The functional specificity of ERECTA-family receptors in Arabidopsis stomatal development is ensured by molecular chaperones in the endoplasmic reticulum.

Stomata are epidermal pores that control gas exchange between plants and the atmosphere. In Arabidopsis, the ERECTA family (ERECTAf) receptors, including ERECTA, ERECTA-LIKE 1 (ERL1) and ERL2, redundantly play pivotal roles in enforcing the 'one-cell-spacing' rule. Accumulating evidence has demonstrated that the functional specificities of receptors are likely associated with their differential subcellular dynamics. The endoplasmic reticulum (ER)-resident chaperone complex SDF2-ERdj3B-BiP functions in many aspects of plant development. We employed pharmacological treatments combined with cell biological and biochemical approaches to demonstrate that the abundance of ERECTA was reduced in the erdj3b-1 mutant, but the localization and dynamics of ERECTA were not noticeably affected. By contrast, the erdj3b mutation caused the retention of ERL1/ERL2 in the ER. Furthermore, we found that the function of SDF2-ERdj3B-BiP is implicated with the distinct roles of ERECTAf receptors. Our findings establish that the ERECTAf receptor-mediated signaling in stomatal development is ensured by the activities of the ER quality control system, which preferentially maintains the protein abundance of ERECTA and proper subcellular dynamics of ERL1/ERL2, prior to the receptors reaching their destination - the plasma membrane - to execute their functions.

Arabidopsis ERdj3B coordinates with ERECTA-family receptor kinases to regulate ovule development and the heat stress response.

The endoplasmic reticulum-localized DnaJ family 3B (ERdj3B), is a component of the stromal cell-derived factor 2 (SDF2)-ERdj3B-binding immunoglobulin protein (BiP) chaperone complex, which functions in protein folding, translocation, and quality control. We found that ERdj3B mutations affected integument development in the Ler ecotype but not in the Col-0 ecotype of Arabidopsis (Arabidopsis thaliana). Map-based cloning identified the ERECTA (ER) gene as a natural modifier of ERdj3B. The double mutation of ERdj3B and ER caused a major defect in the inner integument under heat stress. Additional mutation of the ER paralog ERECTA-LIKE 1 (ERL1) or ERL2 to the erdj3b er double mutant exacerbated the defective integument phenotype. The double mutation of ER and SDF2, the other component of the SDF2-ERdj3B-BiP complex, resulted in similar defects in the inner integument. Furthermore, both the protein abundance and plasma membrane partitioning of ER, ERL1, and ERL2 were markedly reduced in erdj3b plants, indicating that the SDF2-ERdj3B-BiP chaperone complex might control the translocation of ERECTA-family proteins from the endoplasmic reticulum to the plasma membrane. Our results suggest that the SDF2-ERdj3B-BiP complex functions in ovule development and the heat stress response in coordination with ERECTA-family receptor kinases.

Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits.

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

Learning-based lens wavefront aberration recovery.

Wavefront aberration describes the deviation of a wavefront in an imaging system from a desired perfect shape, such as a plane or a sphere, which may be caused by a variety of factors, such as imperfections in optical equipment, atmospheric turbulence, and the physical properties of imaging subjects and medium. Measuring the wavefront aberration of an imaging system is a crucial part of modern optics and optical engineering, with a variety of applications such as adaptive optics, optical testing, microscopy, laser system design, and ophthalmology. While there are dedicated wavefront sensors that aim to measure the phase of light, they often exhibit some drawbacks, such as higher cost and limited spatial resolution compared to regular intensity measurement. In this paper, we introduce a lightweight and practical learning-based method, named LWNet, to recover the wavefront aberration for an imaging system from a single intensity measurement. Specifically, LWNet takes a measured point spread function (PSF) as input and recovers the wavefront aberration with a two-stage network. The first stage network estimates an initial wavefront aberration via supervised learning, and the second stage network further optimizes the wavefront aberration via self-supervised learning by enforcing the statistical priors and physical constraints of wavefront aberrations via Zernike decomposition. For supervised learning, we created a synthetic PSF-wavefront aberration dataset via ray tracing of 88 lenses. Experimental results show that even trained with simulated data, LWNet works well for wavefront aberration estimation of real imaging systems and consistently outperforms prior learning-based methods.

Airborne Nanoplastics Exposure Inducing Irreversible Glucose Increase and Complete Hepatic Insulin Resistance.

