Physiological and molecular responses in phosphorus-hyperaccumulating Polygonum species to high phosphorus exposure.

Phosphorus (P)-hyperaccumulators for phytoextraction from P-polluted areas generally show rapid growth and accumulate large amounts of P without any toxicity symptom, which depends on a range of physiological processes and gene expression patterns that have never been explored. We investigated growth, leaf element concentrations, P fractions, photosynthetic traits, and leaf metabolome and transcriptome response in amphibious P-hyperaccumulators, Polygonum hydropiper and P. lapathifolium, to high-P exposure (5 mmol L-1), with 0.05 mmol L-1 as the control. Under high-P exposure, both species demonstrated good growth, allocating more P to metabolite P and inorganic P (Pi) accompanied by high potassium and calcium. The expression of a cluster of unigenes associated with photosynthesis was maintained or increased in P. lapathifolium, explaining the increase in net photosynthetic rate and the rapid growth under high-P exposure. Metabolites of trehalose metabolism, including trehalose 6-phosphate and trehalose, were sharply increased in both species by the high-P exposure, in line with the enhanced expression of associated unigenes, indicating that trehalose metabolic pathway was closely related to high-P tolerance. These findings elucidated the physiological and molecular responses involved in the photosynthesis and trehalose metabolism in P-hyperaccumulators to high-P exposure, and provides potential regulatory pathways to improve the P-phytoextraction capability.

Bioorthogonal labeling and enrichment of histone monoaminylation reveal its accumulation and regulatory function in cancer cell chromatin.

Histone monoaminylation ( i . e ., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue of H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis of histone monoaminylation is mainly based on site-specific antibodies and mass spectrometry, which either lacks high resolution or is time-consuming. In this study, we report the development of chemical probes for bioorthogonal labeling and enrichment of histone serotonylation and dopaminylation. These probes were successfully applied for the monoaminylation analysis of in vitro biochemical assays, cells, and tissue samples. The enrichment of monoaminylated histones by the probes further confirmed the crosstalk between H3Q5 monoaminylation and H3K4 methylation. Finally, combining the ex vivo and in vitro analyses based on the developed probes, we have shown that both histone serotonylation and dopaminylation are highly enriched in tumor tissues that overexpress transglutaminase 2 (TGM2) and regulate the three-dimensional architecture of cellular chromatin.

Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.

MCL-1 is essential for promoting the survival of many normal cell lineages and confers survival and chemoresistance in cancer. Beyond apoptosis regulation, MCL-1 has been linked to modulating mitochondrial metabolism, but the mechanism(s) by which it does so are unclear. Here, we show in tissues and cells that MCL-1 supports essential steps in long-chain (but not short-chain) fatty acid ß-oxidation (FAO) through its binding to specific long-chain acyl-coenzyme A (CoA) synthetases of the ACSL family. ACSL1 binds to the BH3-binding hydrophobic groove of MCL-1 through a non-conventional BH3-domain. Perturbation of this interaction, via genetic loss of Mcl1, mutagenesis, or use of selective BH3-mimetic MCL-1 inhibitors, represses long-chain FAO in cells and in mouse livers and hearts. Our findings reveal how anti-apoptotic MCL-1 facilitates mitochondrial metabolism and indicate that disruption of this function may be associated with unanticipated cardiac toxicities of MCL-1 inhibitors in clinical trials.

Patient derived model of UBA5-associated encephalopathy identifies defects in neurodevelopment and highlights potential therapies.

UBA5 encodes for the E1 enzyme of the UFMylation cascade, which plays an essential role in ER homeostasis. The clinical phenotypes of UBA5-associated encephalopathy include developmental delays, epilepsy and intellectual disability. To date, there is no humanized neuronal model to study the cellular and molecular consequences of UBA5 pathogenic variants. We developed and characterized patient-derived cortical organoid cultures and identified defects in GABAergic interneuron development. We demonstrated aberrant neuronal firing and microcephaly phenotypes in patient-derived organoids. Mechanistically, we show that ER homeostasis is perturbed along with exacerbated unfolded protein response pathway in cells and organoids expressing UBA5 pathogenic variants. We also assessed two gene expression modalities that augmented UBA5 expression to rescue aberrant molecular and cellular phenotypes. Our study provides a novel humanized model that allows further investigations of UBA5 variants in the brain and highlights novel systemic approaches to alleviate cellular aberrations for this rare, developmental disorder.

Cytoneme signaling provides essential contributions to mammalian tissue patterning.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenous SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

An adaptive stress response that confers cellular resilience to decreased ubiquitination.

