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Abstract Mutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome. In contrast, prostate tumors with high pSHP2 and pACK1 activity exhibited progressive downregulation of pY54-H3 levels and higher AR expression that correlated with disease severity. Overall, pSHP2/pY54-H3 signaling acts as a sentinel of AR homeostasis, explaining not only growth retardation, genital abnormalities and infertility among NSML patients, but also significant AR upregulation in prostate cancer patients.

The Lobster Eye Imager for Astronomy (LEIA) is the pathfinder of the wide-field X-ray telescope used in the Einstein Probe mission. In this study, we present an image of the Virgo Cluster taken by LEIA in the 0.5–4.5 keV band with an exposure time of ∼17.3 ks in the central region. This extended emission is generally consistent with the results obtained by ROSAT. However, the field is affected by bright point sources due to the instrument’s Point Spread Function (PSF) effect. Through fitting of the LEIA spectrum of the Virgo Cluster, we obtained a temperature of 2.1−0.1+0.3 keV, which is consistent with the XMM-Newton results (∼2.3 keV). Above 1.6 keV, the spectrum is dominated by the X-ray background. In summary, this study validates LEIA’s extended source imaging and spectral resolution capabilities for the first time.

The early afterglow of a gamma-ray burst (GRB) can provide critical information on the jet and progenitor of the GRB. The extreme brightness of GRB 221009A allows us to probe its early afterglow in unprecedented detail. In this Letter, we report comprehensive observation results of the early afterglow of GRB 221009A (from T _0 +660 s to T _0 +1860 s, where T _0 is the Insight-HXMT/HE trigger time) in X-ray/gamma-ray energy band (from 20 keV to 20 MeV) by Insight-HXMT High Energy X-ray Telescope, GECAM-C, and Fermi/Gamma-ray Burst Monitor. We find that the spectrum of the early afterglow in 20 keV–20 MeV can be well described by a cutoff power law with an extra power law that dominates the low- and high-energy bands, respectively. The cutoff power law E _peak is ∼30 keV, and the power-law photon index is ∼1.8 throughout the early afterglow phase. By fitting the light curves in different energy bands, we find that a significant achromatic break (from keV to TeV) is required at T _0 + ${1246}_{-26}^{+27}$ s (i.e., 1021 s since the afterglow starting time T _AG = T _0 +225 s), providing compelling evidence of a jet break. Interestingly, both the pre-break and post-break decay slopes vary with energy, and these two slopes become closer in the lower energy band, making the break less identifiable. Intriguingly, the spectrum of the early afterglow experienced a slight hardening before the break and a softening after the break. These results provide new insights into the physics of this remarkable GRB.

The power density spectrum (PDS) is a powerful tool to study light curves of gamma-ray bursts (GRBs). We show the average PDS and individual PDS analysis with GRB data from the Hard X-ray Modulation Telescope (also named Insight-HXMT). The values of the power-law index of the average PDS ( ${\alpha }_{\bar{P}}$ ) for long GRBs (LGRBs) vary from 1.58 to 1.29 (for 100–245, 245–600, and 600–2000 keV). The Insight-HXMT data allow us to extend the energy of the LGRBs up to 2000 keV, and a relation between ${\alpha }_{\bar{P}}$ and energy E is obtained: ${\alpha }_{\bar{P}}\propto {E}^{-0.09}$ (8–2000 keV). We first systematically investigate the average PDS and individual PDSs for short GRBs (SGRBs), and obtain ${\alpha }_{\bar{P}}\propto {E}^{-0.07}$ (8–1000 keV), where the values of ${\alpha }_{\bar{P}}$ vary from 1.86 to 1.34. The distribution of the power-law index of an individual PDS ( α ) of an SGRB is consistent with that of an LGRB, and the α value for the group with a dominant timescale (the bent power law) is higher than that for the group with no dominant timescale (the single power law). Both LGRBs and SGRBs show similar α and ${\alpha }_{\bar{P}}$ , which indicates that they may be the result of similar stochastic processes. Typical values of the dominant timescale τ for LGRBs and SGRBs are 1.58 s and 0.02 s, respectively. It seems that τ varies in proportion to the duration of GRBs T _90 , with a relation $\tau \propto {T}_{90}^{0.86}$ . The GRB light curve may result from superposing a number of pulses with different timescales. No periodic or quasi-periodic signal above the 3 σ significance threshold is found in our sample.