As an emerging type of pollutant, microplastics have become a global environmental problem. Approximately, a fifth of the global burden of type 2 diabetes can be attributed to air particulate pollution. However, scientific knowledge remains limited about the effects of airborne nanoplastics (NPs) exposure on metabolic diseases. In this experiment, a whole-body exposure system was used to simulate the real atmospheric environment, and three exposure concentrations combined with the actual environmental concentration were selected to explore the effects of airborne NPs on metabolic diseases. Based on histological analyses, metabolic studies, gene expression, metabolites, and molecular signaling analyses, mice exposed to airborne NPs were observed to show a phenotype of systemic inflammation and complete insulin resistance featuring excessive drinking and eating, weight loss, elevated blood glucose, and decreased triglyceride levels. After airborne NPs exposure, mice were intolerant to glucose and tolerant to insulin. In addition, airborne NPs exposure could result in long-term irreversible hyperglycemia. Together, the research findings provide a strong basis for understanding the hazards of airborne nanopollution on metabolic disorders.

Nervous system exposure of different classes of nanoparticles: A review on potential toxicity and mechanistic studies.

Nanoparticles (NPs) are generally defined as very small particles in the size range of 1-100 nm. Due to the rapid development of modern society, many new materials have been developed. The widespread use of NPs in medical applications, the food industry and the textile industry has led to an increase in NPs in the environment and the possibility of human contact, which poses a serious threat to human health. The nervous system plays a leading role in maintaining the integrity and unity of the body and maintaining a harmonious balance with the external environment. Therefore, based on two categories of organic and inorganic NPs, this paper systematically summarizes the toxic effects and mechanisms of NPs released into the nervous system. The results showed that exposure to NPs may damage the nervous system, decrease learning and cognitive ability, and affect embryonic development. Finally, a remediation scheme for NPs entering the body via the environment is also introduced. This scheme aims to reduce the neurotoxicity caused by NPs by supplementing NPs with a combination of antioxidant and anti-inflammatory compounds. The results provide a valuable reference for future research in this field.

Efficacy of roxadustat in maintenance hemodialysis patients with erythropoietin-hyporesponsive anemia.

OBJECTIVE: To investigate the efficacy of roxadustat in hemodialysis patients with erythropoietin (EPO) hypo-responsive anemia. MATERIALS AND METHODS: This retrospective study included 55 hemodialysis patients with erythropoietin hypo-responsive anemia at the First Affiliated Hospital of Chongqing Medical University from January to December 2020. We observed their hemoglobin (Hb) changes, inflammatory factors, and adverse reactions before and after 12 weeks of roxadustat treatment. RESULTS: Among the 55 patients, the average age was 60.75 ± 13.96 years old, and the median dialysis age was 48 months. All patients were taken off EPO and switched to roxadustat during the follow-up period. Compared with baseline, patients' Hb was significantly increased (90.64 ± 20.01 g/L, 98.52 ± 15.89 g/L, 104.34 ± 19.15 g/L, and 107.02 ± 20.54 g/L, respectively) (p < 0.05). At 12 weeks of roxadustat treatment, 34 patients (61.82%) met the target Hb levels (100 - 130 g/L). The multivariate logistic analysis showed that Hb response positively correlated with the Hb level before roxadustat treatment (p = 0.046), while responding well to roxadustat negatively correlated with blood platelet-to-lymphocyte ratio (PLR) and duration of dialysis (p = 0.029 and p = 0.046) in patients with EPO hypo-responsive anemia. CONCLUSION: Roxadustat could effectively improve anemia; the PLR and dialysis age were independent predictors of roxadustat efficacy in dialysis patients with EPO hypo-responsive anemia.

Optical bistability in a heterodimer composed of a quantum dot and a metallic nanoshell.

We theoretically explore the conditions for generating optical bistability (OB) in a heterodimer comprised of a semiconductor quantum dot (SQD) and a metallic nanoshell (MNS). The MNS is made of a metallic nanosphere as a core and a dielectric material as a shell. For the specific hybrid system considered, the bistable effect appears only if the frequency of the pump field is equal to (or slightly less than) the exciton frequency for a proper shell thickness. Bistability phase diagrams, when plotted, show that the dipole-induced bistable region can be greatly broadened by changing the shell thickness of the MNS in a strong exciton-plasmon coupling regime. In particular, we demonstrate that the multipole polarization not only narrows the bistable zone but also enlarges the corresponding thresholds for a given intermediate scaled pumping intensity. On the other hand, when the SQD couples strongly with the MNS, the multipole polarization can also significantly broaden the bistable region and induce a great suppression of the FWM (four-wave mixing) signal for a fixed shell thickness. These interesting findings offer a fresh understanding of the bistability conditions in an SQD/MNS heterodimer, and may be useful in the fabrication of high-performance and low-threshold optical bistable nanodevices.