Ubiquitination is a post-translational modification initiated by the E1 enzyme UBA1, which transfers ubiquitin to ~35 E2 ubiquitin-conjugating enzymes. While UBA1 loss is cell lethal, it remains unknown how partial reduction in UBA1 activity is endured. Here, we utilize deep-coverage mass spectrometry to define the E1-E2 interactome and to determine the proteins that are modulated by knockdown of UBA1 and of each E2 in human cells. These analyses define the UBA1/E2-sensitive proteome and the E2 specificity in protein modulation. Interestingly, profound adaptations in peroxisomes and other organelles are triggered by decreased ubiquitination. While the cargo receptor PEX5 depends on its mono-ubiquitination for binding to peroxisomal proteins and importing them into peroxisomes, we find that UBA1/E2 knockdown induces the compensatory upregulation of other PEX proteins necessary for PEX5 docking to the peroxisomal membrane. Altogether, this study defines a homeostatic mechanism that sustains peroxisomal protein import in cells with decreased ubiquitination capacity.

A Novel Method of Wireless Micro Energy Transmission Based on MEMS Micro Coil.

Based on current implantable devices, a battery's rigidity and large size makes it prone to immune rejection and wound incisions. Additionally, it is limited by its finite lifespan, which hinders long-term usage. These limitations greatly restrict the development of implantable medical device systems towards miniaturization and minimally invasive approaches. Consequently, obtaining high-fidelity and stable biological signals from the target tissue area of the organism remains challenging. Therefore, there is a need to develop wireless power transmission technology. In this paper, we propose a wireless micro energy transfer method based on MEMS micro coils for charging implantable devices. Through simulation calculations, we first investigate the influence of coaxial distance, horizontal displacement, and rotation angle between the MEMS micro coil and the transmitting coil on power transmission. Subsequently, we utilize micro nanofabrication technology to create a MEMS micro spiral copper coil with a line width, thickness, and spacing of 50 µm and a total of five turns. Finally, we conduct wireless power transmission tests on the coil. The results show that, when the transmitting coil and the receiving coil are 10 mm apart and the operating frequency is 100 kHz, the power of the wireless power transmission system reaches 45 µW. This power level is sufficient to meet the power supply requirements of implantable pacemakers. Therefore, this technology holds great potential for applications in the field of wireless power transmission for implantable medical devices, including pacemakers and brain neurostimulators.

Pediatric Peroneal Nerve Palsy Secondary to Fibular Osteochondroma.

Peripheral nerve injuries due to mass effect from bony lesions can occur when the nerve exists in an anatomically constrained location, such as the common peroneal nerve at the fibular head which passes into the tight fascia of the lateral leg compartment. We report a case of a pediatric patient who developed a common peroneal nerve palsy secondary to an osteochondroma of the fibular head and describe the clinical evaluation, radiographic findings, and surgical approach. Rapid diagnosis and nerve decompression after the onset of symptoms restored full motor function at the 8-month postoperative mark.

Halomonas ventosae JPT10 promotes salt tolerance in foxtail millet (Setaria italica) by affecting the levels of multiple antioxidants and phytohormones.

Plant growth-promoting bacterias (PGPBs) can increase crop output under normal and abiotic conditions. However, the mechanisms underlying the plant salt tolerance-promoting role of PGPBs still remain largely unknown. In this study, we demonstrated that Halomonas ventosae JPT10 promoted the salt tolerance of both dicots and monocots. Physiological analysis revealed that JPT10 reduced reactive oxygen species accumulation by improving the antioxidant capability of foxtail millet seedlings. The metabolomic analysis of JPT10-inoculated foxtail millet seedlings led to the identification of 438 diversely accumulated metabolites, including flavonoids, phenolic acids, lignans, coumarins, sugar, alkaloids, organic acids, and lipids, under salt stress. Exogenous apigenin and chlorogenic acid increased the salt tolerance of foxtail millet seedlings. Simultaneously, JPT10 led to greater amounts of abscisic acid (ABA), indole-3-acetic acid (IAA), salicylic acid (SA), and their derivatives but lower levels of 12-oxo-phytodienoic acid (OPDA), jasmonate (JA), and JA-isoleucine (JA-Ile) under salt stress. Exogenous JA, methyl-JA, and OPDA intensified, whereas ibuprofen or phenitone, two inhibitors of JA and OPDA biosynthesis, partially reversed, the growth inhibition of foxtail millet seedlings caused by salt stress. Our results shed light on the response of foxtail millet seedlings to H. ventosae under salt stress and provide potential compounds to increase salt tolerance in foxtail millet and other crops.