The milestone discovery of GW170817-GRB 170817A-AT 2017gfo has shown that gravitational waves (GWs) could be produced during the merger of a neutron star–neutron star/black hole and that in electromagnetic (EM) waves, a gamma-ray burst (GRB) and a kilonova (KN) are generated in sequence after the merger. Observationally, however, EM properties before the merger phase are still unclear. Here we report a peculiar precursor in a KN-associated long-duration GRB 211211A, providing evidence of the EM before the merger. This precursor lasts ∼0.2 s, and the waiting time between the precursor and the main burst is ∼1 s, comparable to that between GW170817 and GRB 170817A. The spectrum of the precursor could be well fit with a nonthermal cutoff power-law model instead of a blackbody. In particular, a ∼22 Hz quasiperiodic oscillation candidate (∼3 σ ) is detected in the precursor. These temporal and spectral properties indicate that this precursor is probably produced by a catastrophic flare accompanied with magnetoelastic or crustal oscillations of a magnetar in a binary compact merger. The strong magnetic field of the magnetar can also account for the prolonged duration of GRB 211211A. However, it poses a challenge to reconcile the rather short lifetime of a magnetar with the rather long spiraling time of a binary neutron star system only by the GW radiation before the merger.

As a distributed machine learning method, federated learning (FL) has the advantage of naturally protecting data privacy. It keeps data locally and trains local models through local data to protect the privacy of local data. The federated learning method effectively solves the problem of artificial Smart data islands and privacy protection issues. However, existing research shows that attackers may still steal user information by analyzing the parameters in the federated learning training process and the aggregation parameters on the server side. To solve this problem, differential privacy (DP) techniques are widely used for privacy protection in federated learning. However, adding Gaussian noise perturbations to the data degrades the model learning performance. To address these issues, this paper proposes a differential privacy federated learning scheme based on adaptive Gaussian noise (DPFL-AGN). To protect the data privacy and security of the federated learning training process, adaptive Gaussian noise is specifically added in the training process to hide the real parameters uploaded by the client. In addition, this paper proposes an adaptive noise reduction method. With the convergence of the model, the Gaussian noise in the later stage of the federated learning training process is reduced adaptively. This paper conducts a series of simulation experiments on real MNIST and CIFAR-10 datasets, and the results show that the DPFL-AGN algorithm performs better compared to the other algorithms. Graphic Abstract [ABSTRACT FROM AUTHOR]

Mutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome. In contrast, prostate tumors with high pSHP2 and pACK1 activity exhibited progressive downregulation of pY54-H3 levels and higher AR expression that correlated with disease severity. Overall, pSHP2/pY54-H3 signaling acts as a sentinel of AR homeostasis, explaining not only growth retardation, genital abnormalities and infertility among NSML patients, but also significant AR upregulation in prostate cancer patients. SHP2 interacts with ACK1 kinase to erase pY54-H3 (Tyr54-phosphorylation of histones H3) epigenetic marks and triggers Androgen receptor transcriptional program. It explains genital abnormalities and infertility in LEOPARD syndrome patients, and AR upregulation in prostate cancer. [ABSTRACT FROM AUTHOR]

Herein, the feasibility of artificial black soil (ABS) derived from hydrothermal humification-hydrothermal carbonization (HTH-HTC) for restructuration of weak soil was verified. This study breaks through the long history of soil formation and evolution, and obtains reconstructed anthropogenic soil (AS) system which only takes one month, for the further application of rice seedlings. HTH-HTC derived by-products are slightly acidic, which facilitates the effective nutrient uptake and prevention of wilt diseases for acid-loving rice seedlings. AS mainly consists of the inherent components retained from weak soil such as SiO2 and minerals, and exogenous components such as artificial humic substances and hydrochar, as introduced by hydrothermal humification processes. Results exhibit that AS has high contents of ammonium nitrogen, organic matter, organic carbon, and abundant porous structure for nutrient transport and water holding, especially, the community diversity and richness of microbial system gets the expected recovery and new beneficial bacteria (such as Caballeronia calidae) or fungi (such as Humicola) appear. Positive effects of AS on agronomic traits in rice seedlings are quantified. As a general result, this study supports the application of AS in sustainable agriculture, and provides a novel strategy to tackle the already-omnipresent land degradation by anthropogenic misuse and larger scale accidents. Highlights: • Anthropogenic soil system was rapidly reconstructed through hydrothermal humification-hydrothermal carbonation technology. • Anthropogenic soil possesses multiple components-structure properties for nutrient transport and water retention. • Anthropogenic soil microbial systems recover and spread in 4 weeks. • Anthropogenic soil provides acidic environment to biochemically promote rice seedling growth. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between the expressions of P21, P27 and proliferating cell nuclear antigen (PCNA) in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A (IgA) nephropathy. Methods: A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object. The expressions of P21, P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry. All patients were followed up for 24 months, and the prognosis were counted. The expressions of P21, P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis. Results: The expression rates of P21, P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were (38.69±6.83)%, (55.94±8.08)%, (33.47±5.72)%, respectively. The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%, and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group (P<0.05), while the expression rate of P27 positive cells was lower than that in good prognosis group (P<0.05). Logistic multiple regression analysis showed that elevated diastolic blood pressure, increased 24 h proteinuria, mesangial cell proliferation, segmental glomerulosclerosis, renal tubular atrophy/interstitial fibrosis, crescentic body, increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy (P<0.05). Conclusion: There are positive expressions of P21, P27 and PCNA in glomerular mesangial tissue of IgA nephropathy. The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis, while the expression rate of P27 protein positive cells is lower than those with good prognosis, which are risk factors for poor prognosis of patients with IgA nephropathy. [ABSTRACT FROM AUTHOR]