Exo I signal amplification of a DNA hydrogel film combined with capillary self-driven action for EpCAM detection.

Target-responsive aptamer hydrogels are increasingly used in the field of analytical sensing with different morphologies developed by various strategies. Herein, we developed a DNA hydrogel film combined with capillary self-driven action for the specific detection of the tumor marker EpCAM and further introduced Exo I for signal amplification. EpCAM aptamer was used as a crosslinking agent to construct the DNA hydrogel film. When EpCAM was present, it competed for binding with the EpCAM aptamer, resulting in a permeability change of the DNA hydrogel film attached to one end of the capillary, and leading to different solution flow rates through the capillaries that can be utilized for the quantitative detection of EpCAM. This method did not require any instrument and was easy to use. The distance the solution travelled through the capillary was quantified as the concentration of EpCAM, and only a small amount of DNA hydrogel was required for each detection. The detection limit of EpCAM was as low as 0.018 ng mL-1, while offering the advantages of good stability and specificity, and showing great potential in point-of-care testing.

Two new dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.

Two undescribed dammarane triterpenoid saponins, cypaliurusides O and P (1 and 2), were isolated from the ethanol extracts of the leaves of Cyclocarya paliurus. Bioactivity assay results showed that compound 1 has potential cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 14.55 ± 0.55 to 22.75 ± 1.54 µM. Compound 1 showed better antitumor activity against HepG2 cells with IC50 of 14.55 ± 0.55 µM. In addition, compound 2 showed no obvious antitumor activity.

[Research progress on minimally invasive and non-invasive blood glucose detection methods].

Blood glucose monitoring has become the weakest point in the overall management of diabetes in China. Long-term monitoring of blood glucose levels in diabetic patients has become an important means of controlling the development of diabetes and its complications, so that technological innovations in blood glucose testing methods have far-reaching implications for accurate blood glucose testing. This article discusses the basic principles of minimally invasive and non-invasive blood glucose testing assays, including urine glucose assays, tear assays, methods of extravasation of tissue fluid, and optical detection methods, etc., focuses on the advantages of minimally invasive and non-invasive blood glucose testing methods and the latest relevant results, and summarizes the current problems of various testing methods and prospects for future development trends.

The Arabidopsis AGC kinases NDR2/4/5 interact with MOB1A/1B and play important roles in pollen development and germination.

Pollen formation and pollen tube growth are essential for the delivery of male gametes into the female embryo sac for double fertilization. Little is known about the mechanisms that regulate the late developmental process of pollen formation and pollen germination. In this study, we characterized a group of Arabidopsis AGC kinase proteins, NDR2/4/5, involved in pollen development and pollen germination. The NDR2/4/5 genes are mainly expressed in pollen grains at the late developmental stages and in pollen tubes. They function redundantly in pollen formation and pollen germination. At the tricellular stages, the ndr2 ndr4 ndr5 mutant pollen grains exhibit an abnormal accumulation of callose, precocious germination and burst in anthers, leading to a drastic reduction in fertilization and a reduced seed set. NDR2/4/5 proteins can interact with another group of proteins (MOB1A/1B) homologous to the MOB proteins from the Hippo signaling pathway in yeast and animals. The Arabidopsis mob1a mob1b mutant pollen grains also have a phenotype similar to that of ndr2 ndr4 ndr5 pollen grains. These results provide new evidence demonstrating that the Hippo signaling components are conserved in plants and play important roles in sexual plant reproduction.

Plant-specific small peptide AtZSP1 interacts with ROCK1 to regulate organ size in Arabidopsis.

