC-Pro and evaluated their potential application in cross-protection. The results showed that the maize plants infected with FKNK/C60A double-mutant showed symptomless until 95 days post-inoculation and FKNK/C60A cross-protected plants displayed high resistance to severe SCMV strain. This study provides theoretical and material bases for the control of SCMV through cross-protection.

Recent discoveries of gravitational wave (GW) events most likely originating from black hole (BH) + neutron star (NS) mergers reveal the existence of BH+NS binaries. The formation of BH+NS binaries and their merger rates through isolated binary evolution have been investigated extensively with population synthesis simulations. A detailed stellar evolution modeling of the formation of this population, however, is missing from the literature. In this work, we create the first complete 1D model of more than 30 BH+NS progenitor systems, which are calculated self-consistently until collapse of the iron core with infall velocity exceeding 1000 km s ^−1 . Focusing on the progenitors of BH–NS GW sources, we apply the MESA code starting from a post-common-envelope binary with short orbital period (

Neutron stars (NSs) play essential roles in modern astrophysics. The magnetic fields and spin periods of newborn (zero-age) NSs have a large impact on the further evolution of NSs, which are, however, poorly explored in observations due to the difficulty of finding newborn NSs. In this work, we aim to infer the magnetic fields and spin periods ( B _i and P _i ) of zero-age NSs from the observed properties of the NS population. We select nonaccreting NSs whose evolution is solely determined by magnetic dipole radiation. We find that both B _i and P _i can be described by lognormal distribution, and the fitting sensitively depends on our parameters.

It is widely accepted that quite a number of double compact objects (DCOs) in the Milky Way can be identified by future space-based gravitational wave (GW) detectors, while systematic investigations on the detection of the GW sources in nearby galaxies are still lacking. In this paper, we present calculations of potential populations of GW sources for all types of DCOs in the Local Group galaxy M31. For M31, we use an age-dependent model for the evolution of the metallicity and the star formation rate. By varying assumptions of common-envelope ejection efficiencies and supernova-explosion mechanisms during binary evolution, we make predictions on the properties of DCOs that can be detected by the Laser Interferometer Space Antenna (LISA). Our calculations indicate that a few (a dozen) DCOs are likely to be observed by LISA during its 4 (10) yr mission. We expect that the sources with black hole components are more likely to be first identified during a 4 yr mission since these binaries have relatively large chirp masses, while the systems with white-dwarf components dominate the overall population of detectable GW sources during a 10 yr mission. LISA can only detect very tight fast-merging systems in M31, corresponding to the peak of orbital period distribution from ∼2 minutes for double white dwarfs to ∼20 minutes for double black holes.

The magnetic inclination angle χ , namely the angle between the spin and magnetic axes of a neutron star, plays a vital role in its observational characteristics. However, there are few systematic investigations of its long-term evolution, especially for accreting NSs in binary systems. Applying the model of Biryukov & Abolmasov and the binary evolution code MESA, we simultaneously simulate the evolution of the accretion rate, spin period, magnetic field, and magnetic inclination angle of accreting NSs in intermediate/low X-ray binaries. We show that the evolution of χ depends not only on the initial parameters of the binary systems, but also on the mass transfer history and the efficiency of pulsar loss. Based on the calculated results we present the characteristic distribution of χ for various types of systems including ultracompact X-ray binaries, binary millisecond pulsars, and ultraluminous X-ray sources, and discuss their possible observational implications.

We introduce the New-ANGELS program, an XMM-Newton survey of a ∼7.2 deg ^2 area around M31, which aims to study the X-ray populations in the M31 disk and the X-ray-emitting hot gas in the inner halo of M31 up to 30 kpc. In this first paper, we report the catalog of 4506 detected X-ray sources and attempt to cross-identify or roughly classify them. We identify 352 single stars in the foreground, 35 globular clusters, and 27 supernova remnants associated with M31, as well as 62 active galactic nuclei, 59 galaxies, and one galaxy cluster in the background. We uniquely classify 236 foreground stars and 17 supersoft sources based on their X-ray colors. X-ray binaries (83 low-mass and one high-mass) are classified based on their X-ray colors and X-ray variabilities. The remaining X-ray sources either have too low signal-to-noise ratios to calculate their X-ray colors or do not have a unique classification, so are regarded as unclassified. The X-ray source catalog is published online. Studies of the X-ray source populations and the contribution of X-ray sources in the unresolved X-ray emissions based on this catalog will be published in companion papers.