Hydrothermal humification technology for the preparation of artificial humic matters provides a new strategy, greatly promoting the natural maturation process. Iron, as a common metal, is widely used in the conversion of waste biomass; however, the influence of Fe3+ on hydrothermal humification remains unknown. In this study, FeCl3 is used to catalyze the hydrothermal humification of corn straw, and the influence of Fe3+ on the hydrothermal humification is explored by a series of characterization techniques. Results show that Fe3+ as the catalyst can promote the decomposition of corn straw, shorten the reaction time from 24 h to 6 h, and increase the yield from 6.77 % to 14.08 %. However, artificial humic acid (A‐HA) obtained from Fe3+‐catalysis hydrothermal humification contains more unstable carbon and low amount of aromatics, resulting in a significantly decreased stability of the artificial humic acid. These results provide theoretical guidance for regulating the structure and properties of artificial humic acid to meet various maintenance needs. [ABSTRACT FROM AUTHOR]

The study of quasi-periodic oscillations (QPOs) and power density spectra (PDSs) continuum properties can help shed light on the still elusive emission physics of magnetars and as a window into the interiors of neutron stars using asteroseismology. In this work, we employ a PDS method to search for the QPOs in the hundreds of X-ray bursts from SGR J1935+2154 observed by Insight - HXMT, GECAM , and Fermi/ GBM from 2014 July to 2022 January. Although no definitive QPO signal (significance >3 σ) is detected in individual bursts or the averaged periodogram of the bursts grouped by duration, we identify several bursts exhibiting features at ∼40 Hz, attributed to the the proximity intervals between adjacent pulses and consistent with that reported in the X-ray burst associated with FRB 200428. We investigate the PDS continuum properties and find that the distribution of the PDS slope in the simple power-law model peaks at ∼2.5, which is consistent with other magnetars but higher than 5/3 commonly seen in gamma-ray bursts. Besides, the distribution of the break frequency in the broken power-law model peaks at ∼60 Hz. Finally, we report that the power-law index of PDS has an anti-correlation and power-law dependence on the burst duration as well as the minimum variation time-scale. [ABSTRACT FROM AUTHOR]

Electroactive biomaterials can influence the microenvironment between cells and a material's surface by controlling surface electrical signals, thereby affecting cellular physiological activities. As the most commonly used ferroelectric polymer, Poly(vinylidene fluoride-trifluoroethylene) (PVTF) has attracted widespread attention due to its good stability, biocompatibility and mechanical properties. However, it has limitations such as non-degradability. In this study, PVTF nanoparticles (PVTF NPs), prepared using a phase separation method, were compounded with polylactide (PLA) to prepare PVTF NPs/PLA composite membrane (PN/PLA), which simultaneously achieved electroactivity and degradability. PVTF NPs containing ferroelectric β phase were evenly distributed on the PLA substrate, forming negative potential spots through corona polarization. The PLA substrate gradually degraded in a simulated body fluid environment. The negative surface potential provided by PVTF NPs in PN/PLA enhanced the adhesion, proliferation, and early-stage osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The electrical bioactivity and degradability could be joined together in this study, which is promising for tissue regeneration biomaterials, such as guided bone regeneration membrane. [ABSTRACT FROM AUTHOR]