Organ size is an important agronomic trait. Small peptides function in various stages of plant growth, but their regulatory mechanisms in organ growth remain poorly understood. Here, we characterize a novel small peptide, AtZSP1, which positively regulates organ size in Arabidopsis. Loss-of-function mutant atzsp1-1 exhibited small organs, whereas AtZSP1 overexpression plants (p35S:AtZSP1#1) produced larger organs. Differentially expressed genes in the shoots of atzsp1-1 and p35S:AtZSP1#1 were enriched in the cytokinin pathway. Further analysis on shoots of atzsp1-1 showed that endogenous cytokinin levels were significantly reduced, consistent with reduced expression of the cytokinin response genes ARR5/6/7 and a decrease in pARR5:GUS activity. By contrast, cytokinin levels were elevated in p35S:AtZSP1#1. These results indicate that AtZSP1 affects shoot size via changes in cytokinin levels. AtZSP1 is ubiquitously expressed and encodes a 57-amino acid endomembrane-associated protein that is highly conserved among plant species. AtZSP1 interacts with ROCK1 at the endomembrane. Genetic analysis confirmed that the small organs and low cytokinin levels in atzsp1-1 shoots are partially suppressed by the rock1-4 mutation, suggesting that AtZSP1 may function in a common pathway with ROCK1 to antagonistically regulate organ growth. Our study identified an unknown small peptide, AtZSP1, and defined its function in regulating organ size in Arabidopsis.

Ultra-strong optical four-wave mixing signal induced by strong exciton-phonon and exciton-plasmon couplings.

We propose a scheme to generate ultra-strong four-wave mixing (FWM) signal based on a suspended monolayer graphene nanoribbon nanomechanical resonator (NR) coupled to an Au nanoparticle (NP). It is shown that, the FWM spectrum can switch among two-peaked, three-peaked, four-peaked or five-peaked via the modulation of exciton-phonon and exciton-plasmon couplings. This is mainly attributed to the vibrational properties of NR related to the exciton-phonon coupling, and the energy-level splitting of the localized exciton correlated to three classes of resonances consisting of three-photon resonance, Rayleigh Resonance, and AC-Stark atomic resonance. Especially, in a dual-strong coupling regime, the gains for these peaks can be as high as nine orders of magnitude (∼ 109) around the lower bistable threshold due to a combined effect of two couplings. Our findings not only offer an efficient way to measure the vibrational frequency of NR and the exciton-phonon coupling strength but also provide a possibility to fabricate high-performance optoelectronic nanodevices.

MAP3Kε1/2 Interact with MOB1A/1B and Play Important Roles in Control of Pollen Germination through Crosstalk with JA Signaling in Arabidopsis.

Restriction of pollen germination before the pollen grain is pollinated to stigma is essential for successful fertilization in angiosperms. However, the mechanisms underlying the process remain poorly understood. Here, we report functional characterization of the MAPKKK kinases, MAP3Kε1 and MAP3Kε2, involve in control of pollen germination in Arabidopsis. The two genes were expressed in different tissues with higher expression levels in the tricellular pollen grains. The map3kε1 map3kε2 double mutation caused abnormal callose accumulation, increasing level of JA and precocious pollen germination, resulting in significantly reduced seed set. Furthermore, the map3kε1 map3kε2 double mutations obviously upregulated the expression levels of genes in JA biosynthesis and signaling. The MAP3Kε1/2 interacted with MOB1A/1B which shared homology with the core components of Hippo singling pathway in yeast. The Arabidopsis mob1a mob1b mutant also exhibited a similar phenotype of precocious pollen germination to that in map3kε1 map3kε2 mutants. Taken together, these results suggested that the MAP3Kεs interacted with MOB1s and played important role in restriction of the precocious pollen germination, possibly through crosstalk with JA signaling and influencing callose accumulation in Arabidopsis.

Genome-wide association study reveals the genetic architecture of root hair length in maize.

BACKGROUND: Root hair, a special type of tubular-shaped cell, outgrows from root epidermal cell and plays important roles in the acquisition of nutrients and water, as well as interactions with biotic and abiotic stress. Although many genes involved in root hair development have been identified, genetic basis of natural variation in root hair growth has never been explored. RESULTS: Here, we utilized a maize association panel including 281 inbred lines with tropical, subtropical, and temperate origins to decipher the phenotypic diversity and genetic basis of root hair length. We demonstrated significant associations of root hair length with many metabolic pathways and other agronomic traits. Combining root hair phenotypes with 1.25 million single nucleotide polymorphisms (SNPs) via genome-wide association study (GWAS) revealed several candidate genes implicated in cellular signaling, polar growth, disease resistance and various metabolic pathways. CONCLUSIONS: These results illustrate the genetic basis of root hair length in maize, offering a list of candidate genes predictably contributing to root hair growth, which are invaluable resource for the future functional investigation.