Observations of elliptical galaxies suggest that black holes (BHs) might serve as dark energy candidates, coupled to the expansion of the Universe. According to this hypothesis, the mass of a BH could increase as the Universe expands. BH low-mass X-ray binaries (LMXBs) in the Galactic disk were born several gigayears ago, making the coupling effect potentially significant. In this work, we calculate the evolution of BH binaries with a binary population synthesis method to examine the possible influence of cosmologically coupled growth of BHs, if it really exists. The measured masses of the compact objects in LMXBs show a gap around ∼2.5–5 M _⊙ , separating the most-massive neutron stars from the least-massive BHs. Our calculated results indicate that considering the mass growth seems to (partially) account for the mass gap and the formation of compact BH LMXBs, alleviating the challenges in modeling the formation and evolution of BH LMXBs with traditional theory. However, critical observational evidence like the detection of intermediate-mass BH binaries is required to test this hypothesis.

Long term mining activities can cause significant metal pollution in the environment, thereby showing potential risk to the paddy field. Elucidating the interfacial processes of trace metals from contaminated paddy soil to rice within the rhizosphere can provide important information on metal biogeochemistry and food safety. The current study aims to explore the spatial distribution and molecular speciation of Cu from rhizosphere to rice plant in a mining-impacted paddy soil, and reveal the possible uptake mechanisms. X-ray absorption near edge structure (XANES) analysis indicated that Cu was primarily associated with iron oxide and sulfide in soil with a minor proportion of organic complexed species. In the rice samples, Cu showed much higher concentrations in the roots than the shoots, as most Cu was sequestered in the root surface and epidermis (primarily in the form of C/N ligands bound Cu species), rather than root xylem, as identified by micro X-ray fluorescence (μ-XRF) imaging coupling with μ-XANES. By contrast, in the root xylem, thiol-S bound Cu(I) complex was observed, representing the reduced product of Cu(II) by thiol-S ligands in rice root. The absorbed Cu was probably transported from the root to the aerial part as C/N ligand bound Cu complex such as Cu-histidine like species, which was observed in the root xylem. The large retention capacity and reduction of Cu(II) in rice root alleviated Cu toxicity to rice, which was beneficial for food safety (e.g., lower concentration of Cu in rice grains). These findings showed for the first time that the uptake mechanisms by rice from field contaminated sites, which shed light on Cu detoxification process and potential remediation strategies. Keywords: Speciation and mobilization, Paddy soil, Heavy metal remediation, Tolerance and detoxification, Synchrotron-based X-ray absorption spectroscopy

This paper evaluates a novel sorbent for the removal of potentially toxic elements, inherent cations, and hetero-chloride from hydraulic fracturing wastewater (FWW). A series of iron-biochar (Fe-BC) composites with different Fe/BC impregnation mass ratios (0.5:1, 1:1, and 2:1) were prepared by mixing forestry wood waste-derived BC powder with an aqueous FeCl3 solution and subsequently pyrolyzing them at 1000 °C in a N2-purged tubular furnace. The porosity, surface morphology, crystalline structure, and interfacial chemical behavior of the Fe-BC composites were characterized, revealing that Fe chelated with CO bonds as COFe moieties on the BC surface, which were subsequently reduced to a CC bond and nanoscale zerovalent Fe (nZVI) during pyrolysis. The performance of the Fe-BC composites was evaluated for simultaneous removal of potentially toxic elements (Cu(II), Cr(VI), Zn(II), and As(V)), inherent cations (K, Na, Ca, Mg, Ba, and Sr), hetero-chloride (1,1,2-trichlorethane (1,1,2-TCA)), and total organic carbon (TOC) from high-salinity (233 g L−1 total dissolved solids (TDS)) model FWW. By elucidating the removal mechanisms of different contaminants, we demonstrated that Fe-BC (1:1) had an optimal reducing/charge-transfer reactivity owing to the homogenous distribution of nZVI with the highest Fe0/Fe2+ ratio. A lower Fe content in Fe-BC (0.5:1) resulted in a rapid exhaustion of Fe0, while a higher Fe content in Fe-BC (2:1) caused severe aggregation and oxidization of Fe0, contributing to its complexation/(co-)precipitation with Fe2+/Fe3+. All of the synthesized Fe-BC composites exhibited a high removal capacity for inherent cations (3.2–7.2 g g−1) in FWW through bridging with the CO bonds and cation-π interactions. Overall, this study illustrated the potential efficacy and mechanistic roles of Fe-BC composites for (pre-)treatment of high-salinity and complex FWW. Keywords: Engineered biochar, Mineral-carbon composites, Metals/metalloids, Fracturing wastewater treatment, Sustainable remediation