Pruned litter decomposition primes fluorine bioavailability in soils planted with different tea varieties.

Tea (Camellia sinensis L.) plant is fluoride (F) hyperaccumulator. The decomposition of pruned litter in tea plantations releases a large amount of F back into the soil. However, the effect of pruned litter return on soil F bioavailability has remained unclear. We investigated the decomposition dynamics of pruned litter from four tea varieties (Chuannong Huangyazao, Chuancha No. 3, Chuanmu No. 217 and C. sinensis 'Fuding Dabaicha') and its effect on soil F bioavailability. The decomposition of pruned litter occurred in two distinct periods, with an early period of rapid decomposition during the first 120 days, releasing 26-33 % of F, followed by a late period of slow decomposition during 120-360 days, releasing 2-9 % of F. The decomposition of pruned litter enhanced soil F bioavailability by increasing the concentrations of soil water-soluble F (WS-F), exchangeable F (EX-F), and organic matter-bound F (OR-F). The increase in WS-F, EX-F, and OR-F concentrations was higher than the amount of F released from pruned litter, suggesting that the increases in soil F availability did not solely originate from the release of F from pruned litter. The findings reveal the pathway of pruned litter decomposition priming soil F bioavailability through both the direct release of F and transformation from other fractions. Furthermore, the traits (C, N, lignin, and cellulose) of pruned litter from different tea varieties were the dominant factors controlling F release and soil F bioavailability. Compared with other tea varieties, the pruned litter of Chuanmu No. 217 with low lignin and cellulose content promoted higher mass loss and F release, resulting in the highest soil F bioavailability. These findings provide new insights into the mechanisms underlying the accumulation of bioavailable F in soil. These insights offer valuable support for devising effective management strategies for the incorporation of pruned litter into soil.

Root radial apoplastic transport contributes to shoot cadmium accumulation in a high cadmium-accumulating rice line.

Radial transport of cadmium (Cd) in roots governs the amount of Cd loaded into xylem vessels, where Cd ions are translocated upward into shoots, while the mechanism of differential Cd radial transport between the high Cd-accumulating rice line Lu527-8 and the normal rice line Lu527-4 remains ambiguous. A higher Cd distribution in cross sections and root apoplast and higher bypass flow of Cd were found in Lu527-8, explaining a greater Cd translocation through the apoplastic pathway. The lower relative area of the epidermis and the constant relative area of the cortex in Lu527-8 opened-up root radial transport for Cd. Deposition of apoplastic barriers (Casparian strips and suberin lamellae) was stimulated by Cd, which effectively prevented Cd from entering the stele through the apoplastic pathway. In Lu527-8, apoplastic barriers were further from the root apex with lower expression of genes responsible for biosynthesis of Casparian strips and suberin lamellae, enhancing radial transport of Cd. Our data revealed that the higher radial apoplastic transport of Cd played an integral role in Cd translocation, contributed to a better understanding of the mechanism involved in high Cd accumulation in Lu527-8 and helped achieve the practical application of phytoextraction.

Cumulative effects of drought have an impact on net primary productivity stability in Central Asian grasslands.

Global warming has exacerbated the threat of drought in Central Asia, amplifying its ecological implications within the region's grassland ecosystems. This has become an increasingly prominent issue that requires attention and action. The temporal link between grassland development and drought is asymmetric. However, a quantitative assessment of the temporal effects of multiscale drought on Central Asian grasslands has yet to be explored. Based on correlation analysis and the coefficient of variation method, this study analysed the cumulative and lag effects of multitimescale drought on grassland NPP (net primary productivity) under different climatic zones, altitudes and water availabilities in Central Asia from 1982 to 2018, and discussed the impact of temporal effects on grassland NPP stability. Our results on the cumulative effects of drought on grasslands indicate the 6.72 months preceding NPP measurement was the duration for which, on average, drought was most strongly correlated with NPP. Additionally, we found a mean lagged effect of 5.36 months, meaning that the monthly drought 5.36 months prior to NPP measurement was, on average, most strongly correlated with NPP. The degree to which grassland NPP was affected by cumulative drought at a given level of water availability was inversely proportional to the number of cumulative drought months. Under different water availabilities, the lagged effect of grassland NPP was stronger in dry areas than in wet areas, and the number of lag months tended to decrease and then increase as the water availability increased. The percentage of areas where grassland NPP was dominated by the cumulative and lagging effects of drought was 30.02% and 69.98%, respectively. The stability of grassland NPP was adversely affected by the drought accumulation effect. The findings of this study contribute to a deeper understanding of the long-term effects of drought on grassland ecosystems. Additionally, it will aid in the development of strategies for mitigating and adapting to drought events, thereby minimizing their negative impacts on agriculture, livestock, and ecosystems.