The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1.

Abnormal accumulation of triglycerides in the liver, caused in part by increased de novo lipogenesis, results in non-alcoholic fatty liver disease and insulin resistance. Sterol regulatory element-binding protein 1 (SREBP1), an important transcriptional regulator of lipogenesis, is synthesized as an inactive precursor that binds to the endoplasmic reticulum (ER). In response to insulin signalling, SREBP1 is transported from the ER to the Golgi in a COPII-dependent manner, processed by proteases in the Golgi, and then shuttled to the nucleus to induce lipogenic gene expression; however, the mechanisms underlying enhanced SREBP1 activity in insulin-resistant obesity and diabetes remain unclear. Here we show in mice that CREB regulated transcription coactivator 2 (CRTC2) functions as a mediator of mTOR signalling to modulate COPII-dependent SREBP1 processing. CRTC2 competes with Sec23A, a subunit of the COPII complex, to interact with Sec31A, another COPII subunit, thus disrupting SREBP1 transport. During feeding, mTOR phosphorylates CRTC2 and attenuates its inhibitory effect on COPII-dependent SREBP1 maturation. As hepatic overexpression of an mTOR-defective CRTC2 mutant in obese mice improved the lipogenic program and insulin sensitivity, these results demonstrate how the transcriptional coactivator CRTC2 regulates mTOR-mediated lipid homeostasis in the fed state and in obesity.

The Mildew Resistance Locus O 4 Interacts with CaM/CML and Is Involved in Root Gravity Response.

The plant-specific mildew resistance locus O (MLO) proteins, which contain seven transmembrane domains and a conserved calmodulin-binding domain, play important roles in many plant developmental processes. However, their mechanisms that regulate plant development remain unclear. Here, we report the functional characterization of the MLO4 protein in Arabidopsis roots. The MLO4 was identified as interacting with CML12 in a screening for the interaction between the proteins from Arabidopsis MLO and calmodulin/calmodulin-like (CaM/CML) families using yeast two hybrid (Y2H) assays. Then, the interaction between MLO4 and CML12 was further verified by Luciferase Complementation Imaging (LCI) and Bimolecular Fluorescence Complementation (BiFC) assays. Genetic analysis showed that the mlo4, cml12, and mlo4 cml12 mutants displayed similar defects in root gravity response. These results imply that the MLO4 might play an important role in root gravity response through interaction with CML12. Moreover, our results also demonstrated that the interaction between the MLO and CaM/CML families might be conservative.

[A Cross-sectional Study of Osteoporosis and Cardiovascular Calcification in Patients with Chronic Kidney Disease at Different CKD Stages].

OBJECTIVE: To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. METHODS: A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and ß-crosslaps (ß-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. RESULTS: Compared with control group, levels of serum P, iPTH, BALP, PINP and ß-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). CONCLUSION: The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.

Characterization of LRL5 as a key regulator of root hair growth in maize.

Root hair, a special type of tubular-shaped cell, outgrows from the root epidermal cell and plays important roles in the acquisition of nutrients and water, as well as interactions with biotic and abiotic stresses. Studies in the model plant Arabidopsis have revealed that root-hair initiation and elongation are hierarchically regulated by a group of basic helix-loop-helix (bHLH) transcription factors (TFs). However, knowledge regarding the regulatory pathways of these bHLH TFs in controlling root hair growth remains limited. In this study, RNA-seq analysis was conducted to profile the transcriptome in the elongating maize root hair and >1000 genes with preferential expression in root hair were identified. A consensus cis-element previously featured as the potential bHLH-TF binding sites was present in the regulatory regions for the majority of the root hair-preferentially expressed genes. In addition, an individual change in ZmLRL5, the highest-expressed bHLH-TF in maize root hair resulted in a dramatic reduction in the elongation of root hair, and rendered the growth of root hair hypersensitive to translational inhibition. Moreover, RNA-seq, yeast-one-hybrid and ribosome profile analysis suggested that ZmLRL5 may function as a key player in orchestrating the translational process by directly regulating the expression of translational processes/ribosomal genes during maize root hair growth.