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.

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.

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.

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.

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.

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 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.

Dual-channel bistable switch based on a monolayer graphene nanoribbon nanoresonator coupled to a metal nanoparticle.

We theoretically propose a dual-channel bistable switch based on a monolayer Z-shaped graphene nanoribbon nanoresonator (NR) coupled to a metal nanoparticle (MNP). We show that the bistable nonlinear absorption response can be realized due to a competition and combination of the exciton-plasmon and exciton-phonon interactions. We map out two-dimensional and three-dimensional bistability phase diagrams, which reveal clearly the dynamical evolution of the roles played by these two interactions in managing optical bistability (OB) at all stages. Specifically, the bistable switch proposed can be controlled via a single channel or dual channels by only adjusting the intensity or frequency of the pump field. In/outside these channels, the switch will be turned on/off. The results obtained here not only can be employed to measure precisely the distance between the MNP and the NR but also provide promising applications in optical switching and optical storage.

The Arabidopsis CrRLK1L protein kinases BUPS1 and BUPS2 are required for normal growth of pollen tubes in the pistil.

In flowering plants, the interaction of pollen tubes with female tissues is important for the accomplishment of double fertilization. Little information is known about the mechanisms that underlie signalling between pollen tubes and female tissues. In this study, two Arabidopsis pollen tube-expressed CrRLK1L protein kinases, Buddha's Paper Seal 1 (BUPS1) and BUPS2, were identified as being required for normal tip growth of pollen tubes in the pistil. They are expressed prolifically in pollen and pollen tubes and are localized on the plasma membrane of the pollen tube tip region. Mutations in BUPS1 drastically reduced seed set. Most of the bups1 mutant pollen tubes growing in the pistil exhibited a swollen pollen tube tip, leading to failure of fertilization. The bups2 pollen tubes had a slightly abnormal morphology but could still accomplish double fertilization. The bups1 bups2 double mutant exhibited a slightly enhanced phenotype compared to the single bups1 mutants. The BUPS1 proteins could form homomers and heteromers with BUPS2, whereas BUPS2 could only form heteromers with BUPS1. The BUPS proteins could interact with the Arabidopsis pollen-expressed RopGEFs in the yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. The results indicated that the BUPSs may mediate normal polar growth of pollen tubes in the pistil.

An examination of home-based end-of-life care for cancer patients: a qualitative study.

BACKGROUND: Only a small number of patients have utilized the home-based end-of-life care service in Shanghai that has been offered since 2012. This study explores how home-based end-of-life care is delivered in community health service centers in Shanghai and examines the difficulties in the delivery of the care. METHODS: This was a qualitative study in which data were collected from interviews and analyzed using qualitative content analysis. Nineteen health care providers with experience in delivering home-based end-of-life care in 12 community health service centers were recruited. The interviews were conducted between August 2018 and February 2019. RESULTS: Four themes emerged from the interviews: (i) Patients under home-based end-of-life care: Patients receiving the care were cancer patients with less than 1 year of life expectancy. The criteria for patients were broad. (ii) Service structure: The service was delivered regularly by the physicians and nurses using the approaches of home visits and/or telephone follow-ups. (iii) Service process: The service consisted of multiple components, including monitoring the patient's condition, managing the patient's symptoms, giving daily care instructions, performing nursing procedures, and giving psychological support. However, most of the care focused on monitoring the patients and managing their physical discomfort. (iv) Difficulties in delivering care: Being unable to provide the service and feeling powerless when facing psycho-spiritual problems were the two major difficulties. Three factors contributed to the suspension of the service: The gap between the service and the needs of the patients, a lack of patients, and low work motivation. The demand that the truth be concealed from the families and their attitude of avoiding talking about death were the key factors of the failure of psycho-spiritual care. CONCLUSIONS: Several issues should be addressed before the service can be further developed, including fully understanding the needs and preferences of local patients and their families, securing more financial support and a better supply of drugs, delivering better training for staff, and ensuring greater rewards for individuals and institutions providing the service.

ATX3, ATX4, and ATX5 Encode Putative H3K4 Methyltransferases and Are Critical for Plant Development.