Juvenile myelomonocytic leukemia (JMML), a clonal hematologic malignancy, originates from mutated hematopoietic stem cells (HSCs). The mechanism sustaining the persistence of mutant stem cells, leading to leukemia development, remains elusive. In this study, we conducted comprehensive examination of gene expression profiles, transcriptional factor regulons, and cell compositions/interactions throughout various stages of tumor cell development in Ptpn11 mutation-associated JMML. Our analyses revealed that leukemia-initiating Ptpn11 E76K/+ mutant stem cells exhibited de novo activation of the myeloid transcriptional program and aberrant developmental trajectories. These mutant stem cells displayed significantly elevated expression of innate immunity-associated anti-microbial peptides and pro-inflammatory proteins, particularly S100a9 and S100a8 . Biological experiments confirmed that S100a9/S100a8 conferred a selective advantage to the leukemia-initiating cells through autocrine effects and facilitated immune evasion by recruiting and promoting immune suppressive myeloid-derived suppressor cells (MDSCs) in the microenvironment. Importantly, pharmacological inhibition of S100a9/S100a8 signaling effectively impeded leukemia development from Ptpn11 E76K/+ mutant stem cells. These findings collectively suggest that JMML tumor-initiating cells exploit evolutionarily conserved innate immune and inflammatory mechanisms to establish clonal dominance., Competing Interests: Competing financial interests The authors declare no competing financial interests.

The suppression of soil carbon mineralization has been demonstrated to be effectively facilitated by carbon‑iron interactions, yet the specific mechanisms by which artificial humic substances (A-HS) coupled with ferrihydrite influence this process remain insufficiently explored. This study is to investigate how the A-HS, specifically artificial fulvic acid (A-FA) and artificial humic acid (A-HA), coupled with ferrihydrite, affect carbon mineralization under anaerobic system that simulates paddy flooding conditions. The object is to investigate trends in carbon emissions and to delineate microbial community structure and functional pathways. The findings indicate that A-HA and A-FA substantially reduce CO 2 and CH 4 emissions, with A-FA having a particularly pronounced effect on carbon fixation, halving CO 2 concentrations. The low concentration of Fe(II) observed suggest that A-FA and A-HA impede the dissimilatory iron reduction (DIR) process. Detailed 16S rDNA sequencing and gene prediction analyses reveal changes in microbial community structures and functions, highlighting Methanobacterium as the dominant hydrogenotrophic methanogens. The reductive citric acid cycle, predominantly utilized by Clostridium carboxidivorans, was identified as the principal carbon fixation pathway. This work provides a novel insight into the microbial mechanisms of carbon sequestration and highlights the potential of A-HS in improving soil fertility and contributing to climate change mitigation through enhancing soil carbon storage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xu, Huang, Chen, Cheng, Wang and Chen.)

Hydrothermal humification technology for the preparation of artificial humic matters provides a new strategy, greatly promoting the natural maturation process. Iron, as a common metal, is widely used in the conversion of waste biomass; however, the influence of Fe 3+ on hydrothermal humification remains unknown. In this study, FeCl 3 is used to catalyze the hydrothermal humification of corn straw, and the influence of Fe 3+ on the hydrothermal humification is explored by a series of characterization techniques. Results show that Fe 3+ as the catalyst can promote the decomposition of corn straw, shorten the reaction time from 24 h to 6 h, and increase the yield from 6.77 % to 14.08 %. However, artificial humic acid (A-HA) obtained from Fe 3+ -catalysis hydrothermal humification contains more unstable carbon and low amount of aromatics, resulting in a significantly decreased stability of the artificial humic acid. These results provide theoretical guidance for regulating the structure and properties of artificial humic acid to meet various maintenance needs., (© 2023 Wiley-VCH GmbH.)

Fe (hydr)oxides have a substantial impact on the structure and stability of soil organic carbon (SOC) pools and also drive organic carbon turnover processes via reduction-oxidation reactions. Currently, many studies have paid much attention to organic matter-Fe mineral-microbial interactions on SOC turnover, while there is few research on how exogenous carbon addition abiotically regulates the intrinsic mechanisms of Fe-mediated organic carbon conversion. The study investigated the coupling process of artificial humic acid (A-HA) and Fe(hydr)oxide, the mechanism of inner-sphere ligands, and the capacity for carbon sequestration using transmission electron microscopy, thermogravimetric, x-ray photoelectron spectroscopy, and wet-chemical disposal. Furthermore, spherical aberration-corrected scanning transmission electron microscopy-electron energy loss spectroscopy and Mössbauer spectra have been carried out to demonstrate the spatial heterogeneity of A-HA/Fe (hydr)oxides and reveal the relationship between the increase in Fe-phase crystallinity and redox sensitivity and the accumulation of organic carbon. Additionally, the dynamics of soil structures on a microscale, distribution of carbon-iron microdomains, and the cementing-gluing effect can be observed in the constructing nonliving anthropogenic soils, confirming that the formation of stable aggregates is an effective approach to achieving organic carbon indirect protection. We propose that exogenous organic carbon inputs, specifically A-HA, could exert a substantial but hitherto unexplored effect on the geochemistry of iron-carbon turnover and sequestration in anoxic water/solid soils and sediments., Competing Interests: Competing interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2024 Yibo Lan et al.)