Haustral rhythmic motor patterns of the human large bowel revealed by ultrasound.

Effective and widely available strategies are needed to diagnose colonic motility dysfunction. We investigated whether ultrasonography could generate spatiotemporal maps combined with motor pattern frequency analysis, to become a noninvasive method to characterize human colon motor patterns. Abdominal colonic ultrasonography was performed on healthy subjects (N = 7), focusing on the detailed recording of spontaneous haustral activities. We developed image segmentation and frequency analysis software to analyze the motor patterns captured. Ultrasonography recordings of the ascending, transverse, and descending colon identified three distinct rhythmic motor patterns: the 1 cycle/min and the 3 cycles/min cyclic motor pattern were seen throughout the whole colon, whereas the 12 cycles/min cyclic motor pattern was identified in the ascending colon. The rhythmic motor patterns of the human colon that are associated with interstitial cells of Cajal-associated pacemaking activity can be accurately identified and quantified using ultrasound.NEW & NOTEWORTHY Ultrasonography in the clinical field is an underutilized tool for assessing colonic motility; however, with the addition of frequency analysis techniques, it provides a method to identify human colonic motor patterns. Here we report on the 1, 3, and 12 cpm rhythmic motor patterns. Ultrasound has the potential to become a bedside assessment for colonic dysmotility and may reveal the health of interstitial cells of Cajal (ICC) pacemaker activities.

A murine model of hnRNPH2-related neurodevelopmental disorder reveals a mechanism for genetic compensation by Hnrnph1.

Mutations in HNRNPH2 cause an X-linked neurodevelopmental disorder with features that include developmental delay, motor function deficits, and seizures. More than 90% of patients with hnRNPH2 have a missense mutation within or adjacent to the nuclear localization signal (NLS) of hnRNPH2. Here, we report that hnRNPH2 NLS mutations caused reduced interaction with the nuclear transport receptor Kapß2 and resulted in modest cytoplasmic accumulation of hnRNPH2. We generated 2 knockin mouse models with human-equivalent mutations in Hnrnph2 as well as Hnrnph2-KO mice. Knockin mice recapitulated clinical features of the human disorder, including reduced survival in male mice, impaired motor and cognitive functions, and increased susceptibility to audiogenic seizures. In contrast, 2 independent lines of Hnrnph2-KO mice showed no detectable phenotypes. Notably, KO mice had upregulated expression of Hnrnph1, a paralog of Hnrnph2, whereas knockin mice failed to upregulate Hnrnph1. Thus, genetic compensation by Hnrnph1 may counteract the loss of hnRNPH2. These findings suggest that HNRNPH2-related disorder may be driven by a toxic gain of function or a complex loss of HNRNPH2 function with impaired compensation by HNRNPH1. The knockin mice described here are an important resource for preclinical studies to assess the therapeutic benefit of gene replacement or knockdown of mutant hnRNPH2.

Oxidative Capacity of Oxygen Nanobubbles and Their Mechanism for the Catalytic Oxidation of Ferrous Ions with Copper as a Catalyst in Sulfuric Acid Medium.

Nanobubble (NB) technology has demonstrated the potential to enhance or substitute for current treatment processes in various areas. However, research employing it as a novel advanced oxidation process has thus far been relatively limited. Herein, we focused on the oxidative capacity of oxygen NBs and investigated the feasibility of utilizing their enhanced oxidation of ferrous ions (Fe2+) in a sulfuric acid medium when using copper as a catalyst and their effect mechanism. It was demonstrated that oxygen NBs could collapse to produce hydroxyl radicals (·OH) in the absence of dynamic stimuli using electron spin resonance spectroscopy, and methylene blue was used as a molecular probe for ·OH to illustrate that NB stability, determined by their properties, is the critical factor affecting ·OH release. In subsequent Fe2+ oxidation experiments, it was discovered that both strong acidity and copper ions (Cu2+) contribute to accelerating the collapse of NBs to produce ·OH. While ·OH derived from the collapse of NBs acts on Fe2+, the molecular oxygen generated homologously with ·OH will further activate the catalytic oxidation of Fe2+ by interacting with Cu2+. With the synergistic effect of the above two oxidation-driven mechanisms, the oxidation rate of Fe2+ can be significantly increased up to 88% due to the exceptional properties of oxygen NBs, which facilitate the formation of an atmosphere with persistent oxygen supersaturation and the generation of oxidation radicals. This study provides significant insight into applying NBs as a prospective technology for enhanced oxidation processes.

Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas.

AIMS: Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder caused by hypomorphic mutations of NBS1. NBS1 is a member of the MRE11-RAD50-NBS1 (MRN) complex that binds to DNA double-strand breaks and activates the DNA damage response (DDR). Nbs1 inactivation in neural progenitor cells leads to microcephaly and premature death. Interestingly, p53 homozygous deletion rescues the NBS1-deficient phenotype allowing long-term survival. The objective of this work was to determine whether simultaneous inactivation of Nbs1 and p53 in neural progenitors triggered brain tumorigenesis and if so in which category this tumour could be classified. METHODS: We generated a mouse model with simultaneous genetic inactivation of Nbs1 and p53 in embryonic neural stem cells and analysed the arising tumours with in-depth molecular analyses including immunohistochemistry, array comparative genomic hybridisation (aCGH), whole exome-sequencing and RNA-sequencing. RESULTS: NBS1/P53-deficient mice develop high-grade gliomas (HGG) arising in the olfactory bulbs and in the cortex along the rostral migratory stream. In-depth molecular analyses using immunohistochemistry, aCGH, whole exome-sequencing and RNA-sequencing revealed striking similarities to paediatric human HGG with shared features with radiation-induced gliomas (RIGs). CONCLUSIONS: Our findings show that concomitant inactivation of Nbs1 and p53 in mice promotes HGG with RIG features. This model could be useful for preclinical studies to improve the prognosis of these deadly tumours, but it also highlights the singularity of NBS1 among the other DNA damage response proteins in the aetiology of brain tumours.

MicroRNA 3' ends shorten during adolescent brain maturation.

MicroRNA (miRNA) dysregulation is well-documented in psychiatric disease, but miRNA dynamics remain poorly understood during adolescent and early adult brain maturation, when symptoms often first appear. Here, we use RNA sequencing to examine miRNAs and their mRNA targets in cortex and hippocampus from early-, mid-, and late-adolescent and adult mice. Furthermore, we use quantitative proteomics by tandem mass tag mass spectrometry (TMT-MS) to examine protein dynamics in cortex from the same subjects. We found that ~25% of miRNAs' 3' ends shorten with age due to increased 3' trimming and decreased U tailing. Particularly, shorter but functionally competent isoforms (isomiRs) of miR-338-3p increase up to 10-fold during adolescence and only in brain. MiRNAs that undergo 3' shortening exhibit stronger negative correlations with targets that decrease with age and stronger positive correlations with targets that increase with age, than miRNAs with stable 3' ends. Increased 3' shortening with age was also observed in available mouse and human miRNA-seq data sets, and stronger correlations between miRNAs that undergo shortening and their mRNA targets were observed in two of the three available data sets. We conclude that age-associated miRNA 3' shortening is a well-conserved feature of postnatal brain maturation.

Design and fabrication method of holographic waveguide near-eye display with 2D eye box expansion.

Augmented reality near-eye display (AR-NED) technology has attracted enormous interests for its widespread potential applications. In this paper, two-dimensional (2D) holographic waveguide integrated simulation design and analysis, holographic optical elements (HOEs) exposure fabrication, prototype performance evaluation and imaging analysis are completed. In the system design, a 2D holographic waveguide AR-NED integrated with a miniature projection optical system is presented to achieve a larger 2D eye box expansion (EBE). A design method for controlling the luminance uniformity of 2D-EPE holographic waveguide by dividing the two thicknesses of HOEs is proposed, which is easy to fabricate. The optical principle and design method of the HOE-based 2D-EBE holographic waveguide are described in detail. In the system fabrication, laser exposure fabrication method of eliminating stray light for HOEs is proposed, and a prototype system is fabricated and demonstrated. The properties of the fabricated HOEs and the prototype are analyzed in detail. The experimental results verified that the 2D-EBE holographic waveguide has a diagonal field of view (FOV) of 45°, an ultra-thin thickness of 1 mm, and an eye box of 16 mm × 13 mm at an eye relief (ERF) of 18 mm, the MTF values of different FOVs at different 2D-EPE positions can be better than 0.2 at 20 lp/mm, and the whole luminance uniformity is 58%.