Methylation of Lys residues in the tail of the H3 histone is a key regulator of chromatin state and gene expression, conferred by a large family of enzymes containing an evolutionarily conserved SET domain. One of the main types of SET domain proteins are those controlling H3K4 di- and trimethylation. The genome of Arabidopsis (Arabidopsis thaliana) encodes 12 such proteins, including five ARABIDOPSIS TRITHORAX (ATX) proteins and seven ATX-Related proteins. Here, we examined three until-now-unexplored ATX proteins, ATX3, ATX4, and ATX5. We found that they exhibit similar domain structures and expression patterns and are redundantly required for vegetative and reproductive development. Concurrent disruption of the ATX3, ATX4, and ATX5 genes caused marked reduction in H3K4me2 and H3K4me3 levels genome-wide and resulted in thousands of genes expressed ectopically. Furthermore, atx3/atx4/atx5 triple mutants resulted in exaggerated phenotypes when combined with the atx2 mutant but not with atx1 Together, we conclude that ATX3, ATX4, and ATX5 are redundantly required for H3K4 di- and trimethylation at thousands of sites located across the genome, and genomic features associated with targeted regions are different from the ATXR3/SDG2-controlled sites in Arabidopsis.

Plasmon-modulated bistable four-wave mixing signals from a metal nanoparticle-monolayer MoS2 nanoresonator hybrid system.

We present a study for the impact of exciton-phonon and exciton-plasmon interactions on bistable four-wave mixing (FWM) signals in a metal nanoparticle (MNP)-monolayer MoS2 nanoresonator hybrid system. Via tracing the FWM response we predict that, depending on the excitation conditions and the system parameters, such a system exhibits 'U-shaped' bistable FWM signals. We also map out bistability phase diagrams within the system's parameter space. Especially, we show that compared with the exciton-phonon interaction, a strong exciton-plasmon interaction plays a dominant role in the generation of optical bistability, and the bistable region will be greatly broadened by shortening the distance between the MNP and the monolayer MoS2 nanoresonator. In the weak exciton-plasmon coupling regime, the impact of exciton-phonon interaction on optical bistability will become obvious. The scheme proposed may be used for building optical switches and logic-gate devices for optical computing and quantum information processing.

Bistable four-wave mixing response in a semiconductor quantum dot coupled to a photonic crystal nanocavity.

We perform a theoretical study of the bistable four-wave mixing (FWM) response in a coupled system comprised of a semiconductor quantum dot (SQD) and a photonic crystal (PC) nanocavity in which the SQD is embedded. It is shown that the shape of the FWM spectrum can switch among single-peaked, double-peaked, triple-peaked, and four-peaked arising from the vacuum Rabi splitting and the exciton-nanocavity coupling. Especially, we map out bistability phase diagrams within a parameter subspace of the system, and find that it is easy to turn on or off the bistable FWM response by only adjusting the excitation frequency or the pumping intensity. Our results offer a feasible means for measuring the SQD-PC nanocavity coupling strength and open a new avenue to design optical switches and memories.

Switching freely between superluminal and subluminal light propagation in a monolayer MoS2 nanoresonator.

We theoretically propose a feasible scheme to advance or slow the propagation of light in a monolayer MoS2 nanoresonator (NR). The scheme allows one to easily turn on or off the fast (superluminal) and slow (subluminal) light effects and switch freely between fast and slow light propagation by only adjusting the frequency or intensity of the pump field. As the exciton interacts strongly with the phonons in MoS2, the slow light effect will appear along with a large dispersion with a very steep negative slope and a sharp absorption peak. Especially, the maximal group velocity index of the slow light in the monolayer MoS2 NR can reach two orders of magnitude larger than that in a carbon nanotube resonator. These results provide a new way to measure the exciton-phonon coupling strength and may prove useful in device applications such as optical switching and optical signal processing.

Four-wave mixing signal enhancement and optical bistability of a hybrid metal nanoparticle-quantum dot molecule in a nanomechanical resonator.

We investigate theoretically four-wave mixing (FWM) response and optical bistability (OB) in a hybrid nanosystem composed of a metal nanoparticle (MNP) and a semiconductor quantum dot (SQD) coupled to a nanomechanical resonator (NR). It is shown that the FWM signal is enhanced by more than three orders of magnitude as compared to that of the system without exciton-phonon interaction, and the FWM signal can also be suppressed significantly and broadened due to the exciton-plasmon interaction. As the MNP couples strongly with the SQD, the bistable FWM response can be achieved by adjusting the SQD-MNP distance and the pumping intensity. For a given pumping constant and a fixed SQD-MNP distance, the enhanced exciton-phonon interaction can promote the occurrence of bistability. Our findings not only present a feasible way to detect the spacing between two nanoparticles, but also hold promise for developing quantum switches and nanoscale rulers.