Cross-protection is a promising measure to control plant viral diseases. Reverse genetics had been recently adopted to generate attenuated mutants that have potential in cross-protection. But studies on the variability of the progeny viruses of the attenuated mutants are scarce. Sugarcane mosaic virus (SCMV; genus Potyvirus, family Potyviridae) is the prevalent virus inducing maize dwarf mosaic disease in China. Here, we showed that the substitution of arginine with isoleucine in the FRNK motif at position 184 of helper component-proteinase (HC-Pro) abolished its RNA silencing suppression (RSS) activity, drastically reduced the virulence and accumulation level of SCMV, and impaired the synergism between SCMV and maize chlorotic mottle virus. The attenuated mutant could protect maize plants from a severe infection of SCMV. However, a spontaneous mutation of glycine at position 440 to arginine in HC-Pro rescued the virulence and synergism with maize chlorotic mottle virus of SCMV and the RSS activity of HC-Pro. Similar results were obtained with tobacco vein banding mosaic virus and watermelon mosaic virus. These results provide novel evidence for the complementary mutation of potyviruses in maintaining the HC-Pro RSS activity and potyviral virulence and remind us of evaluating the potential risk of attenuated mutants thoroughly before applying for the control of plant viral diseases via cross-protection.

Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.

Apoptotic lymphocytes can induce specific immune tolerance. This study aimed to investigate the influence of the preoperative transfusion of apoptotic lymphocytes on allograft survival after skin transplantation. In addition, we aimed to determine changes in IL-4, IL-10 and IFN-γ mRNA expression in the grafted skin. A total of 20 New Zealand white rabbits were randomly divided into two groups: lymphocyte preconditioned group (n = 10) and control group (n = 10). Rabbits in the lymphocyte preconditioned group were intravenously injected with 60Co γ-treated donor lymphocytes at seven days before the surgery. Rabbits in the control group were intravenously injected with normal lymphocytes at seven days before skin transplantation. The mRNA expression of IL-4, IL-10 and IFN-γ in the grafted skin was determined using real-time PCR. Skin allograft rejection time was 72.63 ± 2.65 days in the lymphocyte preconditioned group and 6.52 ± 0.64 days in the control group. IL-4, IL-10 and IFN-γ mRNA expression in the skin graft was 4.32 ± 0.48, 7.86 ± 0.56 and 2.63 ± 0.25 respectively in the lymphocyte preconditioned group, and 0.58 ± 0.07, 0.91 ± 0.14 and 8.68 ± 1.23 respectively in the control group. The preoperative transfusion of apoptotic lymphocytes induced immune tolerance in the grafted skin, as demonstrated by longer survival time of the grafts before rejection. This coincided with the increased mRNA expression of IL-4 and IL-10, and the decreased expression of IFN-γ. Keywords: Apoptotic lymphocytes, Skin transplantation, Immune tolerance, Cytokines

Background: The protection of endothelial cells (ECs) against reperfusion injury has received little attention. In this study, we used Tandem Mass Tag (TMT) labeling proteomics to investigate the modulated proteins in an in vitro model of cardiac microvascular endothelial cells (CMECs) subjected to ischemia/reperfusion (I/R) injury and their alteration by traditional Chinese medicine Tongxinluo (TXL). Methods: Human CMECs were subjected to 2 h of hypoxia followed by 2 h of reoxygenation with different concentrations of TXL Protein expression profiles of CMECs were determined using tandem mass spectrometry. We evaluated several proteins with altered expression in I/R injury and summarized some reported proteins related to I/R injury. Results: TXL dose-dependently decreased CMEC apoptosis, and the optimal concentration was 800 µg/mL. I/R significantly altered proteins in CMECs, and 30 different proteins were detected between a normal group and a hypoxia and serum deprivation group. In I/R injury, TXL treatment up-regulated 6 types of proteins including acyl-coenzyme A synthetase ACSM2B mitochondrial (ACSM2B), cyclin-dependent kinase inhibitor 1B (CDKN1B), heme oxygenase 1 (HMOX1), transcription factor SOX-17 (SOX17), sequestosome-1 isoform 1 (SQSTM1), and TBC1 domain family member 10B (TBC1D10B). Also, TXL down-regulated 5 proteins including angiopoietin-2 isoform c precursor (ANGPT2), cytochrome c oxidase assembly factor 5 (COA5), connective tissue growth factor precursor (CTGF), cathepsin L1 isoform 2 (CTSL), and eukaryotic elongation factor 2 kinase (LOC101930123). These types of proteins mainly had vital functions, including cell proliferation, stress response, and regulation of metabolic process. Conclusions: The study presented differential proteins upon I/R injury through a proteomic analysis. TXL modulated the expression of proteins in CMECs and has a protective role in response to I/R.

Young pulsars are thought to be highly magnetized neutron stars (NSs). The crustal magnetic field of a NS usually decays at different timescales in the forms of Hall drift and Ohmic dissipation. The magnetization parameter ω B τ is defined as the ratio of the Ohmic timescale τ O h m to the Hall drift timescale τ H a l l . During the first several million years, the inner temperature of the newly born neutron star cools from T = 10 9 K to T = 1.0 × 10 8 K, and the crustal conductivity increases by three orders of magnitude. In this work, we adopt a unified equations of state for cold non-accreting neutron stars with the Hartree–Fock–Bogoliubov method, developed by Pearson et al. (2018), and choose two fiducial dipole magnetic fields of B = 1.0 × 10 13 G and B = 1.0 × 10 14 G, four different temperatures, T, and two different impurity concentration parameters, Q, and then calculate the conductivity of the inner crust of NSs and give a general expression of magnetization parameter for young pulsars: ω B τ ≃ ( 1 − 50 ) B 0 / ( 10 13 G) by using numerical simulations. It was found when B ≤ 10 15 G, due to the quantum effects, the conductivity increases slightly with the increase in the magnetic field, the enhanced magnetic field has a small effect on the matter in the low-density regions of the crust, and almost has no influence the matter in the high-density regions. Then, we apply the general expression of the magnetization parameter to the high braking-index pulsar PSR J1640-4631. By combining the observed arrival time parameters of PSR J1640-4631 with the magnetic induction equation, we estimated the initial rotation period P 0 , the initial dipole magnetic field B 0 , the Ohm dissipation timescale τ O h m and Hall drift timescale τ H a l l . We model the magnetic field evolution and the braking-index evolution of the pulsar and compare the results with its observations. It is expected that the results of this paper can be applied to more young pulsars.

Background/Aims: Poor viability of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Globular adiponectin (gAPN) exerts anti-apoptotic effects on several types of stem cells. Herein, we investigated the effect of gAPN on the MSCs against apoptosis induced by hypoxia and serum deprivation (H/SD). Methods: MSCs exposed to H/SD conditions were treated with different concentrations of gAPN. To identify the main type of receptor, MSCs were transfected with siRNA targeting adiponectin receptor 1 or 2 (AdipoR1 or AdipoR2). To elucidate the downstream pathway, MSCs were pre-incubated with AMPK inhibitor Compound C. Apoptosis, caspase-3 activity and mitochondrial membrane potential were evaluated. Results: H/SD-induced MSCs apoptosis and caspase-3 activation were attenuated by gAPN in a concentration-dependent manner. gAPN increased Bcl-2 and decreased Bax expressions. The loss of mitochondrial membrane potential induced by H/SD was also abolished by gAPN. The protective effect of gAPN was significantly attenuated after the knockdown of AdipoR1 rather than AdipoR2. Moreover, Compound C partly suppressed the anti-apoptotic effect of gAPN. Conclusions: gAPN inhibits H/SD-induced apoptosis in MSCs via AdipoR1-mediated pathway, possibly linked to the activation of AMPK. gAPN may be a novel survival factor for MSCs in the ischemic engraftment environment.